Potential Inhibitors for Isocitrate Lyase of Mycobacterium tuberculosis and Non-M. tuberculosis: A Summary

PubMed Central

Lee, Yie-Vern; Wahab, Habibah A.

2015-01-01

Isocitrate lyase (ICL) is the first enzyme involved in glyoxylate cycle. Many plants and microorganisms are relying on glyoxylate cycle enzymes to survive upon downregulation of tricarboxylic acid cycle (TCA cycle), especially Mycobacterium tuberculosis (MTB). In fact, ICL is a potential drug target for MTB in dormancy. With the urge for new antitubercular drug to overcome tuberculosis treat such as multidrug resistant strain and HIV-coinfection, the pace of drug discovery has to be increased. There are many approaches to discovering potential inhibitor for MTB ICL and we hereby review the updated list of them. The potential inhibitors can be either a natural compound or synthetic compound. Moreover, these compounds are not necessary to be discovered only from MTB ICL, as it can also be discovered by a non-MTB ICL. Our review is categorized into four sections, namely, (a) MTB ICL with natural compounds; (b) MTB ICL with synthetic compounds; (c) non-MTB ICL with natural compounds; and (d) non-MTB ICL with synthetic compounds. Each of the approaches is capable of overcoming different challenges of inhibitor discovery. We hope that this paper will benefit the discovery of better inhibitor for ICL. PMID:25649791

A denuder-impinger system with in situ derivatization followed by gas chromatography-mass spectrometry for the determination of gaseous iodine-containing halogen species.

PubMed

Huang, Ru-Jin; Hoffmann, Thorsten

2008-11-14

Reactive iodine species have been suggested to play an important role in the atmosphere (e.g. tropospheric ozone depletion, coastal new particle formation). However, there still exist major uncertainties about their atmospheric chemistry, mostly due to the lack of analytical approaches for the accurate speciation of certain key compounds. In this study, 1,3,5-trimethoxybenzene (1,3,5-TMB)-coated denuder proved to be suitable for the differentiation between gaseous interhalogens (iodine monochloride (ICl), iodine monobromide (IBr)) and molecular iodine (I2) based on a selective collection/derivatization method. The results of the denuder sampling were compared with the results of impinger sampling in water, methanol and carbon tetrachloride solutions of 1,3,5-TMB. ICl and IBr are converted into 1-iodo-2,4,6-trimethoxybenzene (1-iodo-2,4,6-TMB) and 1-bromo-2,4,6-trimethoxybenzene (1-bromo-2,4,6-TMB), respectively, in the denuder systems. The respective collection efficiency is 99.2% for ICl and 92.6% for IBr, at 500mLmin(-1) gas flow rate. The collection efficiency for I2 is lower than 1% in the same denuder system, but significantly increases to about 90% in the aqueous 1,3,5-TMB loaded impinger. The denuder-impinger coupled system was then used to differentiate and to collect the ICl, IBr and I2 gas mixtures, followed by gas chromatography-ion trap mass spectrometry (GC-MS) determination. The precision of the method is in general better than 9.1%. The parameters affecting denuder operation including sampling flow rate, sampling duration, and relative humidity have been evaluated. The presented method provides an attractive protocol for iodine species analysis for atmospheric chemistry research.

The SNM1B/APOLLO DNA nuclease functions in resolution of replication stress and maintenance of common fragile site stability.

PubMed

Mason, Jennifer M; Das, Ishita; Arlt, Martin; Patel, Neil; Kraftson, Stephanie; Glover, Thomas W; Sekiguchi, JoAnn M

2013-12-15

SNM1B/Apollo is a DNA nuclease that has important functions in telomere maintenance and repair of DNA interstrand crosslinks (ICLs) within the Fanconi anemia (FA) pathway. SNM1B is required for efficient localization of key repair proteins, such as the FA protein, FANCD2, to sites of ICL damage and functions epistatically to FANCD2 in cellular survival to ICLs and homology-directed repair. The FA pathway is also activated in response to replication fork stalling. Here, we sought to determine the importance of SNM1B in cellular responses to stalled forks in the absence of a blocking lesion, such as ICLs. We found that depletion of SNM1B results in hypersensitivity to aphidicolin, a DNA polymerase inhibitor that causes replication stress. We observed that the SNM1B nuclease is required for efficient localization of the DNA repair proteins, FANCD2 and BRCA1, to subnuclear foci upon aphidicolin treatment, thereby indicating SNM1B facilitates direct repair of stalled forks. Consistent with a role for SNM1B subsequent to recognition of the lesion, we found that SNM1B is dispensable for upstream events, including activation of ATR-dependent signaling and localization of RPA, γH2AX and the MRE11/RAD50/NBS1 complex to aphidicolin-induced foci. We determined that a major consequence of SNM1B depletion is a marked increase in spontaneous and aphidicolin-induced chromosomal gaps and breaks, including breakage at common fragile sites. Thus, this study provides evidence that SNM1B functions in resolving replication stress and preventing accumulation of genomic damage.

Synthesis of structurally diverse major groove DNA interstrand crosslinks using three different aldehyde precursors

PubMed Central

Mukherjee, Shivam; Guainazzi, Angelo; Schärer, Orlando D.

2014-01-01

DNA interstrand crosslinks (ICLs) are extremely cytotoxic lesions that block essential cellular processes, such as replication and transcription. Crosslinking agents are widely used in cancer chemotherapy and form an array of structurally diverse ICLs. Despite the clinical success of these agents, resistance of tumors to crosslinking agents, for example, through repair of these lesions by the cellular machinery remains a problem. We have previously reported the synthesis of site-specific ICLs mimicking those formed by nitrogen mustards to facilitate the studies of cellular responses to ICL formation. Here we extend these efforts and report the synthesis of structurally diverse major groove ICLs that induce severe, little or no distortion in the DNA. Our approach employs the incorporation of aldehyde precursors of different lengths into complementary strands and ICL formation using a double reductive amination with a variety of amines. Our studies provide insight into the structure and reactivity parameters of ICL formation by double reductive amination and yield a set of diverse ICLs that will be invaluable for exploring structure–activity relationships in ICL repair. PMID:24782532

Soil organic carbon assessments in cropping systems using isotopic techniques

NASA Astrophysics Data System (ADS)

Martín De Dios Herrero, Juan; Cruz Colazo, Juan; Guzman, María Laura; Saenz, Claudio; Sager, Ricardo; Sakadevan, Karuppan

2016-04-01

Introduction of improved farming practices are important to address the challenges of agricultural production, food security, climate change and resource use efficiency. The integration of livestock with crops provides many benefits including: (1) resource conservation, (2) ecosystem services, (3) soil quality improvements, and (4) risk reduction through diversification of enterprises. Integrated crop livestock systems (ICLS) with the combination of no-tillage and pastures are useful practices to enhance soil organic carbon (SOC) compared with continuous cropping systems (CCS). In this study, the SOC and its fractions in two cropping systems namely (1) ICLS, and (2) CCS were evaluated in Southern Santa Fe Province in Argentina, and the use of delta carbon-13 technique and soil physical fractionation were evaluated to identify sources of SOC in these systems. Two farms inside the same soil cartographic unit and landscape position in the region were compared. The ICLS farm produces lucerne (Medicago sativa Merrill) and oat (Avena sativa L.) grazed by cattle alternatively with grain summer crops sequence of soybean (Glicine max L.) and corn (Zea mays L.), and the farm under continuous cropping system (CCS) produces soybean and corn in a continuous sequence. The soil in the area is predominantly a Typic Hapludoll. Soil samples from 0-5 and 0-20 cm depths (n=4) after the harvest of grain crops were collected in each system and analyzed for total organic carbon (SOC, 0-2000 μm), particulate organic carbon (POC, 50-100 μm) and mineral organic carbon (MOC, <50 μm). Delta carbon-13 was determined by isotopic ratio mass spectrometry. In addition, a site with natural vegetation (reference site, REF) was also sampled for delta carbon-13 determination. ANOVA and Tukey statistical analysis were carried out for all data. The SOC was higher in ICLS than in CCS at both depths (20.8 vs 17.7 g kg-1 for 0-5 cm and 16.1 vs 12.7 g kg-1 at 0-20 cm, respectively, P<0.05). MOC was similar at both depths, and POC was higher in CCS than in ICLS at 0-5 cm, while at 0-20 cm this trend was opposite. This is probably due to the presence of deep roots under pastures in ICLS. Delta carbon-13 values for 0-5 cm were -22.9, -21.2 and -19.9 per mil for REF, ICLS and CCS, respectively (P<0.05). The lower delta carbon-13 in REF soils is explained by the presence of tree species with high lignin content in natural vegetation. Lignin has lower delta carbon-13 compared to cellulose (dominating in crops and pastures), which is present in greater proportion in plant residues of ICLS and CCS. Delta carbon-13 for 0-20 cm depth was similar for both systems. This means that in CCS there was a higher C input from C4 plants than in ICLS and REF, reflecting corn-plant residue contribution to SOC, meanwhile the main component of SOC in ICLS derived from pasture-plant residues. Results showed that ICLS under no tillage improved SOC levels due to higher plant residue inputs derived mainly from pasture compared to continuous cropping systems.

Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein

PubMed Central

Benitez, Anaid; Yuan, Fenghua; Nakajima, Satoshi; Wei, Leizhen; Qian, Liangyue; Myers, Richard; Hu, Jennifer J.; Lan, Li; Zhang, Yanbin

2014-01-01

MUS81-EME1 is a DNA endonuclease involved in replication-coupled repair of DNA interstrand cross-links (ICLs). A prevalent hypothetical role of MUS81-EME1 in ICL repair is to unhook the damage by incising the leading strand at the 3′ side of an ICL lesion. In this study, we report that purified MUS81-EME1 incises DNA at the 5′ side of a psoralen ICL residing in fork structures. Intriguingly, ICL repair protein, Fanconi anemia complementation group A protein (FANCA), greatly enhances MUS81-EME1-mediated ICL incision. On the contrary, FANCA exhibits a two-phase incision regulation when DNA is undamaged or the damage affects only one DNA strand. Studies using truncated FANCA proteins indicate that both the N- and C-moieties of the protein are required for the incision regulation. Using laser-induced psoralen ICL formation in cells, we find that FANCA interacts with and recruits MUS81 to ICL lesions. This report clarifies the incision specificity of MUS81-EME1 on ICL damage and establishes that FANCA regulates the incision activity of MUS81-EME1 in a damage-dependent manner. PMID:24170812

Regulated expression of a repressor protein: FadR activates iclR.

PubMed Central

Gui, L; Sunnarborg, A; LaPorte, D C

1996-01-01

The control of the glyoxylate bypass operon (aceBAK) of Escherichia coli is mediated by two regulatory proteins, IclMR and FadR. IclMR is a repressor protein which has previously been shown to bind to a site which overlaps the aceBAK promoter. FAR is a repressor/activator protein which participates in control of the genes of fatty acid metabolism. A sequence just upstream of the iclR promoter bears a striking resemblance to FadR binding sites found in the fatty acid metabolic genes. The in vitro binding specificity of FadR, determined by oligonucleotide selection, was in good agreement with the sequences of these sites. The ability of FadR to bind to the site associated with iclR was demonstrated by gel shift and DNase I footprint analyses. Disruption of FadR or inactivation of the FadR binding site of iclR decreased the expression of an iclR::lacZ operon fusion, indicating that FadR activates the expression of iclR. It has been reported that disruption of fadR increases the expression of aceBAK. We observed a similar increase when we inactivated the FadR binding site of an iclR+ allele. This result suggests that FadR regulates aceBAK indirectly by altering the expression of IclR. PMID:8755903

Unveiling the Dynamical State of Massive Clusters through the ICL Fraction

NASA Astrophysics Data System (ADS)

Jiménez-Teja, Yolanda; Dupke, Renato; Benítez, Narciso; Koekemoer, Anton M.; Zitrin, Adi; Umetsu, Keiichi; Ziegler, Bodo L.; Frye, Brenda L.; Ford, Holland; Bouwens, Rychard J.; Bradley, Larry D.; Broadhurst, Thomas; Coe, Dan; Donahue, Megan; Graves, Genevieve J.; Grillo, Claudio; Infante, Leopoldo; Jouvel, Stephanie; Kelson, Daniel D.; Lahav, Ofer; Lazkoz, Ruth; Lemze, Dorom; Maoz, Dan; Medezinski, Elinor; Melchior, Peter; Meneghetti, Massimo; Mercurio, Amata; Merten, Julian; Molino, Alberto; Moustakas, Leonidas A.; Nonino, Mario; Ogaz, Sara; Riess, Adam G.; Rosati, Piero; Sayers, Jack; Seitz, Stella; Zheng, Wei

2018-04-01

We have selected a sample of 11 massive clusters of galaxies observed by the Hubble Space Telescope in order to study the impact of the dynamical state on the intracluster light (ICL) fraction, the ratio of total integrated ICL to the total galaxy member light. With the exception of the Bullet cluster, the sample is drawn from the Cluster Lensing and Supernova Survey and the Frontier Fields program, containing five relaxed and six merging clusters. The ICL fraction is calculated in three optical filters using the CHEFs ICL estimator, a robust and accurate algorithm free of a priori assumptions. We find that the ICL fraction in the three bands is, on average, higher for the merging clusters, ranging between ∼7% and 23%, compared with the ∼2%–11% found for the relaxed systems. We observe a nearly constant value (within the error bars) in the ICL fraction of the regular clusters at the three wavelengths considered, which would indicate that the colors of the ICL and the cluster galaxies are, on average, coincident and, thus, so are their stellar populations. However, we find a higher ICL fraction in the F606W filter for the merging clusters, consistent with an excess of lower-metallicity/younger stars in the ICL, which could have migrated violently from the outskirts of the infalling galaxies during the merger event.

Correlation of Thermal Stability and Structural Distortion of DNA Interstrand Cross-Links Produced from Oxidized Abasic Sites with Their Selective Formation and Repair.

PubMed

Ghosh, Souradyuti; Greenberg, Marc M

2015-10-13

C4'-oxidized (C4-AP) and C5'-oxidized abasic sites (DOB) that are produced following abstraction of a hydrogen atom from the DNA backbone reversibly form cross-links selectively with dA opposite a 3'-adjacent nucleotide, despite the comparable proximity of an opposing dA. A previous report on UvrABC incision of DNA substrates containing stabilized analogues of the ICLs derived from C4-AP and DOB also indicated that the latter is repaired more readily by nucleotide excision repair [Ghosh, S., and Greenberg, M. M. (2014) Biochemistry 53, 5958-5965]. The source for selective cross-link formation was probed by comparing the reactivity of ICL analogues of C4-AP and DOB that mimic the preferred and disfavored cross-links with that of reagents that indirectly detect distortion by reacting with the nucleobases. The disfavored C4-AP and DOB analogues were each more reactive than the corresponding preferred cross-link substrates, suggesting that the latter are more stable, which is consistent with selective ICL formation. In addition, the preferred DOB analogue is more reactive than the respective C4-AP ICL, which is consistent with its more efficient incision by UvrABC. The conclusions drawn from the chemical probing experiments are corroborated by UV melting studies. The preferred ICLs exhibit melting temperatures higher than those of the corresponding disfavored isomers. These studies suggest that oxidized abasic sites form reversible interstrand cross-links with dA opposite the 3'-adjacent thymidine because these products are more stable and the thermodynamic preference is reflected in the transition states for their formation.

EVIDENCE FOR BASE EXCISION REPAIR PROCESSING OF DNA INTERSTRAND CROSSLINKS

PubMed Central

Kothandapani, Anbarasi; Patrick, Steve M

2013-01-01

Many bifunctional alkylating agents and anticancer drugs exert their cytotoxicity by producing cross links between the two complementary strands of DNA, termed interstrand crosslinks (ICLs). This blocks the strand separating processes during DNA replication and transcription, which can lead to cell cycle arrest and apoptosis. Cells use multiple DNA repair systems to eliminate the ICLs. Concerted action of repair proteins involved in Nucleotide Excision Repair and Homologous Recombination pathways are suggested to play a key role in the ICL repair. However, recent studies indicate a possible role for Base Excision Repair (BER) in mediating the cytotoxicity of ICL inducing agents in mammalian cells. Elucidating the mechanism of BER mediated modulation of ICL repair would help in understanding the recognition and removal of ICLs and aid in the development of potential therapeutic agents. In this review, the influence of BER proteins on ICL DNA repair and the possible mechanisms of action are discussed. PMID:23219605

An Investigation of Intracluster Light Evolution Using Cosmological Hydrodynamical Simulations

NASA Astrophysics Data System (ADS)

Tang, Lin; Lin, Weipeng; Cui, Weiguang; Kang, Xi; Wang, Yang; Contini, E.; Yu, Yu

2018-06-01

Intracluster light (ICL) in observations is usually identified through the surface brightness limit (SBL) method. In this paper, for the first time we produce mock images of galaxy groups and clusters, using a cosmological hydrodynamical simulation to investigate the ICL fraction and focus on its dependence on observational parameters, e.g., the SBL, the effects of cosmological redshift-dimming, point-spread function (PSF), and CCD pixel size. Detailed analyses suggest that the width of the PSF has a significant effect on the measured ICL fraction, while the relatively small pixel size shows almost no influence. It is found that the measured ICL fraction depends strongly on the SBL. At a fixed SBL and redshift, the measured ICL fraction decreases with increasing halo mass, while with a much fainter SBL, it does not depend on halo mass at low redshifts. In our work, the measured ICL fraction shows a clear dependence on the cosmological redshift-dimming effect. It is found that there is more mass locked in the ICL component than light, suggesting that the use of a constant mass-to-light ratio at high surface brightness levels will lead to an underestimate of ICL mass. Furthermore, it is found that the radial profile of ICL shows a characteristic radius that is almost independent of halo mass. The current measurement of ICL from observations has a large dispersion due to different methods, and we emphasize the importance of using the same definition when observational results are compared with theoretical predictions.

Photoionization studies with molecular beams

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

Ng, C.Y.

1976-09-01

A molecular beam photoionization apparatus which combines the advantages of both the molecular beam method with photoionization mass spectrometry has been designed and constructed for carrying out some unique photoionization experiments. Rotational cooling during the supersonic expansion has resulted in high resolution photoionization efficiency curves for NO, ICl, C/sub 2/H/sub 2/ and CH/sub 3/I. The analysis of these spectra has yielded ionization potentials for these molecules to an accuracy of +- 3 MeV. Detailed autoionization structures were also resolved. This allows the investigation of the selection rules for autoionization, and the identification of the Rydberg series which converge to themore » excited states of the molecular ions. The degree of relaxation for thermally populated excited states has been examined using NO and ICl as examples. As a result of adiabatic cooling, a small percentage of dimers is also formed during the expansion. The photoionization efficiency curves for (NO)/sub 2/, ArICl, Ar/sub 2/, Kr/sub 2/ and Xe/sub 2/ have been obtained near the thresholds. Using the known dissociation energies of the (NO)/sub 2/, Ar/sub 2/, Kr/sub 2/ and Xe/sub 2/ van der Waals molecules, the corresponding dissociation energies for NO-NO/sup +/, Ar/sub 2//sup +/, Kr/sub 2//sup +/, and Xe/sub 2//sup +/ have been determined. The ionization mechanisms for this class of molecules are examined and discussed.« less

Components of a Fanconi-like pathway control Pso2-independent DNA interstrand crosslink repair in yeast.

PubMed

Ward, Thomas A; Dudášová, Zuzana; Sarkar, Sovan; Bhide, Mangesh R; Vlasáková, Danuša; Chovanec, Miroslav; McHugh, Peter J

2012-01-01

Fanconi anemia (FA) is a devastating genetic disease, associated with genomic instability and defects in DNA interstrand cross-link (ICL) repair. The FA repair pathway is not thought to be conserved in budding yeast, and although the yeast Mph1 helicase is a putative homolog of human FANCM, yeast cells disrupted for MPH1 are not sensitive to ICLs. Here, we reveal a key role for Mph1 in ICL repair when the Pso2 exonuclease is inactivated. We find that the yeast FANCM ortholog Mph1 physically and functionally interacts with Mgm101, a protein previously implicated in mitochondrial DNA repair, and the MutSα mismatch repair factor (Msh2-Msh6). Co-disruption of MPH1, MGM101, MSH6, or MSH2 with PSO2 produces a lesion-specific increase in ICL sensitivity, the elevation of ICL-induced chromosomal rearrangements, and persistence of ICL-associated DNA double-strand breaks. We find that Mph1-Mgm101-MutSα directs the ICL-induced recruitment of Exo1 to chromatin, and we propose that Exo1 is an alternative 5'-3' exonuclease utilised for ICL repair in the absence of Pso2. Moreover, ICL-induced Rad51 chromatin loading is delayed when both Pso2 and components of the Mph1-Mgm101-MutSα and Exo1 pathway are inactivated, demonstrating that the homologous recombination stages of ICL repair are inhibited. Finally, the FANCJ- and FANCP-related factors Chl1 and Slx4, respectively, are also components of the genetic pathway controlled by Mph1-Mgm101-MutSα. Together this suggests that a prototypical FA-related ICL repair pathway operates in budding yeast, which acts redundantly with the pathway controlled by Pso2, and is required for the targeting of Exo1 to chromatin to execute ICL repair.

Mechanism of cell death resulting from DNA interstrand cross-linking in mammalian cells

PubMed Central

Osawa, T; Davies, D; Hartley, J A

2011-01-01

DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced cell death is unclear. Here, we show a novel mechanism of p53-independent apoptotic cell death involving prolonged cell-cycle (G2) arrest, ICL repair involving HR, transient mitosis, incomplete cytokinesis, and gross chromosomal abnormalities resulting from ICLs in mammalian cells. This characteristic ‘giant' cell death, observed by using time-lapse video microscopy, was reduced in ICL repair ERCC1- and XRCC3-deficient cells. Collectively, the results illustrate the coordination of ICL-induced cellular responses, including cell-cycle arrest, DNA damage repair, and cell death. PMID:21814285

Human FAN1 promotes strand incision in 5'-flapped DNA complexed with RPA.

PubMed

Takahashi, Daisuke; Sato, Koichi; Hirayama, Emiko; Takata, Minoru; Kurumizaka, Hitoshi

2015-09-01

Fanconi anaemia (FA) is a human infantile recessive disorder. Seventeen FA causal proteins cooperatively function in the DNA interstrand crosslink (ICL) repair pathway. Dual DNA strand incisions around the crosslink are critical steps in ICL repair. FA-associated nuclease 1 (FAN1) is a DNA structure-specific endonuclease that is considered to be involved in DNA incision at the stalled replication fork. Replication protein A (RPA) rapidly assembles on the single-stranded DNA region of the stalled fork. However, the effect of RPA on the FAN1-mediated DNA incision has not been determined. In this study, we purified human FAN1, as a bacterially expressed recombinant protein. FAN1 exhibited robust endonuclease activity with 5'-flapped DNA, which is formed at the stalled replication fork. We found that FAN1 efficiently promoted DNA incision at the proper site of RPA-coated 5'-flapped DNA. Therefore, FAN1 possesses the ability to promote the ICL repair of 5'-flapped DNA covered by RPA. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Intracluster light at the Frontier - II. The Frontier Fields Clusters

NASA Astrophysics Data System (ADS)

Montes, Mireia; Trujillo, Ignacio

2018-02-01

Multiwavelength deep observations are a key tool to understand the origin of the diffuse light in clusters of galaxies: the intracluster light (ICL). For this reason, we take advantage of the Hubble Frontier Fields (HFF) survey to investigate the properties of the stellar populations of the ICL of its six massive intermediate redshift (0.3 < z < 0.6) clusters. We carry on this analysis down to a radial distance of ˜120 kpc from the brightest cluster galaxy. We found that the average metallicity of the ICL is [Fe/H]ICL ˜ -0.5, compatible with the value of the outskirts of the Milky Way. The mean stellar ages of the ICL are between 2 and 6 Gyr younger than the most massive galaxies of the clusters. Those results suggest that the ICL of these massive (>1015 M⊙) clusters is formed by the stripping of MW-like objects that have been accreted at z < 1, in agreement with current simulations. We do not find any significant increase in the fraction of light of the ICL with cosmic time, although the redshift range explored is narrow to derive any strong conclusion. When exploring the slope of the stellar mass density profile, we found that the ICL of the HFF clusters follows the shape of their underlying dark matter haloes, in agreement with the idea that the ICL is the result of the stripping of galaxies at recent times.

The Fanconi anemia pathway and ICL repair: implications for cancer therapy

PubMed Central

Wang, Lily C; Gautier, Jean

2011-01-01

Fanconi anemia (FA) is an inherited disease caused by mutations in at least 13 genes and characterized by genomic instability. In addition to displaying strikingly heterogenous clinical phenotypes, FA patients are exquisitely sensitive to treatments with crosslinking agents that create interstrand crosslinks (ICL). In contrast to bacteria and yeast, in which ICLs are repaired through replication-dependent and –independent mechanisms, it is thought that ICLs are repaired primarily during DNA replication in vertebrates (Moldovan and D’Andrea, 2009). However, recent data indicate that replication-independent ICL repair also operates in vertebrates. While the precise role of the FA pathway in ICL repair remains elusive, increasing evidence suggests that FA proteins function at different steps in the sensing, recognition and processing of ICLs, as well as in signaling from these very toxic lesions, which can be generated by a wide variety of cancer chemotherapeutic drugs. Here, we discuss some of the recent findings that have shed light on the role of the FA pathway in ICL repair with special emphasis on the implications of these findings for cancer therapy since disruption of FA genes have been associated with cancer predisposition. PMID:20807115

Unique Dynamic Properties of DNA Duplexes Containing Interstrand Crosslinks†

PubMed Central

Friedman, Joshua I.; Jiang, Yu Lin; Miller, Paul S.; Stivers, James T.

2010-01-01

Bifunctional DNA alkylating agents form a diverse assortment of covalent DNA interstrand crosslinked (ICL) structures that are potent cytotoxins. Since it is implausible that cells could possess distinct DNA repair systems for each individual ICL, it is believed that common structural and dynamic features of ICL damage are recognized, rather than specific structural characteristics of each cross-linking agent. Investigation of the structural and dynamic properties of ICLs that might be important for recognition has been complicated by heterogeneous incorporation of these lesions into DNA. To address this problem we have synthesized and characterized several homogenous ICL-DNAs containing site–specific staggered N4-cytosine-ethyl-N4-cytosine crosslinks. Staggered crosslinks were introduced in two ways: in a manner that preserves the overall structure of B-form duplex DNA, and in a manner that highly distorts the DNA structure, with the goal of understanding how structural and dynamic properties of diverse ICL duplexes might flag these sites for repair. Measurements of base pair opening dynamics in the B-form ICL duplex by 1H NMR linewidth or imino proton solvent exchange showed that the guanine base opposite to the crosslinked cytosine opened at least an order of magnitude more slowly than when in a control matched normal duplex. To a lesser degree, the B-form ICL also induced a decrease in base pair opening dynamics that extended from the site of the crosslink to adjacent base pairs. In contrast, the non-B-form ICL showed extensive conformational dynamics at the site of the cross link, which extended over the entire DNA sequence. Since DNA duplexes containing the B-form and non-B-form ICL crosslinks have both been shown to be incised when incubated in mammalian whole cell extracts, while a matched normal duplex is not, we conclude that intrinsic DNA dynamics is not a requirement for specific damage incision of these ICLs. Instead, we propose a general model where destabilized ICL-duplexes serve to energetically facilitate binding of DNA repair factors that must induce bubbles or other distortions in the duplex. However, the essential requirement for incision is an immobile Y-junction where the repair factors are stably bound at the site of the ICL, and the two DNA strands are unpaired. PMID:21174443

Metabolic adaptation via regulated enzyme degradation in the pathogenic yeast Candida albicans.

PubMed

Ting, S Y; Ishola, O A; Ahmed, M A; Tabana, Y M; Dahham, S; Agha, M T; Musa, S F; Muhammed, R; Than, L T L; Sandai, D

2017-03-01

The virulence of Candida albicans is dependent upon fitness attributes as well as virulence factors. These attributes include robust stress responses and metabolic flexibility. The assimilation of carbon sources is important for growth and essential for the establishment of infections by C. albicans. Previous studies showed that the C. albicans ICL1 genes, which encode the glyoxylate cycle enzymes isocitratelyase are required for growth on non-fermentable carbon sources such as lactate and oleic acid and were repressed by 2% glucose. In contrast to S. cerevsiae, the enzyme CaIcl1 was not destabilised by glucose, resulting with its metabolite remaining at high levels. Further glucose addition has caused CaIcl1 to lose its signal and mechanisms that trigger destabilization in response to glucose. Another purpose of this study was to test the stability of the Icl1 enzyme in response to the dietary sugars, fructose, and galactose. In the present study, the ICL1 mRNAs expression was quantified using Quantitative Real Time PCR, whereby the stability of protein was measured and quantified using Western blot and phosphoimager, and the replacing and cloning of ICL1 ORF by gene recombination and ubiquitin binding was conducted via co-immuno-precipitation. Following an analogous experimental approach, the analysis was repeated using S. cerevisiaeas a control. Both galactose and fructose were found to trigger the degradation of the ICL1 transcript in C. albicans. The Icl1 enzyme was stable following galactose addition but was degraded in response to fructose. C. albicans Icl1 (CaIcl1) was also subjected to fructose-accelerated degradation when expressed in S. cerevisiae, indicating that, although it lacks a ubiquitination site, CaIcl1 is sensitive to fructose-accelerated protein degradation. The addition of an ubiquitination site to CaIcl1 resulted in this enzyme becoming sensitive to galactose-accelerated degradation and increases its rate of degradation in the presence of fructose. It can be concluded that ubiquitin-independent pathways of fructose-accelerated enzyme degradation exist in C. albicans. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Visualizing Inhibition of Nucleosome Mobility and Transcription by Cisplatin-DNA Interstrand Crosslinks in Live Mammalian Cells

PubMed Central

Zhu, Guangyu; Song, Lina; Lippard, Stephen J.

2013-01-01

Cisplatin is a widely used anticancer drug that acts by binding DNA and causing the formation of intrastrand and interstrand (ICL) cross-links, but the precise downstream effects of the latter damage are not well understood. In this study, we investigated the influence of cisplatin ICLs on synthetic nucleosomes that were platinated in a site-specific manner in vitro and on gene transcription in live mammalian cells. Nucleosome core particles (NCPs) that we constructed contained site-specific cisplatin 5′-d(G*pC)/5′-d(G*pC) ICLs, where the asterisk denotes the platinated nucleoside, to examine the influence of platinum lesions on the dynamic behavior of nucleosomes in solution. A cisplatin ICL, but not a 1,2-d(GpG) cross-link, significantly inhibited ATP-independent histone octamer-DNA sliding. We also used a novel linearization-recircularization strategy described here to synthesize mammalian expression vectors containing site-specific cisplatin ICLs. Plasmid vectors were tested in live mammalian cellsto study the transcription inhibition effects of cisplatin ICLs in the context of two different repair backgrounds. Cisplatin ICLs inhibit transcription as effectively as 1,2-d(GpG) cross-links. We determined that nucleotide excision repair plays a key role in the removal of cisplatin ICLs, acting in a replication-independent fashion. We also found that loss of mismatch repair function dramatically attenuatesthe transcription inhibition effects by cisplatin ICLs but not 1,2-d(GpG) intrastrand cross-links. Our results revealed the unique properties of cisplatin ICLs on nucleosome mobility and on transcription, and they defined how these adducts act in a manner completely different from that used for cisplatin 1,2-d(GpG) cross-links. These new findings provide direct support for a role of ICLs in the pharmacological activities of cisplatin, despite the lower frequency of their formation. PMID:23695549

Identification of Ser153 in ICL2 of the gonadotropin-releasing hormone (GnRH) receptor as a phosphorylation-independent site for inhibition of Gq coupling.

PubMed

Shacham, Sharon; Cheifetz, Maya N; Fridkin, Mati; Pawson, Adam J; Millar, Robert P; Naor, Zvi

2005-08-12

Type I gonadotropin-releasing hormone (GnRH) receptor (GnRHR) is unique among mammalian G-protein-coupled receptors (GPCRs) in lacking a C-terminal tail, which is involved in desensitization in GPCRs. Therefore, we searched for inhibitory sites in the intracellular loops (ICLs) of the GnRHR. Synthetic peptides corresponding to the three ICLs were inserted into permeabilized alphaT3-1 gonadotrope cells, and GnRH-induced inositol phosphate (InsP) formation was determined. GnRH-induced InsP production was potentiated by ICL2 > ICL3 but not by the ICL1 peptides, suggesting they are acting as decoy peptides. We examined the effects of six peptides in which only one of the Ser or Thr residues was substituted with Ala or Glu. Only substitution of Ser153 with Ala or Glu ablated the potentiating effect upon GnRH-induced InsP elevation. ERK activation was enhanced, and the rate of GnRH-induced InsP formation was about 6.5-fold higher in the first 10 min in COS-1 cells that were transfected with mutants of the GnRHR in which the ICL2 Ser/Thr residues (Ser151, Ser153, and Thr142) or only Ser153 was mutated to Ala as compared with the wild type GnRHR. The data indicate that ICL2 harbors an inhibitory domain, such that exogenous ICL2 peptide serves as a decoy for the inhibitory site (Ser153) of the GnRHR, thus enabling further activation. GnRH does not induce receptor phosphorylation in alphaT3-1 cells. Because the phosphomimetic ICL2-S153E peptide did not mimic the stimulatory effect of the ICL2 peptide, the inhibitory effect of Ser153 operates through a phosphorylation-independent mechanism.

Crystalline lens changes in porcine eyes with implanted phakic IOL (ICL) with a central hole

PubMed Central

Shimizu, Kimiya; Fujisawa, Kunitoshi; Uga, Shigekazu; Nagano, Koichi; Murakami, Yuuki

2008-01-01

Background We calculated the smallest diameter of a hole in the center of the optic at which the optical character of a phakic IOL (ICL) may be maintained. The changes induced in the aqueous humor dynamics and the pathology of cataract development with such a hole were investigated. Methods A simulation was performed using ZEMAX software to calculate the hole diameter that makes possible the maintenance of a stable optical character of a phakic IOL. After a hole of calculated diameter was trepanned in the center of the optic of the ICL, the latter was implanted into one eye of a 5-month-old minipig, and an unperforated ICL into the other. The postoperative course was observed for 3 months. Then, Evans blue was injected into the vitreous body under general anesthesia to stain the anterior capsule of the crystalline lens. Within 30 min, the eye was enucleated and the tissues removed were fixed. Results The MTF of the perforated ICL (hole diameter, 1.0 mm) in the center of the optic resembled that of the unperforated ICL. In all cases with non-perforated ICLs, subcapsular turbidity developed, but no staining caused by EB was observed in the anterior capsule. On the other hand, the anterior capsules of the eyes fitted with ICLs with a 1.0-mm hole were stained, but exhibited no turbidity. Conclusion An ICL with a central hole of diameter 1.0 mm in the optic is similar to an unperforated ICL. The size of the hole influenced the aqueous humor dynamics and increased the aqueous humor perfusion volume over the entire anterior surface of the crystalline lens. The possibility of preventing cataracts was therefore suggested. PMID:18299877

Lost but not forgotten: intracluster light in galaxy groups and clusters

NASA Astrophysics Data System (ADS)

DeMaio, Tahlia; Gonzalez, Anthony H.; Zabludoff, Ann; Zaritsky, Dennis; Connor, Thomas; Donahue, Megan; Mulchaey, John S.

2018-03-01

With Hubble Space Telescope imaging, we investigate the progenitor population and formation mechanisms of the intracluster light (ICL) for 23 galaxy groups and clusters at 0.29 ≤ z ≤ 0.89. The colour gradients of the BCG+ICL become bluer with increasing radius out to 53-100 kpc for all but one system, suggesting that violent relaxation after major mergers with the BCG cannot be the dominant source of ICL. The BCG+ICL luminosities and stellar masses are too large for the ICL stars to come from the dissolution of dwarf galaxies alone, given the observed evolution of the faint end of the cluster galaxy luminosity function, implying instead that the ICL grows from the stripping of more massive galaxies. Using the colours of cluster members from the CLASH high-mass sample, we place conservative lower limits on the luminosities of galaxies from which the ICL at r < 100 kpc could originate via stripping. We find that the ICL at 100 kpc has a colour similar to a 1010.0 M⊙ galaxy and that 75 per cent of the total BCG+ICL luminosity at r < 100 kpc is consistent with originating in galaxies with L > 0.2 L* (log(M★ [M⊙])>10.4), assuming conservatively that these galaxies are completely disrupted. We conclude that the tidal stripping of massive galaxies is the likely source of the intracluster light from 10 to 100 kpc for galaxy groups and clusters.

Recruitment and positioning determine the specific role of the XPF-ERCC1 endonuclease in interstrand crosslink repair.

PubMed

Klein Douwel, Daisy; Hoogenboom, Wouter S; Boonen, Rick Acm; Knipscheer, Puck

2017-07-14

XPF-ERCC1 is a structure-specific endonuclease pivotal for several DNA repair pathways and, when mutated, can cause multiple diseases. Although the disease-specific mutations are thought to affect different DNA repair pathways, the molecular basis for this is unknown. Here we examine the function of XPF-ERCC1 in DNA interstrand crosslink (ICL) repair. We used Xenopus egg extracts to measure both ICL and nucleotide excision repair, and we identified mutations that are specifically defective in ICL repair. One of these separation-of-function mutations resides in the helicase-like domain of XPF and disrupts binding to SLX4 and recruitment to the ICL A small deletion in the same domain supports recruitment of XPF to the ICL, but inhibited the unhooking incisions most likely by disrupting a second, transient interaction with SLX4. Finally, mutation of residues in the nuclease domain did not affect localization of XPF-ERCC1 to the ICL but did prevent incisions on the ICL substrate. Our data support a model in which the ICL repair-specific function of XPF-ERCC1 is dependent on recruitment, positioning and substrate recognition. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

ICL: The Image Composition Language

NASA Technical Reports Server (NTRS)

Foley, James D.; Kim, Won Chul

1986-01-01

The Image Composition Language (ICL) provides a convenient way for programmers of interactive graphics application programs to define how the video look-up table of a raster display system is to be loaded. The ICL allows one or several images stored in the frame buffer to be combined in a variety of ways. The ICL treats these images as variables, and provides arithematic, relational, and conditional operators to combine the images, scalar variables, and constants in image composition expressions. The objective of ICL is to provide programmers with a simple way to compose images, to relieve the tedium usually associated with loading the video look-up table to obtain desired results.

Inhibition of the Nedd8 system sensitizes cells to DNA Inter-strand crosslinking agents

PubMed Central

Kee, Younghoon; Huang, Min; Chang, Sophia; Moreau, Lisa A.; Park, Eunmi; Smith, Peter G.; D’Andrea, Alan D.

2012-01-01

The Fanconi Anemia (FA) pathway is required for repair of DNA interstrand crosslinks (ICLs). FA pathway-deficient cells are hypersensitive to DNA ICL-inducing drugs such as Cisplatin. Conversely, hyperactivation of the FA pathway is a mechanism that may underlie cellular resistance to DNA ICL agents. Modulating FANCD2 monoubiquitination, a key step in the FA pathway, may be an effective therapeutic approach to conferring cellular sensitivity to ICL agents. Here, we show that inhibition of the Nedd8 conjugation system increases cellular sensitivity to DNA ICL-inducing agents. Mechanistically, the Nedd8 inhibition, either by siRNA-mediated knockdown of Nedd8 conjugating enzymes or treatment with a Nedd8 activating enzyme inhibitor MLN4924, suppressed DNA damage-induced FANCD2 monoubiquitination and CHK1 phosphorylation. Our data indicate that inhibition of the FA pathway is largely responsible for the heightened cellular sensitivity to DNA ICLs upon Nedd8 inhibition. These results suggest that a combination of Nedd8 inhibition with ICL-inducing agents may be an effective strategy for sensitizing a subset of drug-resistant cancer cells. PMID:22219386

DNA interstrand cross-link repair: understanding role of Fanconi anemia pathway and therapeutic implications.

PubMed

Shukla, Pallavi; Solanki, Avani; Ghosh, Kanjaksha; Vundinti, Babu Rao

2013-11-01

Interstrand cross-links (ICLs) are extremely toxic DNA lesions that prevent DNA double-helix separation due to the irreversible covalent linkage binding of some agents on DNA strands. Agents that induce these ICLs are thus widely used as chemotherapeutic drugs but may also lead to tumor growth. Fanconi anemia (FA) is a rare genetic disorder that leads to ICL sensitivity. This review provides update on current understanding of the role of FA proteins in repairing ICLs at various stages of cell cycle. We also discuss link between DNA cross-link genotoxicity caused by aldehydes in FA pathway. Besides this, we summarize various ICL agents that act as drugs to treat different types of tumors and highlight strategies for modulating ICL sensitivity for therapeutic interventions that may be helpful in controlling cancer and life-threatening disease, FA. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Long-Term Comparison of Posterior Chamber Phakic Intraocular Lens With and Without a Central Hole (Hole ICL and Conventional ICL) Implantation for Moderate to High Myopia and Myopic Astigmatism: Consort-Compliant Article.

PubMed

Shimizu, Kimiya; Kamiya, Kazutaka; Igarashi, Akihito; Kobashi, Hidenaga

2016-04-01

The study shows a promising next-generation surgical option for the correction of moderate to high ametropia. Hole implantable collamer lens (ICL), STAAR Surgical, is a posterior chamber phakic intraocular lens with a central artificial hole. As yet, however, no long-term comparison of the clinical results of the implantation of ICLs with and without such a hole has hitherto been conducted. A prospective, randomized, controlled trial was carried out in order to compare the long-term clinical outcomes of the implantation, in such eyes, of ICLs with and without a central artificial hole.Examinations were conducted of the 64 eyes of 32 consecutive patients with spherical equivalents of -7.53 ± 2.39 diopters (D) (mean ± standard deviation) in whom implantation of a Hole ICL was performed in 1 eye, and that of a conventional ICL was carried out in the other, by randomized assignment. Before 1, 3, and 6 months, and 1, 3, and 5 years after surgery, the safety, efficacy, predictability, stability, intraocular pressure, endothelial cell density, and adverse events of the 2 surgical techniques were assessed and compared over time.The measurements of LogMAR uncorrected and corrected distance visual acuity 5 years postoperatively were -0.17 ± 0.14 and -0.24 ± 0.08 in the Hole ICL group, and -0.16 ± 0.10 and -0.25 ± 0.08 in the conventional ICL group. In these 2 groups, 96% and 100% of eyes, respectively, were within 1.0 D of the targeted correction 5 years postoperatively. Manifest refraction changed by -0.17 ± 0.41 D and -0.10 ± 0.26 D occurred in from 1 month to 5 years in the Hole and conventional ICL groups, respectively. Only 1 eye (3.1%), which was in the conventional ICL group, developed an asymptomatic anterior subcapsular cataract.Both Hole and conventional ICLs corrected of ametropia successfully throughout the 5-year observation period. It appears likely that the presence of the central hole does not significantly affect these visual and refractive outcomes. UMIN000018771.

A prospective comparison of phakic collamer lenses and wavefront-optimized laser-assisted in situ keratomileusis for correction of myopia

PubMed Central

Parkhurst, Gregory D

2016-01-01

Purpose The aim of this study was to evaluate and compare night vision and low-luminance contrast sensitivity (CS) in patients undergoing implantation of phakic collamer lenses or wavefront-optimized laser-assisted in situ keratomileusis (LASIK). Patients and methods This is a nonrandomized, prospective study, in which 48 military personnel were recruited. Rabin Super Vision Test was used to compare the visual acuity and CS of Visian implantable collamer lens (ICL) and LASIK groups under normal and low light conditions, using a filter for simulated vision through night vision goggles. Results Preoperative mean spherical equivalent was −6.10 D in the ICL group and −6.04 D in the LASIK group (P=0.863). Three months postoperatively, super vision acuity (SVa), super vision acuity with (low-luminance) goggles (SVaG), super vision contrast (SVc), and super vision contrast with (low luminance) goggles (SVcG) significantly improved in the ICL and LASIK groups (P<0.001). Mean improvement in SVaG at 3 months postoperatively was statistically significantly greater in the ICL group than in the LASIK group (mean change [logarithm of the minimum angle of resolution, LogMAR]: ICL =−0.134, LASIK =−0.085; P=0.032). Mean improvements in SVc and SVcG were also statistically significantly greater in the ICL group than in the LASIK group (SVc mean change [logarithm of the CS, LogCS]: ICL =0.356, LASIK =0.209; P=0.018 and SVcG mean change [LogCS]: ICL =0.390, LASIK =0.259; P=0.024). Mean improvement in SVa at 3 months was comparable in both groups (P=0.154). Conclusion Simulated night vision improved with both ICL implantation and wavefront-optimized LASIK, but improvements were significantly greater with ICLs. These differences may be important in a military setting and may also affect satisfaction with civilian vision correction. PMID:27418804

A prospective comparison of phakic collamer lenses and wavefront-optimized laser-assisted in situ keratomileusis for correction of myopia.

PubMed

Parkhurst, Gregory D

2016-01-01

The aim of this study was to evaluate and compare night vision and low-luminance contrast sensitivity (CS) in patients undergoing implantation of phakic collamer lenses or wavefront-optimized laser-assisted in situ keratomileusis (LASIK). This is a nonrandomized, prospective study, in which 48 military personnel were recruited. Rabin Super Vision Test was used to compare the visual acuity and CS of Visian implantable collamer lens (ICL) and LASIK groups under normal and low light conditions, using a filter for simulated vision through night vision goggles. Preoperative mean spherical equivalent was -6.10 D in the ICL group and -6.04 D in the LASIK group (P=0.863). Three months postoperatively, super vision acuity (SVa), super vision acuity with (low-luminance) goggles (SVaG), super vision contrast (SVc), and super vision contrast with (low luminance) goggles (SVcG) significantly improved in the ICL and LASIK groups (P<0.001). Mean improvement in SVaG at 3 months postoperatively was statistically significantly greater in the ICL group than in the LASIK group (mean change [logarithm of the minimum angle of resolution, LogMAR]: ICL =-0.134, LASIK =-0.085; P=0.032). Mean improvements in SVc and SVcG were also statistically significantly greater in the ICL group than in the LASIK group (SVc mean change [logarithm of the CS, LogCS]: ICL =0.356, LASIK =0.209; P=0.018 and SVcG mean change [LogCS]: ICL =0.390, LASIK =0.259; P=0.024). Mean improvement in SVa at 3 months was comparable in both groups (P=0.154). Simulated night vision improved with both ICL implantation and wavefront-optimized LASIK, but improvements were significantly greater with ICLs. These differences may be important in a military setting and may also affect satisfaction with civilian vision correction.

Characterizing Intracluster Light in the Hubble Frontier Fields

NASA Astrophysics Data System (ADS)

Morishita, Takahiro; Abramson, Louis E.; Treu, Tommaso; Schmidt, Kasper B.; Vulcani, Benedetta; Wang, Xin

2017-09-01

We investigate the intracluster light (ICL) in the six Hubble Frontier Field clusters at 0.3< z< 0.6. We employ a new method, which is free from any functional form of the ICL profile, and exploit the unprecedented depth of this Hubble Space Telescope imaging to map the ICL’s diffuse light out to clustrocentric radii R˜ 300 {kpc} ({μ }{ICL}˜ 27 mag arcsec-2). From these maps, we construct radial color and stellar mass profiles via SED fitting and find clear negative color gradients in all systems with increasing distance from the Brightest Cluster Galaxy (BCG). While this implies older/more metal-rich stellar components in the inner part of the ICL, we find that the ICL mostly consists of a ≲ 2 {Gyr} population, and plausibly originated with {log}{M}* /{M}⊙ ≲ 10 cluster galaxies. Furthermore, we find that 10%-15% of the ICL’s mass at large radii (≳ 150 kpc) lies in a younger/bluer stellar population (˜1 Gyr), a phenomenon not seen in local samples. We attribute this light to the higher fraction of star-forming/(post-)starburst galaxies in clusters at z˜ 0.5. Ultimately, we find the ICL’s total mass to be {log}{M}* {ICL}/{M}⊙ ˜ 11-12, constituting 5%-20% of the clusters’ total stellar mass, or about half of the value at z˜ 0. The above implies distinct formation histories for the ICL and BCGs/other massive cluster galaxies; I.e., the ICL at this epoch is still being constructed rapidly (˜ 40 {M}⊙ yr-1), while the BCGs have mostly completed their evolution. To be consistent with the ICL measurements of local massive clusters, such as Virgo, our data suggest mass acquisition mainly from quiescent cluster galaxies is the principal source of ICL material in the subsequent ˜5 Gyr of cosmic time.

Protein kinase C enhances the swelling-induced chloride current in human atrial myocytes.

PubMed

Li, Ye-Tao; Du, Xin-Ling

2016-06-01

Swelling-activated chloride currents (ICl.swell) are thought to play a role in several physiologic and pathophysiologic processes and thus represent a target for therapeutic approaches. However, the mechanism of ICl.swell regulation remains unclear. In this study, we used the whole-cell patch-clamp technique to examine the role of protein kinase C (PKC) in the regulation of ICl.swell in human atrial myocytes. Atrial myocytes were isolated from the right atrial appendages of patients undergoing coronary artery bypass and enzymatically dissociated. ICl.swell was evoked in hypotonic solution and recorded using the whole-cell patch-clamp technique. The PKC agonist phorbol dibutyrate (PDBu) enhanced ICl.swell in a concentration-dependent manner, which was reversed in isotonic solution and by a chloride current inhibitor, 9-anthracenecarboxylicacid. Furthermore, the PKC inhibitor bis-indolylmaleimide attenuated the effect and 4α-PDBu, an inactive PDBu analog, had no effect on ICl.swell. These results, obtained using the whole-cell patch-clamp technique, demonstrate the ability of PKC to activate ICl,swell in human atrial myocytes. This observation was consistent with a previous study using a single-channel patch-clamp technique, but differed from some findings in other species.

The Fanconi Anemia Pathway in Replication Stress and DNA Crosslink Repair

PubMed Central

Jones, Mathew JK.; Huang, Tony T.

2013-01-01

Interstand crosslinks (ICLs) are DNA lesions where the bases of opposing DNA strands are covalently linked, inhibiting critical cellular processes such as transcription and replication. Chemical agents that generate ICLs cause chromosomal abnormalities including breaks, deletions and rearrangements, making them highly genotoxic compounds. This toxicity has proven useful for chemotherapeutic treatment against a wide variety of cancer types. The majority of our understanding of ICL repair in humans has been uncovered thorough analysis of the rare genetic disorder Fanconi anemia, in which patients are extremely sensitive to crosslinking agents. Here, we discuss recent insights into ICL repair gained through new ICL repair assays and highlight the role of the Fanconi Anemia repair pathway during replication stress. PMID:22744751

Intergalactic stellar populations in intermediate redshift clusters

NASA Astrophysics Data System (ADS)

Melnick, J.; Giraud, E.; Toledo, I.; Selman, F.; Quintana, H.

2012-11-01

A substantial fraction of the total stellar mass in rich clusters of galaxies resides in a diffuse intergalactic component usually referred to as the intracluster light (ICL). Theoretical models indicate that these intergalactic stars originate mostly from the tidal interaction of the cluster galaxies during the assembly history of the cluster, and that a significant fraction of these stars could have formed in situ from the late infall of cold metal-poor gas clouds on to the cluster. However, these models also overpredict the fraction of stellar mass in the ICL by a substantial margin, something that is still not well understood. The models also make predictions about the age distribution of the ICL stars, which may provide additional observational constraints. Here we present population synthesis models for the ICL of an intermediate redshift (z = 0.29) X-ray cluster that we have extensively studied in previous papers. The advantage of observing intermediate redshift clusters rather than nearby ones is that the former fit the field of view of multi-object spectrographs in 8-m telescopes and therefore permit us to encompass most of the ICL with only a few well-placed slits. In this paper we show that by stacking spectra at different locations within the ICL it is possible to reach sufficiently high signal-to-noise ratios to fit population synthesis models and derive meaningful results. The models provide ages and metallicities for the dominant populations at several different locations within the ICL and the brightest cluster galaxies (BCG) halo, as well as measures of the kinematics of the stars as a function of distance from the BCG. We thus find that the ICL in our cluster is dominated by old metal-rich stars, at odds with what has been found in nearby clusters where the stars that dominate the ICL are old and metal poor. While we see weak evidence of a young, metal-poor component, if real, these young stars would amount to less than 1 per cent of the total ICL mass, much less than the up to 30 per cent predicted by the models. We propose that the very metal-rich (i.e. 2.5× solar) stars in the ICL of our cluster, which comprise ˜40 per cent of the total mass, originate mostly from the central dumb-bell galaxy, while the remaining solar and metal-poor stars come from spiral, post-starburst (E+A) and metal-poor dwarf galaxies. About 16 per cent of the ICL stars are old and metal poor.

Hybrid tandem quantum dot/organic photovoltaic cells with complementary near infrared absorption

NASA Astrophysics Data System (ADS)

Kim, Taesoo; Palmiano, Elenita; Liang, Ru-Ze; Hu, Hanlin; Murali, Banavoth; Kirmani, Ahmad R.; Firdaus, Yuliar; Gao, Yangqin; Sheikh, Arif; Yuan, Mingjian; Mohammed, Omar F.; Hoogland, Sjoerd; Beaujuge, Pierre M.; Sargent, Edward H.; Amassian, Aram

2017-05-01

Monolithically integrated hybrid tandem solar cells that effectively combine solution-processed colloidal quantum dot (CQD) and organic bulk heterojunction subcells to achieve tandem performance that surpasses the individual subcell efficiencies have not been demonstrated to date. In this work, we demonstrate hybrid tandem cells with a low bandgap PbS CQD subcell harvesting the visible and near-infrared photons and a polymer:fullerene—poly (diketopyrrolopyrrole-terthiophene) (PDPP3T):[6,6]-phenyl-C60-butyric acid methyl ester (PC61BM)—top cell absorbing effectively the red and near-infrared photons of the solar spectrum in a complementary fashion. The two subcells are connected in series via an interconnecting layer (ICL) composed of a metal oxide layer, a conjugated polyelectrolyte, and an ultrathin layer of Au. The ultrathin layer of Au forms nano-islands in the ICL, reducing the series resistance, increasing the shunt resistance, and enhancing the device fill-factor. The hybrid tandems reach a power conversion efficiency (PCE) of 7.9%, significantly higher than the PCE of the corresponding individual single cells, representing one of the highest efficiencies reported to date for hybrid tandem solar cells based on CQD and polymer subcells.

Single-Mode, Distributed Feedback Interband Cascade Lasers

NASA Technical Reports Server (NTRS)

Frez, Clifford F. (Inventor); Borgentun, Carl E. (Inventor); Briggs, Ryan M. (Inventor); Bagheri, Mahmood (Inventor); Forouhar, Siamak (Inventor)

2016-01-01

Single-mode, distributed feedback interband cascade lasers (ICLs) using distributed-feedback gratings (e.g., lateral Bragg gratings) and methods of fabricating such ICLs are provided. The ICLs incorporate distributed-feedback gratings that are formed above the laser active region and adjacent the ridge waveguide (RWG) of the ICL. The ICLs may incorporate a double-ridge system comprising an optical confinement structure (e.g., a RWG) disposed above the laser active region that comprises the first ridge of the double ridge system, a DFB grating (e.g., lateral Bragg grating) disposed above the laser active region and adjacent the optical confinement structure, and an electric confinement structure that passes at least partially through the laser active region and that defines the boundary of the second ridge comprises and the termination of the DFB grating.

Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks

PubMed Central

Federico, María Belén; Vallerga, María Belén; Radl, Analía; Paviolo, Natalia Soledad; Bocco, José Luis; Di Giorgio, Marina; Soria, Gastón; Gottifredi, Vanesa

2016-01-01

Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress. PMID:26765540

Chromosomal Integrity after UV Irradiation Requires FANCD2-Mediated Repair of Double Strand Breaks.

PubMed

Federico, María Belén; Vallerga, María Belén; Radl, Analía; Paviolo, Natalia Soledad; Bocco, José Luis; Di Giorgio, Marina; Soria, Gastón; Gottifredi, Vanesa

2016-01-01

Fanconi Anemia (FA) is a rare autosomal recessive disorder characterized by hypersensitivity to inter-strand crosslinks (ICLs). FANCD2, a central factor of the FA pathway, is essential for the repair of double strand breaks (DSBs) generated during fork collapse at ICLs. While lesions different from ICLs can also trigger fork collapse, the contribution of FANCD2 to the resolution of replication-coupled DSBs generated independently from ICLs is unknown. Intriguingly, FANCD2 is readily activated after UV irradiation, a DNA-damaging agent that generates predominantly intra-strand crosslinks but not ICLs. Hence, UV irradiation is an ideal tool to explore the contribution of FANCD2 to the DNA damage response triggered by DNA lesions other than ICL repair. Here we show that, in contrast to ICL-causing agents, UV radiation compromises cell survival independently from FANCD2. In agreement, FANCD2 depletion does not increase the amount of DSBs generated during the replication of UV-damaged DNA and is dispensable for UV-induced checkpoint activation. Remarkably however, FANCD2 protects UV-dependent, replication-coupled DSBs from aberrant processing by non-homologous end joining, preventing the accumulation of micronuclei and chromatid aberrations including non-homologous chromatid exchanges. Hence, while dispensable for cell survival, FANCD2 selectively safeguards chromosomal stability after UV-triggered replication stress.

Project Management of Army Aircraft Survivability Equipment

DTIC Science & Technology

1976-11-01

develop- ment trade-offs; and request for proposal (RFP) reviews involving advanced development (AD), engineering development (ED), and pro- ducibility...Safety: Ensur~e that adequate consideration is given safetyf throughout the life cycle of aviation surviva- bility equipment. -13. Project Manager Training...rate management effort to assure an orderly progression through its life cyIcle. Many of the items carry an urgent priority for worldwide applicatic

Intracluster light in clusters of galaxies at redshifts 0.4 < z < 0.8

NASA Astrophysics Data System (ADS)

Guennou, L.; Adami, C.; Da Rocha, C.; Durret, F.; Ulmer, M. P.; Allam, S.; Basa, S.; Benoist, C.; Biviano, A.; Clowe, D.; Gavazzi, R.; Halliday, C.; Ilbert, O.; Johnston, D.; Just, D.; Kron, R.; Kubo, J. M.; Le Brun, V.; Marshall, P.; Mazure, A.; Murphy, K. J.; Pereira, D. N. E.; Rabaça, C. R.; Rostagni, F.; Rudnick, G.; Russeil, D.; Schrabback, T.; Slezak, E.; Tucker, D.; Zaritsky, D.

2012-01-01

Context. The study of intracluster light (ICL) can help us to understand the mechanisms taking place in galaxy clusters, and to place constraints on the cluster formation history and physical properties. However, owing to the intrinsic faintness of ICL emission, most searches and detailed studies of ICL have been limited to redshifts z < 0.4. Aims: To help us extend our knowledge of ICL properties to higher redshifts and study the evolution of ICL with redshift, we search for ICL in a subsample of ten clusters detected by the ESO Distant Cluster Survey (EDisCS), at redshifts 0.4 < z < 0.8, that are also part of our DAFT/FADA Survey. Methods: We analyze the ICL by applying the OV WAV package, a wavelet-based technique, to deep HST ACS images in the F814W filter and to V-band VLT/FORS2 images of three clusters. Detection levels are assessed as a function of the diffuse light source surface brightness using simulations. Results: In the F814W filter images, we detect diffuse light sources in all the clusters, with typical sizes of a few tens of kpc (assuming that they are at the cluster redshifts). The ICL detected by stacking the ten F814W images shows an 8σ detection in the source center extending over a ~50 × 50 kpc2 area, with a total absolute magnitude of -21.6 in the F814W filter, equivalent to about two L∗ galaxies per cluster. We find a weak correlation between the total F814W absolute magnitude of the ICL and the cluster velocity dispersion and mass. There is no apparent correlation between the cluster mass-to-light ratio (M/L) and the amount of ICL, and no evidence of any preferential orientation in the ICL source distribution. We find no strong variation in the amount of ICL between z = 0 and z = 0.8. In addition, we find wavelet-detected compact objects (WDCOs) in the three clusters for which data in two bands are available; these objects are probably very faint compact galaxies that in some cases are members of the respective clusters and comparable to the faint dwarf galaxies of the Local Group. Conclusions: We show that the ICL is prevalent in clusters at least up to redshift z = 0.8. In the future, we propose to detect the ICL at even higher redshifts, to determine wether there is a particular stage of cluster evolution where it was stripped from galaxies and spread into the intracluster medium. Based on observations made at ESO Telescopes at the Paranal Observatory under programme ID 082.A-0374. Also based on the use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained from the data archives at the Space Telescope European Coordinating Facility and the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555.

RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for Interstrand Crosslink Repair and Human Health.

PubMed

Feeney, Laura; Muñoz, Ivan M; Lachaud, Christophe; Toth, Rachel; Appleton, Paul L; Schindler, Detlev; Rouse, John

2017-06-01

Defects in the repair of DNA interstrand crosslinks (ICLs) are associated with the genome instability syndrome Fanconi anemia (FA). Here we report that cells with mutations in RFWD3, an E3 ubiquitin ligase that interacts with and ubiquitylates replication protein A (RPA), show profound defects in ICL repair. An amino acid substitution in the WD40 repeats of RFWD3 (I639K) found in a new FA subtype abolishes interaction of RFWD3 with RPA, thereby preventing RFWD3 recruitment to sites of ICL-induced replication fork stalling. Moreover, single point mutations in the RPA32 subunit of RPA that abolish interaction with RFWD3 also inhibit ICL repair, demonstrating that RPA-mediated RFWD3 recruitment to stalled replication forks is important for ICL repair. We also report that unloading of RPA from sites of ICL induction is perturbed in RFWD3-deficient cells. These data reveal important roles for RFWD3 localization in protecting genome stability and preserving human health. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

RPA activates the XPF-ERCC1 endonuclease to initiate processing of DNA interstrand crosslinks.

PubMed

Abdullah, Ummi B; McGouran, Joanna F; Brolih, Sanja; Ptchelkine, Denis; El-Sagheer, Afaf H; Brown, Tom; McHugh, Peter J

2017-07-14

During replication-coupled DNA interstrand crosslink (ICL) repair, the XPF-ERCC1 endonuclease is required for the incisions that release, or "unhook", ICLs, but the mechanism of ICL unhooking remains largely unknown. Incisions are triggered when the nascent leading strand of a replication fork strikes the ICL Here, we report that while purified XPF-ERCC1 incises simple ICL-containing model replication fork structures, the presence of a nascent leading strand, modelling the effects of replication arrest, inhibits this activity. Strikingly, the addition of the single-stranded DNA (ssDNA)-binding replication protein A (RPA) selectively restores XPF-ERCC1 endonuclease activity on this structure. The 5'-3' exonuclease SNM1A can load from the XPF-ERCC1-RPA-induced incisions and digest past the crosslink to quantitatively complete the unhooking reaction. We postulate that these collaborative activities of XPF-ERCC1, RPA and SNM1A might explain how ICL unhooking is achieved in vivo . © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

The Fanconi anemia pathway promotes replication-dependent DNA interstrand crosslink repair

PubMed Central

Knipscheer, Puck; Räschle, Markus; Smogorzewska, Agata; Enoiu, Milica; Ho, The Vinh; Schärer, Orlando D.; Elledge, Stephen J.; Walter, Johannes C.

2010-01-01

Fanconi anemia is a human cancer predisposition syndrome caused by mutations in thirteen Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand crosslinks (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. We make use of a cell-free system to show that the FANCI-FANCD2 complex is required for replication-dependent ICL repair. Removal of FANCD2 from extracts inhibits nucleolytic incisions near the ICL as well as translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised. PMID:19965384

The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.

PubMed

Knipscheer, Puck; Räschle, Markus; Smogorzewska, Agata; Enoiu, Milica; Ho, The Vinh; Schärer, Orlando D; Elledge, Stephen J; Walter, Johannes C

2009-12-18

Fanconi anemia is a human cancer predisposition syndrome caused by mutations in 13 Fanc genes. The disorder is characterized by genomic instability and cellular hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs). A central event in the activation of the Fanconi anemia pathway is the mono-ubiquitylation of the FANCI-FANCD2 complex, but how this complex confers ICL resistance remains enigmatic. Using a cell-free system, we showed that FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. Removal of FANCD2 from extracts inhibits both nucleolytic incisions near the ICL and translesion DNA synthesis past the lesion. Reversal of these defects requires ubiquitylated FANCI-FANCD2. Our results show that multiple steps of the essential S-phase ICL repair mechanism fail when the Fanconi anemia pathway is compromised.

Flexible metabolism in Metarhizium anisopliae and Beauveria bassiana: role of the glyoxylate cycle during insect pathogenesis.

PubMed

Padilla-Guerrero, Israel Enrique; Barelli, Larissa; González-Hernández, Gloria Angélica; Torres-Guzmán, Juan Carlos; Bidochka, Michael J

2011-01-01

Insect pathogenic fungi such as Metarhizium anisopliae and Beauveria bassiana have an increasing role in the control of agricultural insect pests and vectors of human diseases. Many of the virulence factors are well studied but less is known of the metabolism of these fungi during the course of insect infection or saprobic growth. Here, we assessed enzyme activity and gene expression in the central carbon metabolic pathway, including isocitrate dehydrogenase, aconitase, citrate synthase, malate synthase (MLS) and isocitrate lyase (ICL), with particular attention to the glyoxylate cycle when M. anisopliae and B. bassiana were grown under various conditions. We observed that ICL and MLS, glyoxylate cycle intermediates, were upregulated during growth on 2-carbon compounds (acetate and ethanol) as well as in insect haemolymph. We fused the promoter of the M. anisopliae ICL gene (Ma-icl) to a marker gene (mCherry) and showed that Ma-icl was upregulated when M. anisopliae was grown in the presence of acetate. Furthermore, Ma-icl was upregulated when fungi were engulfed by insect haemocytes as well as during appressorium formation. Addition of the ICL inhibitor 3-nitroproprionate delayed conidial germination and inhibited appressorium formation. These results show that these insect pathogenic fungi have a flexible metabolism that includes the glyoxylate cycle as an integral part of germination, pathogenesis and saprobic growth.

Psoralen-induced DNA adducts are substrates for the base excision repair pathway in human cells

PubMed Central

Couvé-Privat, Sophie; Macé, Gaëtane; Saparbaev, Murat K.

2007-01-01

Interstrand cross-link (ICL) is a covalent modification of both strands of DNA, which prevents DNA strand separation during transcription and replication. Upon photoactivation 8-methoxypsoralen (8-MOP+UVA) alkylates both strands of DNA duplex at the 5,6-double bond of thymidines, generating monoadducts (MAs) and ICLs. It was thought that bulky DNA lesions such as MAs are eliminated only in the nucleotide excision repair pathway. Instead, non-bulky DNA lesions are substrates for DNA glycosylases and AP endonucleases which initiate the base excision repair (BER) pathway. Here we examined whether BER might be involved in the removal of psoralen–DNA photoadducts. The results show that in human cells DNA glycosylase NEIL1 excises the MAs in duplex DNA, subsequently the apurinic/apyrimidinic endonuclease 1, APE1, removes the 3′-phosphate residue at single-strand break generated by NEIL1. The apparent kinetic parameters suggest that NEIL1 excises MAs with high efficiency. Consistent with these results HeLa cells lacking APE1 and/or NEIL1 become hypersensitive to 8-MOP+UVA exposure. Furthermore, we demonstrate that bacterial homologues of NEIL1, the Fpg and Nei proteins, also excise MAs. New substrate specificity of the Fpg/Nei protein family provides an alternative repair pathway for ICLs and bulky DNA damage. PMID:17715144

Identification of a novel inhibitor of isocitrate lyase as a potent antitubercular agent against both active and non-replicating Mycobacterium tuberculosis.

PubMed

Liu, Yishuang; Zhou, Shuang; Deng, Qi; Li, Xinghua; Meng, Jianzhou; Guan, Yan; Li, Chuanyou; Xiao, Chunling

2016-03-01

Screen and identify novel inhibitors of isocitrate lyase (ICL) as potent antitubercular agents against Mycobacterium tuberculosis and determine their inhibitory characteristics, antitubercular activities and mechanisms of action. Recombinant ICL of M. tuberculosis was expressed and purified, which was used for high-throughput screening (HTS) and the following experiments. A total of 71,765 compounds were screened to identify ICL inhibitors which were then evaluated for their roles as potent antitubercular agents. To determine the inhibitory characteristics of the agents against latent M. tuberculosis in persistent infections, a macrophage model (mouse J774A.1 cell) infected with Mycobacterium marinum BAA-535 strain was built and assessed. The potent antitubercular agents were identified using the macrophage model. Then, the inhibitory intensity and mode of the agents that exhibit on ICL protein of M. tuberculosis were analyzed, and the interaction mechanisms were preliminarily clarified according to the parameters of enzyme kinetics, circular dichroism experiments, fluorescence quenching assay, and molecular docking. The previously established ICL inhibitor screening model was evaluated to be suitable for HTS assay. Of the 71,765 compounds, 13 of them were identified to inhibit ICL effectively and stably. IMBI-3 demonstrated the most significant inhibitory activity with IC50 of 30.9 μmol/L. Its minimum inhibitory concentration (MIC) for M. tuberculosis, including extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant tuberculosis (MDR-TB), were determined in the range of 0.25-1 μg/mL. When IMBI-3 is used in combination with isoniazid, the colony-forming units (CFU) counting of latent M. tuberculosis in J774A.1 macrophage cells decreased significantly as IMBI-3 concentration increased. The inhibition mode of IMBI-3 on ICL was probably competitive inhibition with an inhibition constant (Ki) of approximate 1.85 μmol/L. The interaction between IMBI-3 and ICL of M. tuberculosis was also confirmed by circular dichroism experiments and fluorescence quenching assay. And seven possible active amino acids of ICL of M. tuberculosis were identified in the active site through molecular docking. IMBI-3, a novel potent antitubercular agent targeting ICL of M. tuberculosis, was identified and evaluated. It inhibited both log-phase M. tuberculosis in vitro and dormant M. tuberculosis in macrophages. It was the first representative compound of this family with the ICL enzyme inhibition and antimycobacterial activities. Copyright © 2016 Elsevier Ltd. All rights reserved.

The different growth pathways of Brightest Cluster Galaxies and the Intra-Cluster Light

NASA Astrophysics Data System (ADS)

Contini, E.; Yi, S. K.; Kang, X.

2018-06-01

We study the growth pathways of Brightest Central Galaxies (BCGs) and Intra-Cluster Light (ICL) by means of a semi-analytic model. We assume that the ICL forms by stellar stripping of satellite galaxies and violent processes during mergers, and implement two independent models: (1) one considers both mergers and stellar stripping (named STANDARD model), and one considers only mergers (named MERGERS model). We find that BCGs and ICL form, grow and overall evolve at different times and with different timescales, but they show a clear co-evolution after redshift z ˜ 0.7 - 0.8. Around 90% of the ICL from stellar stripping is built-up in the innermost 150 Kpc from the halo centre and the dominant contribution comes from disk-like galaxies (B/T<0.4) through a large number of small/intermediate stripping events (Mstrip/Msat < 0.3). The fractions of stellar mass in BCGs and in ICL over the total stellar mass within the virial radius of the halo evolve differently with time. At high redshift, the BCG accounts for the bulk of the mass, but its contribution gradually decreases with time and stays constant after z ˜ 0.4 - 0.5. The ICL, instead, grows very fast and its contribution keeps increasing down to the present time. The STANDARD and the MERGERS models make very similar predictions in most of the cases, but predict different amounts of ICL associated to other galaxies within the virial radius of the group/cluster other than the BCG, at z = 0. We then suggest that this quantity is a valid observable that can shed light on the relative importance of mergers and stellar stripping for the formation of the ICL.

Requirement of the isocitrate lyase gene ICL1 for VPS41-mediated starvation response in Cryptococcus neoformans.

PubMed

Xu, Zhe; Zhi, Yafei; Dong, Jianzhang; Lin, Benfeng; Ye, Di; Liu, Xiaoguang

2016-07-01

Cryptococcus neoformans is a major cause of fungal meningitis in individuals with impaired immunity. Our previous studies have shown that the VPS41 gene plays a critical role in the survival of Cryptococcus neoformans under nitrogen starvation; however, the molecular mechanisms underlying VPS41-mediated starvation response remain to be elucidated. In the present study, we show that, under nitrogen starvation, VPS41 strongly enhanced ICL1 expression in C. neoformans and that overexpression of ICL1 in the vps41 mutant dramatically suppressed its defects in starvation response due to the loss of VPS41 function. Moreover, targeted deletion of ICL1 resulted in a dramatic decline in viability of C. neoformans cells under nitrogen deprivation. Taken together, our data suggest a model in which VPS41 up-regulates ICL1 expression, directly or indirectly, to promote survival of C. neoformans under nitrogen starvation.

NMR structural study of the intracellular loop 3 of the serotonin 5-HT(1A) receptor and its interaction with calmodulin.

PubMed

Chen, Angela Shuyi; Kim, Young Mee; Gayen, Shovanlal; Huang, Qiwei; Raida, Manfred; Kang, Congbao

2011-09-01

The serotonin (5-HT(1A)) receptor, a G-protein-coupled receptor (GPCR), plays important roles in serotonergic signaling in the central nervous system. The third intracellular loop (ICL3) of the 5-HT(1A) receptor has been shown to be important for the regulation of this receptor through interactions with proteins such as G-proteins and calmodulin. In this study, the ICL3 of 5-HT(1A) receptor was expressed in E. coli and purified. Gel filtration and mass spectrometry were used to confirm the molecular weight of the purified ICL3. Secondary structure analysis using circular dichroism (CD) demonstrated the presence of α-helical structures. Backbone assignment of ICL3 was achieved using three-dimensional experiments. A chemical shift index and Talos+ analysis showed that residues E326 to R339 form α-helical structure. Residues G256 to S269 of ICL3 were shown to be a novel region that has a molecular interaction with calmodulin in titration assays. Peptide derived from the ICL3 containing residues from G256 to S269 also showed molecular interaction with calmodulin. Copyright © 2011 Elsevier B.V. All rights reserved.

In vivo confocal Raman microscopic determination of depth profiles of the stratum corneum lipid organization influenced by application of various oils.

PubMed

Choe, ChunSik; Schleusener, Johannes; Lademann, Jürgen; Darvin, Maxim E

2017-08-01

The intercellular lipids (ICL) of stratum corneum (SC) play an important role in maintaining the skin barrier function. The lateral and lamellar packing order of ICL in SC is not homogenous, but rather depth-dependent. This study aimed to analyze the influence of the topically applied mineral-derived (paraffin and petrolatum) and plant-derived (almond oil and jojoba oil) oils on the depth-dependent ICL profile ordering of the SC in vivo. Confocal Raman microscopy (CRM), a unique tool to analyze the depth profile of the ICL structure non-invasively, is employed to investigate the interaction between oils and human SC in vivo. The results show that the response of SC to oils' permeation varies in the depths. All oils remain in the upper layers of the SC (0-20% of SC thickness) and show predominated differences of ICL ordering from intact skin. In these depths, skin treated with plant-derived oils shows more disordered lateral and lamellar packing order of ICL than intact skin (p<0.05). In the intermediate layers of SC (30-50% of SC thickness), the oils do not influence the lateral packing order of SC ICL (p>0.1), except plant-derived oils at the depth 30% of SC thickness. In the deeper layers of the SC (60-100% of SC thickness), no difference between ICL lateral packing order of the oil-treated and intact skin can be observed, except that at the depths of 70-90% of the SC thickness, where slight changes with more disorder states are measured for plant-derived oil treated skin (p<0.1), which could be explained by the penetration of free fatty acid fractions in the deep-located SC areas. Both oil types remain in the superficial layers of the SC (0-20% of the SC thickness). Skin treated with mineral- and plant-derived oils shows significantly higher disordered lateral and lamellar packing order of ICL in these layers of the SC compared to intact skin. Plant-derived oils significantly changed the ICL ordering in the depths of 30% and 70-90% of the SC thickness, which is likely due to the penetration of free fatty acids in the deeper layers of the SC. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

DIFFERENTIAL ROLE OF BASE EXCISION REPAIR PROTEINS IN MEDIATING CISPLATIN CYTOTOXICITY

PubMed Central

Sawant, Akshada; Floyd, Ashley M.; Dangeti, Mohan; Lei, Wen; Sobol, Robert W.; Patrick, Steve M.

2017-01-01

Interstrand crosslinks (ICLs) are covalent lesions formed by cisplatin. The mechanism for the processing and removal of ICLs by DNA repair proteins involves nucleotide excision repair (NER), homologous recombination (HR) and fanconi anemia (FA) pathways. In this report, we monitored the processing of a flanking uracil adjacent to a cisplatin ICL by the proteins involved in the base excision repair (BER) pathway. Using a combination of extracts, purified proteins, inhibitors, functional assays and cell culture studies, we determined the specific BER proteins required for processing a DNA substrate with a uracil adjacent to a cisplatin ICL. Uracil DNA glycosylase (UNG) is the primary glycosylase responsible for the removal of uracils adjacent to cisplatin ICLs, whereas other uracil glycosylases can process uracils in the context of undamaged DNA. Repair of the uracil adjacent to cisplatin ICLs proceeds through the classical BER pathway, highlighting the importance of specific proteins in this redundant pathway. Removal of uracil is followed by the generation of an abasic site and subsequent cleavage by AP endonuclease 1 (APE1). Inhibition of either the repair or redox domain of APE1 gives rise to cisplatin resistance. Inhibition of the lyase domain of Polymerase β (Polβ) does not influence cisplatin cytotoxicity. In addition, lack of XRCC1 leads to increased DNA damage and results in increased cisplatin cytotoxicity. Our results indicate that BER activation at cisplatin ICLs influences crosslink repair and modulates cisplatin cytotoxicity via specific UNG, APE1 and Polβ polymerase functions. PMID:28110804

Conformational Profiling of the AT1 Angiotensin II Receptor Reflects Biased Agonism, G Protein Coupling, and Cellular Context.

PubMed

Devost, Dominic; Sleno, Rory; Pétrin, Darlaine; Zhang, Alice; Shinjo, Yuji; Okde, Rakan; Aoki, Junken; Inoue, Asuka; Hébert, Terence E

2017-03-31

Here, we report the design and use of G protein-coupled receptor-based biosensors to monitor ligand-mediated conformational changes in receptors in intact cells. These biosensors use bioluminescence resonance energy transfer with Renilla luciferase (RlucII) as an energy donor, placed at the distal end of the receptor C-tail, and the small fluorescent molecule FlAsH as an energy acceptor, its binding site inserted at different positions throughout the intracellular loops and C-terminal tail of the angiotensin II type I receptor. We verified that the modifications did not compromise receptor localization or function before proceeding further. Our biosensors were able to capture effects of both canonical and biased ligands, even to the extent of discriminating between different biased ligands. Using a combination of G protein inhibitors and HEK 293 cell lines that were CRISPR/Cas9-engineered to delete Gα q , Gα 11 , Gα 12 , and Gα 13 or β-arrestins, we showed that Gα q and Gα 11 are required for functional responses in conformational sensors in ICL3 but not ICL2. Loss of β-arrestin did not alter biased ligand effects on ICL2P2. We also demonstrate that such biosensors are portable between different cell types and yield context-dependent readouts of G protein-coupled receptor conformation. Our study provides mechanistic insights into signaling events that depend on either G proteins or β-arrestin. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Compact CH 4 sensor system based on a continuous-wave, low power consumption, room temperature interband cascade laser

DOE PAGES

Dong, Lei; Li, Chunguang; Sanchez, Nancy P.; ...

2016-01-05

A tunable diode laser absorption spectroscopy-based methane sensor, employing a dense-pattern multi-pass gas cell and a 3.3 µm, CW, DFB, room temperature interband cascade laser (ICL), is reported. The optical integration based on an advanced folded optical path design and an efficient ICL control system with appropriate electrical power management resulted in a CH 4 sensor with a small footprint (32 x 20 x 17 cm 3) and low-power consumption (6 W). Polynomial and least-squares fit algorithms are employed to remove the baseline of the spectral scan and retrieve CH 4 concentrations, respectively. An Allan-Werle deviation analysis shows that themore » measurement precision can reach 1.4 ppb for a 60 s averaging time. Continuous measurements covering a seven-day period were performed to demonstrate the stability and robustness of the reported CH 4 sensor system.« less

Compact CH 4 sensor system based on a continuous-wave, low power consumption, room temperature interband cascade laser

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

Dong, Lei; Li, Chunguang; Sanchez, Nancy P.

A tunable diode laser absorption spectroscopy-based methane sensor, employing a dense-pattern multi-pass gas cell and a 3.3 µm, CW, DFB, room temperature interband cascade laser (ICL), is reported. The optical integration based on an advanced folded optical path design and an efficient ICL control system with appropriate electrical power management resulted in a CH 4 sensor with a small footprint (32 x 20 x 17 cm 3) and low-power consumption (6 W). Polynomial and least-squares fit algorithms are employed to remove the baseline of the spectral scan and retrieve CH 4 concentrations, respectively. An Allan-Werle deviation analysis shows that themore » measurement precision can reach 1.4 ppb for a 60 s averaging time. Continuous measurements covering a seven-day period were performed to demonstrate the stability and robustness of the reported CH 4 sensor system.« less

Effects of Ti-Based Additives on the Hydrogen Storage Properties of a L i B H 4 / C a H 2 Destabilized System

DOE PAGES

Yang, Hongwei; Ibikunle, Adeola; Goudy, Andrew J.

2010-01-01

Tmore » he hydrogen storage properties of a destabilized LiBH 4 / CaH 2 system ball-milled with iCl 3 , iF 3 , and iO 2 additives have been investigated. It is found that the system with iCl 3 additive has a lower dehydrogenation temperature than the ones with other additives. Further study shows that a higher amount of iCl 3 is more effective in reducing the desorption temperature of the LiBH 4 / CaH 2 system, since it leads to a lower activation energy of dehydrogenation. he activations energies for mixtures containing 4, 10, and 25 mol% of iCl 3 are 141, 126, and 110 kJ/mol, respectively. However, the benefits of higher amounts of iCl 3 are offset by a larger reduction in hydrogen capacity of the mixtures.« less

Inhibitors of the Glyoxylate Cycle Enzyme ICL1 in Candida albicans for Potential Use as Antifungal Agents

PubMed Central

Cheah, Hong-Leong; Lim, Vuanghao; Sandai, Doblin

2014-01-01

Candida albicans is an opportunistic pathogen that causes candidiasis in humans. In recent years, metabolic pathways in C. albicans have been explored as potential antifungal targets to treat candidiasis. The glyoxylate cycle, which enables C. albicans to survive in nutrient-limited host niches and its. Key enzymes (e.g., isocitrate lyase (ICL1), are particularly attractive antifungal targets for C. albicans. In this study, we used a new screening approach that better reflects the physiological environment that C. albicans cells experience during infection to identify potential inhibitors of ICL. Three compounds (caffeic acid (CAFF), rosmarinic acid (ROS), and apigenin (API)) were found to have antifungal activity against C. albicans when tested under glucose-depleted conditions. We further confirmed the inhibitory potential of these compounds against ICL using the ICL enzyme assay. Lastly, we assessed the bioavailability and toxicity of these compounds using Lipinski's rule-of-five and ADMET analysis. PMID:24781056

Differential role of base excision repair proteins in mediating cisplatin cytotoxicity.

PubMed

Sawant, Akshada; Floyd, Ashley M; Dangeti, Mohan; Lei, Wen; Sobol, Robert W; Patrick, Steve M

2017-03-01

Interstrand crosslinks (ICLs) are covalent lesions formed by cisplatin. The mechanism for the processing and removal of ICLs by DNA repair proteins involves nucleotide excision repair (NER), homologous recombination (HR) and fanconi anemia (FA) pathways. In this report, we monitored the processing of a flanking uracil adjacent to a cisplatin ICL by the proteins involved in the base excision repair (BER) pathway. Using a combination of extracts, purified proteins, inhibitors, functional assays and cell culture studies, we determined the specific BER proteins required for processing a DNA substrate with a uracil adjacent to a cisplatin ICL. Uracil DNA glycosylase (UNG) is the primary glycosylase responsible for the removal of uracils adjacent to cisplatin ICLs, whereas other uracil glycosylases can process uracils in the context of undamaged DNA. Repair of the uracil adjacent to cisplatin ICLs proceeds through the classical BER pathway, highlighting the importance of specific proteins in this redundant pathway. Removal of uracil is followed by the generation of an abasic site and subsequent cleavage by AP endonuclease 1 (APE1). Inhibition of either the repair or redox domain of APE1 gives rise to cisplatin resistance. Inhibition of the lyase domain of Polymerase β (Polβ) does not influence cisplatin cytotoxicity. In addition, lack of XRCC1 leads to increased DNA damage and results in increased cisplatin cytotoxicity. Our results indicate that BER activation at cisplatin ICLs influences crosslink repair and modulates cisplatin cytotoxicity via specific UNG, APE1 and Polβ polymerase functions. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of hole size on fluid dynamics of a posterior-chamber phakic intraocular lens with a central perforation by using computational fluid dynamics.

PubMed

Kawamorita, Takushi; Shimizu, Kimiya; Shoji, Nobuyuki

2016-04-01

A modified implantable collamer lens (ICL) with a central hole with a diameter of 0.36 mm, referred to as a hole-ICL, was created to improve aqueous humour circulation. The aim of this study is to investigate the ideal hole size in a hole-ICL from the standpoint of the fluid dynamic characteristics of the aqueous humour using computational fluid dynamics. Fluid dynamics simulation using an ICL was performed with thermal-hydraulic analysis software FloEFD V 12.2 (Mentor Graphics Corp.). In the simulation, three-dimensional eye models based on a modified Liou-Brennan model eye with a conventional ICL (Model ICM, Staar Surgical) and a hole-ICL were used. The hole-ICL was -9.0 dioptres (D) and 12.0 mm in length, with an optic zone of 5.5 mm. The vaulting was 0.50 mm. The quantity of aqueous humour produced by the ciliary body was set at 2.80 μL/min. Flow distribution between the anterior surface of the crystalline lens and the posterior surface of the ICL was calculated, and trajectory analysis was performed. With an increase in the central hole size, the velocity of the aqueous humour increased, with the peak velocity occurring at a diameter of approximately 0.4 mm. Once the diameter had increased above 0.4 mm, the velocity then decreased. The velocity difference between the cases of a central hole size of 0.1 mm and 0.2 mm was significant. The desirable central hole size was 0.2 mm or larger in terms of flow dynamics. The current model, based on a central hole size of 0.36 mm, was close to ideal. The optimisation of the hole size should be performed based on results from a long-term clinical study so as to analyse the incidence rate of secondary cataract and optical performance.

Matched population comparison of visual outcomes and patient satisfaction between 3 modalities for the correction of low to moderate myopic astigmatism

PubMed Central

Ganesh, Sri; Brar, Sheetal; Pawar, Archana

2017-01-01

Purpose To compare toric implantable collamer lens (T-ICL), femto-LASIK, and ReLEx SMILE for the treatment of low to moderate myopic astigmatism in terms of long-term visual and refractive outcomes and predictability of astigmatic correction. Materials and methods The study included 30 eyes from 30 patients between the age groups of 21 and 40 years, undergoing bilateral surgery with any of the three procedures – T-ICL, femto-LASIK, or ReLEx SMILE – for correction of myopic astigmatism within the range of −3 to −8 D spherical equivalent (SE), with a minimum astigmatism of −0.75 D. Patients were followed up at day 1, 1 month, 6 months, and 1 year. Results At 1 year, the mean cylinder reduced to −0.21±0.28, −0.17±0.36, and −0.22±0.28 D in the T-ICL, femto-LASIK, and ReLEx SMILE group, respectively. The predictability of astigmatism correction was comparable, with no statistically significant difference between the 3 groups (P>0.05). A total of 97% of eyes in ReLEx SMILE achieved a uncorrected distance visual acuity of 20/20 or better, compared to T-ICL (93%) and FS-LASIK (90%). However, gain in lines of corrected distant visual acuity (CDVA) was maximum in T-ICL group (60%). Four eyes in the femto-LASIK group had loss of CDVA by one line. Three eyes required exchange due to high vault and rotation of the T-ICL, which did not affect the final outcome. Conclusion All 3 modalities were effective for myopic astigmatism at the end of 1 year. Quality of vision and patient satisfaction with T-ICL and ReLEx SMILE were similar and better than FS-LASIK. However, slight chances of postoperative rotation and exchange exist with T-ICL, which warrant thorough preoperative planning. PMID:28740361

Mitomycin C and decarbamoyl mitomycin C induce p53-independent p21WAF1/CIP1 activation

PubMed Central

Cheng, Shu-Yuan; Seo, Jiwon; Huang, Bik Tzu; Napolitano, Tanya; Champeil, Elise

2016-01-01

Mitomycin C (MC), a commonly used anticancer drug, induces DNA damage via DNA alkylation. Decarbamoyl mitomycin C (DMC), another mitomycin lacking the carbamate at C10, generates similar lesions as MC. Interstrand cross-links (ICLs) are believed to be the lesions primarily responsible for the cytotoxicity of MC and DMC. The major ICL generated by MC (α-ICL) has a trans stereochemistry at the guanine-drug linkage whereas the major ICL from DMC (β-ICL) has the opposite, cis, stereochemistry. In addition, DMC can provoke strong p53-independent cell death. Our hypothesis is that the stereochemistry of the major unique β-ICL generated by DMC is responsible for this p53-independent cell death signaling. p53 gene is inactively mutated in more than half of human cancers. p21WAF1/CIP1 known as a major effector of p53 is involved in p53-dependent and -independent control of cell proliferation and death. This study revealed the role of p21WAF1/CIP1 on MC and DMC triggered cell damage. MCF-7 (p53-proficient) and K562 (p53-deficient) cells were used. Cell cycle distributions were shifted to the G1/S phase in MCF-7 treated with MC and DMC, but were shifted to the S phase in K562. p21WAF1/CIP1 activation was observed in both cells treated with MC and DMC, and DMC triggered more significant activation. Knocking down p53 in MCF-7 did not attenuate MC and DMC induced p21WAF1/CIP1 activation. The α-ICL itself was enough to cause p21WAF1/CIP1 activation. PMID:27666201

High-Speed Stark Wavelength Tuning of MidIR Interband Cascade Lasers

DTIC Science & Technology

2007-03-15

STARK WAVELENGTH TUNING OF MidIR ICLs 361 Fig. 2. Lasing spectra of the tunable ICL at different bias currents. injection region at before tunneling ...the energy separation between and (and hence the emission wavelength) undergoes a linear Stark shift that depends on the bias current which controls...response Fig. 3. Lasing spectra of the tunable ICL at different bias modulation frequen- cies. Fig. 4. Dependence of the intensity of the Line 2 on bias

The Human DNA glycosylases NEIL1 and NEIL3 Excise Psoralen-Induced DNA-DNA Cross-Links in a Four-Stranded DNA Structure.

PubMed

Martin, Peter R; Couvé, Sophie; Zutterling, Caroline; Albelazi, Mustafa S; Groisman, Regina; Matkarimov, Bakhyt T; Parsons, Jason L; Elder, Rhoderick H; Saparbaev, Murat K

2017-12-12

Interstrand cross-links (ICLs) are highly cytotoxic DNA lesions that block DNA replication and transcription by preventing strand separation. Previously, we demonstrated that the bacterial and human DNA glycosylases Nei and NEIL1 excise unhooked psoralen-derived ICLs in three-stranded DNA via hydrolysis of the glycosidic bond between the crosslinked base and deoxyribose sugar. Furthermore, NEIL3 from Xenopus laevis has been shown to cleave psoralen- and abasic site-induced ICLs in Xenopus egg extracts. Here we report that human NEIL3 cleaves psoralen-induced DNA-DNA cross-links in three-stranded and four-stranded DNA substrates to generate unhooked DNA fragments containing either an abasic site or a psoralen-thymine monoadduct. Furthermore, while Nei and NEIL1 also cleave a psoralen-induced four-stranded DNA substrate to generate two unhooked DNA duplexes with a nick, NEIL3 targets both DNA strands in the ICL without generating single-strand breaks. The DNA substrate specificities of these Nei-like enzymes imply the occurrence of long uninterrupted three- and four-stranded crosslinked DNA-DNA structures that may originate in vivo from DNA replication fork bypass of an ICL. In conclusion, the Nei-like DNA glycosylases unhook psoralen-derived ICLs in various DNA structures via a genuine repair mechanism in which complex DNA lesions can be removed without generation of highly toxic double-strand breaks.

Limits of application of initiated chemiluminescence in monitoring of oncological process of mucous membrane of mouth and larynx.

PubMed

Oliynyk, Iryna

2016-09-01

Investigation into the limits of application of chemiluminescence (CL) methods in oncology still attracts the attention of researchers. In the present work we analyze the screening and monitoring of oncological processes (OP) in the mucous membrane of the mouth and larynx by initiated CL (ICL). Chemiluminescence has already been used by stomatologists to define the start of OP, but methods that reflect the metabolic changes in organism under cancer diagnostics still have not found their place. This work presents results of ICL on blood serum (BS) of patients with oncological diseases at different stages of medical treatment compared with those of healthy people. We found an essential metabolic difference only in types of OP that are characterized by two maxima on chemiluminograms. These OP represent only 12.81% of groups of patients with oncological diseases. The possibility to apply ICL methods to monitor operation quality and control medical treatment at different stages when the two ICL maxima are present is established. At present, the chemiluminograms with the two maxima are mostly informative, but this does not exclude the quantitative analysis of other ICL kinetic methods and is encouraging for their investigation. Any OP introduces changes in organism function and these should be reflected in the ICL. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

ABC transporter Cdr1p harbors charged residues in the intracellular loop and nucleotide-binding domain critical for protein trafficking and drug resistance.

PubMed

Shah, Abdul Haseeb; Banerjee, Atanu; Rawal, Manpreet Kaur; Saxena, Ajay Kumar; Mondal, Alok Kumar; Prasad, Rajendra

2015-08-01

The ABC transporter Cdr1 protein of Candida albicans, which plays a major role in antifungal resistance, has two transmembrane domains (TMDs) and two nucleotide-binding domains (NBDs). The 12 transmembrane helices of TMDs that are interconnected by extracellular and intracellular loops (ICLs) mainly harbor substrate recognition sites where drugs bind while cytoplasmic NBDs hydrolyze ATP which powers drug efflux. The coupling of ATP hydrolysis to drug transport requires proper communication between NBDs and TMDs typically accomplished by ICLs. This study examines the role of cytoplasmic ICLs of Cdr1p by rationally predicting the critical residues on the basis of their interatomic distances. Among nine pairs that fall within a proximity of <4 Å, an ion pair between K577 of ICL1 and E315 of NBD1 was found to be critical. The substitution, swapping and changing of the length or charge of K577 or E315 by directed mutagenesis led to a misfolded, non-rescuable protein entrapped in intracellular structures. Furthermore, the equipositional ionic pair-forming residues from ICL3 and NBD2 (R1260 and E1014) did not impact protein trafficking. These results point to a new role for ICL/NBD interacting residues in PDR ABC transporters in protein folding and trafficking. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Epistatic role of base excision repair and mismatch repair pathways in mediating cisplatin cytotoxicity

PubMed Central

Kothandapani, Anbarasi; Sawant, Akshada; Dangeti, Venkata Srinivas Mohan Nimai; Sobol, Robert W.; Patrick, Steve M.

2013-01-01

Base excision repair (BER) and mismatch repair (MMR) pathways play an important role in modulating cis-Diamminedichloroplatinum (II) (cisplatin) cytotoxicity. In this article, we identified a novel mechanistic role of both BER and MMR pathways in mediating cellular responses to cisplatin treatment. Cells defective in BER or MMR display a cisplatin-resistant phenotype. Targeting both BER and MMR pathways resulted in no additional resistance to cisplatin, suggesting that BER and MMR play epistatic roles in mediating cisplatin cytotoxicity. Using a DNA Polymerase β (Polβ) variant deficient in polymerase activity (D256A), we demonstrate that MMR acts downstream of BER and is dependent on the polymerase activity of Polβ in mediating cisplatin cytotoxicity. MSH2 preferentially binds a cisplatin interstrand cross-link (ICL) DNA substrate containing a mismatch compared with a cisplatin ICL substrate without a mismatch, suggesting a novel mutagenic role of Polβ in activating MMR in response to cisplatin. Collectively, these results provide the first mechanistic model for BER and MMR functioning within the same pathway to mediate cisplatin sensitivity via non-productive ICL processing. In this model, MMR participation in non-productive cisplatin ICL processing is downstream of BER processing and dependent on Polβ misincorporation at cisplatin ICL sites, which results in persistent cisplatin ICLs and sensitivity to cisplatin. PMID:23761438

An initial reliability and validity study of the Interaction, Communication, and Literacy Skills Audit.

PubMed

El-Choueifati, Nisrine; Purcell, Alison; McCabe, Patricia; Heard, Robert; Munro, Natalie

2014-06-01

Early childhood educators (ECEs) have an important role in promoting positive outcomes for children's language and literacy development. This paper reports the development of a new tool, The Interaction Communication and Literacy (ICL) Skills Audit, and pilots its reliability and validity. Intra- and inter-rater reliability was examined by three speech-language pathologists (SLPs). Five skill areas relating to ECE language and literacy practice were rated. The face and content validity of the ICL Skills Audit was examined by expert SLPs (n = 8) and expert ECEs (n = 4) via questionnaire. The overall intra-rater reliability for the ICL Skills Audit was excellent with percentage close agreement (PCA) of 91-94. Inter-rater agreement was PCA 68-80. Expert SLPs and ECEs agreed that the content was comprehensive and practical. Based on this preliminary study, the ICL Skills Audit appears to be a promising tool that can be used by SLPs and ECEs in collaboration to measure the skills of ECEs in the areas of language and literacy support. Future psychometric and outcome research on the revised ICL Skills Audit is warranted.

Methylcitrate cycle defines the bactericidal essentiality of isocitrate lyase for survival of Mycobacterium tuberculosis on fatty acids

PubMed Central

Eoh, Hyungjin; Rhee, Kyu Y.

2014-01-01

Few mutations attenuate Mycobacterium tuberculosis (Mtb) more profoundly than deletion of its isocitrate lyases (ICLs). However, the basis for this attenuation remains incompletely defined. Mtb’s ICLs are catalytically bifunctional isocitrate and methylisocitrate lyases required for growth on even and odd chain fatty acids. Here, we report that Mtb’s ICLs are essential for survival on both acetate and propionate because of its methylisocitrate lyase (MCL) activity. Lack of MCL activity converts Mtb’s methylcitrate cycle into a “dead end” pathway that sequesters tricarboxylic acid (TCA) cycle intermediates into methylcitrate cycle intermediates, depletes gluconeogenic precursors, and results in defects of membrane potential and intrabacterial pH. Activation of an alternative vitamin B12-dependent pathway of propionate metabolism led to selective corrections of TCA cycle activity, membrane potential, and intrabacterial pH that specifically restored survival, but not growth, of ICL-deficient Mtb metabolizing acetate or propionate. These results thus resolve the biochemical basis of essentiality for Mtb’s ICLs and survival on fatty acids. PMID:24639517

The Burrell Schmidt Deep Virgo Survey: Tidal Debris, Galaxy Halos, and Diffuse Intracluster Light in the Virgo Cluster

NASA Astrophysics Data System (ADS)

Mihos, J. Christopher; Harding, Paul; Feldmeier, John J.; Rudick, Craig; Janowiecki, Steven; Morrison, Heather; Slater, Colin; Watkins, Aaron

2017-01-01

We present the results of a deep imaging survey of the Virgo cluster of galaxies, concentrated around the cores of Virgo subclusters A and B. The goal of this survey was to detect and study very low surface brightness features present in Virgo, including discrete tidal features, the faint halos of luminous galaxies, and the diffuse intracluster light (ICL). Our observations span roughly 16 degrees2 in two filters, reaching a 3σ limiting depth of {μ }B = 29.5 and {μ }V = 28.5 mag arcsec-2. At these depths, our limiting systematic uncertainties are astrophysical: variations in faint background sources as well as scattered light from galactic dust. We show that this dust-scattered light is well traced by deep far-infrared imaging, making it possible to separate it from true diffuse light in Virgo. We use our imaging to trace and measure the color of the diffuse tidal streams and ICL in the Virgo core near M87, in fields adjacent to the core including the M86/M84 region, and to the south of the core around M49 and subcluster B, along with the more distant W{}\\prime cloud around NGC 4365. Overall, the bulk of the projected ICL is found in the Virgo core and within the W{}\\prime cloud; we find little evidence for an extensive ICL component in the field around M49. The bulk of the ICL we detect is fairly red in color (B - V = 0.7-0.9), indicative of old, evolved stellar populations. Based on the luminosity of the observed ICL features in the cluster, we estimate a total Virgo ICL fraction of 7%-15%. This value is somewhat smaller than that expected for massive, evolved clusters, suggesting that Virgo is still in the process of growing its extended ICL component. We also trace the shape of M87's extremely boxy outer halo out to ˜150 kpc, and show that the current tidal stripping rate from low luminosity galaxies is insufficient to have built M87's outer halo over a Hubble time. We identify a number of previously unknown low surface brightness structures around galaxies projected close to M86 and M84. The extensive diffuse light seen in the infalling W{}\\prime cloud around NGC 4365 is likely to be subsumed in the general Virgo ICL component once the group enters the cluster, illustrating the importance of group infall in generating ICL. Finally, we also identify another large and extremely low surface brightness ultradiffuse galaxy, likely in the process of being shredded by the cluster tidal field. With the survey complete, the full imaging data set is now available for public release.

Control of apical membrane chloride permeability in the renal A6 cell line by nucleotides

PubMed Central

Banderali, U; Brochiero, E; Lindenthal, S; Raschi, C; Bogliolo, S; Ehrenfeld, J

1999-01-01

The effect of extracellular nucleotides applied on the apical side of polarised A6 cells grown on permeant filters was investigated by measuring the changes in (i) the 36Cl efflux through the apical membranes, (ii) the intracellular chloride concentrations (aCli, measured with N-(6-methoxyquinolyl) acetoethyl ester, MQAE), (iii) ICl, the short-circuit current in the absence of Na+ transport and (iv) the characteristics of the apical chloride channels using a patch-clamp approach. ATP or UTP (0.1-500 μm) transiently stimulated ICl. The sequence of purinergic agonist potencies was UTP = ATP > ADP >> the P2X-selective agonist β,γ-methylene ATP = the P2Y-selective agonist 2-methylthioATP. Suramin (100 μm) as the P2Y antagonist Reactive Blue 2 (10 μm) had no effect on the UTP (or ATP)-stimulated current. These findings are consistent with the presence of P2Y2-like receptors located on the apical membranes of A6 cells. Apical application of adenosine also transiently increased ICl. This effect was blocked by theophylline while the UTP-stimulated ICl was not. The existence of a second receptor, of the P1 type is proposed. ATP (or UTP)-stimulated ICl was blocked by apical application of 200 μmN-phenylanthranilic acid (DPC) or 100 μm niflumic acid while 100 μm glibenclamide was ineffective. Ionomycin and thapsigargin both transiently stimulated ICl; the nucleotide stimulation of ICl was not suppressed by pre-treatment with these agents. Chlorpromazin (50 μm), a Ca2+-calmodulin inhibitor strongly inhibited the stimulation of ICl induced either by apical UTP or by ionomycin application. BAPTA-AM pre-treatment of A6 cells blocked the UTP-stimulated ICl. Niflumic acid also blocked the ionomycin stimulated ICl. A fourfold increase in 36Cl effluxes through the apical membranes was observed after ATP or UTP application. These increases of the apical chloride permeability could also be observed when following aCli changes. Apical application of DPC (1 mm) or 5-nitro-2(3-phenylpropylamino)benzoic acid (NPPB; 500 μm) produced an incomplete inhibition of 36Cl effluxes through the apical membranes in ATP-stimulated and in untreated monolayers. In single channel patch-clamp experiments, an apical chloride channel with a unitary single channel conductance of 7.3 ± 0.6 pS (n = 12) was usually observed. ATP application induced the activation of one or more of these channels within a few minutes. These results indicate that multiple purinergic receptor subtypes are present in the apical membranes of A6 cells and that nucleotides can act as modulators of Cl− secretion in renal cells. PMID:10457087

The Fanconi anaemia pathway: new players and new functions.

PubMed

Ceccaldi, Raphael; Sarangi, Prabha; D'Andrea, Alan D

2016-06-01

The Fanconi anaemia pathway repairs DNA interstrand crosslinks (ICLs) in the genome. Our understanding of this complex pathway is still evolving, as new components continue to be identified and new biochemical systems are used to elucidate the molecular steps of repair. The Fanconi anaemia pathway uses components of other known DNA repair processes to achieve proper repair of ICLs. Moreover, Fanconi anaemia proteins have functions in genome maintenance beyond their canonical roles of repairing ICLs. Such functions include the stabilization of replication forks and the regulation of cytokinesis. Thus, Fanconi anaemia proteins are emerging as master regulators of genomic integrity that coordinate several repair processes. Here, we summarize our current understanding of the functions of the Fanconi anaemia pathway in ICL repair, together with an overview of its connections with other repair pathways and its emerging roles in genome maintenance.

Force-induced rupture of double-stranded DNA in the absence and presence of covalently bonded anti-tumor drugs: Insights from molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Upadhyaya, Anurag; Nath, Shesh; Kumar, Sanjay

2018-06-01

DNA intra-strand cross-link (ICL) agents are widely used in the treatment of cancer. ICLs are thought to form a link between the same strand (intra-strand) or complimentary strand (inter-strand) and thereby increase the stability of DNA, which forbids the processes like replication and transcription. As a result, cell death occurs. In this work, we have studied the enhanced stability of a double stranded DNA in the presence of ICLs and compared our findings with the results obtained in the absence of these links. Using atomistic simulations with explicit solvent, a force is applied along and perpendicular to the direction of the helix and we measured the rupture force and the unzipping force of DNA-ICL complexes. Our results show that the rupture and the unzipping forces increase significantly in the presence of these links. The ICLs bind to the minor groove of DNA, which enhance the DNA stabilisation. Such information may be used to design alternative drugs that can stall replication and transcription that are critical to a growing number of anticancer drug discovery efforts.

Chloroethylating nitrosoureas in cancer therapy: DNA damage, repair and cell death signaling.

PubMed

Nikolova, Teodora; Roos, Wynand P; Krämer, Oliver H; Strik, Herwig M; Kaina, Bernd

2017-08-01

Chloroethylating nitrosoureas (CNU), such as lomustine, nimustine, semustine, carmustine and fotemustine are used for the treatment of malignant gliomas, brain metastases of different origin, melanomas and Hodgkin disease. They alkylate the DNA bases and give rise to the formation of monoadducts and subsequently interstrand crosslinks (ICL). ICL are critical cytotoxic DNA lesions that link the DNA strands covalently and block DNA replication and transcription. As a result, S phase progression is inhibited and cells are triggered to undergo apoptosis and necrosis, which both contribute to the effectiveness of CNU-based cancer therapy. However, tumor cells resist chemotherapy through the repair of CNU-induced DNA damage. The suicide enzyme O 6 -methylguanine-DNA methyltransferase (MGMT) removes the precursor DNA lesion O 6 -chloroethylguanine prior to its conversion into ICL. In cells lacking MGMT, the formed ICL evoke complex enzymatic networks to accomplish their removal. Here we discuss the mechanism of ICL repair as a survival strategy of healthy and cancer cells and DNA damage signaling as a mechanism contributing to CNU-induced cell death. We also discuss therapeutic implications and strategies based on sequential and simultaneous treatment with CNU and the methylating drug temozolomide. Copyright © 2017 Elsevier B.V. All rights reserved.

Electronic properties of Al xGa 1- xAs surface passivated by ultrathin silicon interface control layer

NASA Astrophysics Data System (ADS)

Adamowicz, B.; Miczek, M.; Ikeya, K.; Mutoh, M.; Saitoh, T.; Fujikura, H.; Hasegawa, H.

1999-03-01

The photoluminescence surface state spectroscopy (PLS 3) method was applied to a study of the surface state distribution ( NSS), effective surface recombination velocity ( Seff), electron ( EFn) and hole ( EFp) quasi-Fermi levels and band bending ( VS) on the Al 0.33Ga 0.67As surface air-exposed and passivated by the Si interface control layer (ICL) technique. Using the detailed measurements of the PL quantum efficiency for different excitation intensities, combined with the rigorous computer simulations of the bulk and surface recombination processes, the behavior and correlation among the surface characteristics under photo-excitation was determined. The present analysis indicated that forming of a Si 3N 4/Si ICL double layer (with a monolayer level control) on AlGaAs surface reduces the minimum interface state density down to 10 10 cm -2 eV -1 and surface recombination velocity to the range of 10 4 cm/s under low excitations.

Compact CH{sub 4} sensor system based on a continuous-wave, low power consumption, room temperature interband cascade laser

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

Dong, Lei, E-mail: donglei@sxu.edu.cn; State Key Laboratory of Quantum Optics and Quantum Optics Devices, Institute of Laser Spectroscopy, Shanxi University, Taiyuan 030006; Li, Chunguang

A tunable diode laser absorption spectroscopy-based methane sensor, employing a dense-pattern multi-pass gas cell and a 3.3 μm, CW, DFB, room temperature interband cascade laser (ICL), is reported. The optical integration based on an advanced folded optical path design and an efficient ICL control system with appropriate electrical power management resulted in a CH{sub 4} sensor with a small footprint (32 × 20 × 17 cm{sup 3}) and low-power consumption (6 W). Polynomial and least-squares fit algorithms are employed to remove the baseline of the spectral scan and retrieve CH{sub 4} concentrations, respectively. An Allan-Werle deviation analysis shows that the measurement precision can reach 1.4 ppb for amore » 60 s averaging time. Continuous measurements covering a seven-day period were performed to demonstrate the stability and robustness of the reported CH{sub 4} sensor system.« less

Diffuse Optical Intracluster Light as a Measure of Stellar Tidal Stripping: The Cluster CL0024+17 at z ~ 0.4 Observed at the Large Binocular Telescope

NASA Astrophysics Data System (ADS)

Giallongo, E.; Menci, N.; Grazian, A.; Gallozzi, S.; Castellano, M.; Fiore, F.; Fontana, A.; Pentericci, L.; Boutsia, K.; Paris, D.; Speziali, R.; Testa, V.

2014-01-01

We have evaluated the diffuse intracluster light (ICL) in the central core of the galaxy cluster CL0024+17 at z ~ 0.4 observed with the prime focus camera (Large Binocular Camera) at the Large Binocular Telescope. The measure required an accurate removal of the galaxies' light within ~200 kpc from the center. The residual background intensity has then been integrated in circular apertures to derive the average ICL intensity profile. The latter shows an approximate exponential decline as expected from theoretical cold dark matter models where the ICL is due to the integrated contribution of light from stars that are tidally stripped from the halo of their host galaxies due to encounters with other galaxies in the cluster cold dark matter (CDM) potential. The radial profile of the ICL over the galaxies intensity ratio (ICL fraction) is increasing with decreasing radius, but near the cluster center it starts to bend and then decreases where the overlap of the halos of the brightest cluster galaxies becomes dominant. Theoretical expectations in a simplified CDM scenario show that the ICL fraction profile can be estimated from the stripped over galaxy stellar mass ratio in the cluster. It is possible to show that the latter quantity is almost independent of the properties of the individual host galaxies but mainly depends on the average cluster properties. The predicted ICL fraction profile is thus very sensitive to the assumed CDM profile, total mass, and concentration parameter of the cluster. Adopting values very similar to those derived from the most recent lensing analysis in CL0024+17, we find a good agreement with the observed ICL fraction profile. The galaxy counts in the cluster core have then been compared with that derived from composite cluster samples in larger volumes, up to the clusters virial radius. The galaxy counts in the CL0024+17 core appear flatter and the amount of bending with respect to the average cluster galaxy counts imply a loss of total emissivity in broad agreement with the measured ICL fraction. The present analysis shows that the measure of the ICL fraction in clusters can quantitatively account for the stellar stripping activity in their cores and can be used to probe their CDM distribution and evolutionary status. Observations have been carried out using the Large Binocular Telescope at Mt. Graham, AZ. The LBT is an international collaboration among institutions in the United States, Italy, and Germany. LBT Corporation partners are the University of Arizona on behalf of the Arizona university system; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, the Astrophysical Institute Potsdam, and Heidelberg University; the Ohio State University; and The Research Corporation, on behalf of the University of Notre Dame, University of Minnesota, and University of Virginia.

Meta-analysis and review: effectiveness, safety, and central port design of the intraocular collamer lens

PubMed Central

Packer, Mark

2016-01-01

The purpose of this review is to summarize relevant data from publications appearing in the peer-reviewed scientific literature over the past decade since US Food and Drug Administration approval of the implantable collamer lens (ICL), and, in particular, to review studies relating to sizing methodology, safety, and effectiveness, as well as more recent studies reporting clinical outcomes of the V4c Visian ICL with KS Aquaport, VICMO. A literature search was conducted using two databases, PubMed.gov and Science.gov, to identify all articles published after 2005 related to the Visian ICL (STAAR Surgical, Inc.). Articles were examined for their relevance to sizing methodology, clinical safety, and effectiveness, and the references cited in each article were also searched for additional relevant publications. The literature review revealed that all currently reported methods of determining the best-fit size of the ICL achieve similarly satisfactory results in terms of vault, the safe distance between the crystalline lens and the ICL. Specifically, meta-analysis demonstrated that sulcus-to-sulcus and white-to-white measurement-based sizing methods do not result in clinically meaningful nor statistically significant differences in vault (two-sample two-sided t-test using pooled mean and standard deviations; t (2,594)=1.33; P=0.18). The reported rates of complications related to vault are very low, except in two case series where additional risk factors such as higher levels of myopia and older age impacted the incidence of cataract. On the basis of preclinical studies and initial clinical reports, with up to 5 years of follow-up, the new VICMO central port design holds promise for further reduction of complications. Given its safety record and the significant improvement in vision and quality of life that the ICL makes possible, the benefits of ICL implantation outweigh the risks. PMID:27354760

Meta-analysis and review: effectiveness, safety, and central port design of the intraocular collamer lens.

PubMed

Packer, Mark

2016-01-01

The purpose of this review is to summarize relevant data from publications appearing in the peer-reviewed scientific literature over the past decade since US Food and Drug Administration approval of the implantable collamer lens (ICL), and, in particular, to review studies relating to sizing methodology, safety, and effectiveness, as well as more recent studies reporting clinical outcomes of the V4c Visian ICL with KS Aquaport, VICMO. A literature search was conducted using two databases, PubMed.gov and Science.gov, to identify all articles published after 2005 related to the Visian ICL (STAAR Surgical, Inc.). Articles were examined for their relevance to sizing methodology, clinical safety, and effectiveness, and the references cited in each article were also searched for additional relevant publications. The literature review revealed that all currently reported methods of determining the best-fit size of the ICL achieve similarly satisfactory results in terms of vault, the safe distance between the crystalline lens and the ICL. Specifically, meta-analysis demonstrated that sulcus-to-sulcus and white-to-white measurement-based sizing methods do not result in clinically meaningful nor statistically significant differences in vault (two-sample two-sided t-test using pooled mean and standard deviations; t (2,594)=1.33; P=0.18). The reported rates of complications related to vault are very low, except in two case series where additional risk factors such as higher levels of myopia and older age impacted the incidence of cataract. On the basis of preclinical studies and initial clinical reports, with up to 5 years of follow-up, the new VICMO central port design holds promise for further reduction of complications. Given its safety record and the significant improvement in vision and quality of life that the ICL makes possible, the benefits of ICL implantation outweigh the risks.

Chloride currents from the transverse tubular system in adult mammalian skeletal muscle fibers

PubMed Central

DiFranco, Marino; Herrera, Alvaro

2011-01-01

Chloride fluxes are the main contributors to the resting conductance of mammalian skeletal muscle fibers. ClC-1, the most abundant chloride channel isoform in this preparation, is believed to be responsible for this conductance. However, the actual distribution of ClC-1 channels between the surface and transverse tubular system (TTS) membranes has not been assessed in intact muscle fibers. To investigate this issue, we voltageclamped enzymatically dissociated short fibers using a two-microelectrode configuration and simultaneously recorded chloride currents (ICl) and di-8-ANEPPS fluorescence signals to assess membrane potential changes in the TTS. Experiments were conducted in conditions that blocked all but the chloride conductance. Fibers were equilibrated with 40 or 70 mM intracellular chloride to enhance the magnitude of inward ICl, and the specific ClC-1 blocker 9-ACA was used to eliminate these currents whenever necessary. Voltage-dependent di-8-ANEPPS signals and ICl acquired before (control) and after the addition of 9-ACA were comparatively assessed. Early after the onset of stimulus pulses, di-8-ANEPPS signals under control conditions were smaller than those recorded in the presence of 9-ACA. We defined as attenuation the normalized time-dependent difference between these signals. Attenuation was discovered to be ICl dependent since its magnitude varied in close correlation with the amplitude and time course of ICl. While the properties of ICl, and those of the attenuation seen in optical records, could be simultaneously predicted by model simulations when the chloride permeability (PCl) at the surface and TTS membranes were approximately equal, the model failed to explain the optical data if PCl was precluded from the TTS membranes. Since the ratio between the areas of TTS membranes and the sarcolemma is large in mammalian muscle fibers, our results demonstrate that a significant fraction of the experimentally recorded ICl arises from TTS contributions. PMID:21149546

Diffuse Optical Light in Galaxy Clusters. I. Abell 3888

NASA Astrophysics Data System (ADS)

Krick, J. E.; Bernstein, R. A.; Pimbblet, K. A.

2006-01-01

We are undertaking a program to measure the characteristics of the intracluster light (ICL; total flux, profile, color, and substructure) in a sample of 10 galaxy clusters with a range of cluster mass, morphology, and redshift. We present here the methods and results for the first cluster in that sample, A3888. We have identified an ICL component in A3888 in V and r that contains 13%+/-5% of the total cluster light and extends to 700 h-170 kpc (~0.3r200) from the center of the cluster. The ICL color in our smallest radial bin is V-r=0.3+/-0.1, similar to the central cluster elliptical galaxies. The ICL is redder than the galaxies at 400 h-170 kpc1) with a high-metallicity (1.0 Zsolar

Diffuse Optical Light in Galaxy Clusters. II. Correlations with Cluster Properties

NASA Astrophysics Data System (ADS)

Krick, J. E.; Bernstein, R. A.

2007-08-01

We have measured the flux, profile, color, and substructure in the diffuse intracluster light (ICL) in a sample of 10 galaxy clusters with a range of mass, morphology, redshift, and density. Deep, wide-field observations for this project were made in two bands at the 1 m Swope and 2.5 m du Pont telescopes at Las Campanas Observatory. Careful attention in reduction and analysis was paid to the illumination correction, background subtraction, point-spread function determination, and galaxy subtraction. ICL flux is detected in both bands in all 10 clusters ranging from 7.6×1010 to 7.0×1011 h-170 Lsolar in r and 1.4×1010 to 1.2×1011 h-170 Lsolar in the B band. These fluxes account for 6%-22% of the total cluster light within one-quarter of the virial radius in r and 4%-21% in the B band. Average ICL B-r colors range from 1.5 to 2.8 mag when k- and evolution corrected to the present epoch. In several clusters we also detect ICL in group environments near the cluster center and up to 1 h-170 Mpc distant from the cluster center. Our sample, having been selected from the Abell sample, is incomplete in that it does not include high-redshift clusters with low density, low flux, or low mass, and it does not include low-redshift clusters with high flux, high mass, or high density. This bias makes it difficult to interpret correlations between ICL flux and cluster properties. Despite this selection bias, we do find that the presence of a cD galaxy corresponds to both centrally concentrated galaxy profiles and centrally concentrated ICL profiles. This is consistent with ICL either forming from galaxy interactions at the center or forming at earlier times in groups and later combining in the center.

Lysine succinylation of Mycobacterium tuberculosis isocitrate lyase (ICL) fine-tunes the microbial resistance to antibiotics.

PubMed

Zhou, Mingliang; Xie, Longxiang; Yang, Zhaozhen; Zhou, Jiahai; Xie, Jianping

2017-04-01

Lysine succinylation (Ksucc) is a newly identified protein posttranslational modification (PTM), which may play an important role in cellular physiology. However, the role of lysine succinylation in antibiotic resistance remains elusive. Isocitrate lyase (ICL) is crucial for broad-spectrum antibiotics tolerance in Mycobacterium tuberculosis (Mtb). We previously found that MtbICL (Rv0467) has at least three succinylated lysine residues, namely K189, K322, and K334.To explore the effect of succinylation on the activity of MtbICL, mutants' mimicry of the lysine succinylation were generated by site-directed mutagenesis. ICL-K189E mutant strain is more sensitive than the wild-type to rifampicin and streptomycin, but not isoniazid. For the in vitro activity of the purified isocitrate lyase, only K189E mutant showed significantly decreased activity. Crystal structure analysis showed that Lys189 Glu dramatically increased the pKa of Glu188 and decreased the pKa of Lys190, whereas had negligible effect on other residues within 5 Å as well as disruption of the electrostatic interaction between Lys189 and Glu182, which might prevent the closure of the active site loop and cause severe reduction of the enzyme activity. Considering the genetic, biochemical, and crystallographical evidences together, the succinylation of specific ICL residue can fine-tune the bacterial resistance to selected antibiotics. The decreased enzymatic activity resulting from the succinylation-changed electrostatic interaction might underlie this phenotype. This study provided the first insight into the link between lysine succinylation and antibiotic resistance.

Human SNM1B is required for normal cellular response to both DNA interstrand crosslink-inducing agents and ionizing radiation.

PubMed

Demuth, Ilja; Digweed, Martin; Concannon, Patrick

2004-11-11

DNA interstrand crosslinks (ICLs) are critical lesions for the mammalian cell since they affect both DNA strands and block transcription and replication. The repair of ICLs in the mammalian cell involves components of different repair pathways such as nucleotide-excision repair and the double-strand break/homologous recombination repair pathways. However, the mechanistic details of mammalian ICL repair have not been fully delineated. We describe here the complete coding sequence and the genomic organization of hSNM1B, one of at least three human homologs of the Saccharomyces cerevisiae PSO2 gene. Depletion of hSNM1B by RNA interference rendered cells hypersensitive to ICL-inducing agents. This requirement for hSNM1B in the cellular response to ICL has been hypothesized before but never experimentally verified. In addition, siRNA knockdown of hSNM1B rendered cells sensitive to ionizing radiation, suggesting the possibility of hSNM1B involvement in homologous recombination repair of double-strand breaks arising as intermediates of ICL repair. Monoubiquitination of FANCD2, a key step in the FANC/BRCA pathway, is not affected in hSNM1B-depleted HeLa cells, indicating that hSNM1B is probably not a part of the Fanconi anemia core complex. Nonetheless, similarities in the phenotype of hSNM1B-depleted cells and cultured cells from patients suffering from Fanconi anemia make hSNM1B a candidate for one of the as yet unidentified Fanconi anemia genes not involved in monoubiquitination of FANCD2.

Clothing insulation and temperature, layer and mass of clothing under comfortable environmental conditions

PubMed Central

2013-01-01

This study was designed to investigate the relationship between the microclimate temperature and clothing insulation (Icl) under comfortable environmental conditions. In total, 20 subjects (13 women, 7 men) took part in this study. Four environmental temperatures were chosen: 14°C (to represent March/April), 25°C (May/June), 29°C (July/August), and 23°C (September/October). Wind speed (0.14ms-1) and humidity (45%) were held constant. Clothing microclimate temperatures were measured at the chest (Tchest) and on the interscapular region (Tscapular). Clothing temperature of the innermost layer (Tinnermost) was measured on this layer 30 mm above the centre of the left breast. Subjects were free to choose the clothing that offered them thermal comfort under each environmental condition. We found the following results. 1) All clothing factors except the number of lower clothing layers (Llower), showed differences between the different environmental conditions (P<0.05). The ranges of Tchest were 31.6 to 33.5°C and 32.2 to 33.4°C in Tscapular. The range of Tinnermost was 28.6 to 32.0°C. The range of the upper clothing layers (Lupper) and total clothing mass (Mtotal) was 1.1 to 3.2 layers and 473 to 1659 g respectively. The range of Icl was 0.78 to 2.10 clo. 2) Post hoc analyses showed that analysis of Tinnermost produced the same results as for that of Icl. Likewise, the analysis of Lupper produced the same result as the analysis of the number of total layers (Ltotal) within an outfit. 3) Air temperature (ta) had positive relationships with Tchest and Tscapular and with Tinnermost but had inverse correlations with Icl, Mtotal, Lupper and Ltotal. Tchest, Tscapular, and Tinnermost increased as ta rose. 4) Icl had inverse relationships with Tchest and Tinnermost, but positive relationships with Mtotal, Lupper and Ltotal. Icl could be estimated by Mtotal, Lupper, and Tscapular using a multivariate linear regression model. 5) Lupper had positive relationships with Icl and Mtotal, but Llower did not. Subjects hardly changed Llower under environmental comfort conditions between March and October. This indicates that each of the Tchest, Mtotal, and Lupper was a factor in predicting Icl. Tinnermost might also be a more influential factor than the clothing microclimate temperature. PMID:23816370

Assessing oxygen saturation in retinal vessels in high myopia patients pre- and post-implantable collamer lens implantation surgery.

PubMed

Chen, Pei; Cai, Xiaoxiao; Xu, Lijun; Zhang, Jing; Yang, Ying; Gao, Qianying; Ge, Jian; Yu, Keming; Zhuang, Jing

2017-09-01

To determine whether posterior chamber phakic implantable collamer lens (ICL) surgery in high myopia patients impedes oxygen saturation of retinal vessels. Mean oxygen saturation and diameter in retinal blood vessels were measured before and after ICL implantation surgery to correct high myopia refractive errors (i.e. -6.00 to -20.25 dioptres [D]), using an Oxymap T1 retinal oximeter. In 17 eyes of 17 patients, the Oxymap T1 retinal oximeter detected a small but significant decrease in oxygen saturation of retinal venules, 1-week postoperatively (compared to preoperative measurements). Moreover, at 1 week after ICL implantation, the diameter of patient retinal vessels had consistently contracted, compared to preoperative measurements. By 1 month after ICL surgery, however, both the oxygen saturation and retinal vessel diameter had returned to preoperative levels. Otherwise, no statistically significant difference in oxygen saturation and diameter of retinal arterioles was found when comparing their measurements before and 1 week after implantation. Stable levels of oxygen saturation in retinal vessels, as detected by the Oxymap T1 oximeter, show ICL implantation would not leave lasting impact or adverse effects to retina oxygen saturation in high myopia patients. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Weight, Length, and Body Mass Index Growth of Children Under 2 Years of Age With Cleft Lip and Palate.

PubMed

Miranda, Gabriela Serrano; Marques, Ilza Lazarini; de Barros, Suely Prietto; Arena, Eliane Petean; de Souza, Luiz

2016-05-01

To study the growth of length-for-age (L/A), weight-for-age (W/A), and body mass index (BMI) of children with cleft lip and palate receiving a normal diet; to establish specific growth curves for children with cleft palate with or without cleft lip (CLP/ICP) who had not undergone palatoplasty and for children with isolated cleft lip (ICL); and to assess if CLP/ICP growth differed from ICL growth and if CLP/ICP and ICL growth differed from growth for typical children. Prospective and cross-sectional study. Hospital for Rehabilitation of Craniofacial Anomalies, Bauru, São Paulo, Brazil. Weight and length of 381 children with cleft lip and palate and who were younger than 2 years were recorded and used to calculate W/A, L/A, and BMI growth curves. The 2006 World Health Organization growth charts were used as a reference for typical children. All children received a normal diet for age. Children with CLP/ICP had median W/A and BMI growth curves below growth curves for typical children but showed spontaneous recovery starting at approximately 5 months of age, even with nonoperated cleft palate. Children with ICL had growth similar to that of typical children. Children with CLP/ICP, who initially had W/A and BMI values less than those of the ICL group, had W/A and BMI equal to or higher than the ICL group after 9 months of age. Children with CLP/ICP had impaired W/A and BMI growth with spontaneous recovery starting early in childhood. This study established specific W/A, BMI, and L/A growth curves for children with cleft lip and palate.

Preparation and properties of pure, full-length IclR protein of Escherichia coli. Use of time-of-flight mass spectrometry to investigate the problems encountered.

PubMed Central

Donald, L. J.; Chernushevich, I. V.; Zhou, J.; Verentchikov, A.; Poppe-Schriemer, N.; Hosfield, D. J.; Westmore, J. B.; Ens, W.; Duckworth, H. W.; Standing, K. G.

1996-01-01

IclR protein, the repressor of the aceBAK operon of Escherichia coli, has been examined by time-of-flight mass spectrometry, with ionization by matrix assisted laser desorption or by electrospray. The purified protein was found to have a smaller mass than that predicted from the base sequence of the cloned iclR gene. Additional measurements were made on mixtures of peptides derived from IclR by treatment with trypsin and cyanogen bromide. They showed that the amino acid sequence is that predicted from the gene sequence, except that the protein has suffered truncation by removal of the N-terminal eight or, in some cases, nine amino acid residues. The peptide bond whose hydrolysis would remove eight residues is a typical target for the E. coli protease OmpT. We find that, by taking precautions to minimize Omp T proteolysis, or by eliminating it through mutation of the host strain, we can isolate full-length IclR protein (lacking only the N-terminal methionine residue). Full-length IclR is a much better DNA-binding protein than the truncated versions: it binds the aceBAK operator sequence 44-fold more tightly, presumably because of additional contacts that the N-terminal residues make with the DNA. Our experience thus demonstrates the advantages of using mass spectrometry to characterize newly purified proteins produced from cloned genes, especially where proteolysis or other covalent modification is a concern. This technique gives mass spectra from complex peptide mixtures that can be analyzed completely, without any fractionation of the mixtures, by reference to the amino acid sequence inferred from the base sequence of the cloned gene. PMID:8844850

Advanced pigment dispersion glaucoma secondary to phakic intraocular collamer lens implant.

PubMed

Ye, Clara; Patel, Cajal K; Momont, Anna C; Liu, Yao

2018-06-01

We report a case of pigment dispersion glaucoma secondary to uncomplicated phakic intraocular collamer lens (ICL) (Visian ICL™, Staar Inc., Monrovia, CA) implant that resulted in advanced visual field loss. A 50-year-old man presented for routine follow-up status post bilateral phakic intraocular collamer lens (ICL) placement 8 years earlier. He was incidentally found to have a decline in visual acuity from an anterior subcapsular cataract and elevated intraocular pressure (IOP) in the left eye. There were signs of pigment dispersion and no evidence of angle closure. Diffuse optic nerve thinning was consistent with advanced glaucomatous visual field defects. Pigment dispersion was also present in the patient's right eye, but without elevated IOP or visual field defects. The patient was treated with topical glaucoma medications and the phakic ICL in the left eye was removed concurrently with cataract surgery to prevent further visual field loss. Pigment dispersion glaucoma is a serious adverse outcome after phakic ICL implantation and regular post-operative monitoring may prevent advanced visual field loss.

[Long-term results of posterior chamber phakic intraocular lens implantation for correction of high ametropia].

PubMed

Le Loir, M; Cochener, B

2012-06-01

To assess efficacy, stability and safety of posterior chamber phakic intraocular lens implantation with STAAR Visian ICL for correction of high ametropia, with a mean follow-up of 5 years (3.5-10 years). Ninety eyes of 53 highly ametropic patients (45 myopia, ten hyperopia and 35 with mixed astigmatism) were included in a retrospective single-surgeon study, using primarily the V4 ICL model (87 eyes). We studied pre- and postoperative refractive efficacy, endothelial cell density, crystalline lens opacification and intraocular clearances within the various compartments of the eye. Mean uncorrected visual acuity was 0.77 at the 12th postoperative month; 17 of 90 eyes required adjunctive photoablation for residual astigmatism. Forty-eight percent of eyes gained at least one line of best corrected visual acuity. After implantation, the decrease in endothelial cell density remained stable at 0.69%/year, and 91% of eyes showed no opacification of the crystalline lens. Mean endothelium-ICL and ICL-crystalline lens distances were 2.41 mm and 0.52 mm respectively. Overall patient satisfaction achieved was 96% at 36 months postoperatively. These results demonstrate efficacy, stability and safety of the ICL V4 phakic IOL for the correction of high ametropia. Long-term follow-up did not show a significant increase in cataract formation in implanted eyes. Copyright © 2012. Published by Elsevier Masson SAS.

Positional and rotational stability of the toric phakic intraocular lens under high +Gz environments.

PubMed

Tan, Marcus C L; Nah, Gerard K M

2012-02-01

Phakic intraocular lens (PIOL) implantation is a surgical option for correction of refractive errors. PIOLs can be use to correct myopia, hyperopia, and astigmatism. It is a surgical option available to patients in addition to methods such as laser cornea refractive surgery, e.g., laser assisted in-situ keratomileusis (LASIK) and photo-refractive keratectomy (PRK). Visian implantable collamer lens (ICL) are posterior chamber lenses which are surgically positioned in a phakic eye in the sulcus between the iris diaphragm and the natural crystalline lens. This case report describes the stability of Visian toric ICL in a candidate with bilateral implants under high +Gz force exposure in a human centrifuge trainer. The subject was sequentially exposed to three incremental +Gz profiles of +5 Gz, +7 Gz, and +9 Gz. Pre- and post-+Gz exposure, ophthalmic examination revealed no ICL displacement, implant touch or induced cataract, or change in refractive error. The rotational stability of the toric implants was also demonstrated by identical subjective refractions in both eyes taken pre- and post-+Gz, exposure. A search of the literature did not reveal any published articles on intraocular stability of ICL in the +Gz environment. This case report suggests that ICL may be considered an alternative to laser refractive surgery for patients subjected to a high +G, environment such as military aviators.

Hormonal regulation of gluconeogenesis in cereal aleurone is strongly cultivar-dependent and gibberellin action involves SLENDER1 but not GAMYB.

PubMed

Eastmond, Peter J; Jones, Russell L

2005-11-01

Storage oil is a major constituent in the cereal aleurone layer. The aim of this study was to investigate how gibberellin (GA) and abscisic acid (ABA) regulate conversion of oil to sugar in barley aleurone. The activity of the glyoxylate cycle enzyme isocitrate lyase (ICL) was surveyed in eight barley cultivars. Surprisingly, some cultivars do not require GA for the induction of ICL (e.g. Himalaya), whereas some do (e.g. Golden Promise). Furthermore, in Golden Promise, GA also stimulates triacylglycerol breakdown and enhances the net flux of carbon from acetate to sugar. In contrast, ABA strongly represses ICL activity and the flux of carbon from oil to sugar in both Golden Promise and Himalaya. Biolistics using a promoter reporter showed that GA and ABA regulate ICL at the level of transcription. Studies using barley and rice mutants and pharmacological agents show that GA-dependent induction of ICL activity is mediated by SLENDER1 and requires cGMP, but does not involve the transcription factor GAMYB. Gibberellin and ABA therefore act antagonistically to regulate gluconeogenesis in the aleurone layer as well as controlling the production and secretion of hydrolases into the starchy endosperm. We suggest that the variation between different barley cultivars might be a result of selective breeding to alter seed dormancy.

A General Introduction of the Earthquake Early Warning System Technology Developed in China

NASA Astrophysics Data System (ADS)

Wang, T.

2015-12-01

Since the Wenchuan earthquake in 2008, a dramatic progress on earthquake early warning (EEW) has been made by Institute of Care-life (ICL) in China. The research on EEW by ICL covers choosing appropriate sensors, methods of installing the sensors, data automatic process methods of the seismic waves for EEW, methods of applying of EEW warnings for public, schools and life-line projects. ICL innovatively applies distributed computing and cloud computing technology. So far, ICL has deployed over 5500 EEW sensors in China, which is 5 times the number of EEW sensors in Japan, covering more than 2.1 million square kilometers. Since June, 2011, over 5000 earthquakes, with 28 of them are destructive quakes, have triggered the EEWS with no false alert. The root mean square (RMS) error of the magnitude for the 28 destructive quakes is 0.32. In addition, innovative work is done to suppress false alarm and miss alarm, which pushes forward the application of EEW in China. The technology is also being applied in Nepal now.

DOG-1 Is the Caenorhabditis elegans BRIP1/FANCJ Homologue and Functions in Interstrand Cross-Link Repair▿

PubMed Central

Youds, Jillian L.; Barber, Louise J.; Ward, Jordan D.; Collis, Spencer J.; O'Neil, Nigel J.; Boulton, Simon J.; Rose, Ann M.

2008-01-01

Fanconi anemia (FA) is a cancer susceptibility syndrome characterized by defective DNA interstrand cross-link (ICL) repair. Here, we show that DOG-1 is the Caenorhabditis elegans homologue of FANCJ, a helicase mutated in FA-J patients. DOG-1 performs a conserved role in ICL repair, as dog-1 mutants are hypersensitive to ICL-inducing agents, but not to UVC irradiation or X rays. Genetic analysis indicated that dog-1 is epistatic with fcd-2 (C. elegans FANCD2) but is nonepistatic with brc-1 (C. elegans BRCA1), thus establishing the existence of two distinct pathways of ICL repair in worms. Furthermore, DOG-1 is dispensable for FCD-2 and RAD-51 focus formation, suggesting that DOG-1 operates downstream of FCD-2 and RAD-51 in ICL repair. DOG-1 was previously implicated in poly(G)/poly(C) (G/C) tract maintenance during DNA replication. G/C tracts remain stable in the absence of ATL-1, CLK-2 (FA pathway activators), FCD-2, BRC-2, and MLH-1 (associated FA components), implying that DOG-1 is the sole FA component required for G/C tract maintenance in a wild-type background. However, FCD-2 is required to promote deletion-free repair at G/C tracts in dog-1 mutants, consistent with a role for FA factors at the replication fork. The functional conservation between DOG-1 and FANCJ suggests a possible role for FANCJ in G/C tract maintenance in human cells. PMID:18086896

Snm1B/Apollo functions in the Fanconi anemia pathway in response to DNA interstrand crosslinks.

PubMed

Mason, Jennifer M; Sekiguchi, JoAnn M

2011-07-01

Fanconi anemia (FA) is an inherited chromosomal instability disorder characterized by childhood aplastic anemia, developmental abnormalities and cancer predisposition. One of the hallmark phenotypes of FA is cellular hypersensitivity to agents that induce DNA interstrand crosslinks (ICLs), such as mitomycin C (MMC). FA is caused by mutation in at least 14 genes which function in the resolution of ICLs during replication. The FA proteins act within the context of a protein network in coordination with multiple repair factors that function in distinct pathways. SNM1B/Apollo is a member of metallo-β-lactamase/βCASP family of nucleases and has been demonstrated to function in ICL repair. However, the relationship between SNM1B and the FA protein network is not known. In the current study, we establish that SNM1B functions epistatically to the central FA factor, FANCD2, in cellular survival after ICL damage and homology-directed repair of DNA double-strand breaks. We also demonstrate that MMC-induced chromosomal anomalies are increased in SNM1B-depleted cells, and this phenotype is not further exacerbated upon depletion of either FANCD2 or another key FA protein, FANCI. Furthermore, we find that SNM1B is required for proper localization of critical repair factors, including FANCD2, BRCA1 and RAD51, to MMC-induced subnuclear foci. Our findings demonstrate that SNM1B functions within the FA pathway during the repair of ICL damage.

Fanconi Anemia Proteins, DNA Interstrand Crosslink Repair Pathways, and Cancer Therapy

PubMed Central

Andreassen, Paul R.; Ren, Keqin

2016-01-01

DNA interstrand crosslinkers, a chemically diverse group of compounds which also induce alkylation of bases and DNA intrastrand crosslinks, are extensively utilized for cancer therapy. Understanding the cellular response to DNA damage induced by these agents is critical for more effective utilization of these compounds and for the identification of novel therapeutic targets. Importantly, the repair of DNA interstrand crosslinks (ICLs) involves many distinct DNA repair pathways, including nucleotide excision repair, translesion synthesis (TLS), and homologous recombination (HR). Additionally, proteins implicated in the pathophysiology of the multigenic disease Fanconi anemia (FA) have a role in the repair of ICLs that is not well understood. Cells from FA patients are hypersensitive to agents that induce ICLs, therefore FA proteins are potentially novel therapeutic targets. Here we will review current research directed at identifying FA genes and understanding the function of FA proteins in DNA damage responses. We will also examine interactions of FA proteins with other repair proteins and pathways, including signaling networks, which are potentially involved in ICL repair. Potential approaches to the modulation of FA protein function to enhance therapeutic outcome will be discussed. Also, mutation of many genes that encode proteins involved in ICL repair, including FA genes, increases susceptibility to cancer. A better understanding of these pathways is therefore critical for the design of individualized therapies tailored to the genetic profile of a particular malignancy. For this purpose, we will also review evidence for the association of mutation of FA genes with cancer in non-FA patients. PMID:19200054

Integration of health services improves multiple healthcare outcomes among HIV-infected people who inject drugs in Ukraine.

PubMed

Bachireddy, Chethan; Soule, Michael C; Izenberg, Jacob M; Dvoryak, Sergey; Dumchev, Konstantin; Altice, Frederick L

2014-01-01

People who inject drugs (PWID) experience poor outcomes and fuel HIV epidemics in middle-income countries in Eastern Europe and Central Asia. We assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which despite international recommendations, is neither widely available nor empirically examined. A 2010 cross-sectional study randomly sampled 296 HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO) settings are available. ICL settings provide onsite HIV, addiction, and tuberculosis services, NCLs only treat addiction, and HROs provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (OST). The primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (QHI) composite score representing percentage of eight guidelines-based recommended indicators met for HIV, addiction and tuberculosis treatment. The secondary outcomes were individual QHIs and health-related quality-of-life (HRQoL). On average, ICL-participants had significantly higher QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8% versus 37.0%, p<0.001) even after controlling for potential confounders. Compared to NCL-participants, ICL-participants were significantly more likely to receive antiretroviral therapy (49.5% versus 19.2%, p<0.001), especially if CD4 ≤ 200 (93.8% versus 62.5% p<0.05); guideline-recommended OST dosage (57.3% versus 41.4%, p<0.05); and isoniazid preventive therapy (42.3% versus 11.2%, p<0.001). Subjects receiving OST had significantly higher HRQoL than those not receiving it (p<0.001); however, HRQoL did not differ significantly between ICL- and NCL-participants. These findings suggest that OST alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality indicators for PWID. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Changes in the crystalline lens resulting from insertion of a phakic IOL (ICL) into the porcine eye.

PubMed

Fujisawa, Kunitoshi; Shimizu, Kimiya; Uga, Shigekazu; Suzuki, Masanobu; Nagano, Koichi; Murakami, Yuuki; Goseki, Hiroko

2007-01-01

Insertion of a phakic IOL offers these advantages: the corneal optical zone is not dissected or resected; preservation of the crystalline lens results in preservation of the accommodation force; and since the phakic IOL is removable, any error or change in refraction can be countered by exchanging it. However, the cause of secondary cataracts has never been clarified or discussed to date. The following ICL lenses were inserted under general anaesthesia into 20 eyes of ten 3-month-old miniature pigs: a minus lens without holes into five eyes, a plus lens in two eyes, a minus lens with four holes around the lens haptics in three eyes, and a minus lens with a central hole in the optic in three eyes; and seven eyes were used as controls. The anterior segments were then photographed 1 week, 1 month and 3 months after surgery. At 3 months after surgery, Evans blue (EB) was infused into the vitreous under general anaesthesia, and after 30 min, the eyeball was enucleated, fixed and examined. In the case of the ICL without holes, the anterior subcapsular opacities were observed in all the eyes, and the anterior surfaces of the crystalline lenses were not stained with EB. Use of the ICL with four holes around the lens haptics resulted in light staining of the anterior surface of the crystalline lens, but the anterior subcapsular opacities observed were mild. As for the ICL with a hole in the centre of the optic, the anterior surface of the crystalline lens was stained and no anterior subcapsular opacities were observed. The results suggested that the insertion of an ICL brings about a change in the dynamics of the intraocular aqueous humour, reducing its circulation to the anterior surface of the crystalline lens. This is considered to cause a metabolic disturbance of the crystalline lens, resulting in anterior subcapsular opacification.

Integration of Health Services Improves Multiple Healthcare Outcomes Among HIV-infected People Who Inject Drugs in Ukraine

PubMed Central

Bachireddy, Chethan; Soule, Michael C.; Izenberg, Jacob M.; Dvoryak, Sergey; Dumchev, Konstantin; Altice, Frederick L.

2013-01-01

Background People who inject drugs (PWID) experience poor outcomes and fuel HIV epidemics in middle-income countries in Eastern Europe and Central Asia. We assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which despite international recommendations, is neither widely available nor empirically examined. Methods A 2010 cross-sectional study randomly sampled 296 HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO) settings are available. ICL settings provide onsite HIV, addiction, and tuberculosis services, NCLs only treat addiction, and HROs provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (OST). The primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (QHI) composite score representing percentage of eight guidelines-based recommended indicators met for HIV, addiction and tuberculosis treatment. The secondary outcomes were individual QHIs and health-related quality-of-life (HRQoL). Results On average, ICL-participants had significantly higher QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8% versus 37.0%, p<0.001) even after controlling for potential confounders. Compared to NCL-participants, ICL-participants were significantly more likely to receive antiretroviral therapy (49.5% versus 19.2%, p<0.001), especially if CD4≤200 (93.8% versus 62.5% p<0.05); guideline-recommended OST dosage (57.3% versus 41.4%, p<0.05); and isoniazid preventive therapy (42.3% versus 11.2%, p<0.001). Subjects receiving OST had significantly higher HRQoL than those not receiving it (p<0.001); however, HRQoL did not differ significantly between ICL- and NCL-participants. Conclusions These findings suggest that OST alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality for PWID. PMID:24128379

Vortex depinning as a nonequilibrium phase transition phenomenon: Scaling of current-voltage curves near the low and the high critical-current states in 2 H -Nb S2 single crystals

NASA Astrophysics Data System (ADS)

Bag, Biplab; Sivananda, Dibya J.; Mandal, Pabitra; Banerjee, S. S.; Sood, A. K.; Grover, A. K.

2018-04-01

The vortex depinning phenomenon in single crystals of 2 H -Nb S2 superconductors is used as a prototype for investigating properties of the nonequilibrium (NEQ) depinning phase transition. The 2 H -Nb S2 is a unique system as it exhibits two distinct depinning thresholds, viz., a lower critical current Icl and a higher one Ich. While Icl is related to depinning of a conventional, static (pinned) vortex state, the state with Ich is achieved via a negative differential resistance (NDR) transition where the velocity abruptly drops. Using a generalized finite-temperature scaling ansatz, we study the scaling of current (I)-voltage (V) curves measured across Icl and Ich. Our analysis shows that for I >Icl , the moving vortex state exhibits Arrhenius-like thermally activated flow behavior. This feature persists up to a current value where an inflexion in the IV curves is encountered. While past measurements have often reported similar inflexion, our analysis shows that the inflexion is a signature of a NEQ phase transformation from a thermally activated moving vortex phase to a free flowing phase. Beyond this inflection in IV, a large vortex velocity flow regime is encountered in the 2 H -Nb S2 system, wherein the Bardeen-Stephen flux flow limit is crossed. In this regime the NDR transition is encountered, leading to the high Ich state. The IV curves above Ich we show do not obey the generalized finite-temperature scaling ansatz (as obeyed near Icl). Instead, they scale according to the Fisher's scaling form [Fisher, Phys. Rev. B 31, 1396 (1985), 10.1103/PhysRevB.31.1396] where we show thermal fluctuations do not affect the vortex flow, unlike that found for depinning near Icl.

Anomalous Aortic Origin of Coronary Arteries in the Young: Echocardiographic Evaluation With Surgical Correlation.

PubMed

Lorber, Richard; Srivastava, Shubhika; Wilder, Travis J; McIntyre, Susan; DeCampli, William M; Williams, William G; Frommelt, Peter C; Parness, Ira A; Blackstone, Eugene H; Jacobs, Marshall L; Mertens, Luc; Brothers, Julie A; Herlong, J René

2015-11-01

This study sought to compare findings from institutional echocardiographic reports with imaging core laboratory (ICL) review of corresponding echocardiographic images and operative reports in 159 patients with anomalous aortic origin of a coronary artery (AAOCA). The study also sought to develop a "best practice" protocol for imaging and interpreting images in establishing the diagnosis of AAOCA. AAOCA is associated with sudden death in the young. Underlying anatomic risk factors that can cause ischemia-related events include coronary arterial ostial stenosis, intramural course of the proximal coronary within the aortic wall, interarterial course, and potential compression between the great arteries. Consistent protocols for diagnosing and evaluating these features are lacking, potentially precluding the ability to risk stratify patients based on evidence and plan surgical strategy. For a prescribed set of anatomic AAOCA features, percentages of missing data in institutional echocardiographic reports were calculated. For each feature, agreement among institutional echocardiographic reports, ICL review of images, and surgical reports was evaluated using the weighted kappa statistic. An echocardiographic imaging protocol was developed heuristically to reduce differences between institutional reports and ICL review. A total of 13%, 33%, and 62% of echocardiograms were missing images enabling diagnosis of intra-arterial course, proximal intramural course, and high ostial takeoff, respectively. There was poor agreement between institutional reports and ICL review for diagnosis of origin of coronary artery, interarterial course, intramural course, and acute angle takeoff (kappa = 0.74, 0.11, -0.03, 0.13, respectively). Surgical findings were also significantly different from those of reports, and to a lesser extent ICL reviews. The resulting protocol contains technical recommendations for imaging each of these features. Poor agreement between institutional reports and ICL review for AAOCA suggests need for an imaging protocol to permit evidence-based risk stratification and surgical planning. Even then, delineation of echocardiographic details in AAOCA will remain imperfect. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The Phosphatidylinositol 3,5-Bisphosphate (PI(3,5)P2)-dependent Tup1 Conversion (PIPTC) Regulates Metabolic Reprogramming from Glycolysis to Gluconeogenesis*

PubMed Central

Han, Bong-Kwan; Emr, Scott D.

2013-01-01

Glucose/carbon metabolism is a fundamental cellular process in living cells. In response to varying environments, eukaryotic cells reprogram their glucose/carbon metabolism between aerobic or anaerobic glycolysis, oxidative phosphorylation, and/or gluconeogenesis. The distinct type of glucose/carbon metabolism that a cell carries out has significant effects on the cell's proliferation and differentiation. However, it is poorly understood how the reprogramming of glucose/carbon metabolism is regulated. Here, we report a novel endosomal PI(3,5)P2 lipid-dependent regulatory mechanism that is required for metabolic reprogramming from glycolysis to gluconeogenesis in Saccharomyces cerevisiae. Certain gluconeogenesis genes, such as FBP1 (encoding fructose-1,6-bisphosphatase 1) and ICL1 (encoding isocitrate lyase 1) are under control of the Mig1 repressor and Cyc8-Tup1 corepressor complex. We previously identified the PI(3,5)P2-dependent Tup1 conversion (PIPTC), a mechanism to convert Cyc8-Tup1 corepressor to Cti6-Cyc8-Tup1 coactivator. We demonstrate that the PIPTC plays a critical role for transcriptional activation of FBP1 and ICL1. Furthermore, without the PIPTC, the Cat8 and Sip4 transcriptional activators cannot be efficiently recruited to the promoters of FBP1 and ICL1, suggesting a key role for the PIPTC in remodulating the chromatin architecture at the promoters. Our findings expand our understanding of the regulatory mechanisms for metabolic reprogramming in eukaryotes to include key regulation steps outside the nucleus. Given that Tup1 and the metabolic enzymes that control PI(3,5)P2 are highly conserved among eukaryotes, our findings may provide important insights toward understanding glucose/carbon metabolic reprogramming in other eukaryotes, including humans. PMID:23733183

The phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2)-dependent Tup1 conversion (PIPTC) regulates metabolic reprogramming from glycolysis to gluconeogenesis.

PubMed

Han, Bong-Kwan; Emr, Scott D

2013-07-12

Glucose/carbon metabolism is a fundamental cellular process in living cells. In response to varying environments, eukaryotic cells reprogram their glucose/carbon metabolism between aerobic or anaerobic glycolysis, oxidative phosphorylation, and/or gluconeogenesis. The distinct type of glucose/carbon metabolism that a cell carries out has significant effects on the cell's proliferation and differentiation. However, it is poorly understood how the reprogramming of glucose/carbon metabolism is regulated. Here, we report a novel endosomal PI(3,5)P2 lipid-dependent regulatory mechanism that is required for metabolic reprogramming from glycolysis to gluconeogenesis in Saccharomyces cerevisiae. Certain gluconeogenesis genes, such as FBP1 (encoding fructose-1,6-bisphosphatase 1) and ICL1 (encoding isocitrate lyase 1) are under control of the Mig1 repressor and Cyc8-Tup1 corepressor complex. We previously identified the PI(3,5)P2-dependent Tup1 conversion (PIPTC), a mechanism to convert Cyc8-Tup1 corepressor to Cti6-Cyc8-Tup1 coactivator. We demonstrate that the PIPTC plays a critical role for transcriptional activation of FBP1 and ICL1. Furthermore, without the PIPTC, the Cat8 and Sip4 transcriptional activators cannot be efficiently recruited to the promoters of FBP1 and ICL1, suggesting a key role for the PIPTC in remodulating the chromatin architecture at the promoters. Our findings expand our understanding of the regulatory mechanisms for metabolic reprogramming in eukaryotes to include key regulation steps outside the nucleus. Given that Tup1 and the metabolic enzymes that control PI(3,5)P2 are highly conserved among eukaryotes, our findings may provide important insights toward understanding glucose/carbon metabolic reprogramming in other eukaryotes, including humans.

Active tuberculosis patients have high levels of IgA anti-alpha-crystallin and isocitrate lyase proteins.

PubMed

Talavera-Paulín, M; García-Morales, L; Ruíz-Sánchez, B P; Caamal-Ley, Á D; Hernández-Solis, A; Ramírez-Casanova, E; Cicero-Sabido, R; Espitia, C; Helguera-Repetto, C; González-Y-Merchand, J A; Flores-Mejía, R; Estrada-Parra, S; Estrada-García, I; Chacón-Salinas, R; Wong-Baeza, I; Serafín-López, J

2016-12-01

Mexico City, Mexico. To identify proteins synthetised by Mycobacterium tuberculosis in hypoxic culture, which resemble more closely a granuloma environment than aerobic culture, and to determine if they are recognised by antibodies from patients with active pulmonary tuberculosis (PTB). Soluble extracts from M. tuberculosis H37Rv cultured under aerobic or hypoxic conditions were analysed using two-dimensional polyacrylamide gel electrophoresis, and proteins over-expressed under hypoxia were identified by mass spectrometry. The presence of immunoglobulin (Ig) G, IgA and IgM antibodies against these proteins was determined in the serum of 42 patients with active PTB and 42 healthy controls. We selected three M. tuberculosis H37Rv proteins (alpha-crystallin protein [Acr, Rv2031c], universal stress protein Rv2623 and isocitrate lyase [ICL, RV0467]) that were over-expressed under hypoxia. Titres of anti-Acr and anti-ICL IgA antibodies were higher in patients than in healthy controls, with an area under the receiver operating characteristic curve of 0.71 for anti-ICL IgA antibodies. ICL could be used in combination with other M. tuberculosis antigens to improve the sensitivity and specificity of current serological TB diagnostic methods.

The COX-2 Selective Blocker Etodolac Inhibits TNFα-Induced Apoptosis in Isolated Rabbit Articular Chondrocytes

PubMed Central

Kumagai, Kousuke; Kubo, Mitsuhiko; Imai, Shinji; Toyoda, Futoshi; Maeda, Tsutomu; Okumura, Noriaki; Matsuura, Hiroshi; Matsusue, Yoshitaka

2013-01-01

Chondrocyte apoptosis contributes to the disruption of cartilage integrity in osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl− current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the treatment of OA. In the present study, we examined in vitro effects of selective blockers of COX on the TNFα-induced activation of ICl,vol in rabbit chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes to TNFα resulted in an obvious increase in membrane Cl− conductance. The TNFα-evoked Cl− current exhibited electrophysiological and pharmacological properties similar to those of ICl,vol. Pretreatment of cells with selective COX-2 blocker etodolac markedly inhibited ICl,vol activation by TNFα as well as subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on the decrease in cell volume or the increase in caspase-3/7 activity induced by TNFα. Thus, the COX-2-selective blocker had an inhibitory effect on TNFα-induced apoptotic events, which suggests that this drug would have efficacy for the treatment of OA. PMID:24084720

Photostop of iodine atoms from electrically oriented ICl molecules

NASA Astrophysics Data System (ADS)

Bao, Da-Xiao; Deng, Lian-Zhong; Xu, Liang; Yin, Jian-Ping

2015-11-01

The dynamics of photostopping iodine atoms from electrically oriented ICl molecules was numerically studied based on their orientational probability distribution functions. Velocity distributions of the iodine atoms and their production rates were investigated for orienting electrical fields of various intensities. For the ICl precursor beams with an initial rotational temperature of ∼ 1 K, the production of the iodine atoms near zero speed will be improved by about ∼ 5 times when an orienting electrical field of ∼ 200 kV/cm is present. A production rate of ∼ 0.5‰ is obtained for photostopped iodine atoms with speeds less than 10 m/s, which are suitable for magnetic trapping. The electrical orientation of ICl precursors and magnetic trapping of photostopped iodine atoms in situ can be conveniently realized with a pair of charged ring magnets. With the maximal value of the trapping field being ∼ 0.28 T, the largest trapping speed is ∼ 7.0 m/s for the iodine atom. Project supported by the National Natural Science Foundation of China (Grant Nos. 11034002, 61205198, and 11274114) and the National Key Basic Research and Development Program of China (Grant No. 2011CB921602).

Dependence of the electronic absorption spectra of aqueous solutions of iodine monochloride on the conditions of dilution and storage time

NASA Astrophysics Data System (ADS)

Klyubin, V. V.; Klyubina, K. A.; Makovetskaya, K. N.

2017-04-01

The electronic absorption spectra of aqueous solutions of iodine monochloride ICl are studied. The spectra of as-prepared solutions display the absorption band associated with hydrated ICl molecules. An additional band indicating that molecular iodine was formed in the solution emerges in the spectrum as dissolution takes place. Only the band belonging to iodine monochloride remains in the absorption spectra, and no additional bands appear after chloride anions Cl- are added to the solution. The absorption spectrum becomes more complex when ICl is dissolved in an alkaline medium. The band belonging to molecular iodine emerges in the spectra at low alkali concentrations, while being transformed to other shorter-wavelength bands at high alkali concentrations (pH ≥ 12).

The interhalogens IF and ICI as visible oscillators or amplifiers

NASA Technical Reports Server (NTRS)

Eden, J. G.; Dlabal, M. L.; Hutchison, S. B.

1981-01-01

The kinetic and spectroscopic properties of the interhalogens are reviewed, with emphasis on the iodine-monochloride (ICl) and iodine-monofluoride (IF) systems; the latter having produced 140 kW, 30 nsec FWHM pulses at 491 and 485 nm and may be scaled to the tens of millijoules per pulse level. Gain in excess of 1.0%/cm was observed across the entire IF blue-green band, demonstrating potentially wide tunability. Although ICl has not yet lased, its peak small-signal gain of 1.3%/cm and negligible background absorption in discharge plasmas make it an attractive candidate for a violet amplifier. The formation kinetics of IF- and ICl-excimer lasers in electron beam or discharge-produced plasmas, and the potential and limitations of these molecules as visible lasers or amplifiers are also discussed.

Comparison of optical quality after implantable collamer lens implantation and wavefront-guided laser in situ keratomileusis

PubMed Central

Liu, Hong-Ting; Zhou, Zhou; Luo, Wu-Qiang; He, Wen-Jing; Agbedia, Owhofasa; Wang, Jiang-Xia; Huang, Jian-Zhong; Gao, Xin; Kong, Min; Li, Min; Li, Li

2018-01-01

AIM To compare the optical quality after implantation of implantable collamer lens (ICL) and wavefront-guided laser in situ keratomileusis (WG-LASIK). METHODS The study included 40 eyes of 22 patients with myopia who accepted ICL implantation and 40 eyes of 20 patients with myopia who received WG-LASIK. Before surgery and three months after surgery, the objective scattering index (OSI), the values of modulation transfer function (MTF) cutoff frequency, Strehl ratio, and the Optical Quality Analysis System (OQAS) values (OVs) were accessed. The higher order aberrations (HOAs) data including coma, trefoil, spherical, 2nd astigmatism and tetrafoil were also obtained. For patients with pupil size <6 mm, HOAs data were analyzed for 4 mm-pupil diameter. For patients with pupil size ≥6 mm, HOAs data were calculated for 6 mm-pupil diameter. Visual acuity, refraction, pupil size and intraocular pressures were also recorded. RESULTS In both ICL and WG-LASIK group, significant improvements in visual acuities were found postoperatively, with a significant reduction in spherical equivalent (P< 0.001). After the ICL implantation, the OSI decreased slightly from 2.34±1.92 to 2.24±1.18 with no statistical significance (P=0.62). While in WG-LASIK group, the OSI significantly increased from 0.68±0.43 preoperatively to 0.91±0.53 postoperatively (Wilcoxon signed ranks test, P=0.000). None of the mean MTF cutoff frequency, Strehl ratio, OVs showed statistically significant changes in both ICL and WG-LASIK groups. In the ICL group, there were no statistical differences in the total HOAs for either 4 mm-pupil or 6 mm-pupil. In the WG-LASIK group, the HOA parameters increased significantly at 4 mm-pupil. The total ocular HOAs, coma, spherical and 2nd astigmatism were 0.12±0.06, 0.06±0.03, 0.00±0.03, 0.02±0.01, respectively. After the operation, these values were increased into 0.16±0.07, 0.08±0.05, -0.04±0.04, 0.03±0.01 respectively (Wilcoxon signed ranks test, all P<0.05). At 6 mm-pupil, the induction of total HOAs was not statistically significant in the WG-LASIK group. CONCLUSION ICL implantation has a less disturbance to optical quality than WG-LASIK. The OQAS is a valuable complementary measurement to the wavefront aberrometers in evaluating the optical quality. PMID:29675387

Comparison of optical quality after implantable collamer lens implantation and wavefront-guided laser in situ keratomileusis.

PubMed

Liu, Hong-Ting; Zhou, Zhou; Luo, Wu-Qiang; He, Wen-Jing; Agbedia, Owhofasa; Wang, Jiang-Xia; Huang, Jian-Zhong; Gao, Xin; Kong, Min; Li, Min; Li, Li

2018-01-01

To compare the optical quality after implantation of implantable collamer lens (ICL) and wavefront-guided laser in situ keratomileusis (WG-LASIK). The study included 40 eyes of 22 patients with myopia who accepted ICL implantation and 40 eyes of 20 patients with myopia who received WG-LASIK. Before surgery and three months after surgery, the objective scattering index (OSI), the values of modulation transfer function (MTF) cutoff frequency, Strehl ratio, and the Optical Quality Analysis System (OQAS) values (OVs) were accessed. The higher order aberrations (HOAs) data including coma, trefoil, spherical, 2 nd astigmatism and tetrafoil were also obtained. For patients with pupil size <6 mm, HOAs data were analyzed for 4 mm-pupil diameter. For patients with pupil size ≥6 mm, HOAs data were calculated for 6 mm-pupil diameter. Visual acuity, refraction, pupil size and intraocular pressures were also recorded. In both ICL and WG-LASIK group, significant improvements in visual acuities were found postoperatively, with a significant reduction in spherical equivalent ( P < 0.001). After the ICL implantation, the OSI decreased slightly from 2.34±1.92 to 2.24±1.18 with no statistical significance ( P =0.62). While in WG-LASIK group, the OSI significantly increased from 0.68±0.43 preoperatively to 0.91±0.53 postoperatively (Wilcoxon signed ranks test, P =0.000). None of the mean MTF cutoff frequency, Strehl ratio, OVs showed statistically significant changes in both ICL and WG-LASIK groups. In the ICL group, there were no statistical differences in the total HOAs for either 4 mm-pupil or 6 mm-pupil. In the WG-LASIK group, the HOA parameters increased significantly at 4 mm-pupil. The total ocular HOAs, coma, spherical and 2 nd astigmatism were 0.12±0.06, 0.06±0.03, 0.00±0.03, 0.02±0.01, respectively. After the operation, these values were increased into 0.16±0.07, 0.08±0.05, -0.04±0.04, 0.03±0.01 respectively (Wilcoxon signed ranks test, all P <0.05). At 6 mm-pupil, the induction of total HOAs was not statistically significant in the WG-LASIK group. ICL implantation has a less disturbance to optical quality than WG-LASIK. The OQAS is a valuable complementary measurement to the wavefront aberrometers in evaluating the optical quality.

Protein crystal growth in low gravity

NASA Technical Reports Server (NTRS)

Feigelson, Robert S.

1992-01-01

A study is presented of the crystallization of isocitrate lyase (ICL) and the influence of the lack of thermal solutal convection in microgravity on the morphology of ICL crystals is discussed. The latest results of studies with thermonucleation are presented. These include the nucleation of a protein with retrograde solubility and an unknown solubility curve. A new design for a more microgravity compatible thermonuclear is presented.

Structure-based screening and molecular dynamics simulations offer novel natural compounds as potential inhibitors of Mycobacterium tuberculosis isocitrate lyase.

PubMed

Shukla, Rohit; Shukla, Harish; Sonkar, Amit; Pandey, Tripti; Tripathi, Timir

2018-06-01

Mycobacterium tuberculosis is the etiological agent of tuberculosis in humans and is responsible for more than two million deaths annually. M. tuberculosis isocitrate lyase (MtbICL) catalyzes the first step in the glyoxylate cycle, plays a pivotal role in the persistence of M. tuberculosis, which acts as a potential target for an anti-tubercular drug. To identify the potential anti-tuberculosis compound, we conducted a structure-based virtual screening of natural compounds from the ZINC database (n = 1,67,748) against the MtbICL structure. The ligands were docked against MtbICL in three sequential docking modes that resulted in 340 ligands having better docking score. These compounds were evaluated for Lipinski and ADMET prediction, and 27 compounds were found to fit well with re-docking studies. After refinement by molecular docking and drug-likeness analyses, three potential inhibitors (ZINC1306071, ZINC2111081, and ZINC2134917) were identified. These three ligands and the reference compounds were further subjected to molecular dynamics simulation and binding energy analyses to compare the dynamic structure of protein after ligand binding and the stability of the MtbICL and bound complexes. The binding free energy analyses were calculated to validate and capture the intermolecular interactions. The results suggested that the three compounds had a negative binding energy with -96.462, -143.549, and -122.526 kJ mol -1 for compounds with IDs ZINC1306071, ZINC2111081, and ZINC2134917, respectively. These lead compounds displayed substantial pharmacological and structural properties to be drug candidates. We concluded that ZINC2111081 has a great potential to inhibit MtbICL and would add to the drug discovery process against tuberculosis.

Assessment of subjective intraocular forward scattering and quality of vision after posterior chamber phakic intraocular lens with a central hole (Hole ICL) implantation.

PubMed

Iijima, Ayaka; Shimizu, Kimiya; Yamagishi, Mayumi; Kobashi, Hidenaga; Igarashi, Akihito; Kamiya, Kazutaka

2016-12-01

To evaluate the subjective intraocular forward scattering and quality of vision after posterior chamber phakic intraocular lens with a central hole (Hole ICL, STAAR Surgical) implantation. We prospectively examined 29 eyes of 29 consecutive patients (15 men and 14 women; ages, 37.2 ± 8.8 years) undergoing Hole ICL implantation. We assessed the values of the logarithmic straylight value [log (s)] using a straylight meter (C-Quant ™ , Oculus) preoperatively and 3 months postoperatively. The patients completed a questionnaire detailing symptoms on a quantitative grading scale (National Eye Institute Refractive Error Quality of Life Instrument-42; NEI RQL-42) 3 months postoperatively. We compared the preoperative and postoperative values of the log(s) and evaluated the correlation of these values with patient subjective symptoms. The mean log(s) was not significantly changed, from 1.07 ± 0.20 preoperatively, to 1.06 ± 0.17 postoperatively (Wilcoxon signed-rank test, p = 0.641). There was a significant correlation between the preoperative and postoperative log(s) (Spearman's correlation coefficient r = 0.695, p < 0.001). The postoperative log(s) was significantly associated with the scores of glare in the questionnaire (Spearman's correlation coefficient r = -0.575, p = 0.017). According to our experience, Hole ICL implantation does not induce a significant additional change in the subjective intraocular forward scattering. The symptom of glare after Hole ICL implantation was significantly correlated with the postoperative intraocular forward scattering in relation to the preoperative one. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Constrained dynamics of the sole tryptophan in the third intracellular loop of the serotonin1A receptor.

PubMed

Pal, Sreetama; Aute, Ramdas; Sarkar, Parijat; Bose, Shroddha; Deshmukh, Mandar V; Chattopadhyay, Amitabha

2018-06-01

G protein-coupled receptors (GPCRs) are major signaling proteins in eukaryotic cells and are important drug targets. In spite of their role in GPCR function, the extramembranous regions of GPCRs are relatively less appreciated. The third intracellular loop (ICL3), which connects transmembrane helices V and VI, is important in this context since its crucial role in signaling has been documented for a number of GPCRs. Unfortunately, the structure of this loop is generally not visualized in x-ray crystallographic studies since this flexible loop is either stabilized using a monoclonal antibody or replaced with lysozyme. In this work, we expressed and purified the ICL3 region of the serotonin 1A receptor and monitored its motional restriction and organization utilizing red edge excitation shift (REES) of its sole tryptophan and circular dichroism (CD) spectroscopy. Our results show that the tryptophan in ICL3 exhibits REES of 4 nm, implying that it is localized in a restricted microenvironment. These results are further supported by wavelength-selective changes in fluorescence anisotropy and lifetime. This constrained dynamics was relaxed upon denaturation of the peptide, thereby suggesting the involvement of the peptide secondary structure in the observed motional restriction, as evident from CD spectroscopy and apparent rotational correlation time. To the best of our knowledge, these results constitute one of the first measurements of motional constraint in the ICL3 region of GPCRs. Our results are relevant in the context of the reported intrinsically disordered nature of ICL3 and its role in providing functional diversity to GPCRs due to conformational plasticity. Copyright © 2018 Elsevier B.V. All rights reserved.

Central endoscopy reads in inflammatory bowel disease clinical trials: The role of the imaging core lab

PubMed Central

Ahmad, Harris; Berzin, Tyler M.; Yu, Hui Jing; Huang, Christopher S.; Mishkin, Daniel S.

2014-01-01

Clinical trials in inflammatory bowel disease (IBD) are evolving at a rapid pace by employing central reading for endoscopic mucosal assessment in a field that was, historically, largely based on assessments by local physicians. This transition from local to central reading carries with it numerous technical, operational, and scientific challenges, many of which can be resolved by imaging core laboratories (ICLs), a concept that has a longer history in clinical trials in a number of diseases outside the realm of gastroenterology. For IBD trials, ICLs have the dual goals of providing objective, consistent assessments of endoscopic findings using central-reading paradigms whilst providing important expertise with regard to operational issues and regulatory expectations. This review focuses on current approaches to using ICLs for central endoscopic reading in IBD trials. PMID:24994835

Occurrence of a number of enzymes involved in either gluconeogenesis or other processes in the pericarp of three cultivars of grape (Vitis vinifera L.) during development.

PubMed

Famiani, Franco; Moscatello, Stefano; Ferradini, Nicoletta; Gardi, Tiziano; Battistelli, Alberto; Walker, Robert P

2014-11-01

It is uncertain whether the enzymes pyruvate orthophosphate dikinase (PPDK) or isocitrate lyase (ICL) are present in the pericarp of grape, in which they could function in gluconeogenesis. The occurrence of these and other enzymes was investigated in the pericarp of three cultivars of grape (Vitis vinifera L.). In particular, the abundance of the enzymes aldolase, glutamine synthase (GS), acid invertase, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), phosphoenolpyruvate carboxylase (PEPC), PPDK and ICL were determined during the development of the pericarp of the cultivars Cabernet Sauvignon, Chardonnay and Zibibbo. PPDK and ICL were not detected at any stage of development. Each of the other enzymes showed different changes in abundance during development. However, for a given enzyme its changes in abundance were similar in each cultivar. In the ripe pericarp of Cabernet Sauvignon, PEPC, cytosolic GS and aldolase were equally distributed between the vasculature and parenchyma cells of the flesh and skin. The absence or very low abundance of PPDK provides strong evidence that any gluconeogenesis from malate utilises phosphoenolpyruvate carboxykinase (PEPCK). The absence or very low abundance of ICL in the pericarp precludes any gluconeogenesis from ethanol. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Quantum mechanical characterization of the He4ICl weakly bound complex.

PubMed

Valdés, Álvaro; Prosmiti, Rita

2013-08-15

Vibrational calculations are performed for the 12-dimensional He4ICl van der Waals complex using the multiconfiguration time-dependent Hartree (MCTDH) method. The potential energy surface of the cluster is represented as a sum of the triatomic He-ICl ab initio parametrized terms plus the He-He interactions. The topology of the potential presents higher anisotropy compared to the one with a homonuclear dopant, and this is clearly reflected in the structure and energetics of the low-lying conformers of the system. In order to take advantage of the MCTDH method, natural potential fits are employed for the potential energy operator, and also, a mode combination scheme is introduced in order to speed up the computations. Zero-point energy, binding energies, and vibrationally averaged structures of different isomers of the He4ICl cluster are obtained. The present results predict that the (3,1,0) structure, involving three He atoms in the near T-shaped and one He atom in the linear configurations, to be the most stable one in accord with recent experimental findings. Comparisons with previous theoretical and experimental data are presented, and the stability of the high-order conformers is discussed in connection with the multiple minima (global and local) of the underlying potential surface.

The FANCJ/MutLα interaction is required for correction of the cross-link response in FA-J cells

PubMed Central

Peng, Min; Litman, Rachel; Xie, Jenny; Sharma, Sudha; Brosh, Robert M; Cantor, Sharon B

2007-01-01

FANCJ also called BACH1/BRIP1 was first linked to hereditary breast cancer through its direct interaction with BRCA1. FANCJ was also recently identified as a Fanconi anemia (FA) gene product, establishing FANCJ as an essential tumor suppressor. Similar to other FA cells, FANCJ-null (FA-J) cells accumulate 4N DNA content in response to DNA interstrand crosslinks (ICLs). This accumulation is corrected by reintroduction of wild-type FANCJ. Here, we show that FANCJ interacts with the mismatch repair complex MutLα, composed of PMS2 and MLH1. Specifically, FANCJ directly interacts with MLH1 independent of BRCA1, through its helicase domain. Genetic studies reveal that FANCJ helicase activity and MLH1 binding, but not BRCA1 binding, are essential to correct the FA-J cells' ICL-induced 4N DNA accumulation and sensitivity to ICLs. These results suggest that the FANCJ/MutLα interaction, but not FANCJ/BRCA1 interaction, is essential for establishment of a normal ICL-induced response. The functional role of the FANCJ/MutLα complex demonstrates a novel link between FA and MMR, and predicts a broader role for FANCJ in DNA damage signaling independent of BRCA1. PMID:17581638

Preoperative Biometric Parameters Predict the Vault after ICL Implantation: A Retrospective Clinical Study.

PubMed

Zheng, Qian-Yin; Xu, Wen; Liang, Guan-Lu; Wu, Jing; Shi, Jun-Ting

2016-01-01

To investigate the correlation between the preoperative biometric parameters of the anterior segment and the vault after implantable Collamer lens (ICL) implantation via this retrospective study. Retrospective clinical study. A total of 78 eyes from 41 patients who underwent ICL implantation surgery were included in this study. Preoperative biometric parameters, including white-to-white (WTW) diameter, central corneal thickness, keratometer, pupil diameter, anterior chamber depth, sulcus-to-sulcus diameter, anterior chamber area (ACA) and central curvature radius of the anterior surface of the lens (Lenscur), were measured. Lenscur and ACA were measured with Rhinoceros 5.0 software on the image scanned with ultrasound biomicroscopy (UBM). The vault was assessed by UBM 3 months after surgery. Multiple stepwise regression analysis was employed to identify the variables that were correlated with the vault. The results showed that the vault was correlated with 3 variables: ACA (22.4 ± 4.25 mm2), WTW (11.36 ± 0.29 mm) and Lenscur (9.15 ± 1.21 mm). The regressive equation was: vault (mm) = 1.785 + 0.017 × ACA + 0.051 × Lenscur - 0.203 × WTW. Biometric parameters of the anterior segment (ACA, WTW and Lenscur) can predict the vault after ICL implantation using a new regression equation. © 2016 The Author(s) Published by S. Karger AG, Basel.

Multi-species sensing using multi-mode absorption spectroscopy with mid-infrared interband cascade lasers

NASA Astrophysics Data System (ADS)

O'Hagan, S.; Northern, J. H.; Gras, B.; Ewart, P.; Kim, C. S.; Kim, M.; Merritt, C. D.; Bewley, W. W.; Canedy, C. L.; Vurgaftman, I.; Meyer, J. R.

2016-06-01

The application of an interband cascade laser, ICL, to multi-mode absorption spectroscopy, MUMAS, in the mid-infrared region is reported. Measurements of individual mode linewidths of the ICL, derived from the pressure dependence of lineshapes in MUMAS signatures of single, isolated, lines in the spectrum of HCl, were found to be in the range 10-80 MHz. Multi-line spectra of methane were recorded using spectrally limited bandwidths, of approximate width 27 cm-1, defined by an interference filter, and consist of approximately 80 modes at spectral locations spanning the 100 cm-1 bandwidth of the ICL output. Calibration of the methane pressures derived from MUMAS data using a capacitance manometer provided measurements with an uncertainty of 1.1 %. Multi-species sensing is demonstrated by the simultaneous detection of methane, acetylene and formaldehyde in a gas mixture. Individual partial pressures of the three gases are derived from best fits of model MUMAS signatures to the data with an experimental error of 10 %. Using an ICL, with an inter-mode interval of ~10 GHz, MUMAS spectra were recorded at pressures in the range 1-10 mbar, and, based on the data, a potential minimum detection limit of the order of 100 ppmv is estimated for MUMAS at atmospheric pressure using an inter-mode interval of 80 GHz.

Molecular Mechanisms Underlying Genomic Instability in Brca-Deficient Cells

DTIC Science & Technology

2012-03-01

Fanconi anemia pathway for ICL repair. BRCA1 therefore has two separate roles in ICL repair that can be modulated by manipulating NHEJ, whereas FANCD2...repair pathway comprising at least 15 gene products. Mutation of any of these genes causes the human disease Fanconi anemia (FA), which is associated...genetic deficiency in components of the Fanconi anemia (FA) pathway (Wang, 2007). Cells from FA patients, or knockout mice with deficiencies in the FA

Central endoscopy reads in inflammatory bowel disease clinical trials: The role of the imaging core lab.

PubMed

Ahmad, Harris; Berzin, Tyler M; Yu, Hui Jing; Huang, Christopher S; Mishkin, Daniel S

2014-08-01

Clinical trials in inflammatory bowel disease (IBD) are evolving at a rapid pace by employing central reading for endoscopic mucosal assessment in a field that was, historically, largely based on assessments by local physicians. This transition from local to central reading carries with it numerous technical, operational, and scientific challenges, many of which can be resolved by imaging core laboratories (ICLs), a concept that has a longer history in clinical trials in a number of diseases outside the realm of gastroenterology. For IBD trials, ICLs have the dual goals of providing objective, consistent assessments of endoscopic findings using central-reading paradigms whilst providing important expertise with regard to operational issues and regulatory expectations. This review focuses on current approaches to using ICLs for central endoscopic reading in IBD trials. © The Author(s) 2014. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

Transient anterior subcapsular vacuolar change of the crystalline lens in patients after posterior chamber phakic intraocular lens implantation.

PubMed

Chung, Jin Kwon; Shin, Jin Hee; Lee, Sung Jin

2013-10-25

We present two cases of transient vacuolar changes in the anterior subcapsular space of the crystalline lens in patients after posterior chamber phakic intraocular lens implantation. Implantable collamer lenses (ICL) were implanted in healthy myopic patients. Vacuolar changes developed just after the irrigating procedure through the narrow space between the ICL and the crystalline lens. Slit-lamp examinations and spectral domain optical coherence tomography showed bleb-like lesions in the anterior subcapsular space of one eye in each case, though the lesions gradually improved without visual deterioration. Consequently, the lesions turned into a few anterior subcapsular small faint opacities. Direct irrigation of the narrow space confined by the ICL and the crystalline lens is at risk for the development of vacuolar changes in the crystalline lens. The observed spontaneous reversal indicates that surgeons should not rush to surgical intervention but rather opt for close follow over several weeks.

FancJ regulates interstrand crosslinker induced centrosome amplification through the activation of polo-like kinase 1

PubMed Central

Zou, Jianqiu; Tian, Fen; Li, Ji; Pickner, Wyatt; Long, Molly; Rezvani, Khosrow; Wang, Hongmin; Zhang, Dong

2013-01-01

Summary DNA damage response (DDR) and the centrosome cycle are two of the most critical processes for maintaining a stable genome in animals. Sporadic evidence suggests a connection between these two processes. Here, we report our findings that six Fanconi Anemia (FA) proteins, including FancI and FancJ, localize to the centrosome. Intriguingly, we found that the localization of FancJ to the mother centrosome is stimulated by a DNA interstrand crosslinker, Mitomycin C (MMC). We further show that, in addition to its role in interstrand crosslinking (ICL) repair, FancJ also regulates the normal centrosome cycle as well as ICL induced centrosome amplification by activating the polo-like kinase 1 (PLK1). We have uncovered a novel function of FancJ in centrosome biogenesis and established centrosome amplification as an integral part of the ICL response. PMID:24167712

Interferon induction by two 2'-modified double-helical RNAs, poly(2'-fluoro-2'-deoxyinosinic acid) x poly(cytidylic acid) and poly(2'-chloro-2'-deoxyinosinic acid) x poly(cytidylic acid).

PubMed

De Clercq, E; Stollar, B D; Hobbs, J; Fukui, T; Kakiuchi, N; Ikehara, M

1980-01-01

In addition to the 2'-azido analogue of (I)n x (C)n, (dIn3)n x (C)n, we have found two other (I)n x (C)n analogues, (dIfl)n x (C)n and (dIcl)n x (C)n, in which the 2'-hydroxyls of the (I)n strand are replaced by either fluorine or chlorine, to be highly effective in inducing interferon. This contrasted with the lack of interferon-inducing activity noted for various other 2'-halogeno analogues of (I)n x (C)n and (A)n x (U)n, i.e. (I)n x (dCcl)n, (dAfl)n x (U)n, (dAcl)n x (U)n, (A)n x (dUfl)n and (A)n x (dUcl)n. In most assay systems, viz. primary rabbit kidney cells, human diploid fibroblasts, HeLa cells, interferon-primed mouse L-929 cells, and intact rabbits, (dIfl)n x (C)n and (dIcl)n x (C)n induced interferon levels that were comparable to those induced by (I)n x (C)n. There was one particular system (L-929 cells treated with DEAE-dextran), however, in which (dIfl)n x (C)n and (dIcl)n x (C)n, unlike (I)n x (C)n, failed to stimulate interferon production. As monitored by both radiochemical and biological means, (dIfl)n x (C)n and, to a lesser extent, (dIcl)n x (C)n were more resistant to degradation by ribonuclease A, T1 and human serum nucleases than was (I)n x (C)n. In their reactivity towards antibodies to double-stranded RNA (dIfl)n x (C)n and (dIcl)n x (C)n conformed more closely to (I)n x (C)n than did other 2'-substituted (e.g. 2'-O-methyl or 2'-O-ethyl) analogues of (I)n x (C)n. The high interferon-inducing potency of (dIfl)n x (C)n and (dIcl)n x (C)n has both theoretical and practical implications. While our findings suggest that (dIfl)n x (C)n and (dIcl)n x (C)n should be further explored for their therapeutic potentials, they also strengthen the notion that the interferon-inducing capacity, and possibly other biological functions of double-stranded RNAs is dependent on the recognition of the overall conformation of the polynucleotide rather than on the binding of specific functional groups such as the 2'-hydroxyl group.

Development of a coupled diffusion denuder system combined with gas chromatography/mass spectrometry for the separation and quantification of molecular iodine and the activated iodine compounds iodine monochloride and hypoiodous acid in the marine atmosphere.

PubMed

Huang, Ru-Jin; Hoffmann, Thorsten

2009-03-01

This study concerns the development of a coupled diffusion denuder system capable of separating and quantifying gaseous molecular iodine (I(2)) and two other highly reactive iodine species, ICl and HOI, which are collectively named activated iodine compounds (AIC). Both I(2) and AIC are key species in the atmospheric chemistry of iodine. 1,3,5-Trimethoxybenzene (1,3,5-TMB)- and alpha-cyclodextrin/(129)I(-) (alpha-CD/(129)I(-))-coated denuders proved to be suitable for the collection of gaseous AIC and I(2), respectively. The experimental collection efficiencies for AIC (tested as ICl) and I(2) agreed well with the theoretical values for gas flow rates in the range between 300 and 1800 mL min(-1). The coupled denuder system (1,3,5-TMB-coated denuder as front-denuder coupled upstream of an alpha-CD/(129)I(-)-coated denuder) was applied successfully to separate test gas mixtures of ICl and I(2) at various mixing ratios in the laboratory. The operation of both denuder systems was demonstrated to be independent of relative humidity (0-100%) and storage period (at least 2 weeks prior to and after sampling). Detection limits were achieved at sub-parts-per-trillion-by-volume (sub-pptv) level. The presented method provides a reliable and practical approach for the speciation of gaseous iodine compounds. In addition, we report for the first time ambient air measurements of AIC mixing ratios, carried out at the atmospheric research station in Mace Head, Ireland. A maximum concentration of AIC of 30.2 pptv was observed for nighttime measurements and 6.0 pptv for daytime measurements. A similar diurnal pattern was found for I(2) with an average concentration level of 23.2 pptv during daytime and 85.1 pptv during nighttime, indicating a strong correlation with AIC.

Outcome after treatment of ametropia with implantable contact lenses.

PubMed

Lackner, Birgit; Pieh, Stefan; Schmidinger, Gerald; Hanselmayer, Georg; Dejaco-Ruhswurm, Irene; Funovics, Martin A; Skorpik, Christian

2003-11-01

To evaluate long-term results after insertion of implantable contact lenses (ICLs) in phakic eyes. Prospective, noncomparative, interventional case series. Seventy-five phakic eyes (65 myopic, 10 hyperopic eyes) of 45 patients aged 21.7 to 60.6 years were included. STAAR Collamer Implantable Contact Lenses (STAAR Surgical Inc., Nidau, Switzerland) were implanted for correction of high myopia and hyperopia. Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were determined. Presence of lens opacification and the distance between the ICL and the crystalline lens were assessed by slit-lamp examination before surgery and at 1, 3, 6 months, and yearly after lens implantation. Preoperative mean spherical equivalent was -16.23+/-5.29 diopters (D) for myopic eyes and +7.88 +/-1.46 D for hyperopic eyes. After ICL implantation, mean residual refractive error was -1.77+/-2.17 D in myopic patients and +0.44+/-0.69 D in hyperopic patients. Preoperative mean UCVA was Snellen 0.03+/-0.03 for myopic patients and Snellen 0.12+/-0.16 for hyperopic patients. Preoperative mean BCVA was Snellen 0.49+/-0.23 for myopic patients and Snellen 0.82+/-0.23 for hyperopic patients. After ICL implantation, mean UCVA up to the end of individual observation time was Snellen 0.36+/-0.36 for myopic patients and Snellen 0.58+/-0.28 for hyperopic patients. Mean BCVA was Snellen 0.73+/-0.26 for myopic and Snellen 0.80+/-0.24 for hyperopic patients. Mean preoperative IOP was 14.2+/-2.7 mmHg, and mean postoperative IOP was 13.46+/-2.1 mmHg over all follow-up investigations. The main complication was the development of subcapsular anterior opacifications of the crystalline lens in 25 eyes (33.3%), 2 of which showed direct contact to the ICL. Eleven eyes (14.7%) were stable in opacification and 14 eyes (18.7%) had progressive opacifications. The median time to opacification was 27.1 months. In 8 patients (10.7%), the subjective visual impairment mandated cataract surgery. The most significant long-term complication after ICL implantation is the formation of opacifications of the crystalline lens with the risk of the necessity of subsequent cataract surgery (10.7%). Old age, female gender, and contralateral opacification are independent significant risk factors for early formation of opacifications in this patient group.

The Fanconi anemia associated protein FAAP24 uses two substrate specific binding surfaces for DNA recognition

PubMed Central

Wienk, Hans; Slootweg, Jack C.; Speerstra, Sietske; Kaptein, Robert; Boelens, Rolf; Folkers, Gert E.

2013-01-01

To maintain the integrity of the genome, multiple DNA repair systems exist to repair damaged DNA. Recognition of altered DNA, including bulky adducts, pyrimidine dimers and interstrand crosslinks (ICL), partially depends on proteins containing helix-hairpin-helix (HhH) domains. To understand how ICL is specifically recognized by the Fanconi anemia proteins FANCM and FAAP24, we determined the structure of the HhH domain of FAAP24. Although it resembles other HhH domains, the FAAP24 domain contains a canonical hairpin motif followed by distorted motif. The HhH domain can bind various DNA substrates; using nuclear magnetic resonance titration experiments, we demonstrate that the canonical HhH motif is required for double-stranded DNA (dsDNA) binding, whereas the unstructured N-terminus can interact with single-stranded DNA. Both DNA binding surfaces are used for binding to ICL-like single/double-strand junction-containing DNA substrates. A structural model for FAAP24 bound to dsDNA has been made based on homology with the translesion polymerase iota. Site-directed mutagenesis, sequence conservation and charge distribution support the dsDNA-binding model. Analogous to other HhH domain-containing proteins, we suggest that multiple FAAP24 regions together contribute to binding to single/double-strand junction, which could contribute to specificity in ICL DNA recognition. PMID:23661679

Thermal comfort sustained by cold protective clothing in Arctic open-pit mining—a thermal manikin and questionnaire study

PubMed Central

JUSSILA, Kirsi; RISSANEN, Sirkka; AMINOFF, Anna; WAHLSTRÖM, Jens; VAKTSKJOLD, Arild; TALYKOVA, Ljudmila; REMES, Jouko; MÄNTTÄRI, Satu; RINTAMÄKI, Hannu

2017-01-01

Workers in the Arctic open-pit mines are exposed to harsh weather conditions. Employers are required to provide protective clothing for workers. This can be the outer layer, but sometimes also inner or middle layers are provided. This study aimed to determine how Arctic open-pit miners protect themselves against cold and the sufficiency, and the selection criteria of the garments. Workers’ cold experiences and the clothing in four Arctic open-pit mines in Finland, Sweden, Norway and Russia were evaluated by a questionnaire (n=1,323). Basic thermal insulation (Icl) of the reported clothing was estimated (ISO 9920). The Icl of clothing from the mines were also measured by thermal manikin (standing/walking) in 0.3 and 4.0 m/s wind. The questionnaire showed that the Icl of the selected clothing was on average 1.2 and 1.5 clo in mild (−5 to +5°C) and dry cold (−20 to −10°C) conditions, respectively. The Icl of the clothing measured by thermal manikin was 1.9–2.3 clo. The results show that the Arctic open-pit miners’ selected their clothing based on occupational (time outdoors), environmental (temperature, wind, moisture) and individual factors (cold sensitivity, general health). However, the selected clothing was not sufficient to prevent cooling completely at ambient temperatures below −10°C. PMID:29021416

NASA 60 GHz intersatellite communication link definition study. Baseline document

NASA Technical Reports Server (NTRS)

1986-01-01

The overall system and component concepts for a 60 GHz intersatellite communications link system (ICLS) are described. The ICLS was designed to augment the capabilities of the current Tracking and Data Relay Satellite System (TDRSS), providing a data rate capacity large enough to accommodate the expected rates for user satellites (USAT's) in the post-1995 timeframe. The use of 60 GHz for the anticipated successor to TDRSS, the Tracking and Data Acquisition System (TDAS), was selected because of current technology development that will enable multigigibit data rates. Additionally, the attenuation of the earth's atmosphere at 60 GHz means that there is virtually no possibility of terrestrially generated interference (intentional or accidental) or terrestrially based intercept. The ICLS includes the following functional areas: (1) the ICLS payload package on the GEO TDAS satellite that communicates simultaneously with up to five LEO USAT's; (2) the payload package on the USAT that communicates with the TDAS satellite; and (3) the crosslink payload package on the TDAS satellite that communicates with another TDAS satellite. Two methods of data relay on-board the TDAS spacecraft were addressed. One is a complete baseband system (demod and remod) with a bi-directional 2 Gbps data stream; the other is a channelized system wherein some of the channels are baseband and others are merely frequency translated before re-transmission. Descriptions of the TDAS antenna, transmitter, receiver, and mechanical designs are presented.

Soft shape-adaptive gripping device made from artificial muscle

NASA Astrophysics Data System (ADS)

Hamburg, E.; Vunder, V.; Johanson, U.; Kaasik, F.; Aabloo, A.

2016-04-01

We report on a multifunctional four-finger gripper for soft robotics, suitable for performing delicate manipulation tasks. The gripping device is comprised of separately driven gripping and lifting mechanisms, both made from a separate single piece of smart material - ionic capacitive laminate (ICL) also known as artificial muscle. Compared to other similar devices the relatively high force output of the ICL material allows one to construct a device able to grab and lift objects exceeding multiple times its own weight. Due to flexible design of ICL grips, the device is able to adapt the complex shapes of different objects and allows grasping single or multiple objects simultaneously without damage. The performance of the gripper is evaluated in two different configurations: a) the ultimate grasping strength of the gripping hand; and b) the maximum lifting force of the lifting actuator. The ICL is composed of three main layers: a porous membrane consisting of non-ionic polymer poly(vinylidene fluoride-co-hexafluoropropene) (PVdF-HFP), ionic liquid 1-ethyl-3-methylimidazolium trifluoromethane-sulfonate (EMITFS), and a reinforcing layer of woven fiberglass cloth. Both sides of the membrane are coated with a carbonaceous electrode. The electrodes are additionally covered with thin gold layers, serving as current collectors. Device made of this material operates silently, requires low driving voltage (<3 V), and is suitable for performing tasks in open air environment.

Structure of a DNA glycosylase that unhooks interstrand cross-links

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

Mullins, Elwood A.; Warren, Garrett M.; Bradley, Noah P.

DNA glycosylases are important editing enzymes that protect genomic stability by excising chemically modified nucleobases that alter normal DNA metabolism. These enzymes have been known only to initiate base excision repair of small adducts by extrusion from the DNA helix. However, recent reports have described both vertebrate and microbial DNA glycosylases capable of unhooking highly toxic interstrand cross-links (ICLs) and bulky minor groove adducts normally recognized by Fanconi anemia and nucleotide excision repair machinery, although the mechanisms of these activities are unknown. Here we report the crystal structure of Streptomyces sahachiroi AlkZ (previously Orf1), a bacterial DNA glycosylase that protectsmore » its host by excising ICLs derived from azinomycin B (AZB), a potent antimicrobial and antitumor genotoxin. AlkZ adopts a unique fold in which three tandem winged helix-turn-helix motifs scaffold a positively charged concave surface perfectly shaped for duplex DNA. Through mutational analysis, we identified two glutamine residues and a β-hairpin within this putative DNA-binding cleft that are essential for catalytic activity. Additionally, we present a molecular docking model for how this active site can unhook either or both sides of an AZB ICL, providing a basis for understanding the mechanisms of base excision repair of ICLs. Given the prevalence of this protein fold in pathogenic bacteria, this work also lays the foundation for an emerging role of DNA repair in bacteria-host pathogenesis.« less

Anion channel sensitivity to cytosolic organic acids implicates a central role for oxaloacetate in integrating ion flux with metabolism in stomatal guard cells.

PubMed

Wang, Yizhou; Blatt, Michael R

2011-10-01

Stomatal guard cells play a key role in gas exchange for photosynthesis and in minimizing transpirational water loss from plants by opening and closing the stomatal pore. The bulk of the osmotic content driving stomatal movements depends on ionic fluxes across both the plasma membrane and tonoplast, the metabolism of organic acids, primarily Mal (malate), and its accumulation and loss. Anion channels at the plasma membrane are thought to comprise a major pathway for Mal efflux during stomatal closure, implicating their key role in linking solute flux with metabolism. Nonetheless, little is known of the regulation of anion channel current (I(Cl)) by cytosolic Mal or its immediate metabolite OAA (oxaloacetate). In the present study, we have examined the impact of Mal, OAA and of the monocarboxylic acid anion acetate in guard cells of Vicia faba L. and report that all three organic acids affect I(Cl), but with markedly different characteristics and sidedness to their activities. Most prominent was a suppression of ICl by OAA within the physiological range of concentrations found in vivo. These findings indicate a capacity for OAA to co-ordinate organic acid metabolism with I(Cl) through the direct effect of organic acid pool size. The findings of the present study also add perspective to in vivo recordings using acetate-based electrolytes.

The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL*

PubMed Central

Miles, Jennifer A.; Frost, Mark G.; Carroll, Eilis; Rowe, Michelle L.; Howard, Mark J.; Sidhu, Ateesh; Chaugule, Viduth K.; Alpi, Arno F.; Walden, Helen

2015-01-01

The Fanconi Anemia (FA) DNA repair pathway is essential for the recognition and repair of DNA interstrand crosslinks (ICL). Inefficient repair of these ICL can lead to leukemia and bone marrow failure. A critical step in the pathway is the monoubiquitination of FANCD2 by the RING E3 ligase FANCL. FANCL comprises 3 domains, a RING domain that interacts with E2 conjugating enzymes, a central domain required for substrate interaction, and an N-terminal E2-like fold (ELF) domain. The ELF domain is found in all FANCL homologues, yet the function of the domain remains unknown. We report here that the ELF domain of FANCL is required to mediate a non-covalent interaction between FANCL and ubiquitin. The interaction involves the canonical Ile44 patch on ubiquitin, and a functionally conserved patch on FANCL. We show that the interaction is not necessary for the recognition of the core complex, it does not enhance the interaction between FANCL and Ube2T, and is not required for FANCD2 monoubiquitination in vitro. However, we demonstrate that the ELF domain is required to promote efficient DNA damage-induced FANCD2 monoubiquitination in vertebrate cells, suggesting an important function of ubiquitin binding by FANCL in vivo. PMID:26149689

Evaluation of Simultaneous Nutrient and COD Removal with Polyhydroxybutyrate (PHB) Accumulation Using Mixed Microbial Consortia under Anoxic Condition and Their Bioinformatics Analysis

PubMed Central

Jena, Jyotsnarani; Kumar, Ravindra; Dixit, Anshuman; Pandey, Sony; Das, Trupti

2015-01-01

Simultaneous nitrate-N, phosphate and COD removal was evaluated from synthetic waste water using mixed microbial consortia in an anoxic environment under various initial carbon load (ICL) in a batch scale reactor system. Within 6 hours of incubation, enriched DNPAOs (Denitrifying Polyphosphate Accumulating Microorganisms) were able to remove maximum COD (87%) at 2g/L of ICL whereas maximum nitrate-N (97%) and phosphate (87%) removal along with PHB accumulation (49 mg/L) was achieved at 8 g/L of ICL. Exhaustion of nitrate-N, beyond 6 hours of incubation, had a detrimental effect on COD and phosphate removal rate. Fresh supply of nitrate-N to the reaction medium, beyond 6 hours, helped revive the removal rates of both COD and phosphate. Therefore, it was apparent that in spite of a high carbon load, maximum COD and nutrient removal can be maintained, with adequate nitrate-N availability. Denitrifying condition in the medium was evident from an increasing pH trend. PHB accumulation by the mixed culture was directly proportional to ICL; however the time taken for accumulation at higher ICL was more. Unlike conventional EBPR, PHB depletion did not support phosphate accumulation in this case. The unique aspect of all the batch studies were PHB accumulation was observed along with phosphate uptake and nitrate reduction under anoxic conditions. Bioinformatics analysis followed by pyrosequencing of the mixed culture DNA from the seed sludge revealed the dominance of denitrifying population, such as Corynebacterium, Rhodocyclus and Paraccocus (Alphaproteobacteria and Betaproteobacteria). Rarefaction curve indicated complete bacterial population and corresponding number of OTUs through sequence analysis. Chao1 and Shannon index (H’) was used to study the diversity of sampling. “UCI95” and “LCI95” indicated 95% confidence level of upper and lower values of Chao1 for each distance. Values of Chao1 index supported the results of rarefaction curve. PMID:25689047

Evaluation of simultaneous nutrient and COD removal with polyhydroxybutyrate (PHB) accumulation using mixed microbial consortia under anoxic condition and their bioinformatics analysis.

PubMed

Jena, Jyotsnarani; Kumar, Ravindra; Dixit, Anshuman; Pandey, Sony; Das, Trupti

2015-01-01

Simultaneous nitrate-N, phosphate and COD removal was evaluated from synthetic waste water using mixed microbial consortia in an anoxic environment under various initial carbon load (ICL) in a batch scale reactor system. Within 6 hours of incubation, enriched DNPAOs (Denitrifying Polyphosphate Accumulating Microorganisms) were able to remove maximum COD (87%) at 2 g/L of ICL whereas maximum nitrate-N (97%) and phosphate (87%) removal along with PHB accumulation (49 mg/L) was achieved at 8 g/L of ICL. Exhaustion of nitrate-N, beyond 6 hours of incubation, had a detrimental effect on COD and phosphate removal rate. Fresh supply of nitrate-N to the reaction medium, beyond 6 hours, helped revive the removal rates of both COD and phosphate. Therefore, it was apparent that in spite of a high carbon load, maximum COD and nutrient removal can be maintained, with adequate nitrate-N availability. Denitrifying condition in the medium was evident from an increasing pH trend. PHB accumulation by the mixed culture was directly proportional to ICL; however the time taken for accumulation at higher ICL was more. Unlike conventional EBPR, PHB depletion did not support phosphate accumulation in this case. The unique aspect of all the batch studies were PHB accumulation was observed along with phosphate uptake and nitrate reduction under anoxic conditions. Bioinformatics analysis followed by pyrosequencing of the mixed culture DNA from the seed sludge revealed the dominance of denitrifying population, such as Corynebacterium, Rhodocyclus and Paraccocus (Alphaproteobacteria and Betaproteobacteria). Rarefaction curve indicated complete bacterial population and corresponding number of OTUs through sequence analysis. Chao1 and Shannon index (H') was used to study the diversity of sampling. "UCI95" and "LCI95" indicated 95% confidence level of upper and lower values of Chao1 for each distance. Values of Chao1 index supported the results of rarefaction curve.

Posterior chamber phakic intraocular lens implantation: comparative, multicentre study in 351 eyes with low-to-moderate or high myopia.

PubMed

Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kitazawa, Yoshihiro; Kojima, Takashi; Nakamura, Tomoaki; Oka, Yoshitaka; Matsumoto, Rei

2018-02-01

To compare the clinical outcomes of posterior chamber phakic intraocular lens implantation with a central hole (Hole Implantable Collamer Lens (ICL), STAAR Surgical) for low-to-moderate myopia and for high myopia. This multicentre retrospective case series comprised 351 eyes of 351 consecutive patients undergoing ICL implantation. Eyes were divided into groups based on preoperative degree of myopia: group 1; 57 eyes, manifest spherical equivalent less than -6 dioptres (D), and group 2; 294 eyes, -6 D or more. Safety, efficacy, predictability, stability and adverse events were compared preoperatively; and at 1 day, 1 week and 1, 3, 6 and 12 months postoperatively, RESULTS: Uncorrected and corrected visual acuities were -0.17±0.14 and -0.21±0.10 logMAR in group 1, and -0.16±0.09 and -0.21±0.08 logMAR in group 2, 1 year postoperatively. In groups 1 and 2, 98% and 99% of eyes were within 1.0 D of the targeted correction. Manifest refraction changes of -0.12±0.34 D (group 1) and -0.18±0.43 D (group 2) occurred from 1 day to 1 year. ICL exchanges were necessary in two eyes (0.7%) in group 2. No vision-threatening complications occurred at any time. The ICL performed well for the correction of both low-to-moderate myopia and high myopia throughout the 1-year observation period. The clinical outcomes of ICL implantation for low-to-moderate myopia are essentially equivalent to those for high myopia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effects of Implantable Collamer Lens V4c Placement on Iridocorneal Angle Measurements by Fourier-Domain Optical Coherence Tomography.

PubMed

Fernández-Vigo, José Ignacio; Macarro-Merino, Ana; Fernández-Vigo, Cristina; Fernández-Vigo, José Ángel; Martínez-de-la-Casa, José María; Fernández-Pérez, Cristina; García-Feijóo, Julián

2016-02-01

To assess by Fourier-domain optical coherence tomography (FDOCT) changes produced in iridocorneal angle measurements in patients undergoing Visian Implantable Collamer Lens (ICL) V4c (STAAR Surgical AG) placement. Prospective interventional case series. In 50 eyes of 25 myopic subjects consecutively scheduled for ICL implant, FDOCT (RTVue; Optovue Inc) iridocorneal angle measurements were made before and 1 and 3 months after surgery. Trabecular-iris angle (TIA) and angle opening distance 500 μm anterior to the scleral spur (AOD500) were compared among the quadrants nasal, temporal, and inferior, and correlations with ocular variables including lens vault were examined. Preoperative TIA was 48.7 ± 8.7, 48.2 ± 8.7, and 48.7 ± 9.3 degrees for the nasal, temporal, and inferior quadrants, with no differences (P = 1.000). Following ICL implant, corresponding values fell to 31.2 ± 11.5, 30.0 ± 10.7, and 29.7 ± 8.1 degrees at 1 month postsurgery, indicating angle narrowing of 34%-42%, and to 30.6 ± 12.3, 30.1 ± 11.9, and 29.8 ± 12.3 degrees, respectively, at 3 months postsurgery. Angle measurements failed to vary between 1 month and 3 months postsurgery (P = .481). In 8 eyes, iridotrabecular contact attributable to surgery was observed. One month after surgery, vault measurements correlated with TIA (R = -.309; P = .048). Six variables were identified as predictors of TIA at 1 month postsurgery (R(2) = .907). Although considerable angle narrowing was detected 1 month after ICL V4c implant, this narrowing remained stable at 3 months postsurgery. Factors predictive of TIA could serve to identify suitable candidates for ICL placement. Copyright © 2016 Elsevier Inc. All rights reserved.

Anti-Cancer Effects of Imperata cylindrica Leaf Extract on Human Oral Squamous Carcinoma Cell Line SCC-9 in Vitro.

PubMed

Keshava, Rohini; Muniyappa, Nagesh; Gope, Rajalakshmi; Ramaswamaiah, Ananthanarayana Saligrama

2016-01-01

Imperata cylindrica, a tall tufted grass which has multiple pharmacological applications is one of the key ingredients in various traditional medicinal formula used in India. Previous reports have shown that I. cylindrica plant extract inhibited cell proliferation and induced apoptosis in various cancer cell lines. To our knowledge, no studies have been published on the effect of I. cylindrica leaf extract on human oral cancers. The present study was undertaken in order to evaluate the anticancer properties of the leaf extract of I. cylindrica using an oral squamous cell carcinoma cell line SCC-9 as an in vitro model system. A methanol extract from dried leaves of I. cylindrica (ICL) was prepared by standard procedures. Effects of the ICL extract on the morphology of SCC-9 cells was visualized by microscopy. Cytotoxicity was determined by MTT assay. Effects of the ICL extract on colony forming ability of SCC-9 cells was evaluated using clonogenic assay. Cell cycle analysis was performed by flow cytometry and induction of apoptosis was determined by DNA fragmentation assay. The ICL extract treatment caused cytotoxicity and induced cell death in vitro in SCC-9 cells in a dose-dependent manner. This treatment also significantly reduced the clonogenic potential and inhibited cell proliferation by arresting the cell cycle in the G2/M phase. Furthermore, DNA fragmentation assays showed that the observed cell death was caused by apoptosis. This is the first report showing the anticancer activity of the methanol extracts from the leaves of I. cylindrica in human oral cancer cell line. Our data indicates that ICL extract could be considered as one of the lead compounds for the formulation of anticancer therapeutic agents to treat/manage human oral cancers. The natural abundance of I. cylindrica and its wide geographic distribution could render it one of the primary resource materials for preparation of anticancer therapeutic agents.

Protective Role of Acidic pH-Activated Chloride Channel in Severe Acidosis-Induced Contraction from the Aorta of Spontaneously Hypertensive Rats

PubMed Central

Ma, Zhiyong; Qi, Jia; Fu, Zhijie; Ling, Mingying; Li, Li; Zhang, Yun

2013-01-01

Severe acidic pH-activated chloride channel (ICl,acid) has been found in various mammalian cells. In the present study, we investigate whether this channel participates in reactions of the thoracic aorta to severe acidosis and whether it plays a role in hypertension. We measured isometric contraction in thoracic aorta rings from spontaneously hypertensive rats (SHRs) and normotensive Wistar rats. Severe acidosis induced contractions of both endothelium-intact and -denuded thoracic aorta rings. In Wistar rats, contractions did not differ at pH 6.4, 5.4 and 4.4. However, in SHRs, contractions were higher at pH 5.4 or 4.4 than pH 6.4, with no difference between contractions at pH 5.4 and 4.4. Nifedipine, ICl,acid blockers 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and 4,4′-diisothiocyanatostilbene-2, 2′-disulfonic acid (DIDS) inhibited severe acidosis-induced contraction of aortas at different pH levels. When blocking ICl,acid, the remnant contraction was greater at pH 4.4 than pH 5.4 and 6.4 for both SHRs and Wistar rats. With nifedipine, the remnant contraction was greatly reduced at pH 4.4 as compared with at pH 6.4 and 5.4. With NPPB or DIDS, the ratio of remnant contractions at pH 4.4 and 5.4 (R4.4/5.4) was lower for SHRs than Wistar rats (all <1). However, with nifedipine, the R4.4/5.4 was higher for SHRs than Wistar rats (both >1). Furthermore, patch clamp recordings of ICl,acid and intracellular Ca2+ measurements in smooth muscle cells confirmed these findings. ICl,acid may protect arteries against excess vasoconstriction under extremely acidic extracellular conditions. This protective effect may be decreased in hypertension. PMID:23580361

Properties of the calcium-activated chloride current in heart.

PubMed

Zygmunt, A C; Gibbons, W R

1992-03-01

We used the whole cell patch clamp technique to study transient outward currents of single rabbit atrial cells. A large transient current, IA, was blocked by 4-aminopyridine (4AP) and/or by depolarized holding potentials. After block of IA, a smaller transient current remained. It was completely blocked by nisoldipine, cadmium, ryanodine, or caffeine, which indicates that all of the 4AP-resistant current is activated by the calcium transient that causes contraction. Neither calcium-activated potassium current nor calcium-activated nonspecific cation current appeared to contribute to the 4AP-resistant transient current. The transient current disappeared when ECl was made equal to the pulse potential; it was present in potassium-free internal and external solutions. It was blocked by the anion transport blockers SITS and DIDS, and the reversal potential of instantaneous current-voltage relations varied with extracellular chloride as predicted for a chloride-selective conductance. We concluded that the 4AP-resistant transient outward current of atrial cells is produced by a calcium-activated chloride current like the current ICl(Ca) of ventricular cells (1991. Circulation Research. 68:424-437). ICl(Ca) in atrial cells demonstrated outward rectification, even when intracellular chloride concentration was higher than extracellular. When ICa was inactivated or allowed to recover from inactivation, amplitudes of ICl(Ca) and ICa were closely correlated. The results were consistent with the view that ICl(Ca) does not undergo independent inactivation. Tentatively, we propose that ICl(Ca) is transient because it is activated by an intracellular calcium transient. Lowering extracellular sodium increased the peak outward transient current. The current was insensitive to the choice of sodium substitute. Because a recently identified time-independent, adrenergically activated chloride current in heart is reduced in low sodium, these data suggest that the two chloride currents are produced by different populations of channels.

Pathway-selective sensitization of Mycobacterium tuberculosis for target-based whole-cell screening

PubMed Central

Abrahams, Garth L.; Kumar, Anuradha; Savvi, Suzana; Hung, Alvin W.; Wen, Shijun; Abell, Chris; Barry, Clifton E.; Sherman, David R.; Boshoff, Helena I.M.; Mizrahi, Valerie

2012-01-01

SUMMARY Whole-cell screening of Mycobacterium tuberculosis (Mtb) remains a mainstay of drug discovery but subsequent target elucidation often proves difficult. Conditional mutants that under-express essential genes have been used to identify compounds with known mechanism of action by target-based whole-cell screening (TB-WCS). Here, the feasibility of TB-WCS in Mtb was assessed by generating mutants that conditionally express pantothenate synthetase (panC), diaminopimelate decarboxylase (lysA) and isocitrate lyase (icl1). The essentiality of panC and lysA, and conditional essentiality of icl1 for growth on fatty acids, was confirmed. Depletion of PanC and Icl1 rendered the mutants hypersensitive to target-specific inhibitors. Stable reporter strains were generated for use in high-throughput screening, and their utility demonstrated by identifying compounds that display greater potency against a PanC-depleted strain. These findings illustrate the power of TB-WCS as a tool for tuberculosis drug discovery. PMID:22840772

Optical feedback cavity-enhanced absorption spectroscopy with a 3.24 μm interband cascade laser

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

Manfred, K. M.; Ritchie, G. A. D.; Lang, N.

2015-06-01

The development of interband cascade lasers (ICLs) has made the strong C-H transitions in the 3 μm spectral region increasingly accessible. We present the demonstration of a single mode distributed feedback ICL coupled to a V-shaped optical cavity in an optical feedback cavity-enhanced absorption spectroscopy (OF-CEAS) experiment. We achieved a minimum detectable absorption coefficient, α{sub min}, of (7.1±0.2)×10{sup −8} cm{sup −1} for a spectrum of CH{sub 4} at 3.24 μm with a two second acquisition time (100 scans averaged). This corresponds to a detection limit of 3 ppb CH{sub 4} at atmospheric pressure, which is comparable to previously reported OF-CEAS instruments with diodemore » lasers or quantum cascade lasers. The ability to frequency lock an ICL source in the important 3 μm region to an optical cavity holds great promise for future spectroscopic applications.« less

Upper limb load as a function of repetitive task parameters: part 1--a model of upper limb load.

PubMed

Roman-Liu, Danuta

2005-01-01

The aim of the study was to develop a theoretical indicator of upper limb musculoskeletal load based on repetitive task parameters. As such the dimensionless parameter, Integrated Cycle Load (ICL) was accepted. It expresses upper limb load which occurs during 1 cycle. The indicator is based on a model of a repetitive task, which consists of a model of the upper limb, a model of basic types of upper limb forces and a model of parameters of a repetitive task such as length of the cycle, length of periods of the cycle and external force exerted during each of the periods of the cycle. Calculations of the ICL parameter were performed for 12 different variants of external load characterised by different values of repetitive task parameters. A comparison of ICL, which expresses external load with a physiological indicator of upper limb load, is presented in Part 2 of the paper.

Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

PubMed

Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

2005-12-15

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

Effects of V4c-ICL Implantation on Myopic Patients' Vision-Related Daily Activities

PubMed Central

Linghu, Shaorong; Pan, Le; Shi, Rong

2016-01-01

The new type implantable Collamer lens with a central hole (V4c-ICL) is widely used to treat myopia. However, halos occur in some patients after surgery. The aim is to evaluate the effect of V4c-ICL implantation on vision-related daily activities. This retrospective study included 42 patients. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), intraocular pressure (IOP), endothelial cell density (ECD), and vault were recorded and vision-related daily activities were evaluated at 3 months after operation. The average spherical equivalent was −0.12 ± 0.33 D at 3 months after operation. UCVA equal to or better than preoperative BCVA occurred in 98% of eyes. The average BCVA at 3 months after operation was −0.03 ± 0.07 LogMAR, which was significantly better than preoperative BCVA (0.08 ± 0.10 LogMAR) (P = 0.029). Apart from one patient (2.4%) who had difficulty reading computer screens, all patients had satisfactory or very satisfactory results. During the early postoperation, halos occurred in 23 patients (54.8%). However there were no significant differences in the scores of visual functions between patients with and without halos (P > 0.05). Patients were very satisfied with their vision-related daily activities at 3 months after operation. The central hole of V4c-ICL does not affect patients' vision-related daily activities. PMID:27965890

HCl yield and chemical kinetics study of the reaction of Cl atoms with CH3I at the 298K temperature using the infra-red tunable diode laser absorption spectroscopy.

PubMed

Sharma, R C; Blitz, M; Wada, R; Seakins, P W

2014-07-15

Pulsed ArF excimer laser (193 nm)-CW infrared (IR) tunable diode laser Herriott type absorption spectroscopic technique has been made for the detection of product hydrochloric acid HCl. Absorption spectroscopic technique is used in the reaction chlorine atoms with methyl iodide (Cl+CH3I) to the study of kinetics on reaction Cl+CH3I and the yield of (HCl). The reaction of Cl+CH3I has been studied with the support of the reaction Cl+C4H10 (100% HCl) at temperature 298 K. In the reaction Cl+CH3I, the total pressure of He between 20 and 125 Torr at the constant concentration of [CH3I] 7.0×10(14) molecule cm(-3). In the present work, we estimated adduct formation is very important in the reaction Cl+CH3I and reversible processes as well and CH3I molecule photo-dissociated in the methyl [CH3] radical. The secondary chemistry has been studied as CH3+CH3ICl = product, and CH3I+CH3ICl = product2. The system has been modeled theoretically for secondary chemistry in the present work. The calculated and experimentally HCl yield nearly 65% at the concentration 1.00×10(14) molecule cm(-3) of [CH3I] and 24% at the concentration 4.0×10(15) molecule cm(-3) of [CH3I], at constant concentration 4.85×10(12) molecule cm(-3) of [CH3], and at 7.3×10(12) molecule cm(-3) of [Cl]. The pressure dependent also studied product of HCl at the constant [CH3], [Cl] and [CH3I]. The experimental results are also very good matching with the modelling work at the reaction CH3+CH3ICl = product (k = (2.75±0.35)×10(-10) s(-1)) and CH3I+CH3ICl = product2 (k = 1.90±0.15)×10(-12) s(-1). The rate coefficients of the reaction CH3+CH3ICl and CH3I+CH3ICl has been made in the present work. The experimental results has been studied by two method (1) phase locked and (2) burst mode. Copyright © 2014 Elsevier B.V. All rights reserved.

The Average Star Formation Histories of Galaxies in Dark Matter Halos from z = 0-8

NASA Astrophysics Data System (ADS)

Behroozi, Peter S.; Wechsler, Risa H.; Conroy, Charlie

2013-06-01

We present a robust method to constrain average galaxy star formation rates (SFRs), star formation histories (SFHs), and the intracluster light (ICL) as a function of halo mass. Our results are consistent with observed galaxy stellar mass functions, specific star formation rates (SSFRs), and cosmic star formation rates (CSFRs) from z = 0 to z = 8. We consider the effects of a wide range of uncertainties on our results, including those affecting stellar masses, SFRs, and the halo mass function at the heart of our analysis. As they are relevant to our method, we also present new calibrations of the dark matter halo mass function, halo mass accretion histories, and halo-subhalo merger rates out to z = 8. We also provide new compilations of CSFRs and SSFRs; more recent measurements are now consistent with the buildup of the cosmic stellar mass density at all redshifts. Implications of our work include: halos near 1012 M ⊙ are the most efficient at forming stars at all redshifts, the baryon conversion efficiency of massive halos drops markedly after z ~ 2.5 (consistent with theories of cold-mode accretion), the ICL for massive galaxies is expected to be significant out to at least z ~ 1-1.5, and dwarf galaxies at low redshifts have higher stellar mass to halo mass ratios than previous expectations and form later than in most theoretical models. Finally, we provide new fitting formulae for SFHs that are more accurate than the standard declining tau model. Our approach places a wide variety of observations relating to the SFH of galaxies into a self-consistent framework based on the modern understanding of structure formation in ΛCDM. Constraints on the stellar mass-halo mass relationship and SFRs are available for download online.

The outer regions of the giant Virgo galaxy M 87 Kinematic separation of stellar halo and intracluster light

NASA Astrophysics Data System (ADS)

Longobardi, Alessia; Arnaboldi, Magda; Gerhard, Ortwin; Hanuschik, Reinhard

2015-07-01

Aims: We present a spectroscopic study of a sample of 287 planetary nebulas (PNs) around the brightest cluster galaxy (BCG) M 87 in Virgo A, of which 211 are located between 40 kpc and 150 kpc from the galaxy centre. With these data we can distinguish the stellar halo from the co-spatial intracluster light (ICL) and study both components separately. Methods: We obtained PN velocities with a high resolution FLAMES/VLT survey targeting eight fields in a total area of ~0.4 deg2. We identified PNs from their narrow and symmetric redshifted λ5007 Å [OIII] emission line, the presence of the second λ4959 Å [OIII] emission line, and the absence of significant continuum. We implement a robust technique to measure the halo velocity dispersion from the projected phase-space to identify PNs associated with the M 87 halo and ICL. Using photometric magnitudes, we construct PN luminosity functions (PNLFs), which are complete down to m5007 = 28.8. Results: The velocity distribution of the spectroscopically confirmed PNs is bimodal, containing a narrow component centred on the systemic velocity of the BCG and an off-centred broader component, which we identify as halo and ICL, respectively. We find that 243 PNs are part of the velocity distribution of the M 87 halo, while the remaining subsample of 44 PNs are intracluster PNs (ICPNs). Halo and ICPNs have different spatial distributions: the number density of halo PNs follow the galaxy's surface brightness profile, whereas the ICPNs are characterised by a shallower power-law profile, IICL ∝ Rγ with γ in the range [-0.34, -0.04 ]. No evidence is found for an asymmetry in the halo and ICPN density distributions when the NW and SE fields are studied separately. A study of the composite PN number density profile confirms the superposition of different PN populations associated with the M 87 halo and the ICL, characterised by different PN specific numbers α. We derive αhalo = 1.06 × 10-8NPN L⊙,bol-1 and αICL = 2.72 × 10-8NPN L⊙,bol-1, respectively. The M 87 halo PNLF has fewer bright PNs and a steeper slope towards faint magnitudes than the ICPNLF, and both are steeper than the standard PNLF for the M 31 bulge. Moreover, the ICPNLF has a dip at ~1-1.5 mag fainter than the bright cut-off, reminiscent of the PNLFs of systems with extended star formation history, such as M 33 or the Magellanic clouds. Conclusions: The BCG halo of M 87 and the Virgo ICL are dynamically distinct components with different density profiles and velocity distributions. Moreover, the different α-parameter values and PNLF shapes of the halo and ICL indicate distinct parent stellar populations, consistent with the existence of a gradient towards bluer colours at large radii. These results reflect the hierarchical build-up of the Virgo cluster. Based on observations made with the VLT at Paranal Observatory under programs 088.B-0288(A) and 093.B-066(A), and with the SUBARU Telescope under program S10A-039.

The Fanconi Anemia DNA Repair Pathway Is Regulated by an Interaction between Ubiquitin and the E2-like Fold Domain of FANCL.

PubMed

Miles, Jennifer A; Frost, Mark G; Carroll, Eilis; Rowe, Michelle L; Howard, Mark J; Sidhu, Ateesh; Chaugule, Viduth K; Alpi, Arno F; Walden, Helen

2015-08-21

The Fanconi Anemia (FA) DNA repair pathway is essential for the recognition and repair of DNA interstrand crosslinks (ICL). Inefficient repair of these ICL can lead to leukemia and bone marrow failure. A critical step in the pathway is the monoubiquitination of FANCD2 by the RING E3 ligase FANCL. FANCL comprises 3 domains, a RING domain that interacts with E2 conjugating enzymes, a central domain required for substrate interaction, and an N-terminal E2-like fold (ELF) domain. The ELF domain is found in all FANCL homologues, yet the function of the domain remains unknown. We report here that the ELF domain of FANCL is required to mediate a non-covalent interaction between FANCL and ubiquitin. The interaction involves the canonical Ile44 patch on ubiquitin, and a functionally conserved patch on FANCL. We show that the interaction is not necessary for the recognition of the core complex, it does not enhance the interaction between FANCL and Ube2T, and is not required for FANCD2 monoubiquitination in vitro. However, we demonstrate that the ELF domain is required to promote efficient DNA damage-induced FANCD2 monoubiquitination in vertebrate cells, suggesting an important function of ubiquitin binding by FANCL in vivo. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparison between toric and spherical phakic intraocular lenses combined with astigmatic keratotomy for high myopic astigmatism.

PubMed

Zheng, Lin-Yan; Zhu, Shuang-Qian; Su, Yan-Feng; Zou, Hu-Yong; Wang, Qin-Mei; Yu, A-Yong

2017-01-01

To compare the outcomes of a toric phakic intraocular lens (PIOL) and a spherical PIOL combined with astigmatic keratotomy (AK) for the correction of high myopic astigmatism. This study enrolled patients with high myopic astigmatism, including 30 eyes (22 patients) that received a toric PIOL implantation (TICL group), and 32 eyes (24 patients) that received combined AK and a spherical PIOL implantation (AK+ ICL group). The outcomes were compared between the two groups before surgery, and at the following time points after surgery: 1 week, 1, 3, 6 months, and 1, 2 years. Preoperatively, the mean manifest spherical equivalent (SE) was -14.14 ± 2.12 D in the TICL group and -14.83 ± 2.79 D in the AK + ICL group ( P  = 0.28), and the mean manifest refractive cylinder, -2.87 ± 1.09 D and -2.58 ± 0.85 D, respectively ( P  = 0.28). Two years postoperatively, the mean safety index was 1.53 ± 0.55 in the TICL group and 1.60 ± 0.70 in the AK + ICL group ( P  = 1.00), and the mean efficacy index, 1.18 ± 0.45 and 1.38 ± 0.52, respectively ( P  = 0.86). The mean manifest refractive cylinder correction was 1.94 ± 1.07 D in the TICL group and 1.39 ± 0.71 D in the AK + ICL group ( P  = 0.02). The mean changes in SE and refractive cylinder from 1 week to 2 years were less than 0.50 D in both groups. Both TICL implantation and AK + ICL implantation are a good alternative for correction of astigmatism in addition to high myopia. TICL implantation has better predictability in correction of high myopic astigmatism. NCT03202485.

Four-year Follow-up of the Changes in Anterior Segment After Phakic Collamer Lens Implantation.

PubMed

Lu, Yuanyuan; Yang, Na; Li, Xuedong; Kong, Jun

2017-06-01

To assess the changes and relationship in central vaulting, flare intensity, and crystalline lens thickness during a follow-up period of 4 years after implantable collamer lens (ICL) implantation in eyes with high myopia. Retrospective observational study. Ninety-eight eyes of 50 patients were followed up with routine measurements of central vaulting, crystalline lens thickness, endothelial cell density, and aqueous flare postoperatively. Data were analyzed by repeated-measures analysis of variance. The relationship between the annual change in crystal lens thickness after surgery and age was evaluated by Pearson correlation coefficient and linear regression. There was a continuous reduction in central vaulting and endothelial cell density as well as an increase in crystalline lens thickness in ICL eyes from 1 month onward to 5 years postoperatively (P < .001). Although the trend of variation during the individual visit period was accentuated, the variation turned out to be smaller between 12 and 36 months or 60 months postoperatively (P = .42, P = .65). Aqueous flare intensity increased significantly after surgery and returned to normal 1 year later. Additionally, a positive correlation between patient age and crystalline lens thickness (r = 0.617, P < .0001) was observed in eyes with ICL implantation. The changes in central vaulting, endothelial cell density, and crystalline lens thickness are more prominent during the first year after ICL implantation, tending to be relatively stable afterwards. The anterior inflammation during the early postoperative period synchronizes with the sharp progression of crystalline lens changes within the first year. Copyright © 2017 Elsevier Inc. All rights reserved.

Acquisition of relative interstrand crosslinker resistance and PARP inhibitor sensitivity in Fanconi anemia head and neck cancers

PubMed Central

Lombardi, Anne J.; Hoskins, Elizabeth E.; Foglesong, Grant D.; Wikenheiser-Brokamp, Kathryn A.; Wiesmüller, Lisa; Hanenberg, Helmut; Andreassen, Paul R.; Jacobs, Allison J.; Olson, Susan B.; Keeble, Winifred W.; Hays, Laura E.; Wells, Susanne I.

2015-01-01

Purpose Fanconi anemia (FA) is an inherited disorder associated with a constitutional defect in the FA DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with FA are predisposed to formation of head and neck squamous cell carcinomas (HNSCCs) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. Experimental Design Using HNSCC cell lines derived from the tumors of FA patients, and murine HNSCC cell lines derived from the tumors of wild type and Fancc−/− mice, we sought to define FA-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of FA HNSCC cells for non-homologous end joining (NHEJ). Results Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily FA-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in FA cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by poly(ADP-ribose) polymerase (PARP) in FA-deficient cells. Moreover, human and murine FA HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by FA gene complementation. Conclusions The observed reliance upon PARP-mediated mechanisms reveals a means by which FA HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. PMID:25609062

Idiopathic CD4 lymphocytopenia: Pathogenesis, etiologies, clinical presentations and treatment strategies.

PubMed

Yarmohammadi, Hale; Cunningham-Rundles, Charlotte

2017-10-01

Idiopathic CD4 lymphocytopenia (ICL) is a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections. The pathogenesis, etiology, clinical presentation, and best treatment options remain unclear. To describe the clinical presentation, treatment strategies, and outcome of patients with ICL seen in a single referral center. In a retrospective study, from January 1993 to January 2014, the demographic characteristics, clinical presentation, and treatments of patients diagnosed with ICL were reviewed. Twenty-four patients (14 female [58%] and 10 male [42%]) were evaluated. The mean age was 45 ± 17.6 years (range 7-76 years). Mean CD4 and CD8 T-cell counts at the time of diagnosis were 119 ± 84/mm 3 (range 4-294/mm 3 ) and 219 ± 258/mm 3 (range 7-630/mm 3 ), respectively. Seventeen patients (71%) had opportunistic infections, 4 (17%) had malignancies, and 3 (13%) had unexplained demyelinating disease and neurologic problems. Most patients had normal levels of immunoglobulins. Thirteen patients had abnormally low to absent response to phytohemagglutinin, concanavalin A, and antigens (candida and tetanus). Three patients had resolution of warts and 1 had mycobacterial lung infection on interleukin-2 with increases in CD4 count. The 11 patients on trimethoprim and sulfamethoxazole had no further hospital admissions for infections. The pathogenesis of ICL remains unclear. Although only some patients are healthy, most patients present with opportunistic infections. There is no known standard treatment aside from prophylactic antibiotics. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Immunoreactive LH in long-term frozen human urine samples.

PubMed

Singh, Gurmeet Kaur Surindar; Jimenez, Mark; Newman, Ron; Handelsman, David J

2014-04-01

Urine provides a convenient non-invasive alternative to blood sampling for measurement of certain hormones. Urinary luteinizing hormone (LH) measurements have been used for endocrinology research and anti-doping testing. However, the commercially available LH immunoassays are developed and validated for human blood samples but not urine so that LH assays intended for use with urine samples need thorough validation. Therefore, the present study evaluated the measurement of urinary LH immunoreactivity using previously validated immunofluorometric (IF) and immunochemiluminometric (ICL) LH assays after prolonged frozen storage. LH was measured in serial urine samples following administration of a single injection of one of two doses of recombinant human chorionic hormone (rhCG) with assays run at the end of study (2008) and again after four years of frozen (-20 °C) storage where samples were stored without adding preservatives. The ICL assay showed quantitatively reproducible LH measurements after prolonged -20 °C storage. However, the IF immunoassay gave consistently lower LH levels relative to ICL (2008) with a further proportionate reduction after four years of sample storage (2012). Yet, both the assays displayed similar patterns of the time-course of urine LH measurement both before and after four years of frozen storage. In conclusion, we found that both immunoassays are suitable for urinary LH measurements with ICL assay being more robust for quantitative urinary LH measurement such as for anti-doping purposes, whereas the IF could be applicable for research studies where urine LH levels are compared within-study but not in absolute terms. Copyright © 2013 John Wiley & Sons, Ltd.

Solvent isotope-induced equilibrium perturbation for isocitrate lyase.

PubMed

Quartararo, Christine E; Hadi, Timin; Cahill, Sean M; Blanchard, John S

2013-12-23

Isocitrate lyase (ICL) catalyzes the reversible retro-aldol cleavage of isocitrate to generate glyoxylate and succinate. ICL is the first enzyme of the glyoxylate shunt, which allows for the anaplerosis of citric acid cycle intermediates under nutrient limiting conditions. In Mycobacterium tuberculosis, the source of ICL for these studies, ICL is vital for the persistence phase of the bacterium's life cycle. Solvent kinetic isotope effects (KIEs) in the direction of isocitrate cleavage ((D₂O)V = 2.0 ± 0.1, and (D₂O)[V/K(isocitrate)] = 2.2 ± 0.3) arise from the initial deprotonation of the C2 hydroxyl group of isocitrate or the protonation of the aci-acid of the succinate product of the isocitrate aldol cleavage by a solvent-derived proton. This KIE suggested that an equilibrium mixture of all protiated isocitrate, glyoxylate, and succinate prepared in D₂O would undergo transient changes in equilibrium concentrations as a result of the solvent KIE and solvent-derived deuterium incorporation into both succinate and isocitrate. No change in the isotopic composition of glyoxylate was expected or observed. We have directly monitored the changing concentrations of all isotopic species of all reactants and products using a combination of nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. Continuous monitoring of glyoxylate by ¹H NMR spectroscopy shows a clear equilibrium perturbation in D₂O. The final equilibrium isotopic composition of reactants in D₂O revealed dideuterated succinate, protiated glyoxylate, and monodeuterated isocitrate, with the transient appearance and disappearance of monodeuterated succinate. A model for the equilibrium perturbation of substrate species and their time-dependent isotopic composition is presented.

Ubiquitin-like protein UBL5 promotes the functional integrity of the Fanconi anemia pathway.

PubMed

Oka, Yasuyoshi; Bekker-Jensen, Simon; Mailand, Niels

2015-05-12

Ubiquitin and ubiquitin-like proteins (UBLs) function in a wide array of cellular processes. UBL5 is an atypical UBL that does not form covalent conjugates with cellular proteins and which has a known role in modulating pre-mRNA splicing. Here, we report an unexpected involvement of human UBL5 in promoting the function of the Fanconi anemia (FA) pathway for repair of DNA interstrand crosslinks (ICLs), mediated by a specific interaction with the central FA pathway component FANCI. UBL5-deficient cells display spliceosome-independent reduction of FANCI protein stability, defective FANCI function in response to DNA damage and hypersensitivity to ICLs. By mapping the sequence determinants underlying UBL5-FANCI binding, we generated separation-of-function mutants to demonstrate that key aspects of FA pathway function, including FANCI-FANCD2 heterodimerization, FANCD2 and FANCI monoubiquitylation and maintenance of chromosome stability after ICLs, are compromised when the UBL5-FANCI interaction is selectively inhibited by mutations in either protein. Together, our findings establish UBL5 as a factor that promotes the functionality of the FA DNA repair pathway. © 2015 The Authors.

A new study of iodine complexes of oxidized gum arabic: An interaction between iodine monochloride and aldehyde groups.

PubMed

Ali, Akbar; Ganie, Showkat Ali; Mazumdar, Nasreen

2018-01-15

Gum arabic, a plant polysaccharide was oxidized with periodate to produce aldehyde groups by the cleavage of diols present in the sugar units. The oxidized gum was then iodinated with iodine monochloride (ICl) and the interaction between electrophilic iodine, I + and reactive carbonyl groups of the modified gum was studied.Results of titrimetric estimation performed to determine the extent of oxidation and aldehyde content in the oxidized gum showed that degree of oxidation ranged between 19.68-50.19% which was observed to increase with periodate concentration; the corresponding aldehyde content was calculated to be 5.15-40.42%. Different strengths of ICl were used to iodinate the oxidized gum and the iodine content of the complexes varied from 6.11-11.72% as determined by iodometric titration. Structure elucidation of the iodine complexes conclusively established the attachment of ICl molecules to CHO groups. A reaction scheme has been proposed suggesting an electrophilic addition of the reagent to the aldehyde groups, a mechanism that was also supported by iodide ion release studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

The diagnosis and treatment of peripheral lymphedema: 2013 Consensus Document of the International Society of Lymphology.

PubMed

2013-03-01

This International Society of Lymphology (ISL) Consensus Document is the current revision of the 1995 Document for the evaluation and management of peripheral lymphedema (1) for discussion at the XXIV International Congress of Lymphology. It is based upon modifications: [A] suggested and published following the 1997 XVI International Congress of Lymphology (ICL) in Madrid, Spain (2) discussed at the 1999 XVII ICL in Chennai, India (3) and considered/ confirmed at the 2000 (ISL) Executive Committee meeting in Hinterzarten, Germany (4); [B] derived from integration of discussions and written comments obtained during and following the 2001 XVIII ICL in Genoa, Italy as modified at the 2003 ISL Executive Committee meeting in Cordoba, Argentina (5); [C] suggested from comments, criticisms, and rebuttals as published in the December 2004 issue of Lymphology (6); [D] discussed in both the 2005 XX ICL in Salvador, Brazil and the 2007 XXI ICL in Shanghai, China and modified at the 2008 Executive Committee Meeting in Naples, Italy (7,8); and [E] modified from discussions and written comments from the 2009 XXII ICL in Sydney, Australia, the 2011 XXIII ICL in Malmo, Sweden and 2012 Executive Committee Meetings. The document attempts to amalgamate the broad spectrum of protocols advocated worldwide for the diagnosis and treatment of peripheral lymphedema into a coordinated proclamation representing a "Consensus" of the international community. The document is not meant to override individual clinical considerations for problematic patients nor to stifle progress. It is also not meant to be a legal formulation from which variations define medical malpractice. The Society understands that in some clinics the method of treatment derives from national standards while in others access to medical equipment and supplies is limited, and therefore the suggested treatments are impractical. Adaptability and inclusiveness does come at the price that members can rightly be critical of what they see as vagueness or imprecision in definitions, qualifiers in the choice of words (e.g., the use of "may... perhaps... unclear", etc.) and mention (albeit without endorsement) of treatment options supported by limited hard data. Most members are frustrated by the reality that NO treatment method has really undergone a satisfactory meta-analysis (let alone rigorous, randomized, stratified, long-term, controlled study). With this understanding, the absence of definitive answers and optimally conducted clinical trials, and with emerging technologies and new approaches and discoveries on the horizon, some degree of uncertainty, ambiguity, and flexibility along with dissatisfaction with current lymphedema evaluation and management is appropriate and to be expected. We continue to struggle to keep the document concise while balancing the need for depth and details. With these considerations in mind, we believe that this latest version presents a Consensus that embraces the entire ISL membership, rises above national standards, identifies and stimulates promising areas for future research and represents the best judgment of the ISL membership on how to approach patients with peripheral lymphedema as of 2013. Therefore the document has been, and should continue to be, challenged and debated in the pages of Lymphology (e.g., as Letters to the Editor), and ideally will remain a continued focal point for robust discussion at local, national and international conferences in lymphology and related disciplines. We further anticipate as experience evolves and new ideas and technologies emerge that this "living document" will undergo further periodic revision and refinement as the practice and theories of medicine and specifically lymphology change and advance.

Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers.

PubMed

Lombardi, Anne J; Hoskins, Elizabeth E; Foglesong, Grant D; Wikenheiser-Brokamp, Kathryn A; Wiesmüller, Lisa; Hanenberg, Helmut; Andreassen, Paul R; Jacobs, Allison J; Olson, Susan B; Keeble, Winifred W; Hays, Laura E; Wells, Susanne I

2015-04-15

Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ). Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation. The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. ©2015 American Association for Cancer Research.

Solvent Isotope-induced Equilibrium Perturbation for Isocitrate Lyase

PubMed Central

Quartararo, Christine E.; Hadi, Timin; Cahill, Sean M.; Blanchard, John S.

2014-01-01

Isocitrate lyase (ICL) catalyzes the reversible retro-aldol cleavage of isocitrate to generate glyoxylate and succinate. ICL is the first enzyme of the glyoxylate shunt, which allows for the anaplerosis of citric acid cycle intermediates under nutrient limiting conditions. In Mycobacterium tuberculosis, the source of ICL for these studies, ICL is vital for the persistence phase of the bacteria’s life cycle. Solvent kinetic isotope effects (KIEs) in the direction of isocitrate cleavage of D2OV = 2.0 ± 0.1 and D2O[V/Kisocitrate] = 2.2 ± 0.3 arise from the initial deprotonation of the C2 hydroxyl group of isocitrate or the protonation of the aci-acid of succinate product of the isocitrate aldol cleavage by a solvent-derived proton. This KIE suggested that an equilibrium mixture of all protiated isocitrate, glyoxylate and succinate prepared in D2O, would undergo transient changes in equilibrium concentrations as a result of the solvent KIE and solvent-derived deuterium incorporation into both succinate and isocitrate. No change in the isotopic composition of glyoxylate was expected or observed. We have directly monitored the changing concentrations of all isotopic species of all reactants and products using a combination of NMR spectroscopy and mass spectrometry. Continuous monitoring of glyoxylate by 1H NMR spectroscopy shows a clear equilibrium perturbation in D2O. The final equilibrium isotopic composition of reactants in D2O revealed di-deuterated succinate, protiated glyoxylate, and mono-deuterated isocitrate, with the transient appearance and disappearance of mono-deuterated succinate. A model for the equilibrium perturbation of substrate species, and their time-dependent isotopic composition is presented. PMID:24261638

Fanconi anemia: a disorder defective in the DNA damage response.

PubMed

Kitao, Hiroyuki; Takata, Minoru

2011-04-01

Fanconi anemia (FA) is a cancer predisposition disorder characterized by progressive bone marrow failure, congenital developmental defects, chromosomal abnormalities, and cellular hypersensitivity to DNA interstrand crosslink (ICL) agents. So far mutations in 14 FANC genes were identified in FA or FA-like patients. These gene products constitute a common ubiquitin-phosphorylation network called the "FA pathway" and cooperate with other proteins involved in DNA repair and cell cycle control to repair ICL lesions and to maintain genome stability. In this review, we summarize recent exciting discoveries that have expanded our view of the molecular mechanisms operating in DNA repair and DNA damage signaling.

In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection.

PubMed

Aron, Allegra T; Heffern, Marie C; Lonergan, Zachery R; Vander Wal, Mark N; Blank, Brian R; Spangler, Benjamin; Zhang, Yaofang; Park, Hyo Min; Stahl, Andreas; Renslo, Adam R; Skaar, Eric P; Chang, Christopher J

2017-11-28

Iron is an essential metal for all organisms, yet disruption of its homeostasis, particularly in labile forms that can contribute to oxidative stress, is connected to diseases ranging from infection to cancer to neurodegeneration. Iron deficiency is also among the most common nutritional deficiencies worldwide. To advance studies of iron in healthy and disease states, we now report the synthesis and characterization of iron-caged luciferin-1 (ICL-1), a bioluminescent probe that enables longitudinal monitoring of labile iron pools (LIPs) in living animals. ICL-1 utilizes a bioinspired endoperoxide trigger to release d-aminoluciferin for selective reactivity-based detection of Fe 2+ with metal and oxidation state specificity. The probe can detect physiological changes in labile Fe 2+ levels in live cells and mice experiencing iron deficiency or overload. Application of ICL-1 in a model of systemic bacterial infection reveals increased iron accumulation in infected tissues that accompany transcriptional changes consistent with elevations in both iron acquisition and retention. The ability to assess iron status in living animals provides a powerful technology for studying the contributions of iron metabolism to physiology and pathology.

Detection of medically important Candida species by absolute quantitation real-time polymerase chain reaction.

PubMed

Than, Leslie Thian Lung; Chong, Pei Pei; Ng, Kee Peng; Seow, Heng Fong

2015-01-01

The number of invasive candidiasis cases has risen especially with an increase in the number of immunosuppressed and immunocom promised patients. The early detection of Candida species which is specific and sensitive is important in determining the correct administration of antifungal drugs to patients. This study aims to develop a method for the detection, identification and quantitation of medically important Candida species through quantitative polymerase chain reaction (qPCR). The isocitrate lyase (ICL) gene which is not found in mammals was chosen as the target gene of real-time PCR. Absolute quantitation of the gene copy number was achieved by constructing the plasmid containing the ICL gene which is used to generate standard curve. Twenty fungal species, two bacterial species and human DNA were tested to check the specificity of the detection method. All eight Candida species were successfully detected, identified and quantitated based on the ICL gene. A seven-log range of the gene copy number and a minimum detection limit of 10(3) copies were achieved. A one-tube absolute quantification real-time PCR that differentiates medically important Candida species via individual unique melting temperature was achieved. Analytical sensitivity and specificity were not compromised.

Optimization of a Two Stage Pulse Tube Refrigerator for the Integrated Current Lead System

NASA Astrophysics Data System (ADS)

Maekawa, R.; Matsubara, Y.; Okada, A.; Takami, S.; Konno, M.; Tomioka, A.; Imayoshi, T.; Hayashi, H.; Mito, T.

2008-03-01

Implementation of a conventional current lead with a pulse tube refrigerator has been validated to be working as an Integrated Current Lead (ICL) system for the Superconducting Magnetic Energy Storage (SMES). Realization of the system is primarily accounted for the flexibility of a pulse tube refrigerator, which does not posses any mechanical piston and/or displacer. As for an ultimate version of the ICL system, a High Temperature Superconducting (HTS) lead links a superconducting coil with a conventional copper lead. To ensure the minimization of heat loads to the superconducting coil, a pulse tube refrigerator has been upgraded to have a second cooling stage. This arrangement reduces not only the heat loads to the superconducting coil but also the operating cost for a SMES system. A prototype two-stage pulse tube refrigerator, series connected arrangement, was designed and fabricated to satisfy the requirements for the ICL system. Operation of the first stage refrigerator is a four-valve mode, while the second stage utilizes a double inlet configuration to ensure its confined geometry. The paper discusses the optimization of second stage cooling to validate the conceptual design

[Management of financial resources of permanent education in health: challenge of the in-service learning integration committees].

PubMed

Ferraz, Fabiane; Backes, Vânia Marli Schubert; Mercado-Martinez, Francisco Javier; Feuerwerker, Laura Camargo Macruz; Lino, Mônica Motta

2013-06-01

Despite adhering to the dynamics established in the Management Pact, the use of financial resources of Permanent Education in Health (PEH) still features as a problem in Brazil. This study analyzes how the management of these financial resources by two Permanent In-Service Learning Integration Committees (ICLS) evolves in the State of Santa Catarina, Brazil. It involves a qualitative, participatory research study adapted from Paulo Freire's Thematic Research conducted with 56 members from two ICLS between May and December 2009. After setting up the research groups, the members participated in the stages of theme generation surveys, encoding, decoding, and critical exposition of the reality. Participant observation and dialogue were the main data collection techniques. The results indicate that the two ICLS are not dissimilar in terms of issues of management of resources destined for policy, with bureaucracy, the indefinition of forms of financial management and delays that permeate regional structures responsible for resource management being the main factors detected. The participants considered the elaboration of PEH actions in the management of financial resources at state level to be the main opportunities for change.

Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions

PubMed Central

Basourakos, Spyridon P.; Li, Likun; Aparicio, Ana M.; Corn, Paul G.; Kim, Jeri; Thompson, Timothy C.

2017-01-01

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a “molecular landscape,” i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with ”BRCAness”, i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent–induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. PMID:27978798

Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions.

PubMed

Basourakos, Spyridon P; Li, Likun; Aparicio, Ana M; Corn, Paul G; Kim, Jeri; Thompson, Timothy C

2017-01-01

Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a "molecular landscape," i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with "BRCAness", i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a molecular landscape that can be further exploited therapeutically; (2) multiple points of potential intervention after ICL agent-induced crosslinking that further predispose to cell death and can be incorporated into a systematic, therapeutic rationale for combination/ maintenance therapy using DDR-targeting agents; and (3) available agents that can be considered for use in combination/maintenance clinical protocols with platinum-based agents for patients with advanced malignancies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Stimulation of in vivo hepatic uptake and in vitro hepatic binding of (/sup 125/I)2-lodo-3,7,8-trichlorodibenzo-p-dioxin by the administration of agonist for the Ah receptor

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

Poland, A.; Teitelbaum, P.; Glover, E.

1989-07-01

(125I)2-lodo-3,7,8-trichlorodibenzo-p-dioxin ((125I)Cl3DpD), a radiolabeled, isosteric, analogue of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was synthesized and used to study in vivo tissue localization and in vivo tissue binding. Twenty-four hours after the administration of a tracer dose (1 X 10(-10) mol/kg) of (125I) Cl3DpD to C57BL/6J mice, the hepatic concentration of radioactivity was 1-2% of the administered dose, whereas in mice pretreated with TCDD (1 X 10(-7) mol/kg), the hepatic accumulation of radiolabel was 25-30% of that administered. Liver homogenate from TCDD-treated mice bound 4 to 10 times more (125I)Cl3DpD than homogenate from control mice. The enhancement of in vivo uptake and in vitromore » tissue binding of (125I)Cl3DpD by TCDD administration was confined to liver and was not observed in other tissues examined, kidney, lung, spleen, small intestines, and muscle. The administration of TCDD to C57BL/6J mice produces dose-related stimulation of in vivo hepatic uptake of (125I)Cl3DpD, binding of radioligand to liver homogenate, and hepatic aryl hydrocarbon hydroxylase activity, with the dose for half-maximal stimulation, ED50, varying from 1.5 to 4.0 x 10(-9) mol/kg. In congenic C57BL/6J (Ahd/Ahd) mice, which express the lower affinity Ah receptor, the ED50 values for all three responses were shifted to approximately 10-fold higher doses. 3,3',4,4',5,5'-Hexabromobiphenyl, a weak agonist for the Ah receptor produced a dose-related stimulation of these three responses in C57BL/6J mice (ED50 values of approximately 5 X 10(-7) mol/kg), but was without effect in C57BL/6J (Ahd/Ahd) mice. Stimulation of vivo hepatic uptake and in vitro liver homogenate binding of (125I)Cl3DpD was produced by administration of Ah agonists, such as 2,3,7,8-tetrachlorodibenzofuran and beta-naphthoflavone, but inactive congeners and other compounds that do not act via the Ah receptor.« less

Psoriasis associated with idiopathic CD4+ T-cell lymphopenia: a regulatory T-cell defect?

PubMed

Baroudjian, B; Viguier, M; Battistella, M; Beneton, N; Pagès, C; Gener, G; Bégon, E; Bachelez, H

2014-07-01

Idiopathic CD4(+) lymphocytopenia (ICL) is a rare immunodeficiency syndrome of unknown origin for which the increased risks of opportunistic infections and of malignancies have been well established; however, skin dysimmune diseases, including psoriasis, have been scarcely reported up to now. We report herein the severe course of psoriasis in four patients with ICL, and show evidence for a defect in the skin recruitment of regulatory CD4(+) FoxP3(+) T cells. These data raise the apparent paradigm of the occurrence of a severe immunomediated disease together with a profound T-cell defect, a model that might also apply to other immune deficiencies associated with psoriasis. © 2014 British Association of Dermatologists.

On the modified active region design of interband cascade lasers

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

Motyka, M.; Ryczko, K.; Dyksik, M.

2015-02-28

Type II InAs/GaInSb quantum wells (QWs) grown on GaSb or InAs substrates and designed to be integrated in the active region of interband cascade lasers (ICLs) emitting in the mid infrared have been investigated. Optical spectroscopy, combined with band structure calculations, has been used to probe their electronic properties. A design with multiple InAs QWs has been compared with the more common double W-shaped QW and it has been demonstrated that it allows red shifting the emission wavelength and enhancing the transition oscillator strength. This can be beneficial for the improvements of the ICLs performances, especially when considering their long-wavelengthmore » operation.« less

FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link repair.

PubMed

Liu, Ting; Ghosal, Gargi; Yuan, Jingsong; Chen, Junjie; Huang, Jun

2010-08-06

Fanconi anemia (FA) is caused by mutations in 13 Fanc genes and renders cells hypersensitive to DNA interstrand cross-linking (ICL) agents. A central event in the FA pathway is mono-ubiquitylation of the FANCI-FANCD2 (ID) protein complex. Here, we characterize a previously unrecognized nuclease, Fanconi anemia-associated nuclease 1 (FAN1), that promotes ICL repair in a manner strictly dependent on its ability to accumulate at or near sites of DNA damage and that relies on mono-ubiquitylation of the ID complex. Thus, the mono-ubiquitylated ID complex recruits the downstream repair protein FAN1 and facilitates the repair of DNA interstrand cross-links.

Biallelic mutations in BRCA1 cause a new Fanconi anemia subtype.

PubMed

Sawyer, Sarah L; Tian, Lei; Kähkönen, Marketta; Schwartzentruber, Jeremy; Kircher, Martin; Majewski, Jacek; Dyment, David A; Innes, A Micheil; Boycott, Kym M; Moreau, Lisa A; Moilanen, Jukka S; Greenberg, Roger A

2015-02-01

Deficiency in BRCA-dependent DNA interstrand crosslink (ICL) repair is intimately connected to breast cancer susceptibility and to the rare developmental syndrome Fanconi anemia. Bona fide Fanconi anemia proteins, BRCA2 (FANCD1), PALB2 (FANCN), and BRIP1 (FANCJ), interact with BRCA1 during ICL repair. However, the lack of detailed phenotypic and cellular characterization of a patient with biallelic BRCA1 mutations has precluded assignment of BRCA1 as a definitive Fanconi anemia susceptibility gene. Here, we report the presence of biallelic BRCA1 mutations in a woman with multiple congenital anomalies consistent with a Fanconi anemia-like disorder and breast cancer at age 23. Patient cells exhibited deficiency in BRCA1 and RAD51 localization to DNA-damage sites, combined with radial chromosome formation and hypersensitivity to ICL-inducing agents. Restoration of these functions was achieved by ectopic introduction of a BRCA1 transgene. These observations provide evidence in support of BRCA1 as a new Fanconi anemia gene (FANCS). We establish that biallelic BRCA1 mutations cause a distinct FA-S, which has implications for risk counselling in families where both parents harbor BRCA1 mutations. The genetic basis of hereditary cancer susceptibility syndromes provides diagnostic information, insights into treatment strategies, and more accurate recurrence risk counseling to families. ©2014 American Association for Cancer Research.

Immunization by intrabronchial administration to 1-week-old foals of an unmarked double gene disruption strain of Rhodococcus equi strain 103+.

PubMed

Pei, Yanlong; Nicholson, Vivian; Woods, Katharine; Prescott, John F

2007-11-15

Rhodococcus equi causes fatal granulomatous pneumonia in foals and immunocompromised animals and humans. However, there is no effective vaccine against this infection. In this study, the chromosomal genes isocitrate lyase (icl) and cholesterol oxidase (choE) were chosen as targets for mutation and assessment of the double mutant as an intrabronchial vaccine in 1-week-old foals. Using a modification of a suicide plasmid previously developed in this laboratory, we developed a choE-icl unmarked deletion mutant of R. equi strain 103+. Five 1-week-old foals were infected intrabronchially with the mutant and challenged intrabronchially with the parent, virulent, strain 2 weeks later. Three of the foals were protected against pneumonia caused by the virulent strain, but the other two foals developed pneumonia caused by the mutant strain during the post-challenge period. Since infection of 3-week-old foals by an icl mutant in an earlier study had shown complete attenuation of the strain, we conclude that a proportion of foals in the 1st week or so of life are predisposed to developing R. equi pneumonia because of an inability to mount an effective immune response. This has been suspected previously but this is the first time that this has been demonstrated experimentally.

β2-spectrin depletion impairs DNA damage repair

PubMed Central

Horikoshi, Nobuo; Pandita, Raj K.; Mujoo, Kalpana; Hambarde, Shashank; Sharma, Dharmendra; Mattoo, Abid R.; Chakraborty, Sharmistha; Charaka, Vijaya; Hunt, Clayton R.; Pandita, Tej K.

2016-01-01

β2-Spectrin (β2SP/SPTBN1, gene SPTBN1) is a key TGF-β/SMAD3/4 adaptor and transcriptional cofactor that regulates TGF-β signaling and can contribute to liver cancer development. Here we report that cells deficient in β2-Spectrin (β2SP) are moderately sensitive to ionizing radiation (IR) and extremely sensitive to agents that cause interstrand cross-links (ICLs) or replication stress. In response to treatment with IR or ICL agents (formaldehyde, cisplatin, camptothecin, mitomycin), β2SP deficient cells displayed a higher frequency of cells with delayed γ-H2AX removal and a higher frequency of residual chromosome aberrations. Following hydroxyurea (HU)-induced replication stress, β2SP-deficient cells displayed delayed disappearance of γ-H2AX foci along with defective repair factor recruitment (MRE11, CtIP, RAD51, RPA, and FANCD2) as well as defective restart of stalled replication forks. Repair factor recruitment is a prerequisite for initiation of DNA damage repair by the homologous recombination (HR) pathway, which was also defective in β2SP deficient cells. We propose that β2SP is required for maintaining genomic stability following replication fork stalling, whether induced by either ICL damage or replicative stress, by facilitating fork regression as well as DNA damage repair by homologous recombination. PMID:27248179

Perceived body discomfort and trunk muscle activity in three prolonged sitting postures

PubMed Central

Waongenngarm, Pooriput; Rajaratnam, Bala S.; Janwantanakul, Prawit

2015-01-01

[Purpose] This study aimed to investigate the perceived discomfort and trunk muscle activity in three different 1-hour sitting postures. [Subjects] A repeated-measures design study was conducted on 10 healthy subjects. [Methods] Each subject sat for an hour in three sitting postures (i.e., upright, slumped, and forward leaning sitting postures). Subjects rated perceived body discomfort using Borg’s CR-10 scale at the beginning and after 1 hour sitting. The electromyographic activity of the trunk muscle activity was recorded during the 1-hour period of sitting. [Results] The forward leaning sitting posture led to higher Borg scores in the low back than those in the upright (p = 0.002) and slumped sitting postures (p < 0.001). The forward leaning posture was significantly associated with increased iliocostalis lumborum pars thoracis (ICL) and superficial lumbar multifidus (MF) muscle activity compared with the upright and slumped sitting postures. The upright sitting posture was significantly associated with increased internal oblique (IO)/transversus abdominis (TrA) and ICL muscle activity compared with the slumped sitting posture. [Conclusion] The sitting posture with the highest low back discomfort after prolonged sitting was the forward leaning posture. Sitting in an upright posture is recommended because it increases IO/TrA muscle activation and induces only relatively moderate ICL and MF muscle activation. PMID:26311951

Development and Evaluation of a Pedagogical Tool to Improve Understanding of a Quality Checklist: A Randomised Controlled Trial

PubMed Central

Fourcade, Lola; Boutron, Isabelle; Moher, David; Ronceray, Lucie; Baron, Gabriel; Ravaud, Philippe

2007-01-01

Objective: The aim of this study was to develop and evaluate a pedagogical tool to enhance the understanding of a checklist that evaluates reports of nonpharmacological trials (CLEAR NPT). Design: Paired randomised controlled trial. Participants: Clinicians and systematic reviewers. Interventions: We developed an Internet-based computer learning system (ICLS). This pedagogical tool used many examples from published randomised controlled trials to demonstrate the main coding difficulties encountered when using this checklist. Randomised participants received either a specific Web-based training with the ICLS (intervention group) or no specific training. Outcome measures: The primary outcome was the rate of correct answers compared to a criterion standard for coding a report of randomised controlled trials with the CLEAR NPT. Results: Between April and June 2006, 78 participants were randomly assigned to receive training with the ICLS (39) or no training (39). Participants trained by the ICLS did not differ from the control group in performance on the CLEAR NPT. The mean paired difference and corresponding 95% confidence interval was 0.5 (−5.1 to 6.1). The rate of correct answers did not differ between the two groups regardless of the CLEAR NPT item. Combining both groups, the rate of correct answers was high or items related to allocation sequence (79.5%), description of the intervention (82.0%), blinding of patients (79.5%), and follow-up schedule (83.3%). The rate of correct answers was low for items related to allocation concealment (46.1%), co-interventions (30.3%), blinding of outcome assessors (53.8%), specific measures to avoid ascertainment bias (28.6%), and intention-to-treat analysis (60.2%). Conclusions: Although we showed no difference in effect between the intervention and control groups, our results highlight the gap in knowledge and urgency for education on important aspects of trial conduct. PMID:17479163

Compensated Cell Enlargement in fugu5 is Specifically Triggered by Lowered Sucrose Production from Seed Storage Lipids.

PubMed

Takahashi, Kazuki; Morimoto, Ryousuke; Tabeta, Hiromitsu; Asaoka, Mariko; Ishida, Masanori; Maeshima, Masayoshi; Tsukaya, Hirokazu; Ferjani, Ali

2017-04-01

To reveal the logic of size regulation in multicellular organisms, we have used Arabidopsis thaliana as a model organism and its leaves as a model organ. We discovered the existence of a compensatory system, whereby a decrease in leaf cell number often triggers unusual cell enlargement. However, despite the large number of compensation-exhibiting mutants analyzed to date, we have only a limited understanding of the detailed molecular mechanisms triggering the decrease in cell number and subsequent compensated cell enlargement (CCE). CCE in fugu5, the vacuolar type H+-pyrophosphatase loss-of-function mutant, is specific to cotyledons and completely suppressed when sucrose (Suc) is supplied or cytosolic pyrophosphate (PPi) is specifically removed. In addition, several lines of evidence suggest that excess cytosolic PPi in fugu5 impairs gluconeogenesis from triacylglycerol (TAG) to Suc. Here, detailed cellular phenotyping revealed that the loss-of-function mutants icl-2, mls-2 and pck1-2 triggered CCE in cotyledons. All double mutant combinations between fugu5-1 and the above three mutants exhibited compensation, but did not display a further increase in cell size. Importantly, similar phenotypes were observed in icl-2 mls-2, icl-2 pck1-2 and mls-2 pck1-2. Quantification of TAG breakdown and Suc contents further supported our findings. Taken together, we demonstrate that de novo Suc synthesis from TAG is fundamentally important for proper resumption of post-germinative cotyledon development. Moreover, provided that icl-2, mls-2 and pck1-2 are only compromised in Suc biosynthesis de novo from TAG, our findings clearly indicate that lowered Suc production in fugu5, rather than excess cytosolic PPi, is the direct trigger of CCE. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Determination of iodide with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in comparison with the ICl-method. Analytical methods of pharmacopeias with DBH in respect to environmental and economical concern. Part 3.

PubMed

Hilp, M; Senjuk, S

2001-06-01

USP 1995 (The United States Pharmacopeia, 23rd Edit., (1995), potassium iodide p. 1265, sodium iodide p. 1424), PH. EUR. 1997 (European Pharmacopoeia, third ed., Council of Europe, Strasbourg, (1997), potassium iodide p. 1367, sodium iodide p. 1493) and JAP 1996 (The Japanes Pharmacopoeia, 13th ed. (1996), potassium iodide p. 578, sodium iodide p. 630) determine iodide with the ICl-method (J. Am. Chem. Soc. 25 (1903) 756-761; Z. Anorg. Chem. 36 (1903) 76-83; Fresenius Z. Anal. Chem. 106 (1936) 12-23; Arzneibuch-Kommentar, Wissenschaftliche Erläuterungen zum Europäischen Arzneibuch, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, Govi-Verlag - Pharmazeutischer Verlag GmbH, Eschborn, 12th suppl. (1999), K10 p. 2), using chloroform, which is toxic and hazardous to environment. Without the application of chlorinated hydrocarbons USP 2000 (The United State Pharmacopeia, 24th ed. (2000), potassium iodide p. 1368, sodium iodide p. 1535) and Brit 1999 (British Pharmacopoeia London, (1999), Appendix VIII C, p. A162) titrate iodide with the redox indicator amaranth. A titration with potentiometric indication giving two end-points at the step of I(2) and [ICl(2)](-) is described. Due to the high concentration of hydrochloric acid required for the ICl-method, the determination with DBH (1,3-dibromo-5,5-dimethylhydantoin; 1,3-dibromo-5,5-dimethyl-2,4-imidazolidinedione) can be recommended and is performed easily. Similarly, the iodide content of gallamine triethiodide may be analyzed with DBH by application of a visual two-phase titration in water and ethyl acetate or with potentiometric indication in a mixture of 2-propanol and water. During the removal of the excess of DBH 4-bromo-triethylgallamine (2,2',2"-[1-bromo-benzene-2,3,4-triyltris(oxy)]N,N,N-triethylethanium) is formed.

Physiological and enzymatic alterations in sesame seeds submitted to different osmotic potentials.

PubMed

Pires, R M O; Àvila, M A B; Leite, D G; Santos, H O; Souza, G A; Von Pinho, E V R

2017-08-17

With the imminence of global climate changes that affect the temperature and the rainfall uniformity, it is growing the concern about the adaptation of crops to the water deficit. Thus, the objective of this study was to evaluate alterations in physiological and enzymatic mechanisms during the germination process of sesame seeds under different water availability. To simulate the water restriction we used PEG6000, a high molecular weight molecule that does not penetrate the seed structure but allows different osmotic potentials. The treatments were -0.1, -0.2, and -0.3 MPa, and the control. Germination, first-count germination, germination velocity index, and length and dry mass of the hypocotyl and radicle were performed. The seeds were weighed before and after treatments every 3 h. After each weighing, 100 seeds were taken for analysis of the enzymes alcohol dehydrogenase (ADH), malate dehydrogenase, esterase, catalase (CAT), superoxide dismutase (SOD), isocitrate lyase (ICL), and glutamate dehydrogenase (GTDH). The statistical design was completely randomized with five replications. PEG6000 prolonged ADH activity during the beginning of germination, maintaining the anaerobic metabolism for longer. Subsequently, their activity was reduced, as well as ICL, favoring the deterioration of the seeds that take the time to germinate. Behavior was evidenced by the appearance of SOD, CAT, and GTDH isoforms after 24 h of imbibition when water restriction was imposed. Therefore, the PEG600 is efficient in simulating water deficit conditions in future scenarios of climate change, offering impotent information regarding the germination behavior of the plants under these conditions.

Use of inequality constrained least squares estimation in small area estimation

NASA Astrophysics Data System (ADS)

Abeygunawardana, R. A. B.; Wickremasinghe, W. N.

2017-05-01

Traditional surveys provide estimates that are based only on the sample observations collected for the population characteristic of interest. However, these estimates may have unacceptably large variance for certain domains. Small Area Estimation (SAE) deals with determining precise and accurate estimates for population characteristics of interest for such domains. SAE usually uses least squares or maximum likelihood procedures incorporating prior information and current survey data. Many available methods in SAE use constraints in equality form. However there are practical situations where certain inequality restrictions on model parameters are more realistic. It will lead to Inequality Constrained Least Squares (ICLS) estimates if the method used is least squares. In this study ICLS estimation procedure is applied to many proposed small area estimates.

Activity loss by H46A mutation in Mycobacterium tuberculosis isocitrate lyase is due to decrease in structural plasticity and collective motions of the active site.

PubMed

Shukla, Rohit; Shukla, Harish; Tripathi, Timir

2018-01-01

Mycobacterium tuberculosis isocitrate lyase (MtbICL) is a crucial enzyme of the glyoxylate cycle and is a validated anti-tuberculosis drug target. Structurally distant, non-active site mutation (H46A) in MtbICL has been found to cause loss of enzyme activity. The aim of the present work was to explore the structural alterations induced by H46A mutation that caused the loss of enzyme activity. The structural and dynamic consequences of H46A mutation were studied using multiple computational methods such as docking, molecular dynamics simulation and residue interaction network analysis (RIN). Principal component analysis and cross correlation analysis revealed the difference in conformational flexibility and collective modes of motions between the wild-type and mutant enzyme, particularly in the active site region. RIN analysis revealed that the active site geometry was disturbed in the mutant enzyme. Thus, the dynamic perturbation of the active site led to enzyme transition from its active form to inactive form upon mutation. The computational analyses elucidated the mutant-specific conformational alterations, differential dominant motions, and anomalous residue level interactions that contributed to the abrogated function of mutant MtbICL. An understanding of interactions of mutant enzymes may help in modifying the existing drugs and designing improved drugs for successful control of tuberculosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks.

PubMed

Chun, Min Jeong; Kim, Sunshin; Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-08-16

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway.

The novel choline kinase inhibitor ICL-CCIC-0019 reprograms cellular metabolism and inhibits cancer cell growth

PubMed Central

Trousil, Sebastian; Kaliszczak, Maciej; Schug, Zachary; Nguyen, Quang-De; Tomasi, Giampaolo; Favicchio, Rosy; Brickute, Diana; Fortt, Robin; Twyman, Frazer J.; Carroll, Laurence; Kalusa, Andrew; Navaratnam, Naveenan; Adejumo, Thomas; Carling, David; Gottlieb, Eyal; Aboagye, Eric O.

2016-01-01

The glycerophospholipid phosphatidylcholine is the most abundant phospholipid species of eukaryotic membranes and essential for structural integrity and signaling function of cell membranes required for cancer cell growth. Inhibition of choline kinase alpha (CHKA), the first committed step to phosphatidylcholine synthesis, by the selective small-molecule ICL-CCIC-0019, potently suppressed growth of a panel of 60 cancer cell lines with median GI50 of 1.12 μM and inhibited tumor xenograft growth in mice. ICL-CCIC-0019 decreased phosphocholine levels and the fraction of labeled choline in lipids, and induced G1 arrest, endoplasmic reticulum stress and apoptosis. Changes in phosphocholine cellular levels following treatment could be detected non-invasively in tumor xenografts by [18F]-fluoromethyl-[1,2–2H4]-choline positron emission tomography. Herein, we reveal a previously unappreciated effect of choline metabolism on mitochondria function. Comparative metabolomics demonstrated that phosphatidylcholine pathway inhibition leads to a metabolically stressed phenotype analogous to mitochondria toxin treatment but without reactive oxygen species activation. Drug treatment decreased mitochondria function with associated reduction of citrate synthase expression and AMPK activation. Glucose and acetate uptake were increased in an attempt to overcome the metabolic stress. This study indicates that choline pathway pharmacological inhibition critically affects the metabolic function of the cell beyond reduced synthesis of phospholipids. PMID:27206796

An Inequality Constrained Least-Squares Approach as an Alternative Estimation Procedure for Atmospheric Parameters from VLBI Observations

NASA Astrophysics Data System (ADS)

Halsig, Sebastian; Artz, Thomas; Iddink, Andreas; Nothnagel, Axel

2016-12-01

On its way through the atmosphere, radio signals are delayed and affected by bending and attenuation effects relative to a theoretical path in vacuum. In particular, the neutral part of the atmosphere contributes considerably to the error budget of space-geodetic observations. At the same time, space-geodetic techniques become more and more important in the understanding of the Earth's atmosphere, because atmospheric parameters can be linked to the water vapor content in the atmosphere. The tropospheric delay is usually taken into account by applying an adequate model for the hydrostatic component and by additionally estimating zenith wet delays for the highly variable wet component. Sometimes, the Ordinary Least Squares (OLS) approach leads to negative estimates, which would be equivalent to negative water vapor in the atmosphere and does, of course, not reflect meteorological and physical conditions in a plausible way. To cope with this phenomenon, we introduce an Inequality Constrained Least Squares (ICLS) method from the field of convex optimization and use inequality constraints to force the tropospheric parameters to be non-negative allowing for a more realistic tropospheric parameter estimation in a meteorological sense. Because deficiencies in the a priori hydrostatic modeling are almost fully compensated by the tropospheric estimates, the ICLS approach urgently requires suitable a priori hydrostatic delays. In this paper, we briefly describe the ICLS method and validate its impact with regard to station positions.

Stability of bromine, iodine monochloride, copper (II) chloride, and nickel (II) chloride intercalated pitch-based graphite fibers

NASA Technical Reports Server (NTRS)

Gaier, James R.; Slabe, Melissa E.; Shaffer, Nanette

1987-01-01

Four different grades of pitch-based graphite fibers (Amoco P-55, P-75, P-100. and P-120) were intercalated with each of four different intercalates: bromine (Br2), iodine monochloride (ICl), copper (II) chloride (CuCl2), and nickel (II) chloride (NiCl2). The P-55 fibers did not react with Br2 or NiCl2, and the P-75 did not react with NiCl2. The stability of the electrical resistance of the intercalated fibers was monitored over long periods of time in ambient, high humidity (100 percent at 60 C), vacuum (10 to the -6 torr), and high temperature (up to 400 C) conditions. Fibers with lower graphitization form graphite intercalation compounds (GIC's) which are more stable than those with higher graphitization (i.e., P-55 (most stable) greater than P-75 greater than P-100 greater than P-120 (least stable). Br2 formed the most stable GIC's followed in order of decreasing stability by ICl, CuCl2, and NiCl2. While Br2 GIC's had the most stability, ICl had the advantages of forming GIC's with slightly greater reduction in resistance (by about 10%) than Br2, and the ability to intercalate P-55 fiber. Transition metal chlorides are susceptible to water vapor and high temperature. The stability of fibers in composites differs.

Space Transportation System Liftoff Debris Mitigation Process Overview

NASA Technical Reports Server (NTRS)

Mitchell, Michael; Riley, Christopher

2011-01-01

Liftoff debris is a top risk to the Space Shuttle Vehicle. To manage the Liftoff debris risk, the Space Shuttle Program created a team with in the Propulsion Systems Engineering & Integration Office. The Shutt le Liftoff Debris Team harnesses the Systems Engineering process to i dentify, assess, mitigate, and communicate the Liftoff debris risk. T he Liftoff Debris Team leverages off the technical knowledge and expe rtise of engineering groups across multiple NASA centers to integrate total system solutions. These solutions connect the hardware and ana lyses to identify and characterize debris sources and zones contribut ing to the Liftoff debris risk. The solutions incorporate analyses sp anning: the definition and modeling of natural and induced environmen ts; material characterizations; statistical trending analyses, imager y based trajectory analyses; debris transport analyses, and risk asse ssments. The verification and validation of these analyses are bound by conservative assumptions and anchored by testing and flight data. The Liftoff debris risk mitigation is managed through vigilant collab orative work between the Liftoff Debris Team and Launch Pad Operation s personnel and through the management of requirements, interfaces, r isk documentation, configurations, and technical data. Furthermore, o n day of launch, decision analysis is used to apply the wealth of ana lyses to case specific identified risks. This presentation describes how the Liftoff Debris Team applies Systems Engineering in their proce sses to mitigate risk and improve the safety of the Space Shuttle Veh icle.

Inertia critical layers and their impacts on nongeostrophic baroclinic instability

NASA Astrophysics Data System (ADS)

Shen, Bo-Wen

We investigate the effects of critical levels (CLs) on a baroclinic flow over mountains, nongeostrophic (NG) inertia critical layer instability, and NG baroclinic instability (BI) in a three-layer atmosphere with a small Richardson number (Ri) in the middle layer. We develop a numerical wave decomposition method in Chapter 2, which is found to be useful in determining the reflection coefficient (Ref) numerically when the flow system is too complicated to obtain Ref analytically. Effects of CLs on flow over mountains are studied both analytically and numerically in Chapter 3. We define the effective inertia critical level (ICL) as the height above which inertia-gravity waves attenuate significantly. Based on numerical simulations with a broad range of Rossby number (Ro) and Ri, four wave regimes are found: (a) Regime I: inertia- gravity waves. The flow behaves like unsheared inertia- gravity waves and the effective lower ICL plays a similar role as the classical critical level (CCL) does in a nonrotating flow. (b) Regime II: combined inertia-gravity waves and baroclinic lee waves. These waves behave like those in Regime I below the lower effective ICL, and like baroclinic lee waves near the CCL. (c) Regime III: combined evanescent and baroclinic lee waves. These waves still behave like baroclinic lee waves near the CCL, but are trapped near the surface. (d) Regime IV: transient waves. NG baroclinic instability exists, as evidenced by the positive domain-averaged north-south heat flux. Wave regime IV is further investigated in Chapter 5. We identify the NG baroclinic instability in Chapter 3 as an inertia critical layer (ICLY) instability. The role of the upper inertia critical level in this instability has been studied by choosing a periodic mountain. When only the CCL and upper ICL are present in the domain, the mesoscale ICLY instability tends to occur. For a periodic mountain ridge, the ICLY instability selects the mountain's tvavelength as its wavelength of maximum growth. For an isolated mountain ridge, the NG baroclinic lee wave is established in the beginning for flows with small Ri, which then develops its own upper ICL. The stability of Lindzen and Tung's (1976, hereafter LT76) type of three-layer nonrotating/rotating atmosphere is discussed in Chapter 6. We first investigate the transient dynamics of wave ducting by a numerical model. The adjustment time for waves to be ducted depends on the atmospheric structure and horizontal wavelength. Second, we study the effects of Coriolis force on LT76's wave ducting mechanism, and show that a wave with wavelength on the order of 100 km is hardly ducted. (Abstract shortened by UMI.)

Phakic Intraocular Collamer Lens (Visian ICL) Implantation for Correction of Myopia in Spectacle-Aversive Special Needs Children.

PubMed

Tychsen, Lawrence; Faron, Nicholas; Hoekel, James

2017-03-01

A subset of children with high anisometropia or isoametropia and neurobehavioral disorders have chronic difficulties with spectacle or contact lens wear. We report the results of refractive surgery in a series of these children treated using bilateral or unilateral intraocular collamer lens (Visian ICL) implantation for moderate to high myopia. Prospective nonrandomized cohort study. Clinical course and outcome data were collated prospectively for 40 implanted eyes in 23 children (mean age 10.2 ± 5.3 years, range, 1.8-17 years). Myopia ranged from -3.0 to -14.5 diopters (D), mean -9.2 ± 3.5 D. Goal refraction was plano to +1 D. Correction was achieved by sulcus implantation of a Visian ICL (STAAR Surgical, Monrovia, California, USA) under general anesthesia. Mean follow-up was 15.1 months (range, 6-22 months). Thirty-five eyes (88%) were corrected to within ±1.0 D of goal refraction; the other 5 (12%) were corrected to within 1.5 D. Uncorrected distance visual acuity improved substantially in all eyes (from mean 20/1050 [logMAR 1.72] to mean 20/42 [logMAR 0.48]). Spherical regression at last follow-up was an average of +0.59 D. Visuomotor comorbidities (eg, amblyopia, nystagmus, foveopathy, optic neuropathy) accounted for residual postoperative subnormal visual acuity. Thirteen of the 23 children (57%) had a neurobehavioral disorder (eg, developmental delay/intellectual disability/mental retardation, Down syndrome, cerebral palsy, autism spectrum disorder). Eighty-five percent (11/13) of those children were reported to have enhanced visual awareness, attentiveness, or social interactions. Endothelial cell density was measureable in 6 cooperative children (10 eyes), showing an average 1% decline. Central corneal thickness, measured in all children, increased an average of 8 μm. Two children (8%) required unplanned return to the operating room on the first postoperative day to alleviate pupillary block caused by a nonpatent iridotomy. No other complications were encounterd. Visian ICL implantation improves visual function in special needs children who have moderate to high myopia and difficulties wearing glasses or contact lenses. Copyright © 2016 Elsevier Inc. All rights reserved.

Metabolic adaptation of two in silico mutants of Mycobacterium tuberculosis during infection.

PubMed

López-Agudelo, Víctor A; Baena, Andres; Ramirez-Malule, Howard; Ochoa, Silvia; Barrera, Luis F; Ríos-Estepa, Rigoberto

2017-11-21

Up to date, Mycobacterium tuberculosis (Mtb) remains as the worst intracellular killer pathogen. To establish infection, inside the granuloma, Mtb reprograms its metabolism to support both growth and survival, keeping a balance between catabolism, anabolism and energy supply. Mtb knockouts with the faculty of being essential on a wide range of nutritional conditions are deemed as target candidates for tuberculosis (TB) treatment. Constraint-based genome-scale modeling is considered as a promising tool for evaluating genetic and nutritional perturbations on Mtb metabolic reprogramming. Nonetheless, few in silico assessments of the effect of nutritional conditions on Mtb's vulnerability and metabolic adaptation have been carried out. A genome-scale model (GEM) of Mtb, modified from the H37Rv iOSDD890, was used to explore the metabolic reprogramming of two Mtb knockout mutants (pfkA- and icl-mutants), lacking key enzymes of central carbon metabolism, while exposed to changing nutritional conditions (oxygen, and carbon and nitrogen sources). A combination of shadow pricing, sensitivity analysis, and flux distributions patterns allowed us to identify metabolic behaviors that are in agreement with phenotypes reported in the literature. During hypoxia, at high glucose consumption, the Mtb pfkA-mutant showed a detrimental growth effect derived from the accumulation of toxic sugar phosphate intermediates (glucose-6-phosphate and fructose-6-phosphate) along with an increment of carbon fluxes towards the reductive direction of the tricarboxylic acid cycle (TCA). Furthermore, metabolic reprogramming of the icl-mutant (icl1&icl2) showed the importance of the methylmalonyl pathway for the detoxification of propionyl-CoA, during growth at high fatty acid consumption rates and aerobic conditions. At elevated levels of fatty acid uptake and hypoxia, we found a drop in TCA cycle intermediate accumulation that might create redox imbalance. Finally, findings regarding Mtb-mutant metabolic adaptation associated with asparagine consumption and acetate, succinate and alanine production, were in agreement with literature reports. This study demonstrates the potential application of genome-scale modeling, flux balance analysis (FBA), phenotypic phase plane (PhPP) analysis and shadow pricing to generate valuable insights about Mtb metabolic reprogramming in the context of human granulomas.

Incision of trivalent chromium [Cr(III)]-induced DNA damage by Bacillus caldotenax UvrABC endonuclease.

PubMed

O'Brien, Travis J; Jiang, Guohui; Chun, Gina; Mandel, H George; Westphal, Craig S; Kahen, Kaveh; Montaser, Akbar; States, J Christopher; Patierno, Steven R

2006-11-07

Some hexavalent chromium [Cr(VI)]-containing compounds are lung carcinogens. Once within cells, Cr(VI) is reduced to trivalent chromium [Cr(III)] which displays an affinity for both DNA bases and the phosphate backbone. A diverse array of genetic lesions is produced by Cr including Cr-DNA monoadducts, DNA interstrand crosslinks (ICLs), DNA-Cr-protein crosslinks (DPCs), abasic sites, DNA strand breaks and oxidized bases. Despite the large amount of information available on the genotoxicity of Cr, little is known regarding the molecular mechanisms involved in the removal of these lesions from damaged DNA. Recent work indicates that nucleotide excision repair (NER) is involved in the processing of Cr-DNA adducts in human and rodent cells. In order to better understand this process at the molecular level and begin to identify the Cr-DNA adducts processed by NER, the incision of CrCl(3) [Cr(III)]-damaged plasmid DNA was studied using a thermal-resistant UvrABC NER endonuclease from Bacillus caldotenax (Bca). Treatment of plasmid DNA with Cr(III) (as CrCl(3)) increased DNA binding as a function of dose. For example, at a Cr(III) concentration of 1 microM we observed approximately 2 Cr(III)-DNA adducts per plasmid. At this same concentration of Cr(III) we found that approximately 17% of the plasmid DNA contained ICLs ( approximately 0.2 ICLs/plasmid). When plasmid DNA treated with Cr(III) (1 microM) was incubated with Bca UvrABC we observed approximately 0.8 incisions/plasmid. The formation of endonuclease IV-sensitive abasic lesions or Fpg-sensitive oxidized DNA bases was not detected suggesting that the incision of Cr(III)-damaged plasmid DNA by UvrABC was not related to the generation of oxidized DNA damage. Taken together, our data suggest that a sub-fraction of Cr(III)-DNA adducts is recognized and processed by the prokaryotic NER machinery and that ICLs are not necessarily the sole lesions generated by Cr(III) that are substrates for NER.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks

PubMed Central

Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-01-01

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway. PMID:27449087

OPTICAL COLORS OF INTRACLUSTER LIGHT IN THE VIRGO CLUSTER CORE

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

Rudick, Craig S.; Mihos, J. Christopher; Harding, Paul

2010-09-01

We continue our deep optical imaging survey of the Virgo cluster using the CWRU Burrell Schmidt telescope by presenting B-band surface photometry of the core of the Virgo cluster in order to study the cluster's intracluster light (ICL). We find ICL features down to {mu}{sub B} {approx}29 mag arcsec{sup -2}, confirming the results of Mihos et al., who saw a vast web of low surface brightness streams, arcs, plumes, and diffuse light in the Virgo cluster core using V-band imaging. By combining these two data sets, we are able to measure the optical colors of many of the cluster's lowmore » surface brightness features. While much of our imaging area is contaminated by galactic cirrus, the cluster core near the cD galaxy, M87, is unobscured. We trace the color profile of M87 out to over 2000'', and find a blueing trend with radius, continuing out to the largest radii. Moreover, we have measured the colors of several ICL features which extend beyond M87's outermost reaches and find that they have similar colors to the M87's halo itself, B - V {approx}0.8. The common colors of these features suggest that the extended outer envelopes of cD galaxies, such as M87, may be formed from similar streams, created by tidal interactions within the cluster, that have since dissolved into a smooth background in the cluster potential.« less

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-09

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Materials Data on Al(ICl2)3 (SG:15) by Materials Project

DOE Data Explorer

Kristin Persson

2016-02-04

Computed materials data using density functional theory calculations. These calculations determine the electronic structure of bulk materials by solving approximations to the Schrodinger equation. For more information, see https://materialsproject.org/docs/calculations

Towards a Molecular Understanding of the Fanconi Anemia Core Complex

PubMed Central

Hodson, Charlotte; Walden, Helen

2012-01-01

Fanconi Anemia (FA) is a genetic disorder characterized by the inability of patient cells to repair DNA damage caused by interstrand crosslinking agents. There are currently 14 verified FA genes, where mutation of any single gene prevents repair of DNA interstrand crosslinks (ICLs). The accumulation of ICL damage results in genome instability and patients having a high predisposition to cancers. The key event of the FA pathway is dependent on an eight-protein core complex (CC), required for the monoubiquitination of each member of the FANCD2-FANCI complex. Interestingly, the majority of patient mutations reside in the CC. The molecular mechanisms underlying the requirement for such a large complex to carry out a monoubiquitination event remain a mystery. This paper documents the extensive efforts of researchers so far to understand the molecular roles of the CC proteins with regard to its main function in the FA pathway, the monoubiquitination of FANCD2 and FANCI. PMID:22675617

Structure of the FANCI-FANCD2 Complex: Insights into the Fanconi Anemia DNA Repair Pathway

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

Joo, Woo; Xu, Guozhou; Persky, Nicole S.

2011-08-29

Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the {approx}300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each proteinmore » has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.« less

Structure of the FANCI-FANCD2 Complex: Insights into the Fanconi Anemia DNA Repair Pathway

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

W Joo; G Xu; n Persky

2011-12-31

Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I-Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage-induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the {approx}300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each proteinmore » has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.« less

ICL-based TDLAS sensor for real-time breath gas analysis of carbon monoxide isotopes.

PubMed

Ghorbani, Ramin; Schmidt, Florian M

2017-05-29

We present a compact sensor for carbon monoxide (CO) in air and exhaled breath based on a room temperature interband cascade laser (ICL) operating at 4.69 µm, a low-volume circular multipass cell and wavelength modulation absorption spectroscopy. A fringe-limited (1σ) sensitivity of 6.5 × 10 -8 cm -1 Hz -1/2 and a detection limit of 9 ± 5 ppbv at 0.07 s acquisition time are achieved, which constitutes a 25-fold improvement compared to direct absorption spectroscopy. Integration over 10 s increases the precision to 0.6 ppbv. The setup also allows measuring the stable isotope 13 CO in breath. We demonstrate quantification of indoor air CO and real-time detection of CO expirograms from healthy non-smokers and a healthy smoker before and after smoking. Isotope ratio analysis indicates depletion of 13 CO in breath compared to natural abundance.

InAs-based interband-cascade-lasers emitting around 7 μm with threshold current densities below 1 kA/cm{sup 2} at room temperature

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

Dallner, Matthias; Hau, Florian; Kamp, Martin

2015-01-26

Interband cascade lasers (ICLs) grown on InAs substrates with threshold current densities below 1 kA/cm{sup 2} are presented. Two cascade designs with different lengths of the electron injector were investigated. Using a cascade design with 3 InAs quantum wells (QWs) in the electron injector, a device incorporating 22 stages in the active region exhibited a threshold current density of 940 A/cm{sup 2} at a record wavelength of 7 μm for ICLs operating in pulsed mode at room temperature. By investigating the influence of the number of stages on the device performance for a cascade design with 2 QWs in the electron injector, amore » further reduction of the threshold current density to 800 A/cm{sup 2} was achieved for a 30 stage device.« less

The HST Frontier Field MACS 1159.5+2223: Flanking Observations for Intracluster Light

NASA Astrophysics Data System (ADS)

Gonzalez, Anthony

2017-08-01

We propose a 6 orbit WFC3/IR imaging program targeting the environs of the HST Frontier Field cluster MACS 1149.5+2223 to obtain a comprehensive view of the intracluster stellar population in a massive galaxy cluster. WFC3/IR enables a vast improvement over ground-based studies in mapping emission from diffuse stellar populations. Our proposed observations are designed to build upon the existing investment in the Frontier Fields to conduct a new, more complete census of the intracluster light (ICL) extending out to 750 kpc. The requested observations are constructed to span the gap between the primary and parallel HFF pointings, detecting ICL to a surface brightness of 29.5 mag per square arcsec in F160W (equivalent to 31.5 mag per square arcsec in V-band). This depth is sufficient to trace the radial ICL profile out to 750 kpc from the BCG. These data will also yield a high-fidelity calibration of the background sky level, enabling two-dimensional mapping of the distribution and color of intracluster light down to 27 mag per square arcsec in F160W. From these maps we will quantify spatial variation in the ratio of the stellar baryons to the ICM, establishing whether the observed low scatter in the global ratio masks underlying smaller scale inhomogeneities due to astrophysical processes in the cluster. The requested observations further serve as a pilot program, enabling future similar analyses with the full ensemble of HFF clusters, and developing techniques that will be required for such low surface brightness programs with upcoming facilities including Euclid and WFIRST.

Defects in the Fanconi Anemia Pathway and Chromatid Cohesion in Head and Neck Cancer.

PubMed

Stoepker, Chantal; Ameziane, Najim; van der Lelij, Petra; Kooi, Irsan E; Oostra, Anneke B; Rooimans, Martin A; van Mil, Saskia E; Brink, Arjen; Dietrich, Ralf; Balk, Jesper A; Ylstra, Bauke; Joenje, Hans; Feller, Stephan M; Brakenhoff, Ruud H

2015-09-01

Failure to repair DNA damage or defective sister chromatid cohesion, a process essential for correct chromosome segregation, can be causative of chromosomal instability (CIN), which is a hallmark of many types of cancers. We investigated how frequent this occurs in head and neck squamous cell carcinoma (HNSCC) and whether specific mechanisms or genes could be linked to these phenotypes. The genomic instability syndrome Fanconi anemia is caused by mutations in any of at least 16 genes regulating DNA interstrand crosslink (ICL) repair. Since patients with Fanconi anemia have a high risk to develop HNSCC, we investigated whether and to which extent Fanconi anemia pathway inactivation underlies CIN in HNSCC of non-Fanconi anemia individuals. We observed ICL-induced chromosomal breakage in 9 of 17 (53%) HNSCC cell lines derived from patients without Fanconi anemia. In addition, defective sister chromatid cohesion was observed in five HNSCC cell lines. Inactivation of FANCM was responsible for chromosomal breakage in one cell line, whereas in two other cell lines, somatic mutations in PDS5A or STAG2 resulted in inadequate sister chromatid cohesion. In addition, FANCF methylation was found in one cell line by screening an additional panel of 39 HNSCC cell lines. Our data demonstrate that CIN in terms of ICL-induced chromosomal breakage and defective chromatid cohesion is frequently observed in HNSCC. Inactivation of known Fanconi anemia and chromatid cohesion genes does explain CIN in the minority of cases. These findings point to phenotypes that may be highly relevant in treatment response of HNSCC. ©2015 American Association for Cancer Research.

Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1

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

Gwon, Gwang Hyeon; Kim, Youngran; Liu, Yaqi

2014-10-15

Fanconi anemia (FA) is an autosomal recessive genetic disorder caused by defects in any of 15 FA genes responsible for processing DNA interstrand cross-links (ICLs). The ultimate outcome of the FA pathway is resolution of cross-links, which requires structure-selective nucleases. FA-associated nuclease 1 (FAN1) is believed to be recruited to lesions by a monoubiquitinated FANCI–FANCD2 (ID) complex and participates in ICL repair. Here, we determined the crystal structure of Pseudomonas aeruginosa FAN1 (PaFAN1) lacking the UBZ (ubiquitin-binding zinc) domain in complex with 5' flap DNA. All four domains of the right-hand-shaped PaFAN1 are involved in DNA recognition, with each domainmore » playing a specific role in bending DNA at the nick. The six-helix bundle that binds the junction connects to the catalytic viral replication and repair (VRR) nuclease (VRR nuc) domain, enabling FAN1 to incise the scissile phosphate a few bases distant from the junction. The six-helix bundle also inhibits the cleavage of intact Holliday junctions. PaFAN1 shares several conserved features with other flap structure-selective nucleases despite structural differences. A clamping motion of the domains around the wedge helix, which acts as a pivot, facilitates nucleolytic cleavage. The PaFAN1 structure provides insights into how archaeal Holliday junction resolvases evolved to incise 5' flap substrates and how FAN1 integrates with the FA complex to participate in ICL repair.« less

Mid-infrared dual-gas sensor for simultaneous detection of methane and ethane using a single continuous-wave interband cascade laser

DOE PAGES

Ye, Weilin; Li, Chunguang; Zheng, Chuantao; ...

2016-07-18

A continuous-wave (CW) interband cascade laser (ICL) based mid-infrared sensor system was demonstrated for simultaneous detection of atmospheric methane (CH 4) and ethane (C 2H 6). A 3.337 µm CW ICL with an emitting wavenumber range of 2996.0–3001.5 cm –1 was used to simultaneously target two absorption lines, C 2H 6 at 2996.88 cm –1 and CH 4 at 2999.06 cm –1, respectively. The sensor performance was first evaluated for single-gas detection by only targeting the absorption line of one gas species. Allan deviations of 11.2 parts per billion in volume (ppbv) for CH 4 and 1.86 ppbv for Cmore » 2H 6 with an averaging time of 3.4 s were achieved for the detection of these two gases. Dual-gas detection was realized by using a long-term scan signal to target both CH 4 and C 2H 6 lines. The Allan deviations increased slightly to 17.4 ppbv for CH 4 and 2.4 ppbv for C 2H 6 with an averaging time of 4.6 s due to laser temperature and power drift caused by long-term wavelength scanning. Measurements for both indoor and outdoor concentration changes of CH 4 and C 2H 6 were conducted. As a result, the reported single ICL based dual-gas sensor system has the advantages of reduced size and cost compared to two separate sensor systems.« less

Mid-infrared dual-gas sensor for simultaneous detection of methane and ethane using a single continuous-wave interband cascade laser

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

Ye, Weilin; Li, Chunguang; Zheng, Chuantao

A continuous-wave (CW) interband cascade laser (ICL) based mid-infrared sensor system was demonstrated for simultaneous detection of atmospheric methane (CH 4) and ethane (C 2H 6). A 3.337 µm CW ICL with an emitting wavenumber range of 2996.0–3001.5 cm –1 was used to simultaneously target two absorption lines, C 2H 6 at 2996.88 cm –1 and CH 4 at 2999.06 cm –1, respectively. The sensor performance was first evaluated for single-gas detection by only targeting the absorption line of one gas species. Allan deviations of 11.2 parts per billion in volume (ppbv) for CH 4 and 1.86 ppbv for Cmore » 2H 6 with an averaging time of 3.4 s were achieved for the detection of these two gases. Dual-gas detection was realized by using a long-term scan signal to target both CH 4 and C 2H 6 lines. The Allan deviations increased slightly to 17.4 ppbv for CH 4 and 2.4 ppbv for C 2H 6 with an averaging time of 4.6 s due to laser temperature and power drift caused by long-term wavelength scanning. Measurements for both indoor and outdoor concentration changes of CH 4 and C 2H 6 were conducted. As a result, the reported single ICL based dual-gas sensor system has the advantages of reduced size and cost compared to two separate sensor systems.« less

Characterization of the human SNM1A and SNM1B/Apollo DNA repair exonucleases.

PubMed

Sengerová, Blanka; Allerston, Charles K; Abu, Mika; Lee, Sook Y; Hartley, Janet; Kiakos, Konstantinos; Schofield, Christopher J; Hartley, John A; Gileadi, Opher; McHugh, Peter J

2012-07-27

Human SNM1A and SNM1B/Apollo have both been implicated in the repair of DNA interstrand cross-links (ICLs) by cellular studies, and SNM1B is also required for telomere protection. Here, we describe studies on the biochemical characterization of the SNM1A and SNM1B proteins. The results reveal some fundamental differences in the mechanisms of the two proteins. Both SNM1A and SNM1B digest double-stranded and single-stranded DNA with a 5'-to-3' directionality in a reaction that is stimulated by divalent cations, and both nucleases are inhibited by the zinc chelator o-phenanthroline. We find that SNM1A has greater affinity for single-stranded DNA over double-stranded DNA that is not observed with SNM1B. Although both proteins demonstrate a low level of processivity on low molecular weight DNA oligonucleotide substrates, when presented with high molecular weight DNA, SNM1A alone is rendered much more active, being capable of digesting kilobase-long stretches of DNA. Both proteins can digest past ICLs induced by the non-distorting minor groove cross-linking agent SJG-136, albeit with SNM1A showing a greater capacity to achieve this. This is consistent with the proposal that SNM1A and SNM1B might exhibit some redundancy in ICL repair. Together, our work establishes differences in the substrate selectivities of SNM1A and SNM1B that are likely to be relevant to their in vivo roles and which might be exploited in the development of selective inhibitors.

Lamin A/C Depletion Enhances DNA Damage-Induced Stalled Replication Fork Arrest

PubMed Central

Singh, Mayank; Hunt, Clayton R.; Pandita, Raj K.; Kumar, Rakesh; Yang, Chin-Rang; Horikoshi, Nobuo; Bachoo, Robert; Serag, Sara; Story, Michael D.; Shay, Jerry W.; Powell, Simon N.; Gupta, Arun; Jeffery, Jessie; Pandita, Shruti; Chen, Benjamin P. C.; Deckbar, Dorothee; Löbrich, Markus; Yang, Qin; Khanna, Kum Kum; Worman, Howard J.

2013-01-01

The human LMNA gene encodes the essential nuclear envelope proteins lamin A and C (lamin A/C). Mutations in LMNA result in altered nuclear morphology, but how this impacts the mechanisms that maintain genomic stability is unclear. Here, we report that lamin A/C-deficient cells have a normal response to ionizing radiation but are sensitive to agents that cause interstrand cross-links (ICLs) or replication stress. In response to treatment with ICL agents (cisplatin, camptothecin, and mitomycin), lamin A/C-deficient cells displayed normal γ-H2AX focus formation but a higher frequency of cells with delayed γ-H2AX removal, decreased recruitment of the FANCD2 repair factor, and a higher frequency of chromosome aberrations. Similarly, following hydroxyurea-induced replication stress, lamin A/C-deficient cells had an increased frequency of cells with delayed disappearance of γ-H2AX foci and defective repair factor recruitment (Mre11, CtIP, Rad51, RPA, and FANCD2). Replicative stress also resulted in a higher frequency of chromosomal aberrations as well as defective replication restart. Taken together, the data can be interpreted to suggest that lamin A/C has a role in the restart of stalled replication forks, a prerequisite for initiation of DNA damage repair by the homologous recombination pathway, which is intact in lamin A/C-deficient cells. We propose that lamin A/C is required for maintaining genomic stability following replication fork stalling, induced by either ICL damage or replicative stress, in order to facilitate fork regression prior to DNA damage repair. PMID:23319047

Surgical intervention and accommodative responses, I: centripetal ciliary body, capsule, and lens movements in rhesus monkeys of various ages.

PubMed

Croft, Mary Ann; McDonald, Jared P; James, Rebecca J; Heatley, Gregg A; Lin, Ting-Li; Lütjen-Drecoll, Elke; Kaufman, Paul L

2008-12-01

To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. In 18 rhesus monkey eyes (aged 6-27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extracapsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis (ARZ). Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. Centripetal accommodative CP and capsule movement increased in velocity and amplitude after, compared with before, ECLE regardless of age (n = 5). The presence of the lens substance retarded capsule movement by approximately 21% in the young eyes and by approximately 62% in the older eyes. Post-ICLE compared with pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disrupted (n = 7), but not in eyes in which the anterior vitreous was left intact (n = 2). After anterior regional zonulolysis (n = 4), lens position shifted toward the lysed quadrant during accommodation. The presence of the lens substance, capsule zonular attachments, and Wieger's ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce approximately 6 D of accommodation in the presence of a normal, young crystalline lens or a similar surrogate.

Improving Fatty Acid Availability for Bio-Hydrocarbon Production in Escherichia coli by Metabolic Engineering

PubMed Central

Lin, Fengming; Chen, Yu; Levine, Robert; Lee, Kilho; Yuan, Yingjin; Lin, Xiaoxia Nina

2013-01-01

Previous studies have demonstrated the feasibility of producing fatty-acid-derived hydrocarbons in Escherichia coli. However, product titers and yields remain low. In this work, we demonstrate new methods for improving fatty acid production by modifying central carbon metabolism and storing fatty acids in triacylglycerol. Based on suggestions from a computational model, we deleted seven genes involved in aerobic respiration, mixed-acid fermentation, and glyoxylate bypass (in the order of cyoA, nuoA, ndh, adhE, dld, pta, and iclR) to modify the central carbon metabolic/regulatory networks. These gene deletions led to increased total fatty acids, which were the highest in the mutants containing five or six gene knockouts. Additionally, when two key enzymes in the fatty acid biosynthesis pathway were over-expressed, we observed further increase in strain △cyoA△adhE△nuoA△ndh△pta△dld, leading to 202 mg/g dry cell weight of total fatty acids, ~250% of that in the wild-type strain. Meanwhile, we successfully introduced a triacylglycerol biosynthesis pathway into E. coli through heterologous expression of wax ester synthase/acyl-coenzyme:diacylglycerol acyltransferase (WS/DGAT) enzymes. The added pathway improved both the amount and fuel quality of the fatty acids. These new metabolic engineering strategies are providing promising directions for future investigation. PMID:24147139

Exploration of freely available web-interfaces for comparative homology modelling of microbial proteins.

PubMed

Nema, Vijay; Pal, Sudhir Kumar

2013-01-01

This study was conducted to find the best suited freely available software for modelling of proteins by taking a few sample proteins. The proteins used were small to big in size with available crystal structures for the purpose of benchmarking. Key players like Phyre2, Swiss-Model, CPHmodels-3.0, Homer, (PS)2, (PS)(2)-V(2), Modweb were used for the comparison and model generation. Benchmarking process was done for four proteins, Icl, InhA, and KatG of Mycobacterium tuberculosis and RpoB of Thermus Thermophilus to get the most suited software. Parameters compared during analysis gave relatively better values for Phyre2 and Swiss-Model. This comparative study gave the information that Phyre2 and Swiss-Model make good models of small and large proteins as compared to other screened software. Other software was also good but is often not very efficient in providing full-length and properly folded structure.

The contribution of hydrothermally altered ocean crust to the mantle halogen and noble gas cycles

NASA Astrophysics Data System (ADS)

Chavrit, Déborah; Burgess, Ray; Sumino, Hirochika; Teagle, Damon A. H.; Droop, Giles; Shimizu, Aya; Ballentine, Chris J.

2016-06-01

Recent studies suggest that seawater-derived noble gases and halogens are recycled into the deep mantle by the subduction of oceanic crust. To understand the processes controlling the availability of halogens and noble gases for subduction, we determined the noble gas elemental and isotopic ratios and halogen (Cl, Br, I) concentrations in 28 igneous samples from the altered oceanic crust (AOC) from 5 ODP sites in the Eastern and Western Pacific Ocean. Crushing followed by heating experiments enabled determination of noble gases and halogens in fluid inclusions and mineral phases respectively. Except for He and Ar, Ne, Kr and Xe isotopic ratios were all air-like suggesting that primary MORB signatures have been completely overprinted by air and/or seawater interaction. In contrast, 3He/4He ratios obtained by crushing indicate that a mantle helium component is still preserved, and 40Ar/36Ar values are affected by radiogenic decay in the mineral phases. The 130Xe/36Ar and 84Kr/36Ar ratios are respectively up to 15 times and 5 times higher than those of seawater and the highest ratios are found in samples affected by low temperature alteration (shallower than 800-900 m sub-basement). We consider three possible processes: (i) adsorption onto the clays present in the samples; (ii) fluid inclusions with a marine pore fluid composition; and (iii) fractionation of seawater through phase separation caused by boiling. Ninety percent of the Cl, Br and I were released during the heating experiments, showing that halogens are dominantly held in mineral phases prior to subduction. I/Cl ratios vary by 4 orders of magnitude, from 3 × 10-6 to 2 × 10-2. The mean Br/Cl ratio is 30% lower than in MORB and seawater. I/Cl ratios lower than MORB values are attributed to Cl-rich amphibole formation caused by hydrothermal alteration at depths greater than 800-900 m sub-basement together with different extents of I loss during low and high temperature alteration. At shallower depths, I/Cl ratios higher than MORB values can be explained by the addition of organic-rich sediments or the presence of organic detritus, both known to efficiently sequester I. Concentrations of 36Ar of the pre-subducting materials are sufficient to account for the 36Ar and composition of the mantle in the context of existing subduction-flux models. We find the Cl subduction flux of the oceanic crust to be about three times higher than the previous estimates and that sufficient Cl and Br can potentially be delivered by subduction over the last 3 Ga to account for mantle source compositions.

Organic carbon dynamics and soil stability in five semiarid agroecosystems

USDA-ARS?s Scientific Manuscript database

In the semiarid Texas High Plains where continuous cotton (CTN) is the dominate cropping practice, alternative agroecosystems such as integrated crop-livestock agroecosystems (ICL) are gaining interest for their versatility in management approaches to conserve water in this water-limited environment...

40 CFR 82.8 - Grant of essential use allowances and critical use allowances.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-IP America 250,516 19,576 TriCal, Inc 7,800 610 Total ** 1,814,020 141,755 * For production or import.... Degesch America, Inc. Helena Chemical Co. Hendrix & Dail Hy-Yield Products, LLC ICL-IP America Industrial...

40 CFR 82.8 - Grant of essential use allowances and critical use allowances.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-IP America 250,516 19,576 TriCal, Inc 7,800 610 Total ** 1,814,020 141,755 * For production or import.... Degesch America, Inc. Helena Chemical Co. Hendrix & Dail Hy-Yield Products, LLC ICL-IP America Industrial...

Linking Soil Microbial Ecology to Ecosystem Functioning in Integrated Crop-Livestock Systems

USDA-ARS?s Scientific Manuscript database

Enhanced soil stability, nutrient cycling and C sequestration potential are important ecosystem functions driven by soil microbial processes and are directly influenced by agricultural management. Integrated crop-livestock agroecosystems (ICL) can enhance these functions via high-residue returning c...

Photo-Activated Psoralen Binds the ErbB2 Catalytic Kinase Domain, Blocking ErbB2 Signaling and Triggering Tumor Cell Apoptosis

PubMed Central

Xia, Wenle; Gooden, David; Liu, Leihua; Zhao, Sumin; Soderblom, Erik J.; Toone, Eric J.; Beyer, Wayne F.; Walder, Harold; Spector, Neil L.

2014-01-01

Photo-activation of psoralen with UVA irradiation, referred to as PUVA, is used in the treatment of proliferative skin disorders. The anti-proliferative effects of PUVA have been largely attributed to psoralen intercalation of DNA, which upon UV treatment, triggers the formation of interstrand DNA crosslinks (ICL) that inhibit transcription and DNA replication. Here, we show that PUVA exerts antitumor effects in models of human breast cancer that overexpress the ErbB2 receptor tyrosine kinase oncogene, through a new mechanism. Independent of ICL formation, the antitumor effects of PUVA in ErbB2+ breast cancer models can instead be mediated through inhibition of ErbB2 activation and signaling. Using a mass spectroscopy-based approach, we show for the first time that photo-activated 8MOP (8-methoxypsoralen) interacts with the ErbB2 catalytic autokinase domain. Furthermore, PUVA can reverse therapeutic resistance to lapatinib and other ErbB2 targeted therapies, including resistance mediated via expression of a phosphorylated, truncated form of ErbB2 (p85ErbB2) that is preferentially expressed in tumor cell nuclei. Current ErbB2 targeted therapies, small molecule kinase inhibitors or antibodies, do not block the phosphorylated, activated state of p85ErbB2. Here we show that PUVA reduced p85ErbB2 phosphorylation leading to tumor cell apoptosis. Thus, in addition to its effects on DNA and the formation of ICL, PUVA represents a novel ErbB2 targeted therapy for the treatment of ErbB2+ breast cancers, including those that have developed resistance to other ErbB2 targeted therapies. PMID:24551203

The Virgo cD galaxy M87 and its environment as mapped by Planetary Nebulae

NASA Astrophysics Data System (ADS)

Longobardi, Alessia

2015-08-01

Cosmological simulations predict the evolution of galaxy halos in cluster environments. Because of their low surface brightness, 1% of the night sky or lower, it is difficult to measure their spatial distribution and line-of-sight motions of the associated stars. Planetary nebulas (PNs) are very good tracers of their parent stellar populations, and we can use them to investigate these extended halos as consequence of their relatively strong [OIII] emission line. We have used PNs to study the outer halo of M87, the BCG at the center of the Virgo cluster. From the deepest and most extended narrow band survey done with Supruime Cam on Subaru, we carry out the spectroscopic follow up with FLMES at the VLT of more than 300 emission line objects in the halo of M87 out to ~150 kpc in radius. We confirm 254 PNs associated with the M87 halo and 44 with the intracluster light in the Virgo core. We show that the galaxy halo overlaps with the Virgo intracluster light (ICL) at all distance. Halo and ICL are dynamically distinct components, have different density profiles and parent stellar populations. The latter result shows that the halo of M87 is redder and more metal rich than the ICL population. Because of the excellent spectra resolution of our data, we identify a chevron structure in the projected phase space and identify the substructure in light associated to this dynamical sub-component. This accretion event account for a third of the light of the halo at 90 kpc distance from the center. It shows that at these distances the M87 halo is significantly lumpy and still growing by accretion of satellites.

Long-term control of CMV retinitis in a patient with idiopathic CD4+ T lymphocytopenia.

PubMed

Yashiro, Shigeko; Fujino, Yujiro; Tachikawa, Natsuo; Inamochi, Kazuya; Oka, Shinichi

2013-04-01

Cytomegalovirus (CMV) retinitis with idiopathic CD4(+) T lymphocytopenia (ICL) is rare and difficult to control. We report a first case for long-term control of CMV retinitis with ICL using interleukin-2 (IL-2) therapy and succeeded in discontinuation of anti-CMV therapy. A 49-year-old Japanese woman was diagnosed with ICL based on low CD4(+) count (72/μl), negative for HIV-1 and -2 antibodies, and absence of any defined immunodeficiency diseases or immunosuppressive therapy. PCR test of the aqueous humor in the right eye was suggestive of CMV retinitis. She was treated with systemic ganciclovir, but after several relapses of CMV retinitis, rhegmatogenous retinal detachment appeared in the right eye and she became blind in that eye. Three years later, she developed CMV retinitis in the left eye. Although she received systemic and focal anti-CMV treatments, the retinitis showed no improvement. Finally, retinal detachment occurred, and she underwent vitrectomy. IL-2 was injected to increase CD4(+) counts. Because of hyperpyrexia, blepharedema, central scotoma, and color anomaly, we changed to low-dose IL-2 therapy with no side effects. Finally, we succeeded in increasing the CD4(+) count to more than 200/μl after discontinuation of low-dose IL-2 therapy. CMV retinitis never recurred after discontinuation of anti-CMV therapy, with good visual acuity of 20/20 in the left eye. She developed blindness of the first affected right eye, whereas the visual acuity of the left eye remains excellent more than 12 years after the onset of CMV retinitis through the combined use of anti-CMV therapy, IL-2 therapy, and vitrectomy.

A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2

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

Perez-Aguilar, Jose Manuel; Shan, Jufang; LeVine, Michael V.

With recent progress in determination of G protein-coupled receptor (GPCR) structure with crystallography, a variety of other experimental approaches (e.g., NMR spectroscopy, fluorescent-based assays, mass spectrometry techniques) are also being used to characterize state-specific and ligand-specific conformational states. MD simulations offer a powerful complementary approach to elucidate the dynamic features associated with ligand-specific GPCR conformations. To shed light on the conformational elements and dynamics of the important aspect of GPCR functional selectivity, we carried out unbiased microsecond-length MD simulations of the human serotonin 2A receptor (5-HT 2AR) in the absence of ligand and bound to four distinct serotonergic agonists. Themore » 5-HT 2AR is a suitable system to study the structural features involved in the ligand-dependent conformational heterogeneity of GPCRs because it is well-characterized experimentally and exhibits a strong agonist-specific phenotype in that some 5-HT 2AR agonists induce LSD-like hallucinations, while others lack this psychoactive property entirely. Here we report evidence for structural and dynamic differences in 5-HT 2AR interacting with such pharmacologically distinct ligands, hallucinogens, and nonhallucinogens obtained from all-atom MD simulations. Differential ligand binding contacts were identified for structurally similar hallucinogens and nonhallucinogens and found to correspond to different conformations in the intracellular loop 2 (ICL2). From the different ICL2 conformations, functional selective phenotypes are suggested through effects on dimerization and/or distinct direct interaction with effector proteins. Lastly, the findings are presented in the context of currently proposed hallucinogenesis mechanisms, and ICL2 is proposed as a fine-tuning selective switch that can differentiates modes of 5-HT 2AR activation.« less

A functional selectivity mechanism at the serotonin-2A GPCR involves ligand-dependent conformations of intracellular loop 2

DOE PAGES

Perez-Aguilar, Jose Manuel; Shan, Jufang; LeVine, Michael V.; ...

2014-10-14

With recent progress in determination of G protein-coupled receptor (GPCR) structure with crystallography, a variety of other experimental approaches (e.g., NMR spectroscopy, fluorescent-based assays, mass spectrometry techniques) are also being used to characterize state-specific and ligand-specific conformational states. MD simulations offer a powerful complementary approach to elucidate the dynamic features associated with ligand-specific GPCR conformations. To shed light on the conformational elements and dynamics of the important aspect of GPCR functional selectivity, we carried out unbiased microsecond-length MD simulations of the human serotonin 2A receptor (5-HT 2AR) in the absence of ligand and bound to four distinct serotonergic agonists. Themore » 5-HT 2AR is a suitable system to study the structural features involved in the ligand-dependent conformational heterogeneity of GPCRs because it is well-characterized experimentally and exhibits a strong agonist-specific phenotype in that some 5-HT 2AR agonists induce LSD-like hallucinations, while others lack this psychoactive property entirely. Here we report evidence for structural and dynamic differences in 5-HT 2AR interacting with such pharmacologically distinct ligands, hallucinogens, and nonhallucinogens obtained from all-atom MD simulations. Differential ligand binding contacts were identified for structurally similar hallucinogens and nonhallucinogens and found to correspond to different conformations in the intracellular loop 2 (ICL2). From the different ICL2 conformations, functional selective phenotypes are suggested through effects on dimerization and/or distinct direct interaction with effector proteins. Lastly, the findings are presented in the context of currently proposed hallucinogenesis mechanisms, and ICL2 is proposed as a fine-tuning selective switch that can differentiates modes of 5-HT 2AR activation.« less

Learning from a paradox: recent insights into Fanconi anaemia through studying mouse models.

PubMed

Bakker, Sietske T; de Winter, Johan P; te Riele, Hein

2013-01-01

Fanconi anaemia (FA) is a rare autosomal recessive or X-linked inherited disease characterised by an increased incidence of bone marrow failure (BMF), haematological malignancies and solid tumours. Cells from individuals with FA show a pronounced sensitivity to DNA interstrand crosslink (ICL)-inducing agents, which manifests as G2-M arrest, chromosomal aberrations and reduced cellular survival. To date, mutations in at least 15 different genes have been identified that cause FA; the products of all of these genes are thought to function together in the FA pathway, which is essential for ICL repair. Rapidly following the discovery of FA genes, mutant mice were generated to study the disease and the affected pathway. These mutant mice all show the characteristic cellular ICL-inducing agent sensitivity, but only partially recapitulate the developmental abnormalities, anaemia and cancer predisposition seen in individuals with FA. Therefore, the usefulness of modelling FA in mice has been questioned. In this Review, we argue that such scepticism is unjustified. We outline that haematopoietic defects and cancer predisposition are manifestations of FA gene defects in mice, albeit only in certain genetic backgrounds and under certain conditions. Most importantly, recent work has shown that developmental defects in FA mice also arise with concomitant inactivation of acetaldehyde metabolism, giving a strong clue about the nature of the endogenous lesion that must be repaired by the functional FA pathway. This body of work provides an excellent example of a paradox in FA research: that the dissimilarity, rather than the similarity, between mice and humans can provide insight into human disease. We expect that further study of mouse models of FA will help to uncover the mechanistic background of FA, ultimately leading to better treatment options for the disease.

Comparing pymorph and SDSS photometry - II. The differences are more than semantics and are not dominated by intracluster light

NASA Astrophysics Data System (ADS)

Bernardi, M.; Fischer, J.-L.; Sheth, R. K.; Meert, A.; Huertas-Company, M.; Shankar, F.; Vikram, V.

2017-07-01

The Sloan Digital Sky Survey (SDSS) pipeline photometry underestimates the brightnesses of the most luminous galaxies. This is mainly because (I) the SDSS overestimates the sky background, and (II) single-component or two-component Sérsic-based models better fit the surface brightness profile of galaxies, especially at high luminosities, than the de Vaucouleurs model used by the SDSS pipeline. We use the pymorph photometric reductions to isolate effect (II) and show that it is the same in the full sample as in small group environments, and for satellites in the most massive clusters as well. None of these are expected to be significantly affected by intracluster light (ICL). We only see an additional effect for centrals in the most massive haloes, but we argue that even this is not dominated by ICL. Hence, for the vast majority of galaxies, the differences between pymorph and SDSS pipeline photometry cannot be ascribed to the semantics of whether or not one includes the ICL when describing the stellar mass of massive galaxies. Rather, they likely reflect differences in star formation or assembly histories. Failure to account for the SDSS underestimate has significantly biased most previous estimates of the SDSS luminosity and stellar mass functions, and therefore halo model estimates of the z ˜ 0.1 relation between the mass of a halo and that of the galaxy at its centre. We also show that when one studies correlations, at fixed group mass, with a quantity that was not used to define the groups, then selection effects appear. We show why such effects arise and should not be mistaken for physical effects.

SURGICAL INTERVENTION AND ACCOMMODATIVE RESPONSES: I. CENTRIPETAL CILIARY BODY, CAPSULE AND LENS MOVEMENT IN RHESUS MONKEYS OF VARYING AGE

PubMed Central

Croft, Mary Ann; Mcdonald, Jared P.; James, Rebecca J.; Heatley, Gregg A.; Lin, Ting-Li; Lütjen-Drecoll, Elke; Kaufman, Paul L.

2009-01-01

Purpose To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. Methods In 18 rhesus monkey eyes (aged 6–27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal (E–W) nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extra-capsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis. Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. Results Centripetal accommodative CP and capsule movement increased in velocity and amplitude post-ECLE compared to pre-ECLE regardless of age (n=5). The presence of the lens substance retarded capsule movement by ~21% in the young eyes and by ~62% in the older eyes. Post-ICLE compared to pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disturbed (n=7), but not in eyes in which the anterior vitreous was left intact (n=2). Following anterior regional zonulolysis (n=4), lens position shifted toward the lysed quadrant during accommodation. Conclusions The presence of the lens substance, capsule zonular attachments, and Wiegers ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce ~6 diopters of accommodation in the presence of a normal young crystalline lens or a similar surrogate. PMID:18552393

MSH3 mediates sensitization of colorectal cancer cells to cisplatin, oxaliplatin, and a poly(ADP-ribose) polymerase inhibitor.

PubMed

Takahashi, Masanobu; Koi, Minoru; Balaguer, Francesc; Boland, C Richard; Goel, Ajay

2011-04-08

The MSH3 gene is one of the DNA mismatch repair (MMR) genes that has undergone somatic mutation frequently in MMR-deficient cancers. MSH3, together with MSH2, forms the MutSβ heteroduplex, which interacts with interstrand cross-links (ICLs) induced by drugs such as cisplatin and psoralen. However, the precise role of MSH3 in mediating the cytotoxic effects of ICL-inducing agents remains poorly understood. In this study, we first examined the effects of MSH3 deficiency on cytotoxicity caused by cisplatin and oxaliplatin, another ICL-inducing platinum drug. Using isogenic HCT116-derived clones in which MSH3 expression is controlled by shRNA expression in a Tet-off system, we discovered that MSH3 deficiency sensitized cells to both cisplatin and oxaliplatin at clinically relevant doses. Interestingly, siRNA-induced down-regulation of the MLH1 protein did not affect MSH3-dependent toxicity of these drugs, indicating that this process does not require participation of the canonical MMR pathway. Furthermore, MSH3-deficient cells maintained higher levels of phosphorylated histone H2AX and 53BP1 after oxaliplatin treatment in comparison with MSH3-proficient cells, suggesting that MSH3 plays an important role in repairing DNA double strand breaks (DSBs). This role of MSH3 was further supported by our findings that MSH3-deficient cells were sensitive to olaparib, a poly(ADP-ribose) polymerase inhibitor. Moreover, the combination of oxaliplatin and olaparib exhibited a synergistic effect compared with either treatment individually. Collectively, our results provide novel evidence that MSH3 deficiency contributes to the cytotoxicity of platinum drugs through deficient DSB repair. These data lay the foundation for the development of effective prediction and treatments for cancers with MSH3 deficiency.

MSH3 Mediates Sensitization of Colorectal Cancer Cells to Cisplatin, Oxaliplatin, and a Poly(ADP-ribose) Polymerase Inhibitor*

PubMed Central

Takahashi, Masanobu; Koi, Minoru; Balaguer, Francesc; Boland, C. Richard; Goel, Ajay

2011-01-01

The MSH3 gene is one of the DNA mismatch repair (MMR) genes that has undergone somatic mutation frequently in MMR-deficient cancers. MSH3, together with MSH2, forms the MutSβ heteroduplex, which interacts with interstrand cross-links (ICLs) induced by drugs such as cisplatin and psoralen. However, the precise role of MSH3 in mediating the cytotoxic effects of ICL-inducing agents remains poorly understood. In this study, we first examined the effects of MSH3 deficiency on cytotoxicity caused by cisplatin and oxaliplatin, another ICL-inducing platinum drug. Using isogenic HCT116-derived clones in which MSH3 expression is controlled by shRNA expression in a Tet-off system, we discovered that MSH3 deficiency sensitized cells to both cisplatin and oxaliplatin at clinically relevant doses. Interestingly, siRNA-induced down-regulation of the MLH1 protein did not affect MSH3-dependent toxicity of these drugs, indicating that this process does not require participation of the canonical MMR pathway. Furthermore, MSH3-deficient cells maintained higher levels of phosphorylated histone H2AX and 53BP1 after oxaliplatin treatment in comparison with MSH3-proficient cells, suggesting that MSH3 plays an important role in repairing DNA double strand breaks (DSBs). This role of MSH3 was further supported by our findings that MSH3-deficient cells were sensitive to olaparib, a poly(ADP-ribose) polymerase inhibitor. Moreover, the combination of oxaliplatin and olaparib exhibited a synergistic effect compared with either treatment individually. Collectively, our results provide novel evidence that MSH3 deficiency contributes to the cytotoxicity of platinum drugs through deficient DSB repair. These data lay the foundation for the development of effective prediction and treatments for cancers with MSH3 deficiency. PMID:21285347

Mid-infrared dual-gas sensor for simultaneous detection of methane and ethane using a single continuous-wave interband cascade laser.

PubMed

Ye, Weilin; Li, Chunguang; Zheng, Chuantao; Sanchez, Nancy P; Gluszek, Aleksander K; Hudzikowski, Arkadiusz J; Dong, Lei; Griffin, Robert J; Tittel, Frank K

2016-07-25

A continuous-wave (CW) interband cascade laser (ICL) based mid-infrared sensor system was demonstrated for simultaneous detection of atmospheric methane (CH₄) and ethane (C₂H₆). A 3.337 µm CW ICL with an emitting wavenumber range of 2996.0-3001.5 cm^-1 was used to simultaneously target two absorption lines, C₂H₆ at 2996.88 cm^-1 and CH₄ at 2999.06 cm^-1, respectively. The sensor performance was first evaluated for single-gas detection by only targeting the absorption line of one gas species. Allan deviations of 11.2 parts per billion in volume (ppbv) for CH₄ and 1.86 ppbv for C₂H₆ with an averaging time of 3.4 s were achieved for the detection of these two gases. Dual-gas detection was realized by using a long-term scan signal to target both CH₄ and C₂H₆ lines. The Allan deviations increased slightly to 17.4 ppbv for CH₄ and 2.4 ppbv for C₂H₆ with an averaging time of 4.6 s due to laser temperature and power drift caused by long-term wavelength scanning. Measurements for both indoor and outdoor concentration changes of CH₄ and C₂H₆ were conducted. The reported single ICL based dual-gas sensor system has the advantages of reduced size and cost compared to two separate sensor systems.

Characterization of the Human SNM1A and SNM1B/Apollo DNA Repair Exonucleases*

PubMed Central

Sengerová, Blanka; Allerston, Charles K.; Abu, Mika; Lee, Sook Y.; Hartley, Janet; Kiakos, Konstantinos; Schofield, Christopher J.; Hartley, John A.; Gileadi, Opher; McHugh, Peter J.

2012-01-01

Human SNM1A and SNM1B/Apollo have both been implicated in the repair of DNA interstrand cross-links (ICLs) by cellular studies, and SNM1B is also required for telomere protection. Here, we describe studies on the biochemical characterization of the SNM1A and SNM1B proteins. The results reveal some fundamental differences in the mechanisms of the two proteins. Both SNM1A and SNM1B digest double-stranded and single-stranded DNA with a 5′-to-3′ directionality in a reaction that is stimulated by divalent cations, and both nucleases are inhibited by the zinc chelator o-phenanthroline. We find that SNM1A has greater affinity for single-stranded DNA over double-stranded DNA that is not observed with SNM1B. Although both proteins demonstrate a low level of processivity on low molecular weight DNA oligonucleotide substrates, when presented with high molecular weight DNA, SNM1A alone is rendered much more active, being capable of digesting kilobase-long stretches of DNA. Both proteins can digest past ICLs induced by the non-distorting minor groove cross-linking agent SJG-136, albeit with SNM1A showing a greater capacity to achieve this. This is consistent with the proposal that SNM1A and SNM1B might exhibit some redundancy in ICL repair. Together, our work establishes differences in the substrate selectivities of SNM1A and SNM1B that are likely to be relevant to their in vivo roles and which might be exploited in the development of selective inhibitors. PMID:22692201

Comparison of postoperative vault height predictability using white-to-white or sulcus diameter-based sizing for the visian implantable collamer lens.

PubMed

Reinstein, Dan Z; Lovisolo, Carlo F; Archer, Timothy J; Gobbe, Marine

2013-01-01

To compare vault height predictability of Implantable Collamer Lens (ICL; Staar Surgical) sizing using a sulcus diameter-based formula or the manufacturer-recommended white-to-white-based method. In 50 myopic eyes, ICL size was calculated using both a formula including sulcus diameter and the traditional formula based on white-to-white diameter. Sulcus diameter was measured using Artemis 2 very high-frequency (VHF) digital ultrasound (ArcScan Inc). Implantation was based on the sulcus diameter derived size. Actual postoperative vault height achieved was measured by VHF digital ultrasound scanning. Circle segment trigonometry was used to calculate the vault height that would have resulted had lens sizing been based on the white-to-white formula. The same lens size would have been used in 60% of eyes, a smaller lens would have been used in 34% of eyes and a larger lens in 6% of eyes had lens sizing been based on the white-to-white formula. Mean vault for eyes with lenses sized using the sulcus diameter formula was 0.37±0.16 mm (range: 0.08 to 0.92 mm), with 2% <0.09 mm, the recognized low-vault height for risk of cataract. Circle segment trigonometry predicted that the vault height would have been 0.24±0.28 mm (range: -0.31 to 0.92 mm), with 26% <0.09 mm had lens sizing been based on the white-to-white formula. Significantly better predictability of postoperative vault height was achieved by including sulcus diameter into the ICL sizing formula compared with using the traditional white-to-white-based formula. Copyright 2013, SLACK Incorporated.

Integrated Case Learning: Teaching Clinical Reasoning

ERIC Educational Resources Information Center

Radomski, Natalie; Russell, John

2010-01-01

Learning how to "think like doctors" can be difficult for undergraduate medical students in their early clinical years. Our model of collaborative Integrated Case Learning (ICL) and simulated clinical reasoning aims to address these issues. Taking a socio-cultural perspective, this study investigates the reflective learning interactions…

Continuous spectroscopic measurement of methane isotopes and ethane made on board an aircraft: instrument configuration and characterisation

NASA Astrophysics Data System (ADS)

Pitt, Joseph; Young, Stuart; Hopkins, James; Lee, James; Bauguitte, Stéphane; Dorsey, James; Allen, Grant; Gallagher, Martin; Yacovitch, Tara; Zahniser, Mark; Fisher, Rebecca; Lowry, Dave; Nisbet, Euan

2017-04-01

We describe the configuration of two commercially available absorption spectrometers for use on board the UK Facility for Airborne Atmospheric Research (FAAM) aircraft. A dual laser instrument has been used to make continuous measurements of the atmospheric 13CH4:12CH4 ratio and ethane mole fraction, using an interband cascade laser (ICL) and a recently developed type of diode laser respectively. Simultaneous measurements of atmospheric ethane have also been made using a single laser instrument employing an ICL, enabling instrument inter-comparison. Instrument performance is evaluated over a series of test flights, and initial results from the MOYA (Methane Observations and Yearly Assessments) campaign, targeting biomass burning plumes in west Africa, are also presented. We describe the calibration procedure and data analysis approaches for methane isotope measurement, involving calibration over a range of methane isotopic composition and methane mole fraction. We assess the effectiveness of this calibration technique during the first MOYA campaign period using measurements of a target cylinder of known composition.

Centrin diversity and basal body patterning across evolution: new insights from Paramecium

PubMed Central

Balavoine, Guillaume; Lemullois, Michel; Bouhouche, Khaled; Beisson, Janine; Koll, France

2017-01-01

ABSTRACT First discovered in unicellular eukaryotes, centrins play crucial roles in basal body duplication and anchoring mechanisms. While the evolutionary status of the founding members of the family, Centrin2/Vfl2 and Centrin3/cdc31 has long been investigated, the evolutionary origin of other members of the family has received less attention. Using a phylogeny of ciliate centrins, we identify two other centrin families, the ciliary centrins and the centrins present in the contractile filaments (ICL centrins). In this paper, we carry on the functional analysis of still not well-known centrins, the ICL1e subfamily identified in Paramecium, and show their requirement for correct basal body anchoring through interactions with Centrin2 and Centrin3. Using Paramecium as well as a eukaryote-wide sampling of centrins from completely sequenced genomes, we revisited the evolutionary story of centrins. Their phylogeny shows that the centrins associated with the ciliate contractile filaments are widespread in eukaryotic lineages and could be as ancient as Centrin2 and Centrin3. PMID:28432105

Structural insights into 5‧ flap DNA unwinding and incision by the human FAN1 dimer

NASA Astrophysics Data System (ADS)

Zhao, Qi; Xue, Xiaoyu; Longerich, Simonne; Sung, Patrick; Xiong, Yong

2014-12-01

Human FANCD2-associated nuclease 1 (FAN1) is a DNA structure-specific nuclease involved in the processing of DNA interstrand crosslinks (ICLs). FAN1 maintains genomic stability and prevents tissue decline in multiple organs, yet it confers ICL-induced anti-cancer drug resistance in several cancer subtypes. Here we report three crystal structures of human FAN1 in complex with a 5‧ flap DNA substrate, showing that two FAN1 molecules form a head-to-tail dimer to locate the lesion, orient the DNA and unwind a 5‧ flap for subsequent incision. Biochemical experiments further validate our model for FAN1 action, as structure-informed mutations that disrupt protein dimerization, substrate orientation or flap unwinding impair the structure-specific nuclease activity. Our work elucidates essential aspects of FAN1-DNA lesion recognition and a unique mechanism of incision. These structural insights shed light on the cellular mechanisms underlying organ degeneration protection and cancer drug resistance mediated by FAN1.

Thermal effects of an ICL-based mid-infrared CH 4 sensor within a wide atmospheric temperature range

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

Ye, Weilin; Zheng, Chuantao; Sanchez, Nancy P.

Here, thermal effects of an interband cascade laser (ICL) based mid-infrared methane (CH 4) sensor that uses long-path absorption spectroscopy were studied. The sensor performance in the laboratory at a constant temperature of ~ 25°C was measured for 5 hours and its Allan deviation was ~ 2 ppbv with a 1 s averaging time. A LabVIEW-based simulation program was developed to study thermal effects on infrared absorption and a temperature compensation technique was developed to control such effects. An environmental test chamber was employed to investigate thermal effects that occur in the sensor system with variation of the test chambermore » temperature between 10 and 30°C. The thermal response of the sensor in a laboratory setting was observed using a 2.1 ppm CH 4 standard gas sample. indoor/outdoor CH 4 measurements were conducted to evaluate the sensor performance within a wide atmospheric temperature range.« less

A mutation affecting carbon catabolite repression suppresses growth defects in pyruvate carboxylase mutants from Saccharomyces cerevisiae.

PubMed

Blázquez, M A; Gamo, F J; Gancedo, C

1995-12-18

Yeasts with disruptions in the genes PYC1 and PYC2 encoding the isoenzymes of pyruvate carboxylase cannot grow in a glucose-ammonium medium (Stucka et al. (1991) Mol. Gen. Genet. 229, 307-315). We have isolated a dominant mutation, BPC1-1, that allows growth in this medium of yeasts with interrupted PYC1 and PYC2 genes. The BPC1-1 mutation abolishes catabolite repression of a series of genes and allows expression of the enzymes of the glyoxylate cycle during growth in glucose. A functional glyoxylate cycle is necessary for suppression as a disruption of gene ICL1 encoding isocitrate lyase abolished the phenotypic effect of BPC1-1 on growth in glucose-ammonium. Concurrent expression from constitutive promoters of genes ICL1 and MLS1 (encoding malate synthase) also suppressed the growth phenotype of pyc1 pyc2 mutants. The mutation BPC1-1 is either allelic or closely linked to the mutation DGT1-1.

Thermal effects of an ICL-based mid-infrared CH4 sensor within a wide atmospheric temperature range

NASA Astrophysics Data System (ADS)

Ye, Weilin; Zheng, Chuantao; Sanchez, Nancy P.; Girija, Aswathy V.; He, Qixin; Zheng, Huadan; Griffin, Robert J.; Tittel, Frank K.

2018-03-01

The thermal effects of an interband cascade laser (ICL) based mid-infrared methane (CH4) sensor that uses long-path absorption spectroscopy were studied. The sensor performance in the laboratory at a constant temperature of ∼25 °C was measured for 5 h and its Allan deviation was ∼2 ppbv with a 1 s averaging time. A LabVIEW-based simulation program was developed to study thermal effects on infrared absorption and a temperature compensation technique was developed to minimize these effects. An environmental test chamber was employed to investigate the thermal effects that occur in the sensor system with variation of the test chamber temperature between 10 and 30 °C. The thermal response of the sensor in a laboratory setting was observed using a 2.1 ppm CH4 standard gas sample. Indoor/outdoor CH4 measurements were conducted to evaluate the sensor performance within a wide atmospheric temperature range.

DNA Damage Induced by Alkylating Agents and Repair Pathways

PubMed Central

Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

2010-01-01

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

Thermal effects of an ICL-based mid-infrared CH 4 sensor within a wide atmospheric temperature range

DOE PAGES

Ye, Weilin; Zheng, Chuantao; Sanchez, Nancy P.; ...

2018-01-31

Here, thermal effects of an interband cascade laser (ICL) based mid-infrared methane (CH 4) sensor that uses long-path absorption spectroscopy were studied. The sensor performance in the laboratory at a constant temperature of ~ 25°C was measured for 5 hours and its Allan deviation was ~ 2 ppbv with a 1 s averaging time. A LabVIEW-based simulation program was developed to study thermal effects on infrared absorption and a temperature compensation technique was developed to control such effects. An environmental test chamber was employed to investigate thermal effects that occur in the sensor system with variation of the test chambermore » temperature between 10 and 30°C. The thermal response of the sensor in a laboratory setting was observed using a 2.1 ppm CH 4 standard gas sample. indoor/outdoor CH 4 measurements were conducted to evaluate the sensor performance within a wide atmospheric temperature range.« less

76 FR 76619 - International Mail: New Prices and Fee Changes-Mailing Services

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-08

... POSTAL SERVICE 39 CFR Part 20 International Mail: New Prices and Fee Changes--Mailing Services... Individual Country Listings (ICLs) to reflect price adjustments for First-Class Mail International[supreg... mailing services price adjustments with the Postal Regulatory Commission (PRC), effective on January 22...

The Magic Background of Pearl Harbor. Volume 3. Appendix

DTIC Science & Technology

1977-01-01

diplomatic relations and the opening of a warfare of commerce destruc- tion. C a JITSU TO Trans. 1-30-45 No. 406 Washington (Nomura) Tokyo September...icles.) Part 2. 2.Inthesummeroflastyear,FUJI-Elect!i,corderedfromSIEMENSfor(? JU ?)use10 automatic pilot compasses and JINKOSHIKOKra. However, exchange

An efficient mass-preserving interface-correction level set/ghost fluid method for droplet suspensions under depletion forces

NASA Astrophysics Data System (ADS)

Ge, Zhouyang; Loiseau, Jean-Christophe; Tammisola, Outi; Brandt, Luca

2018-01-01

Aiming for the simulation of colloidal droplets in microfluidic devices, we present here a numerical method for two-fluid systems subject to surface tension and depletion forces among the suspended droplets. The algorithm is based on an efficient solver for the incompressible two-phase Navier-Stokes equations, and uses a mass-conserving level set method to capture the fluid interface. The four novel ingredients proposed here are, firstly, an interface-correction level set (ICLS) method; global mass conservation is achieved by performing an additional advection near the interface, with a correction velocity obtained by locally solving an algebraic equation, which is easy to implement in both 2D and 3D. Secondly, we report a second-order accurate geometric estimation of the curvature at the interface and, thirdly, the combination of the ghost fluid method with the fast pressure-correction approach enabling an accurate and fast computation even for large density contrasts. Finally, we derive a hydrodynamic model for the interaction forces induced by depletion of surfactant micelles and combine it with a multiple level set approach to study short-range interactions among droplets in the presence of attracting forces.

78 FR 79446 - Notice of Public Information Collection(s) Being Reviewed by the Federal Communications...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

... collection of information is necessary for the proper performance of the functions of the Commission... rate-of-return carriers (Interstate Common Line Support (ICLS)) to replace implicit support in interstate access charges with explicit support that is portable to all eligible telecommunications carriers...

Soil fungal community and fuctional diversity assessments of agroecosystems in the Southern High Plains

USDA-ARS?s Scientific Manuscript database

Soil fungi perform a variety of ecosystem functions that are crucial to maintaining agroecosystem sustainability including aggregate stability and soil carbon storage. The purpose of this study was to compare soil fungal communities and functional diversity in integrated crop and livestock (ICL) sy...

Supporting Effective Collaboration: Using a Rearview Mirror to Look Forward

ERIC Educational Resources Information Center

McManus, Margaret M.; Aiken, Robert M.

2016-01-01

Our original research, to design and develop an Intelligent Collaborative Learning System (ICLS), yielded the creation of a Group Leader Tutor software system which utilizes a Collaborative Skills Network to monitor students working collaboratively in a networked environment. The Collaborative Skills Network was a conceptualization of…

75 FR 81270 - Notice of Public Information Collection(s) Being Submitted for Review and Approval to the Office...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-27

... performance of the functions of the Commission, including whether the information shall have practical utility...-of-return carriers (Interstate Common Line Support (ICLS)) to replace implicit support in interstate access charges with explicit support that is portable to all eligible telecommunications carriers. The...

Idea-Centered Laboratory Science (I-CLS), [Unit] C, How a Scientist Expects His World To Behave.

ERIC Educational Resources Information Center

Van Deventer, William C.; Duyser, Lucille

The major ideas of this unit are: consistency and uniformity, cause and effect, and parsimony. Laboratory experiences consist of investigations into: projecting expectations, moon and stars, the relationships among different kinds of change (daily, monthly, annual temperature changes), force and motion, chemical reactions, superstitions, origin of…

Interferon Inducers against Infectious Diseases

DTIC Science & Technology

1990-07-13

22 7. Induction of IFN in Micoe by IC-(PLL- monosaccharides ............................... *23 8. ICL- CDS04...seeking to replace both PLL and CM by modifying the PLL with engrafted polysaccharides . 2. Background A number of candidates have been developed in this...expanders, or being closely related to such. These include gelatin, anionically-modified gelatin, oarboxymethyl polysaocharides, sulfated polysaccharides

Interface Circuits for Self-Checking Microprocessors

NASA Technical Reports Server (NTRS)

Rennels, D. A.; Chandramouli, R.

1986-01-01

Fault-tolerant-microcomputer concept based on enhancing "simple" computer with redundancy and self-checking logic circuits detect hardware faults. Interface and checking logic and redundant processors confer on 16-bit microcomputer ability to check itself for hardware faults. Checking circuitry also checks itself. Concept of self-checking complementary pairs (SCCP's) employed throughout ICL unit.

Ppbv-Level Ethane Detection Using Quartz-Enhanced Photoacoustic Spectroscopy with a Continuous-Wave, Room Temperature Interband Cascade Laser

PubMed Central

Li, Chunguang; Dong, Lei; Zheng, Chuantao; Lin, Jun; Wang, Yiding

2018-01-01

A ppbv-level quartz-enhanced photoacoustic spectroscopy (QEPAS)-based ethane (C2H6) sensor was demonstrated by using a 3.3 μm continuous-wave (CW), distributed feedback (DFB) interband cascade laser (ICL). The ICL was employed for targeting a strong C2H6 absorption line located at 2996.88 cm−1 in its fundamental absorption band. Wavelength modulation spectroscopy (WMS) combined with the second harmonic (2f) detection technique was utilized to increase the signal-to-noise ratio (SNR) and simplify data acquisition and processing. Gas pressure and laser frequency modulation depth were optimized to be 100 Torr and 0.106 cm−1, respectively, for maximizing the 2f signal amplitude. Performance of the QEPAS sensor was evaluated using specially prepared C2H6 samples. A detection limit of 11 parts per billion in volume (ppbv) was obtained with a 1-s integration time based on an Allan-Werle variance analysis, and the detection precision can be further improved to ~1.5 ppbv by increasing the integration time up to 230 s. PMID:29495610

Metal-Diazo Radicals of α-Carbonyl Diazomethanes

PubMed Central

Li, Feifei; Xiao, Longqiang; Liu, Lijian

2016-01-01

Metal-diazo radicals of α-carbonyl diazomethanes are new members of the radical family and are precursors to metal-carbene radicals. Herein, using electron paramagnetic resonance spectroscopy with spin-trapping, we detect diazo radicals of α-carbonyl diazomethanes, induced by [RhICl(cod)]2, [CoII(por)] and PdCl2, at room temperature. The unique quintet signal of the Rh-diazo radical was observed in measurements of α-carbonyl diazomethane adducts of [RhICl(cod)]2 in the presence of 5,5-dimethyl-pyrroline-1-N-oxide (DMPO). DFT calculations indicated that 97.2% of spin density is localized on the diazo moiety. Co- and Pd-diazo radicals are EPR silent but were captured by DMPO to form spin adducts of DMPO-N∙ (triplet-of-sextets signal). The spin-trapping also provides a powerful tool for detection of metal-carbene radicals, as evidenced by the DMPO-trapped carbene radicals (DMPO-C∙, sextet signal) and 2-methyl-2-nitrosopropane-carbene adducts (MNP-C∙, doublet-of-triplets signal). The transformation of α-carbonyl diazomethanes to metal-carbene radicals was confirmed to be a two-step process via metal-diazo radicals. PMID:26960916

Metal-Diazo Radicals of α-Carbonyl Diazomethanes

NASA Astrophysics Data System (ADS)

Li, Feifei; Xiao, Longqiang; Liu, Lijian

2016-03-01

Metal-diazo radicals of α-carbonyl diazomethanes are new members of the radical family and are precursors to metal-carbene radicals. Herein, using electron paramagnetic resonance spectroscopy with spin-trapping, we detect diazo radicals of α-carbonyl diazomethanes, induced by [RhICl(cod)]2, [CoII(por)] and PdCl2, at room temperature. The unique quintet signal of the Rh-diazo radical was observed in measurements of α-carbonyl diazomethane adducts of [RhICl(cod)]2 in the presence of 5,5-dimethyl-pyrroline-1-N-oxide (DMPO). DFT calculations indicated that 97.2% of spin density is localized on the diazo moiety. Co- and Pd-diazo radicals are EPR silent but were captured by DMPO to form spin adducts of DMPO-N• (triplet-of-sextets signal). The spin-trapping also provides a powerful tool for detection of metal-carbene radicals, as evidenced by the DMPO-trapped carbene radicals (DMPO-C•, sextet signal) and 2-methyl-2-nitrosopropane-carbene adducts (MNP-C•, doublet-of-triplets signal). The transformation of α-carbonyl diazomethanes to metal-carbene radicals was confirmed to be a two-step process via metal-diazo radicals.

Research on propane leak detection system and device based on mid infrared laser

NASA Astrophysics Data System (ADS)

Jiang, Meng; Wang, Xuefeng; Wang, Junlong; Wang, Yizhao; Li, Pan; Feng, Qiaoling

2017-10-01

Propane is a key component of liquefied petroleum gas (LPG) and crude oil volatile. This issue summarizes the recent progress of propane detection technology. Meanwhile, base on the development trend, our latest progress is also provided. We demonstrated a mid infrared propane sensor system, which is based on wavelength modulation spectroscopy (WMS) technique with a CW interband cascade laser (ICL) emitting at 3370.4nm. The ICL laser scanned over a sharp feature in the broader spectrum of propane, and harmonic signals are obtained by lock-in amplifier for gas concentration deduction. The surrounding gas is extracted into the fine optical absorption cell through the pump to realize online detection. The absorption cell is designed in mid infrared windows range. An example experimental setup is shown. The second harmonic signals 2f and first harmonic signals1f are obtained. We present the sensor performance test data including dynamic precision and temperature stability. The propane detection sensor system and device is portable can carried on the mobile inspection vehicle platforms or intelligent robot inspection platform to realize the leakage monitoring of whole oil gas tank area.

Replication Protein A (RPA) deficiency activates the Fanconi anemia DNA repair pathway.

PubMed

Jang, Seok-Won; Jung, Jin Ki; Kim, Jung Min

2016-09-01

The Fanconi anemia (FA) pathway regulates DNA inter-strand crosslink (ICL) repair. Despite our greater understanding of the role of FA in ICL repair, its function in the preventing spontaneous genome instability is not well understood. Here, we show that depletion of replication protein A (RPA) activates the FA pathway. RPA1 deficiency increases chromatin recruitment of FA core complex, leading to FANCD2 monoubiquitination (FANCD2-Ub) and foci formation in the absence of DNA damaging agents. Importantly, ATR depletion, but not ATM, abolished RPA1 depletion-induced FANCD2-Ub, suggesting that ATR activation mediated FANCD2-Ub. Interestingly, we found that depletion of hSSB1/2-INTS3, a single-stranded DNA-binding protein complex, induces FANCD2-Ub, like RPA1 depletion. More interestingly, depletion of either RPA1 or INTS3 caused increased accumulation of DNA damage in FA pathway deficient cell lines. Taken together, these results indicate that RPA deficiency induces activation of the FA pathway in an ATR-dependent manner, which may play a role in the genome maintenance.

Crystal Structures of the β2-Adrenergic Receptor

NASA Astrophysics Data System (ADS)

Weis, William I.; Rosenbaum, Daniel M.; Rasmussen, Søren G. F.; Choi, Hee-Jung; Thian, Foon Sun; Kobilka, Tong Sun; Yao, Xiao-Jie; Day, Peter W.; Parnot, Charles; Fung, Juan J.; Ratnala, Venkata R. P.; Kobilka, Brian K.; Cherezov, Vadim; Hanson, Michael A.; Kuhn, Peter; Stevens, Raymond C.; Edwards, Patricia C.; Schertler, Gebhard F. X.; Burghammer, Manfred; Sanishvili, Ruslan; Fischetti, Robert F.; Masood, Asna; Rohrer, Daniel K.

G protein coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome, and are responsible for the majority of signal transduction events involving hormones and neuro-transmitters across the cell membrane. GPCRs that bind to diffusible ligands have low natural abundance, are relatively unstable in detergents, and display basal G protein activation even in the absence of ligands. To overcome these problems two approaches were taken to obtain crystal structures of the β2-adrenergic receptor (β2AR), a well-characterized GPCR that binds cate-cholamine hormones. The receptor was bound to the partial inverse agonist carazolol and co-crystallized with a Fab made to a three-dimensional epitope formed by the third intracellular loop (ICL3), or by replacement of ICL3 with T4 lysozyme. Small crystals were obtained in lipid bicelles (β2AR-Fab) or lipidic cubic phase (β2AR-T4 lysozyme), and diffraction data were obtained using microfocus technology. The structures provide insights into the basal activity of the receptor, the structural features that enable binding of diffusible ligands, and the coupling between ligand binding and G-protein activation.

Exploration of freely available web-interfaces for comparative homology modelling of microbial proteins

PubMed Central

Nema, Vijay; Pal, Sudhir Kumar

2013-01-01

Aim: This study was conducted to find the best suited freely available software for modelling of proteins by taking a few sample proteins. The proteins used were small to big in size with available crystal structures for the purpose of benchmarking. Key players like Phyre2, Swiss-Model, CPHmodels-3.0, Homer, (PS)2, (PS)2-V2, Modweb were used for the comparison and model generation. Results: Benchmarking process was done for four proteins, Icl, InhA, and KatG of Mycobacterium tuberculosis and RpoB of Thermus Thermophilus to get the most suited software. Parameters compared during analysis gave relatively better values for Phyre2 and Swiss-Model. Conclusion: This comparative study gave the information that Phyre2 and Swiss-Model make good models of small and large proteins as compared to other screened software. Other software was also good but is often not very efficient in providing full-length and properly folded structure. PMID:24023424

Machine learning for epigenetics and future medical applications.

PubMed

Holder, Lawrence B; Haque, M Muksitul; Skinner, Michael K

2017-07-03

Understanding epigenetic processes holds immense promise for medical applications. Advances in Machine Learning (ML) are critical to realize this promise. Previous studies used epigenetic data sets associated with the germline transmission of epigenetic transgenerational inheritance of disease and novel ML approaches to predict genome-wide locations of critical epimutations. A combination of Active Learning (ACL) and Imbalanced Class Learning (ICL) was used to address past problems with ML to develop a more efficient feature selection process and address the imbalance problem in all genomic data sets. The power of this novel ML approach and our ability to predict epigenetic phenomena and associated disease is suggested. The current approach requires extensive computation of features over the genome. A promising new approach is to introduce Deep Learning (DL) for the generation and simultaneous computation of novel genomic features tuned to the classification task. This approach can be used with any genomic or biological data set applied to medicine. The application of molecular epigenetic data in advanced machine learning analysis to medicine is the focus of this review.

Co-inhibition of Pol η and ATR sensitizes cisplatin-resistant non-small cell lung cancer cells to cisplatin by impeding DNA damage repair.

PubMed

Li, Xiao-Qin; Ren, Jin; Chen, Ping; Chen, Yu-Jiao; Wu, Min; Wu, Yan; Chen, Kang; Li, Jian

2018-05-31

For the majority of patients with advanced non-small cell lung cancer (NSCLC), the standard of care remains platinum-based chemotherapy. However, cisplatin resistance is a big obstacle to the treatment, and elucidation of its mechanism is warranted. In this study, we showed that there was no difference in intracellular uptake of cisplatin or the removal of platinum-DNA adducts between a cisplatin-resistant NSCLC cell line (A549/DR) and a cisplatin-sensitive NSCLC cell line (A549). However, the capacity to repair DNA interstrand crosslinks (ICLs) and double-strand breaks (DSBs) was significantly enhanced in the A549/DR cell line compared to 3 cisplatin-sensitive cell lines. We found that the protein and mRNA expression levels of Pol η, a Y-family translesion synthesis (TLS) polymerase, were markedly increased upon cisplatin exposure in A549/DR cells compared with A549 cells. Furthermore, intracellular co-localization of Pol η and proliferation cell nuclear antigen (PCNA) induced by cisplatin or cisplatin plus gemcitabine treatment was inhibited by depleting ataxia telangiectasia mutated and Rad-3-related (ATR). Pol η depletion by siRNA sensitized A549/DR cells to cisplatin; co-depletion of Pol η and ATR further increased A549/DR cell death induced by cisplatin or cisplatin plus gemcitabine compared to depletion of Pol η or ATR alone, concomitant with inhibition of DNA ICL and DSB repair and accumulation of DNA damage. No additional sensitization effect of co-depleting Pol η and ATR was observed in A549 cells. These results demonstrate that co-inhibition of Pol η and ATR reverses the drug resistance of cisplatin-resistant NSCLC cells by blocking the repair of DNA ICLs and DSBs induced by cisplatin or cisplatin plus gemcitabine.

77 FR 14297 - Connect America Fund; a National Broadband Plan for Our Future; Establishing Just and Reasonable...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... Reduction Act requirements, and finds good cause to delete certain rules that are now obsolete. DATES... Paperwork Reduction Act (PRA) requirements, and finds good cause to delete certain rules that are now... CAF phase I support,'' but excludes Interstate Common Line Support (ICLS) on the basis that it...

Detection of active noise control on the standard motorcycle exhaust Supra X 125 D using PVC pipe technique form Y

NASA Astrophysics Data System (ADS)

Isranuri, I.; Alfisyahrin; Nasution, A. R.

2018-02-01

This detection aims to obtain noise reduction on the supra X 125D motorcycle exhaust by using the Active Noise Control Method. The technique is done using a Y-shaped PVC pipe to be bolted on the exhaust, which then branch Y PVC is placed loudspeaker with impermeable conditions. The function of this loudspeaker is as a secondary noise to counter the primary noise of the sound of exhaust motorcycle Supra X 125D. The sound generator in this study is the ISD 4004 module, which serves to generate noise to counter the source noise. How this ISD 4004 module works is by recording source noise then recording the source noise and then reversed the phase 180° by phase reversing circuit. So that, the noise generated by the sound generator will hit the source noise and encounter or such as addition of two different phase of sound will result in noise reduction when detected at the end of the Y-shaped PVC pipe. Inverted phase reversed using feed-back resistor 1 kΩ and 2 kΩ input resistors, 16V capacitor 2500μf and as amplifier using ICL 7660 and TL 702 CP. Test results on the highest 1000 rpm rotation engine speed on the Z axis of 2 dB, and at the highest 2000 rpm rotation engine speed also occurs on the Z axis of 1.5 dB.

Efficiency bounds for nonequilibrium heat engines

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

Mehta, Pankaj; Polkovnikov, Anatoli, E-mail: asp@bu.edu

2013-05-15

We analyze the efficiency of thermal engines (either quantum or classical) working with a single heat reservoir like an atmosphere. The engine first gets an energy intake, which can be done in an arbitrary nonequilibrium way e.g. combustion of fuel. Then the engine performs the work and returns to the initial state. We distinguish two general classes of engines where the working body first equilibrates within itself and then performs the work (ergodic engine) or when it performs the work before equilibrating (non-ergodic engine). We show that in both cases the second law of thermodynamics limits their efficiency. For ergodicmore » engines we find a rigorous upper bound for the efficiency, which is strictly smaller than the equivalent Carnot efficiency. I.e. the Carnot efficiency can be never achieved in single reservoir heat engines. For non-ergodic engines the efficiency can be higher and can exceed the equilibrium Carnot bound. By extending the fundamental thermodynamic relation to nonequilibrium processes, we find a rigorous thermodynamic bound for the efficiency of both ergodic and non-ergodic engines and show that it is given by the relative entropy of the nonequilibrium and initial equilibrium distributions. These results suggest a new general strategy for designing more efficient engines. We illustrate our ideas by using simple examples. -- Highlights: ► Derived efficiency bounds for heat engines working with a single reservoir. ► Analyzed both ergodic and non-ergodic engines. ► Showed that non-ergodic engines can be more efficient. ► Extended fundamental thermodynamic relation to arbitrary nonequilibrium processes.« less

A Multi-Metric Assessment on the Impact of I Can Learn[R] (ICL) Multimedia on Actual and Perceived Student Achievement in Developmental Mathematics

ERIC Educational Resources Information Center

Stokes, Sandra D.

2011-01-01

This quasi-experimental study focused on the initiatives undertaken by a community college's Academic Skills Enhancement Program (ASEP) commonly known as the Developmental Education Department to find an alternative delivery method to aid its students in learning developmental mathematics. Moreover, this study (1) conducted a comparative…

75 FR 29555 - Medicare Program; Medicare Coverage Gap Discount Program Model Manufacturer Agreement and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... Center Hotel, 101 West Fayette Street, Baltimore, MD 21201. Registration and Special Accommodations... percent of the Part D negotiated price for covered Part D claims above the ICL until their TrOOP costs... of an amount equal to the negotiated price (as defined in section 1860D- 14A(g)(6) of the Act...

Plasma Theory and Simulation.

DTIC Science & Technology

1978-07-01

l l) A paper t i t led “Part icle-Fluid Hybrid Codes Applied to Beam- Plasma , Ring -Plasma Instabi l i ties ” was presented at Monterey (see Section V...ic le-Fluid Hybr id Codes Applied to Beam- Plasma , Ring -Plasma Ins tab i l i t ies”. (2) A. Peiravi and C. K. Birdsall , “Self-Heating of id Therma l

Procurement and Delivery of Joint Service Armor Protected Vehicles

DTIC Science & Technology

2009-01-29

veh icle mi x of MRAPs and UA II and their rcspecti ve cfl ’ccts on opcrationaltactics, technique , Md procedurcs, as we ll as vehic le forma ti ons...rcasonablc price compari sons with prior purchases orthe same 01’ similar items made on a competiti ve bas is 0 1’ supported by va lid cost 0 1’ Iri

Interferon Inducers Against Infectious Diseases.

DTIC Science & Technology

1991-06-15

mouse there was little, if any, difference. b. PLL- Monosaccharide Grafts. The PLL-dextran grafts described above contain long polysaccharide chains...engrafted polysaccharides . Our research has resulted in the demonstration that effective IFN inducers can be formulated without using...Action of IC-(PLL-dextran) .............. 7. Induction of IFN in Mice by IC-(PLL- monosaccharides ). I 8. ICL-SCDS04; Compositions and IFN Titers

Non-covalent Interactions with SUMO and Ubiquitin Orchestrate Distinct Functions of the SLX4 Complex in Genome Maintenance

PubMed Central

Ouyang, Jian; Garner, Elizabeth; Hallet, Alexander; Nguyen, Hai Dang; Rickman, Kimberly A.; Gill, Grace; Smogorzewska, Agata; Zou, Lee

2014-01-01

SLX4, a coordinator of multiple DNA structure-specific endonucleases, is important for several DNA repair pathways. Non-covalent interactions of SLX4 with ubiquitin are required for localizing SLX4 to DNA-interstrand crosslinks (ICLs), yet how SLX4 is targeted to other functional contexts remains unclear. Here, we show that SLX4 binds SUMO-2/3 chains via SUMO-interacting motifs (SIMs). The SIMs of SLX4 are dispensable for ICL repair, but important for processing CPT-induced replication intermediates, suppressing fragile site instability, and localizing SLX4 to ALT telomeres. The localization of SLX4 to laser-induced DNA damage also requires the SIMs, as well as DNA-end resection, UBC9 and MDC1. Furthermore, the SUMO binding of SLX4 enhances its interaction with specific DNA-damage sensors or telomere-binding proteins, including RPA, MRE11-RAD50-NBS1 and TRF2. Thus, the interactions of SLX4 with SUMO and ubiquitin increase its affinity for factors recognizing different DNA lesions or telomeres, helping to direct the SLX4 complex in distinct functional contexts. PMID:25533185

Coexistence of two electronic nano-phases on a CH 3NH 3PbI 3–xCl x surface observed in STM measurements

DOE PAGES

Yost, Andrew J.; Pimachev, Artem; Ho, Chun -Chih; ...

2016-10-10

Scanning tunneling microscopy is utilized to investigate the local density of states of a CH 3NH 3PbI 3-xCl x perovskite in cross-sectional geometry. Two electronic phases, 10-20 nm in size, with different electronic properties inside the CH 3NH 3PbI 3-xCl x perovskite layer are observed by the dI/ dV mapping and point spectra. A power law dependence of the dI/dV point spectra is revealed. In addition, the distinct electronic phases are found to have preferential orientations close to the normal direction of the film surface. Density functional theory calculations indicate that the observed electronic phases are associated with local deviationmore » of I/Cl ratio, rather than different orientations of the electric dipole moments in the ferroelectric phases. Furthermore, by comparing the calculated results with experimental data we conclude that phase A (lower contrast in dI/dV mapping at -2.0 V bias) contains a lower I/Cl ratio than that in phase B (higher contrast in dI/dV).« less

Crosslinking reactions of 4-amino-6-oxo-2-vinylpyrimidine with guanine derivatives and structural analysis of the adducts

PubMed Central

Kusano, Shuhei; Ishiyama, Shogo; Lam, Sik Lok; Mashima, Tsukasa; Katahira, Masato; Miyamoto, Kengo; Aida, Misako; Nagatsugi, Fumi

2015-01-01

DNA interstrand crosslinks (ICLs) are the primary mechanism for the cytotoxic activity of many clinical anticancer drugs, and numerous strategies for forming ICLs have been developed. One such method is using crosslink-forming oligonucleotides (CFOs). In this study, we designed a 4-amino-6-oxo-2-vinylpyrimidine (AOVP) derivative with an acyclic spacer to react selectively with guanine. The AOVP CFO exhibited selective crosslinking reactivity with guanine and thymine in DNA, and with guanine in RNA. These crosslinking reactions with guanine were accelerated in the presence of CoCl2, NiCl2, ZnCl2 and MnCl2. In addition, we demonstrated that the AOVP CFO was reactive toward 8-oxoguanine opposite AOVP in the duplex DNA. The structural analysis of each guanine and 8-oxoguanine adduct in the duplex DNA was investigated by high-resolution NMR. The results suggested that AOVP reacts at the N2 amine in guanine and at the N1 or N2 amines in 8-oxoguanine in the duplex DNA. This study demonstrated the first direct determination of the adduct structure in duplex DNA without enzyme digestion. PMID:26245348

Usefulness of acr expression for monitoring latent Mycobacterium tuberculosis bacilli in 'in vitro' and 'in vivo' experimental models.

PubMed

Gordillo, S; Guirado, E; Gil, O; Díaz, J; Amat, I; Molinos, S; Vilaplana, C; Ausina, V; Cardona, P-J

2006-07-01

Real-time RT-PCR was used to quantify the expression of genes possibly involved in Mycobacterium tuberculosis latency in in vitro and murine models. Exponential and stationary phase (EP and SP) bacilli were exposed to decreasing pH levels (from 6.5 to 4.5) in an unstirred culture, and mRNA levels for 16S rRNA, sigma factors sigA,B,E,F,G,H and M, Rv0834c, icl, nirA, narG, fpbB, acr, rpoA, recA and cysH were quantified. The expression of acr was the one that best correlated with the CFU decrease observed in SP bacilli. In the murine model, the expressions of icl, acr and sigF tended to decrease when bacillary counts increased and vice versa. Values from immunodepressed mice (e.g. alpha/beta T cells, TNF, IFN-gamma and iNOs knock out strains), with accelerated bacillary growth rate, confirmed this fact. Finally, the expression of acr was maintained in mice following long-term treatment with antibiotics. The quantification of acr expression could be useful for monitoring the presence of latent bacilli in some murine models of tuberculosis.

Warrant Officer Examinations. PR-4018

DTIC Science & Technology

1944-10-10

ccouunting, Administrative - Clcorica1, Judge, Advo Ge~nc. De~ptsAdxiiniistrati~ve 1 icl Adi isrtv - Supp:ly, generaile8 ~ Administrativo ’ - Supply, Air...chronological index if action in processing special and summary records of trial. Answers teleph.’nic inquirie’s pertaining to subject matter contain- ed...reproduction by lithopraphy, black and white process printing, and gelatin duplication; moy couidinnte and supervise procurement, storage, and distribution of

Funding Higher Education and Wage Uncertainty: Income Contingent Loan versus Mortgage Loan

ERIC Educational Resources Information Center

Migali, Giuseppe

2012-01-01

We propose a simple theoretical model which shows how the combined effect of wage uncertainty and risk aversion can modify the individual willingness to pay for a HE system financed by an ICL or a ML. We calibrate our model using real data from the 1970 British Cohort Survey together with the features of the English HE financing system. We allow…

RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

PubMed Central

Abdou, Elias; Jiménez de Bagüés, María P.; Martínez-Abadía, Ignacio; Ouahrani-Bettache, Safia; Pantesco, Véronique; Occhialini, Alessandra; Al Dahouk, Sascha; Köhler, Stephan; Jubier-Maurin, Véronique

2017-01-01

For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL), were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work therefore contributes significantly to the unraveling of persistence mechanisms in this important zoonotic pathogen. PMID:28573107

Linking precious metal enrichment and halogen cycling in mafic magmatic systems: insights from the Rum layered intrusion, NW Scotland

NASA Astrophysics Data System (ADS)

Kelly, A. P.; O'Driscoll, B.; Clay, P. L.; Burgess, R.

2017-12-01

Layered intrusions host the world's largest known concentrations of the platinum-group elements (PGE). Emphasis has been attached to the role of halogen-bearing fluids in concentrating the precious metals, but whether this occurs at the magmatic stage, or via subsequent metasomatism, is actively debated. One obstacle to progress has been the analytical difficulty of measuring low abundances of the halogens in the cumulate products of layered intrusions. To elucidate the importance of the halogens in facilitating PGE-mineralisation, as well as fingerprint halogen provenance and assess the importance of halogen cycling in mafic magma systems more generally, a suite of samples encompassing different stages of activity of the Palaeogene Rum layered intrusion was investigated. Halogen abundances were measured by neutron irradiation noble gas mass spectrometric analysis, permitting the detection of relatively low (ppm-ppb) abundances of Cl, Br and I in mg-sized samples. The samples include PGE-enriched chromite seams, various cumulates (e.g., peridotites), picrites (approximating the Rum parental magma), and pegmatites representing volatile-rich melts that circulated the intrusion at a late-stage in its solidification history. The new data reveal that PGE-bearing chromite seams contain relatively low Cl concentrations (2-3 ppm), with high molar ratios of Br/Cl and I/Cl (0.005 and 0.009, respectively). The picrites and cumulates have Br/Cl and I/Cl ratios close to sub-continental lithospheric mantle values of approximately 0.0013 and 0.00002, respectively, and thus likely reflect the Rum magma source region. A positive correlation between Cl and Br signifies comparable partitioning behaviour in all samples. However, I is more variable, displaying a positive correlation with Cl for more primitive samples (e.g. picrite and peridotite), and seemingly decoupling from Br and Cl in chromite seams and pegmatites. The relative enrichment of I over Cl in the chromite seams points to the local involvement of an organic-rich sedimentary assimilant and potentially represents an important trigger for PGE-mineralisation. Similarly high I/Cl signatures in some of the late-stage pegmatites suggest that fluids with this distinctive composition circulated the cooling Rum intrusion for a protracted period of time.

Investigating the structural impact of S311C mutation in DRD2 receptor by molecular dynamics & docking studies.

PubMed

Podder, Avijit; Pandey, Deeksha; Latha, N

2016-04-01

Dopamine receptors (DR) are neuronal cell surface proteins that mediate the action of neurotransmitter dopamine in brain. Dopamine receptor D2 (DRD2) that belongs to G-protein coupled receptors (GPCR) family is a major therapeutic target for of various neurological and psychiatric disorders in human. The third inter cellular loop (ICL3) in DRD2 is essential for coupling G proteins and several signaling scaffold proteins. A mutation in ICL3 can interfere with this binding interface, thereby altering the DRD2 signaling. In this study we have examined the deleterious effect of serine to cysteine mutation at position 311 (S311C) in the ICL3 region that is implicated in diseases like schizophrenia and alcoholism. An in silico structure modeling approach was employed to determine the wild type (WT) and mutant S311C structures of DRD2, scaffold proteins - Gαi/o and NEB2. Protein-ligand docking protocol was exercised to predict the interactions of natural agonist dopamine with both the WT and mutant structures of DRD2. Besides, atomistic molecular dynamics (MD) simulations were performed to provide insights into essential dynamics of the systems-unbound and dopamine bound DRD2 (WT and mutant) and three independent simulations for Gαi, Gαo and NEB2 systems. To provide information on intra-molecular arrangement of the structures, a comprehensive residue interactions network of both dopamine bound WT and mutant DRD2 protein were studied. We also employed a protein-protein docking strategy to find the interactions of scaffold proteins - Gαi/o and NEB2 with both dopamine bound WT and mutant structures of DRD2. We observed a marginal effect of the mutation in dopamine binding mechanism on the trajectories analyzed. However, we noticed a significant structural alteration of the mutant receptor which affects Gαi/o and NEB2 binding that can be causal for malfunctioning in cAMP-dependent signaling and Ca(+) homeostasis in the brain dopaminergic system leading to neuropsychiatric disorders. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Assessment of normal perisellar anatomy in 1.5 T T2-weighted MRI and comparison with the anatomic criteria defining cavernous sinus invasion of pituitary adenomas.

PubMed

Knappe, U J; Jaursch-Hancke, C; Schönmayr, R; Lörcher, U

2009-08-01

The study aimed to evaluate the anatomical relations of sellar and perisellar structures with T2-weighted MRI and to apply criteria for cavernous sinus (CS) invasion by pituitary adenomas to normal sellar anatomy. Thin slice (3 mm) coronal T2-weighted MR-images (1.5 Tesla) were obtained in 117 individuals (234 CS) without pituitary disorders (58 females, 59 males; age 17 months to 87 years). In 99 cases data indicating the presence of arterial hypertension (AH) were available, 25 with AH, 74 without AH. The medial wall of the cavernous sinus was detectable in 33% of cases. The inferior rim of the horizontal part of the ICA was located at the level of the sellar floor in 33%, below in 47%, and above in 20%. The mean distance between the both ICAs was 17.8 mm (range, 7-38 mm). The mean distance between the pituitary and the ICA in AH was significantly shorter than in patients without AH (Chi-square, p=0.01). There was contact between the gland and the ICA in 41.5% of the cases. In 16.7% (39 sides) of all 234 SCs investigated, the area of contact between the ICA and the gland was at least 25% of the vessel's circumference. The medial intercarotid line (ICL) was crossed by the pituitary gland in 9% (21 of 234 CS), the central ICL was touched in another 5% (11 of 234 CS), lateral ICL was never reached. There was a weak correlation with age: a more extensive lateral extension of the gland was seen in individuals older than 40 years compared to younger individuals (Chi-square, p=0.03). There was a marked difference in the anatomical findings between both sides in 41.9% of cases. Inter- and intra-individual variations of the perisellar anatomy and its relation to the pituitary gland exist, which are partly related to age and AH. This must be remembered when the invasiveness of pituitary adenomas is assessed in MRI. Georg Thieme Verlag KG Stuttgart New York.

Xenopus egg extract: A powerful tool to study genome maintenance mechanisms.

PubMed

Hoogenboom, Wouter S; Klein Douwel, Daisy; Knipscheer, Puck

2017-08-15

DNA repair pathways are crucial to maintain the integrity of our genome and prevent genetic diseases such as cancer. There are many different types of DNA damage and specific DNA repair mechanisms have evolved to deal with these lesions. In addition to these repair pathways there is an extensive signaling network that regulates processes important for repair, such as cell cycle control and transcription. Despite extensive research, DNA damage repair and signaling are not fully understood. In vitro systems such as the Xenopus egg extract system, have played, and still play, an important role in deciphering the molecular details of these processes. Xenopus laevis egg extracts contain all factors required to efficiently perform DNA repair outside a cell, using mechanisms conserved in humans. These extracts have been used to study several genome maintenance pathways, including mismatch repair, non-homologous end joining, ICL repair, DNA damage checkpoint activation, and replication fork stability. Here we describe how the Xenopus egg extract system, in combination with specifically designed DNA templates, contributed to our detailed understanding of these pathways. Copyright © 2017. Published by Elsevier Inc.

Machine learning for epigenetics and future medical applications

PubMed Central

Holder, Lawrence B.; Haque, M. Muksitul; Skinner, Michael K.

2017-01-01

ABSTRACT Understanding epigenetic processes holds immense promise for medical applications. Advances in Machine Learning (ML) are critical to realize this promise. Previous studies used epigenetic data sets associated with the germline transmission of epigenetic transgenerational inheritance of disease and novel ML approaches to predict genome-wide locations of critical epimutations. A combination of Active Learning (ACL) and Imbalanced Class Learning (ICL) was used to address past problems with ML to develop a more efficient feature selection process and address the imbalance problem in all genomic data sets. The power of this novel ML approach and our ability to predict epigenetic phenomena and associated disease is suggested. The current approach requires extensive computation of features over the genome. A promising new approach is to introduce Deep Learning (DL) for the generation and simultaneous computation of novel genomic features tuned to the classification task. This approach can be used with any genomic or biological data set applied to medicine. The application of molecular epigenetic data in advanced machine learning analysis to medicine is the focus of this review. PMID:28524769

Geometric Heat Engines Featuring Power that Grows with Efficiency.

PubMed

Raz, O; Subaşı, Y; Pugatch, R

2016-04-22

Thermodynamics places a limit on the efficiency of heat engines, but not on their output power or on how the power and efficiency change with the engine's cycle time. In this Letter, we develop a geometrical description of the power and efficiency as a function of the cycle time, applicable to an important class of heat engine models. This geometrical description is used to design engine protocols that attain both the maximal power and maximal efficiency at the fast driving limit. Furthermore, using this method, we also prove that no protocol can exactly attain the Carnot efficiency at nonzero power.

A new technique for thermodynamic engine modeling

NASA Astrophysics Data System (ADS)

Matthews, R. D.; Peters, J. E.; Beckel, S. A.; Shizhi, M.

1983-12-01

Reference is made to the equations given by Matthews (1983) for piston engine performance, which show that this performance depends on four fundamental engine efficiencies (combustion, thermodynamic cycle or indicated thermal, volumetric, and mechanical) as well as on engine operation and design parameters. This set of equations is seen to suggest a different technique for engine modeling; that is, that each efficiency should be modeled individually and the efficiency submodels then combined to obtain an overall engine model. A simple method for predicting the combustion efficiency of piston engines is therefore required. Various methods are proposed here and compared with experimental results. These combustion efficiency models are then combined with various models for the volumetric, mechanical, and indicated thermal efficiencies to yield three different engine models of varying degrees of sophistication. Comparisons are then made of the predictions of the resulting engine models with experimental data. It is found that combustion efficiency is almost independent of load, speed, and compression ratio and is not strongly dependent on fuel type, at least so long as the hydrogen-to-carbon ratio is reasonably close to that for isooctane.

RCS2 J232727.6-020437: An efficient cosmic telescope at Z = 0.6986

DOE PAGES

Hoag, A.; Bradac, M.; Huang, K. H.; ...

2015-10-27

Here, we present a detailed gravitational lens model of the galaxy cluster RCS2 J232727.6-020437. Due to cosmological dimming of cluster members and ICL, its high redshift (z=0.6986) makes it ideal for studying background galaxies. Using new ACS and WFC3/IR HST data, we identify 16 multiple images. From MOSFIRE follow up, we identify a strong emission line in the spectrum of one multiple image, likely confirming the redshift of that system to z=2.083. With a highly magnified (μ ≳ 2) source plane area of ~ 0.7 arcmin 2 at z = 7, RCS2 J232727.6-020437 has a lensing efficiency comparable to themore » Hubble Frontier Fields clusters. We discover four highly magnified z ~ 7 candidate Lyman-break galaxies behind the cluster, one of which may be multiply-imaged. Correcting for magnification, we find that all four galaxies are fainter than 0.5L *. One candidate is detected at >10σ in both Spitzer/IRAC [3.6] and [4.5] channels. A spectroscopic follow-up with MOSFIRE does not result in the detection of the Lyman-alpha emission line from any of the four candidates. From the MOSFIRE spectra we place median upper limits on the Lyman-alpha flux of 5 – 14 × 10 –19 ergs –1cm –2 (5σ).« less

Room Temperature Interband Cascade Lasers

DTIC Science & Technology

2010-01-01

interband cascade laser (ICL) [6]-[8] is particularly convenient, since the semimetallic band alignment between InAs and GaSb allows the electrons that...superlattice claddings and a non-ohmic part that may be associated with various band discontinuities in the structure . While the latter can probably be...made a radiative transition to the valence band to be transferred readily back to the conduction band via elastic or nearly elastic processes. Our

Carbon Black - Polyethylene Composites for PTC (Positive Temperature Coefficient) Thermistor Applications

DTIC Science & Technology

1987-12-01

triphasic composite. Addition of the third filler yielded two effects. First, the filler provided sufficient mechanical stabilization of the composite...2000C. The stabilization was accomplished without diminishing the magnitude of the PTC effect. The triphasic composites also displayed equivalent or...differences in conductor and insulator --.-+icle size lead to the formation of quasi-compo- -s, resulting in a 3(0-3)-0 connectivity. Triphasic composites

Exjade® (deferasirox, ICL670) in the treatment of chronic iron overload associated with blood transfusion

PubMed Central

Cappellini, Maria Domenica

2007-01-01

Although blood transfusions are important for patients with anemia, chronic transfusions inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. Although the current reference standard iron chelator deferoxamine has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Deferasirox (Exjade®, ICL670, Novartis Pharma AG, Basel, Switzerland) is a once-daily, oral iron chelator approved for the treatment of transfusional iron overload in adult and pediatric patients. The efficacy and safety of deferasirox have been established in a comprehensive clinical development program involving patients with various transfusion-dependent anemias. Deferasirox has a dose-dependent effect on iron burden, and is as efficacious as deferoxamine at comparable therapeutic doses. Deferasirox therapy can be tailored to a patient’s needs, as response is related to both dose and iron intake. Since deferasirox has a long half-life and is present in the plasma for 24 hours with once-daily dosing, it is unique in providing constant chelation coverage with a single dose. The availability of this convenient, effective, and well tolerated therapy represents a significant advance in the management of transfusional iron overload. PMID:18360637

Interband cascade laser based mid-infrared methane sensor system using a novel electrical-domain self-adaptive direct laser absorption spectroscopy (SA-DLAS).

PubMed

Song, Fang; Zheng, Chuantao; Yan, Wanhong; Ye, Weilin; Wang, Yiding; Tittel, Frank K

2017-12-11

To suppress sensor noise with unknown statistical properties, a novel self-adaptive direct laser absorption spectroscopy (SA-DLAS) technique was proposed by incorporating a recursive, least square (RLS) self-adaptive denoising (SAD) algorithm and a 3291 nm interband cascade laser (ICL) for methane (CH 4 ) detection. Background noise was suppressed by introducing an electrical-domain noise-channel and an expectation-known-based RLS SAD algorithm. Numerical simulations and measurements were carried out to validate the function of the SA-DLAS technique by imposing low-frequency, high-frequency, White-Gaussian and hybrid noise on the ICL scan signal. Sensor calibration, stability test and dynamic response measurement were performed for the SA-DLAS sensor using standard or diluted CH 4 samples. With the intrinsic sensor noise considered only, an Allan deviation of ~43.9 ppbv with a ~6 s averaging time was obtained and it was further decreased to 6.3 ppbv with a ~240 s averaging time, through the use of self-adaptive filtering (SAF). The reported SA-DLAS technique shows enhanced sensitivity compared to a DLAS sensor using a traditional sensing architecture and filtering method. Indoor and outdoor atmospheric CH 4 measurements were conducted to validate the normal operation of the reported SA-DLAS technique.

Selective dry etching of III-V nitrides in Cl{sub 2}/Ar, CH{sub 4}/H{sub 2}/Ar, ICi/Ar, and IBr/Ar

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

Vartuli, C.B.; Pearton, S.J.; MacKenzie, J.D.

1996-10-01

The selectivity for etching the binary (GaN, AlN, and InN) and ternary nitrides (InGaN and InAlN) relative to each other in Cl{sub 2}/Ar, CH{sub 4}/H{sub 2}/Ar, ICl/Ar, or IBr/Ar electron cyclotron resonance (ECR) plasmas, and Cl{sub 2}/Ar or CH{sub 4}/H{sub 2}/Ar reactive ion (RIE) plasmas was investigated. Cl-based etches appear to be the best choice for maximizing the selectivity of GaN over the other nitrides. GaN/AlN and GaN/InGaN etch rate ratios of {approximately} 10 were achieved at low RF power in Cl{sub 2}/Ar under ECR and RIE conditions, respectively. GaN/InN selectivity of 10 was found in ICl under ECR conditions.more » A relatively high selectivity (> 6) of InN/GaN was achieved in CH{sub 4}/H{sub 2}/Ar under ECR conditions at low RF powers (50 W). Since the high bond strengths of the nitrides require either high ion energies or densities to achieve practical etch rates it is difficult to achieve high selectivities.« less

Changes in stereoacuity following implantable Collamer lens implantation in patients with myopia

PubMed Central

Khokhar, Sudarshan; Gupta, Shikha; Gogia, Varun; Tewari, Ruchir; Agarwal, Tushar

2015-01-01

The study evaluated the impact of implantable Collamer lens (ICL) implantation on stereoacuity in myopes in a retrospective case series. Ninety-five eyes of 48 patients were recruited. Distance and near stereoacuity were measured using distance Randot stereotest and TNO test, respectively, before surgery and at 4 weeks postoperatively. Mean age of the patients was 23.67 ± 3.7 years. Mean uncorrected distance visual acuity (UDVA) was 1.28 ± 0.37 logarithm of the minimum angle of resolution (logMAR) (median: 1.3; range: 0.3–1.8), and median best-corrected distance visual acuity (BDVA) was 0.18 logMAR (range: 0–0.6). There was a significant improvement in both UDVA and BDVA postsurgery (P < 0.001; Wilcoxon signed rank test). The overall improvement in stereopsis was observed in 15/48 (31.25%) and 13/48 (27.10%) subjects for near and distance, respectively, with no significant difference between the two (P = 0.82; Fisher's exact test). Among stereoblind individuals, the odd's ratio for near stereoacuity to improve in comparison to distance stereoacuity was 8.85 (95% confidence interval: 1.68–46.70; P = 0.01). ICL implantation for refractive correction aided stereoacuity improvement in myopes more so for near. PMID:26655005

Heat engine development for solar thermal power systems

NASA Technical Reports Server (NTRS)

Pham, H. Q.; Jaffe, L. D.

1981-01-01

The technical status of three heat engines (Stirling, high-temperature Brayton, and Combined cycle) for use in solar thermal power systems is presented. Performance goals necessary to develop a system competitive with conventional power requirements include an external heated engine output less than 40 kW, and efficiency power conversion subsystem at least 40% at rated output, and a half-power efficiency of at least 37%. Results show that the Stirling engine can offer a 39% efficiency with 100 hours of life, and a 20% efficiency with 10,000 hours of life, but problems with seals and heater heads exist. With a demonstrated efficiency near 31% at 1500 F and a minimum lifetime of 100,000 hours, the Brayton engine does not offer sufficient engine lifetime, efficiency, and maintenance for solar thermal power systems. Examination of the Rankine bottoming cycle of the Combined cycle engine reveals a 30 year lifetime, but a low efficiency. Additional development of engines for solar use is primarily in the areas of components to provide a long lifetime, high reliability, and low maintenance (no more than $0.001/kW-hr).

The equivalence of minimum entropy production and maximum thermal efficiency in endoreversible heat engines.

PubMed

Haseli, Y

2016-05-01

The objective of this study is to investigate the thermal efficiency and power production of typical models of endoreversible heat engines at the regime of minimum entropy generation rate. The study considers the Curzon-Ahlborn engine, the Novikov's engine, and the Carnot vapor cycle. The operational regimes at maximum thermal efficiency, maximum power output and minimum entropy production rate are compared for each of these engines. The results reveal that in an endoreversible heat engine, a reduction in entropy production corresponds to an increase in thermal efficiency. The three criteria of minimum entropy production, the maximum thermal efficiency, and the maximum power may become equivalent at the condition of fixed heat input.

Holographic heat engine within the framework of massive gravity

NASA Astrophysics Data System (ADS)

Mo, Jie-Xiong; Li, Gu-Qiang

2018-05-01

Heat engine models are constructed within the framework of massive gravity in this paper. For the four-dimensional charged black holes in massive gravity, it is shown that the existence of graviton mass improves the heat engine efficiency significantly. The situation is more complicated for the five-dimensional neutral black holes since the constant which corresponds to the third massive potential also contributes to the efficiency. It is also shown that the existence of graviton mass can improve the heat engine efficiency. Moreover, we probe how the massive gravity influences the behavior of the heat engine efficiency approaching the Carnot efficiency.

A thermoacoustic Stirling heat engine

NASA Astrophysics Data System (ADS)

Backhaus, S.; Swift, G. W.

1999-05-01

Electrical and mechanical power, together with other forms of useful work, are generated worldwide at a rate of about 1012 watts, mostly using heat engines. The efficiency of such engines is limited by the laws of thermodynamics and by practical considerations such as the cost of building and operating them. Engines with high efficiency help to conserve fossil fuels and other natural resources, reducing global-warming emissions and pollutants. In practice, the highest efficiencies are obtained only in the most expensive, sophisticated engines, such as the turbines in central utility electrical plants. Here we demonstrate an inexpensive thermoacoustic engine that employs the inherently efficient Stirling cycle. The design is based on a simple acoustic apparatus with no moving parts. Our first small laboratory prototype, constructed using inexpensive hardware (steel pipes), achieves an efficiency of 0.30, which exceeds the values of 0.10-0.25 attained in other heat engines, with no moving parts. Moreover, the efficiency of our prototype is comparable to that of the common internal combustion engine (0.25-0.40) and piston-driven Stirling engines, (0.20-0.38).

Alternative Fuels DISI Engine Research ? Autoignition Metrics.

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

Sjoberg, Carl Magnus Goran; Vuilleumier, David

Improved engine efficiency is required to comply with future fuel economy standards. Alternative fuels have the potential to enable more efficient engines while addressing concerns about energy security. This project contributes to the science base needed by industry to develop highly efficient direct injection spark igniton (DISI) engines that also beneficially exploit the different properties of alternative fuels. Here, the emphasis is on quantifying autoignition behavior for a range of spark-ignited engine conditions, including directly injected boosted conditions. The efficiency of stoichiometrically operated spark ignition engines is often limited by fuel-oxidizer end-gas autoignition, which can result in engine knock. Amore » fuel’s knock resistance is assessed empirically by the Research Octane Number (RON) and Motor Octane Number (MON) tests. By clarifying how these two tests relate to the autoignition behavior of conventional and alternative fuel formulations, fuel design guidelines for enhanced engine efficiency can be developed.« less

Design study of a kinematic Stirling engine for dispered solar electric power systems

NASA Technical Reports Server (NTRS)

1980-01-01

The concept evaluation shows that the four cylinder double acting U type Stirling engine with annular regenerators is the most suitable engine type for the 15 kW solar application with respect to design, performance and cost. Results show that near term performance for a metallic Stirling engine is 42% efficiency. Further improved components show an impact on efficiency of the future metallic engine to 45%. Increase of heater temperature, through the introduction of ceramic components, contribute the greatest amount to achieve high efficiency goals. Future ceramic Stirling engines for solar applications show an efficiency of around 50%.

The Benefits of Completing Homework for Students with Different Aptitudes in an Introductory Electricity and Magnetism Course

DTIC Science & Technology

2015-02-17

this study, course exams were used to measure student learning rather than research -based concept tests like the Force Concept Inventory [ 19), the...Release Information: This art icles has been accepted by Physical Review Special Topics -- Physics Education Research fo r publication. Previous...portraying official policy. II signed // MONTE D. ANDERSON, Lt Col, USAF Deputy Department Head for Research Department of Physics Tabs 1

Ergonomics and Health Care

DTIC Science & Technology

1994-01-01

consumer ergonomic principles in individual patient treat- products; participating in activities of daily living ment and education, but they have not...psychosocial impacts of illness. Although mists are well aware of the need for implementa- the focus of health care professionals is on patient tion of...h t, a rt icle p rot videe a brief h i ctory’ ol the field of ers,’onomfnicc and explorete the interrelationship beta ee health (tare andi ergjonomic

U.S. EPA, Pesticide Product Label, TRIPLE ACTION 10-6-4 LITE WGT PLNT FD CRABGRSS PREVNTR INSECT CTRL, 04/02/1968

EPA Pesticide Factsheets

2011-04-19

li!"~:'i • 1l1t.

Electrically Tunable Mid-Infrared Single-Mode High-Speed Semiconductor Laser

DTIC Science & Technology

2010-11-01

effective and the net tunnel rate may decrease in spite of progressing carrier density buildup in the accumulation well. Enforcing the bias current at...In te ns ity , a .u . E, eV Regular ICL Figure 4 The dependence of the electroluminescence (EL) quantum energy on the bias voltage for a...spectral maximum energy increases linearly with the bias voltage. Since the dependence is measured in the sub-threshold pumping region, the linear

Sedimentary halogens and noble gases within Western Antarctic xenoliths: Implications of extensive volatile recycling to the sub continental lithospheric mantle

NASA Astrophysics Data System (ADS)

Broadley, Michael W.; Ballentine, Chris J.; Chavrit, Déborah; Dallai, Luigi; Burgess, Ray

2016-03-01

Recycling of marine volatiles back into the mantle at subduction zones has a profound, yet poorly constrained impact on the geochemical evolution of the Earth's mantle. Here we present a combined noble gas and halogen study on mantle xenoliths from the Western Antarctic Rift System (WARS) to better understand the flux of subducted volatiles to the sub continental lithospheric mantle (SCLM) and assess the impact this has on mantle chemistry. The xenoliths are extremely enriched in the heavy halogens (Br and I), with I concentrations up to 1 ppm and maximum measured I/Cl ratios (85.2 × 10-3) being ∼2000 times greater than mid ocean ridge basalts (MORB). The Br/Cl and I/Cl ratios of the xenoliths span a range from MORB-like ratios to values similar to marine pore fluids and serpentinites, whilst the 84Kr/36Ar and 130Xe/36Ar ratios range from modern atmosphere to oceanic sediments. This indicates that marine derived volatiles have been incorporated into the SCLM during an episode of subduction related metasomatism. Helium isotopic analysis of the xenoliths show average 3He/4He ratios of 7.5 ± 0.5 RA (where RA is the 3He/4He ratio of air = 1.39 × 10-6), similar to that of MORB. The 3He/4He ratios within the xenoliths are higher than expected for the xenoliths originating from the SCLM which has been extensively modified by the addition of subducted volatiles, indicating that the SCLM beneath the WARS must have seen a secondary alteration from the infiltration and rise of asthenospheric fluids/melts as a consequence of rifting and lithospheric thinning. Noble gases and halogens within these xenoliths have recorded past episodes of volatile interaction within the SCLM and can be used to reconstruct a tectonic history of the WARS. Marine halogen and noble gas signatures within the SCLM xenoliths provide evidence for the introduction and retention of recycled volatiles within the SCLM by subduction related metasomatism, signifying that not all volatiles that survive subduction are mixed efficiently through the convecting mantle. The global SCLM therefore represents a potentially important reservoir for the long term residence of subducted volatiles.

Ultra-efficient Engine Diameter Study

NASA Technical Reports Server (NTRS)

Daggett, David L.; Brown, Stephen T.; Kawai, Ron T.

2003-01-01

Engine fan diameter and Bypass Ratio (BPR) optimization studies have been conducted since the beginning of the turbofan age with the recognition that reducing the engine core jet velocity and increasing fan mass flow rate generally increases propulsive efficiency. However, performance tradeoffs limit the amount of fan flow achievable without reducing airplane efficiency. This study identifies the optimum engine fan diameter and BPR, given the advanced Ultra-Efficient Engine Technology (UEET) powerplant efficiencies, for use on an advanced subsonic airframe. Engine diameter studies have historically focused on specific engine size options, and were limited by existing technology and transportation infrastructure (e.g., ability to fit bare engines through aircraft doors and into cargo holds). This study is unique in defining the optimum fan diameter and drivers for future 2015 (UEET) powerplants while not limiting engine fan diameter by external constraints. This report follows on to a study identifying the system integration issues of UEET engines. This Engine Diameter study was managed by Boeing Phantom Works, Seattle, Washington through the NASA Glenn Revolutionary Aero Space Engine Research (RASER) contract under task order 10. Boeing Phantom Works, Huntington Beach, completed the engine/airplane sizing optimization, while the Boeing Commercial Airplane group (BCA) provided design oversight. A separate subcontract to support the overall project was issued to Tuskegee University.

NREL Fuels and Engines R&D Revs Up Vehicle Efficiency, Performance (Text

Science.gov Websites

Version) | News | NREL Fuels and Engines R&D Revs Up Vehicle Efficiency, Performance (Text Version) NREL Fuels and Engines R&D Revs Up Vehicle Efficiency, Performance (Text Version) NREL's combustion to the evolution of how fuels interact with engine and vehicle design. This is a text version of

Alternative Fuels Data Center: College Students Engineer Efficient Vehicles

Science.gov Websites

in EcoCAR 2 CompetitionA> College Students Engineer Efficient Vehicles in EcoCAR 2 Competition to someone by E-mail Share Alternative Fuels Data Center: College Students Engineer Efficient Vehicles in EcoCAR 2 Competition on Facebook Tweet about Alternative Fuels Data Center: College Students Engineer

A simulation study of turbofan engine deterioration estimation using Kalman filtering techniques

NASA Technical Reports Server (NTRS)

Lambert, Heather H.

1991-01-01

Deterioration of engine components may cause off-normal engine operation. The result is an unecessary loss of performance, because the fixed schedules are designed to accommodate a wide range of engine health. These fixed control schedules may not be optimal for a deteriorated engine. This problem may be solved by including a measure of deterioration in determining the control variables. These engine deterioration parameters usually cannot be measured directly but can be estimated. A Kalman filter design is presented for estimating two performance parameters that account for engine deterioration: high and low pressure turbine delta efficiencies. The delta efficiency parameters model variations of the high and low pressure turbine efficiencies from nominal values. The filter has a design condition of Mach 0.90, 30,000 ft altitude, and 47 deg power level angle (PLA). It was evaluated using a nonlinear simulation of the F100 engine model derivative (EMD) engine, at the design Mach number and altitude over a PLA range of 43 to 55 deg. It was found that known high pressure turbine delta efficiencies of -2.5 percent and low pressure turbine delta efficiencies of -1.0 percent can be estimated with an accuracy of + or - 0.25 percent efficiency with a Kalman filter. If both the high and low pressure turbine are deteriorated, the delta efficiencies of -2.5 percent to both turbines can be estimated with the same accuracy.

Increasing the volumetric efficiency of Diesel engines by intake pipes

NASA Technical Reports Server (NTRS)

List, Hans

1933-01-01

Development of a method for calculating the volumetric efficiency of piston engines with intake pipes. Application of this method to the scavenging pumps of two-stroke-cycle engines with crankcase scavenging and to four-stroke-cycle engines. The utility of the method is demonstrated by volumetric-efficiency tests of the two-stroke-cycle engines with crankcase scavenging. Its practical application to the calculation of intake pipes is illustrated by example.

Ultra Efficient Engine Technology Systems Integration and Environmental Assessment

NASA Technical Reports Server (NTRS)

Daggett, David L.; Geiselhart, Karl A. (Technical Monitor)

2002-01-01

This study documents the design and analysis of four types of advanced technology commercial transport airplane configurations (small, medium large and very large) with an assumed technology readiness date of 2010. These airplane configurations were used as a platform to evaluate the design concept and installed performance of advanced technology engines being developed under the NASA Ultra Efficient Engine Technology (UEET) program. Upon installation of the UEET engines onto the UEET advanced technology airframes, the small and medium airplanes both achieved an additional 16% increase in fuel efficiency when using GE advanced turbofan engines. The large airplane achieved an 18% increase in fuel efficiency when using the P&W geared fan engine. The very large airplane (i.e. BWB), also using P&W geared fan engines, only achieved an additional 16% that was attributed to a non-optimized airplane/engine combination.

The first of a series of high efficiency, high bmep, turbocharged two-stroke cycle diesel engines; the general motors EMD 645FB engine

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

Kotlin, J.J.; Dunteman, N.R.; Scott, D.I.

1983-01-01

The current Electro-Motive Division 645 Series turbocharged engines are the Model FB and EC. The FB engine combines the highest thermal efficiency with the highest specific output of any EMD engine to date. The FB Series incorporates 16:1 compression ratio with a fire ring piston and an improved turbocharger design. Engine components included in the FB engine provide very high output levels with exceptional reliability. This paper also describes the performance of the lower rated Model EC engine series which feature high thermal efficiency and utilize many engine components well proven in service and basic to the Model FB Series.

Wavelengths, energy levels and hyperfine structure of Mn II and Sc II.

NASA Astrophysics Data System (ADS)

Nave, Gillian; Pickering, Juliet C.; Townley-Smith, Keeley I. M.; Hala, .

2015-08-01

For many decades, the Atomic Spectroscopy Groups at the National Institute of Standards and Technology (NIST) and Imperial College London (ICL) have measured atomic data of astronomical interest. Our spectrometers include Fourier transform (FT) spectrometers at NIST and ICL covering the region 1350 Å to 5.5 μm and a 10.7-m grating spectrometer at NIST covering wavelengths from 300 - 5000 Å. Sources for these spectra include high-current continuous and pulsed hollow cathode (HCL) lamps, Penning discharges, and sliding spark discharges. Recent work has focused on the measurement and analysis of wavelengths, energy levels, and hyperfine structure (HFS) constants for iron-group elements. The analysis of FT spectra of Cr I, Mn I, and Mn II is being led by ICL and is described in a companion poster [1]. Current work being led by NIST includes the analysis of HFS in Mn II, analysis of Mn II in the vacuum ultraviolet, and a comprehensive analysis of Sc II.Comprehensive HFS constants for Mn II are needed for the interpretation of stellar spectra and incorrect abundances may be obtained when HFS is omitted. Holt et al. [2] have measured HFS constants for 59 levels of Mn II using laser spectroscopy. We used FT spectra of Mn/Ni and Mn/Cu HCLs covering wavelength ranges from 1350 Å to 5.4 μm to confirm 26 of the A constants of Holt et al. and obtain values for roughly 40 additional levels. We aim to obtain HFS constants for the majority of lines showing significant HFS that are observed in chemically-peculiar stars.Spectra of Sc HCLs have been recorded from 1800 - 6700 Å using a vacuum ultraviolet FT spectrometer at NIST. Additional measurements to cover wavelengths above 6700 Å and below 1800 Å are in progress. The spectra are being analyzed by NIST and Alighar Muslim University, India in order to derive improved wavelengths, energy levels, and hyperfine structure parameters.This work was partially supported by NASA, the STFC and PPARC (UK), the Royal Society of the UK, and the Leverhulme Trust.[1] J. C. Pickering, F. Liggins, C. Clear, M. Ruffoni, G. Nave, C. Sansonetti (this meeting)[2] R. A. Holt, T. J. Scholl & S. D. Rosner, MNRAS 306, 107 (1999)

Refractive Outcomes of 20 Eyes Undergoing ICL Implantation for Correction of Hyperopic Astigmatism.

PubMed

Coskunseven, Efekan; Kavadarli, Isilay; Sahin, Onurcan; Kayhan, Belma; Pallikaris, Ioannis

2017-09-01

To analyze 1-week, 1-month, and 12-month postoperative refractive outcomes of eyes that under-went ICL implantation to correct hyperopic astigmatism. The study enrolled 20 eyes of patients with an average age of 32 years (range: 21 to 40 years). The outcomes of spherical and cylindrical refraction, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), vault, and angle parameters were evaluated 1 week, 1 month, and 12 months postoperatively. The preoperative mean UDVA was 0.15 ± 0.11 (decimal) (20/133 Snellen) and increased to 0.74 ± 0.25 (20/27 Snellen) postoperatively, with a change of 0.59 (decimal) (20/33.9 Snellen) (P < .0001), which was statistically significant. The preoperative mean CDVA was 0.74 ± 0.25 (decimal) (20/27 Snellen) and increased to 0.78 ± 0.21 (20/25 Snellen), with a change of 0.03 (decimal) (20/666 Snellen) (P < .052), which was not statistically significant. The mean preoperative sphere was 6.86 ± 1.77 diopters (D) and the mean preoperative cylinder was -1.44 ± 0.88 D. The mean 12-month postoperative sphere decreased to 0.46 ± 0.89 D (P < .001) and cylinder decreased to -0.61 ± 0.46 D (P < .001), with a change of 6.40 D, both of which were statistically significant. The mean 1-month postoperative vault was 0.65 ± 0.13 mm and decreased to 0.613 ± 0.10 mm at 1 year postoperatively, with a change of 0.44 mm (P < .003). The preoperative/12-month and 1-month/12-month trabecular-iris angle (TIA), trabecular-iris space area 500 mm from the scleral spur (TISA500), and angle opening distance 500 mm from the scleral spur (AOD500) values were analyzed nasally, temporally, and inferiorly. All differences were statistically significant between preoperative/12-month analysis. The only differences between 1- and 12-month analysis were on TISA500 inferior (P < .002) and AOD500 nasal (0.031) values. ICL hyperopic toric implantation is a safe method and provides stable refractive outcomes in patients with high hyperopia (up to 10.00 D) and astigmatism (up to 6.00 D). [J Refract Surg. 2017;33(9):604-609.]. Copyright 2017, SLACK Incorporated.

Martian fluid and Martian weathering signatures identified in Nakhla, NWA 998 and MIL 03346 by halogen and noble gas analysis

NASA Astrophysics Data System (ADS)

Cartwright, J. A.; Gilmour, J. D.; Burgess, R.

2013-03-01

We report argon (Ar) noble gas, Ar-Ar ages and halogen abundances (Cl, Br, I) of Martian nakhlites Nakhla, NWA 998 and MIL 03346 to determine the presence of Martian hydrous fluids and weathering products. Neutron-irradiated samples were either crushed and step-heated (Nakhla only), or simply step-heated using a laser or furnace, and analysed for noble gases using an extension of the 40Ar-39Ar technique to determine halogen abundances. The data obtained provide the first isotopic evidence for a trapped fluid that is Cl-rich, has a strong correlation with 40ArXS (40ArXS = 40Armeasured - 40Arradiogenic) and displays 40ArXS/36Ar of ˜1000 - consistent with the Martian atmosphere. This component was released predominantly in the low temperature and crush experiments, which may suggest a fluid inclusion host. For the halogens, we observe similar Br/Cl and I/Cl ratios between the nakhlites and terrestrial reservoirs, which is surprising given the absence of crustal recycling, organic matter and frequent fluid activity on Mars. In particular, Br/Cl ratios in our Nakhla samples (especially olivine) are consistent with previously analysed Martian weathering products, and both low temperature and crush analyses show a similar trend to the evaporation of seawater. This may indicate that surface brines play an important role on Mars and on halogen assemblages within Martian meteorites and rocks. Elevated I/Cl ratios in the low temperature NWA 998 and MIL 03346 releases may relate to in situ terrestrial contamination, though we are unable to distinguish between low temperature terrestrial or Martian components. Whilst estimates of the amount of water present based on the 36Ar concentrations are too high to be explained by a fluid component alone, they are consistent with a mixed-phase inclusion (gas and fluid) or with shock-implanted Martian atmospheric argon. The observed fluid is dilute (low salinity, but high Br/Cl and I/Cl ratios), contains a Martian atmospheric component, and may represent a mixture of a shallow fluid with one derived from fluid circulation within the nakhlite cumulate pile - with heat for fluid circulation supplied by either the igneous intrusion or by an impact event.

Advanced Natural Gas Reciprocating Engine(s)

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

Pike, Edward

The objective of the Cummins ARES program, in partnership with the US Department of Energy (DOE), is to develop advanced natural gas engine technologies that increase engine system efficiency at lower emissions levels while attaining lower cost of ownership. The goals of the project are to demonstrate engine system achieving 50% Brake Thermal Efficiency (BTE) in three phases, 44%, 47% and 50% (starting baseline efficiency at 36% BTE) and 0.1 g/bhp-hr NOx system out emissions (starting baseline NOx emissions at 2 – 4 g/bhp-hr NOx). Primary path towards above goals include high Brake Mean Effective Pressure (BMEP), improved closed cyclemore » efficiency, increased air handling efficiency and optimized engine subsystems. Cummins has successfully demonstrated each of the phases of this program. All targets have been achieved through application of a combined set of advanced base engine technologies and Waste Heat Recovery from Charge Air and Exhaust streams, optimized and validated on the demonstration engine and other large engines. The following architectures were selected for each Phase: Phase 1: Lean Burn Spark Ignited (SI) Key Technologies: High Efficiency Turbocharging, Higher Efficiency Combustion System. In production on the 60/91L engines. Over 500MW of ARES Phase 1 technology has been sold. Phase 2: Lean Burn Technology with Exhaust Waste Heat Recovery (WHR) System Key Technologies: Advanced Ignition System, Combustion Improvement, Integrated Waste Heat Recovery System. Base engine technologies intended for production within 2 to 3 years Phase 3: Lean Burn Technology with Exhaust and Charge Air Waste Heat Recovery System Key Technologies: Lower Friction, New Cylinder Head Designs, Improved Integrated Waste Heat Recovery System. Intended for production within 5 to 6 years Cummins is committed to the launch of next generation of large advanced NG engines based on ARES technology to be commercialized worldwide.« less

Energy Efficient Engine: Control system component performance report

NASA Technical Reports Server (NTRS)

Beitler, R. S.; Bennett, G. W.

1984-01-01

An Energy Efficient Engine (E3) program was established to develop technology for improving the energy efficiency of future commercial transport aircraft engines. As part of this program, General Electric designed and tested a new engine. The design, fabrication, bench and engine testing of the Full Authority Digital Electronic Control (FADEC) system used for controlling the E3 Demonstrator Engine is described. The system design was based on many of the proven concepts and component designs used on the General Electric family of engines. One significant difference is the use of the FADEC in place of hydromechanical computation currently used.

Design approaches to more energy efficient engines

NASA Technical Reports Server (NTRS)

Saunders, N. T.; Colladay, R. S.; Macioce, L. E.

1978-01-01

The status of NASA's Energy Efficient Engine Project, a comparative government-industry effort aimed at advancing the technology base for the next generation of large turbofan engines for civil aircraft transports is summarized. Results of recently completed studies are reviewed. These studies involved selection of engine cycles and configurations that offer potential for at least 12% lower fuel consumption than current engines and also are economically attractive and environmentally acceptable. Emphasis is on the advancements required in component technologies and systems design concepts to permit future development of these more energy efficient engines.

Energy Efficient Engine (E3) controls and accessories detail design report

NASA Technical Reports Server (NTRS)

Beitler, R. S.; Lavash, J. P.

1982-01-01

An Energy Efficient Engine program has been established by NASA to develop technology for improving the energy efficiency of future commercial transport aircraft engines. As part of this program, a new turbofan engine was designed. This report describes the fuel and control system for this engine. The system design is based on many of the proven concepts and component designs used on the General Electric CF6 family of engines. One significant difference is the incorporation of digital electronic computation in place of the hydromechanical computation currently used.

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

Van Blarigan, P.

A hydrogen fueled engine is being developed specifically for the auxiliary power unit (APU) in a series type hybrid vehicle. Hydrogen is different from other internal combustion (IC) engine fuels, and hybrid vehicle IC engine requirements are different from those of other IC vehicle engines. Together these differences will allow a new engine design based on first principles that will maximize thermal efficiency while minimizing principal emissions. The experimental program is proceeding in four steps: (1) Demonstration of the emissions and the indicated thermal efficiency capability of a standard CLR research engine modified for higher compression ratios and hydrogen fueledmore » operation. (2) Design and test a new combustion chamber geometry for an existing single cylinder research engine, in an attempt to improve on the baseline indicated thermal efficiency of the CLR engine. (3) Design and build, in conjunction with an industrial collaborator, a new full scale research engine designed to maximize brake thermal efficiency. Include a full complement of combustion diagnostics. (4) Incorporate all of the knowledge thus obtained in the design and fabrication, by an industrial collaborator, of the hydrogen fueled engine for the hybrid vehicle power train illustrator. Results of the CLR baseline engine testing are presented, as well as preliminary data from the new combustion chamber engine. The CLR data confirm the low NOx produced by lean operation. The preliminary indicated thermal efficiency data from the new combustion chamber design engine show an improvement relative to the CLR engine. Comparison with previous high compression engine results shows reasonable agreement.« less

Enabling High Efficiency Ethanol Engines

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

Szybist, J.; Confer, K.

2011-03-01

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

Adapting a Navier-Stokes code to the ICL-DAP

NASA Technical Reports Server (NTRS)

Grosch, C. E.

1985-01-01

The results of an experiment are reported, i.c., to adapt a Navier-Stokes code, originally developed on a serial computer, to concurrent processing on the CL Distributed Array Processor (DAP). The algorithm used in solving the Navier-Stokes equations is briefly described. The architecture of the DAP and DAP FORTRAN are also described. The modifications of the algorithm so as to fit the DAP are given and discussed. Finally, performance results are given and conclusions are drawn.

THE SCATTERING OF K AND Cs BY SEVERAL COMPOUNDS.

DTIC Science & Technology

The nonreactive scattering of K from C10H16, (CH3)3CBr, SiCl4 , Cl2, Br2, I2, ICl, (CN)2C=C(CN)2, and Cs from HBr has been studied in experiments with... SiCl4 , and Cs + HBr and also from the supernumerary rainbows for K + C10H16 and (CH3)3CBr. An optical model analysis on K+(CH3)3CBr and Cs + HBr

Fanconi anemia (cross)linked to DNA repair.

PubMed

Niedernhofer, Laura J; Lalai, Astrid S; Hoeijmakers, Jan H J

2005-12-29

Fanconi anemia is characterized by hypersensitivity to DNA interstrand crosslinks (ICLs) and susceptibility to tumor formation. Despite the identification of numerous Fanconi anemia (FANC) genes, the mechanism by which proteins encoded by these genes protect a cell from DNA interstrand crosslinks remains unclear. The recent discovery of two DNA helicases that, when defective, cause Fanconi anemia tips the balance in favor of the direct involvement of the FANC proteins in DNA repair and the bypass of DNA lesions.

Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

NASA Astrophysics Data System (ADS)

Kalid, Ori; Mense, Martin; Fischman, Sharon; Shitrit, Alina; Bihler, Hermann; Ben-Zeev, Efrat; Schutz, Nili; Pedemonte, Nicoletta; Thomas, Philip J.; Bridges, Robert J.; Wetmore, Diana R.; Marantz, Yael; Senderowitz, Hanoch

2010-12-01

Folding correctors of F508del-CFTR were discovered by in silico structure-based screening utilizing homology models of CFTR. The intracellular segment of CFTR was modeled and three cavities were identified at inter-domain interfaces: (1) Interface between the two Nucleotide Binding Domains (NBDs); (2) Interface between NBD1 and Intracellular Loop (ICL) 4, in the region of the F508 deletion; (3) multi-domain interface between NBD1:2:ICL1:2:4. We hypothesized that compounds binding at these interfaces may improve the stability of the protein, potentially affecting the folding yield or surface stability. In silico structure-based screening was performed at the putative binding-sites and a total of 496 candidate compounds from all three sites were tested in functional assays. A total of 15 compounds, representing diverse chemotypes, were identified as F508del folding correctors. This corresponds to a 3% hit rate, tenfold higher than hit rates obtained in corresponding high-throughput screening campaigns. The same binding sites also yielded potentiators and, most notably, compounds with a dual corrector-potentiator activity (dual-acting). Compounds harboring both activity types may prove to be better leads for the development of CF therapeutics than either pure correctors or pure potentiators. To the best of our knowledge this is the first report of structure-based discovery of CFTR modulators.

Chloride equilibrium potential in salamander cones

PubMed Central

Thoreson, Wallace B; Bryson, Eric J

2004-01-01

Background GABAergic inhibition and effects of intracellular chloride ions on calcium channel activity have been proposed to regulate neurotransmission from photoreceptors. To assess the impact of these and other chloride-dependent mechanisms on release from cones, the chloride equilibrium potential (ECl) was determined in red-sensitive, large single cones from the tiger salamander retinal slice. Results Whole cell recordings were done using gramicidin perforated patch techniques to maintain endogenous Cl- levels. Membrane potentials were corrected for liquid junction potentials. Cone resting potentials were found to average -46 mV. To measure ECl, we applied long depolarizing steps to activate the calcium-activated chloride current (ICl(Ca)) and then determined the reversal potential for the current component that was inhibited by the Cl- channel blocker, niflumic acid. With this method, ECl was found to average -46 mV. In a complementary approach, we used a Cl-sensitive dye, MEQ, to measure the Cl- flux produced by depolarization with elevated concentrations of K+. The membrane potentials produced by the various high K+ solutions were measured in separate current clamp experiments. Consistent with electrophysiological experiments, MEQ fluorescence measurements indicated that ECl was below -36 mV. Conclusions The results of this study indicate that ECl is close to the dark resting potential. This will minimize the impact of chloride-dependent presynaptic mechanisms in cone terminals involving GABAa receptors, glutamate transporters and ICl(Ca). PMID:15579212

The Effect of the Crystalline Lens on Central Vault After Implantable Collamer Lens Implantation.

PubMed

Qi, Meng-Ying; Chen, Qian; Zeng, Qing-Yan

2017-08-01

To identify associations between crystalline lens-related factors and central vault after Implantable Collamer Lens (ICL) (Staar Surgical, Monrovia, CA) implantation. This retrospective clinical study included 320 eyes from 186 patients who underwent ICL implantation surgery. At 1 year after surgery, the central vault was measured using anterior segment optical coherence tomography. Preoperative anterior chamber depth, lens thickness, lens position (lens position = anterior chamber depth + 1/2 lens thickness), and vault were analyzed to investigate the effects of lens-related factors on postoperative vault. The mean vault was 513 ± 215 µm at 1 year after surgery. Vault was positively correlated with preoperative anterior chamber depth (r = 0.495, P < .001) and lens position (r = 0.371, P < .001), but negatively correlated with lens thickness (r = -0.262, P < .001). Eyes with vaults of less than 250 µm had shallower anterior chambers, thicker lenses, and smaller lens position than eyes in the other two vault groups (which had vaults ≥ 250 µm) (P < .001). Eyes with both anterior chamber depth less than 3.1 mm and lens position less than 5.1 mm had greatly reduced vaults (P < .001). The crystalline lens could have an important influence on postoperative vault. Eyes with a shallower anterior chamber and a forward lens position will have lower vaults. [J Refract Surg. 2017;33(8):519-523.]. Copyright 2017, SLACK Incorporated.

The role of ADP-ribosylation in regulating DNA interstrand crosslink repair

PubMed Central

Gunn, Alasdair R.; Banos-Pinero, Benito; Paschke, Peggy; Sanchez-Pulido, Luis; Ariza, Antonio; Day, Joseph; Emrich, Mehera; Leys, David; Ponting, Chris P.

2016-01-01

ABSTRACT ADP-ribosylation by ADP-ribosyltransferases (ARTs) has a well-established role in DNA strand break repair by promoting enrichment of repair factors at damage sites through ADP-ribose interaction domains. Here, we exploit the simple eukaryote Dictyostelium to uncover a role for ADP-ribosylation in regulating DNA interstrand crosslink repair and redundancy of this pathway with non-homologous end-joining (NHEJ). In silico searches were used to identify a protein that contains a permutated macrodomain (which we call aprataxin/APLF-and-PNKP-like protein; APL). Structural analysis reveals that this permutated macrodomain retains features associated with ADP-ribose interactions and that APL is capable of binding poly(ADP-ribose) through this macrodomain. APL is enriched in chromatin in response to cisplatin treatment, an agent that induces DNA interstrand crosslinks (ICLs). This is dependent on the macrodomain of APL and the ART Adprt2, indicating a role for ADP-ribosylation in the cellular response to cisplatin. Although adprt2− cells are sensitive to cisplatin, ADP-ribosylation is evident in these cells owing to redundant signalling by the double-strand break (DSB)-responsive ART Adprt1a, promoting NHEJ-mediated repair. These data implicate ADP-ribosylation in DNA ICL repair and identify that NHEJ can function to resolve this form of DNA damage in the absence of Adprt2. PMID:27587838

Apoptotic depletion of CD4+ T cells in idiopathic CD4+ T lymphocytopenia.

PubMed Central

Laurence, J; Mitra, D; Steiner, M; Lynch, D H; Siegal, F P; Staiano-Coico, L

1996-01-01

Progressive loss of CD4+ T lymphocytes, accompanied by opportunistic infections characteristic of the acquired immune deficiency syndrome, ahs been reported in the absence of any known etiology. The pathogenesis of this syndrome, a subset of idiopathic CD4+ T lymphocytopenia (ICL), is uncertain. We report that CD4+ T cells from seven of eight ICL patients underwent accelerated programmed cell death, a process facilitated by T cell receptor cross-linking. Apoptosis was associated with enhanced expression of Fas and Fas ligand in unstimulated cell populations, and partially inhibited by soluble anti-Fas mAb. In addition, apoptosis was suppressed by aurintricarboxylic acid, an inhibitor of calcium-dependent endonucleases and proteases, in cells from four of seven patients, The in vivo significance of these findings was supported by three factors: the absence of accelerated apoptosis in persons with stable, physiologic CD4 lymphopenia without clinical immune deficiency; detection of serum antihistone H2B autoantibodies, one consequence of DNA fragmentation, in some patients; and its selectivity, with apoptosis limited to the CD4 population in some, and occurring among CD8+ T cells predominantly in those individuals with marked depletion of both CD4+ T lymphocytes linked to clinical immune suppression have evidence for accelerated T cell apoptosis in vitro that may be pathophysiologic and amenable to therapy with apoptosis inhibitors. PMID:8609222

A new strategy to mitigate the initial capacity loss of lithium ion batteries

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

Su, Xin; Lin, Chikai; Wang, Xiaoping

2016-08-01

Hard carbon (non-graphitizable) and related materials, like tin, tin oxide, silicon, and silicon oxide, have a high theoretical lithium delivery capacity (>550 mAh/g depending on their structural and chemical properties) but unfortunately they also exhibit a large initial capacity loss (ICL) that overrides the true reversible capacity in a full cell. Overcoming the large ICL of hard carbon in a full-cell lithium-ion battery (LIB) necessitates a new strategy wherein a sacrificial lithium source additive, such as, Li5FeO4 (LFO), is inserted on the cathode side. Full batteries using hard carbon coupled with LFO-LiCoO2 (LCO) are currently under development at our laboratory.more » We find that the reversible capacity of a cathode containing LFO can be increased by 14%. Furthermore, the cycle performance of full cells with LFO additive is improved from <90% to >95%. We show that the LFO additive not only can address the irreversible capacity loss of the anode, but can also provide the additional lithium ion source required to mitigate the lithium loss caused by side reactions. In addition, we have explored the possibility to achieve higher capacity with hard carbon, whereby the energy density of full cells can be increased from ca. 300 Wh/kg to >400 Wh/kg.« less

Coupling of HRT II and AS-OCT to evaluate corneal endothelial cell loss and in vivo visualization of the Ahmed glaucoma valve implant.

PubMed

Mendrinos, E; Dosso, A; Sommerhalder, J; Shaarawy, T

2009-09-01

To report corneal endothelial cell loss and in vivo visualization of the Ahmed glaucoma valve implant in eyes with refractory glaucoma. Ten eyes underwent Ahmed valve implant surgery and were followed-up for 12 months. Data collected included intraocular pressure (IOP), number of antiglaucoma medications and surgery-related complications. At 6 and 12 months postoperatively, the intracameral length of the drainage tube (ICL) and the distance between the tube and the cornea (T-C distance), and the iris (T-I distance) were assessed using anterior segment optical coherence tomography (AS-OCT). Heidelberg cornea tomograph II (HRT II) was used to measure the corneal endothelial cell density. Mean (+/-SEM) preoperative IOP was 29.5+/-4 mmHg. Mean postoperative IOP was 11.6+/-2 at 12 months (P<0.01). Over a 6-month period, mean corneal endothelial loss was 7.9%+/-2.5 in the central and 7.5%+/-2.4 in the peripheral cornea (P<0.01). There was no correlation between central or peripheral corneal endothelial cell loss and the T-C, T-I distance or the ICL of the tube. Corneal endothelial cell loss occurs following Ahmed valve implant surgery, this appears to be multifactorial. AS-OCT and HRT II are promising methods for the follow-up of patients with a glaucoma drainage device.

FANCJ Helicase Operates in the Fanconi Anemia DNA Repair Pathway and the Response to Replicational Stress

PubMed Central

Wu, Yuliang; Brosh, Robert M.

2009-01-01

Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and high cancer risk. Cells from FA patients exhibit spontaneous chromosomal instability and hypersensitivity to DNA interstrand cross-linking (ICL) agents. Although the precise mechanistic details of the FA/BRCA pathway of ICL-repair are not well understood, progress has been made in the identification of the FA proteins that are required for the pathway. Among the 13 FA complementation groups from which all the FA genes have been cloned, only a few of the FA proteins are predicted to have direct roles in DNA metabolism. One of the more recently identified FA proteins, shown to be responsible for complementation of the FA complementation group J, is the BRCA1 Associated C-terminal Helicase (BACH1, designated FANCJ), originally identified as a protein associated with breast cancer. FANCJ has been proposed to function downstream of FANCD2 monoubiquitination, a critical event in the FA pathway. Evidence supports a role for FANCJ in a homologous recombination (HR) pathway of double strand break (DSB) repair. In this review, we will summarize the current knowledge in terms of FANCJ functions through its enzymatic activities and protein interactions. The molecular roles of FANCJ in DNA repair and the response to replicational stress will be discussed. PMID:19519404

High brightness diode lasers controlled by volume Bragg gratings

NASA Astrophysics Data System (ADS)

Glebov, Leonid

2017-02-01

Volume Bragg gratings (VBGs) recorded in photo-thermo-refractive (PTR) glass are holographic optical elements that are effective spectral and angular filters withstanding high power laser radiation. Reflecting VBGs are narrow-band spectral filters while transmitting VBGs are narrow-band angular filters. The use of these optical elements in external resonators of semiconductor lasers enables extremely resonant feedback that provides dramatic spectral and angular narrowing of laser diodes radiation without significant power and efficiency penalty. Spectral narrowing of laser diodes by reflecting VBGs demonstrated in wide spectral region from near UV to 3 μm. Commercially available VBGs have spectral width ranged from few nanometers to few tens of picometers. Efficient spectral locking was demonstrated for edge emitters (single diodes, bars, modules, and stacks), vertical cavity surface emitting lasers (VCSELs), grating coupled surface emitting lasers (GCSELs), and interband cascade lasers (ICLs). The use of multiplexed VBGs provides multiwavelength emission from a single emitter. Spectrally locked semiconductor lasers demonstrated CW power from milliwatts to a kilowatt. Angular narrowing by transmitting VBGs enables single transverse mode emission from wide aperture diode lasers having resonators with great Fresnel numbers. This feature provides close to diffraction limit divergence along a slow axis of wide stripe edge emitters. Radiation exchange between lasers by means of spatially profiled or multiplexed VBGs enables coherent combining of diode lasers. Sequence of VBGs or multiplexed VBGs enable spectral combining of spectrally narrowed diode lasers or laser modules. Thus the use of VBGs for diode lasers beam control provides dramatic increase of brightness.

Disparate requirements for the Walker A and B ATPase motifs of human RAD51D in homologous recombination.

PubMed

Wiese, Claudia; Hinz, John M; Tebbs, Robert S; Nham, Peter B; Urbin, Salustra S; Collins, David W; Thompson, Larry H; Schild, David

2006-01-01

In vertebrates, homologous recombinational repair (HRR) requires RAD51 and five RAD51 paralogs (XRCC2, XRCC3, RAD51B, RAD51C and RAD51D) that all contain conserved Walker A and B ATPase motifs. In human RAD51D we examined the requirement for these motifs in interactions with XRCC2 and RAD51C, and for survival of cells in response to DNA interstrand crosslinks (ICLs). Ectopic expression of wild-type human RAD51D or mutants having a non-functional A or B motif was used to test for complementation of a rad51d knockout hamster CHO cell line. Although A-motif mutants complement very efficiently, B-motif mutants do not. Consistent with these results, experiments using the yeast two- and three-hybrid systems show that the interactions between RAD51D and its XRCC2 and RAD51C partners also require a functional RAD51D B motif, but not motif A. Similarly, hamster Xrcc2 is unable to bind to the non-complementing human RAD51D B-motif mutants in co-immunoprecipitation assays. We conclude that a functional Walker B motif, but not A motif, is necessary for RAD51D's interactions with other paralogs and for efficient HRR. We present a model in which ATPase sites are formed in a bipartite manner between RAD51D and other RAD51 paralogs.

Weak endogenous Ca2+ buffering supports sustained synaptic transmission by distinct mechanisms in rod and cone photoreceptors in salamander retina

PubMed Central

Van Hook, Matthew J; Thoreson, Wallace B

2015-01-01

Differences in synaptic transmission between rod and cone photoreceptors contribute to different response kinetics in rod- versus cone-dominated visual pathways. We examined Ca2+ dynamics in synaptic terminals of tiger salamander photoreceptors under conditions that mimicked endogenous buffering to determine the influence on kinetically and mechanistically distinct components of synaptic transmission. Measurements of ICl(Ca) confirmed that endogenous Ca2+ buffering is equivalent to ˜0.05 mmol/L EGTA in rod and cone terminals. Confocal imaging showed that with such buffering, depolarization stimulated large, spatially unconstrained [Ca2+] increases that spread throughout photoreceptor terminals. We calculated immediately releasable pool (IRP) size and release efficiency in rods by deconvolving excitatory postsynaptic currents and presynaptic Ca2+ currents. Peak efficiency of ˜0.2 vesicles/channel was similar to that of cones (˜0.3 vesicles/channel). Efficiency in both cell types was not significantly affected by using weak endogenous Ca2+ buffering. However, weak Ca2+ buffering speeded Ca2+/calmodulin (CaM)-dependent replenishment of vesicles to ribbons in both rods and cones, thereby enhancing sustained release. In rods, weak Ca2+ buffering also amplified sustained release by enhancing CICR and CICR-stimulated release of vesicles at nonribbon sites. By contrast, elevating [Ca2+] at nonribbon sites in cones with weak Ca2+ buffering and by inhibiting Ca2+ extrusion did not trigger additional release, consistent with the notion that exocytosis from cones occurs exclusively at ribbons. The presence of weak endogenous Ca2+ buffering in rods and cones facilitates slow, sustained exocytosis by enhancing Ca2+/CaM-dependent replenishment of ribbons in both rods and cones and by stimulating nonribbon release triggered by CICR in rods. PMID:26416977

Increased riboflavin production from activated bleaching earth by a mutant strain of Ashbya gossypii.

PubMed

Tajima, Satoshi; Itoh, Yoko; Sugimoto, Takashi; Kato, Tatsuya; Park, Enoch Y

2009-10-01

The production of riboflavin from vegetable oil was increased using a mutant strain of Ashbya gossypii. This mutant was generated by treating the wild-type strain with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Riboflavin production was 10-fold higher in the mutant compared to the wild-type strain. The specific intracellular catalase activity after 3 d of culture was 6-fold higher in the mutant than in the wild-type strain. For the mutant, riboflavin production in the presence of 40 mM hydrogen peroxide was 16% less than that in the absence of hydrogen peroxide, whereas it was 56% less for the wild-type strain. The isocitrate lyase (ICL) activity of the mutant was 0.26 mU/mg of protein during the active riboflavin production phase, which was 2.6-fold higher than the wild-type strain. These data indicate that the mutant utilizes the carbon flux from the TCA cycle to the glyoxylate cycle more efficiently than the wild-type strain, resulting in enhanced riboflavin production. This novel mutant has the potential to be of use for industrial-scale riboflavin production from waste-activated bleaching earth (ABE), thereby transforming a useless material into a valuable bioproduct.

Cervical Spine Involvement in Mild Traumatic Brain Injury: A Review

PubMed Central

Morin, Michael; Langevin, Pierre

2016-01-01

Background. There is a lack of scientific evidence in the literature on the involvement of the cervical spine in mTBI; however, its involvement is clinically accepted. Objective. This paper reviews evidence for the involvement of the cervical spine in mTBI symptoms, the mechanisms of injury, and the efficacy of therapy for cervical spine with concussion-related symptoms. Methods. A keyword search was conducted on PubMed, ICL, SportDiscus, PEDro, CINAHL, and Cochrane Library databases for articles published since 1990. The reference lists of articles meeting the criteria (original data articles, literature reviews, and clinical guidelines) were also searched in the same databases. Results. 4,854 records were screened and 43 articles were retained. Those articles were used to describe different subjects such as mTBI's signs and symptoms, mechanisms of injury, and treatments of the cervical spine. Conclusions. The hypothesis of cervical spine involvement in post-mTBI symptoms and in PCS (postconcussion syndrome) is supported by increasing evidence and is widely accepted clinically. For the management and treatment of mTBIs, few articles were available in the literature, and relevant studies showed interesting results about manual therapy and exercises as efficient tools for health care practitioners. PMID:27529079

Efficiency versus speed in quantum heat engines: Rigorous constraint from Lieb-Robinson bound

NASA Astrophysics Data System (ADS)

Shiraishi, Naoto; Tajima, Hiroyasu

2017-08-01

A long-standing open problem whether a heat engine with finite power achieves the Carnot efficiency is investgated. We rigorously prove a general trade-off inequality on thermodynamic efficiency and time interval of a cyclic process with quantum heat engines. In a first step, employing the Lieb-Robinson bound we establish an inequality on the change in a local observable caused by an operation far from support of the local observable. This inequality provides a rigorous characterization of the following intuitive picture that most of the energy emitted from the engine to the cold bath remains near the engine when the cyclic process is finished. Using this description, we prove an upper bound on efficiency with the aid of quantum information geometry. Our result generally excludes the possibility of a process with finite speed at the Carnot efficiency in quantum heat engines. In particular, the obtained constraint covers engines evolving with non-Markovian dynamics, which almost all previous studies on this topic fail to address.

Efficiency versus speed in quantum heat engines: Rigorous constraint from Lieb-Robinson bound.

PubMed

Shiraishi, Naoto; Tajima, Hiroyasu

2017-08-01

A long-standing open problem whether a heat engine with finite power achieves the Carnot efficiency is investgated. We rigorously prove a general trade-off inequality on thermodynamic efficiency and time interval of a cyclic process with quantum heat engines. In a first step, employing the Lieb-Robinson bound we establish an inequality on the change in a local observable caused by an operation far from support of the local observable. This inequality provides a rigorous characterization of the following intuitive picture that most of the energy emitted from the engine to the cold bath remains near the engine when the cyclic process is finished. Using this description, we prove an upper bound on efficiency with the aid of quantum information geometry. Our result generally excludes the possibility of a process with finite speed at the Carnot efficiency in quantum heat engines. In particular, the obtained constraint covers engines evolving with non-Markovian dynamics, which almost all previous studies on this topic fail to address.

Aircraft Energy Efficiency (ACEE) status report

NASA Technical Reports Server (NTRS)

Nored, D. L.; Dugan, J. F., Jr.; Saunders, N. T.; Ziemianski, J. A.

1979-01-01

Fuel efficiency in aeronautics, for fuel conservation in general as well as for its effect on commercial aircraft operating economics is considered. Projects of the Aircraft Energy Efficiency Program related to propulsion are emphasized. These include: (1) engine component improvement, directed at performance improvement and engine diagnostics for prolonged service life; (2) energy efficient engine, directed at proving the technology base for the next generation of turbofan engines; and (3) advanced turboprop, directed at advancing the technology of turboprop powered aircraft to a point suitable for commercial airline service. Progress in these technology areas is reported.

Final Report: Utilizing Alternative Fuel Ignition Properties to Improve SI and CI Engine Efficiency

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

Wooldridge, Margaret; Boehman, Andre; Lavoie, George

Experimental and modeling studies were completed to explore leveraging physical and chemical fuel properties for improved thermal efficiency of internal combustion engines. Fundamental studies of the ignition chemistry of ethanol and iso-octane blends and constant volume spray chamber studies of gasoline and diesel sprays supported the core research effort which used several reciprocating engine platforms. Single cylinder spark ignition (SI) engine studies were carried out to characterize the impact of ethanol/gasoline, syngas (H 2 and CO)/gasoline and other oxygenate/gasoline blends on engine performance. The results of the single-cylinder engine experiments and other data from the literature were used to trainmore » a GT Power model and to develop a knock criteria based on reaction chemistry. The models were used to interpret the experimental results and project future performance. Studies were also carried out using a state of the art, direct injection (DI) turbocharged multi- cylinder engine with piezo-actuated fuel injectors to demonstrate the promising spray and spark timing strategies from single-cylinder engine studies on the multi-cylinder engine. Key outcomes and conclusions of the studies were: 1. Efficiency benefits of ethanol and gasoline fuel blends were consistent and substantial (e.g. 5-8% absolute improvement in gross indicated thermal efficiency (GITE)). 2. The best ethanol/gasoline blend (based on maximum thermal efficiency) was determined by the engine hardware and limits based on component protection (e.g. peak in-cylinder pressure or maximum turbocharger inlet temperature) – and not by knock limits. Blends with <50% ethanol delivered significant thermal efficiency gains with conventional SI hardware while maintain good safety integrity to the engine hardware. 3. Other compositions of fuel blends including syngas (H 2 and CO) and other dilution strategies provided significant efficiency gains as well (e.g. 5% absolute improvement in ITE). 4. When the combination of engine and fuel system is not knock limited, multiple fuel injection events maintain thermal efficiency while improving engine-out emissions (e.g. CO, UHC, and particulate number).« less

Energy efficient engine fan component detailed design report

NASA Technical Reports Server (NTRS)

Halle, J. E.; Michael, C. J.

1981-01-01

The fan component which was designed for the energy efficient engine is an advanced high performance, single stage system and is based on technology advancements in aerodynamics and structure mechanics. Two fan components were designed, both meeting the integrated core/low spool engine efficiency goal of 84.5%. The primary configuration, envisioned for a future flight propulsion system, features a shroudless, hollow blade and offers a predicted efficiency of 87.3%. A more conventional blade was designed, as a back up, for the integrated core/low spool demonstrator engine. The alternate blade configuration has a predicted efficiency of 86.3% for the future flight propulsion system. Both fan configurations meet goals established for efficiency surge margin, structural integrity and durability.

A thermoacoustic-Stirling heat engine: detailed study

PubMed

Backhaus; Swift

2000-06-01

A new type of thermoacoustic engine based on traveling waves and ideally reversible heat transfer is described. Measurements and analysis of its performance are presented. This new engine outperforms previous thermoacoustic engines, which are based on standing waves and intrinsically irreversible heat transfer, by more than 50%. At its most efficient operating point, it delivers 710 W of acoustic power to its resonator with a thermal efficiency of 0.30, corresponding to 41% of the Carnot efficiency. At its most powerful operating point, it delivers 890 W to its resonator with a thermal efficiency of 0.22. The efficiency of this engine can be degraded by two types of acoustic streaming. These are suppressed by appropriate tapering of crucial surfaces in the engine and by using additional nonlinearity to induce an opposing time-averaged pressure difference. Data are presented which show the nearly complete elimination of the streaming convective heat loads. Analysis of these and other irreversibilities show which components of the engine require further research to achieve higher efficiency. Additionally, these data show that the dynamics and acoustic power flows are well understood, but the details of the streaming suppression and associated heat convection are only qualitatively understood.

A New Cell-Free System to Study BRCA1 Function

DTIC Science & Technology

2015-05-01

analyzed by denaturing polyacrylamide gel electrophoresis. UbVS treatment had no effect on the arrival of leading strands at the ICL (Figure 2G in [3...of leading strands to the -1 position, as well as formation of all downstream nascent strand products (Figure 2G in [3], compare lanes 7-11 with 13...17). Addition of free ubiquitin with UbVS restored Approach, Insertion, and Extension, albeit with delayed kinetics (Figure 2G in [3], lanes 19-23

Principles of Work Sample Testing. 1. A Non-Empirical Taxonomy of Test Uses

DTIC Science & Technology

1979-04-01

ARI TECHNICAL REPORT TR-79-A8 Principles of Work Sample Testingi I. A Non-Empirical Taxonomy of Test Uses b y Robert M. Guion BOWLING GREEN STATE...UNIVERSITY % ’ Bowling Green , Ohio 43403 e April 1979 Contract DAHC 19-77-C-0007 Cj Prepared for U.S. ARMY RESEARCH INSTITUTEfor the BEHAVIORAL and...M./io DAlICl9-77-Cji11J7 * 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK Bowling Green State UniversityAEAWOKUINMER

Integration of Manpower, Personnel, and Training Issues from the Materiel System Acquisition Process Into the Planning Programming and Budgeting System

DTIC Science & Technology

1981-03-01

89’" ICL THIS DOCUMENT IS BEST QUALITY AVAILABLE. THE COPY FURNISHED TO DTIC CONTAINED A SIGNIFICANT NUMBER OF PAGES WHICH DO NOT REPRODUCE LEGIBLY. U...S. ARMY RESEARCH INSTITUTE FOR THE BEHAVIORAL AND SOCIAL SCIENCES A Field Operating Agency under the Jurisdiction of the Deputy Chief of Staff for...SUPPLEMENTARY NOTES Col. Frank Bettinger (SSC-NCR), LTC Donald Lyman (DCSPER), and Mr. Jacob Barber (DSCPER) provided valuable input and critical

Cleaner, More Efficient Diesel Engines

ScienceCinema

Musculus, Mark

2018-01-16

Mark Musculus, an engine combustion scientist at Sandia National Laboratories, led a study that outlines the science base for auto and engine manufacturers to build the next generation of cleaner, more efficient engines using low-temperature combustion. Here, Musculus discusses the work at Sandia's Combustion Research Facility.

CO2 laser-driven Stirling engine. [space power applications

NASA Technical Reports Server (NTRS)

Lee, G.; Perry, R. L.; Carney, B.

1978-01-01

A 100-W Beale free-piston Stirling engine was powered remotely by a CO2 laser for long periods of time. The engine ran on both continuous-wave and pulse laser input. The working fluid was helium doped with small quantities of sulfur hexafluoride, SF6. The CO2 radiation was absorbed by the vibrational modes of the sulfur hexafluoride, which in turn transferred the energy to the helium to drive the engine. Electrical energy was obtained from a linear alternator attached to the piston of the engine. Engine pressures, volumes, and temperatures were measured to determine engine performance. It was found that the pulse radiation mode was more efficient than the continuous-wave mode. An analysis of the engine heat consumption indicated that heat losses around the cylinder and the window used to transmit the beam into the engine accounted for nearly half the energy input. The overall efficiency, that is, electrical output to laser input, was approximately 0.75%. However, this experiment was not designed for high efficiency but only to demonstrate the concept of a laser-driven engine. Based on this experiment, the engine could be modified to achieve efficiencies of perhaps 25-30%.

Fuel conservative aircraft engine technology

NASA Technical Reports Server (NTRS)

Nored, D. L.

1978-01-01

Technology developments for more fuel-efficiency subsonic transport aircraft are reported. Three major propulsion projects were considered: (1) engine component improvement - directed at current engines; (2) energy efficient engine - directed at new turbofan engines; and (3) advanced turboprops - directed at technology for advanced turboprop-powered aircraft. Each project is reviewed and some of the technologies and recent accomplishments are described.

Energy efficient engine component development and integration program

NASA Technical Reports Server (NTRS)

1980-01-01

The design of an energy efficient commercial turbofan engine is examined with emphasis on lower fuel consumption and operating costs. Propulsion system performance, emission standards, and noise reduction are also investigated. A detailed design analysis of the engine/aircraft configuration, engine components, and core engine is presented along with an evaluation of the technology and testing involved.

Energy efficient engine. Core engine bearings, drives and configuration: Detailed design report

NASA Technical Reports Server (NTRS)

Broman, C. L.

1981-01-01

The detailed design of the forward and aft sumps, the accessory drive system, the lubrication system, and the piping/manifold configuration to be employed in the core engine test of the Energy Efficient Engine is addressed. The design goals for the above components were established based on the requirements of the test cell engine.

The maximum efficiency of nano heat engines depends on more than temperature

NASA Astrophysics Data System (ADS)

Woods, Mischa; Ng, Nelly; Wehner, Stephanie

Sadi Carnot's theorem regarding the maximum efficiency of heat engines is considered to be of fundamental importance in the theory of heat engines and thermodynamics. Here, we show that at the nano and quantum scale, this law needs to be revised in the sense that more information about the bath other than its temperature is required to decide whether maximum efficiency can be achieved. In particular, we derive new fundamental limitations of the efficiency of heat engines at the nano and quantum scale that show that the Carnot efficiency can only be achieved under special circumstances, and we derive a new maximum efficiency for others. A preprint can be found here arXiv:1506.02322 [quant-ph] Singapore's MOE Tier 3A Grant & STW, Netherlands.

A New Method to Measure Temperature and Burner Pattern Factor Sensing for Active Engine Control

NASA Technical Reports Server (NTRS)

Ng, Daniel

1999-01-01

The determination of the temperatures of extended surfaces which exhibit non-uniform temperature variation is very important for a number of applications including the "Burner Pattern Factor" (BPF) of turbine engines. Exploratory work has shown that use of BPF to control engine functions can result in many benefits, among them reduction in engine weight, reduction in operating cost, increase in engine life, while attaining maximum engine efficiency. Advanced engines are expected to operate at very high temperature to achieve high efficiency. Brief exposure of engine components to higher than design temperatures due to non-uniformity in engine burner pattern can reduce engine life. The engine BPF is a measure of engine temperature uniformity. Attainment of maximum temperature uniformity and high temperatures is key to maximum efficiency and long life. A new approach to determine through the measurement of just one radiation spectrum by a multiwavelength pyrometer is possible. This paper discusses a new temperature sensing approach and its application to determine the BPF.

Relations between the efficiency, power and dissipation for linear irreversible heat engine at maximum trade-off figure of merit

NASA Astrophysics Data System (ADS)

Iyyappan, I.; Ponmurugan, M.

2018-03-01

A trade of figure of merit (\\dotΩ ) criterion accounts the best compromise between the useful input energy and the lost input energy of the heat devices. When the heat engine is working at maximum \\dotΩ criterion its efficiency increases significantly from the efficiency at maximum power. We derive the general relations between the power, efficiency at maximum \\dotΩ criterion and minimum dissipation for the linear irreversible heat engine. The efficiency at maximum \\dotΩ criterion has the lower bound \

Quantum engine efficiency bound beyond the second law of thermodynamics.

PubMed

Niedenzu, Wolfgang; Mukherjee, Victor; Ghosh, Arnab; Kofman, Abraham G; Kurizki, Gershon

2018-01-11

According to the second law, the efficiency of cyclic heat engines is limited by the Carnot bound that is attained by engines that operate between two thermal baths under the reversibility condition whereby the total entropy does not increase. Quantum engines operating between a thermal and a squeezed-thermal bath have been shown to surpass this bound. Yet, their maximum efficiency cannot be determined by the reversibility condition, which may yield an unachievable efficiency bound above unity. Here we identify the fraction of the exchanged energy between a quantum system and a bath that necessarily causes an entropy change and derive an inequality for this change. This inequality reveals an efficiency bound for quantum engines energised by a non-thermal bath. This bound does not imply reversibility, unless the two baths are thermal. It cannot be solely deduced from the laws of thermodynamics.

Carnot cycle at finite power: attainability of maximal efficiency.

PubMed

Allahverdyan, Armen E; Hovhannisyan, Karen V; Melkikh, Alexey V; Gevorkian, Sasun G

2013-08-02

We want to understand whether and to what extent the maximal (Carnot) efficiency for heat engines can be reached at a finite power. To this end we generalize the Carnot cycle so that it is not restricted to slow processes. We show that for realistic (i.e., not purposefully designed) engine-bath interactions, the work-optimal engine performing the generalized cycle close to the maximal efficiency has a long cycle time and hence vanishing power. This aspect is shown to relate to the theory of computational complexity. A physical manifestation of the same effect is Levinthal's paradox in the protein folding problem. The resolution of this paradox for realistic proteins allows to construct engines that can extract at a finite power 40% of the maximally possible work reaching 90% of the maximal efficiency. For purposefully designed engine-bath interactions, the Carnot efficiency is achievable at a large power.

Filter-based control of particulate matter from a lean gasoline direct injection engine

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

Parks, II, James E; Lewis Sr, Samuel Arthur; DeBusk, Melanie Moses

New regulations requiring increases in vehicle fuel economy are challenging automotive manufacturers to identify fuel-efficient engines for future vehicles. Lean gasoline direct injection (GDI) engines offer significant increases in fuel efficiency over the more common stoichiometric GDI engines already in the marketplace. However, particulate matter (PM) emissions from lean GDI engines, particularly during stratified combustion modes, are problematic for lean GDI technology to meet U.S. Environmental Protection Agency Tier 3 and other future emission regulations. As such, the control of lean GDI PM with wall-flow filters, referred to as gasoline particulate filter (GPF) technology, is of interest. Since lean GDImore » PM chemistry and morphology differ from diesel PM (where more filtration experience exists), the functionality of GPFs needs to be studied to determine the operating conditions suitable for efficient PM removal. In addition, lean GDI engine exhaust temperatures are generally higher than diesel engines which results in more continuous regeneration of the GPF and less presence of the soot cake layer common to diesel particulate filters. Since the soot layer improves filtration efficiency, this distinction is important to consider. Research on the emission control of PM from a lean GDI engine with a GPF was conducted on an engine dynamometer. PM, after dilution, was characterized with membrane filters, organic vs. elemental carbon characterization, and size distribution techniques at various steady state engine speed and load points. The engine was operated in three primary combustion modes: stoichiometric, lean homogeneous, and lean stratified. In addition, rich combustion was utilized to simulate PM from engine operation during active regeneration of lean NOx control technologies. High (>95%) PM filtration efficiencies were observed over a wide range of conditions; however, some PM was observed to slip through the GPF at high speed and load conditions. The PM characterization at various engine speeds and loads will help enable optimized GPF design and control to achieve more fuel efficient lean GDI vehicles with low PM emissions.« less

Engines with ideal efficiency and nonzero power for sublinear transport laws

NASA Astrophysics Data System (ADS)

Koning, Jesper; Indekeu, Joseph O.

2016-11-01

It is known that an engine with ideal efficiency (η = 1 for a chemical engine and e = eCarnot for a thermal one) has zero power because a reversible cycle takes an infinite time. However, at least from a theoretical point of view, it is possible to conceive (irreversible) engines with nonzero power that can reach ideal efficiency. Here this is achieved by replacing the usual linear transport law by a sublinear one and taking the step-function limit for the particle current (chemical engine) or heat current (thermal engine) versus the applied force. It is shown that in taking this limit exact thermodynamic inequalities relating the currents to the entropy production are not violated.

Study, optimization, and design of a laser heat engine. [for satellite applications

NASA Technical Reports Server (NTRS)

Taussig, R. T.; Cassady, P. E.; Zumdieck, J. F.

1978-01-01

Laser heat engine concepts, proposed for satellite applications, are analyzed to determine which engine concept best meets the requirements of high efficiency (50 percent or better), continuous operation in space using near-term technology. The analysis of laser heat engines includes the thermodynamic cycles, engine design, laser power sources, collector/concentrator optics, receiving windows, absorbers, working fluids, electricity generation, and heat rejection. Specific engine concepts, optimized according to thermal efficiency, are rated by their technological availability and scaling to higher powers. A near-term experimental demonstration of the laser heat engine concept appears feasible utilizing an Otto cycle powered by CO2 laser radiation coupled into the engine through a diamond window. Higher cycle temperatures, higher efficiencies, and scalability to larger sizes appear to be achievable from a laser heat engine design based on the Brayton cycle and powered by a CO laser.

Efficiency and its bounds for thermal engines at maximum power using Newton's law of cooling.

PubMed

Yan, H; Guo, Hao

2012-01-01

We study a thermal engine model for which Newton's cooling law is obeyed during heat transfer processes. The thermal efficiency and its bounds at maximum output power are derived and discussed. This model, though quite simple, can be applied not only to Carnot engines but also to four other types of engines. For the long thermal contact time limit, new bounds, tighter than what were known before, are obtained. In this case, this model can simulate Otto, Joule-Brayton, Diesel, and Atkinson engines. While in the short contact time limit, which corresponds to the Carnot cycle, the same efficiency bounds as that from Esposito et al. [Phys. Rev. Lett. 105, 150603 (2010)] are derived. In both cases, the thermal efficiency decreases as the ratio between the heat capacities of the working medium during heating and cooling stages increases. This might provide instructions for designing real engines. © 2012 American Physical Society

Performance of Maybach 300-horsepower airplane engine

NASA Technical Reports Server (NTRS)

Sparrow, S W

1923-01-01

This report contains the results of a test made upon a Maybach Engine in the altitude chamber of the Bureau of Standards, where controlled conditions of temperature and pressure can be made the same as those of the desired altitude. The results of this test lead to the following conclusions: from the standpoint of thermal efficiency the full-load performance of the engine is excellent at densities corresponding to altitudes up to and including 15,000 feet. The brake mean effective pressure is rather low even at wide-open throttle. This tends to give a high weight per horsepower, in as much as the weight of many engine parts is governed by the size rather than the power of the engine. At part load the thermal efficiency of the engine is low. Judged on a basis of performance the engine's chief claim to interest would appear to lie in the carburetor design, which is largely responsible excellent full-load efficiency and for its poor part-load efficiency.

Middle region of FancM interacts with Mhf and Rmi1 in silkworms, a species lacking the Fanconi anaemia (FA) core complex.

PubMed

Sugahara, R; Mon, H; Lee, J M; Kusakabe, T

2014-04-01

The Fanconi anaemia (FA) pathway is responsible for interstrand crosslink (ICL) repair. Among the FA core complex components, FANCM is believed to act as a damage sensor for the ICL-blocked replication fork and also as a molecular platform for FA core complex assembly and interaction with Bloom's syndrome (BS) complex that is thought to play an important role in the processing of DNA structures such as stalled replication forks. In the present study, we found that in silkworms, Bombyx mori, a species lacking the major FA core complex components (FANCA, B, C, E, F, and G), FancM is required for FancD2 monoubiquitination and cell proliferation in the presence of mitomycin C (MMC). Silkworm FancM (BmFancM) was phosphorylated in the middle regions, and the modification was associated with its subcellular localization. In addition, BmFancM interacted with Mhf1, a histone-fold protein, and Rmi1, a subunit of the BS complex, in the different regions. The interaction region containing at least these two protein-binding domains played an essential role in FancM-dependent resistance to MMC. Our results suggest that BmFancM also acts as a platform for recruitment of both the FA protein and the BS protein, although the silkworm genome seems to lose FAAP24, a FancM-binding partner protein in mammals. © 2013 The Royal Entomological Society.

Non-uniform temperature and species concentration measurements in a laminar flame using multi-band infrared absorption spectroscopy

NASA Astrophysics Data System (ADS)

Ma, Liu Hao; Lau, Lok Yin; Ren, Wei

2017-03-01

We report in situ measurements of non-uniform temperature, H2O and CO2 concentration distributions in a premixed methane-air laminar flame using tunable diode laser absorption spectroscopy (TDLAS). A mid-infrared, continuous-wave, room-temperature interband cascade laser (ICL) at 4183 nm was used for the sensitive detection of CO2 at high temperature.The H2O absorption lines were exploited by one distributed feedback (DFB) diode laser at 1343 nm and one ICL at 2482 nm to achieve multi-band absorption measurements with high species concentration sensitivity, high temperature sensitivity, and immunity to variations in ambient conditions. A novel profile-fitting function was proposed to characterize the non-uniform temperature and species concentrations along the line-of-sight in the flame by detecting six absorption lines of CO2 and H2O simultaneously. The flame temperature distribution was measured at different heights above the burner (5-20 mm), and compared with the thermocouple measurement with heat-transfer correction. Our TDLAS measured temperature of the central flame was in excellent agreement (<1.5% difference) with the thermocouple data.The TDLAS results were also compared with the CFD simulations using a detailed chemical kinetics mechanism (GRI 3.0) and considering the heat loss to the surroundings.The current CFD simulation overpredicted the flame temperature in the gradient region, but was in excellent agreement with the measured temperature and species concentration in the core of the flame.

MUSE spectroscopy and deep observations of a unique compact JWST target, lensing cluster CLIO

NASA Astrophysics Data System (ADS)

Griffiths, Alex; Conselice, Christopher J.; Alpaslan, Mehmet; Frye, Brenda L.; Diego, Jose M.; Zitrin, Adi; Yan, Haojing; Ma, Zhiyuan; Barone-Nugent, Robert; Bhatawdekar, Rachana; Driver, Simon P.; Robotham, Aaron S. G.; Windhorst, Rogier A.; Wyithe, J. Stuart B.

2018-04-01

We present the results of a VLT MUSE/FORS2 and Spitzer survey of a unique compact lensing cluster CLIO at z = 0.42, discovered through the GAMA survey using spectroscopic redshifts. Compact and massive clusters such as this are understudied, but provide a unique prospective on dark matter distributions and for finding background lensed high-z galaxies. The CLIO cluster was identified for follow-up observations due to its almost unique combination of high-mass and dark matter halo concentration, as well as having observed lensing arcs from ground-based images. Using dual band optical and infra-red imaging from FORS2 and Spitzer, in combination with MUSE optical spectroscopy we identify 89 cluster members and find background sources out to z = 6.49. We describe the physical state of this cluster, finding a strong correlation between environment and galaxy spectral type. Under the assumption of an NFW profile, we measure the total mass of CLIO to be M200 = (4.49 ± 0.25) × 1014 M⊙. We build and present an initial strong-lensing model for this cluster, and measure a relatively low intracluster light (ICL) fraction of 7.21 ± 1.53 per cent through galaxy profile fitting. Due to its strong potential for lensing background galaxies and its low ICL, the CLIO cluster will be a target for our 110 h James Webb Space Telescope `Webb Medium-Deep Field' (WMDF) GTO program.

The nuclease hSNM1B/Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP/SLX4.

PubMed

Salewsky, Bastian; Schmiester, Maren; Schindler, Detlev; Digweed, Martin; Demuth, Ilja

2012-11-15

The recessive genetic disorder Fanconi anemia (FA) is clinically characterized by congenital defects, bone marrow failure and an increased incidence of cancer. Cells derived from FA patients exhibit hypersensitivity to DNA interstrand crosslink (ICL)-inducing agents. We have earlier reported a similar cellular phenotype for human cells depleted of hSNM1B/Apollo (siRNA). In fact, hSNM1B/Apollo has a dual role in the DNA damage response and in generation and maintenance of telomeres, the latter function involving interaction with the shelterin protein TRF2. Here we find that ectopically expressed hSNM1B/Apollo co-immunoprecipitates with SLX4, a protein recently identified as a new FA protein, FANCP, and known to interact with several structure-specific nucleases. As shown by immunofluorescence analysis, FANCP/SLX4 depletion (siRNA) resulted in a significant reduction of hSNM1B/Apollo nuclear foci, supporting the functional relevance of this new protein interaction. Interestingly, as an additional consequence of FANCP/SLX4 depletion, we found a reduction of cellular TRF2, in line with its telomere-related function. Finally, analysis of human cells following double knockdown of hSNM1B/Apollo and FANCP/SLX4 indicated that they function epistatically. These findings further substantiate the role of hSNM1B/Apollo in a downstream step of the FA pathway during the repair of DNA ICLs.

A ChIP-chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response.

PubMed

Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-03-01

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP-chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response.

A ChIP–chip approach reveals a novel role for transcription factor IRF1 in the DNA damage response

PubMed Central

Frontini, Mattia; Vijayakumar, Meeraa; Garvin, Alexander; Clarke, Nicole

2009-01-01

IRF1 is a transcription factor that regulates key processes in the immune system and in tumour suppression. To gain further insight into IRF1's role in these processes, we searched for new target genes by performing chromatin immunoprecipitation coupled to a CpG island microarray (ChIP–chip). Using this approach we identified 202 new IRF1-binding sites with high confidence. Functional categorization of the target genes revealed a surprising cadre of new roles that can be linked to IRF1. One of the major functional categories was the DNA damage response pathway. In order to further validate our findings, we show that IRF1 can regulate the mRNA expression of a number of the DNA damage response genes in our list. In particular, we demonstrate that the mRNA and protein levels of the DNA repair protein BRIP1 [Fanconi anemia gene J (FANC J)] are upregulated after IRF1 over-expression. We also demonstrate that knockdown of IRF1 by siRNA results in loss of BRIP1 expression, abrogation of BRIP1 foci after DNA interstrand crosslink (ICL) damage and hypersensitivity to the DNA crosslinking agent, melphalan; a characteristic phenotype of FANC J cells. Taken together, our data provides a more complete understanding of the regulatory networks controlled by IRF1 and reveals a novel role for IRF1 in regulating the ICL DNA damage response. PMID:19129219

Energy efficient engine component development and integration program

NASA Technical Reports Server (NTRS)

1981-01-01

Accomplishments in the Energy Efficient Engine Component Development and Integration program during the period of April 1, 1981 through September 30, 1981 are discussed. The major topics considered are: (1) propulsion system analysis, design, and integration; (2) engine component analysis, design, and development; (3) core engine tests; and (4) integrated core/low spool testing.

Energy efficient engine component development and integration program

NASA Technical Reports Server (NTRS)

1982-01-01

The development of the technology to improve energy efficiency of propulsion systems for subsonic commercial aircrafts was examined. Goals established include: (1) fuel consumption, reduction in flight propulsion system; (2) direct operation cost; (3) noise, with provision for engine growth corresponding to future engine application; and (4) emissions, EPA new engine standards.

Compression Ratio Adjuster

NASA Technical Reports Server (NTRS)

Akkerman, J. W.

1982-01-01

New mechanism alters compression ratio of internal-combustion engine according to load so that engine operates at top fuel efficiency. Ordinary gasoline, diesel and gas engines with their fixed compression ratios are inefficient at partial load and at low-speed full load. Mechanism ensures engines operate as efficiently under these conditions as they do at highload and high speed.

Model predictive control of a lean-burn gasoline engine coupled with a passive selective catalytic reduction system

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

Chen, Pingen; Lin, Qinghua; Prikhodko, Vitaly Y.

Lean-burn gasoline engines have demonstrated 10–20% engine efficiency gain over stoichiometric engines and are widely considered as a promising technology for meeting the 54.5 miles-per-gallon (mpg) Corporate Average Fuel Economy standard by 2025. Nevertheless, NOx emissions control for lean-burn gasoline for meeting the stringent EPA Tier 3 emission standards has been one of the main challenges towards the commercialization of highly-efficient lean-burn gasoline engines in the United States. Passive selective catalytic reduction (SCR) systems, which consist of a three-way catalyst and SCR, have demonstrated great potentials of effectively reducing NOx emissions for lean gasoline engines but may cause significant fuelmore » penalty due to ammonia generation via rich engine combustion. The purpose of this study is to develop a model-predictive control (MPC) scheme for a lean-burn gasoline engine coupled with a passive SCR system to minimize the fuel penalty associated with passive SCR operation while satisfying stringent NOx and NH3 emissions requirements. Simulation results demonstrate that the MPC-based control can reduce the fuel penalty by 47.7% in a simulated US06 cycle and 32.0% in a simulated UDDS cycle, compared to the baseline control, while achieving over 96% deNOx efficiency and less than 15 ppm tailpipe ammonia slip. The proposed MPC control can potentially enable high engine efficiency gain for highly-efficient lean-burn gasoline engine while meeting the stringent EPA Tier 3 emission standards.« less

[Impact of CHA2DS2 VASc score on substrate for persistent atrial fibrillation and outcome post catheter ablation of atrial fibrillation].

PubMed

Ribo, Tang; Jianzeng, Dong; Xiaohui, Liu; Meisheng, Shang; Ronghui, Yu; Deyong, Long; Xin, Du; Junping, Kang; Jiahui, Wu; Man, Ning; Caihua, Sang; Chenxi, Jiang; Rong, Bai; Songnan, Li; Yan, Yao; Songnan, Wen; Changsheng, Ma

2015-08-01

To explore if CHA2DS2 VASc score can predict substrate for persistent atrial fibrillation ( AF) and outcome post catheter ablation of AF. From January 2011 to December 2012,116 patients underwent catheter ablation of persistent AF in our department and were enrolled in this study. CHA2DS2VASc score was calculated as follows: two points were assigned for a history of stroke or transient ischemic attack and age ≥ 75 and 1 point each was assigned for age ≥ 65, a history of hypertension, diabetes,recent cardiac failure, vessel disease, female. Left atrial geometry ( LA) was reconstructed with a 3.5 mm tip ablation catheter with fill-in threshold 10 in CARTO system. The mapping catheter was stabled at each endocardial location for at least 3 seconds for recording. The electrogram recordings at each endocardial location were analyzed with a custom software embedded in the CARTO mapping system. Interval confidence level (ICL) was used to characterize complex fractionated atrial electrograms (CFAEs) . As the default setting of the software, ICL more than or equal to 7 was considered sites with a highly repetitive CFAEs complex. CFAEs index was defined as the fraction of area of ICL more than or equal to 7 to the left atrial surface. The CFAEs index and outcome of catheter ablation among different CHA2DS2VASc groups were compared. Of the 116 patients, CHA2DS2VASc was 0 in 33 patients, 1 in 31 patients and ≥ 2 in 52 patients. Left atrial surface ((121.2 ± 18.9) cm2, (133.6 ± 23.8) cm2, (133.9 ± 16.1) cm2, P = 0.008), left atrial volume ((103.6 ± 24.8) ml, (118.3 ± 27.8) ml, (120.9 ± 20.9) ml, P = 0.005) and CFAEs index (44.6% ± 22.4%, 54.2% ± 22.2%, 58.7% ± 23.1%, P = 0.023) increased in proportion with increasing CHA2DS2VASc. ICLmax, ICLmin and CFAEs spatial distribution were similar among the three groups. During the mean follow-up of (13 ± 8) months, the recurrence rate were 36.4%, 35.5%, 55.8% among the three groups (P = 0.025). A high CHA2DS2VASc score is associated with extensive AF substrate and higher recurrence rate post catheter ablation of persistent AF.

Inhibition to excitation ratio regulates visual system responses and behavior in vivo.

PubMed

Shen, Wanhua; McKeown, Caroline R; Demas, James A; Cline, Hollis T

2011-11-01

The balance of inhibitory to excitatory (I/E) synaptic inputs is thought to control information processing and behavioral output of the central nervous system. We sought to test the effects of the decreased or increased I/E ratio on visual circuit function and visually guided behavior in Xenopus tadpoles. We selectively decreased inhibitory synaptic transmission in optic tectal neurons by knocking down the γ2 subunit of the GABA(A) receptors (GABA(A)R) using antisense morpholino oligonucleotides or by expressing a peptide corresponding to an intracellular loop of the γ2 subunit, called ICL, which interferes with anchoring GABA(A)R at synapses. Recordings of miniature inhibitory postsynaptic currents (mIPSCs) and miniature excitatory PSCs (mEPSCs) showed that these treatments decreased the frequency of mIPSCs compared with control tectal neurons without affecting mEPSC frequency, resulting in an ∼50% decrease in the ratio of I/E synaptic input. ICL expression and γ2-subunit knockdown also decreased the ratio of optic nerve-evoked synaptic I/E responses. We recorded visually evoked responses from optic tectal neurons, in which the synaptic I/E ratio was decreased. Decreasing the synaptic I/E ratio in tectal neurons increased the variance of first spike latency in response to full-field visual stimulation, increased recurrent activity in the tectal circuit, enlarged spatial receptive fields, and lengthened the temporal integration window. We used the benzodiazepine, diazepam (DZ), to increase inhibitory synaptic activity. DZ increased optic nerve-evoked inhibitory transmission but did not affect evoked excitatory currents, resulting in an increase in the I/E ratio of ∼30%. Increasing the I/E ratio with DZ decreased the variance of first spike latency, decreased spatial receptive field size, and lengthened temporal receptive fields. Sequential recordings of spikes and excitatory and inhibitory synaptic inputs to the same visual stimuli demonstrated that decreasing or increasing the I/E ratio disrupted input/output relations. We assessed the effect of an altered I/E ratio on a visually guided behavior that requires the optic tectum. Increasing and decreasing I/E in tectal neurons blocked the tectally mediated visual avoidance behavior. Because ICL expression, γ2-subunit knockdown, and DZ did not directly affect excitatory synaptic transmission, we interpret the results of our study as evidence that partially decreasing or increasing the ratio of I/E disrupts several measures of visual system information processing and visually guided behavior in an intact vertebrate.

The Effect of Compression Ratio, Fuel Octane Rating, and Ethanol Content on Spark-Ignition Engine Efficiency.

PubMed

Leone, Thomas G; Anderson, James E; Davis, Richard S; Iqbal, Asim; Reese, Ronald A; Shelby, Michael H; Studzinski, William M

2015-09-15

Light-duty vehicles (LDVs) in the United States and elsewhere are required to meet increasingly challenging regulations on fuel economy and greenhouse gas (GHG) emissions as well as criteria pollutant emissions. New vehicle trends to improve efficiency include higher compression ratio, downsizing, turbocharging, downspeeding, and hybridization, each involving greater operation of spark-ignited (SI) engines under higher-load, knock-limited conditions. Higher octane ratings for regular-grade gasoline (with greater knock resistance) are an enabler for these technologies. This literature review discusses both fuel and engine factors affecting knock resistance and their contribution to higher engine efficiency and lower tailpipe CO2 emissions. Increasing compression ratios for future SI engines would be the primary response to a significant increase in fuel octane ratings. Existing LDVs would see more advanced spark timing and more efficient combustion phasing. Higher ethanol content is one available option for increasing the octane ratings of gasoline and would provide additional engine efficiency benefits for part and full load operation. An empirical calculation method is provided that allows estimation of expected vehicle efficiency, volumetric fuel economy, and CO2 emission benefits for future LDVs through higher compression ratios for different assumptions on fuel properties and engine types. Accurate "tank-to-wheel" estimates of this type are necessary for "well-to-wheel" analyses of increased gasoline octane ratings in the context of light duty vehicle transportation.

Heat Pipes Reduce Engine-Exhaust Emissions

NASA Technical Reports Server (NTRS)

Schultz, D. F.

1986-01-01

Increased fuel vaporization raises engine efficiency. Heat-pipe technology increased efficiency of heat transfer beyond that obtained by metallic conduction. Resulted in both improved engine operation and reduction in fuel consumption. Raw material conservation through reduced dependence on strategic materials also benefit from this type of heat-pipe technology. Applications result in improved engine performance and cleaner environment.

Highly efficient 6-stroke engine cycle with water injection

DOEpatents

Szybist, James P; Conklin, James C

2012-10-23

A six-stroke engine cycle having improved efficiency. Heat is recovered from the engine combustion gases by using a 6-stroke engine cycle in which combustion gases are partially vented proximate the bottom-dead-center position of the fourth stroke cycle, and water is injected proximate the top-dead-center position of the fourth stroke cycle.

Energy efficient engine high pressure turbine ceramic shroud support technology report

NASA Technical Reports Server (NTRS)

Nelson, W. A.; Carlson, R. G.

1982-01-01

This work represents the development and fabrication of ceramic HPT (high pressure turbine) shrouds for the Energy Efficient Engine (E3). Details are presented covering the work performed on the ceramic shroud development task of the NASA/GE Energy Efficient Engine (E3) component development program. The task consists of four phases which led to the selection of a ZrO2-BY2O3 ceramic shroud material system, the development of an automated plasma spray process to produce acceptable shroud structures, the fabrication of select shroud systems for evaluation in laboratory, component, and CF6-50 engine testing, and finally, the successful fabrication of ZrO2-8Y2O3/superpeg, engine quality shrouds for the E3 engine.

Analysis of an Increase in the Efficiency of a Spark Ignition Engine Through the Application of an Automotive Thermoelectric Generator

NASA Astrophysics Data System (ADS)

Merkisz, Jerzy; Fuc, Pawel; Lijewski, Piotr; Ziolkowski, Andrzej; Galant, Marta; Siedlecki, Maciej

2016-08-01

We have analyzed the increase of the overall efficiency of a spark ignition engine through energy recovery following the application of an automotive thermoelectric generator (ATEG) of our own design. The design of the generator was developed following emission investigations during vehicle driving under city traffic conditions. The measurement points were defined by actual operation conditions (engine speed and load), subsequently reproduced on an engine dynamometer. Both the vehicle used in the on-road tests and the engine dynamometer were fit with the same, downsized spark ignition engine (with high effective power-to-displacement ratio). The thermodynamic parameters of the exhaust gases (temperature and exhaust gas mass flow) were measured on the engine testbed, along with the fuel consumption and electric current generated by the thermoelectric modules. On this basis, the power of the ATEG and its impact on overall engine efficiency were determined.

Maximum efficiency of ideal heat engines based on a small system: correction to the Carnot efficiency at the nanoscale.

PubMed

Quan, H T

2014-06-01

We study the maximum efficiency of a heat engine based on a small system. It is revealed that due to the finiteness of the system, irreversibility may arise when the working substance contacts with a heat reservoir. As a result, there is a working-substance-dependent correction to the Carnot efficiency. We derive a general and simple expression for the maximum efficiency of a Carnot cycle heat engine in terms of the relative entropy. This maximum efficiency approaches the Carnot efficiency asymptotically when the size of the working substance increases to the thermodynamic limit. Our study extends Carnot's result of the maximum efficiency to an arbitrary working substance and elucidates the subtlety of thermodynamic laws in small systems.

Performance and efficiency evaluation and heat release study of a direct-injection stratified-charge rotary engine

NASA Technical Reports Server (NTRS)

Nguyen, H. L.; Addy, H. E.; Bond, T. H.; Lee, C. M.; Chun, K. S.

1987-01-01

A computer simulation which models engine performance of the Direct Injection Stratified Charge (DISC) rotary engines was used to study the effect of variations in engine design and operating parameters on engine performance and efficiency of an Outboard Marine Corporation (OMC) experimental rotary combustion engine. Engine pressure data were used in a heat release analysis to study the effects of heat transfer, leakage, and crevice flows. Predicted engine data were compared with experimental test data over a range of engine speeds and loads. An examination of methods to improve the performance of the rotary engine using advanced heat engine concepts such as faster combustion, reduced leakage, and turbocharging is also presented.

Entropic anomaly and maximal efficiency of microscopic heat engines.

PubMed

Bo, Stefano; Celani, Antonio

2013-05-01

The efficiency of microscopic heat engines in a thermally heterogenous environment is considered. We show that-as a consequence of the recently discovered entropic anomaly-quasistatic engines, whose efficiency is maximal in a fluid at uniform temperature, have in fact vanishing efficiency in the presence of temperature gradients. For slow cycles the efficiency falls off as the inverse of the period. The maximum efficiency is reached at a finite value of the cycle period that is inversely proportional to the square root of the gradient intensity. The relative loss in maximal efficiency with respect to the thermally homogeneous case grows as the square root of the gradient. As an illustration of these general results, we construct an explicit, analytically solvable example of a Carnot stochastic engine. In this thought experiment, a Brownian particle is confined by a harmonic trap and immersed in a fluid with a linear temperature profile. This example may serve as a template for the design of real experiments in which the effect of the entropic anomaly can be measured.

Assessment of total efficiency in adiabatic engines

NASA Astrophysics Data System (ADS)

Mitianiec, W.

2016-09-01

The paper presents influence of ceramic coating in all surfaces of the combustion chamber of SI four-stroke engine on working parameters mainly on heat balance and total efficiency. Three cases of engine were considered: standard without ceramic coating, fully adiabatic combustion chamber and engine with different thickness of ceramic coating. Consideration of adiabatic or semi-adiabatic engine was connected with mathematical modelling of heat transfer from the cylinder gas to the cooling medium. This model takes into account changeable convection coefficient based on the experimental formulas of Woschni, heat conductivity of multi-layer walls and also small effect of radiation in SI engines. The simulation model was elaborated with full heat transfer to the cooling medium and unsteady gas flow in the engine intake and exhaust systems. The computer program taking into account 0D model of engine processes in the cylinder and 1D model of gas flow was elaborated for determination of many basic engine thermodynamic parameters for Suzuki DR-Z400S 400 cc SI engine. The paper presents calculation results of influence of the ceramic coating thickness on indicated pressure, specific fuel consumption, cooling and exhaust heat losses. Next it were presented comparisons of effective power, heat losses in the cooling and exhaust systems, total efficiency in function of engine rotational speed and also comparison of temperature inside the cylinder for standard, semi-adiabatic and full adiabatic engine. On the basis of the achieved results it was found higher total efficiency of adiabatic engines at 2500 rpm from 27% for standard engine to 37% for full adiabatic engine.

Irreversible Brownian Heat Engine

NASA Astrophysics Data System (ADS)

Taye, Mesfin Asfaw

2017-10-01

We model a Brownian heat engine as a Brownian particle that hops in a periodic ratchet potential where the ratchet potential is coupled with a linearly decreasing background temperature. We show that the efficiency of such Brownian heat engine approaches the efficiency of endoreversible engine η =1-√{{Tc/Th}} [23]. On the other hand, the maximum power efficiency of the engine approaches η ^{MAX}=1-({Tc/Th})^{1\\over 4}. It is shown that the optimized efficiency always lies between the efficiency at quasistatic limit and the efficiency at maximum power while the efficiency at maximum power is always less than the optimized efficiency since the fast motion of the particle comes at the expense of the energy cost. If the heat exchange at the boundary of the heat baths is included, we show that such a Brownian heat engine has a higher performance when acting as a refrigerator than when operating as a device subjected to a piecewise constant temperature. The role of time on the performance of the motor is also explored via numerical simulations. Our numerical results depict that the time t and the external load dictate the direction of the particle velocity. Moreover, the performance of the heat engine improves with time. At large t (steady state), the velocity, the efficiency and the coefficient of performance of the refrigerator attain their maximum value. Furthermore, we study the effect of temperature by considering a viscous friction that decreases exponentially as the background temperature increases. Our result depicts that the Brownian particle exhibits a fast unidirectional motion when the viscous friction is temperature dependent than that of constant viscous friction. Moreover, the efficiency of this motor is considerably enhanced when the viscous friction is temperature dependent. On the hand, the motor exhibits a higher performance of the refrigerator when the viscous friction is taken to be constant.

Enhanced and Tunable Optical Quantum Efficiencies from Plasmon Bandwidth Engineering in Bimetallic CoAg Nanoparticles (Open Access Publisher’s Version)

DTIC Science & Technology

2016-08-01

Engineering Engineering -- Faculty Publications and Other Works 8-2016 Enhanced and tunable optical quantum efficiencies from plasmon bandwidth engineering ...this and additional works at: http://trace.tennessee.edu/utk_matepubs Part of the Materials Science and Engineering Commons This Article is brought to...you for free and open access by the Engineering -- Faculty Publications and Other Works at Trace: Tennessee Research and Creative Exchange. It has been

Double-reed exhaust valve engine

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

Bennett, Charles L.

An engine based on a reciprocating piston engine that extracts work from pressurized working fluid. The engine includes a double reed outlet valve for controlling the flow of low-pressure working fluid out of the engine. The double reed provides a stronger force resisting closure of the outlet valve than the force tending to open the outlet valve. The double reed valve enables engine operation at relatively higher torque and lower efficiency at low speed, with lower torque, but higher efficiency at high speed.

The NASA Aircraft Energy Efficiency program

NASA Technical Reports Server (NTRS)

Klineberg, J. M.

1979-01-01

A review is provided of the goals, objectives, and recent progress in each of six aircraft energy efficiency programs aimed at improved propulsive, aerodynamic and structural efficiency for future transport aircraft. Attention is given to engine component improvement, an energy efficient turbofan engine, advanced turboprops, revolutionary gains in aerodynamic efficiency for aircraft of the late 1990s, laminar flow control, and composite primary aircraft structures.

Energy efficient engine: High pressure turbine uncooled rig technology report

NASA Technical Reports Server (NTRS)

Gardner, W. B.

1979-01-01

Results obtained from testing five performance builds (three vane cascades and two rotating rigs of the Energy Efficient Engine uncooled rig have established the uncooled aerodynamic efficiency of the high-pressure turbine at 91.1 percent. This efficiency level was attained by increasing the rim speed and annulus area (AN(2)), and by increasing the turbine reaction level. The increase in AN(2) resulted in a performance improvement of 1.15 percent. At the design point pressure ratio, the increased reaction level rig demonstrated an efficiency of 91.1 percent. The results of this program have verified the aerodynamic design assumptions established for the Energy Efficient Engine high-pressure turbine component.

Advanced General Aviation Turbine Engine (GATE) concepts

NASA Technical Reports Server (NTRS)

Lays, E. J.; Murray, G. L.

1979-01-01

Concepts are discussed that project turbine engine cost savings through use of geometrically constrained components designed for low rotational speeds and low stress to permit manufacturing economies. Aerodynamic development of geometrically constrained components is recommended to maximize component efficiency. Conceptual engines, airplane applications, airplane performance, engine cost, and engine-related life cycle costs are presented. The powerplants proposed offer encouragement with respect to fuel efficiency and life cycle costs, and make possible remarkable airplane performance gains.

Measurement Systems Advisory Group

DTIC Science & Technology

1974-04-01

US NavyLib MSAG- 1 REPORT 001 qL5 ID I APRIL 1974 MA2C91SMAR 2 0 19 81 F Prepared For "LONG RANGE ACOUSTIC PROPAGATION PROJECT 7 opt/ icl S[ D _STRIBU...34 j •( - _> ...ailability Codes IV !VM Avail and/or -~’Dist IspecialL K OFFICE OF NAVAL RESEARCH Department of the Navy Washington, D.C.I L 1 April 23...respect and very much appreciated. The report will be distributed to selected members of the user community for their information and comment. Because 1

Compact TDLAS based sensor design using interband cascade lasers for mid-IR trace gas sensing

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

Dong, Lei; Tittel, Frank K.; Li, Chunguang

2016-02-25

Two compact TDLAS sensor systems based on different structural optical cores were developed. The two optical cores combine two recent developments, gallium antimonide (GaSb)-based ICL and a compact multipass gas cell (MPGC) with the goal to create compact TDLAS based sensors for the mid-IR gas detection with high detection sensitivity and low power consumption. The sensors achieved minimum detection limits of ~5 ppbv and ~8 ppbv, respectively, for CH 4 and C 2H 6 concentration measurements with a 3.7-W power consumption.

Effects of Oscillation Frequency and Amplitude on Separation in an Unsteady Turbulent Flow.

DTIC Science & Technology

1980-09-01

be performed with much of the aircraft immersed in turbulent flow. When in operation near the ground or landing platform , unsteady, turbulent flow...34 - .-,...i ,aXa. 8O- IDa I"l N 0 N( ’A0 󈧨 a r. 0 a 0.a " - M - if l’ . t 1 - o t I.- I.- 𔃻 I I I Ni ilNl 1i * 11 it O ag 0) - -i "NUm M CA myp WiX ~ U’iCL

Local Free Space Mapping and Path Guidance,

DTIC Science & Technology

1987-03-01

Free Space Mapping and Path Guidance 12. PERSONIAL UTI4OFS) William T. Cex and Nancy L. Campbell 1s. TYPE OF REPORT 13b. iME COVERED 14. DATE OF REPORT...84 JAN 52 A" 1OMON MAYBOfUSED NMlLEMIAUSTEO UNCLASSIFIED ALL OTHE EDTIN A’.SL Y2.7cesson For 7 *5~ IT D, TA ........... iCL ... . LOCAL FREE SPACE ... MAPPING AND PATH GUIDANCE By Distribuition/ Availabiliuy C0e William T. Gex and Nancy L. Campbell I Avail and/or Naval Ocean Systems Center ist speci1 l

Epi-Side-Down Mounting of Interband Cascade Lasers for Army Applications

DTIC Science & Technology

2006-11-01

retain the principal advantage of electron recycling . However, unlike the QCL, the ICL relies on the cascading of interband optical transitions as...9.0 Cu 393 17 SiC 120 4 AlN 230 (high grade –Tsekoun 2006) 4.5, 4.3 Indium 83.7 24.8@ 20C 2 device ridge and an effective heat spreader ...65.3 K/W M271 epi-side down 8-μm x 1-mm mesa TmaxCW= 212K 4 were vital and survived multiple cryogenic to room temperature recyclings . Fig. 4

Lean NOx Trap Catalysis for Lean Natural Gas Engine Applications

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

Parks, II, James E; Storey, John Morse; Theiss, Timothy J

Distributed energy is an approach for meeting energy needs that has several advantages. Distributed energy improves energy security during natural disasters or terrorist actions, improves transmission grid reliability by reducing grid load, and enhances power quality through voltage support and reactive power. In addition, distributed energy can be efficient since transmission losses are minimized. One prime mover for distributed energy is the natural gas reciprocating engine generator set. Natural gas reciprocating engines are flexible and scalable solutions for many distributed energy needs. The engines can be run continuously or occasionally as peak demand requires, and their operation and maintenance ismore » straightforward. Furthermore, system efficiencies can be maximized when natural gas reciprocating engines are combined with thermal energy recovery for cooling, heating, and power applications. Expansion of natural gas reciprocating engines for distributed energy is dependent on several factors, but two prominent factors are efficiency and emissions. Efficiencies must be high enough to enable low operating costs, and emissions must be low enough to permit significant operation hours, especially in non-attainment areas where emissions are stringently regulated. To address these issues the U.S. Department of Energy and the California Energy Commission launched research and development programs called Advanced Reciprocating Engine Systems (ARES) and Advanced Reciprocating Internal Combustion Engines (ARICE), respectively. Fuel efficiency and low emissions are two primary goals of these programs. The work presented here was funded by the ARES program and, thus, addresses the ARES 2010 goals of 50% thermal efficiency (fuel efficiency) and <0.1 g/bhp-hr emissions of oxides of nitrogen (NOx). A summary of the goals for the ARES program is given in Table 1-1. ARICE 2007 goals are 45% thermal efficiency and <0.015 g/bhp-hr NOx. Several approaches for improving the efficiency and emissions of natural gas reciprocating engines are being pursued. Approaches include: stoichiometric engine operation with exhaust gas recirculation and three-way catalysis, advanced combustion modes such as homogeneous charge compression ignition, and extension of the lean combustion limit with advanced ignition concepts and/or hydrogen mixing. The research presented here addresses the technical approach of combining efficient lean spark-ignited natural gas combustion with low emissions obtained from a lean NOx trap catalyst aftertreatment system. This approach can be applied to current lean engine technology or advanced lean engines that may result from related efforts in lean limit extension. Furthermore, the lean NOx trap technology has synergy with hydrogen-assisted lean limit extension since hydrogen is produced from natural gas during the lean NOx trap catalyst system process. The approach is also applicable to other lean engines such as diesel engines, natural gas turbines, and lean gasoline engines; other research activities have focused on those applications. Some commercialization of the technology has occurred for automotive applications (both diesel and lean gasoline engine vehicles) and natural gas turbines for stationary power. The research here specifically addresses barriers to commercialization of the technology for large lean natural gas reciprocating engines for stationary power. The report presented here is a comprehensive collection of research conducted by Oak Ridge National Laboratory (ORNL) on lean NOx trap catalysis for lean natural gas reciprocating engines. The research was performed in the Department of Energy's ARES program from 2003 to 2007 and covers several aspects of the technology. All studies were conducted at ORNL on a Cummins C8.3G+ natural gas engine chosen based on industry input to simulate large lean natural gas engines. Specific technical areas addressed by the research include: NOx reduction efficiency, partial oxidation and reforming chemistry, and the effects of sulfur poisons on the partial oxidation, reformer, and lean NOx trap catalysts. The initial work on NOx reduction efficiency demonstrated that NOx emissions <0.1 g/bhp-hr (the ARES goal) can be achieved with the lean NOx trap catalyst technology. Subsequent work focused on cost and size optimization and durability issues which addressed two specific ARES areas of interest to industry ('Cost of Power' and 'Availability, Reliability, and Maintainability', respectively). Thus, the research addressed the approach of the lean NOx trap catalyst technology toward the ARES goals as shown in Table 1-1.« less

Energy efficient engine high-pressure turbine supersonic cascade technology report

NASA Technical Reports Server (NTRS)

Kopper, F. C.; Milano, R.; Davis, R. L.; Dring, R. P.; Stoeffler, R. C.

1981-01-01

The performance of two vane endwall geometries and three blade sections for the high-pressure turbine was evaluated in terms of the efficiency requirements of the Energy Efficient Engine high-pressure turbine component. The van endwall designs featured a straight wall and S-wall configuration. The blade designs included a base blade, straightback blade, and overcambered blade. Test results indicated that the S-wall vane configuration and the base blade configuration offered the most promising performance characteristics for the Energy Efficient Engine high-pressure turbine component.

Overview of CMC Development Activities in NASA's Ultra-Efficient Engine Technology (UEET) Program

NASA Technical Reports Server (NTRS)

Brewer, Dave

2001-01-01

The primary objective of the UEET (Ultra-Efficient Engine Technology) Program is to address two of the most critical propulsion issues: performance/efficiency and reduced emissions. High performance, low emissions engine systems will lead to significant improvement in local air quality, minimum impact on ozone depletion and level to an overall reduction in aviation contribution to global warming. The Materials and Structures for High Performance project will develop and demonstrate advanced high temperature materials to enable high-performance, high efficiency, and environmentally compatible propulsion systems.

Why ceramic engines?

NASA Technical Reports Server (NTRS)

Stadler, H. L.

1984-01-01

Oil is still a problem for the U.S. and its allies. Transportation uses 61 percent of U.S. oil and its share is increasing, so more efficient technology should be concentrated there. Trucks' share of oil use is increasing because they are already much more efficient than autos. The primary truck opportunities are streamlining, more efficient engines, and shifting freight to railroads. More efficient engines are possible using ceramics to allow elimination of cooling systems and better use of waste exhaust heat. A 60 percent improvement seems possible if ceramics can be made tough enough and durable enough.

The thermodynamic efficiency of heat engines with friction

NASA Astrophysics Data System (ADS)

Bizarro, João P. S.

2012-04-01

The presence of the work done against friction is incorporated into the analysis of the efficiency of heat engines based on the first and second laws of thermodynamics. We obtain the efficiencies of Stirling and Brayton engines with friction and recover results known from finite-time thermodynamics. We show that ηfric/η ≈ (1 - Wfric/W), where ηfric/η is the ratio of the efficiencies with and without friction and Wfric/W is the fraction of the work W performed by the working fluid which is spent against friction forces.

Preliminary Results of an Altitude-Wind-Tunnel Investigation of a TG-100A Gas Turbine-Propeller Engine. V; Combustion-Chamber Characteristics

NASA Technical Reports Server (NTRS)

Gensenheyner, Robert M.; Berdysz, Joseph J.

1947-01-01

An investigation to determine the performance and operational characteristics of the TG-1OOA gas turbine-propeller engine was conducted in the Cleveland altitude wind tunnel. As part of this investigation, the combustion-chamber performance was determined at pressure altitudes from 5000 to 35,000 feet, compressor-inlet rm-pressure ratios of 1.00 and 1.09, and engine speeds from 8000 to 13,000 rpm. Combustion-chamber performance is presented as a function of corrected engine speed and.correcte& horsepower. For the range of corrected engine speeds investigated, over-all total-pressure-loss ratio, cycle efficiency, ana the frac%ional loss in cycle efficiency resulting from pressure losses in the combustion chambers were unaffected by a change in altitude or compressor-inlet ram-pressure ratio. The scatter of combustion- efficiency data tended to obscure any effect of altitude or ram-pressure ratio. For the range of corrected horse-powers investigated, the total-pressure-loss ratio an& the fractional loss in cycle efficiency resulting from pressure losses in the combustion chambers decreased with an increase in corrected horsepower at a constant corrected engine speed. The combustion efficiency remained constant for the range of corrected horse-powers investigated at all corrected engine speeds.

Lubricant Formulations to Enhance Engine Efficiency in Modern Internal Combustion Engines

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

Cheng, Wai; Wong, Victor; Plumley, Michael

2017-04-19

The research program presented aimed to investigate, develop, and demonstrate low-friction, environmentally-friendly and commercially-feasible lubricant formulations that would significantly improve the mechanical efficiency of modern engines without incurring increased wear, emissions or deterioration of the emission-aftertreatment system.

A graphical user interface for infant ERP analysis.

PubMed

Kaatiala, Jussi; Yrttiaho, Santeri; Forssman, Linda; Perdue, Katherine; Leppänen, Jukka

2014-09-01

Recording of event-related potentials (ERPs) is one of the best-suited technologies for examining brain function in human infants. Yet the existing software packages are not optimized for the unique requirements of analyzing artifact-prone ERP data from infants. We developed a new graphical user interface that enables an efficient implementation of a two-stage approach to the analysis of infant ERPs. In the first stage, video records of infant behavior are synchronized with ERPs at the level of individual trials to reject epochs with noncompliant behavior and other artifacts. In the second stage, the interface calls MATLAB and EEGLAB (Delorme & Makeig, Journal of Neuroscience Methods 134(1):9-21, 2004) functions for further preprocessing of the ERP signal itself (i.e., filtering, artifact removal, interpolation, and rereferencing). Finally, methods are included for data visualization and analysis by using bootstrapped group averages. Analyses of simulated and real EEG data demonstrated that the proposed approach can be effectively used to establish task compliance, remove various types of artifacts, and perform representative visualizations and statistical comparisons of ERPs. The interface is available for download from http://www.uta.fi/med/icl/methods/eeg.html in a format that is widely applicable to ERP studies with special populations and open for further editing by users.

A micrometre-sized heat engine operating between bacterial reservoirs

NASA Astrophysics Data System (ADS)

Krishnamurthy, Sudeesh; Ghosh, Subho; Chatterji, Dipankar; Ganapathy, Rajesh; Sood, A. K.

2016-12-01

Artificial microscale heat engines are prototypical models to explore the mechanisms of energy transduction in a fluctuation-dominated regime. The heat engines realized so far on this scale have operated between thermal reservoirs, such that stochastic thermodynamics provides a precise framework for quantifying their performance. It remains to be seen whether these concepts readily carry over to situations where the reservoirs are out of equilibrium, a scenario of particular importance to the functioning of synthetic and biological microscale engines and motors. Here, we experimentally realize a micrometre-sized active Stirling engine by periodically cycling a colloidal particle in a time-varying optical potential across bacterial baths characterized by different degrees of activity. We find that the displacement statistics of the trapped particle becomes increasingly non-Gaussian with activity and contributes substantially to the overall power output and the efficiency. Remarkably, even for engines with the same energy input, differences in non-Gaussianity of reservoir noise results in distinct performances. At high activities, the efficiency of our engines surpasses the equilibrium saturation limit of Stirling efficiency, the maximum efficiency of a Stirling engine where the ratio of cold to hot reservoir temperatures is vanishingly small. Our experiments provide fundamental insights into the functioning of micromotors and engines operating out of equilibrium.

FY 2007 Progress Report for Advanced Combustion Engine Technologies

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

None, None

2007-12-01

Advanced combustion engines have great potential for achieving dramatic energy efficiency improvements in light-duty vehicle applications, where it is suited to both conventional and hybrid- electric powertrain configurations. Light-duty vehicles with advanced combustion engines can compete directly with gasoline engine hybrid vehicles in terms of fuel economy and consumer-friendly driving characteristics; also, they are projected to have energy efficiencies that are competitive with hydrogen fuel cell vehicles when used in hybrid applications.Advanced engine technologies being researched and developed by the Advanced Combustion Engine R&D Sub-Program will also allow the use of hydrogen as a fuel in ICEs and will providemore » an energy-efficient interim hydrogen-based powertrain technology during the transition to hydrogen/fuelcell-powered transportation vehicles.« less

An Exact Efficiency Formula for Holographic Heat Engines

DOE PAGES

Johnson, Clifford

2016-03-31

Further consideration is given to the efficiency of a class of black hole heat engines that perform mechanical work via the pdV terms present in the First Law of extended gravitational thermodynamics. It is noted that, when the engine cycle is a rectangle with sides parallel to the (p,V) axes, the efficiency can be written simply in terms of the mass of the black hole evaluated at the corners. Since an arbitrary cycle can be approximated to any desired accuracy by a tiling of rectangles, a general geometrical algorithm for computing the efficiency of such a cycle follows. Finally, amore » simple generalization of the algorithm renders it applicable to broader classes of heat engine, even beyond the black hole context.« less

Prospects for energy efficiency improvement and reduction of emissions and life cycle costs for natural gas vehicles

NASA Astrophysics Data System (ADS)

Kozlov, A. V.; Terenchenko, A. S.; Luksho, V. A.; Karpukhin, K. E.

2017-01-01

This work is devoted to the experimental investigation of the possibilities to reduce greenhouse gas emissions and to increase energy efficiency of engines that use natural gas as the main fuel and the analysis of economic efficiency of use of dual fuel engines in vehicles compared to conventional diesel. The results of experimental investigation of a 190 kW dual-fuel engine are presented; it is shown that quantitative and qualitative working process control may ensure thermal efficiency at the same level as that of the diesel engine and in certain conditions 5...8% higher. The prospects for reduction of greenhouse gas emissions have been assessed. The technical and economic evaluation of use of dual fuel engines in heavy-duty vehicles has been performed, taking into account the total life cycle. It is shown that it is possible to reduce life cycle costs by two times.

Evaluation of the potential of the Stirling engine for heavy duty application

NASA Technical Reports Server (NTRS)

Meijer, R. J.; Ziph, B.

1981-01-01

A 150 hp four cylinder heavy duty Stirling engine was evaluated. The engine uses a variable stroke power control system, swashplate drive and ceramic insulation. The sensitivity of the design to engine size and heater temperature is investigated. Optimization shows that, with porous ceramics, indicated efficiencies as high as 52% can be achieved. It is shown that the gain in engine efficiency becomes insignificant when the heater temperature is raised above 200 degrees F.

A status report on the Energy Efficient Engine Project

NASA Technical Reports Server (NTRS)

Macioce, L. E.; Schaefer, J. W.; Saunders, N. T.

1980-01-01

The Energy Efficient Engine (E3) Project is directed at providing, by 1984, the advanced technologies which could be used for a new generation of fuel conservative turbofan engines. This paper summarizes the scope of the entire project and the current status of these efforts. Included is a description of the preliminary designs of the fully developed engines, the potential benefits of these advanced engines, and highlights of some of the component technology efforts conducted to date.

Energy Efficient Engine: Flight propulsion system final design and analysis

NASA Technical Reports Server (NTRS)

Davis, Donald Y.; Stearns, E. Marshall

1985-01-01

The Energy Efficient Engine (E3) is a NASA program to create fuel saving technology for future transport engines. The Flight Propulsion System (FPS) is the engine designed to achieve E3 goals. Achieving these goals required aerodynamic, mechanical and system technologies advanced beyond that of current production engines. These technologies were successfully demonstrated in component rigs, a core engine and a turbofan ground test engine. The design and benefits of the FPS are presented. All goals for efficiency, environmental considerations, and economic payoff were met. The FPS has, at maximum cruise, 10.67 km (35,000 ft), M0.8, standard day, a 16.9 percent lower installed specific fuel consumption than a CF6-50C. It provides an 8.6 percent reduction in direct operating cost for a short haul domestic transport and a 16.2 percent reduction for an international long distance transport.

Ceramic applications in the advanced Stirling automotive engine

NASA Technical Reports Server (NTRS)

Tomazic, W. A.; Cairelli, J. E.

1977-01-01

The ideal cycle, its application to a practical machine, and the specific advantages of high efficiency, low emissions, multi-fuel capability, and low noise of the stirling engine are discussed. Certain portions of the Stirling engine must operate continuously at high temperature. Ceramics offer the potential of cost reduction and efficiency improvement for advanced engine applications. Potential applications for ceramics in Stirling engines, and some of the special problems pertinent to using ceramics in the Stirling engine are described. The research and technology program in ceramics which is planned to support the development of advanced Stirling engines is outlined.

Modeling of hybrid vehicle fuel economy and fuel engine efficiency

NASA Astrophysics Data System (ADS)

Wu, Wei

"Near-CV" (i.e., near-conventional vehicle) hybrid vehicles, with an internal combustion engine, and a supplementary storage with low-weight, low-energy but high-power capacity, are analyzed. This design avoids the shortcoming of the "near-EV" and the "dual-mode" hybrid vehicles that need a large energy storage system (in terms of energy capacity and weight). The small storage is used to optimize engine energy management and can provide power when needed. The energy advantage of the "near-CV" design is to reduce reliance on the engine at low power, to enable regenerative braking, and to provide good performance with a small engine. The fuel consumption of internal combustion engines, which might be applied to hybrid vehicles, is analyzed by building simple analytical models that reflect the engines' energy loss characteristics. Both diesel and gasoline engines are modeled. The simple analytical models describe engine fuel consumption at any speed and load point by describing the engine's indicated efficiency and friction. The engine's indicated efficiency and heat loss are described in terms of several easy-to-obtain engine parameters, e.g., compression ratio, displacement, bore and stroke. Engine friction is described in terms of parameters obtained by fitting available fuel measurements on several diesel and spark-ignition engines. The engine models developed are shown to conform closely to experimental fuel consumption and motored friction data. A model of the energy use of "near-CV" hybrid vehicles with different storage mechanism is created, based on simple algebraic description of the components. With powertrain downsizing and hybridization, a "near-CV" hybrid vehicle can obtain a factor of approximately two in overall fuel efficiency (mpg) improvement, without considering reductions in the vehicle load.

Integrated thermal and energy management of plug-in hybrid electric vehicles

NASA Astrophysics Data System (ADS)

Shams-Zahraei, Mojtaba; Kouzani, Abbas Z.; Kutter, Steffen; Bäker, Bernard

2012-10-01

In plug-in hybrid electric vehicles (PHEVs), the engine temperature declines due to reduced engine load and extended engine off period. It is proven that the engine efficiency and emissions depend on the engine temperature. Also, temperature influences the vehicle air-conditioner and the cabin heater loads. Particularly, while the engine is cold, the power demand of the cabin heater needs to be provided by the batteries instead of the waste heat of engine coolant. The existing energy management strategies (EMS) of PHEVs focus on the improvement of fuel efficiency based on hot engine characteristics neglecting the effect of temperature on the engine performance and the vehicle power demand. This paper presents a new EMS incorporating an engine thermal management method which derives the global optimal battery charge depletion trajectories. A dynamic programming-based algorithm is developed to enforce the charge depletion boundaries, while optimizing a fuel consumption cost function by controlling the engine power. The optimal control problem formulates the cost function based on two state variables: battery charge and engine internal temperature. Simulation results demonstrate that temperature and the cabin heater/air-conditioner power demand can significantly influence the optimal solution for the EMS, and accordingly fuel efficiency and emissions of PHEVs.

Possible improvements in gasoline engines

NASA Technical Reports Server (NTRS)

Ziembinski, S

1923-01-01

High-compression engines are investigated with the three main objects being elimination of vibration, increase of maximum efficiency, and conservation of this efficiency at the highest possible speeds.

NREL Fuels and Engines R&D Revs Up Vehicle Efficiency, Performance

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

None

NREL bridges fuels and engines R&D to maximize vehicle efficiency and performance. The lab’s fuels and engines research covers the full spectrum of innovation—from fuel chemistry, conversion, and combustion to the evaluation of how fuels interact with engine and vehicle design. This innovative approach has the potential to positively impact our economy, national energy security, and air quality.

Efficiency of single-particle engines

NASA Astrophysics Data System (ADS)

Proesmans, Karel; Driesen, Cedric; Cleuren, Bart; Van den Broeck, Christian

2015-09-01

We study the efficiency of a single-particle Szilard and Carnot engine. Within a first order correction to the quasistatic limit, the work distribution is found to be Gaussian and the correction factor to average work and efficiency only depends on the piston speed. The stochastic efficiency is studied for both models and the recent findings on efficiency fluctuations are confirmed numerically. Special features are revealed in the zero-temperature limit.

Selection Criteria for Sustainable Fuels for High-Efficiency Spark-Ignition Engines with Examination of their Storage Stability, Impact on Engine Knock, and Fine Particle Emissions

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

McCormick, Robert L

It is possible to significantly improve the efficiency of spark-ignition engines given fuels with improved autoignition, evaporative cooling, and particle emission properties. At the same time, a vast range of different fuel chemistries are accessible from biomass - leading to questions about how fuel chemistries outside the range available from petroleum and ethanol can impact engine operation. This presentation will briefly describe the factors leading to poor efficiency in current SI engines, and the technologies available for improving efficiency. Improved fuel properties that enable high efficiency engine designs to be pursued aggressively will be reviewed, including octane index and sensitivity.more » A screening process based on fuel properties was applied to a large set of proposed biomass-derived gasoline blendstocks, and the properties of the best blendstocks were evaluated. Some of these fuels exhibit poor stability towards oxidation in the liquid phase, and storage stability studies for alkyl furans and cyclopentanone will be presented in brief. The importance of fuel heat of vaporization for direct injection engines, along with new research on measurement of this parameter, will be presented including an SI engine study of the impact of heat of vaporization on octane index and engine knock. Fuel effects on fine particle emissions and how our understanding breaks down for oxygenates will be discussed. Engine combustion experiments, droplet evaporation simulations, and heat of vaporization measurements conducted to better understand how oxygenates affect particle emissions will be described. This research defines a process that can be used to evaluate fuels for other types of combustion such as diesel, gasoline compression ignition, or strategies with mixed modes.« less

Combustor kinetic energy efficiency analysis of the hypersonic research engine data

NASA Astrophysics Data System (ADS)

Hoose, K. V.

1993-11-01

A one-dimensional method for measuring combustor performance is needed to facilitate design and development scramjet engines. A one-dimensional kinetic energy efficiency method is used for measuring inlet and nozzle performance. The objective of this investigation was to assess the use of kinetic energy efficiency as an indicator for scramjet combustor performance. A combustor kinetic energy efficiency analysis was performed on the Hypersonic Research Engine (HRE) data. The HRE data was chosen for this analysis due to its thorough documentation and availability. The combustor, inlet, and nozzle kinetic energy efficiency values were utilized to determine an overall engine kinetic energy efficiency. Finally, a kinetic energy effectiveness method was developed to eliminate thermochemical losses from the combustion of fuel and air. All calculated values exhibit consistency over the flight speed range. Effects from fuel injection, altitude, angle of attack, subsonic-supersonic combustion transition, and inlet spike position are shown and discussed. The results of analyzing the HRE data indicate that the kinetic energy efficiency method is effective as a measure of scramjet combustor performance.

Aerodynamic design optimization of a fuel efficient high-performance, single-engine, business airplane

NASA Technical Reports Server (NTRS)

Holmes, B. J.

1980-01-01

A design study has been conducted to optimize a single-engine airplane for a high-performance cruise mission. The mission analyzed included a cruise speed of about 300 knots, a cruise range of about 1300 nautical miles, and a six-passenger payload (5340 N (1200 lb)). The purpose of the study is to investigate the combinations of wing design, engine, and operating altitude required for the mission. The results show that these mission performance characteristics can be achieved with fuel efficiencies competitive with present-day high-performance, single- and twin-engine, business airplanes. It is noted that relaxation of the present Federal Aviation Regulation, Part 23, stall-speed requirement for single-engine airplanes facilitates the optimization of the airplane for fuel efficiency.

Efficiency and large deviations in time-asymmetric stochastic heat engines

DOE PAGES

Gingrich, Todd R.; Rotskoff, Grant M.; Vaikuntanathan, Suriyanarayanan; ...

2014-10-24

In a stochastic heat engine driven by a cyclic non-equilibrium protocol, fluctuations in work and heat give rise to a fluctuating efficiency. Using computer simulations and tools from large deviation theory, we have examined these fluctuations in detail for a model two-state engine. We find in general that the form of efficiency probability distributions is similar to those described by Verley et al (2014 Nat. Commun. 5 4721), in particular featuring a local minimum in the long-time limit. In contrast to the time-symmetric engine protocols studied previously, however, this minimum need not occur at the value characteristic of a reversible Carnot engine. Furthermore, while the local minimum may reside at the global minimum of a large deviation rate function, it does not generally correspond to the least likely efficiency measured over finite time. Lastly, we introduce a general approximation for the finite-time efficiency distribution,more » $$P(\\eta )$$, based on large deviation statistics of work and heat, that remains very accurate even when $$P(\\eta )$$ deviates significantly from its large deviation form.« less

Green engineering education through a U.S. EPA/academia collaboration.

PubMed

Shonnard, David R; Allen, David T; Nguyen, Nhan; Austin, Sharon Weil; Hesketh, Robert

2003-12-01

The need to use resources efficiently and reduce environmental impacts of industrial products and processes is becoming increasingly important in engineering design; therefore, green engineering principles are gaining prominence within engineering education. This paper describes a general framework for incorporating green engineering design principles into engineering curricula, with specific examples for chemical engineering. The framework for teaching green engineering discussed in this paper mirrors the 12 Principles of Green Engineering proposed by Anastas and Zimmerman (Environ. Sci. Technol. 2003, 37, 94A-101A), especially in methods for estimating the hazardous nature of chemicals, strategies for pollution prevention, and approaches leading to efficient energy and material utilization. The key elements in green engineering education, which enlarge the "box" for engineering design, are environmental literacy, environmentally conscious design, and beyond-the-plant boundary considerations.

Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway.

PubMed

Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

2013-10-01

We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of 'fanconizing' cancer cells in order to make them more sensitive to other anti-tumour drugs. © 2013 The British Pharmacological Society.

Searching for Controlled Trials of Complementary and Alternative Medicine: A Comparison of 15 Databases

PubMed Central

Cogo, Elise; Sampson, Margaret; Ajiferuke, Isola; Manheimer, Eric; Campbell, Kaitryn; Daniel, Raymond; Moher, David

2011-01-01

This project aims to assess the utility of bibliographic databases beyond the three major ones (MEDLINE, EMBASE and Cochrane CENTRAL) for finding controlled trials of complementary and alternative medicine (CAM). Fifteen databases were searched to identify controlled clinical trials (CCTs) of CAM not also indexed in MEDLINE. Searches were conducted in May 2006 using the revised Cochrane highly sensitive search strategy (HSSS) and the PubMed CAM Subset. Yield of CAM trials per 100 records was determined, and databases were compared over a standardized period (2005). The Acudoc2 RCT, Acubriefs, Index to Chiropractic Literature (ICL) and Hom-Inform databases had the highest concentrations of non-MEDLINE records, with more than 100 non-MEDLINE records per 500. Other productive databases had ratios between 500 and 1500 records to 100 non-MEDLINE records—these were AMED, MANTIS, PsycINFO, CINAHL, Global Health and Alt HealthWatch. Five databases were found to be unproductive: AGRICOLA, CAIRSS, Datadiwan, Herb Research Foundation and IBIDS. Acudoc2 RCT yielded 100 CAM trials in the most recent 100 records screened. Acubriefs, AMED, Hom-Inform, MANTIS, PsycINFO and CINAHL had more than 25 CAM trials per 100 records screened. Global Health, ICL and Alt HealthWatch were below 25 in yield. There were 255 non-MEDLINE trials from eight databases in 2005, with only 10% indexed in more than one database. Yield varied greatly between databases; the most productive databases from both sampling methods were Acubriefs, Acudoc2 RCT, AMED and CINAHL. Low overlap between databases indicates comprehensive CAM literature searches will require multiple databases. PMID:19468052

Can the PHS model (ISO7933) predict reasonable thermophysiological responses while wearing protective clothing in hot environments?

PubMed

Wang, Faming; Kuklane, Kalev; Gao, Chuansi; Holmér, Ingvar

2011-02-01

In this paper, the prediction accuracy of the PHS (predicted heat strain) model on human physiological responses while wearing protective clothing ensembles was examined. Six human subjects (aged 29 ± 3 years) underwent three experimental trials in three different protective garments (clothing thermal insulation I(cl) ranges from 0.63 to 2.01 clo) in two hot environments (40 °C, relative humidities: 30% and 45%). The observed and predicted mean skin temperature, core body temperature and sweat rate were presented and statistically compared. A significant difference was found in the metabolic rate between FIRE (firefighting clothing) and HV (high visibility clothing) or MIL (military clothing) (p < 0.001). Also, the development of heart rate demonstrated the significant effects of the exposure time and clothing ensembles. In addition, the predicted evaporation rate during HV, MIL and FIRE was much lower than the experimental values. Hence, the current PHS model is not applicable for protective clothing with intrinsic thermal insulations above 1.0 clo. The results showed that the PHS model generated unreliable predictions on body core temperature when human subjects wore thick protective clothing such as firefighting clothing (I(cl) > 1.0 clo). The predicted mean skin temperatures in three clothing ensembles HV, MIL and FIRE were also outside the expected limits. Thus, there is a need for further extension for the clothing insulation validation range of the PHS model. It is recommended that the PHS model should be amended and validated by individual algorithms, physical or physiological parameters, and further subject studies.

Etude analytique et numérique de la réponse en vibration à hautes fréquences d'éprouvettes de fatigue vibratoire des métaux. Application aux aciers

NASA Astrophysics Data System (ADS)

Ben Aich, A.; El Kihel, B.; Kifani, A.; Sahban, F.

1994-07-01

In the present paper, the so-called " ultrasonic fatigue " or fatigue at very high frequency has been studied in the materials elastic behaviour case while neglecting the thermal effects that influence the mechanical fields. The determination of mechanical fields and specimen resonance length has been done both analytically and numerically. The numerical method used for this calculation is the finite element method (FEM). Martensitic steel " Soleil A2 " and austenitic steel " ICL 472 BC " have been considered in order to compare the two methods (analytical and numerical). It is shown that a perfect convergence is obtained between the two solutions. Dans le présent travail, la fatigue vibratoire a été étudiée dans le cas du comportement élastique des matériaux en négligeant les effets thermiques pouvant influencer les champs mécaniques. La détermination de ces champs et de la longueur de résonance des éprouvettes de fatigue a été faite analytiquement et numériquement. Le calcul numérique effectué se base sur la méthode des éléments finis. Dans le but d'une comparaison des solutions analytiques et numériques, deux aciers ont été considérés : un acier martensitique (Soleil A2) et un acier austénitique de type 18-10 (ICL 472 BC). Une parfaite convergence est obtenue entre les deux solutions.

Searching for controlled trials of complementary and alternative medicine: a comparison of 15 databases.

PubMed

Cogo, Elise; Sampson, Margaret; Ajiferuke, Isola; Manheimer, Eric; Campbell, Kaitryn; Daniel, Raymond; Moher, David

2011-01-01

This project aims to assess the utility of bibliographic databases beyond the three major ones (MEDLINE, EMBASE and Cochrane CENTRAL) for finding controlled trials of complementary and alternative medicine (CAM). Fifteen databases were searched to identify controlled clinical trials (CCTs) of CAM not also indexed in MEDLINE. Searches were conducted in May 2006 using the revised Cochrane highly sensitive search strategy (HSSS) and the PubMed CAM Subset. Yield of CAM trials per 100 records was determined, and databases were compared over a standardized period (2005). The Acudoc2 RCT, Acubriefs, Index to Chiropractic Literature (ICL) and Hom-Inform databases had the highest concentrations of non-MEDLINE records, with more than 100 non-MEDLINE records per 500. Other productive databases had ratios between 500 and 1500 records to 100 non-MEDLINE records-these were AMED, MANTIS, PsycINFO, CINAHL, Global Health and Alt HealthWatch. Five databases were found to be unproductive: AGRICOLA, CAIRSS, Datadiwan, Herb Research Foundation and IBIDS. Acudoc2 RCT yielded 100 CAM trials in the most recent 100 records screened. Acubriefs, AMED, Hom-Inform, MANTIS, PsycINFO and CINAHL had more than 25 CAM trials per 100 records screened. Global Health, ICL and Alt HealthWatch were below 25 in yield. There were 255 non-MEDLINE trials from eight databases in 2005, with only 10% indexed in more than one database. Yield varied greatly between databases; the most productive databases from both sampling methods were Acubriefs, Acudoc2 RCT, AMED and CINAHL. Low overlap between databases indicates comprehensive CAM literature searches will require multiple databases.

Hemispheric asymmetry of macroscopic and elementary calcium signals mediated by InsP3 in Xenopus oocytes.

PubMed

Callamaras, N; Sun, X P; Ivorra, I; Parker, I

1998-09-01

1. The mechanisms underlying hemispheric asymmetry of the inositol 1, 4,5-trisphosphate (InsP3)-calcium signalling pathway in Xenopus oocytes were examined by fluorescence imaging of calcium signals and recording calcium-activated Cl- currents (ICl,Ca) evoked by intracellular calcium injections and photorelease of InsP3. 2. The maximal ICl,Ca evoked by strong photorelease of InsP3 was 8 times greater in the animal than the vegetal hemisphere, but the average threshold amounts of InsP3 required to evoke detectable currents were similar in each hemisphere. 3. Currents evoked by injections of calcium were about 2.5 times greater near the animal pole than near the vegetal pole, whereas fluorescence signals evoked by injections were similar in each hemisphere. 4. Calcium waves were evoked by photolysis flashes of similar strengths in both hemispheres of albino oocytes, but peak calcium levels evoked by supramaximal stimuli were 70 % greater in the animal hemisphere. 5. Elementary calcium release events (puffs) in the animal hemisphere had amplitudes about double that in the vegetal hemisphere, and more often involved coupled release from adjacent sites. Calcium release sites were more closely packed in the animal hemisphere, with a mean spacing of about 1.5 micro m compared with 2.25 micro m in the vegetal hemisphere. 6. The larger amplitude of currents mediated by InsP3 in the animal hemisphere, therefore, involves an increased flux of calcium at individual release units, a more dense packing of release units and a higher density of Cl- channels.

Hemispheric asymmetry of macroscopic and elementary calcium signals mediated by InsP3 in Xenopus oocytes

PubMed Central

Callamaras, Nick; Sun, Xiao-Ping; Ivorra, Isabel; Parker, Ian

1998-01-01

The mechanisms underlying hemispheric asymmetry of the inositol 1,4,5-trisphosphate (InsP3)-calcium signalling pathway in Xenopus oocytes were examined by fluorescence imaging of calcium signals and recording calcium-activated Cl− currents (ICl,Ca) evoked by intracellular calcium injections and photorelease of InsP3. The maximal ICl,Ca evoked by strong photorelease of InsP3 was 8 times greater in the animal than the vegetal hemisphere, but the average threshold amounts of InsP3 required to evoke detectable currents were similar in each hemisphere. Currents evoked by injections of calcium were about 2.5 times greater near the animal pole than near the vegetal pole, whereas fluorescence signals evoked by injections were similar in each hemisphere. Calcium waves were evoked by photolysis flashes of similar strengths in both hemispheres of albino oocytes, but peak calcium levels evoked by supramaximal stimuli were 70% greater in the animal hemisphere. Elementary calcium release events (puffs) in the animal hemisphere had amplitudes about double that in the vegetal hemisphere, and more often involved coupled release from adjacent sites. Calcium release sites were more closely packed in the animal hemisphere, with a mean spacing of about 1.5 μm compared with 2.25 μm in the vegetal hemisphere. The larger amplitude of currents mediated by InsP3 in the animal hemisphere, therefore, involves an increased flux of calcium at individual release units, a more dense packing of release units and a higher density of Cl− channels. PMID:9706018

Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway

PubMed Central

Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

2013-01-01

BACKGROUND AND PURPOSE We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. EXPERIMENTAL APPROACH Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. KEY RESULTS While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. CONCLUSIONS AND IMPLICATIONS Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of ‘fanconizing’ cancer cells in order to make them more sensitive to other anti-tumour drugs. PMID:23937566

Targeting Homologous Recombination by Pharmacological Inhibitors Enhances the Killing Response of Glioblastoma Cells Treated with Alkylating Drugs.

PubMed

Berte, Nancy; Piée-Staffa, Andrea; Piecha, Nadine; Wang, Mengwan; Borgmann, Kerstin; Kaina, Bernd; Nikolova, Teodora

2016-11-01

Malignant gliomas exhibit a high level of intrinsic and acquired drug resistance and have a dismal prognosis. First- and second-line therapeutics for glioblastomas are alkylating agents, including the chloroethylating nitrosoureas (CNU) lomustine, nimustine, fotemustine, and carmustine. These agents target the tumor DNA, forming O 6 -chloroethylguanine adducts and secondary DNA interstrand cross-links (ICL). These cross-links are supposed to be converted into DNA double-strand breaks, which trigger cell death pathways. Here, we show that lomustine (CCNU) with moderately toxic doses induces ICLs in glioblastoma cells, inhibits DNA replication fork movement, and provokes the formation of DSBs and chromosomal aberrations. Since homologous recombination (HR) is involved in the repair of DSBs formed in response to CNUs, we elucidated whether pharmacologic inhibitors of HR might have impact on these endpoints and enhance the killing effect. We show that the Rad51 inhibitors RI-1 and B02 greatly ameliorate DSBs, chromosomal changes, and the level of apoptosis and necrosis. We also show that an inhibitor of MRE11, mirin, which blocks the formation of the MRN complex and thus the recognition of DSBs, has a sensitizing effect on these endpoints as well. In a glioma xenograft model, the Rad51 inhibitor RI-1 clearly enhanced the effect of CCNU on tumor growth. The data suggest that pharmacologic inhibition of HR, for example by RI-1, is a reasonable strategy for enhancing the anticancer effect of CNUs. Mol Cancer Ther; 15(11); 2665-78. ©2016 AACR. ©2016 American Association for Cancer Research.

p53 inhibits CRISPR-Cas9 engineering in human pluripotent stem cells.

PubMed

Ihry, Robert J; Worringer, Kathleen A; Salick, Max R; Frias, Elizabeth; Ho, Daniel; Theriault, Kraig; Kommineni, Sravya; Chen, Julie; Sondey, Marie; Ye, Chaoyang; Randhawa, Ranjit; Kulkarni, Tripti; Yang, Zinger; McAllister, Gregory; Russ, Carsten; Reece-Hoyes, John; Forrester, William; Hoffman, Gregory R; Dolmetsch, Ricardo; Kaykas, Ajamete

2018-06-11

CRISPR/Cas9 has revolutionized our ability to engineer genomes and conduct genome-wide screens in human cells 1-3 . Whereas some cell types are amenable to genome engineering, genomes of human pluripotent stem cells (hPSCs) have been difficult to engineer, with reduced efficiencies relative to tumour cell lines or mouse embryonic stem cells 3-13 . Here, using hPSC lines with stable integration of Cas9 or transient delivery of Cas9-ribonucleoproteins (RNPs), we achieved an average insertion or deletion (indel) efficiency greater than 80%. This high efficiency of indel generation revealed that double-strand breaks (DSBs) induced by Cas9 are toxic and kill most hPSCs. In previous studies, the toxicity of Cas9 in hPSCs was less apparent because of low transfection efficiency and subsequently low DSB induction 3 . The toxic response to DSBs was P53/TP53-dependent, such that the efficiency of precise genome engineering in hPSCs with a wild-type P53 gene was severely reduced. Our results indicate that Cas9 toxicity creates an obstacle to the high-throughput use of CRISPR/Cas9 for genome engineering and screening in hPSCs. Moreover, as hPSCs can acquire P53 mutations 14 , cell replacement therapies using CRISPR/Cas9-enginereed hPSCs should proceed with caution, and such engineered hPSCs should be monitored for P53 function.

Energy Efficient Engine integrated core/low spool design and performance report

NASA Technical Reports Server (NTRS)

Stearns, E. Marshall

1985-01-01

The Energy Efficient Engine (E3) is a NASA program to create fuel saving technology for future transport aircraft engines. The E3 technology advancements were demonstrated to operate reliably and achieve goal performance in tests of the Integrated Core/Low Spool vehicle. The first build of this undeveloped technology research engine set a record for low fuel consumption. Its design and detailed test results are herein presented.

Thermodynamics of the mesoscopic thermoelectric heat engine beyond the linear-response regime.

PubMed

Yamamoto, Kaoru; Hatano, Naomichi

2015-10-01

Mesoscopic thermoelectric heat engine is much anticipated as a device that allows us to utilize with high efficiency wasted heat inaccessible by conventional heat engines. However, the derivation of the heat current in this engine seems to be either not general or described too briefly, even inappropriately in some cases. In this paper, we give a clear-cut derivation of the heat current of the engine with suitable assumptions beyond the linear-response regime. It resolves the confusion in the definition of the heat current in the linear-response regime. After verifying that we can construct the same formalism as that of the cyclic engine, we find the following two interesting results within the Landauer-Büttiker formalism: the efficiency of the mesoscopic thermoelectric engine reaches the Carnot efficiency if and only if the transmission probability is finite at a specific energy and zero otherwise; the unitarity of the transmission probability guarantees the second law of thermodynamics, invalidating Benenti et al.'s argument in the linear-response regime that one could obtain a finite power with the Carnot efficiency under a broken time-reversal symmetry [Phys. Rev. Lett. 106, 230602 (2011)]. These results demonstrate how quantum mechanics constrains thermodynamics.

Preliminary Results of an Altitude-Wind-Tunnel Investigation of an Axial-Flow Gas Turbine-Propeller Engine. 5; Combustion-Chamber Characterisitcs

NASA Technical Reports Server (NTRS)

Geisenheyner, Robert M.; Berdysz, Joseph J.

1948-01-01

An investigation to determine the performance and operational characteristics of an axial-flow gas turbine-propeller engine was conducted in the Cleveland altitude wind tunnel. As part of this investigation, the combustion-chamber performance was determined at pressure altitudes from 5000 to 35,000 feet, compressor-inlet ram-pressure ratios of 1.00 and 1.09, and engine speeds from 8000 to 13,000 rpm. Combustion-chamber performance is presented as a function of corrected engine speed and corrected horsepower. For the range of corrected engine speeds investigated, overall total-pressure-loss ratio, cycle efficiency, and the fractional loss in cycle efficiency resulting from pressure losses in the combustion chambers were unaffected by a change in altitude or compressor-inlet ram-pressure ratio. For the range of corrected horsepowers investigated, the total-pressure-loss ratio and the fractional loss in cycle efficiency resulting from pressure losses in the combustion chambers decreased with an increase in corrected horsepower at a constant corrected engine speed. The combustion efficiency remained constant for the range of corrected horsepowers investigated at all corrected engine speeds.

Study on effect of mixing mechanism by the transverse gaseous injection flow in scramjet engine with variable parameters

NASA Astrophysics Data System (ADS)

Yadav, Siddhita; Pandey, K. M.

2018-04-01

In scramjet engine the mixing mechanism of fuel and atmospheric air is very complicated, because the fuel have time in milliseconds for mixing with atmospheric air in combustion chamber having supersonic speed. Mixing efficiency of fuel and atmospheric air depends on mainly these parameters: Aspect ratio of injector, vibration amplitude, shock type, number of injector, jet to transverse flow momentum flux ratio, injector geometry, injection angle, molecular weight, incoming air stream angle, jet to transverse flow pressure ratio, spacing variation, mass flow rate of fuel etc. here is a very brief study of these parameters from previously done research on these parameters for the improvement of mixing efficiency. The mixing process have the significant role for the working of engine, and mixing between the atmospheric air and the jet fuel is significant factor for improving the overall thrust of the engine. The results obtained by study of papers are obtained by the 3D-Reynolds Average-Nervier-Stokes(RANS) equations along with the 2-equation k-ω shear-stress-transport (SST) turbulence model. Engine having multi air jets have 60% more mixing efficiency than single air jet, thus if the jets are increased, the mixing efficiency of engine can also be increased up to 150% by changing jet from 1 to 16. When using delta shape of injector the mixing efficiency is inversely proportional to the pressure ratio. When the fuel is injected inside the combustor from the top and bottom walls of the engine efficiency of mixing in reacting zone is higher than the single wall injection and in comparison to parallel flow, the transverse type flow is better as the atmospheric air jet can penetrate smoothly in the fuel jets and mixes well in less time. Hence this study of parameters and their effects on mixing can enhance the efficiency of mixing in engine.

Hige Compression Ratio Turbo Gasoline Engine Operation Using Alcohol Enhancement

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

Heywood, John; Jo, Young Suk; Lewis, Raymond

The overall objective of this project was to quantify the potential for improving the performance and efficiency of gasoline engine technology by use of alcohols to suppress knock. Knock-free operation is obtained by direct injection of a second “anti-knock” fuel such as ethanol, which suppresses knock when, with gasoline fuel, knock would occur. Suppressing knock enables increased turbocharging, engine downsizing, and use of higher compression ratios throughout the engine’s operating map. This project combined engine testing and simulation to define knock onset conditions, with different mixtures of gasoline and alcohol, and with this information quantify the potential for improving themore » efficiency of turbocharged gasoline spark-ignition engines, and the on-vehicle fuel consumption reductions that could then be realized. The more focused objectives of this project were therefore to: Determine engine efficiency with aggressive turbocharging and downsizing and high compression ratio (up to a compression ratio of 13.5:1) over the engine’s operating range; Determine the knock limits of a turbocharged and downsized engine as a function of engine speed and load; Determine the amount of the knock-suppressing alcohol fuel consumed, through the use of various alcohol-gasoline and alcohol-water gasoline blends, for different driving cycles, relative to the gasoline consumed; Determine implications of using alcohol-boosted engines, with their higher efficiency operation, in both light-duty and medium-duty vehicle sectors.« less

Automotive Stirling Engine Development Program Mod I Stirling engine development

NASA Technical Reports Server (NTRS)

Simetkosky, M. A.

1983-01-01

The development of the Mod I 4-cylinder automotive Stirling engine is discussed and illustrated with drawings, block diagrams, photographs, and graphs and tables of preliminary test data. The engine and its drive, cold-engine, hot-engine, external-heat, air/fuel, power-control, electronic-control, and auxiliary systems are characterized. Performance results from a total of 1900 h of tests on 4 prototype engines include average maximum efficiency (at 2000 rpm) 34.5 percent and maximum output power 54.4 kW. The modifications introduced in an upgraded version of the Mod I are explained; this engine has maximum efficiency 40.4 percent and maximum power output 69.2 kW.

Enhanced Efficiency of Internal Combustion Engines By Employing Spinning Gas

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

Geyko, Vasily; Fisch, Nathaniel

2014-02-27

The efficiency of the internal combustion engine might be enhanced by employing spinning gas. A gas spinning at near sonic velocities has an effectively higher heat capacity, which allows practical fuel cycles, which are far from the Carnot efficiency, to approach more closely the Carnot efficiency. A gain in fuel efficiency of several percent is shown to be theoretically possible for the Otto and Diesel cycles. The use of a flywheel, in principle, could produce even greater increases in the efficiency.

Enhanced efficiency of internal combustion engines by employing spinning gas.

PubMed

Geyko, V I; Fisch, N J

2014-08-01

The efficiency of the internal combustion engine might be enhanced by employing spinning gas. A gas spinning at near sonic velocities has an effectively higher heat capacity, which allows practical fuel cycles, which are far from the Carnot efficiency, to approach more closely the Carnot efficiency. A remarkable gain in fuel efficiency is shown to be theoretically possible for the Otto and Diesel cycles. The use of a flywheel, in principle, could produce even greater increases in efficiency.

Irreversibilities and efficiency at maximum power of heat engines: the illustrative case of a thermoelectric generator.

PubMed

Apertet, Y; Ouerdane, H; Goupil, C; Lecoeur, Ph

2012-03-01

Energy conversion efficiency at maximum output power, which embodies the essential characteristics of heat engines, is the main focus of the present work. The so-called Curzon and Ahlborn efficiency η(CA) is commonly believed to be an absolute reference for real heat engines; however, a different but general expression for the case of stochastic heat engines, η(SS), was recently found and then extended to low-dissipation engines. The discrepancy between η(CA) and η(SS) is here analyzed considering different irreversibility sources of heat engines, of both internal and external types. To this end, we choose a thermoelectric generator operating in the strong-coupling regime as a physical system to qualitatively and quantitatively study the impact of the nature of irreversibility on the efficiency at maximum output power. In the limit of pure external dissipation, we obtain η(CA), while η(SS) corresponds to the case of pure internal dissipation. A continuous transition between from one extreme to the other, which may be operated by tuning the different sources of irreversibility, also is evidenced.

Thermodynamic and Mechanical Analysis of a Thermomagnetic Rotary Engine

NASA Astrophysics Data System (ADS)

Fajar, D. M.; Khotimah, S. N.; Khairurrijal

2016-08-01

A heat engine in magnetic system had three thermodynamic coordinates: magnetic intensity ℋ, total magnetization ℳ, and temperature T, where the first two of them are respectively analogous to that of gaseous system: pressure P and volume V. Consequently, Carnot cycle that constitutes the principle of a heat engine in gaseous system is also valid on that in magnetic system. A thermomagnetic rotary engine is one model of it that was designed in the form of a ferromagnetic wheel that can rotates because of magnetization change at Curie temperature. The study is aimed to describe the thermodynamic and mechanical analysis of a thermomagnetic rotary engine and calculate the efficiencies. In thermodynamic view, the ideal processes are isothermal demagnetization, adiabatic demagnetization, isothermal magnetization, and adiabatic magnetization. The values of thermodynamic efficiency depend on temperature difference between hot and cold reservoir. In mechanical view, a rotational work is determined through calculation of moment of inertia and average angular speed. The value of mechanical efficiency is calculated from ratio between rotational work and heat received by system. The study also obtains exergetic efficiency that states the performance quality of the engine.

Efficiency and its bounds for a quantum Einstein engine at maximum power.

PubMed

Yan, H; Guo, Hao

2012-11-01

We study a quantum thermal engine model for which the heat transfer law is determined by Einstein's theory of radiation. The working substance of the quantum engine is assumed to be a two-level quantum system of which the constituent particles obey Maxwell-Boltzmann (MB), Fermi-Dirac (FD), or Bose-Einstein (BE) distributions, respectively, at equilibrium. The thermal efficiency and its bounds at maximum power of these models are derived and discussed in the long and short thermal contact time limits. The similarity and difference between these models are discussed. We also compare the efficiency bounds of this quantum thermal engine to those of its classical counterpart.

Effects of Altitude on Turbojet Engine Performance

NASA Technical Reports Server (NTRS)

Fleming, William A

1951-01-01

Component and over-all performance characteristics of several turbojet engines investigated in the altitude facilities of the NACA Lewis Laboratory during the last several years are summarized to indicate the effects of altitude on turbojet engine performance. Data presented show that failure of turbojet engine performance to generalize for all altitudes can be traced to reductions in compressor efficiency, corrected air flow, and combustion efficiency at altitude. In addition, it is shown that although engines of different design may have equal thrusts at sea level, the thrusts at altitude may vary widely because of differences in compressor performance characteristics from one engine to another.

Two stroke homogenous charge compression ignition engine with pulsed air supplier

DOEpatents

Clarke, John M.

2003-08-05

A two stroke homogenous charge compression ignition engine includes a volume pulsed air supplier, such as a piston driven pump, for efficient scavenging. The usage of a homogenous charge tends to decrease emissions. The use of a volume pulsed air supplier in conjunction with conventional poppet type intake and exhaust valves results in a relatively efficient scavenging mode for the engine. The engine preferably includes features that permit valving event timing, air pulse event timing and injection event timing to be varied relative to engine crankshaft angle. The principle use of the invention lies in improving diesel engines.

Full Scale Technology Demonstration of a Modern Counterrotating Unducted Fan Engine Concept. Design Report

NASA Technical Reports Server (NTRS)

1987-01-01

The Unducted Fan engine (UDF trademark) concept is based on an ungeared, counterrotating, unducted, ultra-high-bypass turbofan configuration. This engine is being developed to provide a high thrust-to-weight ratio power plant with exceptional fuel efficiency for subsonic aircraft application. This report covers the design methodology and details for the major components of this engine. The design intent of the engine is to efficiently produce 25,000 pounds of static thrust while meeting life and stress requirements. The engine is required to operate at Mach numbers of 0.8 or above.

Study of small civil turbofan engines applicable to military trainer airplanes

NASA Technical Reports Server (NTRS)

Heldenbrand, R. W.; Merrill, G. L.; Burnett, G. A.

1975-01-01

Small turbofan engine design concepts were applied to military trainer airplanes to establish the potential for commonality between civil and military engines. Several trainer configurations were defined and studied. A ""best'' engine was defined for the trainer mission, and sensitivity analyses were performed to determine the effects on airplane size and efficiency of wing loading, power loading, configuration, aerodynamic quality, and engine quality. It is concluded that a small civil aircraft is applicable to military trainer airplanes. Aircraft designed with these engines are smaller, less costly, and more efficient than existing trainer aircraft.

Test results and description of a 1-kW free-piston Stirling engine with a dashpot load

NASA Technical Reports Server (NTRS)

Schreiber, J.

1983-01-01

A 1 kW (1.33 hp) single cylinder free piston Stirling engine was installed in the test facilities at the Lewis laboratory. The engine was designed specifically for research of the dynamics of its operation. A more complete description of the engine and its instrumentation is provided in a prior NASA paper TM-82999 by J. G. Schreiber. Initial tests at Lewis showed the power level and efficiency of the engine to be below design level. Tests were performed to help determine the specific problems in the engine causing the below design level performance. Modifications to engine hardware and to the facility where performed in an effort to bring the power output and efficiency to their design values. As finally configured the engine generated more than 1250 watts of output power at an engine efficiency greater than 32 percent. This report presents the tests performed to help determine the specific problems, the results if the problem was eliminated, the fix performed to the hardware, and the test results after the engine was tested. In cases where the fix did not cause the anticipated effects, a possible explanation is given.

Advanced component technologies for energy-efficient turbofan engines

NASA Technical Reports Server (NTRS)

Saunders, N. T.

1980-01-01

The paper reviews NASA's Energy Efficient Engine Project which was initiated to provide the advanced technology base for a new generation of fuel-conservative engines for introduction into airline service by the late 1980s. Efforts in this project are directed at advancing engine component and systems technologies to a point of demonstrating technology-readiness by 1984. Early results indicate high promise in achieving most of the goals established in the project.

Energy Efficient Engine Flight Propulsion System Preliminary Analysis and Design Report

NASA Technical Reports Server (NTRS)

Bisset, J. W.; Howe, D. C.

1983-01-01

The final design and analysis of the flight propulsion system is presented. This system is the conceptual study engine defined to meet the performance, economic and environmental goals established for the Energy Efficient Engine Program. The design effort included a final definition of the engine, major components, internal subsystems, and nacelle. Various analytical representations and results from component technology programs are used to verify aerodynamic and structural design concepts and to predict performance. Specific design goals and specifications, reflecting future commercial aircraft propulsion system requirements for the mid-1980's, are detailed by NASA and used as guidelines during engine definition. Information is also included which details salient results from a separate study to define a turbofan propulsion system, known as the maximum efficiency engine, which reoptimized the advanced fuel saving technologies for improved fuel economy and direct operating costs relative to the flight propulsion system.

USE Efficiency: an innovative educational programme for energy efficiency in buildings

NASA Astrophysics Data System (ADS)

Papadopoulos, Theofilos A.; Christoforidis, Georgios C.; Papagiannis, Grigoris K.

2017-10-01

Power engineers are expected to play a pivotal role in transforming buildings into smart and energy-efficient structures, which is necessary since buildings are responsible for a considerable amount of the total energy consumption. To fulfil this role, a holistic approach in education is required, tackling subjects traditionally related to other engineering disciplines. In this context, USE Efficiency is an inter-institutional and interdisciplinary educational programme implemented in nine European Universities targeting energy efficiency in buildings. The educational programme effectively links professors, students, engineers and industry experts, creating a unique learning environment. The scope of the paper is to present the methodology and the general framework followed in the USE Efficiency programme. The proposed methodology can be adopted for the design and implementation of educational programmes on energy efficiency and sustainable development in higher education. End-of-course survey results showed positive feedback from the participating students, indicating the success of the programme.

Novikov Engine with Fluctuating Heat Bath Temperature

NASA Astrophysics Data System (ADS)

Schwalbe, Karsten; Hoffmann, Karl Heinz

2018-04-01

The Novikov engine is a model for heat engines that takes the irreversible character of heat fluxes into account. Using this model, the maximum power output as well as the corresponding efficiency of the heat engine can be deduced, leading to the well-known Curzon-Ahlborn efficiency. The classical model assumes constant heat bath temperatures, which is not a reasonable assumption in the case of fluctuating heat sources. Therefore, in this article the influence of stochastic fluctuations of the hot heat bath's temperature on the optimal performance measures is investigated. For this purpose, a Novikov engine with fluctuating heat bath temperature is considered. Doing so, a generalization of the Curzon-Ahlborn efficiency is found. The results can help to quantify how the distribution of fluctuating quantities affects the performance measures of power plants.

Energy efficient engine preliminary design and integration study

NASA Technical Reports Server (NTRS)

Gray, D. E.

1978-01-01

The technology and configurational requirements of an all new 1990's energy efficient turbofan engine having a twin spool arrangement with a directly coupled fan and low-pressure turbine, a mixed exhaust nacelle, and a high 38.6:1 overall pressure ratio were studied. Major advanced technology design features required to provide the overall benefits were a high pressure ratio compression system, a thermally actuated advanced clearance control system, lightweight shroudless fan blades, a low maintenance cost one-stage high pressure turbine, a short efficient mixer and structurally integrated engine and nacelle. A conceptual design analysis was followed by integration and performance analyses of geared and direct-drive fan engines with separate or mixed exhaust nacelles to refine previously designed engine cycles. Preliminary design and more detailed engine-aircraft integration analysis were then conducted on the more promising configurations. Engine and aircraft sizing, fuel burned, and airframe noise studies on projected 1990's domestic and international aircraft produced sufficient definition of configurational and advanced technology requirements to allow immediate initiation of component technology development.

Energy efficient engine component development and integration program

NASA Technical Reports Server (NTRS)

1982-01-01

The objective of the Energy Efficient Engine Component Development and Integration program is to develop, evaluate, and demonstrate the technology for achieving lower installed fuel consumption and lower operating costs in future commercial turbofan engines. Minimum goals have been set for a 12 percent reduction in thrust specific fuel consumption (TSFC), 5 percent reduction in direct operating cost (DOC), and 50 percent reduction in performance degradation for the Energy Efficient Engine (flight propulsion system) relative to the JT9D-7A reference engine. The Energy Efficienct Engine features a twin spool, direct drive, mixed flow exhaust configuration, utilizing an integrated engine nacelle structure. A short, stiff, high rotor and a single stage high pressure turbine are among the major enhancements in providing for both performance retention and major reductions in maintenance and direct operating costs. Improved clearance control in the high pressure compressor and turbines, and advanced single crystal materials in turbine blades and vanes are among the major features providing performance improvement. Highlights of work accomplished and programs modifications and deletions are presented.

On the practical efficiency of shape memory engines

NASA Astrophysics Data System (ADS)

McCormick, P. G.

1987-02-01

The effects of non-ideal behavior, i.e., thermal efficiencies less than perfect, on the efficiency of shape memory (SME) engines are analyzed. Account is taken of the temperature hysteresis between the forward and reverse transformation and the finite elastic compliance of the SM element and the engine. The temperature difference produced by a particular stress cycle and necessary to complete the cycle is quantified, along with the temperature penalty which arises from non-ideal behavior. The hysteresis, elastic compliance and low working strains in cycled materials are shown to yield low thermal efficiencies, e.g., 1.95 pct instead of 6.74 pct in the case of a 20 k hysteresis. Heat recycling can theoretically improve the efficiency to about 3.23 pct.

Energy efficient engine high-pressure turbine detailed design report

NASA Technical Reports Server (NTRS)

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

1982-01-01

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

Energy efficient engine: Turbine intermediate case and low-pressure turbine component test hardware detailed design report

NASA Technical Reports Server (NTRS)

Leach, K.; Thulin, R. D.; Howe, D. C.

1982-01-01

A four stage, low pressure turbine component has been designed to power the fan and low pressure compressor system in the Energy Efficient Engine. Designs for a turbine intermediate case and an exit guide vane assembly also have been established. The components incorporate numerous technology features to enhance efficiency, durability, and performance retention. These designs reflect a positive step towards improving engine fuel efficiency on a component level. The aerodynamic and thermal/mechanical designs of the intermediate case and low pressure turbine components are presented and described. An overview of the predicted performance of the various component designs is given.

Combustion-chamber Performance Characteristics of a Python Turbine-propeller Engine Investigated in Altitude Wind Tunnel

NASA Technical Reports Server (NTRS)

Campbell, Carl E

1951-01-01

Combustion-chamber performance characteristics of a Python turbine-propeller engine were determined from investigation of a complete engine over a range of engine speeds and shaft horsepowers at simulated altitudes. Results indicated the effect of engine operating conditions and altitude on combustion efficiency and combustion-chamber total pressure losses. Performance of this vaporizing type combustion chamber was also compared with several atomizing type combustion chambers. Over the range of test conditions investigated, combustion efficiency varied from approximately 0.95 to 0.99.

The energy efficient engine project

NASA Technical Reports Server (NTRS)

Macioce, L. E.; Schaefer, J. W.; Saunders, N. T.

1980-01-01

The Energy Efficient Engine Project is directed at providing, by 1984, the advanced technologies which could be used for a generation of fuel conservative turbofan engines. The project is conducted through contracts with the General Electric Company and Pratt and Whitney Aircraft. The scope of the entire project and the current status of these efforts are summarized. A description of the preliminary designs of the fully developed engines is included and the potential benefits of these advanced engines, as well as highlights of some of the component technology efforts conducted to date, are discussed.

Method and apparatus for selectively controlling the speed of an engine

DOEpatents

Davis, Roy Inge

2001-02-27

A control assembly 12 for use within a vehicle 10 having an engine 14 and which selectively controls the speed of the engine 14 in order to increase fuel efficiency and to effect relatively smooth starting and stopping of the engine. Particularly, in one embodiment, control assembly 12 cooperatively operates with a starter/alternator assembly 20 and is adapted for use with hybrid vehicles employing a start/stop powertrain assembly, wherein fuel efficiency is increased by selectively stopping engine operation when the vehicle has stopped.

Crank case scavenging of two-stroke-cycle engines

NASA Technical Reports Server (NTRS)

List, Hans

1929-01-01

This report presents the results of tests on two-stroke-cycle Diesel engines to determine the efficiency of the crank case scavenging pump. It was determined that efficiencies were between 95 and 100%.

Energy Efficient Engine core design and performance report

NASA Technical Reports Server (NTRS)

Stearns, E. Marshall

1982-01-01

The Energy Efficient Engine (E3) is a NASA program to develop fuel saving technology for future large transport aircraft engines. Testing of the General Electric E3 core showed that the core component performance and core system performance necessary to meet the program goals can be achieved. The E3 core design and test results are described.

75 FR 67059 - Public Hearings for Greenhouse Gas Emissions Standards and Fuel Efficiency Standards for Medium...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... Greenhouse Gas Emissions Standards and Fuel Efficiency Standards for Medium- and Heavy-Duty Engines and... for Medium- and Heavy-Duty Engines and Vehicles,'' which will be published in the near future in the... Medium- and Heavy-Duty Engines and Vehicles.'' These hearings also offer an opportunity for the public to...

Hybrid and conventional hydrogen engine vehicles that meet EZEV emissions

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

Aceves, S.M.; Smith, J.R.

In this paper, a time-dependent engine model is used for predicting hydrogen engine efficiency and emissions. The model uses basic thermodynamic equations for the compression and expansion processes, along with an empirical correlation for heat transfer, to predict engine indicated efficiency. A friction correlation and a supercharger/turbocharger model are then used to calculate brake thermal efficiency. The model is validated with many experimental points obtained in a recent evaluation of a hydrogen research engine. A The validated engine model is then used to calculate fuel economy and emissions for three hydrogen-fueled vehicles: a conventional, a parallel hybrid, and a seriesmore » hybrid. All vehicles use liquid hydrogen as a fuel. The hybrid vehicles use a flywheel for energy storage. Comparable ultra capacitor or battery energy storage performance would give similar results. This paper analyzes the engine and flywheel sizing requirements for obtaining a desired level of performance. The results indicate that hydrogen lean-burn spark-ignited engines can provide a high fuel economy and Equivalent Zero Emission Vehicle (EZEV) levels in the three vehicle configurations being analyzed.« less

Waste Heat Recovery from a High Temperature Diesel Engine

NASA Astrophysics Data System (ADS)

Adler, Jonas E.

Government-mandated improvements in fuel economy and emissions from internal combustion engines (ICEs) are driving innovation in engine efficiency. Though incremental efficiency gains have been achieved, most combustion engines are still only 30-40% efficient at best, with most of the remaining fuel energy being rejected to the environment as waste heat through engine coolant and exhaust gases. Attempts have been made to harness this waste heat and use it to drive a Rankine cycle and produce additional work to improve efficiency. Research on waste heat recovery (WHR) demonstrates that it is possible to improve overall efficiency by converting wasted heat into usable work, but relative gains in overall efficiency are typically minimal ( 5-8%) and often do not justify the cost and space requirements of a WHR system. The primary limitation of the current state-of-the-art in WHR is the low temperature of the engine coolant ( 90 °C), which minimizes the WHR from a heat source that represents between 20% and 30% of the fuel energy. The current research proposes increasing the engine coolant temperature to improve the utilization of coolant waste heat as one possible path to achieving greater WHR system effectiveness. An experiment was performed to evaluate the effects of running a diesel engine at elevated coolant temperatures and to estimate the efficiency benefits. An energy balance was performed on a modified 3-cylinder diesel engine at six different coolant temperatures (90 °C, 100 °C, 125 °C, 150 °C, 175 °C, and 200 °C) to determine the change in quantity and quality of waste heat as the coolant temperature increased. The waste heat was measured using the flow rates and temperature differences of the coolant, engine oil, and exhaust flow streams into and out of the engine. Custom cooling and engine oil systems were fabricated to provide adequate adjustment to achieve target coolant and oil temperatures and large enough temperature differences across the engine to reduce uncertainty. Changes to exhaust emissions were recorded using a 5-gas analyzer. The engine condition was also monitored throughout the tests by engine compression testing, oil analysis, and a complete teardown and inspection after testing was completed. The integrity of the head gasket seal proved to be a significant problem and leakage of engine coolant into the combustion chamber was detected when testing ended. The post-test teardown revealed problems with oil breakdown at locations where temperatures were highest, with accompanying component wear. The results from the experiment were then used as inputs for a WHR system model using ethanol as the working fluid, which provided estimates of system output and improvement in efficiency. Thermodynamic models were created for eight different WHR systems with coolant temperatures of 90 °C, 150 °C, 175 °C, and 200 °C and condenser temperatures of 60 °C and 90 °C at a single operating point of 3100 rpm and 24 N-m of torque. The models estimated that WHR output for both condenser temperatures would increase by over 100% when the coolant temperature was increased from 90 °C to 200 °C. This increased WHR output translated to relative efficiency gains as high as 31.0% for the 60 °C condenser temperature and 24.2% for the 90 °C condenser temperature over the baseline engine efficiency at 90 °C. Individual heat exchanger models were created to estimate the footprint for a WHR system for each of the eight systems. When the coolant temperature increased from 90 °C to 200 °C, the total heat exchanger volume increased from 16.6 x 103 cm3 to 17.1 x 10 3 cm3 with a 60 °C condenser temperature, but decreased from 15.1 x 103 cm3 to 14.2 x 10 3 cm3 with a 90 °C condenser temperature. For all cases, increasing the coolant temperature resulted in an improvement in the efficiency gain for each cubic meter of heat exchanger volume required. Additionally, the engine oil coolers represented a significant portion of the required heat exchanger volume due to abnormally low engine oil temperatures during the experiment ( 80 °C). Future studies should focus on allowing the engine oil to reach higher operating temperatures which would decrease the heat rejected to the engine oil and reduce the heat duty for the oil coolers resulting in reduced oil cooler volume.

Development for equipment of the milk macromolecules content detection

NASA Astrophysics Data System (ADS)

Ding, Guochao; Li, Weimin; Shang, Tingyi; Xi, Yang; Gao, Yunli; Zhou, Zhen

Developed an experimental device for rapid and accurate detection of milk macromolecular content. This device developed based on laser scattered through principle, the principle use of the ingredients of the scattered light and transmitted light ratio characterization of macromolecules. Peristaltic pump to achieve automatic input and output of the milk samples, designing weak signal detection amplifier circuit for detecting the ratio with ICL7650. Real-time operating system μC / OS-II is the core design of the software part of the whole system. The experimental data prove that the device can achieve a fast real-time measurement of milk macromolecules.

CNA’s Integrated Ship Database: Third Quarter CY 2012 Update

DTIC Science & Technology

2013-11-01

rogram!- -;OJ"’T’-" A "’K"C~¥-go"Shi"~P:----------------t---’~;;1~ ® T- AKR Veh icle-Car o 9 S T- ADT Tran rt 0i1er 1 9 Mitita.y Sealift Command (MSC). in...CNA’s Integrated Ship Database Third Quarter CY 2012 Update Gregory N. Suess • Lynette A . McClain • Linette O. Neal CNA Interactive Software DIS...law, no person shall be subject to a penalty for failing to comply with a collection of information if it does not display a currently valid OMB

The Hereptofauna of Letterkenny Army Depot, South-Central Pennsylvania: A Starting Point to the Long-Term Monitoring and Management of Amphibians and Reptiles

DTIC Science & Technology

2010-06-01

Journal of Kansas Herpetology Number 34 (June 2010) 11 www.cnah.org/khs ARtIClES tHE HERpEtofAUNA of lEttERKENNY ARMY dEpot, SoUtH-CENtRAl...compare the herpetological commu- nity currently present at the site with that expected from prior literature (felbaum, 1995; Hulse et al., 2001; tetra...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Journal of Kansas Herpetology Number 34 (June 2010) 12 www.cnah.org/khs agricultural and other

Ada Compiler Validation Summary Report. Certificate Number 880728S1. 09141 DDC-I, Inc., DACS-386/UNIX, Version 4.2, ICL DRS 300 Host and Target

DTIC Science & Technology

1988-07-28

r R ~l~ F COPV en Data Entered) AT ION PAGE -ErOP RCoMrE-EoNGFOP. A D-A 204 928 1Z. GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER 4...PAGE (When Data Entered) Ada Compiler Validation Summary Repor-: Compiler Name: DACS-386/UNIX, Version 4.2 Certificate Number: 880728S1.09141 Host...which have the STORAGE SIZE length clause were changed to comment lines under the direction of the AVF Manager . These modified tests ran to a successful

Nonlinear Fault Diagnosis,

DTIC Science & Technology

1981-05-01

obtained if one first generates a data base in terms cf the nominal circuit parameters and then extracts the aocrooriate s’pnbo𔃾c transfer functicn from...0 0 0 0 I 0 I 0 0 0 0 Here we initially allow V0 , ICl , VRA ,and IE to be taken as test outputs. The measure of testability 6min is used to extract ...C C IN QQ2M + VB2 R5 R L V 0 LO R2 R Fig. 4 Direct-Coupled Two-Stage Amplifier The component-connection equations for Mode 2 analysis are: VR1 0 0 0 0

Innovative mid-infrared detector concepts

NASA Astrophysics Data System (ADS)

Höfling, Sven; Pfenning, Andreas; Weih, Robert; Ratajczak, Albert; Hartmann, Fabian; Knebl, Georg; Kamp, Martin; Worschech, Lukas

2016-09-01

Gas sensing is a key technology with applications in various industrial, medical and environmental areas. Optical detection mechanisms allow for a highly selective, contactless and fast detection. For this purpose, rotational-vibrational absorption bands within the mid infrared (MIR) spectral region are exploited and probed with appropriate light sources. During the past years, the development of novel laser concepts such as interband cascade lasers (ICLs) and quantum cascade lasers (QCLs) has driven a continuous optimization of MIR laser sources. On the other hand side, there has been relatively little progress on detectors in this wavelength range. Here, we study two novel and promising GaSb-based detector concepts: Interband cascade detectors (ICD) and resonant tunneling diode (RTD) photodetectors. ICDs are a promising approach towards highly sensitive room temperature detection of MIR radiation. They make use of the cascading scheme that is enabled by the broken gap alignment of the two binaries GaSb and InAs. The interband transition in GaSb/InAs-superlattices (SL) allows for normal incidence detection. The cut-off wavelength, which determines the low energy detection limit, can be engineered via the SL period. RTD photodetectors act as low noise and high speed amplifiers of small optically generated electrical signals. In contrast to avalanche photodiodes, where the gain originates from multiplication due to impact ionization, in RTD photodetectors a large tunneling current is modulated via Coulomb interaction by the presence of photogenerated minority charge carriers. For both detector concepts, first devices operational at room temperature have been realized.

Near Zero Emissions at 50 Percent Thermal Efficiency

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

None, None

2012-12-31

Detroit Diesel Corporation (DDC) has successfully completed a 10 year DOE sponsored heavy-duty truck engine program, hereafter referred to as the NZ-50 program. This program was split into two major phases. The first phase was called Near-Zero Emission at 50 Percent Thermal Efficiency, and was completed in 2007. The second phase was initiated in 2006, and this phase was named Advancements in Engine Combustion Systems to Enable High-Efficiency Clean Combustion for Heavy-Duty Engines. This phase was completed in September, 2010. The key objectives of the NZ-50 program for this first phase were to: Quantify thermal efficiency degradation associated with reductionmore » of engine-out NOx emissions to the 2007 regulated level of ~1.1 g/hp-hr. Implement an integrated analytical/experimental development plan for improving subsystem and component capabilities in support of emerging engine technologies for emissions and thermal efficiency goals of the program. Test prototype subsystem hardware featuring technology enhancements and demonstrate effective application on a multi-cylinder, production feasible heavy-duty engine test-bed. Optimize subsystem components and engine controls (calibration) to demonstrate thermal efficiency that is in compliance with the DOE 2005 Joule milestone, meaning greater than 45% thermal efficiency at 2007 emission levels. Develop technology roadmap for meeting emission regulations of 2010 and beyond while mitigating the associated degradation in engine fuel consumption. Ultimately, develop technical prime-path for meeting the overall goal of the NZ-50 program, i.e., 50% thermal efficiency at 2010 regulated emissions. These objectives were successfully met during the course of the NZ-50 program. The most noteworthy achievements in this program are summarized as follows: Demonstrated technologies through advanced integrated experiments and analysis to achieve the technical objectives of the NZ-50 program with 50.2% equivalent thermal efficiency under EPA 2010 emissions regulations. Experimentally demonstrate brake efficiency of 48.5% at EPA 2010 emission level at single steady-state point. Analytically demonstrated additional brake efficiency benefits using advanced aftertreatment configuration concept and air system enhancement including, but not limited to, turbo-compound, variable valve actuator system, and new cylinder head redesign, thus helping to achieve the final program goals. Experimentally demonstrated EPA 2010 emissions over FTP cycles using advanced integrated engine and aftertreatment system. These aggressive thermal efficiency and emissions results were achieved by applying a robust systems technology development methodology. It used integrated analytical and experimental tools for subsystem component optimization encompassing advanced fuel injection system, increased EGR cooling capacity, combustion process optimization, and advanced aftertreatment technologies. Model based controls employing multiple input and output techniques enabled efficient integration of the various subsystems and ensured optimal performance of each system within the total engine package. . The key objective of the NZ-50 program for the second phase was to explore advancements in engine combustion systems using high-efficiency clean combustion (HECC) techniques to minimize cylinder-out emissions, targeting a 10% efficiency improvement. The most noteworthy achievements in this phase of the program are summarized as follows: Experimentally and analytically evaluated numerous air system improvements related to the turbocharger and variable valve actuation. Some of the items tested proved to be very successful and modifications to the turbine discovered in this program have since been incorporated into production hardware. The combustion system development continued with evaluation of various designs of the 2-step piston bowl. Significant improvements in engine emissions have been obtained, but fuel economy improvements have been tougher to realize. Development of a neural network control system progressed to the point that the system was fully functional and showing significant fuel economy gains in transient engine testing. Development of the QuantLogic injector with the capability of both a hollow cone spray during early injection and conventional diesel injection at later injection timings was undertaken and proved to be problematic. This injector was designed to be a key component in a PCCI combustion system, but this innovative fuel injector required significantly more development effort than this programâ's resources or timing would allow.« less

Thermodynamics of a Simple Rubber-Band Heat Engine

ERIC Educational Resources Information Center

Mullen, J. G.; And Others

1975-01-01

Outlines the basic engine design and nomenclature, develops some relations between the state parameters of the rubber-band system, defines engine efficiency, and compares the Archibald engine with the Carnot engine. (GS)

The Tracer Gas Method of Determining the Charging Efficiency of Two-stroke-cycle Diesel Engines

NASA Technical Reports Server (NTRS)

Schweitzer, P H; Deluca, Frank, Jr

1942-01-01

A convenient method has been developed for determining the scavenging efficiency or the charging efficiency of two-stroke-cycle engines. The method consists of introducing a suitable tracer gas into the inlet air of the running engine and measuring chemically its concentration both in the inlet and exhaust gas. Monomethylamine CH(sub 3)NH(sub 2) was found suitable for the purpose as it burns almost completely during combustion, whereas the "short-circuited" portion does not burn at all and can be determined quantitatively in the exhaust. The method was tested both on four-stroke and on two-stroke engines and is considered accurate within 1 percent.

High-output LED-based light engine for profile lighting fixtures with high color uniformity using freeform reflectors.

PubMed

Gadegaard, Jesper; Jensen, Thøger Kari; Jørgensen, Dennis Thykjær; Kristensen, Peter Kjær; Søndergaard, Thomas; Pedersen, Thomas Garm; Pedersen, Kjeld

2016-02-20

In the stage lighting and entertainment market, light engines (LEs) for lighting fixtures are often based on high-intensity discharge (HID) bulbs. Switching to LED-based light engines gives possibilities for fast switching, additive color mixing, a longer lifetime, and potentially, more energy-efficient systems. The lumen output of a single LED is still not sufficient to replace an HID source in high-output profile fixtures, but combining multiple LEDs can create an LE with a similar output, but with added complexity. This paper presents the results of modeling and testing such a light engine. Custom ray-tracing software was used to design a high-output red, green and blue LED-based light engine with twelve CBT-90 LEDs using a dual-reflector principle. The simulated optical system efficiency was 0.626 with a perfect (R=1) reflector coating for light delivered on a target surface through the entire optical system. A profile lighting fixture prototype was created, and provided an output of 6744 lumen and an efficiency of 0.412. The lower efficiency was mainly due to a non-optimal reflector coating, and the optimized design is expected to reach a significantly higher efficiency.

Performance of a multilevel quantum heat engine of an ideal N-particle Fermi system.

PubMed

Wang, Rui; Wang, Jianhui; He, Jizhou; Ma, Yongli

2012-08-01

We generalize the quantum heat engine (QHE) model which was first proposed by Bender et al. [J. Phys. A 33, 4427 (2000)] to the case in which an ideal Fermi gas with an arbitrary number N of particles in a box trap is used as the working substance. Besides two quantum adiabatic processes, the engine model contains two isoenergetic processes, during which the particles are coupled to energy baths at a high constant energy E(h) and a low constant energy E(c), respectively. Directly employing the finite-time thermodynamics, we find that the power output is enhanced by increasing particle number N (or decreasing minimum trap size L(A)) for given L(A) (or N), without reduction in the efficiency. By use of global optimization, the efficiency at possible maximum power output (EPMP) is found to be universal and independent of any parameter contained in the engine model. For an engine model with any particle-number N, the efficiency at maximum power output (EMP) can be determined under the condition that it should be closest to the EPMP. Moreover, we extend the heat engine to a more general multilevel engine model with an arbitrary 1D power-law potential. Comparison between our engine model and the Carnot cycle shows that, under the same conditions, the efficiency η = 1 - E(c)/E(h) of the engine cycle is bounded from above the Carnot value η(c) =1 - T(c)/T(h).

Thermodynamics of the mesoscopic thermoelectric heat engine beyond the linear-response regime

NASA Astrophysics Data System (ADS)

Yamamoto, Kaoru; Hatano, Naomichi

2015-10-01

Mesoscopic thermoelectric heat engine is much anticipated as a device that allows us to utilize with high efficiency wasted heat inaccessible by conventional heat engines. However, the derivation of the heat current in this engine seems to be either not general or described too briefly, even inappropriately in some cases. In this paper, we give a clear-cut derivation of the heat current of the engine with suitable assumptions beyond the linear-response regime. It resolves the confusion in the definition of the heat current in the linear-response regime. After verifying that we can construct the same formalism as that of the cyclic engine, we find the following two interesting results within the Landauer-Büttiker formalism: the efficiency of the mesoscopic thermoelectric engine reaches the Carnot efficiency if and only if the transmission probability is finite at a specific energy and zero otherwise; the unitarity of the transmission probability guarantees the second law of thermodynamics, invalidating Benenti et al.'s argument in the linear-response regime that one could obtain a finite power with the Carnot efficiency under a broken time-reversal symmetry [Phys. Rev. Lett. 106, 230602 (2011), 10.1103/PhysRevLett.106.230602]. These results demonstrate how quantum mechanics constrains thermodynamics.

Fuzzy control based engine sizing optimization for a fuel cell/battery hybrid mini-bus

NASA Astrophysics Data System (ADS)

Kim, Minjin; Sohn, Young-Jun; Lee, Won-Yong; Kim, Chang-Soo

The fuel cell/battery hybrid vehicle has been focused for the alternative engine of the existing internal-combustion engine due to the following advantages of the fuel cell and the battery. Firstly, the fuel cell is highly efficient and eco-friendly. Secondly, the battery has the fast response for the changeable power demand. However, the competitive efficiency of the hybrid fuel cell vehicle is necessary to successfully alternate the conventional vehicles with the fuel cell hybrid vehicle. The most relevant factor which affects the overall efficiency of the hybrid fuel cell vehicle is the relative engine sizing between the fuel cell and the battery. Therefore the design method to optimize the engine sizing of the fuel cell hybrid vehicle has been proposed. The target system is the fuel cell/battery hybrid mini-bus and its power distribution is controlled based on the fuzzy logic. The optimal engine sizes are determined based on the simulator developed in this paper. The simulator includes the several models for the fuel cell, the battery, and the major balance of plants. After the engine sizing, the system efficiency and the stability of the power distribution are verified based on the well-known driving schedule. Consequently, the optimally designed mini-bus shows good performance.

Evaluation of a Stirling engine heater bypass with the NASA Lewis nodal-analysis performance code

NASA Technical Reports Server (NTRS)

Sullivan, T. J.

1986-01-01

In support of the U.S. Department of Energy's Stirling Engine Highway Vehicle Systems program, the NASA Lewis Research Center investigated whether bypassing the P-40 Stirling engine heater during regenerative cooling would improve engine performance. The Lewis nodal-analysis Stirling engine computer simulation was used for this investigation. Results for the heater-bypass concept showed no significant improvement in the indicated thermal efficiency for the P-40 Stirling engine operating at full-power and part-power conditions. Optimizing the heater tube length produced a small increase in the indicated thermal efficiency with the heater-bypass concept.

Effect of ethanol-gasoline blends on small engine generator energy efficiency and exhaust emission.

PubMed

Lin, Wen-Yinn; Chang, Yuan-Yi; Hsieh, You-Ru

2010-02-01

This study was focused on fuel energy efficiency and pollution analysis of different ratios of ethanol-gasoline blended fuels (E0, E3, E6, and E9) under different loadings. In this research, the experimental system consisted of a small engine generator, a particulate matter measurement system, and an exhaust gas analyzer system. Different fuels, unleaded gasoline, and ethanol-gasoline blends (E0, E3, E6, and E9) were used to study their effects on the exhaust gas emission and were expressed as thermal efficiency of the small engine generator energy efficiency. The results suggested that particle number concentration increased as the engine loading increased; however, it decreased as the ethanol content in the blend increased. While using E6 as fuel, the carbon monoxide (CO) concentration was less than other fuels (E0, E3, and E9) for each engine loading. The average of CO concentration reduction by using E3, E6, and E9 is 42, 86, and 83%, respectively. Using an ethanol-gasoline blend led to a significant reduction in exhaust emissions by approximately 78.7, 97.5, and 89.46% of the mean average values of hydrocarbons (HCs) with E3, E6, and E9 fuels, respectively, for all engine loadings. Using an ethanol-gasoline blend led to a significant reduction in exhaust emissions by approximately 35, 86, and 77% of the mean average values of nitrogen oxides (NOx) with E3, E6, and E9 fuels, respectively, at each engine loading. The E6 fuel gave the best results of the exhaust emissions, and the E9 fuel gave the best results of the particle emissions and engine performance. The thermal efficiency of the small engine generator increased as the ethanol content in the blend increased and as the engine loading increased.

Screw expander for light duty diesel engines

NASA Technical Reports Server (NTRS)

1983-01-01

Preliminary selection and sizing of a positive displacement screw compressor-expander subsystem for a light-duty adiabatic diesel engine; development of a mathematical model to describe overall efficiencies for the screw compressor and expander; simulation of operation to establish overall efficiency for a range of design parameters and at given engine operating points; simulation to establish potential net power output at light-duty diesel operating points; analytical determination of mass moments of inertia for the rotors and inertia of the compressor-expander subsystem; and preparation of engineering layout drawings of the compressor and expander are discussed. As a result of this work, it was concluded that the screw compressor and expander designed for light-duty diesel engine applications are viable alternatives to turbo-compound systems, with acceptable efficiencies for both units, and only a moderate effect on the transient response.

Los Alamos National Security, LLC Request for Information on how industry may partner with the Laboratory on KIVA software.

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

Mcdonald, Kathleen Herrera

2016-02-29

KIVA is a family of Fortran-based computational fluid dynamics software developed by LANL. The software predicts complex fuel and air flows as well as ignition, combustion, and pollutant-formation processes in engines. The KIVA models have been used to understand combustion chemistry processes, such as auto-ignition of fuels, and to optimize diesel engines for high efficiency and low emissions. Fuel economy is heavily dependent upon engine efficiency, which in turn depends to a large degree on how fuel is burned within the cylinders of the engine. Higher in-cylinder pressures and temperatures lead to increased fuel economy, but they also create moremore » difficulty in controlling the combustion process. Poorly controlled and incomplete combustion can cause higher levels of emissions and lower engine efficiencies.« less

Installation and testing of a cummins Qsk19 lean burn natural gas engine

NASA Astrophysics Data System (ADS)

Sutley, Franklin H.

The goal for a more efficient engine will never disappear. Over the years many different techniques have been explored within the common goal of higher efficiency. Lean combustion has proven to be effective at increasing efficiencies as well as reducing emissions. The purpose of this thesis is to install a modern Cummins QSK19G and perform certain test that will explore the lean combustion limits and other methods that could possibly increase efficiency even more. The entire installation and instrumentation process is documented within this thesis. The engine was installed in the Engines and Energy Conversion Laboratory at Colorado State University. The engine was installed with the hopes of instilling the desire for endless future tests from Cummins as well as other companies seeking this type of research engine. The lean limit was explored in the most detail. Cummins supplied a test plan that satisfied their desired stopping at a lean limit when the coefficient of variance of indicated mean effective pressure reached 5%. For the curiosity of others involved and this thesis, the lean limit was explored further until the engine could no longer ignite the ultra-lean combustion mixture. Friction accounts for a significant loss in a modern internal combustion engine. One role of the engine oil is to reduce these frictional losses as much as possible without causing increased wear. A test was conducted on the QSK19G to explore the effects of varying the engine oil viscosity. Frictional losses of two different viscosity oils were compared to the stock engine oil losses. The fact that reducing oil viscosity reduces frictional losses was proven in the test.

Selected Systems Engineering Process Deficiencies and Their Consequences

NASA Technical Reports Server (NTRS)

Thomas, Lawrence Dale

2006-01-01

The systems engineering process is well established and well understood. While this statement could be argued in the light of the many systems engineering guidelines and that have been developed, comparative review of these respective descriptions reveal that they differ primarily in the number of discrete steps or other nuances, and are at their core essentially common. Likewise, the systems engineering textbooks differ primarily in the context for application of systems engineering or in the utilization of evolved tools and techniques, not in the basic method. Thus, failures in systems engineering cannot credibly be attributed to implementation of the wrong systems engineering process among alternatives. However, numerous systems failures can be attributed to deficient implementation of the systems engineering process. What may clearly be perceived as a system engineering deficiency in retrospect can appear to be a well considered system engineering efficiency in real time - an efficiency taken to reduce cost or meet a schedule, or more often both. Typically these efficiencies are grounded on apparently solid rationale, such as reuse of heritage hardware or software. Over time, unintended consequences of a systems engineering process deficiency may begin to be realized, and unfortunately often the consequence is system failure. This paper describes several actual cases of system failures that resulted from deficiencies in their systems engineering process implementation, including the Ariane 5 and the Hubble Space Telescope.

Selected systems engineering process deficiencies and their consequences

NASA Astrophysics Data System (ADS)

Thomas, L. Dale

2007-06-01

The systems engineering process is well established and well understood. While this statement could be argued in the light of the many systems engineering guidelines and that have been developed, comparative review of these respective descriptions reveal that they differ primarily in the number of discrete steps or other nuances, and are at their core essentially common. Likewise, the systems engineering textbooks differ primarily in the context for application of systems engineering or in the utilization of evolved tools and techniques, not in the basic method. Thus, failures in systems engineering cannot credibly be attributed to implementation of the wrong systems engineering process among alternatives. However, numerous system failures can be attributed to deficient implementation of the systems engineering process. What may clearly be perceived as a systems engineering deficiency in retrospect can appear to be a well considered system engineering efficiency in real time—an efficiency taken to reduce cost or meet a schedule, or more often both. Typically these efficiencies are grounded on apparently solid rationale, such as reuse of heritage hardware or software. Over time, unintended consequences of a systems engineering process deficiency may begin to be realized, and unfortunately often the consequence is systems failure. This paper describes several actual cases of system failures that resulted from deficiencies in their systems engineering process implementation, including the Ariane 5 and the Hubble Space Telescope.

High Temperature Concentrated Solar Power Using Liquid Metal

NASA Astrophysics Data System (ADS)

Henry, Asegun

One of the most attractive ways to try and reduce the cost of concentrated solar power (CSP) is to increase the system efficiency and the biggest loss in the system occurs in the conversion of heat to electricity via heat engine. Heat engines that utilize turbomachinery currently operate near their thermodynamic limitations and thus one of the only ways to improve heat engine efficiency is to increase the turbine inlet temperature. Significant effort is being devoted to the development of supercritical CO2 heat engines, but the most efficient heat engines are combined cycles, which reach efficiencies as high as 60%. However, such heat engines require turbine inlet temperatures ~1300-1500C, which is far beyond what is currently feasible with the state of the art molten salt infrastructure. In working towards the development of a system that can operate in the 1300-1500C temperature range, the most significant challenges lie in the materials and forming functional and reliable components out of new materials. One of the most attractive options from a cost and heat transfer perspective is to use liquid metals, such as tin and aluminum-silicon alloys along with a ceramic based infrastructure. This talk will overview ongoing efforts in the Atomistic Simulation and Energy (ASE) research group at Georgia Tech to develop prototype components such as an efficient high temperature cavity receiver, pumps and valves that can make a liquid metal based CSP infrastructure realizable.

Efficient protocols for Stirling heat engines at the micro-scale

NASA Astrophysics Data System (ADS)

Muratore-Ginanneschi, Paolo; Schwieger, Kay

2015-10-01

We investigate the thermodynamic efficiency of sub-micro-scale Stirling heat engines operating under the conditions described by overdamped stochastic thermodynamics. We show how to construct optimal protocols such that at maximum power the efficiency attains for constant isotropic mobility the universal law η=2 ηC/(4-ηC) , where ηC is the efficiency of an ideal Carnot cycle. We show that these protocols are specified by the solution of an optimal mass transport problem. Such solution can be determined explicitly using well-known Monge-Ampère-Kantorovich reconstruction algorithms. Furthermore, we show that the same law describes the efficiency of heat engines operating at maximum work over short time periods. Finally, we illustrate the straightforward extension of these results to cases when the mobility is anisotropic and temperature dependent.

The relationship between the thermoelectric generator efficiency and the device engineering figure of merit Zd,eng. The maximum efficiency 𝜼max

NASA Astrophysics Data System (ADS)

Hapenciuc, C. L.; Borca-Tasciuc, T.; Mihailescu, I. N.

2017-04-01

Thermoelectric materials are used today in thermoelectric devices for heat to electricity(thermoelectric generators-TEG) or electricity to heat(heat pumps) conversion in a large range of applications. In the case of TEGs the final measure of their performance is given by a quantity named the maximum efficiency which shows how much from the heat input is converted into electrical power. Therefore it is of great interest to know correctly how much is the efficiency of a device to can make commercial assessments. The concept of engineering figure of merit, Zeng, and engineering power factor, Peng, were already introduced in the field to quantify the efficiency of a single material under temperature dependent thermoelectric properties, with the mention that the formulas derivation was limited to one leg of the thermoelectric generator. In this paper we propose to extend the concept of engineering figure of merit to a thermoelectric generator by introducing a more general concept of device engineering thermoelectric figure of merit, Zd,eng, which depends on the both TEG materials properties and which shall be the right quantity to be used when we are interested in the evaluation of the efficiency. Also, this work takes into account the electrical contact resistance between the electrodes and thermoelement legs in an attempt to quantify its influence upon the performance of a TEG. Finally, a new formula is proposed for the maximum efficiency of a TEG.

LED Provides Effective and Efficient Parking Area Lighting at the NAVFAC Engineering Service Center

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

None

2010-08-12

U.S. Department of Energy (DOE) Federal Energy Management Program (FEMP) emerging technology case study showcasing LED lighting to improve energy efficiency in parking areas at the NAVFAC Engineering Services Center.

Detailed performance analysis of the A.A.D. - concept B

NASA Technical Reports Server (NTRS)

Sekar, R.; Tozzi, L.

1983-01-01

New concepts for engine performance improvement are seen through the adoption of heat regeneration techniques; advanced methods to enhance the combustion; and higher efficiency air handling machinery, such as the positive displacement helical screw expander and compressor. Each of these concepts plays a particular role in engine performance improvement. First regeneration has a great potential for achieving higher engine thermal efficiency through the recovery of waste energy. Although the concept itself is not new (this technique is used in the gas turbine), the application to reciprocating internal combustion engines is quite unusual and presents conceptual difficulties. The second important area is better control of the combustion process in terms of heat transfer characteristics, combustion products, and heat release rate. The third area for performance improvement is in the adoption of high efficiency air handling machinery. In particular, positive displacement helical expander and compressor exhibit an extremely high efficiency over a wide range of operating conditions.

Efficiency at maximum power of low-dissipation Carnot engines.

PubMed

Esposito, Massimiliano; Kawai, Ryoichi; Lindenberg, Katja; Van den Broeck, Christian

2010-10-08

We study the efficiency at maximum power, η*, of engines performing finite-time Carnot cycles between a hot and a cold reservoir at temperatures Th and Tc, respectively. For engines reaching Carnot efficiency ηC=1-Tc/Th in the reversible limit (long cycle time, zero dissipation), we find in the limit of low dissipation that η* is bounded from above by ηC/(2-ηC) and from below by ηC/2. These bounds are reached when the ratio of the dissipation during the cold and hot isothermal phases tend, respectively, to zero or infinity. For symmetric dissipation (ratio one) the Curzon-Ahlborn efficiency ηCA=1-√Tc/Th] is recovered.

High Efficiency, Clean Combustion

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

Donald Stanton

2010-03-31

Energy use in trucks has been increasing at a faster rate than that of automobiles within the U.S. transportation sector. According to the Energy Information Administration (EIA) Annual Energy Outlook (AEO), a 23% increase in fuel consumption for the U.S. heavy duty truck segment is expected between 2009 to 2020. The heavy duty vehicle oil consumption is projected to grow between 2009 and 2050 while light duty vehicle (LDV) fuel consumption will eventually experience a decrease. By 2050, the oil consumption rate by LDVs is anticipated to decrease below 2009 levels due to CAFE standards and biofuel use. In contrast,more » the heavy duty oil consumption rate is anticipated to double. The increasing trend in oil consumption for heavy trucks is linked to the vitality, security, and growth of the U.S. economy. An essential part of a stable and vibrant U.S. economy is a productive U.S. trucking industry. Studies have shown that the U.S. gross domestic product (GDP) is strongly correlated to freight transport. Over 90% of all U.S. freight tonnage is transported by diesel power and over 75% is transported by trucks. Given the vital role that the trucking industry plays in the economy, improving the efficiency of the transportation of goods was a central focus of the Cummins High Efficient Clean Combustion (HECC) program. In a commercial vehicle, the diesel engine remains the largest source of fuel efficiency loss, but remains the greatest opportunity for fuel efficiency improvements. In addition to reducing oil consumption and the dependency on foreign oil, this project will mitigate the impact on the environment by meeting US EPA 2010 emissions regulations. Innovation is a key element in sustaining a U.S. trucking industry that is competitive in global markets. Unlike passenger vehicles, the trucking industry cannot simply downsize the vehicle and still transport the freight with improved efficiency. The truck manufacturing and supporting industries are faced with numerous challenges to reduce oil consumption and greenhouse gases, meet stringent emissions regulations, provide customer value, and improve safety. The HECC program successfully reduced engine fuel consumption and greenhouse gases while providing greater customer valve. The US EPA 2010 emissions standard poses a significant challenge for developing clean diesel powertrains that meet the DoE Vehicle Technologies Multi-Year Program Plan (MYPP) for fuel efficiency improvement while remaining affordable. Along with exhaust emissions, an emphasis on heavy duty vehicle fuel efficiency is being driven by increased energy costs as well as the potential regulation of greenhouse gases. An important element of the success of meeting emissions while significantly improving efficiency is leveraging Cummins component technologies such as fuel injection equipment, aftertreatment, turbomahcinery, electronic controls, and combustion systems. Innovation in component technology coupled with system integration is enabling Cummins to move forward with the development of high efficiency clean diesel products with a long term goal of reaching a 55% peak brake thermal efficiency for the engine plus aftertreatment system. The first step in developing high efficiency clean products has been supported by the DoE co-sponsored HECC program. The objectives of the HECC program are: (1) To design and develop advanced diesel engine architectures capable of achieving US EPA 2010 emission regulations while improving the brake thermal efficiency by 10% compared to the baseline (a state of the art 2007 production diesel engine). (2) To design and develop components and subsystems (fuel systems, air handling, controls, etc) to enable construction and development of multi-cylinder engines. (3) To perform an assessment of the commercial viability of the newly developed engine technology. (4) To specify fuel properties conducive to improvements in emissions, reliability, and fuel efficiency for engines using high-efficiency clean combustion (HECC) technologies. To demonstrate the technology is compatible with B20 (biodiesel). (5) To further improve the brake thermal efficiency of the engine as integrated into the vehicle. To demonstrate robustness and commercial viability of the HECC engine technology as integrated into the vehicles. The Cummins HECC program supported the Advanced Combustion Engine R&D and Fuels Technology initiatives of the DoE Vehicle Technologies Multi-Year Program Plan (MYPP). In particular, the HECC project goals enabled the DoE Vehicle Technologies Program (VTP) to meet energy-efficiency improvement targets for advanced combustion engines suitable for passenger and commercial vehicles, as well as addressing technology barriers and R&D needs that are common between passenger and commercial vehicle applications of advanced combustion engines.« less

The Waukesha Turbocharger Control Module: A tool for improved engine efficiency and response

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

Zurlo, J.R.; Reinbold, E.O.; Mueller, J.

1996-12-31

The Waukesha Turbocharger Control Module allows optimum control of turbochargers on lean burn gaseous fueled engines. The Turbocharger Control Module is user programmed to provide either maximum engine efficiency or best engine response to load changes. In addition, the Turbocharger Control Module prevents undesirable turbocharger surge. The Turbocharger Control Module consists of an electronic control box, engine speed, intake manifold pressure, ambient temperature sensors, and electric actuators driving compressor bypass and wastegate valves. The Turbocharger Control Module expands the steady state operational environment of the Waukesha AT27GL natural gas engine from sea level to 1,525 m altitude with one turbochargermore » match and improves the engine speed turn down by 80 RPM. Finally, the Turbocharger Control Module improves engine response to load changes.« less