Sample records for cycle system kcs
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NASA Astrophysics Data System (ADS)
Khankari, Goutam; Karmakar, Sujit
2017-06-01
This paper proposes a comparative performance analysis based on 4-E (Energy, Exergy, Environment, and Economic) of a bottoming pure Ammonia (NH3) based Organic Rankine Cycle (ORC) and Ammonia-water (NH3-H2O) based Kalina Cycle System 11(KCS 11) for additional power generation through condenser waste heat recovery integrated with a conventional 500MWe Subcritical coal-fired thermal power plant. A typical high-ash Indian coal is used for the analysis. The flow-sheet computer programme `Cycle Tempo' is used to simulate both the cycles for thermodynamic performance analysis at different plant operating conditions. Thermodynamic analysis is done by varying different NH3 mass fraction in KCS11 and at different turbine inlet pressure in both ORC and KCS11. Results show that the optimum operating pressure of ORC and KCS11 with NH3 mass fraction of 0.90 are about 15 bar and 11.70 bar, respectively and more than 14 bar of operating pressure, the plant performance of ORC integrated power plant is higher than the KCS11 integrated power plant and the result is observed reverse below this pressure. The energy and exergy efficiencies of ORC cycle are higher than the KCS11 by about 0.903 % point and 16.605 % points, respectively under similar saturation vapour temperature at turbine inlet for both the cycles. Similarly, plant energy and exergy efficiencies of ORC based combined cycle power plant are increased by 0.460 % point and 0.420 % point, respectively over KCS11 based combined cycle power plant. Moreover, the reduction of CO2 emission in ORC based combined cycle is about 3.23 t/hr which is about 1.5 times higher than the KCS11 based combined cycle power plant. Exergy destruction of the evaporator in ORC decreases with increase in operating pressure due to decrease in temperature difference of heat exchanging fluids. Exergy destruction rate in the evaporator of ORC is higher than KCS11 when the operating pressure of ORC reduces below 14 bar. This happens due to variable boiling temperature of NH3-H2O binary mixture in KCS11 and resulting in less irreversibility during the process of heat transfer. Levelized Cost of Electricity (LCoE) generation and the cost of implementation of ORC integrated power plant is about Rs.1.767/- per kWh and Rs. 2.187/- per kg of fuel saved, respectively whereas, the LCoE for KCS11 based combined power plant is slightly less than the ORC based combined cycle power plant and estimated as about Rs.1.734 /- per kWh. The cost of implementation of KCS11 based combined cycle power plant is about Rs. 0.332/- per kg of fuel saved. Though the energy and exergy efficiencies of ORC is better than KCS11 but considering the huge investment for developing the combined cycle power plant based on ORC in comparison with KCS11 below the operating pressure of 14 bar, KCS11 is superior than NH3 based ORC.
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Lipid oxidation in minced beef meat with added Krebs cycle substrates to stabilise colour.
Yi, G; Grabež, V; Bjelanovic, M; Slinde, E; Olsen, K; Langsrud, O; Phung, V T; Haug, A; Oostindjer, M; Egelandsdal, B
2015-11-15
Krebs cycle substrates (KCS) can stabilise the colour of packaged meat by oxygen reduction. This study tested whether this reduction releases reactive oxygen species that may lead to lipid oxidation in minced meat under two different storage conditions. KCS combinations of succinate and glutamate increased peroxide forming potential (PFP, 1.18-1.32 mmol peroxides/kg mince) and thiobarbituric acid reactive substances (TBARS, 0.30-0.38 mg malondialdehyde (MDA) equivalents/kg mince) under low oxygen storage conditions. Both succinate and glutamate were metabolised. Moreover, under high oxygen (75%) storage conditions, KCS combinations of glutamate, citrate and malate increased PFP (from 1.22 to 1.29 mmol peroxides/kg) and TBARS (from 0.37 to 0.40 mg MDA equivalents/kg mince). Only glutamate was metabolised. The KCS combinations that were added to stabilise colour were metabolised during storage, and acted as pro-oxidants that promoted lipid oxidation in both high and low oxygen conditions. Copyright © 2015. Published by Elsevier Ltd.
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A knowledge-based system design/information tool
NASA Technical Reports Server (NTRS)
Allen, James G.; Sikora, Scott E.
1990-01-01
The objective of this effort was to develop a Knowledge Capture System (KCS) for the Integrated Test Facility (ITF) at the Dryden Flight Research Facility (DFRF). The DFRF is a NASA Ames Research Center (ARC) facility. This system was used to capture the design and implementation information for NASA's high angle-of-attack research vehicle (HARV), a modified F/A-18A. In particular, the KCS was used to capture specific characteristics of the design of the HARV fly-by-wire (FBW) flight control system (FCS). The KCS utilizes artificial intelligence (AI) knowledge-based system (KBS) technology. The KCS enables the user to capture the following characteristics of automated systems: the system design; the hardware (H/W) design and implementation; the software (S/W) design and implementation; and the utilities (electrical and hydraulic) design and implementation. A generic version of the KCS was developed which can be used to capture the design information for any automated system. The deliverable items for this project consist of the prototype generic KCS and an application, which captures selected design characteristics of the HARV FCS.
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Oiki, Shigetoshi; Iwamoto, Masayuki; Sumikama, Takashi
2011-01-31
In narrow pore ion channels, ions and water molecules diffuse in a single-file manner and cannot pass each other. Under such constraints, ion and water fluxes are coupled, leading to experimentally observable phenomena such as the streaming potential. Analysis of this coupled flux would provide unprecedented insights into the mechanism of permeation. In this study, ion and water permeation through the KcsA potassium channel was the focus, for which an eight-state discrete-state Markov model has been proposed based on the crystal structure, exhibiting four ion-binding sites. Random transitions on the model lead to the generation of the net flux. Here we introduced the concept of cycle flux to derive exact solutions of experimental observables from the permeation model. There are multiple cyclic paths on the model, and random transitions complete the cycles. The rate of cycle completion is called the cycle flux. The net flux is generated by a combination of cyclic paths with their own cycle flux. T.L. Hill developed a graphical method of exact solutions for the cycle flux. This method was extended to calculate one-way cycle fluxes of the KcsA channel. By assigning the stoichiometric numbers for ion and water transfer to each cycle, we established a method to calculate the water-ion coupling ratio (CR(w-i)) through cycle flux algebra. These calculations predicted that CR(w-i) would increase at low potassium concentrations. One envisions an intuitive picture of permeation as random transitions among cyclic paths, and the relative contributions of the cycle fluxes afford experimental observables.
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Oiki, Shigetoshi; Iwamoto, Masayuki; Sumikama, Takashi
2011-01-01
In narrow pore ion channels, ions and water molecules diffuse in a single-file manner and cannot pass each other. Under such constraints, ion and water fluxes are coupled, leading to experimentally observable phenomena such as the streaming potential. Analysis of this coupled flux would provide unprecedented insights into the mechanism of permeation. In this study, ion and water permeation through the KcsA potassium channel was the focus, for which an eight-state discrete-state Markov model has been proposed based on the crystal structure, exhibiting four ion-binding sites. Random transitions on the model lead to the generation of the net flux. Here we introduced the concept of cycle flux to derive exact solutions of experimental observables from the permeation model. There are multiple cyclic paths on the model, and random transitions complete the cycles. The rate of cycle completion is called the cycle flux. The net flux is generated by a combination of cyclic paths with their own cycle flux. T.L. Hill developed a graphical method of exact solutions for the cycle flux. This method was extended to calculate one-way cycle fluxes of the KcsA channel. By assigning the stoichiometric numbers for ion and water transfer to each cycle, we established a method to calculate the water-ion coupling ratio (CR w-i) through cycle flux algebra. These calculations predicted that CR w-i would increase at low potassium concentrations. One envisions an intuitive picture of permeation as random transitions among cyclic paths, and the relative contributions of the cycle fluxes afford experimental observables. PMID:21304994
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Kuu, Wei Y; Nail, Steven L; Sacha, Gregory
2009-03-01
The purpose of this study was to perform a rapid determination of vial heat transfer parameters, that is, the contact parameter K(cs) and the separation distance l(v), using the sublimation rate profiles measured by tunable diode laser absorption spectroscopy (TDLAS). In this study, each size of vial was filled with pure water followed by a freeze-drying cycle using a LyoStar II dryer (FTS Systems) with step-changes of the chamber pressure set-point at to 25, 50, 100, 200, 300, and 400 mTorr. K(cs) was independently determined by nonlinear parameter estimation using the sublimation rates measured at the pressure set-point of 25 mTorr. After obtaining K(cs), the l(v) value for each vial size was determined by nonlinear parameter estimation using the pooled sublimation rate profiles obtained at 25 to 400 mTorr. The vial heat transfer coefficient K(v), as a function of the chamber pressure, was readily calculated, using the obtained K(cs) and l(v) values. It is interesting to note the significant difference in K(v) of two similar types of 10 mL Schott tubing vials, primary due to the geometry of the vial-bottom, as demonstrated by the images of the contact areas of the vial-bottom. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association
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Kakinuma, Yuki; Kimura, Takuya
2017-01-01
Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation. PMID:28804705
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Kakinuma, Yuki; Kimura, Takuya; Watanabe, Yoshifumi
2017-01-01
Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation.
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Brooks, Elizabeth S.; Greer, Christina L.; Romero-Calderón, Rafael; Serway, Christine N.; Grygoruk, Anna; Haimovitz, Jasmine M.; Nguyen, Bac T.; Najibi, Rod; Tabone, Christopher J.; de Belle, J. Steven; Krantz, David E.
2011-01-01
Summary Storage and release of classical and amino acid neurotransmitters requires vesicular transporters. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown. Likewise, KCs do not express a known vesicular transporter. We report the identification of a novel Drosophila gene portabella (prt) that is structurally similar to known vesicular transporters. Both larval and adult brains express PRT in the KCs of the MBs. Additional PRT cells project to the central complex and optic ganglia. prt mutation causes an olfactory learning deficit and an unusual defect in the male’s position during copulation that is rescued by expression in KCs. Since prt is expressed in neurons that lack other known vesicular transporters or neurotransmitters, it may define a previously unknown neurotransmitter system responsible for sexual behavior and a component of olfactory learning. PMID:22017990
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Combinatorial Effects of Fatty Acid Elongase Enzymes on Nervonic Acid Production in Camelina sativa
Huai, Dongxin; Zhang, Yuanyuan; Zhang, Chunyu; Cahoon, Edgar B.; Zhou, Yongming
2015-01-01
Very long chain fatty acids (VLCFAs) with chain lengths of 20 carbons and longer provide feedstocks for various applications; therefore, improvement of VLCFA contents in seeds has become an important goal for oilseed enhancement. VLCFA biosynthesis is controlled by a multi-enzyme protein complex referred to as fatty acid elongase, which is composed of β-ketoacyl-CoA synthase (KCS), β-ketoacyl-CoA reductase (KCR), β-hydroxyacyl-CoA dehydratase (HCD) and enoyl reductase (ECR). KCS has been identified as the rate-limiting enzyme, but little is known about the involvement of other three enzymes in VLCFA production. Here, the combinatorial effects of fatty acid elongase enzymes on VLCFA production were assessed by evaluating the changes in nervonic acid content. A KCS gene from Lunaria annua (LaKCS) and the other three elongase genes from Arabidopsis thaliana were used for the assessment. Five seed-specific expressing constructs, including LaKCS alone, LaKCS with AtKCR, LaKCS with AtHCD, LaKCS with AtECR, and LaKCS with AtKCR and AtHCD, were transformed into Camelina sativa. The nervonic acid content in seed oil increased from null in wild type camelina to 6-12% in LaKCS-expressing lines. However, compared with that from the LaKCS-expressing lines, nervonic acid content in mature seeds from the co-expressing lines with one or two extra elongase genes did not show further increases. Nervonic acid content from LaKCS, AtKCR and AtHCD co-expressing line was significantly higher than that in LaKCS-expressing line during early seed development stage, while the ultimate nervonic acid content was not significantly altered. The results from this study thus provide useful information for future engineering of oilseed crops for higher VLCFA production. PMID:26121034
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East Europe Report, Economic and Industrial Affairs
1984-09-11
added (UW) , return on production assets ( RVF ), profit and exports. These categories characterize the results of the work of the whole organization...prescribed goals No of VHJ’s Increase No of VHJ’s Decrease UW (mil. of Kcs) 9 147.5 6 184.8 Profit (mil. of Kcs) 6 66.0 8 289.0 RVF /return on prod. 7... RVF (percentage) No of Workers ZSMP (mil. of Kcs) PSMP (mil. of Kcs) Average Wage (Kcs) Allocation from Profits to FR (mil. of Kcs) VHJ’s with
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A recurrent de novo FAM111A mutation causes Kenny-Caffey syndrome type 2.
Isojima, Tsuyoshi; Doi, Koichiro; Mitsui, Jun; Oda, Yoichiro; Tokuhiro, Etsuro; Yasoda, Akihiro; Yorifuji, Tohru; Horikawa, Reiko; Yoshimura, Jun; Ishiura, Hiroyuki; Morishita, Shinichi; Tsuji, Shoji; Kitanaka, Sachiko
2014-04-01
Kenny-Caffey syndrome (KCS) is a rare dysmorphologic syndrome characterized by proportionate short stature, cortical thickening and medullary stenosis of tubular bones, delayed closure of anterior fontanelle, eye abnormalities, and hypoparathyroidism. The autosomal dominant form of KCS (KCS type 2 [KCS2]) is distinguished from the autosomal recessive form of KCS (KCS type 1 [KCS1]), which is caused by mutations of the tubulin-folding cofactor E (TBCE) gene, by the absence of mental retardation. In this study, we recruited four unrelated Japanese patients with typical sporadic KCS2, and performed exome sequencing in three patients and their parents to elucidate the molecular basis of KCS2. The possible candidate genes were explored by a de novo mutation detection method. A single gene, FAM111A (NM_001142519.1), was shared among three families. An identical missense mutation, R569H, was heterozygously detected in all three patients but not in the unaffected family members. This mutation was also found in an additional unrelated patient. These findings are in accordance with those of a recent independent report by a Swiss group that KCS2 is caused by a de novo mutation of FAM111A, and R569H is a hot spot mutation for KCS2. Although the function of FAM111A is not known, this study would provide evidence that FAM111A is a key molecule for normal bone development, height gain, and parathyroid hormone development and/or regulation. © 2014 American Society for Bone and Mineral Research.
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Radi, Zaher A; Koza-Taylor, Petra H; Bell, Rosonald R; Obert, Leslie A; Runnels, Herbert A; Beebe, Jean S; Lawton, Michael P; Sadis, Seth
2011-07-01
Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that is responsible for the survival and proliferation of monocytes and the differentiation of monocytes into macrophages, including Kupffer cells (KCs) in the liver. KCs play an important role in the clearance of several serum enzymes, including aspartate aminotransferase and creatine kinase, that are typically elevated as a result of liver or skeletal muscle injury. We used three distinct animal models to investigate the hypothesis that increases in the levels of serum enzymes can be the result of decreases in KCs in the apparent absence of hepatic or skeletal muscle injury. Specifically, neutralizing M-CSF activity via a novel human monoclonal antibody reduced the CD14(+)CD16(+) monocyte population, depleted KCs, and increased aspartate aminotransferase and creatine kinase serum enzyme levels in cynomolgus macaques. In addition, the treatment of rats with clodronate liposomes depleted KCs and led to increased serum enzyme levels, again without evidence of tissue injury. Finally, in the osteopetrotic (Csf1(op)/Csf1(op)) mice lacking functional M-CSF and having reduced levels of KCs, the levels of serum enzymes are higher than in wild-type littermates. Together, these findings support a mechanism for increases in serum enzyme levels through M-CSF regulation of tissue macrophage homeostasis without concomitant histopathological changes in either the hepatic or skeletal system. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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[Kenny-Caffey syndrome and its related syndromes].
Isojima, Tsuyoshi; Kitanaka, Sachiko
2015-11-01
Kenny-Caffey syndrome (KCS) is a very rare dysmorphologic syndrome characterized by proportionate short stature, cortical thickening and medullary stenosis of tubular bones, delayed closure of anterior fontanelle, eye abnormalities, and hypoparathyroidism. Two types of KCS were known: the autosomal recessive form (KCS type 1), which is caused by mutations of the TBCE gene, and the autosomal dominant form (KCS type 2), which is caused by mutations of the FAM111A gene. TBCE mutation also causes hypoparathyroidism-retardation-dysmorphism syndrome, and FAM111A mutation also causes gracile bone dysplasia. These two diseases can be called as KCS-related syndromes. In this article, we review the clinical manifestations of KCS and discuss its related syndromes.
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Spontaneous olfactory receptor neuron activity determines follower cell response properties
Joseph, Joby; Dunn, Felice A.; Stopfer, Mark
2012-01-01
Noisy or spontaneous activity is common in neural systems and poses a challenge to detecting and discriminating signals. Here we use the locust to answer fundamental questions about noise in the olfactory system: Where does spontaneous activity originate? How is this activity propagated or reduced throughout multiple stages of neural processing? What mechanisms favor the detection of signals despite the presence of spontaneous activity? We found that spontaneous activity long observed in the secondary projection neurons (PNs) originates almost entirely from the primary olfactory receptor neurons (ORNs) rather than from spontaneous circuit interactions in the antennal lobe, and that spontaneous activity in ORNs tonically depolarizes the resting membrane potentials of their target PNs and local neurons (LNs), and indirectly tonically depolarizes tertiary Kenyon cells (KCs). However, because these neurons have different response thresholds, in the absence of odor stimulation, ORNs and PNs display a high spontaneous firing rate but KCs are nearly silent. Finally, we used a simulation of the olfactory network to show that discrimination of signal and noise in the KCs is best when threshold levels are set so that baseline activity in PNs persists. Our results show how the olfactory system benefits from making a signal detection decision after a point of maximal information convergence, e.g., after KCs pool inputs from many PNs. PMID:22357872
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[Isolation and purification of primary Kupffer cells from mouse liver].
Sun, Chao; Luo, Qingbo; Lu, Xiuxian; Zheng, Daofeng; He, Diao; Wu, Zhongjun
2016-08-01
Objective To isolate and purify Kupffer cells (KCs) from BALB/c mice by an efficient method of low-speed centrifugation and rapid adherence. Methods The mouse liver tissue was perfused in situ and digested with 0.5 g/L collagenase type IV in vitro by water bath. Then, through the low-speed centrifugation, KCs were separated from the mixed hepatocytes, and purified by rapid adherent characteristics. Finally, the production and activity of KCs obtained by this modified method were compared with those isolated by Percoll density gradient centrifugation. We used F4/80 antibody immunofluorescence technique to observe morphological features of KCs, flow cytometry (FCM) to detect the expression of F4/80 antibody and the ink uptake test to observe the phagocytic activity. Moreover, using FCM, we evaluated the expressions of molecules associated with antigen presentation, including major histocompatibility complex class II (MHC II), CD40, CD86 and CD68 on the surface of KCs subjected to hypoxia/reoxygenation (H/R) modeling. And, ELISA was conducted to measure tumor necrosis factor-α (TNF-α) production of the cultured KCs following H/R. Results The yield of KCs was (5.83±0.54)×10(6) per mouse liver and the survival rate of KCs was up to 92% by low-speed centrifugation and rapid adherent method. Compared with Percoll density gradient centrifugation [the yield of KCs was (2.19±0.43)×10(6) per liver], this new method significantly improved the yield of KCs. F4/80 immunofluorescence showed typical morphologic features of KCs such as spindle or polygon shapes and FCM identified nearly 90% F4/80 positive cells. The phagocytic assay showed that lots of ink particles were phagocytosed into the isolated cells. KC H/R models expressed more MHC II, CD40 and CD86 and produced more TNF-α participating in inflammation. Conclusion The efficient method to isolate and purify KCs from BALB /c mice has been successfully established.
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Jemail, Leila; Miyao, Masashi; Kotani, Hirokazu; Kawai, Chihiro; Minami, Hirozo; Abiru, Hitoshi; Tamaki, Keiji
2018-04-23
Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.
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The gating cycle of a K+ channel at atomic resolution
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cuello, Luis G.; Cortes, D. Marien; Perozo, Eduardo
C-type inactivation in potassium channels helps fine-tune long-term channel activity through conformational changes at the selectivity filter. Here, through the use of cross-linked constitutively open constructs, we determined the structures of KcsA’s mutants that stabilize the selectivity filter in its conductive (E71A, at 2.25 Å) and deep C-type inactivated (Y82A at 2.4 Å) conformations. These structural snapshots represent KcsA’s transient open-conductive (O/O) and the stable open deep C-type inactivated states (O/I), respectively. The present structures provide an unprecedented view of the selectivity filter backbone in its collapsed deep C-type inactivated conformation, highlighting the close interactions with structural waters and themore » local allosteric interactions that couple activation and inactivation gating. Together with the structures associated with the closed-inactivated state (C/I) and in the well-known closed conductive state (C/O), this work recapitulates, at atomic resolution, the key conformational changes of a potassium channel pore domain as it progresses along its gating cycle.« less
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Arciniega, Juan Carlos; Wojtowicz, Jadwiga Cristina; Mohamed, Engy Mostafa; McCulley, James Parker
2011-08-01
To evaluate the effect of excess meibum on tear evaporation rate in patients with and without dry eye. Eleven healthy subjects and 16 patients with dry eye were tested. The dry eye group was divided into 2 subgroups: classic keratoconjunctivitis sicca (KCS) with clear and easily expressed meibum and KCS with meibomian gland dysfunction (MGD) with turbid secretions and difficult-to-express meibum. Evaporative measurements were performed at baseline and after digital expression of meibomian glands at 12, 24, 36, and 48 minutes. Two ranges of relative humidity were used, 25% to 35% and 35% to 45%. The data were expressed as microliters per square centimeter per minute. An increase in the evaporation rate of the tear film was noted for all measurements at both relative humidities in the classic KCS and KCS with MGD groups compared with healthy subjects (P < 0.05). The average evaporation rates at relative humidities of 25% to 35% and 35% to 45% were 0.056 ± 0.016 and 0.040 ± 0.008 for the classic KCS group; 0.055 ± 0.026 and 0.037 ± 0.019 for the KCS with MGD group and 0.033 ± 0.012 and 0.023 ± 0.008 for the healthy group. Also, a decrease in the evaporation rate was observed in the healthy and KCS with MGD groups between baseline and the first measurement after digital expression for both relative humidities (P < 0.05). The classic KCS group did not show any changes after expression. Classic KCS and KCS with MGD groups showed an increase in tear evaporation rates compared with the healthy group. Aqueous tear evaporation diminished in the healthy and KCS with MGD groups after expression of meibomian glands. However, this effect was transient and negligible after the second measurement.
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Application of the key characteristics of carcinogens in cancer hazard identification
Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David C; Beland, Frederick A; Smith, Martyn T
2018-01-01
Abstract Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as ‘is genotoxic,’ ‘is immunosuppressive’ or ‘modulates receptor-mediated effects,’ and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification. PMID:29562322
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Application of the key characteristics of carcinogens in cancer hazard identification.
Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David C; Beland, Frederick A; Smith, Martyn T
2018-04-05
Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as 'is genotoxic,' 'is immunosuppressive' or 'modulates receptor-mediated effects,' and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification.
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Whitcher, John P; Shiboski, Caroline H; Shiboski, Stephen C; Heidenreich, Ana Maria; Kitagawa, Kazuko; Zhang, Shunhua; Hamann, Steffen; Larkin, Genevieve; McNamara, Nancy A; Greenspan, John S; Daniels, Troy E
2010-03-01
To describe, apply, and test a new ocular grading system for assessing keratoconjunctivitis sicca (KCS) using lissamine green and fluorescein. Prospective, observational, multicenter cohort study. The National Institutes of Health-funded Sjögren's Syndrome International Registry (called Sjögren's International Collaborative Clinical Alliance [SICCA]) is developing standardized classification criteria for Sjögren syndrome (SS) and is creating a biospecimen bank for future research. Eight SICCA ophthalmologists developed a new quantitative ocular grading system (SICCA ocular staining score [OSS]), and we analyzed OSS distribution among the SICCA cohort and its association with other phenotypic characteristics of SS. The SICCA cohort includes participants ranging from possibly early SS to advanced disease. Procedures include sequenced unanesthetized Schirmer test, tear break-up time, ocular surface staining, and external eye examination at the slit lamp. Using statistical analyses and proportional Venn diagrams, we examined interrelationships between abnormal OSS (>or=3) and other characteristics of SS (labial salivary gland [LSG] biopsy with focal lymphocytic sialadenitis and focus score >1 positive anti-SS A antibodies, anti-SS B antibodies, or both). Among 1208 participants, we found strong associations between abnormal OSS, positive serologic results, and positive LSG focus scores (P < .0001). Analysis of the overlapping relationships of these 3 measures defined a large group of participants who had KCS without other components of SS, representing a clinical entity distinct from the KCS associated with SS. This new method for assessing KCS will become the means for diagnosing the ocular component of SS in future classification criteria. We find 2 forms of KCS whose causes may differ. (c) 2010 Elsevier Inc. All rights reserved.
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Erdenebileg, Zolzaya; Park, So Hyun; Chang, Kyung Ja
2018-04-01
College students are in transition from adolescence to adulthood, and it has been reported that they show poor dietary habits. This study was conducted to compare body image perception, nutrition knowledge, dietary attitudes, dietary habits, and health-related lifestyles between Korean college students (KCS) and Mongolian college students (MCS). Subjects were 314 KCS and 280 MCS. The data includes results of self-administered questionnaires; statistical analysis was performed using the SPSS 23.0 program. With regards to body image perception, KCS perceived themselves to be fatter on current body image than ideal body image compared to MCS; 64.0% of KCS and 34.6% of MCS desired to be thinner. Total score of nutrition knowledge in KCS (17.0) was significantly higher compared to MCS (8.4) ( P < 0.001), but total score of dietary attitudes in KCS (27.0) was significantly lower compared to MCS (31.2) ( P < 0.001). Nutrition knowledge had a significantly positive correlation with dietary attitudes in MCS ( P < 0.01). Meal consumption among male and female subjects was 2 and 3 times, respectively, in order in KCS, and 3 and 2 times, respectively, in order in MCS ( P < 0.001). Rate of skipping breakfast in both genders was significantly higher in KCS than in MCS (male: P < 0.05, female: P < 0.001). In health-related lifestyles, KCS had a significantly higher rate in frequency of alcohol drinking ( P < 0.001), exercise ( P < 0.01), and mobile phone usage ( P < 0.001), compared to MCS. This study suggests that development of nutrition education program which is effective and proper is required to improve healthy dietary habits among college students of both countries. Essential contents should include acquirement of nutrition knowledge and a motivation for its application to actual life for KCS, and improvement of healthy dietary habits for MCS.
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An intra-K-complex oscillation with independent and labile frequency and topography in NREM sleep
Kokkinos, Vasileios; Koupparis, Andreas M.; Kostopoulos, George K.
2013-01-01
NREM sleep is characterized by K-complexes (KCs), over the negative phase of which we identified brief activity in the theta range. We recorded high resolution EEG of whole-night sleep from seven healthy volunteers and visually identified 2nd and 3rd stage NREM spontaneous KCs. We identified three major categories: (1) KCs without intra-KC-activity (iKCa), (2) KCs with non-oscillatory iKCa, and (3) KCs with oscillatory iKCa. The latter group of KCs with intra-KC-oscillation (iKCo), was clustered according to the duration of the iKCo. iKCa was observed in most KCs (1150/1522, 75%). iKCos with 2, 3, and 4 waves were observed in 52% (786/1522) of KCs in respective rates of 49% (386/786), 44%, and 7%. Successive waves of iKCos showed on average a shift of their maximal amplitude in the anterio-posterior axis, while the average amplitude of the slow KC showed no spatial shift in time. The iKCo spatial shift was accompanied by transient increases in instantaneous frequency from the theta band toward the alpha band, followed by decreases to upper theta. The study shows that the KC is most often concurrently accompanied by an independent brief iKCo exhibiting topographical relocation of amplitude maxima with every consecutive peak and transient increases in frequency. The iKCo features are potentially reflecting arousing processes taking place during the KC. PMID:23637656
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Yue, Shi; Zhou, Haoming; Wang, Xuehao; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy W.; Zhai, Yuan
2017-01-01
Although mechanisms of immune activation against liver ischemia reperfusion injury (IRI) have been studied extensively, questions regarding liver resident macrophages, i.e., Kupffer cells, remain controversial. Recent progress in the biology of tissue resident macrophages implicates homeostatic functions of KCs. This study aims to dissect responses and functions of KCs in liver IRI. In a murine liver partial warm ischemia model, we analyzed liver resident vs. infiltrating macrophages by fluorescence-activated cell sorting (FACS) and immunofluorescence staining. Our data showed that liver immune activation by IR was associated with not only infiltrations/activations of peripheral macrophages (iMØ), but also necrotic depletion of KCs. Inhibition of Receptor Interacting Protein 1 (RIP1) by necrostatin-1s protected KCs from ischemia-induce depletion, resulting in the reduction of iMØ infiltration, suppression of pro-inflammatory immune activation and protection of livers from IRI. The depletion of KCs by clodronate-liposomes abrogated these effects of Nec-1s. Additionally, liver reconstitutions with KCs post-ischemia exerted anti-inflammatory/cytoprotective effects against IRI. These results reveal a unique response of KCs against liver IR, i.e., RIP-1-dependent necrosis, which constitutes a novel mechanism of liver inflammatory immune activation in the pathogenesis of liver IRI. PMID:28289160
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The effect of lipopolysaccharides on the expression of CD14 and TLR4 in rat Kupffer cells.
Feng, Jun-Ming; Shi, Jing-Quan; Liu, You-Sheng
2003-05-01
To assess the effect of lipopolysaccharides (LPS) on the expression of CD14 and TLR4 in rat Kupffer cells (KCs). In rat KCs induced by LPS, the changes of CD14 and TLR4 expression were measured by RT-PCR and immunohistochemistry, and the expressions of TNF-alphamRNA, IL-6mRNA or the concentrations of TNF-alpha, IL-6 were estimated by in situ hybridization, radioimmunoassay, and others. The expressions of CD14 and TLR4 in KCs induced by LPS were markedly increased in a dose-dependent manner (10 mg/L-1 microg/L) or in a time-dependent manner (0.5 h-24 h), with the peaked expression of CD14 at 3-6 hours. The expressions of CD14 and TLR4 in KCs stimulated by the active mediators from KCs which had been exposed to LPS for 1 hour were obviously increased. There is a close relationship between LPS or the active mediators from KCs induced by LPS and the expressions of CD14, TLR4. It is implied that the increase of TLR4, CD14 expression may be induced by LPS within 1-3 hours, and further increase of TLR4, CD14 expression may be correlated with the cytokines produced by KCs.
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Taylor, David C; Francis, Tammy; Guo, Yiming; Brost, Jennifer M; Katavic, Vesna; Mietkiewska, Elzbieta; Michael Giblin, E; Lozinsky, Sharla; Hoffman, Travis
2009-12-01
Nervonic acid 24:1 Delta15 (cis-tetracos-15-enoic acid) is a very long-chain monounsaturated fatty acid and exists in nature as an elongation product of oleic acid. There is an increasing interest in production of high nervonic acid oils for pharmaceutical, nutraceutical and industrial applications. Using a polymerase chain reaction approach, we have isolated a gene from Cardamine graeca L., which encodes a 3-ketoacyl-CoA synthase (KCS), the first component of the elongation complex involved in synthesis of nervonic acid. Expression of the Cardamine KCS in yeast resulted in biosynthesis of nervonic acid, which is not normally present in yeast cells. We transformed Arabidopsis and Brassica carinata with the Cardamine KCS under the control of the seed-specific promoter, napin. The T(3) generations of transgenic Arabidopsis and B. carinata plants expressing the Cardamine KCS showed that seed-specific expression resulted in relatively large comparative increases in nervonic acid proportions in Arabidopsis seed oil, and 15-fold increase in nervonic acid proportions in B. carinata seed oil. The highest nervonic acid level in transgenic B. carinata lines reached 44%, with only 6% of residual erucic acid. In contrast, similar transgenic expression of the Cardamine KCS in high erucic B. napus resulted in 30% nervonic acid but with 20% residual erucic acid. Experiments using the Lunaria KCS gene gave results similar to the latter. In both cases, the erucic acid content is too high for human or animal consumption. Thus, the Cardamine KCS: B. carinata high nervonic/highly reduced erucic transgenic seed oils will be the most suitable for testing in pharmaceutical/nutraceutical applications to improve human and animal health.
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NASA Astrophysics Data System (ADS)
Feofanov, Alexey V.; Kudryashova, Kseniya S.; Nekrasova, Oksana V.; Vassilevski, Alexander A.; Kuzmenkov, Alexey I.; Korolkova, Yuliya V.; Grishin, Eugene V.; Kirpichnikov, Mikhail P.
Artificial KcsA-Kv1.x (x = 1, 3) receptors were recently designed by transferring the ligand-binding site from human Kv1.x voltage-gated
potassium channels into corresponding domain of the bacterial KscA channel. We found that KcsA-Kv1.x receptors expressed in E. coli cells are embedded into cell membrane and bind ligands when the cells are transformed to spheroplasts. We supposed that E. coli spheroplasts with membrane-embedded KcsA-Kv1.x and fluorescently labeled ligand agitoxin-2 (R-AgTx2) can be used as elements of an advanced analytical system for search and study of Kv1-channel blockers. To realize this idea, special procedures were developed for measurement and quantitative treatment of fluorescence signals obtained from spheroplast membrane using confocal laser scanning microscopy (CLSM). The worked out analytical "mix and read" systems supported by quantitative CLSM analysis were demonstrated to be reliable alternative to radioligand and electrophysiology techniques in the search and study of selective Kv1.x channel blockers of high scientific and medical importance. -
Use of Adipose-Derived Mesenchymal Stem Cells in Keratoconjunctivitis Sicca in a Canine Model
Villatoro, Antonio J.; Fernández, Viviana; Rico-Llanos, Gustavo A.; Becerra, José; Andrades, José A.
2015-01-01
Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is an immune-mediated multifactorial disease, with high level of prevalence in humans and dogs. Our aim in this study was to investigate the therapeutic effects of allogeneic adipose-derived mesenchymal stromal cells (Ad-MSCs) implanted around the lacrimal glands in 12 dogs (24 eyes) with KCS, which is refractory to current available treatments. Schirmer tear test (STT) and ocular surface integrity were assessed at 0 (before treatment), 3, 6, and 9 months after treatment. Average STT values and all clinical signs showed a statistically significant change (P < 0.001) during the follow-up with reduction in all ocular parameters scored: ocular discharge, conjunctival hyperaemia, and corneal changes, and there were no signs of regression or worsening. Implanted cells were well tolerated and were effective reducing clinical signs of KCS with a sustained effect during the study period. None of the animals showed systemic or local complications during the study. To our knowledge, this is the first time in literature that implantation of allogeneic Ad-MSCs around lacrimal glands has been found as an effective therapeutic alternative to treat dogs with KCS. These results could reinforce a good effective solution to be extrapolated to future studies in human. PMID:25802852
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Oscillatory integration windows in neurons
Gupta, Nitin; Singh, Swikriti Saran; Stopfer, Mark
2016-01-01
Oscillatory synchrony among neurons occurs in many species and brain areas, and has been proposed to help neural circuits process information. One hypothesis states that oscillatory input creates cyclic integration windows: specific times in each oscillatory cycle when postsynaptic neurons become especially responsive to inputs. With paired local field potential (LFP) and intracellular recordings and controlled stimulus manipulations we directly test this idea in the locust olfactory system. We find that inputs arriving in Kenyon cells (KCs) sum most effectively in a preferred window of the oscillation cycle. With a computational model, we show that the non-uniform structure of noise in the membrane potential helps mediate this process. Further experiments performed in vivo demonstrate that integration windows can form in the absence of inhibition and at a broad range of oscillation frequencies. Our results reveal how a fundamental coincidence-detection mechanism in a neural circuit functions to decode temporally organized spiking. PMID:27976720
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NASA Astrophysics Data System (ADS)
Liu, Xuejiao; Lu, Benzhuo
2017-12-01
Potassium channels are much more permeable to potassium than sodium ions, although potassium ions are larger and both carry the same positive charge. This puzzle cannot be solved based on the traditional Poisson-Nernst-Planck (PNP) theory of electrodiffusion because the PNP model treats all ions as point charges, does not incorporate ion size information, and therefore cannot discriminate potassium from sodium ions. The PNP model can qualitatively capture some macroscopic properties of certain channel systems such as current-voltage characteristics, conductance rectification, and inverse membrane potential. However, the traditional PNP model is a continuum mean-field model and has no or underestimates the discrete ion effects, in particular the ion solvation or self-energy (which can be described by Born model). It is known that the dehydration effect (closely related to ion size) is crucial to selective permeation in potassium channels. Therefore, we incorporated Born solvation energy into the PNP model to account for ion hydration and dehydration effects when passing through inhomogeneous dielectric channel environments. A variational approach was adopted to derive a Born-energy-modified PNP (BPNP) model. The model was applied to study a cylindrical nanopore and a realistic KcsA channel, and three-dimensional finite element simulations were performed. The BPNP model can distinguish different ion species by ion radius and predict selectivity for K+ over Na+ in KcsA channels. Furthermore, ion current rectification in the KcsA channel was observed by both the PNP and BPNP models. The I -V curve of the BPNP model for the KcsA channel indicated an inward rectifier effect for K+ (rectification ratio of ˜3 /2 ) but indicated an outward rectifier effect for Na+ (rectification ratio of ˜1 /6 ) .
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Safonova, T N; Gladkova, О V; Boev, V I
2016-01-01
Laser confocal tomography of the cornea enables studying ultrathin sections of corneal layers, which provides additional reliable information on tissue changes in keratoconjunctivitis sicca (KCS). To assess the significance of laser confocal tomography of the cornea in the diagnosis and monitoring of KCS. We investigated 38 eyes of 30 patients with severe KCS. The patients were divided into two groups. Group 1 (15 patients, 19 eyes) was prescribed cyclosporine А 0.05% instillations 2 times daily, artificial tears, and soft contact lenses. Group 2 (15 patients, 19 eyes) received only instillations of cyclosporine А 0.05% 2 times daily and artificial tears. Besides standard ophthalmic examination, additional tests were performed, namely Schirmer's test, tear break-up time test, fluorescein eye stain test, tear osmolarity test (TearLab System, USA), and Heidelberg retinal tomography of the cornea (HRT, Heidelberg Engineering GmbH, Germany). HRT findings revealed a 3 times shorter epithelization period and faster recovery of corneal transparency in group 1 as compared to group 2 (1.5 and 4.5 months, respectively). There was also an evident reduction in the number of immune cells in the cornea, most pronounced in group 1 at 3 months, which is indicative of inflammation termination. The use of HRT of the cornea in KCS patients allows real-time cellular level observation of corneal changes, which together with clinical findings and diagnostic tests not only confirms the diagnosis but also determines treatment effectiveness. It has been also found that soft contact lenses accelerate epithelization of the cornea and relieve inflammation of the ocular surface in KCS patients under cyclosporine A 0.05% instillation therapy. Transparency of financial activity: the authors have no financial interest in the submitted materials and methods.
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Ursolic acid ameliorates CCl4-induced liver fibrosis through the NOXs/ROS pathway.
Gan, Dakai; Zhang, Wang; Huang, Chenkai; Chen, Jiang; He, Wenhua; Wang, Anjiang; Li, Bimin; Zhu, Xuan
2018-04-19
Liver fibrosis is a reversible wound-healing response that occurs after liver injury. NADPH oxidases (NOXs) and reactive oxygen species (ROS) which are expressed in hepatocytes (HCs), hepatic stellate cells (HSCs), and Kupffer cells (KCs) play an important role in the development of hepatic fibrosis. In in vitro studies, we had shown that ursolic acid (UA) could reverse liver fibrosis by inhibiting the activation of NOX-mediated fibrotic signaling networks in HSCs. In this study, we verified that UA could alleviate CCl4-induced liver fibrosis by reducing the expression of NOXs/ROS in HCs, HSCs, KCs. Meanwhile, the phagocytic index α and clearance index K which represent phagocytosis of KCs were unchanged. Together, all our data demonstrated that UA induced the proliferation of HCs, promoted apoptosis in HSCs, and prevented activation of KCs in vivo by reducing the expression of NOXs/ROS in HCs, HSCs, KCs. Besides, UA had no effect on the host defense function. © 2018 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.
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Fluorescence detection of the movement of single KcsA subunits reveals cooperativity
Blunck, Rikard; McGuire, Hugo; Hyde, H. Clark; Bezanilla, Francisco
2008-01-01
The prokaryotic KcsA channel is gated at the helical bundle crossing by intracellular protons and inactivates at the extracellular selectivity filter. The C-terminal transmembrane helix has to undergo a conformational change for potassium ions to access the central cavity. Whereas a partial opening of the tetrameric channel is suggested to be responsible for subconductance levels of ion channels, including KcsA, a cooperative opening of the 4 subunits is postulated as the final opening step. In this study, we used single-channel fluorescence spectroscopy of KcsA to directly observe the movement of each subunit and the temporal correlation between subunits. Purified KcsA channels labeled at the C terminus near the bundle crossing have been inserted into supported lipid bilayer, and the fluorescence traces analyzed by means of a cooperative or independent Markov model. The analysis revealed that the 4 subunits do not move fully independently but instead showed a certain degree of cooperativity. However, the 4 subunits do not simply open in 1 concerted step. PMID:19074286
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Degraded melanocores are incompetent to protect epidermal keratinocytes against UV damage.
Yi, Wen-Juan; Su, Meng-Yun; Shi, Ying; Jiang, Shan; Xu, Shi-Zheng; Lei, Tie-Chi
2018-04-25
Melanosomes are membrane-bound intracellular organelles that are uniquely generated by melanocytes (MCs) in the basal layer of human epidermis. Highly pigmented mature melanosomes are transferred from MCs to keratinocytes (KCs), and then positioned in the supra-nuclear region to ensure protection against ultraviolet radiation (UVR). However, the molecular mechanism underlying melanosome (or melanin pigment) transfer remains enigmatic. Emerging evidence shows that exo-/endo-cytosis of the melanosome core (termed melanocore) has been considered as the main transfer manner between MCs and KCs. As KCs in the skin migrate up from the basal layer and undergo terminal differentiation, the melanocores they have taken up from MCs are subjected to degradation. In this study, we isolated individual melanocores from human MCs in culture and then induced their destruction/disruption using a physical approach. The results demonstrate that the ultrastructural integrity of melanocores is essential for their antioxidant and photoprotective properties. In addition, we also show that cathepsin V (CTSV), a lysosomal acid protease, is involved in melanocore degradation in calcium-induced differentiated KCs and is also suppressed in KCs following exposure to UVA or UVB radiation. Thus, our study demonstrates that change in the proportion of melanocores in the intact/undegraded state by CTSV-related degradation in KCs affects photoprotection of the skin.
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Bronson, Jonathan; Lee, One-Sun; Saven, Jeffery G.
2006-01-01
Poor solubility and low expression levels often make membrane proteins difficult to study. An alternative to the use of detergents to solubilize these aggregation-prone proteins is the partial redesign of the sequence so as to confer water solubility. Recently, computationally assisted membrane protein solubilization (CAMPS) has been reported, where exposed hydrophobic residues on a protein's surface are computationally redesigned. Herein, the structure and fluctuations of a designed, water-soluble variant of KcsA (WSK-3) were studied using molecular dynamics simulations. The root mean square deviation of the protein from its starting structure, where the backbone coordinates are those of KcsA, was 1.8 Å. The structure of salt bridges involved in structural specificity and solubility were examined. The preferred configuration of ions and water in the selectivity filter of WSK-3 was consistent with the reported preferences for KcsA. The structure of the selectivity filter was maintained, which is consistent with WSK-3 having an affinity for agitoxin2 comparable to that of wild-type KcsA. In contrast to KcsA, the central cavity's side chains were observed to reorient, allowing water diffusion through the side of the cavity wall. These simulations provide an atomistic analysis of the CAMPS strategy and its implications for further investigations of membrane proteins. PMID:16299086
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Hegebarth, Daniela; Buschhaus, Christopher; Joubès, Jérôme; Thoraval, Didier; Bird, David; Jetter, Reinhard
2017-09-01
The aliphatic waxes sealing plant surfaces against environmental stress are generated by fatty acid elongase complexes, each containing a β-ketoacyl-CoA synthase (KCS) enzyme that catalyses a crucial condensation forming a new C─C bond to extend the carbon backbone. The relatively high abundance of C 35 and C 37 alkanes derived from C 36 and C 38 acyl-CoAs in Arabidopsis leaf trichomes (relative to other epidermis cells) suggests differences in the elongation machineries of different epidermis cell types, possibly involving KCS16, a condensing enzyme expressed preferentially in trichomes. Here, KCS16 was found expressed primarily in Arabidopsis rosette leaves, flowers and siliques, and the corresponding protein was localized to the endoplasmic reticulum. The cuticular waxes on young leaves and isolated leaf trichomes of ksc16 loss-of-function mutants were depleted of C 35 and C 37 alkanes and alkenes, whereas expression of Arabidopsis KCS16 in yeast and ectopic overexpression in Arabidopsis resulted in accumulation of C 36 and C 38 fatty acid products. Taken together, our results show that KCS16 is the sole enzyme catalysing the elongation of C 34 to C 38 acyl-CoAs in Arabidopsis leaf trichomes and that it contributes to the formation of extra-long compounds in adjacent pavement cells. © 2017 John Wiley & Sons Ltd.
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Mechanism of Cd2+-coordination during Slow Inactivation in Potassium Channels
Raghuraman, H.; Cordero-Morales, Julio F.; Jogini, Vishwanath; Pan, Albert C.; Kollewe, Astrid; Roux, Benoît; Perozo, Eduardo
2013-01-01
Summary In K+ channels, rearrangements of the pore outer-vestibule have been associated with C-type inactivation gating. Paradoxically, the crystal structure of Open/C-type inactivated KcsA suggest these movements to be modest in magnitude. Here, we show that under physiological conditions, the KcsA outer-vestibule undergoes relatively large dynamic rearrangements upon inactivation. External Cd2+ enhances the rate of C-type inactivation in an outer-vestibule cysteine mutant (Y82C) via metal-bridge formation. This effect is not present in a non-inactivating mutant (E71A/Y82C). Tandem dimer and tandem tetramer constructs of equivalent cysteine mutants in KcsA and Shaker K+ channels demonstrate that these Cd2+ metal bridges are formed only between adjacent subunits. This is well supported by molecular dynamics simulations. Based on the crystal structure of Cd2+-bound Y82C-KcsA in the closed state, together with EPR distance measurements in the KcsA outer-vestibule, we suggest that subunits must dynamically come in close proximity as the channels undergo inactivation. PMID:22771214
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NASA Astrophysics Data System (ADS)
Kim, Myojeong; Jo, Byeong Chul; Yoon, Hyun Jung; Wu, Sangwook; Thangappan, Jayaraman; Eun, Changsun
2018-05-01
The selectivity and conduction specificity of the KcsA channel toward potassium ions is crucial to the activity of this protein and this channel is intricately associated with several osmotic regulation and neuronal signaling processes. Despite multi-ion characteristics, the selective conduction behavior of KcsA is controlled by the size and distance specific electrostatic interaction between the selected residues and the potassium ions. The mechanism describing the movement of potassium ions in the channel and the conformational changes to KcsA that facilitate ion movement were investigated by a molecular dynamics (MD) simulation. In this study, we analyze the movement of potassium ions and water molecules at various time intervals during a 90 ns molecular dynamics simulation in the high potassium ion concentration regime and in the absence of the voltage. Examination of specific (3.6, 17.3, 43.38 and 43.44 ns) simulation periods revealed that key residues in the selectivity filter of KcsA influence the movement of potassium ions in the channel.
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Use of primary cultures of Kenyon cells from bumblebee brains to assess pesticide side effects.
Wilson, Daniel E; Velarde, Rodrigo A; Fahrbach, Susan E; Mommaerts, Veerle; Smagghe, Guy
2013-09-01
Bumblebees are important pollinators in natural and agricultural ecosystems. The latter results in the frequent exposure of bumblebees to pesticides. We report here on a new bioassay that uses primary cultures of neurons derived from adult bumblebee workers to evaluate possible side-effects of the neonicotinoid pesticide imidacloprid. Mushroom bodies (MBs) from the brains of bumblebee workers were dissected and dissociated to produce cultures of Kenyon cells (KCs). Cultured KCs typically extend branched, dendrite-like processes called neurites, with substantial growth evident 24-48 h after culture initiation. Exposure of cultured KCs obtained from newly eclosed adult workers to 2.5 parts per billion (ppb) imidacloprid, an environmentally relevant concentration of pesticide, did not have a detectable effect on neurite outgrowth. By contrast, in cultures prepared from newly eclosed adult bumblebees, inhibitory effects of imidacloprid were evident when the medium contained 25 ppb imidacloprid, and no growth was observed at 2,500 ppb. The KCs of older workers (13-day-old nurses and foragers) appeared to be more sensitive to imidacloprid than newly eclosed adults, as strong effects on KCs obtained from older nurses and foragers were also evident at 2.5 ppb imidacloprid. In conclusion, primary cultures using KCs of bumblebee worker brains offer a tool to assess sublethal effects of neurotoxic pesticides in vitro. Such studies also have the potential to contribute to the understanding of mechanisms of plasticity in the adult bumblebee brain. © 2013 Wiley Periodicals, Inc.
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Identification and treatment of the Staphylococcus aureus reservoir in vivo
Surewaard, Bas G.J.; Deniset, Justin F.; Zemp, Franz J.; Amrein, Matthias; Otto, Michael; Conly, John; Omri, Abdelwahab; Yates, Robin M.
2016-01-01
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is reaching epidemic proportions causing morbidity, mortality, and chronic disease due to relapses, suggesting an intracellular reservoir. Using spinning-disk confocal intravital microscopy to track MRSA-GFP in vivo, we identified that within minutes after intravenous infection MRSA is primarily sequestered and killed by intravascular Kupffer cells (KCs) in the liver. However, a minority of the Staphylococci overcome the KC’s antimicrobial defenses. These bacteria survive and proliferate for many days within this intracellular niche, where they remain undetected by recruited neutrophils. Over time, the KCs lyse, releasing bacteria into the circulation, enabling dissemination to other organs such as the kidneys. Vancomycin, the antibiotic of choice to treat MRSA bacteremia, could not penetrate the KCs to eradicate intracellular MRSA. However, based on the intravascular location of these specific macrophages, we designed a liposomal formulation of vancomycin that is efficiently taken up by KCs and diminished the intracellular MRSA. Targeting the source of the reservoir dramatically protected the liver but also dissemination to other organs, and prevented mortality. This vancomycin formulation strategy could help treat patients with Staphylococcal bacteremia without a need for novel antibiotics by targeting the previously inaccessible intracellular reservoir in KCs. PMID:27325887
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Augmenter of liver regeneration attenuates acute rejection after rat liver transplantation.
Chen, Yong; Liang, Shaoyong; Long, Feiwu; Li, Jinzheng; Gong, Jianping
2016-07-01
The role of augmenter of liver regeneration (ALR) on liver transplantation immune regulation remains unknown. Male Lewis and Brown-Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100 μg/kg/d, intramuscular injection postoperatively). Rats were sacrificed at indicated times for assessment of cytokines production, T-cell (TC) activation and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of (3)H-thymidine TCs. (1) Treatment with ALR significantly decreased interleukin-2 and interferon-γ expression, promoted TC apoptosis, and prolonged the survival of allografts; (2) KCs in ALR group and isograft group that had significantly increased interleukin-10 and decreased tumor necrosis factor-α expression were able to inhibit TC proliferation and induce their apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly inhibited TC proliferation and activation and induced TC apoptosis. ALR could inhibit TC proliferation and function both in vivo and in vitro and attenuate acute rejection after liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.
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Mosoian, Arevik; Zhang, Lumin; Hong, Feng; Cunyat, Francesc; Rahman, Adeeb; Bhalla, Riti; Panchal, Ankur; Saiman, Yedidya; Fiel, M Isabel; Florman, Sander; Roayaie, Sasan; Schwartz, Myron; Branch, Andrea; Stevenson, Mario; Bansal, Meena B
2017-05-01
End-stage liver disease is a common cause of non-AIDS-related mortality in HIV + patients, despite effective anti-retroviral therapies (ARTs). HIV-1 infection causes gut CD4 depletion and is thought to contribute to increased gut permeability, bacterial translocation, and immune activation. Microbial products drain from the gut into the liver via the portal vein where Kupffer cells (KCs), the resident liver macrophage, clear translocated microbial products. As bacterial translocation is implicated in fibrogenesis in HIV patients through unclear mechanisms, we tested the hypothesis that HIV infection of KCs alters their response to LPS in a TLR4-dependent manner. We showed that HIV-1 productively infected KCs, enhanced cell-surface TLR4 and CD14 expression, and increased IL-6 and TNF-α expression, which was blocked by a small molecule TLR4 inhibitor. Our study demonstrated that HIV infection sensitizes KCs to the proinflammatory effects of LPS in a TLR4-dependent manner. These findings suggest that HIV-1-infected KCs and their dysregulated innate immune response to LPS may play a role in hepatic inflammation and fibrosis and represent a novel target for therapy. © Society for Leukocyte Biology.
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Cieslak, John A; Focia, Pamela J; Gross, Adrian
2010-02-23
Electron spin-echo envelope modulation (ESEEM) spectroscopy is a well-established technique for the study of naturally occurring paramagnetic metal centers. The technique has been used to study copper complexes, hemes, enzyme mechanisms, micellar water content, and water permeation profiles in membranes, among other applications. In the present study, we combine ESEEM spectroscopy with site-directed spin labeling (SDSL) and X-ray crystallography in order to evaluate the technique's potential as a structural tool to describe the native environment of membrane proteins. Using the KcsA potassium channel as a model system, we demonstrate that deuterium ESEEM can detect water permeation along the lipid-exposed surface of the KcsA outer helix. We further demonstrate that (31)P ESEEM is able to identify channel residues that interact with the phosphate headgroup of the lipid bilayer. In combination with X-ray crystallography, the (31)P data may be used to define the phosphate interaction surface of the protein. The results presented here establish ESEEM as a highly informative technique for SDSL studies of membrane proteins.
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Destefanis, Simona; Giretto, Daniela; Muscolo, Maria Cristina; Di Cerbo, Alessandro; Guidetti, Gianandrea; Canello, Sergio; Giovazzino, Angela; Centenaro, Sara; Terrazzano, Giuseppe
2016-09-22
Canine keratoconjunctivitis sicca (cKCS) is an inflammatory eye condition related to a deficiency in the tear aqueous fraction. Etiopathogenesis of such disease is substantially multifactorial, combining the individual genetic background with environmental factors that contribute to the process of immunological tolerance disruption and, as a consequence, to the emergence of autoimmunity disease. In this occurrence, it is of relevance the role of the physiological immune-dysregulation that results in immune-mediated processes at the basis of cKCS. Current therapies for this ocular disease rely on immunosuppressive treatments. Clinical response to treatment frequently varies from poor to good, depending on the clinical-pathological status of eyes at diagnosis and on individual response to therapy. In the light of the variability of clinical response to therapies, we evaluated the use of an anti-inflammatory/antioxidant nutraceutical diet with potential immune-modulating activity as a therapeutical adjuvant in cKCS pharmacological treatment. Such combination was administered to a cohort of dogs affected by cKCS in which the only immunosuppressive treatment resulted poorly responsive or ineffective in controlling the ocular symptoms. Fifty dogs of different breeds affected by immune-mediated cKCS were equally distributed and randomly assigned to receive either a standard diet (control, n = 25) or the nutraceutical diet (treatment group, n = 25) both combined with standard immunosuppressive therapy over a 60 days period. An overall significant improvement of all clinical parameters (tear production, conjunctival inflammation, corneal keratinization, corneal pigment density and mucus discharge) and the lack of food-related adverse reactions were observed in the treatment group (p < 0.0001). Our results showed that the association of traditional immune-suppressive therapy with the antioxidant/anti-inflammatory properties of the nutraceutical diet resulted in a significant amelioration of clinical signs and symptoms in cKCS. The beneficial effects, likely due to the presence of supplemented nutraceuticals in the diet, appeared to specifically reduce the immune-mediated ocular symptoms in those cKCS-affected dogs that were poorly responsive or unresponsive to classical immunosuppressive drugs. These data suggest that metabolic changes could affect the immune response orchestration in a model of immune-mediated ocular disease, as represented by cKCS.
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Williams, David L; Mann, Brenda K
2014-01-01
Keratoconjunctivitis sicca (KCS), or dry eye, is a significant medical problem in both humans and dogs. Treating KCS often requires the daily application of more than one type of eye drop in order to both stimulate tear prodcution and provide a tear supplement to increase hydration and lubrication. A previous study demonstrated the potential for a crosslinked hyaluronic acid-based hydrogel (xCMHA-S) to reduce the clinical signs associated with KCS in dogs while using a reduced dosing regimen of only twice-daily administration. The present study extended those results by comparing the use of the xCMHA-S to a standard HA-containing tear supplement in a masked, randomized clinical study in dogs with a clinical diagnosis of KCS. The xCMHA-S was found to significantly improve ocular surface health (conjunctival hyperaemia, ocular irritation, and ocular discharge) to a greater degree than the alternative tear supplement (P = 0.0003). Further, owners reported the xCMHA-S treatment as being more highly effective than the alternative tear supplement (P = 0.0024). These results further demonstrate the efficacy of the xCMHA-S in reducing the clinical signs associated with KCS, thereby improving patient health and owner happiness.
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Zhao, Yu-Ying; Yang, Rui; Xiao, Mo; Guan, Min-Jie; Zhao, Ning; Zeng, Tao
2017-09-01
Kupffer cells (KCs) have been suggested to play critical roles in chronic ethanol induced early liver injury, but the role of KCs in binge drinking-induced hepatic steatosis remains unclear. This study was designed to investigate the roles of KCs inhibitor (GdCl 3 ) and TNF-α antagonist (etanercept) on binge drinking-induced liver steatosis and to explore the underlying mechanisms. C57BL/6 mice were exposed to three doses of ethanol (6g/kg body weight) to mimic binge drinking-induced fatty liver. The results showed that both GdCl 3 and etanercept partially but significantly alleviated binge drinking-induced increase of hepatic triglyceride (TG) level, and reduced fat droplets accumulation in mice liver. GdCl 3 but not etanercept significantly blocked binge drinking-induced activation of KCs. However, neither GdCl 3 nor etanercept could affect binge drinking-induced decrease of PPAR-α, ACOX, FAS, ACC and SCD protein levels, or increase of the LC3 II/LC3 I ratio and p62 protein level. Interestingly, both GdCl 3 and etanercept significantly suppressed binge drinking-induced phosphorylation of HSL in epididymal adipose tissues. Results of in vitro studies with cultured epididymal adipose tissues showed that TNF-α could increase the phosphorylation of HSL in adipose tissues and upgrade the secretion of free fatty acid (FFA) in the culture medium. Taken together, KCs inhibitor and TNF-α antagonist could partially attenuate binge drinking-induced liver steatosis, which might be attributed to the suppression of mobilization of white adipose tissues. These results suggest that KCs activation may promote binge drinking-induced fatty liver by TNF-α mediated activation of lipolysis in white adipose tissues. Copyright © 2017 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Junyong, E-mail: zhangmachine@hotmail.com; Guo, Shipeng, E-mail: guoshipeng2008@126.com; Zhang, Wenfeng, E-mail: Sadengren8881@163.com
The currently available techniques for transferring exogenous genes into macrophages, especially the targeted import of exogenous genes into Kupffer cells (KCs) in vivo, are inefficient and achieve only low targeting. Novel Large-Pore Mesoporous Silica Nanospheres (LPMSNs) may be a promising gene transfection agent for KCs because of their superior biodegradation and hypotoxic characteristics, as well as their ability to retain the biological function of KCs and the high loading-rate of exogenous plasmid. LPMSNs were able to completely adsorb shRNA-TRAF3 (tumor necrosis factor receptor-associated factor-3) plasmid at a mass ratio as low as 30:1, and exhibited a low cytotoxicity for KCs. LPMSNsmore » were detected in KC cytoplasm in vitro, and transmission electron microscopy (TEM) revealed that they were present only in KCs in liver tissue in vivo. The max KC transfection efficiency with LPMSNs was 34.8± 0.07%, as evaluated using flow cytometry, and the protein and mRNA levels of TRAF3 were significantly inhibited (P < 0.05) by shRNA-TRAF3 plasmid transfection after 24 h in vitro and 48 h in vivo. In conclusion, KC targeted transfection was achieved successfully by LPMSNs carrying shRNA-TRAF3 plasmids in vitro and vivo. The protein and mRNA levels of TRAF3 were suppressed significantly. These results suggest that LPMSNs are a promising vehicle for delivering exogenous genes into KCs in vitro and vivo. - Highlights: • We constructed Large-Pore Mesoporous Silica Nanospheres (LPMSNs). • LPMSNs adsorbed high quantity of plasmid. • Low cytotoxicity of LPMSNs to Kupffer cells. • LPMSNs delivered plasmid into Kupffer cells.« less
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Gonnet, J; Perrin, H; Hutton, A J; Boccara, D; Bonduelle, O; Mimoun, M; Atlan, M; Soria, A; Combadière, B
2018-05-28
Cross-talk between skin keratinocytes (KCs) and Langerhans cells (LCs) plays a fundamental role in the body's first line of immunological defences. However, the mechanism behind the interaction between these two major epidermal cells is unknown. Interleukin (IL)-32 is produced in inflammatory skin disorders. We questioned the role of IL-32 in the epidermis. We aimed to determine the role of IL-32 produced by KCs on surrounding LCs. We used an ex vivo human explant model from healthy donors and investigated the role of IL-32 on LC activation using imaging, flow cytometry, reverse transcriptase quantitative polymerase chain reaction and small interfering (si)RNA treatment. Modified vaccinia virus ankara (MVA) infection induced KC death alongside the early production of the proinflammatory cytokine IL-32. We demonstrated that IL-32 produced by MVA-infected KCs induced modest but significant morphological changes in LCs and downregulation of adhesion molecules, such as epithelial cell adhesion molecule and very late antigen-4, and CXCL10 production. The treatment of KCs with IL-32-specific siRNA, and anti-IL-32 blocking antibody significantly inhibited LC activation, demonstrating the role of IL-32 in LC activation. We also found that some Toll-like receptor ligands induced a very high level of IL-32 production by KCs, which initiated LC activation. We propose, for the first time, that IL-32 is a molecular link between KCs and LCs in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes. © 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
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Sebbag, Lionel; Park, Shin Ae; Kass, Philip H; Maggs, David J; Attar, Mayssa; Murphy, Christopher J
2017-07-01
To evaluate repeatability and reproducibility of tear osmolarity measured using the TearLab ™ osmometer in normal dogs and to assess its diagnostic potential in dogs with keratoconjunctivitis sicca (KCS). Beagle dogs; six normal and five with KCS. Tear osmolarity and Schirmer tear test-1 (STT-1) values were obtained at various times. Normal dogs were assessed for diurnal variation and repeatability and reproducibility of measurements. Dogs with KCS were evaluated before and after 5 months' topical twice-daily therapy with 2% cyclosporine. Mean ± SD tear osmolarity (mOsm/L) was significantly higher in normal dogs (337.4 ± 16.2) than in dogs with KCS before therapy (306.2 ± 18.0; P < 0.0001), but not following therapy with 2% cyclosporine (330.5 ± 13.7; P = 1.00). Osmolarity readings lower than 325.5 mOsm/L were suggestive of KCS (84.8% sensitivity and 87.1% specificity). In normal dogs, tear osmolarity readings were stable during the daytime (P = 0.99). Repeated measurements revealed high variability and typically poor-to-moderate repeatability and reproducibility, although this was improved by taking three successive measurements at each session. Considering combined data from all dogs, a positive correlation existed between STT-1 and tear osmolarity measurements (Pearson's correlation test, P = 0.04, r = 0.62). Canine tear osmolarity as determined by TearLab ™ osmometer was variable, required multiple readings to be informative, and differed from values reported for humans. Dogs with KCS had a lower tear osmolarity than did normal dogs, and this increased following cyclosporine therapy. © 2016 American College of Veterinary Ophthalmologists.
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Li, Jinzheng; Gong, Junhua; Li, Peizhi; Li, Min; Liu, Yiming; Liang, Shaoyong; Gong, Jianping
2014-03-27
Our previous studies have shown that Kupffer cells (KCs) play a crucial role in postoperative pathologic changes. Recent reports have demonstrated that microRNA-155 (miR-155) is associated with inflammation and upregulation of proinflammatory mediators in the peripheral blood and allografts of transplant patients. However, the precise mechanism for this remains unknown. KCs isolated from BALB/c mice were transfected with miR-155 mimic or inhibitor. Levels of suppressor of cytokine signaling 1/Janus kinase/signal transducer and activator of transcription (SOCS1/JAK/STAT) proteins and surface molecules (MHC-II, CD40, and CD86) were then measured. T-cell proliferation and apoptosis were evaluated in mixed lymphocyte reactions. Orthotopic liver transplantation was performed in mice after miR-155 short hairpin RNA lentivirus treatment, and postoperative survival, liver function and histology, and mRNA and protein expression were analyzed. miR-155 knockdown in KCs decreased MHC-II, CD40, and CD86 expression, suppressed antigen-presenting function, and affected SOCS1/JAK/STAT inflammatory pathways. In addition, KCs transfected with miR-155 inhibitor and cocultured with T lymphocytes showed reduced T-cell responses but a greater number of apoptotic T cells. Finally, miR-155 suppression in graft liver prolonged liver allograft survival and improved liver function. The changes were closely associated with the levels of T helper 1 and 2 (Th1/Th2) cytokines and T-cell apoptosis, but a direct mechanistic link in vivo was not established. These data suggest miR-155 regulates the balance of Th1/Th2 cytokines and the maturation and function of KCs in mice. miR-155 repression in KCs positively regulates KC function toward immunosuppression and prolongs liver allograft survival.
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Zheng, Fang; Sparkes, Amanda; De Baetselier, Patrick; Schoonooghe, Steve; Stijlemans, Benoit; Muyldermans, Serge; Flamand, Véronique; Van Ginderachter, Jo A; Devoogdt, Nick; Raes, Geert; Beschin, Alain
2017-02-01
Kupffer cells (KCs), the liver resident macrophages, are important mediators of tissue homeostasis and pathogen clearance. However, depending on the inflammatory stimuli, KCs have been involved in divergent hepato-protective or hepato-destructive immune responses. The versatility of KCs in response to environmental triggers, in combination with the specific biomarkers they express, make these macrophages attractive in vivo targets for non-invasive monitoring of liver inflammation or pathogenicity. This study aims to determine whether V-set and Ig domain-containing 4 (Vsig4) and C-type lectin domain family (Clec) 4, member F (Clec4F) can be used as imaging biomarkers for non-invasive monitoring of KCs during distinct liver inflammation models. Flow cytometry (FACS), immuno-histochemistry (IHC), and single-photon emission computed tomography (SPECT) with Tc-99m labeled anti-Vsig4 or anti-Clec4F nanobodies (Nbs) was performed to evaluate in mice KC dynamics in concanavalin A (ConA)-induced hepatitis and in non-alcoholic steatohepatitis induced via methionine choline deficiency (MCD). In homeostatic mice, Nbs targeting Clec4F were found to accumulate and co-localize with Vsig4-targeting Nbs only in the liver. Upon induction of acute hepatitis using ConA, down-regulation of the in vivo Nb imaging signal was observed, reflecting reduction in KC numbers as confirmed by FACS and IHC. On the other hand, induction of steatohepatitis resulted in higher signals in the liver corresponding to higher density of KCs. The Nb-imaging signals returned to normal levels after resolution of the investigated liver diseases. Anti-Clec4F and anti-Vsig4 Nbs targeting KCs as molecular imaging biomarkers could allow non-invasive monitoring/staging of liver pathogenesis.
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Takahide, Kikuchi; Parker, Pablo M.; Wu, Michael; Hwang, William Y.K.; Carpenter, Paul A.; Moravec, Carina; Stehr, Barbara; Martin, Paul J.; Rosenthal, Perry; Forman, Stephen J.; Flowers, Mary E.D.
2007-01-01
Keratoconjunctivitis sicca (KCS) occurs in 40-60 % of patients with chronic graft-versus-host-disease (GVHD) after allogeneic hematopoietic cell transplantation. While immunosuppressive therapy is the primary treatment of chronic GVHD, ocular symptoms require measures to improve ocular lubrication, decrease inflammation and maintain mucosal integrity. The liquid corneal bandage provided by a fluid-ventilated, gas-permeable scleral lens (SL) has been effective in mitigating symptoms and resurfacing corneal erosions in patients with KCS related to causes other than chronic GVHD. We report outcomes in 9 consecutive patients referred for SL fitting for chronic GVHD-related severe KCS that was refractory to standard treatments. All patients reported improvement of ocular symptoms and reduced the use of topical lubricants after SL fitting resulting from decrease evaporation. No serious adverse events or infections attributable to the SL occurred. The median Ocular Surface Disease Index improved from 81 (75-100) to 21 (6-52) within 2 weeks after SL fitting and was 12 (2-53) at the time of last contact, 1-23 months (median, 8.0) after SL fitting. Disability related to KCS resolved in 7 patients after SL fitting. The use of SL appears to be safe and effective in patients with severe chronic GVHD-related KCS refractory to conventional therapies. PMID:17697963
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Lassner, M W; Lardizabal, K; Metz, J G
1996-01-01
beta-Ketoacyl-coenzyme A (CoA) synthase (KCS) catalyzes the condensation of malonyl-CoA with long-chain acyl-CoA. This reaction is the initial step of the microsomal fatty acyl-CoA elongation pathway responsible for formation of very long chain fatty acids (VLCFAs, or fatty acids with chain lengths > 18 carbons). Manipulation of this pathway is significant for agriculture, because it is the basis of conversion of high erucic acid rapeseed into canola. High erucic acid rapeseed oil, used as an industrial feedstock, is rich in VLCFAs, whereas the edible oil extracted from canola is essentially devoid of VLCFAs. Here, we report the cloning of a cDNA from developing jojoba embryos involved in microsomal fatty acid elongation. The jojoba cDNA is homologous to the recently cloned Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene that has been suggested to encode KCS. We characterize the jojoba enzyme and present biochemical data indicating that the jojoba cDNA does indeed encode KCS. Transformation of low erucic acid rapeseed with the jojoba cDNA restored KCS activity to developing embryos and altered the transgenic seed oil composition to contain high levels of VLCFAs. The data reveal the key role KCS plays in determining the chain lengths of fatty acids found in seed oils. PMID:8742713
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Lassner, M W; Lardizabal, K; Metz, J G
1996-02-01
beta-Ketoacyl-coenzyme A (CoA) synthase (KCS) catalyzes the condensation of malonyl-CoA with long-chain acyl-CoA. This reaction is the initial step of the microsomal fatty acyl-CoA elongation pathway responsible for formation of very long chain fatty acids (VLCFAs, or fatty acids with chain lengths > 18 carbons). Manipulation of this pathway is significant for agriculture, because it is the basis of conversion of high erucic acid rapeseed into canola. High erucic acid rapeseed oil, used as an industrial feedstock, is rich in VLCFAs, whereas the edible oil extracted from canola is essentially devoid of VLCFAs. Here, we report the cloning of a cDNA from developing jojoba embryos involved in microsomal fatty acid elongation. The jojoba cDNA is homologous to the recently cloned Arabidopsis FATTY ACID ELONGATION1 (FAE1) gene that has been suggested to encode KCS. We characterize the jojoba enzyme and present biochemical data indicating that the jojoba cDNA does indeed encode KCS. Transformation of low erucic acid rapeseed with the jojoba cDNA restored KCS activity to developing embryos and altered the transgenic seed oil composition to contain high levels of VLCFAs. The data reveal the key role KCS plays in determining the chain lengths of fatty acids found in seed oils.
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Zheng, Fang; Devoogdt, Nick; Sparkes, Amanda; Morias, Yannick; Abels, Chloé; Stijlemans, Benoit; Lahoutte, Tony; Muyldermans, Serge; De Baetselier, Patrick; Schoonooghe, Steve; Beschin, Alain; Raes, Geert
2015-02-01
Kupffer cells (KCs) are liver resident macrophages which are important for tissue homeostasis and have been implicated in immunogenic, tolerogenic and pathogenic immune reactions depending on the insult. These cells and the biomarkers they express thus represent interesting in vivo sensors for monitoring liver inflammation. In the current study, we explored whether KCs can be monitored non-invasively using single-photon-emission computed tomography (SPECT) with (99m)Tc labeled nanobodies (Nbs) targeting selected biomarkers. Nbs targeting V-set and immunoglobulin domain-containing 4 (Vsig4) or macrophage mannose receptor (MMR) accumulated in the liver of untreated mice. The liver targeting of anti-Vsig4 Nbs, but not anti-MMR Nbs, was blunted upon depletion of macrophages, highlighting specificity of anti-Vsig4 Nbs for liver macrophage imaging. Ex vivo flow cytometry and immunohistochemistry analysis confirmed that anti-Vsig4 Nbs specifically targeted KCs but no other cell types in the liver. Upon induction of acute hepatitis using concanavalin A (ConA), down-regulation of the in vivo imaging signal obtained using anti-Vsig4 Nbs reflected reduction in KC numbers and transient modulation of Vsig4 expression on KCs. Overall, these results indicate that Nbs targeting Vsig4 as molecular imaging biomarker enable non-invasive monitoring of KCs during hepatic inflammation. Copyright © 2014 Elsevier GmbH. All rights reserved.
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[PSI+] prion propagation is controlled by inositol polyphosphates
Wickner, Reed B.; Kelly, Amy C.; Bezsonov, Evgeny E.; Edskes, Herman K.
2017-01-01
The yeast prions [PSI+] and [URE3] are folded in-register parallel β-sheet amyloids of Sup35p and Ure2p, respectively. In a screen for antiprion systems curing [PSI+] without protein overproduction, we detected Siw14p as an antiprion element. An array of genetic tests confirmed that many variants of [PSI+] arising in the absence of Siw14p are cured by restoring normal levels of the protein. Siw14p is a pyrophosphatase specifically cleaving the β phosphate from 5-diphosphoinositol pentakisphosphate (5PP-IP5), suggesting that increased levels of this or some other inositol polyphosphate favors [PSI+] propagation. In support of this notion, we found that nearly all variants of [PSI+] isolated in a WT strain were lost upon loss of ARG82, which encodes inositol polyphosphate multikinase. Inactivation of the Arg82p kinase by D131A and K133A mutations (preserving Arg82p’s nonkinase transcription regulation functions) resulted the loss of its ability to support [PSI+] propagation. The loss of [PSI+] in arg82Δ is independent of Hsp104’s antiprion activity. [PSI+] variants requiring Arg82p could propagate in ipk1Δ (IP5 kinase), kcs1Δ (IP6 5-kinase), vip1Δ (IP6 1-kinase), ddp1Δ (inositol pyrophosphatase), or kcs1Δ vip1Δ mutants but not in ipk1Δ kcs1Δ or ddp1Δ kcs1Δ double mutants. Thus, nearly all [PSI+] prion variants require inositol poly-/pyrophosphates for their propagation, and at least IP6 or 5PP-IP4 can support [PSI+] propagation. PMID:28923943
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ERIC Educational Resources Information Center
Brudevold-Iversen, Tessa; Peterson, Elizabeth R.; Cartwright, Claire
2013-01-01
In its 2007 curriculum, New Zealand introduced Key Competencies (KCs) that are intended to ensure students' future participation in the economy, communities, and also to introduce metacognitive and socio-emotional dimensions to learning. The KCs also have important implications for contributing to students' wellbeing and resilience. However, they…
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OECD, "Key Competencies" and the New Challenges of Educational Inequality
ERIC Educational Resources Information Center
Takayama, Keita
2013-01-01
In this paper, I develop a critique of the Organization for Economic Cooperation and Development (OECD)-based lifelong learning policy discourse with a particular focus on "key competencies" (KCs) and its equity implications for school curricular policies. First, I review the discussion of KCs in the writings by the OECD-affiliated…
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Propeller Analysis Using RANS/BEM Coupling Accounting for Blade Blockage
2015-07-04
described. Estimates of the importance of the blade blockage effect are obtained by analyzing the propeller of the well-known KRISO container ship (KCS...2 and 3 were applied to the KRISO Container Ship (KCS), a test case that has often been reported in the scientific literature, in particular the
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78 FR 13241 - Drawbridge Operation Regulation; Sabine River, Near Ruliff, LA
Federal Register 2010, 2011, 2012, 2013, 2014
2013-02-27
... Kansas City Southern (KCS) Railroad drawbridge across Sabine River, mile 36.2, between Newton County, TX... this rule because the Kansas City Southern Railroad Bridge over the Sabine River, mile 36.2, that once... the Kansas City Southern (KCS) Railroad Bridge over the Sabine River, mile 36.2, draw operation...
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A Crosslinked HA-Based Hydrogel Ameliorates Dry Eye Symptoms in Dogs
Williams, David L.; Mann, Brenda K.
2013-01-01
Keratoconjunctivitis sicca, commonly referred to as dry eye or KCS, can affect both humans and dogs. The standard of care in treating KCS typically includes daily administration of eye drops to either stimulate tear production or to hydrate and lubricate the corneal surface. Lubricating eye drops are often applied four to six times daily for the life of the patient. In order to reduce this dosing regimen yet still provides sufficient hydration and lubrication, we have developed a crosslinked hydrogel based on a modified, thiolated hyaluronic acid (HA), xCMHA-S. This xCMHA-S gel was found to have different viscosity and rheologic behavior than solutions of noncrosslinked HA. The gel was also able to increase tear breakup time in rabbits, indicating a stabilization of the tear film. Further, in a preliminary clinical study of dogs with KCS, the gel significantly reduced the symptoms associated with KCS within two weeks while only being applied twice daily. The reduction of symptoms combined with the low dosing regimen indicates that this gel may lead to both improved patient health and owner compliance in applying the treatment. PMID:23840213
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Kim, Dorothy M.; Dikiy, Igor; Upadhyay, Vikrant; Posson, David J.
2016-01-01
The process of ion channel gating—opening and closing—involves local and global structural changes in the channel in response to external stimuli. Conformational changes depend on the energetic landscape that underlies the transition between closed and open states, which plays a key role in ion channel gating. For the prokaryotic, pH-gated potassium channel KcsA, closed and open states have been extensively studied using structural and functional methods, but the dynamics within each of these functional states as well as the transition between them is not as well understood. In this study, we used solution nuclear magnetic resonance (NMR) spectroscopy to investigate the conformational transitions within specific functional states of KcsA. We incorporated KcsA channels into lipid bicelles and stabilized them into a closed state by using either phosphatidylcholine lipids, known to favor the closed channel, or mutations designed to trap the channel shut by disulfide cross-linking. A distinct state, consistent with an open channel, was uncovered by the addition of cardiolipin lipids. Using selective amino acid labeling at locations within the channel that are known to move during gating, we observed at least two different slowly interconverting conformational states for both closed and open channels. The pH dependence of these conformations and the predictable disruptions to this dependence observed in mutant channels with altered pH sensing highlight the importance of conformational heterogeneity for KcsA gating. PMID:27432996
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Ioannides, Andreas A.; Liu, Lichan; Poghosyan, Vahe; Kostopoulos, George K.
2017-01-01
We used tomographic analysis of MEG signals to characterize regional spectral changes in the brain at sleep onset and during light sleep. We identified two key processes that may causally link to loss of consciousness during the quiet or “core” periods of NREM1. First, active inhibition in the frontal lobe leads to delta and theta spectral power increases. Second, activation suppression leads to sharp drop of spectral power in alpha and higher frequencies in posterior parietal cortex. During NREM2 core periods, the changes identified in NREM1 become more widespread, but focal increases also emerge in alpha and low sigma band power in frontal midline cortical structures, suggesting reemergence of some monitoring of internal and external environment. Just before spindles and K-complexes (KCs), the hallmarks of NREM2, we identified focal spectral power changes in pre-frontal cortex, mid cingulate, and areas involved in environmental and internal monitoring, i.e., the rostral and sub-genual anterior cingulate. During both spindles and KCs, alpha and low sigma bands increases. Spindles emerge after further active inhibition (increase in delta power) of the frontal areas responsible for environmental monitoring, while in posterior parietal cortex, power increases in low and high sigma bands. KCs are correlated with increase in alpha power in the monitoring areas. These specific regional changes suggest strong and varied vigilance changes for KCs, but vigilance suppression and sharpening of cognitive processing for spindles. This is consistent with processes designed to ensure accurate and uncorrupted memory consolidation. The changes during KCs suggest a sentinel role: evaluation of the salience of provoking events to decide whether to increase processing and possibly wake up, or to actively inhibit further processing of intruding influences. The regional spectral patterns of NREM1, NREM2, and their dynamic changes just before spindles and KCs reveal an edge effect facilitating the emergence of spindles and KCs and defining the precise loci where they might emerge. In the time domain, the spindles are seen in widespread areas of the cortex just as reported from analysis of intracranial data, consistent with the emerging consensus of a differential topography that depends on the kind of memory stored. PMID:28670270
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Christodoulou, Loucas; Krishnaiah, Anil; Spyridou, Christina; Salpietro, Vincenzo; Hannan, Siobhan; Saggar, Anand; Mankad, Kshitij; Deep, Akash
2015-01-01
Kenny Caffey syndrome (KCS) is a rare syndrome reported almost exclusively in Middle Eastern populations. It is characterized by severe growth retardation—short stature, dysmorphic features, episodic hypocalcaemia, hypoparathyroidism, seizures, and medullary stenosis of long bones with thickened cortices. We report a 10-year-old boy with KCS with an unusually severe respiratory and gastrointestinal system involvement—features not previously described in the literature. He had severe psychomotor retardation and regressed developmentally from walking unaided to sitting with support. MRI brain showed bilateral hippocampal sclerosis, marked supra-tentorial volume loss and numerous calcifications. A 12 bp deletion of exon 2 of tubulin-specific chaperone E (TBCE) gene was identified and the diagnosis of KCS was confirmed. Hypercarbia following a sleep study warranted nocturnal continuous positive airway pressure (CPAP) when aged 6. When boy aged 8, persistent hypercarbia with increasing oxygen requirement and increased frequency and severity of lower respiratory tract infections led to progressive respiratory failure. He became fully dependent on non-invasive ventilation and by 9 years he had a tracheotomy and was established on long-term ventilation. He developed retching, vomiting and diarrhea. Chest CT showed changes consistent with chronic aspiration, but no interstitial pulmonary fibrosis. He died aged 10 from respiratory complications. PMID:26029652
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Christodoulou, Loucas; Krishnaiah, Anil; Spyridou, Christina; Salpietro, Vincenzo; Hannan, Siobhan; Saggar, Anand; Mankad, Kshitij; Deep, Akash; Kinali, Maria
2015-06-01
Kenny Caffey syndrome (KCS) is a rare syndrome reported almost exclusively in Middle Eastern populations. It is characterized by severe growth retardation-short stature, dysmorphic features, episodic hypocalcaemia, hypoparathyroidism, seizures, and medullary stenosis of long bones with thickened cortices. We report a 10-year-old boy with KCS with an unusually severe respiratory and gastrointestinal system involvement-features not previously described in the literature. He had severe psychomotor retardation and regressed developmentally from walking unaided to sitting with support. MRI brain showed bilateral hippocampal sclerosis, marked supra-tentorial volume loss and numerous calcifications. A 12 bp deletion of exon 2 of tubulin-specific chaperone E (TBCE) gene was identified and the diagnosis of KCS was confirmed. Hypercarbia following a sleep study warranted nocturnal continuous positive airway pressure (CPAP) when aged 6. When boy aged 8, persistent hypercarbia with increasing oxygen requirement and increased frequency and severity of lower respiratory tract infections led to progressive respiratory failure. He became fully dependent on non-invasive ventilation and by 9 years he had a tracheotomy and was established on long-term ventilation. He developed retching, vomiting and diarrhea. Chest CT showed changes consistent with chronic aspiration, but no interstitial pulmonary fibrosis. He died aged 10 from respiratory complications.
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Autoimmunity in the pathogenesis and treatment of keratoconjunctivitis sicca.
Liu, Katy C; Huynh, Kyle; Grubbs, Joseph; Davis, Richard M
2014-01-01
Dry eye is a chronic corneal disease that impacts the quality of life of many older adults. Keratoconjunctivitis sicca (KCS), a form of aqueous-deficient dry eye, is frequently associated with Sjögren's syndrome and mechanisms of autoimmunity. For KCS and other forms of dry eye, current treatments are limited, with many medications providing only symptomatic relief rather than targeting the pathophysiology of disease. Here, we review proposed mechanisms in the pathogenesis of autoimmune-based KCS: genetic susceptibility and disruptions in antigen recognition, immune response, and immune regulation. By understanding the mechanisms of immune dysfunction through basic science and translational research, potential drug targets can be identified. Finally, we discuss current dry eye therapies as well as promising new treatment options and drug therapy targets.
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A Kenyan Cloud School. Massive Open Online & Ongoing Courses for Blended and Lifelong Learning
ERIC Educational Resources Information Center
Jobe, William
2013-01-01
This research describes the predicted outcomes of a Kenyan Cloud School (KCS), which is a MOOC that contains all courses taught at the secondary school level in Kenya. This MOOC will consist of online, ongoing subjects in both English and Kiswahili. The KCS subjects offer self-testing and peer assessment to maximize scalability, and digital badges…
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Probing the Energy Landscape of Activation Gating of the Bacterial Potassium Channel KcsA
Linder, Tobias; de Groot, Bert L.; Stary-Weinzinger, Anna
2013-01-01
The bacterial potassium channel KcsA, which has been crystallized in several conformations, offers an ideal model to investigate activation gating of ion channels. In this study, essential dynamics simulations are applied to obtain insights into the transition pathways and the energy profile of KcsA pore gating. In agreement with previous hypotheses, our simulations reveal a two phasic activation gating process. In the first phase, local structural rearrangements in TM2 are observed leading to an intermediate channel conformation, followed by large structural rearrangements leading to full opening of KcsA. Conformational changes of a highly conserved phenylalanine, F114, at the bundle crossing region are crucial for the transition from a closed to an intermediate state. 3.9 µs umbrella sampling calculations reveal that there are two well-defined energy barriers dividing closed, intermediate, and open channel states. In agreement with mutational studies, the closed state was found to be energetically more favorable compared to the open state. Further, the simulations provide new insights into the dynamical coupling effects of F103 between the activation gate and the selectivity filter. Investigations on individual subunits support cooperativity of subunits during activation gating. PMID:23658510
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Autoimmunity in the Pathogenesis and Treatment of Keratoconjunctivitis Sicca
Liu, Katy C.; Huynh, Kyle; Grubbs, Joseph; Davis, Richard M.
2014-01-01
Dry eye is a chronic corneal disease that impacts the quality of life of many older adults. keratoconjunctivitis sicca (KCS), a form of aqueous-deficient dry eye, is frequently associated with Sjögren’s syndrome and mechanisms of autoimmunity. For KCS and other forms of dry eye, current treatments are limited, with many medications providing only symptomatic relief rather than targeting the pathophysiology of disease. Here, we review proposed mechanisms in the pathogenesis of autoimmune-based KCS: genetic susceptibility and disruptions in antigen recognition, immune response, and immune regulation. By understanding the mechanisms of immune dysfunction through basic science and translational research, potential drug targets can be identified. Finally, we discuss current dry eye therapies as well as promising new treatment options and drug therapy targets. PMID:24395332
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Mirshafiee, Vahid; Sun, Bingbing; Chang, Chong Hyun; Liao, Yu-Pei; Jiang, Wen; Jiang, Jinhong; Liu, Xiangsheng; Wang, Xiang; Xia, Tian; Nel, André E
2018-04-24
The liver and the mononuclear phagocyte system are a frequent target for engineered nanomaterials, either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. We not only observed differences between KCs and hepatocytes, but also differences in the toxicological profiles of transition-metal oxides (TMOs, e. g., Co 3 O 4 ) versus rare-earth oxide (REO) NPs ( e. g., Gd 2 O 3 ). While pro-oxidative TMOs induced the activation of caspases 3 and 7, resulting in apoptotic cell death in both cell types, REOs induced lysosomal damage, NLRP3 inflammasome activation, caspase 1 activation, and pyroptosis in KCs. Pyroptosis was accompanied by cell swelling, membrane blebbing, IL-1β release, and increased membrane permeability, which could be reversed by knockdown of the pore forming protein, gasdermin D. Though similar features were not seen in hepatocytes, the investigation of the cytotoxic effects of REO NPs could also be seen to affect macrophage cell lines such as J774A.1 and RAW 264.7 cells as well as bone marrow-derived macrophages. These phagocytic cell types also demonstrated features of pyroptosis and increased IL-1β production. Collectively, these findings demonstrate important mechanistic considerations that can be used for safety evaluation of metal oxides, including commercial products that are developed from these materials.
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2012-01-01
Background Over half of kidney cancer survivors (KCS) are completely inactive and only a quarter are meeting physical activity (PA) guidelines. This highlights the need to identify and understand the determinants of PA in this understudied population. The purpose of this study is to determine the social cognitive correlates of PA intention and behavior in KCS using the Theory of Planned Behavior (TPB). Methods All 1,985 KCS diagnosed between 1996 and 2010 in Alberta, Canada were mailed a self-report survey that consisted of the Godin Leisure Time Exercise Questionnaire and standard TPB items for intention, planning, perceived behavioral control (PBC), affective and instrumental attitudes, and descriptive and injunctive norms. Standard demographic and medical variables were also collected. Results Completed surveys were received from 703 of 1,654 (43%) eligible KCS. The TPB was tested using structural equation modelling and demonstrated an adequate-to-good fit to the data [χ² = 256.88, p < .001; TLI = 0.97; CFI = 0.98; RMSEA = 0.06, 90% CI = 0.05-0.06]. There were significant pathways to PA from PBC (ß = 0.18, p = 0.02), planning (ß = 0.22, p < 0.01), and intention (ß = 0.31, p < 0.01); and to planning from intention (ß = 0.81, p < 0.01). In addition, there were significant model pathways to intention from instrumental attitude (ß = 0.28, p = 0.03), descriptive norm (ß = 0.09, p = 0.01), and PBC (ß = 0.52, p < 0.01). Overall, the TPB accounted for 69%, 63%, and 42% of the variance in intention, planning and PA, respectively. Conclusion The TPB appears to be a useful model for explaining PA in KCS. All TPB constructs except injunctive norm and affective attitude were useful for explaining intention with PBC emerging as the largest correlate. Developing PA interventions based on the TPB may be effective in promoting PA in KCS and may lead to important improvements in health. PMID:22866956
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Antimitochondrial Autoantibodies in Pemphigus Vulgaris
Marchenko, Steve; Chernyavsky, Alexander I.; Arredondo, Juan; Gindi, Vivian; Grando, Sergei A.
2010-01-01
A loss of epidermal cohesion in pemphigus vulgaris (PV) results from autoantibody action on keratinocytes (KCs) activating the signaling kinases and executioner caspases that damage KCs, causing their shrinkage, detachment from neighboring cells, and rounding up (apoptolysis). In this study, we found that PV antibody binding leads to activation of epidermal growth factor receptor kinase, Src, p38 MAPK, and JNK in KCs with time pattern variations from patient to patient. Both extrinsic and intrinsic apoptotic pathways were also activated. Although Fas ligand neutralizing antibody could inhibit the former pathway, the mechanism of activation of the latter remained unknown. PV antibodies increased cytochrome c release, suggesting damage to mitochondria. The immunoblotting experiments revealed penetration of PVIgG into the subcellular mitochondrial fraction. The antimitochondrial antibodies from different PV patients recognized distinct combinations of antigens with apparent molecular sizes of 25, 30, 35, 57, 60, and 100 kDa. Antimitochondrial antibodies were pathogenic because their absorption abolished the ability of PVIgG to cause keratinocyte detachment both in vitro and in vivo. The downstream signaling of antimitochondrial antibodies involved JNK and late p38 MAPK activation, whereas the signaling of anti-desmoglein 3 (Dsg3) antibody involved JNK and biphasic p38 MAPK activation. Using KCs grown from Dsg3−/− mice, we determined that Dsg3 did not serve as a surrogate antigen allowing antimitochondrial antibodies to enter KCs. The PVIgG-induced activation of epidermal growth factor receptor and Src was affected neither in Dsg3−/− KCs nor due to absorption of antimitochondrial antibodies. These results demonstrated that apoptolysis in PV is a complex process initiated by at least three classes of autoantibodies directed against desmosomal, mitochondrial, and other keratinocyte self-antigens. These autoantibodies synergize with the proapoptotic serum and tissue factors to trigger both extrinsic and intrinsic pathways of cell death and break the epidermal cohesion, leading to blisters. Further elucidation of the primary signaling events downstream of PV autoantigens will be crucial for the development of a more successful therapy for PV patients. PMID:20007702
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Zhang, Danke; Li, Yuanqing; Wu, Si; Rasch, Malte J.
2013-01-01
Sensory systems face the challenge to represent sensory inputs in a way to allow easy readout of sensory information by higher brain areas. In the olfactory system of the fly drosopohila melanogaster, projection neurons (PNs) of the antennal lobe (AL) convert a dense activation of glomeruli into a sparse, high-dimensional firing pattern of Kenyon cells (KCs) in the mushroom body (MB). Here we investigate the design principles of the olfactory system of drosophila in regard to the capabilities to discriminate odor quality from the MB representation and its robustness to different types of noise. We focus on understanding the role of highly correlated homotypic projection neurons (“sister cells”) found in the glomeruli of flies. These cells are coupled by gap-junctions and receive almost identical sensory inputs, but target randomly different KCs in MB. We show that sister cells might play a crucial role in increasing the robustness of the MB odor representation to noise. Computationally, sister cells thus might help the system to improve the generalization capabilities in face of noise without impairing the discriminability of odor quality at the same time. PMID:24167488
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Trapping of oxidized LDL in lysosomes of Kupffer cells is a trigger for hepatic inflammation.
Bieghs, Veerle; Walenbergh, Sofie M A; Hendrikx, Tim; van Gorp, Patrick J; Verheyen, Fons; Olde Damink, Steven W; Masclee, Ad A; Koek, Ger H; Hofker, Marten H; Binder, Christoph J; Shiri-Sverdlov, Ronit
2013-08-01
Non-alcoholic steatohepatitis (NASH) is characterized by steatosis and inflammation. The transition from steatosis towards NASH represents a key step in pathogenesis, as it will set the stage for further severe liver damage. Under normal conditions, lipoproteins that are endocytosed by Kupffer cells (KCs) are easily transferred from the lysosomes into the cytoplasm. Oxidized LDL (oxLDL) that is taken up by the macrophages in vitro is trapped within the lysosomes, while acetylated LDL (acLDL) is leading to normal lysosomal hydrolysis, resulting in cytoplasmic storage. We have recently demonstrated that hepatic inflammation is correlated with lysosomal trapping of lipids. So far, a link between lysosomal trapping of oxLDL and inflammation was not established. We hypothesized that lysosomal trapping of oxLDL in KCs will lead to hepatic inflammation. Ldlr(-/-) mice were injected with LDL, acLDL and oxLDL and sacrificed after 2, 6 and 24 h. Electron microscopy of KCs demonstrated that after oxLDL injection, small lipid inclusions were present inside the lysosomes after all time points and were mostly pronounced after 6 and 24 h. In contrast, no lipid inclusions were present inside KCs after LDL or acLDL injection. Hepatic expression of several inflammatory genes and scavenger receptors was higher after oxLDL injections compared with LDL or acLDL. These data suggest that trapping of oxLDL inside lysosomes of KCs in vivo is causally linked to increased hepatic inflammatory gene expression. Our novel observations provide new bases for prevention and treatment of NASH. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Li, Jing; Boulanger, Eliot; Rui, Huan; Perozo, Eduardo; Roux, Benoît
2017-01-01
In many K+ channels, prolonged activating stimuli lead to a time-dependent reduction in ion conduction, a phenomenon known as C-type inactivation. X-ray structures of the KcsA channel suggest that this inactivated state corresponds to a “constricted” conformation of the selectivity filter. However, the functional significance of the constricted conformation has become a matter of debate. Functional and structural studies based on chemically modified semisynthetic KcsA channels along the selectivity filter led to the conclusion that the constricted conformation does not correspond to the C-type inactivated state. The main results supporting this view include the observation that C-type inactivation is not suppressed by a substitution of D-alanine at Gly77, even though this modification is believed to lock the selectivity filter into its conductive conformation, whereas it is suppressed following amide-to-ester backbone substitutions at Gly77 and Tyr78, even though these structure-conserving modifications are not believed to prevent the selectivity filter from adopting the constricted conformation. However, several untested assumptions about the structural and functional impact of these chemical modifications underlie these arguments. To make progress, molecular dynamics simulations based on atomic models of the KcsA channel were performed. The computational results support the notion that the constricted conformation of the selectivity filter corresponds to the functional C-type inactivated state of the KcsA. Importantly, MD simulations reveal that the semisynthetic KcsAD-ala77 channel can adopt an asymmetrical constricted-like nonconductive conformation and that the amide-to-ester backbone substitutions at Gly77 and Tyr78 perturb the hydrogen bonding involving the buried water molecules stabilizing the constricted conformation. PMID:28973956
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Vermeulen, Pieter; Dickens, Stijn; Degezelle, Karlien; Van den Berge, Stefaan; Hendrickx, Benoit; Vranckx, Jan Jeroen
2009-07-01
In search of an autologous vascularized skin substitute, we treated full-thickness wounds (FTWs) with autologous platelet-rich plasma gel (APG) in which we embedded endothelial progenitor cells (EPCs) and basal cell keratinocytes (KCs). We cultivated autologous KCs in low-serum conditions and expanded autologous EPCs from venous blood. FTWs (n = 55) were created on the backs of four pigs, covered with wound chambers, and randomly assigned to the following treatments: (1) APG, (2) APG + KCs, (3) APG + EPCs, (4) APG + KCs + EPCs, and (5) saline. All wounds were biopsied to measure neovascularization (lectin Bandeiraea Simplicifolia-1 (BS-1), alpha smooth muscle actin [alphaSMA], and membrane type 1 matrix metalloproteinase (MT1-MMP)), matrix deposition (fibronectin, collagen type I/III, and alphavbeta3), and reepithelialization. Wound fluids were analyzed for protein expression. All APG-treated wounds showed more vascular structures (p < 0.001), and the addition of EPCs further improved neovascularization, as confirmed by higher lectin, alphaSMA, and MT1-MMP. APG groups had higher collagen I/III (p < 0.05), alphavbeta3, and fibronectin content (p < 0.001), and they exhibited higher concentrations of platelet-derived growth factor subunit bb, basic fibroblast growth factor, hepatocyte growth factor, insulin growth factor-1, transforming growth factor-beta1 and -beta3, matrix metalloproteinase-1 and -z9, and tissue-inhibiting matrix metalloproteinase-1 and -2. Applying APG + KCs resulted in the highest reepithelialization rates (p < 0.001). No differences were found for wound contraction by planimetry. In this porcine FTW model, APG acts as a supportive biomatrix that, along with the embedded cells, improves extracellular matrix organization, promotes angiogenesis, and accelerates reepithelialization.
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Garuti, Cinzia; Tian, Yinghua; Montosi, Giuliana; Sabelli, Manuela; Corradini, Elena; Graf, Rolf; Ventura, Paolo; Vegetti, Alberto; Clavien, Pierre-Alain; Pietrangelo, Antonello
2010-07-01
Hemochromatosis is a common hereditary disease caused by mutations in HFE and characterized by increased absorption of iron in the intestine. However, the intestine does not appear to be the site of mutant HFE activity in the disease; we investigated the role of the liver-the source of the iron regulatory hormone hepcidin-in pathogenesis in mice. We exchanged livers between Hfe wild-type (+/+) and Hfe null (-/-) mice by orthotopic liver transplantation (OLT) and assessed histopathology, serum and tissue iron parameters, and hepatic hepcidin messenger RNA expression. At 6-8 months after OLT, Hfe(-/-) mice that received Hfe(-/-) livers maintained the hemochromatosis phenotype: iron accumulation in hepatocytes but not Kupffer cells (KC), increased transferrin levels, and low levels of iron in the spleen. Hfe(+/+) mice that received Hfe(-/-) livers had increased levels of iron in serum and liver and low levels of iron in spleen. However, they did not develop the iron-poor KCs that characterize hemochromatosis: KCs appeared iron rich, although hepatic hepcidin expression was low. Transplantation of Hfe(+/+) livers into Hfe(-/-) mice prevented hepatic iron accumulation but did not return spleen and plasma levels of iron to normal; KCs still appeared to be iron poor, despite normal hepcidin expression. In Hfe(-/-) mice, transplantation of livers from Hfe(+/+) mice reversed the iron-loading phenotype associated with hemochromatosis (regardless of Hfe expression in intestine). However, KCs still had low levels of iron that were not affected by hepatic hepcidin expression. These findings indicate an independent, iron-modifying effect of HFE in KCs. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Mitchell, Michael R.; Leibler, Stanislas
2018-05-01
The abundance of available static protein structural data makes the more effective analysis and interpretation of this data a valuable tool to supplement the experimental study of protein mechanics. Structural displacements can be difficult to analyze and interpret. Previously, we showed that strains provide a more natural and interpretable representation of protein deformations, revealing mechanical coupling between spatially distinct sites of allosteric proteins. Here, we demonstrate that other transformations of displacements yield additional insights. We calculate the divergence and curl of deformations of the transmembrane channel KcsA. Additionally, we introduce quantities analogous to bend, splay, and twist deformation energies of nematic liquid crystals. These transformations enable the decomposition of displacements into different modes of deformation, helping to characterize the type of deformation a protein undergoes. We apply these calculations to study the filter and gating regions of KcsA. We observe a continuous path of rotational deformations physically coupling these two regions, and, we propose, underlying the allosteric interaction between these regions. Bend, splay, and twist distinguish KcsA gate opening, filter opening, and filter-gate coupling, respectively. In general, physically meaningful representations of deformations (like strain, curl, bend, splay, and twist) can make testable predictions and yield insights into protein mechanics, augmenting experimental methods and more fully exploiting available structural data.
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Mechanism of activation at the selectivity filter of the KcsA K+ channel
Heer, Florian T; Posson, David J; Wojtas-Niziurski, Wojciech
2017-01-01
Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K+ affinity, and increased ion permeation. Such activation of the selectivity filter may be a universal gating mechanism within K+ channels. The occlusion of the pore at the level of the intracellular gate appears to be secondary. PMID:28994652
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Wong, Connie H. Y.; Jenne, Craig N.; Petri, Björn; Chrobok, Navina L.; Kubes, Paul
2016-01-01
Using intravital imaging of the liver, we unveil a collaborative role for platelets with Kupffer cells (KCs) in eradicating bloodborne bacterial infections. Under basal conditions, platelets via glycoprotein Ib (GPIb) formed transient “touch-and-go” interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria, such as Bacillus cereus and Methicillin-resistant Staphylococcus aureus (MRSA), were rapidly caught by KCs and triggered platelets to switch from “touch-and-go” to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GpIbα−/− mice demonstrated increased endothelial and KC damage, leading to increased fluid leakage, significant polycythemia and rapid mortality. This study identifies a novel surveillance mechanism of intravascular macrophage by platelets that rapidly converts to a critical host response against bloodborne bacteria. PMID:23770641
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Wong, Connie H Y; Jenne, Craig N; Petri, Björn; Chrobok, Navina L; Kubes, Paul
2013-08-01
Through the use of intravital imaging of the liver, we demonstrate a collaborative role for platelets with Kupffer cells (KCs) in eradicating blood-borne bacterial infection. Under basal conditions, platelets, via the platelet-adhesion receptor GPIb, formed transient 'touch-and-go' interactions with von Willebrand factor (vWF) constitutively expressed on KCs. Bacteria such as Bacillus cereus and methicillin-resistant Staphylococcus aureus (MRSA) were rapidly caught by KCs and triggered platelets to switch from 'touch-and-go' adhesion to sustained GPIIb-mediated adhesion on the KC surface to encase the bacterium. Infected GPIbα-deficient mice had more endothelial and KC damage than did their wild-type counterparts, which led to more fluid leakage, substantial polycythemia and rapid mortality. Our study identifies a previously unknown surveillance mechanism by which platelets survey macrophages that rapidly converts to a critical host response to blood-borne bacteria.
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Leyton, V; Goles, N I; Fuenzalida-Uribe, N; Campusano, J M
2014-02-07
In Drosophila associative olfactory learning, an odor, the conditioned stimulus (CS), is paired to an unconditioned stimulus (US). The CS and US information arrive at the Mushroom Bodies (MB), a Drosophila brain region that processes the information to generate new memories. It has been shown that olfactory information is conveyed through cholinergic inputs that activate nicotinic acetylcholine receptors (nAChRs) in the MB, while the US is coded by biogenic amine (BA) systems that innervate the MB. In this regard, the MB acts as a coincidence detector. A better understanding of the properties of the responses gated by nicotinic and BA receptors is required to get insights on the cellular and molecular mechanisms responsible for memory formation. In recent years, information has become available on the properties of the responses induced by nAChR activation in Kenyon Cells (KCs), the main neuronal MB population. However, very little information exists on the responses induced by aminergic systems in fly MB. Here we have evaluated some of the properties of the calcium responses gated by Dopamine (DA) and Octopamine (Oct) in identified KCs in culture. We report that exposure to BAs induces a fast but rather modest increase in intracellular calcium levels in cultured KCs. The responses to Oct and DA are fully blocked by a VGCC blocker, while they are differentially modulated by cAMP. Moreover, co-application of BAs and nicotine has different effects on intracellular calcium levels: while DA and nicotine effects are additive, Oct and nicotine induce a synergistic increase in calcium levels. These results suggest that a differential modulation of nicotine-induced calcium increase by DA and Oct could contribute to the events leading to learning and memory in flies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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75 FR 55633 - Petition for Waiver of Compliance
Federal Register 2010, 2011, 2012, 2013, 2014
2010-09-13
.... 229.49(a)(1), which states that main reservoir system of each locomotives shall have a safety valve to... 4650-4679, and KCSM 4710-4759. KCS seeks authority to continue to operate with the main reservoir... adverse effects on the safety of operations and that safety is in no way compromised. Interested parties...
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Wong, Martin C S; Ching, Jessica Y L; Ng, Simpson; Lam, Thomas Y T; Luk, Arthur K C; Wong, Sunny H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y
2016-02-03
We evaluated the performance of seven existing risk scoring systems in predicting advanced colorectal neoplasia in an asymptomatic Chinese cohort. We prospectively recruited 5,899 Chinese subjects aged 50-70 years in a colonoscopy screening programme(2008-2014). Scoring systems under evaluation included two scoring tools from the US; one each from Spain, Germany, and Poland; the Korean Colorectal Screening(KCS) scores; and the modified Asia Pacific Colorectal Screening(APCS) scores. The c-statistics, sensitivity, specificity, positive predictive values(PPVs), and negative predictive values(NPVs) of these systems were evaluated. The resources required were estimated based on the Number Needed to Screen(NNS) and the Number Needed to Refer for colonoscopy(NNR). Advanced neoplasia was detected in 364 (6.2%) subjects. The German system referred the least proportion of subjects (11.2%) for colonoscopy, whilst the KCS scoring system referred the highest (27.4%). The c-statistics of all systems ranged from 0.56-0.65, with sensitivities ranging from 0.04-0.44 and specificities from 0.74-0.99. The modified APCS scoring system had the highest c-statistics (0.65, 95% C.I. 0.58-0.72). The NNS (12-19) and NNR (5-10) were similar among the scoring systems. The existing scoring systems have variable capability to predict advanced neoplasia among asymptomatic Chinese subjects, and further external validation should be performed.
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Wang, Zi-Kai; Xiao, Jian-Guo; Huang, Xue-Fei; Gong, Yi-Chun; Li, Wen
2013-01-01
AIM: To investigate the effect of biliary drainage on inducible nitric oxide synthase (iNOS), CD14 and TGR5 expression in rats with obstructive jaundice (OJ). METHODS: Male adult Sprague-Dawley rats were randomly assigned to four groups: OJ, sham operation (SH), internal biliary drainage (ID) and external biliary drainage (ED). Rat models were successfully established by two operations and succumbed for extraction of Kupffer cells (KCs) and liver tissue collection on the 8th and 15th day. KCs were isolated by in situ hepatic perfusion and digested with collagen IV, density gradient centrifuged by percoll reagent and purified by cell culture attachment. The isolated KCs were cultured with the endotoxin lipopolysaccharide (LPS) with and without the addition of ursodeoxycholic acid (UDCA). The expression of iNOS, CD14 and bile acid receptor-TGR5 protein in rat liver tissues was determined by immunohistochemistry. The expression of iNOS and CD14 messenger RNA (mRNA) on the isolated KCs was detected by reverse transcription polymerase chain reaction (PCR) and the TGR5 mRNA level in KCs was measured by real-time quantitative PCR. RESULTS: The iNOS protein was markedly expressed in the liver of OJ rats, but rare expressed in SH rats. After relief of OJ, the iNOS expression was decidedly suppressed in the ID group (ID vs OJ, P < 0.01), but obviously increased in rats of ED (ED vs OJ, P = 0.004). When interfered only with LPS, the expression of iNOS mRNA by KCs was increased in the OJ group compared with the SH group (P = 0.004). After relief of biliary obstruction, the iNOS mRNA expression showed slight changes in the ED group (ED vs OJ, P = 0.71), but dropped in the ID group (ID vs OJ, P = 0.001). Compared with the simple intervention with LPS, the expressions of iNOS mRNA were significantly inhibited in all four groups after interfered with both LPS and UDCA (P < 0.01, respectively). After bile duct ligation, the CD14 protein expression in rat liver was significantly strengthened (OJ vs SH, P < 0.01), but the CD14 mRNA level by KCs was not up-regulated (OJ vs SH, P = 0.822). After relieving the OJ, the expression of CD14 protein was reduced in the ID group (ID vs OJ, P < 0.01), but not reduced in ED group (ED vs OJ, P = 0.591). And then the CD14 mRNA expression was aggravated by ED (ED vs OJ, P < 0.01), but was not significantly different between the ID group and the SH and OJ groups (ID vs SH, P = 0.944; ID vs OJ, P = 0.513, respectively). The expression of TGR5 protein and mRNA increased significantly in OJ rats (OJ vs SH, P = 0.001, respectively). After relief of OJ, ID could reduce the expression of TGR5 protein and mRNA to the levels of SH group (ID vs SH, P = 0.22 and P = 0.354, respectively), but ED could not (ED vs SH, P = 0.001, respectively). CONCLUSION: ID could be attributed to the regulatory function of activation of KCs and release of inflammatory mediators. PMID:23613625
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Jemnitz, Katalin; Bátai-Konczos, Attila; Szabó, Mónika; Ioja, Enikő; Kolacsek, Orsolya; Orbán, Tamás I; Török, György; Homolya, László; Kovács, Eszter; Jablonkai, István; Veres, Zsuzsa
2017-02-01
Increasing number of papers demonstrate that Kupffer cells (KCs) play a role in the development of drug induced liver injury (DILI). Furthermore, elevated intracellular Ca 2+ level of hepatocytes is considered as a common marker of DILI. Here we applied an in vitro model based on hepatocyte mono- and hepatocyte/KC co-cultures (H/KC) isolated from transgenic rats stably expressing the GCaMP2 fluorescent Ca 2+ sensor protein to investigate the effects of polycationic (G5), polyanionic (G4.5) and polyethylene-glycol coated neutral (G5 Peg) dendrimers known to accumulate in the liver, primarily in KCs. Following dendrimer exposure, hepatocyte homeostasis was measured by MTT cytotoxicity assay and by Ca 2+ imaging, while hepatocyte functions were studied by CYP2B1/2 inducibility, and bilirubin and taurocholate transport. G5 was significantly more cytotoxic than G4.5 for hepatocytes and induced Ca 2+ oscillation and sustained Ca 2+ signals at 1μM and10 μM, respectively both in hepatocytes and KCs. Dendrimer-induced Ca 2+ signals in hepatocytes were attenuated by macrophages. Activation of KCs by lipopolysaccharide and G5 decreased the inducibility of CYP2B1/2, which was restored by depleting the KCs with gadolinium-chloride and pentoxyphylline, suggesting a role of macrophages in the hindrance of CYP2B1/2 induction by G5 and lipopolysaccharide. In the H/KC, but not in the hepatocyte mono-culture, G5 reduced the canalicular efflux of bilirubin and stimulated the uptake and canalicular efflux of taurocholate. In conclusion, H/KC provides a good model for the prediction of hepatotoxic potential of drugs, especially of nanomaterials known to be trapped by macrophages, activation of which presumably contributes to DILI. Copyright © 2016 Elsevier B.V. All rights reserved.
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He, Kun; Zhu, Xiwen; Liu, Yan; Miao, Chunmu; Wang, Tao; Li, Peizhi; Zhao, Lei; Chen, Yaxi; Gong, Junhua; Cai, Can; Li, Jinzheng; Li, Shengwei; Ruan, Xiong Z.; Gong, Jianping
2017-01-01
NOD-like receptor (NLR) NLRP3 inflammasome activation has been implicated in the progression of non-alcoholic fatty liver disease (NAFLD) from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It has been also shown that palmitic acid (PA) activates NLRP3 inflammasome and promotes interleukin-1β (IL-1β) secretion in Kupffer cells (KCs). However, the specific mechanism of the NLRP3 inflammasome activation is unclear. We studies the molecular mechanisms by investigating the roles of Thioredoxin-interacting protein (TXNIP) and NLRP3 on NAFLD development in patients, high-fat diet (HFD)-induced NAFL and methionine choline deficient (MCD) diet-induced NASH in wild type (WT), TXNIP−/− (thioredoxin-interacting protein) and NLRP3−/− mice, and isolated KCs. We found that the expressions of NLRP3 and TXNIP in human liver tissues were higher in NASH group than in NAFL group. Furthermore, co-immunoprecipitation analyses show that activation of the TXNIP-NLRP3 inflammasome protein complex occurred in KCs of NASH WT mice rather than NAFL WT mice, thus suggesting that the formation and activation of this protein complex is mainly involved in the development of NASH. NLRP3−/− mice exhibited less severe NASH than WT mice in MCD diet model, whereas TXNIP deficiency enhanced NLRP3 inflammasome activation and exacerbated liver injury. PA triggered the activation and co-localization of the NLRP3 inflammasome protein complex in KCs isolated from WT and TXNIP−/− but not NLRP3−/− mice, and most of the complex co-localized with mitochondria of KCs following PA stimulation. Taken together, our novel findings indicate that TXNIP plays a protective and anti-inflammatory role in the development of NAFLD through binding and suppressing NLRP3. PMID:28499273
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Deaciuc, I V; Fortunato, F; D'Souza, N B; Hill, D B; Schmidt, J; Lee, E Y; McClain, C J
1999-02-01
The purpose of this study was to determine if exacerbation of apoptosis precedes liver injury during chronic exposure of rats to alcohol. After 7 weeks of feeding an alcohol- or dextrin-containing liquid diet, the animals were treated with gram-negative bacterial lipopolysaccharide (1 mg x kg(-1) body weight, intravenously) or sterile saline and sacrificed 3 hr after the treatment. Alanine:2-oxoglutarate aminotransferase (ALT) and lactate:NAD oxidoreductase [lactate dehydrogenase (LDH)] were measured in plasma. The caudate lobe of the liver was resected for histology, while the rest of the organ was perfused with collagenase to isolate hepatocytes, Kupffer cells (KCs), and sinusoidal endothelial cells (SECs) by centrifugal elutriation. Hepatocyte mitochondria were isolated by differential centrifugation of the cell homogenate. Reduced and oxidized glutathione (GSH and GSSG) in isolated hepatocytes and hepatocyte mitochondria, and malondialdehyde in hepatocytes were assayed. Caspase-3 activity and Fas ligand mRNA expression were determined in hepatocytes, KCs, and SECs. Plasma ALT and LDH activity, liver histology, GSH, GSSG and their ratio, and malondialdehyde content were not affected by alcohol treatment Caspase-3 activity was significantly increased in alcohol-treated rats in all three cell types, with the lowest response observed in hepatocytes and the highest in KCs. Fas ligand mRNA expression, which had the highest level in SECs, followed by KCs and hepatocytes, was not affected by alcohol administration. Lipopolysaccharide had the following effects: an increase in ALT in both pair- and alcohol-fed rats, and LDH only in alcohol-fed rats, a decrease in GSH + GSSG levels in both mitochondria and hepatocytes, an elevation of malondialdehyde content in hepatocytes, a raise in caspase-3 activity in all groups and cell types, and an augmentation of Fas ligand expression in hepatocytes and KCs, but not in SECs. These data suggest that, during chronic alcohol consumption, an exacerbated apoptosis precedes alcohol-induced liver injury.
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Linares-Alba, Mónica Anayántzin; Gómez-Guajardo, Magda Berenice; Fonzar, Joice Furtado; Brooks, Dennis E.; García-Sánchez, Gustavo Adolfo
2016-01-01
Abstract Purpose: The aim of this study was to develop and characterize a liposomal product containing sirolimus to be administered subconjunctivally for the treatment of nonresponsive keratoconjunctivitis sicca (KCS) or dry eye. Methods: Formulations were prepared using an ethanol injection method and an adaptation of the heating method in pursuance of the most suitable methodology for future industrial production. Liposomes were loaded with either a high dose of 1 mg/mL of sirolimus or a less toxic dose of 0.4 mg/mL. The effects of critical process and formulation parameters were investigated. Liposomes were characterized in terms of size, zeta potential, polydispersity, differential scanning calorimetry, morphology, entrapment efficiency, phospholipid content, thermal stability, and sterility. The formulation was evaluated clinically in dogs with spontaneous KCS. Results: Sterile liposomal dispersions with sizes ranging from 140 to 211 nm, were successfully obtained. High entrapment efficiency of 93%–98% was achieved. The heating method allowed an easier production of liposomes with high entrapment efficiency, to significantly shorten production time and the elimination of the use of alcohol. The poor stability of the obtained liposomes in aqueous dispersion made the inclusion of a lyophilization step necessary to the manufacturing process. In vivo testing of the liposomal sirolimus formulations in the spontaneous KCS dog model have produced promising results, particularly with a sirolimus dose of 1 mg/mL, indicating the need for further development and study of proposed formulations in the treatment of canine KCS. Clinical improvement in tear production in dogs with spontaneous KCS treated with the 1 mg/mL dose product was observed. Conclusions: The heating method allowed easier production of high entrapment efficiency liposomes to significantly shorten production time and the elimination of the use of alcohol. Tear production was increased in dogs administered with the formulation. PMID:26469946
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Sperandio, Felipe F.; Simões, Alyne; Corrêa, Luciana; Aranha, Ana Cecília C.; Giudice, Fernanda S.; Hamblin, Michael R.; Sousa, Suzana C.O.M.
2015-01-01
Low-level laser therapy (LLLT) has been extensively employed to improve epithelial wound healing, though the exact response of epithelium maturation and stratification after LLLT is unknown. Thus, this study aimed to assess the in vitro growth and differentiation of keratinocytes (KCs) and in vivo wound healing response when treated with LLLT. Human KCs (HaCaT cells) showed an enhanced proliferation with all the employed laser energy densities (3, 6 and 12 J/cm2, 660nm, 100mW), together with an increased expression of Cyclin D1. Moreover, the immunoexpression of proteins related to epithelial proliferation and maturation (p63, CK10, CK14) all indicated a faster maturation of the migrating KCs in the LLLT-treated wounds. In that way, an improved epithelial healing was promoted by LLLT with the employed parameters; this improvement was confirmed by changes in the expression of several proteins related to epithelial proliferation and maturation. PMID:25411997
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Boiteux, Céline; Bernèche, Simon
2011-01-12
Potassium channels are membrane proteins that selectively conduct K(+) across cellular membranes. The narrowest part of their pore, the selectivity filter, is responsible for distinguishing K(+) from Na(+), and can also act as a gate through a mechanism known as C-type inactivation. It has been proposed that a conformation of the KcsA channel obtained by crystallization in presence of low concentration of K(+) (PDB 1K4D) could correspond to the C-type inactivated state. Here, we show using molecular mechanics simulations that such conformation has little ion-binding affinity and that ions do not contribute to its stability. The simulations suggest that, in this conformation, the selectivity filter is mostly occupied by water molecules. Whether such ion-free state of the KcsA channel is physiologically accessible and representative of the inactivated state of eukaryotic channels remains unclear. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Sierro, Frederic; Evrard, Maximilien; Rizzetto, Simone; Melino, Michelle; Mitchell, Andrew J; Florido, Manuela; Beattie, Lynette; Walters, Shaun B; Tay, Szun Szun; Lu, Bo; Holz, Lauren E; Roediger, Ben; Wong, Yik Chun; Warren, Alessandra; Ritchie, William; McGuffog, Claire; Weninger, Wolfgang; Le Couteur, David G; Ginhoux, Florent; Britton, Warwick J; Heath, William R; Saunders, Bernadette M; McCaughan, Geoffrey W; Luciani, Fabio; MacDonald, Kelli P A; Ng, Lai Guan; Bowen, David G; Bertolino, Patrick
2017-08-15
The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver. Copyright © 2017 Elsevier Inc. All rights reserved.
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Ma, Dejian; Tillman, Tommy S; Tang, Pei; Meirovitch, Eva; Eckenhoff, Roderic; Carnini, Anna; Xu, Yan
2008-10-28
Structural studies of polytopic membrane proteins are often hampered by the vagaries of these proteins in membrane mimetic environments and by the difficulties in handling them with conventional techniques. Designing and creating water-soluble analogues with preserved native structures offer an attractive alternative. We report here solution NMR studies of WSK3, a water-soluble analogue of the potassium channel KcsA. The WSK3 NMR structure (PDB ID code 2K1E) resembles the KcsA crystal structures, validating the approach. By more stringent comparison criteria, however, the introduction of several charged residues aimed at improving water solubility seems to have led to the possible formations of a few salt bridges and hydrogen bonds not present in the native structure, resulting in slight differences in the structure of WSK3 relative to KcsA. NMR dynamics measurements show that WSK3 is highly flexible in the absence of a lipid environment. Reduced spectral density mapping and model-free analyses reveal dynamic characteristics consistent with an isotropically tumbling tetramer experiencing slow (nanosecond) motions with unusually low local ordering. An altered hydrogen-bond network near the selectivity filter and the pore helix, and the intrinsically dynamic nature of the selectivity filter, support the notion that this region is crucial for slow inactivation. Our results have implications not only for the design of water-soluble analogues of membrane proteins but also for our understanding of the basic determinants of intrinsic protein structure and dynamics.
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Non-Equilibrium Dynamics Contribute to Ion Selectivity in the KcsA Channel
Haas, Stephan; Farley, Robert A.
2014-01-01
The ability of biological ion channels to conduct selected ions across cell membranes is critical for the survival of both animal and bacterial cells. Numerous investigations of ion selectivity have been conducted over more than 50 years, yet the mechanisms whereby the channels select certain ions and reject others are not well understood. Here we report a new application of Jarzynski’s Equality to investigate the mechanism of ion selectivity using non-equilibrium molecular dynamics simulations of Na+ and K+ ions moving through the KcsA channel. The simulations show that the selectivity filter of KcsA adapts and responds to the presence of the ions with structural rearrangements that are different for Na+ and K+. These structural rearrangements facilitate entry of K+ ions into the selectivity filter and permeation through the channel, and rejection of Na+ ions. A mechanistic model of ion selectivity by this channel based on the results of the simulations relates the structural rearrangement of the selectivity filter to the differential dehydration of ions and multiple-ion occupancy and describes a mechanism to efficiently select and conduct K+. Estimates of the K+/Na+ selectivity ratio and steady state ion conductance for KcsA from the simulations are in good quantitative agreement with experimental measurements. This model also accurately describes experimental observations of channel block by cytoplasmic Na+ ions, the “punch through” relief of channel block by cytoplasmic positive voltages, and is consistent with the knock-on mechanism of ion permeation. PMID:24465882
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Ioannou, George N.; Van Rooyen, Derrick M.; Savard, Christopher; Haigh, W. Geoffrey; Yeh, Matthew M.; Teoh, Narci C.; Farrell, Geoffrey C.
2015-01-01
Cholesterol crystals form within hepatocyte lipid droplets in human and experimental nonalcoholic steatohepatitis (NASH) and are the focus of crown-like structures (CLSs) of activated Kupffer cells (KCs). Obese, diabetic Alms1 mutant (foz/foz) mice were a fed high-fat (23%) diet containing 0.2% cholesterol for 16 weeks and then assigned to four intervention groups for 8 weeks: a) vehicle control, b) ezetimibe (5 mg/kg/day), c) atorvastatin (20 mg/kg/day), or d) ezetimibe and atorvastatin. Livers of vehicle-treated mice developed fibrosing NASH with abundant cholesterol crystallization within lipid droplets calculated to extend over 3.3% (SD, 2.2%) of liver surface area. Hepatocyte lipid droplets with prominent cholesterol crystallization were surrounded by TNFα-positive (activated) KCs forming CLSs (≥3 per high-power field). KCs that formed CLSs stained positive for NLRP3, implicating activation of the NLRP3 inflammasome in response to cholesterol crystals. In contrast, foz/foz mice treated with ezetimibe and atorvastatin showed near-complete resolution of cholesterol crystals [0.01% (SD, 0.02%) of surface area] and CLSs (0 per high-power field), with amelioration of fibrotic NASH. Ezetimibe or atorvastatin alone had intermediate effects on cholesterol crystallization, CLSs, and NASH. These findings are consistent with a causative link between exposure of hepatocytes and KCs to cholesterol crystals and with the development of NASH possibly mediated by NLRP3 activation. PMID:25520429
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Ioannou, George N; Van Rooyen, Derrick M; Savard, Christopher; Haigh, W Geoffrey; Yeh, Matthew M; Teoh, Narci C; Farrell, Geoffrey C
2015-02-01
Cholesterol crystals form within hepatocyte lipid droplets in human and experimental nonalcoholic steatohepatitis (NASH) and are the focus of crown-like structures (CLSs) of activated Kupffer cells (KCs). Obese, diabetic Alms1 mutant (foz/foz) mice were a fed high-fat (23%) diet containing 0.2% cholesterol for 16 weeks and then assigned to four intervention groups for 8 weeks: a) vehicle control, b) ezetimibe (5 mg/kg/day), c) atorvastatin (20 mg/kg/day), or d) ezetimibe and atorvastatin. Livers of vehicle-treated mice developed fibrosing NASH with abundant cholesterol crystallization within lipid droplets calculated to extend over 3.3% (SD, 2.2%) of liver surface area. Hepatocyte lipid droplets with prominent cholesterol crystallization were surrounded by TNFα-positive (activated) KCs forming CLSs (≥ 3 per high-power field). KCs that formed CLSs stained positive for NLRP3, implicating activation of the NLRP3 inflammasome in response to cholesterol crystals. In contrast, foz/foz mice treated with ezetimibe and atorvastatin showed near-complete resolution of cholesterol crystals [0.01% (SD, 0.02%) of surface area] and CLSs (0 per high-power field), with amelioration of fibrotic NASH. Ezetimibe or atorvastatin alone had intermediate effects on cholesterol crystallization, CLSs, and NASH. These findings are consistent with a causative link between exposure of hepatocytes and KCs to cholesterol crystals and with the development of NASH possibly mediated by NLRP3 activation.
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Crouzy, S; Bernèche, S; Roux, B
2001-08-01
TEA is a classical blocker of K(+) channels. From mutagenesis studies, it has been shown that external blockade by TEA is strongly dependent upon the presence of aromatic residue at Shaker position 449 which is located near the extracellular entrance to the pore (Heginbotham, L., and R. MacKinnon. 1992. Neuron. 8:483-491). The data suggest that TEA interacts simultaneously with the aromatic residues of the four monomers. The determination of the 3-D structure of the KcsA channel using X-ray crystallography (Doyle, D.A., J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, and R. MacKinnon. 1998. Science. 280:69-77) has raised some issues that remain currently unresolved concerning the interpretation of these observations. In particular, the center of the Tyr82 side chains in KcsA (corresponding to position 449 in Shaker) forms a square of 11.8-A side, a distance which is too large to allow simultaneous interactions of a TEA molecule with the four aromatic side chains. In this paper, the external blockade by TEA is explored by molecular dynamics simulations of an atomic model of KcsA in an explicit phospholipid bilayer with aqueous salt solution. It is observed, in qualitative accord with the experimental results, that TEA is stable when bound to the external side of the wild-type KcsA channel (with Tyr82), but is unstable when bound to a mutant channel in which the tyrosine residue has been substituted by a threonine. The free energy profile of TEA relative to the pore is calculated using umbrella sampling simulations to characterize quantitatively the extracellular blockade. It is found, in remarkable agreement with the experiment, that the TEA is more stably bound by 2.3 kcal/mol to the channel with four tyrosine residues. In the case of the wild-type KcsA channel, TEA (which has the shape of a flattened oblate spheroid) acts as an ideal plug blocking the pore. In contrast, it is considerably more off-centered and tilted in the case of the mutant channel. The enhanced stability conferred by the tyrosine residues does not arise from Pi-cation interactions, but appears to be due to differences in the hydration structure of the TEA. Finally, it is shown that the experimentally observed voltage dependence of TEA block, which is traditionally interpreted in terms of the physical position of the TEA along the axis of the pore, must arise indirectly via coupling with the ions in the pore.
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Ion-binding properties of a K+ channel selectivity filter in different conformations.
Liu, Shian; Focke, Paul J; Matulef, Kimberly; Bian, Xuelin; Moënne-Loccoz, Pierre; Valiyaveetil, Francis I; Lockless, Steve W
2015-12-08
K(+) channels are membrane proteins that selectively conduct K(+) ions across lipid bilayers. Many voltage-gated K(+) (KV) channels contain two gates, one at the bundle crossing on the intracellular side of the membrane and another in the selectivity filter. The gate at the bundle crossing is responsible for channel opening in response to a voltage stimulus, whereas the gate at the selectivity filter is responsible for C-type inactivation. Together, these regions determine when the channel conducts ions. The K(+) channel from Streptomyces lividians (KcsA) undergoes an inactivation process that is functionally similar to KV channels, which has led to its use as a practical system to study inactivation. Crystal structures of KcsA channels with an open intracellular gate revealed a selectivity filter in a constricted conformation similar to the structure observed in closed KcsA containing only Na(+) or low [K(+)]. However, recent work using a semisynthetic channel that is unable to adopt a constricted filter but inactivates like WT channels challenges this idea. In this study, we measured the equilibrium ion-binding properties of channels with conductive, inactivated, and constricted filters using isothermal titration calorimetry (ITC). EPR spectroscopy was used to determine the state of the intracellular gate of the channel, which we found can depend on the presence or absence of a lipid bilayer. Overall, we discovered that K(+) ion binding to channels with an inactivated or conductive selectivity filter is different from K(+) ion binding to channels with a constricted filter, suggesting that the structures of these channels are different.
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Ion conduction in the KcsA potassium channel analyzed with a minimal kinetic model.
Mafé, Salvador; Pellicer, Julio
2005-02-01
We use a model by Nelson to study the current-voltage and conductance-concentration curves of bacterial potassium channel KcsA without assuming rapid ion translocation. Ion association to the channel filter is rate controlling at low concentrations, but dissociation and transport in the filter can limit conduction at high concentration for ions other than K+. The absolute values of the effective rate constants are tentative but the relative changes in these constants needed to qualitatively explain the experiments should be of significance.
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Cheung, Ocean; Wardecki, Dariusz; Bacsik, Zoltán; Vasiliev, Petr; McCusker, Lynne B; Hedin, Niklas
2016-06-28
The|Na10.2KCs0.8|8[Al12Si12O48]8(Fm3[combining macron]c)-LTA zeolite adsorbs CO2-over-CH4 with a high selectivity (over 1500). The uptake of carbon dioxide is also high (3.31 mmol g(-1), 293 K, 101 kPa). This form of zeolite A is a very promising adsorbent for applications such as biogas upgrading, where keeping the adsorption of methane to a minimum is crucial.
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Synthesis of Toll-like receptor 4 in Kupffer cells and its role in alcohol-induced liver disease.
Zuo, Guoqing; Gong, Jianping; Liu, Chang'an; Wu, Chuanxin; Li, Shengwei; Dai, Lili
2003-02-01
To observe the synthesis of Toll-like receptor (TLR) 4 protein and its mRNA expression in Kupffer cells (KCs) and evaluate the role of TLR 4 in liver injury to rats through alcohol-induced liver disease. Twenty-eight Wistar rats were divided into two groups: ethanol-fed (group E) and control (group C). Group E rats were given ethanol at a dose of 5 - 12 g x kg(-1) x d(-1), while group C received dextrose. Animals from both groups were killed at 4 and 8 weeks. The KCs were isolated and synthesis of TLR 4 protein was determined by laser scanning confocal microscopy. TLR 4 mRNA expression in KCs was determined by reverse transcription polymerase chain reaction (RT-PCR) analysis. The levels of endotoxin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in plasma were determined. Changes in liver pathology were observed. Laser scanning confocal microscopy showed that the intensity of fluorescence of TLR 4 protein in group E was stronger than group C. Ethanol administration led to a significant increase in TLR 4 mRNA expression in group E compared with group C (P < 0.05). The concentrations of plasma endotoxin, TNF-alpha and IL-6 were higher in group E than in group C (P < 0.05). Liver sections from rats in group E demonstrated marked pathological changes. Ethanol administration can lead to the synthesis of TLR 4 protein and its gene expression in KCs, indicating that TLR 4 may play a major role in the development of alcohol-induced liver injury.
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2017-01-01
The selectivity filter of the KcsA K+ channel has two typical conformations—the conductive and the collapsed conformations, respectively. The transition from the conductive to the collapsed filter conformation can represent the process of inactivation that depends on many environmental factors. Water molecules permeating behind the filter can influence the collapsed filter stability. Here we perform the molecular dynamics simulations to study the stability of the collapsed filter of the KcsA K+ channel under the different water patterns. We find that the water patterns are dynamic behind the collapsed filter and the filter stability increases with the increasing number of water molecules. In addition, the stability increases significantly when water molecules distribute uniformly behind the four monomeric filter chains, and the stability is compromised if water molecules only cluster behind one or two adjacent filter chains. The altered filter stabilities thus suggest that the collapsed filter can inactivate gradually under the dynamic water patterns. We also demonstrate how the different water patterns affect the filter recovery from the collapsed conformation. PMID:29049423
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Wu, Di
2017-01-01
The selectivity filter of the KcsA K+ channel has two typical conformations-the conductive and the collapsed conformations, respectively. The transition from the conductive to the collapsed filter conformation can represent the process of inactivation that depends on many environmental factors. Water molecules permeating behind the filter can influence the collapsed filter stability. Here we perform the molecular dynamics simulations to study the stability of the collapsed filter of the KcsA K+ channel under the different water patterns. We find that the water patterns are dynamic behind the collapsed filter and the filter stability increases with the increasing number of water molecules. In addition, the stability increases significantly when water molecules distribute uniformly behind the four monomeric filter chains, and the stability is compromised if water molecules only cluster behind one or two adjacent filter chains. The altered filter stabilities thus suggest that the collapsed filter can inactivate gradually under the dynamic water patterns. We also demonstrate how the different water patterns affect the filter recovery from the collapsed conformation.
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Comparative Study of the Energetics of Ion Permeation in Kv1.2 and KcsA Potassium Channels
Baştuğ, Turgut; Kuyucak, Serdar
2011-01-01
Biological ion channels rely on a multi-ion transport mechanism for fast yet selective permeation of ions. The crystal structure of the KcsA potassium channel provided the first microscopic picture of this process. A similar mechanism is assumed to operate in all potassium channels, but the validity of this assumption has not been well investigated. Here, we examine the energetics of ion permeation in Shaker Kv1.2 and KcsA channels, which exemplify the six-transmembrane voltage-gated and two-transmembrane inward-rectifier channels. We study the feasibility of binding a third ion to the filter and the concerted motion of ions in the channel by constructing the potential of mean force for K+ ions in various configurations. For both channels, we find that a pair of K+ ions can move almost freely within the filter, but a relatively large free-energy barrier hinders the K+ ion from stepping outside the filter. We discuss the effect of the CMAP dihedral energy correction that was recently incorporated into the CHARMM force field on ion permeation dynamics. PMID:21281577
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Kenny-Caffey Syndrome: oral findings and 4-year follow-up of overlay denture therapy.
Demir, Tahsin; Kecik, Defne; Cehreli, Zafer C
2007-01-01
Kenny-Caffey Syndrome (KCS) is an extremely rare osteosclerotic bone dysplasia associated with hypocalcemia and ocular abnormalities. Although the condition is well reported in the medical literature, dental manifestations have not been discussed in great detail. The purpose of this report is to present specific oral features and prosthetic management in a KCS patient. Overlay dentures were utilized in the management of low vertical dimension of occlusion, congenital absence of several permanent teeth, and problems associated with function and esthetics. Results of the 4-year follow-up overlay denture therapy are presented.
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NASA Astrophysics Data System (ADS)
Wise, Stephen A.; Phinney, Karen W.; Duewer, David L.; Sniegoski, Lorna T.; Welch, Michael J.; Pritchett, Jeanita; Pabello, Guiomar; Avila Calderon, Marco A.; Balderas, Miryan; Qinde, Liu; Kooi, Lee Tong; Rego, Eliane; Garrido, Bruno; Allegri, Gabriella; de La Cruz, Marcia; Barrabin, Juliana; Monteiro, Tânia; Lee, Hwashim; Kim, Byungjoo; Delatour, Vincent; Peignaux, Maryline; Kawaguchi, Migaku; Bei, Xu; Can, Quan; Nammoonnoy, Jintana; Schild, Katrin; Ohlendorf, Rüdiger; Henrion, Andre; Ceyhan Gören, Ahmet; Yılmaz, Hasibe; Bilsel, Mine; Konopelko, L.; Krylov, A.; Lopushanskaya, E.
2018-01-01
Glucose and creatinine are two of the most frequently measured substances in human blood/serum for assessing the health status of individuals. Because of their clinical significance, CCQM-K11 glucose in human serum and CCQM-K12 creatinine in human serum were the fourth and fifth key comparisons (KCs) performed by the Organic Analysis Working Group (OAWG). These KCs were conducted in parallel and were completed in 2001. The initial subsequent KCs for glucose, CCQM-K11.1, and creatinine, CCQM-K12.1, were completed in 2005. Measurements for the next KCs for these two measurands, CCQM-K11.2 and CCQM-K12.2, were completed in 2013. While designed as subsequent KCs, systematic discordances between the participants' and the anchor institution's results in both comparisons lead the OAWG to request reference results from two experienced laboratories that had participated in the 2001 comparisons. Based on the totality of the available information, the OAWG converted both CCQM-K11.2 and CCQM-K12.2 to 'Track C' KCs where the key comparison reference value is estimated by consensus. These comparisons highlighted that carrying out comparisons for complex chemical measurements and expecting to be able to treat them under the approaches used for formal CIPM subsequent comparisons is not an appropriate strategy. The approach used here is a compromise to gain the best value from the comparison; it is not an approach that will be used in the future. Instead, the OAWG will focus on Track A and Track C comparisons that are treated as stand-alone entities. Participation in CCQM-K11.2 demonstrates a laboratory's capabilities to measure a polar (pKow > 2), low molecular mass (100 g/mol to 500 g/mol) metabolite in human serum at relatively high concentrations (0.1 mg/g to 10 mg/g). Participation in CCQM-K12.2 demonstrates capabilities to measure similar classes of metabolites at relatively low concentrations (1 μg/g to 30 μg/g). The capabilities required for the analysis of complex biological matrices include sample preparation (protein precipitation, extraction, derivatization), gas chromatographic (GC) or liquid chromatographic (LC) separation, and quantification using an isotope dilution mass spectrometry (IDMS) approach. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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Shenkarev, Zakhar O; Lyukmanova, Ekaterina N; Butenko, Ivan O; Petrovskaya, Lada E; Paramonov, Alexander S; Shulepko, Mikhail A; Nekrasova, Oksana V; Kirpichnikov, Mikhail P; Arseniev, Alexander S
2013-02-01
Production of helical integral membrane proteins (IMPs) in a folded state is a necessary prerequisite for their functional and structural studies. In many cases large-scale expression of IMPs in cell-based and cell-free systems results in misfolded proteins, which should be refolded in vitro. Here using examples of the bacteriorhodopsin ESR from Exiguobacterium sibiricum and full-length homotetrameric K(+) channel KcsA from Streptomyces lividans we found that the efficient in vitro folding of the transmembrane domains of the polytopic and multimeric IMPs could be achieved during the protein encapsulation into the reconstructed high-density lipoprotein particles, also known as lipid-protein nanodiscs. In this case the self-assembly of the IMP/nanodisc complexes from a mixture containing apolipoprotein, lipids and the partially denatured protein solubilized in a harsh detergent induces the folding of the transmembrane domains. The obtained folding yields showed significant dependence on the properties of lipids used for nanodisc formation. The largest recovery of the spectroscopically active ESR (~60%) from the sodium dodecyl sulfate (SDS) was achieved in the nanodiscs containing anionic saturated lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPG) and was approximately twice lower in the zwitterionic DMPC lipid. The reassembly of tetrameric KcsA from the acid-dissociated monomer solubilized in SDS was the most efficient (~80%) in the nanodiscs containing zwitterionic unsaturated lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The charged and saturated lipids provided lower tetramer quantities, and the lowest yield (<20%) was observed in DMPC. The overall yield of the ESR and KcsA folding was mainly restricted by the efficiency of the protein encapsulation into the nanodiscs. Copyright © 2012 Elsevier B.V. All rights reserved.
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Izci, Celal; Celik, Ilhami; Alkan, Fahrettin; Ogurtan, Zeki; Ceylan, Cengiz; Sur, Emrah; Ozkan, Yasemin
2002-05-01
To evaluate the efficacy of topical administration of a 2% solution of cyclosporine (CsA) for treatment of dogs with keratoconjunctivitis sicca (KCS) and to correlate results with histopathologic characteristics and local cellular immunity of the gland of the third eyelid. 24 dogs with bilateral KCS. Lacrimal secretion was measured, using Schirmer tear test (STT) strips. Leukocyte and T-lymphocyte subsets were determined in blood samples. Histopathologic changes as well as CD4+, CD8+, and alpha-naphthyl-acetate esterase-positive (ANAE+) lymphocytes were evaluated. Clinical signs resolved at the end of 1 month in conjunction with significantly increased STT values, compared with baseline values. Fifteen and 30 days after discontinuation of CsA treatment, a decrease was observed in STT values in both eyes; however, only values for the right eye were significantly different. There was a significant decrease in the number of lymphocytes and ANAE+ lymphocytes 15 and 30 days after discontinuation of CsA treatment, compared with baseline values. Differences were not observed in number of CD4+ lymphocytes among treatment groups. However, there was a significant decrease in number of CD8+ lymphocytes with reversal of the CD4+:CD8+ in both eyes after CsA treatment for 30 days, compared with the control group. Increased secretory activity and decreased lymphocyte infiltration were characteristic histopathologic findings. Topical administration of a 2% solution of CsA was effective for the treatment of dogs with KCS. Strict follow-up monitoring is required after the cessation of treatment because of the possibility of recurrence of KCS.
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Weinstock, Martin A.; Lee, Kachiu C.; Chren, Mary-Margaret; Marcolivio, Kimberly
2013-01-01
Background Keratinocyte carcinomas (KCs) are the most common malignancies of the skin. As lesions have a low mortality rate, understanding quality-of-life (QoL) factors is necessary in their management. Objective To assess QoL and associated patient characteristics in those with a history of keratinocyte carcinomas. Methods We conducted a cross-sectional study of veterans with a history of KCs enrolled in a randomized controlled trial for chemoprevention of keratinocyte carcinomas. Study dermatologists counted actinic keratoses (AKs) and assessed for skin photodamage. QoL was assessed using Skindex-29 and KC-specific questions. Demographics were self-reported. Results Participants (n = 931) enrolled at 5 clinical sites had worse QoL on all subscales (emotions, functioning, and symptoms) compared to a reference group of patients without skin disease. Univariate analysis demonstrated worse QoL associated with higher AK count, past 5-fluorouracil (5-FU) use, and greater sun sensitivity. Multivariate analysis demonstrated that higher AK count and past 5-FU use were independently related to diminished QoL. Higher comorbidities showed modest associations on the symptoms and functioning subscales. Number of previous KCs was not independently associated with any QoL differences. Limitations Study population may not be generalizable to the general population. Counting of AKs is of limited reliability. Previous 5-FU use is self reported. Conclusions A history of ever use of 5-FU and present AKs was strongly associated with worse QoL. We find it more useful to consider these patients as having the chronic condition “actinic neoplasia syndrome,” whose burden may be best measured by factors other than their history of KCs. PMID:19398145
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NASA Astrophysics Data System (ADS)
Kruzins, A.; Klincare, I.; Nikolayeva, O.; Tamanis, M.; Ferber, R.; Pazyuk, E. A.; Stolyarov, A. V.
2010-04-01
The laser-induced fluorescence (LIF) A1Σ+-b3Π→X1Σ+ spectra of the KCs molecule were recorded in a near infrared region by a Fourier-transform spectrometer with a resolution of 0.03 cm-1. Overall more than 200 collisionally enhanced LIF spectra were rotationally assigned to K39Cs133 and K41Cs133 isotopomers yielding more than 3400 rovibronic term values of the strongly mixed singlet A1Σ+ and triplet b3Π states with the uncertainty of 0.003-0.01 cm-1. Experimental data massive starts from the lowest vibrational level vA=0 of the singlet and nonuniformly covers the energy range E∈[10040,13250] cm-1 with rotational quantum numbers J'∈[7,225]. Besides the dominating regular A1Σ+-b3ΠΩ=0 interactions, the weak local heterogeneous A1Σ+-b3ΠΩ=1 perturbations have been discovered and analyzed. Coupled-channels deperturbation analysis of the experimental K39Cs133 e-parity term values of the A1Σ+-b3ΠΩ=0,1,2 complex was accomplished in the framework of the phenomenological 4×4 Hamiltonian accounting implicitly for regular interactions with the remote 1Π and 3Σ+ states. The diabatic potential energy curves of the A1Σ+ and b3Π states, as well as relevant spin-orbit coupling matrix elements, were defined analytically with the expanded Morse oscillators model. The obtained parameters reproduce 95% of experimental data field of the K39Cs133 isotopomer with a standard deviation of 0.004 cm-1, which is consistent with the uncertainty of the experiment. Reliability of the derived parameters was confirmed by a good agreement between the predicted and experimental term values of the K41Cs133 isotopomer. The calculated relative intensity distributions in A-b→X LIF progressions are also consistent with their experimental counterparts. The deperturbation model was applied for simulation of a pump-dump optical cycle a3Σ+→A1Σ+-b3Π→X1Σ+ proposed for transformation of ultracold KCs molecules to their absolute ground state vX=0;JX=0.
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Studies on the influence on flexural wall deformations on the development of the flow boundary layer
NASA Technical Reports Server (NTRS)
Schilz, W.
1978-01-01
Flexural wave-like deformations can be used to excite boundary layer waves which in turn lead to the onset of turbulence in the boundary layer. The investigations were performed with flow velocities between 5 m/s and 40 m/s. With four different flexural wave transmissions a frequency range from 0.2 kc/s to 1.5 kc/s and a phase velocity range from 3.5 m/s to 12 m/s was covered. The excitation of boundary layer waves becomes most effective if the phase velocity of the flexural wave coincides with the phase velocity region of unstable boundary layer waves.
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Molecular interactions involved in proton-dependent gating in KcsA potassium channels
Posson, David J.; Thompson, Ameer N.; McCoy, Jason G.
2013-01-01
The bacterial potassium channel KcsA is gated open by the binding of protons to amino acids on the intracellular side of the channel. We have identified, via channel mutagenesis and x-ray crystallography, two pH-sensing amino acids and a set of nearby residues involved in molecular interactions that influence gating. We found that the minimal mutation of one histidine (H25) and one glutamate (E118) near the cytoplasmic gate completely abolished pH-dependent gating. Mutation of nearby residues either alone or in pairs altered the channel’s response to pH. In addition, mutations of certain pairs of residues dramatically increased the energy barriers between the closed and open states. We proposed a Monod–Wyman–Changeux model for proton binding and pH-dependent gating in KcsA, where H25 is a “strong” sensor displaying a large shift in pKa between closed and open states, and E118 is a “weak” pH sensor. Modifying model parameters that are involved in either the intrinsic gating equilibrium or the pKa values of the pH-sensing residues was sufficient to capture the effects of all mutations. PMID:24218397
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Sperandio, Felipe F; Simões, Alyne; Corrêa, Luciana; Aranha, Ana Cecília C; Giudice, Fernanda S; Hamblin, Michael R; Sousa, Suzana C O M
2015-10-01
Low-level laser therapy (LLLT) has been extensively employed to improve epithelial wound healing, though the exact response of epithelium maturation and stratification after LLLT is unknown. Thus, this study aimed to assess the in vitro growth and differentiation of keratinocytes (KCs) and in vivo wound healing response when treated with LLLT. Human KCs (HaCaT cells) showed an enhanced proliferation with all the employed laser energy densities (3, 6 and 12 J/cm(2) , 660 nm, 100 mW), together with an increased expression of Cyclin D1. Moreover, the immunoexpression of proteins related to epithelial proliferation and maturation (p63, CK10, CK14) all indicated a faster maturation of the migrating KCs in the LLLT-treated wounds. In that way, an improved epithelial healing was promoted by LLLT with the employed parameters; this improvement was confirmed by changes in the expression of several proteins related to epithelial proliferation and maturation. Immunofluorescent expression of cytokeratin 10 (red) and Cyclin D1 (green) in (A) Control keratinocytes and (B) Low-level laser irradiated cells. Blue color illustrates the nuclei of the cells (DAPI staining). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Chiapa-Labastida, Mariana; Zentella-Dehesa, Alejandro; León-Dorantes, Gladys; Becker, Ingeborg
2011-01-01
Apoptotic cells are present in the epidermis of pemphigus vulgaris (PV) patients and their accumulation has been linked to chronic inflammatory disorders. TNF-α is elevated in sera of PV patients and has only been detected in acantholytic and periacantholytic keratinocytes (KC), therefore another TNF-α source might exist. We analyzed, in lesional and perilesional skin of 5 active untreated PV patients, the presence of apoptotic cells, TNF-α and phagocytic infiltrate. In vitro, we analyzed whether phagocytosis of apoptotic KCs by monocytes causes TNF-α release. We found a significant increase of apoptotic cells in the epidermis and dermis of PV patients, by TUNEL, and activated caspase-3. TNF-α was present in the skin of PV patients, especially in the dermis. Phagocytic CD14+ cells were increased, mostly in the dermis of PV patients. In vitro phagocytosis of apoptotic KCs by monocytes caused enhanced TNF-α production, which correlated with the number of apoptotic KCs in the co-culture. Thus, accumulation of apoptotic cells in PV could promote TNF-α production by monocytes, which could, in turn, cause further apoptosis, closing a vicious circle.
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Liu, Jia; Huang, Xuan; Werner, Melanie; Broering, Ruth; Yang, Dongliang; Lu, Mengji
2017-01-01
Separation of pure cell populations from the liver is a prerequisite to study the role of hepatic parenchymal and non-parenchymal cells in liver physiology, pathophysiology, and immunology. Traditional methods for hepatic cell separation usually purify only single cell types from liver specimens. Here, we describe an efficient method that can simultaneously purify populations of hepatocytes (HCs), liver sinusoidal endothelial cells (LSECs), and Kupffer cells (KCs) from a single mouse liver specimen. A liberase-based perfusion technique in combination with a low-speed centrifugation and magnetic-activated cell sorting (MACS) led to the isolation and purification of HCs, KCs, and LSECs with high yields and purity.
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Li, Chao; Haslam, Tegan M; Krüger, Anna; Schneider, Lizette M; Mishina, Kohei; Samuels, Lacey; Yang, Hongxing; Kunst, Ljerka; Schaffrath, Ulrich; Nawrath, Christiane; Chen, Guoxiong; Komatsuda, Takao; von Wettstein-Knowles, Penny
2018-04-01
The cuticle coats the primary aerial surfaces of land plants. It consists of cutin and waxes, which provide protection against desiccation, pathogens and herbivores. Acyl cuticular waxes are synthesized via elongase complexes that extend fatty acyl precursors up to 38 carbons for downstream modification pathways. The leaves of 21 barley eceriferum (cer) mutants appear to have less or no epicuticular wax crystals, making these mutants excellent tools for identifying elongase and modification pathway biosynthetic genes. Positional cloning of the gene mutated in cer-zh identified an elongase component, β-ketoacyl-CoA synthase (CER-ZH/HvKCS1) that is one of 34 homologous KCSs encoded by the barley genome. The biochemical function of CER-ZH was deduced from wax and cutin analyses and by heterologous expression in yeast. Combined, these experiments revealed that CER-ZH/HvKCS1 has a substrate specificity for C16-C20, especially unsaturated, acyl chains, thus playing a major role in total acyl chain elongation for wax biosynthesis. The contribution of CER-ZH to water barrier properties of the cuticle and its influence on the germination of barley powdery mildew fungus were also assessed.
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Nickoloff, B J; Fivenson, D P; Kunkel, S L; Strieter, R M; Turka, L A
1994-10-01
Despite the highly diverse reaction patterns of benign and malignant skin diseases involving T lymphocytes, polymerase chain reaction analysis of cytokine mRNAs present in biopsy samples has revealed that many cutaneous responses can be categorized into essentially two discrete groups. One group exemplified by psoriasis is characterized by consistently detectable mRNAs for IL-2, IFN-gamma, and TNF-alpha, but not IL-4, IL-5, IL-10, thereby closely resembling the murine Th1-type cell-mediated response. The second group exemplified by tape-stripped skin, poison ivy dermatitis, and Sezary syndrome contains predominantly IL-4, IL-5, and IL-10 mRNAs resembling the Th2-type cytokine profile. Because of the growing interest in the immunoregulatory role of IL-10, which can suppress IFN-gamma production and inhibit cell-mediated reactions, we produced a rabbit antiserum that was used to immunohistochemically localize IL-10 in a total of 27 biopsies. The results revealed that in Th2-type skin diseases, IL-10 was predominantly identified throughout all levels of epidermis in the cytoplasm of keratinocytes (KCs), with accentuation of their membranes in upper level cells. In Sezary syndrome, T cells were also immunoreactive for IL-10, which was confirmed using the HUT 78 T cell line derived from a Sezary syndrome patient. While normal skin was devoid of IL-10 expression, KCs began expressing it as early as 6 hr following tape stripping or application of poison ivy antigen and became strongly and diffusely positive by 18-24 hr. In contrast, psoriatic plaques contained no IL-10 immunoreactivity in either the parakeratotic scale or the epidermal KCs. These results confirm the earlier IL-10 mRNA analysis using whole skin samples and immunolocalize IL-10 to epidermal KCs in the Th2 diseases.
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Lam, Yee Ling; Zeng, Weizhong; Sauer, David Bryant
2014-01-01
Potassium channels are highly selective for K+ over the smaller Na+. Intriguingly, they are permeable to larger monovalent cations such as Rb+ and Cs+ but are specifically blocked by the similarly sized Ba2+. In this study, we used structural analysis to determine the binding profiles for these permeant and blocking ions in the selectivity filter of the potassium-selective NaK channel mutant NaK2K and also performed permeation experiments using single-channel recordings. Our data revealed that some ion binding properties of NaK2K are distinct from those of the canonical K+ channels KcsA and MthK. Rb+ bound at sites 1, 3, and 4 in NaK2K, as it does in KcsA. Cs+, however, bound predominantly at sites 1 and 3 in NaK2K, whereas it binds at sites 1, 3, and 4 in KcsA. Moreover, Ba2+ binding in NaK2K was distinct from that which has been observed in KcsA and MthK, even though all of these channels show similar Ba2+ block. In the presence of K+, Ba2+ bound to the NaK2K channel at site 3 in conjunction with a K+ at site 1; this led to a prolonged block of the channel (the external K+-dependent Ba2+ lock-in state). In the absence of K+, however, Ba2+ acts as a permeating blocker. We found that, under these conditions, Ba2+ bound at sites 1 or 0 as well as site 3, allowing it to enter the filter from the intracellular side and exit from the extracellular side. The difference in the Ba2+ binding profile in the presence and absence of K+ thus provides a structural explanation for the short and prolonged Ba2+ block observed in NaK2K. PMID:25024267
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Lam, Yee Ling; Zeng, Weizhong; Sauer, David Bryant; Jiang, Youxing
2014-08-01
Potassium channels are highly selective for K(+) over the smaller Na(+). Intriguingly, they are permeable to larger monovalent cations such as Rb(+) and Cs(+) but are specifically blocked by the similarly sized Ba(2+). In this study, we used structural analysis to determine the binding profiles for these permeant and blocking ions in the selectivity filter of the potassium-selective NaK channel mutant NaK2K and also performed permeation experiments using single-channel recordings. Our data revealed that some ion binding properties of NaK2K are distinct from those of the canonical K(+) channels KcsA and MthK. Rb(+) bound at sites 1, 3, and 4 in NaK2K, as it does in KcsA. Cs(+), however, bound predominantly at sites 1 and 3 in NaK2K, whereas it binds at sites 1, 3, and 4 in KcsA. Moreover, Ba(2+) binding in NaK2K was distinct from that which has been observed in KcsA and MthK, even though all of these channels show similar Ba(2+) block. In the presence of K(+), Ba(2+) bound to the NaK2K channel at site 3 in conjunction with a K(+) at site 1; this led to a prolonged block of the channel (the external K(+)-dependent Ba(2+) lock-in state). In the absence of K(+), however, Ba(2+) acts as a permeating blocker. We found that, under these conditions, Ba(2+) bound at sites 1 or 0 as well as site 3, allowing it to enter the filter from the intracellular side and exit from the extracellular side. The difference in the Ba(2+) binding profile in the presence and absence of K(+) thus provides a structural explanation for the short and prolonged Ba(2+) block observed in NaK2K. © 2014 Lam et al.
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Coulomb interaction rules timescales in potassium ion channel tunneling
NASA Astrophysics Data System (ADS)
De March, N.; Prado, S. D.; Brunnet, L. G.
2018-06-01
Assuming the selectivity filter of KcsA potassium ion channel may exhibit quantum coherence, we extend a previous model by Vaziri and Plenio (2010 New J. Phys. 12 085001) to take into account Coulomb repulsion between potassium ions. We show that typical ion transit timescales are determined by this interaction, which imposes optimal input/output parameter ranges. Also, as observed in other examples of quantum tunneling in biological systems, the addition of moderate noise helps coherent ion transport.
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Tang, Hongbo; Chen, Hongli; Jia, Yajing; Liu, Xiaoyan; Han, Zhaohong; Wang, Aihua; Liu, Qi; Li, Xinlei; Feng, Xin
2017-01-01
The regular accumulation of nanoparticles in the liver makes them hepatotoxic and decreases the circulation time, thus reducing their therapeutic effect. Resolving this problem will be significant in improving bioavailability and reducing side effects. In this study, we reduced the phagocytosis of epirubicin (EPI)-loaded folic acid-conjugated pullulan acetate (FPA/EPI) nanoparticles by Kupffer cells (KCs) through internalization and nuclear factor kappa B (NF-kB) signal pathway inhibitors, thus allowing development of FPA/EPI nanoparticles as a nanodrug delivery system (NDDS) based on our previous study. FPA/EPI nanoparticles were prepared by the dialysis method. Rat KCs were preincubated with the following individual or compound inhibitors: chlorpromazine (CPZ), nystatin (NY), colchicine (Col), amiloride (AMR), and pyrrolidine dithiocarbamate (PDTC). Dose- and time-dependent cellular uptake effects of inhibitors on FPA/EPI nanoparticles were determined through fluorometry. The cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 were tested in culture supernatants by bead-based multiplex flow cytometry. The uptake study demonstrated that inhibitors had an obvious inhibitory effect ( P <0.05 or P <0.01), with NY, AMR and Col all showing time-dependent inhibitory effects. PDTC + NY had the strongest inhibitory effect, with an uptake rate of 14.62%. The levels of the three proinflammatory cytokines were changed significantly by the compound inhibitors. TNF-α was significantly inhibited ( P <0.05 or P <0.01), but IL-1β and IL-6 showed smaller decreases. These results suggested that clathrin- and caveolae-mediated endocytosis were the main routes via which nanoparticles entered KCs and that the NF-kB signal pathway was very important too. In summary, multiple mechanisms, including clathrin- and caveolae-mediated endocytosis, contribute to cytokine production in macrophages following exposure to folic acid-conjugated pullulan acetate nanoparticles. Thus, the endocytosis inhibition strategy has great potential for improving therapy and reducing toxicity of an NDDS in the treatment of cancer.
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The KMOS Cluster Survey - KCS: Timing the Formation of Passive Galaxies in Clusters at 1.4
NASA Astrophysics Data System (ADS)
Beifiori, Alessandra
2017-07-01
In this talk I will discuss recent progress studying the rest-frame optical properties of quiescent galaxies at this critical epoch using KMOS, the K-band Multi-Object Spectrograph on the ESO/VLT. I will highlight recent results form the KMOS Custer Survey (KCS), whose aim is to provide a census of quiescent galaxy kinematics at 1.4 ≤ z ≤ 1.8 in know overdensities. The combination of kinematic measurements from KMOS and structural parameters measured from deep HST imaging allowed us to place constraints on the formation ages of passive galaxies at 1.4
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Molecular determinants of tetramerization in the KcsA cytoplasmic domain.
Kamnesky, Guy; Hirschhorn, Orel; Shaked, Hadassa; Chen, Jingfei; Yao, Lishan; Chill, Jordan H
2014-10-01
The cytoplasmic C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is an amphiphilic domain that forms a helical bundle with four-fold symmetry mediated by hydrophobic and electrostatic interactions. Previously we have established that a CTD-derived 34-residue peptide associates into a tetramer in a pH-dependent manner (Kamnesky et al., JMB 2012;418:237-247). Here we further investigate the molecular determinants of tetramer formation in the CTD by characterizing the kinetics of monomer-tetramer equilibrium for 10 alanine mutants using NMR, sedimentation equilibrium (SE) and molecular dynamics simulation. NMR and SE concur in finding single-residue contributions to tetramer stability to be in the 0.5 to 3.5 kcal/mol range. Hydrophobic interactions between residues lining the tetramer core generally contributed more to formation of tetramer than electrostatic interactions between residues R147, D149 and E152. In particular, alanine replacement of residue R147, a key contributor to inter-subunit salt bridges, resulted in only a minor effect on tetramer dissociation. Mutations outside of the inter-subunit interface also influenced tetramer stability by affecting the tetramerization on-rate, possibly by changing the inherent helical propensity of the peptide. These findings are interpreted in the context of established paradigms of protein-protein interactions and protein folding, and lay the groundwork for further studies of the CTD in full-length KcsA channels. © 2014 The Protein Society.
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Molecular determinants of tetramerization in the KcsA cytoplasmic domain
Kamnesky, Guy; Hirschhorn, Orel; Shaked, Hadassa; Chen, Jingfei; Yao, Lishan; Chill, Jordan H
2014-01-01
The cytoplasmic C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is an amphiphilic domain that forms a helical bundle with four-fold symmetry mediated by hydrophobic and electrostatic interactions. Previously we have established that a CTD-derived 34-residue peptide associates into a tetramer in a pH-dependent manner (Kamnesky et al., JMB 2012;418:237-247). Here we further investigate the molecular determinants of tetramer formation in the CTD by characterizing the kinetics of monomer-tetramer equilibrium for 10 alanine mutants using NMR, sedimentation equilibrium (SE) and molecular dynamics simulation. NMR and SE concur in finding single-residue contributions to tetramer stability to be in the 0.5 to 3.5 kcal/mol range. Hydrophobic interactions between residues lining the tetramer core generally contributed more to formation of tetramer than electrostatic interactions between residues R147, D149 and E152. In particular, alanine replacement of residue R147, a key contributor to inter-subunit salt bridges, resulted in only a minor effect on tetramer dissociation. Mutations outside of the inter-subunit interface also influenced tetramer stability by affecting the tetramerization on-rate, possibly by changing the inherent helical propensity of the peptide. These findings are interpreted in the context of established paradigms of protein-protein interactions and protein folding, and lay the groundwork for further studies of the CTD in full-length KcsA channels. PMID:25042120
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Numerical simulation and experimental research on wake field of ships under off-design conditions
NASA Astrophysics Data System (ADS)
Guo, Chun-yu; Wu, Tie-cheng; Zhang, Qi; Gong, Jie
2016-10-01
Different operating conditions (e.g. design and off-design) may lead to a significant difference in the hydrodynamics performance of a ship, especially in the total resistance and wake field of ships. This work investigated the hydrodynamic performance of the well-known KRISO 3600 TEU Container Ship (KCS) under three different operating conditions by means of Particle Image Velocimetry (PIV) and Computational Fluid Dynamics (CFD). The comparison results show that the use of PIV to measure a ship's nominal wake field is an important method which has the advantages of being contactless and highly accurate. Acceptable agreements between the results obtained by the two different methods are achieved. Results indicate that the total resistances of the KCS model under two off-design conditions are 23.88% and 13.92% larger than that under the designed condition, respectively.
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Rössler, Wolfgang
2018-01-01
The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN) convey olfactory information on ~900 projection neurons (PN) in the antennal lobe (AL). To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB). This pathway comprises the medial (m-ALT) and the lateral antennal lobe tract (l-ALT). PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties. In the MBs, PNs form synapses with many Kenyon cells (KC) that encode odors in a spatially and temporally sparse way. The transformation from complex information coding to sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic neuronal properties as well as GABAergic inhibition are thought to contribute to this change in odor representation. In the present study, we identified intrinsic neuronal properties promoting coding differences between PNs and KCs using in-situ patch-clamp recordings in the intact brain. We found very prominent K+ currents in KCs clearly differing from the PN currents. This suggests that odor coding differences between PNs and KCs may be caused by differences in their specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs did not reveal any differences at a qualitative level. PMID:29351552
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Cholesterol crystallization within hepatocyte lipid droplets and its role in murine NASH[S
Ioannou, George N.; Subramanian, Savitha; Chait, Alan; Haigh, W. Geoffrey; Yeh, Matthew M.; Farrell, Geoffrey C.; Lee, Sum P.; Savard, Christopher
2017-01-01
We recently reported that cholesterol crystals form in hepatocyte lipid droplets (LDs) in human and experimental nonalcoholic steatohepatitis. Herein, we assigned WT C57BL/6J mice to a high-fat (15%) diet for 6 months, supplemented with 0%, 0.25%, 0.5%, 0.75%, or 1% dietary cholesterol. Increasing dietary cholesterol led to cholesterol loading of the liver, but not of adipose tissue, resulting in fibrosing steatohepatitis at a dietary cholesterol concentration of ≥0.5%, whereas mice on lower-cholesterol diets developed only simple steatosis. Hepatic cholesterol crystals and crown-like structures also developed at a dietary cholesterol concentration ≥0.5%. Crown-like structures consisted of activated Kupffer cells (KCs) staining positive for NLRP3 and activated caspase 1, which surrounded and processed cholesterol crystal-containing remnant LDs of dead hepatocytes. The KCs processed LDs at the center of crown-like structures in the extracellular space by lysosomal enzymes, ultimately transforming into lipid-laden foam cells. When HepG2 cells were exposed to LDL cholesterol, they developed cholesterol crystals in LD membranes, which caused activation of THP1 cells (macrophages) grown in coculture; upregulation of TNF-alpha, NLRP3, and interleukin 1beta (IL1β) mRNA; and secretion of IL-1beta. In conclusion, cholesterol crystals form on the LD membrane of hepatocytes and cause activation and cholesterol loading of KCs that surround and process these LDs by lysosomal enzymes. PMID:28404639
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Pietrzak-Nguyen, Anette; Fichter, Michael; Dedters, Marvin; Pretsch, Leah; Gregory, Stephen H; Meyer, Claudius; Doganci, Aysefa; Diken, Mustafa; Landfester, Katharina; Baier, Grit; Gehring, Stephan
2014-07-14
A broad spectrum of infectious liver diseases emphasizes the need of microparticles for targeted delivery of immunomodulatory substances to the liver. Microcapsules (MCs) are particularly attractive for innovative drug and vaccine formulations, enabling the combination of antigen, drugs, and adjuvants. The present study aimed to develop microcapsules characterized by an enhanced liver deposition and accelerated uptake by nonparenchymal liver cells (NPCs). Initially, two formulations of biodegradable microcapsules were synthesized from either hydroxyethyl starch (HES) or mannose. Notably, HES-MCs accumulated primarily in the liver, while mannose particles displayed a lung preference. Functionalization of HES-MCs with anti-CD40, anti-DEC205, and/or monophosphoryl lipid A (MPLA) enhanced uptake of MCs by nonparenchymal liver cells in vitro. In contrast, only MPLA-coated HES-MCs promoted significantly the in vivo uptake by NPCs. Finally, HES-MCs equipped with MPLA, anti-CD40, and anti-DEC205 induced the secretion of TNF-α, IL-6 by Kupffer cells (KCs), and IFN-γ and IL-12p70 by liver dendritic cells (DCs). The enhanced uptake and activation of KCs by MPLA-HES-MCs is a promising approach to prevent or treat infection, since KCs are exploited as an entry gate in various infectious diseases, such as malaria. In parallel, loading and activating liver DCs, usually prone to tolerance, bears the potential to induce antigen specific, intrahepatic immune responses necessary to prevent and treat infections affecting the liver.
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Kawase, Jun; Asakura, Hiroshi; Kurosaki, Morito; Oshiro, Hitoshi; Etoh, Yoshiki; Ikeda, Tetsuya; Watahiki, Masanori; Kameyama, Mitsuhiro; Hayashi, Fumi; Kawakami, Yuta; Murakami, Yoshiko; Tsunomori, Yoshie
2018-01-23
We previously developed a multiplex real-time PCR assay (Rapid Foodborne Bacterial Screening 24 ver.5, [RFBS24 ver.5]) for simultaneous detection of 24 foodborne bacterial targets. Here, to overcome the discrepancy of the results from RFBS24 ver.5 and bacterial culture methods (BC), we analyzed 246 human clinical samples from 49 gastroenteritis outbreaks using RFBS24 ver.5 and evaluated the correlation between the cycle threshold (CT) value of RFBS24 ver.5 and the BC results. The results showed that the RFBS24 ver.5 was more sensitive than BC for Campylobacter jejuni and Escherichia coli harboring astA or eae, with positive predictive values (PPV) of 45.5-87.0% and a kappa coefficient (KC) of 0.60-0.92, respectively. The CTs were significantly different between BC-positive and -negative samples (p ＜ 0.01). All RFBS24 ver.5-positive samples were BC-positive under the lower confidence interval (CI) limit of 95% or 99% for the CT of the BC-negative samples. We set the 95% or 99% CI lower limit to the determination CT (d-CT) to discriminate for assured BC-positive results (d-CTs: 27.42-30.86), and subsequently the PPVs (94.7%-100.0%) and KCs (0.89-0.95) of the 3 targets were increased. Together, we concluded that the implication of a d-CT-based approach would be a valuable tool for rapid and accurate diagnoses using the RFBS24 ver.5 system.
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NASA Astrophysics Data System (ADS)
Shantappa, Anil; Talukdar, Keka
2018-04-01
Ion channels are proteins forming pore inside the body of all living organisms. This potassium ion channel known as KcsA channel and it is found in the each cell and nervous system. Flow of various ions is regulated by the function of the ion channels. The nerve ion channel protein with protein data bank entry 1BL8, which is basically an ion channel protein in Streptomyces Lividans and which is taken up to form micelle-protein system and the system is analyzed by using molecular dynamics simulation. Firstly, ion channel pore is engineered by CHARMM potential and then Micelle-protein system is subjected to molecular dynamics simulation. For some specific micelle concentration, the protein unfolding is observed.
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Direct neural pathways convey distinct visual information to Drosophila mushroom bodies
Vogt, Katrin; Aso, Yoshinori; Hige, Toshihide; Knapek, Stephan; Ichinose, Toshiharu; Friedrich, Anja B; Turner, Glenn C; Rubin, Gerald M; Tanimoto, Hiromu
2016-01-01
Previously, we demonstrated that visual and olfactory associative memories of Drosophila share mushroom body (MB) circuits (Vogt et al., 2014). Unlike for odor representation, the MB circuit for visual information has not been characterized. Here, we show that a small subset of MB Kenyon cells (KCs) selectively responds to visual but not olfactory stimulation. The dendrites of these atypical KCs form a ventral accessory calyx (vAC), distinct from the main calyx that receives olfactory input. We identified two types of visual projection neurons (VPNs) directly connecting the optic lobes and the vAC. Strikingly, these VPNs are differentially required for visual memories of color and brightness. The segregation of visual and olfactory domains in the MB allows independent processing of distinct sensory memories and may be a conserved form of sensory representations among insects. DOI: http://dx.doi.org/10.7554/eLife.14009.001 PMID:27083044
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Cherry, Rose L; Smith, Jodi D; Ben-Shlomo, Gil
2018-01-01
Labial mucosa transplantation for the treatment of canine keratoconjunctivitis sicca (KCS) has been reported recently. Postoperative alleviation of clinical signs was noted and assumed to be the result of labial salivary glands providing lubrication to the ocular tissue. The aim of this study was to evaluate the presence of minor salivary glands (MSG) in the canine oral mucosa. Oral mucosal biopsies were collected from six dogs that died (n = 1) or were euthanized (n = 5) for reasons unrelated to this study. The breeds included were two Doberman Pinschers, one Labrador Retriever, one Portuguese Water Dog, one German Shepherd Dog, and one mixed canine. Three were spayed females, and three were castrated males with the median age of 9 years (range, 6-13 years). Samples were obtained by an 8-mm punch biopsy at the following locations of the canine oral cavity: upper rostral labial mucosa at midline, lower rostral labial mucosa at midline, upper labial mucosa near the commissure, lower labial mucosa near the commissure, and buccal mucosa approximately 1 cm caudal to the commissure. Samples were routinely processed with hematoxylin and eosin, and periodic acid-Schiff stains. Samples were evaluated by light microscopy. At the selected locations, no MSG or other secreting cells were detected. Minor salivary glands are not associated with alleviation of canine KCS symptoms following labial mucosa transplantation. Further studies are needed to determine the mechanism leading to the transient improvement of KCS symptoms in canine patients following labial mucosa transplantation. © 2017 American College of Veterinary Ophthalmologists.
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Weidenbach, Denise; Jansen, Marcus; Franke, Rochus B; Hensel, Goetz; Weissgerber, Wiebke; Ulferts, Sylvia; Jansen, Irina; Schreiber, Lukas; Korzun, Viktor; Pontzen, Rolf; Kumlehn, Jochen; Pillen, Klaus; Schaffrath, Ulrich
2014-11-01
For plant pathogenic fungi, such as powdery mildews, that survive only on a limited number of host plant species, it is a matter of vital importance that their spores sense that they landed on the right spot to initiate germination as quickly as possible. We investigated a barley (Hordeum vulgare) mutant with reduced epicuticular leaf waxes on which spores of adapted and nonadapted powdery mildew fungi showed reduced germination. The barley gene responsible for the mutant wax phenotype was cloned in a forward genetic screen and identified to encode a 3-KETOACYL-CoA SYNTHASE (HvKCS6), a protein participating in fatty acid elongation and required for synthesis of epicuticular waxes. Gas chromatography-mass spectrometry analysis revealed that the mutant has significantly fewer aliphatic wax constituents with a chain length above C-24. Complementation of the mutant restored wild-type wax and overcame germination penalty, indicating that wax constituents less present on the mutant are a crucial clue for spore germination. Investigation of Arabidopsis (Arabidopsis thaliana) transgenic plants with sense silencing of Arabidopsis REQUIRED FOR CUTICULAR WAX PRODUCTION1, the HvKCS6 ortholog, revealed the same germination phenotype against adapted and nonadapted powdery mildew fungi. Our findings hint to an evolutionary conserved mechanism for sensing of plant surfaces among distantly related powdery mildews that is based on KCS6-derived wax components. Perception of such a signal must have been evolved before the monocot-dicot split took place approximately 150 million years ago. © 2014 American Society of Plant Biologists. All Rights Reserved.
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Weidenbach, Denise; Jansen, Marcus; Franke, Rochus B.; Hensel, Goetz; Weissgerber, Wiebke; Ulferts, Sylvia; Jansen, Irina; Schreiber, Lukas; Korzun, Viktor; Pontzen, Rolf; Kumlehn, Jochen; Pillen, Klaus; Schaffrath, Ulrich
2014-01-01
For plant pathogenic fungi, such as powdery mildews, that survive only on a limited number of host plant species, it is a matter of vital importance that their spores sense that they landed on the right spot to initiate germination as quickly as possible. We investigated a barley (Hordeum vulgare) mutant with reduced epicuticular leaf waxes on which spores of adapted and nonadapted powdery mildew fungi showed reduced germination. The barley gene responsible for the mutant wax phenotype was cloned in a forward genetic screen and identified to encode a 3-KETOACYL-CoA SYNTHASE (HvKCS6), a protein participating in fatty acid elongation and required for synthesis of epicuticular waxes. Gas chromatography-mass spectrometry analysis revealed that the mutant has significantly fewer aliphatic wax constituents with a chain length above C-24. Complementation of the mutant restored wild-type wax and overcame germination penalty, indicating that wax constituents less present on the mutant are a crucial clue for spore germination. Investigation of Arabidopsis (Arabidopsis thaliana) transgenic plants with sense silencing of Arabidopsis REQUIRED FOR CUTICULAR WAX PRODUCTION1, the HvKCS6 ortholog, revealed the same germination phenotype against adapted and nonadapted powdery mildew fungi. Our findings hint to an evolutionary conserved mechanism for sensing of plant surfaces among distantly related powdery mildews that is based on KCS6-derived wax components. Perception of such a signal must have been evolved before the monocot-dicot split took place approximately 150 million years ago. PMID:25201879
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Dory, Daniel; Echchannaoui, Hakim; Letiembre, Maryse; Ferracin, Fabrizia; Pieters, Jean; Adachi, Yoshiyuki; Akashi, Sachiko; Zimmerli, Werner; Landmann, Regine
2003-07-01
Murine Kupffer cells (KCs) are heterogeneous and survive only for a short time in vitro. Here, a clonal, murine KC line was generated from transgenic mice, expressing the thermolabile mutant tsA58 of the Simian virus 40 large T antigen under the control of the H-2K(b) promoter. Thirty-three degrees Celsius and 37 degrees C but not 39 degrees C have been permissive for growth of the clone; it required conditioned media from hepatocytes and endothelial cells for proliferation. In contrast to primary cells, the cells of the clone were uniform, survived detachment, and could therefore be analyzed by cytofluorimetry. The clone, as primary KCs, constitutively expressed nonspecific esterase, peroxidase, MOMA-2, BM8, scavenger receptor A, CD14, and Toll-like receptor 4 (TLR4); the antigen-presenting molecules CD40, CD80, and CD1d; and endocytosed dextran-fluorescein isothiocyanate. It lacked complement, Fc receptors, F4/80 marker, and the phagosomal coat protein tryptophan aspartate-containing coat protein (TACO). The clone exhibited CD14- and TLR4/MD2-independent, plasma-dependent lipopolysaccharide (LPS) binding, Escherichia coli and Streptococcus pneumoniae phagocytosis, and LPS- and interferon-gamma-induced NO production but no tumor necrosis factor alpha, interleukin (IL)-6, or IL-10 release. The large size, surface-marker expression, and capacity to clear gram-negative and -positive bacteria indicate that the clone was derived from the periportal, large KC subpopulation. The clone allows molecular studies of anti-infective and immune functions of KCs.
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Odors enhance slow-wave activity in non-rapid eye movement sleep
Perl, Ofer; Arzi, Anat; Sela, Lee; Secundo, Lavi; Holtzman, Yael; Samnon, Perry; Oksenberg, Arie; Sobel, Noam
2016-01-01
Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9–15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5–4 Hz) and slow spindle (9–12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations. PMID:26888107
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The distal C-terminal region of the KcsA potassium channel is a pH-dependent tetramerization domain.
Kamnesky, Guy; Shaked, Hadassa; Chill, Jordan H
2012-05-04
The intracellular C-terminal domain (CTD) of KcsA, a bacterial homotetrameric potassium channel, is a 40-residue-long segment that natively adopts a helical bundle conformation with 4-fold symmetry. A hallmark of KcsA behavior is pH-induced conformational change, which leads to the opening of the channel at acidic pH. Previous studies have reached conflicting conclusions as to the role of the CTD in this transition. Here, we investigate the involvement of this domain in pH-mediated channel opening by NMR using a soluble peptide corresponding to residues 128-160 of the CTD (CTD34). At neutral pH, CTD34 exhibits concentration-dependent spectral changes consistent with oligomer formation. We prove this slowly tumbling species to be a tetramer with a dissociation constant of (2.0±0.5)×10(-)(11) M(3) by NMR and sedimentation equilibrium experiments. Whereas monomeric CTD34 is only mildly helical, secondary chemical shifts prove that the tetrameric species adopts a tight native-like helical bundle conformation. The tetrameric species undergoes pH-dependent dissociation, and CTD34 is fully monomeric below pH 5.0. The structural basis for this phenomenon is the destabilization of the tetrameric CTD34 by protonation of residue H145 in the monomeric form of the peptide. We conclude that (i) the CTD34 peptide is independently capable of forming a tetrameric helical bundle, and (ii) this structurally significant conformational shift is modulated by the effects of solution pH on residue H145. Therefore, the involvement of this domain in the pH gating of the channel is strongly suggested. Copyright © 2012 Elsevier Ltd. All rights reserved.
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Grant, Estée C; Grant, Vincent J; Bhanji, Farhan; Duff, Jonathan P; Cheng, Adam; Lockyer, Jocelyn M
2012-07-01
It is critical that competency in pediatric resuscitation is achieved and assessed during residency or post graduate medical training. The purpose of this study was to create and evaluate a tool to measure all elements of pediatric resuscitation team leadership competence. An initial set of items, derived from a literature review and a brainstorming session, were refined to a 26 item assessment tool through the use of Delphi methodology. The tool was tested using videos of standardized resuscitations. A psychometric assessment of the evidence for instrument validity and reliability was undertaken. The performance of 30 residents on two videotaped scenarios was assessed by 4 pediatricians using the tool, with 12 items assessing 'leadership and communication skills' (LCS) and 14 items assessing 'knowledge and clinical skills' (KCS). The instrument showed evidence of reliability; the Cronbach's alpha and generalizability co-efficients for the overall instrument were α=0.818 and Ep(2)=0.76, for LCS were α=0.827 and Ep(2)=0.844, and for KCS were α=0.673 and Ep(2)=0.482. While validity was initially established through literature review and brainstorming by the panel of experts, it was further built through the high strength of correlation between global scores and scores for overall performance (r=0.733), LCS (r=0.718) and KCS (r=0.662) as well as the factor analysis which accounted for 40.2% of the variance. The results of the study demonstrate that the instrument is a valid and reliable tool to evaluate pediatric resuscitation team leader competence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Pan, Albert C; Cuello, Luis G; Perozo, Eduardo; Roux, Benoît
2011-12-01
The amount of ionic current flowing through K(+) channels is determined by the interplay between two separate time-dependent processes: activation and inactivation gating. Activation is concerned with the stimulus-dependent opening of the main intracellular gate, whereas inactivation is a spontaneous conformational transition of the selectivity filter toward a nonconductive state occurring on a variety of timescales. A recent analysis of multiple x-ray structures of open and partially open KcsA channels revealed the mechanism by which movements of the inner activation gate, formed by the inner helices from the four subunits of the pore domain, bias the conformational changes at the selectivity filter toward a nonconductive inactivated state. This analysis highlighted the important role of Phe103, a residue located along the inner helix, near the hinge position associated with the opening of the intracellular gate. In the present study, we use free energy perturbation molecular dynamics simulations (FEP/MD) to quantitatively elucidate the thermodynamic basis for the coupling between the intracellular gate and the selectivity filter. The results of the FEP/MD calculations are in good agreement with experiments, and further analysis of the repulsive, van der Waals dispersive, and electrostatic free energy contributions reveals that the energetic basis underlying the absence of inactivation in the F103A mutation in KcsA is the absence of the unfavorable steric interaction occurring with the large Ile100 side chain in a neighboring subunit when the intracellular gate is open and the selectivity filter is in a conductive conformation. Macroscopic current analysis shows that the I100A mutant indeed relieves inactivation in KcsA, but to a lesser extent than the F103A mutant.
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[New approaches to the treatment of keratoconjunctivitis sicca].
Safonova, T N; Gladkova, O V; Novikov, I A; Boev, V I; Fedorov, A A
A new method has been developed for the treatment of severe forms of keratoconjunctivitis sicca (KCS) that involves the use of an original cyclosporine A (CyA) saturated soft contact lens (SCL) together with preservative-free artificial tears therapy. to evaluate the effectiveness of the newly developed treatment for KCS based on the use of medical SCL saturated with 0.05% CyA. The patients (43 men, 60 eyes) with severe KCS were divided into 2 groups. Group 1 included 21 patients (30 eyes), who received artificial tears and wore 0.05% CyA-saturated silicone-hydrogel SCLs. Group 2 included 22 patients (30 eyes), who wore unsaturated original SCLs and received CyA instillations 2 times daily and, also, artificial tears. Apart from a standard ophthalmic examination, the assessment included Schirmer's test, Norn's test, vital eye stain tests, tear osmometry, laser confocal tomography of the cornea, optical coherence tomography of the anterior segment with meniscometry, impression cytology of the conjunctiva, tear pH measurement, plating of the content of the conjunctival cavity, measurement of the width of the palpebral fissure, and calculation of the ocular surface disease index. Treatment results were followed up at 1, 3, 6, and 12 months. The use of 0.05% CyA-saturated SCLs allows to halve treatment time for patients with severe KSC (down to 1 week - 1 month) as compared to unsaturated original SCLs in combination with 0.05% CyA instillations and to reduce it 5 times as compared to 0.05% CyA instillations only. The new method of KSC treatment that involves the use of medical SCL of original design (ensures even distribution of 0.05% CyA across the ocular surface) and preservative-free artificial tears has demonstrated high therapeutic effectiveness as compared to existing methods.
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Odors enhance slow-wave activity in non-rapid eye movement sleep.
Perl, Ofer; Arzi, Anat; Sela, Lee; Secundo, Lavi; Holtzman, Yael; Samnon, Perry; Oksenberg, Arie; Sobel, Noam; Hairston, Ilana S
2016-05-01
Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9-15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5-4 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations. Copyright © 2016 the American Physiological Society.
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Liu, Chieh-Lun; Place, Allen R.; Jagus, Rosemary
2017-01-01
Most dinoflagellates in culture are bacterized, complicating the quantification of protein synthesis, as well as the analysis of its regulation. In bacterized cultures of Amphidinium carterae Hulbert, up to 80% of protein synthetic activity appears to be predominantly bacterial based on responses to inhibitors of protein synthesis. To circumvent this, axenic cultures of A. carterae were obtained and shown to respond to inhibitors of protein synthesis in a manner characteristic of eukaryotes. However, these responses changed with time in culture correlating with the reappearance of bacteria. Here we show that culture with kanamycin (50 μg/mL), carbenicillin (100 μg/mL), and streptomycin sulfate (50 μg/mL) (KCS), but not 100 units/mL of penicillin and streptomycin (PS), prevents the reappearance of bacteria and allows A. carterae protein synthesis to be quantified without the contribution of an associated bacterial community. We demonstrate that A. carterae can grow in the absence of a bacterial community. Furthermore, maintenance in KCS does not inhibit the growth of A. carterae cultures but slightly extends the growth phase and allows accumulation to somewhat higher saturation densities. We also show that cultures of A. carterae maintained in KCS respond to the eukaryotic protein synthesis inhibitors cycloheximide, emetine, and harringtonine. Establishment of these culture conditions will facilitate our ability to use polysome fractionation and ribosome profiling to study mRNA recruitment. Furthermore, this study shows that a simple and fast appraisal of the presence of a bacterial community in A. carterae cultures can be made by comparing responses to cycloheximide and chloramphenicol rather than depending on lengthier culture-based assessments. PMID:28763019
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Arimoto, Atsushi; Kitagawa, Kazuko; Mita, Norihiro; Takahashi, Yoriko; Shibuya, Eri; Sasaki, Hiroshi
2014-08-01
The aim of this study was to investigate the efficacy of 2% rebamipide suspension in treatment of keratoconjunctivitis sicca (KCS) in patients with Sjögren syndrome (SS) with or without punctal occlusions. Thirty patients with SS, diagnosed based on the presence of autoantibodies and/or focus score >1 on lip biopsies, with corneal fluorescein staining scores (FSS) >3, and conjunctival lissamine green-staining scores (LSS) >3, were treated 4 times daily for 4 weeks with 2% rebamipide ocular suspension. Ocular examinations were performed before treatment and 2 and 4 weeks after treatment to evaluate FSS (0-9), LSS (0-6), and tear film break-up time (BUT). Hyaluronate and/or artificial tears were not discontinued. The patients were interviewed regarding the 5 major KCS symptoms, foreign body sensation, dry eye sensation, photophobia, ocular pain, and blurred vision, with each graded from none (0) to very severe (4). Of the 30 patients, 3 failed to attend all sessions, leaving 27 (25 females, 2 males, mean age 62.5 ± 10.8 years) to be studied. FSS and LSS showed improvement at week 2, but BUT showed improvement later, at week 4. All 5 symptoms improved significantly. When the patients were divided into 3 groups according to the presence of punctal occlusions, FSS and LSS were found to improve in all groups, but BUT improved only in patients with both puncta occluded at week 4. Rebamipide ophthalmic suspension was effective in treating KCS of patients with SS, probably by increasing mucins and suppressing inflammatory cytokines. Punctal occlusions resulted in sufficient retention of tear fluid to enhance the activities of rebamipide and improve BUT.
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Spatola, Ronald; Nadelstein, Brad; Berdoulay, Andrew; English, Robert V
2018-05-01
To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS). Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly. Eighteen dogs with refractory KCS were randomly assigned to receive 0.02% sirolumus ophthalmic solution or 0.02% tacrolimus ophthalmic solution twice daily. Complete ophthalmic examinations were was performed at 2 and 6 weeks following treatment. Tear production in the sirolimus-treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95% CI 1.17, 5.75; P = 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95% CI 1.95, 8.05; P = 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production >4 mm/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (P = 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle-treatment. Side effects were not reported in any treated eyes with chronic KCS. Topical 0.02% sirolimus might be an alternative treatment for canine patients with keratoconjunctivits sicca. The drug appears safe when applied topically in an aqueous suspension for up to 6 weeks. While initial results are promising, further studies are warranted. © 2017 American College of Veterinary Ophthalmologists.
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A controllable molecular sieve for Na+ and K+ ions.
Gong, Xiaojing; Li, Jichen; Xu, Ke; Wang, Jianfeng; Yang, Hui
2010-02-17
The selective rate of specific ion transport across nanoporous material is critical to biological and nanofluidic systems. Molecular sieves for ions can be achieved by steric and electrical effects. However, the radii of Na(+) and K(+) are quite similar; they both carry a positive charge, making them difficult to separate. Biological ionic channels contain precisely arranged arrays of amino acids that can efficiently recognize and guide the passage of K(+) or Na(+) across the cell membrane. However, the design of inorganic channels with novel recognition mechanisms that control the ionic selectivity remains a challenge. We present here a design for a controllable ion-selective nanopore (molecular sieve) based on a single-walled carbon nanotube with specially arranged carbonyl oxygen atoms modified inside the nanopore, which was inspired by the structure of potassium channels in membrane spanning proteins (e.g., KcsA). Our molecular dynamics simulations show that the remarkable selectivity is attributed to the hydration structure of Na(+) or K(+) confined in the nanochannels, which can be precisely tuned by different patterns of the carbonyl oxygen atoms. The results also suggest that a confined environment plays a dominant role in the selectivity process. These studies provide a better understanding of the mechanism of ionic selectivity in the KcsA channel and possible technical applications in nanotechnology and biotechnology, including serving as a laboratory-in-nanotube for special chemical interactions and as a high-efficiency nanodevice for purification or desalination of sea and brackish water.
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A localized interaction surface for voltage-sensing domains on the pore domain of a K+ channel.
Li-Smerin, Y; Hackos, D H; Swartz, K J
2000-02-01
Voltage-gated K+ channels contain a central pore domain and four surrounding voltage-sensing domains. How and where changes in the structure of the voltage-sensing domains couple to the pore domain so as to gate ion conduction is not understood. The crystal structure of KcsA, a bacterial K+ channel homologous to the pore domain of voltage-gated K+ channels, provides a starting point for addressing this question. Guided by this structure, we used tryptophan-scanning mutagenesis on the transmembrane shell of the pore domain in the Shaker voltage-gated K+ channel to localize potential protein-protein and protein-lipid interfaces. Some mutants cause only minor changes in gating and when mapped onto the KcsA structure cluster away from the interface between pore domain subunits. In contrast, mutants producing large changes in gating tend to cluster near this interface. These results imply that voltage-sensing domains interact with localized regions near the interface between adjacent pore domain subunits.
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A connectome of a learning and memory center in the adult Drosophila brain
Takemura, Shin-ya; Aso, Yoshinori; Hige, Toshihide; Wong, Allan; Lu, Zhiyuan; Xu, C Shan; Rivlin, Patricia K; Hess, Harald; Zhao, Ting; Parag, Toufiq; Berg, Stuart; Huang, Gary; Katz, William; Olbris, Donald J; Plaza, Stephen; Umayam, Lowell; Aniceto, Roxanne; Chang, Lei-Ann; Lauchie, Shirley; Ogundeyi, Omotara; Ordish, Christopher; Shinomiya, Aya; Sigmund, Christopher; Takemura, Satoko; Tran, Julie; Turner, Glenn C; Rubin, Gerald M; Scheffer, Louis K
2017-01-01
Understanding memory formation, storage and retrieval requires knowledge of the underlying neuronal circuits. In Drosophila, the mushroom body (MB) is the major site of associative learning. We reconstructed the morphologies and synaptic connections of all 983 neurons within the three functional units, or compartments, that compose the adult MB’s α lobe, using a dataset of isotropic 8 nm voxels collected by focused ion-beam milling scanning electron microscopy. We found that Kenyon cells (KCs), whose sparse activity encodes sensory information, each make multiple en passant synapses to MB output neurons (MBONs) in each compartment. Some MBONs have inputs from all KCs, while others differentially sample sensory modalities. Only 6% of KC>MBON synapses receive a direct synapse from a dopaminergic neuron (DAN). We identified two unanticipated classes of synapses, KC>DAN and DAN>MBON. DAN activation produces a slow depolarization of the MBON in these DAN>MBON synapses and can weaken memory recall. DOI: http://dx.doi.org/10.7554/eLife.26975.001 PMID:28718765
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76 FR 26606 - Drawbridge Operation Regulation; Neches River, Beaumont, TX
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-09
... deviation from the regulation governing the operation of the KCS vertical lift span bridge across the Neches... Southern Railroad has requested a temporary deviation from the operating schedule of the vertical lift span... in the open-to-navigation position. In accordance with 33 CFR 117.971, the vertical lift span of the...
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College and Career Readiness Assessment: Validation of the Key Cognitive Strategies Framework
ERIC Educational Resources Information Center
Lombardi, Allison R.; Conley, David T.; Seburn, Mary A.; Downs, Andrew M.
2013-01-01
In this study, the authors examined the psychometric properties of the key cognitive strategies (KCS) within the CollegeCareerReady[TM] School Diagnostic, a self-report measure of critical thinking skills intended for high school students. Using a cross-validation approach, an exploratory factor analysis was conducted with a randomly selected…
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Battle Experience; Solomon Islands Actions Information. Bulletin Number 4
1942-11-01
BE COAST WATCHER AND RADAR. Planes were picked up by binoculars, radar and naked eye as they approached over Florida Island. Type radar 11 FD" and...2070-2080 kcs. earlier at about 2130, became excited and very numerous. Some thir- teen different stations were or this frequency at one time. Firing
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Exploiting Natural Variation to Uncover an Alkene Biosynthetic Enzyme in Poplar
Gonzales-Vigil, Eliana; Hefer, Charles A.; von Loessl, Michelle E.; ...
2017-07-20
Alkenes are linear hydrocarbons with one or more double bonds. Despite their potential as biofuels and precursors for specialty chemicals, the underlying biochemistry and genetics of alkene biosynthesis in plants remain elusive. Here, we report on a screen of natural accessions of poplar (Populus trichocarpa), revealing that the leaf cuticular waxes are predominantly composed of alkanes and alkenes. Interestingly, the accumulation of alkenes increases with leaf development, is limited to the abaxial side of the leaf, and is impaired in a few accessions. Among other genes, a b-ketoacyl CoA synthase gene (PotriKCS1) was downregulated in leaves from non-alkene-producing accessions. Wemore » demonstrated biochemically that PotriKCS1 elongates monounsaturated fatty acids and is responsible for the recruitment of unsaturated substrates to the cuticular wax. Moreover, we found significant associations between the presence of alkenes and tree growth and resistance to leaf spot. These findings highlight the crucial role of cuticular waxes as the first point of contact with the environment, and they provide a foundation for engineering long-chain monounsaturated oils in other species.« less
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Exploiting Natural Variation to Uncover an Alkene Biosynthetic Enzyme in Poplar
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gonzales-Vigil, Eliana; Hefer, Charles A.; von Loessl, Michelle E.
Alkenes are linear hydrocarbons with one or more double bonds. Despite their potential as biofuels and precursors for specialty chemicals, the underlying biochemistry and genetics of alkene biosynthesis in plants remain elusive. Here, we report on a screen of natural accessions of poplar (Populus trichocarpa), revealing that the leaf cuticular waxes are predominantly composed of alkanes and alkenes. Interestingly, the accumulation of alkenes increases with leaf development, is limited to the abaxial side of the leaf, and is impaired in a few accessions. Among other genes, a b-ketoacyl CoA synthase gene (PotriKCS1) was downregulated in leaves from non-alkene-producing accessions. Wemore » demonstrated biochemically that PotriKCS1 elongates monounsaturated fatty acids and is responsible for the recruitment of unsaturated substrates to the cuticular wax. Moreover, we found significant associations between the presence of alkenes and tree growth and resistance to leaf spot. These findings highlight the crucial role of cuticular waxes as the first point of contact with the environment, and they provide a foundation for engineering long-chain monounsaturated oils in other species.« less
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Functional diversity of the superfamily of K⁺ transporters to meet various requirements.
Diskowski, Marina; Mikusevic, Vedrana; Stock, Charlott; Hänelt, Inga
2015-09-01
The superfamily of K+ transporters unites proteins from plants, fungi, bacteria, and archaea that translocate K+ and/or Na+ across membranes. These proteins are key components in osmotic regulation, pH homeostasis, and resistance to high salinity and dryness. The members of the superfamily are closely related to K+ channels such as KcsA but also show several striking differences that are attributed to their altered functions. This review highlights these functional differences, focusing on the bacterial superfamily members KtrB, TrkH, and KdpA. The functional variations within the family and comparison to MPM-type K+ channels are discussed in light of the recently solved structures of the Ktr and Trk systems.
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Dzul-Caamal, Ricardo; Hernández-López, Abigail; Gonzalez-Jáuregui, Mauricio; Padilla, Sergio E; Girón-Pérez, Manuel Ivan; Vega-López, Armando
2016-10-01
In this study, we assessed the effects of inorganic and organic pollutants [As, Cu, Fe, Mn, Pb, Zn, PAHs (11 compounds) and total phenols] from a panel of biomarkers [O2, H2O2, thiobarbituric acid reactive substances (TBARS), carbonyl proteins (RCO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total cytochrome P450 activities] evaluated in the Snout Scraping (SS), Serum (S) and Peripheral Blood Cells (PBC) of the Morelet's crocodile (Crocodylus moreletii) inhabiting the reference locality (Lake Mocu) and polluted locality (Champoton River) using Principal Component Analysis (PCA). In male crocodiles from the reference site, only H2O2 in PBC was related to levels of fluoranthene on the Keel of Caudal Scales (KCS), but, in females, no association was detected. In contrast, a sex-linked response was detected in specimens from the polluted locality. Levels of benzo[a]pyrene, benzo[a]anthracene, chrysene, pyrene, phenanthrene, acenaphthene, Zn, Cu, and Pb in KCS of the female crocodil were related to the oxidative stress biomarkers on PBC, incluing the total CYP450 activity and levels of O2, H2O2 in serum. However, in male crocodiles, the oxidative stress in SS and in the serum (TBARS, RCO, CAT, GPx), and SOD in PBC was related to As, Pb, Cu, Fe, and benzo[a]pyrene water concentrations and to the burdens of As, Fe, Mn, indeno[1,2,3cd]pyrene in KCS. These results confirm the usefulness of minimal or non-invasive methods of evaluating the oxidative stress response for the environmental monitoring program on the wild Morelet's crocodile that is subject to special protection in Mexican guidelines. Copyright © 2016 Elsevier Inc. All rights reserved.
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Modeling the concentration-dependent permeation modes of the KcsA potassium ion channel.
Nelson, Peter Hugo
2003-12-01
The potassium channel from Streptomyces lividans (KcsA) is an integral membrane protein with sequence similarity to all known potassium channels, particularly in the selectivity filter region. A recently proposed model for ion channels containing either n or (n-1) single-file ions in their selectivity filters [P. H. Nelson, J. Chem. Phys. 177, 11396 (2002)] is applied to published KcsA channel K+ permeation data that exhibit a high-affinity process at low concentrations and a low-affinity process at high concentrations [M. LeMasurier et al., J. Gen. Physiol. 118, 303 (2001)]. The kinetic model is shown to provide a reasonable first-order explanation for both the high- and low-concentration permeation modes observed experimentally. The low-concentration mode ([K+]<200 mM) has a 200-mV dissociation constant of 56 mM and a conductance of 88 pS. The high-concentration mode ([K+]>200 mM) has a 200-mV dissociation constant of 1100 mM and a conductance of 500 pS. Based on the permeation model, and x-ray analysis [J. H. Morais-Cabral et al., Nature (London) 414, 37 (2001)], it is suggested that the experimentally observed K+ permeation modes correspond to an n=3 mechanism at high concentrations and an n=2 mechanism at low concentrations. The ratio of the electrical dissociation distances for the high- and low-concentration modes is 3:2, also consistent with the proposed n=3 and n=2 modes. Model predictions for K+ channels that exhibit asymmetric current-voltage (I-V) curves are presented, and further validation of the kinetic model via molecular simulation and experiment is discussed. The qualitatively distinct I-V characteristics exhibited experimentally by Tl+, NH+4, and Rb+ ions at 100 mM concentration can also be explained using the model, but more extensive experimental tests are required for quantitative validation of the model predictions.
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Jung, Yoon Suk; Park, Chan Hyuk; Kim, Nam Hee; Lee, Mi Yeon; Park, Dong Il
2017-09-01
The incidence of colorectal cancer is decreasing in adults aged ≥50 years and increasing in those aged <50 years. We aimed to establish risk stratification model for advanced colorectal neoplasia (ACRN) in persons aged <50 years. We reviewed the records of participants who had undergone a colonoscopy as part of a health examination at two large medical examination centers in Korea. By using logistic regression analysis, we developed predicted probability models for ACRN in a population aged 30-49 years. Of 96,235 participants, 57,635 and 38,600 were included in the derivation and validation cohorts, respectively. The predicted probability model considered age, sex, body mass index, family history of colorectal cancer, and smoking habits, as follows: Y ACRN = -8.755 + 0.080·X age - 0.055·X male + 0.041·X BMI + 0.200·X family_history_of_CRC + 0.218·X former_smoker + 0.644·X current_smoker . The optimal cutoff value for the predicted probability of ACRN by Youden index was 1.14%. The area under the receiver-operating characteristic curve (AUROC) values of our model for ACRN were higher than those of the previously established Asia-Pacific Colorectal Screening (APCS), Korean Colorectal Screening (KCS), and Kaminski's scoring models [AUROC (95% confidence interval): model in the current study, 0.673 (0.648-0.697); vs. APCS, 0.588 (0.564-0.611), P < 0.001; vs. KCS, 0.602 (0.576-0.627), P < 0.001; and vs. Kaminski's model, 0.586 (0.560-0.612), P < 0.001]. In a young population, a predicted probability model can assess the risk of ACRN more accurately than existing models, including the APCS, KCS, and Kaminski's scoring models.
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Modeling the concentration-dependent permeation modes of the KcsA potassium ion channel
NASA Astrophysics Data System (ADS)
Nelson, Peter Hugo
2003-12-01
The potassium channel from Streptomyces lividans (KcsA) is an integral membrane protein with sequence similarity to all known potassium channels, particularly in the selectivity filter region. A recently proposed model for ion channels containing either n or (n-1) single-file ions in their selectivity filters [P. H. Nelson, J. Chem. Phys. 177, 11396 (2002)] is applied to published KcsA channel K+ permeation data that exhibit a high-affinity process at low concentrations and a low-affinity process at high concentrations [M. LeMasurier et al., J. Gen. Physiol. 118, 303 (2001)]. The kinetic model is shown to provide a reasonable first-order explanation for both the high- and low-concentration permeation modes observed experimentally. The low-concentration mode ([K+]<200 mM) has a 200-mV dissociation constant of 56 mM and a conductance of 88 pS. The high-concentration mode ([K+]>200 mM) has a 200-mV dissociation constant of 1100 mM and a conductance of 500 pS. Based on the permeation model, and x-ray analysis [J. H. Morais-Cabral et al., Nature (London) 414, 37 (2001)], it is suggested that the experimentally observed K+ permeation modes correspond to an n=3 mechanism at high concentrations and an n=2 mechanism at low concentrations. The ratio of the electrical dissociation distances for the high- and low-concentration modes is 3:2, also consistent with the proposed n=3 and n=2 modes. Model predictions for K+ channels that exhibit asymmetric current-voltage (I-V) curves are presented, and further validation of the kinetic model via molecular simulation and experiment is discussed. The qualitatively distinct I-V characteristics exhibited experimentally by Tl+, NH+4, and Rb+ ions at 100 mM concentration can also be explained using the model, but more extensive experimental tests are required for quantitative validation of the model predictions.
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Kang, Jung-Woo; Lee, Sun-Mee
2016-09-01
Resolution of inflammation is an active process involving a novel category of lipid factors known as specialized pro-resolving lipid mediators, which includes Resolvin D1 (RvD1). While accumulating evidence suggests that RvD1 counteracts proinflammatory signaling and promotes resolution, the specific cellular targets and mechanisms of action of RvD1 remain largely unknown. In the present study, we investigated the role and molecular mechanisms of RvD1 in ischemia/reperfusion (IR)-induced sterile liver inflammation. Male C57BL/6 mice underwent 70% hepatic ischemia for 60min, followed by reperfusion. RvD1 (5, 10, and 15μg/kg, i.p.) was administered to the mice 1h before ischemia and then immediately prior to reperfusion. RvD1 attenuated IR-induced hepatocellular damage and the proinflammatory response. In purified Kupffer cells (KCs) from mice exposed to IR, the levels of M1 marker genes (Nos2a and Cd40) increased, while those of M2 marker genes (Arg1, Cd206, and Mst1r) decreased, demonstrating a proinflammatory shift. RvD1 markedly attenuated these changes. Depletion of KCs by liposome clodronate abrogated the effects of RvD1 on proinflammatory mediators and macrophage polarization. In addition, RvD1 attenuated increases in myeloperoxidase activity and Cxcl1 and Cxcl2 mRNA expression. RvD1 markedly augmented the efferocytic activity of KCs, as indicated by increases in F4/80(+)Gr-1(+) cells in the liver. However, antagonist pretreatment or gene silencing of the RvD1 receptor, ALX/FPR2, abrogated the anti-inflammatory and pro-resolving actions of RvD1. These data indicate that RvD1 ameliorates IR-induced liver injury, and this protection is associated with enhancement of M2 polarization and efferocytosis via ALX/FPR2 activation. Copyright © 2016 Elsevier B.V. All rights reserved.
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Ship Trim Optimization: Assessment of Influence of Trim on Resistance of MOERI Container Ship
Duan, Wenyang
2014-01-01
Environmental issues and rising fuel prices necessitate better energy efficiency in all sectors. Shipping industry is a stakeholder in environmental issues. Shipping industry is responsible for approximately 3% of global CO2 emissions, 14-15% of global NOX emissions, and 16% of global SOX emissions. Ship trim optimization has gained enormous momentum in recent years being an effective operational measure for better energy efficiency to reduce emissions. Ship trim optimization analysis has traditionally been done through tow-tank testing for a specific hullform. Computational techniques are increasingly popular in ship hydrodynamics applications. The purpose of this study is to present MOERI container ship (KCS) hull trim optimization by employing computational methods. KCS hull total resistances and trim and sinkage computed values, in even keel condition, are compared with experimental values and found in reasonable agreement. The agreement validates that mesh, boundary conditions, and solution techniques are correct. The same mesh, boundary conditions, and solution techniques are used to obtain resistance values in different trim conditions at Fn = 0.2274. Based on attained results, optimum trim is suggested. This research serves as foundation for employing computational techniques for ship trim optimization. PMID:24578649
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NASA Technical Reports Server (NTRS)
Goodwin, Lisa Ann; Frey, Mary Anne Bassett; Merz, Marion P.; Alford, William R.
1987-01-01
Kennedy Space Center (KSC) employees are reported to be at high risk for coronary heart disease (CHD). Risk factors for CHD include high serum total cholesterol levels, low levels of high-density lipoprotein cholesterol (HDLC), elevated triglyceride, smoking, inactivity, high blood pressure, being male, and being older. Higher dietary and/or serum calcium Ca(++) may be related to a lower risk for CHD. Fifty men and 37 women participated. Subjects were tested in the morning after fasting 12 hours. Information relative to smoking and exercise habits was obtained; seated blood pressures were measured; and blood drawn. KCS men had higher risk values than KCS women as related to HDLC, triglycerides, systolic blood pressure, and diastolic blood pressure. Smoking and nonsmoking groups did not differ for other risk factors or for serum Ca(++) levels. Exercise and sedentary groups differed in total cholesterol and triglyceride levels. Serum Ca(++) levels were related to age, increasing with age in the sedentary group and decreasing in the exercisers, equally for men and women. It is concluded that these relationships may be significant to the risk of CHD and/or the risk of bone demineralization in an aging population.
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Mackenzie, Catriona J; Carslake, Harry B; Robin, Matthew; Kent, Rebecca J; Malalana, Fernando
2017-01-01
An 8-year-old mare was presented for investigation of a 1-month history of blepharospasm, eyelid swelling, corneal edema, and ocular discharge of the right eye (OD). Ophthalmic examination confirmed mucopurulent ocular discharge, conjunctival hyperemia, and a dry, dull appearance to the cornea OD. Schirmer tear test results confirmed an absence of tear production OD (0 mm/min) consistent with keratoconjunctivitis sicca. Treatment with topical 0.2% cyclosporine A resulted in an improvement in clinical signs. An episcleral cyclosporine A implant was placed under standing sedation 5 days after initial presentation. Re-examination 9 days post-operatively confirmed that the mare's tear production in the right eye had improved and no further clinical signs had been observed. Topical medications were gradually discontinued. Re-examinations performed up to 12 months postsurgery showed no recurrence of clinical signs and no adverse effects of the implant. To our knowledge, this is the first report of the use of a cyclosporine A implant in the management of KCS in a horse and highlights its potential as an effective, alternative therapy in the management of KCS in horses. © 2016 American College of Veterinary Ophthalmologists.
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Long-lasting perceptual priming and semantic learning in amnesia: a case experiment.
Tulving, E; Hayman, C A; Macdonald, C A
1991-07-01
An investigation of perceptual priming and semantic learning in the severely amnesic subject K.C. is reported. He was taught 64 three-word sentences and tested for his ability to produce the final word of each sentence. Despite a total lack of episodic memory, he exhibited (a) strong perceptual priming effects in word-fragment completion, which were retained essentially in full strength for 12 months, and (b) independent of perceptual priming, learning of new semantic facts, many of which were also retained for 12 months. K.C.'s semantic learning may be at least partly attributable to repeated study trials and minimal interference during learning. The findings suggest that perceptual priming and semantic learning are subserved by two memory systems different from episodic memory and that both systems (perceptual representation and semantic memory) are at least partially preserved in some amnesic subjects.
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Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation
Johnston, Andrew; Fritz, Yi; Dawes, Sean M.; Diaconu, Doina; Al-Attar, Paul M.; Guzman, Andrew M.; Chen, Cynthia S.; Fu, Wen; Gudjonsson, Johann E.; McCormick, Thomas S.; Ward, Nicole L.
2013-01-01
IL-17C is a functionally distinct member of the IL-17 family that binds IL-17RE/A to promote innate defense in epithelial cells and regulate Th17 cell differentiation. We demonstrate that IL-17C (not IL-17A) is the most abundant IL-17 isoform in lesional psoriasis skin (1058pg/ml vs. 8pg/ml; p<0.006) and localizes to keratinocytes (KCs), endothelial cells (ECs) and leukocytes. ECs stimulated with IL-17C produce increased TNFα and KCs stimulated with IL-17C/TNFα produce similar inflammatory gene response patterns as those elicited by IL-17A/TNFα, including increases in IL-17C, TNFα, IL-8, IL-1α/β, IL-1F5, IL-1F9, IL-6, IL-19, CCL20, S100A7/A8/A9, DEFB4, LCN2 and PI3 (p<0.05); indicating a positive pro-inflammatory feedback loop between the epidermis and ECs. Psoriasis patients treated with etanercept rapidly decrease cutaneous IL-17C levels, suggesting IL-17C/TNFα-mediated inflammatory signaling is critical for psoriasis pathogenesis. Mice genetically engineered to overexpress IL-17C in KCs develop well-demarcated areas of erythematous, flakey “involved” skin adjacent to areas of normal appearing “uninvolved” skin despite increased IL-17C expression in both areas (p<0.05). Uninvolved skin displays increased angiogenesis and elevated S100A8/A9expression (p<0.05) but no epidermal hyperplasia; whereas involved skin exhibits robust epidermal hyperplasia, increased angiogenesis and leukocyte infiltration and upregulated TNFα, IL-1α/β, IL-17A/F, IL-23p19, VEGF, IL-6 and CCL20 (p<0.05) suggesting that IL-17C, when coupled with other pro-inflammatory signals, initiates the development of psoriasiform dermatitis. This skin phenotype was significantly improved following 8 weeks of TNFα inhibition. These findings identify a role for IL-17C in skin inflammation and suggest a pathogenic function for the elevated IL-17C observed in lesional psoriasis skin. PMID:23359500
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Correlation of laboratory and production freeze drying cycles.
Kuu, Wei Y; Hardwick, Lisa M; Akers, Michael J
2005-09-30
The purpose of this study was to develop the correlation of cycle parameters between a laboratory and a production freeze-dryer. With the established correlation, key cycle parameters obtained using a laboratory dryer may be converted to those for a production dryer with minimal experimental efforts. In order to develop the correlation, it was important to consider the contributions from the following freeze-drying components: (1) the dryer, (2) the vial, and (3) the formulation. The critical parameters for the dryer are the shelf heat transfer coefficient and shelf surface radiation emissivity. The critical parameters for the vial are the vial bottom heat transfer coefficients (the contact parameter Kcs and separation distance lv), and vial top heat transfer coefficient. The critical parameter of the formulation is the dry layer mass transfer coefficient. The above heat and mass transfer coefficients were determined by freeze-drying experiments in conjunction with mathematical modeling. With the obtained heat and mass transfer coefficients, the maximum product temperature, Tbmax, during primary drying was simulated using a primary drying subroutine as a function of the shelf temperature and chamber pressure. The required shelf temperature and chamber pressure, in order to perform a successful cycle run without product collapse, were then simulated based on the resulting values of Tbmax. The established correlation approach was demonstrated by the primary drying of the model formulation 5% mannitol solution. The cycle runs were performed using a LyoStar dryer as the laboratory dryer and a BOC Edwards dryer as the production dryer. The determined normalized dried layer mass transfer resistance for 5% mannitol is expressed as RpN=0.7313+17.19l, where l is the receding dry layer thickness. After demonstrating the correlation approach using the model formulation 5% mannitol, a practical comparison study was performed for the actual product, the lactate dehydrogenase (LDH) formulation. The determined normalized dried layer mass transfer resistance for the LDH formulation is expressed as RpN=4.344+10.85l. The operational templates Tbmax and primary drying time were also generated by simulation. The cycle run for the LDH formulation using the Edwards production dryer verified that the cycle developed in a laboratory freeze-dryer was transferable at the production scale.
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Kinetic modeling of ion conduction in KcsA potassium channel.
Mafé, Salvador; Pellicer, Julio; Cervera, Javier
2005-05-22
KcsA constitutes a potassium channel of known structure that shows both high conduction rates and selectivity among monovalent cations. A kinetic model for ion conduction through this channel that assumes rapid ion transport within the filter has recently been presented by Nelson. In a recent, brief communication, we used the model to provide preliminary explanations to the experimental current-voltage J-V and conductance-concentration g-S curves obtained for a series of monovalent ions (K(+),Tl(+), and Rb(+)). We did not assume rapid ion transport in the calculations, since ion transport within the selectivity filter could be rate limiting for ions other than native K(+). This previous work is now significantly extended to the following experimental problems. First, the outward rectification of the J-V curves in K(+) symmetrical solutions is analyzed using a generalized kinetic model. Second, the J-V and g-S curves for NH(4) (+) are obtained and compared with those of other ions (the NH(4) (+) J-V curve is qualitatively different from those of Rb(+) and Tl(+)). Third, the effects of Na(+) block on K(+) and Rb(+) currents through single KcsA channels are studied and the different blocking behavior is related to the values of the translocation rate constants characteristic of ion transport within the filter. Finally, the significantly decreased K(+) conductance caused by mutation of the wild-type channel is also explained in terms of this rate constant. In order to keep the number of model parameters to a minimum, we do not allow the electrical distance (an empirical parameter of kinetic models that controls the exponential voltage dependence of the dissociation rate) to vary with the ionic species. Without introducing the relatively high number of adjustable parameters of more comprehensive site-based models, we show that ion association to the filter is rate controlling at low concentrations, but ion dissociation from the filter and ion transport within the filter could limit conduction at high concentration. Although some experimental data from other authors were included to allow qualitative comparison with model calculations, the absolute values of the effective rate constants obtained are only tentative. However, the relative changes in these constants needed to explain qualitatively the experiments should be of significance.
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Saha, Banishree; Momen-Heravi, Fatemeh; Furi, Istvan; Kodys, Karen; Catalano, Donna; Gangopadhyay, Anwesha; Haraszti, Reka; Satishchandran, Abhishek; Iracheta-Vellve, Arvin; Adejumo, Adeyinka; Shaffer, Scott A; Szabo, Gyongyi
2018-05-01
A salient feature of alcoholic liver disease (ALD) is Kupffer cell (KC) activation and recruitment of inflammatory monocytes and macrophages (MØs). These key cellular events of ALD pathogenesis may be mediated by extracellular vesicles (EVs). EVs transfer biomaterials, including proteins and microRNAs, and have recently emerged as important effectors of intercellular communication. We hypothesized that circulating EVs from mice with ALD have a protein cargo characteristic of the disease and mediate biological effects by activating immune cells. The total number of circulating EVs was increased in mice with ALD compared to pair-fed controls. Mass spectrometric analysis of circulating EVs revealed a distinct signature for proteins involved in inflammatory responses, cellular development, and cellular movement between ALD EVs and control EVs. We also identified uniquely important proteins in ALD EVs that were not present in control EVs. When ALD EVs were injected intravenously into alcohol-naive mice, we found evidence of uptake of ALD EVs in recipient livers in hepatocytes and MØs. Hepatocytes isolated from mice after transfer of ALD EVs, but not control EVs, showed increased monocyte chemoattractant protein 1 mRNA and protein expression, suggesting a biological effect of ALD EVs. Compared to control EV recipient mice, ALD EV recipient mice had increased numbers of F4/80 hi cluster of differentiation 11b (CD11b) lo KCs and increased percentages of tumor necrosis factor alpha-positive/interleukin 12/23-positive (inflammatory/M1) KCs and infiltrating monocytes (F4/80 int CD11b hi ), while the percentage of CD206 + CD163 + (anti-inflammatory/M2) KCs was decreased. In vitro, ALD EVs increased tumor necrosis factor alpha and interleukin-1β production in MØs and reduced CD163 and CD206 expression. We identified heat shock protein 90 in ALD EVs as the mediator of ALD-EV-induced MØ activation. Our study indicates a specific protein signature of ALD EVs and demonstrates a functional role of circulating EVs containing heat shock protein 90 in mediating KC/MØ activation in the liver. (Hepatology 2018;67:1986-2000). © 2017 by the American Association for the Study of Liver Diseases.
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Beer, Lucian; Mlitz, Veronika; Gschwandtner, Maria; Berger, Tanja; Narzt, Marie-Sophie; Gruber, Florian; Brunner, Patrick M; Tschachler, Erwin; Mildner, Michael
2015-10-01
Reverse transcription polymerase chain reaction (qRT-PCR) has become a mainstay in many areas of skin research. To enable quantitative analysis, it is necessary to analyse expression of reference genes (RGs) for normalization of target gene expression. The selection of reliable RGs therefore has an important impact on the experimental outcome. In this study, we aimed to identify and validate the best suited RGs for qRT-PCR in human primary keratinocytes (KCs) over a broad range of experimental conditions using the novel bioinformatics tool 'RefGenes', which is based on a manually curated database of published microarray data. Expression of 6 RGs identified by RefGenes software and 12 commonly used RGs were validated by qRT-PCR. We assessed whether these 18 markers fulfilled the requirements for a valid RG by the comprehensive ranking of four bioinformatics tools and the coefficient of variation (CV). In an overall ranking, we found GUSB to be the most stably expressed RG, whereas the expression values of the commonly used RGs, GAPDH and B2M were significantly affected by varying experimental conditions. Our results identify RefGenes as a powerful tool for the identification of valid RGs and suggest GUSB as the most reliable RG for KCs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Reda, Flaminia; Gorgoni, Maurizio; Lauri, Giulia; Truglia, Ilaria; Cordone, Susanna; Scarpelli, Serena; Mangiaruga, Anastasia; D’Atri, Aurora; Ferrara, Michele; Lacidogna, Giordano; Marra, Camillo; Rossini, Paolo Maria; De Gennaro, Luigi
2017-01-01
The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer’s disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioration. PMID:28468235
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Chung, Shin-Ho; Corry, Ben
2007-01-01
In the narrow segment of an ion conducting pathway, it is likely that a permeating ion influences the positions of the nearby atoms that carry partial or full electronic charges. Here we introduce a method of incorporating the motion of charged atoms lining the pore into Brownian dynamics simulations of ion conduction. The movements of the carbonyl groups in the selectivity filter of the KcsA channel are calculated explicitly, allowing their bond lengths, bond angles, and dihedral angels to change in response to the forces acting upon them. By systematically changing the coefficients of bond stretching and of angle bending, the carbon and oxygen atoms can be made to fluctuate from their fixed positions by varying mean distances. We show that incorporating carbonyl motion in this way does not alter the mechanism of ion conduction and only has a small influence on the computed current. The slope conductance of the channel increases by ∼25% when the root mean-square fluctuations of the carbonyl groups are increased from 0.01 to 0.61 Å. The energy profiles and the number of resident ions in the channel remain unchanged. The method we utilized here can be extended to allow the movement of glutamate or aspartate side chains lining the selectivity filters of other ionic channels. PMID:17434934
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Spatial-Temporal Data Collection with Compressive Sensing in Mobile Sensor Networks
Li, Jiayin; Guo, Wenzhong; Chen, Zhonghui; Xiong, Neal
2017-01-01
Compressive sensing (CS) provides an energy-efficient paradigm for data gathering in wireless sensor networks (WSNs). However, the existing work on spatial-temporal data gathering using compressive sensing only considers either multi-hop relaying based or multiple random walks based approaches. In this paper, we exploit the mobility pattern for spatial-temporal data collection and propose a novel mobile data gathering scheme by employing the Metropolis-Hastings algorithm with delayed acceptance, an improved random walk algorithm for a mobile collector to collect data from a sensing field. The proposed scheme exploits Kronecker compressive sensing (KCS) for spatial-temporal correlation of sensory data by allowing the mobile collector to gather temporal compressive measurements from a small subset of randomly selected nodes along a random routing path. More importantly, from the theoretical perspective we prove that the equivalent sensing matrix constructed from the proposed scheme for spatial-temporal compressible signal can satisfy the property of KCS models. The simulation results demonstrate that the proposed scheme can not only significantly reduce communication cost but also improve recovery accuracy for mobile data gathering compared to the other existing schemes. In particular, we also show that the proposed scheme is robust in unreliable wireless environment under various packet losses. All this indicates that the proposed scheme can be an efficient alternative for data gathering application in WSNs. PMID:29117152
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Parvari, Ruti; Hershkovitz, Eli; Grossman, Nili; Gorodischer, Rafael; Loeys, Bart; Zecic, Alexandra; Mortier, Geert; Gregory, Simon; Sharony, Reuven; Kambouris, Marios; Sakati, Nadia; Meyer, Brian F; Al Aqeel, Aida I; Al Humaidan, Abdul Karim; Al Zanhrani, Fatma; Al Swaid, Abdulrahman; Al Othman, Johara; Diaz, George A; Weiner, Rory; Khan, K Tahseen S; Gordon, Ronald; Gelb, Bruce D
2002-11-01
The syndrome of congenital hypoparathyroidism, mental retardation, facial dysmorphism and extreme growth failure (HRD or Sanjad-Sakati syndrome; OMIM 241410) is an autosomal recessive disorder reported almost exclusively in Middle Eastern populations. A similar syndrome with the additional features of osteosclerosis and recurrent bacterial infections has been classified as autosomal recessive Kenny-Caffey syndrome (AR-KCS; OMIM 244460). Both traits have previously been mapped to chromosome 1q43-44 (refs 5,6) and, despite the observed clinical variability, share an ancestral haplotype, suggesting a common founder mutation. We describe refinement of the critical region to an interval of roughly 230 kb and identification of deletion and truncation mutations of TBCE in affected individuals. The gene TBCE encodes one of several chaperone proteins required for the proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers. Analysis of diseased fibroblasts and lymphoblastoid cells showed lower microtubule density at the microtubule-organizing center (MTOC) and perturbed microtubule polarity in diseased cells. Immunofluorescence and ultrastructural studies showed disturbances in subcellular organelles that require microtubules for membrane trafficking, such as the Golgi and late endosomal compartments. These findings demonstrate that HRD and AR-KCS are chaperone diseases caused by a genetic defect in the tubulin assembly pathway, and establish a potential connection between tubulin physiology and the development of the parathyroid.
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Fourier-transform spectroscopy and potential construction of the (2){sup 1}Π state in KCs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Birzniece, I.; Nikolayeva, O.; Tamanis, M.
The paper presents an empirical pointwise potential energy curve (PEC) of the (2){sup 1}Π state of the KCs molecule constructed by applying the Inverted Perturbation Approach routine. The experimental term values in the energy range E(v′, J′) ∈ [15 407; 16 579] cm{sup −1} involved in the fit were based on Fourier-Transform spectroscopy data obtained with 0.01 cm{sup −1} accuracy from the laser-induced (2){sup 1}Π → X{sup 1}Σ{sup +} fluorescence spectra. Buffer gas Ar was used to facilitate the appearance of rotation relaxation lines in the spectra, thus enlarging the (2){sup 1}Π data set and allowing determination of the Λ-splitting constants. Themore » data set included vibrational v′ ∈ [0, 28] and rotational J′ ∈ [7, 274] quantum numbers covering about 67% of the potential well. The present PEC reproduces the overall set of data included in the fit with a standard deviation of 0.5 cm{sup −1}. The obtained value of the Λ-doubling constant q = + 1.8 × 10{sup −6} cm{sup −1} for J′ > 50 and v′ ∈ [0, 6] is in an excellent agreement with q = + 1.84 × 10{sup −6} cm{sup −1} reported in Kim, Lee, and Stolyarov [J. Mol. Spectrosc. 256, 57-67 (2009)].« less
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Burgess, Don E; Bartos, Daniel C; Reloj, Allison R; Campbell, Kenneth S; Johnson, Jonathan N; Tester, David J; Ackerman, Michael J; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J; Ohno, Seiko; Horie, Minoru; Delisle, Brian P
2012-11-13
Type 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1 gene, which encodes the K(+) channel (Kv7.1) that underlies the slowly activating delayed rectifier K(+) current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss of function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confers a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated nonfunctional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamics simulations of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K(+)-K(+) repulsive forces required for rapid K(+) permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K(+) channel selectivity filter.
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Chung, Shin-Ho; Corry, Ben
2007-07-01
In the narrow segment of an ion conducting pathway, it is likely that a permeating ion influences the positions of the nearby atoms that carry partial or full electronic charges. Here we introduce a method of incorporating the motion of charged atoms lining the pore into Brownian dynamics simulations of ion conduction. The movements of the carbonyl groups in the selectivity filter of the KcsA channel are calculated explicitly, allowing their bond lengths, bond angles, and dihedral angels to change in response to the forces acting upon them. By systematically changing the coefficients of bond stretching and of angle bending, the carbon and oxygen atoms can be made to fluctuate from their fixed positions by varying mean distances. We show that incorporating carbonyl motion in this way does not alter the mechanism of ion conduction and only has a small influence on the computed current. The slope conductance of the channel increases by approximately 25% when the root mean-square fluctuations of the carbonyl groups are increased from 0.01 to 0.61 A. The energy profiles and the number of resident ions in the channel remain unchanged. The method we utilized here can be extended to allow the movement of glutamate or aspartate side chains lining the selectivity filters of other ionic channels.
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Spatial-Temporal Data Collection with Compressive Sensing in Mobile Sensor Networks.
Zheng, Haifeng; Li, Jiayin; Feng, Xinxin; Guo, Wenzhong; Chen, Zhonghui; Xiong, Neal
2017-11-08
Compressive sensing (CS) provides an energy-efficient paradigm for data gathering in wireless sensor networks (WSNs). However, the existing work on spatial-temporal data gathering using compressive sensing only considers either multi-hop relaying based or multiple random walks based approaches. In this paper, we exploit the mobility pattern for spatial-temporal data collection and propose a novel mobile data gathering scheme by employing the Metropolis-Hastings algorithm with delayed acceptance, an improved random walk algorithm for a mobile collector to collect data from a sensing field. The proposed scheme exploits Kronecker compressive sensing (KCS) for spatial-temporal correlation of sensory data by allowing the mobile collector to gather temporal compressive measurements from a small subset of randomly selected nodes along a random routing path. More importantly, from the theoretical perspective we prove that the equivalent sensing matrix constructed from the proposed scheme for spatial-temporal compressible signal can satisfy the property of KCS models. The simulation results demonstrate that the proposed scheme can not only significantly reduce communication cost but also improve recovery accuracy for mobile data gathering compared to the other existing schemes. In particular, we also show that the proposed scheme is robust in unreliable wireless environment under various packet losses. All this indicates that the proposed scheme can be an efficient alternative for data gathering application in WSNs .
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Wojtas-Niziurski, Wojciech; Meng, Yilin; Roux, Benoit; Bernèche, Simon
2013-01-01
The potential of mean force describing conformational changes of biomolecules is a central quantity that determines the function of biomolecular systems. Calculating an energy landscape of a process that depends on three or more reaction coordinates might require a lot of computational power, making some of multidimensional calculations practically impossible. Here, we present an efficient automatized umbrella sampling strategy for calculating multidimensional potential of mean force. The method progressively learns by itself, through a feedback mechanism, which regions of a multidimensional space are worth exploring and automatically generates a set of umbrella sampling windows that is adapted to the system. The self-learning adaptive umbrella sampling method is first explained with illustrative examples based on simplified reduced model systems, and then applied to two non-trivial situations: the conformational equilibrium of the pentapeptide Met-enkephalin in solution and ion permeation in the KcsA potassium channel. With this method, it is demonstrated that a significant smaller number of umbrella windows needs to be employed to characterize the free energy landscape over the most relevant regions without any loss in accuracy. PMID:23814508
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Disruption of Inhibitory Function in the Ts65Dn Mouse Hippocampus Through Overexpression of GIRK2
2007-10-24
are prominent (Galdzicki and Siarey, 2003). We found that GIRK2 mRNA and protein subunits are highly overexpressed in multiple CNS structures ... STRUCTURE GIRK channels are members of the large family of potassium inward rectifiers (Kir). The seven subfamilies of Kir channels (Kir1-7) differ as...This ability to discriminate against the smaller Na+ (atomic radius: 0.95 Å) was elucidated by examining the pore structure of the bacterial KcsA
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New insights into the diagnosis and treatment of dry eye.
Dogru, Murat; Tsubota, Kazuo
2004-04-01
Over the past decade, numerous advances have been made in relation to dry eye diagnostic markers, technologies, and treatment options. The mainstay of treatment of dry eye is the use of artificial tear solutions and punctum plugs. A goal is the development of agents that provide symptomatic treatment and, at the same time, improve ocular surface keratinization. It is the authors' opinion that the functional visual acuity tester and the new tear stability analysis system will be widely used to improve diagnosis and evaluate treatment outcomes in KCS. Advances in treatment will utilize anti-inflammatory agents, immune suppressants such as Cyclosporin A and FK-506, growth hormones, androgens, topical mucins and ocular surface stimulating drugs, like INS365. Although aqueous-deficient dry eye is most commonly not associated with Sjogren syndrome (SS), aqueous-deficient dry eye is often most severe in patients with SS; thus, this article focuses mainly on SS-associated dry eye.
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Co-expression analysis identifies CRC and AP1 the regulator of Arabidopsis fatty acid biosynthesis.
Han, Xinxin; Yin, Linlin; Xue, Hongwei
2012-07-01
Fatty acids (FAs) play crucial rules in signal transduction and plant development, however, the regulation of FA metabolism is still poorly understood. To study the relevant regulatory network, fifty-eight FA biosynthesis genes including de novo synthases, desaturases and elongases were selected as "guide genes" to construct the co-expression network. Calculation of the correlation between all Arabidopsis thaliana (L.) genes with each guide gene by Arabidopsis co-expression dating mining tools (ACT) identifies 797 candidate FA-correlated genes. Gene ontology (GO) analysis of these co-expressed genes showed they are tightly correlated to photosynthesis and carbohydrate metabolism, and function in many processes. Interestingly, 63 transcription factors (TFs) were identified as candidate FA biosynthesis regulators and 8 TF families are enriched. Two TF genes, CRC and AP1, both correlating with 8 FA guide genes, were further characterized. Analyses of the ap1 and crc mutant showed the altered total FA composition of mature seeds. The contents of palmitoleic acid, stearic acid, arachidic acid and eicosadienoic acid are decreased, whereas that of oleic acid is increased in ap1 and crc seeds, which is consistent with the qRT-PCR analysis revealing the suppressed expression of the corresponding guide genes. In addition, yeast one-hybrid analysis and electrophoretic mobility shift assay (EMSA) revealed that CRC can bind to the promoter regions of KCS7 and KCS15, indicating that CRC may directly regulate FA biosynthesis. © 2012 Institute of Botany, Chinese Academy of Sciences.
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Courtens, Winnie; Wuyts, Wim; Poot, Martin; Szuhai, Karoly; Wauters, Jan; Reyniers, Edwin; Eleveld, Marc; Diaz, George; Nöthen, Markus M; Parvari, Ruti
2006-03-15
Hypoparathyroidism-retardation-dysmorphism (HRD) or Sanjad-Sakati syndrome (SSS) (OMIM 241410) is a rare autosomal recessive (AR) inherited condition, characterized by congenital hypoparathyroidism (hypoPTH), retardation, seizures, and a typical facial dysmorphism, consisting of prominent forehead, deep-set eyes, and abnormal external ears. This disorder has been mapped to the long arm of chromosome 1 (1q42-q43) and mutations in the gene coding for tubulin-specific chaperone E (TBCE) have been identified as the cause of the disease. Mutations in the same gene were also reported in patients with AR Kenny-Caffey syndrome (KCS). We report on a 41/2-year-old girl with congenital hypoPTH, seizures, developmental delay, and a facial dysmorphism, compatible with HRD syndrome. Mutation analyses revealed no mutations in the TBCE gene. In addition, normal TBCE protein and alpha-tubulin immunostaining were observed in a lymphoblastoid line derived from the patient, excluding the TBCE gene as the causative gene of the syndrome in this patient. A de novo microduplication of probe RP11-262I1 on 4q35 in the proposita was detected by microarray analyses, but this could not be confirmed by additional studies. We review and discuss the clinical findings of our case and those of the other reported cases with SSS and AR KCS. We conclude that a second gene locus for this disorder seems probable and that 4q35 needs further evaluation as a candidate region.
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Burgess, Don E.; Bartos, Daniel C.; Reloj, Allison R.; Campbell, Kenneth S.; Johnson, Jonathan N.; Tester, David J.; Ackerman, Michael J.; Fressart, Véronique; Denjoy, Isabelle; Guicheney, Pascale; Moss, Arthur J.; Ohno, Seiko; Horie, Minoru; Delisle, Brian P.
2012-01-01
Type 1 long QT syndrome (LQT1) syndrome is caused by loss-of-function mutations in the KCNQ1, which encodes the K+ channel (Kv7.1) that underlies the slowly activating delayed rectifier K+ current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss-of-function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confer a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated non-functional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamic simulations (MDS) of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K+-K+ repulsive forces required for rapid K+ permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K+ channel selectivity filter. PMID:23092362
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East Europe Report, Economic and Industrial Affairs.
1984-05-04
Unity of Actual Percentage of total measurement 1981 CSSR CSR km 7,810 6.1 9.9 thousands 1,169 7.6 11.3 million Kcs 70,969 11.0 15.3 thousands...1981 Percentage of total in CSR 19.2 41.7 28.1 8.0 15.3 8.1 41.0 53.7 24.7 The percentage of the total capital assets for the pertinent...in the composition of the capital assets, while in the industries of the CSR and CSSR as a whole machinery assets account for only about one-half
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Nickoloff, B. J.; Mitra, R. S.; Riser, B. L.; Dixit, V. M.; Varani, J.
1988-01-01
Normal human epidermal keratinocytes (KC) grown under conditions that maintain the undifferentiated state are highly motile. Migration of these cells as measured in two different assays (migration out of an agarose drop explant, and into micropore filters in a modified Boyden chamber), is stimulated by fibronectin (FN) and to a lesser extent by thrombospondin (TSP). In contrast, laminin (LN) inhibits KC migration. Cultivation of the cells for 1 day under conditions that induce differentiation (ie, in the presence of 1.4 mM Ca2+) suppresses KC motility. A number of soluble growth modulating polypeptide factors also influence KC migration. Transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF) stimulate KC motility. These factors simultaneously induce KC production of FN and a significant portion of the stimulated motility can be inhibited with antibodies to FN. EGF and somatomedin-C (SM-C), but not TGF-beta, also stimulate TSP production while EGF and SM-C (but not TGF-beta) induce KC proliferation. In contrast to these factors, interferon-gamma (INF-gamma) inhibits KC production of both FN and TSP and concomitantly inhibits both motility and proliferation. These data suggest that KC properties essential for normal wound healing (ie, motility and proliferation) are regulated by both extracellular matrix molecules and soluble peptide factors. Finally, these effects of various growth promoting and antiproliferative factors on KCs may, in part, be mediated through alteration in the endogenous production of extracellular matrix molecules by KCs. Images Figure 2 PMID:2458044
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Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age
Oiki, Shigetoshi
2015-01-01
The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the ‘frozen’ crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. PMID:25833254
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Channel function reconstitution and re-animation: a single-channel strategy in the postcrystal age.
Oiki, Shigetoshi
2015-06-15
The most essential properties of ion channels for their physiologically relevant functions are ion-selective permeation and gating. Among the channel species, the potassium channel is primordial and the most ubiquitous in the biological world, and knowledge of this channel underlies the understanding of features of other ion channels. The strategy applied to studying channels changed dramatically after the crystal structure of the potassium channel was resolved. Given the abundant structural information available, we exploited the bacterial KcsA potassium channel as a simple model channel. In the postcrystal age, there are two effective frameworks with which to decipher the functional codes present in the channel structure, namely reconstitution and re-animation. Complex channel proteins are decomposed into essential functional components, and well-examined parts are rebuilt for integrating channel function in the membrane (reconstitution). Permeation and gating are dynamic operations, and one imagines the active channel by breathing life into the 'frozen' crystal (re-animation). Capturing the motion of channels at the single-molecule level is necessary to characterize the behaviour of functioning channels. Advanced techniques, including diffracted X-ray tracking, lipid bilayer methods and high-speed atomic force microscopy, have been used. Here, I present dynamic pictures of the KcsA potassium channel from the submolecular conformational changes to the supramolecular collective behaviour of channels in the membrane. These results form an integrated picture of the active channel and offer insights into the processes underlying the physiological function of the channel in the cell membrane. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.
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Hao, Suxiao; Ma, Yiyi; Zhao, Shuang; Ji, Qianlong; Zhang, Kezhong; Yang, Mingfeng; Yao, Yuncong
2017-01-01
Cuticular waxes of plant and organ surfaces play an important role in protecting plants from biotic and abiotic stress and extending the freshness, storage time and shelf life in the post-harvest agricultural products. WRI1, a transcription factor of AP2/SHEN families, had been found to trigger the related genes taking part in the biosynthesis of seed oil in many plants. But whether WRI1 is involved in the biosynthesis of the cuticular waxes on the Malus fruits surface has been unclear. We investigated the changes of wax composition and structure, the related genes and WRI1 expression on Malus asiatica Nakai and sieversii fruits with the low temperature treatments, found that low temperature induced the up-regulated expression of McWRI1, which promoted gene expression of McKCS, McLACs and McWAX in very-long-chain fatty acid biosynthesis pathway, resulting in the accumulation of alkanes component and alteration of wax structure on the fruit surface. Corresponding results were verified in McWRI1 silenced by VIGS, and WRI1 silenced down-regulated the related genes on two kinds of fruits, it caused the diversity alteration in content of some alkanes, fatty acid and ester component in two kinds of fruits. We further conducted Y1H assay to find that McWRI1 transcription factor activated the promoter of McKCS, McLAC and McWAX to regulate their expression. These results demonstrated that McWRI1 is involved in regulating the genes related synthesis of very long chain fatty acid on surface of apple fruits in storage process, providing a highlight for improvement of the modified atmosphere storage of apple fruits.
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Ji, Qianlong; Zhang, Kezhong; Yang, Mingfeng
2017-01-01
Cuticular waxes of plant and organ surfaces play an important role in protecting plants from biotic and abiotic stress and extending the freshness, storage time and shelf life in the post-harvest agricultural products. WRI1, a transcription factor of AP2/SHEN families, had been found to trigger the related genes taking part in the biosynthesis of seed oil in many plants. But whether WRI1 is involved in the biosynthesis of the cuticular waxes on the Malus fruits surface has been unclear. We investigated the changes of wax composition and structure, the related genes and WRI1 expression on Malus asiatica Nakai and sieversii fruits with the low temperature treatments, found that low temperature induced the up-regulated expression of McWRI1, which promoted gene expression of McKCS, McLACs and McWAX in very-long-chain fatty acid biosynthesis pathway, resulting in the accumulation of alkanes component and alteration of wax structure on the fruit surface. Corresponding results were verified in McWRI1 silenced by VIGS, and WRI1 silenced down-regulated the related genes on two kinds of fruits, it caused the diversity alteration in content of some alkanes, fatty acid and ester component in two kinds of fruits. We further conducted Y1H assay to find that McWRI1 transcription factor activated the promoter of McKCS, McLAC and McWAX to regulate their expression. These results demonstrated that McWRI1 is involved in regulating the genes related synthesis of very long chain fatty acid on surface of apple fruits in storage process, providing a highlight for improvement of the modified atmosphere storage of apple fruits. PMID:29073205
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Genders, Roel E; Mazlom, Hadi; Michel, Angelika; Plasmeijer, Elsemieke I; Quint, Koen D; Pawlita, Michael; van der Meijden, Els; Waterboer, Tim; de Fijter, Hans; Claas, Frans H; Wolterbeek, Ron; Feltkamp, Mariet C W; Bouwes Bavinck, Jan Nico
2015-05-01
Organ transplant recipients (OTRs) have an increased risk of developing keratinocyte carcinomas (KCs). The aim of this study was to correlate infection with human papillomaviruses (HPVs) belonging to the beta genus (Beta-papillomavirus (Beta-PV)) at transplantation with later development of KCs. In a cohort study, sera collected between 1 year before and 1 year after transplantation of OTRs transplanted between 1990 and 2006 were tested for antibody responses against the L1 capsid antigen of Beta-PV and other HPV genera (Gamma-, Mu-, Nu-, and Alpha-PV) using multiplex serology. The OTRs were followed for a maximum of 22 years. Cox regression models with KC, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) as outcome variables were used. Out of 445 OTRs, 60 had developed KC: 14 developed only SCC, 24 only BCC, and 22 both types of KC. The time-dependent hazard ratio (HR) to develop either or both types of KC, adjusted for age, sex, and transplanted organ, in tested Beta-PV-seropositive OTR around the time of transplantation compared with Beta-PV-seronegative OTR was 2.9 (95% confidence interval (CI) 1.3-6.4). The HR for SCC was 2.9 (95% CI 0.99-8.5) and for BCC it was 3.1 (95% CI 1.2-8.0). There was also an association between Mu-PV seropositivity and KC, but there were no significant associations between other HPV genera tested and KC. A positive seroresponse for Beta-PV around transplantation significantly predicted the development of KC in OTRs up to 22 years later, providing additional evidence that infection with Beta-PV has a role in KC carcinogenesis.
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Conomos, Matthew P.; Laurie, Cecelia A.; Stilp, Adrienne M.; Gogarten, Stephanie M.; McHugh, Caitlin P.; Nelson, Sarah C.; Sofer, Tamar; Fernández-Rhodes, Lindsay; Justice, Anne E.; Graff, Mariaelisa; Young, Kristin L.; Seyerle, Amanda A.; Avery, Christy L.; Taylor, Kent D.; Rotter, Jerome I.; Talavera, Gregory A.; Daviglus, Martha L.; Wassertheil-Smoller, Sylvia; Schneiderman, Neil; Heiss, Gerardo; Kaplan, Robert C.; Franceschini, Nora; Reiner, Alex P.; Shaffer, John R.; Barr, R. Graham; Kerr, Kathleen F.; Browning, Sharon R.; Browning, Brian L.; Weir, Bruce S.; Avilés-Santa, M. Larissa; Papanicolaou, George J.; Lumley, Thomas; Szpiro, Adam A.; North, Kari E.; Rice, Ken; Thornton, Timothy A.; Laurie, Cathy C.
2016-01-01
US Hispanic/Latino individuals are diverse in genetic ancestry, culture, and environmental exposures. Here, we characterized and controlled for this diversity in genome-wide association studies (GWASs) for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We simultaneously estimated population-structure principal components (PCs) robust to familial relatedness and pairwise kinship coefficients (KCs) robust to population structure, admixture, and Hardy-Weinberg departures. The PCs revealed substantial genetic differentiation within and among six self-identified background groups (Cuban, Dominican, Puerto Rican, Mexican, and Central and South American). To control for variation among groups, we developed a multi-dimensional clustering method to define a “genetic-analysis group” variable that retains many properties of self-identified background while achieving substantially greater genetic homogeneity within groups and including participants with non-specific self-identification. In GWASs of 22 biomedical traits, we used a linear mixed model (LMM) including pairwise empirical KCs to account for familial relatedness, PCs for ancestry, and genetic-analysis groups for additional group-associated effects. Including the genetic-analysis group as a covariate accounted for significant trait variation in 8 of 22 traits, even after we fit 20 PCs. Additionally, genetic-analysis groups had significant heterogeneity of residual variance for 20 of 22 traits, and modeling this heteroscedasticity within the LMM reduced genomic inflation for 19 traits. Furthermore, fitting an LMM that utilized a genetic-analysis group rather than a self-identified background group achieved higher power to detect previously reported associations. We expect that the methods applied here will be useful in other studies with multiple ethnic groups, admixture, and relatedness. PMID:26748518
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Sa, Susan M; Valdez, Patricia A; Wu, Jianfeng; Jung, Kenneth; Zhong, Fiona; Hall, Linda; Kasman, Ian; Winer, Jane; Modrusan, Zora; Danilenko, Dimitry M; Ouyang, Wenjun
2007-02-15
IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor complex R1 subunits that are preferentially expressed on cells of epithelial origin; thus, we henceforth refer to them as the IL-20 subfamily cytokines. In this study, we show that primary human keratinocytes (KCs) express receptors for these cytokines and that IL-19, IL-20, IL-22, and IL-24 induce acanthosis in reconstituted human epidermis (RHE) in a dose-dependent manner. These cytokines also induce expression of the psoriasis-associated protein S100A7 and keratin 16 in RHE and cause persistent activation of Stat3 with nuclear localization. IL-22 had the most pronounced effects on KC proliferation and on the differentiation of KCs in RHE, inducing a decrease in the granular cell layer (hypogranulosis). Furthermore, gene expression analysis performed on cultured RHE treated with these cytokines showed that IL-19, IL-20, IL-22, and IL-24 regulate many of these same genes to variable degrees, inducing a gene expression profile consistent with inflammatory responses, wound healing re-epithelialization, and altered differentiation. Many of these genes have also been found to be up-regulated in psoriatic skin, including several chemokines, beta-defensins, S100 family proteins, and kallikreins. These results confirm that IL-20 subfamily cytokines are important regulators of epidermal KC biology with potentially pivotal roles in the immunopathology of psoriasis.
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Wu, Zhongping; Kong, Xiangliang; Zhang, Tong; Ye, Jin; Fang, Zhaoqin; Yang, Xuejun
2014-02-05
The anti-inflammatory effects of pseudoephedrine/ephedrine were investigated using the experimental model of lipopolysaccharide (LPS)-induced acute liver failure in D-galactosamine (D-GalN)-sensitised male rats in order to elucidate effects other than sympathomimetic effects. Rats were intraperitoneally injected with D-GalN (400 mg/kg) and LPS (40 μg/kg) to induce acute liver failure. The treatment groups were then intraperitoneally administered pseudoephedrine/ephedrine at 0 h and 4 h after induction and the activation induced by treatment with pseudoephedrine and/or LPS on the primary Kupffer cells (KCs) was monitored. Compared with controls induced by GalN/LPS alone, pseudoephedrine dramatically reduced the infiltration of inflammatory cells and bile ductular hyperplasia and hepatic necrosis observed in liver sections. It inhibited both hepatocellular apoptosis and the expression of monocyte chemotactic protein-1. It lowered the production of tumour necrosis factor-α (TNF-α) in the beginning of acute liver failure induced by D-GalN/LPS. Correspondingly, levels of alanine aminotransferase (ALT), total bilirubin (TBIL) and malondialdehyde were attenuated. Ephedrine demonstrated all these identical protective effects as well. In addition, pseudoephedrine significantly suppressed the production of p-IκB-α, reducing the degradation of sequestered nuclear factor kappa B (NF-κB) in the cytoplasm, and inhibited the translocation of NF-κB/p65 to the nucleus, the transcription of TNF-α mRNA and the production of TNF-α in primary KCs. These results suggest that pseudoephedrine and ephedrine have a potent anti-inflammatory activity against D-GalN/LPS-induced acute liver failure in rats, and this comprehensive anti-inflammatory effect may result from the inhibition of TNF-α production. Copyright © 2013 Elsevier B.V. All rights reserved.
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Orlov, Maxim D; Chernyavsky, Alex I; Arredondo, Juan; Grando, Sergei A
2006-11-01
This study tested a recently proposed "Basal Cell Shrinkage" hypothesis of pemphigus acantholysis through a quantitative analysis of individual and cooperative effects of pemphigus vulgaris (PV) IgG, Fas-ligand (Fas-L) and tumor necrosis factor-alpha (TNFalpha) on keratinocyte (KC) volume (i.e. cell size) and adhesive properties. Exposure of KC monolayers and MatTek EpiDermFT tissues cultures to the physiologic concentrations of Fas-L, TNFalpha or IgGs from two PV patients resulted in various degrees of reversible changes, which were not observed in control cultures either exposed to normal IgG or left intact. Within 12-24 h of exposure, basal cells in experimental cultures lost their ability to form stress fibers, retracted cytoplasmic aprons and formed keratin aggregates, indicating that their cytoskeleton collapsed. The cell volume decreased significantly (p < 0.05) as the polygonal cell shape changed to a round one. The shrunk cells detached from their neighbors and the substrate, resulting in a reciprocal increase of both the areas of acantholysis and the number of detached KCs, respectively. Since in the skin of PV patients, KCs are targeted by autoantibodies concomitantly with being exposed to autocrine and paracrine pro-apoptotic and pro-inflammatory cytokines, we combined PV IgG with Fas-L and/or TNFalpha in the cell culture experiments. This amplified several fold an ability of PV IgG to cause basal cell shrinkage and detachment. The obtained results demonstrated for the first time that PV IgG works together with Fas-L and TNFalpha to induce acantholysis via basal cell shrinkage, which provides a novel mechanism explaining successful treatment of PV patients with TNFalpha inhibitors.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Cheng, Yahui; Tian, Yuanyao; Xia, Jialu
Activation of Kupffer cells (KCs) plays a pivotal role in the pathogenesis of liver fibrosis. The progression and reversal of CCl{sub 4}-induced mouse liver fibrosis showed a mixed induction of hepatic classical (M1) and alternative (M2) macrophage markers. Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in modulating myeloid cell activation has recently been identified, its function in macrophage activation during hepatic fibrosis remains to be fully appreciated. In our study, PTEN expression of KCs was remarkably decreased in CCl{sub 4}-induced mice but increased to a near-normal level in reversed mice. Moreover, PTEN was significantlymore » decreased in IL4-induced RAW 264.7 cells in vitro and lower expression of PTEN was observed in M2 macrophages in vivo. In addition, loss- and gain-of-function studies suggested that PTEN regulates M2 macrophages polarization via activation of PI3K/Akt/STAT6 signaling, but had a limited effect on M1 macrophages polarization in vitro. Additionally, Ly294002, a chemical inhibitor of PI3K/Akt, could dramatically down-regulate the hallmarks of M2 macrophages. In conclusion, PTEN mediates macrophages activation by PI3K/Akt/STAT6 signaling pathway, which provides novel compelling evidences on the potential of PTEN in liver injury and opens new cellular target for the pharmacological therapy of liver fibrosis. - Highlights: • CCl{sub 4} treatment triggered a mixed M1/M2 macrophage phenotype in fibrosis. • Lower expression of PTEN in murine M2 macrophages in vivo and vitro. • PTEN modulates M2 macrophages activation via PI3K/Akt/STAT6 signaling. • Provide a new cellular target modulate macrophage mediated hepatic fibrosis.« less
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NASA Astrophysics Data System (ADS)
Prichard, Laura Jane; Davies, Roger L.; Beifiori, Alessandra; Chan, Jeffrey C. C.; Cappellari, Michele; Houghton, Ryan C. W.; Mendel, Trevor; Bender, Ralf; Galametz, Audrey; Saglia, Roberto P.; Smith, Russell; Stott, John P.; Wilman, David J.; Lewis, Ian J.; Sharples, Ray; Wegner, Michael
2018-01-01
Galaxy clusters are the largest gravitationally bound structures in the Universe, and we know that early type galaxies (ETGs) are more common towards their centers. Clusters of galaxies are increasingly rare at early times, but are essential for understanding the formation of these massive structures and how they alter the fate of their member galaxies. However, long integration times are required to constrain the stellar properties of these distant cluster ETGs. Now with the advent of the multiplexed near-infrared integral field instrument, the K-band Multi-Object Spectrograph (KMOS) on the Very Large Telescope, we can target the ETGs in these valuable high-redshift clusters more efficiently than ever. The KMOS guaranteed observing program, the KMOS Cluster Survey (KCS; P.I.s Bender & Davies), has enabled a study of cluster galaxies in overdensities spanning z=1-2 through absorption-line spectroscopy obtained from 20-hour integrations. We will present spectra for 16 galaxies in the furthest KCS overdensity, JKCS 041, an ETG-rich cluster at z=1.80. We measured seven velocity dispersions from the quiescent galaxy spectra, expanding the sample of like measurements in the literature at or above z=1.80 by more than 40%. Through the analysis of Hubble Space Telescope photometry and deep absorption-line spectroscopy, we were able to construct the highest redshift fundamental plane (FP) within a single system for galaxies in JKCS 041. From the redshift evolution of the FP zero-point, we derived a mean age of the galaxies in this cluster of 1.4 +/- 0.2 Gyrs. We determined relative velocities of the galaxies to study the three-dimensional structure of this overdensity. We noticed from the dynamics of JKCS 041 that a group of galaxies was infalling towards the cluster center. When measuring FP ages for the infalling group, we found these galaxies had significantly younger mean ages (0.3 +/- 0.2 Gyrs) than the other galaxies in the cluster (2.0 +0.3/-0.1 Gyrs). Based on the galaxy dynamics, cluster morphology, and galaxy stellar age results, we concluded that JKCS 041 is in formation and consists of two merging groups of galaxies. This could link galaxy ages to large-scale structure for the first time at this redshift.
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A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording.
Crescentini, Marco; Bennati, Marco; Saha, Shimul Chandra; Ivica, Josip; de Planque, Maurits; Morgan, Hywel; Tartagni, Marco
2016-05-19
High-throughput screening (HTS) using ion channel recording is a powerful drug discovery technique in pharmacology. Ion channel recording with planar bilayer lipid membranes (BLM) is scalable and has very high sensitivity. A HTS system based on BLM ion channel recording faces three main challenges: (i) design of scalable microfluidic devices; (ii) design of compact ultra-low-noise transimpedance amplifiers able to detect currents in the pA range with bandwidth >10 kHz; (iii) design of compact, robust and scalable systems that integrate these two elements. This paper presents a low-noise transimpedance amplifier with integrated A/D conversion realized in CMOS 0.35 μm technology. The CMOS amplifier acquires currents in the range ±200 pA and ±20 nA, with 100 kHz bandwidth while dissipating 41 mW. An integrated digital offset compensation loop balances any voltage offsets from Ag/AgCl electrodes. The measured open-input input-referred noise current is as low as 4 fA/√Hz at ±200 pA range. The current amplifier is embedded in an integrated platform, together with a microfluidic device, for current recording from ion channels. Gramicidin-A, α-haemolysin and KcsA potassium channels have been used to prove both the platform and the current-to-digital converter.
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A Low-Noise Transimpedance Amplifier for BLM-Based Ion Channel Recording
Crescentini, Marco; Bennati, Marco; Saha, Shimul Chandra; Ivica, Josip; de Planque, Maurits; Morgan, Hywel; Tartagni, Marco
2016-01-01
High-throughput screening (HTS) using ion channel recording is a powerful drug discovery technique in pharmacology. Ion channel recording with planar bilayer lipid membranes (BLM) is scalable and has very high sensitivity. A HTS system based on BLM ion channel recording faces three main challenges: (i) design of scalable microfluidic devices; (ii) design of compact ultra-low-noise transimpedance amplifiers able to detect currents in the pA range with bandwidth >10 kHz; (iii) design of compact, robust and scalable systems that integrate these two elements. This paper presents a low-noise transimpedance amplifier with integrated A/D conversion realized in CMOS 0.35 μm technology. The CMOS amplifier acquires currents in the range ±200 pA and ±20 nA, with 100 kHz bandwidth while dissipating 41 mW. An integrated digital offset compensation loop balances any voltage offsets from Ag/AgCl electrodes. The measured open-input input-referred noise current is as low as 4 fA/√Hz at ±200 pA range. The current amplifier is embedded in an integrated platform, together with a microfluidic device, for current recording from ion channels. Gramicidin-A, α-haemolysin and KcsA potassium channels have been used to prove both the platform and the current-to-digital converter. PMID:27213382
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Dynamique moléculaire et canaux ioniques
NASA Astrophysics Data System (ADS)
Crouzy, S.
2005-11-01
Diffusion de neutrons et Dynamique Moléculaire (DM) sont deux techniques intimement liées car elles portent sur les mêmes échelles de temps: la première apporte des informations structurales ou dynamiques sur le système physique ou biologique, la seconde permet de décoder ces informations à travers un modèle facilitant l'interprétation des résultats. Au delà de l'intérêt que la technique de DM peut avoir en relation directe avec les neutrons, il est intéressant de comprendre comment les modèles sont construits et comment les techniques de simulation peuvent aller beaucoup plus loin que de simples modélisations. Nous décrirons brièvement, dans la suite de cet exposé, la technique de DM et les méthodes plus sophistiquées de calculs d'énergie libre et de potentiels de force moyenne à partir des simulations de DM. Puis nous verrons avec deux exemples tirés de nos travaux théoriques sur les canaux ioniques comment ces calculs peuvent nous donner accès à des vitesses de réaction ou des constantes d'affinité ou de liaison. La première étude porte sur un analogue de la gramicidine A qui forme un canal conducteur d'ions interrompus par le basculement d'un cycle dioxolane [1]. La seconde concerne le canal potassique KcsA dont nous avons étudié le blocage du coté extracellulaire par l'ion Tetra Ethyl Ammonium [2].
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NASA Astrophysics Data System (ADS)
Choi, Hee-Jong; Chun, Ho-Hwan; Park, Il-Ryong; Kim, Jin
2011-12-01
In the present study, a new hull panel generation algorithm, namely panel cutting method, was developed to predict flow phenomena around a ship using the Rankine source potential based panel method, where the iterative method was used to satisfy the nonlinear free surface condition and the trim and sinkage of the ship was taken into account. Numerical computations were performed to investigate the validity of the proposed hull panel generation algorithm for Series 60 (CB=0.60) hull and KRISO container ship (KCS), a container ship designed by Maritime and Ocean Engineering Research Institute (MOERI). The computational results were validated by comparing with the existing experimental data.
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Linking results of key and supplementary comparisons of AC/DC voltage transfer references
NASA Astrophysics Data System (ADS)
Velychko, Oleh
2018-04-01
A regional key comparison (KC) COOMET.EM-K6.a and a supplementary comparison (SC) COOMET.EM-S1 of AC/DC voltage transfer references were conducted between participating laboratories from the Eurasian region. Measurements were made over the period 2004-2014. The results showed good agreement between all but one of the participating laboratories. The proposed procedure of linking results of key and SCs of regional metrology organization of AC/DC voltage transfer references is presented. Linking results is realized for COOMET.EM-K6.a and CCEM-K6.a KCs, and for COOMET.EM-K6.a KC and COOMET.EM-S1 SC.
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Kurpińska, Małgorzata; Gorczyńska, Ewa; Owoc-Lempach, Joanna; Bernacka, Aleksandra; Misiuk-Hojło, Marta; Chybicka, Alicja
2011-01-01
Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS) is recognized as the most frequent ocular complication after allogeneic stem cell transplantation (allo-SCT). KCS can appear either due to insufficient tear production or excessive tear evaporation, both resulting in tears hyperosmolarity that leads to ocular damage. The evaporation rate and better film stability is determined primarily by the status of the lipid layer. Observation and classification of tear film lipid layer interference patterns in normal and dry eyes in patients after allogeneic stem cell transplantation with a follow-up time of 6 months-5 years (median 26.54 months). Investigation of the relation between the lipid layer interference patterns in normal and dry eyes and the results of other dry eye examinations and complaints. Relation between DES and conditioning regimes, including total body irradiation and high-dose chemotherapy, immunosuppressive drugs, the time after allogeneic stem cell transplantation and chronic graft-versus-host disease. Precorneal tears lipid layer interference patterns, were examined in 114 eyes in treatment group with the Tearscope-plus. Patient with dry eye were identified on the basis of Schirmer test scores and/or tear breakup time, and positive lissamine and/or fluorescein staining. 42 of 114 eyes (36.8%) developed DES after allo-SCT A significant correlation between thickness of lipid layer and BUT, Schirmer test, lissamine green and fluorescein staining was found in the treatment group. A significant association was found between present chronic GVHD and DES in children. DES was not associated with TBI, corticosteroids, immunosuppressive drugs and the time in the present study. Tears lipid layer interference patterns are highly correlated with the diagnosis of DES. Tears lipid layer interference patterns ( noninvasive method), can be used to diagnose early DES in children after allo-SCT. Chronic GVHD play a major role in development of DES. dry eye syndrome, graft versus host disease, stem cell transplantation.
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The KMOS Cluster Survey (KCS). III. Fundamental Plane of Cluster Galaxies at z ≃ 1.80 in JKCS 041
NASA Astrophysics Data System (ADS)
Prichard, Laura J.; Davies, Roger L.; Beifiori, Alessandra; Chan, Jeffrey C. C.; Cappellari, Michele; Houghton, Ryan C. W.; Mendel, J. Trevor; Bender, Ralf; Galametz, Audrey; Saglia, Roberto P.; Stott, John P.; Wilman, David J.; Lewis, Ian J.; Sharples, Ray; Wegner, Michael
2017-12-01
We present data for 16 galaxies in the overdensity JKCS 041 at z≃ 1.80 as part of the K-band Multi-Object Spectrograph (KMOS) Cluster Survey (KCS). With 20 hr integrations, we have obtained deep absorption-line spectra from which we derived velocity dispersions for seven quiescent galaxies. We combined photometric parameters derived from Hubble Space Telescope images with the dispersions to construct a fundamental plane (FP) for quiescent galaxies in JKCS 041. From the zero-point evolution of the FP, we derived a formation redshift for the galaxies of {z}{form}=3.0+/- 0.3, corresponding to a mean age of 1.4 ± 0.2 Gyr. We tested the effect of structural and velocity dispersion evolution on our FP zero-point and found a negligible contribution when using dynamical mass-normalized parameters (˜ 3 % ) but a significant contribution from stellar-mass-normalized parameters (˜ 42 % ). From the relative velocities of the galaxies, we probed the 3D structure of these 16 confirmed members of JKCS 041 and found that a group of galaxies in the southwest of the overdensity had systematically higher velocities. We derived ages for the galaxies in the different groups from the FP. We found that the east-extending group had typically older galaxies ({2.1}-0.2+0.3 Gyr) than those in the southwest group (0.3 ± 0.2 Gyr). Although based on small numbers, the overdensity dynamics, morphology, and age results could indicate that JKCS 041 is in formation and may comprise two merging groups of galaxies. This result could link large-scale structure to ages of galaxies for the first time at this redshift. Based on observations obtained at the Very Large Telescope (VLT) of the European Southern Observatory (ESO), Paranal, Chile (ESO program IDs: 095.A-0137(A) and 096.A-0189(A)).
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Chernyavsky, Alex; Chen, Yumay; Wang, Ping H; Grando, Sergei A
2015-11-01
The mechanism of detachment and death of keratinocytes in pemphigus vulgaris (PV) involves pro-apoptotic action of constellations of autoantibodies determining disease severity and response to treatment. The presence of antibodies to nicotinic acetylcholine receptors (nAChRs) and the therapeutic efficacy of cholinomimetics in PV is well-established. Recently, adsorption of anti-mitochondrial antibodies abolished the ability of PVIgGs to cause acantholysis, demonstrating their pathophysiological significance. Since, in addition to cell membrane, nAChRs are also present on the mitochondrial outer membrane, wherein they act to prevent activation of intrinsic (mitochondrial apoptosis), we hypothesized that mitochondrial (mt)-nAChRs might be targeted by PVIgGs. To test this hypothesis, we employed the immunoprecipitation-western blot assay of keratinocyte mitochondrial proteins that visualized the α3, α5, α7, α9, α10, β2 and β4 mt-nAChR subunits precipitated by PV IgGs, suggesting that functions of mt-nAChRs are compromised in PV. To pharmacologically counteract the pro-apoptotic action of anti-mitochondrial antibodies in PV, we exposed naked keratinocyte mitochondria to PVIgGs in the presence of the nicotinic agonist nicotine ± antagonists, and measured cytochrome c (CytC) release. Nicotine abolished PVIgG-dependent CytC release, showing a dose-dependent effect, suggesting that protection of mitochondria can be a novel mechanism of therapeutic action of nicotinic agonists in PV. The obtained results indicated that the mt-nAChRs targeted by anti-mitochondrial antibodies produced by PV patients are coupled to inhibition of CytC release, and that nicotinergic stimulation can abolish PVIgG-dependent activation of intrinsic apoptosis in KCs. Future studies should determine if and how the distinct anti-mt-nAChR antibodies penetrate KCs and correlate with disease severity. Copyright © 2015 Elsevier B.V. All rights reserved.
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Measurement of flows around modern commercial ship models
NASA Astrophysics Data System (ADS)
Kim, W. J.; Van, S. H.; Kim, D. H.
To document the details of flow characteristics around modern commercial ships, global force, wave pattern, and local mean velocity components were measured in the towing tank. Three modern commercial hull models of a container ship (KRISO container ship = KCS) and of two very large crude-oil carriers (VLCCs) with the same forebody and slightly different afterbody (KVLCC and KVLCC2) having bow and stern bulbs were selected for the test. Uncertainty analysis was performed for the measured data using the procedure recommended by the ITTC. Obtained experimental data will provide a good opportunity to explore integrated flow phenomena around practical hull forms of today. Those can be also used as the validation data for the computational fluid dynamics (CFD) code of both inviscid and viscous flow calculations.
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Tracing the Evolution of Passive Galaxies in Clusters at 1.4
NASA Astrophysics Data System (ADS)
Beifiori, Alessandra
2017-08-01
In this talk I will discuss recent progress studying the rest-frame optical properties of quiescent galaxies at this critical epoch using KMOS, the K-band Multi-Object Spectrograph on the ESO/VLT. I will highlight recent results form the KMOS Custer Survey (KCS), whose aim is to provide a census of quiescent galaxy kinematics at 1.4 ≤ z ≤ 1.8 in know overdensities. The combination of kinematic measurements from KMOS and structural parameters measured from deep HST imaging allowed us to place constraints on the formation ages of passive galaxies at 1.4
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NASA Technical Reports Server (NTRS)
Evans, Randolph J.; Tremback, Craig J.; Lyons, Walter A.
1996-01-01
The Emergency Response Dose Assessment System (ERDAS) is a system which combines the mesoscale meteorological prediction model RAMS with the diffusion models REEDM and HYPACT. Operators use a graphical user interface to run the models for emergency response and toxic hazard planning at CCAS/KCS. The Applied Meteorology Unit has been evaluating the ERDAS meteorological and diffusion models and obtained the following results: (1) RAMS adequately predicts the occurrence of the daily sea breeze during non-cloudy conditions for several cases. (2) RAMS shows a tendency to predict the sea breeze to occur slightly earlier and to move it further inland than observed. The sea breeze predictions could most likely be improved by better parameterizing the soil moisture and/or sea surface temperatures. (3) The HYPACT/REEDM/RAMS models accurately predict launch plume locations when RAMS winds are accurate and when the correct plume layer is modeled. (4) HYPACT does not adequately handle plume buoyancy for heated plumes since all plumes are presently treated as passive tracers. Enhancements should be incorporated into the ERDAS as it moves toward being a fully operational system and as computer workstations continue to increase in power and decrease in cost. These enhancements include the following: activate RAMS moisture physics; use finer RAMS grid resolution; add RAMS input parameters (e.g. soil moisture, radar, and/or satellite data); automate data quality control; implement four-dimensional data assimilation; modify HYPACT plume rise and deposition physics; and add cumulative dosage calculations in HYPACT.
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Vijmasi, Trinka; Chen, Feeling Y T; Chen, Ying Ting; Gallup, Marianne; McNamara, Nancy
2013-01-01
Dry eye is commonly associated with autoimmune diseases such as Sjögren's syndrome (SS), in which exocrinopathy of the lacrimal gland leads to aqueous tear deficiency and keratoconjunctivitis sicca (KCS). KCS is among the most common and debilitating clinical manifestations of SS that is often recalcitrant to therapy. We established mice deficient in the autoimmune regulator (Aire) gene as a model for autoimmune-mediated aqueous-deficient dry eye. In Aire-deficient mice, CD4+ T cells represent the main effector cells and local signaling via the interleukin-1 (IL-1/IL-1R1) pathway provides an essential link between autoreactive CD4+ T cells and ocular surface disease. In the current study, we evaluated the efficacy of topical administration of IL-1R1 antagonist (IL-1RA) anakinra in alleviating ocular surface damage resulting from aqueous-deficient dry eye in the setting of autoimmune disease. We compared the effect of commercially available IL-1R1 antagonist, anakinra (50 μg/mL concentration) to that of carboxymethylcellulose (CMC) vehicle control as a treatment for dry eye. Age-matched, Aire-deficient mice were treated three times daily with anakinra or CMC vehicle for 14 days using side-by-side (n = 4 mice/group) and paired-eye (n = 5) comparisons. We assessed (1) ocular surface damage with lissamine green staining; (2) tear secretion with wetting of phenol-red threads; (3) goblet cell (GC) mucin glycosylation with lectin histochemistry; (4) immune cell infiltration using anti-F4/80, CD11c, and CD4 T cell antibodies; and (5) gene expression of cornified envelope protein, Small Proline-Rich Protein-1B (SPRR1B) with real-time quantitative polymerase chain reaction. Aire-deficient mice treated with anakinra experienced significant improvements in ocular surface integrity and tear secretion. After 7 days of treatment, lissamine green staining decreased in eyes treated with anakinra compared to an equivalent increase in staining following treatment with CMC vehicle alone. By day 14, lissamine green staining in anakinra-treated eyes remained stable while eyes treated with CMC vehicle continued to worsen. Accordingly, there was a progressive decline in tear secretion in eyes treated with the CMC vehicle compared to a progressive increase in the anakinra-treated eyes over the 2-week treatment period. Aberrant acidification of GC mucins and pathological keratinization of the ocular surface were significantly reduced in anakinra-treated eyes. Significantly fewer Maackia amurensis leukoagglutinin positive goblet cells were noted in the conjunctiva of anakinra-treated eyes with a corresponding decrease in the expression of the pathological keratinization marker, SPRR1B. Finally, there was a downward trend in the infiltration of each immune cell type following anakinra treatment, but the cell counts compared to eyes treated with the vehicle alone were not significantly different. IL-1R antagonist, anakinra, demonstrates therapeutic benefits as a topical treatment for aqueous-deficient dry eye in a spontaneous mouse model of autoimmune KCS that mimics the clinical characteristics of SS. Targeting the IL-1/IL-1R1 signaling pathway through topical administration of IL-1RA may provide a novel option to improve ocular surface integrity, increase tear secretion, and restore the normal glycosylation pattern of GC mucins in patients with SS.
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Vijmasi, Trinka; Chen, Feeling YT; Chen, Ying Ting; Gallup, Marianne
2013-01-01
Purpose Dry eye is commonly associated with autoimmune diseases such as Sjögren’s syndrome (SS), in which exocrinopathy of the lacrimal gland leads to aqueous tear deficiency and keratoconjunctivitis sicca (KCS). KCS is among the most common and debilitating clinical manifestations of SS that is often recalcitrant to therapy. We established mice deficient in the autoimmune regulator (Aire) gene as a model for autoimmune-mediated aqueous-deficient dry eye. In Aire-deficient mice, CD4+ T cells represent the main effector cells and local signaling via the interleukin-1 (IL-1/IL-1R1) pathway provides an essential link between autoreactive CD4+ T cells and ocular surface disease. In the current study, we evaluated the efficacy of topical administration of IL-1R1 antagonist (IL-1RA) anakinra in alleviating ocular surface damage resulting from aqueous-deficient dry eye in the setting of autoimmune disease. Methods We compared the effect of commercially available IL-1R1 antagonist, anakinra (50 μg/mL concentration) to that of carboxymethylcellulose (CMC) vehicle control as a treatment for dry eye. Age-matched, Aire-deficient mice were treated three times daily with anakinra or CMC vehicle for 14 days using side-by-side (n=4 mice/group) and paired-eye (n=5) comparisons. We assessed (1) ocular surface damage with lissamine green staining; (2) tear secretion with wetting of phenol-red threads; (3) goblet cell (GC) mucin glycosylation with lectin histochemistry; (4) immune cell infiltration using anti-F4/80, CD11c, and CD4 T cell antibodies; and (5) gene expression of cornified envelope protein, Small Proline-Rich Protein-1B (SPRR1B) with real-time quantitative polymerase chain reaction. Results Aire-deficient mice treated with anakinra experienced significant improvements in ocular surface integrity and tear secretion. After 7 days of treatment, lissamine green staining decreased in eyes treated with anakinra compared to an equivalent increase in staining following treatment with CMC vehicle alone. By day 14, lissamine green staining in anakinra-treated eyes remained stable while eyes treated with CMC vehicle continued to worsen. Accordingly, there was a progressive decline in tear secretion in eyes treated with the CMC vehicle compared to a progressive increase in the anakinra-treated eyes over the 2-week treatment period. Aberrant acidification of GC mucins and pathological keratinization of the ocular surface were significantly reduced in anakinra-treated eyes. Significantly fewer Maackia amurensis leukoagglutinin positive goblet cells were noted in the conjunctiva of anakinra-treated eyes with a corresponding decrease in the expression of the pathological keratinization marker, SPRR1B. Finally, there was a downward trend in the infiltration of each immune cell type following anakinra treatment, but the cell counts compared to eyes treated with the vehicle alone were not significantly different. Conclusions IL-1R antagonist, anakinra, demonstrates therapeutic benefits as a topical treatment for aqueous-deficient dry eye in a spontaneous mouse model of autoimmune KCS that mimics the clinical characteristics of SS. Targeting the IL-1/IL-1R1 signaling pathway through topical administration of IL-1RA may provide a novel option to improve ocular surface integrity, increase tear secretion, and restore the normal glycosylation pattern of GC mucins in patients with SS. PMID:24068863
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Conformational dynamics of the inner pore helix of voltage-gated potassium channels
NASA Astrophysics Data System (ADS)
Choe, Seungho; Grabe, Michael
2009-06-01
Voltage-gated potassium (Kv) channels control the electrical excitability of neurons and muscles. Despite this key role, how these channels open and close or gate is not fully understood. Gating is usually attributed to the bending and straightening of pore-lining helices at glycine and proline residues. In this work we focused on the role of proline in the Pro-Val-Pro (PVP) motif of the inner S6 helix in the Kv1.2 channel. We started by developing a simple hinged-rod model to fully explore the configurational space of bent helices and we related these configurations to the degree of pore opening. We then carried out fully atomistic simulations of the S6 helices and compared these simulations to the hinged-rod model. Both methods suggest that Kv1 channels are not tightly closed when the inner helices are straight, unlike what is seen in the non-PVP containing channels KcsA and KirBac. These results invite the possibility that the S6 helices may be kinked when Kv1 channels are closed. Our simulations indicate that the wild-type helix adopts multiple spatially distinct configurations, which is consistent with its role in adopting a closed state and an open state. The two most dominant configurational basins correspond to a 6 Å movement of the helix tail accompanied by the PVP region undergoing a local α-helix to 310-helix transition. We explored how single point mutations affect the propensity of the S6 helix to adopt particular configurations. Interestingly, mutating the first proline, P405 (P473 in Shaker), to alanine completely removed the bistable nature of the S6 helix possibly explaining why this mutation compromises the channel. Next, we considered four other mutations in the area known to affect channel gating and we saw similarly dramatic changes to the helix's dynamics and range of motion. Our results suggest a possible mechanism of helix pore closure and they suggest differences in the closed state of glycine-only channels, like KcsA, and PVP containing channels.
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Jago, Russell; Sebire, Simon J; Davies, Ben; Wood, Lesley; Banfield, Kathryn; Edwards, Mark J; Powell, Jane E; Montgomery, Alan A; Thompson, Janice L; Fox, Kenneth R
2015-02-18
Many children do not engage in recommended levels of physical activity (PA), highlighting the need to find ways to increase children's PA. Process evaluations play an important role in improving the science of randomised controlled trials. We recently reported the results of the Action 3:30 cluster randomised feasibility trial illustrating higher levels of moderate to vigorous intensity PA among boys but not girls. The aim of this paper is to report the process evaluation results including intervention fidelity, implementation, context and how intervention components and trial design could be improved before proceeding to a definitive RCT. Children's session enjoyment was assessed every two weeks. Reasons for non-attendance were provided by questionnaire at the end of the intervention. Post intervention interviews were held with participating teaching assistants (TAs) and school key contacts (KCs), and focus groups were conducted with children in all 10 intervention schools. Interviews and focus groups examined how recruitment and session attendance might be improved and established which elements of the programme that were and were not well received. Data indicated good intervention fidelity with TA's adopting enjoyment-focussed teaching styles and the sessions improving children's skills and self-esteem. Several positive aspects of implementation were identified, including high session variety, the opportunity to work in teams, the child-led sessions and the engaging leader style. In terms of context there was evidence that TA's faced difficulties managing challenging behaviour and that further training in this area was needed. TAs and KCs felt that recruitment could be improved by providing taster sessions during PE lessons and clarifying the days that the clubs would run at the point of recruitment. The programme could be improved to enhance interest for girls, by including training for managing disruptive behaviour and making some activities more age-group appropriate. Action 3.30 showed promise but could be improved by ensuring age appropriate activities, providing more appeal to girls and improving recruitment through taster sessions and early establishment of days of the week it is to be offered on. ISRCTN58502739.
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Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating
Kim, Dorothy M.; Nimigean, Crina M.
2016-01-01
Voltage-gated potassium channels play a fundamental role in the generation and propagation of the action potential. The discovery of these channels began with predictions made by early pioneers, and has culminated in their extensive functional and structural characterization by electrophysiological, spectroscopic, and crystallographic studies. With the aid of a variety of crystal structures of these channels, a highly detailed picture emerges of how the voltage-sensing domain reports changes in the membrane electric field and couples this to conformational changes in the activation gate. In addition, high-resolution structural and functional studies of K+ channel pores, such as KcsA and MthK, offer a comprehensive picture on how selectivity is achieved in K+ channels. Here, we illustrate the remarkable features of voltage-gated potassium channels and explain the mechanisms used by these machines with experimental data. PMID:27141052
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Moyo, Daniel; Beattie, Lynette; Andrews, Paul S; Moore, John W J; Timmis, Jon; Sawtell, Amy; Hoehme, Stefan; Sampson, Adam T; Kaye, Paul M
2018-01-01
Cellular activation in trans by interferons, cytokines, and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and/or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling, and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani -infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation.
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Flow measurement around a model ship with propeller and rudder
NASA Astrophysics Data System (ADS)
van, S. H.; Kim, W. J.; Yoon, H. S.; Lee, Y. Y.; Park, I. R.
2006-04-01
For the design of hull forms with better resistance and propulsive performance, it is essential to understand flow characteristics, such as wave and wake development, around a ship. Experimental data detailing the local flow characteristics are invaluable for the validation of the physical and numerical modeling of computational fluid dynamics (CFD) codes, which are recently gaining attention as efficient tools for hull form evaluation. This paper describes velocity and wave profiles measured in the towing tank for the KRISO 138,000 m3 LNG carrier model with propeller and rudder. The effects of propeller and rudder on the wake and wave profiles in the stern region are clearly identified. The results contained in this paper can provide an opportunity to explore integrated flow phenomena around a model ship in the self-propelled condition, and can be added to the International Towing Tank Conference benchmark data for CFD validation as the previous KCS and KVLCC cases.
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Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity
Ader, Christian; Schneider, Robert; Hornig, Sönke; Velisetty, Phanindra; Vardanyan, Vitya; Giller, Karin; Ohmert, Iris; Becker, Stefan; Pongs, Olaf; Baldus, Marc
2009-01-01
Potassium (K+)-channel gating is choreographed by a complex interplay between external stimuli, K+ concentration and lipidic environment. We combined solid-state NMR and electrophysiological experiments on a chimeric KcsA–Kv1.3 channel to delineate K+, pH and blocker effects on channel structure and function in a membrane setting. Our data show that pH-induced activation is correlated with protonation of glutamate residues at or near the activation gate. Moreover, K+ and channel blockers distinctly affect the open probability of both the inactivation gate comprising the selectivity filter of the channel and the activation gate. The results indicate that the two gates are coupled and that effects of the permeant K+ ion on the inactivation gate modulate activation-gate opening. Our data suggest a mechanism for controlling coordinated and sequential opening and closing of activation and inactivation gates in the K+-channel pore. PMID:19661921
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Functional characterization of a prokaryotic Kir channel.
Enkvetchakul, Decha; Bhattacharyya, Jaya; Jeliazkova, Iana; Groesbeck, Darcy K; Cukras, Catherine A; Nichols, Colin G
2004-11-05
The Kir gene family encodes inward rectifying K+ (Kir) channels that are widespread and critical regulators of excitability in eukaryotic cells. A related gene family (KirBac) has recently been identified in prokaryotes. While a crystal structure of one member, Kir-Bac1.1, has been solved, there has been no functional characterization of any KirBac gene products. Here we present functional characterization of KirBac1.1 reconstituted in liposomes. Utilizing a 86Rb+ uptake assay, we demonstrate that KirBac1.1 generates a K+ -selective permeation path that is inhibited by extraliposomal Ba2+ and Ca2+ ions. In contrast to KcsA (an acid-activated bacterial potassium channel), KirBac1.1 is inhibited by extraliposomal acid (pKa approximately 6). This characterization of KirBac1.1 activity now paves the way for further correlation of structure and function in this model Kir channel.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Moczydlowski, Edward G.
Ion channel proteins regulate complex patterns of cellular electrical activity and ionic signaling. Certain K+ channels play an important role in immunological biodefense mechanisms of adaptive and innate immunity. Most ion channel proteins are oligomeric complexes with the conductive pore located at the central subunit interface. The long-term activity of many K+ channel proteins is dependent on the concentration of extracellular K+; however, the mechanism is unclear. Thus, this project focused on mechanisms underlying structural stability of tetrameric K+ channels. Using KcsA of Streptomyces lividans as a model K+ channel of known structure, the molecular basis of tetramer stability wasmore » investigated by: 1. Bioinformatic analysis of the tetramer interface. 2. Effect of two local anesthetics (lidocaine, tetracaine) on tetramer stability. 3. Molecular simulation of drug docking to the ion conduction pore. The results provide new insights regarding the structural stability of K+ channels and its possible role in cell physiology.« less
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Contributions of microtubule rotation and dynamic instability to kinetochore capture
NASA Astrophysics Data System (ADS)
Sweezy-Schindler, Oliver; Edelmaier, Christopher; Blackwell, Robert; Glaser, Matt; Betterton, Meredith
2014-03-01
The capture of lost kinetochores (KCs) by microtubules (MTs) is a crucial part of prometaphase during mitosis. Microtubule dynamic instability has been considered the primary mechanism of KC capture, but recent work discovered that lateral KC attachment to pivoting MTs enabled rapid capture even with significantly reduced MT dynamics. We aim to understand the relative contributions of MT rotational diffusion and dynamic instability to KC capture, as well as KC capture through end-on and/or lateral attachment. Our model consists of rigid MTs and a spherical KC, which are allowed to diffuse inside a spherical nuclear envelope consistent with the geometry of fission yeast. For simplicity, we include a single spindle pole body, which is anchored to the nuclear membrane, and its associated polar MTs. Brownian dynamics treats the diffusion of the MTs and KC and kinetic Monte Carlo models stochastic processes such as dynamic instability. NSF 1546021.
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Gonzales, John A; Chou, Annie; Rose-Nussbaumer, Jennifer R; Bunya, Vatinee Y; Criswell, Lindsey A; Shiboski, Caroline H; Lietman, Thomas M
2018-07-01
To determine whether ocular phenotypic features of keratoconjunctivitis sicca (KCS) and/or participant-reported symptoms of dry eye disease are associated with depression in women participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA). Cross-sectional study. Women enrolled in the SICCA registry from 9 international research sites. Participants met at least 1 of 5 inclusion criteria for registry enrollment (including complaints of dry eyes or dry mouth, a previous diagnosis of Sjögren syndrome (SS), abnormal serology (positive anti-Sjögren syndrome antigen A and/or B [anti-SSA and/or anti-SSB]), or elevated antinuclear antibody and rheumatoid factor), bilateral parotid gland enlargement, or multiple dental caries). At baseline, participants had oral, ocular, and rheumatologic examination; blood and saliva collection; and a labial salivary gland biopsy (LSGB). They also completed an interview and questionnaires including assessment of depression with the Patient Health Questionnaire 9 (PHQ-9). Univariate logistic regression was used to assess the association between depression and demographic characteristics, participant-reported health, phenotypic features of Sjögren syndrome, and participant-reported symptoms. Mixed-effects modeling was performed to determine if phenotypic features of KCS and/or participant-reported symptoms of dry eye disease were associated with depression, controlling for health, age, country or residence, and sex and allowing for nonindependence within geographic site. Dry eye complaints produced a 1.82-fold (95% confidence interval [CI] 1.38-2.40) higher odds of having depression compared to being symptom-free (P < .001). Additionally, complaints of specific ocular sensations were associated with a higher odds of depression including burning sensation (odds ratio 2.25, 95% CI 1.87-2.72, P < .001) compared to those without complaints. In both women with and without SS, the presence of symptoms of dry eyes and/or dry mouth rather than SS itself resulted in higher odds of depression. One particular ocular phenotypic feature of SS, a positive ocular staining score, was inversely correlated with depression. Participant-reported eye symptoms, particularly specific ocular sensations such as burning, were found to be positively associated with individual American College of Rheumatology/EUropean League Against Rheumatism (ACR/EULAR) SS criteria items. Copyright © 2018 Elsevier Inc. All rights reserved.
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Decoy receptor 3 analogous supplement protects steatotic rat liver from ischemia-reperfusion injury.
Li, Tzu-Hao; Liu, Chih-Wei; Lee, Pei-Chang; Huang, Chia-Chang; Lee, Kuei-Chuan; Hsieh, Yun-Cheng; Yang, Ying-Ying; Hsieh, Shie-Liang; Lin, Han-Chieh; Tsai, Chang-Youh
2017-07-01
For steatotic livers, pharmacological approaches to minimize the hepatic neutrophil and macrophage infiltration, and cytokine and chemokine release in ischemia-reperfusion (IR) injury are still limited. Tumor necrosis factor (TNF)-α superfamily-stimulated pathogenic cascades and M1 macrophage/Kupffer cells (KC) polarization from Th1 cytokines are important in the pathogenesis of IR liver injury with hepatic steatosis (HS). Conversely, anti-inflammatory M2 macrophages produce Th2 cytokine (interleukin-4), which reciprocally enhances M2 polarization. Toll-like receptor 4-activated KCs can release proinflammatory mediators, skew M1 polarization and escalate liver IR injury. Decoy receptor 3 (DcR 3 ) could be potential agents simultaneously blocking the IR liver injury-related pathogenic changes and extend the survival of steatotic graft. Rats were fed with methionine and choline-deficient high-fat diet (MCD HFD) for 6 weeks to induce HS. Preliminary experiments with HS group and IR group were conducted, and either immunoglobulin G Fc protein or DcR3 analogue was treated for 14 days in all groups to evaluate the severity. In the Zucker rat-focused experiments, various serum and hepatic substances, M1 polarization, and hepatic microcirculation were assessed. We found that serum/hepatic DcR 3 levels were lower in nonalcoholic fatty liver disease patients with HS. DcR 3 a protected Zucker rats with HS from IR liver injury. The beneficial effects of DcR 3 a supplement were mediated by inhibiting hepatic M1 polarization of KCs, decreasing serum/hepatic TNFα, nitric oxide, nitrotyrosine, soluble TNF-like cytokine 1A, Fas ligand, and interferon-γ levels, neutrophil infiltration, and improving hepatic microcirculatory failure among rats with IR-injured steatotic livers. Additionally, downregulated hepatic TNF-like cytokine 1A/Fas-ligand and toll-like receptor 4/nuclear factor-κB signals were found to mediate the DcR 3 a-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR 3 a analogue was a potential agent to protect steatotic liver against IR injury by simultaneous blockade of the multiple IR injury-related pathogenic changes. Copyright © 2017. Published by Elsevier Taiwan LLC.
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Weinstock, Martin A; Bingham, Stephen F; Digiovanna, John J; Rizzo, Amilcar E; Marcolivio, Kim; Hall, Russell; Eilers, David; Naylor, Mark; Kirsner, Robert; Kalivas, James; Cole, Gary; Vertrees, Julia E
2012-06-01
Keratinocyte carcinoma (KC) is the most common cancer in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. Topical tretinoin has been used for KC chemoprevention, although this use is unproven. Hence, we conducted the randomized Veterans Affairs Topical Tretinoin Chemoprevention Trial of high-dose topical tretinoin for KC prevention. We randomized 1,131 patients to topical 0.1% tretinoin or a matching vehicle control for 1.5-5.5 years. The primary outcomes were time to development of new basal cell carcinoma (BCC) and new invasive squamous cell carcinoma (SCC) on the face or ears. The effects were not significant (P=0.3 for BCC and P=0.4 for SCC). The proportions of the tretinoin and control groups who developed a BCC at 5 years were 53 and 54% and an invasive SCC at 5 years were 28 and 31%. These differences (95% confidence intervals) were: for BCC, 1.0% (-6.5, 8.6%); for SCC, 3.6% (-3.1, 10.3%). No differences were observed in any cancer-related end points or in actinic keratosis counts. The only quality of life difference was worse symptoms in the tretinoin group at 12 months after randomization. This trial in high-risk patients demonstrates that high-dose topical tretinoin is ineffective at reducing risk of KCs.
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Mandal, Gopa; Bhattacharya, Sudeshna; Das, Subrata; Ganguly, Tapan
2012-01-01
Steady state and time resolved spectroscopic measurements were made at the ambient temperature on an organic dyad, 1-(4-Chloro-phenyl)-3-(4-methoxy-naphthalen-1-yl)-propenone (MNCA), where the donor 1-methoxynaphthalene (1 MNT) is connected with the acceptor p-chloroacetophenone (PCA) by an unsaturated olefinic bond, in presence of Ag@TiO2 nanoparticles. Time resolved fluorescence and absorption measurements reveal that the rate parameters associated with charge separation, k(CS), within the dyad increases whereas charge recombination rate k(CR) reduces significantly when the surrounding medium is changed from only chloroform to mixture of chloroform and Ag@TiO2 (noble metal-semiconductor) nanocomposites. The observed results indicate that the dyad being combined with core-shell nanocomposites may form organic-inorganic nanocomposite system useful for developing light energy conversion devices. Use of metal-semiconductor nanoparticles may provide thus new ways to modulate charge recombination processes in light energy conversion devices. From comparison with the results obtained in our earlier investigations with only TiO2 nanoparticles, it is inferred that much improved version of light energy conversion device, where charge-separated species could be protected for longer period of time of the order of millisecond, could be designed by using metal-semiconductor core-shell nanocomposites rather than semiconductor nanoparticles only.
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Dutta Pal, Gopa; Paul, Abhijit; Yadav, Somnath; Bardhan, Munmun; De, Asish; Chowdhury, Joydeep; Jana, Aindrila; Ganguly, Tapan
2015-08-01
UV-vis absorption, steady state and time resolved spectroscopic investigations in pico and nanosecond time domain were made in the different environments on a novel synthesized dyad, 3-(2-methoxynaphthalen-1-yl)-1-(4-methoxyphenyl)prop-2-en-1-one (MNTMA) in its pristine form and when combined with gold (Au) nanoparticles i.e., in its nanocomposite structure. Both steady state and time resolved measurements coupled with the DFT calculations performed by using Gaussian 03 suit of software operated in the linux operating system show that though the dyad exhibits mainly the folded conformation in the ground state but on photoexcitation the nanocomposite form of dyad prefers to be in elongated structure in the excited state indicating its photoswitchable nature. Due to the predominancy of elongated isomeric form of the dyad in the excited state in presence of Au Nps, it appears that the dyad MNTMA may behave as a good light energy converter specially in its nanocomposite form. As larger charge separation rate (kcs ~ 4 x 10(8) s-1) is found relative to the rate associated with the energy wasting charge recombination processes (kcR ~ 3 x 10(5) s-1) in the nanocomposite form of the dyad, it demonstrates the suitability of constructing the efficient light energy conversion devices with Au-dyad hybrid nanomaterials.
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Kuzmenkov, Alexey I; Vassilevski, Alexander A; Kudryashova, Kseniya S; Nekrasova, Oksana V; Peigneur, Steve; Tytgat, Jan; Feofanov, Alexey V; Kirpichnikov, Mikhail P; Grishin, Eugene V
2015-05-08
The lesser Asian scorpion Mesobuthus eupeus (Buthidae) is one of the most widely spread and dispersed species of the Mesobuthus genus, and its venom is actively studied. Nevertheless, a considerable amount of active compounds is still under-investigated due to the high complexity of this venom. Here, we report a comprehensive analysis of putative potassium channel toxins (KTxs) from the cDNA library of M. eupeus venom glands, and we compare the deduced KTx structures with peptides purified from the venom. For the transcriptome analysis, we used conventional tools as well as a search for structural motifs characteristic of scorpion venom components in the form of regular expressions. We found 59 candidate KTxs distributed in 30 subfamilies and presenting the cysteine-stabilized α/β and inhibitor cystine knot types of fold. M. eupeus venom was then separated to individual components by multistage chromatography. A facile fluorescent system based on the expression of the KcsA-Kv1.1 hybrid channels in Escherichia coli and utilization of a labeled scorpion toxin was elaborated and applied to follow Kv1.1 pore binding activity during venom separation. As a result, eight high affinity Kv1.1 channel blockers were identified, including five novel peptides, which extend the panel of potential pharmacologically important Kv1 ligands. Activity of the new peptides against rat Kv1.1 channel was confirmed (IC50 in the range of 1-780 nm) by the two-electrode voltage clamp technique using a standard Xenopus oocyte system. Our integrated approach is of general utility and efficiency to mine natural venoms for KTxs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
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Variability of Potassium Channel Blockers in Mesobuthus eupeus Scorpion Venom with Focus on Kv1.1
Kuzmenkov, Alexey I.; Vassilevski, Alexander A.; Kudryashova, Kseniya S.; Nekrasova, Oksana V.; Peigneur, Steve; Tytgat, Jan; Feofanov, Alexey V.; Kirpichnikov, Mikhail P.; Grishin, Eugene V.
2015-01-01
The lesser Asian scorpion Mesobuthus eupeus (Buthidae) is one of the most widely spread and dispersed species of the Mesobuthus genus, and its venom is actively studied. Nevertheless, a considerable amount of active compounds is still under-investigated due to the high complexity of this venom. Here, we report a comprehensive analysis of putative potassium channel toxins (KTxs) from the cDNA library of M. eupeus venom glands, and we compare the deduced KTx structures with peptides purified from the venom. For the transcriptome analysis, we used conventional tools as well as a search for structural motifs characteristic of scorpion venom components in the form of regular expressions. We found 59 candidate KTxs distributed in 30 subfamilies and presenting the cysteine-stabilized α/β and inhibitor cystine knot types of fold. M. eupeus venom was then separated to individual components by multistage chromatography. A facile fluorescent system based on the expression of the KcsA-Kv1.1 hybrid channels in Escherichia coli and utilization of a labeled scorpion toxin was elaborated and applied to follow Kv1.1 pore binding activity during venom separation. As a result, eight high affinity Kv1.1 channel blockers were identified, including five novel peptides, which extend the panel of potential pharmacologically important Kv1 ligands. Activity of the new peptides against rat Kv1.1 channel was confirmed (IC50 in the range of 1–780 nm) by the two-electrode voltage clamp technique using a standard Xenopus oocyte system. Our integrated approach is of general utility and efficiency to mine natural venoms for KTxs. PMID:25792741
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Comparison of water extraction methods in Tibet based on GF-1 data
NASA Astrophysics Data System (ADS)
Jia, Lingjun; Shang, Kun; Liu, Jing; Sun, Zhongqing
2018-03-01
In this study, we compared four different water extraction methods with GF-1 data according to different water types in Tibet, including Support Vector Machine (SVM), Principal Component Analysis (PCA), Decision Tree Classifier based on False Normalized Difference Water Index (FNDWI-DTC), and PCA-SVM. The results show that all of the four methods can extract large area water body, but only SVM and PCA-SVM can obtain satisfying extraction results for small size water body. The methods were evaluated by both overall accuracy (OAA) and Kappa coefficient (KC). The OAA of PCA-SVM, SVM, FNDWI-DTC, PCA are 96.68%, 94.23%, 93.99%, 93.01%, and the KCs are 0.9308, 0.8995, 0.8962, 0.8842, respectively, in consistent with visual inspection. In summary, SVM is better for narrow rivers extraction and PCA-SVM is suitable for water extraction of various types. As for dark blue lakes, the methods using PCA can extract more quickly and accurately.
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Scenario based optimization of a container vessel with respect to its projected operating conditions
NASA Astrophysics Data System (ADS)
Wagner, Jonas; Binkowski, Eva; Bronsart, Robert
2014-06-01
In this paper the scenario based optimization of the bulbous bow of the KRISO Container Ship (KCS) is presented. The optimization of the parametrically modeled vessel is based on a statistically developed operational profile generated from noon-to-noon reports of a comparable 3600 TEU container vessel and specific development functions representing the growth of global economy during the vessels service time. In order to consider uncertainties, statistical fluctuations are added. An analysis of these data lead to a number of most probable upcoming operating conditions (OC) the vessel will stay in the future. According to their respective likeliness an objective function for the evaluation of the optimal design variant of the vessel is derived and implemented within the parametrical optimization workbench FRIENDSHIP Framework. In the following this evaluation is done with respect to vessel's calculated effective power based on the usage of potential flow code. The evaluation shows, that the usage of scenarios within the optimization process has a strong influence on the hull form.
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Tsao, Chang-Hui; Chen, Chien-Chun; Lin, Chen-Han; Yang, Hao-Yu; Lin, Suewei
2018-03-16
The fruit fly can evaluate its energy state and decide whether to pursue food-related cues. Here, we reveal that the mushroom body (MB) integrates hunger and satiety signals to control food-seeking behavior. We have discovered five pathways in the MB essential for hungry flies to locate and approach food. Blocking the MB-intrinsic Kenyon cells (KCs) and the MB output neurons (MBONs) in these pathways impairs food-seeking behavior. Starvation bi-directionally modulates MBON responses to a food odor, suggesting that hunger and satiety controls occur at the KC-to-MBON synapses. These controls are mediated by six types of dopaminergic neurons (DANs). By manipulating these DANs, we could inhibit food-seeking behavior in hungry flies or promote food seeking in fed flies. Finally, we show that the DANs potentially receive multiple inputs of hunger and satiety signals. This work demonstrates an information-rich central circuit in the fly brain that controls hunger-driven food-seeking behavior. © 2018, Tsao et al.
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Study of ground state optical transfer for ultracold alkali dimers
NASA Astrophysics Data System (ADS)
Bouloufa-Maafa, Nadia; Londono, Beatriz; Borsalino, Dimitri; Vexiau, Romain; Mahecha, Jorge; Dulieu, Olivier; Luc-Koenig, Eliane
2013-05-01
Control of molecular states by laser pulses offer promising potential applications. The manipulation of molecules by external fields requires precise knowledge of the molecular structure. Our motivation is to perform a detailed analysis of the spectroscopic properties of alkali dimers, with the aim to determine efficient optical paths to form molecules in the absolute ground state and to determine the optimal parameters of the optical lattices where those molecules are manipulated to avoid losses by collisions. To this end, we use state of the art molecular potentials, R-dependent spin-orbit coupling and transition dipole moment to perform our calculations. R-dependent SO coupling are of crucial importance because the transitions occur at internuclear distances where they are affected by this R-dependence. Efficient schemes to transfer RbCs, KRb and KCs to the absolute ground state as well as the optimal parameters of the optical lattices will be presented. This work was supported in part by ``Triangle de la Physique'' under contract 2008-007T-QCCM (Quantum Control of Cold Molecules).
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Li-Smerin, Yingying; Swartz, Kenton J.
2000-01-01
Hanatoxin inhibits voltage-gated K+ channels by modifying the energetics of activation. We studied the molecular determinants and physical location of the Hanatoxin receptors on the drk1 voltage-gated K+ channel. First, we made multiple substitutions at three previously identified positions in the COOH terminus of S3 to examine whether these residues interact intimately with the toxin. We also examined a region encompassing S1–S3 using alanine-scanning mutagenesis to identify additional determinants of the toxin receptors. Finally, guided by the structure of the KcsA K+ channel, we explored whether the toxin interacts with the peripheral extracellular surface of the pore domain in the drk1 K+ channel. Our results argue for an intimate interaction between the toxin and the COOH terminus of S3 and suggest that the Hanatoxin receptors are confined within the voltage-sensing domains of the channel, at least 20–25 Å away from the central pore axis. PMID:10828242
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Siksik, May; Krishnamurthy, Vikram
2017-09-01
This paper proposes a multi-dielectric Brownian dynamics simulation framework for design-space-exploration (DSE) studies of ion-channel permeation. The goal of such DSE studies is to estimate the channel modeling-parameters that minimize the mean-squared error between the simulated and expected "permeation characteristics." To address this computational challenge, we use a methodology based on statistical inference that utilizes the knowledge of channel structure to prune the design space. We demonstrate the proposed framework and DSE methodology using a case study based on the KcsA ion channel, in which the design space is successfully reduced from a 6-D space to a 2-D space. Our results show that the channel dielectric map computed using the framework matches with that computed directly using molecular dynamics with an error of 7%. Finally, the scalability and resolution of the model used are explored, and it is shown that the memory requirements needed for DSE remain constant as the number of parameters (degree of heterogeneity) increases.
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Liu, Jian-Yong; El-Khouly, Mohamed E; Fukuzumi, Shunichi; Ng, Dennis K P
2012-06-04
A ferrocene-distyryl BODIPY dyad and a ferrocene-distyryl BODIPY-C(60) triad are synthesized and characterized. Upon photoexcitation at the distyryl BODIPY unit, these arrays undergo photoinduced electron transfer to form the corresponding charge-separated species. Based on their redox potentials, determined by cyclic voltammetry, the direction of the charge separation and the energies of these states are revealed. Femtosecond transient spectroscopic studies reveal that a fast charge separation (k(CS) =1.0×10(10) s(-1)) occurs for both the ferrocene-distyryl BODIPY dyad and the ferrocene-distyryl BODIPY-C(60) triad, but that a relatively slow charge recombination is observed only for the triad. The lifetime of the charge-separated state is 500 ps. Charge recombination of the dyad and triad leads to population of the triplet excited sate of ferrocene and the ground state, respectively. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Tsao, Chang-Hui; Chen, Chien-Chun; Lin, Chen-Han; Yang, Hao-Yu
2018-01-01
The fruit fly can evaluate its energy state and decide whether to pursue food-related cues. Here, we reveal that the mushroom body (MB) integrates hunger and satiety signals to control food-seeking behavior. We have discovered five pathways in the MB essential for hungry flies to locate and approach food. Blocking the MB-intrinsic Kenyon cells (KCs) and the MB output neurons (MBONs) in these pathways impairs food-seeking behavior. Starvation bi-directionally modulates MBON responses to a food odor, suggesting that hunger and satiety controls occur at the KC-to-MBON synapses. These controls are mediated by six types of dopaminergic neurons (DANs). By manipulating these DANs, we could inhibit food-seeking behavior in hungry flies or promote food seeking in fed flies. Finally, we show that the DANs potentially receive multiple inputs of hunger and satiety signals. This work demonstrates an information-rich central circuit in the fly brain that controls hunger-driven food-seeking behavior. PMID:29547121
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Various supercritical carbon dioxide cycle layouts study for molten carbonate fuel cell application
NASA Astrophysics Data System (ADS)
Bae, Seong Jun; Ahn, Yoonhan; Lee, Jekyoung; Lee, Jeong Ik
2014-12-01
Various supercritical carbon dioxide (S-CO2) cycles for a power conversion system of a Molten Carbonate Fuel Cell (MCFC) hybrid system are studied in this paper. Re-Compressing Brayton (RCB) cycle, Simple Recuperated Brayton (SRB) cycle and Simple Recuperated Transcritical (SRT) cycle layouts were selected as candidates for this study. In addition, a novel concept of S-CO2 cycle which combines Brayton cycle and Rankine cycle is proposed and intensively studied with other S-CO2 layouts. A parametric study is performed to optimize the total system to be compact and to achieve wider operating range. Performances of each S-CO2 cycle are compared in terms of the thermal efficiency, net electricity of the MCFC hybrid system and approximate total volumes of each S-CO2 cycle. As a result, performance and total physical size of S-CO2 cycle can be better understood for MCFC S-CO2 hybrid system and especially, newly suggested S-CO2 cycle shows some success.
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Exciplex formation and excited state deactivation of difluoroborondipyrromethene (Bodipy) dyads.
Benniston, Andrew C; Copley, Graeme; Lemmetyinen, Helge; Tkachenko, Nikolai V
2010-06-07
Two series of geometrically-related dyads are discussed based on the difluoroborondipyrromethene (Bodipy) unit, and incorporating covalently attached hydroquinone/quinone groups. These units are anchored directly, or via a phenylene spacer, to the Bodipy core at the meso position in one series (BD-MHQ, BD-MQ, BD-MPHQ, BD-MPQ), but for the second series the attachment site is the 2-position (BD-SHQ, BD-SQ, BD-SPHQ, BD-SPQ). The compounds show various levels of fluorescence depending on the oxidation state of the appended group and the substitution pattern. In non-polar solvents such as toluene, diethyl ether and dichlorobenzene, the S(1) state deactivation of the Bodipy unit in BD-SPQ and BD-MPQ is dominated by (1, 3)exciplex formation, which has not been reported for Bodipy derivatives so far. In the latter molecule, the decay of the exciplex is divided between population of the Bodipy triplet state (13 %-21 %) and ground state reformation. This partitioning is not seen for the side-on substituted derivative, BD-SPQ, and only ground state reformation is observed following decay of the exciplex. This difference in behavior is explained by the radical-pair inter-system-crossing mechanism, which more effectively operates in BD-MPQ because of the orthogonality of the donor-acceptor units. In the more polar solvent CH(3)CN all the quinone derivatives show fast formation of the charge-separated state (k(CS)) followed by slower charge recombination (k(CR)). The ratio k(CS)/k(CR)
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Quantum mechanical calculations of charge effects on gating the KcsA channel.
Kariev, Alisher M; Znamenskiy, Vasiliy S; Green, Michael E
2007-05-01
A series of ab initio (density functional) calculations were carried out on side chains of a set of amino acids, plus water, from the (intracellular) gating region of the KcsA K(+) channel. Their atomic coordinates, except hydrogen, are known from X-ray structures [D.A. Doyle, J.M. Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait, R. MacKinnon, The structure of the potassium channel: molecular basis of K(+) conduction and selectivity, Science 280 (1998) 69-77; R. MacKinnon, S.L. Cohen, A. Kuo, A. Lee, B.T. Chait, Structural conservation in prokaryotic and eukaryotic potassium channels, Science 280 (1998) 106-109; Y. Jiang, A. Lee, J. Chen, M. Cadene, B.T. Chait, R. MacKinnon, The open pore conformation of potassium channels. Nature 417 (2001) 523-526], as are the coordinates of some water oxygen atoms. The 1k4c structure is used for the starting coordinates. Quantum mechanical optimization, in spite of the starting configuration, places the atoms in positions much closer to the 1j95, more tightly closed, configuration. This state shows four water molecules forming a "basket" under the Q119 side chains, blocking the channel. When a hydrated K(+) approaches this "basket", the optimized system shows a strong set of hydrogen bonds with the K(+) at defined positions, preventing further approach of the K(+) to the basket. This optimized structure with hydrated K(+) added shows an ice-like 12 molecule nanocrystal of water. If the water molecules exchange, unless they do it as a group, the channel will remain blocked. The "basket" itself appears to be very stable, although it is possible that the K(+) with its hydrating water molecules may be more mobile, capable of withdrawing from the gate. It is also not surprising that water essentially freezes, or forms a kind of glue, in a nanometer space; this agrees with experimental results on a rather different, but similarly sized (nm dimensions) system [K.B. Jinesh, J.W.M. Frenken, Capillary condensation in atomic scale friction: how water acts like a glue, Phys. Rev. Lett. 96 (2006) 166103/1-4]. It also agrees qualitatively with simulations on channels [A. Anishkin, S. Sukharev, Water dynamics and dewetting transitions in the small mechanosensitive channel MscS, Biophys. J. 86 (2004) 2883-2895; O. Beckstein, M.S.P. Sansom, Liquid-vapor oscillations of water in hydrophobic nanopores, Proc. Natl Acad. Sci. U. S. A. 100 (2003) 7063-7068] and on featureless channel-like systems [J. Lu, M.E. Green, Simulation of water in a pore with charges: application to a gating mechanism for ion channels, Prog. Colloid Polym. Sci. 103 (1997) 121-129], in that it forms a boundary on water that is not obvious from the liquid state. The idea that a structure is stable, even if individual molecules exchange, is well known, for example from the hydration shell of ions. We show that when charges are added in the form of protons to the domains (one proton per domain), the optimized structure is open. No stable water hydrogen bonds hold it together; an opening of 11.0 A appears, measured diagonally between non-neighboring domains as glutamine 119 carbonyl O-O distance. This is comparable to the opening in the MthK potassium channel structure that is generally agreed to be open. The appearance of the opening is in rather good agreement with that found by Perozo and coworkers. In contrast, in the uncharged structure this diagonal distance is 6.5 A, and the water "basket" constricts the uncharged opening still further, with the ice-like structure that couples the K(+) ion to the gating region freezing the entrance to the channel. Comparison with our earlier model for voltage gated channels suggests that a similar mechanism may apply in those channels.
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Innovative open air brayton combined cycle systems for the next generation nuclear power plants
NASA Astrophysics Data System (ADS)
Zohuri, Bahman
The purpose of this research was to model and analyze a nuclear heated multi-turbine power conversion system operating with atmospheric air as the working fluid. The air is heated by a molten salt, or liquid metal, to gas heat exchanger reaching a peak temperature of 660 0C. The effects of adding a recuperator or a bottoming steam cycle have been addressed. The calculated results are intended to identify paths for future work on the next generation nuclear power plant (GEN-IV). This document describes the proposed system in sufficient detail to communicate a good understanding of the overall system, its components, and intended uses. The architecture is described at the conceptual level, and does not replace a detailed design document. The main part of the study focused on a Brayton --- Rankine Combined Cycle system and a Recuperated Brayton Cycle since they offer the highest overall efficiencies. Open Air Brayton power cycles also require low cooling water flows relative to other power cycles. Although the Recuperated Brayton Cycle achieves an overall efficiency slightly less that the Brayton --- Rankine Combined Cycle, it is completely free of a circulating water system and can be used in a desert climate. Detailed results of modeling a combined cycle Brayton-Rankine power conversion system are presented. The Rankine bottoming cycle appears to offer a slight efficiency advantage over the recuperated Brayton cycle. Both offer very significant advantages over current generation Light Water Reactor steam cycles. The combined cycle was optimized as a unit and lower pressure Rankine systems seem to be more efficient. The combined cycle requires a lot less circulating water than current power plants. The open-air Brayton systems appear to be worth investigating, if the higher temperatures predicted for the Next Generation Nuclear Plant do materialize.
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D'Souza, Francis; El-Khouly, Mohamed E; Gadde, Suresh; McCarty, Amy L; Karr, Paul A; Zandler, Melvin E; Araki, Yasuyaki; Ito, Osamu
2005-05-26
Spectroscopic, redox, and electron transfer reactions of a self-assembled donor-acceptor dyad formed by axial coordination of magnesium meso-tetraphenylporphyrin (MgTPP) and fulleropyrrolidine appended with an imidazole coordinating ligand (C(60)Im) were investigated. Spectroscopic studies revealed the formation of a 1:1 C(60)Im:MgTPP supramolecular complex, and the anticipated 1:2 complex could not be observed because of the needed large amounts of the axial coordinating ligand. The formation constant, K(1), for the 1:1 complex was found to be (1.5 +/- 0.3) x 10(4) M(-1), suggesting fairly stable complex formation. The geometric and electronic structures of the dyads were probed by ab initio B3LYP/3-21G() methods. The majority of the highest occupied frontier molecular orbital (HOMO) was found to be located on the MgTPP entity, while the lowest unoccupied molecular orbital (LUMO) was on the fullerene entity, suggesting that the charge-separated state of the supramolecular complex is C(60)Im(*-):MgTPP(*+). Redox titrations involving MgTPP and C(60)Im allowed accurate determination of the oxidation and reduction potentials of the donor and acceptor entities in the supramolecular complex. These studies revealed more difficult oxidation, by about 100 mV, for MgTPP in the pentacoordinated C(60)Im:MgTPP compared to pristine MgTPP in o-dichlorobenzene. A total of six one-electron redox processes corresponding to the oxidation and reduction of the zinc porphyrin ring and the reduction of fullerene entities was observed within the accessible potential window of the solvent. The excited state events were monitored by both steady state and time-resolved emission as well as transient absorption techniques. In o-dichlorobenzene, upon coordination of C(60)Im to MgTPP, the main quenching pathway involved electron transfer from the singlet excited MgTPP to the C(60)Im moiety. The rate of forward electron transfer, k(CS), calculated from the picosecond time-resolved emission studies was found to be 1.1 x 10(10) s(-1) with a quantum yield, Phi(CS), of 0.99, indicating fast and efficient charge separation. The rate of charge recombination, k(CR), evaluated from nanosecond transient absorption studies, was found to be 8.3 x 10(7) s(-1). A comparison between k(CS) and k(CR) suggested an excellent opportunity to utilize the charge-separated state for further electron-mediating processes.
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2014-01-01
Introduction Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice. Methods The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse’s back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors. Results We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15–17 days of controls. RT2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs’ migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay. Conclusions Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans. PMID:24423450
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Navone, Stefania Elena; Pascucci, Luisa; Dossena, Marta; Ferri, Anna; Invernici, Gloria; Acerbi, Francesco; Cristini, Silvia; Bedini, Gloria; Tosetti, Valentina; Ceserani, Valentina; Bonomi, Arianna; Pessina, Augusto; Freddi, Giuliano; Alessandrino, Antonio; Ceccarelli, Piero; Campanella, Rolando; Marfia, Giovanni; Alessandri, Giulio; Parati, Eugenio Agostino
2014-01-14
Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice. The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse's back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors. We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15-17 days of controls. RT2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs' migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay. Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans.
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Kim, Ilsoo; Allen, Toby W
2012-04-28
Free energy perturbation, a method for computing the free energy difference between two states, is often combined with non-Boltzmann biased sampling techniques in order to accelerate the convergence of free energy calculations. Here we present a new extension of the Bennett acceptance ratio (BAR) method by combining it with umbrella sampling (US) along a reaction coordinate in configurational space. In this approach, which we call Bennett acceptance ratio with umbrella sampling (BAR-US), the conditional histogram of energy difference (a mapping of the 3N-dimensional configurational space via a reaction coordinate onto 1D energy difference space) is weighted for marginalization with the associated population density along a reaction coordinate computed by US. This procedure produces marginal histograms of energy difference, from forward and backward simulations, with higher overlap in energy difference space, rendering free energy difference estimations using BAR statistically more reliable. In addition to BAR-US, two histogram analysis methods, termed Bennett overlapping histograms with US (BOH-US) and Bennett-Hummer (linear) least square with US (BHLS-US), are employed as consistency and convergence checks for free energy difference estimation by BAR-US. The proposed methods (BAR-US, BOH-US, and BHLS-US) are applied to a 1-dimensional asymmetric model potential, as has been used previously to test free energy calculations from non-equilibrium processes. We then consider the more stringent test of a 1-dimensional strongly (but linearly) shifted harmonic oscillator, which exhibits no overlap between two states when sampled using unbiased Brownian dynamics. We find that the efficiency of the proposed methods is enhanced over the original Bennett's methods (BAR, BOH, and BHLS) through fast uniform sampling of energy difference space via US in configurational space. We apply the proposed methods to the calculation of the electrostatic contribution to the absolute solvation free energy (excess chemical potential) of water. We then address the controversial issue of ion selectivity in the K(+) ion channel, KcsA. We have calculated the relative binding affinity of K(+) over Na(+) within a binding site of the KcsA channel for which different, though adjacent, K(+) and Na(+) configurations exist, ideally suited to these US-enhanced methods. Our studies demonstrate that the significant improvements in free energy calculations obtained using the proposed methods can have serious consequences for elucidating biological mechanisms and for the interpretation of experimental data.
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Technical and economic evaluation of a Brayton-Rankine combined cycle solar-thermal power plant
NASA Astrophysics Data System (ADS)
Wright, J. D.; Copeland, R. J.
1981-05-01
An assessment of gas-liquid direct-contact heat exchange and of a new storage-coupled system was conducted. Both technical and economic issues are evaluated. Specifically, the storage-coupled combined cycle is compared with a molten salt system. The open Brayton cycle system is used as a topping cycle, and the reject heat powers the molten salt/Rankine system. In this study the molten salt system is left unmodified, the Brayton cycle is integrated on top of a Marietta description of an existing molten salt plant. This compares a nonoptimized combined cycle with an optimized molten salt system.
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NASA Technical Reports Server (NTRS)
Brown, D. H.; Corman, J. C.
1976-01-01
Ten energy conversion systems are defined and analyzed in terms of efficiency. These include: open-cycle gas turbine recuperative; open-cycle gas turbine; closed-cycle gas turbine; supercritical CO2 cycle; advanced steam cycle; liquid metal topping cycle; open-cycle MHD; closed-cycle inert gas MHD; closed-cycle liquid metal MHD; and fuel cells. Results are presented.
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Performance and economics of advanced energy conversion systems for coal and coal-derived fuels
NASA Technical Reports Server (NTRS)
Corman, J. C.; Fox, G. R.
1978-01-01
The desire to establish an efficient Energy Conversion System to utilize the fossil fuel of the future - coal - has produced many candidate systems. A comparative technical/economic evaluation was performed on the seven most attractive advanced energy conversion systems. The evaluation maintains a cycle-to-cycle consistency in both performance and economic projections. The technical information base can be employed to make program decisions regarding the most attractive concept. A reference steam power plant was analyzed to the same detail and, under the same ground rules, was used as a comparison base. The power plants were all designed to utilize coal or coal-derived fuels and were targeted to meet an environmental standard. The systems evaluated were two advanced steam systems, a potassium topping cycle, a closed cycle helium system, two open cycle gas turbine combined cycles, and an open cycle MHD system.
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Exergy analysis of helium liquefaction systems based on modified Claude cycle with two-expanders
NASA Astrophysics Data System (ADS)
Thomas, Rijo Jacob; Ghosh, Parthasarathi; Chowdhury, Kanchan
2011-06-01
Large-scale helium liquefaction systems, being energy-intensive, demand judicious selection of process parameters. An effective tool for design and analysis of thermodynamic cycles for these systems is exergy analysis, which is used to study the behavior of a helium liquefaction system based on modified Claude cycle. Parametric evaluation using process simulator Aspen HYSYS® helps to identify the effects of cycle pressure ratio and expander flow fraction on the exergetic efficiency of the liquefaction cycle. The study computes the distribution of losses at different refrigeration stages of the cycle and helps in selecting optimum cycle pressures, operating temperature levels of expanders and mass flow rates through them. Results from the analysis may help evolving guidelines for designing appropriate thermodynamic cycles for practical helium liquefaction systems.
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Assessment of disk MHD generators for a base load powerplant
NASA Technical Reports Server (NTRS)
Chubb, D. L.; Retallick, F. D.; Lu, C. L.; Stella, M.; Teare, J. D.; Loubsky, W. J.; Louis, J. F.; Misra, B.
1981-01-01
Results from a study of the disk MHD generator are presented. Both open and closed cycle disk systems were investigated. Costing of the open cycle disk components (nozzle, channel, diffuser, radiant boiler, magnet and power management) was done. However, no detailed costing was done for the closed cycle systems. Preliminary plant design for the open cycle systems was also completed. Based on the system study results, an economic assessment of the open cycle systems is presented. Costs of the open cycle disk conponents are less than comparable linear generator components. Also, costs of electricity for the open cycle disk systems are competitive with comparable linear systems. Advantages of the disk design simplicity are considered. Improvements in the channel availability or a reduction in the channel lifetime requirement are possible as a result of the disk design.
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A comparison of production system life cycle models
NASA Astrophysics Data System (ADS)
Attri, Rajesh; Grover, Sandeep
2012-09-01
Companies today need to keep up with the rapidly changing market conditions to stay competitive. The main issues in this paper are related to a company's market and its competitors. The prediction of market behavior is helpful for a manufacturing enterprise to build efficient production systems. However, these predictions are usually not reliable. A production system is required to adapt to changing markets, but such requirement entails higher cost. Hence, analyzing different life cycle models of the production system is necessary. In this paper, different life cycle models of the production system are compared to evaluate the distinctive features and the limitations of each model. Furthermore, the difference between product life cycle and production life cycle is summarized, and the effect of product life cycle on production life cycle is explained. Finally, a production system life cycle model, along with key activities to be performed in each stage, is proposed specifically for the manufacturing sector.
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Combined rankine and vapor compression cycles
Radcliff, Thomas D.; Biederman, Bruce P.; Brasz, Joost J.
2005-04-19
An organic rankine cycle system is combined with a vapor compression cycle system with the turbine generator of the organic rankine cycle generating the power necessary to operate the motor of the refrigerant compressor. The vapor compression cycle is applied with its evaporator cooling the inlet air into a gas turbine, and the organic rankine cycle is applied to receive heat from a gas turbine exhaust to heat its boiler within one embodiment, a common condenser is used for the organic rankine cycle and the vapor compression cycle, with a common refrigerant, R-245a being circulated within both systems. In another embodiment, the turbine driven generator has a common shaft connected to the compressor to thereby eliminate the need for a separate motor to drive the compressor. In another embodiment, an organic rankine cycle system is applied to an internal combustion engine to cool the fluids thereof, and the turbo charged air is cooled first by the organic rankine cycle system and then by an air conditioner prior to passing into the intake of the engine.
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Supercritical CO2 Power Cycles: Design Considerations for Concentrating Solar Power
DOE Office of Scientific and Technical Information (OSTI.GOV)
Neises, Ty; Turchi, Craig
2014-09-01
A comparison of three supercritical CO2 Brayton cycles: the simple cycle, recompression cycle and partial-cooling cycle indicates the partial-cooling cycle is favored for use in concentrating solar power (CSP) systems. Although it displays slightly lower cycle efficiency versus the recompression cycle, the partial-cooling cycle is estimated to have lower total recuperator size, as well as a lower maximum s-CO2 temperature in the high-temperature recuperator. Both of these effects reduce recuperator cost. Furthermore, the partial-cooling cycle provides a larger temperature differential across the turbine, which translates into a smaller, more cost-effective thermal energy storage system. The temperature drop across the turbinemore » (and by extension, across a thermal storage system) for the partial-cooling cycle is estimated to be 23% to 35% larger compared to the recompression cycle of equal recuperator conductance between 5 and 15 MW/K. This reduces the size and cost of the thermal storage system. Simulations by NREL and Abengoa Solar indicate the partial-cooling cycle results in a lower LCOE compared with the recompression cycle, despite the former's slightly lower cycle efficiency. Advantages of the recompression cycle include higher thermal efficiency and potential for a smaller precooler. The overall impact favors the use of a partial-cooling cycle for CSP compared to the more commonly analyzed recompression cycle.« less
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Murakami, Satoshi; Minami-Ohtsubo, Maki; Nakato, Ryuichiro; Shirahige, Katsuhiko; Tabata, Tetsuya
2017-05-31
Multiple components have been identified that exhibit different stabilities for aversive olfactory memory in Drosophila These components have been defined by behavioral and genetic studies and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies, which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact. SIGNIFICANCE STATEMENT Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model with which to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term, and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila , Rgk1, which plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Copyright © 2017 the authors 0270-6474/17/375496-•$15.00/0.
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Environmental tests of metallization systems for terrestrial photovoltaic cells
NASA Technical Reports Server (NTRS)
Alexander, P., Jr.
1985-01-01
Seven different solar cell metallization systems were subjected to temperature cycling tests and humidity tests. Temperature cycling excursions were -50 deg C to 150 deg C per cycle. Humidity conditions were 70 deg C at 98% relative humidity. The seven metallization systems were: Ti/Ag, Ti/Pd/Ag, Ti/Pd/Cu, Ni/Cu, Pd/Ni/Solder, Cr/Pd/Ag, and thick film Ag. All metallization systems showed a slight to moderate decrease in cell efficiencies after subjection to 1000 temperature cycles. Six of the seven metallization systems also evidenced slight increases in cell efficiencies after moderate numbers of cycles, generally less than 100 cycles. The copper based systems showed the largest decrease in cell efficiencies after temperature cycling. All metallization systems showed moderate to large decreases in cell efficiencies after 123 days of humidity exposure. The copper based systems again showed the largest decrease in cell efficiencies after humidity exposure. Graphs of the environmental exposures versus cell efficiencies are presented for each metallization system, as well as environmental exposures versus fill factors or series resistance.
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21 CFR 866.1645 - Fully automated short-term incubation cycle antimicrobial susceptibility system.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fully automated short-term incubation cycle... Diagnostic Devices § 866.1645 Fully automated short-term incubation cycle antimicrobial susceptibility system. (a) Identification. A fully automated short-term incubation cycle antimicrobial susceptibility system...
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Thermodynamic analysis of a new dual evaporator CO2 transcritical refrigeration cycle
NASA Astrophysics Data System (ADS)
Abdellaoui, Ezzaalouni Yathreb; Kairouani, Lakdar Kairouani
2017-03-01
In this work, a new dual-evaporator CO2 transcritical refrigeration cycle with two ejectors is proposed. In this new system, we proposed to recover the lost energy of condensation coming off the gas cooler and operate the refrigeration cycle ejector free and enhance the system performance and obtain dual-temperature refrigeration simultaneously. The effects of some key parameters on the thermodynamic performance of the modified cycle are theoretically investigated based on energetic and exergetic analysis. The simulation results for the modified cycle indicate more effective system performance improvement than the single ejector in the CO2 vapor compression cycle using ejector as an expander ranging up to 46%. The exergetic analysis for this system is made. The performance characteristics of the proposed cycle show its promise in dual-evaporator refrigeration system.
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5 CFR 930.301 - Information systems security awareness training program.
Code of Federal Regulations, 2012 CFR
2012-01-01
... training in system/application life cycle management, risk management, and contingency planning. (4) Chief... security management, system/application life cycle management, risk management, and contingency planning... management; and management and implementation level training in system/application life cycle management...
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DOT National Transportation Integrated Search
2015-05-01
The research team developed a comprehensive Benefit/Cost (B/C) analysis framework to evaluate existing and anticipated : intelligent transportation system (ITS) strategies, particularly, adaptive traffic control systems and ramp metering systems, : i...
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Nuclear Aircraft Feasibility Study. Volume 1
1975-03-01
Cycle 6-36 6.2.2 Helium Mass Flow 6-42 6.2.3 Fan Pressure Ratio 6-42 6.2.4 Regenerative Cycle Application 6-43 6.2.5 Brayton Cycle...6-8 Engine Systems Summary 6-9 T-S Diagram of Ideal Brayton Cycle 6-13 T-S Diagram of Brayton Cycle for Turbofan Engine 6-15 Comparison of... Brayton Closed Cycle Thermodynamic Analysis 6-50 6.2.8-1 Indirect Cycle Gas Circulation System 6-53 6.2.8-2 Gas Turbine Generator — Pump Cycle
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Schnoor, Jerald L.
2014-01-01
Theoretically, sequential cycles of dechlorination followed by aerobic bio-oxidation are desirable to achieve complete degradation of a mixture of higher and lower chlorinated PCBs. In this research, soil was artificially contaminated with polychlorinated biphenyls (PCBs) in mixture and as single congeners, aged, and planted with two different plant species. Alternating redox cycles were created in the root zone of plants by flooding and draining the soil. Over 32 weeks, switchgrass (Panicum virgatum) and poplar (Populus deltoids x nigra DN34) planted systems that were exposed to alternate cycles of flooding performed better in reducing parent PCBs than planted systems that were not cycled (p<0.05). The cycled systems also had a higher mass of PCB transformation products than the uncycled systems. Multiple cycles were necessary to achieve significant differences between the cycled and uncycled treatments. PMID:24860241
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Cascaded organic rankine cycles for waste heat utilization
Radcliff, Thomas D [Vernon, CT; Biederman, Bruce P [West Hartford, CT; Brasz, Joost J [Fayetteville, NY
2011-05-17
A pair of organic Rankine cycle systems (20, 25) are combined and their respective organic working fluids are chosen such that the organic working fluid of the first organic Rankine cycle is condensed at a condensation temperature that is well above the boiling point of the organic working fluid of the second organic Rankine style system, and a single common heat exchanger (23) is used for both the condenser of the first organic Rankine cycle system and the evaporator of the second organic Rankine cycle system. A preferred organic working fluid of the first system is toluene and that of the second organic working fluid is R245fa.
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Wright, Steven A.; Pickard, Paul S.; Vernon, Milton E.; Radel, Ross F.
2017-08-29
Various technologies pertaining to tuning composition of a fluid mixture in a supercritical Brayton cycle power generation system are described herein. Compounds, such as Alkanes, are selectively added or removed from an operating fluid of the supercritical Brayton cycle power generation system to cause the critical temperature of the fluid to move up or down, depending upon environmental conditions. As efficiency of the supercritical Brayton cycle power generation system is substantially optimized when heat is rejected near the critical temperature of the fluid, dynamically modifying the critical temperature of the fluid based upon sensed environmental conditions improves efficiency of such a system.
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Sompornpisut, Pornthep; Roux, Benoît; Perozo, Eduardo
2008-01-01
We present an approach for incorporating solvent accessibility data from electron paramagnetic resonance experiments in the structural refinement of membrane proteins through restrained molecular dynamics simulations. The restraints have been parameterized from oxygen (ΠO2) and nickel-ethylenediaminediacetic acid (ΠNiEdda) collision frequencies, as indicators of lipid or aqueous exposed spin-label sites. These are enforced through interactions between a pseudoatom representation of the covalently attached Nitroxide spin-label and virtual “solvent” particles corresponding to O2 and NiEdda in the surrounding environment. Interactions were computed using an empirical potential function, where the parameters have been optimized to account for the different accessibilities of the spin-label pseudoatoms to the surrounding environment. This approach, “pseudoatom-driven solvent accessibility refinement”, was validated by refolding distorted conformations of the Streptomyces lividans potassium channel (KcsA), corresponding to a range of 2–30 Å root mean-square deviations away from the native structure. Molecular dynamics simulations based on up to 58 electron paramagnetic resonance restraints derived from spin-label mutants were able to converge toward the native structure within 1–3 Å root mean-square deviations with minimal computational cost. The use of energy-based ranking and structure similarity clustering as selection criteria helped in the convergence and identification of correctly folded structures from a large number of simulations. This approach can be applied to a variety of integral membrane protein systems, regardless of oligomeric state, and should be particularly useful in calculating conformational changes from a known reference crystal structure. PMID:18676641
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The Barium Site in a Potassium Channel by X-Ray Crystallography
Jiang, Youxing; MacKinnon, Roderick
2000-01-01
X-ray diffraction data were collected from frozen crystals (100°K) of the KcsA K+ channel equilibrated with solutions containing barium chloride. Difference electron density maps (Fbarium − Fnative, 5.0 Å resolution) show that Ba2+ resides at a single location within the selectivity filter. The Ba2+ blocking site corresponds to the internal aspect (adjacent to the central cavity) of the “inner ion” position where an alkali metal cation is found in the absence of the blocking Ba2+ ion. The location of Ba2+ with respect to Rb+ ions in the pore is in good agreement with the findings on the functional interaction of Ba2+ with K+ (and Rb+) in Ca2+-activated K+ channels (Neyton, J., and C. Miller. 1988. J. Gen. Physiol. 92:549–567). Taken together, these structural and functional data imply that at physiological ion concentrations a third ion may interact with two ions in the selectivity filter, perhaps by entering from one side and displacing an ion on the opposite side. PMID:10694255
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A Potential Role for CHH DNA Methylation in Cotton Fiber Growth Patterns
Jin, Xiang; Pang, Yu; Jia, Fangxing; Xiao, Guanghui; Li, Qin; Zhu, Yuxian
2013-01-01
DNA methylation controls many aspects of plant growth and development. Here, we report a novel annual growth potential change that may correlate with changes in levels of the major DNA demethylases and methyltransferases in cotton ovules harvested at different times of the year. The abundances of DNA demethylases, at both the mRNA and protein levels, increased significantly from February to August and decreased during the remainder of the 12-month period, with the opposite pattern observed for DNA methyltransferases. Over the course of one year, substantial changes in methylcytosine content was observed at certain CHH sites (H = A, C, or T) in the promoter regions of the ETHYLENE RESPONSIVE FACTOR 6 (ERF6), SUPPRESSION OF RVS 161 DELTA 4 (SUR4) and 3-KETOACYL-COA SYNTHASE 13 (KCS13), which regulate cotton fiber growth. Three independent techniques were used to confirm the annual fluctuations in DNA methylation. Furthermore, in homozygous RNAi lines specifically targeting REPRESSOR OF SILENCING 1 (ROS1, a conserved DNA demethylase domain), promotion of DNA methylation significantly reduced fiber growth during August. PMID:23593241
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Zhou, Ding'an; Wei, Zhiyun; Deng, Shanshan; Wang, Teng; Zai, Meiqing; Wang, Honglian; Guo, Luo; Zhang, Junyu; Zhong, Hailei; He, Lin; Xing, Qinghe
2013-06-01
One important function of melanocytes (MCs) is to produce and transfer melanin to neighbouring keratinocytes (KCs) to protect epithelial cells from UV radiation. The mechanisms regulating the specific migration and localisation of the MC lineage remain unknown. We have found three heterozygous mutations that cause amino acid substitutions in the SASH1 gene in individuals with a kind of dyschromatosis. In epidermal tissues from an affected individual, we observed the increased transepithelial migration of melanocytes. Functional analyses indicate that these SASH1 mutations not only cause the increased migration of A375 cells and but also induce intensive bindings with two novel cell adhesion partners IQGAP1 and Gαs. Further, SASH1 mutations induce uniform loss of E-Cadherin in human A375 cells. Our findings suggest a new scaffold protein SASH1 to regulate IQGAP1-E-Cadherin signalling and demonstrate a novel crosstalking between GPCR signalling, calmodulin signalling for the modulation of MCs invasion. Copyright © 2013 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Leavy, Aisling
2015-09-01
In the evolving field of mathematics education, there is the need to maintain the relationship between what is presented in college level preparation courses and the skills required to teach mathematics in classrooms. This research examines the knowledge demands placed on 73 pre-service primary teachers as they use lesson study to plan and teach data handling in primary classrooms. Pre-service teachers are observed as they plan, teach and re-teach data lessons in classrooms. Problems of practice are identified and categorized using the Ball, Thames and Phelps (2008) subdomains of common content knowledge (CCK), specialized content knowledge (SCK), knowledge of content and students (KCS) and knowledge of content and teaching (KCT). The results provide insights into the specific knowledge demands placed on early career teachers when teaching data and statistics and identifies foci area that can be addressed in teacher preparation programs. The results illustrate that development of understandings in one knowledge subdomain can motivate and impact learning in another subdomain. These interrelationships were found to exist both within and between the domains of content and pedagogical content knowledge.
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2006-12-01
warfighters requirements and identifies system performance short-comings over its life cycle. 15. NUMBER OF PAGES 89 14. SUBJECT TERMS Information...the system performs to warfighters requirements and identifies system performance short-comings over its life cycle. vi...3 II. DEFENSE ACQUISITION LIFE CYCLE CURRENT STAGE ANALYSIS.......5 A. INTRODUCTION
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Evaluation of undeveloped rocket engine cycle applications to advanced transportation
NASA Technical Reports Server (NTRS)
1990-01-01
Undeveloped pump-fed, liquid propellant rocket engine cycles were assessed and evaluated for application to Next Manned Transportation System (NMTS) vehicles, which would include the evolving Space Transportation System (STS Evolution), the Personnel Launch System (PLS), and the Advanced Manned Launch System (AMLS). Undeveloped engine cycles selected for further analysis had potential for increased reliability, more maintainability, reduced cost, and improved (or possibly level) performance when compared to the existing SSME and proposed STME engines. The split expander (SX) cycle, the full flow staged combustion (FFSC) cycle, and a hybrid version of the FFSC, which has a LOX expander drive for the LOX pump, were selected for definition and analysis. Technology requirements and issues were identified and analyses of vehicle systems weight deltas using the SX and FFSC cycles in AMLS vehicles were performed. A strawman schedule and cost estimate for FFSC subsystem technology developments and integrated engine system demonstration was also provided.
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Information system life-cycle and documentation standards, volume 1
NASA Technical Reports Server (NTRS)
Callender, E. David; Steinbacher, Jody
1989-01-01
The Software Management and Assurance Program (SMAP) Information System Life-Cycle and Documentation Standards Document describes the Version 4 standard information system life-cycle in terms of processes, products, and reviews. The description of the products includes detailed documentation standards. The standards in this document set can be applied to the life-cycle, i.e., to each phase in the system's development, and to the documentation of all NASA information systems. This provides consistency across the agency as well as visibility into the completeness of the information recorded. An information system is software-intensive, but consists of any combination of software, hardware, and operational procedures required to process, store, or transmit data. This document defines a standard life-cycle model and content for associated documentation.
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Singh, N; Lim, R B; Sawyer, M A
2000-07-01
The cell cycle and the cell cycle control system are the engines that drive life. They allow for the processes of cell renewal and the growth of organisms, under controlled conditions. The control system is essential for the monitoring of normal cell growth and replication of genetic material and to ensure that normal, functional daughter cells are produced at completion of each cell cycle. Although certain clinical applications exist which take advantage of the events of the cell cycle, our understanding of its mechanisms and how to manipulate them is infantile. The next decades will continue to see the effort of many researchers focused upon unlocking the mysteries of the cell cycle and the cell cycle control system.
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Phase-amplitude reduction of transient dynamics far from attractors for limit-cycling systems
NASA Astrophysics Data System (ADS)
Shirasaka, Sho; Kurebayashi, Wataru; Nakao, Hiroya
2017-02-01
Phase reduction framework for limit-cycling systems based on isochrons has been used as a powerful tool for analyzing the rhythmic phenomena. Recently, the notion of isostables, which complements the isochrons by characterizing amplitudes of the system state, i.e., deviations from the limit-cycle attractor, has been introduced to describe the transient dynamics around the limit cycle [Wilson and Moehlis, Phys. Rev. E 94, 052213 (2016)]. In this study, we introduce a framework for a reduced phase-amplitude description of transient dynamics of stable limit-cycling systems. In contrast to the preceding study, the isostables are treated in a fully consistent way with the Koopman operator analysis, which enables us to avoid discontinuities of the isostables and to apply the framework to system states far from the limit cycle. We also propose a new, convenient bi-orthogonalization method to obtain the response functions of the amplitudes, which can be interpreted as an extension of the adjoint covariant Lyapunov vector to transient dynamics in limit-cycling systems. We illustrate the utility of the proposed reduction framework by estimating the optimal injection timing of external input that efficiently suppresses deviations of the system state from the limit cycle in a model of a biochemical oscillator.
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Building upon previously published life cycle assessment (LCA) methodologies, we conducted an LCA of a commercial rainwater harvesting (RWH) system and compared it to a municipal water supply (MWS) system adapted to Washington, D.C. Eleven life cycle impact assessment (LCIA) indi...
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Thermal analysis of heat and power plant with high temperature reactor and intermediate steam cycle
NASA Astrophysics Data System (ADS)
Fic, Adam; Składzień, Jan; Gabriel, Michał
2015-03-01
Thermal analysis of a heat and power plant with a high temperature gas cooled nuclear reactor is presented. The main aim of the considered system is to supply a technological process with the heat at suitably high temperature level. The considered unit is also used to produce electricity. The high temperature helium cooled nuclear reactor is the primary heat source in the system, which consists of: the reactor cooling cycle, the steam cycle and the gas heat pump cycle. Helium used as a carrier in the first cycle (classic Brayton cycle), which includes the reactor, delivers heat in a steam generator to produce superheated steam with required parameters of the intermediate cycle. The intermediate cycle is provided to transport energy from the reactor installation to the process installation requiring a high temperature heat. The distance between reactor and the process installation is assumed short and negligable, or alternatively equal to 1 km in the analysis. The system is also equipped with a high temperature argon heat pump to obtain the temperature level of a heat carrier required by a high temperature process. Thus, the steam of the intermediate cycle supplies a lower heat exchanger of the heat pump, a process heat exchanger at the medium temperature level and a classical steam turbine system (Rankine cycle). The main purpose of the research was to evaluate the effectiveness of the system considered and to assess whether such a three cycle cogeneration system is reasonable. Multivariant calculations have been carried out employing the developed mathematical model. The results have been presented in a form of the energy efficiency and exergy efficiency of the system as a function of the temperature drop in the high temperature process heat exchanger and the reactor pressure.
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Closed-cycle gas dynamic laser design investigation
NASA Technical Reports Server (NTRS)
Ketch, G. W.; Young, W. E.
1977-01-01
A conceptual design study was made of a closed cycle gas-dynamic laser to provide definition of the major components in the laser loop. The system potential application is for long range power transmission by way of high power laser beams to provide satellite propulsion energy for orbit changing or station keeping. A parametric cycle optimization was conducted to establish the thermodynamic requirements for the system components. A conceptual design was conducted of the closed cycle system and the individual components to define physical characteristics and establish the system size and weight. Technology confirmation experimental demonstration programs were outlined to develop, evaluate, and demonstrate the technology base needed for this closed cycle GDL system.
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Bifurcation of small limit cycles in cubic integrable systems using higher-order analysis
NASA Astrophysics Data System (ADS)
Tian, Yun; Yu, Pei
2018-05-01
In this paper, we present a method of higher-order analysis on bifurcation of small limit cycles around an elementary center of integrable systems under perturbations. This method is equivalent to higher-order Melinikov function approach used for studying bifurcation of limit cycles around a center but simpler. Attention is focused on planar cubic polynomial systems and particularly it is shown that the system studied by Żoła¸dek (1995) [24] can indeed have eleven limit cycles under perturbations at least up to 7th order. Moreover, the pattern of numbers of limit cycles produced near the center is discussed up to 39th-order perturbations, and no more than eleven limit cycles are found.
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Building Maintenance and Repair Data for Life-Cycle Cost Analyses: Electrical Systems.
1991-05-01
Repair Data for Life-Cycle Cost Analyses: Electrical Systems by Edgar S. Neely Robert D. Neathammer James R. Stirn Robert P. Winkler This research...systems have been developed to assist planners in preparing DD Form 1391 documentation, designers in life-cycle cost component selection, and maintainers...Maintenance and Repair Data for Life-Cycle Cost Analyses: RDTE dated 1980 Electrical Systems REIMB 1984 - 1989 6. AUTH4OR(S) Edgar S. Neely, Robert D
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Analysis of a topping-cycle, aircraft, gas-turbine-engine system which uses cryogenic fuel
NASA Technical Reports Server (NTRS)
Turney, G. E.; Fishbach, L. H.
1984-01-01
A topping-cycle aircraft engine system which uses a cryogenic fuel was investigated. This system consists of a main turboshaft engine that is mechanically coupled (by cross-shafting) to a topping loop, which augments the shaft power output of the system. The thermodynamic performance of the topping-cycle engine was analyzed and compared with that of a reference (conventional) turboshaft engine. For the cycle operating conditions selected, the performance of the topping-cycle engine in terms of brake specific fuel consumption (bsfc) was determined to be about 12 percent better than that of the reference turboshaft engine. Engine weights were estimated for both the topping-cycle engine and the reference turboshaft engine. These estimates were based on a common shaft power output for each engine. Results indicate that the weight of the topping-cycle engine is comparable with that of the reference turboshaft engine.
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Thermally regenerative hydrogen/oxygen fuel cell power cycles
NASA Technical Reports Server (NTRS)
Morehouse, J. H.
1986-01-01
Two innovative thermodynamic power cycles are analytically examined for future engineering feasibility. The power cycles use a hydrogen-oxygen fuel cell for electrical energy production and use the thermal dissociation of water for regeneration of the hydrogen and oxygen. The TDS (thermal dissociation system) uses a thermal energy input at over 2000 K to thermally dissociate the water. The other cycle, the HTE (high temperature electrolyzer) system, dissociates the water using an electrolyzer operating at high temperature (1300 K) which receives its electrical energy from the fuel cell. The primary advantages of these cycles is that they are basically a no moving parts system, thus having the potential for long life and high reliability, and they have the potential for high thermal efficiency. Both cycles are shown to be classical heat engines with ideal efficiency close to Carnot cycle efficiency. The feasibility of constructing actual cycles is investigated by examining process irreversibilities and device efficiencies for the two types of cycles. The results show that while the processes and devices of the 2000 K TDS exceed current technology limits, the high temperature electrolyzer system appears to be a state-of-the-art technology development. The requirements for very high electrolyzer and fuel cell efficiencies are seen as determining the feasbility of the HTE system, and these high efficiency devices are currently being developed. It is concluded that a proof-of-concept HTE system experiment can and should be conducted.
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NASA Astrophysics Data System (ADS)
Jiang, Jifa; Niu, Lei
2017-12-01
We study three dimensional competitive differential equations with linearly determined nullclines and prove that they always have 33 stable nullcline classes in total. Each class is given in terms of inequalities on the intrinsic growth rates and competitive coefficients and is independent of generating functions. The common characteristics are that every trajectory converges to an equilibrium in classes 1-25, that Hopf bifurcations do not occur within class 32, and that there is always a heteroclinic cycle in class 27. Nontrivial dynamical behaviors, such as the existence and multiplicity of limit cycles, only may occur in classes 26-33, but these nontrivial dynamical behaviors depend on generating functions. We show that Hopf bifurcation can occur within each of classes 26-31 for continuous-time Leslie/Gower system and Ricker system, the same as Lotka-Volterra system; but it only occurs in classes 26 and 27 for continuous-time Atkinson/Allen system and Gompertz system. There is an apparent distinction between Lotka-Volterra system and Leslie/Gower system, Ricker system, Atkinson/Allen system, and Gompertz system with the identical growth rate. Lotka-Volterra system with the identical growth rate has no limit cycle, but admits a center on the carrying simplex in classes 26 and 27. But Leslie/Gower system, Ricker system, Atkinson/Allen system, and Gompertz system with the identical growth rate do possess limit cycles. At last, we provide examples to show that Leslie/Gower system and Ricker system can also admit two limit cycles. This general classification greatly widens applications of Zeeman's method and makes it possible to investigate the existence and multiplicity of limit cycles, centers and stability of heteroclinic cycles for three dimensional competitive systems with linearly determined nullclines, as done in planar systems.
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Scaling of chew cycle duration in primates.
Ross, Callum F; Reed, David A; Washington, Rhyan L; Eckhardt, Alison; Anapol, Fred; Shahnoor, Nazima
2009-01-01
The biomechanical determinants of the scaling of chew cycle duration are important components of models of primate feeding systems at all levels, from the neuromechanical to the ecological. Chew cycle durations were estimated in 35 species of primates and analyzed in conjunction with data on morphological variables of the feeding system estimating moment of inertia of the mandible and force production capacity of the chewing muscles. Data on scaling of primate chew cycle duration were compared with the predictions of simple pendulum and forced mass-spring system models of the feeding system. The gravity-driven pendulum model best predicts the observed cycle duration scaling but is rejected as biomechanically unrealistic. The forced mass-spring model predicts larger increases in chew cycle duration with size than observed, but provides reasonable predictions of cycle duration scaling. We hypothesize that intrinsic properties of the muscles predict spring-like behavior of the jaw elevator muscles during opening and fast close phases of the jaw cycle and that modulation of stiffness by the central nervous system leads to spring-like properties during the slow close/power stroke phase. Strepsirrhines show no predictable relationship between chew cycle duration and jaw length. Anthropoids have longer chew cycle durations than nonprimate mammals with similar mandible lengths, possibly due to their enlarged symphyses, which increase the moment of inertia of the mandible. Deviations from general scaling trends suggest that both scaling of the jaw muscles and the inertial properties of the mandible are important in determining the scaling of chew cycle duration in primates.
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SNTP propellant management system
NASA Technical Reports Server (NTRS)
Tippetts, Tom
1993-01-01
Viewgraphs on the following are presented: (1) space nuclear thermal propulsion (SNTP) propellant management system; (2) SNTP cycle selection; (3) NTP system components unique design constraints; (4) bleed cycle unique design requirement for turbopump; (5) bleed cycle turbopump; (6) SNTP carbon-carbon turbine wheel; and (7) turbine development program.
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Liquid-metal binary cycles for stationary power
NASA Technical Reports Server (NTRS)
Gutstein, M.; Furman, E. R.; Kaplan, G. M.
1975-01-01
The use of topping cycles to increase electric power plant efficiency is discussed, with particular attention to mercury and alkali metal Rankine cycle systems that could be considered for topping cycle applications. An overview of this technology, possible system applications, the required development, and possible problem areas is presented.
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-22
... NUCLEAR REGULATORY COMMISSION [NRC-2012-0195] Developing Software Life Cycle Processes for Digital... Software Life Cycle Processes for Digital Computer Software used in Safety Systems of Nuclear Power Plants... clarifications, the enhanced consensus practices for developing software life-cycle processes for digital...
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Dilution cycle control for an absorption refrigeration system
Reimann, Robert C.
1984-01-01
A dilution cycle control system for an absorption refrigeration system is disclosed. The control system includes a time delay relay for sensing shutdown of the absorption refrigeration system and for generating a control signal only after expiration of a preselected time period measured from the sensed shutdown of the absorption refrigeration system, during which the absorption refrigeration system is not restarted. A dilution cycle for the absorption refrigeration system is initiated in response to generation of a control signal by the time delay relay. This control system is particularly suitable for use with an absorption refrigeration system which is frequently cycled on and off since the time delay provided by the control system prevents needless dilution of the absorption refrigeration system when the system is turned off for only a short period of time and then is turned back on.
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Adsorption Refrigeration System
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Kai; Vineyard, Edward Allan
Adsorption refrigeration is an environmentally friendly cooling technology which could be driven by recovered waste heat or low-grade heat such as solar energy. In comparison with absorption system, an adsorption system has no problems such as corrosion at high temperature and salt crystallization. In comparison with vapor compression refrigeration system, it has the advantages of simple control, no moving parts and less noise. This paper introduces the basic theory of adsorption cycle as well as the advanced adsorption cycles such as heat and mass recovery cycle, thermal wave cycle and convection thermal wave cycle. The types, characteristics, advantages and drawbacksmore » of different adsorbents used in adsorption refrigeration systems are also summarized. This article will increase the awareness of this emerging cooling technology among the HVAC engineers and help them select appropriate adsorption systems in energy-efficient building design.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Pasch, James Jay
A method of resolving a balanced condition that generates control parameters for start-up and steady state operating points and various component and cycle performances for a closed split flow recompression cycle system. The method provides for improved control of a Brayton cycle thermal to electrical power conversion system. The method may also be used for system design, operational simulation and/or parameter prediction.
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Woodard, Kenneth R; French, Edwin C; Sweat, Lewin A; Graetz, Donald A; Sollenberger, Lynn E; Macoon, Bisoondat; Portier, Kenneth M; Rymph, Stuart J; Wade, Brett L; Prine, Gordon M; Van Horn, Harold H
2003-01-01
In northern Florida, year-round forage systems are used in dairy effluent sprayfields to reduce nitrate leaching. Our purpose was to quantify forage N removal and monitor nitrate N (NO3(-)-N) concentration below the rooting zone for two perennial, sod-based, triple-cropping systems over four 12-mo cycles (1996-2000). The soil is an excessively drained Kershaw sand (thermic, uncoated Typic Quartzip-samment). Effluent N rates were 500, 690, and 910 kg ha(-1) per cycle. Differences in N removal between a corn (Zea mays L.)-bermudagrass (Cynodon spp.)-rye (Secale cereale L.) system (CBR) and corn-perennial peanut (Arachis glabrata Benth.)-rye system (CPR) were primarily related to the performance of the perennial forages. Nitrogen removal of corn (125-170 kg ha(-1)) and rye (62-90 kg ha(-1)) was relatively stable between systems and among cycles. The greatest N removal was measured for CBR in the first cycle (408 kg ha(-1)), with the bermudagrass removing an average of 191 kg N ha(-1). In later cycles, N removal for bermudagrass declined because dry matter (DM) yield declined. Yield and N removal of perennial peanut increased over the four cycles. Nitrate N concentrations below the rooting zone were lower for CBR than CPR in the first two cycles, but differences were inconsistent in the latter two. The CBR system maintained low NO3(-)-N leaching in the first cycle when the bermudagrass was the most productive; however, it was not a sustainable system for long-term prevention of NO3(-)-N leaching due to declining bermudagrass yield in subsequent cycles. For CPR, effluent N rates > or = 500 kg ha(-1) yr(-1) have the potential to negatively affect ground water quality.
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Analytically tractable climate-carbon cycle feedbacks under 21st century anthropogenic forcing
NASA Astrophysics Data System (ADS)
Lade, Steven J.; Donges, Jonathan F.; Fetzer, Ingo; Anderies, John M.; Beer, Christian; Cornell, Sarah E.; Gasser, Thomas; Norberg, Jon; Richardson, Katherine; Rockström, Johan; Steffen, Will
2018-05-01
Changes to climate-carbon cycle feedbacks may significantly affect the Earth system's response to greenhouse gas emissions. These feedbacks are usually analysed from numerical output of complex and arguably opaque Earth system models. Here, we construct a stylised global climate-carbon cycle model, test its output against comprehensive Earth system models, and investigate the strengths of its climate-carbon cycle feedbacks analytically. The analytical expressions we obtain aid understanding of carbon cycle feedbacks and the operation of the carbon cycle. Specific results include that different feedback formalisms measure fundamentally the same climate-carbon cycle processes; temperature dependence of the solubility pump, biological pump, and CO2 solubility all contribute approximately equally to the ocean climate-carbon feedback; and concentration-carbon feedbacks may be more sensitive to future climate change than climate-carbon feedbacks. Simple models such as that developed here also provide
workbenches
for simple but mechanistically based explorations of Earth system processes, such as interactions and feedbacks between the planetary boundaries, that are currently too uncertain to be included in comprehensive Earth system models. -
NASA Astrophysics Data System (ADS)
Hayat, Nasir; Ameen, Muhammad Tahir; Tariq, Muhammad Kashif; Shah, Syed Nadeem Abbas; Naveed, Ahmad
2017-08-01
Exploitation of low potential waste thermal energy for useful net power output can be done by manipulating organic Rankine cycle systems. In the current article dual-objectives (η_{th} and SIC) optimization of ORC systems [basic organic Rankine cycle (BORC) and recuperative organic Rankine cycle (RORC)] has been done using non-dominated sorting genetic algorithm (II). Seven organic compounds (R-123, R-1234ze, R-152a, R-21, R-236ea, R-245ca and R-601) have been employed in basic cycle and four dry compounds (R-123, R-236ea, R-245ca and R-601) have been employed in recuperative cycle to investigate the behaviour of two systems and compare their performance. Sensitivity analyses show that recuperation boosts the thermodynamic behaviour of systems but it also raises specific investment cost significantly. R-21, R-245ca and R-601 show attractive performance in BORC whereas R-601 and R-236ea in RORC. RORC, due to higher total investment cost and operation & maintenance costs, has longer payback periods as compared to BORC.
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Infection as a Trigger for Portal Hypertension.
Steib, Christian J; Schewe, Julia; Gerbes, Alexander L
2015-01-01
Microbial infections are a relevant problem for patients with liver cirrhosis. Different types of bacteria are responsible for different kinds of infections: Escherichia coli and Klebsiella pneumoniae are frequently observed in spontaneous bacterial peritonitis or urinary tract infections, and Streptococcus pneumoniae and Mycoplasma pneumoniae in pulmonary infections. Mortality is up to 4-fold higher in infected patients with liver cirrhosis than in patients without infections. Key Messages: Infections in patients with liver cirrhosis are due to three major reasons: bacterial translocation, immune deficiency and an increased incidence of systemic infections. Nonparenchymal liver cells like Kupffer cells, sinusoidal endothelial cells and hepatic stellate cells are the first liver cells to come into contact with microbial products when systemic infection or bacterial translocation occurs. Kupffer cell (KC) activation by Toll-like receptor (TLR) agonists and endothelial sinusoidal dysfunction have been shown to be important mechanisms increasing portal pressure following intraperitoneal lipopolysaccharide pretreatment in cirrhotic rat livers. Reduced intrahepatic vasodilation and increased intrahepatic vasoconstriction are the relevant pathophysiological pathways. Thromboxane A2 and leukotriene (LT) C4/D4 have been identified as important vasoconstrictors. Accordingly, treatment with montelukast to inhibit the cysteinyl-LT1 receptor reduced portal pressure in cirrhotic rat livers. Clinical studies have demonstrated that activation of KCs, estimated by the amount of soluble CD163 in the blood, correlates with the risk for variceal bleeding. Additionally, intestinal decontamination with rifaximin in patients with alcohol-associated liver cirrhosis reduced the portal pressure and the risk for variceal bleeding. TLR activation of nonparenchymal liver cells by pathogens results in portal hypertension. This might explain the pathophysiologic correlation between microbial infections and portal hypertension in patients with liver cirrhosis. These findings are the basis for both better risk stratifying and new treatment options, such as specific inhibition of TLR for patients with liver cirrhosis and portal hypertension. © 2015 S. Karger AG, Basel.
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Two inhibitory systems and CKIs regulate cell cycle exit of mammalian cardiomyocytes after birth
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tane, Shoji; Okayama, Hitomi; Ikenishi, Aiko
Mammalian cardiomyocytes actively proliferate during embryonic stages, following which they exit their cell cycle after birth, and the exit is maintained. Previously, we showed that two inhibitory systems (the G1-phase inhibitory system: repression of cyclin D1 expression; the M-phase inhibitory system: inhibition of CDK1 activation) maintain the cell cycle exit of mouse adult cardiomyocytes. We also showed that two CDK inhibitors (CKIs), p21{sup Cip1} and p27{sup Kip1}, regulate the cell cycle exit in a portion of postnatal cardiomyocytes. It remains unknown whether the two inhibitory systems are involved in the cell cycle exit of postnatal cardiomyocytes and whether p21{sup Cip1}more » and p27{sup Kip1} also inhibit entry to M-phase. Here, we showed that more than 40% of cardiomyocytes entered an additional cell cycle by induction of cyclin D1 expression at postnatal stages, but M-phase entry was inhibited in the majority of cardiomyocytes. Marked cell cycle progression and endoreplication were observed in cardiomyocytes of p21{sup Cip1} knockout mice at 4 weeks of age. In addition, tri- and tetranucleated cardiomyocytes increased significantly in p21{sup Cip1} knockout mice. These data showed that the G1-phase inhibitory system and two CKIs (p21{sup Cip1} and p27{sup Kip1}) inhibit entry to an additional cell cycle in postnatal cardiomyocytes, and that the M-phase inhibitory system and p21{sup Cip1} inhibit M-phase entry of cardiomyocytes which have entered the additional cell cycle. - Highlights: • Many postnatal cardiomyocytes entered an additional cell cycle by cyclin D1 induction. • The majority of cardiomyocytes could not enter M-phase after cyclin D1 induction. • Cell cycle progressed markedly in p21{sup Cip1} knockout mice after postnatal day 14. • Tri- and tetranucleated cardiomyocytes increased in p21{sup Cip1} knockout mice.« less
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40 CFR 86.1309-90 - Exhaust gas sampling system; Otto-cycle and non-petroleum-fueled engines.
Code of Federal Regulations, 2010 CFR
2010-07-01
...-cycle and non-petroleum-fueled engines. 86.1309-90 Section 86.1309-90 Protection of Environment... HIGHWAY VEHICLES AND ENGINES (CONTINUED) Emission Regulations for New Otto-Cycle and Diesel Heavy-Duty...-cycle and non-petroleum-fueled engines. (a)(1) General. The exhaust gas sampling system described in...
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Shift of a limit cycle in biology: From pathological to physiological homeostasia*
NASA Astrophysics Data System (ADS)
Claude, Daniel
1995-03-01
Biological systems may show homeostatic behaviors that are similar to the ones of forced dynamic systems with a stable limit cycle. For a large class of dynamic systems, it is shown that a shift of a pathological limit cycle over the physiological limit cycle can never be executed by means of a control with a desired periodicity. The above statement shows that the only possibility is to reduce as much as possible the dimensions of a small residual limit cycle. Moreover, it is possible to give some information about the structure of feedback laws that would allow the shift of the limit cycle. The fact that it is generally not possible to recover a physiological limit cycle from a pathological one, results into the fear of never or hardly ever reaching a physiological behavior, and it seems that any hope of therapeutics is given up. This leads to introduce the locking concept, which permits system parameters to change and provides the basis for an adaptive and iterative control, which allows a step by step approach and to finally reach the physiological limit cycle.
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Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 18 2011-07-01 2011-07-01 false Exhaust gas sampling system; diesel... Heavy-Duty Vehicles; Test Procedures § 86.110-94 Exhaust gas sampling system; diesel-cycle vehicles, and..., this is indicated by the statement “[Reserved].” (a) General. The exhaust gas sampling system described...
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Performance and Mass Modeling Subtleties in Closed-Brayton-Cycle Space Power Systems
NASA Technical Reports Server (NTRS)
Barrett, Michael J.; Johnson, Paul K.
2005-01-01
Contents include the following: 1. Closed-Brayton-cycle (CBC) thermal energy conversion is one available option for future spacecraft and surface systems. 2. Brayton system conceptual designs for milliwatt to megawatt power converters have been developed 3. Numerous features affect overall optimized power conversion system performance: Turbomachinery efficiency. Heat exchanger effectiveness. Working-fluid composition. Cycle temperatures and pressures.
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Heat Transfer Analysis of a Closed Brayton Cycle Space Radiator
NASA Technical Reports Server (NTRS)
Juhasz, Albert J.
2007-01-01
This paper presents a mathematical analysis of the heat transfer processes taking place in a radiator for a closed cycle gas turbine (CCGT), also referred to as a Closed Brayton Cycle (CBC) space power system. The resulting equations and relationships have been incorporated into a radiator sub-routine of a numerical triple objective CCGT optimization program to determine operating conditions yielding maximum cycle efficiency, minimum radiator area and minimum overall systems mass. Study results should be of interest to numerical modeling of closed cycle Brayton space power systems and to the design of fluid cooled radiators in general.
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Assessment for advanced fuel cycle options in CANDU
DOE Office of Scientific and Technical Information (OSTI.GOV)
Morreale, A.C.; Luxat, J.C.; Friedlander, Y.
2013-07-01
The possible options for advanced fuel cycles in CANDU reactors including actinide burning options and thorium cycles were explored and are feasible options to increase the efficiency of uranium utilization and help close the fuel cycle. The actinide burning TRUMOX approach uses a mixed oxide fuel of reprocessed transuranic actinides from PWR spent fuel blended with natural uranium in the CANDU-900 reactor. This system reduced actinide content by 35% and decreased natural uranium consumption by 24% over a PWR once through cycle. The thorium cycles evaluated used two CANDU-900 units, a generator and a burner unit along with a drivermore » fuel feedstock. The driver fuels included plutonium reprocessed from PWR, from CANDU and low enriched uranium (LEU). All three cycles were effective options and reduced natural uranium consumption over a PWR once through cycle. The LEU driven system saw the largest reduction with a 94% savings while the plutonium driven cycles achieved 75% savings for PWR and 87% for CANDU. The high neutron economy, online fuelling and flexible compact fuel make the CANDU system an ideal reactor platform for many advanced fuel cycles.« less
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NASA Technical Reports Server (NTRS)
Lin, C. H.; Meyer, M. S.
1983-01-01
The systems engineering aspects of developing a conceptual design of the Space Station Environmental Control and Life Support System (ECLSS) are discussed. Topics covered include defining system requirements and groundrules for approach, formulating possible cycle closure options, and establishing a system-level mass balance on the essential materials processed in oxygen and water cycles. Consideration is also given to the performance of a system trade-off study to determine the best degree of cycle closure for the ECLSS, and the construction of a conceptual design of the ECLSS with subsystem performance specifications and candidate concepts. For the optimum balance between development costs, technological risks, and resupply penalties, a partially closed cycle ECLSS option is suggested.
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NASA Astrophysics Data System (ADS)
Silverberg, S. K.; Ollinger, S. V.; Martin, M. E.; Gengarelly, L. M.; Schloss, A. L.; Bourgeault, J. L.; Randolph, G.; Albrechtova, J.
2009-12-01
National Science Content Standards identify systems as an important unifying concept across the K-12 curriculum. While this standard exists, there is a recognized gap in the ability of students to use a systems thinking approach in their learning. In a similar vein, both popular media as well as some educational curricula move quickly through climate topics to carbon footprint analyses without ever addressing the nature of carbon or the carbon cycle. If students do not gain a concrete understanding of carbon’s role in climate and energy they will not be able to successfully tackle global problems and develop innovative solutions. By participating in the GLOBE Carbon Cycle project, students learn to use a systems thinking approach, while at the same time, gaining a foundation in the carbon cycle and it's relation to climate and energy. Here we present the GLOBE Carbon Cycle project and materials, which incorporate a diverse set of activities geared toward upper middle and high school students with a variety of learning styles. A global carbon cycle adventure story and game let students see the carbon cycle as a complete system, while introducing them to systems thinking concepts including reservoirs, fluxes and equilibrium. Classroom photosynthesis experiments and field measurements of schoolyard vegetation brings the global view to the local level. And the use of computer models at varying levels of complexity (effects on photosynthesis, biomass and carbon storage in global biomes, global carbon cycle) not only reinforces systems concepts and carbon content, but also introduces students to an important scientific tool necessary for understanding climate change.
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NASA Astrophysics Data System (ADS)
Oke, Shinichiro; Kemmoku, Yoshishige; Takikawa, Hirofumi; Sakakibara, Tateki
The reduction effect of life cycle CO2 emission is examined in case of introducing a PV/solar heat/cogeneration system into public welfare facilities(hotel and hospital). Life cycle CO2 emission is calculated as the sum of that when operating and that when manufacturing equipments. The system is operated with the dynamic programming method, into which hourly data of electric and heat loads, solar insolation, and atmospheric temperature during a year are input. The proposed system is compared with a conventional system and a cogeneration system. The life cycle CO2 emission of the PV/solar heat/cogeneration system is lower than that of the conventional system by 20% in hotel and by 14% in hospital.
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NASA Astrophysics Data System (ADS)
Song, Jinghui; Yuan, Hui; Xia, Yunfeng; Kan, Weimin; Deng, Xiaowen; Liu, Shi; Liang, Wanlong; Deng, Jianhua
2018-03-01
This paper introduces the working principle and system constitution of the linear Fresnel solar lithium bromide absorption refrigeration cycle, and elaborates several typical structures of absorption refrigeration cycle, including single-effect, two-stage cycle and double-effect lithium bromide absorption refrigeration cycle A 1.n effect absorption chiller system based on the best parameters was introduced and applied to a linear Fresnel solar absorption chiller system. Through the field refrigerator performance test, the results show: Based on this heat cycle design and processing 1.n lithium bromide absorption refrigeration power up to 35.2KW, It can meet the theoretical expectations and has good flexibility and reliability, provides guidance for the use of solar thermal energy.
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Limit Cycle Bifurcations by Perturbing a Piecewise Hamiltonian System with a Double Homoclinic Loop
NASA Astrophysics Data System (ADS)
Xiong, Yanqin
2016-06-01
This paper is concerned with the bifurcation problem of limit cycles by perturbing a piecewise Hamiltonian system with a double homoclinic loop. First, the derivative of the first Melnikov function is provided. Then, we use it, together with the analytic method, to derive the asymptotic expansion of the first Melnikov function near the loop. Meanwhile, we present the first coefficients in the expansion, which can be applied to study the limit cycle bifurcation near the loop. We give sufficient conditions for this system to have 14 limit cycles in the neighborhood of the loop. As an application, a piecewise polynomial Liénard system is investigated, finding six limit cycles with the help of the obtained method.
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Intermediate Fidelity Closed Brayton Cycle Power Conversion Model
NASA Technical Reports Server (NTRS)
Lavelle, Thomas M.; Khandelwal, Suresh; Owen, Albert K.
2006-01-01
This paper describes the implementation of an intermediate fidelity model of a closed Brayton Cycle power conversion system (Closed Cycle System Simulation). The simulation is developed within the Numerical Propulsion Simulation System architecture using component elements from earlier models. Of particular interest, and power, is the ability of this new simulation system to initiate a more detailed analysis of compressor and turbine components automatically and to incorporate the overall results into the general system simulation.
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Code of Federal Regulations, 2010 CFR
2010-07-01
...-cycle vehicles not requiring particulate emission measurements. 86.109-94 Section 86.109-94 Protection... Year New Light-Duty Vehicles and New Light-Duty Trucks and New Otto-Cycle Complete Heavy-Duty Vehicles; Test Procedures § 86.109-94 Exhaust gas sampling system; Otto-cycle vehicles not requiring particulate...
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ERIC Educational Resources Information Center
Goclowski, John C.; Baran, H. Anthony
This report gives a managerial overview of the Life Cycle Cost Impact Modeling System (LCCIM), which was designed to provide the Air Force with an in-house capability of assessing the life cycle cost impact of weapon system design alternatives. LCCIM consists of computer programs and the analyses which the user must perform to generate input data.…
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Rapid microfluidic thermal cycler for nucleic acid amplification
Beer, Neil Reginald; Vafai, Kambiz
2015-10-27
A system for thermal cycling a material to be thermal cycled including a microfluidic heat exchanger; a porous medium in the microfluidic heat exchanger; a microfluidic thermal cycling chamber containing the material to be thermal cycled, the microfluidic thermal cycling chamber operatively connected to the microfluidic heat exchanger; a working fluid at first temperature; a first system for transmitting the working fluid at first temperature to the microfluidic heat exchanger; a working fluid at a second temperature, a second system for transmitting the working fluid at second temperature to the microfluidic heat exchanger; a pump for flowing the working fluid at the first temperature from the first system to the microfluidic heat exchanger and through the porous medium; and flowing the working fluid at the second temperature from the second system to the heat exchanger and through the porous medium.
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Forster, Dionys; Andres, Christian; Verma, Rajeev; Zundel, Christine; Messmer, Monika M.; Mäder, Paul
2013-01-01
The debate on the relative benefits of conventional and organic farming systems has in recent time gained significant interest. So far, global agricultural development has focused on increased productivity rather than on a holistic natural resource management for food security. Thus, developing more sustainable farming practices on a large scale is of utmost importance. However, information concerning the performance of farming systems under organic and conventional management in tropical and subtropical regions is scarce. This study presents agronomic and economic data from the conversion phase (2007–2010) of a farming systems comparison trial on a Vertisol soil in Madhya Pradesh, central India. A cotton-soybean-wheat crop rotation under biodynamic, organic and conventional (with and without Bt cotton) management was investigated. We observed a significant yield gap between organic and conventional farming systems in the 1st crop cycle (cycle 1: 2007–2008) for cotton (−29%) and wheat (−27%), whereas in the 2nd crop cycle (cycle 2: 2009–2010) cotton and wheat yields were similar in all farming systems due to lower yields in the conventional systems. In contrast, organic soybean (a nitrogen fixing leguminous plant) yields were marginally lower than conventional yields (−1% in cycle 1, −11% in cycle 2). Averaged across all crops, conventional farming systems achieved significantly higher gross margins in cycle 1 (+29%), whereas in cycle 2 gross margins in organic farming systems were significantly higher (+25%) due to lower variable production costs but similar yields. Soybean gross margin was significantly higher in the organic system (+11%) across the four harvest years compared to the conventional systems. Our results suggest that organic soybean production is a viable option for smallholder farmers under the prevailing semi-arid conditions in India. Future research needs to elucidate the long-term productivity and profitability, particularly of cotton and wheat, and the ecological impact of the different farming systems. PMID:24324659
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Forster, Dionys; Andres, Christian; Verma, Rajeev; Zundel, Christine; Messmer, Monika M; Mäder, Paul
2013-01-01
The debate on the relative benefits of conventional and organic farming systems has in recent time gained significant interest. So far, global agricultural development has focused on increased productivity rather than on a holistic natural resource management for food security. Thus, developing more sustainable farming practices on a large scale is of utmost importance. However, information concerning the performance of farming systems under organic and conventional management in tropical and subtropical regions is scarce. This study presents agronomic and economic data from the conversion phase (2007-2010) of a farming systems comparison trial on a Vertisol soil in Madhya Pradesh, central India. A cotton-soybean-wheat crop rotation under biodynamic, organic and conventional (with and without Bt cotton) management was investigated. We observed a significant yield gap between organic and conventional farming systems in the 1(st) crop cycle (cycle 1: 2007-2008) for cotton (-29%) and wheat (-27%), whereas in the 2(nd) crop cycle (cycle 2: 2009-2010) cotton and wheat yields were similar in all farming systems due to lower yields in the conventional systems. In contrast, organic soybean (a nitrogen fixing leguminous plant) yields were marginally lower than conventional yields (-1% in cycle 1, -11% in cycle 2). Averaged across all crops, conventional farming systems achieved significantly higher gross margins in cycle 1 (+29%), whereas in cycle 2 gross margins in organic farming systems were significantly higher (+25%) due to lower variable production costs but similar yields. Soybean gross margin was significantly higher in the organic system (+11%) across the four harvest years compared to the conventional systems. Our results suggest that organic soybean production is a viable option for smallholder farmers under the prevailing semi-arid conditions in India. Future research needs to elucidate the long-term productivity and profitability, particularly of cotton and wheat, and the ecological impact of the different farming systems.
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Development and Validation of a Slurry Model for Chemical Hydrogen Storage in Fuel Cell Applications
DOE Office of Scientific and Technical Information (OSTI.GOV)
Brooks, Kriston P.; Pires, Richard P.; Simmons, Kevin L.
2014-07-25
The US Department of Energy's (DOE) Hydrogen Storage Engineering Center of Excellence (HSECoE) is developing models for hydrogen storage systems for fuel cell-based light duty vehicle applications for a variety of promising materials. These transient models simulate the performance of the storage system for comparison to the DOE’s Technical Targets and a set of four drive cycles. The purpose of this research is to describe the models developed for slurry-based chemical hydrogen storage materials. The storage systems of both a representative exothermic system based on ammonia borane and endothermic system based on alane were developed and modeled in Simulink®. Oncemore » complete the reactor and radiator components of the model were validated with experimental data. The model was then run using a highway cycle, an aggressive cycle, cold-start cycle and hot drive cycle. The system design was adjusted to meet these drive cycles. A sensitivity analysis was then performed to identify the range of material properties where these DOE targets and drive cycles could be met. Materials with a heat of reaction greater than 11 kJ/mol H2 generated and a slurry hydrogen capacity of greater than 11.4% will meet the on-board efficiency and gravimetric capacity targets, respectively.« less
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Pseudo-simple heteroclinic cycles in R4
NASA Astrophysics Data System (ADS)
Chossat, Pascal; Lohse, Alexander; Podvigina, Olga
2018-06-01
We study pseudo-simple heteroclinic cycles for a Γ-equivariant system in R4 with finite Γ ⊂ O(4) , and their nearby dynamics. In particular, in a first step towards a full classification - analogous to that which exists already for the class of simple cycles - we identify all finite subgroups of O(4) admitting pseudo-simple cycles. To this end we introduce a constructive method to build equivariant dynamical systems possessing a robust heteroclinic cycle. Extending a previous study we also investigate the existence of periodic orbits close to a pseudo-simple cycle, which depends on the symmetry groups of equilibria in the cycle. Moreover, we identify subgroups Γ ⊂ O(4) , Γ ⊄ SO(4) , admitting fragmentarily asymptotically stable pseudo-simple heteroclinic cycles. (It has been previously shown that for Γ ⊂ SO(4) pseudo-simple cycles generically are completely unstable.) Finally, we study a generalized heteroclinic cycle, which involves a pseudo-simple cycle as a subset.
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Quantifying the Adaptive Cycle | Science Inventory | US EPA
The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994–2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and
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Mathematical modeling and characteristic analysis for over-under turbine based combined cycle engine
NASA Astrophysics Data System (ADS)
Ma, Jingxue; Chang, Juntao; Ma, Jicheng; Bao, Wen; Yu, Daren
2018-07-01
The turbine based combined cycle engine has become the most promising hypersonic airbreathing propulsion system for its superiority of ground self-starting, wide flight envelop and reusability. The simulation model of the turbine based combined cycle engine plays an important role in the research of performance analysis and control system design. In this paper, a turbine based combined cycle engine mathematical model is built on the Simulink platform, including a dual-channel air intake system, a turbojet engine and a ramjet. It should be noted that the model of the air intake system is built based on computational fluid dynamics calculation, which provides valuable raw data for modeling of the turbine based combined cycle engine. The aerodynamic characteristics of turbine based combined cycle engine in turbojet mode, ramjet mode and mode transition process are studied by the mathematical model, and the influence of dominant variables on performance and safety of the turbine based combined cycle engine is analyzed. According to the stability requirement of thrust output and the safety in the working process of turbine based combined cycle engine, a control law is proposed that could guarantee the steady output of thrust by controlling the control variables of the turbine based combined cycle engine in the whole working process.
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NASA Technical Reports Server (NTRS)
Rosenbush, F. M.
1982-01-01
Materials illustrating a presentation on environment control systems for electric flight systems are presented. Schematics and flow diagrams of fresh air source and air conditioning systems, and vapor cycle and air cycle parts lists are presented.
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Identification of limit cycles in multi-nonlinearity, multiple path systems
NASA Technical Reports Server (NTRS)
Mitchell, J. R.; Barron, O. L.
1979-01-01
A method of analysis which identifies limit cycles in autonomous systems with multiple nonlinearities and multiple forward paths is presented. The FORTRAN code for implementing the Harmonic Balance Algorithm is reported. The FORTRAN code is used to identify limit cycles in multiple path and nonlinearity systems while retaining the effects of several harmonic components.
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An Integrated Approach to Life Cycle Analysis
NASA Technical Reports Server (NTRS)
Chytka, T. M.; Brown, R. W.; Shih, A. T.; Reeves, J. D.; Dempsey, J. A.
2006-01-01
Life Cycle Analysis (LCA) is the evaluation of the impacts that design decisions have on a system and provides a framework for identifying and evaluating design benefits and burdens associated with the life cycles of space transportation systems from a "cradle-to-grave" approach. Sometimes called life cycle assessment, life cycle approach, or "cradle to grave analysis", it represents a rapidly emerging family of tools and techniques designed to be a decision support methodology and aid in the development of sustainable systems. The implementation of a Life Cycle Analysis can vary and may take many forms; from global system-level uncertainty-centered analysis to the assessment of individualized discriminatory metrics. This paper will focus on a proven LCA methodology developed by the Systems Analysis and Concepts Directorate (SACD) at NASA Langley Research Center to quantify and assess key LCA discriminatory metrics, in particular affordability, reliability, maintainability, and operability. This paper will address issues inherent in Life Cycle Analysis including direct impacts, such as system development cost and crew safety, as well as indirect impacts, which often take the form of coupled metrics (i.e., the cost of system unreliability). Since LCA deals with the analysis of space vehicle system conceptual designs, it is imperative to stress that the goal of LCA is not to arrive at the answer but, rather, to provide important inputs to a broader strategic planning process, allowing the managers to make risk-informed decisions, and increase the likelihood of meeting mission success criteria.
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1993-12-01
5-6 5.6.1 Large Cycle Slip Simulation ............................. 5-7 5.6.2 Small Cycle Slip Simulation ........................... 5-9...Appendix J. Small Cycle Slip Simulation Results ............................. J-1 Bibliography ........................................................ BIB-I...when subjected to large and small cycle slips. Results of the simulations indicate that the PNRS can provide an improved navigation solution over
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Study of LH2-fueled topping cycle engine for aircraft propulsion
NASA Technical Reports Server (NTRS)
Turney, G. E.; Fishbach, L. H.
1983-01-01
An analytical investigation was made of a topping cycle aircraft engine system which uses a cryogenic fuel. This system consists of a main turboshaft engine which is mechanically coupled (by cross-shafting) to a topping loop which augments the shaft power output of the system. The thermodynamic performance of the topping cycle engine was analyzed and compared with that of a reference (conventional-type) turboshaft engine. For the cycle operating conditions selected, the performance of the topping cycle engine in terms of brake specific fuel consumption (bsfc) was determined to be about 12 percent better than that of the reference turboshaft engine. Engine weights were estimated for both the topping cycle engine and the reference turboshaft engine. These estimates were based on a common shaft power output for each engine. Results indicate that the weight of the topping cycle engine is comparable to that of the reference turboshaft engine.
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Immune tolerance: what is unique about the liver.
Tiegs, Gisa; Lohse, Ansgar W
2010-02-01
The 'liver tolerance effect' mediates local and systemic tolerance to self and foreign antigens and has been attributed to specialized resident cells expressing anti-inflammatory mediators and inhibitory cell surface ligands for T cell activation. Non-parenchymal liver cells responsible for the tolerogenic properties of the liver are the resident dendritic cells (DCs), which comprise myeloid as well as plasmacytoid DCs, liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs) as well as hepatic stellate cells (HSCs), also known as Ito cells. These cells mediate immunosuppression by production of anti-inflammatory cytokines such as IL-10 and TGFbeta as well as by expression of the negative co-stimulator for T cell activation programmed cell death ligand-1 (PD-L1). An interesting observation in this context is that knockout of IL-10 or PD-L1 (or the receptor PD-1) does not necessarily result in inflammatory liver damage whereas transgenic inhibition of TGFbeta signaling induces liver disease in mice resembling chronic cholangitis. However, depending on the mouse model and on the type of injury, e.g. autoimmune disease, allograft rejection or viral infection, IL-10 or TGFbeta and/or PD-1 as well as cytotoxic T lymphocyte antigen-4 (CTLA-4) contribute to the immunosuppressive mechanisms of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which seem to be converted in the liver from infiltrating conventional naïve CD4(+) T cells and/or effector CD4(+) T cells to control the disease. Finally, hepatocytes also contribute to the 'liver tolerance effect' by expression of MHC class II molecules, probably low levels of co-stimulatory molecules and high levels of the co-inhibitory molecule PD-L1. Copyright 2009 Elsevier Ltd. All rights reserved.
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VRACK: measuring pedal kinematics during stationary bike cycling.
Farjadian, Amir B; Kong, Qingchao; Gade, Venkata K; Deutsch, Judith E; Mavroidis, Constantinos
2013-06-01
Ankle impairment and lower limb asymmetries in strength and coordination are common symptoms for individuals with selected musculoskeletal and neurological impairments. The virtual reality augmented cycling kit (VRACK) was designed as a compact mechatronics system for lower limb and mobility rehabilitation. The system measures interaction forces and cardiac activity during cycling in a virtual environment. The kinematics measurement was added to the system. Due to the constrained problem definition, the combination of inertial measurement unit (IMU) and Kalman filtering was recruited to compute the optimal pedal angular displacement during dynamic cycling exercise. Using a novel benchmarking method the accuracy of IMU-based kinematics measurement was evaluated. Relatively accurate angular measurements were achieved. The enhanced VRACK system can serve as a rehabilitation device to monitor biomechanical and physiological variables during cycling on a stationary bike.
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Advanced technology cogeneration system conceptual design study: Closed cycle gas turbines
NASA Technical Reports Server (NTRS)
Mock, E. A. T.; Daudet, H. C.
1983-01-01
The results of a three task study performed for the Department of Energy under the direction of the NASA Lewis Research Center are documented. The thermal and electrical energy requirements of three specific industrial plants were surveyed and cost records for the energies consumed were compiled. Preliminary coal fired atmospheric fluidized bed heated closed cycle gas turbine and steam turbine cogeneration system designs were developed for each industrial plant. Preliminary cost and return-on-equity values were calculated and the results compared. The best of the three sites was selected for more detailed design and evaluation of both closed cycle gas turbine and steam turbine cogeneration systems during Task II. Task III involved characterizing the industrial sector electrical and thermal loads for the 48 contiguous states, applying a family of closed cycle gas turbine and steam turbine cogeneration systems to these loads, and conducting a market penetration analysis of the closed cycle gas turbine cogeneration system.
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Feasibility of interactive biking exercise system for telemanagement in elderly.
Finkelstein, Joseph; Jeong, In Cheol
2013-01-01
Inexpensive cycling equipment is widely available for home exercise however its use is hampered by lack of tools supporting real-time monitoring of cycling exercise in elderly and coordination with a clinical care team. To address these barriers, we developed a low-cost mobile system aimed at facilitating safe and effective home-based cycling exercise. The system used a miniature wireless 3-axis accelerometer that transmitted the cycling acceleration data to a tablet PC that was integrated with a multi-component disease management system. An exercise dashboard was presented to a patient allowing real-time graphical visualization of exercise progress. The system was programmed to alert patients when exercise intensity exceeded the levels recommended by the patient care providers and to exchange information with a central server. The feasibility of the system was assessed by testing the accuracy of cycling speed monitoring and reliability of alerts generated by the system. Our results demonstrated high validity of the system both for upper and lower extremity exercise monitoring as well as reliable data transmission between home unit and central server.
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Batu Pahat Driving Cycle for Light Duty Gasoline Engine
NASA Astrophysics Data System (ADS)
Zainul Abidin, Zainul Ameerul Ikhsan B.; Faisal Hushim, Mohd; Ahmad, Osman Bin
2017-08-01
Driving cycle is a series of data points that represents the vehicle speed versus time. Transient driving cycles involve many changes such as frequent speed changes during typical on-road driving condition [2]. Model driving cycles involve protracted periods at constant speeds. The Batu Pahat Driving Cycle (BPDC) developed to represent the driving pattern of people in a district of Batu Pahat. Based on this driving cycle, it will be a reference to other researchers to study about the gases emission release and fuel consumption by the vehicle on the dynamometer or automotive simulation based on this driving cycle. Existing driving cycles used such as the New European Driving Cycle (NEDC), the Federal Test Procedure (FTP-72/75, and Japan 10-15 Mode Cycle is not appropriate for Batu Pahat district because of different road conditions, driving habits and environmental of developed driving cycle countries are not same [2][14]. Batu Pahat drive cycle was developed for low-capacity gasoline engine under 150 cc and operating on urban roads, rural roads and road around Universiti Tun Hussein Onn. The importance of these driving cycle as the reference for other research to measure and do automotive simulation regarding fuel consumption and gas emission release from the motorcycle for these three type of driving cycle area. Another use for driving cycles is in vehicle simulations [3]. More specifically, they are used in propulsion system simulations to predict the performance of internal combustion engines, transmissions, electric drive systems, batteries, fuel cell systems, and similar components [18]. Data collection methods used in this study is the use of Global Positioning System (GPS). The results obtained are not similar to each other due to differences in congestion on data taken. From the driving cycle graph obtained, such as the average velocity, maximum velocity, the duration and Positive Acceleration Kinetic Energy (PKE) can be determined. In addition, the best driving cycle sample can be determined from the sum of error calculated. The least sum of error means the best driving cycle
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Quantum thermodynamic cycles and quantum heat engines. II.
Quan, H T
2009-04-01
We study the quantum-mechanical generalization of force or pressure, and then we extend the classical thermodynamic isobaric process to quantum-mechanical systems. Based on these efforts, we are able to study the quantum version of thermodynamic cycles that consist of quantum isobaric processes, such as the quantum Brayton cycle and quantum Diesel cycle. We also consider the implementation of the quantum Brayton cycle and quantum Diesel cycle with some model systems, such as single particle in a one-dimensional box and single-mode radiation field in a cavity. These studies lay the microscopic (quantum-mechanical) foundation for Szilard-Zurek single-molecule engine.
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1983-10-01
SYSTEMS OBJECTIVES. This study was conducted as part of a continuing effort to obtain actual (historical) life cycle costs of major Army systems from...Procurement, AMS Code for RDTE, etc.). System life cycle costs cut across appropriation lines. A common architecture should be prerequisite to... life cycle costs of major Army systems have not been successful, but attention recently has been directed toward the possibility that a significant
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Valero, E; Varón, R; García-Carmona, F
1995-01-01
A kinetic study is made of a system consisting of a specific enzymic cycling assay coupled to an enzymic reaction. A kinetic analysis of this system is presented, and the accumulation of chromophore involved in the cycle is seen to be parabolic, i.e. the rate of the reaction increases continuously with constant acceleration. The system is illustrated by the measurement of alkaline phosphatase activity using beta-NADP+ as substrate. The enzymes alcohol dehydrogenase and diaphorase are used to cycle beta-NAD+ in the presence of ethanol and p-Iodonitrotetrazolium Violet. During each turn of the cycle, one molecule of the tetrazolium salt is reduced to an intensely coloured formazan. A simple procedure for evaluating the kinetic parameters involved in the system and for optimizing this cycling assay is described. The method is applicable to the measurement of any enzyme, and its amplification capacity as well as the simplicity of determining kinetic parameters enable it to be employed in enzyme immunoassays to increase the magnitude of the measured response. PMID:7619054
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2013-06-01
ER D C/ CE RL C R- 13 -5 Ontology for Life-Cycle Modeling of Water Distribution Systems : Application of Model View Definition...2013 Ontology for Life-Cycle Modeling of Water Distribution Systems : Application of Model View Definition Attributes Kristine K. Fallon, Robert A...interior plumbing systems and the information exchange requirements for every participant in the design. The findings were used to develop an
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Evaluation of absorption cycle for space station environmental control system application
NASA Technical Reports Server (NTRS)
Sims, W. H.; Oneill, M. J.; Reid, H. C.; Bisenius, P. M.
1972-01-01
The study to evaluate an absorption cycle refrigeration system to provide environmental control for the space stations is reported. A zero-gravity liquid/vapor separator was designed and tested. The results were used to design a light-weight, efficient generator for the absorption refrigeration system. It is concluded that absorption cycle refrigeration is feasible for providing space station environmental control.
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Estimation of Soil-Water Characteristic Curves in Multiple-Cycles Using Membrane and TDR System
Hong, Won-Taek; Jung, Young-Seok; Kang, Seonghun; Lee, Jong-Sub
2016-01-01
The objective of this study is to estimate multiple-cycles of the soil-water characteristic curve (SWCC) using an innovative volumetric pressure plate extractor (VPPE), which is incorporated with a membrane and time domain reflectometry (TDR). The pressure cell includes the membrane to reduce the experimental time and the TDR probe to automatically estimate the volumetric water content. For the estimation of SWCC using the VPPE system, four specimens with different grain size and void ratio are prepared. The volumetric water contents of the specimens according to the matric suction are measured by the burette system and are estimated in the TDR system during five cycles of SWCC tests. The volumetric water contents estimated by the TDR system are almost identical to those determined by the burette system. The experimental time significantly decreases with the new VPPE. The hysteresis in the SWCC is largest in the first cycle and is nearly identical after 1.5 cycles. As the initial void ratio decreases, the air entry value increases. This study suggests that the new VPPE may effectively estimate multiple-cycles of the SWCC of unsaturated soils. PMID:28774139
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Comparing the Life Cycle Energy Consumption, Global ...
Managing the water-energy-nutrient nexus for the built environment requires, in part, a full system analysis of energy consumption, global warming and eutrophication potentials of municipal water services. As an example, we evaluated the life cycle energy use, greenhouse gas (GHG) emissions and aqueous nutrient releases of the whole anthropogenic municipal water cycle starting from raw water extraction to wastewater treatment and reuse/discharge for five municipal water and wastewater systems. The assessed options included conventional centralized services and four alternative options following the principles of source-separation and water fit-for-purpose. The comparative life cycle assessment identified that centralized drinking water supply coupled with blackwater energy recovery and on-site greywater treatment and reuse was the most energyand carbon-efficient water service system evaluated, while the conventional (drinking water and sewerage) centralized system ranked as the most energy- and carbon-intensive system. The electricity generated from blackwater and food residuals co-digestion was estimated to offset at least 40% of life cycle energy consumption for water/waste services. The dry composting toilet option demonstrated the lowest life cycle eutrophication potential. The nutrients in wastewater effluent are the dominating contributors for the eutrophication potential for the assessed system configurations. Among the parameters for which variability
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NASA Astrophysics Data System (ADS)
Scholze, Marko; Buchwitz, Michael; Dorigo, Wouter; Guanter, Luis; Quegan, Shaun
2017-07-01
The global carbon cycle is an important component of the Earth system and it interacts with the hydrology, energy and nutrient cycles as well as ecosystem dynamics. A better understanding of the global carbon cycle is required for improved projections of climate change including corresponding changes in water and food resources and for the verification of measures to reduce anthropogenic greenhouse gas emissions. An improved understanding of the carbon cycle can be achieved by data assimilation systems, which integrate observations relevant to the carbon cycle into coupled carbon, water, energy and nutrient models. Hence, the ingredients for such systems are a carbon cycle model, an algorithm for the assimilation and systematic and well error-characterised observations relevant to the carbon cycle. Relevant observations for assimilation include various in situ measurements in the atmosphere (e.g. concentrations of CO2 and other gases) and on land (e.g. fluxes of carbon water and energy, carbon stocks) as well as remote sensing observations (e.g. atmospheric composition, vegetation and surface properties).We briefly review the different existing data assimilation techniques and contrast them to model benchmarking and evaluation efforts (which also rely on observations). A common requirement for all assimilation techniques is a full description of the observational data properties. Uncertainty estimates of the observations are as important as the observations themselves because they similarly determine the outcome of such assimilation systems. Hence, this article reviews the requirements of data assimilation systems on observations and provides a non-exhaustive overview of current observations and their uncertainties for use in terrestrial carbon cycle data assimilation. We report on progress since the review of model-data synthesis in terrestrial carbon observations by Raupach et al.(2005), emphasising the rapid advance in relevant space-based observations.
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Life Cycle Cost of C-130E Weapon System.
1977-07-01
AFHRL-TR-7746 A-,I K lR FORCE g•r ___ FORCELIFE CYCLE COST OF C-130E WEAPON SYSTEM H By U Frank D. Brown "Gary A. WalkerU David H. WilsonBooing Awsp...I REPORT DOCUMENTO ON PAGE BEFORE COMPLETING FORM I?~ AFHR R.77-46 ( ~ LIFE CYCLE COST OF:C413A~ WEAPON SYSTEMteim.e M- 29 June 116- 3 June...human resources cost data life cycle cost historical weapon system analysis (I-WSA) inateuial resources 20). ABSTRACT (Con tinue on reverse siLa Mf
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Understanding bicycling in cities using system dynamics modelling.
Macmillan, Alexandra; Woodcock, James
2017-12-01
Increasing urban bicycling has established net benefits for human and environmental health. Questions remain about which policies are needed and in what order, to achieve an increase in cycling while avoiding negative consequences. Novel ways of considering cycling policy are needed, bringing together expertise across policy, community and research to develop a shared understanding of the dynamically complex cycling system. In this paper we use a collaborative learning process to develop a dynamic causal model of urban cycling to develop consensus about the nature and order of policies needed in different cycling contexts to optimise outcomes. We used participatory system dynamics modelling to develop causal loop diagrams (CLDs) of cycling in three contrasting contexts: Auckland, London and Nijmegen. We combined qualitative interviews and workshops to develop the CLDs. We used the three CLDs to compare and contrast influences on cycling at different points on a "cycling trajectory" and drew out policy insights. The three CLDs consisted of feedback loops dynamically influencing cycling, with significant overlap between the three diagrams. Common reinforcing patterns emerged: growing numbers of people cycling lifts political will to improve the environment; cycling safety in numbers drives further growth; and more cycling can lead to normalisation across the population. By contrast, limits to growth varied as cycling increases. In Auckland and London, real and perceived danger was considered the main limit, with added barriers to normalisation in London. Cycling congestion and "market saturation" were important in the Netherlands. A generalisable, dynamic causal theory for urban cycling enables a more ordered set of policy recommendations for different cities on a cycling trajectory. Participation meant the collective knowledge of cycling stakeholders was represented and triangulated with research evidence. Extending this research to further cities, especially in low-middle income countries, would enhance generalizability of the CLDs.
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Hult, Johan; Richter, Mattias; Nygren, Jenny; Aldén, Marcus; Hultqvist, Anders; Christensen, Magnus; Johansson, Bengt
2002-08-20
High-repetition-rate laser-induced fluorescence measurements of fuel and OH concentrations in internal combustion engines are demonstrated. Series of as many as eight fluorescence images, with a temporal resolution ranging from 10 micros to 1 ms, are acquired within one engine cycle. A multiple-laser system in combination with a multiple-CCD camera is used for cycle-resolved imaging in spark-ignition, direct-injection stratified-charge, and homogeneous-charge compression-ignition engines. The recorded data reveal unique information on cycle-to-cycle variations in fuel transport and combustion. Moreover, the imaging system in combination with a scanning mirror is used to perform instantaneous three-dimensional fuel-concentration measurements.
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Bifurcation of Limit Cycles in a Near-Hamiltonian System with a Cusp of Order Two and a Saddle
NASA Astrophysics Data System (ADS)
Bakhshalizadeh, Ali; Zangeneh, Hamid R. Z.; Kazemi, Rasool
In this paper, the asymptotic expansion of first-order Melnikov function of a heteroclinic loop connecting a cusp of order two and a hyperbolic saddle for a planar near-Hamiltonian system is given. Next, we consider the limit cycle bifurcations of a hyper-elliptic Liénard system with this kind of heteroclinic loop and study the least upper bound of limit cycles bifurcated from the period annulus inside the heteroclinic loop, from the heteroclinic loop itself and the center. We find that at most three limit cycles can be bifurcated from the period annulus, also we present different distributions of bifurcated limit cycles.
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Angle comparison using an autocollimator
NASA Astrophysics Data System (ADS)
Geckeler, Ralf D.; Just, Andreas; Vasilev, Valentin; Prieto, Emilio; Dvorácek, František; Zelenika, Slobodan; Przybylska, Joanna; Duta, Alexandru; Victorov, Ilya; Pisani, Marco; Saraiva, Fernanda; Salgado, Jose-Antonio; Gao, Sitian; Anusorn, Tonmueanwai; Leng Tan, Siew; Cox, Peter; Watanabe, Tsukasa; Lewis, Andrew; Chaudhary, K. P.; Thalmann, Ruedi; Banreti, Edit; Nurul, Alfiyati; Fira, Roman; Yandayan, Tanfer; Chekirda, Konstantin; Bergmans, Rob; Lassila, Antti
2018-01-01
Autocollimators are versatile optical devices for the contactless measurement of the tilt angles of reflecting surfaces. An international key comparison (KC) on autocollimator calibration, EURAMET.L-K3.2009, was initiated by the European Association of National Metrology Institutes (EURAMET) to provide information on the capabilities in this field. The Physikalisch-Technische Bundesanstalt (PTB) acted as the pilot laboratory, with a total of 25 international participants from EURAMET and from the Asia Pacific Metrology Programme (APMP) providing measurements. This KC was the first one to utilise a high-resolution electronic autocollimator as a standard. In contrast to KCs in angle metrology which usually involve the full plane angle, it focused on relatively small angular ranges (+/-10 arcsec and +/-1000 arcsec) and step sizes (10 arcsec and 0.1 arcsec, respectively). This document represents the approved final report on the results of the KC. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCL, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
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Ríha, J; Minár, J; Skaloud, J; Janes, K; Králík, O
1986-03-01
Dipterous blood-sucking insects (horseflies, black flies, gnats, midges) have negative impacts on the performance of draught horses in forest enterprises. For the protection of these animals, the following preparations were applied at the interval of 24 hours: diethyltoluamide, Oxamat (N,N-diethyloxamine acid, USSR) and Stomoxin (synthetic pyrethroid, product of the firm Wellcome, England). In the course of 66 working days, the performance of test animals treated with 10% water emulsion of diethyltoluamide increased by 49.25 cu. m. of skidded wood, i.e. by 0.74 cu. m. wood per horse/day (21.65%), as compared with the control group. The daily savings of prime costs per test horse/day made 16.99 Kcs (Czechoslovak crowns). In comparison with the control group, the performance of horses treated with 5% water emulsion of Oxamat increased by 85.50 cu. m. wood, i.e. by 1.29 cu. m. wood per horse/day (38.00%). Stomoxin at the concentration of 0.05% acted as a good insecticide but had no marked repellent effect. The results of this study document that the production of effective repellents should be introduced in the Czechoslovak Socialist Republic.
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Toxin-induced conformational changes in a potassium channel revealed by solid-state NMR
NASA Astrophysics Data System (ADS)
Lange, Adam; Giller, Karin; Hornig, Sönke; Martin-Eauclaire, Marie-France; Pongs, Olaf; Becker, Stefan; Baldus, Marc
2006-04-01
The active site of potassium (K+) channels catalyses the transport of K+ ions across the plasma membrane-similar to the catalytic function of the active site of an enzyme-and is inhibited by toxins from scorpion venom. On the basis of the conserved structures of K+ pore regions and scorpion toxins, detailed structures for the K+ channel-scorpion toxin binding interface have been proposed. In these models and in previous solution-state nuclear magnetic resonance (NMR) studies using detergent-solubilized membrane proteins, scorpion toxins were docked to the extracellular entrance of the K+ channel pore assuming rigid, preformed binding sites. Using high-resolution solid-state NMR spectroscopy, here we show that high-affinity binding of the scorpion toxin kaliotoxin to a chimaeric K+ channel (KcsA-Kv1.3) is associated with significant structural rearrangements in both molecules. Our approach involves a combined analysis of chemical shifts and proton-proton distances and demonstrates that solid-state NMR is a sensitive method for analysing the structure of a membrane protein-inhibitor complex. We propose that structural flexibility of the K+ channel and the toxin represents an important determinant for the high specificity of toxin-K+ channel interactions.
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Computational prediction of atomic structures of helical membrane proteins aided by EM maps.
Kovacs, Julio A; Yeager, Mark; Abagyan, Ruben
2007-09-15
Integral membrane proteins pose a major challenge for protein-structure prediction because only approximately 100 high-resolution structures are available currently, thereby impeding the development of rules or empirical potentials to predict the packing of transmembrane alpha-helices. However, when an intermediate-resolution electron microscopy (EM) map is available, it can be used to provide restraints which, in combination with a suitable computational protocol, make structure prediction feasible. In this work we present such a protocol, which proceeds in three stages: 1), generation of an ensemble of alpha-helices by flexible fitting into each of the density rods in the low-resolution EM map, spanning a range of rotational angles around the main helical axes and translational shifts along the density rods; 2), fast optimization of side chains and scoring of the resulting conformations; and 3), refinement of the lowest-scoring conformations with internal coordinate mechanics, by optimizing the van der Waals, electrostatics, hydrogen bonding, torsional, and solvation energy contributions. In addition, our method implements a penalty term through a so-called tethering map, derived from the EM map, which restrains the positions of the alpha-helices. The protocol was validated on three test cases: GpA, KcsA, and MscL.
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Ion Move Brownian Dynamics (IMBD)--simulations of ion transport.
Kurczynska, Monika; Kotulska, Malgorzata
2014-01-01
Comparison of the computed characteristics and physiological measurement of ion transport through transmembrane proteins could be a useful method to assess the quality of protein structures. Simulations of ion transport should be detailed but also timeefficient. The most accurate method could be Molecular Dynamics (MD), which is very time-consuming, hence is not used for this purpose. The model which includes ion-ion interactions and reduces the simulation time by excluding water, protein and lipid molecules is Brownian Dynamics (BD). In this paper a new computer program for BD simulation of the ion transport is presented. We evaluate two methods for calculating the pore accessibility (round and irregular shape) and two representations of ion sizes (van der Waals diameter and one voxel). Ion Move Brownian Dynamics (IMBD) was tested with two nanopores: alpha-hemolysin and potassium channel KcsA. In both cases during the simulation an ion passed through the pore in less than 32 ns. Although two types of ions were in solution (potassium and chloride), only ions which agreed with the selectivity properties of the channels passed through the pores. IMBD is a new tool for the ion transport modelling, which can be used in the simulations of wide and narrow pores.
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Closed Cycle Engine Program Used in Solar Dynamic Power Testing Effort
NASA Technical Reports Server (NTRS)
Ensworth, Clint B., III; McKissock, David B.
1998-01-01
NASA Lewis Research Center is testing the world's first integrated solar dynamic power system in a simulated space environment. This system converts solar thermal energy into electrical energy by using a closed-cycle gas turbine and alternator. A NASA-developed analysis code called the Closed Cycle Engine Program (CCEP) has been used for both pretest predictions and post-test analysis of system performance. The solar dynamic power system has a reflective concentrator that focuses solar thermal energy into a cavity receiver. The receiver is a heat exchanger that transfers the thermal power to a working fluid, an inert gas mixture of helium and xenon. The receiver also uses a phase-change material to store the thermal energy so that the system can continue producing power when there is no solar input power, such as when an Earth-orbiting satellite is in eclipse. The system uses a recuperated closed Brayton cycle to convert thermal power to mechanical power. Heated gas from the receiver expands through a turbine that turns an alternator and a compressor. The system also includes a gas cooler and a radiator, which reject waste cycle heat, and a recuperator, a gas-to-gas heat exchanger that improves cycle efficiency by recovering thermal energy.
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Design of catalytic monoliths for closed-cycle carbon dioxide lasers
NASA Technical Reports Server (NTRS)
Herz, R. K.; Guinn, K.; Goldblum, S.; Noskowski, E.
1989-01-01
Pulsed carbon dioxide (CO2) lasers have many applications in aeronautics, space research, weather monitoring and other areas. Full exploitation of the potential of these lasers in hampered by the dissociation of CO2 that occurs during laser operation. The development of closed-cycle CO2 lasers requires active CO-O2 recombination (CO oxidation) catalyst and design methods for implementation of catalysts in CO2 laser systems. A monolith catalyst section model and associated design computer program, LASCAT, are presented to assist in the design of a monolith catalyst section of a closed cycle CO2 laser system. Using LASCAT,the designer is able to specify a number of system parameters and determine the monolith section performance. Trade-offs between the catalyst activity, catalyst dimensions, monolith dimensions, pressure drop, O2 conversion, and other variables can be explored and adjusted to meet system design specifications. An introduction describes a typical closed-cycle CO2 system, and indicates some advantages of a closed cycle laser system over an open cycle system and some advantages of monolith support over other types of supports. The development and use of a monolith catalyst model is presented. The results of a design study and a discussion of general design rules are given.
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Hoenen, Thomas; Groseth, Allison; de Kok-Mercado, Fabian; Kuhn, Jens H.; Wahl-Jensen, Victoria
2012-01-01
Reverse-genetics systems are powerful tools enabling researchers to study the replication cycle of RNA viruses, including filoviruses and other hemorrhagic fever viruses, as well as to discover new antivirals. They include full-length clone systems as well as a number of life cycle modeling systems. Full-length clone systems allow for the generation of infectious, recombinant viruses, and thus are an important tool for studying the virus replication cycle in its entirety. In contrast, life cycle modeling systems such as minigenome and transcription and replication competent virus-like particle systems can be used to simulate and dissect parts of the virus life cycle outside of containment facilities. Minigenome systems are used to model viral genome replication and transcription, whereas transcription and replication competent virus-like particle systems also model morphogenesis and budding as well as infection of target cells. As such, these modeling systems have tremendous potential to further the discovery and screening of new antivirals targeting hemorrhagic fever viruses. This review provides an overview of currently established reverse genetics systems for hemorrhagic fever-causing negative-sense RNA viruses, with a particular emphasis on filoviruses, and the potential application of these systems for antiviral research. PMID:21699921
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Gouhier, Tarik C; Guichard, Frédéric
2007-03-01
In marine systems, the occurrence and implications of disturbance-recovery cycles have been revealed at the landscape level, but only in demographically open or closed systems where landscape-level dynamics are assumed to have no feedback effect on regional dynamics. We present a mussel metapopulation model to elucidate the role of landscape-level disturbance cycles for regional response of mussel populations to onshore productivity and larval transport. Landscape dynamics are generated through spatially explicit rules, and each landscape is connected to its neighbor through unidirectional larval dispersal. The role of landscape disturbance cycles in the regional system behavior is elucidated (1) in demographically open vs. demographically coupled systems, in relation to (2) onshore reproductive output and (3) the temporal scale of landscape disturbance dynamics. By controlling for spatial structure at the landscape and metapopulation levels, we first demonstrate the interaction between landscape and oceanographic connectivity. The temporal scale of disturbance cycles, as controlled by mussel colonization rate, plays a critical role in the regional behavior of the system. Indeed, fast disturbance cycles are responsible for regional synchrony in relation to onshore reproductive output. Slow disturbance cycles, however, lead to increased robustness to changes in productivity and to demographic coupling. These testable predictions indicate that the occurrence and temporal scale of local disturbance-recovery dynamics can drive large-scale variability in demographically open systems, and the response of metapopulations to changes in nearshore productivity.
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Quantifying the adaptive cycle
Angeler, David G.; Allen, Craig R.; Garmestani, Ahjond S.; Gunderson, Lance H.; Hjerne, Olle; Winder, Monika
2015-01-01
The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994–2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems.
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Quantifying the Adaptive Cycle.
Angeler, David G; Allen, Craig R; Garmestani, Ahjond S; Gunderson, Lance H; Hjerne, Olle; Winder, Monika
2015-01-01
The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994-2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems.
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Learner Performance Accounting: A Tri-Cycle Process
ERIC Educational Resources Information Center
Brown, Thomas C.; McCleary, Lloyd E.
1973-01-01
The Tri-Cycle Process described in the model permits for the first time an integrated system for designing an individualized instructional system that would permit a rational, diagnosis-prescription-evaluation system keyed to an accounting system. (Author)
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NASA Astrophysics Data System (ADS)
Ma, Junhai; Ren, Wenbo; Zhan, Xueli
2017-04-01
Based on the study of scholars at home and abroad, this paper improves the three-dimensional IS-LM model in macroeconomics, analyzes the equilibrium point of the system and stability conditions, focuses on the parameters and complex dynamic characteristics when Hopf bifurcation occurs in the three-dimensional IS-LM macroeconomics system. In order to analyze the stability of limit cycles when Hopf bifurcation occurs, this paper further introduces the first Lyapunov coefficient to judge the limit cycles, i.e. from a practical view of the business cycle. Numerical simulation results show that within the range of most of the parameters, the limit cycle of 3D IS-LM macroeconomics is stable, that is, the business cycle is stable; with the increase of the parameters, limit cycles becomes unstable, and the value range of the parameters in this situation is small. The research results of this paper have good guide significance for the analysis of macroeconomics system.
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Predictive modeling and reducing cyclic variability in autoignition engines
Hellstrom, Erik; Stefanopoulou, Anna; Jiang, Li; Larimore, Jacob
2016-08-30
Methods and systems are provided for controlling a vehicle engine to reduce cycle-to-cycle combustion variation. A predictive model is applied to predict cycle-to-cycle combustion behavior of an engine based on observed engine performance variables. Conditions are identified, based on the predicted cycle-to-cycle combustion behavior, that indicate high cycle-to-cycle combustion variation. Corrective measures are then applied to prevent the predicted high cycle-to-cycle combustion variation.
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Advanced Launch Technology Life Cycle Analysis Using the Architectural Comparison Tool (ACT)
NASA Technical Reports Server (NTRS)
McCleskey, Carey M.
2015-01-01
Life cycle technology impact comparisons for nanolauncher technology concepts were performed using an Affordability Comparison Tool (ACT) prototype. Examined are cost drivers and whether technology investments can dramatically affect the life cycle characteristics. Primary among the selected applications was the prospect of improving nanolauncher systems. As a result, findings and conclusions are documented for ways of creating more productive and affordable nanolauncher systems; e.g., an Express Lane-Flex Lane concept is forwarded, and the beneficial effect of incorporating advanced integrated avionics is explored. Also, a Functional Systems Breakdown Structure (F-SBS) was developed to derive consistent definitions of the flight and ground systems for both system performance and life cycle analysis. Further, a comprehensive catalog of ground segment functions was created.
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Proterozoic Milankovitch cycles and the history of the solar system.
Meyers, Stephen R; Malinverno, Alberto
2018-06-19
The geologic record of Milankovitch climate cycles provides a rich conceptual and temporal framework for evaluating Earth system evolution, bestowing a sharp lens through which to view our planet's history. However, the utility of these cycles for constraining the early Earth system is hindered by seemingly insurmountable uncertainties in our knowledge of solar system behavior (including Earth-Moon history), and poor temporal control for validation of cycle periods (e.g., from radioisotopic dates). Here we address these problems using a Bayesian inversion approach to quantitatively link astronomical theory with geologic observation, allowing a reconstruction of Proterozoic astronomical cycles, fundamental frequencies of the solar system, the precession constant, and the underlying geologic timescale, directly from stratigraphic data. Application of the approach to 1.4-billion-year-old rhythmites indicates a precession constant of 85.79 ± 2.72 arcsec/year (2σ), an Earth-Moon distance of 340,900 ± 2,600 km (2σ), and length of day of 18.68 ± 0.25 hours (2σ), with dominant climatic precession cycles of ∼14 ky and eccentricity cycles of ∼131 ky. The results confirm reduced tidal dissipation in the Proterozoic. A complementary analysis of Eocene rhythmites (∼55 Ma) illustrates how the approach offers a means to map out ancient solar system behavior and Earth-Moon history using the geologic archive. The method also provides robust quantitative uncertainties on the eccentricity and climatic precession periods, and derived astronomical timescales. As a consequence, the temporal resolution of ancient Earth system processes is enhanced, and our knowledge of early solar system dynamics is greatly improved.
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[Bologna process and higher health education in Europe].
Decsi, Tamás; Barakonyi, Károly
2006-08-27
Introduction of the two cycles (Bachelor/Master) system represents sensitive aspect of the implementation of the Bologna process into higher health education. The authors used the methods of evidence based medicine to analyse available documents on the implementation of the Bologna process into the education of health sciences. Electronic search in the closed MEDLINE and open Internet databases. Electronic data collection resulted in so-called country reports (n=47) and in professional statements (n=7) of health education bodies. Majority of the country reports (n=26) did not mention at all the peculiar position of health education within the Bologna process. Many country reports stated with (n=8) or without (n=9) explanation that health sciences should be excluded from the introduction of the two educational cycles system. Only 4 country reports discussed future conditions and possibilities of introducing the two cycles system into higher health education; the German country report definitely declared that the two cycles educational system may be introduced also into health education. The seven statements of professional health educational bodies (including an ad hoc committee of the Hungarian medical faculties) did not support the introduction of the two cycles system into health education. The low demand for health professionals with Bachelor (i.e. unfinished) degree was repeatedly mentioned as strong argument for not introducing the two cycles system into health education. It should be noted, however, that the process of introducing the two cycles system has began: recent survey of EUA (European University Association) indicates that in three countries (Denmark, Flanders and Switzerland) the introduction in under current discussion. Among the principles of the Bologna process, the introduction of the two cycles system has not gain acceptance in the higher health education in Europe. However, most documents firmly support the introduction of other elements of the Bologna process (comparable degrees, system of credits, promotion of mobility of students and tutors, quality control, life long learning).
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A large-scale perspective on ecosystems
NASA Technical Reports Server (NTRS)
Mizutani, Hiroshi
1987-01-01
Interactions between ecological elements must be better understood in order to construct an ecological life support system in space. An index was devised to describe the complexity of material cyclings within a given ecosystem. It was then applied to the cyclings of bioelements in various systems of material cyclings including the whole Earth and national economies. The results show interesting characteristics of natural and man-made systems.
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Comparison of energy-based indicators used in life cycle assessment tools for buildings
Traditionally, building rating systems focused on, among others, energy used during operational stage. Recently, there is a strong push by these rating systems to include the life cycle energy use of buildings, particularly using Life Cycle Assessment (LCA), by offering credits t...
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Integrated Metrics for Improving the Life Cycle Approach to Assessing Product System Sustainability
Life cycle approaches are critical for identifying and managing to reduce burdens in the sustainability of product systems. While these methods can indicate potential environmental impacts of a product, current Life Cycle Assessment (LCA) methods fail to integrate the multiple im...
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NASA Astrophysics Data System (ADS)
Song, Xiaolong; Yang, Jianxin; Lu, Bin; Yang, Dong
2017-01-01
China is now facing e-waste problems from both growing domestic generation and illegal imports. Many stakeholders are involved in the e-waste treatment system due to the complexity of e-waste life cycle. Beginning with the state of the e-waste treatment industry in China, this paper summarizes the latest progress in e-waste management from such aspects as the new edition of the China RoHS Directive, new Treatment List, new funding subsidy standard, and eco-design pilots. Thus, a conceptual model for life cycle management of e-waste is generalized. The operating procedure is to first identify the life cycle stages of the e-waste and extract the important life cycle information. Then, life cycle tools can be used to conduct a systematic analysis to help decide how to maximize the benefits from a series of life cycle engineering processes. Meanwhile, life cycle thinking is applied to improve the legislation relating to e-waste so as to continuously improve the sustainability of the e-waste treatment system. By providing an integrative framework, the life cycle management of e-waste should help to realize sustainable management of e-waste in developing countries.
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NASA Technical Reports Server (NTRS)
Beecher, D. T.
1976-01-01
Nine advanced energy conversion concepts using coal or coal-derived fuels are summarized. They are; (1) open-cycle gas turbines, (2) combined gas-steam turbine cycles, (3) closed-cycle gas turbines, (4) metal vapor Rankine topping, (5) open-cycle MHD; (6) closed-cycle MHD; (7) liquid-metal MHD; (8) advanced steam; and (9) fuel cell systems. The economics, natural resource requirements, and performance criteria for the nine concepts are discussed.
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Study of a LH2-fueled topping cycle engine for aircraft propulsion
NASA Technical Reports Server (NTRS)
Turney, G. E.; Fishbach, L. H.
1983-01-01
An analytical investigation was made of a topping cycle aircraft engine system which uses a cryogenic fuel. This system consists of a main turboshaft engine which is mechanically coupled (by cross-shafting) to a topping loop which augments the shaft power output of the system. The thermodynamic performance of the topping cycle engine was analyzed and compared with that of a reference (conventional-type) turboshaft engine. For the cycle operating conditions selected, the performance of the topping cycle engine in terms of brake specific fuel consumption (bsfc) was determined to be about 12 percent better than that of the reference turboshaft engine. Engine weights were estimated for both the topping cycle engine and the reference turboshaft engine. These estimates were based on a common shaft power output for each engine. Results indicate that the weight of the topping cycle engine is comparable to that of the reference turboshaft engine. Previously announced in STAR as N83-34942
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Advanced Multi-Effect Distillation System for Desalination Using Waste Heat fromGas Brayton Cycles
DOE Office of Scientific and Technical Information (OSTI.GOV)
Haihua Zhao; Per F. Peterson
2012-10-01
Generation IV high temperature reactor systems use closed gas Brayton Cycles to realize high thermal efficiency in the range of 40% to 60%. The waste heat is removed through coolers by water at substantially greater average temperature than in conventional Rankine steam cycles. This paper introduces an innovative Advanced Multi-Effect Distillation (AMED) design that can enable the production of substantial quantities of low-cost desalinated water using waste heat from closed gas Brayton cycles. A reference AMED design configuration, optimization models, and simplified economics analysis are presented. By using an AMED distillation system the waste heat from closed gas Brayton cyclesmore » can be fully utilized to desalinate brackish water and seawater without affecting the cycle thermal efficiency. Analysis shows that cogeneration of electricity and desalinated water can increase net revenues for several Brayton cycles while generating large quantities of potable water. The AMED combining with closed gas Brayton cycles could significantly improve the sustainability and economics of Generation IV high temperature reactors.« less
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NASA Astrophysics Data System (ADS)
Guo, Yuan
2017-05-01
This paper proposed a new concept named airborne power generation system based on Rankine cycle by heat energy, namely, the presented system combined the Rankine cycle with environmental control system in aircraft to recycle the waste heat of engine bleed air with high temperature and generate power. This paper mainly discussed the choosing of optimum working fluid which could apply in the combined power generation system mentioned above when the temperature of the coming bleed air was about 400 degree centigrade.
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Spatio-temporal characterisation of a 100 kHz 24 W sub-3-cycle NOPCPA laser system
NASA Astrophysics Data System (ADS)
Witting, Tobias; Furch, Federico J.; Vrakking, Marc J. J.
2018-04-01
In recent years, OPCPA and NOPCPA laser systems have shown the potential to supersede Ti:sapphire plus post-compression based laser systems to drive next generation attosecond light sources via direct amplification of few-cycle pulses to high pulse energies at high repetition rates. In this paper, we present a sub 3-cycle, 100 kHz, 24 W NOPA laser system and characterise its spatio-temporal properties using the SEA-F-SPIDER technique. Our results underline the importance of spatio-temporal diagnostics for these emerging laser systems.
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NASA Technical Reports Server (NTRS)
Sagerman, G. D.; Barna, G. J.; Burns, R. K.
1979-01-01
An overview of the organization and methodology of the Cogeneration Technology Alternatives Study is presented. The objectives of the study were to identify the most attractive advanced energy conversion systems for industrial cogeneration applications in the future and to assess the advantages of advanced technology systems compared to those systems commercially available today. Advanced systems studied include steam turbines, open and closed cycle gas turbines, combined cycles, diesel engines, Stirling engines, phosphoric acid and molten carbonate fuel cells and thermionics. Steam turbines, open cycle gas turbines, combined cycles, and diesel engines were also analyzed in versions typical of today's commercially available technology to provide a base against which to measure the advanced systems. Cogeneration applications in the major energy consuming manufacturing industries were considered. Results of the study in terms of plant level energy savings, annual energy cost savings and economic attractiveness are presented for the various energy conversion systems considered.
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A life cycle greenhouse gas inventory of a tree production system
Alissa Kendall; E. Gregory McPherson
2012-01-01
PurposeThis study provides a detailed, process-based life cycle greenhouse gas (GHG) inventory of an ornamental tree production system for urban forestry. The success of large-scale tree planting initiatives for climate protection depends on projects being net sinks for CO2 over their entire life cycle....
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ERIC Educational Resources Information Center
Kintzer, Frederick C.
1992-01-01
Defines short-cycle higher education (postcompulsory, subbaccalaureate education). Identifies characteristics shared by short-cycle systems worldwide and the ways in which individual systems differ. Discusses issues of low esteem, community education, articulation and transfer, business/industry relations, financial support. Offers recommendations…
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Characterizing Observed Limit Cycles in the Cassini Main Engine Guidance Control System
NASA Technical Reports Server (NTRS)
Rizvi, Farheen; Weitl, Raquel M.
2011-01-01
The Cassini spacecraft dynamics-related telemetry during long Main Engine (ME) burns has indicated the presence of stable limit cycles between 0.03-0.04 Hz frequencies. These stable limit cycles cause the spacecraft to possess non-zero oscillating rates for extended periods of time. This indicates that the linear ME guidance control system does not model the complete dynamics of the spacecraft. In this study, we propose that the observed limit cycles in the spacecraft dynamics telemetry appear from a stable interaction between the unmodeled nonlinear elements in the ME guidance control system. Many nonlinearities in the control system emerge from translating the linear engine gimbal actuator (EGA) motion into a spacecraft rotation. One such nonlinearity comes from the gear backlash in the EGA system, which is the focus of this paper. The limit cycle characteristics and behavior can be predicted by modeling this gear backlash nonlinear element via a describing function and studying the interaction of this describing function with the overall dynamics of the spacecraft. The linear ME guidance controller and gear backlash nonlinearity are modeled analytically. The frequency, magnitude, and nature of the limit cycle are obtained from the frequency response of the ME guidance controller and nonlinear element. In addition, the ME guidance controller along with the nonlinearity is simulated. The simulation response contains a limit cycle with similar characterstics as predicted analytically: 0.03-0.04 Hz frequency and stable, sustained oscillations. The analytical and simulated limit cycle responses are compared to the flight telemetry for long burns such as the Saturn Orbit Insertion and Main Engine Orbit Trim Maneuvers. The analytical and simulated limit cycle characteristics compare well with the actual observed limit cycles in the flight telemetry. Both have frequencies between 0.03-0.04 Hz and stable oscillations. This work shows that the stable limit cycles occur due to the interaction between the unmodeled nonlinear elements and linear ME guidance controller.
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Color stability of shade guides after autoclave sterilization.
Schmeling, Max; Sartori, Neimar; Monteiro, Sylvio; Baratieri, Luiz
2014-01-01
This study evaluated the influence of 120 autoclave sterilization cycles on the color stability of two commercial shade guides (Vita Classical and Vita System 3D-Master). The specimens were evaluated by spectrophotometer before and after the sterilization cycles. The color was described using the three-dimensional CIELab system. The statistical analysis was performed in three chromaticity coordinates, before and after sterilization cycles, using the paired samples t test. All specimens became darker after autoclave sterilization cycles. However, specimens of Vita Classical became redder, while those of the Vita System 3D-Master became more yellow. Repeated cycles of autoclave sterilization caused statistically significant changes in the color coordinates of the two shade guides. However, these differences are considered clinically acceptable.
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Rocket Based Combined Cycle (RBCC) Propulsion Workshop, volume 2
NASA Technical Reports Server (NTRS)
Chojnacki, Kent T.
1992-01-01
The goal of the Rocket Based Combined Cycle (RBCC) Propulsion Technology Workshop, was to impart technology information to the propulsion community with respect to hypersonic combined cycle propulsion capabilities. The major recommendation resulting from this technology workshop was as follows: conduct a systems-level applications study to define the desired propulsion system and vehicle technology requirements for LEO launch vehicles. All SSTO and TSTO options using the various propulsion systems (airbreathing combined cycle, rocket-based combined cycle, and all rocket) must be considered. Such a study should be accomplished as soon as possible. It must be conducted with a consistent set of ground rules and assumptions. Additionally, the study should be conducted before any major expenditures on a RBCC technology development program occur.
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5 CFR 930.301 - Information systems security awareness training program.
Code of Federal Regulations, 2011 CFR
2011-01-01
... training in system/application life cycle management, risk management, and contingency planning. (4) Chief... security management, system/application life cycle management, risk management, and contingency planning..., risk management, and contingency planning. (b) Provide the Federal information systems security...
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5 CFR 930.301 - Information systems security awareness training program.
Code of Federal Regulations, 2010 CFR
2010-01-01
... training in system/application life cycle management, risk management, and contingency planning. (4) Chief... security management, system/application life cycle management, risk management, and contingency planning..., risk management, and contingency planning. (b) Provide the Federal information systems security...
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Composite turbine blade design options for Claude (open) cycle OTEC power systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Penney, T R
1985-11-01
Small-scale turbine rotors made from composites offer several technical advantages for a Claude (open) cycle ocean thermal energy conversion (OTEC) power system. Westinghouse Electric Corporation has designed a composite turbine rotor/disk using state-of-the-art analysis methods for large-scale (100-MW/sub e/) open cycle OTEC applications. Near-term demonstrations using conventional low-pressure turbine blade shapes with composite material would achieve feasibility and modern credibility of the open cycle OTEC power system. Application of composite blades for low-pressure turbo-machinery potentially improves the reliability of conventional metal blades affected by stress corrosion.
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Conceptual design of closed Brayton cycle for coal-fired power generation
NASA Technical Reports Server (NTRS)
Shah, R. P.; Corman, J. C.
1977-01-01
The objectives to be realized in developing a closed cycle gas turbine are (1) to exploit high temperature gas turbine technology while maintaining a working fluid which is free from combustion gas contamination, (2) to achieve compact turbo-equipment designs through pressurization of the working fluid, and (3) to obtain relatively simple cycle configurations. The technical/economic performance of a specific closed cycle gas turbine system was evaluated through the development of a conceptual plant and system design. This energy conversion system is designed for electric utility service and to utilize coal directly in an environmentally acceptable manner.
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NASA Astrophysics Data System (ADS)
Hesselbrock, Andrew; Minton, David A.
2017-10-01
We recently reported that the orbital architecture of the Martian environment allows for material in orbit around the planet to ``cycle'' between orbiting the planet as a ring, or as coherent satellites. Here we generalize our previous analysis to examine several factors that determine whether satellites accreting at the edge of planetary rings will cycle. In order for the orbiting material to cycle, tidal evolution must decrease the semi-major axis of any accreting satellites. In some systems, the density of the ring/satellite material, the surface mass density of the ring, the tidal parameters of the system, and the rotation rate of the primary body contribute to a competition between resonant ring torques and tidal dissipation that prevent this from occurring, either permanently or temporarily. Analyzing these criteria, we examine various bodies in our solar system (such as Saturn, Uranus, and Eris) to identify systems where cycling may occur. We find that a ring-satellite cycle may give rise to the current Uranian ring-satellite system, and suggest that Miranda may have formed from an early, more massive Uranian ring.
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Addressing software security and mitigations in the life cycle
NASA Technical Reports Server (NTRS)
Gilliam, David; Powell, John; Haugh, Eric; Bishop, Matt
2003-01-01
Traditionally, security is viewed as an organizational and Information Technology (IIJ systems function comprising of Firewalls, intrusion detection systems (IDS), system security settings and patches to the operating system (OS) and applications running on it. Until recently, little thought has been given to the importance of security as a formal approach in the software life cycle. The Jet Propulsion Laboratory has approached the problem through the development of an integrated formal Software Security Assessment Instrument (SSAI) with six foci for the software life cycle.
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Addressing software security and mitigations in the life cycle
NASA Technical Reports Server (NTRS)
Gilliam, David; Powell, John; Haugh, Eric; Bishop, Matt
2004-01-01
Traditionally, security is viewed as an organizational and Information Technology (IT) systems function comprising of firewalls, intrusion detection systems (IDS), system security settings and patches to the operating system (OS) and applications running on it. Until recently, little thought has been given to the importance of security as a formal approach in the software life cycle. The Jet Propulsion Laboratory has approached the problem through the development of an integrated formal Software Security Assessment Instrument (SSAI) with six foci for the software life cycle.
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NASA Technical Reports Server (NTRS)
Nainiger, J. J.; Burns, R. K.
1977-01-01
A comparison and an assessment of 10 advanced utility power systems on a consistent basis and to a common level of detail were analyzed. Substantial emphasis was given to a combined cycle systems integrated with low-Btu gasifiers. Performance and cost results from that study were presented for these combined cycle systems, together with a comparative evaluation. The effect of the gasifier type and performance and the interface between the gasifier and the power system were discussed.
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NASA Technical Reports Server (NTRS)
Hamilton, M. L.; Burriss, W. L.
1972-01-01
Detailed cycle steady-state performance data are presented for the final auxiliary power unit (APU) system configuration. The selection configuration is a hydrogen-oxygen APU incorporating a recuperator to utilize the exhaust energy and using the cycle hydrogen flow as a means of cooling the component heat loads. The data are given in the form of computer printouts and provide the following: (1) verification of the adequacy of the design to meet the problem statement for steady-state performance; (2) overall system performance data for the vehicle system analyst to determine propellant consumption and hydraulic fluid temperature as a function for varying mission profiles, propellant inlet conditions, etc.; and (3) detailed component performance and cycle state point data to show what is happening in the cycle as a function of the external forcing functions.
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New device to measure dynamic intrusion/extrusion cycles of lyophobic heterogeneous systems.
Guillemot, Ludivine; Galarneau, Anne; Vigier, Gérard; Abensur, Thierry; Charlaix, Élisabeth
2012-10-01
Lyophobic heterogeneous systems (LHS) are made of mesoporous materials immersed in a non-wetting liquid. One application of LHS is the nonlinear damping of high frequency vibrations. The behaviour of LHS is characterized by P - ΔV cycles, where P is the pressure applied to the system, and ΔV its volume change due to the intrusion of the liquid into the pores of the material, or its extrusion out of the pores. Very few dynamic studies of LHS have been performed until now. We describe here a new apparatus that allows us to carry out dynamic intrusion/extrusion cycles with various liquid/porous material systems, controlling the temperature from ambient to 120 °C and the frequency from 0.01 to 20 Hz. We show that for two LHS: water/MTS and Galinstan/CPG, the energy dissipated during one cycle depends very weakly on the cycle frequency, in strong contrast to conventional dampers.
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ERIC Educational Resources Information Center
Human Engineering Inst., Cleveland, OH.
THIS MODULE OF A 30-MODULE COURSE IS DESIGNED TO DEVELOP AN UNDERSTANDING OF DIFFERENCES BETWEEN TWO AND FOUR CYCLE ENGINES, THE OPERATION AND MAINTENANCE OF THE DIESEL ENGINE FUEL SYSTEM, AND THE PROCEDURES FOR DIESEL ENGINE REMOVAL. TOPICS ARE (1) REVIEW OF TWO CYCLE AND FOUR CYCLE CONCEPT, (2) SOME BASIC CHARACTERISTICS OF FOUR CYCLE ENGINES,…
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Rank one chaos in a class of planar systems with heteroclinic cycle.
Chen, Fengjuan; Han, Maoan
2009-12-01
In this paper, we study rank one chaos in a class of planar systems with heteroclinic cycle. We first find a stable limit cycle inside the heteroclinic cycle. We then add an external periodic forcing to create rank one chaos. We follow a step-by-step procedure guided by the theory of rank one chaos to find experimental evidence of strange attractors with Sinai, Ruelle, and Bowen measures.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
None
BEETIT Project: Battelle is developing a new air conditioning system that uses a cascade reverse osmosis (RO)-based absorption cycle. Analyses show that this new cycle can be as much as 60% more efficient than vapor compression, which is used in 90% of air conditioners. Traditional vapor-compression systems use polluting liquids for a cooling effect. Absorption cycles use benign refrigerants such as water, which is absorbed in a salt solution and pumped as liquid—replacing compression of vapor. The refrigerant is subsequently separated from absorbing salt using heat for re-use in the cooling cycle. Battelle is replacing thermal separation of refrigerant withmore » a more efficient reverse osmosis process. Research has shown that the cycle is possible, but further investment will be needed to reduce the number of cascade reverse osmosis stages and therefore cost.« less
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NASA Technical Reports Server (NTRS)
Borden, C. S.; Volkmer, K.; Cochrane, E. H.; Lawson, A. C.
1984-01-01
A simple methodology to estimate photovoltaic system size and life-cycle costs in stand-alone applications is presented. It is designed to assist engineers at Government agencies in determining the feasibility of using small stand-alone photovoltaic systems to supply ac or dc power to the load. Photovoltaic system design considerations are presented as well as the equations for sizing the flat-plate array and the battery storage to meet the required load. Cost effectiveness of a candidate photovoltaic system is based on comparison with the life-cycle cost of alternative systems. Examples of alternative systems addressed are batteries, diesel generators, the utility grid, and other renewable energy systems.
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Brown, Nicholas R.; Powers, Jeffrey J.; Feng, B.; ...
2015-05-21
This paper presents analyses of possible reactor representations of a nuclear fuel cycle with continuous recycling of thorium and produced uranium (mostly U-233) with thorium-only feed. The analysis was performed in the context of a U.S. Department of Energy effort to develop a compendium of informative nuclear fuel cycle performance data. The objective of this paper is to determine whether intermediate spectrum systems, having a majority of fission events occurring with incident neutron energies between 1 eV and 10 5 eV, perform as well as fast spectrum systems in this fuel cycle. The intermediate spectrum options analyzed include tight latticemore » heavy or light water-cooled reactors, continuously refueled molten salt reactors, and a sodium-cooled reactor with hydride fuel. All options were modeled in reactor physics codes to calculate their lattice physics, spectrum characteristics, and fuel compositions over time. Based on these results, detailed metrics were calculated to compare the fuel cycle performance. These metrics include waste management and resource utilization, and are binned to accommodate uncertainties. The performance of the intermediate systems for this selfsustaining thorium fuel cycle was similar to a representative fast spectrum system. However, the number of fission neutrons emitted per neutron absorbed limits performance in intermediate spectrum systems.« less
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The architecture and conservation pattern of whole-cell control circuitry.
McAdams, Harley H; Shapiro, Lucy
2011-05-27
The control circuitry that directs and paces Caulobacter cell cycle progression involves the entire cell operating as an integrated system. This control circuitry monitors the environment and the internal state of the cell, including the cell topology, as it orchestrates orderly activation of cell cycle subsystems and Caulobacter's asymmetric cell division. The proteins of the Caulobacter cell cycle control system and its internal organization are co-conserved across many alphaproteobacteria species, but there are great differences in the regulatory apparatus' functionality and peripheral connectivity to other cellular subsystems from species to species. This pattern is similar to that observed for the "kernels" of the regulatory networks that regulate development of metazoan body plans. The Caulobacter cell cycle control system has been exquisitely optimized as a total system for robust operation in the face of internal stochastic noise and environmental uncertainty. When sufficient details accumulate, as for Caulobacter cell cycle regulation, the system design has been found to be eminently rational and indeed consistent with good design practices for human-designed asynchronous control systems. Copyright © 2011 Elsevier Ltd. All rights reserved.
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High-speed thermal cycling system and method of use
Hansen, A.D.A.; Jaklevic, J.M.
1996-04-16
A thermal cycling system and method of use are described. The thermal cycling system is based on the circulation of temperature-controlled water directly to the underside of thin-walled polycarbonate plates. The water flow is selected from a manifold fed by pumps from heated reservoirs. The plate wells are loaded with typically 15-20 microliters of reagent mix for the PCR process. Heat transfer through the thin polycarbonate is sufficiently rapid that the contents reach thermal equilibrium with the water in less than 15 seconds. Complete PCR amplification runs of 40 three-step cycles have been performed in as little as 14.5 minutes, with the results showing substantially enhanced specificity compared to conventional technology requiring run times in excess of 100 minutes. The plate clamping station is designed to be amenable to robotic loading and unloading of the system. It includes a heated lid, thus eliminating the need for mineral oil overlay of the reactants. The present system includes three or more plate holder stations, fed from common reservoirs but operating with independent switching cycles. The system can be modularly expanded. 13 figs.
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High-speed thermal cycling system and method of use
Hansen, Anthony D. A.; Jaklevic, Joseph M.
1996-01-01
A thermal cycling system and method of use are described. The thermal cycling system is based on the-circulation of temperature-controlled water directly to the underside of thin-walled polycarbonate microtiter plates. The water flow is selected from a manifold fed by pumps from heated reservoirs. The plate wells are loaded with typically 15-20 .mu.l of reagent mix for the PCR process. Heat transfer through the thin polycarbonate is sufficiently rapid that the contents reach thermal equilibrium with the water in less than 15 seconds. Complete PCR amplification runs of 40 three-step cycles have been performed in as little as 14.5 minutes, with the results showing substantially enhanced specificity compared to conventional technology requiring run times in excess of 100 minutes. The plate clamping station is designed to be amenable to robotic loading and unloading of the system. It includes a heated lid, thus eliminating the need for mineral oil overlay of the reactants. The present system includes three or more plate holder stations, fed from common reservoirs but operating with independent switching cycles. The system can be modularly expanded.
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Indirect-fired gas turbine dual fuel cell power cycle
Micheli, Paul L.; Williams, Mark C.; Sudhoff, Frederick A.
1996-01-01
A fuel cell and gas turbine combined cycle system which includes dual fuel cell cycles combined with a gas turbine cycle wherein a solid oxide fuel cell cycle operated at a pressure of between 6 to 15 atms tops the turbine cycle and is used to produce CO.sub.2 for a molten carbonate fuel cell cycle which bottoms the turbine and is operated at essentially atmospheric pressure. A high pressure combustor is used to combust the excess fuel from the topping fuel cell cycle to further heat the pressurized gas driving the turbine. A low pressure combustor is used to combust the excess fuel from the bottoming fuel cell to reheat the gas stream passing out of the turbine which is used to preheat the pressurized air stream entering the topping fuel cell before passing into the bottoming fuel cell cathode. The CO.sub.2 generated in the solid oxide fuel cell cycle cascades through the system to the molten carbonate fuel cell cycle cathode.
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NASA Astrophysics Data System (ADS)
Meier, Paul Joseph
This research uses Life-Cycle Assessment (LCA) to better understand the energy and environmental performance for two electricity generation systems, a 620 MW combined-cycle natural gas plant, and an 8kW building-integrated photovoltaic system. The results of the LCA are used to provide an effective and accurate means for evaluating greenhouse gas emission reduction strategies for U.S. electricity generation. The modern combined-cycle plant considered in this thesis is nominally 48% thermally efficient, but it is only 43% energy efficient when evaluated across its entire life-cycle, due primarily to energy losses during the natural gas fuel cycle. The emission rate for the combined-cycle natural gas plant life-cycle (469 tonnes CO2-equivalent per GWeh), was 23% higher than the emission rate from plant operation alone (382 tonnes CO2-equivalent per GWeh). Uncertainty in the rate of fuel-cycle methane releases results in a potential range of emission rates between 457 to 534 tonnes CO 2-equivalent per GWeh for the studied plant. The photovoltaic system modules have a sunlight to DC electricity conversion efficiency of 5.7%. However, the system's sunlight to AC electricity conversion efficiency is 4.3%, when accounting for life-cycle energy inputs, as well as losses due to system wiring, AC inversion, and module degradation. The LCA illustrates that the PV system has a low, but not zero, life-cycle greenhouse gas emission rate of 39 Tonnes CO2-equivalent per GWeh. A ternary method of evaluation is used to evaluate three greenhouse gas mitigation alternatives: (1) fuel-switching from coal to natural gas for Kyoto-based compliance, (2) fuel-switching from coal to nuclear/renewable for Kyoto based compliance, and (3) fuel-switching to meet the White House House's Global Climate Change Initiative. In a moderate growth scenario, fuel-switching from coal to natural gas fails to meet a Kyoto-based emission target, while fuel-switching to nuclear/renewable meets the emission objective by reducing coal generated electricity 32% below 2000 levels. The Global Climate Change Initiative allows annual greenhouse gas emissions to increase to levels that are 54% higher than the proposed U.S. commitment under the Kyoto Protocol.
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Rankine cycle waste heat recovery system
Ernst, Timothy C.; Nelson, Christopher R.
2016-05-10
This disclosure relates to a waste heat recovery (WHR) system and to a system and method for regulation of a fluid inventory in a condenser and a receiver of a Rankine cycle WHR system. Such regulation includes the ability to regulate the pressure in a WHR system to control cavitation and energy conversion.
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Rankine cycle waste heat recovery system
Ernst, Timothy C.; Nelson, Christopher R.
2014-08-12
This disclosure relates to a waste heat recovery (WHR) system and to a system and method for regulation of a fluid inventory in a condenser and a receiver of a Rankine cycle WHR system. Such regulation includes the ability to regulate the pressure in a WHR system to control cavitation and energy conversion.
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A vision for an ultra-high resolution integrated water cycle observation and prediction system
NASA Astrophysics Data System (ADS)
Houser, P. R.
2013-05-01
Society's welfare, progress, and sustainable economic growth—and life itself—depend on the abundance and vigorous cycling and replenishing of water throughout the global environment. The water cycle operates on a continuum of time and space scales and exchanges large amounts of energy as water undergoes phase changes and is moved from one part of the Earth system to another. We must move toward an integrated observation and prediction paradigm that addresses broad local-to-global science and application issues by realizing synergies associated with multiple, coordinated observations and prediction systems. A central challenge of a future water and energy cycle observation strategy is to progress from single variable water-cycle instruments to multivariable integrated instruments in electromagnetic-band families. The microwave range in the electromagnetic spectrum is ideally suited for sensing the state and abundance of water because of water's dielectric properties. Eventually, a dedicated high-resolution water-cycle microwave-based satellite mission may be possible based on large-aperture antenna technology that can harvest the synergy that would be afforded by simultaneous multichannel active and passive microwave measurements. A partial demonstration of these ideas can even be realized with existing microwave satellite observations to support advanced multivariate retrieval methods that can exploit the totality of the microwave spectral information. The simultaneous multichannel active and passive microwave retrieval would allow improved-accuracy retrievals that are not possible with isolated measurements. Furthermore, the simultaneous monitoring of several of the land, atmospheric, oceanic, and cryospheric states brings synergies that will substantially enhance understanding of the global water and energy cycle as a system. The multichannel approach also affords advantages to some constituent retrievals—for instance, simultaneous retrieval of vegetation biomass would improve soil-moisture retrieval by avoiding the need for auxiliary vegetation information. This multivariable water-cycle observation system must be integrated with high-resolution, application relevant prediction systems to optimize their information content and utility is addressing critical water cycle issues. One such vision is a real-time ultra-high resolution locally-moasiced global land modeling and assimilation system, that overlays regional high-fidelity information over a baseline global land prediction system. Such a system would provide the best possible local information for use in applications, while integrating and sharing information globally for diagnosing larger water cycle variability. In a sense, this would constitute a hydrologic telecommunication system, where the best local in-situ gage, Doppler radar, and weather station can be shared internationally, and integrated in a consistent manner with global observation platforms like the multivariable water cycle mission. To realize such a vision, large issues must be addressed, such as international data sharing policy, model-observation integration approaches that maintain local extremes while achieving global consistency, and methods for establishing error estimates and uncertainty.
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Patterns, structures and regulations of domestic water cycle systems in China
NASA Astrophysics Data System (ADS)
Chu, Junying; Wang, Hao; Wang, Jianhua; Qin, Dayong
2010-05-01
Domestic water cycle systems serving as one critical component of artificial water cycle at the catchment's scale, is so closely related to public healthy, human rights and social-economic development, and has gained the highest priority in strategic water resource and municipal infrastructure planning. In this paper, three basic patterns of domestic water cycle systems are identified and analyzed, including rural domestic water system (i.e. primary level), urban domestic water system (i.e. intermediate level) and metropolitan domestic water system (i.e. senior level), with different "abstract-transport-consume-discharge" mechanisms and micro-components of water consumption (such as drinking, cooking, toilet flushing, showering or cleaning). The rural domestic water system is general simple with three basic "abstract-consume-discharge" mechanisms and micro-components of basic water consumption such as drinking, cooking, washing and sanitation. The urban domestic water system has relative complex mechanisms of "abstract-supply-consume-treatment-discharge" and more micro-components of water consumption such as bath, dishwashing or car washing. The metropolitan domestic water system (i.e. senior level) has the most complex mechanisms by considering internal water reuse, external wastewater reclamation, and nutrient recycling processes. The detailed structures for different water cycle pattern are presented from the aspects of water quantity, wastewater quality and nutrients flow. With the speed up of urbanization and development of social-economy in China, those three basic patterns are interacting, transforming and upgrading. According to the past experiences and current situations, urban domestic water system (i.e. intermediate level) is the dominant pattern based on indicator of system number or system scale. The metropolitan domestic water system (i.e. senior level) is the idealized model for the future development and management. Current domestic water system management efforts typically fail in China, because the approach is generally narrowly-focused and fragmented. This paper put forward a total-process control framework following the water and pollutants (or nutrients) flows along the dualistic domestic water cycle process. Five key objectives of domestic water cycle system regulation are identified including water use safety, water use equity, water saving, wastewater reduction and nutrient recycling. Comprehensive regulatory framework regarding administrative, economic, technical and social measures is recommended to promote sustainable domestic water usage and demand management. Considering the relatively low affordability in rural area, economic measures should be mainly applied in urban domestic water systems and metropolitan domestic water systems. Engineering or technological measures which are suitable to the three domestic water cycle systems are discussed respectively.
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A post-Cassini view of Titan's methane-based hydrologic cycle
NASA Astrophysics Data System (ADS)
Hayes, Alexander G.; Lorenz, Ralph D.; Lunine, Jonathan I.
2018-05-01
The methane-based hydrologic cycle on Saturn's largest moon, Titan, is an extreme analogue to Earth's water cycle. Titan is the only planetary body in the Solar System, other than Earth, that is known to have an active hydrologic cycle. With a surface pressure of 1.5 bar and temperatures of 90 to 95 K, methane and ethane condense out of a nitrogen-based atmosphere and flow as liquids on the moon's surface. Exchange processes between atmospheric, surface and subsurface reservoirs produce methane and ethane cloud systems, as well as erosional and depositional landscapes that have strikingly similar forms to their terrestrial counterparts. Over its 13-year exploration of the Saturn system, the Cassini-Huygens mission revealed that Titan's hydrocarbon-based hydrology is driven by nested methane cycles that operate over a range of timescales, including geologic, orbital (for example, Croll-Milankovitch cycles), seasonal and that of a single convective storm. In this Review Article, we describe the dominant exchange processes that operate over these timescales and present a post-Cassini view of Titan's methane-based hydrologic system.
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NASA Astrophysics Data System (ADS)
Leung, L. R.; Thornton, P. E.; Riley, W. J.; Calvin, K. V.
2017-12-01
Towards the goal of understanding the contributions from natural and managed systems to current and future greenhouse gas fluxes and carbon-climate and carbon-CO2 feedbacks, efforts have been underway to improve representations of the terrestrial, river, and human components of the ACME earth system model. Broadly, our efforts include implementation and comparison of approaches to represent the nutrient cycles and nutrient limitations on ecosystem production, extending the river transport model to represent sediment and riverine biogeochemistry, and coupling of human systems such as irrigation, reservoir operations, and energy and land use with the ACME land and river components. Numerical experiments have been designed to understand how terrestrial carbon, nitrogen, and phosphorus cycles regulate climate system feedbacks and the sensitivity of the feedbacks to different model treatments, examine key processes governing sediment and biogeochemistry in the rivers and their role in the carbon cycle, and exploring the impacts of human systems in perturbing the hydrological and carbon cycles and their interactions. This presentation will briefly introduce the ACME modeling approaches and discuss preliminary results and insights from numerical experiments that lay the foundation for improving understanding of the integrated climate-biogeochemistry-human system.
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NASA Technical Reports Server (NTRS)
Csank, Jeffrey; Stueber, Thomas
2012-01-01
An inlet system is being tested to evaluate methodologies for a turbine based combined cycle propulsion system to perform a controlled inlet mode transition. Prior to wind tunnel based hardware testing of controlled mode transitions, simulation models are used to test, debug, and validate potential control algorithms. One candidate simulation package for this purpose is the High Mach Transient Engine Cycle Code (HiTECC). The HiTECC simulation package models the inlet system, propulsion systems, thermal energy, geometry, nozzle, and fuel systems. This paper discusses the modification and redesign of the simulation package and control system to represent the NASA large-scale inlet model for Combined Cycle Engine mode transition studies, mounted in NASA Glenn s 10-foot by 10-foot Supersonic Wind Tunnel. This model will be used for designing and testing candidate control algorithms before implementation.
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NASA Technical Reports Server (NTRS)
Csank, Jeffrey T.; Stueber, Thomas J.
2012-01-01
An inlet system is being tested to evaluate methodologies for a turbine based combined cycle propulsion system to perform a controlled inlet mode transition. Prior to wind tunnel based hardware testing of controlled mode transitions, simulation models are used to test, debug, and validate potential control algorithms. One candidate simulation package for this purpose is the High Mach Transient Engine Cycle Code (HiTECC). The HiTECC simulation package models the inlet system, propulsion systems, thermal energy, geometry, nozzle, and fuel systems. This paper discusses the modification and redesign of the simulation package and control system to represent the NASA large-scale inlet model for Combined Cycle Engine mode transition studies, mounted in NASA Glenn s 10- by 10-Foot Supersonic Wind Tunnel. This model will be used for designing and testing candidate control algorithms before implementation.
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Variable pressure power cycle and control system
Goldsberry, Fred L.
1984-11-27
A variable pressure power cycle and control system that is adjustable to a variable heat source is disclosed. The power cycle adjusts itself to the heat source so that a minimal temperature difference is maintained between the heat source fluid and the power cycle working fluid, thereby substantially matching the thermodynamic envelope of the power cycle to the thermodynamic envelope of the heat source. Adjustments are made by sensing the inlet temperature of the heat source fluid and then setting a superheated vapor temperature and pressure to achieve a minimum temperature difference between the heat source fluid and the working fluid.
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Variable Cycle Intake for Reverse Core Engine
NASA Technical Reports Server (NTRS)
Chandler, Jesse M (Inventor); Staubach, Joseph B (Inventor); Suciu, Gabriel L (Inventor)
2016-01-01
A gas generator for a reverse core engine propulsion system has a variable cycle intake for the gas generator, which variable cycle intake includes a duct system. The duct system is configured for being selectively disposed in a first position and a second position, wherein free stream air is fed to the gas generator when in the first position, and fan stream air is fed to the gas generator when in the second position.
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Open-Cycle Gas Turbine/Steam Turbine Combined Cycles with synthetic fuels from coal
NASA Technical Reports Server (NTRS)
Shah, R. P.; Corman, J. C.
1977-01-01
The Open-Cycle Gas Turbine/Steam Turbine Combined Cycle can be an effective energy conversion system for converting coal to electricity. The intermediate step in this energy conversion process is to convert the coal into a fuel acceptable to a gas turbine. This can be accomplished by producing a synthetic gas or liquid, and by removing, in the fuel conversion step, the elements in the fuel that would be harmful to the environment if combusted. In this paper, two open-cycle gas turbine combined systems are evaluated: one employing an integrated low-Btu gasifier, and one utilizing a semi-clean liquid fuel. A consistent technical/economic information base is developed for these two systems, and is compared with a reference steam plant burning coal directly in a conventional furnace.
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Performance estimates for the Space Station power system Brayton Cycle compressor and turbine
NASA Technical Reports Server (NTRS)
Cummings, Robert L.
1989-01-01
The methods which have been used by the NASA Lewis Research Center for predicting Brayton Cycle compressor and turbine performance for different gases and flow rates are described. These methods were developed by NASA Lewis during the early days of Brayton cycle component development and they can now be applied to the task of predicting the performance of the Closed Brayton Cycle (CBC) Space Station Freedom power system. Computer programs are given for performing these calculations and data from previous NASA Lewis Brayton Compressor and Turbine tests is used to make accurate estimates of the compressor and turbine performance for the CBC power system. Results of these calculations are also given. In general, calculations confirm that the CBC Brayton Cycle contractor has made realistic compressor and turbine performance estimates.
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Summary of the research and development effort on the supercritical CO2 cycle
NASA Astrophysics Data System (ADS)
Fraas, A. P.
1981-06-01
The supercritical CO2 cycle has the advantage over a conventional closed cycle gas turbine in that the compression work phase of the cycle can be carried out close to the critical point and hence aerodynamic losses in the compressor are reduced and the cycle efficiency increased for a given turbine inlet temperature. However, the practicable turbine inlet temperature is reduced by permissible stresses in the heater tubes because the peak pressure in the cycle must be approx. 260 atm in order to have the compression process take place close to the critical point of the working fluid. The high system pressure also makes the capital cost of the heat exchangers and gas piping higher than that for a conventional closed cycle gas turbine. Further, the waste heat from the cycle must be rejected at too low a temperature for it to be useful for industrial process heat or for district heating systems.
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NASA Technical Reports Server (NTRS)
Baker, C. E.
1977-01-01
A pure thermochemical cycle is a system of linked regenerative chemical reactions which accepts only water and heat and produces hydrogen. Thermochemical cycles are potentially a more efficient and cheaper means of producing hydrogen from water than is the generation of electricity followed by electrolysis. The Energy Storage Systems Division of the Department of Energy is currently funding a national program on thermochemical hydrogen production. The National Aeronautics and Space Administration is responsible for the technical management of this program. The goal is to develop a cycle which can potentially operate with an efficiency greater than 40% using a heat source providing a maximum available temperature of 1150 K. A closed bench-scale demonstration of such a cycle would follow. This cycle would be labeled a 'reference cycle' and would serve as a baseline against which future cycles would be compared.
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Moderate temperature control technology for a lunar base
NASA Technical Reports Server (NTRS)
Swanson, Theodore D.; Sridhar, K. R.; Gottmann, Matthias
1993-01-01
A parametric analysis is performed to compare different heat pump based thermal control systems for a Lunar Base. Rankine cycle and absorption cycle heat pumps are compared and optimized for a 100 kW cooling load. Variables include the use or lack of an interface heat exchanger, and different operating fluids. Optimization of system mass to radiator rejection temperature is performed. The results indicate a relatively small sensitivity of Rankine cycle system mass to these variables, with optimized system masses of about 6000 kg for the 100 kW thermal load. It is quantitaively demonstrated that absorption based systems are not mass competitive with Rankine systems.
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The US business cycle: power law scaling for interacting units with complex internal structure
NASA Astrophysics Data System (ADS)
Ormerod, Paul
2002-11-01
In the social sciences, there is increasing evidence of the existence of power law distributions. The distribution of recessions in capitalist economies has recently been shown to follow such a distribution. The preferred explanation for this is self-organised criticality. Gene Stanley and colleagues propose an alternative, namely that power law scaling can arise from the interplay between random multiplicative growth and the complex structure of the units composing the system. This paper offers a parsimonious model of the US business cycle based on similar principles. The business cycle, along with long-term growth, is one of the two features which distinguishes capitalism from all previously existing societies. Yet, economics lacks a satisfactory theory of the cycle. The source of cycles is posited in economic theory to be a series of random shocks which are external to the system. In this model, the cycle is an internal feature of the system, arising from the level of industrial concentration of the agents and the interactions between them. The model-in contrast to existing economic theories of the cycle-accounts for the key features of output growth in the US business cycle in the 20th century.
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Solar thermal organic rankine cycle for micro-generation
NASA Astrophysics Data System (ADS)
Alkahli, N. A.; Abdullah, H.; Darus, A. N.; Jalaludin, A. F.
2012-06-01
The conceptual design of an Organic Rankine Cycle (ORC) driven by solar thermal energy is developed for the decentralized production of electricity of up to 50 kW. Conventional Rankine Cycle uses water as the working fluid whereas ORC uses organic compound as the working fluid and it is particularly suitable for low temperature applications. The ORC and the solar collector will be sized according to the solar flux distribution in the Republic of Yemen for the required power output of 50 kW. This will be a micro power generation system that consists of two cycles, the solar thermal cycle that harness solar energy and the power cycle, which is the ORC that generates electricity. As for the solar thermal cycle, heat transfer fluid (HTF) circulates the cycle while absorbing thermal energy from the sun through a parabolic trough collector and then storing it in a thermal storage to increase system efficiency and maintains system operation during low radiation. The heat is then transferred to the organic fluid in the ORC via a heat exchanger. The organic fluids to be used and analyzed in the ORC are hydrocarbons R600a and R290.
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NASA Technical Reports Server (NTRS)
Bailey, M. M.
1985-01-01
Three alternative power cycles were compared in application as an exhaust-gas heat-recovery system for use with advanced adiabatic diesel engines. The power cycle alternatives considered were steam Rankine, organic Rankine with RC-1 as the working fluid, and variations of an air Brayton cycle. The comparison was made in terms of fuel economy and economic payback potential for heavy-duty trucks operating in line-haul service. The results indicate that, in terms of engine rated specific fuel consumption, a diesel/alternative-power-cycle engine offers a significant improvement over the turbocompound diesel used as the baseline for comparison. The maximum imporvement resulted from the use of a Rankine cycle heat-recovery system in series with turbocompounding. The air Brayton cycle alternatives studied, which included both simple-cycle and compression-intercooled configurations, were less effective and provided about half the fuel consumption improvement of the Rankine cycle alternatives under the same conditions. Capital and maintenance cost estimates were also developed for each of the heat-recovery power cycle systems. These costs were integrated with the fuel savings to identify the time required for net annual savings to pay back the initial capital investment. The sensitivity of capital payback time to arbitrary increases in fuel price, not accompanied by corresponding hardware cost inflation, was also examined. The results indicate that a fuel price increase is required for the alternative power cycles to pay back capital within an acceptable time period.
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Effects of hysteresis and Brayton cycle constraints on magnetocaloric refrigerant performance
NASA Astrophysics Data System (ADS)
Brown, T. D.; Buffington, T.; Shamberger, P. J.
2018-05-01
Despite promising proofs of concept, system-level implementation of magnetic refrigeration has been critically limited by history-dependent refrigerant losses that interact with governing thermodynamic cycles to adversely impact refrigeration performance. Future development demands a more detailed understanding of how hysteresis limits performance, and of how different types of cycles can mitigate these limitations, but without the extreme cost of experimental realization. Here, the utility of Brayton cycles for magnetic refrigeration is investigated via direct simulation, using a combined thermodynamic-hysteresis modeling framework to compute the path-dependent magnetization and entropy of a model alloy for a variety of feasible Brayton cycles between 0-1.5 T and 0-5 T. By simultaneously varying the model alloy's hysteresis properties and applying extensions of the thermodynamic laws to non-equilibrium systems, heat transfers and efficiencies are quantified throughout the space of hystereses and Brayton cycles and then compared with a previous investigation using Ericsson cycles. It is found that (1) hysteresis losses remain a critical obstacle to magnetic refrigeration implementation, with efficiencies >80% in the model system requiring hysteresis <0.5 K at 1.5 T; (2) optimal-efficiency Brayton cycles for given field and hysteresis constraints exist and are determined uniquely by the refrigerant transformation temperatures at the relevant fields; (3) for a given hysteresis and field constraint, Brayton and Ericsson-type cycles generate similar efficiencies; for a given temperature span, Ericsson cycles lift more heat per cycle, with the difference decreasing with the refrigerant heat capacity outside the phase transformation region.
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Quantifying the Adaptive Cycle
The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative...
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A summary of the ECAS MHD power plant results
NASA Technical Reports Server (NTRS)
Seikel, G. R.; Harris, L. P.
1976-01-01
The performance and the cost of electricity (COE) for MHD systems utilizing coal or coal derived fuels are summarized along with a conceptual open cycle MHD plant design. The results show that open cycle coal fired recuperatively preheated MHD systems have potentially one of the highest coal-pile-to-bus bar efficiencies (48.3%) and also one of the lowest COE of the systems studied. Closed cycle, inert gas systems do not appear to have the potential of exceeding the efficiency of or competing with the COE of advanced steam plants.
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Research on large equipment maintenance system in life cycle
NASA Astrophysics Data System (ADS)
Xu, Xiaowei; Wang, Hongxia; Liu, Zhenxing; Zhang, Nan
2017-06-01
In order to change the current disadvantages of traditional large equipment maintenance concept, this article plans to apply the technical method of prognostics and health management to optimize equipment maintenance strategy and develop large equipment maintenance system. Combined with the maintenance procedures of various phases in life cycle, it concluded the formulation methods of maintenance program and implement plans of maintenance work. In the meantime, it takes account into the example of the dredger power system of the Waterway Bureau to establish the auxiliary platform of ship maintenance system in life cycle.
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Systems and methods for initializing a charging system
Ransom, Ray M.; Perisic, Milun; Kajouke, Lateef A.
2014-09-09
Systems and methods are provided for initiating a charging system. The method, for example, may include, but is not limited to, providing, by the charging system, an incrementally increasing voltage to a battery up to a first predetermined threshold while the energy conversion module has a zero-percent duty cycle, providing, by the charging system, an incrementally increasing voltage to the battery from an initial voltage level of the battery up to a peak voltage of a voltage source while the energy conversion module has a zero-percent duty cycle, and providing, by the charging system, an incrementally increasing voltage to the battery by incrementally increasing the duty cycle of the energy conversion module.
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Geometric criteria for the non-existence of cycles in predator-prey systems with group defense.
Liu, Yaping
2007-07-01
In this paper, we study the existence of cycles in a predator-prey system in which the prey species is equipped with the group defense capability. Some geometric criteria are developed, relating the location of the two positive equilibria on the prey isocline and the non-existence of cycles. We show that under a general geometric condition, if both positive equilibria lie on a downslope or both lie on an upslope of the prey isocline, cycles do not exist.
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NASA Astrophysics Data System (ADS)
Yegoshina, O. V.; Voronov, V. N.; Yarovoy, V. O.; Bolshakova, N. A.
2017-11-01
There are many problems in domestic energy at the present that require urgent solutions in the near future. One of these problems - the aging of the main and auxiliary equipment. Wear of equipment is the cause of decrease reliability and efficiency of power plants. Reliability of the equipment are associated with the introduction of cycle chemistry monitoring system. The most damageable equipment’s are boilers (52.2 %), turbines (12.6 %) and heating systems (12.3 %) according to the review of failure rate on the power plants. The most part of the damageability of the boiler is heated surfaces (73.2 %). According to the Russian technical requirements, the monitoring systems are responsible to reduce damageability the boiler heating surfaces and to increase the reliability of the equipment. All power units capacity of over 50 MW are equipped with cycle chemistry monitoring systems in order to maintain water chemistry within operating limits. The main idea of cycle chemistry monitoring systems is to improve water chemistry at power plants. According to the guidelines, cycle chemistry monitoring systems of a single unit depends on its type (drum or once-through boiler) and consists of: 20…50 parameters of on-line chemical analyzers; 20…30 «grab» sample analyses (daily) and about 15…20 on-line monitored operating parameters. The operator of modern power plant uses with many data at different points of steam/water cycle. Operators do not can estimate quality of the cycle chemistry due to the large volume of daily and every shift information and dispersion of data, lack of systematization. In this paper, an algorithm for calculating the quality index developed for improving control the water chemistry of the condensate, feed water and prevent scaling and corrosion in the steam/water cycle.
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Nitrogen removal and nitrate leaching for forage systems receiving dairy effluent.
Woodard, Kenneth R; French, Edwin C; Sweat, Lewin A; Graetz, Donald A; Sollenberger, Lynn E; Macoon, Bisoondat; Portier, Kenneth M; Wade, Brett L; Rymph, Stuart J; Prine, Gordon M; Van Horn, Harold H
2002-01-01
Florida dairies need year-round forage systems that prevent loss of N to ground water from waste effluent sprayfields. Our purpose was to quantify forage N removal and monitor nitrate N (NO3(-)-N) concentrations in soil water below the rooting zone for two forage systems during four 12-mo cycles (1996-2000). Soil in the sprayfield is an excessively drained Kershaw sand (thermic, uncoated Typic Quartzipsamment). Over four cycles, average loading rates of effluent N were 500, 690, and 910 kg ha(-1) per cycle. Nitrogen removed by the bermudagrass (Cynodon spp.)-rye (Secale cereale L.) system (BR) during the first three cycles was 465 kg ha(-1) per cycle for the low loading rate, 528 kg ha(-1) for the medium rate, and 585 kg ha(-1) for the high. For the corn (Zea mays L.)-forage sorghum [Sorghum bicolor (L.) Moench]-rye system (CSR), N removals were 320 kg ha(-1) per cycle for the low rate, 327 kg ha(-1) for the medium, and 378 kg ha(-1) for the high. The higher N removals for BR were attributed to higher N concentration in bermudagrass (18.1-24.2 g kg(-1)) than in corn and forage sorghum (10.3-14.7 g kg(-1)). Dry matter yield declined in the fourth cycle for bermudagrass but N removal continued to be higher for BR than CSR. The BR system was much more effective at preventing NO3(-)-N leaching. For CSR, NO3(-)-N levels in soil water (1.5 m below surface) increased steeply during the period between the harvest of one forage and canopy dosure of the next. Overall, the BR system was better than CSR at removing N from the soil and maintaining low NO3(-)-N concentrations below the rooting zone.
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USDA-ARS?s Scientific Manuscript database
Long-term crop-livestock integration enables constant and high nutrient cycling because animal, pasture and crop residues release nutrients at different rates. Therefore, appropriate management of these systems is needed to maximize the benefits of nutrient cycling. The objective of this study was t...
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Defense ADP Acquisition Study.
1981-11-30
Logistics ALS - Advanced Logistics System AMP - ADPS Master Plan ANSI - American National Standards Institute APR - Agency Procurement Request ASD(C...Computers IRM - Information Resources Management ISO - International Standards Organization L LCC - Life Cycle Costs LCM - Life Cycle Management LE...man- agement in the process * Lack of a mission orientation . Lack of systems management and life cycle perspectives * Lack of effective leadership
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Internet Enabled Remote Driving of a Combat Hybrid Electric Power System for Duty Cycle Measurement
2007-06-01
INTERNET ENABLED REMOTE DRIVING OF A COMBAT HYBRID ELECTRIC POWER SYSTEM FOR DUTY CYCLE MEASUREMENT Jarrett Goodell1 Marc Compere , Ph.D.2...Orlando, FL, April 2006. 2. Compere , M.; M.; Goodell, J.; Simon, M; Smith, W.; Brudnak, M, “Robust Control Techniques Enabling Duty Cycle...2006-01-3077, SAE Power Systems Conference, Nov. 2006. 3. Compere , M.; Simon, M.; Kajs, J.; Pozolo, M., “Tracked Vehicle Mobility Load Emulation for a
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The embedded software life cycle - An expanded view
NASA Technical Reports Server (NTRS)
Larman, Brian T.; Loesh, Robert E.
1989-01-01
Six common issues that are encountered in the development of software for embedded computer systems are discussed from the perspective of their interrelationships with the development process and/or the system itself. Particular attention is given to concurrent hardware/software development, prototyping, the inaccessibility of the operational system, fault tolerance, the long life cycle, and inheritance. It is noted that the life cycle for embedded software must include elements beyond simply the specification and implementation of the target software.
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Brayton cycle heat exchanger and duct assembly (HXDA, preliminary design and technology tests
NASA Technical Reports Server (NTRS)
Coombs, M. G.; Morse, C. J.; Graves, R. F.; Gibson, J. C.
1972-01-01
A preliminary design of the heat exchanger and duct assembly (HXDA) for a 60 kwe, closed loop, Brayton cycle space power system is presented. This system is weight optimized within the constraints imposed by the defined structural and operational requirements. Also presented are the results of several small scale tests, directed to obtaining specific design data and/or the resolution of a design approach for long life Brayton cycle heat exchanger systems.
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A Systems Development Life Cycle Project for the AIS Class
ERIC Educational Resources Information Center
Wang, Ting J.; Saemann, Georgia; Du, Hui
2007-01-01
The Systems Development Life Cycle (SDLC) project was designed for use by an accounting information systems (AIS) class. Along the tasks in the SDLC, this project integrates students' knowledge of transaction and business processes, systems documentation techniques, relational database concepts, and hands-on skills in relational database use.…
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Influence of Geographic Factors on the Life Cycle Climate Change Impacts of Renewable Energy Systems
NASA Astrophysics Data System (ADS)
Fortier, M. O. P.
2017-12-01
Life cycle assessment (LCA) is a valuable tool to measure the cradle-to-grave climate change impacts of the sustainable energy systems that are planned to replace conventional fossil energy-based systems. The recent inclusion of geographic specificity in bioenergy LCAs has shown that the relative sustainability of these energy sources is often dependent on geographic factors, such as the climate change impact of changing the land cover and local resource availability. However, this development has not yet been implemented to most LCAs of energy systems that do not have biological feedstocks, such as wind, water, and solar-based energy systems. For example, the tidal velocity where tidal rotors are installed can significantly alter the life cycle climate change impacts of electricity generated using the same technology in different locations. For LCAs of solar updraft towers, the albedo change impacts arising from changing the reflectivity of the land that would be converted can be of the same magnitude as other life cycle process climate change impacts. Improvements to determining the life cycle climate change impacts of renewable energy technologies can be made by utilizing GIS and satellite data and by conducting site-specific analyses. This practice can enhance our understanding of the life cycle environmental impacts of technologies that are aimed to reduce the impacts of our current energy systems, and it can improve the siting of new systems to optimize a reduction in climate change impacts.
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Liu, Wanke; Jin, Xueyuan; Wu, Mingkui; Hu, Jie; Wu, Yun
2018-02-01
Cycle slip detection and repair is a prerequisite for high-precision global navigation satellite system (GNSS)-based positioning. With the modernization and development of GNSS systems, more satellites are available to transmit triple-frequency signals, which allows the introduction of additional linear combinations and provides new opportunities for cycle slip detection and repair. In this paper, we present a new real-time cycle slip detection and repair method under high ionospheric activity for undifferenced Global Positioning System (GPS)/BeiDou Navigation Satellite System (BDS) triple-frequency observations collected with a single receiver. First, three optimal linearly independent geometry-free pseudorange minus phase combinations are selected to correctly and uniquely determine the cycle slips on the original triple-frequency carrier phase observations. Then, a second-order time-difference algorithm is employed for the pseudorange minus phase combinations to mitigate the impact of between-epoch ionospheric residuals on cycle slip detection, which is especially beneficial under high ionospheric activity. The performance of the approach is verified with static GPS/BDS triple-frequency observations that are collected with a 30 s sampling interval under active ionospheric conditions, and observations are manually inserted with simulated cycle slips. The results show that the method can correctly detect and repair cycle slips at a resolution as small as 1 cycle. Moreover, kinematic data collected from car-driven and airborne experiments are also processed to verify the performance of the method. The experimental results also demonstrate that the method is effective in processing kinematic data.
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Liu, Wanke; Wu, Mingkui; Hu, Jie; Wu, Yun
2018-01-01
Cycle slip detection and repair is a prerequisite for high-precision global navigation satellite system (GNSS)-based positioning. With the modernization and development of GNSS systems, more satellites are available to transmit triple-frequency signals, which allows the introduction of additional linear combinations and provides new opportunities for cycle slip detection and repair. In this paper, we present a new real-time cycle slip detection and repair method under high ionospheric activity for undifferenced Global Positioning System (GPS)/BeiDou Navigation Satellite System (BDS) triple-frequency observations collected with a single receiver. First, three optimal linearly independent geometry-free pseudorange minus phase combinations are selected to correctly and uniquely determine the cycle slips on the original triple-frequency carrier phase observations. Then, a second-order time-difference algorithm is employed for the pseudorange minus phase combinations to mitigate the impact of between-epoch ionospheric residuals on cycle slip detection, which is especially beneficial under high ionospheric activity. The performance of the approach is verified with static GPS/BDS triple-frequency observations that are collected with a 30 s sampling interval under active ionospheric conditions, and observations are manually inserted with simulated cycle slips. The results show that the method can correctly detect and repair cycle slips at a resolution as small as 1 cycle. Moreover, kinematic data collected from car-driven and airborne experiments are also processed to verify the performance of the method. The experimental results also demonstrate that the method is effective in processing kinematic data. PMID:29389879
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The coal-fired gas turbine locomotive - A new look
NASA Technical Reports Server (NTRS)
Liddle, S. G.; Bonzo, B. B.; Purohit, G. P.
1983-01-01
Advances in turbomachine technology and novel methods of coal combustion may have made possible the development of a competitive coal fired gas turbine locomotive engine. Of the combustor, thermodynamic cycle, and turbine combinations presently assessed, an external combustion closed cycle regenerative gas turbine with a fluidized bed coal combustor is judged to be the best suited for locomotive requirements. Some merit is also discerned in external combustion open cycle regenerative systems and internal combustion open cycle regenerative gas turbine systems employing a coal gasifier. The choice of an open or closed cycle depends on the selection of a working fluid and the relative advantages of loop pressurization, with air being the most attractive closed cycle working fluid on the basis of cost.
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Systems and methods for compensating for electrical converter nonlinearities
Perisic, Milun; Ransom, Ray M.; Kajouke, Lateef A.
2013-06-18
Systems and methods are provided for delivering energy from an input interface to an output interface. An electrical system includes an input interface, an output interface, an energy conversion module coupled between the input interface and the output interface, and a control module. The control module determines a duty cycle control value for operating the energy conversion module to produce a desired voltage at the output interface. The control module determines an input power error at the input interface and adjusts the duty cycle control value in a manner that is influenced by the input power error, resulting in a compensated duty cycle control value. The control module operates switching elements of the energy conversion module to deliver energy to the output interface with a duty cycle that is influenced by the compensated duty cycle control value.
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Open-cycle systems performance analysis programming guide
DOE Office of Scientific and Technical Information (OSTI.GOV)
Olson, D.A.
1981-12-01
The Open-Cycle OTEC Systems Performance Analysis Program is an algorithm programmed on SERI's CDC Cyber 170/720 computer to predict the performance of a Claude-cycle, open-cycle OTEC plant. The algorithm models the Claude-cycle system as consisting of an evaporator, a turbine, a condenser, deaerators, a condenser gas exhaust, a cold water pipe and cold and warm seawater pumps. Each component is a separate subroutine in the main program. A description is given of how to write Fortran subroutines to fit into the main program for the components of the OTEC plant. An explanation is provided of how to use the algorithm.more » The main program and existing component subroutines are described. Appropriate common blocks and input and output variables are listed. Preprogrammed thermodynamic property functions for steam, fresh water, and seawater are described.« less
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... to the Professional version Home Women's Health Issues Biology of the Female Reproductive System Menstrual Cycle Follicular ... Version. DOCTORS: Click here for the Professional Version Biology of the Female Reproductive System Overview of the ...
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NASA Astrophysics Data System (ADS)
Azharuddin; Santarelli, Massimo
2016-09-01
Thermodynamic analysis of a closed cycle, solar powered Brayton gas turbine power plant with Concentrating Receiver system has been studied. A Brayton cycle is simpler than a Rankine cycle and has an advantage where the water is scarce. With the normal Brayton cycle a Concentrating Receiver System has been analysed which has a dependence on field density and optical system. This study presents a method of optimization of design parameter, such as the receiver working temperature and the heliostats density. This method aims at maximizing the overall efficiency of the three major subsystem that constitute the entire plant, namely, the heliostat field and the tower, the receiver and the power block. The results of the optimization process are shown and analysed.
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Second law analysis of advanced power generation systems using variable temperature heat sources
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bliem, C.J.; Mines, G.L.
1990-01-01
Many systems produce power using variable temperature (sensible) heat sources. The Heat Cycle Research Program is currently investigating the potential improvements to such power cycles utilizing moderate temperature geothermal resources to produce electrical power. It has been shown that mixtures of saturated hydrocarbons (alkanes) or halogenated hydrocarbons operating with a supercritical Rankine cycle gave improved performance over boiling Rankine cycles with the pure working fluids for typical applications. Recently, in addition to the supercritical Rankine Cycle, other types of cycles have been proposed for binary geothermal service. This paper explores the limits on efficiency of a feasible plant and discussesmore » the methods used in these advanced concept plants to achieve the maximum possible efficiency. The advanced plants considered appear to be approaching the feasible limit of performance so that the designer must weigh all considerations to fine the best plant for a given service. These results would apply to power systems in other services as well as to geothermal power plants. 17 refs., 15 figs.« less
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Mantziaras, I D; Stamou, A; Katsiri, A
2011-06-01
This paper refers to nitrogen removal optimization of an alternating oxidation ditch system through the use of a mathematical model and pilot testing. The pilot system where measurements have been made has a total volume of 120 m(3) and consists of two ditches operating in four phases during one cycle and performs carbon oxidation, nitrification, denitrification and settling. The mathematical model consists of one-dimensional mass balance (convection-dispersion) equations based on the IAWPRC ASM 1 model. After the calibration and verification of the model, simulation system performance was made. Optimization is achieved by testing operational cycles and phases with different time lengths. The limits of EU directive 91/271 for nitrogen removal have been used for comparison. The findings show that operational cycles with smaller time lengths can achieve higher nitrogen removals and that an "equilibrium" between phase time percentages in the whole cycle, for a given inflow, must be achieved.
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Inertial aided cycle slip detection and identification for integrated PPP GPS and INS.
Du, Shuang; Gao, Yang
2012-10-25
The recently developed integrated Precise Point Positioning (PPP) GPS/INS system can be useful to many applications, such as UAV navigation systems, land vehicle/machine automation and mobile mapping systems. Since carrier phase measurements are the primary observables in PPP GPS, cycle slips, which often occur due to high dynamics, signal obstructions and low satellite elevation, must be detected and repaired in order to ensure the navigation performance. In this research, a new algorithm of cycle slip detection and identification has been developed. With the aiding from INS, the proposed method jointly uses WL and EWL phase combinations to uniquely determine cycle slips in the L1 and L2 frequencies. To verify the efficiency of the algorithm, both tactical-grade and consumer-grade IMUs are tested by using a real dataset collected from two field tests. The results indicate that the proposed algorithm can efficiently detect and identify the cycle slips and subsequently improve the navigation performance of the integrated system.
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NASA Astrophysics Data System (ADS)
Watanabe, Masakazu; Fujita, Shigeru; Tanaka, Takashi; Kubota, Yasubumi; Shinagawa, Hiroyuki; Murata, Ken T.
2018-01-01
We perform numerical modeling of the interchange cycle in the magnetosphere-ionosphere convection system for oblique northward interplanetary magnetic field (IMF). The interchange cycle results from the coupling of IMF-to-lobe reconnection and lobe-to-closed reconnection. Using a global magnetohydrodynamic simulation code, for an IMF clock angle of 20° (measured from due north), we successfully reproduced the following features of the interchange cycle. (1) In the ionosphere, for each hemisphere, there appears a reverse cell circulating exclusively in the closed field line region (the reciprocal cell). (2) The topology transition of the magnetic field along a streamline near the equatorial plane precisely represents the magnetic flux reciprocation during the interchange cycle. (3) Field-aligned electric fields on the interplanetary-open separatrix and on the open-closed separatrix are those that are consistent with IMF-to-lobe reconnection and lobe-to-closed reconnection, respectively. These three features prove the existence of the interchange cycle in the simulated magnetosphere-ionosphere system. We conclude that the interchange cycle does exist in the real solar wind-magnetosphere-ionosphere system. In addition, the simulation revealed that the reciprocal cell described above is not a direct projection of the diffusion region as predicted by the "vacuum" model in which diffusion is added a priori to the vacuum magnetic topology. Instead, the reciprocal cell is a consequence of the plasma convection system coupled to the so-called NBZ ("northward
B z ") field-aligned current system. -
Method for converting heat energy to mechanical energy with 1,2-dichloro-1,1-difluoroethane
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, C.C.; Stiel, L.I.
1980-09-30
1,2-dichloro-1,1-difluoroethane is useful as a power fluid with particular suitability for moderate scale Rankine cycle applications based on systems with moderate temperature heat sources. The fluid is utilized in a Rankine cycle application by vaporizing the fluid by passing the same in heat exchange relationship with a heat source and utilizing the kinetic energy of the resulting expanding vapors to perform work. In this manner heat energy is converted to mechanical energy. The fluid is particularly advantageous in a dual cycle system consisting of a Rankine power cycle combined with a vapor compression cooling or heating cycle.
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Maisotsenko cycle applications for multistage compressors cooling
NASA Astrophysics Data System (ADS)
Levchenko, D.; Yurko, I.; Artyukhov, A.; Baga, V.
2017-08-01
The present study provides the overview of Maisotsenko Cycle (M-Cycle) applications for gas cooling in compressor systems. Various schemes of gas cooling systems are considered regarding to their thermal efficiency and cooling capacity. Preliminary calculation of M-cycle HMX has been conducted. It is found that M-cycle HMX scheme allows to brake the limit of the ambient wet bulb temperature for evaporative cooling. It has demonstrated that a compact integrated heat and moisture exchange process can cool product fluid to the level below the ambient wet bulb temperature, even to the level of dew point temperature of the incoming air with substantially lower water and energy consumption requirements.
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HFL-10 lifting body flight control system characteristics and operational experience
NASA Technical Reports Server (NTRS)
Painter, W. D.; Sitterle, G. J.
1974-01-01
A flight evaluation was made of the mechanical hydraulic flight control system and the electrohydraulic stability augmentation system installed in the HL-10 lifting body research vehicle. Flight tests performed in the speed range from landing to a Mach number of 1.86 and the altitude range from 697 meters (2300 feet) to 27,550 meters (90,300 feet) were supplemented by ground tests to identify and correct structural resonance and limit-cycle problems. Severe limit-cycle and control sensitivity problems were encountered during the first flight. Stability augmentation system structural resonance electronic filters were modified to correct the limit-cycle problem. Several changes were made to control stick gearing to solve the control sensitivity problem. Satisfactory controllability was achieved by using a nonlinear system. A limit-cycle problem due to hydraulic fluid contamination was encountered during the first powered flight, but the problem did not recur after preflight operations were improved.
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NASA Astrophysics Data System (ADS)
Fu, Rong-Huan; Zhang, Xing
2016-09-01
Supercritical carbon dioxide operated in a Brayton cycle offers a numerous of potential advantages for a power generation system, and a lot of thermodynamics analyses have been conducted to increase its efficiency. Because there are a lot of heat-absorbing and heat-lossing subprocesses in a practical thermodynamic cycle and they are implemented by heat exchangers, it will increase the gross efficiency of the whole power generation system to optimize the system combining thermodynamics and heat transfer theory. This paper analyzes the influence of the performance of heat exchangers on the actual efficiency of an ideal Brayton cycle with a simple configuration, and proposes a new method to optimize the power generation system, which aims at the minimum energy consumption. Although the method is operated only for the ideal working fluid in this paper, its merits compared to that only with thermodynamic analysis are fully shown.
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NASA Astrophysics Data System (ADS)
García-Barberena, Javier; Olcoz, Asier; Sorbet, Fco. Javier
2017-06-01
CSP technologies are essential to allow large shares of renewables into the grid due to their unique ability to cope with the large variability of the energy resource by means of technically and economically feasible thermal energy storage (TES) systems. However, there is still the need and sought to achieve technological breakthroughs towards cost reductions and increased efficiencies. For this, research on advanced power cycles, like the Decoupled Solar Combined Cycle (DSCC) is, are regarded as a key objective. The DSCC concept is, basically, a Combined Brayton-Rankine cycle in which the bottoming cycle is decoupled from the operation of the topping cycle by means of an intermediate storage system. According to this concept, one or several solar towers driving a solar air receiver and a Gas Turbine (Brayton cycle) feed through their exhaust gasses a single storage system and bottoming cycle. This general concept benefits from a large flexibility in its design. On the one hand, different possible schemes related to number and configuration of solar towers, storage systems media and configuration, bottoming cycles, etc. are possible. On the other, within a specific scheme a large number of design parameters can be optimized, including the solar field size, the operating temperatures and pressures of the receiver, the power of the Brayton and Rankine cycles, the storage capacity and others. Heretofore, DSCC plants have been analyzed by means of simple steady-state models with pre-stablished operating parameters in the power cycles. In this work, a detailed transient simulation model for DSCC plants has been developed and is used to analyze different DSCC plant schemes. For each of the analyzed plant schemes, a sensitivity analysis and selection of the main design parameters is carried out. Results show that an increase in annual solar to electric efficiency of 30% (from 12.91 to 16.78) can be achieved by using two bottoming Rankine cycles at two different temperatures, enabling low temperature heat recovery from the receiver and Gas Turbine exhaust gasses.
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The Thermodynamics of a Refrigeration System.
ERIC Educational Resources Information Center
Azevedo e Silva, J. F. M.
1991-01-01
An attempt to clarify the teaching of some of the concepts of thermodynamics through the observation of an experiment with an ordinary refrigeration system is presented. The cycle of operation in the refrigeration system and the individual processes in the cycle are described. (KR)
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A summary of the ECAS performance and cost results for MHD systems
NASA Technical Reports Server (NTRS)
Seikel, G. R.; Sovie, R. J.; Burns, R. K.; Barna, G. J.; Burkhart, J. A.; Nainiger, J. J.; Smith, J. M.
1976-01-01
The potential is examined of various advanced power plant concepts using coal and coal-derived fuel. The results indicate that open cycle coal fired direct preheat MHD systems have potentially one of the highest coal-pile-to-bus-bar efficiencies and also one of the lowest costs of electricity (COE) of the systems studied. Closed cycle MHD systems may have the potential to approach the efficiency and COE of open cycle MHD. The 1200-1500 F liquid metal MHD systems studied do not appear to have the potential of exceeding the efficiency or competing with the COE of advanced steam plants.
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NASA Astrophysics Data System (ADS)
Sánchez, D.; Muñoz de Escalona, J. M.; Chacartegui, R.; Muñoz, A.; Sánchez, T.
A proposal for high efficiency hybrid systems based on molten carbonate fuel cells is presented in this paper. This proposal is based on adopting a closed cycle bottoming gas turbine using supercritical carbon dioxide as working fluid as opposed to open cycle hot air turbines typically used in this type of power generators. First, both bottoming cycles are compared for the same operating conditions, showing that their performances do not differ as much as initially expected, even if the initial objective of reducing compression work is accomplished satisfactorily. In view of these results, a profound review of research and industrial literature is carried out in order to determine realistic specifications for the principal components of the bottoming systems. From this analysis, it is concluded that an appropriate set of specifications must be developed for each bottoming cycle as the performances of compressor, turbine and recuperator differ significantly from one working fluid to another. Thus, when the operating conditions are updated, the performances of the resulting systems show a remarkable advantage of carbon dioxide based systems over conventional air units. Actually, the proposed hybrid system shows its capability to achieve 60% net efficiency, what represents a 10% increase with respect to the reference system.
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76 FR 59392 - Notice of Intent To Grant Exclusive Patent License; Enhanced Energy Group, LLC
Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-26
... inventions, and they are covered by U.S. Patent No. 7,926,275: Closed Brayton Cycle Direct Contact Reactor/ Storage Tank With Chemical Scrubber.//U.S. Patent No. 7,926,276: Closed Cycle Brayton Propulsion System With Direct Heat Transfer.//U.S. Patent No. 7,937,930: Semiclosed Brayton Cycle Power System With...
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A Language Translator for a Computer Aided Rapid Prototyping System.
1988-03-01
PROBLEM ................... S B. THE TRADITIONAL "WATERFALL LIFE CYCLE" .. ............... 14 C. RAPID PROTOTYPING...feature of everyday life for almost the entire industrialized world. Few governments or businesses function without the aid of computer systems. Com...engineering. B. TIE TRADITIONAL "WATERFALL LIFE CYCLE" I. Characteristics The traditional method of software engineering is the "waterfall life cycle
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Navy Program Manager’s Guide, 1985 Edition
1985-01-01
1-7 Relationship of Development Cost in System Life -Cycle Cost (LCC) ......................... 1-7 Realistic Costing and Budgeting...Review (PROR)..... 4-53 x MI *) First-Article Configuration Inspection (FACI) ...... 4-54 Cost Management- Life -Cycle Costing (LCC) ..................... 4...innovation and minimize costs. 4. Consideration of life -cycle cost (LCC) such that affordability is put on an equal basis with system performance, schedule
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Chapter 11: Concentrating Solar Power
DOE Office of Scientific and Technical Information (OSTI.GOV)
Turchi, Craig S; Stekli, J.; Bueno, P. C.
2017-01-02
This chapter summarizes the applications of the supercritical CO2 (sCO2) Brayton cycle in concentrating solar power (CSP) plants. The design and operation of CSP plants are reviewed to highlight the requirements for the power cycle and attributes that are advantageous for the solar-thermal application. The sCO2 Brayton cycle offers the potential of higher cycle efficiency versus superheated or supercritical steam cycles at temperatures relevant for CSP applications. In addition, Brayton cycle systems using sCO2 are anticipated to have smaller weight and volume, lower thermal mass, and less complex power blocks compared with Rankine cycles due to the higher density ofmore » the fluid and simpler cycle design. The simpler machinery and compact size of the sCO2 process may also reduce the installation, maintenance, and operation cost of the system. Power cycle capacities in the range of 10-150 MWe are anticipated for the CSP application. In this chapter, we explore sCO2 Brayton cycle configurations that have attributes that are desirable from the perspective of a CSP application, such as the ability to accommodate dry cooling and daily cycling, as well as integration with thermal energy storage.« less
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NASA Technical Reports Server (NTRS)
Tsu, T. C.
1976-01-01
A closed-cycle MHD system for an electric power plant was studied. It consists of 3 interlocking loops, an external heating loop, a closed-cycle cesium seeded argon nonequilibrium ionization MHD loop, and a steam bottomer. A MHD duct maximum temperature of 2366 K (3800 F), a pressure of 0.939 MPa (9.27 atm) and a Mach number of 0.9 are found to give a topping cycle efficiency of 59.3%; however when combined with an integrated gasifier and optimistic steam bottomer the coal to bus bar efficiency drops to 45.5%. A 1978 K (3100 F) cycle has an efficiency of 55.1% and a power plant efficiency of 42.2%. The high cost of the external heating loop components results in a cost of electricity of 21.41 mills/MJ (77.07 mills/kWh) for the high temperature system and 19.0 mills/MJ (68.5 mills/kWh) for the lower temperature system. It is, therefore, thought that this cycle may be more applicable to internally heated systems such as some futuristic high temperature gas cooled reactor.
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Viscoelastic-coupling model for the earthquake cycle driven from below
Savage, J.C.
2000-01-01
In a linear system the earthquake cycle can be represented as the sum of a solution which reproduces the earthquake cycle itself (viscoelastic-coupling model) and a solution that provides the driving force. We consider two cases, one in which the earthquake cycle is driven by stresses transmitted along the schizosphere and a second in which the cycle is driven from below by stresses transmitted along the upper mantle (i.e., the schizosphere and upper mantle, respectively, act as stress guides in the lithosphere). In both cases the driving stress is attributed to steady motion of the stress guide, and the upper crust is assumed to be elastic. The surface deformation that accumulates during the interseismic interval depends solely upon the earthquake-cycle solution (viscoelastic-coupling model) not upon the driving source solution. Thus geodetic observations of interseismic deformation are insensitive to the source of the driving forces in a linear system. In particular, the suggestion of Bourne et al. [1998] that the deformation that accumulates across a transform fault system in the interseismic interval is a replica of the deformation that accumulates in the upper mantle during the same interval does not appear to be correct for linear systems.
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Closed-Cycle Hydrogen-Oxygen Regenerative Fuel Cell at the NASA Glenn Research Center-An Update
NASA Technical Reports Server (NTRS)
Bents, David J.; Chang, Bei-Jiann; Johnson, Donald W.; Garcia, Christopher P.
2008-01-01
The closed cycle hydrogen-oxygen proton exchange membrane (PEM) regenerative fuel cell (RFC) at the NASA Glenn Research Center has demonstrated multiple back-to-back contiguous cycles at rated power and round-trip efficiencies up to 52 percent. It is the first fully closed cycle RFC ever demonstrated. (The entire system is sealed; nothing enters or escapes the system other than electrical power and heat.) During fiscal year fiscal year (FY) FY06 to FY07, the system s numerous modifications and internal improvements focused on reducing parasitic power, heat loss, and noise signature; increasing its functionality as an unattended automated energy storage device; and in-service reliability.
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Potential efficiencies of open- and closed-cycle CO, supersonic, electric-discharge lasers
NASA Technical Reports Server (NTRS)
Monson, D. J.
1976-01-01
Computed open- and closed-cycle system efficiencies (laser power output divided by electrical power input) are presented for a CW carbon monoxide, supersonic, electric-discharge laser. Closed-system results include the compressor power required to overcome stagnation pressure losses due to supersonic heat addition and a supersonic diffuser. The paper shows the effect on the system efficiencies of varying several important parameters. These parameters include: gas mixture, gas temperature, gas total temperature, gas density, total discharge energy loading, discharge efficiency, saturated gain coefficient, optical cavity size and location with respect to the discharge, and supersonic diffuser efficiency. Maximum open-cycle efficiency of 80-90% is predicted; the best closed-cycle result is 60-70%.
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Enhanced absorption cycle computer model
NASA Astrophysics Data System (ADS)
Grossman, G.; Wilk, M.
1993-09-01
Absorption heat pumps have received renewed and increasing attention in the past two decades. The rising cost of electricity has made the particular features of this heat-powered cycle attractive for both residential and industrial applications. Solar-powered absorption chillers, gas-fired domestic heat pumps, and waste-heat-powered industrial temperature boosters are a few of the applications recently subjected to intensive research and development. The absorption heat pump research community has begun to search for both advanced cycles in various multistage configurations and new working fluid combinations with potential for enhanced performance and reliability. The development of working absorption systems has created a need for reliable and effective system simulations. A computer code has been developed for simulation of absorption systems at steady state in a flexible and modular form, making it possible to investigate various cycle configurations with different working fluids. The code is based on unit subroutines containing the governing equations for the system's components and property subroutines containing thermodynamic properties of the working fluids. The user conveys to the computer an image of his cycle by specifying the different subunits and their interconnections. Based on this information, the program calculates the temperature, flow rate, concentration, pressure, and vapor fraction at each state point in the system, and the heat duty at each unit, from which the coefficient of performance (COP) may be determined. This report describes the code and its operation, including improvements introduced into the present version. Simulation results are described for LiBr-H2O triple-effect cycles, LiCl-H2O solar-powered open absorption cycles, and NH3-H2O single-effect and generator-absorber heat exchange cycles. An appendix contains the user's manual.
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Mort, Richard Lester; Ford, Matthew Jonathan; Sakaue-Sawano, Asako; Lindstrom, Nils Olof; Casadio, Angela; Douglas, Adam Thomas; Keighren, Margaret Anne; Hohenstein, Peter; Miyawaki, Atsushi; Jackson, Ian James
2014-01-01
Markers of cell cycle stage allow estimation of cell cycle dynamics in cell culture and during embryonic development. The Fucci system incorporates genetically encoded probes that highlight G1 and S/G2/M phases of the cell cycle allowing live imaging. However the available mouse models that incorporate Fucci are beset by problems with transgene inactivation, varying expression level, lack of conditional potential and/or the need to maintain separate transgenes-there is no transgenic mouse model that solves all these problems. To address these shortfalls we re-engineered the Fucci system to create 2 bicistronic Fucci variants incorporating both probes fused using the Thosea asigna virus 2A (T2A) self cleaving peptide. We characterize these variants in stable 3T3 cell lines. One of the variants (termed Fucci2a) faithfully recapitulated the nuclear localization and cell cycle stage specific florescence of the original Fucci system. We go on to develop a conditional mouse allele (R26Fucci2aR) carefully designed for high, inducible, ubiquitous expression allowing investigation of cell cycle status in single cell lineages within the developing embryo. We demonstrate the utility of R26Fucci2aR for live imaging by using high resolution confocal microscopy of ex vivo lung, kidney and neural crest development. Using our 3T3 system we describe and validate a method to estimate cell cycle times from relatively short time-lapse sequences that we then apply to our neural crest data. The Fucci2a system and the R26Fucci2aR mouse model are compelling new tools for the investigation of cell cycle dynamics in cell culture and during mouse embryonic development.
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Life Cycle of Tropical Convection and Anvil in Observations and Models
NASA Astrophysics Data System (ADS)
McFarlane, S. A.; Hagos, S. M.; Comstock, J. M.
2011-12-01
Tropical convective clouds are important elements of the hydrological cycle and produce extensive cirrus anvils that strongly affect the tropical radiative energy balance. To improve simulations of the global water and energy cycles and accurately predict both precipitation and cloud radiative feedbacks, models need to realistically simulate the lifecycle of tropical convection, including the formation and radiative properties of ice anvil clouds. By combining remote sensing datasets from precipitation and cloud radars at the Atmospheric Radiation Measurement (ARM) Darwin site with geostationary satellite data, we can develop observational understanding of the lifetime of convective systems and the links between the properties of convective systems and their associated anvil clouds. The relationships between convection and anvil in model simulations can then be compared to those seen in the observations to identify areas for improvement in the model simulations. We identify and track tropical convective systems in the Tropical Western Pacific using geostationary satellite observations. We present statistics of the tropical convective systems including size, age, and intensity and classify the lifecycle stage of each system as developing, mature, or dissipating. For systems that cross over the ARM Darwin site, information on convective intensity and anvil properties are obtained from the C-Pol precipitation radar and MMCR cloud radar, respectively, and are examined as a function of the system lifecycle. Initial results from applying the convective identification and tracking algorithm to a tropical simulation from the Weather Research and Forecasting (WRF) model run show that the model produces reasonable overall statistics of convective systems, but details of the life cycle (such as diurnal cycle, system tracks) differ from the observations. Further work will focus on the role of atmospheric temperature and moisture profiles in the model's convective life cycle.
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NASA Technical Reports Server (NTRS)
Foster, Lancert E.; Saunders, John D., Jr.; Sanders, Bobby W.; Weir, Lois J.
2012-01-01
NASA is focused on technologies for combined cycle, air-breathing propulsion systems to enable reusable launch systems for access to space. Turbine Based Combined Cycle (TBCC) propulsion systems offer specific impulse (Isp) improvements over rocket-based propulsion systems in the subsonic takeoff and return mission segments along with improved safety. Among the most critical TBCC enabling technologies are: 1) mode transition from the low speed propulsion system to the high speed propulsion system, 2) high Mach turbine engine development and 3) innovative turbine based combined cycle integration. To address these challenges, NASA initiated an experimental mode transition task including analytical methods to assess the state-of-the-art of propulsion system performance and design codes. One effort has been the Combined-Cycle Engine Large Scale Inlet Mode Transition Experiment (CCE-LIMX) which is a fully integrated TBCC propulsion system with flowpath sizing consistent with previous NASA and DoD proposed Hypersonic experimental flight test plans. This experiment was tested in the NASA GRC 10 by 10-Foot Supersonic Wind Tunnel (SWT) Facility. The goal of this activity is to address key hypersonic combined-cycle engine issues including: (1) dual integrated inlet operability and performance issues-unstart constraints, distortion constraints, bleed requirements, and controls, (2) mode-transition sequence elements caused by switching between the turbine and the ramjet/scramjet flowpaths (imposed variable geometry requirements), and (3) turbine engine transients (and associated time scales) during transition. Testing of the initial inlet and dynamic characterization phases were completed and smooth mode transition was demonstrated. A database focused on a Mach 4 transition speed with limited off-design elements was developed and will serve to guide future TBCC system studies and to validate higher level analyses.
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Shortening tobacco life cycle accelerates functional gene identification in genomic research.
Ning, G; Xiao, X; Lv, H; Li, X; Zuo, Y; Bao, M
2012-11-01
Definitive allocation of function requires the introduction of genetic mutations and analysis of their phenotypic consequences. Novel, rapid and convenient techniques or materials are very important and useful to accelerate gene identification in functional genomics research. Here, over-expression of PmFT (Prunus mume), a novel FT orthologue, and PtFT (Populus tremula) lead to shortening of the tobacco life cycle. A series of novel short life cycle stable tobacco lines (30-50 days) were developed through repeated self-crossing selection breeding. Based on the second transformation via a gusA reporter gene, the promoter from BpFULL1 in silver birch (Betula pendula) and the gene (CPC) from Arabidopsis thaliana were effectively tested using short life cycle tobacco lines. Comparative analysis among wild type, short life cycle tobacco and Arabidopsis transformation system verified that it is optional to accelerate functional gene studies by shortening host plant material life cycle, at least in these short life cycle tobacco lines. The results verified that the novel short life cycle transgenic tobacco lines not only combine the advantages of economic nursery requirements and a simple transformation system, but also provide a robust, effective and stable host system to accelerate gene analysis. Thus, shortening tobacco life cycle strategy is feasible to accelerate heterologous or homologous functional gene identification in genomic research. © 2012 German Botanical Society and The Royal Botanical Society of the Netherlands.
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Circadian and estrous cycle-dependent variations in blood pressure and heart rate in female rats.
Takezawa, H; Hayashi, H; Sano, H; Saito, H; Ebihara, S
1994-11-01
To determine whether cardiovascular functions are controlled by the endogenous circadian system and whether they change with the estrous cycle in female rats, we measured mean arterial pressure (MAP), heart rate (HR), and spontaneous activity (ACT) of female rats using an implantable radiotelemetry device and a computerized data-collecting system. Under a 12:12-h light-dark (LD) cycle, these parameters exhibited daily rhythms that were entrained to the photic cycle. The patterns of the daily rhythms varied with estrous cycles, and variations were particularly marked in the proestrous stage. During the dark period of this stage, ACT levels were significantly higher, but HR was significantly lower than in other stages. Although the peak MAP occurred within 2 h after the onset of the dark phase in three of the estrous stages, it occurred around midnight in the proestrous stage. Such estrous cycle-dependent variations were eliminated by ovariectomy. The implantation of 17 beta-estradiol produced a gradual increase in MAP and an abrupt decrease in HR. During constant darkness, all three parameters were free running, maintaining the same internal phase relationships with each other as during LD cycles. These results indicate that daily variations in these parameters were controlled by the endogenous circadian oscillating system, that they vary with the estrous cycle in female rats, and that estrogen may be responsible for these estrous cycle-dependent variations.
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NASA Technical Reports Server (NTRS)
Habegger, L. J.; Gasper, J. R.; Brown, C.
1980-01-01
Data readily available from the literature were used to make an initial comparison of the health and safety risks of a fission power system with fuel reprocessing; a combined-cycle coal power system with a low-Btu gasifier and open-cycle gas turbine; a central-station, terrestrial, solar photovoltaic power system; the satellite power system; and a first-generation fusion system. The assessment approach consists of the identification of health and safety issues in each phase of the energy cycle from raw material extraction through electrical generation, waste disposal, and system deactivation; quantitative or qualitative evaluation of impact severity; and the rating of each issue with regard to known or potential impact level and level of uncertainty.
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Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-16
... ``Pharmaceutical Quality System (ICH Q10) Conference: A Practical Approach to Effective Life- Cycle Implementation... Pharmaceutical Quality System across the product life cycle according to the ICH Q10 model. These companies are...] Conference on the International Conference on Harmonisation Q10 Pharmaceutical Quality System: A Practical...
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Describing Elementary Teachers' Operative Systems: A Case Study
ERIC Educational Resources Information Center
Dotger, Sharon; McQuitty, Vicki
2014-01-01
This case study introduces the notion of an operative system to describe elementary teachers' knowledge and practice. Drawing from complex systems theory, the operative system is defined as the network of knowledge and practices that constituted teachers' work within a lesson study cycle. Data were gathered throughout a lesson study cycle in which…
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NASA Astrophysics Data System (ADS)
Mehrpooya, Mehdi; Dehghani, Hossein; Ali Moosavian, S. M.
2016-02-01
A combined system containing solid oxide fuel cell-gas turbine power plant, Rankine steam cycle and ammonia-water absorption refrigeration system is introduced and analyzed. In this process, power, heat and cooling are produced. Energy and exergy analyses along with the economic factors are used to distinguish optimum operating point of the system. The developed electrochemical model of the fuel cell is validated with experimental results. Thermodynamic package and main parameters of the absorption refrigeration system are validated. The power output of the system is 500 kW. An optimization problem is defined in order to finding the optimal operating point. Decision variables are current density, temperature of the exhaust gases from the boiler, steam turbine pressure (high and medium), generator temperature and consumed cooling water. Results indicate that electrical efficiency of the combined system is 62.4% (LHV). Produced refrigeration (at -10 °C) and heat recovery are 101 kW and 22.1 kW respectively. Investment cost for the combined system (without absorption cycle) is about 2917 kW-1.
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Comolli, Lorenzo; Ferrante, Simona; Pedrocchi, Alessandra; Bocciolone, Marco; Ferrigno, Giancarlo; Molteni, Franco
2010-05-01
Functional electrical stimulation (FES) is a well established method in the rehabilitation of stroke patients. Indeed, a bilateral movement such as cycling induced by FES would be crucial for these patients who had an unilateral motor impairment and had to recover an equivalent use of limbs. The aim of this study was to develop a low-cost meteorologically qualified cycle-ergometer, optimized for patients with stroke. A commercial ergometer was instrumented with resistive strain gauges and was able to provide the torque produced at the right and left crank, independently. The developed system was integrated with a stimulator, obtaining a novel FES cycling device able to control in real-time the movement unbalance. A dynamic calibration of the sensors was performed and a total torque uncertainty was computed. The system was tested on a healthy subject and on a stroke patient. Results demonstrated that the proposed sensors could be successfully used during FES cycling sessions where the maximum torque produced is about 9Nm, an order of magnitude less than the torque produced during voluntary cycling. This FES cycling system will assist in future investigations on stroke rehabilitation by means of FES and in new exercise regimes designed specifically for patients with unilateral impairments.
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A tide prediction and tide height control system for laboratory mesocosms
Long, Jeremy D.
2015-01-01
Experimental mesocosm studies of rocky shore and estuarine intertidal systems may benefit from the application of natural tide cycles to better replicate variation in immersion time, water depth, and attendant fluctuations in abiotic and edaphic conditions. Here we describe a stand-alone microcontroller tide prediction open-source software program, coupled with a mechanical tidal elevation control system, which allows continuous adjustment of aquarium water depths in synchrony with local tide cycles. We used this system to monitor the growth of Spartina foliosa marsh cordgrass and scale insect herbivores at three simulated shore elevations in laboratory mesocosms. Plant growth decreased with increasing shore elevation, while scale insect population growth on the plants was not strongly affected by immersion time. This system shows promise for a range of laboratory mesocosm studies where natural tide cycling could impact organism performance or behavior, while the tide prediction system could additionally be utilized in field experiments where treatments need to be applied at certain stages of the tide cycle. PMID:26623195
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Abroudi, Ali; Samarasinghe, Sandhya; Kulasiri, Don
2017-09-21
Not many models of mammalian cell cycle system exist due to its complexity. Some models are too complex and hard to understand, while some others are too simple and not comprehensive enough. Moreover, some essential aspects, such as the response of G1-S and G2-M checkpoints to DNA damage as well as the growth factor signalling, have not been investigated from a systems point of view in current mammalian cell cycle models. To address these issues, we bring a holistic perspective to cell cycle by mathematically modelling it as a complex system consisting of important sub-systems that interact with each other. This retains the functionality of the system and provides a clearer interpretation to the processes within it while reducing the complexity in comprehending these processes. To achieve this, we first update a published ODE mathematical model of cell cycle with current knowledge. Then the part of the mathematical model relevant to each sub-system is shown separately in conjunction with a diagram of the sub-system as part of this representation. The model sub-systems are Growth Factor, DNA damage, G1-S, and G2-M checkpoint signalling. To further simplify the model and better explore the function of sub-systems, they are further divided into modules. Here we also add important new modules of: chk-related rapid cell cycle arrest, p53 modules expanded to seamlessly integrate with the rapid arrest module, Tyrosine phosphatase modules that activate Cyc_Cdk complexes and play a crucial role in rapid and delay arrest at both G1-S and G2-M, Tyrosine Kinase module that is important for inactivating nuclear transport of CycB_cdk1 through Wee1 to resist M phase entry, Plk1-Related module that is crucial in activating Tyrosine phosphatases and inactivating Tyrosine kinase, and APC-Related module to show steps in CycB degradation. This multi-level systems approach incorporating all known aspects of cell cycle allowed us to (i) study, through dynamic simulation of an ODE model, comprehensive details of cell cycle dynamics under normal and DNA damage conditions revealing the role and value of the added new modules and elements, (ii) assess, through a global sensitivity analysis, the most influential sub-systems, modules and parameters on system response, such as G1-S and G2-M transitions, and (iii) probe deeply into the relationship between DNA damage and cell cycle progression and test the biological evidence that G1-S is relatively inefficient in arresting damaged cells compared to G2-M checkpoint. To perform sensitivity analysis, Self-Organizing Map with Correlation Coefficient Analysis (SOMCCA) is developed which shows that Growth Factor and G1-S Checkpoint sub-systems and 13 parameters in the modules within them are crucial for G1-S and G2-M transitions. To study the relative efficiency of DNA damage checkpoints, a Checkpoint Efficiency Evaluator (CEE) is developed based on perturbation studies and statistical Type II error. Accordingly, cell cycle is about 96% efficient in arresting damaged cells with G2-M checkpoint being more efficient than G1-S. Further, both checkpoint systems are near perfect (98.6%) in passing healthy cells. Thus this study has shown the efficacy of the proposed systems approach to gain a better understanding of different aspects of mammalian cell cycle system separately and as an integrated system that will also be useful in investigating targeted therapy in future cancer treatments. Copyright © 2017 Elsevier Ltd. All rights reserved.
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A Feasibility Study of CO2-Based Rankine Cycle Powered by Solar Energy
NASA Astrophysics Data System (ADS)
Zhang, Xin-Rong; Yamaguchi, Hiroshi; Fujima, Katsumi; Enomoto, Masatoshi; Sawada, Noboru
An experiment study was carried out in order to investigate feasibility of CO2-based Rankine cycle powered by solar energy. The proposed cycle is to achieve a cogeneration of heat and power, which consists of evacuated solar tube collectors, power generating turbine, heat recovery system, and feed pump. The Rankine cycle of the system utilizes solar collectors to convert CO2 into high-temperature supercritical state, used to drive a turbine and produce electrical power. The cycle also recovers thermal energy, which can be used for absorption refrigerator, air conditioning, hot water supply so on for a building. A set of experimental set-up was constructed to investigate the performance of the CO2-based Rankine cycle. The results show the cycle can achieve production of heat and power with reasonable thermodynamics efficiency and has a great potential of the application of the CO2-based Rankine cycle powered by solar energy. In addition, some research interests related to the present study will also be discussed in this paper.
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Evaluation and selection of refrigeration systems for lunar surface and space applications
NASA Technical Reports Server (NTRS)
Copeland, R. J.; Blount, T. D.; Williams, J. L.
1971-01-01
Evaluated are the various refrigeration machines which could be used to provide heat rejection in environmental control systems for lunar surface and spacecraft applications, in order to select the best refrigeration machine for satisfying each individual application and the best refrigeration machine for satisfying all of the applications. The refrigeration machine considered include: (1) vapor comparison cycle (work-driven); (2) vapor adsorption cycle (heat-driven); (3) vapor absorption cycle (heat-driven); (4) thermoelectric (electrically-driven); (5) gas cycle (work driven); (6) steam-jet (heat-driven).
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Low Leakage Turbine Shaft Seals for Advanced Combined Cycle Systems.
1984-11-01
Both used feedwater -supplied buffer water as required by advanced combined cycle steam turbomachinery. It was shown to be advantageous, at least from...RD-fi149 372 LOW LEAKAGE’TURBINE SHAFT SEALS FOR ADVANCED COMBINED 1/2- CYCLE SYSTEMS(U) SOLAR TURBINES INC SAN DIEGO CA G W HOSANG NOV 84 SR84-R...4622-36 N88824-7B-C-5345 UNCLASSIFIED F/1 i/i NL AIONA L RUEA OF B 20NADS16 Final Report N 4 <Low Leakage Turbine Shaft Seals for Advanced Combined Cycle
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Green supply chain: Simulating road traffic congestion
NASA Astrophysics Data System (ADS)
Jalal, Muhammad Zulqarnain Hakim Abd; Nawawi, Mohd Kamal Mohd; Laailatul Hanim Mat Desa, Wan; Khalid, Ruzelan; Khalid Abduljabbar, Waleed; Ramli, Razamin
2017-09-01
With the increasing awareness of the consumers about environmental issues, businesses, households and governments increasingly want use green products and services which lead to green supply chain. This paper discusses a simulation study of a selected road traffic system that will contribute to the air pollution if in the congestion state. Road traffic congestion (RTC) can be caused by a temporary obstruction, a permanent capacity bottleneck in the network itself, and stochastic fluctuation in demand within a particular sector of the network, leading to spillback and queue propagation. A discrete-event simulation model is developed to represent the real traffic light control (TLC) system condition during peak hours. Certain performance measures such as average waiting time and queue length were measured using the simulation model. Existing system uses pre-set cycle time to control the light changes which is fixed time cycle. In this research, we test several other combination of pre-set cycle time with the objective to find the best system. In addition, we plan to use a combination of the pre-set cycle time and a proximity sensor which have the authority to manipulate the cycle time of the lights. The sensors work in such situation when the street seems to have less occupied vehicles, obviously it may not need a normal cycle for green light, and automatically change the cycle to street where vehicle is present.
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NASA Technical Reports Server (NTRS)
Mclennan, G. A.
1986-01-01
This report describes, and is a User's Manual for, a computer code (ANL/RBC) which calculates cycle performance for Rankine bottoming cycles extracting heat from a specified source gas stream. The code calculates cycle power and efficiency and the sizes for the heat exchangers, using tabular input of the properties of the cycle working fluid. An option is provided to calculate the costs of system components from user defined input cost functions. These cost functions may be defined in equation form or by numerical tabular data. A variety of functional forms have been included for these functions and they may be combined to create very general cost functions. An optional calculation mode can be used to determine the off-design performance of a system when operated away from the design-point, using the heat exchanger areas calculated for the design-point.
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Criteria for robustness of heteroclinic cycles in neural microcircuits
2011-01-01
We introduce a test for robustness of heteroclinic cycles that appear in neural microcircuits modeled as coupled dynamical cells. Robust heteroclinic cycles (RHCs) can appear as robust attractors in Lotka-Volterra-type winnerless competition (WLC) models as well as in more general coupled and/or symmetric systems. It has been previously suggested that RHCs may be relevant to a range of neural activities, from encoding and binding to spatio-temporal sequence generation. The robustness or otherwise of such cycles depends both on the coupling structure and the internal structure of the neurons. We verify that robust heteroclinic cycles can appear in systems of three identical cells, but only if we require perturbations to preserve some invariant subspaces for the individual cells. On the other hand, heteroclinic attractors can appear robustly in systems of four or more identical cells for some symmetric coupling patterns, without restriction on the internal dynamics of the cells. PMID:22656192
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Fincke uses Cycle Ergometer with Vibration Isolation System (CEVIS)
2009-03-26
ISS018-E-043414 (26 March 2009) --- Astronaut Michael Fincke, Expedition 18 commander, exercises on the Cycle Ergometer with Vibration Isolation System (CEVIS) in the Destiny laboratory of the International Space Station.
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Life cycle design metrics for energy generation technologies: Method, data, and case study
NASA Astrophysics Data System (ADS)
Cooper, Joyce; Lee, Seung-Jin; Elter, John; Boussu, Jeff; Boman, Sarah
A method to assist in the rapid preparation of Life Cycle Assessments of emerging energy generation technologies is presented and applied to distributed proton exchange membrane fuel cell systems. The method develops life cycle environmental design metrics and allows variations in hardware materials, transportation scenarios, assembly energy use, operating performance and consumables, and fuels and fuel production scenarios to be modeled and comparisons to competing systems to be made. Data and results are based on publicly available U.S. Life Cycle Assessment data sources and are formulated to allow the environmental impact weighting scheme to be specified. A case study evaluates improvements in efficiency and in materials recycling and compares distributed proton exchange membrane fuel cell systems to other distributed generation options. The results reveal the importance of sensitivity analysis and system efficiency in interpreting case studies.
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Experimental Validation of a Closed Brayton Cycle System Transient Simulation
NASA Technical Reports Server (NTRS)
Johnson, Paul K.; Hervol, David S.
2006-01-01
The Brayton Power Conversion Unit (BPCU) is a closed cycle system with an inert gas working fluid. It is located in Vacuum Facility 6 at NASA Glenn Research Center. Was used in previous solar dynamic technology efforts (SDGTD). Modified to its present configuration by replacing the solar receiver with an electrical resistance heater. The first closed-Brayton-cycle to be coupled with an ion propulsion system. Used to examine mechanical dynamic characteristics and responses. The focus of this work was the validation of a computer model of the BPCU. Model was built using the Closed Cycle System Simulation (CCSS) design and analysis tool. Test conditions were then duplicated in CCSS. Various steady-state points. Transients involving changes in shaft rotational speed and heat input. Testing to date has shown that the BPCU is able to generate meaningful, repeatable data that can be used for computer model validation. Results generated by CCSS demonstrated that the model sufficiently reproduced the thermal transients exhibited by the BPCU system. CCSS was also used to match BPCU steady-state operating points. Cycle temperatures were within 4.1% of the data (most were within 1%). Cycle pressures were all within 3.2%. Error in alternator power (as much as 13.5%) was attributed to uncertainties in the compressor and turbine maps and alternator and bearing loss models. The acquired understanding of the BPCU behavior gives useful insight for improvements to be made to the CCSS model as well as ideas for future testing and possible system modifications.
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Luo, Jia-Yan; Cui, Wang-Jun; He, Ping; Xia, Yong-Yao
2010-09-01
Aqueous lithium-ion batteries may solve the safety problem associated with lithium-ion batteries that use highly toxic and flammable organic solvents, and the poor cycling life associated with commercialized aqueous rechargeable batteries such as lead-acid and nickel-metal hydride systems. But all reported aqueous lithium-ion battery systems have shown poor stability: the capacity retention is typically less than 50% after 100 cycles. Here, the stability of electrode materials in an aqueous electrolyte was extensively analysed. The negative electrodes of aqueous lithium-ion batteries in a discharged state can react with water and oxygen, resulting in capacity fading upon cycling. By eliminating oxygen, adjusting the pH values of the electrolyte and using carbon-coated electrode materials, LiTi(2)(PO(4))(3)/Li(2)SO(4)/LiFePO(4) aqueous lithium-ion batteries exhibited excellent stability with capacity retention over 90% after 1,000 cycles when being fully charged/discharged in 10 minutes and 85% after 50 cycles even at a very low current rate of 8 hours for a full charge/discharge offering an energy storage system with high safety, low cost, long cycling life and appropriate energy density.
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Architecture and inherent robustness of a bacterial cell-cycle control system.
Shen, Xiling; Collier, Justine; Dill, David; Shapiro, Lucy; Horowitz, Mark; McAdams, Harley H
2008-08-12
A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.
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Fuel cycle for a fusion neutron source
NASA Astrophysics Data System (ADS)
Ananyev, S. S.; Spitsyn, A. V.; Kuteev, B. V.
2015-12-01
The concept of a tokamak-based stationary fusion neutron source (FNS) for scientific research (neutron diffraction, etc.), tests of structural materials for future fusion reactors, nuclear waste transmutation, fission reactor fuel production, and control of subcritical nuclear systems (fusion-fission hybrid reactor) is being developed in Russia. The fuel cycle system is one of the most important systems of FNS that provides circulation and reprocessing of the deuterium-tritium fuel mixture in all fusion reactor systems: the vacuum chamber, neutral injection system, cryogenic pumps, tritium purification system, separation system, storage system, and tritium-breeding blanket. The existing technologies need to be significantly upgraded since the engineering solutions adopted in the ITER project can be only partially used in the FNS (considering the capacity factor higher than 0.3, tritium flow up to 200 m3Pa/s, and temperature of reactor elements up to 650°C). The deuterium-tritium fuel cycle of the stationary FNS is considered. The TC-FNS computer code developed for estimating the tritium distribution in the systems of FNS is described. The code calculates tritium flows and inventory in tokamak systems (vacuum chamber, cryogenic pumps, neutral injection system, fuel mixture purification system, isotope separation system, tritium storage system) and takes into account tritium loss in the fuel cycle due to thermonuclear burnup and β decay. For the two facility versions considered, FNS-ST and DEMO-FNS, the amount of fuel mixture needed for uninterrupted operation of all fuel cycle systems is 0.9 and 1.4 kg, consequently, and the tritium consumption is 0.3 and 1.8 kg per year, including 35 and 55 g/yr, respectively, due to tritium decay.
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Teaching Systems Thinking in the Context of the Water Cycle
NASA Astrophysics Data System (ADS)
Lee, Tammy D.; Gail Jones, M.; Chesnutt, Katherine
2017-06-01
Complex systems affect every part of our lives from the ecosystems that we inhabit and share with other living organisms to the systems that supply our water (i.e., water cycle). Evaluating events, entities, problems, and systems from multiple perspectives is known as a systems thinking approach. New curriculum standards have made explicit the call for teaching with a systems thinking approach in our science classrooms. However, little is known about how elementary in-service or pre-service teachers understand complex systems especially in terms of systems thinking. This mixed methods study investigated 67 elementary in-service teachers' and 69 pre-service teachers' knowledge of a complex system (e.g., water cycle) and their knowledge of systems thinking. Semi-structured interviews were conducted with a sub-sample of participants. Quantitative and qualitative analyses of content assessment data and questionnaires were conducted. Results from this study showed elementary in-service and pre-service teachers applied different levels of systems thinking from novice to intermediate. Common barriers to complete systems thinking were identified with both in-service and pre-service teachers and included identifying components and processes, recognizing multiple interactions and relationships between subsystems and hidden dimensions, and difficulty understanding the human impact on the water cycle system.
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A Systems Analysis Role Play Case: We Sell Stuff, Inc.
ERIC Educational Resources Information Center
Mitri, Michel; Cole, Carey
2007-01-01
Most systems development projects incorporate some sort of life cycle approach in their development. Whether the development methodology involves a traditional life cycle, prototyping, rapid application development, or some other approach, the first step usually involves a system investigation, which includes problem identification, feasibility…
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Focused training boosts revenue cycle skills, accountability.
Richmond, Craig
2011-09-01
In 2009, the MetroHealth System took its first steps toward creating a comprehensive revenue cycle university, with the goal of developing revenue cycle staff talent and achieving best-in-class revenue cycle operations. MetroHealth became a beta site for HFMA's online Credentialed Revenue Cycle Representative (CRCR) program, and asked its revenue cycle leaders to present classes on key revenue cycle issues. As of June 2011, 62 percent of 122 revenue cycle employees who had taken the CRCR course passed the exam. The CRCR designation is now a prerequisite for career advancement in certain revenue cycle areas at MetroHealth.
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Some single-piston closed-cycle machines and Peter Tailer's thermal lag engine
DOE Office of Scientific and Technical Information (OSTI.GOV)
West, C.D.
1993-01-01
Peter Tailer has devised, built, and operated a beautifully simple engine with a closed working gas cycle, external heating, and only a single piston. The aim of this paper is to cast some light on the possible modes of operation for his machine. The methods develops to analyze certain aspects of Stirling cycle engines, and especially the thermodynamic losses incurred in systems that are neither perfectly isothermal nor perfectly adiabatic, can be applied to Tailer's system. The results identify two idealized cycles fr such machines; relate those cycles to a single piston, ported cylinder machine proposed earlier; and offer amore » possible explanation for the success of the thermal lag engine.« less
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40 CFR 86.1509 - Exhaust gas sampling system.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Otto-Cycle Heavy-Duty Engines, New Methanol-Fueled Natural Gas-Fueled, and Liquefied Petroleum Gas-Fueled Diesel-Cycle Heavy-Duty Engines, New Otto-Cycle Light-Duty Trucks, and New Methanol-Fueled Natural Gas-Fueled, and Liquefied Petroleum Gas-Fueled Diesel-Cycle Light-Duty Trucks; Idle Test Procedures...
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A critical examination of the dual system theory in Ostrinia nubilalis.
Skopik, S D; Takeda, M; Holyoke, C W
1981-11-01
Beck's dual system theory (DST) is examined theoretically and experimentally by investigating the oviposition rhythm of Ostrinia nubilalis and its entrainment by light cycles. Several well-known circadian phenomena are not accounted for by the DST. 1) It does not generate transient cycles when light pulses fall during the advance portion of the circadian cycle. This is also reflected in DST-predicted phase-response curves (PRC's) for both Drosophila pseudoobscura and O. nubilalis. Steady-state phase advances are predicted to occur on day 1 after the light pulses by the DST, not several cycles later as has been observed in many cases. 2) It does not account for the observation that the magnitude of a phase shift (delta phi) is often a function of pulse duration of both delays and advances. The DST predicts the same + delta phi, for example, for a 0.5-h and a 6.0-h light pulse beginning 5.0 h after dusk. 3) The DST does not accurately predict steady-state phase relationships between the light cycle and the gating oscillation (P-system) in non-24-h light cycles. 4) The driver (S-system) is given the property of being temperature sensitive whereas the driven rhythm (P-system) is temperature compensated. This is contrary to accumulated data suggesting that the circadian pacemaker is temperature compensated.
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Targeting methionine cycle as a potential therapeutic strategy for immune disorders.
Li, Heng; Lu, Huimin; Tang, Wei; Zuo, Jianping
2017-08-23
Methionine cycle plays an essential role in regulating many cellular events, especially transmethylation reactions, incorporating the methyl donor S-adenosylmethionine (SAM). The transmethylations and substances involved in the cycle have shown complicated effects and mechanisms on immunocytes developments and activations, and exert crucial impacts on the pathological processes in immune disorders. Areas covered: Methionine cycle has been considered as an effective means of drug developments. This review discussed the role of methionine cycle in immune responses and summarized the potential therapeutic strategies based on the cycle, including SAM analogs, methyltransferase inhibitors, S-adenosylhomocysteine hydrolase (SAHH) inhibitors, adenosine receptors specific agonists or antagonists and homocysteine (Hcy)-lowering reagents, in treating human immunodeficiency virus (HIV) infections, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis (SSc) and other immune disorders. Expert opinion: New targets and biomarkers grown out of methionine cycle have developed rapidly in the past decades. However, impacts of epigenetic regulations on immune disorders are unclear and whether the substances in methionine cycle can be clarified as biomarkers remains controversial. Therefore, further elucidation on the role of epigenetic regulations and substances in methionine cycle may contribute to exploring the cycle-derived biomarkers and drugs in immune disorders.
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NASA Technical Reports Server (NTRS)
Kubo, I.
1987-01-01
Bottoming cycle concepts for heavy duty transport engine applications were studied. In particular, the following tasks were performed: (1) conceptual design and cost data development for Stirling systems; (2) life-cycle cost evaluation of three bottoming systems - organic Rankine, steam Rankine, and Stirling cycles; and (3) assessment of future directions in waste heat utilization research. Variables considered for the second task were initial capital investments, fuel savings, depreciation tax benefits, salvage values, and service/maintenance costs. The study shows that none of the three bottoming systems studied are even marginally attractive. Manufacturing costs have to be reduced by at least 65%. As a new approach, an integrated Rankine/Diesel system was proposed. It utilizes one of the diesel cylinders as an expander and capitalizes on the in-cylinder heat energy. The concept eliminates the need for the power transmission device and a sophisticated control system, and reduces the size of the exhaust evaporator. Results of an economic evaluation indicate that the system has the potential to become an attractive package for end users.
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Fuel economy of hybrid fuel-cell vehicles
NASA Astrophysics Data System (ADS)
Ahluwalia, Rajesh K.; Wang, X.; Rousseau, A.
The potential improvement in fuel economy of a mid-size fuel-cell vehicle by combining it with an energy storage system has been assessed. An energy management strategy is developed and used to operate the direct hydrogen, pressurized fuel-cell system in a load-following mode and the energy storage system in a charge-sustaining mode. The strategy places highest priority on maintaining the energy storage system in a state where it can supply unanticipated boost power when the fuel-cell system alone cannot meet the power demand. It is found that downsizing a fuel-cell system decreases its efficiency on a drive cycle which is compensated by partial regenerative capture of braking energy. On a highway cycle with limited braking energy the increase in fuel economy with hybridization is small but on the stop-and-go urban cycle the fuel economy can improve by 27%. On the combined highway and urban drive cycles the fuel economy of the fuel-cell vehicle is estimated to increase by up to 15% by hybridizing it with an energy storage system.
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Airbreathing combined cycle engine systems
NASA Technical Reports Server (NTRS)
Rohde, John
1992-01-01
The Air Force and NASA share a common interest in developing advanced propulsion systems for commercial and military aerospace vehicles which require efficient acceleration and cruise operation in the Mach 4 to 6 flight regime. The principle engine of interest is the turboramjet; however, other combined cycles such as the turboscramjet, air turborocket, supercharged ejector ramjet, ejector ramjet, and air liquefaction based propulsion are also of interest. Over the past months careful planning and program implementation have resulted in a number of development efforts that will lead to a broad technology base for those combined cycle propulsion systems. Individual development programs are underway in thermal management, controls materials, endothermic hydrocarbon fuels, air intake systems, nozzle exhaust systems, gas turbines and ramjet ramburners.
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Results of electric-vehicle propulsion system performance on three lead-acid battery systems
NASA Technical Reports Server (NTRS)
Ewashinka, J. G.
1984-01-01
Three types of state of the art 6 V lead acid batteries were tested. The cycle life of lead acid batteries as a function of the electric vehicle propulsion system design was determined. Cycle life, degradation rate and failure modes with different battery types (baseline versus state of the art tubular and thin plate batteries were compared. The effects of testing strings of three versus six series connected batteries on overall performance were investigated. All three types do not seem to have an economically feasible battery system for the propulsion systems. The tubular plate batteries on the load leveled profile attained 235 cycles with no signs of degradation and minimal capacity loss.
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Results of electric-vehicle propulsion system performance on three lead-acid battery systems
NASA Technical Reports Server (NTRS)
Ewashinka, J. G.
1984-01-01
Three types of state of the art 6 V lead acid batteries were tested. The cycle life of lead acid batteries as a function of the electric vehicle propulsion system design was determined. Cycle life, degradation rate and failure modes with different battery types (baseline versus state of the art tubular and thin plate batteries) were compared. The effects of testing strings of three versus six series connected batteries on overall performance were investigated. All three types do not seem to have an economically feasible battery system for the propulsion systems. The tubular plate batteries on the load leveled profile attained 235 cycles with no signs of degradation and minimal capacity loss.
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Accelerator–Reactor Coupling for Energy Production in Advanced Nuclear Fuel Cycles
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heidet, Florent; Brown, Nicholas R.; Haj Tahar, Malek
2015-01-01
This article is a review of several accelerator-reactor interface issues and nuclear fuel cycle applications of accelerator-driven subcritical systems. The systems considered here have the primary goal of energy production, but that goal is accomplished via a specific application in various proposed nuclear fuel cycles, such as breed-and-burn of fertile material or burning of transuranic material. Several basic principles are reviewed, starting from the proton beam window including the target, blanket, reactor core, and up to the fuel cycle. We focused on issues of interest, e.g. the impact of the energy required to run the accelerator and associated systems onmore » the potential electricity delivered to the grid. Accelerator-driven systems feature many of the constraints and issues associated with critical reactors, with the added challenges of subcritical operation and coupling to an accelerator. Reliable accelerator operation and avoidance of beam trips are a critically important. One interesting challenge is measurement of blanket subcriticality level during operation. We also reviewed the potential benefits of accelerator-driven systems in various nuclear fuel cycle applications. Ultimately, accelerator-driven subcritical systems with the goal of transmutation of transuranic material have lower 100,000-year radioactivity versus a critical fast reactor with recycle of uranium and plutonium.« less
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Accelerator-Reactor Coupling for Energy Production in Advanced Nuclear Fuel Cycles
NASA Astrophysics Data System (ADS)
Heidet, Florent; Brown, Nicholas R.; Haj Tahar, Malek
This article is a review of several accelerator-reactor interface issues and nuclear fuel cycle applications of accelerator-driven subcritical systems. The systems considered here have the primary goal of energy production, but that goal is accomplished via a specific application in various proposed nuclear fuel cycles, such as breed-and-burn of fertile material or burning of transuranic material. Several basic principles are reviewed, starting from the proton beam window including the target, blanket, reactor core, and up to the fuel cycle. We focus on issues of interest, such as the impact of the energy required to run the accelerator and associated systems on the potential electricity delivered to the grid. Accelerator-driven systems feature many of the constraints and issues associated with critical reactors, with the added challenges of subcritical operation and coupling to an accelerator. Reliable accelerator operation and avoidance of beam trips are critically important. One interesting challenge is measurement of blanket subcriticality level during operation. We also review the potential benefits of accelerator-driven systems in various nuclear fuel cycle applications. Ultimately, accelerator-driven subcritical systems with the goal of transmutation of transuranic material have lower 100,000-year radioactivity than a critical fast reactor with recycling of uranium and plutonium.
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Biedenkopf, Nadine; Hoenen, Thomas
2017-01-01
Ebolaviruses are the causative agent of a severe hemorrhagic fever with high case fatality rates, for which no approved specific therapy is available. As biosafety level 4 (BSL4) agents, work with live ebolaviruses is restricted to maximum containment laboratories. Transcription and replication-competent viruslike particle (trVLP) systems are reverse genetics-based life cycle modeling systems that allow researchers to model virtually the entire ebolavirus life cycle outside of a maximum containment laboratory. These systems can be used to dissect the virus life cycle, and thus increase our understanding of virus biology, as well as for more applied uses such as the screening and development of novel antivirals, and thus represent powerful tools for work on ebolaviruses.
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Zoukhri, Driss
2011-01-01
The non-keratinized epithelia of the ocular surface are constantly challenged by environmental insults, such as smoke, dust, and airborne pathogens. Tears are the sole physical protective barrier for the ocular surface. Production of tears in inadequate quantity or of inadequate quality results in constant irritation of the ocular surface, leading to dry eye disease, also referred to as keratoconjunctivitis sicca (KCS). Inflammation of the lacrimal gland, such as occurs in Sjögren’s syndrome, sarcoidosis, chronic graft versus-host disease, and other pathological conditions, results in inadequate secretion of the aqueous layer of the tear film, and is a leading cause of dry eye disease. The hallmarks of lacrimal gland inflammation are the presence of immune cell infiltrates, loss of acinar epithelial cells (the secreting cells), and increased production of proinflammatory cytokines. To date, the mechanisms leading to acinar cell loss and the associated decline in lacrimal gland secretion are still poorly understood. It is also not understood why the remaining lacrimal gland cells are unable to proliferate in order to regenerate a functioning lacrimal gland. This article reviews recent advances in exocrine tissue injury and repair, with emphasis on the roles of programmed cell death and stem/progenitor cells. PMID:20427009
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Computational Prediction of Atomic Structures of Helical Membrane Proteins Aided by EM Maps
Kovacs, Julio A.; Yeager, Mark; Abagyan, Ruben
2007-01-01
Integral membrane proteins pose a major challenge for protein-structure prediction because only ≈100 high-resolution structures are available currently, thereby impeding the development of rules or empirical potentials to predict the packing of transmembrane α-helices. However, when an intermediate-resolution electron microscopy (EM) map is available, it can be used to provide restraints which, in combination with a suitable computational protocol, make structure prediction feasible. In this work we present such a protocol, which proceeds in three stages: 1), generation of an ensemble of α-helices by flexible fitting into each of the density rods in the low-resolution EM map, spanning a range of rotational angles around the main helical axes and translational shifts along the density rods; 2), fast optimization of side chains and scoring of the resulting conformations; and 3), refinement of the lowest-scoring conformations with internal coordinate mechanics, by optimizing the van der Waals, electrostatics, hydrogen bonding, torsional, and solvation energy contributions. In addition, our method implements a penalty term through a so-called tethering map, derived from the EM map, which restrains the positions of the α-helices. The protocol was validated on three test cases: GpA, KcsA, and MscL. PMID:17496035
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Kalsi, Sumit; Powl, Andrew M.; Wallace, B.A.; Morgan, Hywel; de Planque, Maurits R.R.
2014-01-01
Planar lipid bilayers suspended in apertures provide a controlled environment for ion channel studies. However, short lifetimes and poor mechanical stability of suspended bilayers limit the experimental throughput of bilayer electrophysiology experiments. Although bilayers are more stable in smaller apertures, ion channel incorporation through vesicle fusion with the suspended bilayer becomes increasingly difficult. In an alternative bilayer stabilization approach, we have developed shaped apertures in SU8 photoresist that have tapered sidewalls and a minimum diameter between 60 and 100 μm. Bilayers formed at the thin tip of these shaped apertures, either with the painting or the folding method, display drastically increased lifetimes, typically >20 h, and mechanical stability, being able to withstand extensive perturbation of the buffer solution. Single-channel electrical recordings of the peptide alamethicin and of the proteoliposome-delivered potassium channel KcsA demonstrate channel conductance with low noise, made possible by the small capacitance of the 50 μm thick SU8 septum, which is only thinned around the aperture, and unimpeded proteoliposome fusion, enabled by the large aperture diameter. We anticipate that these shaped apertures with micrometer edge thickness can substantially enhance the throughput of channel characterization by bilayer lipid membrane electrophysiology, especially in combination with automated parallel bilayer platforms. PMID:24739164
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Designing Tasks to Examine Mathematical Knowledge for Teaching Statistics for Primary Teachers
NASA Astrophysics Data System (ADS)
Siswono, T. Y. E.; Kohar, A. W.; Hartono, S.
2018-01-01
Mathematical knowledge for teaching (MKT) is viewed as fuel resources for conducting an orchestra in a teaching and learning process. By understanding MKT, especially for primary teachers, it can predict the success of a goal of an instruction and analyze the weaknesses and improvements of it. To explore what teachers think about subject matters, pedagogical terms, and appropriate curriculum, it needs a task which can be identified the teachers’ MKT including the subject matter knowledge (SMK) and pedagogical content knowledge (PCK). This study aims to design an appropriate task for exploring primary teachers’ MKT for statistics in primary school. We designed six tasks to examine 40 primary teachers’ MKT, of which each respectively represents the categories of SMK (common content knowledge (CCK) and specialised content knowledge (SCK)) and PCK (knowledge of content and students (KCS), knowledge of content and teaching (KCT), and knowledge of content and curriculum (KCC)). While MKT has much attention of numbers of scholars, we consider knowledge of content and culture (KCCl) to be hypothesized in the domains of MKT. Thus, we added one more task examining how the primary teachers used their knowledge of content (KC) regarding to MKT in statistics. Some examples of the teachers’ responses on the tasks are discussed and some refinements of MKT task in statistics for primary teachers are suggested.
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[Sjögren syndrome in ORL. Diagnostic considerations].
Leache Pueyo, J J; Sevil Navarro, J; Del Agua, C
2001-01-01
A presentation the history of a 51-year-old woman with xerostomia and keratoconjunctivitis sicca (KCS), developed in 10 months, investigations revealed the presence in serum of antibodies against cytoplasmic antigens SS-A (Ac anti-Ro/SS-A), antinuclear antibodies (ANAs) and rheumatoid factor (RF). The Rose Bengal test was positive and in the salivary gammagraphy, made with pertecnate 99 mTc, it was observed a decrease of the captation and excretion of the designer for salivary glands. The histopathology and immunohistochemical study of minor salivary glands showed the presence of a focal lymphocitic sialadenitis (fsa) and a predominance of lymphocites CD4+. It was diagnosed as primary Sjögren's syndrome (PSS) and the patient treated with salivary substitutes, artificial tears and corticoids. We analyse the current diagnostic criteria of the group of study of the European Community for the Sjögren's syndrome (SS) and emphasize the importance of histologic and immunochemical studies, that together with the rest of complementary tests will led us to distinguish not only the different forms of the presentation of the illness but also those of all patients with pathologies which are nowadays very prevalent in our environment, such as the hepatitis C (HCV) an the human immune deficiency (HIV) virus infections.
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Squeezed light from multi-level closed-cycling atomic systems
NASA Technical Reports Server (NTRS)
Xiao, Min; Zhu, Yi-Fu
1994-01-01
Amplitude squeezing is calculated for multi-level closed-cycling atomic systems. These systems can last without atomic population inversion in any atomic bases. Maximum squeezing is obtained for the parameters in the region of lasing without inversion. A practical four-level system and an ideal three-level system are presented. The latter system is analyzed in some detail and the mechanism of generating amplitude squeezing is discussed.
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Information technology security system engineering methodology
NASA Technical Reports Server (NTRS)
Childs, D.
2003-01-01
A methodology is described for system engineering security into large information technology systems under development. The methodology is an integration of a risk management process and a generic system development life cycle process. The methodology is to be used by Security System Engineers to effectively engineer and integrate information technology security into a target system as it progresses through the development life cycle. The methodology can also be used to re-engineer security into a legacy system.
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NASA Astrophysics Data System (ADS)
Lai, Bang-Cheng; He, Jian-Jun
2018-03-01
In this paper, we construct a novel 4D autonomous chaotic system with four cross-product nonlinear terms and five equilibria. The multiple coexisting attractors and the multiscroll attractor of the system are numerically investigated. Research results show that the system has various types of multiple attractors, including three strange attractors with a limit cycle, three limit cycles, two strange attractors with a pair of limit cycles, two coexisting strange attractors. By using the passive control theory, a controller is designed for controlling the chaos of the system. Both analytical and numerical studies verify that the designed controller can suppress chaotic motion and stabilise the system at the origin. Moreover, an electronic circuit is presented for implementing the chaotic system.
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Code of Federal Regulations, 2011 CFR
2011-10-01
..., although by virtue of the life cycle costs, it would otherwise be identified as “major” in response to OMB... information system. Within the Department of Justice, a major automated information system is one whose life-cycle cost is in excess of $100 million. (b) Major real property system. (1) By purchase, when the...
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Code of Federal Regulations, 2013 CFR
2013-10-01
..., although by virtue of the life cycle costs, it would otherwise be identified as “major” in response to OMB... information system. Within the Department of Justice, a major automated information system is one whose life-cycle cost is in excess of $100 million. (b) Major real property system. (1) By purchase, when the...
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Development Activities on Airbreathing Combined Cycle Engines
NASA Technical Reports Server (NTRS)
McArthur, J. Craig; Lyles, Garry (Technical Monitor)
2000-01-01
Contents include the following: Advanced reusable transportation(ART); aerojet and rocketdyne tests, RBCC focused concept flowpaths,fabricate flight weigh, test select components, document ART project, Istar (Integrated system test of an airbreathing rocket); combined cycle propulsion testbed;hydrocarbon demonstrator tracebility; Istar engine system and vehicle system closure study; and Istar project planning.
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Using Modified Fagan Inspections to Control Rapid System Development
NASA Technical Reports Server (NTRS)
Griesel, M. A.; Welz, L. L.
1994-01-01
The Jet Propulsion Laboratory (JPL) has been developing new approaches to software and system development to shorten life cycle time and reduce total life-cycle cost, while maintaining product quality. One such approach has been taken by the Just-In-Time (JIT) Materiel Acquisition System Development Project.
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Strategic Planning, 2000-2005.
ERIC Educational Resources Information Center
Tennessee State Board of Regents, Nashville.
This report presents cycle four of the strategic planning process at the State University and Community College System of Tennessee. The cycle extends for five fiscal years from 2000 to 2005, and is meant to: (1) provide a blueprint of the systems vision; (2) provide guidelines to facilitate setting system policy and priorities; (3) provide…
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A "Rainmaker" Process for Developing Internet-Based Retail Businesses
ERIC Educational Resources Information Center
Abrahams, Alan S.; Singh, Tirna
2011-01-01
Various systems development life cycles and business development models have been popularized by information systems researchers and practitioners over a number of decades. In the case of systems development life cycles, these have been targeted at software development projects within an organization, typically involving analysis, design,…
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Evolution of engine cycles for STOVL propulsion concepts
NASA Technical Reports Server (NTRS)
Bucknell, R. L.; Frazier, R. H.; Giulianetti, D. J.
1990-01-01
Short Take-off, Vertical Landing (STOVL) demonstrator concepts using a common ATF engine core are discussed. These concepts include a separate fan and core flow engine cycle, mixed flow STOVL cycles, separate flow cycles convertible to mixed flow, and reaction control system engine air bleed. STOVL propulsion controls are discussed.
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Nuclear Power Systems for Manned Mission to Mars
2004-12-01
Brayton Cycle ..........................................................................30 c. Stirling Cycle ...specific mass as the power level increases. This graph also shows the upward scalability of Brayton and Rankine cycles , predicting that higher...Orbit, 1985), 79. 47Joseph A. Angelo, Jr. and David Buden, Space Nuclear Power, (Malabar, Florida: Orbit, 1985), 80. 30 b. Brayton Cycle
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40 CFR 86.1509 - Exhaust gas sampling system.
Code of Federal Regulations, 2012 CFR
2012-07-01
... Regulations for Otto-Cycle Heavy-Duty Engines, New Methanol-Fueled Natural Gas-Fueled, and Liquefied Petroleum Gas-Fueled Diesel-Cycle Heavy-Duty Engines, New Otto-Cycle Light-Duty Trucks, and New Methanol-Fueled Natural Gas-Fueled, and Liquefied Petroleum Gas-Fueled Diesel-Cycle Light-Duty Trucks; Idle Test...