Hydroacoustic Evaluation of Juvenile Salmonid Passage at The Dalles Dam Spillway, 2006

Energy Technology Data Exchange (ETDEWEB)

Johnson, Gary E.; Khan, Fenton; Skalski, John R.; Rakowski, Cynthia L.; Richmond, Marshall C.; Serkowski, John A.

2007-05-24

The objective of this study was to determine detailed vertical, horizontal, intensive, and diel distributions of juvenile salmonid passage at the spillway at The Dalles Dam from April 12 to July16, 2006. These data are being applied in the Spillway Improvements Program to position release pipes for direct injury and mortality studies and to provide baseline data for assessment of the vortex suppression devices scheduled for deployment in 2007. We estimated fish distributions from hydroacoustic data collected with split-beam transducers arrayed across Bays 1 through 9 and 14. Spill at ~20 kcfs per bay was bulked at Bays 1-6, although the other bays were opened at times during the study to maintain a 40% spill percentage out of total project discharge. The vertical distribution of fish was skewed toward the surface during spring, but during summer, passage peaked at 2-3 m above the spillway ogee. Fish passage rates (number per hour) and fish densities (number per kcfs) were highest at Bay 6, followed by passage at Bay 5. This result comports with spillway horizontal distribution data from radio telemetry and hydroacoustic studies in 2004. The vertical and horizontal distribution of fish passage at bays 5 and 6 was much more variable during spring than summer and more variable at bay 5 than bay 6. Diel distribution data revealed that fish passage was highest during 0600-0700 h in spring; otherwise passage was reasonably uniform on a diel basis. This study substantiates the purpose of the spillway vortex suppression device to re-distribute downstream migrants away from Bay 6 toward Bays 1-5.

Passage of American shad: paradigms and realities

Science.gov (United States)

Haro, Alex; Castro-Santos, Theodore

2012-01-01

Despite more than 250 years of development, the passage of American shad Alosa sapidissima at dams and other barriers frequently remains problematic. Few improvements in design based on knowledge of the swimming, schooling, and migratory behaviors of American shad have been incorporated into passage structures. Large-scale technical fishways designed for the passage of adult salmonids on the Columbia River have been presumed to have good performance for American shad but have never been rigorously evaluated for this species. Similar but smaller fishway designs on the East Coast frequently have poor performance. Provision of effective downstream passage for both juvenile and postspawning adult American shad has been given little consideration in most passage projects. Ways to attract and guide American shad to both fishway entrances and downstream bypasses remain marginally understood. The historical development of passage structures for American shad has resulted in assumptions and paradigms about American shad behavior and passage that are frequently unsubstantiated by supporting data or appropriate experimentation. We propose that many of these assumptions and paradigms are either unfounded or invalid and that significant improvements to American shad upstream and downstream passage can be made via a sequential program of behavioral experimentation, application of experimental results to the physical and hydraulic design of new structures, and controlled tests of large-scale prototype structures in the laboratory and field.

A model for the mechanism of strand passage by DNA gyrase

DEFF Research Database (Denmark)

Kampranis, S C; Bates, A D; Maxwell, A

1999-01-01

this mechanism by probing the topology of the bound DNA segment at distinct steps of the catalytic cycle. We propose a model in which gyrase captures a contiguous DNA segment with high probability, irrespective of the superhelical density of the DNA substrate, setting up an equilibrium of the transported segment......The mechanism of type II DNA topoisomerases involves the formation of an enzyme-operated gate in one double-stranded DNA segment and the passage of another segment through this gate. DNA gyrase is the only type II topoisomerase able to introduce negative supercoils into DNA, a feature that requires...... the enzyme to dictate the directionality of strand passage. Although it is known that this is a consequence of the characteristic wrapping of DNA by gyrase, the detailed mechanism by which the transported DNA segment is captured and directed through the DNA gate is largely unknown. We have addressed...

Direct and quantitative characterization of dynamic ligand exchange between coordination-driven self-assembled supramolecular polygons.

Science.gov (United States)

Zheng, Yao-Rong; Stang, Peter J

2009-03-18

The direct observation of dynamic ligand exchange between Pt-N coordination-driven self-assembled supramolecular polygons (triangles and rectangles) has been achieved using stable (1)H/(2)D isotope labeling of the pyridyl donors and electrospray ionization mass spectrometry combined with NMR spectroscopy. Both the thermodynamic and kinetic aspects of such exchange processes have been established on the basis of quantitative mass spectral results. Further investigation has shown that the exchange is highly dependent on experimental conditions such as temperature, solvent, and the counteranions.

Passage relevance models for genomics search

Directory of Open Access Journals (Sweden)

Frieder Ophir

2009-03-01

Full Text Available Abstract We present a passage relevance model for integrating syntactic and semantic evidence of biomedical concepts and topics using a probabilistic graphical model. Component models of topics, concepts, terms, and document are represented as potential functions within a Markov Random Field. The probability of a passage being relevant to a biologist's information need is represented as the joint distribution across all potential functions. Relevance model feedback of top ranked passages is used to improve distributional estimates of query concepts and topics in context, and a dimensional indexing strategy is used for efficient aggregation of concept and term statistics. By integrating multiple sources of evidence including dependencies between topics, concepts, and terms, we seek to improve genomics literature passage retrieval precision. Using this model, we are able to demonstrate statistically significant improvements in retrieval precision using a large genomics literature corpus.

Protein-scaffold Directed Nanoscale Assembly of T Cell Ligands: Artificial Antigen Presentation with Defined Valency, Density and Ratio.

Science.gov (United States)

Smith, Mason R; Tolbert, Stephanie V; Wen, Fei

2018-05-07

Tuning antigen presentation to T cells is a critical step in investigating key aspects of T cell activation. However, existing technologies have limited ability to control the spatial and stoichiometric organization of T cell ligands on 3D surfaces. Here, we developed an artificial antigen presentation platform based on protein-scaffold directed assembly that allows fine control over the spatial and stoichiometric organization of T cell ligands on a 3D yeast-cell surface. Using this system, we observed that the T cell activation threshold on a 3D surface is independent of peptide-major histocompatibility complex (pMHC) valency, but instead determined by the overall pMHC surface density. When intercellular adhesion molecule 1 (ICAM-1) was co-assembled with pMHC, it enhanced antigen recognition sensitivity by 6-fold. Further, T cells responded with different magnitudes to varying ratios of pMHC and ICAM-1 and exhibited a maximum response at a ratio of 15% pMHC and 85% ICAM-1, introducing an additional parameter for tuning T cell activation. This protein-scaffold directed assembly technology is readily transferrable to acellular surfaces for translational research as well as large-scale T-cell manufacturing.

Effect of electric barrier on passage and physical condition of juvenile and adult rainbow trout

Science.gov (United States)

Layhee, Megan J.; Sepulveda, Adam; Shaw, Amy; Smuckall, Matthew; Kapperman, Kevin; Reyes, Alejandro

2016-01-01

Electric barriers can inhibit passage and injure fish. Few data exist on electric barrier parameters that minimize these impacts and on how body size affects susceptibility, especially to nontarget fish species. The goal of this study was to determine electric barrier voltage and pulse-width settings that inhibit passage of larger bodied rainbow trout Oncorhynchus mykiss (215–410 mm fork length) while allowing passage of smaller bodied juvenile rainbow trout (52–126 mm) in a static laboratory setting. We exposed rainbow trout to 30-Hz pulsed-direct current voltage gradients (0.00–0.45 V cm−1) and pulse widths (0.0–0.7 ms) and recorded their movement, injury incidence, and mortality. No settings tested allowed all juveniles to pass while impeding all adult passage. Juvenile and adult rainbow trout avoided the barrier at higher pulse widths, and fewer rainbow trout passed the barrier at 0.7-ms pulse width compared to 0.1 ms and when the barrier was turned off. We found no effect of voltage gradient on fish passage. No mortality occurred, and we observed external bruising in 5 (7%) juvenile rainbow trout and 15 (21%) adult rainbow trout. This study may aid managers in selecting barrier settings that allow for increased juvenile passage.

Identification and characterization of PPARα ligands in the hippocampus.

Science.gov (United States)

Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Mishra, Rama K; Yung, Yeni; Luan, Chi-Hao; Gonzalez, Frank J; Pahan, Kalipada

2016-12-01

Peroxisome proliferator-activated receptor-α (PPARα) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently we found that PPARα is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here we report the discovery of three endogenous PPARα ligands-3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide-in mouse brain hippocampus. Mass spectrometric detection of these compounds in mouse hippocampal nuclear extracts, in silico interaction studies, time-resolved FRET analyses, and thermal shift assay results clearly indicated that these three compounds served as ligands of PPARα. Site-directed mutagenesis studies further revealed that PPARα Y464 and Y314 are involved in binding these hippocampal ligands. Moreover, these ligands activated PPARα and upregulated the synaptic function of hippocampal neurons. These results highlight the discovery of hippocampal ligands of PPARα capable of modulating synaptic functions.

Ligand-receptor Interactions by NMR Spectroscopy

Directory of Open Access Journals (Sweden)

Novak. P.

2008-04-01

Full Text Available Today NMR spectroscopy is a method of choice for elucidation of interactions between biomolecules and the potential ligands. Knowledge on these interactions is an essential prerequisite for the rational drug design. The most important contribution of NMR to drug design a few years ago was the 3D structure determination of proteins. Besides delivering the 3D structures of the free proteins as a raw material for the modeling studies on ligand binding, NMR can directly yield valuable experimental data on the biologically important protein-ligand complexes. In addition to X-ray diffraction, NMR spectroscopy can provide information on the internal protein dynamics ordynamics of intermolecular interactions. Changes in NMR parameters allow us to detect ("SAR by NMR" and quantitatively determine binding affinities (titration, diffusion NMR experiments, etc. of potential ligands. Also, it is possible to determine the binding site and conformations of ligands, receptors and receptor-ligand complexes with the help of NMR methods such as tr-NOESY. Epitopes or functional groups responsible for binding of ligands to the receptor can be identified by employing STD or WaterLOGSY experiments. In this review are described some of the most frequent NMR methods for the characterization of the interactions between biomolecules and ligands, together with their advantages and disadvantages.

Glucagon-like peptide-1 receptor ligand interactions: structural cross talk between ligands and the extracellular domain.

Directory of Open Access Journals (Sweden)

Graham M West

Full Text Available Activation of the glucagon-like peptide-1 receptor (GLP-1R in pancreatic β-cells potentiates insulin production and is a current therapeutic target for the treatment of type 2 diabetes mellitus (T2DM. Like other class B G protein-coupled receptors (GPCRs, the GLP-1R contains an N-terminal extracellular ligand binding domain. N-terminal truncations on the peptide agonist generate antagonists capable of binding to the extracellular domain, but not capable of activating full length receptor. The main objective of this study was to use Hydrogen/deuterium exchange (HDX to identify how the amide hydrogen bonding network of peptide ligands and the extracellular domain of GLP-1R (nGLP-1R were altered by binding interactions and to then use this platform to validate direct binding events for putative GLP-1R small molecule ligands. The HDX studies presented here for two glucagon-like peptide-1 receptor (GLP-1R peptide ligands indicates that the antagonist exendin-4[9-39] is significantly destabilized in the presence of nonionic detergents as compared to the agonist exendin-4. Furthermore, HDX can detect stabilization of exendin-4 and exendin-4[9-39] hydrogen bonding networks at the N-terminal helix [Val19 to Lys27] upon binding to the N-terminal extracellular domain of GLP-1R (nGLP-1R. In addition we show hydrogen bonding network stabilization on nGLP-1R in response to ligand binding, and validate direct binding events with the extracellular domain of the receptor for putative GLP-1R small molecule ligands.

Radial lean direct injection burner

Science.gov (United States)

Khan, Abdul Rafey; Kraemer, Gilbert Otto; Stevenson, Christian Xavier

2012-09-04

A burner for use in a gas turbine engine includes a burner tube having an inlet end and an outlet end; a plurality of air passages extending axially in the burner tube configured to convey air flows from the inlet end to the outlet end; a plurality of fuel passages extending axially along the burner tube and spaced around the plurality of air passage configured to convey fuel from the inlet end to the outlet end; and a radial air swirler provided at the outlet end configured to direct the air flows radially toward the outlet end and impart swirl to the air flows. The radial air swirler includes a plurality of vanes to direct and swirl the air flows and an end plate. The end plate includes a plurality of fuel injection holes to inject the fuel radially into the swirling air flows. A method of mixing air and fuel in a burner of a gas turbine is also provided. The burner includes a burner tube including an inlet end, an outlet end, a plurality of axial air passages, and a plurality of axial fuel passages. The method includes introducing an air flow into the air passages at the inlet end; introducing a fuel into fuel passages; swirling the air flow at the outlet end; and radially injecting the fuel into the swirling air flow.

The future of fish passage science, engineering, and practice

DEFF Research Database (Denmark)

Silva, Ana T.; Lucas, Martyn C.; Castro-Santos, Theodore

2018-01-01

science today involves a wide range of disciplines from fish behaviour to socioeconomics to complex modelling of passage prioritization options in river networks. River barrier impacts on fish migration and dispersal are currently better understood than historically, but basic ecological knowledge......Much effort has been devoted to developing, constructing and refining fish passage facilities to enable target species to pass barriers on fluvial systems, and yet, fishway science, engineering and practice remain imperfect. In this review, 17 experts from different fish passage research fields (i...... underpinning the need for effective fish passage in many regions of the world, including in biodiversity hotspots (e.g., equatorial Africa, South-East Asia), remains largely unknown. Designing efficient fishways, with minimal passage delay and post-passage impacts, requires adaptive management and continued...

Pd(II)-Catalyzed Hydroxyl-Directed C–H Olefination Enabled by Mono-Protected Amino Acid Ligands

Science.gov (United States)

Lu, Yi; Wang, Dong-Hui; Engle, Keary M.

2010-01-01

A novel Pd(II)-catalyzed ortho-C–H olefination protocol has been developed using spatially remote, unprotected tertiary, secondary, and primary alcohols as the directing groups. Mono-N-protected amino acid ligands were found to promote the reaction, and an array of olefin coupling partners could be used. When electron-deficient alkenes were used, the resulting olefinated intermediates underwent subsequent Pd(II)-catalyzed oxidative intramolecular cyclization to give the corresponding pyran products, which could be converted into ortho-alkylated alcohols under hydrogenolysis conditions. The mechanistic details of the oxidative cyclization step are discussed and situated in the context of the overall catalytic cycle. PMID:20359184

Expression of nociceptive ligands in canine osteosarcoma.

Science.gov (United States)

Shor, S; Fadl-Alla, B A; Pondenis, H C; Zhang, X; Wycislo, K L; Lezmi, S; Fan, T M

2015-01-01

Canine osteosarcoma (OS) is associated with localized pain as a result of tissue injury from tumor infiltration and peritumoral inflammation. Malignant bone pain is caused by stimulation of peripheral pain receptors, termed nociceptors, which reside in the localized tumor microenvironment, including the periosteal and intramedullary bone cavities. Several nociceptive ligands have been determined to participate directly or indirectly in generating bone pain associated with diverse skeletal abnormalities. Canine OS cells actively produce nociceptive ligands with the capacity to directly or indirectly activate peripheral pain receptors residing in the bone tumor microenvironment. Ten dogs with appendicular OS. Expression of nerve growth factor, endothelin-1, and microsomal prostaglandin E synthase-1 was characterized in OS cell lines and naturally occurring OS samples. In 10 dogs with OS, circulating concentrations of nociceptive ligands were quantified and correlated with subjective pain scores and tumor volume in patients treated with standardized palliative therapies. Canine OS cells express and secrete nerve growth factor, endothelin-1, and prostaglandin E2. Naturally occurring OS samples uniformly express nociceptive ligands. In a subset of OS-bearing dogs, circulating nociceptive ligand concentrations were detectable but failed to correlate with pain status. Localized foci of nerve terminal proliferation were identified in a minority of primary bone tumor samples. Canine OS cells express nociceptive ligands, potentially permitting active participation of OS cells in the generation of malignant bone pain. Specific inhibitors of nociceptive ligand signaling pathways might improve pain control in dogs with OS. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

Improving hydroturbine pressures to enhance salmon passage survival and recovery

Energy Technology Data Exchange (ETDEWEB)

Trumbo, Bradly A. [U.S. Army Corp. of Engineers, Walla Walla, WA (United States); Ahmann, Martin L. [U.S. Army Corp. of Engineers, Walla Walla, WA (United States); Renholods, Jon F. [U.S. Army Corp. of Engineers, Walla Walla, WA (United States); Brown, Richard S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Colotelo, Alison H. A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Deng, Zhiqun [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2013-12-12

This paper provides an overview of turbine pressure data collection and barotrauma studies relative to fish passage through large Kaplan turbines and how this information may be applied to safer fish passage through turbines. The specific objectives are to 1) discuss turbine pressures defined by Sensor Fish releases; 2) discuss what has been learned about pressure effects on fish and the factors influencing barotrauma associated with simulated turbine passage; 3) elucidate data gaps associated with fish behavior and passage that influence barotrauma during turbine passage; 4) discuss how the results of these studies have led to turbine design criteria for safer fish passage; and 5) relate this information to salmon recovery efforts and safer fish passage for Atlantic and Pacific salmonids.

Experimental study of the influence of flow passage subtle variation on mixed-flow pump performance

Science.gov (United States)

Bing, Hao; Cao, Shuliang

2014-05-01

In the mixed-flow pump design, the shape of the flow passage can directly affect the flow capacity and the internal flow, thus influencing hydraulic performance, cavitation performance and operation stability of the mixed-flow pump. However, there is currently a lack of experimental research on the influence mechanism. Therefore, in order to analyze the effects of subtle variations of the flow passage on the mixed-flow pump performance, the frustum cone surface of the end part of inlet contraction flow passage of the mixed-flow pump is processed into a cylindrical surface and a test rig is built to carry out the hydraulic performance experiment. In this experiment, parameters, such as the head, the efficiency, and the shaft power, are measured, and the pressure fluctuation and the noise signal are also collected. The research results suggest that after processing the inlet flow passage, the head of the mixed-flow pump significantly goes down; the best efficiency of the mixed-flow pump drops by approximately 1.5%, the efficiency decreases more significantly under the large flow rate; the shaft power slightly increases under the large flow rate, slightly decreases under the small flow rate. In addition, the pressure fluctuation amplitudes on both the impeller inlet and the diffuser outlet increase significantly with more drastic pressure fluctuations and significantly lower stability of the internal flow of the mixed-flow pump. At the same time, the noise dramatically increases. Overall speaking, the subtle variation of the inlet flow passage leads to a significant change of the mixed-flow pump performance, thus suggesting a special attention to the optimization of flow passage. This paper investigates the influence of the flow passage variation on the mixed-flow pump performance by experiment, which will benefit the optimal design of the flow passage of the mixed-flow pump.

Specific ability of sulfur-ligands on removal of 203Hg-labeled organomercury from hemoglobin in comparison with nitrogen-ligands

International Nuclear Information System (INIS)

Hojo, Yasuji; Sugiura, Yukio; Tanaka, Hisashi

1975-01-01

Removal of 203 Hg-labeled organomercurials, bound to sulfhydryl groups of hemoglobin, by various chelating agents was investigated by the use of equilibrium dialysis. Organomercurials employed were chlormerodrin, methylmercury, ethylmercury and phenylmercury compounds. Higher and more specific effects of the sulfur-ligands, such as penicillamine and glutathione, on removal of organomercurial were found as compared with those of the nitrogen-ligands such as EDTA, glycine and polymethylenediamines. Linear correlation was observed between the degree of organomercury elimination from hemoglobin and the stability constant (log K 1 ) of 1:1 organomercury complex in both the sulfur- and nitrogen-ligand systems and at the same value of log K 1 , the elimination-effect of sulfur-ligands was extremely greater than that of the nitrogen-ligands. The relationship between the average percentage of removal and the Taft's polar substituent constant of organic moiety of the metal was also linear among the organomercury compounds other than chlormerodrin. The average removal percentage by sulfur-ligands increased in the order, ethylmercury>methylmercury>phenylmercury, while that of the nitrogen-ligands was not different among the organomercurials investigated. In addition, direct ligand-exchange reaction between hemoglobin-SH and the ligand coordinating-atom (S or N) against organomercurials rather than Ssub(N2) reaction via the ternary complex, hemoglobin-S-RHg-ligand, is postulated. (auth.)

Skeptical notes on a physics of passage.

Science.gov (United States)

Huggett, Nick

2014-10-01

This paper investigates the mathematical representation of time in physics. In existing theories, time is represented by the real numbers, hence their formal properties represent properties of time: these are surveyed. The central question of the paper is whether the existing representation of time is adequate, or whether it can or should be supplemented: especially, do we need a physics incorporating some kind of "dynamical passage" of time? The paper argues that the existing mathematical framework is resistant to such changes, and might have to be rejected by anyone seeking a physics of passage. Then it rebuts two common arguments for incorporating passage into physics, especially the claim that it is an element of experience. Finally, the paper investigates whether, as has been claimed, causal set theory provides a physics of passage. © 2014 New York Academy of Sciences.

Flow Cytometry-Based Bead-Binding Assay for Measuring Receptor Ligand Specificity

NARCIS (Netherlands)

Sprokholt, Joris K.; Hertoghs, Nina; Geijtenbeek, Teunis B. H.

2016-01-01

In this chapter we describe a fluorescent bead-binding assay, which is an efficient and feasible method to measure interaction between ligands and receptors on cells. In principle, any ligand can be coated on fluorescent beads either directly or via antibodies. Binding between ligand-coated beads

Critical behavior of the two-dimensional first passage time

International Nuclear Information System (INIS)

Chayes, J.T.; Chayes, L.; Durrett, R.

1986-01-01

We study the two-dimensional first passage problem in which bonds have zero and unit passage times with probability p and 1-p, respectively. We provide that as the zero-time bonds approach the percolation threshold p/sub c/, the first passage time exhibits the same critical behavior as the correlation function of the underlying percolation problem. In particular, if the correlation length obeys ξ(p)--chemical bondp-p/sub c/chemical bond/sup -//sup v/, then the first passage time constant satisfies μ(p)--chemical bondp-p/sub c/chemical bond/sup v/. At p/sub c/, where it has been asserted that the first passage time from 0 to x scales as chemical bondxchemical bond to a power psi with 0< psi<1, we show that the passage times grow like log chemical bondxchemical bond, i.e., the fluid spreads exponentially rapidly

A meta-selective C-H borylation directed by a secondary interaction between ligand and substrate

Science.gov (United States)

Kuninobu, Yoichiro; Ida, Haruka; Nishi, Mitsumi; Kanai, Motomu

2015-09-01

Regioselective C-H bond transformations are potentially the most efficient method for the synthesis of organic molecules. However, the presence of many C-H bonds in organic molecules and the high activation barrier for these reactions make these transformations difficult. Directing groups in the reaction substrate are often used to control regioselectivity, which has been especially successful for the ortho-selective functionalization of aromatic substrates. Here, we describe an iridium-catalysed meta-selective C-H borylation of aromatic compounds using a newly designed catalytic system. The bipyridine-derived ligand that binds iridium contains a pendant urea moiety. A secondary interaction between this urea and a hydrogen-bond acceptor in the substrate places the iridium in close proximity to the meta-C-H bond and thus controls the regioselectivity. 1H NMR studies and control experiments support the participation of hydrogen bonds in inducing regioselectivity. Reversible direction of the catalyst through hydrogen bonds is a versatile concept for regioselective C-H transformations.

Endocytosis via galactose receptors in vivo. Ligand size directs uptake by hepatocytes and/or liver macrophages

International Nuclear Information System (INIS)

Schlepper-Schaefer, J.; Huelsmann, D.; Djovkar, A.; Meyer, H.E.; Herbertz, L.; Kolb, H.; Kolb-Bachofen, V.

1986-01-01

The intrahepatic binding and uptake of variously sized ligands with terminal galactosyl residues is rat liver was followed. The ligands were administered to prefixed livers in binding studies and in vivo and in situ (serum-free perfused livers) in uptake studies. Gold sols with different particle diameters were prepared: 5 nm (Au 5 ), 17 nm (Au 17 ), 50 nm (Au 50 ) and coated with galactose exposing glycoproteins (asialofetuin (ASF) or lactosylated BSA (LacBSA)). Electron microscopy of mildly prefixed livers perfused with LacBSA-Au 5 in serum-free medium showed ligand binding to liver macrophages, hepatocytes and endothelial cells. Ligands bound to prefixed cell surfaces reflect the initial distribution of receptor activity: pre-aggregated clusters of ligands are found on liver macrophages, single particles statistically distributed on hepatocytes and pre-aggregated clusters of particles restricted to coated pits on endothelial cells. Ligand binding is prevented in the presence of 80 mM N-acetylgalactosamine (GalNAc), while N-acetylglucosamine (GlcNAc) is without effect. Electron microscopy of livers after ligand injection into the tail vein shows that in vivo uptake of electron-dense galactose particles by liver cells is size-dependent. In vivo uptake by liver macrophages is mediated by galactose-specific recognition as shown by inhibition with GalNAc

First Passage Probability Estimation of Wind Turbines by Markov Chain Monte Carlo

DEFF Research Database (Denmark)

Sichani, Mahdi Teimouri; Nielsen, Søren R.K.

2013-01-01

Markov Chain Monte Carlo simulation has received considerable attention within the past decade as reportedly one of the most powerful techniques for the first passage probability estimation of dynamic systems. A very popular method in this direction capable of estimating probability of rare events...... of the method by modifying the conditional sampler. In this paper, applicability of the original SS is compared to the recently introduced modifications of the method on a wind turbine model. The model incorporates a PID pitch controller which aims at keeping the rotational speed of the wind turbine rotor equal...... to its nominal value. Finally Monte Carlo simulations are performed which allow assessment of the accuracy of the first passage probability estimation by the SS methods....

Navigable windows of the Northwest Passage

Science.gov (United States)

Liu, Xing-he; Ma, Long; Wang, Jia-yue; Wang, Ye; Wang, Li-na

2017-09-01

Artic sea ice loss trends support a greater potential for Arctic shipping. The information of sea ice conditions is important for utilizing Arctic passages. Based on the shipping routes given by ;Arctic Marine Shipping Assessment 2009 Report;, the navigable windows of these routes and the constituent legs were calculated by using sea ice concentration product data from 2006 to 2015, by which a comprehensive knowledge of the sea ice condition of the Northwest Passage was achieved. The results showed that Route 4 (Lancaster Sound - Barrow Strait - Prince Regent Inlet and Bellot Strait - Franklin Strait - Larsen Sound - Victoria Strait - Queen Maud Gulf - Dease Strait - Coronation Gulf - Dolphin and Union Strait - Amundsen Gulf) had the best navigable expectation, Route 2 (Parry Channel - M'Clure Strait) had the worst, and the critical legs affecting the navigation of Northwest Passage were Viscount Melville Sound, Franklin Strait, Victoria Strait, Bellot Strait, M'Clure Strait and Prince of Wales Strait. The shortest navigable period of the routes of Northwest Passage was up to 69 days. The methods used and the results of the study can help the selection and evaluation of Arctic commercial routes.

Hydroacoustic Evaluation of Juvenile Salmonid Passage and Distribution at Lookout Point Dam, 2010

Energy Technology Data Exchange (ETDEWEB)

Khan, Fenton; Johnson, Gary E.; Royer, Ida M.; Hughes, James S.; Fischer, Eric S.; Trott, Donna M.; Ploskey, Gene R.

2011-07-01

-size fish passed through turbine penstock intakes. • Diel periodicity of smolt-size fish showing crepuscular peaks was evident in fish passage into turbine penstock intakes. • Run timing for small-size fish (~65-90 mm) peaked (702 fish) on December 18. Downstream passage of small-size juvenile fish was variable, occurring on two days in the spring, eight days in the summer, and at times throughout late fall and winter. A total of 7,017 ± 690 small-size fish passed through the turbine penstock intakes during the study period. • Relatively few fish passed into the ROs when they were open in summer (2 fish/d) and winter (8 fish/d). • Fish were surface-oriented with 62-80% above 10 m deep. The highest percentage of fish (30-60%) was in the 5-10 m depth bin. We draw the following conclusions from the study. • The non-obtrusive hydroacoustic data from this study are reliable because passage estimates and patterns were similar with those observed in the direct capture data from the tailrace screw trap and were consistent with distribution patterns observed in other studies of juvenile salmonid passage at dams. • Fish passage at LOP was apparently affected but not dominated by dam operations and reservoir elevation. • The surface-oriented vertical distribution of fish we observed supports development of surface passage or collector devices. In summary, the high-resolution spatially and temporally data reported herein provide detailed estimates of vertical, horizontal, diel, daily, and seasonal passage and distributions at LOP during March 2010 through January 2011. This information is applicable to management decisions on design and development of surface passage and collections devices to help restore Chinook salmon populations in the Middle Fork Willamette River watershed above Lookout Point Dam.

Water as a complex system: its role in ligand diffusion, general anesthesia, and sleep.

Science.gov (United States)

Kier, Lemont B

2007-10-01

The work and inspiration of Robert Rosen is stated and expressed in personal tones. The concept of passages through water (H2O) near protein surfaces is reviewed in terms of its influence on ligand diffusion to an effector. This is offered as a target for interference by a non-specific general anesthetic agent. In view of the similarities between this anesthetic state and sleep, this mechanism is proposed to be operative for the sleep/wake states. Based on this mechanism and other factors, nitrogen (N2) is proposed as an exogenous sleep factor.

Interactions between alkaline earth cations and oxo ligands. DFT study of the affinity of the Mg²+ cation for phosphoryl ligands.

Science.gov (United States)

da Costa, Leonardo Moreira; de Mesquita Carneiro, José Walkimar; Paes, Lilian Weitzel Coelho

2011-08-01

DFT (B3LYP/6-31+G(d)) calculations of Mg(2+) affinities for a set of phosphoryl ligands were performed. Two types of ligands were studied: a set of trivalent [O = P(R)] and a set of pentavalent phosphoryl ligands [O = P(R)(3)] (R = H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either bound directly to the phosphorus atom or to the para position of a phenyl ring. The affinity of the Mg(2+) cation for the ligands was quantified by means of the enthalpy for the substitution of one water molecule in the [Mg(H(2)O)(6)](2+) complex for a ligand. The enthalpy of substitution was correlated with electronic and geometric parameters. Electron-donor groups increase the interaction between the cation and the ligand, while electron-acceptor groups decrease the interaction enthalpy.

Heat transfer in rotating serpentine passages with trips normal to the flow

Science.gov (United States)

Wagner, J. H.; Johnson, B. V.; Graziani, R. A.; Yeh, F. C.

1991-01-01

Experiments were conducted to determine the effects of buoyancy and Coriolis forces on heat transfer in turbine blade internal coolant passages. The experiments were conducted with a large scale, multipass, heat transfer model with both radially inward and outward flow. Trip strips on the leading and trailing surfaces of the radial coolant passages were used to produce the rough walls. An analysis of the governing flow equations showed that four parameters influence the heat transfer in rotating passages: coolant-to-wall temperature ratio, Rossby number, Reynolds number, and radius-to-passage hydraulic diameter ratio. The first three of these four parameters were varied over ranges which are typical of advanced gas turbine engine operating conditions. Results were correlated and compared to previous results from stationary and rotating similar models with trip strips. The heat transfer coefficients on surfaces, where the heat increased with rotation and buoyancy, varied by as much as a factor of four. Maximum values of the heat transfer coefficients with high rotation were only slightly above the highest levels obtained with the smooth wall model. The heat transfer coefficients on surfaces, where the heat transfer decreased with rotation, varied by as much as a factor of three due to rotation and buoyancy. It was concluded that both Coriolis and buoyancy effects must be considered in turbine blade cooling designs with trip strips and that the effects of rotation were markedly different depending upon the flow direction.

Excess bottom radon 222 distribution in deep ocean passages

International Nuclear Information System (INIS)

Sarmiento, J.L.; Broecker, W.S.; Biscaye, P.E.

1978-01-01

Radon 222 and STD profiles were obtained as part of the Geosecs program in the Vema Channel in the southwest Atlantic Ocean and in the Samoan, Clarion, and Wake Island passages in the Pacific Ocean. The standing crop of excess radon 222 is higher in the passages than at other nearby locations. The most likely explanation for this is that there is a high flux of radon 222 from the floor of the passages. Since much of the floor is covered with manganese nodules and encrustations, the high flux of radon 222 may be attributable to the high concentrations of radium 226 in the outer few millimeters of such deposits. Laboratory measurements of radon 222 emissivity from maganese encrustations obtained in Vema Channel support this hypothesis. The excess radon 222 in the Vema Channel and Wake Island Passage is found in substantial quantities at heights above bottom greatly exceeding the heights at which excess radon 222 is found in nonpassage areas. The horizontal diffusion of radon emanating from the walls of the passages is unlikely to be the cause of the observed concentrations because the ratio of wall surface area to water volume is very low. The profiles must therefore be a result of exceptionally high apparent vertical mixing in the passages. Further work is needed to determine the nature of this apparent vertical mixing. The excess radon 222 and STD data in all four passages have been fit with an empirical model in which it is assumed that the bouyancy flux is constant with distance above bottom. The fits are very good and yield apparent buoyancy fluxes that are between 1 and 3 orders of magnitude greater than those obtained at nearby stations outside the passages for three of the four passages

Magnetic ligand fishing as a targeting tool for HPLC-HRMS-SPE-NMR: α-glucosidase inhibitory ligands and alkylresorcinol glycosides from Eugenia catharinae

DEFF Research Database (Denmark)

Wubshet, Sileshi Gizachew; Brighente, Inês M. C.; Moaddel, Ruin

2015-01-01

A bioanalytical platform combining magnetic ligand fishing for α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR for structural identification of α-glucosidase inhibitory ligands, both directly from crude plant extracts, is presented. Magnetic beads with N-terminus-coupled α-glucosidase we...

Free-energy relationships in ion channels activated by voltage and ligand

Science.gov (United States)

Chowdhury, Sandipan

2013-01-01

Many ion channels are modulated by multiple stimuli, which allow them to integrate a variety of cellular signals and precisely respond to physiological needs. Understanding how these different signaling pathways interact has been a challenge in part because of the complexity of underlying models. In this study, we analyzed the energetic relationships in polymodal ion channels using linkage principles. We first show that in proteins dually modulated by voltage and ligand, the net free-energy change can be obtained by measuring the charge-voltage (Q-V) relationship in zero ligand condition and the ligand binding curve at highly depolarizing membrane voltages. Next, we show that the voltage-dependent changes in ligand occupancy of the protein can be directly obtained by measuring the Q-V curves at multiple ligand concentrations. When a single reference ligand binding curve is available, this relationship allows us to reconstruct ligand binding curves at different voltages. More significantly, we establish that the shift of the Q-V curve between zero and saturating ligand concentration is a direct estimate of the interaction energy between the ligand- and voltage-dependent pathway. These free-energy relationships were tested by numerical simulations of a detailed gating model of the BK channel. Furthermore, as a proof of principle, we estimate the interaction energy between the ligand binding and voltage-dependent pathways for HCN2 channels whose ligand binding curves at various voltages are available. These emerging principles will be useful for high-throughput mutagenesis studies aimed at identifying interaction pathways between various regulatory domains in a polymodal ion channel. PMID:23250866

Multi-target directed donepezil-like ligands for Alzheimer's disease

Directory of Open Access Journals (Sweden)

Mercedes eUnzeta

2016-05-01

Full Text Available Alzheimer's disease (AD, the most common form of adult onset dementia, is an age-related neurodegenerative disorder characterized by progressive memory loss, decline in language skills and other cognitive impairments. Although its etiology is not completely known, several factors including deficits of acetylcholine, β-amyloid deposits, τ-protein phosphorylation, oxidative stress and neuroinflammation are considered to play significant roles in the pathophysiology of this disease. For a long time, AD patients have been treated with acetylcholinesterase inhibitors such as donepezil (Aricept® but with limited therapeutic success. This might be due to the complex multifactorial nature of AD, a fact that has prompted the design of new Multi-Target-Directed Ligands (MTDL based on the one molecule, multiple targets paradigm. Thus, in this context, different series of novel multifunctional molecules with antioxidant, anti-amyloid, anti-inflammatory and metal-chelating properties able to interact with multiple enzymes of therapeutic interest in AD pathology including acetylcholinesterase, butyrylcholinesterase and monoamine oxidases A and B have been designed and assessed biologically. This review describes the multiple targets, the design rationale and an in-house MTDL library, bearing the N-benzylpiperidine motif present in donepezil, linked to different heterocyclic ring systems (indole, pyridine or 8-hydroxyquinoline with special emphasis on compound ASS234, an N-propargylindole derivative. The description of the in vitro biological properties of the compounds and discussion of the corresponding structure-activity-relationships allows us to highlight new issues for the identification of more efficient MTDL for use in AD therapy.

The future of fish passage science, engineering, and practice

Science.gov (United States)

Silva, Ana T.; Lucas, Martyn C.; Castro-Santos, Theodore R.; Katopodis, Christos; Baumgartner, Lee J.; Thiem, Jason D.; Aarestrup, Kim; Pompeu, Paulo S.; O'Brien, Gordon C.; Braun, Douglas C.; Burnett, Nicholas J.; Zhu, David Z.; Fjeldstad, Hans-Petter; Forseth, Torbjorn; Rajarathnam, Nallamuthu; Williams, John G.; Cooke, Steven J.

2018-01-01

Much effort has been devoted to developing, constructing and refining fish passage facilities to enable target species to pass barriers on fluvial systems, and yet, fishway science, engineering and practice remain imperfect. In this review, 17 experts from different fish passage research fields (i.e., biology, ecology, physiology, ecohydraulics, engineering) and from different continents (i.e., North and South America, Europe, Africa, Australia) identified knowledge gaps and provided a roadmap for research priorities and technical developments. Once dominated by an engineering‐focused approach, fishway science today involves a wide range of disciplines from fish behaviour to socioeconomics to complex modelling of passage prioritization options in river networks. River barrier impacts on fish migration and dispersal are currently better understood than historically, but basic ecological knowledge underpinning the need for effective fish passage in many regions of the world, including in biodiversity hotspots (e.g., equatorial Africa, South‐East Asia), remains largely unknown. Designing efficient fishways, with minimal passage delay and post‐passage impacts, requires adaptive management and continued innovation. While the use of fishways in river restoration demands a transition towards fish passage at the community scale, advances in selective fishways are also needed to manage invasive fish colonization. Because of the erroneous view in some literature and communities of practice that fish passage is largely a proven technology, improved international collaboration, information sharing, method standardization and multidisciplinary training are needed. Further development of regional expertise is needed in South America, Asia and Africa where hydropower dams are currently being planned and constructed.

An Improved Path-Generating Regulator for Two-Wheeled Robots to Track the Circle/Arc Passage

Directory of Open Access Journals (Sweden)

Jun Dai

2014-01-01

Full Text Available The improved path-generating regulator (PGR is proposed to path track the circle/arc passage for two-wheeled robots. The PGR, which is a control method for robots so as to orient its heading toward the tangential direction of one of the curves belonging to the family of path functions, is applied to navigation problem originally. Driving environments for robots are usually roads, streets, paths, passages, and ridges. These tracks can be seen as they consist of straight lines and arcs. In the case of small interval, arc can be regarded as straight line approximately; therefore we extended the PGR to drive the robot move along circle/arc passage based on the theory that PGR to track the straight passage. In addition, the adjustable look-ahead method is proposed to improve the robot trajectory convergence property to the target circle/arc. The effectiveness is proved through MATLAB simulations on both the comparisons with the PGR and the improved PGR with adjustable look-ahead method. The results of numerical simulations show that the adjustable look-ahead method has better convergence property and stronger capacity of resisting disturbance.

Selective high-affinity polydentate ligands and methods of making such

Energy Technology Data Exchange (ETDEWEB)

Denardo, Sally J.; Denardo, Gerald L.; Balhorn, Rodney L.

2018-02-06

This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

Behaviour and locomotor activity of a migratory catostomid during fishway passage.

Directory of Open Access Journals (Sweden)

Ana T Silva

Full Text Available Fishways have been developed to restore longitudinal connectivity in rivers. Despite their potential for aiding fish passage, fishways may represent a source of significant energetic expenditure for fish as they are highly turbulent environments. Nonetheless, our understanding of the physiological mechanisms underpinning fishway passage of fish is still limited. We examined swimming behaviour and activity of silver redhorse (Moxostoma anisurum during its upriver spawning migration in a vertical slot fishway. We used an accelerometer-derived instantaneous activity metric (overall dynamic body acceleration to estimate location-specific swimming activity. Silver redhorse demonstrated progressive increases in activity during upstream fishway passage. Moreover, location-specific passage duration decreased with an increasing number of passage attempts. Turning basins and the most upstream basin were found to delay fish passage. No relationship was found between basin-specific passage duration and activity and the respective values from previous basins. The results demonstrate that successful fishway passage requires periods of high activity. The resultant energetic expenditure may affect fitness, foraging behaviour and increase susceptibility to predation, compromising population sustainability. This study highlights the need to understand the physiological mechanisms underpinning fishway passage to improve future designs and interpretation of biological evaluations.

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

Science.gov (United States)

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

A ligand channel through the G protein coupled receptor opsin.

Directory of Open Access Journals (Sweden)

Peter W Hildebrand

Full Text Available The G protein coupled receptor rhodopsin contains a pocket within its seven-transmembrane helix (TM structure, which bears the inactivating 11-cis-retinal bound by a protonated Schiff-base to Lys296 in TM7. Light-induced 11-cis-/all-trans-isomerization leads to the Schiff-base deprotonated active Meta II intermediate. With Meta II decay, the Schiff-base bond is hydrolyzed, all-trans-retinal is released from the pocket, and the apoprotein opsin reloaded with new 11-cis-retinal. The crystal structure of opsin in its active Ops* conformation provides the basis for computational modeling of retinal release and uptake. The ligand-free 7TM bundle of opsin opens into the hydrophobic membrane layer through openings A (between TM1 and 7, and B (between TM5 and 6, respectively. Using skeleton search and molecular docking, we find a continuous channel through the protein that connects these two openings and comprises in its central part the retinal binding pocket. The channel traverses the receptor over a distance of ca. 70 A and is between 11.6 and 3.2 A wide. Both openings are lined with aromatic residues, while the central part is highly polar. Four constrictions within the channel are so narrow that they must stretch to allow passage of the retinal beta-ionone-ring. Constrictions are at openings A and B, respectively, and at Trp265 and Lys296 within the retinal pocket. The lysine enforces a 90 degrees elbow-like kink in the channel which limits retinal passage. With a favorable Lys side chain conformation, 11-cis-retinal can take the turn, whereas passage of the all-trans isomer would require more global conformational changes. We discuss possible scenarios for the uptake of 11-cis- and release of all-trans-retinal. If the uptake gate of 11-cis-retinal is assigned to opening B, all-trans is likely to leave through the same gate. The unidirectional passage proposed previously requires uptake of 11-cis-retinal through A and release of photolyzed all

Effect on the mean first passage time in symmetrical bistable systems by cross-correlation between noises

International Nuclear Information System (INIS)

Wang, J.; Cao, L.; Wu, D.J.

2003-01-01

We present an analytic investigation of the mean first passage time in two opposite directions (from the left well to the right well and from right to left) by studying symmetrical bistable systems driven by correlated Gaussian white noises, and prove that the mean first passage time in two opposite directions is not symmetrical any more when noises are correlated. As examples, the mean first passage time in the quartic bistable model and the sawtooth bistable model are calculated, respectively. From the analytic results of the mean first passage time, we testify further the relation T(from x - to x + ,λ)≠T(from x + to x - ,λ) in the same area of the parameter plan. Moreover, it is found that the dependences of T + (i.e., T(from x - to x + ,λ)) and T - (i.e., T(from x + to x - ,λ)) upon the multiplicative noise intensity Q and the additive noise intensity D exhibit entirely different properties. For same areas of the parameter plan: in the quartic bistable system, when the T + vs. Q curve exhibits a maximum, while the T - vs. Q curve is monotonous; when the T + vs. D curve is monotonous, while the T - vs. D curve experiences a phase transition from decreasing monotonously to possessing one minimum. Increasing Q, when the T + vs. D curve experiences a phase transition from decreasing monotonously to possessing one maximum, while the T - vs. D curve only increases monotonously. Similar behaviours also exist in the sawtooth bistable model

Force spectroscopy studies on protein-ligand interactions: a single protein mechanics perspective.

Science.gov (United States)

Hu, Xiaotang; Li, Hongbin

2014-10-01

Protein-ligand interactions are ubiquitous and play important roles in almost every biological process. The direct elucidation of the thermodynamic, structural and functional consequences of protein-ligand interactions is thus of critical importance to decipher the mechanism underlying these biological processes. A toolbox containing a variety of powerful techniques has been developed to quantitatively study protein-ligand interactions in vitro as well as in living systems. The development of atomic force microscopy-based single molecule force spectroscopy techniques has expanded this toolbox and made it possible to directly probe the mechanical consequence of ligand binding on proteins. Many recent experiments have revealed how ligand binding affects the mechanical stability and mechanical unfolding dynamics of proteins, and provided mechanistic understanding on these effects. The enhancement effect of mechanical stability by ligand binding has been used to help tune the mechanical stability of proteins in a rational manner and develop novel functional binding assays for protein-ligand interactions. Single molecule force spectroscopy studies have started to shed new lights on the structural and functional consequence of ligand binding on proteins that bear force under their biological settings. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Hydroacoustic Evaluation of Fish Passage through Bonneville Dam in 2004

Energy Technology Data Exchange (ETDEWEB)

Ploskey, Gene R.; Weiland, Mark A.; Schilt, Carl R.; Kim, Jina; Johnson, Peter N.; Hanks, Michael E.; Patterson, Deborah S.; Skalski, John R.; Hedgepeth, J

2005-12-22

The Portland District of the U.S. Army Corps of Engineers requested that the Pacific Northwest National Laboratory (PNNL) conduct fish-passage studies at Bonneville Dam in 2004. These studies support the Portland District's goal of maximizing fish-passage efficiency (FPE) and obtaining 95% survival for juvenile salmon passing Bonneville Dam. Major passage routes include 10 turbines and a sluiceway at Powerhouse 1 (B1), an 18-bay spillway, and eight turbines and a sluiceway at Powerhouse 2 (B2). In this report, we present results of four studies related to juvenile salmonid passage at Bonneville Dam. The studies were conducted between April 15 and July 15, 2004, encompassing most of the spring and summer migrations. Studies included evaluations of (1) Project fish passage efficiency and other major passage metrics, (2) B2 fish guidance efficiency and gap loss, (3) smolt approach and fate at the B2 Corner Collector (B2CC), and (4) B2 vertical barrier screen head differential.

Quantum first passage problem

International Nuclear Information System (INIS)

Kumar, N.

1984-07-01

Quantum first passage problem (QUIPP) is formulated and solved in terms of a constrained Feynman path integral. The related paradox of blocking of unitary evolution by continuous observation on the system implicit in QUIPP is briefly discussed. (author)

Proceedings of a workshop on American Eel passage technologies

Science.gov (United States)

Haro, Alexander J.

2013-01-01

Recent concerns regarding a decline in recruitment of American eels (Anguilla rostrata) have prompted efforts to restore this species to historic habitats by providing passage for both upstream migrant juveniles and downstream migrant adults at riverine barriers, including low-head and hydroelectric dams (Castonguay et al. 1994, Haro et al. 2000). These efforts include development of management plans and stock assessment reviews in both the US and Canada (COSEWIC 2006, Canadian Eel Working Group 2009, DFO 2010, MacGregor et al. 2010, ASMFC 2000, ASMFC 2006, ASMFC 2008, Williams and Threader 2007), which target improvement of upstream and downstream passage for eels, as well as identification and prioritization of research needs for development of new and more effective passage technologies for American eels. Traditional upstream fish passage structures, such as fishways and fish lifts, are often ineffective passing juvenile eels, and specialized passage structures for this species are needed. Although designs for such passage structures are available and diverse (Knights and White 1998, Porcher 2002, FAO/DVWK 2002, Solomon and Beach 2004a,b, Environment Agency UK 2011), many biologists, managers, and engineers are unfamiliar with eel pass design and operation, or unaware of the technical options available for upstream eel passage, Better coordination is needed to account for eel passage requirements during restoration efforts for other diadromous fish species. Also, appropriately siting eel passes at hydropower projects is critical, and siting can be difficult and complex due to physical restrictions in access to points of natural concentrations of eels, dynamic hydraulics of tailrace areas, and presence of significant competing flows from turbine outfalls or spill. As a result, some constructed eel passes are sited poorly and may pass only a fraction of the number of eels attempting to pass the barrier. When sited and constructed appropriately, however, eel passes

Ebola virus genome plasticity as a marker of its passaging history: a comparison of in vitro passaging to non-human primate infection.

Directory of Open Access Journals (Sweden)

Jeffrey R Kugelman

Full Text Available To identify polymorphic sites that could be used as biomarkers of Ebola virus passage history, we repeatedly amplified Ebola virus (Kikwit variant in vitro and in vivo and performed deep sequencing analysis of the complete genomes of the viral subpopulations. We then determined the sites undergoing selection during passage in Vero E6 cells. Four locations within the Ebola virus Kikwit genome were identified that together segregate cell culture-passaged virus and virus obtained from infected non-human primates. Three of the identified sites are located within the glycoprotein gene (GP sequence: the poly-U (RNA editing site at position 6925, as well as positions 6677, and 6179. One site was found in the VP24 gene at position 10833. In all cases, in vitro and in vivo, both populations (majority and minority variants were maintained in the viral swarm, with rapid selections occurring after a few passages or infections. This analysis approach will be useful to differentiate whether filovirus stocks with unknown history have been passaged in cell culture and may support filovirus stock standardization for medical countermeasure development.

The Zenith Passage of the Sun at the Mesoamerican Sites of Tula and Chichen Itza

OpenAIRE

Sparavigna, Amelia Carolina

2017-01-01

International audience; Using software SunCalc.org we can easily observe the alignments of buildings along the direction of the sunset on the day of the zenith passage of the sun, at two Mesoamerican sites. These sites are those of Tula and Chichen Itza.

The relativistic titls of Giza pyramids' entrance-passages

Science.gov (United States)

Aboulfotouh, H.

The tilts of Giza pyramids' entrance-passages have never been considered as if they were the result of relativistic mathematical equations, and never been thought to encode the Earth's obliquity parameters. This paper presents an attempt to retrieve the method of establishing the equations that the pyramids' designer used to quantify the entrance-passages' tilts of these architectonic masterpieces. It proves that the pyramids' designer was able to include the geographic, astronomical and time parameters in one relativistic equation, encoding the date of the design of the Giza pyramids in the tilt of the entrance passage of the great pyramid.

Novel multi-target-directed ligands for Alzheimer's disease: Combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation.

Science.gov (United States)

Więckowska, Anna; Kołaczkowski, Marcin; Bucki, Adam; Godyń, Justyna; Marcinkowska, Monika; Więckowski, Krzysztof; Zaręba, Paula; Siwek, Agata; Kazek, Grzegorz; Głuch-Lutwin, Monika; Mierzejewski, Paweł; Bienkowski, Przemysław; Sienkiewicz-Jarosz, Halina; Knez, Damijan; Wichur, Tomasz; Gobec, Stanislav; Malawska, Barbara

2016-11-29

As currently postulated, a complex treatment may be key to an effective therapy for Alzheimer's disease (AD). Recent clinical trials in patients with moderate AD have shown a superior effect of the combination therapy of donepezil (a selective acetylcholinesterase inhibitor) with idalopirdine (a 5-HT 6 receptor antagonist) over monotherapy with donepezil. Here, we present the first report on the design, synthesis and biological evaluation of a novel class of multifunctional ligands that combines a 5-HT 6 receptor antagonist with a cholinesterase inhibitor. Novel multi-target-directed ligands (MTDLs) were designed by combining pharmacophores directed against the 5-HT 6 receptor (1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole) and cholinesterases (tacrine or N-benzylpiperidine analogues). In vitro evaluation led to the identification of tacrine derivative 12 with well-balanced potencies against the 5-HT 6 receptor (K b  = 27 nM), acetylcholinesterase and butyrylcholinesterase (IC 50 hAChE  = 12 nM, IC 50 hBuChE  = 29 nM). The compound also showed good in vitro blood-brain-barrier permeability (PAMPA-BBB assay), which was confirmed in vivo (open field study). Central cholinomimetic activity was confirmed in vivo in rats using a scopolamine-induced hyperlocomotion model. A novel class of multifunctional ligands with compound 12 as the best derivative in a series represents an excellent starting point for the further development of an effective treatment for AD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Interaction between alkaline earth cations and oxo-ligands. DFT study of the affinity of the Ca2+ cation for carbonyl ligands.

Science.gov (United States)

da Costa, Leonardo Moreira; Carneiro, José Walkimar de Mesquita; Romeiro, Gilberto Alves; Paes, Lilian Weitzel Coelho

2011-02-01

The affinity of the Ca(2+) ion for a set of substituted carbonyl ligands was analyzed with both the DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6) methods. Two types of ligands were studied: a set of monosubstituted [O=CH(R)] and a set of disubstituted ligands [O=C(R)(2)] (R=H, F, Cl, Br, OH, OCH(3), CH(3), CN, NH(2) and NO(2)), with R either directly bound to the carbonyl carbon atom or to the para position of a phenyl ring. The interaction energy was calculated to quantify the affinity of the Ca(2+) cation for the ligands. Geometric and electronic parameters were correlated with the intensity of the metal-ligand interaction. The electronic nature of the substituent is the main parameter that determines the interaction energy. Donor groups make the interaction energy more negative (stabilizing the complex formed), while acceptor groups make the interaction energy less negative (destabilizing the complex formed).

Insertable fluid flow passage bridgepiece and method

Science.gov (United States)

Jones, Daniel O.

2000-01-01

A fluid flow passage bridgepiece for insertion into an open-face fluid flow channel of a fluid flow plate is provided. The bridgepiece provides a sealed passage from a columnar fluid flow manifold to the flow channel, thereby preventing undesirable leakage into and out of the columnar fluid flow manifold. When deployed in the various fluid flow plates that are used in a Proton Exchange Membrane (PEM) fuel cell, bridgepieces of this invention prevent mixing of reactant gases, leakage of coolant or humidification water, and occlusion of the fluid flow channel by gasket material. The invention also provides a fluid flow plate assembly including an insertable bridgepiece, a fluid flow plate adapted for use with an insertable bridgepiece, and a method of manufacturing a fluid flow plate with an insertable fluid flow passage bridgepiece.

Behavior and dam passage of juvenile Chinook salmon at Cougar Reservoir and Dam, Oregon, March 2011 - February 2012

Science.gov (United States)

Beeman, John W.; Hansel, Hal C.; Hansen, Amy C.; Haner, Philip V.; Sprando, Jamie M.; Smith, Collin D.; Evans, Scott D.; Hatton, Tyson W.

2013-01-01

The movements and dam passage of juvenile Chinook salmon implanted with acoustic transmitters and passive integrated transponder tags were studied at Cougar Reservoir and Dam, near Springfield, Oregon. The purpose of the study was to provide information to aid with decisions about potential alternatives for improving downstream passage conditions for juvenile salmonids in this flood-control reservoir. In 2011, a total of 411 hatchery fish and 26 wild fish were tagged and released during a 3-month period in the spring, and another 356 hatchery fish and 117 wild fish were released during a 3-month period in the fall. A series of 16 autonomous hydrophones throughout the reservoir and 12 hydrophones in a collective system near the dam outlet were used to determine general movements and dam passage of the fish over the life of the acoustic transmitter, which was expected to be about 3 months. Movements within the reservoir were directional, and it was common for fish to migrate repeatedly from the head of the reservoir downstream to the dam outlet and back to the head of the reservoir. Most fish were detected near the temperature control tower at least once. The median time from release near the head of the reservoir to detection within about 100 meters of the dam outlet at the temperature control tower was between 5.7 and 10.8 days, depending on season and fish origin. Dam passage events occurred over a wider range of dates in the spring and summer than in the fall and winter, but dam passage numbers were greatest during the fall and winter. A total of 10.5 percent (43 of 411) of the hatchery fish and 15.4 percent (4 of 26) of the wild fish released in the spring are assumed to have passed the dam, whereas a total of 25.3 percent (90 of 356) of the hatchery fish and 16.9 percent (30 of 117) of the wild fish released in the fall are assumed to have passed the dam. A small number of fish passed the dam after their transmitters had stopped working and were detected at

Boundaries, transitions and passages

NARCIS (Netherlands)

Koenderink, Jan; van Doorn, Andrea J.; Pinna, Baingio; Wagemans, Johan

2016-01-01

Many pictures are approximately piecewise uniform quilts. The patches meet in transitional areas that have a vague, ribbon-like geometry. These borders may occasionally get lost and sometimes pick up again, creating a 'passage' that partly blends adjacent patches. This type of structure is widely

First passage Brownian functional properties of snowmelt dynamics

Science.gov (United States)

Dubey, Ashutosh; Bandyopadhyay, Malay

2018-04-01

In this paper, we model snow-melt dynamics in terms of a Brownian motion (BM) with purely time dependent drift and difusion and examine its first passage properties by suggesting and examining several Brownian functionals which characterize the lifetime and reactivity of such stochastic processes. We introduce several probability distribution functions (PDFs) associated with such time dependent BMs. For instance, for a BM with initial starting point x0, we derive analytical expressions for : (i) the PDF P(tf|x0) of the first passage time tf which specify the lifetime of such stochastic process, (ii) the PDF P(A|x0) of the area A till the first passage time and it provides us numerous valuable information about the total fresh water availability during melting, (iii) the PDF P(M) associated with the maximum size M of the BM process before the first passage time, and (iv) the joint PDF P(M; tm) of the maximum size M and its occurrence time tm before the first passage time. These P(M) and P(M; tm) are useful in determining the time of maximum fresh water availability and in calculating the total maximum amount of available fresh water. These PDFs are examined for the power law time dependent drift and diffusion which matches quite well with the available data of snowmelt dynamics.

Yakima Basin Fish Passage Project, Phase 2

International Nuclear Information System (INIS)

1991-08-01

Implementation of the Yakima Basin Fish Passage Project -- Phase 2 would significantly improve the production of anadromous fish in the Yakima River system. The project would provide offsite mitigation and help to compensate for lower Columbia River hydroelectric fishery losses. The Phase 2 screens would allow greater numbers of juvenile anadromous fish to survive. As a consequence, there would be higher returns of adult salmon and steelhead to the Yakima River. The proposed action would play an integral part in the overall Yakima River anadromous fish enhancement program (fish passage improvement, habitat enhancement, hatchery production increases, and harvest management). These would be environmental benefits associated with implementation of the Fish Passage and Protective Facilities Phase 2 Project. Based on the evaluation presented in this assessment, there would be no significant adverse environmental impacts if the proposed action was carried forward. No significant adverse environmental effects have been identified from construction and operation of the Yakima Phase 2 fish passage project. Proper design and implementation of the project will ensure no adverse effects will occur. Based on the information in this environmental analysis, BPA's and Reclamation's proposal to construct these facilities does not constitute a major Federal action that could significantly affect the quality of the human environment. 8 refs., 4 figs., 6 tabs

Determining the magnitude and direction of photoinduced ligand field switching in photochromic metal-organic complexes: molybdenum-tetracarbonyl spirooxazine complexes.

Science.gov (United States)

Paquette, Michelle M; Patrick, Brian O; Frank, Natia L

2011-07-06

The ability to optically switch or tune the intrinsic properties of transition metals (e.g., redox potentials, emission/absorption energies, and spin states) with photochromic metal-ligand complexes is an important strategy for developing "smart" materials. We have described a methodology for using metal-carbonyl complexes as spectroscopic probes of ligand field changes associated with light-induced isomerization of photochromic ligands. Changes in ligand field between the ring-closed spirooxazine (SO) and ring-opened photomerocyanine (PMC) forms of photochromic azahomoadamantyl and indolyl phenanthroline-spirooxazine ligands are demonstrated through FT-IR, (13)C NMR, and computational studies of their molybdenum-tetracarbonyl complexes. The frontier molecular orbitals (MOs) of the SO and PMC forms differ considerably in both electron density distributions and energies. Of the multiple π* MOs in the SO and PMC forms of the ligands, the LUMO+1, a pseudo-b(1)-symmetry phenanthroline-based MO, mixes primarily with the Mo(CO)(4) fragment and provides the major pathway for Mo(d)→phen(π*) backbonding. The LUMO+1 is found to be 0.2-0.3 eV lower in energy in the SO form relative to the PMC form, suggesting that the SO form is a better π-acceptor. Light-induced isomerization of the photochromic ligands was therefore found to lead to changes in the energies of their frontier MOs, which in turn leads to changes in π-acceptor ability and ligand field strength. Ligand field changes associated with photoisomerizable ligands allow tuning of excited-state and ground-state energies that dictate energy/electron transfer, optical/electrical properties, and spin states of a metal center upon photoisomerization, positioning photochromic ligand-metal complexes as promising targets for smart materials.

Algorithms for Brownian first-passage-time estimation

Science.gov (United States)

Adib, Artur B.

2009-09-01

A class of algorithms in discrete space and continuous time for Brownian first-passage-time estimation is considered. A simple algorithm is derived that yields exact mean first-passage times (MFPTs) for linear potentials in one dimension, regardless of the lattice spacing. When applied to nonlinear potentials and/or higher spatial dimensions, numerical evidence suggests that this algorithm yields MFPT estimates that either outperform or rival Langevin-based (discrete time and continuous space) estimates.

Flow in Rotating Serpentine Coolant Passages With Skewed Trip Strips

Science.gov (United States)

Tse, David G.N.; Steuber, Gary

1996-01-01

Laser velocimetry was utilized to map the velocity field in serpentine turbine blade cooling passages with skewed trip strips. The measurements were obtained at Reynolds and Rotation numbers of 25,000 and 0.24 to assess the influence of trips, passage curvature and Coriolis force on the flow field. The interaction of the secondary flows induced by skewed trips with the passage rotation produces a swirling vortex and a corner recirculation zone. With trips skewed at +45 deg, the secondary flows remain unaltered as the cross-flow proceeds from the passage to the turn. However, the flow characteristics at these locations differ when trips are skewed at -45 deg. Changes in the flow structure are expected to augment heat transfer, in agreement with the heat transfer measurements of Johnson, et al. The present results show that trips are skewed at -45 deg in the outward flow passage and trips are skewed at +45 deg in the inward flow passage maximize heat transfer. Details of the present measurements were related to the heat transfer measurements of Johnson, et al. to relate fluid flow and heat transfer measurements.

Direct synthesis of aqueous quantum dots through 4,4'-bipyridine-based twin ligand strategy.

Science.gov (United States)

Kalita, Mausam; Cingarapu, Sreeram; Roy, Santanu; Park, Seok Chan; Higgins, Daniel; Jankowiak, Ryszard; Chikan, Viktor; Klabunde, Kenneth J; Bossmann, Stefan H

2012-04-16

We report a new class of derivatized 4,4'-bipyridinium ligands for use in synthesizing highly fluorescent, extremely stable, water-soluble CdSe and CdTe quantum dots (QDs) for bioconjugation. We employed an evaporation-condensation technique, also known as solvated metal atom dispersion (SMAD), followed by a digestive ripening procedure. This method has been used to synthesize both metal nanoparticles and semiconductors in the gram scale with several stabilizing ligands in various solvents. The SMAD technique comprised evaporation condensation and stabilization of CdSe or CdTe in tetrahydrofuran. The as-prepared product was then digestively ripened in both water and dimethyl formamide, leading to narrowing of the particle size distributions. The ligands were synthesized by nucleophilic substitution (S(N)2) reactions using 4,4'-bipyridine as a nucleophile. Confocal microscopy images revealed the orange color of the nanocrystalline QDs with diameters of ~5 nm. The size has been confirmed by using transmission electron microscopy. As a part of our strategy, 85% of the 4,4'-bipyridinium salt was synthesized as propionic acid derivative and used to both stabilize the QDs in water and label basic amino acids and different biomarkers utilizing the carboxylic acid functional group. Fifteen percent of the 4,4'-bipyridinium salt was synthesized as N-propyl maleimide and used as a second ligand to label any protein containing the amino acid cysteine by means of a 1,4-Michael addition. © 2012 American Chemical Society

First-Passage-Time Distribution for Variable-Diffusion Processes

Science.gov (United States)

Barney, Liberty; Gunaratne, Gemunu H.

2017-05-01

First-passage-time distribution, which presents the likelihood of a stock reaching a pre-specified price at a given time, is useful in establishing the value of financial instruments and in designing trading strategies. First-passage-time distribution for Wiener processes has a single peak, while that for stocks exhibits a notable second peak within a trading day. This feature has only been discussed sporadically—often dismissed as due to insufficient/incorrect data or circumvented by conversion to tick time—and to the best of our knowledge has not been explained in terms of the underlying stochastic process. It was shown previously that intra-day variations in the market can be modeled by a stochastic process containing two variable-diffusion processes (Hua et al. in, Physica A 419:221-233, 2015). We show here that the first-passage-time distribution of this two-stage variable-diffusion model does exhibit a behavior similar to the empirical observation. In addition, we find that an extended model incorporating overnight price fluctuations exhibits intra- and inter-day behavior similar to those of empirical first-passage-time distributions.

Multitarget-directed tricyclic pyridazinones as G protein-coupled receptor ligands and cholinesterase inhibitors.

Science.gov (United States)

Pau, Amedeo; Catto, Marco; Pinna, Giovanni; Frau, Simona; Murineddu, Gabriele; Asproni, Battistina; Curzu, Maria M; Pisani, Leonardo; Leonetti, Francesco; Loza, Maria Isabel; Brea, José; Pinna, Gérard A; Carotti, Angelo

2015-06-01

By following a multitarget ligand design approach, a library of 47 compounds was prepared, and they were tested as binders of selected G protein-coupled receptors (GPCRs) and inhibitors of acetyl and/or butyryl cholinesterase. The newly designed ligands feature pyridazinone-based tricyclic scaffolds connected through alkyl chains of variable length to proper amine moieties (e.g., substituted piperazines or piperidines) for GPCR and cholinesterase (ChE) molecular recognition. The compounds were tested at three different GPCRs, namely serotoninergic 5-HT1A, adrenergic α1A, and dopaminergic D2 receptors. Our main goal was the discovery of compounds that exhibit, in addition to ChE inhibition, antagonist activity at 5-HT1A because of its involvement in neuronal deficits typical of Alzheimer's and other neurodegenerative diseases. Ligands with nanomolar affinity for the tested GPCRs were discovered, but most of them behaved as dual antagonists of α1A and 5-HT1A receptors. Nevertheless, several compounds displaying this GPCR affinity profile also showed moderate to good inhibition of AChE and BChE, thus deserving further investigations to exploit the therapeutic potential of such unusual biological profiles. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Force loading explains spatial sensing of ligands by cells

Science.gov (United States)

Oria, Roger; Wiegand, Tina; Escribano, Jorge; Elosegui-Artola, Alberto; Uriarte, Juan Jose; Moreno-Pulido, Cristian; Platzman, Ilia; Delcanale, Pietro; Albertazzi, Lorenzo; Navajas, Daniel; Trepat, Xavier; García-Aznar, José Manuel; Cavalcanti-Adam, Elisabetta Ada; Roca-Cusachs, Pere

2017-12-01

Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin-ligand bonds are separated by more than a few tens of nanometres. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model, in which individual integrin-ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds

Scaling of the first-passage time of biased diffusion on hierarchical comb structures

International Nuclear Information System (INIS)

Lin Zhifang; Tao Ruibao.

1989-12-01

Biased diffusion on hierarchical comb structures is studied within an exact renormalization group scheme. The scaling exponents of the moments of the first-passage time for random walks are obtained. It is found that the scaling properties of the diffusion depend only on the direction of bias. In this particular case, the presence of bias may give rise to a new multifractality. (author). 7 refs, 2 figs

Iron and Zinc Complexes of Bulky Bis-Imidazole Ligands : Enzyme Mimicry and Ligand-Centered Redox Activity

NARCIS (Netherlands)

Folkertsma, E.

2016-01-01

The research described in this thesis is directed to the development of cheap and non-toxic iron-based homogeneous catalysts, using enzyme models and redox non-innocent ligands. Inspired by nature, the first approach focuses on the synthesis of structural models of the active site of non-heme iron

A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor.

Science.gov (United States)

Poznański, Jarosław; Poznańska, Anna; Shugar, David

2014-01-01

Halogen bonding in ligand-protein complexes is currently widely exploited, e.g. in drug design or supramolecular chemistry. But little attention has been directed to other effects that may result from replacement of a hydrogen by a strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between protein and ligand demonstrates that the length of a hydrogen bond depends on the type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a protein and a halogenated ligand are visibly shorter than those estimated for the same family of proteins in complexes with non-halogenated ligands. Taking into account the effect of halogenation on hydrogen bonding is thus important when evaluating structural and/or energetic parameters of ligand-protein complexes. All these observations are consistent with the concept that halogenation increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes them better, i.e. stronger, H-bond donors.

Providing Aquatic Organism Passage in Vertically Unstable Streams

Directory of Open Access Journals (Sweden)

JanineM Castro

2016-04-01

Full Text Available Aquatic organism passage barriers have been identified as one of the key impediments to recovery of salmonids and other migratory aquatic organisms in the Pacific Northwest of the United States. As such, state and federal agencies invest millions of dollars annually to address passage barriers. Because many barriers function as ad hoc grade control structures, their removal and/or replacement can unwittingly set off a cascade of effects that can negatively impact the very habitat and passage that project proponents seek to improve. The resultant vertical instability can result in a suite of effects that range from floodplain disconnection and loss of backwater and side channel habitat, to increased levels of turbidity. Risk assessment, including an evaluation of both the stage of stream evolution and a longitudinal profile analysis, provides a framework for determining if grade control is warranted, and if so, what type of structure is most geomorphically appropriate. Potential structures include placement of large wood and roughness elements, and constructed riffles, step-pools, and cascades. The use of structure types that mimic natural reach scale geomorphic analogues should result in improved aquatic organism passage, increased structural resilience, and reduced maintenance.

Australian experience of fish passage past instream structures

International Nuclear Information System (INIS)

Lewis, B.

2008-01-01

The growth in hydropower has resulted in the construction of various structures across rivers and streams, such as dams and weirs, which may impede essential fish movements and result in local extinctions of some fish species. When it is not practical to build instream structures that provide for fish passage, it may be appropriate to install some type of fishway. Site specific factors such as the fish species present, topography, flow characteristics and cost effectiveness will determine how best to provide for fish passage. The types of fishways suitable at small dams and weirs up to five metres high were described in this paper along with their benefits and effectiveness. The purpose was to provide simple and appropriate solutions that can improve the health of rivers considerably by managing the native aquatic habitat. The upstream passage past obstacles can be provided for through several types of fishways such as pool-type fishways, Denil fish passes, rock ramps, nature-like bypass channels, fish lifts or locks, collection and transportation facilities. In addition to environmental benefits, providing for fish passage can have long term social and economic benefits as well. 17 refs., 3 figs

An extraction machine for the passage of a chamber

Energy Technology Data Exchange (ETDEWEB)

Ponomarev, B Ia; Krupnik, V S; Krut, V S; Nenakhov, D F; Niugai, M V; Sagatov, B S

1980-05-18

The subject of the invention is the extraction machine for the passage of a chamber with a direct path of a narrow face and the reverse path of a wide face, comprising an actuation unit, a drive reducer, a shield and hydraulic jack for the control brush, is characterized in that for the purpose of insuring the effectiveness of the overlapping, the zones for the loading of the brushes are equipped with chains, whose one end is reinforced on it in a hinge-like fashion, and the other, on the reducer, with which one of the chains is connected to the hydraulic jack by the control brush.

Teleportation of an Unknown Atomic State via Adiabatic Passage

Institute of Scientific and Technical Information of China (English)

无

2007-01-01

We propose a scheme for teleporting an unknown atomic state via adiabatic passage. Taking advantage of adiabatic passage, the atom has no probability of being excited and thus the atomic spontaneous emission is suppressed.We also show that the fidelity can reach 1 under certain condition.

First passage time probability in risk analysis

International Nuclear Information System (INIS)

Karmeshu; Ariaratnam, S.T.

1982-01-01

Many natural phenomena are subject to uncertain fluctuations due to a variety of internal or external factors. These phenomena can be described using stochastic models. An important quantity of interest involves the time lapse before some variables reach unacceptable values: the first passage time. A related question pertains to the statistical distributions of the extreme values of these variables in a given period of time. The authors discuss some problems drawn from population ecology and environmental engineering to illustrate the usefulness of the first passage time concept

Physical passaging of embryoid bodies generated from human pluripotent stem cells.

Directory of Open Access Journals (Sweden)

Mi-Young Son

Full Text Available Spherical three-dimensional cell aggregates called embryoid bodies (EBs, have been widely used in in vitro differentiation protocols for human pluripotent stem cells including human embryonic stem cells (hESCs and human induced pluripotent stem cells (hiPSCs. Recent studies highlight the new devices and techniques for hEB formation and expansion, but are not involved in the passaging or subculture process. Here, we provide evidence that a simple periodic passaging markedly improved hEB culture condition and thus allowed the size-controlled, mass production of human embryoid bodies (hEBs derived from both hESCs and hiPSCs. hEBs maintained in prolonged suspension culture without passaging (>2 weeks showed a progressive decrease in the cell growth and proliferation and increase in the apoptosis compared to 7-day-old hEBs. However, when serially passaged in suspension, hEB cell populations were significantly increased in number while maintaining the normal rates of cell proliferation and apoptosis and the differentiation potential. Uniform-sized hEBs produced by manual passaging using a 1∶4 split ratio have been successfully maintained for over 20 continuous passages. The passaging culture method of hEBs, which is simple, readily expandable, and reproducible, could be a powerful tool for improving a robust and scalable in vitro differentiation system of human pluripotent stem cells.

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

Directory of Open Access Journals (Sweden)

Koehler Karl R

2011-08-01

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

A Protein Data Bank survey reveals shortening of intermolecular hydrogen bonds in ligand-protein complexes when a halogenated ligand is an H-bond donor.

Directory of Open Access Journals (Sweden)

Jarosław Poznański

Full Text Available Halogen bonding in ligand-protein complexes is currently widely exploited, e.g. in drug design or supramolecular chemistry. But little attention has been directed to other effects that may result from replacement of a hydrogen by a strongly electronegative halogen. Analysis of almost 30000 hydrogen bonds between protein and ligand demonstrates that the length of a hydrogen bond depends on the type of donor-acceptor pair. Interestingly, lengths of hydrogen bonds between a protein and a halogenated ligand are visibly shorter than those estimated for the same family of proteins in complexes with non-halogenated ligands. Taking into account the effect of halogenation on hydrogen bonding is thus important when evaluating structural and/or energetic parameters of ligand-protein complexes. All these observations are consistent with the concept that halogenation increases the acidity of the proximal amino/imino/hydroxyl groups and thus makes them better, i.e. stronger, H-bond donors.

Molecular investigations of protriptyline as a multi-target directed ligand in Alzheimer's disease.

Directory of Open Access Journals (Sweden)

Sneha B Bansode

Full Text Available Alzheimer's disease (AD is a complex neurodegenerative disorder involving multiple cellular and molecular processes. The discovery of drug molecules capable of targeting multiple factors involved in AD pathogenesis would greatly facilitate in improving therapeutic strategies. The repositioning of existing non-toxic drugs could dramatically reduce the time and costs involved in developmental and clinical trial stages. In this study, preliminary screening of 140 FDA approved nervous system drugs by docking suggested the viability of the tricyclic group of antidepressants against three major AD targets, viz. Acetylcholinesterase (AChE, β-secretase (BACE-1, and amyloid β (Aβ aggregation, with one member, protriptyline, showing highest inhibitory activity. Detailed biophysical assays, together with isothermal calorimetry, fluorescence quenching experiments, kinetic studies and atomic force microscopy established the strong inhibitory activity of protriptyline against all three major targets. The molecular basis of inhibition was supported with comprehensive molecular dynamics simulations. Further, the drug inhibited glycation induced amyloid aggregation, another important causal factor in AD progression. This study has led to the discovery of protriptyline as a potent multi target directed ligand and established its viability as a promising candidate for AD treatment.

Substituent-directed structural and physicochemical controls of diruthenium catecholate complexes with ligand-unsupported Ru-Ru bonds.

Science.gov (United States)

Chang, Ho-Chol; Mochizuki, Katsunori; Kitagawa, Susumu

2005-05-30

A family of diruthenium complexes with ligand-unsupported Ru-Ru bonds has been systematically synthesized, and their crystal structures and physical properties have been examined. A simple, useful reaction between Ru2(OAc)4Cl (OAc- = acetate) and catechol derivatives in the presence of bases afforded a variety of diruthenium complexes, generally formulated as [Na(n){Ru2(R4Cat)4}] (n = 2 or 3; R4 = -F4, -Cl4, -Br4, -H4, -3,5-di-t-Bu, and -3,6-di-t-Bu; Cat(2-) = catecholate). The most characteristic feature of the complexes is the formation of short ligand-unsupported Ru-Ru bonds (2.140-2.273 A). These comprehensive studies were carried out to evaluate the effects of the oxidation states and the substituents governing the molecular structures and physicochemical properties. The Ru-Ru bond distances, rotational conformations, and bending structures of the complexes were successfully varied. The results presented in this manuscript clearly demonstrate that the complexes with ligand-unsupported Ru-Ru bonds can sensitively respond to redox reactions and ligand substituents on the basis of the greater degree of freedom in their molecular structures.

Towards a Novel Class of Multitarget-Directed Ligands: Dual P2X7–NMDA Receptor Antagonists

Directory of Open Access Journals (Sweden)

Olga Karoutzou

2018-01-01

Full Text Available Multi-target-directed ligands (MTDLs offer new hope for the treatment of multifactorial complex diseases such as Alzheimer’s Disease (AD. Herein, we present compounds aimed at targeting the NMDA and the P2X7 receptors, which embody a different approach to AD therapy. On one hand, we are seeking to delay neurodegeneration targeting the glutamatergic NMDA receptors; on the other hand, we also aim to reduce neuroinflammation, targeting P2X7 receptors. Although the NMDA receptor is a widely recognized therapeutic target in treating AD, the P2X7 receptor remains largely unexplored for this purpose; therefore, the dual inhibitor presented herein—which is open to further optimization—represents the first member of a new class of MTDLs.

First Passage Time Intervals of Gaussian Processes

Science.gov (United States)

Perez, Hector; Kawabata, Tsutomu; Mimaki, Tadashi

1987-08-01

The first passage time problem of a stationary Guassian process is theretically and experimentally studied. Renewal functions are derived for a time-dependent boundary and numerically calculated for a Gaussian process having a seventh-order Butterworth spectrum. The results show a multipeak property not only for the constant boundary but also for a linearly increasing boundary. The first passage time distribution densities were experimentally determined for a constant boundary. The renewal functions were shown to be a fairly good approximation to the distribution density over a limited range.

50 years of first-passage percolation

CERN Document Server

Auffinger, Antonio; Hanson, Jack

2017-01-01

First-passage percolation (FPP) is a fundamental model in probability theory that has a wide range of applications to other scientific areas (growth and infection in biology, optimization in computer science, disordered media in physics), as well as other areas of mathematics, including analysis and geometry. FPP was introduced in the 1960s as a random metric space. Although it is simple to define, and despite years of work by leading researchers, many of its central problems remain unsolved. In this book, the authors describe the main results of FPP, with two purposes in mind. First, they give self-contained proofs of seminal results obtained until the 1990s on limit shapes and geodesics. Second, they discuss recent perspectives and directions including (1) tools from metric geometry, (2) applications of concentration of measure, and (3) related growth and competition models. The authors also provide a collection of old and new open questions. This book is intended as a textbook for a graduate course or as a...

AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

Science.gov (United States)

Ravindranath, Pradeep Anand; Sanner, Michel F.

2016-01-01

Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

Marine litter on the seafloor of the Faial-Pico Passage, Azores Archipelago.

Science.gov (United States)

Rodríguez, Yasmina; Pham, Christopher K

2017-03-15

Plastic pollution in the marine environment attracts much attention from both researchers and the general public. Plastic items and other debris are commonly observed everywhere in the ocean, from the surface down to the deep ocean floor. In this study, we analysed 45.2km of video footage, collected during 56 transects surveying the seafloor of the Faial-Pico Passage in order to quantify the abundance of marine litter and its interactions with benthic fauna. The footage was collected by a Remotely Operated Vehicle (ROV) and a manned submersible at depths ranging between 40 and 525m. The mean litter density in the passage was 0.26±0.03 items·100m -1 (±SE) and was significantly higher between 151 and 250m compared to other depth strata. Overall, derelict fishing gear, mostly made of plastic, were the most common objects found on the seafloor, representing 64% of all items. Although we observed few evidence of direct deleterious effects by the litter, interactions with fauna were observed in more than half of the items. This study makes an important contribution in quantifying the abundance of marine litter on the seafloor of the Azores. The location of the Faial-Pico Passage, close to shore, makes it an appropriate site for long-term monitoring of litter on the seafloor and evaluate the efficiency of upcoming public policies aimed at reducing litter input into the oceans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanomedicine: Perspective and promises with ligand-directed molecular imaging

Energy Technology Data Exchange (ETDEWEB)

Pan Dipanjan [Department of Medicine, Washington University Medical School, St. Louis, MO (United States)], E-mail: dipanjan@wustl.edu; Lanza, Gregory M.; Wickline, Samuel A. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Caruthers, Shelton D. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Philips Healthcare, Andover, MA (United States)], E-mail: scaruthers@cmrl.wustl.edu

2009-05-15

Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

Nanomedicine: Perspective and promises with ligand-directed molecular imaging

International Nuclear Information System (INIS)

Pan Dipanjan; Lanza, Gregory M.; Wickline, Samuel A.; Caruthers, Shelton D.

2009-01-01

Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

Review of mitigation methods for fish passage, instream flows, and water quality

International Nuclear Information System (INIS)

Railsback, S.F.

1991-01-01

This paper reports on current environmental mitigation practices at nonfederal hydropower projects. Information was obtained from project operators on dissolved oxygen (DO) mitigation, instream flows, upstream fish passage facilities, and downstream fish passage facilities. The most common method for DO mitigation is the use of spill flows, which are costly because of lost power generation. DO concentrations are commonly monitored, but biological effects of DO mitigation are not. At many projects, instream flow requirements have been set without reference to formalized methods. About half of the projects with instream flow requirements monitor flow rates, but few monitor fish populations to verify that instream flows are effective. Angled bar racks are the most commonly used downstream fish passage devices and fish ladders are the most commonly used upstream fish passage devices. Fish passage rates or populations have been monitored to verify the effectiveness of passage mitigation at few projects. This analysis is the first phase of an evaluation of the costs, benefits, and effectiveness of mitigation measures

Shape design of internal cooling passages within a turbine blade

Science.gov (United States)

Nowak, Grzegorz; Nowak, Iwona

2012-04-01

The article concerns the optimization of the shape and location of non-circular passages cooling the blade of a gas turbine. To model the shape, four Bezier curves which form a closed profile of the passage were used. In order to match the shape of the passage to the blade profile, a technique was put forward to copy and scale the profile fragments into the component, and build the outline of the passage on the basis of them. For so-defined cooling passages, optimization calculations were carried out with a view to finding their optimal shape and location in terms of the assumed objectives. The task was solved as a multi-objective problem with the use of the Pareto method, for a cooling system composed of four and five passages. The tool employed for the optimization was the evolutionary algorithm. The article presents the impact of the population on the task convergence, and discusses the impact of different optimization objectives on the Pareto optimal solutions obtained. Due to the problem of different impacts of individual objectives on the position of the solution front which was noticed during the calculations, a two-step optimization procedure was introduced. Also, comparative optimization calculations for the scalar objective function were carried out and set up against the non-dominated solutions obtained in the Pareto approach. The optimization process resulted in a configuration of the cooling system that allows a significant reduction in the temperature of the blade and its thermal stress.

Characterization of Colloidal Quantum Dot Ligand Exchange by X-ray Photoelectron Spectroscopy

Science.gov (United States)

Atewologun, Ayomide; Ge, Wangyao; Stiff-Roberts, Adrienne D.

2013-05-01

Colloidal quantum dots (CQDs) are chemically synthesized semiconductor nanoparticles with size-dependent wavelength tunability. Chemical synthesis of CQDs involves the attachment of long organic surface ligands to prevent aggregation; however, these ligands also impede charge transport. Therefore, it is beneficial to exchange longer surface ligands for shorter ones for optoelectronic devices. Typical characterization techniques used to analyze surface ligand exchange include Fourier-transform infrared spectroscopy, x-ray diffraction, transmission electron microscopy, and nuclear magnetic resonance spectroscopy, yet these techniques do not provide a simultaneously direct, quantitative, and sensitive method for evaluating surface ligands on CQDs. In contrast, x-ray photoelectron spectroscopy (XPS) can provide nanoscale sensitivity for quantitative analysis of CQD surface ligand exchange. A unique aspect of this work is that a fingerprint is identified for shorter surface ligands by resolving the regional XPS spectrum corresponding to different types of carbon bonds. In addition, a deposition technique known as resonant infrared matrix-assisted pulsed laser evaporation is used to improve the CQD film uniformity such that stronger XPS signals are obtained, enabling more accurate analysis of the ligand exchange process.

Direct synthesis of ligand-based radicals by the addition of bipyridine to chromium(II) compounds.

Science.gov (United States)

Zhou, Wen; Desnoyer, Addison N; Bailey, James A; Patrick, Brian O; Smith, Kevin M

2013-03-04

The reaction of 2,2'-bipyridine (bpy) with monomeric chromium(II) precursors was used to prepare the S = 1 complexes Cr(tBu-acac)2(bpy) (1) and (η(5)-Cp)(η(1)-Cp)Cr(bpy) (3), as well as the S = 2 compound Cr[N(SiMe3)2]2(bpy) (4). The crystallographically determined bond lengths indicate that the bpy ligands in 1 and 3 are best regarded as radical anions, while 4 shows no structural evidence for electron transfer from Cr(II) to the neutral bpy ligand.

Spark PRM: Using RRTs within PRMs to efficiently explore narrow passages

KAUST Repository

Shi, Kensen; Denny, Jory; Amato, Nancy M.

2014-01-01

© 2014 IEEE. Probabilistic RoadMaps (PRMs) have been successful for many high-dimensional motion planning problems. However, they encounter difficulties when mapping narrow passages. While many PRM sampling methods have been proposed to increase the proportion of samples within narrow passages, such difficult planning areas still pose many challenges. We introduce a novel algorithm, Spark PRM, that sparks the growth of Rapidly-expanding Random Trees (RRTs) from narrow passage samples generated by a PRM. The RRT rapidly generates further narrow passage samples, ideally until the passage is fully mapped. After reaching a terminating condition, the tree stops growing and is added to the roadmap. Spark PRM is a general method that can be applied to all PRM variants. We study the benefits of Spark PRM with a variety of sampling strategies in a wide array of environments. We show significant speedups in computation time over RRT, Sampling-based Roadmap of Trees (SRT), and various PRM variants.

Spark PRM: Using RRTs within PRMs to efficiently explore narrow passages

KAUST Repository

Shi, Kensen

2014-05-01

© 2014 IEEE. Probabilistic RoadMaps (PRMs) have been successful for many high-dimensional motion planning problems. However, they encounter difficulties when mapping narrow passages. While many PRM sampling methods have been proposed to increase the proportion of samples within narrow passages, such difficult planning areas still pose many challenges. We introduce a novel algorithm, Spark PRM, that sparks the growth of Rapidly-expanding Random Trees (RRTs) from narrow passage samples generated by a PRM. The RRT rapidly generates further narrow passage samples, ideally until the passage is fully mapped. After reaching a terminating condition, the tree stops growing and is added to the roadmap. Spark PRM is a general method that can be applied to all PRM variants. We study the benefits of Spark PRM with a variety of sampling strategies in a wide array of environments. We show significant speedups in computation time over RRT, Sampling-based Roadmap of Trees (SRT), and various PRM variants.

PatchSurfers: Two methods for local molecular property-based binding ligand prediction.

Science.gov (United States)

Shin, Woong-Hee; Bures, Mark Gregory; Kihara, Daisuke

2016-01-15

Protein function prediction is an active area of research in computational biology. Function prediction can help biologists make hypotheses for characterization of genes and help interpret biological assays, and thus is a productive area for collaboration between experimental and computational biologists. Among various function prediction methods, predicting binding ligand molecules for a target protein is an important class because ligand binding events for a protein are usually closely intertwined with the proteins' biological function, and also because predicted binding ligands can often be directly tested by biochemical assays. Binding ligand prediction methods can be classified into two types: those which are based on protein-protein (or pocket-pocket) comparison, and those that compare a target pocket directly to ligands. Recently, our group proposed two computational binding ligand prediction methods, Patch-Surfer, which is a pocket-pocket comparison method, and PL-PatchSurfer, which compares a pocket to ligand molecules. The two programs apply surface patch-based descriptions to calculate similarity or complementarity between molecules. A surface patch is characterized by physicochemical properties such as shape, hydrophobicity, and electrostatic potentials. These properties on the surface are represented using three-dimensional Zernike descriptors (3DZD), which are based on a series expansion of a 3 dimensional function. Utilizing 3DZD for describing the physicochemical properties has two main advantages: (1) rotational invariance and (2) fast comparison. Here, we introduce Patch-Surfer and PL-PatchSurfer with an emphasis on PL-PatchSurfer, which is more recently developed. Illustrative examples of PL-PatchSurfer performance on binding ligand prediction as well as virtual drug screening are also provided. Copyright © 2015 Elsevier Inc. All rights reserved.

Ligand Depot: a data warehouse for ligands bound to macromolecules.

Science.gov (United States)

Feng, Zukang; Chen, Li; Maddula, Himabindu; Akcan, Ozgur; Oughtred, Rose; Berman, Helen M; Westbrook, John

2004-09-01

Ligand Depot is an integrated data resource for finding information about small molecules bound to proteins and nucleic acids. The initial release (version 1.0, November, 2003) focuses on providing chemical and structural information for small molecules found as part of the structures deposited in the Protein Data Bank. Ligand Depot accepts keyword-based queries and also provides a graphical interface for performing chemical substructure searches. A wide variety of web resources that contain information on small molecules may also be accessed through Ligand Depot. Ligand Depot is available at http://ligand-depot.rutgers.edu/. Version 1.0 supports multiple operating systems including Windows, Unix, Linux and the Macintosh operating system. The current drawing tool works in Internet Explorer, Netscape and Mozilla on Windows, Unix and Linux.

Magnetic Ligand Fishing as a Targeting Tool for HPLC-HRMS-SPE-NMR: α-Glucosidase Inhibitory Ligands and Alkylresorcinol Glycosides from Eugenia catharinae.

Science.gov (United States)

Wubshet, Sileshi G; Brighente, Inês M C; Moaddel, Ruin; Staerk, Dan

2015-11-25

A bioanalytical platform combining magnetic ligand fishing for α-glucosidase inhibition profiling and HPLC-HRMS-SPE-NMR for structural identification of α-glucosidase inhibitory ligands, both directly from crude plant extracts, is presented. Magnetic beads with N-terminus-coupled α-glucosidase were synthesized and characterized for their inherent catalytic activity. Ligand fishing with the immobilized enzyme was optimized using an artificial test mixture consisting of caffeine, ferulic acid, and luteolin before proof-of-concept with the crude extract of Eugenia catharinae. The combination of ligand fishing and HPLC-HRMS-SPE-NMR identified myricetin 3-O-α-L-rhamnopyranoside, myricetin, quercetin, and kaempferol as α-glucosidase inhibitory ligands in E. catharinae. Furthermore, HPLC-HRMS-SPE-NMR analysis led to identification of six new alkylresorcinol glycosides, i.e., 5-(2-oxopentyl)resorcinol 4-O-β-D-glucopyranoside, 5-propylresorcinol 4-O-β-D-glucopyranoside, 5-pentylresorcinol 4-O-[α-D-apiofuranosyl-(1→6)]-β-D-glucopyranoside, 5-pentylresorcinol 4-O-β-D-glucopyranoside, 4-hydroxy-3-O-methyl-5-pentylresorcinol 1-O-β-D-glucopyranoside, and 3-O-methyl-5-pentylresorcinol 1-O-[β-D-glucopyranosyl-(1→6)]-β-D-glucopyranoside.

Reversible Size Control of Silver Nanoclusters via Ligand-exchange

KAUST Repository

Bootharaju, Megalamane Siddaramappa

2015-05-21

The properties of atomically monodisperse noble metal nanoclusters (NCs) are intricately intertwined with their precise molecular formula. The vast majority of size-specific NC syntheses start from the reduction of the metal salt and thiol ligand mixture. Only in gold was it recently shown that ligand-exchange could induce the growth of NCs from one atomically precise species to another; a process of yet unknown reversibility. Here, we present a process for the ligand-exchange-induced growth of atomically precise silver NCs, in a biphasic liquid-liquid system, which is particularly of interest because of its complete reversibility and ability to occur at room temperature. We explore this phenomenon in-depth using Ag35(SG)18 [SG= glutathionate] and Ag44(4-FTP)30 [4-FTP= 4-fluorothiophenol] as model systems. We show that the ligand-exchange conversion of Ag35(SG)18 into Ag44(4-FTP)30 is rapid (< 5 min) and direct, while the reverse process proceeds slowly through intermediate cluster sizes. We adapt a recently developed theory of reverse Ostwald ripening to model the NCs’ interconvertibility. The model’s predictions are in good agreement with the experimental observations, and they highlight the importance of small changes in the ligand-metal binding energy in determining the final equilibrium NC size. Based on the insight provided by this model, we demonstrated experimentally that by varying the choice of ligands, ligand-exchange can be used to obtain different sized NCs. The findings in this work establish ligand-exchange as a versatile tool for tuning cluster sizes.

Reversible Size Control of Silver Nanoclusters via Ligand-exchange

KAUST Repository

Bootharaju, Megalamane Siddaramappa; Burlakov, Victor M.; Besong, Tabot M.D.; Joshi, Chakra Prasad; AbdulHalim, L; Black, David; Whetten, Robert; Goriely, Alain; Bakr, Osman

2015-01-01

The properties of atomically monodisperse noble metal nanoclusters (NCs) are intricately intertwined with their precise molecular formula. The vast majority of size-specific NC syntheses start from the reduction of the metal salt and thiol ligand mixture. Only in gold was it recently shown that ligand-exchange could induce the growth of NCs from one atomically precise species to another; a process of yet unknown reversibility. Here, we present a process for the ligand-exchange-induced growth of atomically precise silver NCs, in a biphasic liquid-liquid system, which is particularly of interest because of its complete reversibility and ability to occur at room temperature. We explore this phenomenon in-depth using Ag35(SG)18 [SG= glutathionate] and Ag44(4-FTP)30 [4-FTP= 4-fluorothiophenol] as model systems. We show that the ligand-exchange conversion of Ag35(SG)18 into Ag44(4-FTP)30 is rapid (< 5 min) and direct, while the reverse process proceeds slowly through intermediate cluster sizes. We adapt a recently developed theory of reverse Ostwald ripening to model the NCs’ interconvertibility. The model’s predictions are in good agreement with the experimental observations, and they highlight the importance of small changes in the ligand-metal binding energy in determining the final equilibrium NC size. Based on the insight provided by this model, we demonstrated experimentally that by varying the choice of ligands, ligand-exchange can be used to obtain different sized NCs. The findings in this work establish ligand-exchange as a versatile tool for tuning cluster sizes.

Aquatic organism passage at road-stream crossings—synthesis and guidelines for effectiveness monitoring

Science.gov (United States)

Hoffman, Robert L.; Dunham, Jason B.; Hansen, Bruce P.

2012-01-01

Restoration and maintenance of passage for aquatic organisms at road-stream crossings represents a major management priority, involving an investment of hundreds of millions of dollars (for example, U.S. Government Accounting Office, 2001). In recent years, passage at hundreds of crossings has been restored, primarily by replacing barrier road culverts with bridges or stream simulation culverts designed to pass all species and all life stages of aquatic life and simulate natural hydro-geomorphic processes (U.S. Forest Service, 2008). The current situation has motivated two general questions: 1. Are current design standards for stream simulation culverts adequately re-establishing passage for aquatic biota? and 2. How do we monitor and evaluate effectiveness of passage restoration? To address the latter question, a national workshop was held in March 2010, in Portland, Oregon. The workshop included experts on aquatic organism passage from across the nation (see table of participants, APPENDIX) who addressed four classes of methods for monitoring effectiveness of aquatic organism passage—individual movement, occupancy, demography, and genetics. This report has been written, in part, for field biologists who will be undertaking and evaluating the effectiveness of aquatic organism passage restoration projects at road-stream crossings. The report outlines basic methods for evaluating road-stream crossing passage impairment and restoration and discusses under what circumstances and conditions each method will be useful; what questions each method can potentially answer; how to design and implement an evaluation study; and points out the fundamental reality that most evaluation projects will require special funding and partnerships among researchers and resource managers. The report is organized into the following sections, which can be read independently: 1. Historical context: In this section, we provide a brief history of events leading up to the present situation

Expanding the Library of Uranyl Amide Derivatives: New Complexes Featuring the tert-Butyldimethylsilylamide Ligand.

Science.gov (United States)

Pattenaude, Scott A; Coughlin, Ezra J; Collins, Tyler S; Zeller, Matthias; Bart, Suzanne C

2018-04-16

New uranyl derivatives featuring the amide ligand, -N(SiHMe 2 ) t Bu, were synthesized and characterized by X-ray crystallography, multinuclear NMR spectroscopy, and absorption spectroscopies. Steric properties of these complexes were also quantified using the computational program Solid-G. The increased basicity of the free ligand -N(SiHMe 2 ) t Bu was demonstrated by direct comparison to -N(SiMe 3 ) 2 , a popular supporting ligand for uranyl. Substitutional lability on a uranyl center was also demonstrated by exchange with the -N(SiMe 3 ) 2 ligand. The increased basicity of this ligand and diverse characterization handles discussed here will make these compounds useful synthons for future reactivity.

Impact of protein and ligand impurities on ITC-derived protein-ligand thermodynamics.

Science.gov (United States)

Grüner, Stefan; Neeb, Manuel; Barandun, Luzi Jakob; Sielaff, Frank; Hohn, Christoph; Kojima, Shun; Steinmetzer, Torsten; Diederich, François; Klebe, Gerhard

2014-09-01

The thermodynamic characterization of protein-ligand interactions by isothermal titration calorimetry (ITC) is a powerful tool in drug design, giving valuable insight into the interaction driving forces. ITC is thought to require protein and ligand solutions of high quality, meaning both the absence of contaminants as well as accurately determined concentrations. Ligands synthesized to deviating purity and protein of different pureness were titrated by ITC. Data curation was attempted also considering information from analytical techniques to correct stoichiometry. We used trypsin and tRNA-guanine transglycosylase (TGT), together with high affinity ligands to investigate the effect of errors in protein concentration as well as the impact of ligand impurities on the apparent thermodynamics. We found that errors in protein concentration did not change the thermodynamic properties obtained significantly. However, most ligand impurities led to pronounced changes in binding enthalpy. If protein binding of the respective impurity is not expected, the actual ligand concentration was corrected for and the thus revised data compared to thermodynamic properties obtained with the respective pure ligand. Even in these cases, we observed differences in binding enthalpy of about 4kJ⋅mol(-1), which is considered significant. Our results indicate that ligand purity is the critical parameter to monitor if accurate thermodynamic data of a protein-ligand complex are to be recorded. Furthermore, artificially changing fitting parameters to obtain a sound interaction stoichiometry in the presence of uncharacterized ligand impurities may lead to thermodynamic parameters significantly deviating from the accurate thermodynamic signature. Copyright © 2014 Elsevier B.V. All rights reserved.

Vascular smooth muscle cells exhibit a progressive loss of rigidity with serial culture passaging.

Science.gov (United States)

Dinardo, Carla Luana; Venturini, Gabriela; Omae, Samantha Vieira; Zhou, Enhua H; da Motta-Leal-Filho, Joaquim Maurício; Dariolli, Rafael; Krieger, José Eduardo; Alencar, Adriano Mesquita; Costa Pereira, Alexandre

2012-01-01

One drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.

Quality of Vision in Eyes With Epiphora Undergoing Lacrimal Passage Intubation.

Science.gov (United States)

Koh, Shizuka; Inoue, Yasushi; Ochi, Shintaro; Takai, Yoshihiro; Maeda, Naoyuki; Nishida, Kohji

2017-09-01

To investigate visual function and optical quality in eyes with epiphora undergoing lacrimal passage intubation. Prospective case series. Thirty-four eyes of 30 patients with lacrimal passage obstruction were enrolled. Before and 1 month after lacrimal passage intubation, functional visual acuity (FVA), higher-order aberrations (HOAs), lower tear meniscus, and tear clearance were assessed. An FVA measurement system was used to examine changes in continuous visual acuity (VA) over time, and visual function parameters such as FVA, visual maintenance ratio, and blink frequency were obtained. Sequential ocular HOAs were measured for 10 seconds after the blink using a wavefront sensor. Aberration data were analyzed in the central 4 mm for coma-like, spherical-like, and total HOAs. Fluctuation and stability indices of the total HOAs over time were calculated. Lower tear meniscus was assessed by anterior segment optical coherence tomography. After lacrimal passage intubation, visual function significantly improved, as indicated by improved FVA (P = .003) and visual maintenance ratio (P function and optical quality via patency of the lacrimal passage. Copyright © 2017 Elsevier Inc. All rights reserved.

Fire passage on geomorphic fractures in Cerrado: effect on vegetation

Directory of Open Access Journals (Sweden)

Otacílio Antunes Santana

2017-01-01

Full Text Available Geomorphic fracture is a natural geologic formation that sometimes forms a deep fissure in the rock with the establishment of soil and vegetation. The objective of this work was to analyze vegetation within geomorphic fractures under the effect of wildfire passage. The biometric variables evaluated before and after fire passage were: diameter, height, leaf area index, timber volume, grass biomass, number of trees and shrubs and of species. Results (in fractures were compared to adjacent areas (control. The effect of wildfire passage on vegetation within geomorphic fractures was not significant because fire followed plant biomass bed and when it met the fracture (wetter, it changed from soil surface to canopy surface (jump fire effect, affecting without significance the number of plants or species; so, fracture could be plants refuge against fire passage. We could infer in our experimental model that quality of plant biomass bed could be more significant than quantity, and microclimate variability recruits plants to the refuge (geomorphic fracture.

Knotting probabilities after a local strand passage in unknotted self-avoiding polygons

International Nuclear Information System (INIS)

Szafron, M L; Soteros, C E

2011-01-01

We investigate, both theoretically and numerically, the knotting probabilities after a local strand passage is performed in an unknotted self-avoiding polygon (SAP) on the simple cubic lattice. In the polygons studied, it is assumed that two polygon segments have already been brought close together for the purpose of performing a strand passage. This restricts the polygons considered to those that contain a specific pattern called Θ at a fixed location; an unknotted polygon containing Θ is called a Θ-SAP. It is proved that the number of n-edge Θ-SAPs grows exponentially (with n) at the same rate as the total number of n-edge unknotted SAPs (those with no prespecified strand passage structure). Furthermore, it is proved that the same holds for subsets of n-edge Θ-SAPs that yield a specific after-strand-passage knot-type. Thus, the probability of a given after-strand-passage knot-type does not grow (or decay) exponentially with n. Instead, it is conjectured that these after-strand-passage knot probabilities approach, as n goes to infinity, knot-type dependent amplitude ratios lying strictly between 0 and 1. This conjecture is supported by numerical evidence from Monte Carlo data generated using a composite (aka multiple) Markov chain Monte Carlo BFACF algorithm developed to study Θ-SAPs. A new maximum likelihood method is used to estimate the critical exponents relevant to this conjecture. We also obtain strong numerical evidence that the after-strand-passage knotting probability depends on the local structure around the strand-passage site. If the local structure and the crossing sign at the strand-passage site are considered, then we observe that the more 'compact' the local structure, the less likely the after-strand-passage polygon is to be knotted. This trend for compactness versus knotting probability is consistent with results obtained for other strand-passage models; however, we are the first to note the influence of the crossing-sign information. We

First-passage exponents of multiple random walks

International Nuclear Information System (INIS)

Ben-Naim, E; Krapivsky, P L

2010-01-01

We investigate first-passage statistics of an ensemble of N noninteracting random walks on a line. Starting from a configuration in which all particles are located in the positive half-line, we study S n (t), the probability that the nth rightmost particle remains in the positive half-line up to time t. This quantity decays algebraically, S n (t)∼t -β n , in the long-time limit. Interestingly, there is a family of nontrivial first-passage exponents, β 1 2 N-1 ; the only exception is the two-particle case where β 1 = 1/3. In the N → ∞ limit, however, the exponents attain a scaling form, β n (N) → β(z) with z=(n-N/2)/√N. We also demonstrate that the smallest exponent decays exponentially with N. We deduce these results from first-passage kinetics of a random walk in an N-dimensional cone and confirm them using numerical simulations. Additionally, we investigate the family of exponents that characterizes leadership statistics of multiple random walks and find that in this case, the cone provides an excellent approximation.

Flow characteristics in nuclear steam turbine blade passage

International Nuclear Information System (INIS)

Ahn, H.J.; Yoon, W.H.; Kwon, S.B.

1995-01-01

The rapid expansion of condensable gas such as moist air or steam gives rise to nonequilibrium condensation. As a result of irreversibility of condensation process in the nuclear steam turbine blade passage, the entropy of the flow increases, and the efficiency of the turbine decreases. In the present study, in order to investigate the flow characteristics of moist air in two-dimensional turbine blade passage which is made from the configuration of the last stage tip section of the actual nuclear steam turbine moving blade, the static pressures along both pressure and suction sides of blade are measured by static pressure taps and the distribution of Mach number on both sides of the blade are obtained by using the measured static pressure. Also, the flow field is visualized by a Schlieren system. From the experimental results, the effects of the stagnation temperature and specific humidity on the flow properties in the two dimensional steam turbine blade passage are clearly identified

First Passage Moments of Finite-State Semi-Markov Processes

Energy Technology Data Exchange (ETDEWEB)

Warr, Richard [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Cordeiro, James [Air Force Research Lab. (AFRL), Wright-Patterson AFB, OH (United States)

2014-03-31

In this paper, we discuss the computation of first-passage moments of a regular time-homogeneous semi-Markov process (SMP) with a finite state space to certain of its states that possess the property of universal accessibility (UA). A UA state is one which is accessible from any other state of the SMP, but which may or may not connect back to one or more other states. An important characteristic of UA is that it is the state-level version of the oft-invoked process-level property of irreducibility. We adapt existing results for irreducible SMPs to the derivation of an analytical matrix expression for the first passage moments to a single UA state of the SMP. In addition, consistent point estimators for these first passage moments, together with relevant R code, are provided.

Ligands in PSI structures

International Nuclear Information System (INIS)

Kumar, Abhinav; Chiu, Hsiu-Ju; Axelrod, Herbert L.; Morse, Andrew; Elsliger, Marc-André; Wilson, Ian A.; Deacon, Ashley

2010-01-01

A survey of the types and frequency of ligands that are bound to PSI structures is analyzed as well as their utility in functional annotation of previously uncharacterized proteins. Approximately 65% of PSI structures report some type of ligand(s) that is bound in the crystal structure. Here, a description is given of how such ligands are handled and analyzed at the JCSG and a survey of the types, variety and frequency of ligands that are observed in the PSI structures is also compiled and analyzed, including illustrations of how these bound ligands have provided functional clues for annotation of proteins with little or no previous experimental characterization. Furthermore, a web server was developed as a tool to mine and analyze the PSI structures for bound ligands and other identifying features

On correlations between certain random variables associated with first passage Brownian motion

International Nuclear Information System (INIS)

Kearney, Michael J; Pye, Andrew J; Martin, Richard J

2014-01-01

We analyse how the area swept out by a Brownian motion up to its first passage time correlates with the first passage time itself, obtaining several exact results in the process. Additionally, we analyse the relationship between the time average of a Brownian motion during a first passage and the maximum value attained. The results, which find various applications, are in excellent agreement with simulations. (paper)

Ligand screening by saturation-transfer difference (STD) NMR spectroscopy.

Energy Technology Data Exchange (ETDEWEB)

Krishnan, V V

2005-04-26

NMR based methods to screen for high-affinity ligands have become an indispensable tool for designing rationalized drugs, as these offer a combination of good experimental design of the screening process and data interpretation methods, which together provide unprecedented information on the complex nature of protein-ligand interactions. These methods rely on measuring direct changes in the spectral parameters, that are often simpler than the complex experimental procedures used to study structure and dynamics of proteins. The goal of this review article is to provide the basic details of NMR based ligand-screening methods, with particular focus on the saturation transfer difference (STD) experiment. In addition, we provide an overview of other NMR experimental methods and a practical guide on how to go about designing and implementing them.

Ligand photo-isomerization triggers conformational changes in iGluR2 ligand binding domain.

Directory of Open Access Journals (Sweden)

Tino Wolter

Full Text Available Neurological glutamate receptors bind a variety of artificial ligands, both agonistic and antagonistic, in addition to glutamate. Studying their small molecule binding properties increases our understanding of the central nervous system and a variety of associated pathologies. The large, oligomeric multidomain membrane protein contains a large and flexible ligand binding domains which undergoes large conformational changes upon binding different ligands. A recent application of glutamate receptors is their activation or inhibition via photo-switchable ligands, making them key systems in the emerging field of optochemical genetics. In this work, we present a theoretical study on the binding mode and complex stability of a novel photo-switchable ligand, ATA-3, which reversibly binds to glutamate receptors ligand binding domains (LBDs. We propose two possible binding modes for this ligand based on flexible ligand docking calculations and show one of them to be analogues to the binding mode of a similar ligand, 2-BnTetAMPA. In long MD simulations, it was observed that transitions between both binding poses involve breaking and reforming the T686-E402 protein hydrogen bond. Simulating the ligand photo-isomerization process shows that the two possible configurations of the ligand azo-group have markedly different complex stabilities and equilibrium binding modes. A strong but slow protein response is observed after ligand configuration changes. This provides a microscopic foundation for the observed difference in ligand activity upon light-switching.

A differentiated plane wave: its passage through a slab

International Nuclear Information System (INIS)

Hannay, J H; Nye, J F

2013-01-01

Differentiating a monochromatic uniform plane electromagnetic wavefield with respect to its direction produces, from a field that is completely lacking in localized specific features, one that contains a straight vortex-like line, a ‘C-line’ of defined circular polarization. There is also a second separate C-line of opposite handedness; indeed, in a sense, a straight line of every polarization is realized. Because of its primitive construction it is analytically simple to study the passage of a differentiated wave obliquely through a plane interface into a medium of different refractive index, to trace its C-line. This was done in an earlier paper. Here we extend the method to passage through a parallel-sided transparent slab. There are multiple reflections within the slab, as in a Fabry–Pérot interferometer. The exiting wave, as a single differentiated plane wave, has a straight oblique C-line. Inside the slab, and in front of it, there is wave interference. The result is a coiled, helix-like, C-line in front of the slab and another inside it. The two coils wrap around separate hyperboloids of one sheet, like cooling towers. The emerging straight C-line is shifted (with respect to a C-line in a notional undisturbed incident plane wave) both in the plane of incidence and transversely to it, and the second C-line behaves similarly. The analysis is exact and could be extended in a straightforward way to a general stratified medium. (paper)

Direct versus ligand-exchange synthesis of [PtAg28(BDT)12(TPP)4]4− nanoclusters: effect of a single-atom dopant on the optoelectronic and chemical properties

KAUST Repository

Bootharaju, Megalamane Siddaramappa; Kozlov, Sergey M.; Cao, Zhen; Harb, Moussab; Parida, Manas R.; Hedhili, Mohamed N.; Mohammed, Omar F.; Bakr, Osman; Cavallo, Luigi; Basset, Jean-Marie

2017-01-01

to offer monodisperse doped NCs. For instance, the direct synthesis of PtAg28 NCs produces a mixture of [Ag29(BDT)12(TPP)4]3- and [PtAg28(BDT)12(TPP)4]4- NCs (TPP: triphenylphosphine; BDT: 1,3-benzenedithiolate). Here, we designed a ligand-exchange (LE

The Northwest Passage Dispute

DEFF Research Database (Denmark)

Burke, Danita Catherine

2018-01-01

This is an article written for the Oxford Research Group "Sustainable Security" series. It gives an overview of the dispute of the Northwest Passage and discusses factors which will contribute to the evolution of the dispute in the 21st century. This short contribution summarizes and adds to the ...... to the research recently published by the author through Palgrave Macmillan, Danita Catherine Burke, 2018, International Disputes and Cultural Ideas in the Canadian Arctic...

A comparison of metrics to evaluate the effects of hydro-facility passage stressors on fish

Energy Technology Data Exchange (ETDEWEB)

Colotelo, Alison H.; Goldman, Amy E.; Wagner, Katie A.; Brown, Richard S.; Deng, Z. Daniel; Richmond, Marshall C.

2017-03-01

Hydropower is the most common form of renewable energy, and countries worldwide are considering expanding hydropower to new areas. One of the challenges of hydropower deployment is mitigation of the environmental impacts including water quality, habitat alterations, and ecosystem connectivity. For fish species that inhabit river systems with hydropower facilities, passage through the facility to access spawning and rearing habitats can be particularly challenging. Fish moving downstream through a hydro-facility can be exposed to a number of stressors (e.g., rapid decompression, shear forces, blade strike and collision, and turbulence), which can all affect fish survival in direct and indirect ways. Many studies have investigated the effects of hydro-turbine passage on fish; however, the comparability among studies is limited by variation in the metrics and biological endpoints used. Future studies investigating the effects of hydro-turbine passage should focus on using metrics and endpoints that are easily comparable. This review summarizes four categories of metrics that are used in fisheries research and have application to hydro-turbine passage (i.e., mortality, injury, molecular metrics, behavior) and evaluates them based on several criteria (i.e., resources needed, invasiveness, comparability among stressors and species, and diagnostic properties). Additionally, these comparisons are put into context of study setting (i.e., laboratory vs. field). Overall, injury and molecular metrics are ideal for studies in which there is a need to understand the mechanisms of effect, whereas behavior and mortality metrics provide information on the whole body response of the fish. The study setting strongly influences the comparability among studies. In laboratory-based studies, stressors can be controlled by both type and magnitude, allowing for easy comparisons among studies. In contrast, field studies expose fish to realistic passage environments but the comparability is

Gender Differences in Implicit and Explicit Memory for Affective Passages

Science.gov (United States)

Burton, Leslie A.; Rabin, Laura; Vardy, Susan Bernstein.; Frohlich, Jonathan; Wyatt, Gwinne; Dimitri, Diana; Constante, Shimon; Guterman, Elan

2004-01-01

Thirty-two participants were administered 4 verbal tasks, an Implicit Affective Task, an Implicit Neutral Task, an Explicit Affective Task, and an Explicit Neutral Task. For the Implicit Tasks, participants were timed while reading passages aloud as quickly as possible, but not so quickly that they did not understand. A target verbal passage was…

Trapped Ion Quantum Computation by Adiabatic Passage

International Nuclear Information System (INIS)

Feng Xuni; Wu Chunfeng; Lai, C. H.; Oh, C. H.

2008-01-01

We propose a new universal quantum computation scheme for trapped ions in thermal motion via the technique of adiabatic passage, which incorporates the advantages of both the adiabatic passage and the model of trapped ions in thermal motion. Our scheme is immune from the decoherence due to spontaneous emission from excited states as the system in our scheme evolves along a dark state. In our scheme the vibrational degrees of freedom are not required to be cooled to their ground states because they are only virtually excited. It is shown that the fidelity of the resultant gate operation is still high even when the magnitude of the effective Rabi frequency moderately deviates from the desired value.

Consequences of the Solar System passage through dense interstellar clouds

Directory of Open Access Journals (Sweden)

A. G. Yeghikyan

2003-06-01

Full Text Available Several consequences of the passage of the solar system through dense interstellar molecular clouds are discussed. These clouds, dense (more than 100 cm-3, cold (10–50 K and extended (larger than 1 pc, are characterized by a gas-to-dust mass ratio of about 100, by a specific power grain size spectrum (grain radii usually cover the range 0.001–3 micron and by an average dust-to-gas number density ratio of about 10-12. Frequently these clouds contain small-scale (10–100 AU condensations with gas concentrations ranging up to 10 5 cm-3. At their casual passage over the solar system they exert pressures very much enhanced with respect to today’s standards. Under these conditions it will occur that the Earth is exposed directly to the interstellar flow. It is shown first that even close to the Sun, at 1 AU, the cloud’s matter is only partly ionized and should mainly interact with the solar wind by charge exchange processes. Dust particles of the cloud serve as a source of neutrals, generated by the solar UV irradiation of dust grains, causing the evaporation of icy materials. The release of neutral atoms from dust grains is then followed by strong influences on the solar wind plasma flow. The behavior of the neutral gas inflow parameters is investigated by a 2-D hydrodynamic approach to model the interaction processes. Because of a reduction of the heliospheric dimension down to 1 AU, direct influence of the cloud’s matter to the terrestrial environment and atmosphere could be envisaged.Key words. Interplanetary physics (heliopause and solar wind termination; interplanetary dust; interstellar gas

Consequences of the Solar System passage through dense interstellar clouds

Directory of Open Access Journals (Sweden)

A. G. Yeghikyan

Full Text Available Several consequences of the passage of the solar system through dense interstellar molecular clouds are discussed. These clouds, dense (more than 100 cm^-3, cold (10–50 K and extended (larger than 1 pc, are characterized by a gas-to-dust mass ratio of about 100, by a specific power grain size spectrum (grain radii usually cover the range 0.001–3 micron and by an average dust-to-gas number density ratio of about 10^-12. Frequently these clouds contain small-scale (10–100 AU condensations with gas concentrations ranging up to 10 5 cm^-3. At their casual passage over the solar system they exert pressures very much enhanced with respect to today’s standards. Under these conditions it will occur that the Earth is exposed directly to the interstellar flow. It is shown first that even close to the Sun, at 1 AU, the cloud’s matter is only partly ionized and should mainly interact with the solar wind by charge exchange processes. Dust particles of the cloud serve as a source of neutrals, generated by the solar UV irradiation of dust grains, causing the evaporation of icy materials. The release of neutral atoms from dust grains is then followed by strong influences on the solar wind plasma flow. The behavior of the neutral gas inflow parameters is investigated by a 2-D hydrodynamic approach to model the interaction processes. Because of a reduction of the heliospheric dimension down to 1 AU, direct influence of the cloud’s matter to the terrestrial environment and atmosphere could be envisaged.

Key words. Interplanetary physics (heliopause and solar wind termination; interplanetary dust; interstellar gas

Factors Influencing the Successful Passage of a School Bond Referendum as Identified by New Jersey School Superintendents

Science.gov (United States)

Godown, Michael P.

2011-01-01

The passage of a school bond can determine the direction of a district for many years to come (Faltys, 2006). Upkeep of older facilities and the building of new facilities can have an impact on instruction, teacher job satisfaction, student achievement, and perceptions toward the district (Moore, 2003). Despite the fact there is often state money…

Enhanced reactivities toward amines by introducing an imine arm to the pincer ligand: Direct coupling of two amines to form an imine without oxidant

KAUST Repository

He, Lipeng

2012-07-23

Dehydrogenative homocoupling of primary alcohols to form esters and coupling of amines to form imines was accomplished using a class of novel pincer ruthenium complexes. The reactivities of the ruthenium pincer complexes for the direct coupling of amines to form imines were enhanced by introducing an imine arm to the pincer ligand. Selective oxidation of benzylamines to imines was achieved using aniline derivatives as the substrate and solvent. © 2012 American Chemical Society.

Enhanced reactivities toward amines by introducing an imine arm to the pincer ligand: Direct coupling of two amines to form an imine without oxidant

KAUST Repository

He, Lipeng; Chen, Tao; Gong, Dirong; Lai, Zhiping; Huang, Kuo-Wei

2012-01-01

Dehydrogenative homocoupling of primary alcohols to form esters and coupling of amines to form imines was accomplished using a class of novel pincer ruthenium complexes. The reactivities of the ruthenium pincer complexes for the direct coupling of amines to form imines were enhanced by introducing an imine arm to the pincer ligand. Selective oxidation of benzylamines to imines was achieved using aniline derivatives as the substrate and solvent. © 2012 American Chemical Society.

Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

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Stéphanie Pérot

Full Text Available Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely

Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

Science.gov (United States)

Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

2013-01-01

Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket

Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

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Swati Kaushik

Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

Role of ligand-ligand vs. core-core interactions in gold nanoclusters.

Science.gov (United States)

Milowska, Karolina Z; Stolarczyk, Jacek K

2016-05-14

The controlled assembly of ligand-coated gold nanoclusters (NCs) into larger structures paves the way for new applications ranging from electronics to nanomedicine. Here, we demonstrate through rigorous density functional theory (DFT) calculations employing novel functionals accounting for van der Waals forces that the ligand-ligand interactions determine whether stable assemblies can be formed. The study of NCs with different core sizes, symmetry forms, ligand lengths, mutual crystal orientations, and in the presence of a solvent suggests that core-to-core van der Waals interactions play a lesser role in the assembly. The dominant interactions originate from combination of steric effects, augmented by ligand bundling on NC facets, and related to them changes in electronic properties induced by neighbouring NCs. We also show that, in contrast to standard colloidal theory approach, DFT correctly reproduces the surprising experimental trends in the strength of the inter-particle interaction observed when varying the length of the ligands. The results underpin the importance of understanding NC interactions in designing gold NCs for a specific function.

Hypoxia and exercise increase the transpulmonary passage of 99mTc-labeled albumin particles in humans.

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Melissa L Bates

Full Text Available Intrapulmonary arteriovenous anastomoses (IPAVs are large diameter connections that allow blood to bypass the lung capillaries and may provide a route for right-to-left embolus transmission. These anastomoses are recruited by exercise and catecholamines and hypoxia. Yet, whether IPAVs are recruited via direct, oxygen sensitive regulatory mechanisms or indirect effects secondary to redistribution pulmonary blood flow is unknown. Here, we hypothesized that the addition of exercise to hypoxic gas breathing, which increases cardiac output, would augment IPAVs recruitment in healthy humans. To test this hypothesis, we measured the transpulmonary passage of 99mTc-macroaggregated albumin particles (99mTc-MAA in seven healthy volunteers, at rest and with exercise at 85% of volitional max, with normoxic (FIO2 = 0.21 and hypoxic (FIO2 = 0.10 gas breathing. We found increased 99mTc-MAA passage in both exercise conditions and resting hypoxia. However, contrary to our hypothesis, we found the greatest 99mTc-MAA passage with resting hypoxia. As an additional, secondary endpoint, we also noted that the transpulmonary passage of 99mTc-MAA was well-correlated with the alveolar-arterial oxygen difference (A-aDO2 during exercise. While increased cardiac output has been proposed as an important modulator of IPAVs recruitment, we provide evidence that the modulation of blood flow through these pathways is more complex and that increasing cardiac output does not necessarily increase IPAVs recruitment. As we discuss, our data suggest that the resistance downstream of IPAVs is an important determinant of their perfusion.

Hydroacoustic Evaluation of Juvenile Salmonid Passage and Distribution at Detroit Dam, 2011

Energy Technology Data Exchange (ETDEWEB)

Khan, Fenton; Royer, Ida M.; Johnson, Gary E.; Ham, Kenneth D.

2012-11-15

Pacific Northwest National Laboratory evaluated juvenile salmonid passage and distribution at Detroit Dam (DET) on the North Santiam River, Oregon for the U.S. Army Corps of Engineers (USACE) to provide data to support decisions on long-term measures to enhance downstream passage at DET and others dams in USACE’s Willamette Valley Project. This study was conducted in response to regulatory requirements necessitated by the listing of Upper Willamette River Spring Chinook salmon (Oncorhynchus tshawytscha) and Upper Willamette River steelhead (O. mykiss) as threatened under the Endangered Species Act. The goal of the study was to provide information of juvenile salmonid passage and distribution at DET from February 2011 through February 2012. The results of the hydroacoustic study provide new and, in some cases, first-ever data on passage estimates, run timing, distributions, and relationships between fish passage and environmental variables at the dam. This information will inform management decisions on the design and development of surface passage and collection devices to help restore Chinook salmon populations in the North Santiam River watershed above DET. During the entire study period, an estimated total of 182,526 smolt-size fish (±4,660 fish, 95% CI) passed through turbine penstock intakes. Run timing peaked in winter and early spring months. Passage rates were highest during late fall, winter and early spring months and low during summer. Horizontal distribution for hours when both turbine units were operated simultaneously indicated Unit 2 passed almost twice as much fish as Unit 1. Diel distribution for smolt-size fish during the study period was fairly uniform, indicating fish were passing the turbines at all times of the day. A total of 5,083 smolt-size fish (± 312 fish, 95% CI) were estimated passed via the spillway when it was open between June 23 and September 27, 2011. Daily passage was low at the spillway during the June-August period, and

Rediscovering Rites of Passage: Education, Transformation, and the Transition to Sustainability

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David Adam Lertzman

2002-01-01

Full Text Available This paper focuses on rites of passage as a model for wilderness programs. It draws on my experience in the field, particularly with Native youth in a community-based program called "Rediscovery." The Rediscovery program is discussed, along with concepts of traditional indigenous knowledge and education. Foundational concepts of rites of passage are described in terms of their relevance to youth, outdoor education, and the Rediscovery program in particular. Using Rediscovery as a model, rites of passage are put forward as an educational process for youth from various cultural backgrounds. In this context, the purpose of education is to cultivate self-knowledge and to foster core personal development: the making of whole human beings. The paper closes with a reflection on my work with traditional indigenous people and the significance of rites of passage for education, cultural transformation, and the transition to ecological sustainability.

Controlling Nanocrystal Superlattice Symmetry and Shape-Anisotropic Interactions through Variable Ligand Surface Coverage

KAUST Repository

Choi, Joshua J.; Bealing, Clive R.; Bian, Kaifu; Hughes, Kevin J.; Zhang, Wenyu; Smilgies, Detlef-M.; Hennig, Richard G.; Engstrom, James R.; Hanrath, Tobias

2011-01-01

The assembly of colloidal nanocrystals (NCs) into superstructures with long-range translational and orientational order is sensitive to the molecular interactions between ligands bound to the NC surface. We illustrate how ligand coverage on colloidal PbS NCs can be exploited as a tunable parameter to direct the self-assembly of superlattices with predefined symmetry. We show that PbS NCs with dense ligand coverage assemble into face-centered cubic (fcc) superlattices whereas NCs with sparse ligand coverage assemble into body-centered cubic (bcc) superlattices which also exhibit orientational ordering of NCs in their lattice sites. Surface chemistry characterization combined with density functional theory calculations suggest that the loss of ligands occurs preferentially on {100} than on reconstructed {111} NC facets. The resulting anisotropic ligand distribution amplifies the role of NC shape in the assembly and leads to the formation of superlattices with translational and orientational order. © 2011 American Chemical Society.

Controlling Nanocrystal Superlattice Symmetry and Shape-Anisotropic Interactions through Variable Ligand Surface Coverage

KAUST Repository

Choi, Joshua J.

2011-03-09

The assembly of colloidal nanocrystals (NCs) into superstructures with long-range translational and orientational order is sensitive to the molecular interactions between ligands bound to the NC surface. We illustrate how ligand coverage on colloidal PbS NCs can be exploited as a tunable parameter to direct the self-assembly of superlattices with predefined symmetry. We show that PbS NCs with dense ligand coverage assemble into face-centered cubic (fcc) superlattices whereas NCs with sparse ligand coverage assemble into body-centered cubic (bcc) superlattices which also exhibit orientational ordering of NCs in their lattice sites. Surface chemistry characterization combined with density functional theory calculations suggest that the loss of ligands occurs preferentially on {100} than on reconstructed {111} NC facets. The resulting anisotropic ligand distribution amplifies the role of NC shape in the assembly and leads to the formation of superlattices with translational and orientational order. © 2011 American Chemical Society.

Fish passage hydroelectric power plant Linne, Netherlands. Didson measurements

International Nuclear Information System (INIS)

Van Keeken, O.A.; Griffioen, A.B.

2011-11-01

The hydroelectric power plant in the Dutch Maas River near Linne has a fish deflection and passage system. For this study, two evenings in the months of August and September 2011 were dedicated to examining the extent to which fish approached and used the fish passage system. To establish the swimming behavior of the fish, a high-resolution sonar (DIDSON) was used, which generates moving images of fish in turbid waters, to study their behavior. [nl

Effect of passage number on cellular response to DNA-damaging agents: Cell survival and gene expression

International Nuclear Information System (INIS)

Chang-Liu, C.M.; Woloschak, G.E.

1997-01-01

The effect of different passage numbers on plating efficiency, doubling time, cell growth, and radiation sensitivity was assessed in Syrian hamster embryo (SHE) cells. Changes in gene expression after UV or γ-ray irradiation at different passage numbers were also examined. The SHE cells were maintained in culture medium for up to 64 passages. Cells were exposed to 60 Co γ rays or 254-nm UV radiation. Differential display of cDNAs and northern blots were used for the study of gene expression. With increasing passage number, SHE cells demonstrated decreased doubling time, increased plating efficiency, and a decreased yield in the number of cells per plate. Between passages 41 and 48 a crisis period was evident during which time cell growth in high serum was no longer optimal, and serum concentrations were reduced to maintain cell growth. Sensitivity to ionizing radiation was no different between early- and intermediate-passage cells. However, after UV exposure at low passages (passage 3), confluent cells were more sensitive to the killing effects of UV than were log-phase cells. At intermediate passages (passages 43, 48), confluent cells were slightly more radioresistant than were log-phase cells. By passage 64, however, both confluent and log-phase cells showed similar patterns of UV sensitivity. Expression of γ-actin, PCNA, and p53 transcripts did not change following UV exposure. p53 mRNA was induced following γ-ray exposure of the intermediate (passage 45) epithelial cells. The observed differences in radiation sensitivity associated with increasing passage number may be influenced by radiation-induced gene expression. The authors are conducted experiments to identify these genes

Different effects of resveratrol on early and late passage mesenchymal stem cells through β-catenin regulation

Energy Technology Data Exchange (ETDEWEB)

Yoon, Dong Suk; Choi, Yoorim; Choi, Seong Mi [Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul (Korea, Republic of); Park, Kwang Hwan [Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Lee, Jin Woo, E-mail: ljwos@yuhs.ac [Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul (Korea, Republic of); Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul (Korea, Republic of)

2015-11-27

Resveratrol is a sirtuin 1 (SIRT1) activator and can function as an anti-inflammatory and antioxidant factor. In mesenchymal stem cells (MSCs), resveratrol enhances the proliferation and differentiation potential and has an anti-aging effect. However, contradictory effects of resveratrol on MSC cultures have been reported. In this study, we found that resveratrol had different effects on MSC cultures according to their cell passage and SIRT1 expression. Resveratrol enhanced the self-renewal potential and multipotency of early passage MSCs, but accelerated cellular senescence of late passage MSCs. In early passage MSCs expressing SIRT1, resveratrol decreased ERK and GSK-3β phosphorylation, suppressing β-catenin activity. In contrast, in late passage MSCs, which did not express SIRT1, resveratrol increased ERK and GSK-3β phosphorylation, activating β-catenin. We confirmed that SIRT1-deficient early passage MSCs treated with resveratrol lost their self-renewal potential and multipotency, and became senescent due to increased β-catenin activity. Sustained treatment with resveratrol at early passages maintained the self-renewal potential and multipotency of MSCs up to passage 10. Our findings suggest that resveratrol can be effectively applied to early passage MSC cultures, whereas parameters such as cell passage and SIRT1 expression must be taken into consideration before applying resveratrol to late passage MSCs. - Highlights: • Resveratrol enhances self-renewal potential and multipotency of early passage MSCs. • Resveratrol accelerates the cellular senescence of late passage MSCs. • The effects of resveratrol on MSCs are dependent on the presence of SIRT1. • SIRT1 modulates ERK/GSK-3β/β-catenin signaling. • Sustained resveratrol treatment maintains MSC stemness up to P10.

Stationary Probability and First-Passage Time of Biased Random Walk

International Nuclear Information System (INIS)

Li Jing-Wen; Tang Shen-Li; Xu Xin-Ping

2016-01-01

In this paper, we consider the stationary probability and first-passage time of biased random walk on 1D chain, where at each step the walker moves to the left and right with probabilities p and q respectively (0 ⩽ p, q ⩽ 1, p + q = 1). We derive exact analytical results for the stationary probability and first-passage time as a function of p and q for the first time. Our results suggest that the first-passage time shows a double power-law F ∼ (N − 1) γ , where the exponent γ = 2 for N < |p − q| −1 and γ = 1 for N > |p − q| −1 . Our study sheds useful insights into the biased random-walk process. (paper)

Fish passage post-construction issues: analysis of distribution, attraction and passage efficiency metrics at the Baguari Dam fish ladder to approach the problem

Directory of Open Access Journals (Sweden)

Luiz Gustavo Martins da Silva

Full Text Available Fish passages are considered the oldest management tool used to minimize the impact of blocking fish migratory routes by hydroelectric power plants. However, fish passages are being installed without specific criteria in Brazil, with severe consequences to the conservation of the local fish fauna. Therefore, basic data gathered for fish passages already constructed could contribute to define operational rules, in addition to offer subsidies to decision-making and design of future facilities. Thus, the fish ladder of Baguari Dam was evaluated regarding temporal distribution, attraction, and ascension of the local fish fauna. A total of 20 fish samples were conducted immediately downstream of the dam and inside the fish ladder, from January 2010 to June 2011. Seasonal variation in fish abundance and richness was registered below the dam and inside the passage, with higher number of migratory fish in the reproductive season (Kruskall-Wallis, p = 0.04 and p = 0.05. Furthermore, higher concentration of migratory allochthonous and non-migratory species was registered for the spill bay (Wilcoxon, p = 0.009 and p = 0.006 compared to the tailrace, where the fish ladder entrance is located. This result suggests low efficiency of the attraction system of the mechanism during the reproductive period. Once entering the fish ladder, migratory species apparently ascend the facility due to the similar distribution throughout different stretches. Generally, the results showed that an operational rule for the Baguari Dam fish ladder should consider running the facility only during the reproductive period, unless the objectives of the passage are well defined. The attraction system must be more precisely evaluated, using technologies such as radiotelemetry. Similarly, fish ascension also should be better analyzed to evaluate the time spent to ascend and its influence in the reproductive biology of the species using the ladder. Pit-tag system could be used to

Walla Walla River Fish Passage Operations Program, 2004-2005 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

Bronson, James P. (Confederated Tribes of the Umatilla Indian Reservation, Department of Natural Resources, Pendleton, OR); Duke, Bill B. (Oregon Department of Fish and Wildlife, Pendleton, OR)

2006-02-01

In the late 1990s, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate fish migration conditions in the basin. The migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow requirements, and providing trap and haul efforts when needed. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survival of migrating adult and juvenile salmonids in the Walla Walla River basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage criteria and passage and trapping facility design and operation. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. During the 2004-2005 project year, there were 590 adult summer steelhead, 31 summer steelhead kelts (Oncorhynchus mykiss), 70 adult bull trout (Salvelinus confluentus); 80 adult and 1 jack spring Chinook (O. tshawytscha) enumerated at the Nursery Bridge Dam fishway video counting window between December 13, 2004, and June 16, 2005. Summer steelhead and spring chinook were observed moving upstream while bull trout were observed moving both upstream and downstream of the facility. In addition, the old ladder trap was operated by ODFW in order to enumerate fish passage. Of the total, 143 adult summer steelhead and 15 summer steelhead kelts were enumerated at the west ladder at Nursery Bridge Dam during the video efforts between February 4 and May 23, 2005. Operation of the Little Walla Walla River

77 FR 28253 - Safety Zone; America's Cup World Series, East Passage, Narragansett Bay, RI

Science.gov (United States)

2012-05-14

...-AA00 Safety Zone; America's Cup World Series, East Passage, Narragansett Bay, RI AGENCY: Coast Guard... navigable waters of the East Passage, Narragansett Bay, Rhode Island, during the America's Cup World Series... rulemaking (NPRM) entitled ``Safety Zones; America's Cup World Series, East Passage, Narragansett Bay, RI...

Passage times of asymmetric anomalous walks with multiple paths

International Nuclear Information System (INIS)

Caceres, Manuel O; Insua, G Liliana

2005-01-01

We investigate the transient and the long-time behaviour of asymmetric anomalous walks in heterogeneous media. Two types of disorder are worked out explicitly: weak and strong disorder; in addition, the occurrence of disordered multiple paths is considered. We calculate the first passage time distribution of the associated stochastic transport process. We discuss the occurrence of the crossover from a power law to an exponential decay for the long-time behaviour of the distribution of the first passage times of disordered biased walks

LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

KAUST Repository

Chen, Peng

2014-12-03

Background Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction for protein-ligand binding sites, the state-of-the-art methods search for similar, known structures of the query and predict the binding sites based on the solved structures. However, such structural information is not commonly available. Results In this paper, we propose a sequence-based approach to identify protein-ligand binding residues. We propose a combination technique to reduce the effects of different sliding residue windows in the process of encoding input feature vectors. Moreover, due to the highly imbalanced samples between the ligand-binding sites and non ligand-binding sites, we construct several balanced data sets, for each of which a random forest (RF)-based classifier is trained. The ensemble of these RF classifiers forms a sequence-based protein-ligand binding site predictor. Conclusions Experimental results on CASP9 and CASP8 data sets demonstrate that our method compares favorably with the state-of-the-art protein-ligand binding site prediction methods.

Walla Walla River Fish Passage Operations Program, 2000-2001 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

Zimmerman, Brian C. (Confederated Tribes of the Umatilla Indian Reservation, Department of Natural Resources, Pendleton, OR); Duke, Bill B. (Oregon Department of Fish and Wildlife, Pendleton, OR)

2004-02-01

In the late 1990's, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate migration conditions in the basin. The migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow measures, and initiating trap and haul efforts. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survival of migrating adult and juvenile salmonids in the basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage criteria and passage and trapping facility design and operation. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. During the 2000-2001 project year, there were 624 summer steelhead (Oncorhynchus mykiss), 24 bull trout (Salvelinus confluentus), and 47 spring chinook (O. tshawytscha) counted at the Nursery Bridge Dam adult trap between December 27, 2000 and June 7, 2001. The Little Walla Walla River juvenile trap was not operated this year. The project transported 1600 adult spring chinook from Ringold Springs Hatchery to the South Fork Walla Walla Brood Holding Facility and outplanted 1156 for natural spawning in the basin. The project also provided equipment for transportation of juveniles captured during the construction fish salvage at Nursery Bridge Dam.

Crystallization of protein–ligand complexes

International Nuclear Information System (INIS)

Hassell, Anne M.; An, Gang; Bledsoe, Randy K.; Bynum, Jane M.; Carter, H. Luke III; Deng, Su-Jun J.; Gampe, Robert T.; Grisard, Tamara E.; Madauss, Kevin P.; Nolte, Robert T.; Rocque, Warren J.; Wang, Liping; Weaver, Kurt L.; Williams, Shawn P.; Wisely, G. Bruce; Xu, Robert; Shewchuk, Lisa M.

2007-01-01

Methods presented for growing protein–ligand complexes fall into the categories of co-expression of the protein with the ligands of interest, use of the ligands during protein purification, cocrystallization and soaking the ligands into existing crystals. Obtaining diffraction-quality crystals has long been a bottleneck in solving the three-dimensional structures of proteins. Often proteins may be stabilized when they are complexed with a substrate, nucleic acid, cofactor or small molecule. These ligands, on the other hand, have the potential to induce significant conformational changes to the protein and ab initio screening may be required to find a new crystal form. This paper presents an overview of strategies in the following areas for obtaining crystals of protein–ligand complexes: (i) co-expression of the protein with the ligands of interest, (ii) use of the ligands during protein purification, (iii) cocrystallization and (iv) soaks

Differentiation potential of STRO-1+ dental pulp stem cells changes during cell passaging

Directory of Open Access Journals (Sweden)

Wang Ruoning

2010-05-01

Full Text Available Abstract Background Dental pulp stem cells (DPSCs can be driven into odontoblast, osteoblast, and chondrocyte lineages in different inductive media. However, the differentiation potential of naive DPSCs after serial passaging in the routine culture system has not been fully elucidated. Results DPSCs were isolated from human/rat dental pulps by the magnetic activated cell sorting based on STRO-1 expression, cultured and passaged in the conventional culture media. The biological features of STRO-1+ DPSCs at the 1st and 9th passages were investigated. During the long-term passage, the proliferation ability of human STRO-1+ DPSCs was downregulated as indicated by the growth kinetics. When compared with STRO-1+ DPSCs at the 1st passage (DPSC-P1, the expression of mature osteoblast-specific genes/proteins (alkaline phosphatase, bone sialoprotein, osterix, and osteopontin, odontoblast-specific gene/protein (dentin sialophosphoprotein and dentin sialoprotein, and chondrocyte-specific gene/protein (type II collagen was significantly upregulated in human STRO-1+ DPSCs at the 9th passage (DPSC-P9. Furthermore, human DPSC-P9 cells in the mineralization-inducing media presented higher levels of alkaline phosphatase at day 3 and day 7 respectively, and produced more mineralized matrix than DPSC-P9 cells at day 14. In vivo transplantation results showed that rat DPSC-P1 cell pellets developed into dentin, bone and cartilage structures respectively, while DPSC-P9 cells can only generate bone tissues. Conclusions These findings suggest that STRO-1+ DPSCs consist of several interrelated subpopulations which can spontaneously differentiate into odontoblasts, osteoblasts, and chondrocytes. The differentiation capacity of these DPSCs changes during cell passaging, and DPSCs at the 9th passage restrict their differentiation potential to the osteoblast lineage in vivo.

Hydroacoustic Evaluation of Juvenile Salmonid Passage and Distribution at Lookout Point Dam, 2010

Energy Technology Data Exchange (ETDEWEB)

Khan, Fenton; Johnson, Gary E.; Royer, Ida M.; Hughes, James S.; Fischer, Eric S.; Trott, Donna M.; Ploskey, Gene R.

2012-05-31

Pacific Northwest National Laboratory evaluated juvenile salmonid passage and distribution at Lookout Point Dam (LOP) on the Middle Fork Willamette River for the U.S. Army Corps of Engineers, Portland District (USACE), to provide data to support decisions on long-term measures to enhance downstream passage at LOP and others dams in USACE's Willamette Valley Project. This study was conducted in response to the listing of Upper Willamette River Spring Chinook salmon (Oncorhynchus tshawytscha) and Upper Willamette River steelhead (O. mykiss) as threatened under the Endangered Species Act. We conducted a hydroacoustic evaluation of juvenile salmonid passage and distribution at LOP during February 2010 through January 2011. Findings from this 1 year of study should be applied carefully because annual variation can be expected due to variability in adult salmon escapement, egg-to-fry and fry-to-smolt survival rates, reservoir rearing and predation, dam operations, and weather. Fish passage rates for smolt-size fish (> {approx}90 mm and < 300 mm) were highest during December-January and lowest in mid-summer through early fall. Passage peaks were also evident in early spring, early summer, and late fall. During the entire study period, an estimated total of 142,463 fish {+-} 4,444 (95% confidence interval) smolt-size fish passed through turbine penstock intakes. Of this total, 84% passed during December-January. Run timing for small-size fish ({approx}65-90 mm) peaked (702 fish) on December 18. Diel periodicity of smolt-size fish showing crepuscular peaks was evident in fish passage into turbine penstock intakes. Relatively few fish passed into the Regulating Outlets (ROs) when they were open in summer (2 fish/d) and winter (8 fish/d). Overall, when the ROs were open, RO efficiency (RO passage divided by total project passage) was 0.004. In linear regression analyses, daily fish passage (turbines and ROs combined) for smolt-size fish was significantly related to

Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage

DEFF Research Database (Denmark)

Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf

2015-01-01

, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. METHODS: In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface...

Targeting interleukin-11 receptor in leukemia and lymphoma: A functional ligand-directed study and hematopathology analysis of patient-derived specimens

Science.gov (United States)

Karjalainen, Katja; Jaalouk, Diana E.; Bueso-Ramos, Carlos; Bover, Laura; Sun, Yan; Kuniyasu, Akihiko; Driessen, Wouter H. P.; Cardó-Vila, Marina; Rietz, Cecilia; Zurita, Amado J.; O’Brien, Susan; Kantarjian, Hagop M.; Cortes, Jorge E.; Calin, George A.; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2015-01-01

Purpose The interleukin-11 receptor (IL-11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here we evaluated the IL-11R as a candidate therapeutic target in human leukemia and lymphoma. Experimental Design and Results First, we show that the IL-11R protein is expressed in a variety of human leukemia- and lymphoma derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, while expression is absent from non-malignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11) specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL-11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analog with an apparent improved anti-leukemia cell profile. Conclusion These results indicate (i) that the IL-11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. PMID:25779950

Targeting IL11 Receptor in Leukemia and Lymphoma: A Functional Ligand-Directed Study and Hematopathology Analysis of Patient-Derived Specimens.

Science.gov (United States)

Karjalainen, Katja; Jaalouk, Diana E; Bueso-Ramos, Carlos; Bover, Laura; Sun, Yan; Kuniyasu, Akihiko; Driessen, Wouter H P; Cardó-Vila, Marina; Rietz, Cecilia; Zurita, Amado J; O'Brien, Susan; Kantarjian, Hagop M; Cortes, Jorge E; Calin, George A; Koivunen, Erkki; Arap, Wadih; Pasqualini, Renata

2015-07-01

The IL11 receptor (IL11R) is an established molecular target in primary tumors of bone, such as osteosarcoma, and in secondary bone metastases from solid tumors, such as prostate cancer. However, its potential role in management of hematopoietic malignancies has not yet been determined. Here, we evaluated the IL11R as a candidate therapeutic target in human leukemia and lymphoma. First, we show that the IL11R protein is expressed in a variety of human leukemia- and lymphoma-derived cell lines and in a large panel of bone marrow samples from leukemia and lymphoma patients, whereas expression is absent from nonmalignant control bone marrow. Moreover, a targeted peptidomimetic prototype (termed BMTP-11), specifically bound to leukemia and lymphoma cell membranes, induced ligand-receptor internalization mediated by the IL11R, and resulted in a specific dose-dependent cell death induction in these cells. Finally, a pilot drug lead-optimization program yielded a new myristoylated BMTP-11 analogue with an apparent improved antileukemia cell profile. These results indicate (i) that the IL11R is a suitable cell surface target for ligand-directed applications in human leukemia and lymphoma and (ii) that BMTP-11 and its derivatives have translational potential against this group of malignant diseases. ©2015 American Association for Cancer Research.

Walla Walla River Fish Passage Operations Program, 2002-2003 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

Bronson, James P. (Confederated Tribes of the Umatilla Indian Reservation, Department of Natural Resources, Pendleton, OR); Duke, Bill B. (Oregon Department of Fish and Wildlife, Pendleton, OR)

2004-03-01

In the late 1990's, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate fish migration conditions in the basin. The migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow requirements, and initiating trap and haul efforts. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survival of migrating adult and juvenile salmonids in the Walla Walla River basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage criteria and passage and trapping facility design and operation. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. During the 2002-2003 project year, there were 545 adult summer steelhead (Oncorhynchus mykiss), 29 adult bull trout (Salvelinus confluentus); 1 adult and 1 jack spring chinook (O. tshawytscha) enumerated at the Nursery Bridge Dam fishway adult trap between January 1 and June 23, 2003. Summer steelhead and spring chinook were observed moving upstream while bull trout were observed moving both upstream and downstream of the facility. Operation of the Little Walla Walla River juvenile trap for trap and haul purposes was not necessary this year. The project transported 21 adult spring chinook from Ringold Springs Hatchery and 281 from Threemile Dam to the South Fork Walla Walla Brood Holding Facility. Of these, 290 were outplanted in August for natural spawning in the basin.

Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.

Science.gov (United States)

Chen, Qiang; Kinde, Monica N; Arjunan, Palaniappa; Wells, Marta M; Cohen, Aina E; Xu, Yan; Tang, Pei

2015-09-08

Pentameric ligand-gated ion channels (pLGICs) are targets of general anesthetics, but molecular mechanisms underlying anesthetic action remain debatable. We found that ELIC, a pLGIC from Erwinia chrysanthemi, can be functionally inhibited by isoflurane and other anesthetics. Structures of ELIC co-crystallized with isoflurane in the absence or presence of an agonist revealed double isoflurane occupancies inside the pore near T237(6') and A244(13'). A pore-radius contraction near the extracellular entrance was observed upon isoflurane binding. Electrophysiology measurements with a single-point mutation at position 6' or 13' support the notion that binding at these sites renders isoflurane inhibition. Molecular dynamics simulations suggested that isoflurane binding was more stable in the resting than in a desensitized pore conformation. This study presents compelling evidence for a direct pore-binding mechanism of isoflurane inhibition, which has a general implication for inhibitory action of general anesthetics on pLGICs.

Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

International Nuclear Information System (INIS)

Poór, Miklós; Li, Yin; Matisz, Gergely; Kiss, László; Kunsági-Máté, Sándor; Kőszegi, Tamás

2014-01-01

Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin

Formation of Hyaline Cartilage Tissue by Passaged Human Osteoarthritic Chondrocytes.

Science.gov (United States)

Bianchi, Vanessa J; Weber, Joanna F; Waldman, Stephen D; Backstein, David; Kandel, Rita A

2017-02-01

When serially passaged in standard monolayer culture to expand cell number, articular chondrocytes lose their phenotype. This results in the formation of fibrocartilage when they are used clinically, thus limiting their use for cartilage repair therapies. Identifying a way to redifferentiate these cells in vitro is critical if they are to be used successfully. Transforming growth factor beta (TGFβ) family members are known to be crucial for regulating differentiation of fetal limb mesenchymal cells and mesenchymal stromal cells to chondrocytes. As passaged chondrocytes acquire a progenitor-like phenotype, the hypothesis of this study was that TGFβ supplementation will stimulate chondrocyte redifferentiation in vitro in serum-free three-dimensional (3D) culture. Human articular chondrocytes were serially passaged twice (P2) in monolayer culture. P2 cells were then placed in high-density (3D) culture on top of membranes (Millipore) and cultured for up to 6 weeks in chemically defined serum-free redifferentiation media (SFRM) in the presence or absence of TGFβ. The tissues were evaluated histologically, biochemically, by immunohistochemical staining, and biomechanically. Passaged human chondrocytes cultured in SFRM supplemented with 10 ng/mL TGFβ3 consistently formed a continuous layer of articular-like cartilage tissue rich in collagen type 2 and aggrecan and lacking collagen type 1 and X in the absence of a scaffold. The tissue developed a superficial zone characterized by expression of lubricin and clusterin with horizontally aligned collagen fibers. This study suggests that passaged human chondrocytes can be used to bioengineer a continuous layer of articular cartilage-like tissue in vitro scaffold free. Further study is required to evaluate their ability to repair cartilage defects in vivo.

Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites.

Science.gov (United States)

Marsh, Lorraine

2015-01-01

Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorable ΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorable ΔG because of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total binding ΔG arising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where "nonspecific" interactions contribute to biological function.

Alternatives and passages

DEFF Research Database (Denmark)

Hansbøl, Mikala

2010-01-01

While much research into serious games focus on following teaching and/or learning activities, and particularly the human and institutional actors involved in these, the central actors of game based learning research (i.e. the games) seldom get much attention (unless the focus is so......-called "technological"). This brief positioning paper takes point of departure in an ongoing postdoc project following circulations and establishments of http://www.mingoville.com/ , which is a virtual universe with game based elements developed for beginning English teaching and learning.  The paper presents a Science...... and Technology Studies (STS) and Actor-Network-Theory (ANT) inspired approach to researching emerging passages between beginning English teaching and learning and Mingoville....

Effect of urea on protein-ligand association.

Science.gov (United States)

Stepanian, Lora; Son, Ikbae; Chalikian, Tigran V

2017-12-01

We combine experimental and theoretical approaches to investigate the influence of a cosolvent on a ligand-protein association event. We apply fluorescence measurements to determining the affinity of the inhibitor tri-N-acetylglucosamine [(GlcNAc) 3 ] for lysozyme at urea concentrations ranging from 0 to 8M. Notwithstanding that, at room temperature and neutral pH, lysozyme retains its native conformation up to the solubility limit of urea, the affinity of (GlcNAc) 3 for the protein steadily decreases as the concentration of urea increases. We analyze the urea dependence of the binding free energy within the framework of a simplified statistical thermodynamics-based model that accounts for the excluded volume effect and direct solute-solvent interactions. The analysis reveals that the detrimental action of urea on the inhibitor-lysozyme binding originates from competition between the free energy contributions of the excluded volume effect and direct solute-solvent interactions. The free energy contribution of direct urea-solute interactions narrowly overcomes the excluded volume contribution thereby resulting in urea weakening the protein-ligand association. More broadly, the successful application of the simple model employed in this work points to the possibility of its use in quantifying the stabilizing/destabilizing action of individual cosolvents on biochemical folding and binding reactions. Copyright © 2016 Elsevier B.V. All rights reserved.

LigandRFs: random forest ensemble to identify ligand-binding residues from sequence information alone

KAUST Repository

Chen, Peng; Huang, Jianhua Z; Gao, Xin

2014-01-01

Protein-ligand binding is important for some proteins to perform their functions. Protein-ligand binding sites are the residues of proteins that physically bind to ligands. Despite of the recent advances in computational prediction

Using chemical shift perturbation to characterise ligand binding.

Science.gov (United States)

Williamson, Mike P

2013-08-01

Chemical shift perturbation (CSP, chemical shift mapping or complexation-induced changes in chemical shift, CIS) follows changes in the chemical shifts of a protein when a ligand is added, and uses these to determine the location of the binding site, the affinity of the ligand, and/or possibly the structure of the complex. A key factor in determining the appearance of spectra during a titration is the exchange rate between free and bound, or more specifically the off-rate koff. When koff is greater than the chemical shift difference between free and bound, which typically equates to an affinity Kd weaker than about 3μM, then exchange is fast on the chemical shift timescale. Under these circumstances, the observed shift is the population-weighted average of free and bound, which allows Kd to be determined from measurement of peak positions, provided the measurements are made appropriately. (1)H shifts are influenced to a large extent by through-space interactions, whereas (13)Cα and (13)Cβ shifts are influenced more by through-bond effects. (15)N and (13)C' shifts are influenced both by through-bond and by through-space (hydrogen bonding) interactions. For determining the location of a bound ligand on the basis of shift change, the most appropriate method is therefore usually to measure (15)N HSQC spectra, calculate the geometrical distance moved by the peak, weighting (15)N shifts by a factor of about 0.14 compared to (1)H shifts, and select those residues for which the weighted shift change is larger than the standard deviation of the shift for all residues. Other methods are discussed, in particular the measurement of (13)CH3 signals. Slow to intermediate exchange rates lead to line broadening, and make Kd values very difficult to obtain. There is no good way to distinguish changes in chemical shift due to direct binding of the ligand from changes in chemical shift due to allosteric change. Ligand binding at multiple sites can often be characterised, by

Migratory delay leads to reduced passage success of Atlantic salmon smolts at a hydroelectric dam

Science.gov (United States)

Nyqvist, Daniel; Greenberg, L.; Goerig, E.; Calles, O.; Bergman, E.; Ardren, William R.; Castro-Santos, Theodore R.

2017-01-01

Passage of fish through hydropower dams is associated with mortality, delay, increased energy expenditure and migratory failure for migrating fish and the need for remedial measures for both upstream and downstream migration is widely recognised. A functional fish passage must ensure safe and timely passage routes that a substantial portion of migrating fish will use. Passage solutions must address not only the number or percentage of fish that successfully pass a barrier, but also the time it takes to pass. Here, we used radiotelemetry to study the functionality of a fish bypass for downstream-migrating wild-caught and hatchery-released Atlantic salmon smolts. We used time-to-event analysis to model the influence of fish characteristics and environmental variables on the rates of a series of events associated with dam passage. Among the modelled events were approach rate to the bypass entry zone, retention rates in both the forebay and the entry zone and passage rates. Despite repeated attempts, only 65% of the tagged fish present in the forebay passed the dam. Fish passed via the bypass (33%), via spill (18%) and via turbines (15%). Discharge was positively related to approach, passage and retention rates. We did not detect any differences between wild and hatchery fish. Even though individual fish visited the forebay and the entry zone on multiple occasions, most fish passed during the first exposures to these zones. This study underscores the importance of timeliness to passage success and the usefulness of time-to-event analysis for understanding factors governing passage performance.

Quantifying high-affinity binding of hydrophobic ligands by isothermal titration calorimetry.

Science.gov (United States)

Krainer, Georg; Broecker, Jana; Vargas, Carolyn; Fanghänel, Jörg; Keller, Sandro

2012-12-18

A fast and reliable quantification of the binding thermodynamics of hydrophobic high-affinity ligands employing a new calorimetric competition experiment is described. Although isothermal titration calorimetry is the method of choice for a quantitative characterization of intermolecular interactions in solution, a reliable determination of a dissociation constant (K(D)) is typically limited to the range 100 μM > K(D) > 1 nM. Interactions displaying higher or lower K(D) values can be assessed indirectly, provided that a suitable competing ligand is available whose K(D) falls within the directly accessible affinity window. This established displacement assay, however, requires the high-affinity ligand to be soluble at high concentrations in aqueous buffer and, consequently, poses serious problems in the study of protein binding involving small-molecule ligands dissolved in organic solvents--a familiar case in many drug-discovery projects relying on compound libraries. The calorimetric competition assay introduced here overcomes this limitation, thus allowing for a detailed thermodynamic description of high-affinity receptor-ligand interactions involving poorly water-soluble compounds. Based on a single titration of receptor into a dilute mixture of the two competing ligands, this competition assay provides accurate and precise values for the dissociation constants and binding enthalpies of both high- and moderate-affinity ligands. We discuss the theoretical background underlying the approach, demonstrate its practical application to metal ion chelation and high-affinity protein-inhibitor interactions, and explore its potential and limitations with the aid of simulations and statistical analyses.

Contrasting roles for TLR ligands in HIV-1 pathogenesis.

Directory of Open Access Journals (Sweden)

Beda Brichacek

2010-09-01

Full Text Available The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs. Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs 5 and 9, we examined their effect on human immunodeficiency virus (HIV-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist treatment enhanced replication of CC chemokine receptor 5 (CCR 5-tropic and CXC chemokine receptor 4 (CXCR4-tropic HIV-1, treatment with oligodeoxynucleotide (ODN M362 (TLR9 agonist suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.

Ligand recognition by RAR and RXR receptors: binding and selectivity.

Science.gov (United States)

Sussman, Fredy; de Lera, Angel R

2005-10-06

Fundamental biological functions, most notably embriogenesis, cell growth, cell differentiation, and cell apoptosis, are in part regulated by a complex genomic network that starts with the binding (and activation) of retinoids to their cognate receptors, members of the superfamily of nuclear receptors. We have studied ligand recognition of retinoic receptors (RXRalpha and RARgamma) using a molecular-mechanics-based docking method. The protocol used in this work is able to rank the affinity of pairs of ligands for a single retinoid receptor, the highest values corresponding to those that adapt better to the shape of the binding site and generate the optimal set of electrostatic and apolar interactions with the receptor. Moreover, our studies shed light onto some of the energetic contributions to retinoid receptor ligand selectivity. In this regard we show that there is a difference in polarity between the binding site regions that anchor the carboxylate in RAR and RXR, which translates itself into large differences in the energy of interaction of both receptors with the same ligand. We observe that the latter energy change is canceled off by the solvation energy penalty upon binding. This energy compensation is borne out as well by experiments that address the effect of site-directed mutagenesis on ligand binding to RARgamma. The hypothesis that the difference in binding site polarity might be exploited to build RXR-selective ligands is tested with some compounds having a thiazolidinedione anchoring group.

Protein-ligand interfaces are polarized: discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes.

Science.gov (United States)

Raschka, Sebastian; Wolf, Alex J; Bemister-Buffington, Joseph; Kuhn, Leslie A

2018-04-01

Understanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze data across non-homologous proteins in complex with small biological ligands to address observations made in our inhibitor discovery projects: that proteins favor donating H-bonds to ligands and avoid using groups with both H-bond donor and acceptor capacity. The resulting clear and significant chemical group matching preferences elucidate the code for protein-native ligand binding, similar to the dominant patterns found in nucleic acid base-pairing. On average, 90% of the keto and carboxylate oxygens occurring in the biological ligands formed direct H-bonds to the protein. A two-fold preference was found for protein atoms to act as H-bond donors and ligand atoms to act as acceptors, and 76% of all intermolecular H-bonds involved an amine donor. Together, the tight chemical and geometric constraints associated with satisfying donor groups generate a hydrogen-bonding lock that can be matched only by ligands bearing the right acceptor-rich key. Measuring an index of H-bond preference based on the observed chemical trends proved sufficient to predict other protein-ligand complexes and can be used to guide molecular design. The resulting Hbind and Protein Recognition Index software packages are being made available for rigorously defining intermolecular H-bonds and measuring the extent to which H-bonding patterns in a given complex match the preference key.

Protein-ligand interfaces are polarized: discovery of a strong trend for intermolecular hydrogen bonds to favor donors on the protein side with implications for predicting and designing ligand complexes

Science.gov (United States)

Raschka, Sebastian; Wolf, Alex J.; Bemister-Buffington, Joseph; Kuhn, Leslie A.

2018-02-01

Understanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze data across non-homologous proteins in complex with small biological ligands to address observations made in our inhibitor discovery projects: that proteins favor donating H-bonds to ligands and avoid using groups with both H-bond donor and acceptor capacity. The resulting clear and significant chemical group matching preferences elucidate the code for protein-native ligand binding, similar to the dominant patterns found in nucleic acid base-pairing. On average, 90% of the keto and carboxylate oxygens occurring in the biological ligands formed direct H-bonds to the protein. A two-fold preference was found for protein atoms to act as H-bond donors and ligand atoms to act as acceptors, and 76% of all intermolecular H-bonds involved an amine donor. Together, the tight chemical and geometric constraints associated with satisfying donor groups generate a hydrogen-bonding lock that can be matched only by ligands bearing the right acceptor-rich key. Measuring an index of H-bond preference based on the observed chemical trends proved sufficient to predict other protein-ligand complexes and can be used to guide molecular design. The resulting Hbind and Protein Recognition Index software packages are being made available for rigorously defining intermolecular H-bonds and measuring the extent to which H-bonding patterns in a given complex match the preference key.

Is motivation important to brook trout passage through culverts?

Science.gov (United States)

Goerig, Elsa; Castro-Santos, Theodore R.

2017-01-01

Culverts can restrict movement of stream-dwelling fish. Motivation to enter and ascend these structures is an essential precursor for successful passage. However, motivation is challenging to quantify. Here, we use attempt rate to assess motivation of 447 brook trout (Salvelinus fontinalis) entering three culverts under a range of hydraulic, environmental, and biological conditions. A passive integrated transponder system allowed for the identification of passage attempts and success of individual fish. Attempt rate was quantified using time-to-event analysis allowing for time-varying covariates and recurrent events. Attempt rate was greatest during the spawning period, at elevated discharge, at dusk, and for longer fish. It decreased during the day and with increasing number of conspecifics downstream of the culvert. Results also show a positive correlation between elevated motivation and successful passage. This study enhances understanding of factors influencing brook trout motivation to ascend culverts and shows that attempt rate is a dynamic phenomenon, variable over time and among individuals. It also presents methods that could be used to investigate other species’ motivation to pass natural or anthropogenic barriers.

Lake Roosevelt Rainbow Trout : Habitat/Passage Improvement Project Annual Report 2000.

Energy Technology Data Exchange (ETDEWEB)

Sear, Sheri

2001-02-01

Lake Franklin D. Roosevelt was created with the completion of the Grand Coulee Dam in 1942. The lake stretches 151 miles up-stream to the International border between the United States and Canada at the 49th parallel. Increased recreational use, subsistence and sport fishing has resulted in intense interest and possible exploitation of the resources within the lake. Previous studies of the lake and its fishery have been limited. Early studies indicate that natural reproduction within the lake and tributaries are not sufficient to support a rainbow trout (Onchoryhnchus mykiss) fishery (Scholz et. al., 1988). These studies indicate that the rainbow trout population may be limited by lack of suitable habitat for spawning and rearing (Scholz et. al., 1988). The initial phase of this project (Phase I, baseline data collection- 1990-91) was directed at the assessment of limiting factors such as quality and quantity of available spawning gravel, identification of passage barriers, and assessment of other limiting factors. Population estimates were conducted using the Seber/LeCren removal/depletion method. After the initial assessment of stream parameters, several streams were selected for habitat/passage improvement projects (Phase II, implementation-1992-96). At the completion of project habitat improvements, the final phase (Phase III, monitoring) began. This phase will assess changes and gauge the success achieved through the improvements. The objective of the project is to correct passage barriers and improve habitat conditions of selected tributaries to Lake Roosevelt for adfluvial rainbow trout that utilize tributary streams for spawning and rearing. Streams with restorable habitats were selected for improvements. Completion of improvement efforts should increase the adfluvial rainbow trout contribution to the resident fishery in Lake Roosevelt. Three co-operating agencies, the Confederated Tribes of the Colville Reservation (CCT), the Spokane Tribe of Indians (STI

Lake Roosevelt Rainbow Trout : Habitat/Passage Improvement Project Annual Report 1999.

Energy Technology Data Exchange (ETDEWEB)

Jones, Charles D.

2000-02-01

Lake Franklin D. Roosevelt was created with the completion of the Grand Coulee Dam in 1942. The lake stretches 151 miles up-stream to the International border between the United States and Canada at the 49th parallel. Increased recreational use, subsistence and sport fishing has resulted in intense interest and possible exploitation of the resources within the lake. Previous studies of the lake and its fishery have been limited. Early studies indicate that natural reproduction within the lake and tributaries are not sufficient to support a rainbow trout (Onchoryhnchus mykiss) fishery (Scholz et. al., 1988). These studies indicate that the rainbow trout population may be limited by lack of suitable habitat for spawning and rearing (Scholz et. al., 1988). The initial phase of this project (Phase I, baseline data collection- 1990-91) was directed at the assessment of limiting factors such as quality and quantity of available spawning gravel, identification of passage barriers, and assessment of other limiting factors. Population estimates were conducted using the Seber/LeCren removal/depletion method. After the initial assessment of stream parameters, several streams were selected for habitat/passage improvement projects (Phase II, implementation-1992-96). At the completion of project habitat improvements, the final phase (Phase III, monitoring) began. This phase will assess changes and gauge the success achieved through the improvements. The objective of the project is to correct passage barriers and improve habitat conditions of selected tributaries to Lake Roosevelt for adfluvial rainbow trout that utilize tributary streams for spawning and rearing. Streams with restorable habitats were selected for improvements. Completion of improvement efforts should increase the adfluvial rainbow trout contribution to the resident fishery in Lake Roosevelt. Three co-operating agencies, the Confederated Tribes of the Colville Reservation (CCT), the Spokane Tribe of Indians (STI

Seeking Ligand Bias: Assessing GPCR Coupling to Beta-Arrestins for Drug Discovery

OpenAIRE

Bohn, Laura M.; McDonald, Patricia H.

2010-01-01

G protein-coupled receptors (GPCR) are the major site of action for endogenous hormones and neurotransmitters. Early drug discovery efforts focused on determining whether ligands could engage G protein coupling and subsequently activate or inhibit cognate “second messengers.” Gone are those simple days as we now realize that receptors can also couple βarrestins. As we delve into the complexity of ligand-directed signaling and receptosome scaffolds, we are faced with what may seem like endless...

An Economic Analysis of Container Shipping Through Canadian Northwest Passage

Directory of Open Access Journals (Sweden)

Dongqin Lu

2014-12-01

This paper considers Canada's sovereignty in matters of navigation over the waters at the Arctic Archipelago, in the form of a toll fee for passage usage. We concluded that the NWP has an advantage over the Panama Canal if it is open for free international passage, regardless of ship size. However, if it is not free, its advantages depend on its toll fee. The lower the toll fee is, the more advantages the NWP will boast.

Fire passage on geomorphic fractures in Cerrado: effect on vegetation

OpenAIRE

Otacílio Antunes Santana; José Marcelo Imaña Encinas; Flávio Luiz de Souza Silveira

2017-01-01

Geomorphic fracture is a natural geologic formation that sometimes forms a deep fissure in the rock with the establishment of soil and vegetation. The objective of this work was to analyze vegetation within geomorphic fractures under the effect of wildfire passage. The biometric variables evaluated before and after fire passage were: diameter, height, leaf area index, timber volume, grass biomass, number of trees and shrubs and of species. Results (in fractures) were compared to adjacent area...

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

KAUST Repository

Li, Huaifeng

2014-12-01

Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands\\' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

A new class of PN3-pincer ligands for metal–ligand cooperative catalysis

KAUST Repository

Li, Huaifeng; Zheng, Bin; Huang, Kuo-Wei

2014-01-01

Work on a new class of PN3-pincer ligands for metal-ligand cooperative catalysis is reviewed. While the field of the pyridine-based PN3-transition metal pincer complexes is still relatively young, many important applications of these complexes have already emerged. In several cases, the PN3-pincer complexes for metal-ligand cooperative catalysis result in significantly improved or unprecedented activities. The synthesis and coordination chemistry of PN3-pincer ligands are briefly summarized first to cover the synthetic routes for their preparation, followed by a focus review on their applications in catalysis. A specific emphasis is placed on the later section about the role of PN3-pincer ligands' dearomatization-rearomatization steps during the catalytic cycles. The mechanistic insights from density functional theory (DFT) calculations are also discussed.

Architecture effects on multivalent interactions by polypeptide-based multivalent ligands

Science.gov (United States)

Liu, Shuang

protein materials, including structural as well as functional proteins. Therefore, polypeptide-based multivalent scaffolds are used to display ligands to assess the contribution of different architectural parameters to the multivalent binding events. In this work, a family of alanine-rich alpha-helical glycopolypeptides was designed and synthesized by a combination of protein engineering and chemical coupling, to display two types of saccharide ligands for two different multivalent binding systems. The valencies, chain length and spacing between adjacent ligands of these multivalent ligands were designed in order to study architecture effects on multivalent interactions. The polypeptides and their glycoconjugates were characterized via various methods, including SDS-PAGE, NMR, HPLC, amino acid analysis (AAA), MALDI, circular dichroism (CD) and GPC. In the first multivalent binding system, cholera toxin B pentamer (CT B5) was chosen to be the protein receptor due to its well-characterized structure, lack of significant steric interference of binding to multiple binding sites, and requirement of only simple monosaccharide as ligands. Galactopyranoside was incorporated into polypeptide scaffolds through amine-carboxylic acid coupling to the side chains of glutamic acid residues. The inhibition and binding to CT B5 of these glycopolypeptide ligands were evaluated by direct enzyme-linked assay (DELA). As a complement method, weak affinity chromatography (WAC) was also used to evaluate glycopolypeptides binding to a CT B5 immobilized column. The architecture effects on CT B 5 inhibition are discussed. In the second system, cell surface receptor L-selectin was targeted by polypeptide-based multivalent ligands containing disulfated galactopyranoside ligands, due to its important roles in various immunological activities. The effects of glycopolypeptide architectural variables L-selectin shedding were evaluated via ELISA-based assays. These polypeptide-based multivalent ligands

Statistical Analysis of the First Passage Path Ensemble of Jump Processes

Science.gov (United States)

von Kleist, Max; Schütte, Christof; Zhang, Wei

2018-02-01

The transition mechanism of jump processes between two different subsets in state space reveals important dynamical information of the processes and therefore has attracted considerable attention in the past years. In this paper, we study the first passage path ensemble of both discrete-time and continuous-time jump processes on a finite state space. The main approach is to divide each first passage path into nonreactive and reactive segments and to study them separately. The analysis can be applied to jump processes which are non-ergodic, as well as continuous-time jump processes where the waiting time distributions are non-exponential. In the particular case that the jump processes are both Markovian and ergodic, our analysis elucidates the relations between the study of the first passage paths and the study of the transition paths in transition path theory. We provide algorithms to numerically compute statistics of the first passage path ensemble. The computational complexity of these algorithms scales with the complexity of solving a linear system, for which efficient methods are available. Several examples demonstrate the wide applicability of the derived results across research areas.

Reduction of dinitrogen ligands

International Nuclear Information System (INIS)

Richards, R.L.

1983-01-01

Processes of dinitrogen ligand reduction in complexes of transition metals are considered. The basic character of the dinitrogen ligand is underlined. Data on X-ray photoelectronic spectroscopy and intensities of bands ν (N 2 ) in IR-spectra of nitrogen complexes are given. The mechanism of protonation of an edge dinitrogen ligand is discussed. Model systems and mechanism of nitrogenogenase are compared

"The Caterpillar": A Novel Reading Passage for Assessment of Motor Speech Disorders

Science.gov (United States)

Patel, Rupal; Connaghan, Kathryn; Franco, Diana; Edsall, Erika; Forgit, Dory; Olsen, Laura; Ramage, Lianna; Tyler, Emily; Russell, Scott

2013-01-01

Purpose: A review of the salient characteristics of motor speech disorders and common assessment protocols revealed the need for a novel reading passage tailored specifically to differentiate between and among the dysarthrias (DYSs) and apraxia of speech (AOS). Method: "The Caterpillar" passage was designed to provide a contemporary, easily read,…

Neutron Imaging for Selective Laser Melting Inconel Hardware with Internal Passages

Science.gov (United States)

Tramel, Terri L.; Norwood, Joseph K.; Bilheux, Hassina

2014-01-01

Additive Manufacturing is showing great promise for the development of new innovative designs and large potential life cycle cost reduction for the Aerospace Industry. However, more development work is required to move this technology into space flight hardware production. With selective laser melting (SLM), hardware that once consisted of multiple, carefully machined and inspected pieces, joined together can be made in one part. However standard inspection techniques cannot be used to verify that the internal passages are within dimensional tolerances or surface finish requirements. NASA/MSFC traveled to Oak Ridge National Lab's (ORNL) Spallation Neutron Source to perform some non-destructive, proof of concept imaging measurements to assess the capabilities to understand internal dimensional tolerances and internal passages surface roughness. This presentation will describe 1) the goals of this proof of concept testing, 2) the lessons learned when designing and building these Inconel 718 test specimens to minimize beam time, 3) the neutron imaging test setup and test procedure to get the images, 4) the initial results in images, volume and a video, 4) the assessment of using this imaging technique to gather real data for designing internal flow passages in SLM manufacturing aerospace hardware, and lastly 5) how proper cleaning of the internal passages is critically important. In summary, the initial results are very promising and continued development of a technique to assist in SLM development for aerospace components is desired by both NASA and ORNL. A plan forward that benefits both ORNL and NASA will also be presented, based on the promising initial results. The initial images and volume reconstruction showed that clean, clear images of the internal passages geometry are obtainable. These clear images of the internal passages of simple geometries will be compared to the build model to determine any differences. One surprising result was that a new cleaning

Time Perspective and Emotion Regulation as Predictors of Age-Related Subjective Passage of Time.

Science.gov (United States)

Wittmann, Marc; Rudolph, Tina; Linares Gutierrez, Damisela; Winkler, Isabell

2015-12-17

Hardly any empirical work exists concerning the relationship between the intra-individually stable time perspective relating to the past, present, and future and the subjective speed of time passing in everyday life. Moreover, studies consistently show that the subjective passage of time over the period of the last ten years speeds up as we get older. Modulating variables influencing this phenomenon are still unknown. To investigate these two unresolved issues, we conducted an online survey with n = 423 participants ranging in age between 17 and 81 assessing trait time perspective of the past, present, and future, and relating these subscales with a battery of measures pertaining to the subjective passage of time. Moreover, the subjective passage of time as an age-dependent variable was probed in relationship to emotion awareness, appraisal and regulation. Results show how present hedonism is linked with having fewer routines in life and a faster passage of the last week; the past negative perspective is related to time pressure, time expansion and more routine; a pronounced future perspective is related to a general faster passage of time. Importantly, increased emotion regulation and a balanced time perspective are related to a slower passage of the last ten years. These novel findings are discussed within models of time perception and the time perspective.

Ligand modeling and design

Energy Technology Data Exchange (ETDEWEB)

Hay, B.P. [Pacific Northwest National Lab., Richland, WA (United States)

1997-10-01

The purpose of this work is to develop and implement a molecular design basis for selecting organic ligands that would be used in the cost-effective removal of specific radionuclides from nuclear waste streams. Organic ligands with metal ion specificity are critical components in the development of solvent extraction and ion exchange processes that are highly selective for targeted radionuclides. The traditional approach to the development of such ligands involves lengthy programs of organic synthesis and testing, which in the absence of reliable methods for screening compounds before synthesis, results in wasted research effort. The author`s approach breaks down and simplifies this costly process with the aid of computer-based molecular modeling techniques. Commercial software for organic molecular modeling is being configured to examine the interactions between organic ligands and metal ions, yielding an inexpensive, commercially or readily available computational tool that can be used to predict the structures and energies of ligand-metal complexes. Users will be able to correlate the large body of existing experimental data on structure, solution binding affinity, and metal ion selectivity to develop structural design criteria. These criteria will provide a basis for selecting ligands that can be implemented in separations technologies through collaboration with other DOE national laboratories and private industry. The initial focus will be to select ether-based ligands that can be applied to the recovery and concentration of the alkali and alkaline earth metal ions including cesium, strontium, and radium.

Ligand identification using electron-density map correlations

International Nuclear Information System (INIS)

Terwilliger, Thomas C.; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

2007-01-01

An automated ligand-fitting procedure is applied to (F o − F c )exp(iϕ c ) difference density for 200 commonly found ligands from macromolecular structures in the Protein Data Bank to identify ligands from density maps. A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F o − F c )exp(iϕ c ) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule

Diffusive spatio-temporal noise in a first-passage time model for intracellular calcium release

KAUST Repository

Flegg, Mark B.

2013-01-01

The intracellular release of calcium from the endoplasmic reticulum is controlled by ion channels. The resulting calcium signals exhibit a rich spatio-temporal signature, which originates at least partly from microscopic fluctuations. While stochasticity in the gating transition of ion channels has been incorporated into many models, the distribution of calcium is usually described by deterministic reaction-diffusion equations. Here we test the validity of the latter modeling approach by using two different models to calculate the frequency of localized calcium signals (calcium puffs) from clustered IP3 receptor channels. The complexity of the full calcium system is here limited to the basic opening mechanism of the ion channels and, in the mathematical reduction simplifies to the calculation of a first passage time. Two models are then studied: (i) a hybrid model, where channel gating is treated stochastically, while calcium concentration is deterministic and (ii) a fully stochastic model with noisy channel gating and Brownian calcium ion motion. The second model utilises the recently developed two-regime method [M. B. Flegg, S. J. Chapman, and R. Erban, "The two-regime method for optimizing stochastic reaction-diffusion simulations," J. R. Soc., Interface 9, 859-868 (2012)] in order to simulate a large domain with precision required only near the Ca2+ absorbing channels. The expected time for a first channel opening that results in a calcium puff event is calculated. It is found that for a large diffusion constant, predictions of the interpuff time are significantly overestimated using the model (i) with a deterministic non-spatial calcium variable. It is thus demonstrated that the presence of diffusive noise in local concentrations of intracellular Ca2+ ions can substantially influence the occurrence of calcium signals. The presented approach and results may also be relevant for other cell-physiological first-passage time problems with small ligand concentration

Passage and survival probabilities of juvenile Chinook salmon at Cougar Dam, Oregon, 2012

Science.gov (United States)

Beeman, John W.; Evans, Scott D.; Haner, Philip V.; Hansel, Hal C.; Hansen, Amy C.; Smith, Collin D.; Sprando, Jamie M.

2014-01-01

survival probabilities were estimated using the Route-Specific-Survival Model with data from surface-acclimated fish released near the water surface directly upstream of the temperature control tower (treatment group) and slightly downstream of the dam (control group). In this study, apparent survival is the joint probability of surviving and migrating through the study area during the life of the transmitters. Two rearing groups were used to enable sufficient sample sizes for the studies. The groups differed in feed type, and for the December study only, the rearing location. Fish from each group were divided nearly equally among all combinations of release sites, release times, and surgeons. The sizes, travel times, and survivals of the two rearing groups were similar. There were statistical differences in fish lengths and travel times of the two groups, but they were small and likely were not biologically meaningful. There also was evidence of a difference in single-release estimates of survival between the rearing groups during the December study, but the differences had little effect on the relative survival estimates so the analyses of passage and survival were based on data from the rearing groups pooled. Conditions during the December study were more conducive to passing volitionally migrating fish than conditions during the November study. The passage percentage of the fish released in the reservoir was similar between studies (about 70 percent), but the passage occurred in a median of 1.0 day during the December study and a median of 9.3 days during the November study. More than 93 percent of the dam passage of volitionally migrating fish occurred at night during each study. This finding corroborates results of previous studies at Cougar Dam and suggests that the operating conditions at night are most important to volitionally migrating fish, given the current configuration of the dam. Most fish released near the temperature control tower passed through the RO. A

Schiff base ligand

Indian Academy of Sciences (India)

Unknown

Low-temperature stoichiometric Schiff base reaction in air in 3 : 1 mole ratio between benz- aldehyde and triethylenetetramine (trien) in methanol yields a novel tetraaza µ-bis(bidentate) acyclic ligand L. It was .... electrochemical work was performed as reported in ..... change in ligand shape through change in oxidation.

The Influence of Tag Presence on the Mortality of Juvenile Chinook Salmon Exposed to Simulated Hydroturbine Passage: Implications for Survival Estimates and Management of Hydroelectric Facilities

Energy Technology Data Exchange (ETDEWEB)

Carlson, Thomas J.; Brown, Richard S.; Stephenson, John R.; Pflugrath, Brett D.; Colotelo, Alison HA; Gingerich, Andrew J.; Benjamin, Piper L.; Langeslay, Mike; Ahmann, Martin L.; Johnson, Robert L.; Skalski, John R.; Seaburg, Adam; Townsend, Richard L.

2012-05-01

Each year, millions of fish have telemetry tags (acoustic, radio, inductive) surgically implanted to assess their passage and survival through hydropower facilities. One route of passage of particular concern is through hydro turbines, in which fish may be exposed to a range of potential injuries, including barotraumas from rapid decompression. The change in pressure from acclimation to exposure (nadir) has been found to be an important factor in predicting the likelihood of mortality and injury for juvenile Chinook salmon undergoing rapid decompression associated with simulated turbine passage. The presence of telemetry tags has also been shown to influence the likelihood of injury and mortality for juvenile Chinook salmon. This research investigated the likelihood of mortality and injury for juvenile Chinook salmon carrying telemetry tags and exposed to a range of simulated turbine passage. Several factors were examined as predictors of mortal injury for fish undergoing rapid decompression, and the ratio of pressure change and tag burden were determined to be the most predictive factors. As the ratio of pressure change and tag burden increase, the likelihood of mortal injury also increases. The results of this study suggest that previous survival estimates of juvenile Chinook salmon passing through hydro turbines may have been biased due to the presence of telemetry tags, and this has direct implications to the management of hydroelectric facilities. Realistic examples indicate how the bias in turbine passage survival estimates could be 20% or higher, depending on the mass of the implanted tags and the ratio of acclimation to exposure pressures. Bias would increase as the tag burden and pressure ratio increase, and have direct implications on survival estimates. It is recommended that future survival studies use the smallest telemetry tags possible to minimize the potential bias that may be associated with carrying the tag.

Spin-Label CW Microwave Power Saturation and Rapid Passage with Triangular Non-Adiabatic Rapid Sweep (NARS) and Adiabatic Rapid Passage (ARP) EPR Spectroscopy

Science.gov (United States)

Kittell, Aaron W.; Hyde, James S.

2015-01-01

Non-adiabatic rapid passage (NARS) electron paramagnetic resonance (EPR) spectroscopy was introduced by Kittell, A.W., Camenisch, T.G., Ratke, J.J. Sidabras, J.W., Hyde, J.S., 2011 as a general purpose technique to collect the pure absorption response. The technique has been used to improve sensitivity relative to sinusoidal magnetic field modulation, increase the range of inter-spin distances that can be measured under near physiological conditions, and enhance spectral resolution in copper (II) spectra. In the present work, the method is extended to CW microwave power saturation of spin-labeled T4 Lysozyme (T4L). As in the cited papers, rapid triangular sweep of the polarizing magnetic field was superimposed on slow sweep across the spectrum. Adiabatic rapid passage (ARP) effects were encountered in samples undergoing very slow rotational diffusion as the triangular magnetic field sweep rate was increased. The paper reports results of variation of experimental parameters at the interface of adiabatic and non-adiabatic rapid sweep conditions. Comparison of the forward (up) and reverse (down) triangular sweeps is shown to be a good indicator of the presence of rapid passage effects. Spectral turning points can be distinguished from spectral regions between turning points in two ways: differential microwave power saturation and differential passage effects. Oxygen accessibility data are shown under NARS conditions that appear similar to conventional field modulation data. However, the sensitivity is much higher, permitting, in principle, experiments at substantially lower protein concentrations. Spectral displays were obtained that appear sensitive to rotational diffusion in the range of rotational correlation times of 10−3 to 10−7 s in a manner that is analogous to saturation transfer spectroscopy. PMID:25917132

Geomagnetic, ionospheric and cosmic ray variations around the passages of different magnetic clouds

International Nuclear Information System (INIS)

Maercz, F.

1992-01-01

Thirty-four interplanetary magnetic clouds have been divided into two groups on the basis of Wilson's (J.geophys. Res. 95, 215, 1990) classification: NS clouds (whose B z near cloud onset at Earth is directed northward, and soon after B z is turning southward) and SN clouds (those with an opposite behaviour with respect to B z ). Using the days of cloud onsets as key days, geomagnetic, ionospheric and cosmic ray data have been analysed by the superposed epoch analysis method for passages of both NS and SN clouds. On the basis of the daily ΣK p values, geomagnetic activity is found to suddenly increase in the vicinity of both types of cloud passages. Afterwards, the variation shown by the geomagnetic indices is found to differ for NS clouds in comparison with SN clouds. Namely, on average the recovery to a normal activity level is much slower for NS clouds. Similarly, the enhancements in the ionospheric absorption of radio waves (the so-called ''after-effects'') are found to show different signatures according to cloud type, an interpretation also valid for variations in cosmic ray intensity. The latter results are based on analyses of neutron monitor counts observed at two stations (Apatity: 67 N; and Moscow: 55 o N). (author)

Passages of high energy hadrons through atomic nuclei

International Nuclear Information System (INIS)

Strugalska-Gola, E.; Strugalski, Z.

2001-01-01

The subject matter in this paper are descriptions of more important results of investigations of the intranuclear matter properties by means of hadronic probes (pionic, e.g.). The projectile-nucleus collisions occurred in liquid xenon in the 180 litre xenon bubble chamber. The chamber in the experiments was practically a total 4π angle aperture for detection of the secondary products from the hadron-nucleus collision reactions. All the π +-0 mesons were practically registered with an efficiency near to 100 %. The hadron passages through nuclei (through layers of intranuclear matter) in their pure sort, when multiparticle creation does not occur, were observed. Conclusive information, obtained on the hadron passages, is presented here. It may be used for new nuclear power technology, in radioactive waste neutralization, in other works on intranuclear matter properties

Fish passage mitigation of impacts from hydroelectric power projects in the United States

International Nuclear Information System (INIS)

Cada, G.F.

1996-01-01

Obstruction of fish movements by dams continues to be the major environmental issue facing the hydropower industry in the US. Dams block upstream migrations, which can cut off adult fish form their historical spawning grounds and severely curtail reproduction. Conversely, downstream-migrating fish may be entrained into the turbine intake flow and suffer turbine-passage injury or mortality. Hydroelectric projects can interfere with the migrations of a wide variety of fish. Maintenance, restoration or enhancement of populations of these species may require the construction of facilities to allow for upstream and downstream fish passage. The Federal Energy Regulatory Commission (FERC), by law, must give fish and wildlife resources equal consideration with power production in its licensing decisions, must be satisfied that a project is consistent with comprehensive plans for a waterway (including fisheries management plans), and must consider all federal and state resource agency terms and conditions for the protection of fish and wildlife. As a consequence, FERC often requires fish passage mitigation measures as a condition of the hydropower license when such measures are deemed necessary for the protection of fish. Much of the recent research and development efforts of the US Department of Energy's Hydropower Program have focused on the mitigation of impacts to upstream and downstream fish passage. This paper descries three components of that effort: (1) a survey of environmental mitigation measures at hydropower sites across the country; (2) a critical review of the effectiveness of fish passage mitigation measures at 16 case study sites; and (3) ongoing efforts to develop new turbine designs that minimize turbine-passage mortality

Establishment of an attenuated strain of porcine parvovirus by serial passage at low temperature.

Science.gov (United States)

Fujisaki, Y; Murakami, Y; Suzuki, H

1982-01-01

To prepare a live virus vaccine strain for the prevention of porcine parvovirus infection, the 90HS strain, isolated from the brain of a stillborn porcine fetus, was subjected to the first 45 serial passages in swine kidney established (ESK) cells of porcine kidney origin at 30-35 degrees C and to the 46th and later serial passages in the same cells as these at 32 degrees C. When swine were inoculated with the strain at the 38th passage level possessing such properties as expressed with rct/37+ and rct/40-, they presented viremia, virus discharge, and the transmission of virus to other swine. When swine were inoculated with the strain at the 54th and 55th passage level possessing such properties as expressed with rct/37- and rct/40-, they failed to exhibit viremia, virus discharge, and the transmission of virus to other swine, but retained for a long time hemagglutination-inhibiting antibody which had been produced after inoculation. A low virulent variant strain was obtained after 54 serial passages at low temperature. It was called the HT- strain.

ProBiS-ligands: a web server for prediction of ligands by examination of protein binding sites.

Science.gov (United States)

Konc, Janez; Janežič, Dušanka

2014-07-01

The ProBiS-ligands web server predicts binding of ligands to a protein structure. Starting with a protein structure or binding site, ProBiS-ligands first identifies template proteins in the Protein Data Bank that share similar binding sites. Based on the superimpositions of the query protein and the similar binding sites found, the server then transposes the ligand structures from those sites to the query protein. Such ligand prediction supports many activities, e.g. drug repurposing. The ProBiS-ligands web server, an extension of the ProBiS web server, is open and free to all users at http://probis.cmm.ki.si/ligands. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Both direct and indirect effects account for the pro-inflammatory activity of enteropathogenic mycotoxins on the human intestinal epithelium: Stimulation of interleukin-8 secretion, potentiation of interleukin-1β effect and increase in the transepithelial passage of commensal bacteria

International Nuclear Information System (INIS)

Maresca, Marc; Yahi, Nouara; Younes-Sakr, Lama; Boyron, Marilyn; Caporiccio, Bertrand; Fantini, Jacques

2008-01-01

Mycotoxins are fungal secondary metabolites responsible of food-mediated intoxication in animals and humans. Deoxynivalenol, ochratoxin A and patulin are the best known enteropathogenic mycotoxins able to alter intestinal functions resulting in malnutrition, diarrhea, vomiting and intestinal inflammation in vivo. Although their effects on intestinal barrier and transport activities have been extensively characterized, the mechanisms responsible for their pro-inflammatory effect are still poorly understood. Here we investigated if mycotoxin-induced intestinal inflammation results from a direct and/or indirect pro-inflammatory activity of these mycotoxins on human intestinal epithelial cells, using differentiated Caco-2 cells as model and interleukin 8 (IL-8) as an indicator of intestinal inflammation. Deoxynivalenol was the only mycotoxin able to directly increase IL-8 secretion (10- to 15-fold increase). We also investigated if these mycotoxins could indirectly stimulate IL-8 secretion through: (i) a modulation of the action of pro-inflammatory molecules such as the interleukin-1beta (IL-1β), and/or (ii) an increase in the transepithelial passage of non-invasive commensal Escherichia coli. We found that deoxynivalenol, ochratoxin A and patulin all potentiated the effect of IL-1β on IL-8 secretion (ranging from 35% to 138% increase) and increased the transepithelial passage of commensal bacteria (ranging from 12- to 1544-fold increase). In addition to potentially exacerbate established intestinal inflammation, these mycotoxins may thus participate in the induction of sepsis and intestinal inflammation in vivo. Taken together, our results suggest that the pro-inflammatory activity of enteropathogenic mycotoxins is mediated by both direct and indirect effects

Time Perspective and Emotion Regulation as Predictors of Age-Related Subjective Passage of Time

Science.gov (United States)

Wittmann, Marc; Rudolph, Tina; Linares Gutierrez, Damisela; Winkler, Isabell

2015-01-01

Hardly any empirical work exists concerning the relationship between the intra-individually stable time perspective relating to the past, present, and future and the subjective speed of time passing in everyday life. Moreover, studies consistently show that the subjective passage of time over the period of the last ten years speeds up as we get older. Modulating variables influencing this phenomenon are still unknown. To investigate these two unresolved issues, we conducted an online survey with n = 423 participants ranging in age between 17 and 81 assessing trait time perspective of the past, present, and future, and relating these subscales with a battery of measures pertaining to the subjective passage of time. Moreover, the subjective passage of time as an age-dependent variable was probed in relationship to emotion awareness, appraisal and regulation. Results show how present hedonism is linked with having fewer routines in life and a faster passage of the last week; the past negative perspective is related to time pressure, time expansion and more routine; a pronounced future perspective is related to a general faster passage of time. Importantly, increased emotion regulation and a balanced time perspective are related to a slower passage of the last ten years. These novel findings are discussed within models of time perception and the time perspective. PMID:26694439

Time Perspective and Emotion Regulation as Predictors of Age-Related Subjective Passage of Time

Directory of Open Access Journals (Sweden)

Marc Wittmann

2015-12-01

Full Text Available Hardly any empirical work exists concerning the relationship between the intra-individually stable time perspective relating to the past, present, and future and the subjective speed of time passing in everyday life. Moreover, studies consistently show that the subjective passage of time over the period of the last ten years speeds up as we get older. Modulating variables influencing this phenomenon are still unknown. To investigate these two unresolved issues, we conducted an online survey with n = 423 participants ranging in age between 17 and 81 assessing trait time perspective of the past, present, and future, and relating these subscales with a battery of measures pertaining to the subjective passage of time. Moreover, the subjective passage of time as an age-dependent variable was probed in relationship to emotion awareness, appraisal and regulation. Results show how present hedonism is linked with having fewer routines in life and a faster passage of the last week; the past negative perspective is related to time pressure, time expansion and more routine; a pronounced future perspective is related to a general faster passage of time. Importantly, increased emotion regulation and a balanced time perspective are related to a slower passage of the last ten years. These novel findings are discussed within models of time perception and the time perspective.

A semi-automated method of monitoring dam passage of American Eels Anguilla rostrata

Science.gov (United States)

Welsh, Stuart A.; Aldinger, Joni L.

2014-01-01

Fish passage facilities at dams have become an important focus of fishery management in riverine systems. Given the personnel and travel costs associated with physical monitoring programs, automated or semi-automated systems are an attractive alternative for monitoring fish passage facilities. We designed and tested a semi-automated system for eel ladder monitoring at Millville Dam on the lower Shenandoah River, West Virginia. A motion-activated eel ladder camera (ELC) photographed each yellow-phase American Eel Anguilla rostrata that passed through the ladder. Digital images (with date and time stamps) of American Eels allowed for total daily counts and measurements of eel TL using photogrammetric methods with digital imaging software. We compared physical counts of American Eels with camera-based counts; TLs obtained with a measuring board were compared with TLs derived from photogrammetric methods. Data from the ELC were consistent with data obtained by physical methods, thus supporting the semi-automated camera system as a viable option for monitoring American Eel passage. Time stamps on digital images allowed for the documentation of eel passage time—data that were not obtainable from physical monitoring efforts. The ELC has application to eel ladder facilities but can also be used to monitor dam passage of other taxa, such as crayfishes, lampreys, and water snakes.

Interaction of calreticulin with CD40 ligand, TRAIL and Fas ligand

DEFF Research Database (Denmark)

Duus, K; Pagh, R T; Holmskov, U

2007-01-01

is utilized by many other functionally diverse molecules and in this work the interaction of calreticulin with C1q and structurally similar molecules was investigated. In addition to C1q and MBL, CD40 ligand (CD40L), tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) were...... found to bind calreticulin strongly. A low level or no binding was observed for adiponectin, tumour necrosis factor-alpha (TNF-alpha), CD30L, surfactant protein-A and -D and collagen VIII. The interaction with calreticulin required a conformational change in CD40L, TRAIL and FasL and showed the same...

Compliance Monitoring of Subyearling Chinook Salmon Survival and Passage at The Dalles Dam, Summer 2012

Energy Technology Data Exchange (ETDEWEB)

Skalski, J. R.; Townsend, Richard L.; Seaburg, Adam; Ploskey, Gene R.; Weiland, Mark A.; Hughes, James S.; Woodley, Christa M.; Deng, Zhiqun; Carlson, Thomas J.; Johnson, Gary E.

2013-05-01

The purpose of this compliance study was to estimate dam passage survival of subyearling Chinook salmon at The Dalles Dam during summer 2012. Under the 2008 Federal Columbia River Power System Biological Opinion, dam passage survival is required to be greater than or equal to 0.93 and estimated with a standard error (SE) less than or equal to 0.015. The study also estimated survival from the forebay 2 km upstream of the dam and through the tailrace to 2 km downstream of the dam, forebay residence time, tailrace egress time, spill passage efficiency (SPE), and fish passage efficiency (FPE), as required by the 2008 Columbia Basin Fish Accords.

Tamsulosin and spontaneous passage of ureteral stones in children: a multi-institutional cohort study.

Science.gov (United States)

Tasian, Gregory E; Cost, Nicholas G; Granberg, Candace F; Pulido, Jose E; Rivera, Marcelino; Schwen, Zeyad; Schulte, Marion; Fox, Janelle A

2014-08-01

Tamsulosin is associated with increased passage of ureteral stones in adults but its effectiveness in children is uncertain. We determined the association between tamsulosin and the spontaneous passage of ureteral stones in children. We performed a multi-institutional retrospective cohort study of patients 18 years or younger who presented between 2007 and 2012 with ureteral stones up to 10 mm and who were treated with tamsulosin or oral analgesics alone. The outcome was spontaneous stone passage, defined as radiographic clearance and/or patient report of passage. Subjects prescribed tamsulosin were matched with subjects prescribed analgesics alone, using nearest neighbor propensity score matching to adjust for treatment selection. Conditional logistic regression models were used to estimate the association between tamsulosin and spontaneous passage of ureteral stones, adjusting for stone size and location. Of 449 children with ureteral stones 334 were eligible for inclusion, and complete data were available for 274 patients from 4 institutions (99 receiving tamsulosin, 175 receiving analgesics alone). Following case matching, there were no differences in age, gender, weight, height, stone size or stone location between the 99 subjects prescribed tamsulosin and the 99 propensity score matched subjects prescribed analgesics alone. In the tamsulosin cohort 55% of ureteral stones passed, compared to 44% in the analgesics alone cohort (p=0.03). In multivariate analysis adjusting for stone size and location tamsulosin was associated with spontaneous passage of ureteral stones (OR 3.31, 95% CI 1.49-7.34). The odds of spontaneous passage of ureteral stones were greater in children prescribed tamsulosin vs analgesics alone. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Quantitation of species differences in albumin–ligand interactions for bovine, human and rat serum albumins using fluorescence spectroscopy: A test case with some Sudlow's site I ligands

Energy Technology Data Exchange (ETDEWEB)

Poór, Miklós [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary); Li, Yin; Matisz, Gergely [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kiss, László [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); Kunsági-Máté, Sándor [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, Pécs H-7624 (Hungary); Kőszegi, Tamás, E-mail: koszegit@freemail.hu [Institute of Laboratory Medicine, University of Pécs, Ifjúság u. 13, Pécs H-7624 (Hungary)

2014-01-15

Albumin, the most abundant plasma protein is an approximately 67 kDa sized water-soluble macromolecule. Since several drugs and xenobiotics circulate in the blood at least partially in albumin-bound form, albumin plays a key role in the pharmacokinetics/toxicokinetics of these chemicals. Most of the drugs and xenobiotics are Sudlow's site I ligands. In numerous studies, bovine serum albumin (BSA) is used for modeling albumin–ligand interactions and the results are extrapolated to human serum albumin (HSA). Furthermore, only limited information is available related to albumin–ligand interactions of different albumin species. Therefore, in our study, we have focused on the quantification of differences between bovine, human and rat serum albumin (RSA) using four Sudlow's site I ligands (luteolin, ochratoxin A, phenylbutazone and warfarin). Interactions were analyzed by fluorescence spectroscopy. Stability constants as well as competing capacities of the ligands were determined, and thermodynamic study was also performed. Our results highlight that there could be major differences between BSA, HSA and RSA in their ligand binding properties. Based on our observations we emphasize that in molecular aspects BSA behaves considerably differently from HSA or from albumins of other species therefore, it is strongly recommended to apply at least some confirmatory measurements when data obtained from other species are attempted to be extrapolated to HSA. -- Highlights: • Albumin–ligand interactions of human, bovine and rat albumins were studied. • Four Sudlow's site I ligands were tested by fluorescence spectroscopy. • Substantial differences were found in stability constants among albumin complexes. • Competing capacity of ligands showed major differences in the studied species. • Data obtained for BSA cannot be directly extrapolated to human albumin.

RITES OF PASSAGE AND SUSTANABLE DEVELOPMENT IN ...

African Journals Online (AJOL)

throughout the world experience and perform rites of passage in their different cultures ... The various stages of human development starting from birth, puberty ... one is momentary stripped of former self and status and recreate to something new ... culture of African and X-ray their attachment to their gods and supernatural ...

First-passage percolation on the random graph

NARCIS (Netherlands)

Hofstad, van der R.W.; Hooghiemstra, G.; Van Mieghem, P.

2001-01-01

We study first-passage percolation on the random graph Gp(N) with exponentially distributed weights on the links. For the special case of the complete graph, this problem can be described in terms of a continuous-time Markov chain and recursive trees. The Markov chain X(t) describes the number of

Walla Walla River Fish Passage Operations Program, 2003-2004 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

Bronson, James P. (Confederated Tribes of the Umatilla Indian Reservation, Department of Natural Resources, Pendleton, OR)

2004-12-01

In the late 1990s, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate fish migration conditions in the basin. The migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow requirements, and providing trap and haul efforts when needed. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survival of migrating adult and juvenile salmonids in the Walla Walla River basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage criteria and passage and trapping facility design and operation. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. During the 2003-2004 project year, there were 379 adult summer steelhead (Oncorhynchus mykiss), 36 adult bull trout (Salvelinus confluentus); 108 adult and 3 jack spring chinook (O. tshawytscha) enumerated at the Nursery Bridge Dam fishway video counting window between December 21, 2003, and June 30, 2004. Summer steelhead and spring chinook were observed moving upstream while bull trout were observed moving both upstream and downstream of the facility. In addition, the old ladder trap was operated by the WWBNPME project in order to radio tag spring chinook adults. A total of 2 adult summer steelhead, 4 bull trout, and 23 adult spring chinook were enumerated at the west ladder at Nursery Bridge Dam during the trapping operations between May 6 and May 23, 2004. Operation of the Little Walla Walla

Monitoring lysin motif-ligand interactions via tryptophan analog fluorescence spectroscopy

NARCIS (Netherlands)

Petrovic, Dejan M.; Leenhouts, Kees; van Roosmalen, Maarten L.; KleinJan, Fenneke; Broos, Jaap

2012-01-01

The lysin motif (LysM) is a peptidoglycan binding protein domain found in a wide range of prokaryotes and eukaryotes. Various techniques have been used to study the LysM-ligand interaction, but a sensitive spectroscopic method to directly monitor this interaction has not been reported. Here a

Evaluation of Fish Passage Conditions for Juvenile Salmonids Using Sensor Fish at Detroit Dam, Oregon

International Nuclear Information System (INIS)

Duncan, Joanne P.

2010-01-01

Fish passage conditions through two spillways at Detroit Dam on the North Santiam River in Oregon were evaluated by Pacific Northwest National Laboratory for the U.S. Army Corps of Engineers (USACE), Portland District, using Sensor Fish devices. The objective of the study was to describe and compare passage exposure conditions through Spillbay 3 and Spillbay 6 at 1.5- and 3.5-ft gate openings, identifying potential fish injury regions of the routes. The study was performed in July 2009, concurrent with HI-Z balloon-tag studies by Normandeau Associates, Inc. Sensor Fish and live fish were deployed at elevations approximately 3 ft above structure at depths determined using a computational fluid dynamics model. Data collected were analyzed to estimate (1) exposure conditions, particularly exposure to severe collision and shear events by passage route sub-regions; (2) differences in passage conditions between passage routes; and (3) relationships to live-fish injury and mortality data estimates.

Ligand-directed tosyl chemistry for in situ native protein labeling and engineering in living systems: from basic properties to applications.

Science.gov (United States)

Tsukiji, Shinya; Hamachi, Itaru

2014-08-01

The ability to introduce any chemical probe to any endogenous target protein in its native environment, that is in cells and in vivo, is anticipated to provide various new exciting tools for biological and biomedical research. Although still at the prototype stage, the ligand-directed tosyl (LDT) chemistry is a novel type of affinity labeling technique that we developed for such a dream. This chemistry allows for modifying native proteins by various chemical probes with high specificity in various biological settings ranging from in vitro (in test tubes) to in living cells and in vivo. Since the first report, the list of proteins that are successfully labeled by the LDT chemistry has been increasing. A growing number of studies have demonstrated its utility to create semisynthetic proteins directly in cellular contexts. The in situ generated semisynthetic proteins are applicable for various types of analysis and imaging of intracellular biological processes. In this review, we summarize the basic properties of the LDT chemistry and its applications toward in situ engineering and analysis of native proteins in living systems. Current limitations and future challenges of this area are also described. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bitopic Ligands and Metastable Binding Sites

DEFF Research Database (Denmark)

Fronik, Philipp; Gaiser, Birgit I; Sejer Pedersen, Daniel

2017-01-01

of orthosteric binding sites. Bitopic ligands have been employed to address the selectivity problem by combining (linking) an orthosteric ligand with an allosteric modulator, theoretically leading to high-affinity subtype selective ligands. However, it remains a challenge to identify suitable allosteric binding...... that have been reported to date, this type of bitopic ligands would be composed of two identical pharmacophores. Herein, we outline the concept of bitopic ligands, review metastable binding sites, and discuss their potential as a new source of allosteric binding sites....

Pd(II)-Catalyzed Olefination of Electron-Deficient Arenes Using 2,6-Dialkylpyridine Ligands

Science.gov (United States)

Zhang, Yang-Hui; Shi, Bing-Feng; Yu, Jin-Quan

2009-01-01

Pd(II)-catalyzed meta-olefination of highly electron deficient arenes is achieved through the use of a rationally designed mutually repulsive ligand. The combination of directed and non-directed C–H functionalization of arenes provides a versatile route for the synthesis of highly sought-after 1,2,4-trisubstituted arenes. PMID:19296661

A multi-year analysis of passage and survival at McNary Dam, 2004-09

Science.gov (United States)

Adams, Noah S.; Walker, C.E.; Perry, R.W.

2011-01-01

We analyzed 6 years (2004–09) of passage and survival data collected at McNary Dam to determine how dam operations and environmental conditions affect passage and survival of juvenile salmonids. A multinomial logistic regression was used to examine how environmental variables and dam operations relate to passage behavior of juvenile salmonids at McNary Dam. We used the Cormack-Jolly-Seber release-recapture model to determine how the survival of juvenile salmonids passing through McNary Dam relates to environmental variables and dam operations. Total project discharge and the proportion of flow passing the spillway typically had a positive effect on survival for all species and routes. As the proportion of water through the spillway increased, the number of fish passing the spillway increased, as did overall survival. Additionally, survival generally was higher at night. There was no meaningful difference in survival for fish that passed through the north or south portions of the spillway or powerhouse. Similarly, there was no difference in survival for fish released in the north, middle, or south portions of the tailrace. For subyearling Chinook salmon migrating during the summer season, increased temperatures had a drastic effect on passage and survival. As temperature increased, survival of subyearling Chinook salmon decreased through all passage routes and the number of fish that passed through the turbines increased. During years when the temporary spillway weirs (TSWs) were installed, passage through the spillway increased for spring migrants. However, due to the changes made in the location of the TSW between years and the potential effect of other confounding environmental conditions, it is not certain if the increase in spillway passage was due solely to the presence of the TSWs. The TSWs appeared to improve forebay survival during years when they were operated.

Walla Walla River Fish Passage Operations Project : Annual Progress Report October 2007 - September 2008.

Energy Technology Data Exchange (ETDEWEB)

Bronson, James P.; Duke, Bill; Loffink, Ken

2008-12-30

In the late 1990s, the Confederated Tribes of the Umatilla Indian Reservation, Oregon Department of Fish and Wildlife, and Washington Department of Fish and Wildlife, along with many other agencies, began implementing fisheries restoration activities in the Walla Walla Basin. An integral part of these efforts is to alleviate the inadequate fish migration conditions in the basin. Migration concerns are being addressed by removing diversion structures, constructing fish passage facilities, implementing minimum instream flow requirements, and providing trap and haul efforts when needed. The objective of the Walla Walla River Fish Passage Operations Project is to increase the survival of migrating adult and juvenile salmonids in the Walla Walla River basin. The project is responsible for coordinating operation and maintenance of ladders, screen sites, bypasses, trap facilities, and transportation equipment. In addition, the project provides technical input on passage and trapping facility design, operation, and criteria. Operation of the various passage facilities and passage criteria guidelines are outlined in an annual operations plan that the project develops. Beginning in March of 2007, two work elements from the Walla Walla Fish Passage Operations Project were transferred to other projects. The work element Enumeration of Adult Migration at Nursery Bridge Dam is now conducted under the Walla Walla Basin Natural Production Monitoring and Evaluation Project and the work element Provide Transportation Assistance is conducted under the Umatilla Satellite Facilities Operation and Maintenance Project. Details of these activities can be found in those project's respective annual reports.

Evaluation of the novel algorithm of flexible ligand docking with moveable target-protein atoms.

Science.gov (United States)

Sulimov, Alexey V; Zheltkov, Dmitry A; Oferkin, Igor V; Kutov, Danil C; Katkova, Ekaterina V; Tyrtyshnikov, Eugene E; Sulimov, Vladimir B

2017-01-01

We present the novel docking algorithm based on the Tensor Train decomposition and the TT-Cross global optimization. The algorithm is applied to the docking problem with flexible ligand and moveable protein atoms. The energy of the protein-ligand complex is calculated in the frame of the MMFF94 force field in vacuum. The grid of precalculated energy potentials of probe ligand atoms in the field of the target protein atoms is not used. The energy of the protein-ligand complex for any given configuration is computed directly with the MMFF94 force field without any fitting parameters. The conformation space of the system coordinates is formed by translations and rotations of the ligand as a whole, by the ligand torsions and also by Cartesian coordinates of the selected target protein atoms. Mobility of protein and ligand atoms is taken into account in the docking process simultaneously and equally. The algorithm is realized in the novel parallel docking SOL-P program and results of its performance for a set of 30 protein-ligand complexes are presented. Dependence of the docking positioning accuracy is investigated as a function of parameters of the docking algorithm and the number of protein moveable atoms. It is shown that mobility of the protein atoms improves docking positioning accuracy. The SOL-P program is able to perform docking of a flexible ligand into the active site of the target protein with several dozens of protein moveable atoms: the native crystallized ligand pose is correctly found as the global energy minimum in the search space with 157 dimensions using 4700 CPU ∗ h at the Lomonosov supercomputer.

FUNCTIONS OF VATA (BASED ON CHARAKA) A Passage from Vaatkalaakaleeyam.

Science.gov (United States)

Trivedi, A R

1982-04-01

The author has chosen 12(th) Chapter from the Sutra Sthana of this great epic containing 12,000 verses and passages which is replete with materials to revive the whole art of healing even if the whole medical literatures is lost. The passage puts in a nutshell the key role played by Vayu / Vata in the working of the tantra and yantra of the body. Though exploration of the humours is yet to be done by modern physiologists to explain the Ayurvedic Vata which is responsible to no less than 18 functions of the normal body mechanism.

Titration ELISA as a Method to Determine the Dissociation Constant of Receptor Ligand Interaction.

Science.gov (United States)

Eble, Johannes A

2018-02-15

The dissociation constant describes the interaction between two partners in the binding equilibrium and is a measure of their affinity. It is a crucial parameter to compare different ligands, e.g., competitive inhibitors, protein isoforms and mutants, for their binding strength to a binding partner. Dissociation constants are determined by plotting concentrations of bound versus free ligand as binding curves. In contrast, titration curves, in which a signal that is proportional to the concentration of bound ligand is plotted against the total concentration of added ligand, are much easier to record. The signal can be detected spectroscopically and by enzyme-linked immunosorbent assay (ELISA). This is exemplified in a protocol for a titration ELISA that measures the binding of the snake venom-derived rhodocetin to its immobilized target domain of α2β1 integrin. Titration ELISAs are versatile and widely used. Any pair of interacting proteins can be used as immobilized receptor and soluble ligand, provided that both proteins are pure, and their concentrations are known. The difficulty so far has been to determine the dissociation constant from a titration curve. In this study, a mathematical function underlying titration curves is introduced. Without any error-prone graphical estimation of a saturation yield, this algorithm allows processing of the raw data (signal intensities at different concentrations of added ligand) directly by mathematical evaluation via non-linear regression. Thus, several titration curves can be recorded simultaneously and transformed into a set of characteristic parameters, among them the dissociation constant and the concentration of binding-active receptor, and they can be evaluated statistically. When combined with this algorithm, titration ELISAs gain the advantage of directly presenting the dissociation constant. Therefore, they may be used more efficiently in the future.

A passage retrieval method based on probabilistic information retrieval model and UMLS concepts in biomedical question answering.

Science.gov (United States)

Sarrouti, Mourad; Ouatik El Alaoui, Said

2017-04-01

Passage retrieval, the identification of top-ranked passages that may contain the answer for a given biomedical question, is a crucial component for any biomedical question answering (QA) system. Passage retrieval in open-domain QA is a longstanding challenge widely studied over the last decades. However, it still requires further efforts in biomedical QA. In this paper, we present a new biomedical passage retrieval method based on Stanford CoreNLP sentence/passage length, probabilistic information retrieval (IR) model and UMLS concepts. In the proposed method, we first use our document retrieval system based on PubMed search engine and UMLS similarity to retrieve relevant documents to a given biomedical question. We then take the abstracts from the retrieved documents and use Stanford CoreNLP for sentence splitter to make a set of sentences, i.e., candidate passages. Using stemmed words and UMLS concepts as features for the BM25 model, we finally compute the similarity scores between the biomedical question and each of the candidate passages and keep the N top-ranked ones. Experimental evaluations performed on large standard datasets, provided by the BioASQ challenge, show that the proposed method achieves good performances compared with the current state-of-the-art methods. The proposed method significantly outperforms the current state-of-the-art methods by an average of 6.84% in terms of mean average precision (MAP). We have proposed an efficient passage retrieval method which can be used to retrieve relevant passages in biomedical QA systems with high mean average precision. Copyright © 2017 Elsevier Inc. All rights reserved.

Three Dimensional Viscous Flow Field in an Axial Flow Turbine Nozzle Passage

Science.gov (United States)

Ristic, D.; Lakshminarayana, B.

1997-01-01

The objective of this investigation is experimental and computational study of three dimensional viscous flow field in the nozzle passage of an axial flow turbine stage. The nozzle passage flow field has been measured using a two sensor hot-wire probe at various axial and radial stations. In addition, two component LDV measurements at one axial station (x/c(sum m) = 0.56) were performed to measure the velocity field. Static pressure measurements and flow visualization, using a fluorescent oil technique, were also performed to obtain the location of transition and the endwall limiting streamlines. A three dimensional boundary layer code, with a simple intermittency transition model, was used to predict the viscous layers along the blade and endwall surfaces. The boundary layers on the blade surface were found to be very thin and mostly laminar, except on the suction surface downstream of 70% axial chord. Strong radial pressure gradient, especially close to the suction surface, induces strong cross flow components in the trailing edge regions of the blade. On the end-walls the boundary layers were much thicker, especially near the suction corner of the casing surface, caused by secondary flow. The secondary flow region near the suction-casing surface corner indicates the presence of the passage vortex detached from the blade surface. The corner vortex is found to be very weak. The presence of a closely spaced rotor downstream (20% of the nozzle vane chord) introduces unsteadiness in the blade passage. The measured instantaneous velocity signal was filtered using FFT square window to remove the periodic unsteadiness introduced by the downstream rotor and fans. The filtering decreased the free stream turbulence level from 2.1% to 0.9% but had no influence on the computed turbulence length scale. The computation of the three dimensional boundary layers is found to be accurate on the nozzle passage blade surfaces, away from the end-walls and the secondary flow region. On

Tamsulosin and the spontaneous passage of ureteral stones in children: A multi-institutional cohort study

Science.gov (United States)

Tasian, Gregory E.; Cost, Nicholas G.; Granberg, Candace F.; Pulido, Jose E.; Rivera, Marcelino; Schwen, Zeyad; Schulte, Marion; Fox, Janelle A.

2014-01-01

Purpose Tamsulosin is associated with increased passage of ureteral stones in adults, but its effectiveness in children is uncertain. We determined the association between tamsulosin and the spontaneous passage of ureteral stones in children. Methods We performed a multi-institutional retrospective cohort study of children ≤ 18 years who presented between 2007 and 2012 with a ureteral stone ≤ 10 mm and were managed with tamsulosin or oral analgesics alone. The outcome was spontaneous stone passage defined as radiographic clearance and/or patient report of passage. Subjects prescribed tamsulosin were matched with subjects prescribed analgesics alone using nearest neighbor propensity score matching to adjust for treatment selection. Conditional logistic regression models were used to estimate the association between tamsulosin and spontaneous passage of ureteral stones, adjusting for stone size and location. Results Of 449 children with ureteral stones, 334 were eligible for inclusion, and complete data were available for 274 children from 4 institutions (99 tamsulosin; 175 analgesics alone). Following case matching, there were no differences in patient age, gender, weight, height, stone size, or stone location between the 99 subjects prescribed tamsulosin and the 99 propensity-score matched subjects prescribed analgesics alone. In the tamsulosin cohort, 55% of ureteral stones passed versus 44% in the analgesics alone cohort (p = 0.03). In multivariate analysis adjusting for stone size and location, tamsulosin was associated with spontaneous passage of ureteral stones (OR 3.31; 95% CI 1.49–7.34). Conclusions The odds of spontaneous passage of ureteral stones were higher in children prescribed tamsulosin versus analgesics alone. PMID:24518765

Practical calibration of design data to technical capabilities of horizontal directional drilling rig

Science.gov (United States)

Toropov, S. Yu; Toropov, V. S.

2018-05-01

In order to design more accurately trenchless pipeline passages, a technique has been developed for calculating the passage profile, based on specific parameters of the horizontal directional drilling rig, including the range of possible drilling angles and a list of compatible drill pipe sets. The algorithm for calculating the parameters of the trenchless passage profile is shown in the paper. This algorithm is based on taking into account the features of HDD technology, namely, three different stages of production. The authors take into account that the passage profile is formed at the first stage of passage construction, that is, when drilling a pilot well. The algorithm involves calculating the profile by taking into account parameters of the drill pipes used and angles of their deviation relative to each other during the pilot drilling. This approach allows us to unambiguously calibrate the designed profile for the HDD rig capabilities and the auxiliary and navigation equipment used in the construction process.

Compliance Monitoring of Subyearling Chinook Salmon Smolt Survival and Passage at Bonneville Dam, Summer 2012

Energy Technology Data Exchange (ETDEWEB)

Skalski, J. R.; Townsend, Richard L.; Seaburg, Adam; Ploskey, Gene R.; Weiland, Mark A.; Hughes, James S.; Woodley, Christa M.; Deng, Zhiqun; Carlson, Thomas J.

2013-05-01

The purpose of this compliance study was to estimate dam passage survival of subyearling Chinook salmon at Bonneville Dam during summer 2012, as required by the 2008 Federal Columbia River Power System Biological Opinion. The study also estimated smolt passage survival from the forebay 2 km upstream of the dam to the tailrace 1 km below the dam, as well as forebay residence time, tailrace egress, and spill passage efficiency, as required in the 2008 Columbia Basin Fish Accords.

Mesenchymal stromal cell secretomes are modulated by suspension time, delivery vehicle, passage through catheter, and exposure to adjuvants.

Science.gov (United States)

Parsha, Kaushik; Mir, Osman; Satani, Nikunj; Yang, Bing; Guerrero, Waldo; Mei, Zhuyong; Cai, Chunyan; Chen, Peng R; Gee, Adrian; Hanley, Patrick J; Aronowski, Jaroslaw; Savitz, Sean I

2017-01-01

Extensive animal data indicate that mesenchymal stromal cells (MSCs) improve outcome in stroke models. Intra-arterial (IA) injection is a promising route of delivery for MSCs. Therapeutic effect of MSCs in stroke is likely based on the broad repertoire of secreted trophic and immunomodulatory cytokines produced by MSCs. We determined the differential effects of exposing MSCs to different types of clinically relevant vehicles, and/or different additives and passage through a catheter relevant to IA injections. MSCs derived from human bone marrow were tested in the following vehicles: 5% albumin (ALB), 6% Hextend (HEX) and 40% dextran (DEX). Each solution was tested (i) alone, (ii) with low-dose heparin, (iii) with 10% Omnipaque, or (iv) a combination of heparin and Omnipaque. Cells in vehicles were collected directly or passed through an IA catheter, and MSC viability and cytokine release profiles were assessed. Cell viability remained above 90% under all tested conditions with albumin being the highest at 97%. Viability was slightly reduced after catheter passage or exposure to heparin or Omnipaque. Catheter passage had little effect on MSC cytokine secretion. ALB led to increased release of angiogenic factors such as vascular endothelial growth factor compared with other vehicles, while HEX and DEX led to suppression of pro-inflammatory cytokines such as interleukin-6. However, when these three vehicles were subjected to catheter passage and/or exposure to additives, the cytokine release profile varied depending on the combination of conditions to which MSCs were exposed. Exposure of MSCs to certain types of vehicles or additives changes the profile of cytokine secretion. The activation phenotype of MSCs may therefore be affected by the vehicles used for these cells or the exposure to the adjuvants used in their administration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Stable isotope-labelled feed nutrients to assess nutrient-specific feed passage kinetics in ruminants

NARCIS (Netherlands)

Warner, D.; Dijkstra, J.; Hendriks, W.H.; Pellikaan, W.F.

2014-01-01

Knowledge of digesta passage kinetics in ruminants is essential to predict nutrient supply to the animal in relation to optimal animal performance, environmental pollution and animal health. Fractional passage rates (FPR) of feed are widely used in modern feed evaluation systems and mechanistic

Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates

International Nuclear Information System (INIS)

Dadachova, E.; Chappell, L.L.; Brechbiel, M.W.

1999-01-01

A simple spectrophotometric assay for determination of bifunctional polyazacarboxylate-macrocyclic ligands of different sizes that are conjugated to proteins has been developed for: 12-membered macrocycle DOTA (2-[4-nitrobenzyl]-1, 4, 7, 10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) and analogs, the 15-membered PEPA macrocycle (2-[4-nitrobenzyl]-1,4,7,10,13-pentaazacyclopentadecane-N,N',N'',N''',N'''' -pentaacetic acid), and the large 18-membered macrocycle HEHA (1,4,7,10,13,16-hexaazacyclooctadecane-N,N',N'',N''',N''''-hexaacetic acid). The method is based on titration of the blue-colored 1:1 Pb(II)-Arsenazo III (AAIII) complex with the polyazacarboxylate macrocyclic ligand in the concentration range of 0-2.5 μM, wherein color change occurring upon transchelation of the Pb(II) from the AAIII to the polyazamacrocyclic ligand is monitored at 656 nm. The assay is performed at ambient temperature within 20 min without any interfering interaction between the protein and Pb(II)-AA(III) complex. Thus, this method also provides a ligand-to-protein ratio (L/P ratio) that reflects the effective number of ligands per protein molecule available to radiolabeling. The method is not suitable for 14-membered TETA macrocycle (2-[4-nitrobenzyl]-1, 4, 8, 11-tetraazacyclotetradecane N,N',N'',N'''-tetraacetic acid) because of low stability constant of Pb(II)-TETA complex. The method is rapid, simple and may be customized for other polyazacarboxylate macrocyclic ligands

Phase Variation Analysis of Coxiella burnetii during Serial Passage in Cell Culture by Use of Monoclonal Antibodies

OpenAIRE

Hotta, Akitoyo; Kawamura, Midori; To, Ho; Andoh, Masako; Yamaguchi, Tsuyoshi; Fukushi, Hideto; Hirai, Katsuya

2002-01-01

Antigenic changes in Coxiella burnetii Nine Mile strain phase I during serial passages in cell culture were analyzed with three groups of monoclonal antibodies (MAbs) against lipopolysaccharide. The MAbs of group 1 did not react with organisms that were passaged over five times, and the MAbs of group 2 did not react with organisms that were passaged over eight times. The MAbs of group 3 reacted with organisms passaged up to 15 times but did not react with phase II cells. These results suggest...

Monitoring of Subyearling Chinook Salmon Survival and Passage at Bonneville Dam, Summer 2010

Energy Technology Data Exchange (ETDEWEB)

Ploskey, Gene R.; Weiland, Mark A.; Carlson, Thomas J.

2012-09-01

The purpose of this study was to estimate dam passage and route specific survival rates for subyearling Chinook salmon smolts to a primary survival-detection array located 81 km downstream of the dam, evaluate a BGS located in the B2 forebay, and evaluate effects of two spill treatments. The 2010 study also provided estimates of forebay residence time, tailrace egress time, spill passage efficiency (SPE), and spill + B2 Corner Collector (B2CC) efficiency, as required in the Columbia Basin Fish Accords. In addition, the study estimated forebay passage survival and survival of fish traveling from the forebay entrance array, through the dam and downstream through 81 km of tailwater.

Rosetta Ligand docking with flexible XML protocols.

Science.gov (United States)

Lemmon, Gordon; Meiler, Jens

2012-01-01

RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

Benefits of fish passage and protection measures at hydroelectric projects

International Nuclear Information System (INIS)

Cada, G.F.; Jones, D.W.

1993-01-01

The US Department of Energy's Hydropower Program is engaged in a multi-year study of the costs and benefits of environmental mitigation measures at nonfederal hydroelectric power plants. An initial report (Volume 1) reviewed and surveyed the status of mitigation methods for fish passage, instream flows, and water quality; this paper focuses on the fish passage/protection aspects of the study. Fish ladders were found to be the most common means of passing fish upstream; elevators/lifts were less common, but their use appears to be increasing. A variety of mitigative measures is employed to prevent fish from being drawn into turbine intakes, including spill flows, narrow-mesh intake screens, angled bar racks, and lightor sound-based guidance measures. Performance monitoring and detailed, quantifiable performance criteria were frequently lacking at non-federal hydroelectric projects. Volume 2 considers the benefits and costs of fish passage and protection measures, as illustrated by case studies for which performance monitoring has been conducted. The report estimates the effectiveness of particular measures, the consequent impacts on the fish populations that are being maintained or restored, and the resulting use and non-use values of the maintained or restored fish populations

Characterization of Fish Passage Conditions through a Francis Turbine, Spillway, and Regulating Outlet at Detroit Dam, Oregon, Using Sensor Fish, 2009

Energy Technology Data Exchange (ETDEWEB)

Duncan, Joanne P.; Carlson, Thomas J.

2011-05-06

Fish passage conditions through two spillways, a Francis turbine, and a regulating outlet (RO) at Detroit Dam on the North Santiam River in Oregon were evaluated by Pacific Northwest National Laboratory for the U.S. Army Corps of Engineers (USACE), Portland District, using Sensor Fish devices. The objective of the study was to describe and compare passage exposure conditions, identifying potential fish injury regions within the routes. The study was performed in July, October, and December 2009 concurrent with HI-Z balloon-tag studies by Normandeau Associates, Inc. Sensor Fish data were analyzed to estimate 1) exposure conditions, particularly exposure to severe strike, collision, and shear events by passage route sub-regions; 2) differences in passage conditions between passage routes; and 3) relationships to live-fish injury and mortality data estimates. Comparison of the three passage routes evaluated at Detroit Dam indicates that the RO passage route through the 5-ft gate opening was relatively the safest route for fish passage under the operating conditions tested; turbine passage was the most deleterious. These observations were supported also by the survival and malady estimates obtained from live-fish testing. Injury rates were highest for turbine and spillway passage. However, none of the passage routes tested is safe for juvenile salmonid passage.

Migration depth and residence time of juvenile salmonids in the forebays of hydropower dams prior to passage through turbines or juvenile bypass systems: implications for turbine-passage survival.

Science.gov (United States)

Li, Xinya; Deng, Zhiqun D; Brown, Richard S; Fu, Tao; Martinez, Jayson J; McMichael, Geoffrey A; Skalski, John R; Townsend, Richard L; Trumbo, Bradly A; Ahmann, Martin L; Renholds, Jon F

2015-01-01

Little is known about the three-dimensional depth distributions in rivers of individually marked fish that are in close proximity to hydropower facilities. Knowledge of the depth distributions of fish approaching dams can be used to understand how vulnerable fish are to injuries such as barotrauma as they pass through dams. To predict the possibility of barotrauma injury caused by pressure changes during turbine passage, it is necessary to understand fish behaviour relative to acclimation depth in dam forebays as they approach turbines. A guiding study was conducted using high-resolution three-dimensional tracking results of salmonids implanted with Juvenile Salmon Acoustic Telemetry System transmitters to investigate the depth distributions of subyearling and yearling Chinook salmon (Oncorhynchus tshawytscha) and juvenile steelhead (Oncorhynchus mykiss) passing two dams on the Snake River in Washington State. Multiple approaches were evaluated to describe the depth at which fish were acclimated, and statistical analyses were performed on large data sets extracted from ∼28 000 individually tagged fish during 2012 and 2013. Our study identified patterns of depth distributions of juvenile salmonids in forebays prior to passage through turbines or juvenile bypass systems. This research indicates that the median depth at which juvenile salmonids approached turbines ranged from 2.8 to 12.2 m, with the depths varying by species/life history, year, location (which dam) and diel period (between day and night). One of the most enlightening findings was the difference in dam passage associated with the diel period. The amount of time that turbine-passed fish spent in the immediate forebay prior to entering the powerhouse was much lower during the night than during the day. This research will allow scientists to understand turbine-passage survival better and enable them to assess more accurately the effects of dam passage on juvenile salmon survival.

Rites of Passage and their Role in the Socializationof the Spartan Youth

Directory of Open Access Journals (Sweden)

Metaxia Papapostolou; Pantelis Konstantinakos; Costas Mountakis; Kostas Georgiadis

2010-01-01

Full Text Available The aim of this paper is to investigate the role of rites of passage in the socialization of Spartan youth. Methodologically, our discussion will be based upon a ancient literary sources, in particular Plutarch, Xenophon and Pausanias, b interdisciplinary approaches initiated by modern historians and sociologists, and c archaeological evidence. Discussion will begin with an overview of the ancient Spartan educational system and, in particular, an assessment of the evidence for the participation of both boys and girls in festivals. It is concluded that the Spartans incorporated a system of rites of passage in their educational programme with the aim to achieving the greatest levels of socialization of their youth, both boys and girls, the main reason for which was the important role that kinetic activities played in the context of rites of passage.

Centrifugation assay for measuring adhesion of serially passaged bovine chondrocytes to polystyrene surfaces.

Science.gov (United States)

Kaplan, David S; Hitchins, Victoria M; Vegella, Thomas J; Malinauskas, Richard A; Ferlin, Kimberly M; Fisher, John P; Frondoza, Carmelita G

2012-07-01

A major obstacle in chondrocyte-based therapy for cartilage repair is the limited availability of cells that maintain their original phenotype. Propagation of chondrocytes as monolayer cultures on polystyrene surfaces is used extensively for amplifying cell numbers. However, chondrocytes undergo a phenotypic shift when propagated in this manner and display characteristics of more adherent fibroblastic cells. Little information is available about the effect of this phenotypic shift on cellular adhesion properties. We evaluated changes in adhesion property as bovine chondrocytes were serially propagated up to five passages in monolayer culture using a centrifugation cell adhesion assay, which was based on counting of cells before and after being exposed to centrifugal dislodgement forces of 120 and 350 g. Chondrocytes proliferated well in a monolayer culture with doubling times of 2-3 days, but they appeared more fibroblastic and exhibited elongated cell morphology with continued passage. The centrifugation cell adhesion assay showed that chondrocytes became more adhesive with passage as the percentage of adherent cells after centrifugation increased and was not statistically different from the adhesion of the fibroblast cell line, L929, starting at passage 3. This increased adhesiveness correlated with a shift to a fibroblastic morphology and increased collagen I mRNA expression starting at passage 2. Our findings indicate that the centrifugation cell adhesion assay may serve as a reproducible tool to track alterations in chondrocyte phenotype during their extended propagation in culture.

Lake Roosevelt Rainbow Trout Habitat/Passage Improvement Project, Annual Report 2002-2003.

Energy Technology Data Exchange (ETDEWEB)

Sears, Sheryl

2004-01-01

Tribes (CCT), Spokane Tribe of Indians (STI) and Washington Department of Fish and Wildlife (WDFW) to develop and propose a comprehensive fishery management plan for Lake Roosevelt. The Rainbow Trout Habitat/Passage Improvement Project (LRHIP) was designed with goals directed towards increasing natural production while maintaining genetic integrity among current tributary stocks. The initial phase of the Lake Roosevelt Habitat Improvement Project (Phase I, baseline data collection: 1990-91) was focused on the assessment of limiting factors, including the quality and quantity of available spawning gravel, identification of passage barriers, and assessment of other constraints. After the initial assessment of stream parameters, five streams meeting specific criteria were selected for habitat/passage improvement projects (Phase II, implementation -1992-1995). Four of these projects were on the Colville Indian Reservation South Nanamkin, North Nanamkin, Louie and Iron Creeks and one Blue Creek was on the Spokane Indian Reservation. At the completion of project habitat improvements, the final phase (Phase III, monitoring-1996-2000) began. This phase assessed the changes and determined the success achieved through the improvements. Data analysis showed that passage improvements are successful for increasing habitat availability and use. The results of in-stream habitat improvements were inconclusive. Project streams, to the last monitoring date, have shown increases in fish density following implementation of the improvements. In 2000 Bridge Creek, on the Colville Reservation was selected for the next phase of improvements. Data collection, including baseline stream survey and population data collection, was carried out during 2001 in preparation for the design and implementation of stream habitat/passage improvements. Agencies cooperating on the project include the Colville Confederated Tribes (CCT), Natural Resource Conservation Service (NRCS, Ferry County District), Ferry

Lake Roosevelt Rainbow Trout Habitat/Passage Improvement Project, Annual Report 2001-2002.

Energy Technology Data Exchange (ETDEWEB)

Sears, Sheryl

2003-01-01

Tribes (CCT), Spokane Tribe of Indians (STI) and Washington Department of Fish and Wildlife (WDFW) to develop and propose a comprehensive fishery management plan for Lake Roosevelt. The Rainbow Trout Habitat/Passage Improvement Project (LRHIP) was designed with goals directed towards increasing natural production while maintaining genetic integrity among current tributary stocks. The initial phase of the Lake Roosevelt Habitat Improvement Project (Phase I, baseline data collection: 1990-91) was focused on the assessment of limiting factors, including the quality and quantity of available spawning gravel, identification of passage barriers, and assessment of other constraints. After the initial assessment of stream parameters, five streams meeting specific criteria were selected for habitat/passage improvement projects (Phase II, implementation -1992-1995). Four of these projects were on the Colville Indian Reservation South Nanamkin, North Nanamkin, Louie and Iron Creeks and one Blue Creek was on the Spokane Indian Reservation. At the completion of project habitat improvements, the final phase (Phase III, monitoring-1996-2000) began. This phase assessed the changes and determined the success achieved through the improvements. Data analysis showed that passage improvements are successful for increasing habitat availability and use. The results of in-stream habitat improvements were inconclusive. Project streams, to the last monitoring date, have shown increases in fish density following implementation of the improvements. In 2000 Bridge Creek, on the Colville Reservation was selected for the next phase of improvements. Data collection, including baseline stream survey and population data collection, was carried out during 2001 in preparation for the design and implementation of stream habitat/passage improvements. Agencies cooperating on the project include the Colville Confederated Tribes (CCT), Natural Resource Conservation Service (NRCS, Ferry County District), Ferry

Virulence-associated genome mutations of murine rotavirus identified by alternating serial passages in mice and cell cultures.

Science.gov (United States)

Tsugawa, Takeshi; Tatsumi, Masatoshi; Tsutsumi, Hiroyuki

2014-05-01

Although significant clinical efficacy and safety of rotavirus vaccines were recently revealed in many countries, the mechanism of their attenuation is not well understood. We passaged serially a cell culture-adapted murine rotavirus EB strain in mouse pups or in cell cultures alternately and repeatedly and fully sequenced all 11 genes of 21 virus samples passaged in mice or in cell cultures. Sequence analysis revealed that mouse-passaged viruses that regained virulence almost consistently acquired four kinds of amino acid (aa) substitutions in VP4 and substitution in aa 37 (Val to Ala) in NSP4. In addition, they gained and invariably conserved the 3' consensus sequence in NSP1. The molecular changes occurred along with the acquisition of virulence during passages in mice and then disappeared following passages in cell cultures. Intraperitoneal injection of recombinant NSP4 proteins confirmed the aa 37 site as important for its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence. Serial passage of a virulent wild-type virus in vitro often results in loss of virulence of the virus in an original animal host, while serial passage of a cell culture-adapted avirulent virus in vivo often gains virulence in an animal host. Actually, live attenuated virus vaccines were originally produced by serial passage in cell cultures. Although clinical efficacy and safety of rotavirus vaccines were recently revealed, the mechanism of their attenuation is not well understood. We passaged serially a murine rotavirus by alternating switch of host (mice or cell cultures) repeatedly and sequenced the eleven genes of the passaged viruses to identify mutations associated with the emergence or disappearance of virulence. Sequence analysis revealed that changes in three genes (VP4, NSP1, and NSP4) were associated with virulence in mice. Intraperitoneal injection of recombinant NSP4 proteins confirmed its diarrheagenic activity in mice

Virulence-Associated Genome Mutations of Murine Rotavirus Identified by Alternating Serial Passages in Mice and Cell Cultures

Science.gov (United States)

Tatsumi, Masatoshi; Tsutsumi, Hiroyuki

2014-01-01

ABSTRACT Although significant clinical efficacy and safety of rotavirus vaccines were recently revealed in many countries, the mechanism of their attenuation is not well understood. We passaged serially a cell culture-adapted murine rotavirus EB strain in mouse pups or in cell cultures alternately and repeatedly and fully sequenced all 11 genes of 21 virus samples passaged in mice or in cell cultures. Sequence analysis revealed that mouse-passaged viruses that regained virulence almost consistently acquired four kinds of amino acid (aa) substitutions in VP4 and substitution in aa 37 (Val to Ala) in NSP4. In addition, they gained and invariably conserved the 3′ consensus sequence in NSP1. The molecular changes occurred along with the acquisition of virulence during passages in mice and then disappeared following passages in cell cultures. Intraperitoneal injection of recombinant NSP4 proteins confirmed the aa 37 site as important for its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence. IMPORTANCE Serial passage of a virulent wild-type virus in vitro often results in loss of virulence of the virus in an original animal host, while serial passage of a cell culture-adapted avirulent virus in vivo often gains virulence in an animal host. Actually, live attenuated virus vaccines were originally produced by serial passage in cell cultures. Although clinical efficacy and safety of rotavirus vaccines were recently revealed, the mechanism of their attenuation is not well understood. We passaged serially a murine rotavirus by alternating switch of host (mice or cell cultures) repeatedly and sequenced the eleven genes of the passaged viruses to identify mutations associated with the emergence or disappearance of virulence. Sequence analysis revealed that changes in three genes (VP4, NSP1, and NSP4) were associated with virulence in mice. Intraperitoneal injection of recombinant NSP4 proteins confirmed its

Sulfur ligand mediated electrochemistry of gold surfaces and nanoparticles: what, how, and why

DEFF Research Database (Denmark)

Chi, Qijin; Ford, Michael J.; Halder, Arnab

2017-01-01

Gold surfaces are widely used in electrochemistry whilst gold nanoparticles have very many uses, with both the surfaces and the particles often being protected by sulfur-bound organic ligands. The ligands not only provide chemical stability but also directly participate in many desired processes....... This review considers the diversity of known atomic structures for gold-sulfur interfaces, how these structures facilitate a diversity of mechanisms in electrochemical applications, and why this is possible based on recent advances in the basic understanding of the electronic structure of gold-sulfur bonds...

Spontaneous passage of long, sharp gastrointestinal foreign body in a child.

Science.gov (United States)

Karthikeyan, Vilvapathy Senguttuvan; Ansari, Mohammed Gaffoor; Suresh, Ramasamy; Easwaran, Bettaiyagowder

2015-01-19

Foreign body (FB) ingestion is a common problem in children. Up to 90% of these FBs pass spontaneously. FBs reaching the stomach usually pass out spontaneously. Exceptions to this spontaneous passage include a long FB that cannot cross the pylorus, duodenum or ileocaecal junction. We present a case of a 9-year boy who accidentally ingested a long paper pin, which spontaneously passed in 26 h. This case is being reported to highlight the successful spontaneous passage of a 4 cm long sharp foreign body in a child. 2015 BMJ Publishing Group Ltd.

A Herpesviral induction of RAE-1 NKG2D ligand expression occurs through release of HDAC mediated repression.

Science.gov (United States)

Greene, Trever T; Tokuyama, Maria; Knudsen, Giselle M; Kunz, Michele; Lin, James; Greninger, Alexander L; DeFilippis, Victor R; DeRisi, Joseph L; Raulet, David H; Coscoy, Laurent

2016-11-22

Natural Killer (NK) cells are essential for control of viral infection and cancer. NK cells express NKG2D, an activating receptor that directly recognizes NKG2D ligands. These are expressed at low level on healthy cells, but are induced by stresses like infection and transformation. The physiological events that drive NKG2D ligand expression during infection are still poorly understood. We observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands. We demonstrate that RAE-1 is transcriptionally repressed by histone deacetylase inhibitor 3 (HDAC3) in healthy cells, and m18 relieves this repression by directly interacting with Casein Kinase II and preventing it from activating HDAC3. Accordingly, we found that HDAC inhibiting proteins from human herpesviruses induce human NKG2D ligand ULBP-1. Thus our findings indicate that virally mediated HDAC inhibition can act as a signal for the host to activate NK-cell recognition.

Macrocyclic G-quadruplex ligands

DEFF Research Database (Denmark)

Nielsen, M C; Ulven, Trond

2010-01-01

are macrocyclic structures which have been modeled after the natural product telomestatin or from porphyrin-based ligands discovered in the late 1990s. These two structural classes of G-quadruplex ligands are reviewed here with special attention to selectivity and structure-activity relationships, and with focus...

California's tobacco tax initiative: the development and passage of Proposition 99.

Science.gov (United States)

Traynor, M P; Glantz, S A

1996-01-01

In this case study, we describe and analyze the development and passage of California's tobacco tax initiative, Proposition 99, the Tobacco Tax and Health Promotion Act of 1988. We gathered information from published reports, public documents, personal correspondence, internal memorandums, polling data, and interviews with representatives from organizations that participated in the Proposition 99 campaign. Proposition 99 passed as a result of the efforts of a coalition of voluntary health agencies, medical organizations, and environmental groups. They organized a long-term effort by conducting essential polling, planning strategies, gaining media exposure, developing a coalition, and running a successful campaign to enact the tax by shifting the venue from legislative to initiative politics. To build the coalition that was needed to pass Proposition 99, public health proponents enlisted the help of medical organizations in exchange for additional revenue to be allocated to medical services. By shifting the venue from the legislature to the general public, advocates capitalized on public concern about tobacco and for youth and took advantage of the tobacco industry's low credibility. The passage of Proposition 99, despite a massive campaign against it by the tobacco industry, represents a milestone in the tobacco control and public health fields. From its passage in 1988 through 1993, tobacco use in California declined by 27 percent, which is three times faster than the United States average. As a result, Proposition 99 has served as a national model for other states and the federal government. Although allocation of tobacco tax revenues specifically to health education and prevention was a primary goal during the development and passage of Proposition 99, when the venue shifted back to the legislature for implementation, medical organizations successfully advocated illegal diversions of Proposition 99 tobacco control and research funds to medical services

Nonstationary Narrow-Band Response and First-Passage Probability

DEFF Research Database (Denmark)

Krenk, Steen

1979-01-01

The notion of a nonstationary narrow-band stochastic process is introduced without reference to a frequency spectrum, and the joint distribution function of two consecutive maxima is approximated by use of an envelope. Based on these definitions the first passage problem is treated as a Markov po...

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

International Nuclear Information System (INIS)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei

2015-01-01

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H_2ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H_2hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd_2(2,6-ndc)_2(bpp)(DMF)]·2DMF (1) and [Cd_3(hmdb)_3(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

Conformational diversity of flexible ligand in metal-organic frameworks controlled by size-matching mixed ligands

Energy Technology Data Exchange (ETDEWEB)

Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei, E-mail: hanlei@nbu.edu.cn

2015-12-15

Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.

Intermediate-level crossings of a first-passage path

International Nuclear Information System (INIS)

Bhat, Uttam; Redner, S

2015-01-01

We investigate some simple and surprising properties of a one-dimensional Brownian trajectory with diffusion coefficient D that starts at the origin and: (i) is at X at time T, or (ii) first reaches X at time T. We determine the most likely location of the first-passage trajectory from (0, 0) to (X, T) and its distribution at any intermediate time t < T. A first-passage path typically starts out by being repelled from its final location when X 2 /DT ≪ 1. We also determine the distribution of times when the trajectory first crosses and last crosses an arbitrary intermediate position x < X. The distribution of first-crossing times may be unimodal or bimodal, depending on whether X 2 /DT ≪ 1 or X 2 /DT ≫ 1. The form of the first-crossing probability in the bimodal regime is qualitatively similar to, but more singular than, the well-known arcsine law. (paper)

Analysis of conditions favourable for small vertical axis wind turbines between building passages in urban areas of Sweden

Science.gov (United States)

Awan, Muhammad Rizwan; Riaz, Fahid; Nabi, Zahid

2017-05-01

This paper presents the analysis of installing the vertical axis wind turbines between the building passages on an island in Stockholm, Sweden. Based on the idea of wind speed amplification due to the venture effect in passages, practical measurements were carried out to study the wind profile for a range of passage widths in parallel building passages. Highest increment in wind speed was observed in building passages located on the periphery of sland as wind enters from free field. Wind mapping was performed in the island to choose the most favourable location to install the vertical axis wind turbines (VAWT). Using the annual wind speed data for location and measured amplification factor, energy potential of the street was calculated. This analysis verified that small vertical axis wind turbines can be installed in the passage centre line provided that enough space is provided for traffic and passengers.

Female listeners’ autonomic responses to dramatic shifts between loud and soft music/sound passages: a study of heavy metal songs

Directory of Open Access Journals (Sweden)

Tzu-Han eCheng

2016-02-01

Full Text Available Although music and the emotion it conveys unfold over time, little is known about how listeners respond to shifts in musical emotions. A special technique in heavy metal music utilizes dramatic shifts between loud and soft passages. Loud passages are penetrated by distorted sounds conveying aggression, whereas soft passages are often characterized by a clean, calm singing voice and light accompaniment. The present study used heavy metal songs and soft sea sounds to examine how female listeners’ respiration rates and heart rates responded to the arousal changes associated with auditory stimuli. The high-frequency power of heart rate variability (HF-HRV was used to assess cardiac parasympathetic activity. The results showed that the soft passages of heavy metal songs and soft sea sounds expressed lower arousal and induced significantly higher HF-HRVs than the loud passages of heavy metal songs. Listeners’ respiration rate was determined by the arousal level of the present music passage, whereas the heart rate was dependent on both the present and preceding passages. Compared with soft sea sounds, the loud music passage led to greater deceleration of the heart rate at the beginning of the following soft music passage. The sea sounds delayed the heart rate acceleration evoked by the following loud music passage. The data provide evidence that sound-induced parasympathetic activity affects listener’s heart rate in response to the following music passage. These findings have potential implications for future research of the temporal dynamics of musical emotions.

Pokemon decreases the transcriptional activity of RARα in the absence of ligand.

Science.gov (United States)

Yang, Yutao; Li, Yueting; Di, Fei; Cui, Jiajun; Wang, Yue; David Xu, Zhi-Qing

2016-12-20

Pokemon is a transcriptional repressor that belongs to the POZ and Krüppel (POK) protein family. In this study, we investigated the potential interaction between Pokemon and retinoic acid receptor alpha (RARα) and determined the role of Pokemon in regulation of RARα transcriptional activity in the absence of ligand. We found that Pokemon could directly interact with RARα. Moreover, we demonstrated that Pokemon could decrease the transcriptional activity of RARα in the absence of ligand. Furthermore, we showed that Pokemon could repress the transcriptional activity of RARα by increasing the recruitment of nuclear receptor co-repressor (NCoR) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) to the retinoic acid response element (RARE) element. Taken together, these data suggest that Pokemon is a novel partner of RARα that acts as a co-repressor to regulate RARα transcriptional activity in the absence of ligand.

Uptake of γ-emitting radionuclides by aquatic biota exposed to contaminated water before and after passage through the ground

International Nuclear Information System (INIS)

Cushing, C.E.; Rickard, W.H.; Watson, D.G.

1984-01-01

Three experimental systems were designed to investigate the differential accumulation of radionuclides by biota from low-level aqueous effluents after passage through the ground. One system received river water (control), one received dilute low-level radioactive effluents (trench), and the third received the low-level effluents after it had percolated through about 260 m or porous gravel (springs). Biota studied included filamentous green algae, clams (Corbicula), goldfish (Carassius auratus), carp (Cyprinus carpio), and Veronica. Trophic level differences in accumulation of the various radionuclides from the diluted trench water were not consistent but generally followed the pattern algae > goldfish > molluscs > carp. Cobalt-60 was accumulated to the highest level of any radionuclide, and accumulation levels at the three sites were directly related to the concentration of 60 Co in the water. Manganese-54, 59 Fe, and 106 Ru were also accumulated to measurable levels in biota at the springs site indicating their bioavailability after passage through the ground

Phase Variation Analysis of Coxiella burnetii during Serial Passage in Cell Culture by Use of Monoclonal Antibodies

Science.gov (United States)

Hotta, Akitoyo; Kawamura, Midori; To, Ho; Andoh, Masako; Yamaguchi, Tsuyoshi; Fukushi, Hideto; Hirai, Katsuya

2002-01-01

Antigenic changes in Coxiella burnetii Nine Mile strain phase I during serial passages in cell culture were analyzed with three groups of monoclonal antibodies (MAbs) against lipopolysaccharide. The MAbs of group 1 did not react with organisms that were passaged over five times, and the MAbs of group 2 did not react with organisms that were passaged over eight times. The MAbs of group 3 reacted with organisms passaged up to 15 times but did not react with phase II cells. These results suggest that C. burnetii could be differentiated into four phase states during phase variation. PMID:12117996

Environmental mitigation at hydroelectric projects. Volume 2, Benefits and costs of fish passage and protection

Energy Technology Data Exchange (ETDEWEB)

Francfort, J.E.; Rinehart, B.N.; Sommers, G.L. [EG and G Idaho, Inc., Idaho Falls, ID (United States); Cada, G.F.; Jones, D.W. [Oak Ridge National Lab., TN (United States); Dauble, D.D. [Pacific Northwest Lab., Richland, WA (United States); Hunt, R.T. [Hunt (Richard) Associates, Inc., Concord, NH (United States); Costello, R.J. [Northwest Water Resources Advisory Services (United States)

1994-01-01

This study examines envirorunental mitigation practices that provide upstream and downstream fish passage and protection at hydroelectric projects. The study includes a survey of fish passage and protection mitigation practices at 1,825 hydroelectric plants regulated by the Federal Energy Regulatory Commission (FERC) to determine frequencies of occurrence, temporal trends, and regional practices based on FERC regions. The study also describes, in general terms, the fish passage/protection mitigation costs at 50 non-Federal hydroelectric projects. Sixteen case studies are used to examine in detail the benefits and costs of fish passage and protection. The 16 case studies include 15 FERC licensed or exempted hydroelectric projects and one Federally-owned and-operated hydroelectric project. The 16 hydroelectric projects are located in 12 states and range in capacity from 400 kilowatts to 840 megawatts. The fish passage and protection mitigation methods at the case studies include fish ladders and lifts, an Eicher screen, spill flows, airburst-cleaned inclined and cylindrical wedgewire screens, vertical barrier screens, and submerged traveling screens. The costs, benefits, monitoring methods, and operating characteristics of these and other mitigation methods used at the 16 case studies are examined.

Identification and characterization of PPAR? ligands in the hippocampus

OpenAIRE

Roy, Avik; Kundu, Madhuchhanda; Jana, Malabendu; Mishra, Rama K.; Yung, Yeni; Luan, Chi-Hao; Gonzalez, Frank J.; Pahan, Kalipada

2016-01-01

Peroxisome proliferator-activated receptor alpha (PPAR?) regulates hepatic fatty acid catabolism and mediates the metabolic response to starvation. Recently, we have found that PPAR? is constitutively activated in nuclei of hippocampal neurons and controls plasticity via direct transcriptional activation of CREB. Here, three endogenous ligands of PPAR?, 3-hydroxy-(2,2)-dimethyl butyrate, hexadecanamide, and 9-octadecenamide were discovered in mouse brain hippocampus. Mass spectrometric detect...

Validation of a Functional Pyelocalyceal Renal Model for the Evaluation of Renal Calculi Passage While Riding a Roller Coaster.

Science.gov (United States)

Mitchell, Marc A; Wartinger, David D

2016-10-01

The identification and evaluation of activities capable of dislodging calyceal renal calculi require a patient surrogate or validated functional pyelocalyceal renal model. To evaluate roller coaster facilitation of calyceal renal calculi passage using a functional pyelocalyceal renal model. A previously described adult ureteroscopy and renoscopy simulator (Ideal Anatomic) was modified and remolded to function as a patient surrogate. Three renal calculi of different sizes from the patient who provided the original computed tomographic urograph on which the simulator was based were used. The renal calculi were suspended in urine in the model and taken for 20 rides on the Big Thunder Mountain Railroad roller coaster at Walt Disney World in Orlando, Florida. The roller coaster rides were analyzed using variables of renal calculi volume, calyceal location, model position on the roller coaster, and renal calculi passage. Sixty renal calculi rides were analyzed. Independent of renal calculi volume and calyceal location, front seating on the roller coaster resulted in a passage rate of 4 of 24. Independent of renal calculi volume and calyceal location, rear seating on the roller coaster resulted in a passage rate of 23 of 36. Independent of renal calculi volume in rear seating, calyceal location differed in passage rates, with an upper calyceal calculi passage rate of 100%; a middle calyceal passage rate of 55.6%; and a lower calyceal passage rate of 40.0%. The functional pyelocalyceal renal model serves as a functional patient surrogate to evaluate activities that facilitate calyceal renal calculi passage. The rear seating position on the roller coaster led to the most renal calculi passages.

77 FR 7025 - Safety Zones; America's Cup World Series, East Passage, Narragansett Bay, RI

Science.gov (United States)

2012-02-10

...-AA00 Safety Zones; America's Cup World Series, East Passage, Narragansett Bay, RI AGENCY: Coast Guard... the America's Cup World Series sailing vessel racing event. This safety zone is intended to safeguard...'s Cup-class races on the waters of the East Passage, Narragansett Bay, Rhode Island. Vessels will be...

Impact of habitat-specific GPS positional error on detection of movement scales by first-passage time analysis.

Directory of Open Access Journals (Sweden)

David M Williams

Full Text Available Advances in animal tracking technologies have reduced but not eliminated positional error. While aware of such inherent error, scientists often proceed with analyses that assume exact locations. The results of such analyses then represent one realization in a distribution of possible outcomes. Evaluating results within the context of that distribution can strengthen or weaken our confidence in conclusions drawn from the analysis in question. We evaluated the habitat-specific positional error of stationary GPS collars placed under a range of vegetation conditions that produced a gradient of canopy cover. We explored how variation of positional error in different vegetation cover types affects a researcher's ability to discern scales of movement in analyses of first-passage time for white-tailed deer (Odocoileus virginianus. We placed 11 GPS collars in 4 different vegetative canopy cover types classified as the proportion of cover above the collar (0-25%, 26-50%, 51-75%, and 76-100%. We simulated the effect of positional error on individual movement paths using cover-specific error distributions at each location. The different cover classes did not introduce any directional bias in positional observations (1 m≤mean≤6.51 m, 0.24≤p≤0.47, but the standard deviation of positional error of fixes increased significantly with increasing canopy cover class for the 0-25%, 26-50%, 51-75% classes (SD = 2.18 m, 3.07 m, and 4.61 m, respectively and then leveled off in the 76-100% cover class (SD = 4.43 m. We then added cover-specific positional errors to individual deer movement paths and conducted first-passage time analyses on the noisy and original paths. First-passage time analyses were robust to habitat-specific error in a forest-agriculture landscape. For deer in a fragmented forest-agriculture environment, and species that move across similar geographic extents, we suggest that first-passage time analysis is robust with regard to

Simple relations between mean passage times and Kramers' stationary rate

International Nuclear Information System (INIS)

Boilley, David; Jurado, Beatriz; Schmitt, Christelle

2004-01-01

The classical problem of the escape time of a metastable potential well in a thermal environment is generally studied by various quantities like Kramers' stationary escape rate, mean first passage time, nonlinear relaxation time, or mean last passage time. In addition, numerical simulations lead to the definition of other quantities as the long-time limit escape rate and the transient time. In this paper, we propose some simple analytical relations between all these quantities. In particular, we point out the hypothesis used to evaluate these various times in order to clarify their comparison and applicability, and show how average times include the transient time and the long-time limit of the escape rate

Meridional contrasts in productivity changes driven by the Cenozoic opening of Drake Passage

Science.gov (United States)

Donnadieu, Y.; Ladant, J. B.; Bopp, L.; Wilson, P. A.; Lear, C. H.

2017-12-01

The progressive opening of Drake Passage across the Eocene and the Oligocene occurs contemporaneously to the long-term global cooling of the late Eocene, which culminated with the Eocene-Oligocene glaciation of Antarctica. Atmospheric pCO2 decline during the late Eocene is thought to have played a major role in the climatic shifts of the Eocene-Oligocene boundary, yet reasons behind CO2 variations remain obscure. Changes in marine productivity affecting the biological oceanic carbon pump represent a possible cause. Here, we explore whether and how the opening of Drake Passage may have affected the marine biogeochemistry, and in particular paleoproductivity changes, with the use of a fully coupled atmosphere-ocean-biogeochemical model (IPSL-CM5A). We find that the simulated changes to Drake Passage opening exhibit a uniform decrease in the low latitudes while the high latitude response is more spatially heterogeneous. Mechanistically, the low latitude productivity decrease is a consequence of the dramatic reorganization of the ocean circulation when Drake Passage opens, as the shift from a well ventilated to a swampier ocean drives nutrient depletion in the low latitudes. In the high latitudes, the onset of the Antarctic Circumpolar Current in the model exerts a strong control both on nutrient availability but also on regions of deep water formation, which results in non-uniform patterns of productivity change in the Southern Ocean. The qualitative agreement between geographically diverse long-term paleoproductivity records and the simulated variations suggests that the opening of Drake Passage may contribute to part of the long-term paleoproductivity signal recorded in the data.

Bathymetry and oceanic flow structure at two deep passages crossing the Lomonosov Ridge

Science.gov (United States)

Björk, Göran; Jakobsson, Martin; Assmann, Karen; Andersson, Leif G.; Nilsson, Johan; Stranne, Christian; Mayer, Larry

2018-01-01

The Lomonosov Ridge represents a major topographical feature in the Arctic Ocean which has a large effect on the water circulation and the distribution of water properties. This study presents detailed bathymetric survey data along with hydrographic data at two deep passages across the ridge: a southern passage (80-81° N), where the ridge crest meets the Siberian continental slope, and a northern passage around 84.5° N. The southern channel is characterized by smooth and flat bathymetry around 1600-1700 m with a sill depth slightly shallower than 1700 m. A hydrographic section across the channel reveals an eastward flow with Amundsen Basin properties in the southern part and a westward flow of Makarov Basin properties in the northern part. The northern passage includes an approximately 72 km long and 33 km wide trough which forms an intra-basin in the Lomonosov Ridge morphology (the Oden Trough). The eastern side of the Oden Trough is enclosed by a narrow and steep ridge rising 500-600 m above a generally 1600 m deep trough bottom. The deepest passage (the sill) is 1470 m deep and located on this ridge. Hydrographic data show irregular temperature and salinity profiles indicating that water exchange occurs as midwater intrusions bringing water properties from each side of the ridge in well-defined but irregular layers. There is also morphological evidence that some rather energetic flows may occur in the vicinity of the sill. A well expressed deepening near the sill may be the result of seabed erosion by bottom currents.

Rapid, radiochemical-ligand binding assay for methotrexate

International Nuclear Information System (INIS)

Caston, J.D.

1976-01-01

A radiochemical ligand binding assay for methotrexate is provided. A binder factor comprising a partially purified dihydrofolic acid reductase preparation is employed. The binder factor is conveniently prepared by homogenizing a factor containing animal organ such as liver, and extracting with isotonic saline and ammonium sulfate. A binder cofactor, NADPH 2 , is also employed in the binding reaction. The procedure contemplates both direct and sequential assay techniques, and it is not interfered with by vast excesses of many natural folate derivatives. 12 claims, 6 drawing figures

Dosimetric characteristics of PASSAG as a new polymer gel dosimeter with negligible toxicity

Science.gov (United States)

Farhood, Bagher; Abtahi, Seyed Mohammad Mahdi; Geraily, Ghazale; Ghorbani, Mehdi; Mahdavi, Seied Rabi; Zahmatkesh, Mohammad Hasan

2018-06-01

Despite many advantages of polymer gel dosimeters, their clinical use is only not realized now. Toxicity of polymer gel dosimeters can be considered as one of their main limitations for use in routine clinical applications. In the current study, a new polymer gel dosimeter is introduced with negligible toxicity. For this purpose, 2-Acrylamido-2-Methy-1-PropaneSulfonic acid (AMPS) sodium salt monomer was replaced instead of acrylamide monomer used in PAGAT gel dosimeter by using %6 T and %50 C to the gel formula and the new formulation is called PASSAG (Poly AMPS Sodium Salt and Gelatin) polymer gel dosimeter. The irradiation of gel dosimeters was carried out using a Co-60 therapy machine. MRI technique was used to quantify the dose responses of the PASSAG gel dosimeter. Then, the MRI responses (R2) of the gel dosimeter was analyzed at different dose values, post-irradiation times, and scanning temperatures. The results showed that the new gel formulation has a negligible toxicity and it is also eco-friendly. In addition, carcinogenicity and genetic toxicity tests are negative for the monomer used in PASSAG. The radiological properties of PASSAG gel dosimeter showed that this substance can be considered as a soft tissue/water equivalent material. Furthermore, dosimetric evaluation of the new polymer gel dosimeter revealed an excellent linear R2-dose response in the evaluated dose range (0-15 Gy). The R2-dose sensitivity and dose resolution of PASSAG gel dosimeter were 0.081 s-1Gy-1 (in 0-15 Gy dose range) and 1 Gy (in 0-10 Gy dose range), respectively. Moreover, it was shown that the R2-dose sensitivity and dose resolution of the new gel dosimeter improves over time after irradiation. It was also found that the R2 response of the PASSAG gel dosimeter has less dependency to the 18, 20, and 24 °C scanning temperature in comparison to that of room temperature (22 °C).

Ligand cluster-based protein network and ePlatton, a multi-target ligand finder.

Science.gov (United States)

Du, Yu; Shi, Tieliu

2016-01-01

Small molecules are information carriers that make cells aware of external changes and couple internal metabolic and signalling pathway systems with each other. In some specific physiological status, natural or artificial molecules are used to interact with selective biological targets to activate or inhibit their functions to achieve expected biological and physiological output. Millions of years of evolution have optimized biological processes and pathways and now the endocrine and immune system cannot work properly without some key small molecules. In the past thousands of years, the human race has managed to find many medicines against diseases by trail-and-error experience. In the recent decades, with the deepening understanding of life and the progress of molecular biology, researchers spare no effort to design molecules targeting one or two key enzymes and receptors related to corresponding diseases. But recent studies in pharmacogenomics have shown that polypharmacology may be necessary for the effects of drugs, which challenge the paradigm, 'one drug, one target, one disease'. Nowadays, cheminformatics and structural biology can help us reasonably take advantage of the polypharmacology to design next-generation promiscuous drugs and drug combination therapies. 234,591 protein-ligand interactions were extracted from ChEMBL. By the 2D structure similarity, 13,769 ligand emerged from 156,151 distinct ligands which were recognized by 1477 proteins. Ligand cluster- and sequence-based protein networks (LCBN, SBN) were constructed, compared and analysed. For assisting compound designing, exploring polypharmacology and finding possible drug combination, we integrated the pathway, disease, drug adverse reaction and the relationship of targets and ligand clusters into the web platform, ePlatton, which is available at http://www.megabionet.org/eplatton. Although there were some disagreements between the LCBN and SBN, communities in both networks were largely the same

Passage survival of juvenile steelhead, coho salmon, and Chinook salmon in Lake Scanewa and at Cowlitz Falls Dam, Cowlitz River, Washington, 2010–16

Science.gov (United States)

Liedtke, Theresa L.; Kock, Tobias J.; Hurst, William

2018-04-03

A multi-year evaluation was conducted during 2010–16 to evaluate passage survival of juvenile steelhead (Oncorhynchus mykiss), Chinook salmon (O. tshawytscha), and coho salmon (O. kisutch) in Lake Scanewa, and at Cowlitz Falls Dam in the upper Cowlitz River Basin, Washington. Reservoir passage survival was evaluated in 2010, 2011, and 2016, and included the tagging and release of 1,127 juvenile salmonids. Tagged fish were released directly into the Cowlitz and Cispus Rivers, 22.3 and 8.9 km, respectively, upstream of the reservoir, and were monitored as they moved downstream into, and through the reservoir. A single release-recapture survival model was used to analyze detection records and estimate reservoir passage survival, which was defined as successful passage from reservoir entry to arrival at Cowlitz Falls Dam. Tagged fish generally moved quickly downstream of the release sites and, on average, arrived in the dam forebay within 2 d of release. Median travel time from release to first detection at the dam ranged from 0.23 to 0.96 d for juvenile steelhead, from 0.15 to 1.11 d for juvenile coho salmon, and from 0.18 to 1.89 d for juvenile Chinook salmon. Minimum reservoir passage survival probabilities were 0.960 for steelhead, 0.855 for coho salmon and 0.900 for Chinook salmon.Dam passage survival was evaluated at the pilot-study level during 2013–16 and included the tagging and release of 2,512 juvenile salmonids. Juvenile Chinook salmon were evaluated during 2013–14, and juvenile steelhead and coho salmon were evaluated during 2015–16. A paired-release study design was used that included release sites located upstream and downstream of Cowlitz Falls Dam. The downstream release site was positioned at the downstream margin of the dam’s tailrace, which allowed dam passage survival to be measured in a manner that included mortality that occurred in the passage route and in the dam tailrace. More than one-half of the tagged Chinook salmon (52 percent

Passage of sediment through flumes and over weirs

NARCIS (Netherlands)

Bos, M.G.; Wijbenga, J.H.A.

1997-01-01

This paper reports on laboratory research on the sediment passage capability through long-throated flumes and broad-crested weirs with which the Froude number in the approach channel does not exceed 0.6 over a distance of about 20 times the water depth upstream of the structure. Design rules are

An Incidence Loss Model for Wave Rotors with Axially Aligned Passages

Science.gov (United States)

Paxson, Daniel E.

1998-01-01

A simple mathematical model is described to account for the losses incurred when the flow in the duct (port) of a wave rotor is not aligned with the passages. The model, specifically for wave rotors with axially aligned passages, describes a loss mechanism which is sensitive to incident flow angle and Mach number. Implementation of the model in a one-dimensional CFD based wave rotor simulation is presented. Comparisons with limited experimental results are consistent with the model. Sensitivity studies are presented which highlight the significance of the incidence loss relative to other loss mechanisms in the wave rotor.

Immobilisation of ligands by radio-derivatized polymers; Immobilisering av ligander med radioderiverte polymerer

Energy Technology Data Exchange (ETDEWEB)

Varga, J.M.; Fritsch, P.

1995-01-30

The invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligand of organic or inorganic nature to immobilize such ligands. 2 figs., 5 tabs.

Size matters. The width and location of a ureteral stone accurately predict the chance of spontaneous passage

Energy Technology Data Exchange (ETDEWEB)

Jendeberg, Johan; Geijer, Haakan; Alshamari, Muhammed; Liden, Mats [Oerebro University Hospital, Department of Radiology, Faculty of Medicine and Health, Oerebro (Sweden); Cierzniak, Bartosz [Oerebro University, Department of Surgery, Faculty of Medicine and Health, Oerebro (Sweden)

2017-11-15

To determine how to most accurately predict the chance of spontaneous passage of a ureteral stone using information in the diagnostic non-enhanced computed tomography (NECT) and to create predictive models with smaller stone size intervals than previously possible. Retrospectively 392 consecutive patients with ureteric stone on NECT were included. Three radiologists independently measured the stone size. Stone location, side, hydronephrosis, CRP, medical expulsion therapy (MET) and all follow-up radiology until stone expulsion or 26 weeks were recorded. Logistic regressions were performed with spontaneous stone passage in 4 weeks and 20 weeks as the dependent variable. The spontaneous passage rate in 20 weeks was 312 out of 392 stones, 98% in 0-2 mm, 98% in 3 mm, 81% in 4 mm, 65% in 5 mm, 33% in 6 mm and 9% in ≥6.5 mm wide stones. The stone size and location predicted spontaneous ureteric stone passage. The side and the grade of hydronephrosis only predicted stone passage in specific subgroups. Spontaneous passage of a ureteral stone can be predicted with high accuracy with the information available in the NECT. We present a prediction method based on stone size and location. (orig.)

Mechanical properties of cancer cells depend on number of passages: Atomic force microscopy indentation study

Science.gov (United States)

Dokukin, Maxim E.; Guz, Natalia V.; Sokolov, Igor

2017-08-01

Here we investigate one of the key questions in cell biology, if the properties of cell lines depend on the number of passages in-vitro. It is generally assumed that the change of cell properties (phenotypic drift) is insignificant when the number of passages is low (cell body and parameters of the pericellular brush layer from indentation force curves, which are recorded by means of atomic force microscopy (AFM). Using this method, we tested the change of the cell properties of human cancer breast epithelial cell line, MCF-7 (ATCC® HTB-22™), within the passages between 2 and 10. In contrast to the previous expectations, we observed a substantial transient change of the elastic modulus of the cell body during the first four passages (up to 4 times). The changes in the parameters of the pericellular coat were less dramatic (up to 2 times) but still statistically significant.

Mean first passage time for random walk on dual structure of dendrimer

Science.gov (United States)

Li, Ling; Guan, Jihong; Zhou, Shuigeng

2014-12-01

The random walk approach has recently been widely employed to study the relations between the underlying structure and dynamic of complex systems. The mean first-passage time (MFPT) for random walks is a key index to evaluate the transport efficiency in a given system. In this paper we study analytically the MFPT in a dual structure of dendrimer network, Husimi cactus, which has different application background and different structure (contains loops) from dendrimer. By making use of the iterative construction, we explicitly determine both the partial mean first-passage time (PMFT, the average of MFPTs to a given target) and the global mean first-passage time (GMFT, the average of MFPTs over all couples of nodes) on Husimi cactus. The obtained closed-form results show that PMFPT and EMFPT follow different scaling with the network order, suggesting that the target location has essential influence on the transport efficiency. Finally, the impact that loop structure could bring is analyzed and discussed.

Evolutionary characteristics of morbilliviruses during serial passages in vitro: Gradual attenuation of virus virulence.

Science.gov (United States)

Liu, Fuxiao; Wu, Xiaodong; Li, Lin; Zou, Yanli; Liu, Shan; Wang, Zhiliang

2016-08-01

The genus Morbillivirus is classified into the family Paramyxoviridae, and is composed of 6 members, namely measles virus (MV), rinderpest virus (RPV), peste-des-petits-ruminants virus (PPRV), canine distemper virus (CDV), phocine distemper virus (PDV) and cetacean morbillivirus (CeMV). The MV, RPV, PPRV and CDV have been successfully attenuated through their serial passages in vitro for the production of live vaccines. It has been demonstrated that the morbilliviral virulence in animals was progressively attenuated with their consecutive passages in vitro. However, only a few reports were involved in explanation of an attenuation-related mechanism on them until many years after the establishment of a quasispecies theory. RNA virus quasispecies arise from rapid evolution of viruses with high mutation rate during genomic replication, and play an important role in gradual loss of viral virulence by serial passages. Here, we overviewed the development of live-attenuated vaccine strains against morbilliviruses by consecutive passages in vitro, and further discussed a related mechanism concerning the relationship between virulence attenuation and viral evolution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Field-effect measurements of mobility and carrier concentration of Cu2S colloidal quantum dot thin films after ligand exchange

International Nuclear Information System (INIS)

Brewer, Adam S.; Arnold, Michael S.

2014-01-01

Colloidal quantum dots (CQDs) of copper sulfide (Cu 2 S), an earth-abundant semiconductor, have a number of intriguing applications that require knowledge of their electrical properties. Depending on stoichiometry, mobility, and surface treatment, applications include photoabsorbers for solar cells, tunable plasmonics, and counter-electrodes for polysulfate electrolytes. However, there have not been any direct measurements of electrical properties in Cu 2 S CQD thin films. Here, we exchange as synthesized dodecanethiol ligands with short ethanedithiol or ethylenediamine ligands to form thin films of coupled Cu 2 S CQDs. The mobility and carrier concentration were found to vary by ligand treatment from 10 −5 cm 2 /Vs and 10 19 holes/cm 3 for ethanedithiol ligands to 10 −3 cm 2 /Vs and 10 20 holes/cm 3 for ethylenediamine. These results are consistent with the carrier concentrations inferred from sub-bandgap surface-plasmon-resonances measured by infrared spectroscopy. These results will be useful when designing Cu 2 S materials for future applications. - Highlights: • Colloidal Cu2S quantum dots were synthesized and characterized. • Ligand exchange was performed to alter the Cu2S nanocrystal properties. • Ligand exchange was studied using photoluminescence and infrared spectroscopy. • Field effect mobility and carrier concentration were directly measured. • Carrier concentration was compared to estimates from surface plasmon resonances

Metal-ligand cooperative activation of nitriles by a ruthenium complex with a de-aromatized PNN pincer ligand

NARCIS (Netherlands)

Eijsink, Linda E; Perdriau, Sébastien C P; de Vries, Johannes G; Otten, Edwin

2016-01-01

The pincer complex (PNN)RuH(CO), with a de-aromatized pyridine in the ligand backbone, is shown to react with nitriles in a metal-ligand cooperative manner. This leads to the formation of a series of complexes with new Ru-N(nitrile) and C(ligand)-C(nitrile) bonds. The initial nitrile cycloaddition

Tobacco Smoke Pollution in Hospitality Venues Before and After Passage of Statewide Smoke-Free Legislation.

Science.gov (United States)

Buettner-Schmidt, Kelly; Boursaw, Blake; Lobo, Marie L; Travers, Mark J

2017-03-01

In 2012, North Dakota enacted a comprehensive statewide law prohibiting smoking in enclosed public places. Disparities in tobacco control exist in rural areas. This study's objective was to determine the extent to which the passage of a comprehensive, statewide, smoke-free law in a predominantly rural state influenced tobacco smoke pollution in rural and nonrural venues. A longitudinal cohort design study comparing the levels of tobacco smoke pollution before and after passage of the statewide smoke-free law was conducted in 64 restaurants and bars statewide in North Dakota. Particulate matter with a median aerodynamic diameter of <2.5 μm (a valid atmospheric marker of tobacco smoke pollution) was assessed. A significant 83% reduction in tobacco smoke pollution levels occurred after passage of the law. Significant reductions in tobacco smoke pollution levels occurred in each of the rural categories; however, no difference by rurality was noted in the analysis after passage of the law, in contrast to the study before passage. To our knowledge, this was the largest, single, rural postlaw study globally. A comprehensive statewide smoke-free law implemented in North Dakota dramatically decreased the level of tobacco smoke pollution in bars and restaurants. © 2016 The Authors. Public Health Nursing Published by Wiley Periodicals, Inc.

An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis

Science.gov (United States)

Quintana, Francisco J.; Murugaiyan, Gopal; Farez, Mauricio F.; Mitsdoerffer, Meike; Tukpah, Ann-Marcia; Burns, Evan J.; Weiner, Howard L.

2010-01-01

The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) participates in the differentiation of FoxP3+ Treg, Tr1 cells, and IL-17–producing T cells (Th17). Most of our understanding on the role of AHR on the FoxP3+ Treg compartment results from studies using the toxic synthetic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin. Thus, the physiological relevance of AHR signaling on FoxP3+ Treg in vivo is unclear. We studied mice that carry a GFP reporter in the endogenous foxp3 locus and a mutated AHR protein with reduced affinity for its ligands, and found that AHR signaling participates in the differentiation of FoxP3+ Treg in vivo. Moreover, we found that treatment with the endogenous AHR ligand 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) given parenterally or orally induces FoxP3+ Treg that suppress experimental autoimmune encephalomyelitis. ITE acts not only on T cells, but also directly on dendritic cells to induce tolerogenic dendritic cells that support FoxP3+ Treg differentiation in a retinoic acid-dependent manner. Thus, our work demonstrates that the endogenous AHR ligand ITE promotes the induction of active immunologic tolerance by direct effects on dendritic and T cells, and identifies nontoxic endogenous AHR ligands as potential unique compounds for the treatment of autoimmune disorders. PMID:21068375

Delayed Release from Proactive Interference with Meaningful Material: How Much Do We Remember After Reading Brief Prose Passages?

Science.gov (United States)

Blumenthal, Gary B.; Robbins, Donald

1977-01-01

Three experiments were conducted, investigating the buildup of and the release from proactive interference, in which the stimulus materials were brief prose passages about specific topics. Each passage was followed by a multiple-choice test, and then a final test on all the passages read was given. Implications of the data for standardized tests…

Analysis of primary cilia in directional cell migration in fibroblasts

DEFF Research Database (Denmark)

Christensen, Søren Tvorup; Veland, Iben; Schwab, Albrecht

2013-01-01

summarize selected methods in analyzing ciliary function in directional cell migration, including immunofluorescence microscopy, scratch assay, and chemotaxis assay by micropipette addition of PDGFRα ligands to cultures of fibroblasts. These methods should be useful not only in studying cell migration....... In particular, platelet-derived growth factor receptor alpha (PDGFRα) is compartmentalized to the primary cilium to activate signaling pathways that regulate reorganization of the cytoskeleton required for lamellipodium formation and directional migration in the presence of a specific ligand gradient. We...

Towards ligand docking including explicit interface water molecules.

Directory of Open Access Journals (Sweden)

Gordon Lemmon

Full Text Available Small molecule docking predicts the interaction of a small molecule ligand with a protein at atomic-detail accuracy including position and conformation the ligand but also conformational changes of the protein upon ligand binding. While successful in the majority of cases, docking algorithms including RosettaLigand fail in some cases to predict the correct protein/ligand complex structure. In this study we show that simultaneous docking of explicit interface water molecules greatly improves Rosetta's ability to distinguish correct from incorrect ligand poses. This result holds true for both protein-centric water docking wherein waters are located relative to the protein binding site and ligand-centric water docking wherein waters move with the ligand during docking. Protein-centric docking is used to model 99 HIV-1 protease/protease inhibitor structures. We find protease inhibitor placement improving at a ratio of 9:1 when one critical interface water molecule is included in the docking simulation. Ligand-centric docking is applied to 341 structures from the CSAR benchmark of diverse protein/ligand complexes [1]. Across this diverse dataset we see up to 56% recovery of failed docking studies, when waters are included in the docking simulation.

The emotion potential of words and passages in reading Harry Potter--an fMRI study.

Science.gov (United States)

Hsu, Chun-Ting; Jacobs, Arthur M; Citron, Francesca M M; Conrad, Markus

2015-03-01

Previous studies suggested that the emotional connotation of single words automatically recruits attention. We investigated the potential of words to induce emotional engagement when reading texts. In an fMRI experiment, we presented 120 text passages from the Harry Potter book series. Results showed significant correlations between affective word (lexical) ratings and passage ratings. Furthermore, affective lexical ratings correlated with activity in regions associated with emotion, situation model building, multi-modal semantic integration, and Theory of Mind. We distinguished differential influences of affective lexical, inter-lexical, and supra-lexical variables: differential effects of lexical valence were significant in the left amygdala, while effects of arousal-span (the dynamic range of arousal across a passage) were significant in the left amygdala and insula. However, we found no differential effect of passage ratings in emotion-associated regions. Our results support the hypothesis that the emotion potential of short texts can be predicted by lexical and inter-lexical affective variables. Copyright © 2015 Elsevier Inc. All rights reserved.

Unnatural amino acids as probes of ligand-receptor interactions and their conformational consequences

DEFF Research Database (Denmark)

Pless, Stephan Alexander; Ahern, Christopher A

2013-01-01

-edge synthetic and chemical biological approaches. Here we summarize recent advances in the use of site-directed incorporation of unnatural amino acids and chemical probes to study ligand-receptor interactions, determine the location of binding sites, and examine the downstream conformational consequences...

Australian experience of providing for fish passage at small instream structures

Energy Technology Data Exchange (ETDEWEB)

Lewis, B. [Forest Hill, Victoria (Australia)

2006-07-01

Various instream structures have been constructed in Australia as a result of increasing agricultural activities. However, even small structures such as culverts and stream gauging stations can restrict essential fish movements and result in the extinction of local fish species. This paper discussed methods of modifying and designing new structures to ensure adequate fish passage. It was suggested that instream structures can provide for fish passage through the provision of bridges, or through the use of low profile structures for small weirs. Recommendations for site-specific instream structures included an assessment of fish species, topography, flow characteristics and cost effectiveness. Solutions for reducing the impact of small instream barriers to fish movement were also discussed. Provision for fish passage is an important consideration for planners and designers of dams. Legislation is now in place to ensure a planning and approval process prior to the commencement of construction and operation. It was concluded that significant works are now being undertaken to restore fish migration pathways caused by barriers that restrict fish movement. However, monitoring is needed to ensure that designs operate effectively. 17 refs., 3 figs.

Australian experience of providing for fish passage at small instream structures

International Nuclear Information System (INIS)

Lewis, B.

2006-01-01

Various instream structures have been constructed in Australia as a result of increasing agricultural activities. However, even small structures such as culverts and stream gauging stations can restrict essential fish movements and result in the extinction of local fish species. This paper discussed methods of modifying and designing new structures to ensure adequate fish passage. It was suggested that instream structures can provide for fish passage through the provision of bridges, or through the use of low profile structures for small weirs. Recommendations for site-specific instream structures included an assessment of fish species, topography, flow characteristics and cost effectiveness. Solutions for reducing the impact of small instream barriers to fish movement were also discussed. Provision for fish passage is an important consideration for planners and designers of dams. Legislation is now in place to ensure a planning and approval process prior to the commencement of construction and operation. It was concluded that significant works are now being undertaken to restore fish migration pathways caused by barriers that restrict fish movement. However, monitoring is needed to ensure that designs operate effectively. 17 refs., 3 figs

First passage time in a two-layer system

International Nuclear Information System (INIS)

Lee, J.; Koplik, J.

1995-01-01

As a first step in the first passage problem for passive tracer in stratified porous media, we consider the case of a two-dimensional system consisting of two layers with different convection velocities. Using a lattice generating function formalism and a variety of analytic and numerical techniques, we calculate the asymptotic behavior of the first passage time probability distribution. We show analytically that the asymptotic distribution is a simple exponential in time for any choice of the velocities. The decay constant is given in terms of the largest eigenvalue of an operator related to a half-space Green's function. For the anti-symmetric case of opposite velocities in the layers, we show that the decay constant for system length L crosses over from L -2 behavior in the diffusive limit to L -1 behavior in the convective regime, where the crossover length L* is given in terms of the velocities. We also have formulated a general self-consistency relation, from which we have developed a recursive approach which is useful for studying the short-time behavior

Prediction of spontaneous ureteral stone passage: Automated 3D-measurements perform equal to radiologists, and linear measurements equal to volumetric.

Science.gov (United States)

Jendeberg, Johan; Geijer, Håkan; Alshamari, Muhammed; Lidén, Mats

2018-01-24

To compare the ability of different size estimates to predict spontaneous passage of ureteral stones using a 3D-segmentation and to investigate the impact of manual measurement variability on the prediction of stone passage. We retrospectively included 391 consecutive patients with ureteral stones on non-contrast-enhanced CT (NECT). Three-dimensional segmentation size estimates were compared to the mean of three radiologists' measurements. Receiver-operating characteristic (ROC) analysis was performed for the prediction of spontaneous passage for each estimate. The difference in predicted passage probability between the manual estimates in upper and lower stones was compared. The area under the ROC curve (AUC) for the measurements ranged from 0.88 to 0.90. Between the automated 3D algorithm and the manual measurements the 95% limits of agreement were 0.2 ± 1.4 mm for the width. The manual bone window measurements resulted in a > 20 percentage point (ppt) difference between the readers in the predicted passage probability in 44% of the upper and 6% of the lower ureteral stones. All automated 3D algorithm size estimates independently predicted the spontaneous stone passage with similar high accuracy as the mean of three readers' manual linear measurements. Manual size estimation of upper stones showed large inter-reader variations for spontaneous passage prediction. • An automated 3D technique predicts spontaneous stone passage with high accuracy. • Linear, areal and volumetric measurements performed similarly in predicting stone passage. • Reader variability has a large impact on the predicted prognosis for stone passage.

Effect of stress on turbine fish passage mortality estimates

International Nuclear Information System (INIS)

Ruggles, C.P.

1993-01-01

Tests were conducted with juvenile alewife to determine the effects of four experimental protocols upon turbine fish passage mortality estimates. Three protocols determined the effect of cumulative stresses upon fish, while the fourth determined the effect of long range truck transportation prior to release into the penstock or tailrace. The wide range in results were attributed to the presence or absence of additional stress factors associated with the experiments. For instance, fish may survive passage through a turbine, or non-turbine related stresses imposed by the investigator; however, when both are imposed, the cumulative stresses may be lethal. The impact of protocol stress on turbine mortality estimates becomes almost exponential after control mortality exceeds 10%. Valid turbine related mortalities may be determined only after stresses associated with experimental protocol are adequately reduced. This is usually indicated by a control mortality of less than 10%. 14 refs., 5 figs., 6 tabs

Ligand-Receptor Interaction-Mediated Transmembrane Transport of Dendrimer-like Soft Nanoparticles: Mechanisms and Complicated Diffusive Dynamics.

Science.gov (United States)

Liang, Junshi; Chen, Pengyu; Dong, Bojun; Huang, Zihan; Zhao, Kongyin; Yan, Li-Tang

2016-05-09

Nearly all nanomedical applications of dendrimer-like soft nanoparticles rely on the functionality of attached ligands. Understanding how the ligands interact with the receptors in cell membrane and its further effect on the cellular uptake of dendrimer-like soft nanoparticles is thereby a key issue for their better application in nanomedicine. However, the essential mechanism and detailed kinetics for the ligand-receptor interaction-mediated transmembrane transport of such unconventional nanoparticles remain poorly elucidated. Here, using coarse-grained simulations, we present the very first study of molecular mechanism and kinetics behaviors for the transmembrane transport of dendrimer-like soft nanoparticles conjugated with ligands. A phase diagram of interaction states is constructed through examining ligand densities and membrane tensions that allows us to identify novel endocytosis mechanisms featured by the direct wrapping and the penetration-extraction vesiculation. The results provide an in-depth insight into the diffusivity of receptors and dendrimer in the membrane plane and demonstrate how the ligand density influences receptor diffusion and uptake kinetics. It is interesting to find that the ligand-conjugated dendrimers present superdiffusive behaviors on a membrane, which is revealed to be driven by the random fluctuation dynamics of the membrane. The findings facilitate our understanding of some recent experimental observations and could establish fundamental principles for the future development of such important nanomaterials for widespread nanomedical applications.

Connection between optimal control theory and adiabatic-passage techniques in quantum systems

Science.gov (United States)

Assémat, E.; Sugny, D.

2012-08-01

This work explores the relationship between optimal control theory and adiabatic passage techniques in quantum systems. The study is based on a geometric analysis of the Hamiltonian dynamics constructed from Pontryagin's maximum principle. In a three-level quantum system, we show that the stimulated Raman adiabatic passage technique can be associated to a peculiar Hamiltonian singularity. One deduces that the adiabatic pulse is solution of the optimal control problem only for a specific cost functional. This analysis is extended to the case of a four-level quantum system.

Crystallization of bi-functional ligand protein complexes.

Science.gov (United States)

Antoni, Claudia; Vera, Laura; Devel, Laurent; Catalani, Maria Pia; Czarny, Bertrand; Cassar-Lajeunesse, Evelyn; Nuti, Elisa; Rossello, Armando; Dive, Vincent; Stura, Enrico Adriano

2013-06-01

Homodimerization is important in signal transduction and can play a crucial role in many other biological systems. To obtaining structural information for the design of molecules able to control the signalization pathways, the proteins involved will have to be crystallized in complex with ligands that induce dimerization. Bi-functional drugs have been generated by linking two ligands together chemically and the relative crystallizability of complexes with mono-functional and bi-functional ligands has been evaluated. There are problems associated with crystallization with such ligands, but overall, the advantages appear to be greater than the drawbacks. The study involves two matrix metalloproteinases, MMP-12 and MMP-9. Using flexible and rigid linkers we show that it is possible to control the crystal packing and that by changing the ligand-enzyme stoichiometric ratio, one can toggle between having one bi-functional ligand binding to two enzymes and having the same ligand bound to each enzyme. The nature of linker and its point of attachment on the ligand can be varied to aid crystallization, and such variations can also provide valuable structural information about the interactions made by the linker with the protein. We report here the crystallization and structure determination of seven ligand-dimerized complexes. These results suggest that the use of bi-functional drugs can be extended beyond the realm of protein dimerization to include all drug design projects. Copyright © 2013 Elsevier Inc. All rights reserved.

Autocrine signal transmission with extracellular ligand degradation

Science.gov (United States)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-03-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand-receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers.

Passage of stable isotope-labeled grass silage fiber and fiber-bound protein through the gastroinstestinal tract of dairy cows

NARCIS (Netherlands)

Warner, D.; Dijkstra, J.; Hendriks, W.H.; Pellikaan, W.F.

2013-01-01

Fractional passage rates are required to predict nutrient absorption in ruminants but data on nutrient-specific passage kinetics are largely lacking. With the use of the stable isotope ratio (d) as an internal marker, we assessed passage kinetics of fiber and fiber-bound nitrogen (N) of

Cell-specific targeting by heterobivalent ligands.

Science.gov (United States)

Josan, Jatinder S; Handl, Heather L; Sankaranarayanan, Rajesh; Xu, Liping; Lynch, Ronald M; Vagner, Josef; Mash, Eugene A; Hruby, Victor J; Gillies, Robert J

2011-07-20

Current cancer therapies exploit either differential metabolism or targeting to specific individual gene products that are overexpressed in aberrant cells. The work described herein proposes an alternative approach--to specifically target combinations of cell-surface receptors using heteromultivalent ligands ("receptor combination approach"). As a proof-of-concept that functionally unrelated receptors can be noncovalently cross-linked with high avidity and specificity, a series of heterobivalent ligands (htBVLs) were constructed from analogues of the melanocortin peptide ligand ([Nle(4), dPhe(7)]-α-MSH) and the cholecystokinin peptide ligand (CCK-8). Binding of these ligands to cells expressing the human Melanocortin-4 receptor and the Cholecystokinin-2 receptor was analyzed. The MSH(7) and CCK(6) were tethered with linkers of varying rigidity and length, constructed from natural and/or synthetic building blocks. Modeling data suggest that a linker length of 20-50 Å is needed to simultaneously bind these two different G-protein coupled receptors (GPCRs). These ligands exhibited up to 24-fold enhancement in binding affinity to cells that expressed both (bivalent binding), compared to cells with only one (monovalent binding) of the cognate receptors. The htBVLs had up to 50-fold higher affinity than that of a monomeric CCK ligand, i.e., Ac-CCK(6)-NH(2). Cell-surface targeting of these two cell types with labeled heteromultivalent ligand demonstrated high avidity and specificity, thereby validating the receptor combination approach. This ability to noncovalently cross-link heterologous receptors and target individual cells using a receptor combination approach opens up new possibilities for specific cell targeting in vivo for therapy or imaging.

Condensation phenomena in a turbine blade passage

International Nuclear Information System (INIS)

Skillings, S.A.

1989-02-01

The mechanisms associated with the formation and growth of water droplets in the large low-pressure (LP) turbines used for electrical power generation are poorly understood and recent measurements have indicated that an unusually high loss is associated with the initial nucleation of these droplets. In order to gain an insight into the phenomena which arise in the turbine situation, some experiments were performed to investigate the behaviour of condensing steam flows in a blade passage. This study has revealed the fundamental significance of droplet nucleation in modifying the single-phase flow structure and results are presented which show the change in shock wave pattern when inlet superheat and outlet Mach number are varied. The trailing-edge shock wave structure appears considerably more robust towards variation of inlet superheat than purely one-dimensional considerations may suggest and the inadequacies of adopting a one-dimensional theory to analyse multi-dimensional condensing flows are demonstrated. Over a certain range of outlet Mach numbers an oscillating shock wave will establish in the throat region of the blade passage and this has been shown to interact strongly with droplet nucleation, resulting in a considerably increased mean droplet size. The possible implications of these results for turbine performance are also discussed. (author)

GalaxyDock BP2 score: a hybrid scoring function for accurate protein-ligand docking

Science.gov (United States)

Baek, Minkyung; Shin, Woong-Hee; Chung, Hwan Won; Seok, Chaok

2017-07-01

Protein-ligand docking is a useful tool for providing atomic-level understanding of protein functions in nature and design principles for artificial ligands or proteins with desired properties. The ability to identify the true binding pose of a ligand to a target protein among numerous possible candidate poses is an essential requirement for successful protein-ligand docking. Many previously developed docking scoring functions were trained to reproduce experimental binding affinities and were also used for scoring binding poses. However, in this study, we developed a new docking scoring function, called GalaxyDock BP2 Score, by directly training the scoring power of binding poses. This function is a hybrid of physics-based, empirical, and knowledge-based score terms that are balanced to strengthen the advantages of each component. The performance of the new scoring function exhibits significant improvement over existing scoring functions in decoy pose discrimination tests. In addition, when the score is used with the GalaxyDock2 protein-ligand docking program, it outperformed other state-of-the-art docking programs in docking tests on the Astex diverse set, the Cross2009 benchmark set, and the Astex non-native set. GalaxyDock BP2 Score and GalaxyDock2 with this score are freely available at http://galaxy.seoklab.org/softwares/galaxydock.html.

Synthesis of heterocycles: Indolo (2,1-a) isoquinolines, renewables, and aptamer ligands for cellular imaging

Energy Technology Data Exchange (ETDEWEB)

Beasley, Jonathan [Ames Laboratory (AMES), Ames, IA (United States)

2013-01-01

In this thesis, we explore both total syntheses and methodologies of several aromatic heterocyclic molecules. Extensions of the Kraus indole synthesis toward 2-substituted and 2,3-disubstituted indoles, as well as biologically attractive indolo[2,1-a]isoquinolines are described. Recent renewable efforts directed to commodity maleic acid and the first reported furan-based ionic liquids are described. Our total synthesis of mRNA aptamer ligand PDC-Gly, and its dye coupled forms, plus aminoglycoside dye coupled ligands used in molecular imaging, are described.

Spray-coated ligand-free Cu2ZnSnS4 nanoparticle thin films

DEFF Research Database (Denmark)

Engberg, Sara Lena Josefin; Murthy, Swathi; Kofod, Guggi

We have fabricated Cu2ZnSnS4 (CZTS) thin films from spray-coating ligand-free nanoparticle inks. The as-synthesized CZTS nanoparticles were inherently ligand-free [1], which allows the use of polar solvents, such as water and ethanol. Another advantage of these particles is that user- and environ......We have fabricated Cu2ZnSnS4 (CZTS) thin films from spray-coating ligand-free nanoparticle inks. The as-synthesized CZTS nanoparticles were inherently ligand-free [1], which allows the use of polar solvents, such as water and ethanol. Another advantage of these particles is that user......- and environmentally-friendly alkali metal chloride salts can be directly dissolved in controllable amounts. The homogeneous distribution of alkali metals in the ink allows uniform grain growth within the deposited absorber layer as a result of liquid phase assisted sintering. We find that particularly beneficial...... as an unquantifiable amount of ZnS. A Sono-tek spray-coating system is used which utilizes ultrasonic atomization. We investigate the effect of different binders, ink concentration, and spray-coating conditions, i.e. spray power, flow rate from syringe pump, distance between spray nozzle and the substrate, and time...

Universality for first passage percolation on sparse random graphs

NARCIS (Netherlands)

Bhamidi, S.; Van Der Hofstad, R.W.; Hooghiemstra, G.

2017-01-01

We consider first passage percolation on the configuration model with n vertices, and general independent and identically distributed edge weights assumed to have a density. Assuming that the degree distribution satisfies a uniform X2 logX-condition, we analyze the asymptotic distribution for the

Universality for first passage percolation on sparse random graphs

NARCIS (Netherlands)

Bhamidi, S.; Hofstad, van der R.W.; Hooghiemstra, G.

2014-01-01

We consider first passage percolation on the conguration model with n vertices, and general independent and identically distributed edge weights assumed to have a density. Assuming that the degree distribution satisfies a uniform X2 logX-condition, we analyze the asymptotic distribution for the

Mixed-ligand Pt(II) dithione-dithiolato complexes: influence of the dicyanobenzodithiolato ligand on the second-order NLO properties.

Science.gov (United States)

Espa, Davide; Pilia, Luca; Marchiò, Luciano; Artizzu, Flavia; Serpe, Angela; Mercuri, Maria Laura; Simão, Dulce; Almeida, Manuel; Pizzotti, Maddalena; Tessore, Francesca; Deplano, Paola

2012-03-28

The mixed-ligand dithiolene complex [Pt(Bz(2)pipdt)(dcbdt)] (1) bearing the two ligands Bz(2)pipdt = 1,4-dibenzyl-piperazine-3,2-dithione and dcbdt = dicyanobenzodithiolato, has been synthesized, characterized and studied to evaluate its second-order optical nonlinearity. The dithione/dithiolato character of the two ligands gives rise to an asymmetric distribution of the charge in the molecule. This is reflected by structural data showing that in the C(2)S(2)PtS(2)C(2) dithiolene core the four sulfur atoms define a square-planar coordination environment of the metal where the Pt-S bond distances involving the two ligands are similar, while the C-S bond distances in the C(2)S(2) units exhibit a significant difference in Bz(2)pipdt (dithione) and dcbdt (dithiolato). 1 shows a moderately strong absorption peak in the visible region, which can be related to a HOMO-LUMO transition, where the dcbdt ligand (dithiolato) contributes mostly to the HOMO, and the Bz(2)pipdt one (dithione) mostly to the LUMO. Thus this transition has ligand-to-ligand charge transfer (CT) character with some contribution of the metal and undergoes negative solvatochromism and molecular quadratic optical nonlinearity (μβ(0) = -1296 × 10(-48) esu), which was determined by the EFISH (electric-field-induced second-harmonic generation) technique and compared with the values of similar complexes on varying the dithiolato ligand (mnt = maleonitriledithiolato, dmit = 2-thioxo-1,3-dithiole-4,5-dithiolato). Theoretical calculations help to elucidate the role of the dithiolato ligands in affecting the molecular quadratic optical nonlinearity of these complexes.

Dissolved Fe across the Weddell Sea and Drake Passage: impact of DFe on nutrient uptake

NARCIS (Netherlands)

Klunder, M.B.; Laan, P.; de Baar, H.J.W.; Middag, R.; Neven, I.; Van Ooijen, J.

2014-01-01

This manuscript reports the first full depth distributions of dissolved iron (DFe) over a high-resolution Weddell Sea and Drake Passage transect. Very low dissolved DFe concentrations (0.01-0.1 nM range) were observed in the surface waters of the Weddell Sea, and within the Drake Passage polar

Dissolved Fe across the Weddell Sea and Drake Passage : Impact of DFe on nutrient uptake

NARCIS (Netherlands)

Klunder, M. B.; Laan, P.; De Baar, H. J. W.; Middag, R.; Neven, I.; Van Ooijen, J.

2014-01-01

This manuscript reports the first full depth distributions of dissolved iron (DFe) over a high-resolution Weddell Sea and Drake Passage transect. Very low dissolved DFe concentrations (0.01-0.1 nM range) were observed in the surface waters of the Weddell Sea, and within the Drake Passage polar

Substrate-Directed Catalytic Selective Chemical Reactions.

Science.gov (United States)

Sawano, Takahiro; Yamamoto, Hisashi

2018-05-04

The development of highly efficient reactions at only the desired position is one of the most important subjects in organic chemistry. Most of the reactions in current organic chemistry are reagent- or catalyst-controlled reactions, and the regio- and stereoselectivity of the reactions are determined by the inherent nature of the reagent or catalyst. In sharp contrast, substrate-directed reaction determines the selectivity of the reactions by the functional group on the substrate and can strictly distinguish sterically and electronically similar multiple reaction sites in the substrate. In this Perspective, three topics of substrate-directed reaction are mainly reviewed: (1) directing group-assisted epoxidation of alkenes, (2) ring-opening reactions of epoxides by various nucleophiles, and (3) catalytic peptide synthesis. Our newly developed synthetic methods with new ligands including hydroxamic acid derived ligands realized not only highly efficient reactions but also pinpointed reactions at the expected position, demonstrating the substrate-directed reaction as a powerful method to achieve the desired regio- and stereoselective functionalization of molecules from different viewpoints of reagent- or catalyst-controlled reactions.

Numerical modeling of the 1964 Alaska tsunami in western Passage Canal and Whittier, Alaska

Directory of Open Access Journals (Sweden)

D. J. Nicolsky

2010-12-01

Full Text Available A numerical model of the wave dynamics in Passage Canal, Alaska during the M_w 9.2 megathrust earthquake is presented. During the earthquake, several types of waves were identified at the city of Whittier, located at the head of Passage Canal. The first wave is thought to have been a seiche, while the other two waves were probably triggered by submarine landslides. We model the seiche wave, landslide-generated tsunami, and tectonic tsunami in Passage Canal and compute inundation by each type of wave during the 1964 event. Modeled results are compared with eyewitness reports and an observed inundation line. Results of the numerical experiments let us identify where the submarine landslides might have occurred during the 1964 event. We identify regions at the head and along the northern shore of Passage Canal, where landslides triggered a wave that caused most of the damage in Whittier. An explanation of the fact that the 1964 tectonic tsunami in Whittier was unnoticed is presented as well. The simulated inundation by the seiche, landslide-generated tsunami, and tectonic tsunami can help to mitigate tsunami hazards and prepare Whittier for a potential tsunami.

Role of ligands in permanganate oxidation of organics.

Science.gov (United States)

Jiang, Jin; Pang, Su-Yan; Ma, Jun

2010-06-01

We previously demonstrated that several ligands such as phosphate, pyrophosphate, EDTA, and humic acid could significantly enhance permanganate oxidation of triclosan (one phenolic biocide), which was explained by the contribution of ligand-stabilized reactive manganese intermediates in situ formed upon permanganate reduction. To further understand the underlying mechanism, we comparatively investigated the influence of ligands on permanganate oxidation of bisphenol A (BPA, one phenolic endocrine-disrupting chemical), carbamazepine (CBZ, a pharmaceutical containing the olefinic group), and methyl p-tolyl sulfoxide (TMSO, a typical oxygen-atom acceptor). Selected ligands exerted oxidation enhancement for BPA but had negligible influence for CBZ and TMSO. This was mainly attributed to the effects of identified Mn(III) complexes, which would otherwise disproportionate spontaneously in the absence of ligands. The one-electron oxidant Mn(III) species exhibited no reactivity toward CBZ and TMSO for which the two-electron oxygen donation may be the primary oxidation mechanism but readily oxidized BPA. The latter case was a function of pH, the complexing ligand, and the molar [Mn(III)]:[ligand] ratio, generally consistent with the patterns of ligand-affected permanganate oxidation. Moreover, the combination of the one-electron reduction of Mn(III) (Mn(III) + e(-) -->Mn(II)) and the Mn(VII)/Mn(II) reaction in excess ligands (Mn(VII) + 4Mn(II) ----> (ligands) 5Mn(III)) suggested a catalytic role of the Mn(III)/Mn(II) pair in permanganate oxidation of some phenolics in the presence of ligands.

Downstream passage of fish larvae and eggs through a small-sized reservoir, Mucuri river, Brazil

Directory of Open Access Journals (Sweden)

Paulo S. Pompeu

2011-12-01

Full Text Available In South America, one important symptom of the failure of fish passages to sustain fish migratory recruitment is the inability of eggs and larvae to reach the nurseries. This is especially so when the breeding areas are located upstream of a reservoir, and the floodplain is downstream of the dam. Therefore, the transport of fish larvae and eggs across reservoir barriers is a key factor in the development of effective conservation strategies. In this paper, we evaluate the potential for migratory fish larvae and egg transportation across a small size reservoir in eastern Brazil. We sampled fish daily between 15th October 2002 and 15th February 2003 (spawning period in the Mucuri River, immediately upstream of the reservoir and downstream of the Santa Clara Power Plant dam. Our study was the first to indicate the possibility of successful larval passage through the reservoir of a hydroelectric reservoir and dam in South America, and showed that the passage of migratory fish larvae was associated significantly with residence time of water in the reservoir. The relatively short water residence time and elevated turbidity of the Santa Clara's reservoir waters during the rainy season certainly contributed to the successful passage, and can be considered as key factors for a priori evaluations of the feasibility of a downstream larval passage.

Assembly of fibronectin into the extracellular matrix of early and late passage human skin fibroblasts

International Nuclear Information System (INIS)

Mann, D.M.

1987-01-01

The specific binding of soluble 125 I-human plasma fibronectin ( 125 I-HFN-P) to confluent cultures of early and late passage human skin fibroblasts was investigated. Previous studies HFN-P bound to fibroblast cell layers indicated that HNF-P was present in the cultures in two separate pools, distinguishable on the basis of their solubility in 1% deoxycholate. Examination of the kinetics of 125 I-HFN-P binding to Pool I of early and late passage cultures revealed that both cultures required 2-4 h to approach steady-state conditions. Other kinetic studies showed that the rates of low of 125 I-HFN-P from either Pool I or Pool II were similar for both cultures. Further, Scatchard analysis revealed a single class of Pool I binding sites with apparent dissociation constants (K/sub d/) of 5.3 x 10 -8 M (early passage) and 4.2 x 10 -8 M (late passage). These results indicate that early and late passage cultures of human fibroblasts exhibit differences in the number of cell surface biding sites for soluble fibronectin, and in the extent to which they incorporate soluble fibronectin into the extracellular matrix. Parameters which affect the fibronectin matrix assembly system of human skin fibroblasts were also examined. In addition, several monoclonal anti-fibronectin antibodies were characterized and developed as experimental probes for fibronectin structure and function

Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal.

Science.gov (United States)

Yan, Kelley S; Janda, Claudia Y; Chang, Junlei; Zheng, Grace X Y; Larkin, Kathryn A; Luca, Vincent C; Chia, Luis A; Mah, Amanda T; Han, Arnold; Terry, Jessica M; Ootani, Akifumi; Roelf, Kelly; Lee, Mark; Yuan, Jenny; Li, Xiao; Bolen, Christopher R; Wilhelmy, Julie; Davies, Paige S; Ueno, Hiroo; von Furstenberg, Richard J; Belgrader, Phillip; Ziraldo, Solongo B; Ordonez, Heather; Henning, Susan J; Wong, Melissa H; Snyder, Michael P; Weissman, Irving L; Hsueh, Aaron J; Mikkelsen, Tarjei S; Garcia, K Christopher; Kuo, Calvin J

2017-05-11

The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands. For example, individual mutations in Wnt ligands have not revealed homeostatic phenotypes in the intestinal epithelium-an archetypal canonical, Wnt pathway-dependent, rapidly self-renewing tissue, the regeneration of which is fueled by proliferative crypt Lgr5 + intestinal stem cells (ISCs). R-spondin ligands (RSPO1-RSPO4) engage distinct LGR4-LGR6, RNF43 and ZNRF3 receptor classes, markedly potentiate canonical Wnt/β-catenin signalling, and induce intestinal organoid growth in vitro and Lgr5 + ISCs in vivo. However, the interchangeability, functional cooperation and relative contributions of Wnt versus RSPO ligands to in vivo canonical Wnt signalling and ISC biology remain unknown. Here we identify the functional roles of Wnt and RSPO ligands in the intestinal crypt stem-cell niche. We show that the default fate of Lgr5 + ISCs is to differentiate, unless both RSPO and Wnt ligands are present. However, gain-of-function studies using RSPO ligands and a new non-lipidated Wnt analogue reveal that these ligands have qualitatively distinct, non-interchangeable roles in ISCs. Wnt proteins are unable to induce Lgr5 + ISC self-renewal, but instead confer a basal competency by maintaining RSPO receptor expression that enables RSPO ligands to actively drive and specify the extent of stem-cell expansion. This functionally non-equivalent yet cooperative interaction

Determination of ligand binding modes in weak protein–ligand complexes using sparse NMR data

Energy Technology Data Exchange (ETDEWEB)

Mohanty, Biswaranjan; Williams, Martin L.; Doak, Bradley C.; Vazirani, Mansha; Ilyichova, Olga [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); Wang, Geqing [La Trobe University, La Trobe Institute for Molecular Bioscience (Australia); Bermel, Wolfgang [Bruker Biospin GmbH (Germany); Simpson, Jamie S.; Chalmers, David K. [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia); King, Glenn F. [The University of Queensland, Institute for Molecular Bioscience (Australia); Mobli, Mehdi, E-mail: m.mobli@uq.edu.au [The University of Queensland, Centre for Advanced Imaging (Australia); Scanlon, Martin J., E-mail: martin.scanlon@monash.edu [Monash University, Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences (Australia)

2016-11-15

We describe a general approach to determine the binding pose of small molecules in weakly bound protein–ligand complexes by deriving distance constraints between the ligand and methyl groups from all methyl-containing residues of the protein. We demonstrate that using a single sample, which can be prepared without the use of expensive precursors, it is possible to generate high-resolution data rapidly and obtain the resonance assignments of Ile, Leu, Val, Ala and Thr methyl groups using triple resonance scalar correlation data. The same sample may be used to obtain Met {sup ε}CH{sub 3} assignments using NOESY-based methods, although the superior sensitivity of NOESY using [U-{sup 13}C,{sup 15}N]-labeled protein makes the use of this second sample more efficient. We describe a structural model for a weakly binding ligand bound to its target protein, DsbA, derived from intermolecular methyl-to-ligand nuclear Overhauser enhancements, and demonstrate that the ability to assign all methyl resonances in the spectrum is essential to derive an accurate model of the structure. Once the methyl assignments have been obtained, this approach provides a rapid means to generate structural models for weakly bound protein–ligand complexes. Such weak complexes are often found at the beginning of programs of fragment based drug design and can be challenging to characterize using X-ray crystallography.

Fish Passage Center : Fish Passage Center of the Columbia Basin Fish and Wildlife Authority; Annual report 1998

International Nuclear Information System (INIS)

DeHart, Michele

1999-01-01

The 1998 operations of the Columbia and Snake rivers system illustrated that there was potential flexibility in the operation of the hydrosystem to improve fish passage for juvenile salmon and increase the degree to which the NMS Biological Opinion measures could have been implemented successfully. This additional flexibility was not exercised. Some measures of the Biological Opinion were not implemented. The 1998 operation showed that the Hells Canyon Complex, operation, the Upper Snake River operation and Non-treaty storage operation could have provided flexibility to meet early spring and later summer flows

Radiation induced ligand loss from cobalt complexes

International Nuclear Information System (INIS)

Funston, A. M.; McFadyen, W.D.; Tregloan, P.A.

2000-01-01

Full text: Due to the rapid nature of ligand dissociation from cobalt(II) complexes the study of the rate of ligand dissociation necessitates the use of a technique such as pulse radiolysis. This allows the rapid reduction of the corresponding cobalt(III) complex by a reducing radical, such as the aquated electron, to form the cobalt(II) complex. However, to date, no systematic study of either the mechanism of reduction or the influence of the electronic structure on the rate of ligand dissociation has been carried out. In order to understand these processes more fully the mechanism of reduction of a range of related cobalt(III) complexes by the aquated electron and the subsequent rate of ligand dissociation from the resulting cobalt(II) complexes is being investigated. It has been found that a number of processes are observed following the initial rapid reaction of the cobalt(III) complex with the aquated electron. Ultimately ligand loss is observed. Depending upon the complex, the initial processes observed may include the formation of coordinated radicals and electron transfer within the complex. For complexes containing aromatic ligands such as 2,2'-bipyridine, 1,10-phenanthroline and dipyrido[3,2-a:2',3'-c]phenazine the formation of a coordinated radical is observed as the initial reduction step. The kinetics of ligand dissociation of these complexes has been determined. The loss of monodentate ligands is fast and has been indistinguishable from the reduction processes when aromatic ligands are also present in the complex. However, for diamine chelates and diimine chelates spectra of the transient species can be resolved

Introducing Intertextuality-Aware Instruction as a Novel Approach of Teaching Reading Passages in EFL Context

Science.gov (United States)

Khaghaninejad, Mohammad Saber

2014-01-01

This study was an attempt to investigate the possible effect of intertextuality-aware instruction of reading passages on a sample of intermediate EFL learners of both genders. First, the intertextuality deployed through the reading passages of the study's course-book was focused inspired by Fairclough's (192) framework in terms of genre, text…

Hydroacoustic Evaluation of Juvenile Salmonid Passage at The Dalles Dam Sluiceway, 2005

Energy Technology Data Exchange (ETDEWEB)

Johnson, Gary E.; Khan, Fenton; Hedgepeth, J; Mueller, Robert P.; Rakowski, Cynthia L.; Richmond, Marshall C.; Serkowski, John A.; Skalski, John R.

2006-06-01

The U.S. Army Corps of Engineers Portland District engaged the Pacific Northwest National Laboratory to evaluate fish passage at The Dalles Dam powerhouse in 2005. The goal of the study was to provide information on smolt passage that will inform decisions on long-term measures and operations to enhance sluiceway passage and reduce turbine passage to improve smolt survival at the dam. The study addressed one of the main programs dedicated to improving juvenile salmonid survival at The Dalles Dam: Surface Flow Bypass. The study objectives (see below) were met using a combination of hydroacoustic and hydraulic data. The study incorporated fixed-location hydroacoustic methods across the entire powerhouse, with especially intense sampling using multiple split-beam transducers at all sluiceway portals. We did not sample fish passage at the spillway in 2005. In the sluiceway nearfield, we used an acoustic camera to track fish movements. The fish data were interpreted with hydraulic data from a computational fluid dynamics (CFD) model. Fish passage data were collected in the framework of an “experiment” using a randomized block design (3-day treatments; two treatments) to compare two sluiceway operational configurations: Sluice 2+5 and Sluice 2+19 (six gates open for each configuration). Total project outflow was 76% of the 10-year average for spring and 71% of the 10-year average for summer. Based on these findings, we make the following recommendations: 1) The sluice should be operated 24 h/d from April until November. 2) Open six rather than three sluice gates to take advantage of the maximum hydraulic capacity of the sluiceway. 3) Open the three gates above the western-most operating main turbine unit and the three gates at MU 8 where turbine passage rates are relatively high. 4) Operate the turbine units below open sluice gates as a standard fish operations procedure. 5) Develop hydraulic and entrance enhancements to the sluiceway to tap the potential of The

Regulation mechanisms of the FLT3-ligand after irradiation; Mecanismes de regulation du FLT3-ligand apres irradiation

Energy Technology Data Exchange (ETDEWEB)

Prat-Lepesant, M

2005-06-15

The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

Synthesis and characterization of mixed ligand chiral nanoclusters

KAUST Repository

Guven, Zekiye P.; Ustbas, Burcin; Harkness, Kellen M.; Coskun, Hikmet; Joshi, Chakra Prasad; Besong, Tabot M.D.; Stellacci, Francesco; Bakr, Osman; Akbulut, Ozge

2016-01-01

Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

Synthesis and characterization of mixed ligand chiral nanoclusters

KAUST Repository

Guven, Zekiye P.

2016-06-22

Chiral mixed ligand silver nanoclusters were synthesized in the presence of a chiral and an achiral ligand. While the chiral ligand led mostly to the formation of nanoparticles, the presence of the achiral ligand drastically increased the yield of nanoclusters with enhanced chiral properties. © 2016 The Royal Society of Chemistry.

Identifying Marine Copper-Binding Ligands in Seawater

Science.gov (United States)

Whitby, H.; Hollibaugh, J. T.; Maldonado, M. T.; Ouchi, S.; van den Berg, S. M.

2016-02-01

Complexation reactions are important because they affect the bioavailability of trace metals such as copper and iron. For example, organic complexation can determine whether copper is a limiting or a toxic micronutrient at natural levels. Copper competes with iron for complexing ligands, and when iron is limiting, copper can also substitute for iron in some metabolic pathways. The speciation of copper can be measured using complexing capacity titrations, which provide the concentration of individual ligand classes (L1, L2 etc.) and the complex stabilities (log K). Using methods recently developed in our laboratory, we show that the ligands within these classes can be measured independently of titrations, thus confirming the titration method and simultaneously identifying the ligands within each class. Thiols were identified as the L1 ligand class and humic compounds as the weaker L2 class in samples from coastal Georgia, USA, collected monthly from April to December. Log K values of the ligand complexes were consistent with values expected for thiols and humic substances. Recent results from culture studies and from samples collected along Line P, a coastal - oceanic transect in the HNLC region of the NE subarctic Pacific, will be presented in comparison to the estuarine results. This comparison will help to broaden our perspective on copper complexation and the ligands responsible, furthering our understanding of ligand sources and life cycles.

Substrate coated with receptor and labelled ligand for assays

International Nuclear Information System (INIS)

1980-01-01

Improvements in the procedures for assaying ligands are described. The assay consists of a polystyrene tube on which receptors are present for both the ligand to be assayed and a radioactively labelled form of the ligand. The receptors on the bottom portion of the tube are also coated with labelled ligands, thus eliminating the necessity for separate addition of the labelled ligand and sample during an assay. Examples of ligands to which this method is applicable include polypeptides, nucleotides, nucleosides and proteins. Specific examples are given in which the ligand to be assayed is digoxin, the labelled form of the ligand is 3-0-succinyl digoxyigenin tyrosine ( 125 I) and the receptor is digoxin antibody. (U.K.)

Genetic diversity of chicken anemia virus following cell culture passaging in MSB-1 cells.

Science.gov (United States)

Hasmah, M S; Omar, A R; Wan, K F; Hair-Bejo, M; Aini, I

2004-01-01

It has been shown that a chicken anemia virus (CAV) isolates which had undergone 60 passages in MSB-1 cells (SMSC-1/P60, 3-1/P60) acquired 33-66 nucleotide substitutions at the coding region resulting in 13-16 amino acid changes as compared to the CAV isolates passaged only 5 times in MSB-1 cells (SMSC-1 and 3-1) (Chowdhury et al., Arch. Virol. 148, 2437-2448, 2003). In this study we found that a low CAV (BL-5) and a high CAV passage (BL-5/P90) differed by only 15 nucleotide substitutions resulting in 11 amino acid changes. Phylogenetic analysis based on VP1 also revealed that both isolates were close to each other but not to other CAV isolates from Malaysia, namely SMSC-1 and 3-1.

Time-to-event analysis as a framework for quantifying fish passage performance: Chapter 9.1

Science.gov (United States)

Castro-Santos, Theodore R.; Perry, Russell W.; Adams, Noah S.; Beeman, John W.; Eiler, John H.

2012-01-01

Fish passage is the result of a sequence of processes, whereby fish must approach, enter, and pass a structure. Each of these processes takes time, and fishway performance is best quantified in terms of the rates at which each process is completed. Optimal performance is achieved by maximizing the rates of approach, entry, and passage through safe and desirable routes. Sometimes, however, it is necessary to reduce rates of passage through less desirable routes in order to increase proportions passing through the preferred route. Effectiveness of operational or structural modifications for achieving either of these goals is best quantified by applying time-to-event analysis, commonly known as survival analysis methods, to telemetry data. This set of techniques allows for accurate estimation of passage rates and covariate effects on those rates. Importantly, it allows researchers to quantify rates that vary over time, as well as the effects of covariates that also vary over time. Finally, these methods are able to control for competing risks, i.e., the presence of alternate passage routes, failure to pass, or other fates that remove fish from the pool of candidates available to pass through a particular route. In this chapter, we present a model simulation of telemetered fish passing a hydroelectric dam, and provide step-by-step guidance and rationales for performing time-to-event analysis on the resulting data. We demonstrate how this approach removes bias from performance estimates that can result from using methods that focus only on proportions passing each route. Time-to-event analysis, coupled with multinomial models for measuring survival, provides a comprehensive set of techniques for quantifying fish passage, and a framework from which performance among different sites can be better understood.

Ligand-Enabled γ-C(sp(3))-H Olefination of Amines: En Route to Pyrrolidines.

Science.gov (United States)

Jiang, Heng; He, Jian; Liu, Tao; Yu, Jin-Quan

2016-02-17

Pd(II)-catalyzed olefination of γ-C(sp(3))-H bonds of triflyl (Tf) and 4-nitrobenzenesulfonyl (Ns) protected amines is achieved. Subsequent aza-Wacker oxidative cyclization or conjugate addition of the olefinated intermediates provides a variety of C-2 alkylated pyrrolidines. Three pyridine- and quinoline-based ligands are developed to match different classes of amine substrates, demonstrating a rare example of ligand-enabled C(sp(3))-H olefination reactions. The use of Ns protecting group to direct C(sp(3))-H activation of alkyl amines is also a significant step toward practical C-H functionalizations of alkyl amines.

Synthesis and evaluation of peptide and nucleic acid based Toll-like receptor ligands

NARCIS (Netherlands)

Weterings, Josephus Johannes

2008-01-01

Toll-like receptors (TLRs) are receptors that continuously scour their direct surroundings for pathogen associated molecular patterns (PAMPs) of bacterial, viral or fungal origin. TLRs can be found at cells that play a role in the immune system. Binding of the TLR with its corresponding ligand

S,O-Ligand-Promoted Palladium-Catalyzed C-H Functionalization Reactions of Nondirected Arenes

NARCIS (Netherlands)

Naksomboon, K.; Valderas, C.; Gomez-Martinez, M.; Alvarez-Casao, Y.; Fernández Ibáñez, M.A.

Pd(II)-catalyzed C-H functionalization of non directed arenes has been realized using an inexpensive and easily accessible type of bidentate S,O-ligand. The catalytic system shows high efficiency in the C-H olefination reaction of electron-rich and electron-poor arenes. This methodology is

Correcting binding parameters for interacting ligand-lattice systems

Science.gov (United States)

Hervy, Jordan; Bicout, Dominique J.

2017-07-01

Binding of ligands to macromolecules is central to many functional and regulatory biological processes. Key parameters characterizing ligand-macromolecule interactions are the stoichiometry, inducing the number of ligands per macromolecule binding site, and the dissociation constant, quantifying the ligand-binding site affinity. Both these parameters can be obtained from analyses of classical saturation experiments using the standard binding equation that offers the great advantage of mathematical simplicity but becomes an approximation for situations of interest when a ligand binds and covers more than one single binding site on the macromolecule. Using the framework of car-parking problem with latticelike macromolecules where each ligand can cover simultaneously several consecutive binding sites, we showed that employing the standard analysis leads to underestimation of binding parameters, i.e., ligands appear larger than they actually are and their affinity is also greater than it is. Therefore, we have derived expressions allowing to determine the ligand size and true binding parameters (stoichiometry and dissociation constant) as a function of apparent binding parameters retrieved from standard saturation experiments.

THERMODYNAMICS OF PROTEIN-LIGAND INTERACTIONS AND THEIR ANALYSIS

Directory of Open Access Journals (Sweden)

Rummi Devi Saini

2017-11-01

Full Text Available Physiological processes are controlled mainly by intermolecular recognition mechanisms which involve protein–protein and protein–ligand interactions with a high specificity and affinity to form a specific complex. Proteins being an important class of macromolecules in biological systems, it is important to understand their actions through binding to other molecules of proteins or ligands. In fact, the binding of low molecular weight ligands to proteins plays a significant role in regulating biological processes such as cellular metabolism and signal transmission. Therefore knowledge of the protein–ligand interactions and the knowledge of the mechanisms involved in the protein-ligand recognition and binding are key in understanding biology at molecular level which will facilitate the discovery, design, and development of drugs. In this review, the mechanisms involved in protein–ligand binding, the binding kinetics, thermodynamic concepts and binding driving forces are discussed. Thermodynamic mechanisms involved in a few important protein-ligand binding are described. Various spectroscopic, non-spectroscopic and computational method for analysis of protein–ligand binding are also discussed.

Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states.

Science.gov (United States)

LeBon, Lauren; Lee, Tom V; Sprinzak, David; Jafar-Nejad, Hamed; Elowitz, Michael B

2014-09-25

The Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we analyzed same-cell (cis) Notch-ligand interactions for Notch1, Dll1, and Jag1, and their dependence on Fringe protein expression in mammalian cells. We found that Dll1 and Jag1 can cis-inhibit Notch1, and Fringe proteins modulate these interactions in a way that parallels their effects on trans interactions. Fringe similarly modulated Notch-ligand cis interactions during Drosophila development. Based on these and previously identified interactions, we show how the design of the Notch signaling pathway leads to a restricted repertoire of signaling states that promote heterotypic signaling between distinct cell types, providing insight into the design principles of the Notch signaling system, and the specific developmental process of Drosophila dorsal-ventral boundary formation.

Enloe Dam Passage Project, Volume I, 1984 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

Fanning, M.L.

1985-07-01

This report discusses issues related to the provision of fish passage facilities at Enloe Dam and the introduction of anadromous salmonid fish to the upper Similkameen River basin. The species of fish being considered is a summer run of steelhead trout adapted to the upper Columbia basin. (ACR)

Development of immobilized ligands for actinide separations

International Nuclear Information System (INIS)

Paine, R.T.

1994-01-01

Primary goals during this grant period were to (1) synthesize new bifunctional chelating ligands, (2) characterize the structural features of the Ln and An coordination complexes formed by these ligands, (3) use structural data to iteratively design new classes of multifunctional ligands, and (4) explore additional routes for attachment of key ligands to solid supports that could be useful for chromatographic separations. Some highlights of recently published work as well as a summary of submitted, unpublished and/or still in progress research are outlined

Effective conductivity, dielectric constant, and diffusion coefficient of digitized composite media via first-passage-time equations

International Nuclear Information System (INIS)

Torquato, S.; Kim, I.C.; Cule, D.

1999-01-01

We generalize the Brownian motion simulation method of Kim and Torquato [J. Appl. Phys. 68, 3892 (1990)] to compute the effective conductivity, dielectric constant and diffusion coefficient of digitized composite media. This is accomplished by first generalizing the first-passage-time equations to treat first-passage regions of arbitrary shape. We then develop the appropriate first-passage-time equations for digitized media: first-passage squares in two dimensions and first-passage cubes in three dimensions. A severe test case to prove the accuracy of the method is the two-phase periodic checkerboard in which conduction, for sufficiently large phase contrasts, is dominated by corners that join two conducting-phase pixels. Conventional numerical techniques (such as finite differences or elements) do not accurately capture the local fields here for reasonable grid resolution and hence lead to inaccurate estimates of the effective conductivity. By contrast, we show that our algorithm yields accurate estimates of the effective conductivity of the periodic checkerboard for widely different phase conductivities. Finally, we illustrate our method by computing the effective conductivity of the random checkerboard for a wide range of volume fractions and several phase contrast ratios. These results always lie within rigorous four-point bounds on the effective conductivity. copyright 1999 American Institute of Physics

Structure and function of the selectin ligand PSGL-1

Directory of Open Access Journals (Sweden)

Cummings R.D.

1999-01-01

Full Text Available P-selectin glycoprotein ligand-1 (PSGL-1 is a dimeric mucin-like 120-kDa glycoprotein on leukocyte surfaces that binds to P- and L-selectin and promotes cell adhesion in the inflammatory response. The extreme amino terminal extracellular domain of PSGL-1 is critical for these interactions, based on site-directed mutagenesis, blocking monoclonal antibodies, and biochemical analyses. The current hypothesis is that for high affinity interactions with P-selectin, PSGL-1 must contain O-glycans with a core-2 branched motif containing the sialyl Lewis x antigen (NeuAca2®3Galß1®4[Fuca1®3]GlcNAcß1®R. In addition, high affinity interactions require the co-expression of tyrosine sulfate on tyrosine residues near the critical O-glycan structure. This review addresses the biochemical evidence for this hypothesis and the evidence that PSGL-1 is an important in vivo ligand for cell adhesion.

Entangled zinc-ditetrazolate frameworks involving in situ ligand synthesis and topological modulation by various secondary N-donor ligands

International Nuclear Information System (INIS)

Li Yunwu; Chen Weilin; Wang Yonghui; Li Yangguang; Wang Enbo

2009-01-01

The introduction of various secondary N-donor ligands into an in situ ditetrazolate-ligand synthesis system of terephthalonitrile, NaN 3 and ZnCl 2 led to the formation of three new entangled frameworks Zn(pdtz)(4,4'-bipy).3H 2 O (1), [Zn(pdtz)(bpp)] 2 .3H 2 O (2) and Zn(pdtz) 0.5 (N 3 )(2,2'-bipy) (3) (4,4'-bipy=4,4'-bipyridine; bpp=1,3-bis(4-pyridyl)propane; 2,2'-bipy=2,2'-bipyridine; H 2 pdtz=5,5'-1,4-phenylene-ditetrazole). The formation of pdtz 2- ligand involves the Sharpless [2+3] cycloaddition reaction between terephthalonitrile and NaN 3 in the presence of Zn 2+ ion as a Lewis-acid catalyst under hydrothermal conditions. Compound 1 exhibits a fivefold interpenetrating 3D framework based on the diamondoid topology. Compound 2 displays a twofold parallel interpenetrating framework based on the wavelike individual network. Compound 3 possesses a 2D puckered network. These new Zn-ditetrazolate frameworks are highly dependent on the modulation of different secondary N-donor ligands. Their luminescent properties were investigated. - Graphical abstract: Three new entangled frameworks were prepared by an in situ ditetrazolate-ligand synthesis system assisted with various auxiliary N-donor ligands. The entangled structures can be modulated by different secondary ligands.

Natural Propagation and Habitat Improvement, Volume 1, Oregon, Supplement B, White River Falls Fish Passage, 1983 Annual Report.

Energy Technology Data Exchange (ETDEWEB)

United States. Bonneville Power Administration.

1984-04-01

White River Falls are located in north central Oregon approximately 25 miles south of the City of The Dalles. The project site is characterized by a series of three natural waterfalls with a combined fall of 180 ft. In the watershed above the falls are some 120 miles of mainstem habitat and an undetermined amount of tributary stream habitat that could be opened to anadromous fish, if passage is provided around the falls. The purpose of this project is to determine feasibility of passage, select a passage scheme, and design and construct passage facilities. This report provides information on possible facilities that would pass adult anadromous fish over the White River Falls. 25 references, 29 figures, 12 tables. (ACR)

Culvert Length and Interior Lighting Impacts to Topeka Shiner Passage

Science.gov (United States)

2017-11-01

Culverts can act as barriers to fish passage for a number of reasons including insufficient water depth or excess velocity. In addition, concern is being raised over behavioral barriers where culvert conditions elicit an avoidance response that deter...

First passage time problems in time-dependent fields

International Nuclear Information System (INIS)

Fletcher, J.E.; Havlin, S.; Weiss, G.H.

1988-01-01

This paper discusses the simplest first passage time problems for random walks and diffusion processes on a line segment. When a diffusing particle moves in a time-varying field, use of the adjoint equation does not lead to any simplification in the calculation of moments of the first passage time as is the case for diffusion in a time-invariant field. We show that for a discrete random walk in the presence of a sinusoidally varying field there is a resonant frequency omega* for which the mean residence time on the line segment in a minimum. It is shown that for a random walk on a line segment of length L the mean residence time goes like L 2 for large L when omega omega*, but when omega = omega* the dependence is proportional to L. The results of our simulation are numerical, but can be regarded as exact. Qualitatively similar results are shown to hold for diffusion processes by a perturbation expansion in powers of a dimensionless velocity. These results are extended to higher values of this parameter by a numerical solution of the forward equation

Detection of site-specific binding and co-binding of ligands to macromolecules using 19F NMR

International Nuclear Information System (INIS)

Jenkins, B.G.

1991-01-01

Study of ligand-macromolecular interactions by 19 F nuclear magnetic resonance (NMR) spectroscopy affords many opportunities for obtaining molecular biochemical and pharmaceutical information. This is due to the absence of a background fluorine signal, as well as the relatively high sensitivity of 19 F NMR. Use of fluorine-labeled ligands enables one to probe not only binding and co-binding phenomena to macromolecules, but also can provide data on binding constants, stoichiometries, kinetics, and conformational properties of these complexes. Under conditions of slow exchange and macromolecule-induced chemical shifts, multiple 19 F NMR resonances can be observed for free and bound ligands. These shifted resonances are a direct correlate of the concentration of ligand bound in a specific state rather than the global concentrations of bound or free ligand which are usually determined using other techniques such as absorption spectroscopy or equilibrium dialysis. Examples of these interactions are demonstrated both from the literature and from interactions of 5-fluorotryptophan, 5-fluorosalicylic acid, flurbiprofen, and sulindac sulfide with human serum albumin. Other applications of 19 F NMR to study of these interactions in vivo, as well for receptor binding and metabolic tracing of fluorinated drugs and proteins are discussed

Selective extraction of trivalent actinides with hard-soft mixed donor ligands: role of intra-ligand synergism

International Nuclear Information System (INIS)

Ghanty, Tapan K.

2016-01-01

In recent years, considerable attention has been given to understand the coordination chemistry of trivalent lanthanide (Ln) and actinide (An) with various ligands because of its close link with the nuclear waste management processes. It is well known that lanthanide-actinide separation is a challenging and difficult task because of very similar chemical properties of these two series of ions, which are associated with similar ionic radii and coordination numbers. Recently, we have introduced a new concept, 'intra-ligand synergism', where hard donor atom, such as, oxygen preferentially binds to trivalent actinides (An(III)) as compared to the valence iso-electronic trivalent lanthanides (Ln(III)) in presence of another soft donor centre. In the present work, the conventional concept of selective complexation of actinides with soft donor ligands (either S or N donor) has been modified through exploiting this concept, and thereby the higher selectivity of 1,10-phenanthroline-2,9-dicarboxylamide (PDAM) based ligands, namely PDAM and its isobutyl and decyl derivatives towards Am(III) ion has been predicted theoretically through density functional calculations. Subsequently, several such amide derivatives have been synthesized to optimize the solubility of the ligands in organic phase. Finally, solvent extraction experiments have been carried out to validate the theoretical prediction on the selectivity of oxygen donor ligands towards Am(III) as compared to Eu(III), and a maximum separation factor of about 51 has been achieved experimentally using 2,9-bis(N-decylaminocarbonyl)-1,10-phenanthroline ligand. The separation factor is increased with the decrease in pH, which is very interesting since extraction of the Am 3+ ion is considered to be important under highly acidic conditions from the nuclear waste management point of view. (author)

Spatio-temporal Characterization of Ligand-Receptor Interactions in Blood Stem-Cell Rolling

KAUST Repository

Al Alwan, Bader

2017-08-16

One of the most important issues in the research on hematopoietic stem/progenitor cells (HSPCs) is to understand the mechanism of the homing process of these cells to the bone marrow after being transplanted into patients and establish the production of various blood cell types. The HSPCs first come in contact with the endothelial cells. This contact is known as adhesion and occurs through a multi-step paradigm ending with transmigration to the bone marrow niche. The initial step of the homing, tethering and rolling of HSPCs is mediated by P- and E-Selectins expressed on the endothelial cell surface through their interactions with the ligands expressed by HSPCs. Here we developed a novel experimental method to unravel the molecular mechanisms of the selectin-ligands interactions in vitro at the single molecule level by combining microfluidics and single-molecule fluorescence imaging. Our method enables direct visualization of the nanoscale spatiotemporal dynamics of the E-selectin-ligand (PSGL-1) interactions under conditions of shear stress acting on the cells at the molecular level in real time.

Synthesis, spectral, thermal and biological studies of mixed ligand complexes with newly prepared Schiff base and 1,10-phenanthroline ligands

Science.gov (United States)

Abd El-Halim, Hanan F.; Mohamed, Gehad G.; Khalil, Eman A. M.

2017-10-01

A series of mixed ligand complexes were prepared from the Schiff base (L1) as a primary ligand, prepared by condensation of oxamide and furan-2-carbaldehyde, and 1,10-phenanthroline (1,10-phen) as a secondary ligand. The Schiff base ligand and its mixed ligand chelates were characterized based on elemental analysis, IR, 1H NMR, thermal analysis, UV-Visible, mass, molar conductance, magnetic moment. X-ray diffraction, solid reflectance and ESR also have been studied. The mixed ligand complexes were found to have the formulae of [M(L1) (1,10-phen)]Clm.nH2O (M = Cr(III) and Fe(III) (m = 3) (n = 0); M = Mn(II), Cu(II) and Cd(II) (m = 2) (n = 0); and M = Co(II) (m = 2) (n = 1), Ni(II) (m = 2) (n = 2) and Zn(II) (m = 2) (n = 3)) and that the geometrical structure of the complexes were octahedral. The parameters of thermodynamic using Coats-Redfern and Horowitz-Metzger equations were calculated. The synthesized Schiff base ligand, 1,10-phenanthroline ligand and Their mixed ligand complexes were also investigated for their antibacterial and antifungal activity against bacterial species (Gram-Ve bacteria: Pseudomonas aeruginosa and Escherichia coli) and (Gram + Ve bacteria: Bacillus subtilis and Streptococcus pneumonia) and fungi (Aspergillus fumigates and Candida albicans). The anticancer activity of the new compounds had been tested against breast (MFC7) and colon (HCT-116) cell lines. The results showed high activity for the synthesized compounds.

Autocrine signal transmission with extracellular ligand degradation

International Nuclear Information System (INIS)

Muratov, C B; Posta, F; Shvartsman, S Y

2009-01-01

Traveling waves of cell signaling in epithelial layers orchestrate a number of important processes in developing and adult tissues. These waves can be mediated by positive feedback autocrine loops, a mode of cell signaling where binding of a diffusible extracellular ligand to a cell surface receptor can lead to further ligand release. We formulate and analyze a biophysical model that accounts for ligand-induced ligand release, extracellular ligand diffusion and ligand–receptor interaction. We focus on the case when the main mode for ligand degradation is extracellular and analyze the problem with the sharp threshold positive feedback nonlinearity. We derive expressions that link the speed of propagation and other characteristics of traveling waves to the parameters of the biophysical processes, such as diffusion rates, receptor expression level, etc. Analyzing the derived expressions we found that traveling waves in such systems can exhibit a number of unusual properties, e.g. non-monotonic dependence of the speed of propagation on ligand diffusivity. Our results for the fully developed traveling fronts can be used to analyze wave initiation from localized perturbations, a scenario that frequently arises in the in vitro models of epithelial wound healing, and guide future modeling studies of cell communication in epithelial layers

Planning Guide for Fish Passage at Pittsburgh District Dams

Science.gov (United States)

2013-08-01

attracted to a downstream flow at the entrance gate of the lift. 2) Immigrants pass around a moveable crowder that, when engaged, forces fish into the...might influence fish passage over a large number of sites. REFERENCES Bailey, M. M., J. J. Isely, and W. C. Bridges , Jr. 2004. Movement and

Rites of passage and sustainable development in traditional Africa ...

African Journals Online (AJOL)

This study attempts to exhume the instrumentality of rites of passage with particular attention to puberty andmarriage rites in fostering and sustaining development. The study further proffers strategic choices for the retrieval of this integral part of African life for the moral development of the averageNigerian youth. The present ...

Dockomatic - automated ligand creation and docking.

Science.gov (United States)

Bullock, Casey W; Jacob, Reed B; McDougal, Owen M; Hampikian, Greg; Andersen, Tim

2010-11-08

The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI) application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

Dockomatic - automated ligand creation and docking

Directory of Open Access Journals (Sweden)

Hampikian Greg

2010-11-01

Full Text Available Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

Effects of Serial Passage on the Characteristics and Chondrogenic Differentiation of Canine Umbilical Cord Matrix Derived Mesenchymal Stem Cells

Directory of Open Access Journals (Sweden)

K. S. Lee

2013-04-01

Full Text Available Mesenchymal stem cells (MSCs are often known to have a therapeutic potential in the cell-mediated repair for fatal or incurable diseases. In this study, canine umbilical cord MSCs (cUC-MSCs were isolated from umbilical cord matrix (n = 3 and subjected to proliferative culture for 5 consecutive passages. The cells at each passage were characterized for multipotent MSC properties such as proliferation kinetics, expression patterns of MSC surface markers and self-renewal associated markers, and chondrogenic differentiation. In results, the proliferation of the cells as determined by the cumulative population doubling level was observed at its peak on passage 3 and stopped after passage 5, whereas cell doubling time dramatically increased after passage 4. Expression of MSC surface markers (CD44, CD54, CD61, CD80, CD90 and Flk-1, molecule (HMGA2 and pluripotent markers (sox2, nanog associated with self-renewal was negatively correlated with the number of passages. However, MSC surface marker (CD105 and pluripotent marker (Oct3/4 decreased with increasing the number of subpassage. cUC-MSCs at passage 1 to 5 underwent chondrogenesis under specific culture conditions, but percentage of chondrogenic differentiation decreased with increasing the number of subpassage. Collectively, the present study suggested that sequential subpassage could affect multipotent properties of cUC-MSCs and needs to be addressed before clinical applications.

Survival and Passage of Juvenile Chinook Salmon and Steelhead Passing through Bonneville Dam, 2011

Energy Technology Data Exchange (ETDEWEB)

Ploskey, Gene R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Batten, G. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Cushing, Aaron W. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Kim, Jin A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Johnson, Gary E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Skalski, J. R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Townsend, Richard L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Seaburg, Adam [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Weiland, Mark A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Woodley, Christa M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hughes, James S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Carlson, Thomas J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Carpenter, Scott M. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Deng, Zhiqun [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Etherington, D. J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fischer, Eric S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Fu, Tao [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Greiner, Michael J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Hennen, Matthew J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Martinez, Jayson J. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mitchell, T. D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Rayamajhi, Bishes [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zimmerman, Shon A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2013-02-15

Pacific Northwest National Laboratory (PNNL) and subcontractors conducted an acoustic-telemetry study of juvenile salmonid fish passage and survival at Bonneville Dam in 2011. The study was conducted to assess the readiness of the monitoring system for official compliance studies under the 2008 Biological Opinion and Fish Accords and to assess performance measures including route-specific fish passage proportions, travel times, and survival based upon a virtual/paired-release model. The study relied on releases of live Juvenile Salmon Acoustic Telemetry System tagged smolts in the Columbia River and used acoustic telemetry to evaluate the approach, passage, and survival of passing juvenile salmon using a virtual release, paired reference release survival model. This study supports the U.S. Army Corps of Engineers’ continual effort to improve conditions for juvenile anadromous fish passing through Columbia River dams.

Interaction Entropy: A New Paradigm for Highly Efficient and Reliable Computation of Protein-Ligand Binding Free Energy.

Science.gov (United States)

Duan, Lili; Liu, Xiao; Zhang, John Z H

2016-05-04

Efficient and reliable calculation of protein-ligand binding free energy is a grand challenge in computational biology and is of critical importance in drug design and many other molecular recognition problems. The main challenge lies in the calculation of entropic contribution to protein-ligand binding or interaction systems. In this report, we present a new interaction entropy method which is theoretically rigorous, computationally efficient, and numerically reliable for calculating entropic contribution to free energy in protein-ligand binding and other interaction processes. Drastically different from the widely employed but extremely expensive normal mode method for calculating entropy change in protein-ligand binding, the new method calculates the entropic component (interaction entropy or -TΔS) of the binding free energy directly from molecular dynamics simulation without any extra computational cost. Extensive study of over a dozen randomly selected protein-ligand binding systems demonstrated that this interaction entropy method is both computationally efficient and numerically reliable and is vastly superior to the standard normal mode approach. This interaction entropy paradigm introduces a novel and intuitive conceptual understanding of the entropic effect in protein-ligand binding and other general interaction systems as well as a practical method for highly efficient calculation of this effect.

Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.

Science.gov (United States)

Singer, M S; Shepherd, G M

1994-06-02

Olfactory receptors belong to the superfamily of seven transmembrane domain, G protein-coupled receptors. In order to begin analysis of mechanisms of receptor activation, a computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily. We have tested docking of the odor molecule lyral, which is known to activate the OR5 receptor. The results point to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor. Some of these residues occupy sequence positions identical to ligand-binding residues conserved among other superfamily members. The results provide new insights into possible molecular mechanisms of odor recognition and suggest hypotheses to guide future experimental studies using site-directed mutagenesis.

First passage times for multiple particles with reversible target-binding kinetics

Science.gov (United States)

Grebenkov, Denis S.

2017-10-01

We investigate the first passage problem for multiple particles that diffuse towards a target, partially adsorb there, and then desorb after a finite exponentially distributed residence time. We search for the first time when m particles undergoing such reversible target-binding kinetics are found simultaneously on the target that may trigger an irreversible chemical reaction or a biophysical event. Even if the particles are independent, the finite residence time on the target yields an intricate temporal coupling between particles. We compute analytically the mean first passage time (MFPT) for two independent particles by mapping the original problem to higher-dimensional surface-mediated diffusion and solving the coupled partial differential equations. The respective effects of the adsorption and desorption rates on the MFPT are revealed and discussed.

NMR studies of DNA oligomers and their interactions with minor groove binding ligands

Energy Technology Data Exchange (ETDEWEB)

Fagan, Patricia A. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry

1996-05-01

The cationic peptide ligands distamycin and netropsin bind noncovalently to the minor groove of DNA. The binding site, orientation, stoichiometry, and qualitative affinity of distamycin binding to several short DNA oligomers were investigated by NMR spectroscopy. The oligomers studied contain A,T-rich or I,C-rich binding sites, where I = 2-desaminodeoxyguanosine. I•C base pairs are functional analogs of A•T base pairs in the minor groove. The different behaviors exhibited by distamycin and netropsin binding to various DNA sequences suggested that these ligands are sensitive probes of DNA structure. For sites of five or more base pairs, distamycin can form 1:1 or 2:1 ligand:DNA complexes. Cooperativity in distamycin binding is low in sites such as AAAAA which has narrow minor grooves, and is higher in sites with wider minor grooves such as ATATAT. The distamycin binding and base pair opening lifetimes of I,C-containing DNA oligomers suggest that the I,C minor groove is structurally different from the A,T minor groove. Molecules which direct chemistry to a specific DNA sequence could be used as antiviral compounds, diagnostic probes, or molecular biology tools. The author studied two ligands in which reactive groups were tethered to a distamycin to increase the sequence specificity of the reactive agent.

readability of comprehension passages in junior high school (jhs)

African Journals Online (AJOL)

CHARLES

... to enhance readability. Key Words: readability formulas, comprehension passages, Junior High School, .... Index has a manual version but in this study the electronic version was used. The ..... probably the majority of the people heard the news by word of mouth. A critical look ..... The Journal of Tourism Studies 9.2: 49-60.

Speeding up the first-passage for subdiffusion by introducing a finite potential barrier

International Nuclear Information System (INIS)

Palyulin, Vladimir V; Metzler, Ralf

2014-01-01

We show that for a subdiffusive continuous time random walk with scale-free waiting time distribution the first-passage dynamics on a finite interval can be optimized by introduction of a piecewise linear potential barrier. Analytical results for the survival probability and first-passage density based on the fractional Fokker–Planck equation are shown to agree well with Monte Carlo simulations results. As an application we discuss an improved design for efficient translocation of gradient copolymers compared to homopolymer translocation in a quasi-equilibrium approximation. (fast track communications)

Synthesis of novel '4+1' Tc(III)/Re(III) mixed-ligand complexes with dendritically modified ligands

International Nuclear Information System (INIS)

Gniazdowska, E.; Kuenstler, J.U.; Stephan, H.; Pietzsch, H.J.

2006-01-01

Coordination chemistry of technetium and rhenium attracts a considerable interest due to the nuclear medicine applications of their radionuclides. Inert, so-called '3+1' or '4+1' technetium/rhenium mixed-ligand complexes open a new way to application of 99 mTc/ 188 Re labeled compounds in tumor diagnosis and therapy. In the presented paper, authors describe the synthesis and study of novel 99 mTc/ 188 Re complexes with dendritically functionalized tetradentate (tripodal chelator 2,2',2''-nitrilotris(ethanethiol), NS 3 and carboxyl group-bearing ligand, NS 3 (COOH) 3 ) and monodentate (dendritically modified isocyanide, CN-R(COOMe) 3 and isocyanide-modified peptide, CN-GGY) ligands. To verify the identity of the prepared n.c.a. complexes, non-radioactive analogous '4+1' Re compounds were synthesized. The experimental data show that a dendritic modification of the tetradentate/monodentate ligands changes the complex lipophilicity and does not influence its stability

Bexarotene ligand pharmaceuticals.

Science.gov (United States)

Hurst, R E

2000-12-01

Bexarotene (LGD-1069), from Ligand, was the first retinoid X receptor (RXR)-selective, antitumor retinoid to enter clinical trials. The company launched the drug for the treatment of cutaneous T-cell lymphoma (CTCL), as Targretin capsules, in the US in January 2000 [359023]. The company filed an NDA for Targretin capsules in June 1999, and for topical gel in December 1999 [329011], [349982] specifically for once-daily oral administration for the treatment of patients with early-stage CTCL who have not tolerated other therapies, patients with refractory or persistent early stage CTCL and patients with refractory advanced stage CTCL. The FDA approved Targretin capsules at the end of December 1999 for once-daily oral treatment of all stages of CTCL in patients refractory to at least one prior systemic therapy, at an initial dose of 300 mg/m2/day. After an NDA was submitted in December 1999 for Targretin gel, the drug received Priority Review status for use as a treatment of cutaneous lesions in patients with stage IA, IB or IIA CTCL [354836]. The FDA issued an approvable letter in June 2000, and granted marketing clearance for CTCL in the same month [370687], [372768], [372769], [373279]. Ligand had received Orphan Drug designation for this indication [329011]. At the request of the FDA, Ligand agreed to carry out certain post-approval phase IV and pharmacokinetic studies [351604]. The company filed an MAA with the EMEA for Targretin Capsules to treat lymphoma in November 1999 [348944]. The NDA for Targretin gel is based on a multicenter phase III trial that was conducted in the US, Canada, Europe and Australia involving 50 patients and a multicenter phase I/II clinical program involving 67 patients. Targretin gel was evaluated for the treatment of patients with early stage CTCL (IA-IIA) who were refractory to, intolerant to, or reached a response plateau for at least 6 months on at least two prior therapies. Efficacy results exceeded the protocol-defined response

Anchoring effect on first passage process in Taiwan financial market

Science.gov (United States)

Liu, Hsing; Liao, Chi-Yo; Ko, Jing-Yuan; Lih, Jiann-Shing

2017-07-01

Empirical analysis of the price fluctuations of financial markets has received extensive attention because a substantial amount of financial market data has been collected and because of advances in data-mining techniques. Price fluctuation trends can help investors to make informed trading decisions, but such decisions may also be affected by a psychological factors-the anchoring effect. This study explores the intraday price time series of Taiwan futures, and applies diffusion model and quantitative methods to analyze the relationship between the anchoring effect and price fluctuations during first passage process. Our results indicate that power-law scaling and anomalous diffusion for stock price fluctuations are related to the anchoring effect. Moreover, microscopic price fluctuations before switching point in first passage process correspond with long-term price fluctuations of Taiwan's stock market. We find that microscopic trends could provide useful information for understanding macroscopic trends in stock markets.

Predictions of first passage times in sparse discrete fracture networks using graph-based reductions

Science.gov (United States)

Hyman, J.; Hagberg, A.; Srinivasan, G.; Mohd-Yusof, J.; Viswanathan, H. S.

2017-12-01

We present a graph-based methodology to reduce the computational cost of obtaining first passage times through sparse fracture networks. We derive graph representations of generic three-dimensional discrete fracture networks (DFNs) using the DFN topology and flow boundary conditions. Subgraphs corresponding to the union of the k shortest paths between the inflow and outflow boundaries are identified and transport on their equivalent subnetworks is compared to transport through the full network. The number of paths included in the subgraphs is based on the scaling behavior of the number of edges in the graph with the number of shortest paths. First passage times through the subnetworks are in good agreement with those obtained in the full network, both for individual realizations and in distribution. Accurate estimates of first passage times are obtained with an order of magnitude reduction of CPU time and mesh size using the proposed method.

Survival and Passage of Juvenile Chinook Salmon and Steelhead Passing through Bonneville Dam, 2010

Energy Technology Data Exchange (ETDEWEB)

Ploskey, Gene R.; Weiland, Mark A.; Hughes, James S.; Woodley, Christa M.; Deng, Zhiqun; Carlson, Thomas J.; Kim, Jin A.; Royer, Ida M.; Batten, George W.; Cushing, Aaron W.; Carpenter, Scott M.; Etherington, D. J.; Faber, Derrek M.; Fischer, Eric S.; Fu, Tao; Hennen, Matthew J.; Mitchell, Tyler; Monter, Tyrell J.; Skalski, John R.; Townsend, Richard L.; Zimmerman, Shon A.

2011-12-01

Pacific Northwest National Laboratory (PNNL) and subcontractors conducted an acoustic-telemetry study of juvenile salmonid fish passage and survival at Bonneville Dam in 2010. The study was conducted to assess the readiness of the monitoring system for official compliance studies under the 2008 Biological Opinion and Fish Accords and to assess performance measures including route-specific fish passage proportions, travel times, and survival based upon a single-release model. This also was the last year of evaluation of effects of a behavioral guidance device installed in the Powerhouse 2 forebay. The study relied on releases of live Juvenile Salmon Acoustic Telemetry System tagged smolts in the Columbia River and used acoustic telemetry to evaluate the approach, passage, and survival of passing juvenile salmon. This study supports the U.S. Army Corps of Engineers continual effort to improve conditions for juvenile anadromous fish passing through Columbia River dams.

Survival and Passage of Juvenile Chinook Salmon and Steelhead Passing Through Bonneville Dam, 2010

Energy Technology Data Exchange (ETDEWEB)

Ploskey, Gene R.; Weiland, Mark A.; Hughes, James S.; Woodley, Christa M.; Deng, Zhiqun; Carlson, Thomas J.; Kim, Jin A.; Royer, Ida M.; Batten, George W.; Cushing, Aaron W.; Carpenter, Scott M.; Etherington, D. J.; Faber, Derrek M.; Fischer, Eric S.; Fu, Tao; Hennen, Matthew J.; Mitchell, T. D.; Monter, Tyrell J.; Skalski, J. R.; Townsend, Richard L.; Zimmerman, Shon A.

2012-09-01

Pacific Northwest National Laboratory (PNNL) and subcontractors conducted an acoustic-telemetry study of juvenile salmonid fish passage and survival at Bonneville Dam in 2010. The study was conducted to assess the readiness of the monitoring system for official compliance studies under the 2008 Biological Opinion and Fish Accords and to assess performance measures including route-specific fish passage proportions, travel times, and survival based upon a single-release model. This also was the last year of evaluation of effects of a behavioral guidance device installed in the Powerhouse 2 forebay. The study relied on releases of live Juvenile Salmon Acoustic Telemetry System tagged smolts in the Columbia River and used acoustic telemetry to evaluate the approach, passage, and survival of passing juvenile salmon. This study supports the U.S. Army Corps of Engineers continual effort to improve conditions for juvenile anadromous fish passing through Columbia River dams.

LASSO-ligand activity by surface similarity order: a new tool for ligand based virtual screening.

Science.gov (United States)

Reid, Darryl; Sadjad, Bashir S; Zsoldos, Zsolt; Simon, Aniko

2008-01-01

Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

LASSO—ligand activity by surface similarity order: a new tool for ligand based virtual screening

Science.gov (United States)

Reid, Darryl; Sadjad, Bashir S.; Zsoldos, Zsolt; Simon, Aniko

2008-06-01

Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more successful. eHiTS LASSO uses a new interacting surface point types (ISPT) molecular descriptor that is generated from the 3D structure of the ligand, but unlike most 3D descriptors it is conformation independent. Combined with a neural network machine learning technique, LASSO screens molecular databases at an ultra fast speed of 1 million structures in under 1 min on a standard PC. The results obtained from eHiTS LASSO trained on relatively small training sets of just 2, 4 or 8 actives are presented using the diverse directory of useful decoys (DUD) dataset. It is shown that over a wide range of receptor families, eHiTS LASSO is consistently able to enrich screened databases and provides scaffold hopping ability.

Adaptation of H9N2 AIV in guinea pigs enables efficient transmission by direct contact and inefficient transmission by respiratory droplets

Science.gov (United States)

Sang, Xiaoyu; Wang, Airong; Ding, Jie; Kong, Huihui; Gao, Xiaolong; Li, Lin; Chai, Tongjie; Li, Yuanguo; Zhang, Kun; Wang, Chengyu; Wan, Zhonghai; Huang, Geng; Wang, Tiecheng; Feng, Na; Zheng, Xuexing; Wang, Hualei; Zhao, Yongkun; Yang, Songtao; Qian, Jun; Hu, Guixue; Gao, Yuwei; Xia, Xianzhu

2015-01-01

H9N2 avian influenza viruses circulate worldwide in poultry and have sporadically infected humans, raising concern whether H9N2 viruses have pandemic potential. Here, we use a guinea pig model to examine whether serial passage results in adaptive viral changes that confer a transmissible phenotype to a wild-type H9N2 virus. After nine serial passages of an H9N2 virus through guinea pigs, productive transmission by direct contact occurred in 2/3 guinea pig pairs. The efficiency of transmission by direct contact increased following the fifteenth passage and occurred in 3/3 guinea pig pairs. In contrast, airborne transmission of the passaged virus was less efficient and occurred in 1/6 guinea pig pairs and 0/6 ferret pairs after the fifteenth passage. Three amino acid substitutions, HA1-Q227P, HA2-D46E, and NP-E434K, were sufficient for contact transmission in guinea pigs (2/3 pairs). The two HA amino acid substitutions enhanced receptor binding to α2,3-linked sialic acid receptors. Additionally, the HA2-D46E substitution increased virus thermostability whereas the NP-E434K mutation enhanced viral RNA polymerase activity in vitro. Our findings suggest that adaptive changes that enhance viral receptor binding, thermostability, and replicative capacity in mammalian cells can collectively enhance the transmissibility of H9N2 AIVs by direct contact in the guinea pig model. PMID:26552719

Monitoring of Juvenile Yearling Chinook Salmon and Steelhead Survival and Passage at John Day Dam, Spring 2010

Energy Technology Data Exchange (ETDEWEB)

Weiland, Mark A.; Ploskey, Gene R.; Hughes, James S.; Woodley, Christa M.; Deng, Zhiqun; Carlson, Thomas J.; Skalski, J. R.; Townsend, Richard L.

2012-11-15

The purpose of this study was to compare dam passage survival, at two spill treatment levels, of yearling Chinook salmon and steelhead smolts at John Day Dam during spring 2010. The two treatments were 30% and 40% spill out of total project discharge. Under the 2008 Federal Columbia River Power System (FCRPS) Biological Opinion (BiOp), dam passage survival should be greater than or equal to 0.96 and estimated with a standard error (SE) less than or equal 0.015. The study also estimated forebay residence time, tailrace egress time, and spill passage efficiency (SPE), as required in the Columbia Basin Fish Accords. However, by agreement among the stakeholders, this study was not an official BiOp compliance test because the long-term passage measures at John Day Dam have yet to be finalized and another year of spill-treatment testing was desired.

Synthesis and characterization β-ketoamine ligands

Science.gov (United States)

Zaid, Nurzati Amani Mohamed; Hassan, Nur Hasyareeda; Karim, Nurul Huda Abd

2018-04-01

β-ketoamine ligands are important members of heterodonor ligand because of their ease of preparation and modification of both steric and/or electronic effects. Complexes with β-ketoamine has received much less attention and there has been no study about this complex with β-ketoamine in ionic liquid reported. Two type of β-ketoamine ligands which are 4-amino-3-pentene-2-onato (A) and 3-amino-2-butenoic acid methyl ester (B) have been synthesized in this work. The resulting compound formed was characterized using standard spectroscopic and structural techniques which includes 1H and 13C, NMR spectroscopy and FTIR spectroscopy. The 1H and 13C NMR spectrum displayed all the expected signals with correct integration and multiplicity. And it is proved that there are some differences between two ligands as observed in NMR and FTIR spectrum.

Ligand combination strategy for the preparation of novel low-dimensional and open-framework metal cluster materials

Science.gov (United States)

Anokhina, Ekaterina V.

Low-dimensional and open-framework materials containing transition metals have a wide range of applications in redox catalysis, solid-state batteries, and electronic and magnetic devices. This dissertation reports on research carried out with the goal to develop a strategy for the preparation of low-dimensional and open-framework materials using octahedral metal clusters as building blocks. Our approach takes its roots from crystal engineering principles where the desired framework topologies are achieved through building block design. The key idea of this work is to induce directional bonding preferences in the cluster units using a combination of ligands with a large difference in charge density. This investigation led to the preparation and characterization of a new family of niobium oxychloride cluster compounds with original structure types exhibiting 1ow-dimensional or open-framework character. Most of these materials have framework topologies unprecedented in compounds containing octahedral clusters. Comparative analysis of their structural features indicates that the novel cluster connectivity patterns in these systems are the result of complex interplay between the effects of anisotropic ligand arrangement in the cluster unit and optimization of ligand-counterion electrostatic interactions. The important role played by these factors sets niobium oxychloride systems apart from cluster compounds with one ligand type or statistical ligand distribution where the main structure-determining factor is the total number of ligands. These results provide a blueprint for expanding the ligand combination strategy to other transition metal cluster systems and for the future rational design of cluster-based materials.

Designer TGFβ superfamily ligands with diversified functionality.

Directory of Open Access Journals (Sweden)

George P Allendorph

Full Text Available Transforming Growth Factor--beta (TGFβ superfamily ligands, including Activins, Growth and Differentiation Factors (GDFs, and Bone Morphogenetic Proteins (BMPs, are excellent targets for protein-based therapeutics because of their pervasiveness in numerous developmental and cellular processes. We developed a strategy termed RASCH (Random Assembly of Segmental Chimera and Heteromer, to engineer chemically-refoldable TGFβ superfamily ligands with unique signaling properties. One of these engineered ligands, AB208, created from Activin-βA and BMP-2 sequences, exhibits the refolding characteristics of BMP-2 while possessing Activin-like signaling attributes. Further, we find several additional ligands, AB204, AB211, and AB215, which initiate the intracellular Smad1-mediated signaling pathways more strongly than BMP-2 but show no sensitivity to the natural BMP antagonist Noggin unlike natural BMP-2. In another design, incorporation of a short N-terminal segment from BMP-2 was sufficient to enable chemical refolding of BMP-9, without which was never produced nor refolded. Our studies show that the RASCH strategy enables us to expand the functional repertoire of TGFβ superfamily ligands through development of novel chimeric TGFβ ligands with diverse biological and clinical values.

An interaction scenario of the galaxy pair NGC 3893/96 (KPG 302): A single passage?

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Gabbasov, R. F.; Rosado, M. [Instituto de Astronomía, Universidad Nacional Autónoma de Mexico (UNAM), A.P. 70-264,04510 México D.F. (Mexico); Klapp, J., E-mail: ruslan.gabb@gmail.com [Instituto Nacional de Investigaciones Nucleares, Carretera México-Toluca S/N, La Marquesa, Ocoyoacac, 52750 Estado de México (Mexico)

2014-05-20

Using the data obtained previously from Fabry-Perot interferometry, we study the orbital characteristics of the interacting pair of galaxies KPG 302 with the aim to estimate a possible interaction history, the conditions necessary for the spiral arm formation, and initial satellite mass. We found by performing N-body/smoothed particle hydrodynamics simulations of the interaction that a single passage can produce a grand design spiral pattern in less than 1 Gyr. Although we reproduce most of the features with the single passage, the required satellite to host mass ratio should be ∼1:5, which is not confirmed by the dynamical mass estimate made from the measured rotation curve. We conclude that a more realistic interaction scenario would require several passages in order to explain the mass ratio discrepancy.

Autobiographical Memory Retrieval and Hippocampal Activation as a Function of Repetition and the Passage of Time

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Lynn Nadel

2007-01-01

Full Text Available Multiple trace theory (MTT predicts that hippocampal memory traces expand and strengthen as a function of repeated memory retrievals. We tested this hypothesis utilizing fMRI, comparing the effect of memory retrieval versus the mere passage of time on hippocampal activation. While undergoing fMRI scanning, participants retrieved remote autobiographical memories that had been previously retrieved either one month earlier, two days earlier, or multiple times during the preceding month. Behavioral analyses revealed that the number and consistency of memory details retrieved increased with multiple retrievals but not with the passage of time. While all three retrieval conditions activated a similar set of brain regions normally associated with autobiographical memory retrieval including medial temporal lobe structures, hippocampal activation did not change as a function of either multiple retrievals or the passage of time. However, activation in other brain regions, including the precuneus, lateral prefrontal cortex, parietal cortex, lateral temporal lobe, and perirhinal cortex increased after multiple retrievals, but was not influenced by the passage of time. These results have important implications for existing theories of long-term memory consolidation.

Multiscale simulations of ligand adsorption and exchange on gold nanoparticles.

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Gao, Hui-Min; Liu, Hong; Qian, Hu-Jun; Jiao, Gui-Sheng; Lu, Zhong-Yuan

2018-01-17

We have developed a multiscale model that combines first-principles methods with atomistic and mesoscopic simulations to explore the molecular structures and packing density of the ligands present on the gold nanoparticle (AuNP) surface, as well as the adsorption/exchange reaction kinetics of cetyltrimethylammonium bromide (CTAB)/PEG-SH ligands on different facets of gold, namely, Au(111), Au(100), and Au(110). Our model predicts that on clean gold surfaces, CTAB adsorption is diffusion limited. Specifically, CTAB has the preferentially higher adsorption rate and coverage density on Au(100) and Au(110) surfaces, forming a more compact layer with respect to that on the Au(111) surface, which could result in greater growth of gold nanoparticles along the (111) direction. As opposed to CTAB adsorption, the exchange reaction between PEG-SH with CTAB shows no selectivity to different crystal faces, and the reaction process follows Langmuir diffusion kinetics. Kinetic analysis reveals that, in water, the exchange reaction is zeroth order with respect to the concentration of an incoming PEG-SH, indicative of a dissociative exchange mechanism. The observed rate constant decreases exponentially with the PEG-SH chain length, consistent with a diffusion process for the free PEG-SH in water. In particular, we show that the exchange efficiency increases as the chain rigidness and size of the incoming ligand and/or steric bulk of the initial protecting ligand shell are decreased. Our objectives are to provide a model to assess the kinetics and thermodynamics of the adsorption/exchange reaction process, and we expect that these findings will have important implications for routine surface characterization of AuNPs.

Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

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Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni; Lupia, Enrico

2017-01-01

CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

Directory of Open Access Journals (Sweden)

Sophie Doublier

Full Text Available CD40/CD40 ligand (CD40L dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs. We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS, and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS, and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

Prediction of GPCR-Ligand Binding Using Machine Learning Algorithms

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Sangmin Seo

2018-01-01

Full Text Available We propose a novel method that predicts binding of G-protein coupled receptors (GPCRs and ligands. The proposed method uses hub and cycle structures of ligands and amino acid motif sequences of GPCRs, rather than the 3D structure of a receptor or similarity of receptors or ligands. The experimental results show that these new features can be effective in predicting GPCR-ligand binding (average area under the curve [AUC] of 0.944, because they are thought to include hidden properties of good ligand-receptor binding. Using the proposed method, we were able to identify novel ligand-GPCR bindings, some of which are supported by several studies.

New pinene-derived pyridines as bidentate chiral ligands

Czech Academy of Sciences Publication Activity Database

Malkov, A. V.; Stewart-Liddon, A.; Teplý, Filip; Kobr, L.; Muir, K. W.; Haigh, D.; Kočovský, P.

2008-01-01

Roč. 64, č. 18 (2008), s. 4011-4025 ISSN 0040-4020 Institutional research plan: CEZ:AV0Z40550506 Keywords : chiral ligands * transition metal catalysis * asymmetric catalysis * pyridine ligands * oxazoline ligands Subject RIV: CC - Organic Chemistry Impact factor: 2.897, year: 2008

Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel-Lindau Gene Mutation Status.

Science.gov (United States)

Messai, Yosra; Gad, Sophie; Noman, Muhammad Zaeem; Le Teuff, Gwenael; Couve, Sophie; Janji, Bassam; Kammerer, Solenne Florence; Rioux-Leclerc, Nathalie; Hasmim, Meriem; Ferlicot, Sophie; Baud, Véronique; Mejean, Arnaud; Mole, David Robert; Richard, Stéphane; Eggermont, Alexander M M; Albiges, Laurence; Mami-Chouaib, Fathia; Escudier, Bernard; Chouaib, Salem

2016-10-01

Clear cell renal cell carcinomas (ccRCC) frequently display a loss of function of the von Hippel-Lindau (VHL) gene. To elucidate the putative relationship between VHL mutation status and immune checkpoint ligand programmed death-ligand 1 (PD-L1) expression. A series of 32 renal tumors composed of 11 VHL tumor-associated and 21 sporadic RCCs were used to evaluate PD-L1 expression levels after sequencing of the three exons and exon-intron junctions of the VHL gene. The 786-O, A498, and RCC4 cell lines were used to investigate the mechanisms of PD-L1 regulation. Fisher's exact test was used for VHL mutation and Kruskal-Wallis test for PD-L1 expression. If no covariate accounted for the association of VHL and PD-L1, then a Kruskal-Wallis test was used; otherwise Cochran-Mantel-Haenzsel test was used. We also used the Fligner-Policello test to compare two medians when the distributions had different dispersions. We demonstrated that tumors from ccRCC patients with VHL biallelic inactivation (ie, loss of function) display a significant increase in PD-L1 expression compared with ccRCC tumors carrying one VHL wild-type allele. Using the inducible VHL 786-O-derived cell lines with varying hypoxia-inducible factor-2 alpha (HIF-2α) stabilization levels, we showed that PD-L1 expression levels positively correlate with VHL mutation and HIF-2α expression. Targeting HIF-2α decreased PD-L1, while HIF-2α overexpression increased PD-L1 mRNA and protein levels in ccRCC cells. Interestingly, chromatin immunoprecipitation and luciferase assays revealed a direct binding of HIF-2α to a transcriptionally active hypoxia-response element in the human PD-L1 proximal promoter in 786-O cells. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. We investigated the relationship between von Hippel-Lindau mutations and programmed death-ligand 1 expression. We

First passage time for a diffusive process under a geometric constraint

International Nuclear Information System (INIS)

Tateishi, A A; Michels, F S; Dos Santos, M A F; Lenzi, E K; Ribeiro, H V

2013-01-01

We investigate the solutions, survival probability, and first passage time for a two-dimensional diffusive process subjected to the geometric constraints of a backbone structure. We consider this process governed by a fractional Fokker–Planck equation by taking into account the boundary conditions ρ(0,y;t) = ρ(∞,y;t) = 0, ρ(x, ± ∞;t) = 0, and an arbitrary initial condition. Our results show an anomalous spreading and, consequently, a nonusual behavior for the survival probability and for the first passage time distribution that may be characterized by different regimes. In addition, depending on the choice of the parameters present in the fractional Fokker–Planck equation, the survival probability indicates that part of the system may be trapped in the branches of the backbone structure. (paper)

Processing of false belief passages during natural story comprehension: An fMRI study.

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Kandylaki, Katerina D; Nagels, Arne; Tune, Sarah; Wiese, Richard; Bornkessel-Schlesewsky, Ina; Kircher, Tilo

2015-11-01

The neural correlates of theory of mind (ToM) are typically studied using paradigms which require participants to draw explicit, task-related inferences (e.g., in the false belief task). In a natural setup, such as listening to stories, false belief mentalizing occurs incidentally as part of narrative processing. In our experiment, participants listened to auditorily presented stories with false belief passages (implicit false belief processing) and immediately after each story answered comprehension questions (explicit false belief processing), while neural responses were measured with functional magnetic resonance imaging (fMRI). All stories included (among other situations) one false belief condition and one closely matched control condition. For the implicit ToM processing, we modeled the hemodynamic response during the false belief passages in the story and compared it to the hemodynamic response during the closely matched control passages. For implicit mentalizing, we found activation in typical ToM processing regions, that is the angular gyrus (AG), superior medial frontal gyrus (SmFG), precuneus (PCUN), middle temporal gyrus (MTG) as well as in the inferior frontal gyrus (IFG) billaterally. For explicit ToM, we only found AG activation. The conjunction analysis highlighted the left AG and MTG as well as the bilateral IFG as overlapping ToM processing regions for both implicit and explicit modes. Implicit ToM processing during listening to false belief passages, recruits the left SmFG and billateral PCUN in addition to the "mentalizing network" known form explicit processing tasks. © 2015 Wiley Periodicals, Inc.

Wireless Sensor Network Deployment for Monitoring Wildlife Passages

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Garcia-Sanchez, Antonio-Javier; Garcia-Sanchez, Felipe; Losilla, Fernando; Kulakowski, Pawel; Garcia-Haro, Joan; Rodríguez, Alejandro; López-Bao, José-Vicente; Palomares, Francisco

2010-01-01

Wireless Sensor Networks (WSNs) are being deployed in very diverse application scenarios, including rural and forest environments. In these particular contexts, specimen protection and conservation is a challenge, especially in natural reserves, dangerous locations or hot spots of these reserves (i.e., roads, railways, and other civil infrastructures). This paper proposes and studies a WSN based system for generic target (animal) tracking in the surrounding area of wildlife passages built to establish safe ways for animals to cross transportation infrastructures. In addition, it allows target identification through the use of video sensors connected to strategically deployed nodes. This deployment is designed on the basis of the IEEE 802.15.4 standard, but it increases the lifetime of the nodes through an appropriate scheduling. The system has been evaluated for the particular scenario of wildlife monitoring in passages across roads. For this purpose, different schemes have been simulated in order to find the most appropriate network operational parameters. Moreover, a novel prototype, provided with motion detector sensors, has also been developed and its design feasibility demonstrated. Original software modules providing new functionalities have been implemented and included in this prototype. Finally, main performance evaluation results of the whole system are presented and discussed in depth. PMID:22163601

Wireless Sensor Network Deployment for Monitoring Wildlife Passages

Directory of Open Access Journals (Sweden)

José-Vicente López-Bao

2010-08-01

Full Text Available Wireless Sensor Networks (WSNs are being deployed in very diverse application scenarios, including rural and forest environments. In these particular contexts, specimen protection and conservation is a challenge, especially in natural reserves, dangerous locations or hot spots of these reserves (i.e., roads, railways, and other civil infrastructures. This paper proposes and studies a WSN based system for generic target (animal tracking in the surrounding area of wildlife passages built to establish safe ways for animals to cross transportation infrastructures. In addition, it allows target identification through the use of video sensors connected to strategically deployed nodes. This deployment is designed on the basis of the IEEE 802.15.4 standard, but it increases the lifetime of the nodes through an appropriate scheduling. The system has been evaluated for the particular scenario of wildlife monitoring in passages across roads. For this purpose, different schemes have been simulated in order to find the most appropriate network operational parameters. Moreover, a novel prototype, provided with motion detector sensors, has also been developed and its design feasibility demonstrated. Original software modules providing new functionalities have been implemented and included in this prototype. Finally, main performance evaluation results of the whole system are presented and discussed in depth.

Compliance Monitoring of Yearling Chinook Salmon and Juvenile Steelhead Survival and Passage at Bonneville Dam, Spring 2011

Energy Technology Data Exchange (ETDEWEB)

Skalski, John R.; Townsend, Richard L.; Seaburg, Adam; Ploskey, Gene R.; Carlson, Thomas J.

2012-06-07

The study was designed to estimate dam passage survival at Bonneville Dam as stipulated by the 2008 Federal Columbia River Power System (FCRPS) Biological Opinion (BiOp) and to provide additional fish passage performance measures at that site as stipulated in the Columbia Basin Fish Accords.

Compliance Monitoring of Yearling Chinook Salmon and Juvenile Steelhead Survival and Passage at Bonneville Dam, Spring 2011

Energy Technology Data Exchange (ETDEWEB)

Skalski, J. R.; Townsend, Richard L.; Seaburg, Adam; Ploskey, Gene R.; Carlson, Thomas J.

2012-03-01

The study was designed to estimate dam passage survival at Bonneville Dam as stipulated by the 2008 Federal Columbia River Power System (FCRPS) Biological Opinion (BiOp) and to provide additional fish passage performance measures at that site as stipulated in the Columbia Basin Fish Accords.

EXAFS Studies of Some Copper(II) Mixed-Ligand Complexes

International Nuclear Information System (INIS)

Joshi, S. K.; Katare, R. K.; Shrivastava, B. D.

2007-01-01

X-ray K-absorption spectroscopic studies have been carried out on copper (II) mixed-ligand complexes with glutamic acid and aspartic acid as the primary ligands, where as water, pyridine, imidazole and benz-imidazole have been used as secondary ligands. Chemical shifts obtained from the X-ray absorption data have indicated that the glutamic acid complexes are more ionic as compared to their corresponding aspartic acid complexes having similar secondary ligands. Further, we have estimated the average metal-ligand bond distances from the from structure data. For the different complexes studied under the present investigation, the studies reveal that the bonding parameter α1 decreases with the increase in the percentage covalency of the metal-ligand bond. Thus, the bonding parameter α1 may be used for the estimation of percentage covalency of the metal-ligand bond in other similar complexes

Pathos and the Mundane in the Symbolic Space of 1956 Revolution: the Case of Corvin-passage, Budapest

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Ágnes Erőss

2016-11-01

Full Text Available The Corvin passage is one of the most important symbolic spaces of 1956 revolution in Hungary. The majority of armed conflicts took place in Budapest, where the largest resistance group had to battle against Soviet tanks in the neighbourhood of the Corvin Passage. This study aims to highlight the fact that, even though a general shift has taken place from the pre-1990 policy to ‘forget’ to today’s established remembrance practices, the Corvin Passage still does not have a prominent position as a major historic site. Our research is based on a study of relevant national and international literature, on an analysis of documents relating to tourism site management, on historical sources related to the Corvin Passage, and on a content analysis of guide-books and websites. The authors would tribute to 70 anniversary of treading out of Hungarian revolution and war of independence with this paper.

Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage.

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Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf; Edvinsson, Lars

2015-01-01

Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.

Dual Ligand-Enabled Nondirected C-H Olefination of Arenes.

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Chen, Hao; Wedi, Philipp; Meyer, Tim; Tavakoli, Ghazal; van Gemmeren, Manuel

2018-02-23

The application of the Pd-catalyzed oxidative C-H olefination of arenes, also known as the Fujiwara-Moritani reaction, has traditionally been limited by the requirement for directing groups on the substrate or the need to use the arene in large excess, typically as a (co)solvent. Herein the development of a catalytic system is described that, through the combined action of two complementary ligands, makes it possible to use directing-group-free arenes as limiting reagents for the first time. The reactions proceed under a combination of both steric and electronic control and enable the application of this powerful reaction to valuable arenes, which cannot be utilized in excess. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Semiconductor Quantum Dots with Photoresponsive Ligands.

Science.gov (United States)

Sansalone, Lorenzo; Tang, Sicheng; Zhang, Yang; Thapaliya, Ek Raj; Raymo, Françisco M; Garcia-Amorós, Jaume

2016-10-01

Photochromic or photocaged ligands can be anchored to the outer shell of semiconductor quantum dots in order to control the photophysical properties of these inorganic nanocrystals with optical stimulations. One of the two interconvertible states of the photoresponsive ligands can be designed to accept either an electron or energy from the excited quantum dots and quench their luminescence. Under these conditions, the reversible transformations of photochromic ligands or the irreversible cleavage of photocaged counterparts translates into the possibility to switch luminescence with external control. As an alternative to regulating the photophysics of a quantum dot via the photochemistry of its ligands, the photochemistry of the latter can be controlled by relying on the photophysics of the former. The transfer of excitation energy from a quantum dot to a photocaged ligand populates the excited state of the species adsorbed on the nanocrystal to induce a photochemical reaction. This mechanism, in conjunction with the large two-photon absorption cross section of quantum dots, can be exploited to release nitric oxide or to generate singlet oxygen under near-infrared irradiation. Thus, the combination of semiconductor quantum dots and photoresponsive ligands offers the opportunity to assemble nanostructured constructs with specific functions on the basis of electron or energy transfer processes. The photoswitchable luminescence and ability to photoinduce the release of reactive chemicals, associated with the resulting systems, can be particularly valuable in biomedical research and can, ultimately, lead to the realization of imaging probes for diagnostic applications as well as to therapeutic agents for the treatment of cancer.

Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.

Science.gov (United States)

Heusser, Stephanie A; Yoluk, Özge; Klement, Göran; Riederer, Erika A; Lindahl, Erik; Howard, Rebecca J

2016-07-01

The superfamily of pentameric ligand-gated ion channels includes neurotransmitter receptors that mediate fast synaptic transmission in vertebrates, and are targets for drugs including alcohols, anesthetics, benzodiazepines, and anticonvulsants. However, the mechanisms of ion channel opening, gating, and modulation in these receptors leave many open questions, despite their pharmacological importance. Subtle conformational changes in both the extracellular and transmembrane domains are likely to influence channel opening, but have been difficult to characterize given the limited structural data available for human membrane proteins. Recent crystal structures of a modified Caenorhabditis elegans glutamate-gated chloride channel (GluCl) in multiple states offer an appealing model system for structure-function studies. However, the pharmacology of the crystallographic GluCl construct is not well established. To establish the functional relevance of this system, we used two-electrode voltage-clamp electrophysiology in Xenopus oocytes to characterize activation of crystallographic and native-like GluCl constructs by L-glutamate and ivermectin. We also tested modulation by ethanol and other anesthetic agents, and used site-directed mutagenesis to explore the role of a region of Loop F which was implicated in ligand gating by molecular dynamics simulations. Our findings indicate that the crystallographic construct functionally models concentration-dependent agonism and allosteric modulation of pharmacologically relevant receptors. Specific substitutions at residue Leu174 in loop F altered direct L-glutamate activation, consistent with computational evidence for this region's role in ligand binding. These insights demonstrate conservation of activation and modulation properties in this receptor family, and establish a framework for GluCl as a model system, including new possibilities for drug discovery. In this study, we elucidate the validity of a modified glutamate

Sherlock Holmes and the Strange Case of the Missing Attribution: A Historical Note on "The Grandfather Passage"

Science.gov (United States)

Reilly, Jamie; Fisher, Jamie L.

2012-01-01

Purpose: In 1963, Charles Van Riper published "My Grandfather," a short reading passage that has evolved into a ubiquitous metric of reading ability and speech intelligibility. In this historical note, we describe several heretofore unacknowledged similarities between "The Grandfather Passage" (Darley, Aronson, & Brown, 1975) and a portion of "The…

Impact of the vibrations on the environment caused by passages of trains at variable speed

Directory of Open Access Journals (Sweden)

Kożuch Barbara

2016-01-01

Full Text Available The paper deals with negative environmental impact caused by the passages of different kinds of trains at variable speed. The study is based on the measurement results which took place in Poland in 2013 on the railway line no. 4. The effect of the traction unit – Pendolino (EMU 250 on the vibration climate was analysed. The impact of passages of new trains was compared to currently operated rolling stock. The speed of trains was varying between 40 and 250 km/h. Vibration measurements were conducted by stuff of an accredited Laboratory of Structural Mechanics at Cracow University of Technology (Accreditation No. AB 826. The influence of the indicated vibrations due to passages of the trains on the building in the neighbourhood of the line was investigated. The vibration assessment was done for horizontal components of vibrations according to Polish standard code. Assessment of environmental impact was presented by indicator of perceptibility of vibration through construction (WODB, which refers to the Scales of Dynamic Influences (SDI scales. The limits specified by standards in any of the passages have not been exceeded. The change of speed or rolling stock resulted in a change in the characteristic of the vibration spectrum.

An unbiased method to build benchmarking sets for ligand-based virtual screening and its application to GPCRs.

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Xia, Jie; Jin, Hongwei; Liu, Zhenming; Zhang, Liangren; Wang, Xiang Simon

2014-05-27

Benchmarking data sets have become common in recent years for the purpose of virtual screening, though the main focus had been placed on the structure-based virtual screening (SBVS) approaches. Due to the lack of crystal structures, there is great need for unbiased benchmarking sets to evaluate various ligand-based virtual screening (LBVS) methods for important drug targets such as G protein-coupled receptors (GPCRs). To date these ready-to-apply data sets for LBVS are fairly limited, and the direct usage of benchmarking sets designed for SBVS could bring the biases to the evaluation of LBVS. Herein, we propose an unbiased method to build benchmarking sets for LBVS and validate it on a multitude of GPCRs targets. To be more specific, our methods can (1) ensure chemical diversity of ligands, (2) maintain the physicochemical similarity between ligands and decoys, (3) make the decoys dissimilar in chemical topology to all ligands to avoid false negatives, and (4) maximize spatial random distribution of ligands and decoys. We evaluated the quality of our Unbiased Ligand Set (ULS) and Unbiased Decoy Set (UDS) using three common LBVS approaches, with Leave-One-Out (LOO) Cross-Validation (CV) and a metric of average AUC of the ROC curves. Our method has greatly reduced the "artificial enrichment" and "analogue bias" of a published GPCRs benchmarking set, i.e., GPCR Ligand Library (GLL)/GPCR Decoy Database (GDD). In addition, we addressed an important issue about the ratio of decoys per ligand and found that for a range of 30 to 100 it does not affect the quality of the benchmarking set, so we kept the original ratio of 39 from the GLL/GDD.

Murine interleukin 1 receptor. Direct identification by ligand blotting and purification to homogeneity of an interleukin 1-binding glycoprotein

International Nuclear Information System (INIS)

Bird, T.A.; Gearing, A.J.; Saklatvala, J.

1988-01-01

Functional receptors (IL1-R) for the proinflammatory cytokine interleukin 1 (IL1) were solubilized from plasma membranes of the NOB-1 subclone of murine EL4 6.1 thymoma cells using the zwitterionic detergent 3[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Membrane extracts were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose membranes, and ligand blotted with 125 I-labeled recombinant human IL1 alpha in order to reveal proteins capable of specifically binding IL1. A single polydisperse polypeptide of Mr approximately equal to 80,000 was identified in this way, which bound IL1 alpha and IL1 beta with the same affinity as the IL1-R on intact NOB-1 cells (approximately equal to 10(-10) M). The IL1-binding polypeptide was only seen in membranes from IL1-R-bearing cells and did not react with interleukin 2, tumor necrosis factor alpha, or interferon. IL1-R was purified to apparent homogeneity from solubilized NOB-1 membranes by affinity chromatography on wheat germ agglutinin-Sepharose and IL1 alpha-Sepharose. Gel electrophoresis and silver staining of purified preparations revealed a single protein of Mr approximately equal to 80,000 which reacted positively in the ligand-blotting procedure and which we identify as the ligand-binding moiety of the murine IL1-R. Purified IL1-R exhibited the same affinity and specificity as the receptor on intact cells. The relationship of this protein to proteins identified by covalent cross-linking studies is discussed

Discovering protein-ligand chalcogen bonding in the protein data bank using endocyclic sulfur-containing heterocycles as ligand search subsets.

Science.gov (United States)

Mitchell, Miguel O

2017-09-24

The chalcogen bond, the noncovalent, electrostatic attraction between covalently bonded atoms in group 16 and Lewis bases, is present in protein-ligand interactions based on X-ray structures deposited in the Protein Data Bank (PDB). Discovering protein-ligand chalcogen bonding in the PDB employed a strategy that focused on searching the database for protein complexes of five-membered, heterocyclic ligands containing endocyclic sulfur with endo electron-withdrawing groups (isothiazoles; thiazoles; 1,2,3-, 1,2.4-, 1,2,5-, 1,3,4-thiadiazoles) and thiophenes with exo electron-withdrawing groups, e.g., 2-chloro, 2-bromo, 2-amino, 2-alkylthio. Out of 930 ligands investigated, 33 or 3.5% have protein-ligand S---O interactions of which 31 are chalcogen bonds and two appear to be S---HO hydrogen bonds. The bond angles for some of the chalcogen bonds found in the PDB are less than 90°, and an electrostatic model is proposed to explain this phenomenon.

Production of erythrocytes from directly isolated or Delta1 Notch ligand expanded CD34+ hematopoietic progenitor cells: process characterization, monitoring and implications for manufacture.

Science.gov (United States)

Glen, Katie E; Workman, Victoria L; Ahmed, Forhad; Ratcliffe, Elizabeth; Stacey, Adrian J; Thomas, Robert J

2013-09-01

Economic ex vivo manufacture of erythrocytes at 10(12) cell doses requires an efficiently controlled bio-process capable of extensive proliferation and high terminal density. High-resolution characterization of the process would identify production strategies for increased efficiency, monitoring and control. CD34(+) cord blood cells or equivalent cells that had been pre-expanded for 7 days with Delta1 Notch ligand were placed in erythroid expansion and differentiation conditions in a micro-scale ambr suspension bioreactor. Multiple culture parameters were varied, and phenotype markers and metabolites measured to identify conserved trends and robust monitoring markers. The cells exhibited a bi-modal erythroid differentiation pattern with an erythroid marker peak after 2 weeks and 3 weeks of culture; differentiation was comparatively weighted toward the second peak in Delta1 pre-expanded cells. Both differentiation events were strengthened by omission of stem cell factor and dexamethasone. The cumulative cell proliferation and death, or directly measured CD45 expression, enabled monitoring of proliferative rate of the cells. The metabolic activities of the cultures (glucose, glutamine and ammonia consumption or production) were highly variable but exhibited systematic change synchronized with the change in differentiation state. Erythroid differentiation chronology is partly determined by the heterogeneous CD34(+) progenitor compartment with implications for input control; Delta1 ligand-mediated progenitor culture can alter differentiation profile with control benefits for engineering production strategy. Differentiation correlated changes in cytokine response, markers and metabolic state will enable scientifically designed monitoring and timing of manufacturing process steps. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Acoustic Telemetry Evaluation of Juvenile Salmonid Passage and Survival at John Day Dam, 2011

Energy Technology Data Exchange (ETDEWEB)

Weiland, Mark A.; Woodley, Christa M.; Ploskey, Gene R.; Hughes, James S.; Hennen, Matthew J.; Kim, Jin A.; Deng, Zhiqun; Fu, Tao; Skalski, J. R.; Townsend, Richard L.; Wagner, Katie A.; Fischer, Eric S.; Duncan, Joanne P.; Batten, G.; Carlson, Thomas J.; Carpenter, Scott M.; Cushing, Aaron W.; Elder, T.; Etherington, D. J.; Johnson, Gary E.; Khan, Fenton; Miracle, Ann L.; Mitchell, T. D.; Prather, K.; Rayamajhi, Bishes; Royer, Ida; Seaburg, Adam; Zimmerman, Shon A.

2013-06-21

This report presents survival, behavioral, and fish passage results for tagged yearling Chinook salmon and juvenile steelhead as part of a survival study conducted at John Day Dam during spring 2011. This study was designed to evaluate the passage and survival of yearling Chinook salmon and juvenile steelhead to assist managers in identifying dam operations for compliance testing as stipulated by the 2008 Federal Columbia River Power System Biological Opinion and the 2008 Columbia Basin Fish Accords. Survival estimates were based on a paired-release survival model.

Field Observations of Changes in SST, Chlorophyll and POC Flux in the Southern East China Sea Before and After the Passage of Typhoon Jangmi

Directory of Open Access Journals (Sweden)

Yung-Yen Shih

2013-01-01

Full Text Available Severe tropical storms play an important role in triggering phytoplankton blooms, yet direct field observation of evidence of the effects of a typhoon is very rare. Sea surface temperature (SST, nitrate concentration, chlorophyll a (chl a concentration, and particulate organic carbon (POC flux were measured before and shortly after Typhoon Jangmi which affected the southern East China Sea (SECS on September 28 ~ 29, 2008. In situ SST (27.5 ~ 28.0°C on September 19 ~ 21, decreased to ~24.0°C (October 3 ~ 6 in the SECS 4 ~ 7 days after the passage of Typhoon Jangmi. In situ nitrate and chl a concentrations 7-days (on October 6 after the passage of Jangmi were 1.9 μM and 1.61 mg m-3, respectively, much higher than those (nitrate: 0.3 μM and chl a: 0.73 mg m-3 concentrations before the typhoon (September 21. The enhanced chl a concentration is thus caused by a nutrient supply via vertical mixing or upwelling in the euphotic zone. The POC flux 7-days after Jangmi¡¦s passage was 552 ± 28 mg-C m-2 d-1, a ~2.5-fold increases before the typhoon (224 ± 33 mg-C m-2 d-1, on September 21. Our results suggest that typhoons indeed can stimulate efficient POC export out of the euphotic zone, while it is still poorly understood with regard to the total effects of a typhoon on nutrient dynamics and detailed carbon sequestration due to sampling difficulty. Therefore, successional sea-going observations ought to be conducted in the affected area after the passage of typhoons.

Progranulin-derived Atsttrin directly binds to TNFRSF25 (DR3 and inhibits TNF-like ligand 1A (TL1A activity.

Directory of Open Access Journals (Sweden)

Cui Liu

Full Text Available Atsttrin, a progranulin (PGRN-derived molecule composed of three TNFR-binding domains of PGRN, binds to TNF receptors (TNFR and is therapeutic against inflammatory arthritis. Here we screened the associations of Atsttrin and other members in TNFR subfamily, which led to the discovery of TNFRSF25 (DR3 as an additional Atsttrin-interacting member in TNFR family. Similar to TNFR1 and TNFR2, DR3 also directly bound to Atsttrin. The first three cysteine-rich domains (CRD in the extracellular portion of DR3 were required for this interaction. Atsttrin inhibited the interaction between DR3 and its TNF-Like Ligand 1A (TL1A. In addition, Atsttrin inhibited TL1A-stimulated target gene expressions and neutralized TL1A-enhanced osteoclastogenesis in vitro. Furthermore, Atsttrin ameliorated the pathology in dextran sulfate sodium induced colitis. Taken together, these findings not only provide the new insights into Atsttrin's therapeutic action in inflammatory arthritis, but may also present Atsttrin as a novel biological agent for treating various types of diseases associated with TL1A/DR3 pathway.

THE 2011 PERIASTRON PASSAGE OF THE Be BINARY {delta} Scorpii

Energy Technology Data Exchange (ETDEWEB)

Miroshnichenko, A. S. [Department of Physics and Astronomy, University of North Carolina at Greensboro, Greensboro, NC 27402-6170 (United States); Pasechnik, A. V. [Tuorla Observatory, Department of Physics and Astronomy, University of Turku, FI-21500 Puekkioe (Finland); Manset, N. [CFHT Corporation, 65-1238 Mamalahoa Hwy, Kamuela, HI 96743 (United States); Carciofi, A. C. [Instituto de Astronomia, Geofisica e Ciencias Atmosfericas, Universidade de Sao Paulo (Brazil); Rivinius, Th. [European Organisation for Astronomical Research in the Southern Hemisphere, Casilla 19001, Santiago 19 (Chile); Stefl, S. [ESO/ALMA, Alonso de Cordova 3107, Vitacura, Santiago (Chile); Gvaramadze, V. V. [Sternberg Astronomical Institute, Lomonosov Moscow State University, Universitetskij Pr. 13, Moscow 119992 (Russian Federation); Ribeiro, J. [Observatorio do Instituto Geografico do Exercito, Lisboa (Portugal); Fernando, A. [ATALAIA.org Group, Lisboa (Portugal); Garrel, T. [Observatoire de Juvignac, 19 avenue de Hameau du Golf F-34990, Juvignac (France); Knapen, J. H. [Instituto de Astrofisica de Canarias, E-38205 La Laguna, Tenerife (Spain); Buil, C. [Castanet Tolosan Observatory, 6 place Clemence Isaure F-31320 Castanet Tolosan (France); Heathcote, B. [Barfold Observatory, Glenhope, Victoria 3444 (Australia); Pollmann, E. [Emil-Nolde-Str. 12, D-51375, Leverkusen (Germany); Mauclaire, B. [Observatoire du Val d' Arc, route de Peynier F-13530, Trets (France); Thizy, O. [Shelyak Instruments, 1116 route de Chambery, F-38330, Saint-Ismier (France); Martin, J. [Barber Research Observatory, Department of Physics and Astronomy, University of Illinois-Springfield, IL 62703 (United States); Zharikov, S. V. [Instituto de Astronomia, Universidad Nacional Autonoma de Mexico, Apdo. Postal 877, Ensenada, 22800, Baja California (Mexico); Okazaki, A. T. [Faculty of Engineering, Hokkai-Gakuen University, Toyohira-ku, Sapporo 062-8605 (Japan); others, and

2013-04-01

We describe the results of the world-wide observing campaign of the highly eccentric Be binary system {delta} Scorpii 2011 periastron passage which involved professional and amateur astronomers. Our spectroscopic observations provided a precise measurement of the system orbital period at 10.8092 {+-} 0.0005 yr. Fitting of the He II 4686 A line radial velocity curve determined the periastron passage time on 2011 July 3, UT 9:20 with a 0.9-day uncertainty. Both these results are in a very good agreement with recent findings from interferometry. We also derived new evolutionary masses of the binary components (13 and 8.2 M{sub Sun }) and a new distance of 136 pc from the Sun, consistent with the HIPPARCOS parallax. The radial velocity and profile variations observed in the H{alpha} line near the 2011 periastron reflected the interaction of the secondary component and the circumstellar disk around the primary component. Using these data, we estimated a disk radius of 150 R{sub Sun }. Our analysis of the radial velocity variations measured during the periastron passage time in 2000 and 2011 along with those measured during the 20th century, the high eccentricity of the system, and the presence of a bow shock-like structure around it suggest that {delta} Sco might be a runaway triple system. The third component should be external to the known binary and move on an elliptical orbit that is tilted by at least 40 Degree-Sign with respect to the binary orbital plane for such a system to be stable and responsible for the observed long-term radial velocity variations.

THE 2011 PERIASTRON PASSAGE OF THE Be BINARY δ Scorpii

International Nuclear Information System (INIS)

Miroshnichenko, A. S.; Pasechnik, A. V.; Manset, N.; Carciofi, A. C.; Rivinius, Th.; Štefl, S.; Gvaramadze, V. V.; Ribeiro, J.; Fernando, A.; Garrel, T.; Knapen, J. H.; Buil, C.; Heathcote, B.; Pollmann, E.; Mauclaire, B.; Thizy, O.; Martin, J.; Zharikov, S. V.; Okazaki, A. T.

2013-01-01

We describe the results of the world-wide observing campaign of the highly eccentric Be binary system δ Scorpii 2011 periastron passage which involved professional and amateur astronomers. Our spectroscopic observations provided a precise measurement of the system orbital period at 10.8092 ± 0.0005 yr. Fitting of the He II 4686 Å line radial velocity curve determined the periastron passage time on 2011 July 3, UT 9:20 with a 0.9-day uncertainty. Both these results are in a very good agreement with recent findings from interferometry. We also derived new evolutionary masses of the binary components (13 and 8.2 M ☉ ) and a new distance of 136 pc from the Sun, consistent with the HIPPARCOS parallax. The radial velocity and profile variations observed in the Hα line near the 2011 periastron reflected the interaction of the secondary component and the circumstellar disk around the primary component. Using these data, we estimated a disk radius of 150 R ☉ . Our analysis of the radial velocity variations measured during the periastron passage time in 2000 and 2011 along with those measured during the 20th century, the high eccentricity of the system, and the presence of a bow shock-like structure around it suggest that δ Sco might be a runaway triple system. The third component should be external to the known binary and move on an elliptical orbit that is tilted by at least 40° with respect to the binary orbital plane for such a system to be stable and responsible for the observed long-term radial velocity variations.

A tandem regression-outlier analysis of a ligand cellular system for key structural modifications around ligand binding.

Science.gov (United States)

Lin, Ying-Ting

2013-04-30

A tandem technique of hard equipment is often used for the chemical analysis of a single cell to first isolate and then detect the wanted identities. The first part is the separation of wanted chemicals from the bulk of a cell; the second part is the actual detection of the important identities. To identify the key structural modifications around ligand binding, the present study aims to develop a counterpart of tandem technique for cheminformatics. A statistical regression and its outliers act as a computational technique for separation. A PPARγ (peroxisome proliferator-activated receptor gamma) agonist cellular system was subjected to such an investigation. Results show that this tandem regression-outlier analysis, or the prioritization of the context equations tagged with features of the outliers, is an effective regression technique of cheminformatics to detect key structural modifications, as well as their tendency of impact to ligand binding. The key structural modifications around ligand binding are effectively extracted or characterized out of cellular reactions. This is because molecular binding is the paramount factor in such ligand cellular system and key structural modifications around ligand binding are expected to create outliers. Therefore, such outliers can be captured by this tandem regression-outlier analysis.

Ligand-Enabled γ-C(sp3)–H Olefination of Amines: En Route to Pyrrolidines

Science.gov (United States)

Jiang, Heng; He, Jian; Liu, Tao

2016-01-01

Pd(II)-catalyzed olefination of γ-C(sp3)–H bonds of triflyl (Tf) and 4-nitrobenzenesulfonyl (Ns) protected amines is achieved. Subsequent aza-Wacker oxidative cyclization or conjugate addition of the olefinated intermediates provides a variety of C-2 alkylated pyrrolidines. Three pyridine- and quinoline-based ligands are developed to match different classes of amine substrates, demonstrating a rare example of ligand-enabled C(sp3)–H olefination reaction. The use of Ns protecting group to direct C(sp3)–H activation of alkyl amine is also a significant step towards practical C–H functionalizations of alkyl amines. PMID:26796676

Adiabatic fast passage application in solid state NMR study of cross relaxation and molecular dynamics in heteronuclear systems.

Science.gov (United States)

Baranowski, M; Woźniak-Braszak, A; Jurga, K

2016-01-01

The paper presents the benefits of using fast adiabatic passage for the study of molecular dynamics in the solid state heteronuclear systems in the laboratory frame. A homemade pulse spectrometer operating at the frequency of 30.2MHz and 28.411MHz for protons and fluorines, respectively, has been enhanced with microcontroller direct digital synthesizer DDS controller [1-4]. This work briefly describes how to construct a low-cost and easy-to-assemble adiabatic extension set for homemade and commercial spectrometers based on recently very popular Arduino shields. The described set was designed for fast adiabatic generation. Timing and synchronization problems are discussed. The cross-relaxation experiments with different initial states of the two spin systems have been performed. Contrary to our previous work [5] where the steady-state NOE experiments were conducted now proton spins (1)H are polarized in the magnetic field B0 while fluorine spins (19)F are perturbed by selective saturation for a short time and then the system is allowed to evolve for a period in the absence of a saturating field. The adiabatic passage application leads to a reversal of magnetization of fluorine spins and increases the amplitude of the signal. Copyright © 2015 Elsevier Inc. All rights reserved.

-Pincer Ligand Family through Ligand Post-Modification

KAUST Repository

Huang, Mei-Hui; Hu, Jinsong; Huang, Kuo-Wei

2017-01-01

A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

-Pincer Ligand Family through Ligand Post-Modification

KAUST Repository

Huang, Mei-Hui

2017-10-02

A series of air-stable nickel complexes containing triazine-based PN3P-pincer ligands were synthesized and fully characterized. Complex 3 contains a de-aromatized central triazine ring from the deprotonation of one of the N–H arms. With a post-modification strategy, the Me-PN3P*NiCl complex (3) could be converted into a new class of diimine–traizine PN3P-pincer nickel complexes.

Tuning the allosteric regulation of artificial muscarinic and dopaminergic ligand-gated potassium channels by protein engineering of G protein-coupled receptors

Science.gov (United States)

Moreau, Christophe J.; Revilloud, Jean; Caro, Lydia N.; Dupuis, Julien P.; Trouchet, Amandine; Estrada-Mondragón, Argel; Nieścierowicz, Katarzyna; Sapay, Nicolas; Crouzy, Serge; Vivaudou, Michel

2017-01-01

Ligand-gated ion channels enable intercellular transmission of action potential through synapses by transducing biochemical messengers into electrical signal. We designed artificial ligand-gated ion channels by coupling G protein-coupled receptors to the Kir6.2 potassium channel. These artificial channels called ion channel-coupled receptors offer complementary properties to natural channels by extending the repertoire of ligands to those recognized by the fused receptors, by generating more sustained signals and by conferring potassium selectivity. The first artificial channels based on the muscarinic M2 and the dopaminergic D2L receptors were opened and closed by acetylcholine and dopamine, respectively. We find here that this opposite regulation of the gating is linked to the length of the receptor C-termini, and that C-terminus engineering can precisely control the extent and direction of ligand gating. These findings establish the design rules to produce customized ligand-gated channels for synthetic biology applications. PMID:28145461

Database of ligand-induced domain movements in enzymes

Directory of Open Access Journals (Sweden)

Hayward Steven

2009-03-01

Full Text Available Abstract Background Conformational change induced by the binding of a substrate or coenzyme is a poorly understood stage in the process of enzyme catalysed reactions. For enzymes that exhibit a domain movement, the conformational change can be clearly characterized and therefore the opportunity exists to gain an understanding of the mechanisms involved. The development of the non-redundant database of protein domain movements contains examples of ligand-induced domain movements in enzymes, but this valuable data has remained unexploited. Description The domain movements in the non-redundant database of protein domain movements are those found by applying the DynDom program to pairs of crystallographic structures contained in Protein Data Bank files. For each pair of structures cross-checking ligands in their Protein Data Bank files with the KEGG-LIGAND database and using methods that search for ligands that contact the enzyme in one conformation but not the other, the non-redundant database of protein domain movements was refined down to a set of 203 enzymes where a domain movement is apparently triggered by the binding of a functional ligand. For these cases, ligand binding information, including hydrogen bonds and salt-bridges between the ligand and specific residues on the enzyme is presented in the context of dynamical information such as the regions that form the dynamic domains, the hinge bending residues, and the hinge axes. Conclusion The presentation at a single website of data on interactions between a ligand and specific residues on the enzyme alongside data on the movement that these interactions induce, should lead to new insights into the mechanisms of these enzymes in particular, and help in trying to understand the general process of ligand-induced domain closure in enzymes. The website can be found at: http://www.cmp.uea.ac.uk/dyndom/enzymeList.do

Overview of Stabilizing Ligands for Biocompatible Quantum Dot Nanocrystals

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Aaron Clapp

2011-11-01

Full Text Available Luminescent colloidal quantum dots (QDs possess numerous advantages as fluorophores in biological applications. However, a principal challenge is how to retain the desirable optical properties of quantum dots in aqueous media while maintaining biocompatibility. Because QD photophysical properties are directly related to surface states, it is critical to control the surface chemistry that renders QDs biocompatible while maintaining electronic passivation. For more than a decade, investigators have used diverse strategies for altering the QD surface. This review summarizes the most successful approaches for preparing biocompatible QDs using various chemical ligands.

Receptor-ligand binding sites and virtual screening.

Science.gov (United States)

Hattotuwagama, Channa K; Davies, Matthew N; Flower, Darren R

2006-01-01

Within the pharmaceutical industry, the ultimate source of continuing profitability is the unremitting process of drug discovery. To be profitable, drugs must be marketable: legally novel, safe and relatively free of side effects, efficacious, and ideally inexpensive to produce. While drug discovery was once typified by a haphazard and empirical process, it is now increasingly driven by both knowledge of the receptor-mediated basis of disease and how drug molecules interact with receptors and the wider physiome. Medicinal chemistry postulates that to understand a congeneric ligand series, or set thereof, is to understand the nature and requirements of a ligand binding site. Likewise, structural molecular biology posits that to understand a binding site is to understand the nature of ligands bound therein. Reality sits somewhere between these extremes, yet subsumes them both. Complementary to rules of ligand design, arising through decades of medicinal chemistry, structural biology and computational chemistry are able to elucidate the nature of binding site-ligand interactions, facilitating, at both pragmatic and conceptual levels, the drug discovery process.

Rumen passage kinetics of forage and concentrate derived fiber in dairy cows

DEFF Research Database (Denmark)

Krämer, Monika; Lund, Peter; Weisbjerg, Martin Riis

2013-01-01

, were used in a completely randomized block experiment. Treatments differed in forage type (corn silage versus grass silage) and forage:concentrate ratio (50:50 versus 75:25 on organic matter basis). Fiber passage kinetics were studied based on rumen evacuations and on marker excretion profiles in feces....... The forage type itself (corn silage and grass silage) rather than ration composition seemed to determine the total tract retention time of forage fiber......Rumen passage kinetics of forage and concentrate fiber were analyzed to determine intrinsic feed effects and extrinsic ration effects on the retention time of fiber in the rumen. Sixteen Danish Holstein cows (557 + 37 kg body weight, 120 + 21 days in milk, mean + SD), 8 fitted with ruminal cannulas...

Enhanced chlorine resistance of tap water-adapted Legionella pneumophila as compared with agar medium-passaged strains.

Science.gov (United States)

Kuchta, J M; States, S J; McGlaughlin, J E; Overmeyer, J H; Wadowsky, R M; McNamara, A M; Wolford, R S; Yee, R B

1985-07-01

Previous studies have shown that bacteria maintained in a low-nutrient "natural" environment such as swimming pool water are much more resistant to disinfection by various chemical agents than strains maintained on rich media. In the present study a comparison was made of the chlorine (Cl2) susceptibility of hot-water tank isolates of Legionella pneumophila maintained in tap water and strains passaged on either nonselective buffered charcoal-yeast extract or selective differential glycine-vancomycin-polymyxin agar medium. Our earlier work has shown that environmental and clinical isolates of L. pneumophila maintained on agar medium are much more resistant to Cl2 than coliforms are. Under the present experimental conditions (21 degrees C, pH 7.6 to 8.0, and 0.25 mg of free residual Cl2 per liter, we found the tap water-maintained L. pneumophila strains to be even more resistant than the agar-passaged isolates. Under these conditions, 99% kill of tap water-maintained strains of L. pneumophila was usually achieved within 60 to 90 min compared with 10 min for agar-passaged strains. Samples from plumbing fixtures in a hospital yielded legionellae which were "super"-chlorine resistant when assayed under natural conditions. After one agar passage their resistance dropped to levels of comparable strains which had not been previously exposed to additional chlorination. These studies more closely approximate natural conditions than our previous work and show that tap water-maintained L. pneumophila is even more resistant to Cl2 than its already resistant agar medium-passaged counterpart.

The affinity plutonium(IV) for nitrogen donor ligands

International Nuclear Information System (INIS)

Jarvis, N.V.; Hancock, R.D.

1994-01-01

Established ligand design principles are used to predict the solution chemistry of Pu(IV) with nitrogen donor ligands which do not contain carboxylate donors. pK a 's of the nitrogen donors are lowered by addition of hydroxyalkyl groups causing Pu(IV) to have a greater affinity for these ligands than for hydroxide. Potentiometric studies using the ligands N,N,N'N',N''-pentakis(2-hydroxypropyl)-1,4,7-triazaheptane; N,N,N',N',N''-pentakis(2-hydroxyethyl)-1,4,7-triazaheptane; N,N,N',N',N'-tetrakis(2-hydroxyethyl)-1,2-diaminoethane; N,N,N',N'-tetrakis(2-hydroxyethyl)-trans-1,2-diaminocyclohexane; 1,4,8,11-tetrakis(2-hydroxyethyl)-1,4,8,11-tetraazacyclotetradecane and N,N-bis(2-hydroxyethyl)glycine with Pu(IV) showed that Pu(IV) has a considerable aqueous solution chemistry with these ligands. Data were processed by the ESTA library of programs and stability constants for all the systems are reported. Implications for selective ligand design for Pu(IV) are discussed. (orig.)

Assessment of ecological passages along road networks within the Mediterranean forest using GIS-based multi criteria evaluation approach.

Science.gov (United States)

Gülci, Sercan; Akay, Abdullah Emin

2015-12-01

Major roads cause barrier effect and fragmentation on wildlife habitats that are suitable places for feeding, mating, socializing, and hiding. Due to wildlife collisions (Wc), human-wildlife conflicts result in lost lives and loss of biodiversity. Geographical information system (GIS)-based multi criteria evaluation (MCE) methods have been successfully used in short-term planning of road networks considering wild animals. Recently, wildlife passages have been effectively utilized as road engineering structures provide quick and certain solutions for traffic safety and wildlife conservation problems. GIS-based MCE methods provide decision makers with optimum location for ecological passages based on habitat suitability models (HSMs) that classify the areas based on ecological requirements of target species. In this study, ecological passages along Motorway 52 within forested areas in Mediterranean city of Osmaniye in Turkey were evaluated. Firstly, HSM coupled with nine eco-geographic decision variables were developed based on ecological requirements of roe deer (Capreolus capreolus) that were chosen as target species. Then specified decision variables were evaluated using GIS-based weighted linear combination (WLC) method to estimate movement corridors and mitigation points along the motorway. In the solution process, two linkage nodes were evaluated for eco-passages which were determined based on the least-cost movement corridor intersecting with the motorway. One of the passages was identified as a natural wildlife overpass while the other was suggested as underpass construction. The results indicated that computer-based models provide accurate and quick solutions for positioning ecological passages to reduce environmental effects of road networks on wild animals.

Predicting Nanocrystal Shape through Consideration of Surface-Ligand Interactions

KAUST Repository

Bealing, Clive R.

2012-03-27

Density functional calculations for the binding energy of oleic acid-based ligands on Pb-rich {100} and {111} facets of PbSe nanocrystals determine the surface energies as a function of ligand coverage. Oleic acid is expected to bind to the nanocrystal surface in the form of lead oleate. The Wulff construction predicts the thermodynamic equilibrium shape of the PbSe nanocrystals. The equilibrium shape is a function of the ligand surface coverage, which can be controlled by changing the concentration of oleic acid during synthesis. The different binding energy of the ligand on the {100} and {111} facets results in different equilibrium ligand coverages on the facets, and a transition in the equilibrium shape from octahedral to cubic is predicted when increasing the ligand concentration during synthesis. © 2012 American Chemical Society.

Mixed ligand chelates of rare earths in aqueous solution

International Nuclear Information System (INIS)

Lakhani, S.U.; Thakur, G.S.; Sangal, S.P.

1981-01-01

Mixed ligand chelates of the 1:1 trivalent lanthanoids-EDTA, HEDTA and NTA chelates-1, 2-Dihydroxybenzene (Pyrocatechol) have been investigated at 35degC and 0.2 M ionic strength maintained by NaC10 4 . The formation of mixed ligand chelates has been found in all cases. The formation of mixed ligand chelates with EDTA shows the coordination number of lanthanoids to be eight, while the mixed ligand chelates with HEDTA and NTA shows the coordination number to be seven and six respectively. The stability constants of mixed ligand chelates are smaller than the binary complexes. The order of stability constants with respect to primary ligands follows the order NTA>HEDTA>EDTA. With respect to metal ions the stability constants increases with the decrease in ionic radii such as Gd< Er< Yb. (author)

Calculating the mean time to capture for tethered ligands and its effect on the chemical equilibrium of bound ligand pairs.

Science.gov (United States)

Shen, Lu; Decker, Caitlin G; Maynard, Heather D; Levine, Alex J

2016-09-01

We present here the calculation of the mean time to capture of a tethered ligand to the receptor. This calculation is then used to determine the shift in the partitioning between (1) free, (2) singly bound, and (3) doubly bound ligands in chemical equilibrium as a function of the length of the tether. These calculations are used in the research article Fibroblast Growth Factor 2 Dimer with Superagonist in vitro Activity Improves Granulation Tissue Formation During Wound Healing (Decker et al., in press [1]) to explain quantitatively how changes in polymeric linker length in the ligand dimers modifies the efficacy of these molecules relative to that of free ligands.

Ligand-Enabled γ-C–H Olefination and Carbonylation: Construction of β-Quaternary Carbon Centers

Science.gov (United States)

2015-01-01

Monoselective γ-C–H olefination and carbonylation of aliphatic acids has been accomplished by using a combination of a quinoline-based ligand and a weakly coordinating amide directing group. The reaction provides a new route for constructing richly functionalized all-carbon quaternary carbon centers at the β-position of aliphatic acids. PMID:24666182

Impact of beta thalassemia on maxillary sinuses and sino-nasal passages: A case control study.

Science.gov (United States)

Ragab, Ahmed; Ragab, Seham Mohammed; Shawki, Mohammed

2015-12-01

Skeletal changes among beta (β) thalassemia children are well documented, but without available data regarding sino-nasal passages alterations. The authors investigated the maxillary sinuses and sino-nasal passages changes in β-thalassemia children and correlated such changes with the amount of transfused red cells and the erythroid marrow activity. Clinical analyses including otorhinolaryngical examination (ORL) were obtained in twenty β-thalassemia children and 20 matched healthy controls. Hemoglobin (Hb), serum ferritin, soluble transferrin receptor (sTfR) levels and bone mineral density of the lumbar spine (BMD ls) were assayed. The two groups were analyzed for the CT image parameters: bone thickness, anterior and posterior choanae diameters, extramedullary hematopoiesis and chronic rhinosinusitis (CRS) RESULTS: Nasal congestion/obstruction was identified in 14 (70%) children. Eight patients (40%) had criteria of chronic rhinosinusitis. In comparison with the normal controls, the increase in the roof, floor, medial, anterior, lateral and posterior maxillary bony walls thickness was significantly higher (1.26, 2.46, 2.6, 2.9, 3.23 and 5.34-folds, respectively). The mean posterior choanae horizontal, vertical diameters and their surface area were significantly reduced in the patients compared to the controls. The mean anterior maxillary wall bone thickness directly correlated with sTfR (P=0.047) while that of the posterior wall correlated inversely with Hb level (P=0.013). The mean vertical posterior choanae diameter had positive correlation with the amount of transfused red cells (P=0.001) and negative correlation with sTfR (P=0.001). The Hounsfield unit of maxillary sinus wall had direct relation with BMDls (P=0.003) CONCLUSIONS: Thalassemia children are at risk of different folds increase of maxillary sinuses walls thicknesses utmost at posterior and lateral walls. Other sino-nasal morbidities include diminished posterior choanal diameter, nasal obstruction

Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

Science.gov (United States)

Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

2014-10-27

The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

Environmental Burkholderia cenocepacia Strain Enhances Fitness by Serial Passages during Long-Term Chronic Airways Infection in Mice

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Alessandra Bragonzi

2017-11-01

Full Text Available Burkholderia cenocepacia is an important opportunistic pathogen in cystic fibrosis (CF patients, and has also been isolated from natural environments. In previous work, we explored the virulence and pathogenic potential of environmental B. cenocepacia strains and demonstrated that they do not differ from clinical strains in some pathogenic traits. Here, we investigated the ability of the environmental B. cenocepacia Mex1 strain, isolated from the maize rhizosphere, to persist and increase its virulence after serial passages in a mouse model of chronic infection. B. cenocepacia Mex1 strain, belonging to the recA lineage IIIA, was embedded in agar beads and challenged into the lung of C57Bl/6 mice. The mice were sacrificed after 28 days from infection and their lungs were tested for bacterial loads. Agar beads containing the pool of B. cenocepacia colonies from the four sequential passages were used to infect the mice. The environmental B. cenocepacia strain showed a low incidence of chronic infection after the first passage; after the second, third and fourth passages in mice, its ability to establish chronic infection increased significantly and progressively up to 100%. Colonial morphology analysis and genetic profiling of the Mex1-derived clones recovered after the fourth passage from infected mice revealed that they were indistinguishable from the challenged strain both at phenotypic and genetic level. By testing the virulence of single clones in the Galleria mellonella infection model, we found that two Mex1-derived clones significantly increased their pathogenicity compared to the parental Mex1 strain and behaved similarly to the clinical and epidemic B. cenocepacia LMG16656T. Our findings suggest that serial passages of the environmental B. cenocepacia Mex1 strain in mice resulted in an increased ability to determine chronic lung infection and the appearance of clonal variants with increased virulence in non-vertebrate hosts.

A Versatile Dinucleating Ligand Containing Sulfonamide Groups

DEFF Research Database (Denmark)

Sundberg, Jonas; Witt, Hannes; Cameron, Lisa

2014-01-01

ligand can be prepared in aqueous solutions using only divalent metal ions. Two of the copper(II) complexes, [Cu2(psmp)(OH)] and [Cu2(psmp)(OAc)2]-, demonstrate the anticipated 1:2 ligand/metal stoichiometry and show that the dimetallic binding site created for exogenous ligands possesses high inherent...... of antiferromagnetic coupling. This is corroborated computationally by broken-symmetry density functional theory, which for isotropic modeling of the coupling predicts an antiferromagnetic coupling strength of J = 70.5 cm-1....

Implicit ligand theory for relative binding free energies

Science.gov (United States)

Nguyen, Trung Hai; Minh, David D. L.

2018-03-01

Implicit ligand theory enables noncovalent binding free energies to be calculated based on an exponential average of the binding potential of mean force (BPMF)—the binding free energy between a flexible ligand and rigid receptor—over a precomputed ensemble of receptor configurations. In the original formalism, receptor configurations were drawn from or reweighted to the apo ensemble. Here we show that BPMFs averaged over a holo ensemble yield binding free energies relative to the reference ligand that specifies the ensemble. When using receptor snapshots from an alchemical simulation with a single ligand, the new statistical estimator outperforms the original.

Superior serum half life of albumin tagged TNF ligands

International Nuclear Information System (INIS)

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

2010-01-01

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

Quantitative chemogenomics: machine-learning models of protein-ligand interaction.

Science.gov (United States)

Andersson, Claes R; Gustafsson, Mats G; Strömbergsson, Helena

2011-01-01

Chemogenomics is an emerging interdisciplinary field that lies in the interface of biology, chemistry, and informatics. Most of the currently used drugs are small molecules that interact with proteins. Understanding protein-ligand interaction is therefore central to drug discovery and design. In the subfield of chemogenomics known as proteochemometrics, protein-ligand-interaction models are induced from data matrices that consist of both protein and ligand information along with some experimentally measured variable. The two general aims of this quantitative multi-structure-property-relationship modeling (QMSPR) approach are to exploit sparse/incomplete information sources and to obtain more general models covering larger parts of the protein-ligand space, than traditional approaches that focuses mainly on specific targets or ligands. The data matrices, usually obtained from multiple sparse/incomplete sources, typically contain series of proteins and ligands together with quantitative information about their interactions. A useful model should ideally be easy to interpret and generalize well to new unseen protein-ligand combinations. Resolving this requires sophisticated machine-learning methods for model induction, combined with adequate validation. This review is intended to provide a guide to methods and data sources suitable for this kind of protein-ligand-interaction modeling. An overview of the modeling process is presented including data collection, protein and ligand descriptor computation, data preprocessing, machine-learning-model induction and validation. Concerns and issues specific for each step in this kind of data-driven modeling will be discussed. © 2011 Bentham Science Publishers

Compliance Monitoring of Yearling Chinook Salmon and Juvenile Steelhead Survival and Passage at John Day Dam, Spring 2011

Energy Technology Data Exchange (ETDEWEB)

Skalski, J. R.; Townsend, Richard L.; Seaburg, Adam; Weiland, Mark A.; Woodley, Christa M.; Hughes, James S.; Carlson, Thomas J.

2012-06-01

The study was designed to estimate dam passage survival at John Day Dam as stipulated by the 2008 Federal Columbia River Power System (FCRPS) Biological Opinion (BiOp) and to provide additional fish passage performance measures at that site as stipulated in the Columbia Basin Fish Accords.

Compliance Monitoring of Yearling Chinook Salmon and Juvenile Steelhead Survival and Passage at John Day Dam, Spring 2011

Energy Technology Data Exchange (ETDEWEB)

Skalski, J. R.; Townsend, Richard L.; Seaburg, Adam; Weiland, Mark A.; Woodley, Christa M.; Hughes, James S.; Carlson, Thomas J.

2012-02-01

The study was designed to estimate dam passage survival at John Day Dam as stipulated by the 2008 Federal Columbia River Power System (FCRPS) Biological Opinion (BiOp) and to provide additional fish passage performance measures at that site as stipulated in the Columbia Basin Fish Accords.

Effects of electrostatic interactions on ligand dissociation kinetics

Science.gov (United States)

Erbaş, Aykut; de la Cruz, Monica Olvera; Marko, John F.

2018-02-01

We study unbinding of multivalent cationic ligands from oppositely charged polymeric binding sites sparsely grafted on a flat neutral substrate. Our molecular dynamics simulations are suggested by single-molecule studies of protein-DNA interactions. We consider univalent salt concentrations spanning roughly a 1000-fold range, together with various concentrations of excess ligands in solution. To reveal the ionic effects on unbinding kinetics of spontaneous and facilitated dissociation mechanisms, we treat electrostatic interactions both at a Debye-Hückel (DH) (or implicit ions, i.e., use of an electrostatic potential with a prescribed decay length) level and by the more precise approach of considering all ionic species explicitly in the simulations. We find that the DH approach systematically overestimates unbinding rates, relative to the calculations where all ion pairs are present explicitly in solution, although many aspects of the two types of calculation are qualitatively similar. For facilitated dissociation (FD) (acceleration of unbinding by free ligands in solution) explicit-ion simulations lead to unbinding at lower free-ligand concentrations. Our simulations predict a variety of FD regimes as a function of free-ligand and ion concentrations; a particularly interesting regime is at intermediate concentrations of ligands where nonelectrostatic binding strength controls FD. We conclude that explicit-ion electrostatic modeling is an essential component to quantitatively tackle problems in molecular ligand dissociation, including nucleic-acid-binding proteins.

Chimera grids in the simulation of three-dimensional flowfields in turbine-blade-coolant passages

Science.gov (United States)

Stephens, M. A.; Rimlinger, M. J.; Shih, T. I.-P.; Civinskas, K. C.

1993-01-01

When computing flows inside geometrically complex turbine-blade coolant passages, the structure of the grid system used can affect significantly the overall time and cost required to obtain solutions. This paper addresses this issue while evaluating and developing computational tools for the design and analysis of coolant-passages, and is divided into two parts. In the first part, the various types of structured and unstructured grids are compared in relation to their ability to provide solutions in a timely and cost-effective manner. This comparison shows that the overlapping structured grids, known as Chimera grids, can rival and in some instances exceed the cost-effectiveness of unstructured grids in terms of both the man hours needed to generate grids and the amount of computer memory and CPU time needed to obtain solutions. In the second part, a computational tool utilizing Chimera grids was used to compute the flow and heat transfer in two different turbine-blade coolant passages that contain baffles and numerous pin fins. These computations showed the versatility and flexibility offered by Chimera grids.

[Supercomputer investigation of the protein-ligand system low-energy minima].

Science.gov (United States)

Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

2015-01-01

The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

Mutual control of axial and equatorial ligands: model studies with [Ni]-bacteriochlorophyll-a.

Science.gov (United States)

Yerushalmi, Roie; Noy, Dror; Baldridge, Kim K; Scherz, Avigdor

2002-07-17

Modification of the metal's electronic environment by ligand association and dissociation in metalloenzymes is considered cardinal to their catalytic activity. We have recently presented a novel system that utilizes the bacteriochlorophyll (BChl) macrocycle as a ligand and reporter. This system allows for charge mobilization in the equatorial plane and experimental estimate of changes in the electronic charge density around the metal with no modification of the metal's chemical environment. The unique spectroscopy, electrochemistry and coordination chemistry of [Ni]-bacteriochlorophyll ([Ni]-BChl) enable us to follow directly fine details and steps involved in the function of the metal redox center. This approach is utilized here whereby electro-chemical reduction of [Ni]-BChl to the monoanion [Ni]-BChl(-) results in reversible dissociation of biologically relevant axial ligands. Similar ligand dissociation was previously detected upon photoexcitation of [Ni]-BChl (Musewald, C.; Hartwich, G.; Lossau, H.; Gilch, P.; Pollinger-Dammer, F.; Scheer, H.; Michel-Beyerle, M. E. J. Phys. Chem. B 1999, 103, 7055-7060 and Noy, D.; Yerushalmi, R.; Brumfeld, V.; Ashur, I.; Baldridge, K. K.; Scheer, H.; Scherz, A. J. Am. Chem. Soc. 2000, 122, 3937-3944). The electrochemical measurements and quantum mechanical (QM) calculations performed here for the neutral, singly reduced, monoligated, and singly reduced, monoligated [Ni]-BChl suggest the following: (a) Electroreduction, although resulting in a pi anion [Ni]-BChl(-) radical, causes electron density migration to the [Ni]-BChl core. (b) Reduction of nonligated [Ni]-BChl does not change the macrocycle conformation, whereas axial ligation results in a dramatic expansion of the metal core and a flattening of the highly ruffled macrocycle conformation. (c) In both the monoanion and singly excited [Ni]-BChl ([Ni]-BChl*), the frontier singly occupied molecular orbital (SOMO) has a small but nonnegligible metal character. Finally, (d

A new technique for assessing fish passage survival at hydro power stations

International Nuclear Information System (INIS)

Heisey, P.G.; Mathur, D.; D'Allesandro, L.

1993-01-01

The HI-Z Turb'N Tag recovery method is presented as a new technique that has been successfully used at ten hydropower stations to determine turbine or spillway passage survival of fish. According to this technique, fish are tagged with the Turb'N Tag, which is pear-shaped, made of inflatable latex, and ca 35 mm long and 13 mm wide. The tag is designed to inflate after passage through the turbine, where it then floats the fish to the surface where it can be easily spotted and netted. One tag is sufficient to retrieve fish less than 18 cm long, while three tags may be needed for fish longer than 30 cm. In tests, fish were recovered in under 10 minutes from the tailrace after being tagged and released into a turbine. The tag allowed over 90% recovery of fish in most tests. The technique had minimal effect on the well-being of both hardy and sensitive species and provided an opportunity to examine recovered fish for injuries and retain them up to 72 h to assess possible delayed effects. The technique overcomes most of the logistical problems associated with conventional methods (netting, radio telemetry, mass mark-recapture) to determine turbine passage survival. The technique can also be used to assess effects of spill and fish bypass structures. 9 refs., 2 figs., 1 tab

Mussel Spat Ropes Assist Redfin Bully Gobiomorphus huttoni Passage through Experimental Culverts with Velocity Barriers

Directory of Open Access Journals (Sweden)

Jonathan D. Tonkin

2012-09-01

Full Text Available The application of mussel spat rope for enabling the passage of redfin bully Gobiomorphus huttoni through culverts, which create velocity barriers, was trialled in the laboratory. No fish were able to access the un-roped control pipes whereas 52% successfully negotiated the pipes in the rope treatments. The success of fish ascending treatment pipes suggests mussel spat rope may be effective for enabling the passage of this and other similar fish species through otherwise impassable culverts with velocity barriers.

Ligands specify estrogen receptor alpha nuclear localization and degradation

Directory of Open Access Journals (Sweden)

Caze-Subra Stéphanie

2010-12-01

Full Text Available Abstract Background The estrogen receptor alpha (ERα is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate. Results A MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα. Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2, and pure antagonists (selective estrogen regulator disruptor; SERD, ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM, 4-hydroxytamoxifen (OHT or RU39,411, diffuse nuclear staining persisted. Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels of ESR1 were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus. Conclusions Our results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on

The impact of mouse passaging of Mycobacterium tuberculosis strains prior to virulence testing in the mouse and guinea pig aerosol models.

Directory of Open Access Journals (Sweden)

Paul J Converse

2010-04-01

Full Text Available It has been hypothesized that the virulence of lab-passaged Mycobacterium tuberculosis and recombinant M. tuberculosis mutants might be reduced due to multiple in vitro passages, and that virulence might be augmented by passage of these strains through mice before quantitative virulence testing in the mouse or guinea pig aerosol models.By testing three M. tuberculosis H37Rv samples, one deletion mutant, and one recent clinical isolate for survival by the quantitative organ CFU counting method in mouse or guinea pig aerosol or intravenous infection models, we could discern no increase in bacterial fitness as a result of passaging of M. tuberculosis strains in mice prior to quantitative virulence testing in two animal models. Surface lipid expression as assessed by neutral red staining and thin-layer chromatography for PDIM analysis also failed to identify virulence correlates.These results indicate that animal passaging of M. tuberculosis strains prior to quantitative virulence testing in mouse or guinea pig models does not enhance or restore potency to strains that may have lost virulence due to in vitro passaging. It is critical to verify virulence of parental strains before genetic manipulations are undertaken and comparisons are made.

Silver(I)-directed growth of metal-organic complex nanocrystals with bidentate ligands of hydroquinine anthraquinone-1,4-diyl diethers as linkers at the water-chloroform interface

Science.gov (United States)

Tang, Ying; Wang, Hui-Ting; Chen, Meng; Qian, Dong-Jin; Zhang, Li; Liu, Minghua

2014-09-01

Immiscible liquid-liquid interfaces provide unique double phase regions for the design and construction of nanoscale materials. Here, we reported Ag(I)-directed growth of metal-organic complex nanocrystals by using AgNO3 as a connector in the aqueous solution and bidentate ligand of 1,4-bis(9-O-dihydroquininyl)anthraquinone [(DHQ)2AQN] and its enantiomer of (DHQD)2AQN in the chloroform solutions as linkers. The Ag-(DHQ)2AQN and Ag-(DHQD)2AQN complex nanocrystals were formed at the liquid-liquid interfaces and characterized by using UV-vis absorption and fluorescence spectroscopy and X-ray photoelectron spectroscopy, as well as by using scanning electron microscopy. Screw-like nanocrystals were formed at the initial 30 min after the interfacial coordination reaction started, then they grew into nanorods after several days, and finally became cubic microcrystals after 2 weeks. The pure ligand showed two emission bands centered at about 363 and 522 nm in the methanol solution, the second one of which was quenched and shifted to about 470 nm in the Ag-complex nanocrystals. Two couples of reversible redox waves were recorded for the Ag-complex nanocrystals; one centered at about -0.25 V (vs. Ag/AgCl) was designated to one electron transfer process of Ag - (DHQ)2AQN and Ag - (DHQ)2AQN+, and the other one centered at about 0.2 V was designated to one electron transfer process of Ag - (DHQ)2AQN and Ag+ - (DHQ)2AQN.

Sensor Fish: an autonomous sensor package for characterizing complex flow fields and fish passage

Energy Technology Data Exchange (ETDEWEB)

Deng, Zhiqun; Martinez, Jayson J.; Lu, Jun

2016-10-04

Fish passing through dams or other hydraulic structures may be injured or killed despite advances in turbine design, project operations, and other fish bypass systems. The Sensor Fish (SF) device is an autonomous sensor package that characterizes the physical conditions and stressors to which fish are exposed during passage through hydro facilities. It was designed to move passively as a neutrally buoyant object through severe hydraulic environments, while collecting high-resolution sensor data. Since its first generation1, the SF device has been successfully deployed in many fish passage studies and has evolved to be a major tool for characterizing fish passage conditions during fish passage in the Columbia River Basin. To better accelerate hydropower development, the U.S. Department of Energy Water Power Program provided funding to develop a new generation (Gen 2 SF) to incorporate more capabilities and accommodate a wider range of users over a broader range of turbine designs and operating environments. The Gen 2 SF (Figure 1) is approximately the size and density of a yearling salmon smolt and is nearly neutrally buoyant. It contains three-dimensional (3D) rotation sensors, 3D linear acceleration sensors, a pressure sensor, a temperature sensor, a 3D orientation sensor, a radiofrequency (RF) transmitter, and a recovery module2. A low-power microcontroller collects data from the sensors and stores up to 5 min of data on internal flash memory at a sampling frequency of 2048 Hz. The recovery module makes the SF positively buoyant after a pre-programmed period of time, causing it to float to the surface for recovery.

Rational Ligand Design for U(VI) and Pu(IV)

International Nuclear Information System (INIS)

Szigethy, Geza

2009-01-01

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO 2 2+ ). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative saturation, these

Rational Ligand Design for U(VI) and Pu(IV)

Energy Technology Data Exchange (ETDEWEB)

Szigethy, Geza [Univ. of California, Berkeley, CA (United States)

2009-08-12

Nuclear power is an attractive alternative to hydrocarbon-based energy production at a time when moving away from carbon-producing processes is widely accepted as a significant developmental need. Hence, the radioactive actinide power sources for this industry are necessarily becoming more widespread, which is accompanied by the increased risk of exposure to both biological and environmental systems. This, in turn, requires the development of technology designed to remove such radioactive threats efficiently and selectively from contaminated material, whether that be contained nuclear waste streams or the human body. Raymond and coworkers (University of California, Berkeley) have for decades investigated the interaction of biologically-inspired, hard Lewis-base ligands with high-valent, early-actinide cations. It has been established that such ligands bind strongly to the hard Lewis-acidic early actinides, and many poly-bidentate ligands have been developed and shown to be effective chelators of actinide contaminants in vivo. Work reported herein explores the effect of ligand geometry on the linear U(IV) dioxo dication (uranyl, UO₂ ²⁺). The goal is to utilize rational ligand design to develop ligands that exhibit shape selectivity towards linear dioxo cations and provides thermodynamically favorable binding interactions. The uranyl complexes with a series of tetradentate 3-hydroxy-pyridin-2-one (3,2-HOPO) ligands were studied in both the crystalline state as well as in solution. Despite significant geometric differences, the uranyl affinities of these ligands vary only slightly but are better than DTPA, the only FDA-approved chelation therapy for actinide contamination. The terepthalamide (TAM) moiety was combined into tris-beidentate ligands with 1,2- and 3,2-HOPO moieties were combined into hexadentate ligands whose structural preferences and solution thermodynamics were measured with the uranyl cation. In addition to achieving coordinative

Rites of Passage, Aboriginal Education and Learning for the 21st Century: Walkabout as a Radical-and Workable-Alternative

Directory of Open Access Journals (Sweden)

Blane DESPRS

2008-07-01

Full Text Available The Walkabout Program is an alternative and experiential learning practice that helps students to develop necessary skills for authentic learning and real world preparation through the completion of six learning passages. This aboriginal-based program celebrates the vital transition-or passage-from adolescence to adulthood. The six learning passages include philosophical, practical, emotional/physical/spiritual challenge, career exploration, community/global response, and creative endeavour. Although its primary focus is to challenge First Nations educators to rethink status quo schooling, the Program has equally beneficial opportunities for all students.

Cellular trafficking of quantum dot-ligand bioconjugates and their induction of changes in normal routing of unconjugated ligands

DEFF Research Database (Denmark)

Tekle, Christina; van Deurs, Bo; Sandvig, Kirsten

2008-01-01

Can quantum dots (Qdots) act as relevant intracellular probes to investigate routing of ligands in live cells? The intracellular trafficking of Qdots that were coupled to the plant toxin ricin, Shiga toxin, or the ligand transferrin (Tf) was studied by confocal fluorescence microscopy. The Tf...

Predicting Efficient Antenna Ligands for Tb(III) Emission

Energy Technology Data Exchange (ETDEWEB)

Samuel, Amanda P.S.; Xu, Jide; Raymond, Kenneth

2008-10-06

A series of highly luminescent Tb(III) complexes of para-substituted 2-hydroxyisophthalamide ligands (5LI-IAM-X) has been prepared (X = H, CH{sub 3}, (C=O)NHCH{sub 3}, SO{sub 3}{sup -}, NO{sub 2}, OCH{sub 3}, F, Cl, Br) to probe the effect of substituting the isophthalamide ring on ligand and Tb(III) emission in order to establish a method for predicting the effects of chromophore modification on Tb(III) luminescence. The energies of the ligand singlet and triplet excited states are found to increase linearly with the {pi}-withdrawing ability of the substituent. The experimental results are supported by time-dependent density functional theory (TD-DFT) calculations performed on model systems, which predict ligand singlet and triplet energies within {approx}5% of the experimental values. The quantum yield ({Phi}) values of the Tb(III) complex increases with the triplet energy of the ligand, which is in part due to the decreased non-radiative deactivation caused by thermal repopulation of the triplet. Together, the experimental and theoretical results serve as a predictive tool that can be used to guide the synthesis of ligands used to sensitize lanthanide luminescence.

Supramolecular architectures constructed using angular bipyridyl ligands

International Nuclear Information System (INIS)

Barnett, Sarah Ann

2003-01-01

This work details the synthesis and characterization of a series of coordination frameworks that are formed using bidentate angular N-donor ligands. Pyrimidine was reacted with metal(ll) nitrate salts. Reactions using Cd(NO 3 ) 2 receive particular focus and the analogous reactions using the linear ligand, pyrazine, were studied for comparison. In all cases, two-dimensional coordination networks were prepared. Structural diversity is observed for the Cd(ll) centres including metal-nitrate bridging. In contrast, first row transition metal nitrates form isostructural one-dimensional chains with only the bridging N-donor ligands generating polymeric propagation. The angular ligand, 2,4-bis(4-pyridyl)-1,3,5-triazine (dpt), was reacted with Cd(NO 3 ) 2 and Zn(NO 3 ) 2 . Whereas Zn(NO 3 ) 2 compounds exhibit solvent mediated polymorphism, a range of structures were obtained for the reactions with Cd(NO 3 ) 2 , including the first example of a doubly parallel interpenetrated 4.8 2 net. 4,7-phenanthroline, was reacted with various metal(ll) nitrates as well as cobalt(ll) and copper(ll) halides. The ability of 4,7-phenanthroline to act as both a N-donor ligand and a hydrogen bond acceptor has been discussed. Reactions of CuSCN with pyrimidine yield an unusual three-dimensional structure in which polymeric propagation is not a result of ligand bridging. The reaction of CuSCN with dpt yielded structural supramolecular isomers. (author)

Dynamic ligand-based pharmacophore modeling and virtual ...

Indian Academy of Sciences (India)

Five ligand-based pharmacophore models were generated from 40 different .... the Phase module of the Schrodinger program.35 Each model consisted of six types of ... ligand preparation included the OPLS_2005 force field and to retain the ...

The Application of Traits-Based Assessment Approaches to Estimate the Effects of Hydroelectric Turbine Passage on Fish Populations

Energy Technology Data Exchange (ETDEWEB)

Cada, Glenn F [ORNL; Schweizer, Peter E [ORNL

2012-04-01

One of the most important environmental issues facing the hydropower industry is the adverse impact of hydroelectric projects on downstream fish passage. Fish that migrate long distances as part of their life cycle include not only important diadromous species (such as salmon, shads, and eels) but also strictly freshwater species. The hydropower reservoirs that downstream-moving fish encounter differ greatly from free-flowing rivers. Many of the environmental changes that occur in a reservoir (altered water temperature and transparency, decreased flow velocities, increased predation) can reduce survival. Upon reaching the dam, downstream-migrating fish may suffer increased mortality as they pass through the turbines, spillways and other bypasses, or turbulent tailraces. Downstream from the dam, insufficient environmental flow releases may slow downstream fish passage rates or decrease survival. There is a need to refine our understanding of the relative importance of causative factors that contribute to turbine passage mortality (e.g., strike, pressure changes, turbulence) so that turbine design efforts can focus on mitigating the most damaging components. Further, present knowledge of the effectiveness of turbine improvements is based on studies of only a few species (mainly salmon and American shad). These data may not be representative of turbine passage effects for the hundreds of other fish species that are susceptible to downstream passage at hydroelectric projects. For example, there are over 900 species of fish in the United States. In Brazil there are an estimated 3,000 freshwater fish species, of which 30% are believed to be migratory (Viana et al. 2011). Worldwide, there are some 14,000 freshwater fish species (Magurran 2009), of which significant numbers are susceptible to hydropower impacts. By comparison, in a compilation of fish entrainment and turbine survival studies from over 100 hydroelectric projects in the United States, Winchell et al. (2000

Identification of VDR Antagonists among Nuclear Receptor Ligands Using Virtual Screening

Directory of Open Access Journals (Sweden)

Kelly Teske

2014-04-01

Full Text Available Herein, we described the development of two virtual screens to identify new vitamin D receptor (VDR antagonists among nuclear receptor (NR ligands. Therefore, a database of 14330 nuclear receptor ligands and their NR affinities was assembled using the online available “Binding Database.” Two different virtual screens were carried out in conjunction with a reported VDR crystal structure applying a stringent and less stringent pharmacophore model to filter docked NR ligand conformations. The pharmacophore models were based on the spatial orientation of the hydroxyl functionalities of VDR's natural ligands 1,25(OH2D3 and 25(OH2D3. The first virtual screen identified 32 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. All but nordihydroguaiaretic acid (NDGA are VDR ligands, which inhibited the interaction between VDR and coactivator peptide SRC2-3 with an IC50 value of 15.8 μM. The second screen identified 162 NR ligands with a calculated free energy of VDR binding of more than -6.0 kJ/mol. More than half of these ligands were developed to bind VDR followed by ERα/β ligands (26%, TRα/β ligands (7%, and LxRα/β ligands (7%. The binding between VDR and ERα ligand H6036 as well as TRα/β ligand triiodothyronine and a homoserine analog thereof was confirmed by fluorescence polarization.

Acoustic Telemetry Evaluation of Juvenile Salmonid Passage and Survival at John Day Dam, 2010

Energy Technology Data Exchange (ETDEWEB)

Weiland, Mark A.; Woodley, Christa M.; Ploskey, Gene R.; Hughes, James S.; Kim, Jin A.; Deng, Zhiqun; Fu, Tao; Fischer, Eric S.; Skalski, J. R.; Townsend, Richard L.; Duncan, Joanne P.; Hennen, Matthew J.; Wagner, Katie A.; Arntzen, Evan V.; Miller, Benjamin L.; Miracle, Ann L.; Zimmerman, Shon A.; Royer, Ida M.; Khan, Fenton; Cushing, Aaron W.; Etherington, D. J.; Mitchell, T. D.; Elder, T.; Batton, George; Johnson, Gary E.; Carlson, Thomas J.

2013-05-01

This report presents survival, behavioral, and fish passage results for yearling and subyearling Chinook salmon smolts and juvenile steelhead tagged with JSATS acoustic micro-transmitters as part of a survival study conducted at John Day Dam during 2010. This study was designed to evaluate the passage and survival of yearling and subyearling Chinook salmon and juvenile steelhead to assist managers in identifying dam operations for compliance testing as stipulated by the 2008 Federal Columbia River Power System Biological Opinion and the 2008 Columbia Basin Fish Accords. Survival estimates were based on a single-release survival estimate model.

The frontal structure in Drake Passage based on the data of the section in January 2010

Science.gov (United States)

Tarakanov, Roman

2014-05-01

The frontal structure in the region of Drake Passage is investigated on the basis of data of Absolute Dynamic Topography (ADT) of French agency CLS (DT-Global-MADT-Upd product, http://aviso.oceanobs.com), and CTD- and SADCP-measurements along the hydrophysical section carried out across the passage from Smith Isl. (just to the east of the Hero F.Z.) to the Cape Horn onboard R/V "Akademik Ioffe" in January 2010. The investigation was similar to the analysis performed on the basis of data of the section carried out two weeks earlier onboard the same vessel south of Africa. Fine-jet structure of the ACC was detected in Drake Passage as well as to the south of Africa where twelve ACC jets were found. Eleven jets of the Antarctic Circumpolar Current (ACC) were revealed in Drake Passage. These were five jets of the Subantarctic Current (the band of Subantarctic Front), four jets of the South Polar Current (the band of Polar Front), and two jets of the South Antarctic Current (the band of Southern ACC Front). Two jets of the South Antarctic Current were joined in a single "super-jet" according to the velocity measurements in the section. The others were manifested by the local velocity maxima in the surface layer.

Water oxidation catalyzed by mononuclear ruthenium complexes with a 2,2'-bipyridine-6,6'-dicarboxylate (bda) ligand: how ligand environment influences the catalytic behavior.

Science.gov (United States)

Staehle, Robert; Tong, Lianpeng; Wang, Lei; Duan, Lele; Fischer, Andreas; Ahlquist, Mårten S G; Sun, Licheng; Rau, Sven

2014-02-03

A new water oxidation catalyst [Ru(III)(bda)(mmi)(OH2)](CF3SO3) (2, H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid; mmi = 1,3-dimethylimidazolium-2-ylidene) containing an axial N-heterocyclic carbene ligand and one aqua ligand was synthesized and fully characterized. The kinetics of catalytic water oxidation by 2 were measured using stopped-flow technique, and key intermediates in the catalytic cycle were probed by density functional theory calculations. While analogous Ru-bda water oxidation catalysts [Ru(bda)L2] (L = pyridyl ligands) are supposed to catalyze water oxidation through a bimolecular coupling pathway, our study points out that 2, surprisingly, undergoes a single-site water nucleophilic attack (acid-base) pathway. The diversion of catalytic mechanisms is mainly ascribed to the different ligand environments, from nonaqua ligands to an aqua ligand. Findings in this work provide some critical proof for our previous hypothesis about how alternation of ancillary ligands of water oxidation catalysts influences their catalytic efficiency.

Modulating p-hydroxycinnamate behavior as a ditopic linker or photoacid in copper(ii) complexes with an auxiliary pyridine ligand.

Science.gov (United States)

Soldevila-Sanmartín, Joan; Calvet, Teresa; Font-Bardia, Merce; Domingo, Concepción; Ayllón, José A; Pons, Josefina

2018-05-08

The reaction of copper(ii) acetate monohydrate with p-hydroxycinnamic acid (HpOHcinn) and different pyridine derivatives (4-tert-butylpyridine, 4-tBupy; 4-acetylpyridine, 4-Acpy; 3-phenylpyridine, 3-Phpy; 4-phenylpyridine, 4-Phpy) was essayed in methanol solvent at room temperature. The crystal structures of the resulting compounds were elucidated. Their analysis shows that the choice of pyridine ligands determines different coordination modes of the pOHcinn ligand and the Cu(ii) coordination, nuclearity and geometry. The pOHcinn acts as a monodentate carboxylate ligand in combination with 4-tBupy or 4-Phpy, yielding monomers and dimers, associated by hydrogen bonds into supramolecular networks in which the phenol group plays a key role. Conversely, in combination with 4-Acpy or 3-Phpy, the phenol group coordinates directly to the Cu(ii), acting as a ditopic ligand and yielding 2D coordination polymers. The compound containing 3-Phpy shows interesting MeOH-H2O reversible exchange behavior. Not only has the pyridine auxiliary ligand had a tremendous effect on the coordination mode of pOHcinn, but also its reactivity is influenced. Particularly, in the case of the compound containing 4-Phpy, it undergoes a photoinduced process, in which the phenol group deprotonates and coordinates to Cu(ii) as a phenoxy ligand. This yields a coordination polymer in which two different dimers alternate, bridged by the resulting pOcinn ligand. The magneto-structural correlation of this compound is also discussed.

Systematic study of ligand structures of metal oxide EUV nanoparticle photoresists

KAUST Repository

Jiang, Jing

2015-03-19

Ligand stabilized metal oxide nanoparticle resists are promising candidates for EUV lithography due to their high sensitivity for high-resolution patterning and high etching resistance. As ligand exchange is responsible for the patterning mechanism, we systematically studied the influence of ligand structures of metal oxide EUV nanoparticles on their sensitivity and dissolution behavior. ZrO2 nanoparticles were protected with various aromatic ligands with electron withdrawing and electron donating groups. These nanoparticles have lower sensitivity compared to those with aliphatic ligands suggesting the structures of these ligands is more important than their pka on resist sensitivity. The influence of ligand structure was further studied by comparing the nanoparticles’ solubility for a single type ligand to mixtures of ligands. The mixture of nanoparticles showed improved pattern quality. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Bridging-ligand-substitution strategy for the preparation of metal-organic polyhedra

Science.gov (United States)

Li, Jian-Rong; Zhou, Hong-Cai

2010-10-01

Metal-organic polyhedra-discrete molecular architectures constructed through the coordination of metal ions and organic linkers-have recently attracted considerable attention due to their intriguing structures, their potential for a variety of applications and their relevance to biological self-assembly. Several synthetic routes have been investigated to prepare these complexes. However, to date, these preparative methods have typically been based on the direct assembly of metal ions and organic linkers. Although these routes are convenient, it remains difficult to find suitable reaction conditions or to control the outcome of the assembly process. Here, we demonstrate a synthetic strategy based on the substitution of bridging ligands in soluble metal-organic polyhedra. The introduction of linkers with different properties from those of the initial metal-organic polyhedra can thus lead to new metal-organic polyhedra with distinct properties (including size and shape). Furthermore, partial substitution can also occur and form mixed-ligand species that may be difficult to access by means of other approaches.

Elimination of a ligand gating site generates a supersensitive olfactory receptor.

Science.gov (United States)

Sharma, Kanika; Ahuja, Gaurav; Hussain, Ashiq; Balfanz, Sabine; Baumann, Arnd; Korsching, Sigrun I

2016-06-21

Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaverine/TAAR13c interaction, exchanged predicted binding residues by site-directed mutagenesis, and measured the activity of the mutant receptors. Unexpectedly we observed a binding site for cadaverine at the external surface of the receptor, in addition to an internal binding site, whose mutation resulted in complete loss of activity. In stark contrast, elimination of the external binding site generated supersensitive receptors. Modeling suggests this site to act as a gate, limiting access of the ligand to the internal binding site and thereby downregulating the affinity of the native receptor. This constitutes a novel mechanism to fine-tune physiological sensitivity to socially relevant odors.

The expression of β-galactosidase during long-term cultured goat skin fibroblasts and the effect of donor cell passage on in vitro development of nuclear transfer embryos.

Science.gov (United States)

Liu, Haijun; Peng, Hui; Liu, Fang; Ma, Qun; Zhang, Wenchang

2016-05-01

The present study aimed to detect the expression of β-galactosidase during long-term cultured goat skin fibroblasts and investigate the effects of donor goat age, sex, and cell passage on senescence and the effects of donor cell passage on in vitro development of nuclear transfer embryos. The results showed that, in the same cell passage, more β-galactosidase-positive cells were detected in cells from older donors than younger donors. Irrespective of the donor age, the number of positive cells was higher in later passages from passages 20 to 50. In the same passage from 20 to 50, the β-galactosidase-positive rate was higher in cells from 5-yr female goat than 5-yr male goat. Using fibroblasts from male goats at various passages as donor cells, reconstructed embryos had similar fusion and cleavage rates, but the blastocyst rate was higher for cells at passages 10 and 20 than passage 30. In conclusion, donor goat age and cell passage had significant effects on the β-galactosidase-positive rate; also, cells from 5-yr female goat had a higher β-galactosidase-positive rate than those from 5-yr male goat, and the donor cell passage affected the developmental potential of nuclear transfer embryos.

LIBRA: LIgand Binding site Recognition Application.

Science.gov (United States)

Hung, Le Viet; Caprari, Silvia; Bizai, Massimiliano; Toti, Daniele; Polticelli, Fabio

2015-12-15

In recent years, structural genomics and ab initio molecular modeling activities are leading to the availability of a large number of structural models of proteins whose biochemical function is not known. The aim of this study was the development of a novel software tool that, given a protein's structural model, predicts the presence and identity of active sites and/or ligand binding sites. The algorithm implemented by ligand binding site recognition application (LIBRA) is based on a graph theory approach to find the largest subset of similar residues between an input protein and a collection of known functional sites. The algorithm makes use of two predefined databases for active sites and ligand binding sites, respectively, derived from the Catalytic Site Atlas and the Protein Data Bank. Tests indicate that LIBRA is able to identify the correct binding/active site in 90% of the cases analyzed, 90% of which feature the identified site as ranking first. As far as ligand binding site recognition is concerned, LIBRA outperforms other structure-based ligand binding sites detection tools with which it has been compared. The application, developed in Java SE 7 with a Swing GUI embedding a JMol applet, can be run on any OS equipped with a suitable Java Virtual Machine (JVM), and is available at the following URL: http://www.computationalbiology.it/software/LIBRAv1.zip. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Spatial variability of the aspect sensitivity of VHF radar echoes in the troposphere and lower stratosphere during jet stream passages

Directory of Open Access Journals (Sweden)

J. G. Yoe

Full Text Available The aspect sensitivity of SOUSY-VHF-radar oblique-beam echoes from the troposphere and lower stratosphere has been examined for a number of jet stream passages during the years 1990 - 1992. When the core of the jet is overhead or nearly so, vertical profiles of the aspect sensitivity display two notable features. First, the distinction between mainly isotropic and strongly aspect-sensitive echoes in the troposphere and the lower stratosphere, respectively, often reported for measurements made during calm conditions, does not necessarily prevail in the vicinity of the jet stream. Second, echoes obtained at altitudes near the height of the horizontal wind maximum are found to be more aspect sensitive for beams directed parallel to the horizontal flow or nearly so, than for other beam directions. It is demonstrated that time-averaged horizontal wind speeds estimated from the radar data, taking into account the reduced effective oblique-beam zenith angle resulting from aspect sensitivity, may exceed uncorrected wind speeds by as much as 10 m s^-1 in these circumstances. Implications for wind profiling and for describing the backscattering process are discussed. Doppler spectral widths examined for one jet stream passage are found to be narrower in a beam aligned with the horizontal wind at heights near the wind speed maximum than corresponding widths measured in a beam projected at right angles to the jet. The narrowest spectra thus coincide with the most aspect-sensitive echoes, consistent with the hypothesis that such returns result from specular backscattering processes.

Synthesis and labelling of Df-DUPA-Pep with gallium-68 and zirconium-89 as new PSMA ligands

International Nuclear Information System (INIS)

Benjamin Baur; Ehab Al-Momani; Noeen Malik; Hans-Juergen Machulla; Reske, S.N.; Christoph Solbach; Elena Andreolli; University of Milano-Bicocca, Milan

2014-01-01

Prostate-specific membrane antigen (PSMA) is a cell surface protein that is overexpressed in prostate cancer. Due to the specificity of expression of PSMA, numerous urea-based ligands have been synthesized until now. In the current study, we describe the coupling of the chelator desferrioxamine to DUPA-Pep and the subsequent labelling with Ga-68 and Zr-89 as new PSMA ligands. The labelling step is performed at room temperature and pH 7.5. In both radiosyntheses, the RCYs were higher than 95 % within 10 min, making dispensable any further purification and providing the radiotracers directly applicable for further utilization. (author)

Extreme sequence divergence but conserved ligand-binding specificity in Streptococcus pyogenes M protein.

Directory of Open Access Journals (Sweden)

2006-05-01

Full Text Available Many pathogenic microorganisms evade host immunity through extensive sequence variability in a protein region targeted by protective antibodies. In spite of the sequence variability, a variable region commonly retains an important ligand-binding function, reflected in the presence of a highly conserved sequence motif. Here, we analyze the limits of sequence divergence in a ligand-binding region by characterizing the hypervariable region (HVR of Streptococcus pyogenes M protein. Our studies were focused on HVRs that bind the human complement regulator C4b-binding protein (C4BP, a ligand that confers phagocytosis resistance. A previous comparison of C4BP-binding HVRs identified residue identities that could be part of a binding motif, but the extended analysis reported here shows that no residue identities remain when additional C4BP-binding HVRs are included. Characterization of the HVR in the M22 protein indicated that two relatively conserved Leu residues are essential for C4BP binding, but these residues are probably core residues in a coiled-coil, implying that they do not directly contribute to binding. In contrast, substitution of either of two relatively conserved Glu residues, predicted to be solvent-exposed, had no effect on C4BP binding, although each of these changes had a major effect on the antigenic properties of the HVR. Together, these findings show that HVRs of M proteins have an extraordinary capacity for sequence divergence and antigenic variability while retaining a specific ligand-binding function.

A response calculus for immobilized T cell receptor ligands

DEFF Research Database (Denmark)

Andersen, P S; Menné, C; Mariuzza, R A

2001-01-01

determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated...

Nonlinear Stimulated Raman Exact Passage by Resonance-Locked Inverse Engineering

Science.gov (United States)

Dorier, V.; Gevorgyan, M.; Ishkhanyan, A.; Leroy, C.; Jauslin, H. R.; Guérin, S.

2017-12-01

We derive an exact and robust stimulated Raman process for nonlinear quantum systems driven by pulsed external fields. The external fields are designed with closed-form expressions from the inverse engineering of a given efficient and stable dynamics. This technique allows one to induce a controlled population inversion which surpasses the usual nonlinear stimulated Raman adiabatic passage efficiency.

First-passage time in a bistable potential with colored noise

International Nuclear Information System (INIS)

Ramirez-Piscina, L.; Maria Sancho, J.; Javier de la Rubia, F.; Lindenberg, K.; Tsironis, G.P.

1989-01-01

A precise digital simulation of a bistable system under the effect of colored noise is carried out. A set of data for the mean first-passage time is obtained. The results are interpreted and compared with presently available theories, which are revisited following a new insight. Discrepancies that have been discussed in the literature are understood within our framework

Stimulated Raman adiabatic passage in Tm3+:YAG

International Nuclear Information System (INIS)

Alexander, A. L.; Lauro, R.; Louchet, A.; Chaneliere, T.; Le Goueet, J. L.

2008-01-01

We report on the experimental demonstration of stimulated Raman adiabatic passage in a Tm 3+ :YAG crystal. Tm 3+ :YAG is a promising material for use in quantum information processing applications, but as yet there are few experimental investigations of coherent Raman processes in this material. We investigate the effect of inhomogeneous broadening and Rabi frequency on the transfer efficiency and the width of the two-photon spectrum. Simulations of the complete Tm 3+ :YAG system are presented along with the corresponding experimental results

AMPA receptor ligands

DEFF Research Database (Denmark)

Strømgaard, Kristian; Mellor, Ian

2004-01-01

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player in the f......Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPAR), subtype of the ionotropic glutamate receptors (IGRs), mediate fast synaptic transmission in the central nervous system (CNS), and are involved in many neurological disorders, as well as being a key player...... in the formation of memory. Hence, ligands affecting AMPARs are highly important for the study of the structure and function of this receptor, and in this regard polyamine-based ligands, particularly polyamine toxins, are unique as they selectively block Ca2+ -permeable AMPARs. Indeed, endogenous intracellular...

New synthetic routes toward enantiopure nitrogen donor ligands.

Science.gov (United States)

Sala, Xavier; Rodríguez, Anna M; Rodríguez, Montserrat; Romero, Isabel; Parella, Teodor; von Zelewsky, Alexander; Llobet, Antoni; Benet-Buchholz, Jordi

2006-12-08

New polypyridylic chiral ligands, having either C3 or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kröhnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-alpha-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has been achieved through a new aldehyde building block ((-)-16). As an example, the synthesis of a chiral derivative of N,N-bis(2-pyridylmethyl)ethylamine (bpea) ligand, (-)-19, has been performed to illustrate the viability of the method. The coordinative ability of the ligands has been tested through the synthesis and characterization of complexes [Mn((-)-19)Br2], (-)-20, and [RuCl((-)-10)(bpy)](BF4), (-)-21. Some preliminary results related to the enantioselective catalytic epoxidation of styrene with the ruthenium complex are also presented.

Cloud computing for protein-ligand binding site comparison.

Science.gov (United States)

Hung, Che-Lun; Hua, Guan-Jie

2013-01-01

The proteome-wide analysis of protein-ligand binding sites and their interactions with ligands is important in structure-based drug design and in understanding ligand cross reactivity and toxicity. The well-known and commonly used software, SMAP, has been designed for 3D ligand binding site comparison and similarity searching of a structural proteome. SMAP can also predict drug side effects and reassign existing drugs to new indications. However, the computing scale of SMAP is limited. We have developed a high availability, high performance system that expands the comparison scale of SMAP. This cloud computing service, called Cloud-PLBS, combines the SMAP and Hadoop frameworks and is deployed on a virtual cloud computing platform. To handle the vast amount of experimental data on protein-ligand binding site pairs, Cloud-PLBS exploits the MapReduce paradigm as a management and parallelizing tool. Cloud-PLBS provides a web portal and scalability through which biologists can address a wide range of computer-intensive questions in biology and drug discovery.

Automated ligand fitting by core-fragment fitting and extension into density

International Nuclear Information System (INIS)

Terwilliger, Thomas C.; Klei, Herbert; Adams, Paul D.; Moriarty, Nigel W.; Cohn, Judith D.

2006-01-01

An automated ligand-fitting procedure has been developed and tested on 9327 ligands and (F o − F c )exp(iϕ c ) difference density from macromolecular structures in the Protein Data Bank. A procedure for fitting of ligands to electron-density maps by first fitting a core fragment of the ligand to density and then extending the remainder of the ligand into density is presented. The approach was tested by fitting 9327 ligands over a wide range of resolutions (most are in the range 0.8-4.8 Å) from the Protein Data Bank (PDB) into (F o − F c )exp(iϕ c ) difference density calculated using entries from the PDB without these ligands. The procedure was able to place 58% of these 9327 ligands within 2 Å (r.m.s.d.) of the coordinates of the atoms in the original PDB entry for that ligand. The success of the fitting procedure was relatively insensitive to the size of the ligand in the range 10–100 non-H atoms and was only moderately sensitive to resolution, with the percentage of ligands placed near the coordinates of the original PDB entry for fits in the range 58–73% over all resolution ranges tested