Simultaneous introduction of various palladium active sites into MOF via one-pot synthesis: Pd@[Cu3-xPdx(BTC)2]n.

PubMed

Zhang, Wenhua; Chen, Zhihao; Al-Naji, Majd; Guo, Penghu; Cwik, Stefan; Halbherr, Olesia; Wang, Yuemin; Muhler, Martin; Wilde, Nicole; Gläser, Roger; Fischer, Roland A

2016-10-14

Simultaneous incorporation of palladium within Pd-Pd and/or Pd-Cu paddlewheels as framework-nodes and Pd nanoparticle (NP) dispersion into MOF have been achieved for the first time via one-pot synthesis. In particular, the framework substitution of Cu(2+) by Pd(2+) as well as the pore loading with PdNPs have been confirmed and characterized by XPS. The obtained solids featuring such multiple Pd-sites show enhanced catalytic activity in the aqueous-phase hydrogenation of p-nitrophenol (PNP) with NaBH4 to p-aminophenol (PAP).

Integrated multiple patch-clamp array chip via lateral cell trapping junctions

NASA Astrophysics Data System (ADS)

Seo, J.; Ionescu-Zanetti, C.; Diamond, J.; Lal, R.; Lee, L. P.

2004-03-01

We present an integrated multiple patch-clamp array chip by utilizing lateral cell trapping junctions. The intersectional design of a microfluidic network provides multiple cell addressing and manipulation sites for efficient electrophysiological measurements at a number of patch sites. The patch pores consist of openings in the sidewall of a main fluidic channel, and a membrane patch is drawn into a smaller horizontal channel. This device geometry not only minimizes capacitive coupling between the cell reservoir and the patch channel, but also allows simultaneous optical and electrical measurements of ion channel proteins. Evidence of the hydrodynamic placement of mammalian cells at the patch sites as well as measurements of patch sealing resistance is presented. Device fabrication is based on micromolding of polydimethylsiloxane, thus allowing inexpensive mass production of disposable high-throughput biochips.

Different enzyme kinetic models.

PubMed

Seibert, Eleanore; Tracy, Timothy S

2014-01-01

As described in Chapter 2 , a large number of enzymatic reactions can be adequately described by Michaelis-Menten kinetics. The Michaelis-Menten equation represents a rectangular hyperbola, with a y-asymptote at the V max value. In many cases, more complex kinetic models are required to explain the observed data. Atypical kinetic profiles are believed to arise from the simultaneous binding of multiple molecules within the active site of the enzyme (Tracy and Hummel, Drug Metab Rev 36:231-242, 2004). Several cytochromes P450 have large active sites that enable binding of multiple molecules (Wester et al. J Biol Chem 279:35630-35637, 2004; Yano et al. J Biol Chem 279:38091-38094, 2004). Thus, atypical kinetics are not uncommon in in vitro drug metabolism studies. This chapter covers enzyme kinetic reactions in which a single enzyme has multiple binding sites for substrates and/or inhibitors as well as reactions catalyzed by multiple enzymes.

Tunable multiple emissions in manganese-concentrated sulfide through simultaneous tailoring of Mn-site coordination and Mn-Mn pair geometry

NASA Astrophysics Data System (ADS)

Chen, Zitao; Song, Enhai; Ye, Shi; Zhang, Qinyuan

2017-12-01

In contrast to generally single-band visible emission feature from Mn2+, simultaneous visible (VIS) and near-infrared (NIR) multiple emissions are demonstrated in Mn2+ concentrated sulfide (MnS) by only involving a single crystallographic site. Upon varying the Mn2+-site coordination and/or Mn-Mn pairs geometry in different structural MnS, the multiple emissions from divalent manganese can be easily tuned from 575 to 720 nm (VIS) or from 880 to 900 or 1380 nm (NIR), respectively. The excitation spectroscopy and the luminescent decay, together with crystal structural analyses, are employed to investigate the electronic transition and the excited state dynamics of these Mn2+ concentrated systems. It is found that the VIS and NIR emissions can be ascribed to the isolated Mn2+ ion and exchange coupled Mn-Mn pair center, respectively. The effect of crystal field and bridging geometry, as well as temperature on the exchange coupled Mn2+ pairs NIR emissive center, is also investigated in detail. This work not only provides keen insights into the de-excitation pathway of Mn2+-concentrated material, but also offers the possibilities of designing a novel NIR emitting source for various photonic applications.

S4MPLE--Sampler for Multiple Protein-Ligand Entities: Methodology and Rigid-Site Docking Benchmarking.

PubMed

Hoffer, Laurent; Chira, Camelia; Marcou, Gilles; Varnek, Alexandre; Horvath, Dragos

2015-05-19

This paper describes the development of the unified conformational sampling and docking tool called Sampler for Multiple Protein-Ligand Entities (S4MPLE). The main novelty in S4MPLE is the unified dealing with intra- and intermolecular degrees of freedom (DoF). While classically programs are either designed for folding or docking, S4MPLE transcends this artificial specialization. It supports folding, docking of a flexible ligand into a flexible site and simultaneous docking of several ligands. The trick behind it is the formal assimilation of inter-molecular to intra-molecular DoF associated to putative inter-molecular contact axes. This is implemented within the genetic operators powering a Lamarckian Genetic Algorithm (GA). Further novelty includes differentiable interaction fingerprints to control population diversity, and fitting a simple continuum solvent model and favorable contact bonus terms to the AMBER/GAFF force field. Novel applications-docking of fragment-like compounds, simultaneous docking of multiple ligands, including free crystallographic waters-were published elsewhere. This paper discusses: (a) methodology, (b) set-up of the force field energy functions and (c) their validation in classical redocking tests. More than 80% success in redocking was achieved (RMSD of top-ranked pose < 2.0 Å).

Wide-field in vivo neocortical calcium dye imaging using a convection-enhanced loading technique combined with simultaneous multiwavelength imaging of voltage-sensitive dyes and hemodynamic signals

PubMed Central

Ma, Hongtao; Harris, Samuel; Rahmani, Redi; Lacefield, Clay O.; Zhao, Mingrui; Daniel, Andy G. S.; Zhou, Zhiping; Bruno, Randy M.; Berwick, Jason; Schwartz, Theodore H.

2014-01-01

Abstract. In vivo calcium imaging is an incredibly powerful technique that provides simultaneous information on fast neuronal events, such as action potentials and subthreshold synaptic activity, as well as slower events that occur in the glia and surrounding neuropil. Bulk-loading methods that involve multiple injections can be used for single-cell as well as wide-field imaging studies. However, multiple injections result in inhomogeneous loading as well as multiple sites of potential cortical injury. We used convection-enhanced delivery to create smooth, continuous loading of a large area of the cortical surface through a solitary injection site and demonstrated the efficacy of the technique using confocal microscopy imaging of single cells and physiological responses to single-trial events of spontaneous activity, somatosensory-evoked potentials, and epileptiform events. Combinations of calcium imaging with voltage-sensitive dye and intrinsic signal imaging demonstrate the utility of this technique in neurovascular coupling investigations. Convection-enhanced loading of calcium dyes may be a useful technique to advance the study of cortical processing when widespread loading of a wide-field imaging is required. PMID:25525611

Wide-field in vivo neocortical calcium dye imaging using a convection-enhanced loading technique combined with simultaneous multiwavelength imaging of voltage-sensitive dyes and hemodynamic signals.

PubMed

Ma, Hongtao; Harris, Samuel; Rahmani, Redi; Lacefield, Clay O; Zhao, Mingrui; Daniel, Andy G S; Zhou, Zhiping; Bruno, Randy M; Berwick, Jason; Schwartz, Theodore H

2014-07-24

In vivo calcium imaging is an incredibly powerful technique that provides simultaneous information on fast neuronal events, such as action potentials and subthreshold synaptic activity, as well as slower events that occur in the glia and surrounding neuropil. Bulk-loading methods that involve multiple injections can be used for single-cell as well as wide-field imaging studies. However, multiple injections result in inhomogeneous loading as well as multiple sites of potential cortical injury. We used convection-enhanced delivery to create smooth, continuous loading of a large area of the cortical surface through a solitary injection site and demonstrated the efficacy of the technique using confocal microscopy imaging of single cells and physiological responses to single-trial events of spontaneous activity, somatosensory-evoked potentials, and epileptiform events. Combinations of calcium imaging with voltage-sensitive dye and intrinsic signal imaging demonstrate the utility of this technique in neurovascular coupling investigations. Convection-enhanced loading of calcium dyes may be a useful technique to advance the study of cortical processing when widespread loading of a wide-field imaging is required.

Estimating hydraulic properties using a moving-model approach and multiple aquifer tests

USGS Publications Warehouse

Halford, K.J.; Yobbi, D.

2006-01-01

A new method was developed for characterizing geohydrologic columns that extended >600 m deep at sites with as many as six discrete aquifers. This method was applied at 12 sites within the Southwest Florida Water Management District. Sites typically were equipped with multiple production wells, one for each aquifer and one or more observation wells per aquifer. The average hydraulic properties of the aquifers and confining units within radii of 30 to >300 m were characterized at each site. Aquifers were pumped individually and water levels were monitored in stressed and adjacent aquifers during each pumping event. Drawdowns at a site were interpreted using a radial numerical model that extended from land surface to the base of the geohydrologic column and simulated all pumping events. Conceptually, the radial model moves between stress periods and recenters on the production well during each test. Hydraulic conductivity was assumed homogeneous and isotropic within each aquifer and confining unit. Hydraulic property estimates for all of the aquifers and confining units were consistent and reasonable because results from multiple aquifers and pumping events were analyzed simultaneously. Copyright ?? 2005 National Ground Water Association.

Estimating hydraulic properties using a moving-model approach and multiple aquifer tests.

PubMed

Halford, Keith J; Yobbi, Dann

2006-01-01

A new method was developed for characterizing geohydrologic columns that extended >600 m deep at sites with as many as six discrete aquifers. This method was applied at 12 sites within the Southwest Florida Water Management District. Sites typically were equipped with multiple production wells, one for each aquifer and one or more observation wells per aquifer. The average hydraulic properties of the aquifers and confining units within radii of 30 to >300 m were characterized at each site. Aquifers were pumped individually and water levels were monitored in stressed and adjacent aquifers during each pumping event. Drawdowns at a site were interpreted using a radial numerical model that extended from land surface to the base of the geohydrologic column and simulated all pumping events. Conceptually, the radial model moves between stress periods and recenters on the production well during each test. Hydraulic conductivity was assumed homogeneous and isotropic within each aquifer and confining unit. Hydraulic property estimates for all of the aquifers and confining units were consistent and reasonable because results from multiple aquifers and pumping events were analyzed simultaneously.

Multipoint sensing with a low-coherence source using single-arm frequency-shifted interferometry

DOE PAGES

Zhang, Yiwei; Ye, Fei; Qi, Bing; ...

2016-07-12

We demonstrate that multiple-site sensing along an optical fiber can be done with incoherent continuous-wave light. Here, using a broadband low-coherence noise source, a slow detector, and an optical modulator, we construct a single-arm frequency-shifted interferometer (SA-FSI) capable of simultaneously sensing multiple weak-reflection sites distributed either in parallel or in series along fiber links. By scanning the driving frequency of an electro-optic amplitude modulator in the range of 2.7–3.2 GHz at steps of 41.7 KHz, we demonstrate a spatial resolution of 0.3 m and a measurement range of over 1 km.

Simultaneous statistical bias correction of multiplePM2.5 species from a regional photochemical grid model

EPA Science Inventory

In recent years environmental epidemiologists have begun utilizing regionalscale air quality computer models to predict ambient air pollution concentrations in health studies instead of or in addition to monitoring data from central sites. The advantages of using such models i...

A Training Program for Unlicensed Assistive Personnel

ERIC Educational Resources Information Center

Gursky, Beverly S.; Ryser, Barbara J.

2007-01-01

In many school districts, school nurses are assigned multiple schools with responsibility for the health care needs of all students at those schools. Because they cannot be physically present at all sites simultaneously, it is necessary to delegate tasks to unlicensed assistive personnel (UAP). Educating and supervising UAP are critical steps in…

Simultaneous inhibition of multiple oncogenic miRNAs by a multi-potent microRNA sponge.

PubMed

Jung, Jaeyun; Yeom, Chanjoo; Choi, Yeon-Sook; Kim, Sinae; Lee, EunJi; Park, Min Ji; Kang, Sang Wook; Kim, Sung Bae; Chang, Suhwan

2015-08-21

The roles of oncogenic miRNAs are widely recognized in many cancers. Inhibition of single miRNA using antagomiR can efficiently knock-down a specific miRNA. However, the effect is transient and often results in subtle phenotype, as there are other miRNAs contribute to tumorigenesis. Here we report a multi-potent miRNA sponge inhibiting multiple miRNAs simultaneously. As a model system, we targeted miR-21, miR-155 and miR-221/222, known as oncogenic miRNAs in multiple tumors including breast and pancreatic cancers. To achieve efficient knockdown, we generated perfect and bulged-matched miRNA binding sites (MBS) and introduced multiple copies of MBS, ranging from one to five, in the multi-potent miRNA sponge. Luciferase reporter assay showed the multi-potent miRNA sponge efficiently inhibited 4 miRNAs in breast and pancreatic cancer cells. Furthermore, a stable and inducible version of the multi-potent miRNA sponge cell line showed the miRNA sponge efficiently reduces the level of 4 target miRNAs and increase target protein level of these oncogenic miRNAs. Finally, we showed the miRNA sponge sensitize cells to cancer drug and attenuate cell migratory activity. Altogether, our study demonstrates the multi-potent miRNA sponge is a useful tool to examine the functional impact of simultaneous inhibition of multiple miRNAs and proposes a therapeutic potential.

Surface NMR imaging with simultaneously energized transmission loops

NASA Astrophysics Data System (ADS)

Irons, T. P.; Kass, A.; Parsekian, A.

2016-12-01

Surface nuclear magnetic resonance (sNMR) is a unique geophysical technique which allows for the direct detection of liquid-phase water. In saturated media the sNMR response also provides estimates of hydrologic properties including porosity and permeability. The most common survey deployment consists of a single coincident loop performing both transmission and receiving. Because the sNMR method is relatively slow, tomography using coincident loops is time-intensive. Surveys using multiple receiver loops (but a single transmitter) provide additional sensitivity; however, they still require iterating transmission over the loops, and do not decrease survey acquisition time. In medical rotating frame imaging, arrays of transmitters are employed in order to decrease acquisition time, whilst optimizing image resolving power-a concept which we extend to earth's field imaging. Using simultaneously energized transmission loops decreases survey time linearly with the number of channels. To demonstrate the efficacy and benefits of multiple transmission loops, we deployed simultaneous sNMR transmission arrays using minimally coupled loops and a specially modified instrument at the Red Buttes Hydrogeophysics Experiment Site-a well-characterized location near Laramie, Wyoming. The proposed survey proved capable of acquiring multiple-channel imaging data with comparable noise levels to figure-eight configurations. Finally, the channels can be combined after acquisition or inverted simultaneously to provide composite datasets and images. This capability leverages the improved near surface resolving power of small loops but retains sensitivity to deep media through the use of synthetic aperature receivers. As such, simultaneously acquired loop arrays provide a great deal of flexibility.

Loading, Release, Biodegradation, and Biocompatibility of a Nanovector Delivery System

NASA Technical Reports Server (NTRS)

Ferrai, Mauro; Tasciotti, Ennio

2012-01-01

A nanovector multistage system has been created to overcome or bypass sequential barriers within the human body, in order to deliver a therapeutic or imaging agent to a specific location. This innovation consists of a composition that includes two or more stages of particles, such that smaller, later-stage particles are contained in the larger, early-stage particles. An active agent, such as a therapeutic agent or imaging agent, is preferentially delivered and/or localized to a particular target site in the body of a subject. The multistage composition overcomes multiple biological barriers in the body. The multistage composition also allows for simultaneous delivery and localization at the same or different target sites of multiple active agents.

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

Debnath, Mithu; Iungo, Giacomo Valerio; Brewer, W. Alan

During the eXperimental Planetary boundary layer Instrumentation Assessment (XPIA) campaign, which was carried out at the Boulder Atmospheric Observatory (BAO) in spring 2015, multiple-Doppler scanning strategies were carried out with scanning wind lidars and Ka-band radars. Specifically, step–stare measurements were collected simultaneously with three scanning Doppler lidars, while two scanning Ka-band radars carried out simultaneous range height indicator (RHI) scans. The XPIA experiment provided the unique opportunity to compare directly virtual-tower measurements performed simultaneously with Ka-band radars and Doppler wind lidars. Furthermore, multiple-Doppler measurements were assessed against sonic anemometer data acquired from the meteorological tower (met-tower) present at the BAOmore » site and a lidar wind profiler. As a result, this survey shows that – despite the different technologies, measurement volumes and sampling periods used for the lidar and radar measurements – a very good accuracy is achieved for both remote-sensing techniques for probing horizontal wind speed and wind direction with the virtual-tower scanning technique.« less

Methods, caveats and the future of large-scale microelectrode recordings in the non-human primate

PubMed Central

Dotson, Nicholas M.; Goodell, Baldwin; Salazar, Rodrigo F.; Hoffman, Steven J.; Gray, Charles M.

2015-01-01

Cognitive processes play out on massive brain-wide networks, which produce widely distributed patterns of activity. Capturing these activity patterns requires tools that are able to simultaneously measure activity from many distributed sites with high spatiotemporal resolution. Unfortunately, current techniques with adequate coverage do not provide the requisite spatiotemporal resolution. Large-scale microelectrode recording devices, with dozens to hundreds of microelectrodes capable of simultaneously recording from nearly as many cortical and subcortical areas, provide a potential way to minimize these tradeoffs. However, placing hundreds of microelectrodes into a behaving animal is a highly risky and technically challenging endeavor that has only been pursued by a few groups. Recording activity from multiple electrodes simultaneously also introduces several statistical and conceptual dilemmas, such as the multiple comparisons problem and the uncontrolled stimulus response problem. In this perspective article, we discuss some of the techniques that we, and others, have developed for collecting and analyzing large-scale data sets, and address the future of this emerging field. PMID:26578906

Computational design of trimeric influenza-neutralizing proteins targeting the hemagglutinin receptor binding site

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

Strauch, Eva-Maria; Bernard, Steffen M.; La, David

Many viral surface glycoproteins and cell surface receptors are homo-oligomers1, 2, 3, 4, and thus can potentially be targeted by geometrically matched homo-oligomers that engage all subunits simultaneously to attain high avidity and/or lock subunits together. The adaptive immune system cannot generally employ this strategy since the individual antibody binding sites are not arranged with appropriate geometry to simultaneously engage multiple sites in a single target homo-oligomer. We describe a general strategy for the computational design of homo-oligomeric protein assemblies with binding functionality precisely matched to homo-oligomeric target sites5, 6, 7, 8. In the first step, a small protein ismore » designed that binds a single site on the target. In the second step, the designed protein is assembled into a homo-oligomer such that the designed binding sites are aligned with the target sites. We use this approach to design high-avidity trimeric proteins that bind influenza A hemagglutinin (HA) at its conserved receptor binding site. The designed trimers can both capture and detect HA in a paper-based diagnostic format, neutralizes influenza in cell culture, and completely protects mice when given as a single dose 24 h before or after challenge with influenza.« less

Fulfilling Multiple Missions Concurrently: An Ethnographic Study of a Campus Children's Center's Trials and Triumphs in Serving Six Populations

ERIC Educational Resources Information Center

Calica, Corinna Dy-Liacco

2017-01-01

The study is a comprehensive ethnographic investigation into how a campus children's center and laboratory school site can simultaneously serve six major population groups (i.e., parents, college students, teachers, faculty, administrators, and researchers) while maintaining program operations. The study carefully examines the converging and…

Assessment of virtual towers performed with scanning wind lidars and Ka-band radars during the XPIA experiment

DOE PAGES

Debnath, Mithu; Iungo, Giacomo Valerio; Brewer, W. Alan; ...

2017-03-29

During the eXperimental Planetary boundary layer Instrumentation Assessment (XPIA) campaign, which was carried out at the Boulder Atmospheric Observatory (BAO) in spring 2015, multiple-Doppler scanning strategies were carried out with scanning wind lidars and Ka-band radars. Specifically, step–stare measurements were collected simultaneously with three scanning Doppler lidars, while two scanning Ka-band radars carried out simultaneous range height indicator (RHI) scans. The XPIA experiment provided the unique opportunity to compare directly virtual-tower measurements performed simultaneously with Ka-band radars and Doppler wind lidars. Furthermore, multiple-Doppler measurements were assessed against sonic anemometer data acquired from the meteorological tower (met-tower) present at the BAOmore » site and a lidar wind profiler. As a result, this survey shows that – despite the different technologies, measurement volumes and sampling periods used for the lidar and radar measurements – a very good accuracy is achieved for both remote-sensing techniques for probing horizontal wind speed and wind direction with the virtual-tower scanning technique.« less

Multi-Site Simultaneous Time-Resolved Photometry with a Low Cost Electro-Optics System †

PubMed Central

Gasdia, Forrest; Barjatya, Aroh; Bilardi, Sergei

2017-01-01

Sunlight reflected off of resident space objects can be used as an optical signal for astrometric orbit determination and for deducing geometric information about the object. With the increasing population of small satellites and debris in low Earth orbit, photometry is a powerful tool in operational support of space missions, whether for anomaly resolution or object identification. To accurately determine size, shape, spin rate, status of deployables, or attitude information of an unresolved resident space object, multi-hertz sample rate photometry is required to capture the relatively rapid changes in brightness that these objects can exhibit. OSCOM, which stands for Optical tracking and Spectral characterization of CubeSats for Operational Missions, is a low cost and portable telescope system capable of time-resolved small satellite photometry, and is field deployable on short notice for simultaneous observation from multiple sites. We present the electro-optical design principles behind OSCOM and light curves of the 1.5 U DICE-2 CubeSat and simultaneous observations of the main body of the ASTRO-H satellite after its fragmentation event. PMID:28556802

Multi-Site Simultaneous Time-Resolved Photometry with a Low Cost Electro-Optics System.

PubMed

Gasdia, Forrest; Barjatya, Aroh; Bilardi, Sergei

2017-05-30

Sunlight reflected off of resident space objects can be used as an optical signal for astrometric orbit determination and for deducing geometric information about the object. With the increasing population of small satellites and debris in low Earth orbit, photometry is a powerful tool in operational support of space missions, whether for anomaly resolution or object identification. To accurately determine size, shape, spin rate, status of deployables, or attitude information of an unresolved resident space object, multi-hertz sample rate photometry is required to capture the relatively rapid changes in brightness that these objects can exhibit. OSCOM, which stands for Optical tracking and Spectral characterization of CubeSats for Operational Missions, is a low cost and portable telescope system capable of time-resolved small satellite photometry, and is field deployable on short notice for simultaneous observation from multiple sites. We present the electro-optical design principles behind OSCOM and light curves of the 1.5 U DICE-2 CubeSat and simultaneous observations of the main body of the ASTRO-H satellite after its fragmentation event.

High-risk human papillomavirus infection involving multiple anatomic sites of the female lower genital tract: a multiplex real-time polymerase chain reaction-based study.

PubMed

Hui, Yiang; Manna, Pradip; Ou, Joyce J; Kerley, Spencer; Zhang, Cunxian; Sung, C James; Lawrence, W Dwayne; Quddus, M Ruhul

2015-09-01

High-risk human papillomavirus infection usually is seen at one anatomic site in an individual. Rarely, infection at multiple anatomic sites of the female lower genital tract in the same individual is encountered either simultaneously and/or at a later date. The current study identifies the various subtypes of high-risk human papillomavirus infection in these scenarios and analyzes the potential significance of these findings. High-risk human papillomavirus infection involving 22 anatomic sites from 7 individuals was identified after institutional review board approval. Residual paraffin-embedded tissue samples were retrieved, and all 15 high-risk human papillomavirus were identified and viral load quantified using multiplex real-time polymerase chain reaction-based method. Multiple high-risk human papillomavirus subtypes were identified in 32% of the samples and as many as 5 different subtypes of high-risk human papillomavirus infection in a single anatomic site. In general, each anatomic site has unique combination of viral subtypes, although one individual showed overlapping subtypes in the vagina, cervix, and vulvar samples. Higher viral load and rare subtypes are more frequent in younger patients and in dysplasia compared with carcinoma. Follow-up ranging from 3 to 84 months revealed persistent high-risk human papillomavirus infection in 60% of cases. Copyright © 2015 Elsevier Inc. All rights reserved.

Synchronous volvulus of the sigmoid colon and caecum, a very rare cause of large bowel obstruction.

PubMed

Islam, Shariful; Hosein, Devin; Bheem, Vinoo; Dan, Dilip

2016-10-14

Colonic volvulus usually occurs as a single event that can affect various parts of the colon. The usual sites affected being the sigmoid colon (75%) and the caecum (22%). The phenomenon of multiple sites simultaneously undergoing volvulus is an extremely rare occurrence. Synchronous double colonic volvulus is extremely rare and to the best of our knowledge, this is the 4th reported case of simultaneous sigmoid and caecal volvulus in the English literature. The clinical presentation and the radiological findings are that of large bowel obstruction. Classic radiological findings may not be present or may be overlooked due to its rarity. Treatment of this condition is early surgical intervention to prevent the sequalae of a colonic volvulus and its associated mortality. We report a case of an 80-year-old man with synchronous volvulus of the sigmoid colon and caecum. 2016 BMJ Publishing Group Ltd.

Utilization of satellite-satellite tracking data for determination of the geocentric gravitational constant (GM)

NASA Technical Reports Server (NTRS)

Martin, C. F.; Oh, I. H.

1979-01-01

Range rate tracking of GEOS 3 through the ATS 6 satellite was used, along with ground tracking of GEOS 3, to estimate the geocentric gravitational constant (GM). Using multiple half day arcs, a GM of 398600.52 + or - 0.12 cu km/sq sec was estimated using the GEM 10 gravity model, based on speed of light of 299792.458 km/sec. Tracking station coordinates were simultaneously adjusted, leaving geopotential model error as the dominant error source. Baselines between the adjusted NASA laser sites show better than 15 cm agreement with multiple short arc GEOS 3 solutions.

Feasibility study for combination of field-flow fractionation (FFF)-based separation of size-coded particle probes with amplified surface enhanced Raman scattering (SERS) tagging for simultaneous detection of multiple miRNAs.

PubMed

Shin, Kayeong; Choi, Jaeyeong; Kim, Yeoju; Lee, Yoonjeong; Kim, Joohoon; Lee, Seungho; Chung, Hoeil

2018-06-29

We propose a new analytical scheme in which field-flow fractionation (FFF)-based separation of target-specific polystyrene (PS) particle probes of different sizes are incorporated with amplified surface-enhanced Raman scattering (SERS) tagging for the simultaneous and sensitive detection of multiple microRNAs (miRNAs). For multiplexed detection, PS particles of three different diameters (15, 10, 5 μm) were used for the size-coding, and a probe single stranded DNA (ssDNA) complementary to a target miRNA was conjugated on an intended PS particle. After binding of a target miRNA on PS probe, polyadenylation reaction was executed to generate a long tail composed of adenine (A) serving as a binding site to thymine (T) conjugated Au nanoparticles (T-AuNPs) to increase SERS intensity. The three size-coded PS probes bound with T-AuNPs were then separated in a FFF channel. With the observation of extinction-based fractograms, separation of three size-coded PS probes was clearly confirmed, thereby enabling of measuring three miRNAs simultaneously. Raman intensities of FFF fractions collected at the peak maximum of 15, 10 and 5 μm PS probes varied fairy quantitatively with the change of miRNA concentrations, and the reproducibility of measurement was acceptable. The proposed method is potentially useful for simultaneous detection of multiple miRNAs with high sensitivity. Copyright © 2018 Elsevier B.V. All rights reserved.

Amplified Rate Acceleration by Simultaneous Up-Regulation of Multiple Active Sites in an Endo-Functionalized Porous Capsule.

PubMed

Kopilevich, Sivil; Müller, Achim; Weinstock, Ira A

2015-10-14

Using the hydrolysis of epoxides in water as a model reaction, the effect of multiple active sites on Michaelis-Menten compliant rate accelerations in a porous capsule is demonstrated. The capsule is a water-soluble Ih-symmetry Keplerate-type complex of the form, [{Mo(VI)6O21(H2O)6}12{Mo(V)2O4(L)}30](42-), in which 12 pentagonal "ligands," {(Mo(VI))Mo(VI)5O21(H2O)6}(6-), are coordinated to 30 dimolybdenum sites, {Mo(V)2O4L}(1+) (L = an endohedrally coordinated η(2)-bound carboxylate anion), resulting in 20 Mo9O9 pores. When "up-regulated" by removal of ca. one-third of the blocking ligands, L, an equal number of dimolybdenum sites are activated, and the newly freed-up space allows for encapsulation of nearly twice as many substrate guests, leading to a larger effective molarity (amplification), and an increase in the rate acceleration (k(cat)/k(uncat)) from 16,000 to an enzyme-like value of 182,800.

A Multi-criteria Decision Analysis System for Prioritizing Sites and Types of Low Impact Development Practices

NASA Astrophysics Data System (ADS)

Song, Jae Yeol; Chung, Eun-Sung

2017-04-01

This study developed a multi-criteria decision analysis framework to prioritize sites and types of low impact development (LID) practices. This framework was systemized as a web-based system coupled with the Storm Water Management Model (SWMM) from the Environmental Protection Agency (EPA). Using the technique for order of preference by similarity to ideal solution (TOPSIS), which is a type of multi-criteria decision-making (MCDM) method, multiple types and sites of designated LID practices are prioritized. This system is named the Water Management Prioritization Module (WMPM) and is an improved version of the Water Management Analysis Module (WMAM) that automatically generates and simulates multiple scenarios of LID design and planning parameters for a single LID type. WMPM can simultaneously determine the priority of multiple LID types and sites. In this study, an infiltration trench and permeable pavement were considered for multiple sub-catchments in South Korea to demonstrate the WMPM procedures. The TOPSIS method was manually incorporated to select the vulnerable target sub-catchments and to prioritize the LID planning scenarios for multiple types and sites considering socio-economic, hydrologic and physical-geometric factors. In this application, the Delphi method and entropy theory were used to determine the subjective and objective weights, respectively. Comparing the ranks derived by this system, two sub-catchments, S16 and S4, out of 18 were considered to be the most suitable places for installing an infiltration trench and porous pavement to reduce the peak and total flow, respectively, considering both socio-economic factors and hydrological effectiveness. WMPM can help policy-makers to objectively develop urban water plans for sustainable development. Keywords: Low Impact Development, Multi-Criteria Decision Analysis, SWMM, TOPSIS, Water Management Prioritization Module (WMPM)

Statistical mechanical model of coupled transcription from multiple promoters due to transcription factor titration

PubMed Central

Rydenfelt, Mattias; Cox, Robert Sidney; Garcia, Hernan; Phillips, Rob

2014-01-01

Transcription factors (TFs) with regulatory action at multiple promoter targets is the rule rather than the exception, with examples ranging from the cAMP receptor protein (CRP) in E. coli that regulates hundreds of different genes simultaneously to situations involving multiple copies of the same gene, such as plasmids, retrotransposons, or highly replicated viral DNA. When the number of TFs heavily exceeds the number of binding sites, TF binding to each promoter can be regarded as independent. However, when the number of TF molecules is comparable to the number of binding sites, TF titration will result in correlation (“promoter entanglement”) between transcription of different genes. We develop a statistical mechanical model which takes the TF titration effect into account and use it to predict both the level of gene expression for a general set of promoters and the resulting correlation in transcription rates of different genes. Our results show that the TF titration effect could be important for understanding gene expression in many regulatory settings. PMID:24580252

An efficient method to transcription factor binding sites imputation via simultaneous completion of multiple matrices with positional consistency.

PubMed

Guo, Wei-Li; Huang, De-Shuang

2017-08-22

Transcription factors (TFs) are DNA-binding proteins that have a central role in regulating gene expression. Identification of DNA-binding sites of TFs is a key task in understanding transcriptional regulation, cellular processes and disease. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) enables genome-wide identification of in vivo TF binding sites. However, it is still difficult to map every TF in every cell line owing to cost and biological material availability, which poses an enormous obstacle for integrated analysis of gene regulation. To address this problem, we propose a novel computational approach, TFBSImpute, for predicting additional TF binding profiles by leveraging information from available ChIP-seq TF binding data. TFBSImpute fuses the dataset to a 3-mode tensor and imputes missing TF binding signals via simultaneous completion of multiple TF binding matrices with positional consistency. We show that signals predicted by our method achieve overall similarity with experimental data and that TFBSImpute significantly outperforms baseline approaches, by assessing the performance of imputation methods against observed ChIP-seq TF binding profiles. Besides, motif analysis shows that TFBSImpute preforms better in capturing binding motifs enriched in observed data compared with baselines, indicating that the higher performance of TFBSImpute is not simply due to averaging related samples. We anticipate that our approach will constitute a useful complement to experimental mapping of TF binding, which is beneficial for further study of regulation mechanisms and disease.

Splicing predictions reliably classify different types of alternative splicing

PubMed Central

Busch, Anke; Hertel, Klemens J.

2015-01-01

Alternative splicing is a key player in the creation of complex mammalian transcriptomes and its misregulation is associated with many human diseases. Multiple mRNA isoforms are generated from most human genes, a process mediated by the interplay of various RNA signature elements and trans-acting factors that guide spliceosomal assembly and intron removal. Here, we introduce a splicing predictor that evaluates hundreds of RNA features simultaneously to successfully differentiate between exons that are constitutively spliced, exons that undergo alternative 5′ or 3′ splice-site selection, and alternative cassette-type exons. Surprisingly, the splicing predictor did not feature strong discriminatory contributions from binding sites for known splicing regulators. Rather, the ability of an exon to be involved in one or multiple types of alternative splicing is dictated by its immediate sequence context, mainly driven by the identity of the exon's splice sites, the conservation around them, and its exon/intron architecture. Thus, the splicing behavior of human exons can be reliably predicted based on basic RNA sequence elements. PMID:25805853

Visualizing multiple inter-organelle contact sites using the organelle-targeted split-GFP system.

PubMed

Kakimoto, Yuriko; Tashiro, Shinya; Kojima, Rieko; Morozumi, Yuki; Endo, Toshiya; Tamura, Yasushi

2018-04-18

Functional integrity of eukaryotic organelles relies on direct physical contacts between distinct organelles. However, the entity of organelle-tethering factors is not well understood due to lack of means to analyze inter-organelle interactions in living cells. Here we evaluate the split-GFP system for visualizing organelle contact sites in vivo and show its advantages and disadvantages. We observed punctate GFP signals from the split-GFP fragments targeted to any pairs of organelles among the ER, mitochondria, peroxisomes, vacuole and lipid droplets in yeast cells, which suggests that these organelles form contact sites with multiple organelles simultaneously although it is difficult to rule out the possibilities that these organelle contacts sites are artificially formed by the irreversible associations of the split-GFP probes. Importantly, split-GFP signals in the overlapped regions of the ER and mitochondria were mainly co-localized with ERMES, an authentic ER-mitochondria tethering structure, suggesting that split-GFP assembly depends on the preexisting inter-organelle contact sites. We also confirmed that the split-GFP system can be applied to detection of the ER-mitochondria contact sites in HeLa cells. We thus propose that the split-GFP system is a potential tool to observe and analyze inter-organelle contact sites in living yeast and mammalian cells.

Incorporating 3D-printing technology in the design of head-caps and electrode drives for recording neurons in multiple brain regions.

PubMed

Headley, Drew B; DeLucca, Michael V; Haufler, Darrell; Paré, Denis

2015-04-01

Recent advances in recording and computing hardware have enabled laboratories to record the electrical activity of multiple brain regions simultaneously. Lagging behind these technical advances, however, are the methods needed to rapidly produce microdrives and head-caps that can flexibly accommodate different recording configurations. Indeed, most available designs target single or adjacent brain regions, and, if multiple sites are targeted, specially constructed head-caps are used. Here, we present a novel design style, for both microdrives and head-caps, which takes advantage of three-dimensional printing technology. This design facilitates targeting of multiple brain regions in various configurations. Moreover, the parts are easily fabricated in large quantities, with only minor hand-tooling and finishing required. Copyright © 2015 the American Physiological Society.

Incorporating 3D-printing technology in the design of head-caps and electrode drives for recording neurons in multiple brain regions

PubMed Central

DeLucca, Michael V.; Haufler, Darrell; Paré, Denis

2015-01-01

Recent advances in recording and computing hardware have enabled laboratories to record the electrical activity of multiple brain regions simultaneously. Lagging behind these technical advances, however, are the methods needed to rapidly produce microdrives and head-caps that can flexibly accommodate different recording configurations. Indeed, most available designs target single or adjacent brain regions, and, if multiple sites are targeted, specially constructed head-caps are used. Here, we present a novel design style, for both microdrives and head-caps, which takes advantage of three-dimensional printing technology. This design facilitates targeting of multiple brain regions in various configurations. Moreover, the parts are easily fabricated in large quantities, with only minor hand-tooling and finishing required. PMID:25652930

Using Simultaneous Prompting Procedure to Promote Recall of Multiplication Facts by Middle School Students with Cognitive Impairment

ERIC Educational Resources Information Center

Rao, Shaila; Mallow, Lynette

2009-01-01

This study examined effectiveness of simultaneous prompting system in teaching students with cognitive impairment to automate recall of multiplication facts. A multiple probes design with multiple sets of math facts and replicated across multiple subjects was used to assess effectiveness of simultaneous prompting on recall of basic multiplication…

SnipViz: a compact and lightweight web site widget for display and dissemination of multiple versions of gene and protein sequences.

PubMed

Jaschob, Daniel; Davis, Trisha N; Riffle, Michael

2014-07-23

As high throughput sequencing continues to grow more commonplace, the need to disseminate the resulting data via web applications continues to grow. Particularly, there is a need to disseminate multiple versions of related gene and protein sequences simultaneously--whether they represent alleles present in a single species, variations of the same gene among different strains, or homologs among separate species. Often this is accomplished by displaying all versions of the sequence at once in a manner that is not intuitive or space-efficient and does not facilitate human understanding of the data. Web-based applications needing to disseminate multiple versions of sequences would benefit from a drop-in module designed to effectively disseminate these data. SnipViz is a client-side software tool designed to disseminate multiple versions of related gene and protein sequences on web sites. SnipViz has a space-efficient, interactive, and dynamic interface for navigating, analyzing and visualizing sequence data. It is written using standard World Wide Web technologies (HTML, Javascript, and CSS) and is compatible with most web browsers. SnipViz is designed as a modular client-side web component and may be incorporated into virtually any web site and be implemented without any programming. SnipViz is a drop-in client-side module for web sites designed to efficiently visualize and disseminate gene and protein sequences. SnipViz is open source and is freely available at https://github.com/yeastrc/snipviz.

Social grooming among wild bonobos (Pan paniscus) at Wamba in the Luo Scientific Reserve, DR Congo, with special reference to the formation of grooming gatherings.

PubMed

Sakamaki, Tetsuya

2013-10-01

Chimpanzees (Pan troglodytes) groom in gatherings in which many individuals may be connected via multiple chains of grooming and they often exchange partners with each other. They sometimes groom another while receiving grooming; that is, one animal can play two roles (i.e., groomer and groomee) simultaneously. Although this feature of chimpanzees is notable from the viewpoint of the evolution of human sociality, information on our other closest living relative, the bonobo (Pan paniscus), is still lacking. In this study, I describe grooming interactions of bonobos at Wamba in the Luo Scientific Reserve, Democratic Republic of the Congo (DR Congo), with a particular focus on the formation of grooming gatherings. Like chimpanzees, the bonobos also performed mutual grooming (two individuals grooming each other simultaneously) and polyadic grooming (three or more individuals). However, unlike chimpanzees, these sessions lasted for only a short time. Bonobos rarely groomed another while receiving grooming. Because social grooming occurred not only in trees but also in open spaces, including treefall gaps, the conditions did not necessarily limit the opportunity to make multiple chains of grooming. However, bonobos also engaged in social grooming in different ways from chimpanzees; That is, many individuals were involved simultaneously at a site, in which they separated for dyadic grooming. Some cases clearly showed that bonobos preferred a third party not to join while grooming in a dyad, suggesting that bonobos have a preference for grooming in dyads and that immature individuals formed the preference that was shared among adults while growing up. Most members of the study group ranged together during the majority of the study period. Although bonobos show a fission-fusion grouping pattern, when group members frequently encounter one another on a daily basis, they may not be motivated to form multiple grooming chains at this site, as do chimpanzees.

Simultaneous Biatrial High-Density (510-512 Electrodes) Epicardial Mapping of Persistent and Long-Standing Persistent Atrial Fibrillation in Patients: New Insights Into the Mechanism of Its Maintenance.

PubMed

Lee, Seungyup; Sahadevan, Jayakumar; Khrestian, Celeen M; Cakulev, Ivan; Markowitz, Alan; Waldo, Albert L

2015-12-01

The mechanism(s) of persistent and long-standing persistent (LSP) atrial fibrillation (AF) is/are poorly understood. We performed high-density, simultaneous, biatrial, epicardial mapping of persistent and LSP AF in patients undergoing open heart surgery (1) to test the hypothesis that persistent and LSP AF are due to ≥ 1 drivers, either focal or reentrant, and (2) to characterize associated atrial activation. Twelve patients with persistent and LSP AF (1 month to 9 years duration) were studied at open heart surgery. During AF, electrograms were recorded from both atria simultaneously for 1 to 5 minutes from 510 to 512 epicardial electrodes with ECG lead II. Thirty-two consecutive seconds of activation sequence maps were produced per patient. During AF, multiple foci (QS unipolar atrial electrograms) of different cycle lengths (mean, 175 ± 18 ms) were present in both atria in 11 of 12 patients. Foci (2-4 per patient, duration 5-32 s) were either sustained or intermittent, were predominantly found in the lateral left atrial free wall, and likely acted as drivers. Random and nonrandom breakthrough activation sites (initial r or R in unipolar atrial electrograms) were also found. In 1 of 12 patients, only breakthrough sites were found. All wave fronts emanated from foci and breakthrough sites, and largely either collided or merged with each other at variable sites. Repetitive focal QS activation occasionally generated repetitive wannabe reentrant activation in 5 of 12 patients. No actual reentry was found. During persistent and LSP AF in 12 patients, wave fronts emanating from foci and breakthrough sites maintained AF. No reentry was demonstrated. © 2015 American Heart Association, Inc.

Nanotechnology as a therapeutic tool to combat microbial resistance.

PubMed

Pelgrift, Robert Y; Friedman, Adam J

2013-11-01

Use of nanoparticles is among the most promising strategies to overcome microbial drug resistance. This review article consists of three parts. The first part discusses the epidemiology of microbial drug resistance. The second part describes mechanisms of drug resistance used by microbes. The third part explains how nanoparticles can overcome this resistance, including the following: Nitric oxide-releasing nanoparticles (NO NPs), chitosan-containing nanoparticles (chitosan NPs), and metal-containing nanoparticles all use multiple mechanisms simultaneously to combat microbes, thereby making development of resistance to these nanoparticles unlikely. Packaging multiple antimicrobial agents within the same nanoparticle also makes development of resistance unlikely. Nanoparticles can overcome existing drug resistance mechanisms, including decreased uptake and increased efflux of drug from the microbial cell, biofilm formation, and intracellular bacteria. Finally, nanoparticles can target antimicrobial agents to the site of infection, so that higher doses of drug are given at the infected site, thereby overcoming resistance. © 2013.

Principal component analysis of chemical shift perturbation data of a multiple-ligand-binding system for elucidation of respective binding mechanism.

PubMed

Konuma, Tsuyoshi; Lee, Young-Ho; Goto, Yuji; Sakurai, Kazumasa

2013-01-01

Chemical shift perturbations (CSPs) in NMR spectra provide useful information about the interaction of a protein with its ligands. However, in a multiple-ligand-binding system, determining quantitative parameters such as a dissociation constant (K(d) ) is difficult. Here, we used a method we named CS-PCA, a principal component analysis (PCA) of chemical shift (CS) data, to analyze the interaction between bovine β-lactoglobulin (βLG) and 1-anilinonaphthalene-8-sulfonate (ANS), which is a multiple-ligand-binding system. The CSP on the binding of ANS involved contributions from two distinct binding sites. PCA of the titration data successfully separated the CSP pattern into contributions from each site. Docking simulations based on the separated CSP patterns provided the structures of βLG-ANS complexes for each binding site. In addition, we determined the K(d) values as 3.42 × 10⁻⁴ M² and 2.51 × 10⁻³ M for Sites 1 and 2, respectively. In contrast, it was difficult to obtain reliable K(d) values for respective sites from the isothermal titration calorimetry experiments. Two ANS molecules were found to bind at Site 1 simultaneously, suggesting that the binding occurs cooperatively with a partial unfolding of the βLG structure. On the other hand, the binding of ANS to Site 2 was a simple attachment without a significant conformational change. From the present results, CS-PCA was confirmed to provide not only the positions and the K(d) values of binding sites but also information about the binding mechanism. Thus, it is anticipated to be a general method to investigate protein-ligand interactions. Copyright © 2012 Wiley Periodicals, Inc.

Paraneoplastic Sarcoidosis in Multiple Myeloma.

PubMed

Kusaba, Kana; Kojima, Kensuke; Naito, Shinji; Taba, Mitsuru; Kai, Keita; Ureshino, Hiroshi; Nishida, Yuki; Kimura, Shinya

2017-01-01

Sarcoidosis predominantly affects the lungs, intrathoracic lymph nodes, and eyes; it less frequently affects the musculoskeletal system. We herein report a case of paraneoplastic sarcoidosis in a patient presenting with multiple myeloma. The patient developed ocular sarcoidosis and showed an increased 18 F-fluorodeoxyglucose uptake in the mediastinal lymph nodes and vertebral column. A lymph node specimen showed the histological features of sarcoidosis, while an examination of the vertebral tumor revealed myeloma. Although the simultaneous occurrence of sarcoidosis and myeloma is extremely rare, our case indicates the importance of exculing any underlying malignancies before establishing a diagnosis of skeletal sarcoidosis when bone lesions are observed at unusual sites.

Coronary artery aneurysm combined with other multiple aneurysms at multiple locations: A case report and systematic review.

PubMed

Jiang, Li-Cheng; Cao, Jia-Yu; Chen, Mao

2017-12-01

Coronary artery aneurysm (CAA) with concomitant aneurysms at multiple sites is quite unusual and rare. The characteristics and the etiology of this phenomenon are unknown. Herein, we present a case with right coronary aneurysm with concomitant abdominal aorta as well as right renal artery aneurysm. A systematic review of the literatures regarding CAA with other coexisting aneurysms at multiple locations was also conducted on Medline and Embase databases. A total of 76 patients (male gender: 58; age: 37.4 ± 26.5) including the present case were included in the final study. The most common etiology of CAA with multiple aneurysms was Kawasaki (43.3%) and atherosclerotic disease (16.4%). CAA was the most frequently found at the right coronary artery (62.7%), following, left anterior descending (51%), left main (43.1%), and left circumflex (35.3%). The most common concomitant aneurysms were abdominal aorta (52.6%) and iliac artery (50%). In addition, 60.5% of the patients had an involved bilateral peripheral artery. CAA with coexisting systemic aneurysms in multiple sites is quite rare. And it usually involves multiple aneurysms at the coronary and bilateral peripheral arteries simultaneously. Currently, there are no general consensus regarding the clinical characteristics, diagnostic method, and treatment of these cases. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Microfabricated capillary electrophoresis chip and method for simultaneously detecting multiple redox labels

DOEpatents

Mathies, Richard A.; Singhal, Pankaj; Xie, Jin; Glazer, Alexander N.

2002-01-01

This invention relates to a microfabricated capillary electrophoresis chip for detecting multiple redox-active labels simultaneously using a matrix coding scheme and to a method of selectively labeling analytes for simultaneous electrochemical detection of multiple label-analyte conjugates after electrophoretic or chromatographic separation.

Multiple-robot drug delivery strategy through coordinated teams of microswimmers

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

Kei Cheang, U; Kim, Min Jun, E-mail: mkim@coe.drexel.edu; Lee, Kyoungwoo

2014-08-25

Untethered robotic microswimmers are very promising to significantly improve various types of minimally invasive surgeries by offering high accuracy at extremely small scales. A prime example is drug delivery, for which a large number of microswimmers is required to deliver sufficient dosages to target sites. For this reason, the controllability of groups of microswimmers is essential. In this paper, we demonstrate simultaneous control of multiple geometrically similar but magnetically different microswimmers using a single global rotating magnetic field. By exploiting the differences in their magnetic properties, we triggered different swimming behaviors from the microswimmers by controlling the frequency and themore » strength of the global field, for example, one swim and the other does not while exposed to the same control input. Our results show that the balance between the applied magnetic torque and the hydrodynamic torque can be exploited for simultaneous control of two microswimmers to swim in opposite directions, with different velocities, and with similar velocities. This work will serve to establish important concepts for future developments of control systems to manipulate multiple magnetically actuated microswimmers and a step towards using swarms of microswimmers as viable workforces for complex operations.« less

Calculations of the thermal and fast neutron fluxes in the Syrian miniature neutron source reactor using the MCNP-4C code.

PubMed

Khattab, K; Sulieman, I

2009-04-01

The MCNP-4C code, based on the probabilistic approach, was used to model the 3D configuration of the core of the Syrian miniature neutron source reactor (MNSR). The continuous energy neutron cross sections from the ENDF/B-VI library were used to calculate the thermal and fast neutron fluxes in the inner and outer irradiation sites of MNSR. The thermal fluxes in the MNSR inner irradiation sites were also measured experimentally by the multiple foil activation method ((197)Au (n, gamma) (198)Au and (59)Co (n, gamma) (60)Co). The foils were irradiated simultaneously in each of the five MNSR inner irradiation sites to measure the thermal neutron flux and the epithermal index in each site. The calculated and measured results agree well.

Simultaneous quantification of protein phosphorylation sites using liquid chromatography-tandem mass spectrometry-based targeted proteomics: a linear algebra approach for isobaric phosphopeptides.

PubMed

Xu, Feifei; Yang, Ting; Sheng, Yuan; Zhong, Ting; Yang, Mi; Chen, Yun

2014-12-05

As one of the most studied post-translational modifications (PTM), protein phosphorylation plays an essential role in almost all cellular processes. Current methods are able to predict and determine thousands of phosphorylation sites, whereas stoichiometric quantification of these sites is still challenging. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)-based targeted proteomics is emerging as a promising technique for site-specific quantification of protein phosphorylation using proteolytic peptides as surrogates of proteins. However, several issues may limit its application, one of which relates to the phosphopeptides with different phosphorylation sites and the same mass (i.e., isobaric phosphopeptides). While employment of site-specific product ions allows for these isobaric phosphopeptides to be distinguished and quantified, site-specific product ions are often absent or weak in tandem mass spectra. In this study, linear algebra algorithms were employed as an add-on to targeted proteomics to retrieve information on individual phosphopeptides from their common spectra. To achieve this simultaneous quantification, a LC-MS/MS-based targeted proteomics assay was first developed and validated for each phosphopeptide. Given the slope and intercept of calibration curves of phosphopeptides in each transition, linear algebraic equations were developed. Using a series of mock mixtures prepared with varying concentrations of each phosphopeptide, the reliability of the approach to quantify isobaric phosphopeptides containing multiple phosphorylation sites (≥ 2) was discussed. Finally, we applied this approach to determine the phosphorylation stoichiometry of heat shock protein 27 (HSP27) at Ser78 and Ser82 in breast cancer cells and tissue samples.

Optimal Design of Multitype Groundwater Monitoring Networks Using Easily Accessible Tools.

PubMed

Wöhling, Thomas; Geiges, Andreas; Nowak, Wolfgang

2016-11-01

Monitoring networks are expensive to establish and to maintain. In this paper, we extend an existing data-worth estimation method from the suite of PEST utilities with a global optimization method for optimal sensor placement (called optimal design) in groundwater monitoring networks. Design optimization can include multiple simultaneous sensor locations and multiple sensor types. Both location and sensor type are treated simultaneously as decision variables. Our method combines linear uncertainty quantification and a modified genetic algorithm for discrete multilocation, multitype search. The efficiency of the global optimization is enhanced by an archive of past samples and parallel computing. We demonstrate our methodology for a groundwater monitoring network at the Steinlach experimental site, south-western Germany, which has been established to monitor river-groundwater exchange processes. The target of optimization is the best possible exploration for minimum variance in predicting the mean travel time of the hyporheic exchange. Our results demonstrate that the information gain of monitoring network designs can be explored efficiently and with easily accessible tools prior to taking new field measurements or installing additional measurement points. The proposed methods proved to be efficient and can be applied for model-based optimal design of any type of monitoring network in approximately linear systems. Our key contributions are (1) the use of easy-to-implement tools for an otherwise complex task and (2) yet to consider data-worth interdependencies in simultaneous optimization of multiple sensor locations and sensor types. © 2016, National Ground Water Association.

Parallel, confocal, and complete spectrum imager for fluorescent detection of high-density microarray

NASA Astrophysics Data System (ADS)

Bogdanov, Valery L.; Boyce-Jacino, Michael

1999-05-01

Confined arrays of biochemical probes deposited on a solid support surface (analytical microarray or 'chip') provide an opportunity to analysis multiple reactions simultaneously. Microarrays are increasingly used in genetics, medicine and environment scanning as research and analytical instruments. A power of microarray technology comes from its parallelism which grows with array miniaturization, minimization of reagent volume per reaction site and reaction multiplexing. An optical detector of microarray signals should combine high sensitivity, spatial and spectral resolution. Additionally, low-cost and a high processing rate are needed to transfer microarray technology into biomedical practice. We designed an imager that provides confocal and complete spectrum detection of entire fluorescently-labeled microarray in parallel. Imager uses microlens array, non-slit spectral decomposer, and high- sensitive detector (cooled CCD). Two imaging channels provide a simultaneous detection of localization, integrated and spectral intensities for each reaction site in microarray. A dimensional matching between microarray and imager's optics eliminates all in moving parts in instrumentation, enabling highly informative, fast and low-cost microarray detection. We report theory of confocal hyperspectral imaging with microlenses array and experimental data for implementation of developed imager to detect fluorescently labeled microarray with a density approximately 103 sites per cm2.

Simultaneous and Sequential Integration by Cre/loxP Site-Specific Recombination in Saccharomyces cerevisiae.

PubMed

Choi, Ho-Jung; Kim, Yeon-Hee

2018-05-28

A Cre/ loxP -δ-integration system was developed to allow sequential and simultaneous integration of a multiple gene expression cassette in Saccharomyces cerevisiae . To allow repeated integrations, the reusable Candida glabrata MARKER ( CgMARKER ) carrying loxP sequences was used, and the integrated CgMARKER was efficiently removed by inducing Cre recombinase. The XYLP and XYLB genes encoding endoxylanase and β-xylosidase, respectively, were used as model genes for xylan metabolism in this system, and the copy number of these genes was increased to 15.8 and 16.9 copies/cell, respectively, by repeated integration. This integration system is a promising approach for the easy construction of yeast strains with enhanced metabolic pathways through multicopy gene expression.

Surgical treatment of traumatic multiple intracranial hematomas

PubMed Central

Yang, Chaohua; Li, Qiang; Wu, Cong; Zan, Xin; You, Chao

2014-01-01

Objective: To summarize our experience with the surgical treatment of traumatic multiple intracranial hematomas (TMIHs) and discuss the surgical indications. Methods: We analyzed the clinical data of 118 patients with TMIHs who were treated at the West China Hospital in Sichuan University, Chengdu, China between October 2008 and October 2011, including age, gender, cause of injury, diagnosis, treatment, and outcomes. Results: Among the 118 patients, there were 12 patients with different types of hematomas at the same site, 69 with one hematoma type in different compartments, and 37 with different types of hematomas in different compartments. In total, 106 patients had obliteration of basal cisterns, and 34 had a simultaneous midline shift ≥5 mm. Eighty-nine patients underwent single-site surgery, 19 had 2-site surgeries, and 10 patients did not undergo surgery. Based on the Glasgow Outcome Scale 6 months post-injury, 41 patients had favorable outcomes, and 77 had unfavorable outcomes. Basal cisterns obliteration was a strong indicator for surgical treatment. Single- or 2-site surgery was not related to outcome (p=0.234). Conclusion: Obliteration of the basal cisterns is a strong indication for surgical treatment of TMIHs. After evacuation of the major hematomas, the remaining hematomas can be treated conservatively. Most patients only require single-site surgical treatment. PMID:25274591

Multi-focal multiphoton lithography.

PubMed

Ritschdorff, Eric T; Nielson, Rex; Shear, Jason B

2012-03-07

Multiphoton lithography (MPL) provides unparalleled capabilities for creating high-resolution, three-dimensional (3D) materials from a broad spectrum of building blocks and with few limitations on geometry, qualities that have been key to the design of chemically, mechanically, and biologically functional microforms. Unfortunately, the reliance of MPL on laser scanning limits the speed at which fabrication can be performed, making it impractical in many instances to produce large-scale, high-resolution objects such as complex micromachines, 3D microfluidics, etc. Previously, others have demonstrated the possibility of using multiple laser foci to simultaneously perform MPL at numerous sites in parallel, but use of a stage-scanning system to specify fabrication coordinates resulted in the production of identical features at each focal position. As a more general solution to the bottleneck problem, we demonstrate here the feasibility for performing multi-focal MPL using a dynamic mask to differentially modulate foci, an approach that enables each fabrication site to create independent (uncorrelated) features within a larger, integrated microform. In this proof-of-concept study, two simultaneously scanned foci produced the expected two-fold decrease in fabrication time, and this approach could be readily extended to many scanning foci by using a more powerful laser. Finally, we show that use of multiple foci in MPL can be exploited to assign heterogeneous properties (such as differential swelling) to micromaterials at distinct positions within a fabrication zone.

Dynamic Neurovascular Coupling and Uncoupling during Ictal Onset, Propagation, and Termination Revealed by Simultaneous In Vivo Optical Imaging of Neural Activity and Local Blood Volume

PubMed Central

Zhao, Mingrui; Schwartz, Theodore H.

2013-01-01

Traditional models of ictal propagation involve the concept of an initiation site and a progressive outward march of activation. The process of neurovascular coupling, whereby the brain supplies oxygenated blood to metabolically active neurons presumably results in a similar outward cascade of hyperemia. However, ictal neurovascular coupling has never been assessed in vivo using simultaneous measurements of membrane potential change and hyperemia with wide spatial sampling. In an acute rat ictal model, using simultaneous intrinsic optical signal (IOS) and voltage-sensitive dye (VSD) imaging of cerebral blood volume and membrane potential changes, we demonstrate that seizures consist of multiple dynamic multidirectional waves of membrane potential change with variable onset sites that spread through a widespread network. Local blood volume evolves on a much slower spatiotemporal scale. At seizure onset, the VSD waves extend beyond the IOS signal. During evolution, spatial correlation with hemodynamic signal only exists briefly at the maximal spread of the VSD signal. At termination, the IOS signal extends spatially and temporally beyond the VSD waves. Hence, vascular reactivity evolves in a separate but parallel fashion to membrane potential changes resulting in a mechanism of neurovascular coupling and uncoupling, which is as dynamic as the seizure itself. PMID:22499798

DETECTION OF FAST RADIO TRANSIENTS WITH MULTIPLE STATIONS: A CASE STUDY USING THE VERY LONG BASELINE ARRAY

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

Thompson, David R.; Wagstaff, Kiri L.; Majid, Walid A.

2011-07-10

Recent investigations reveal an important new class of transient radio phenomena that occur on submillisecond timescales. Often, transient surveys' data volumes are too large to archive exhaustively. Instead, an online automatic system must excise impulsive interference and detect candidate events in real time. This work presents a case study using data from multiple geographically distributed stations to perform simultaneous interference excision and transient detection. We present several algorithms that incorporate dedispersed data from multiple sites, and report experiments with a commensal real-time transient detection system on the Very Long Baseline Array. We test the system using observations of pulsar B0329+54.more » The multiple-station algorithms enhanced sensitivity for detection of individual pulses. These strategies could improve detection performance for a future generation of geographically distributed arrays such as the Australian Square Kilometre Array Pathfinder and the Square Kilometre Array.« less

Semantics-based distributed I/O with the ParaMEDIC framework.

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

Balaji, P.; Feng, W.; Lin, H.

2008-01-01

Many large-scale applications simultaneously rely on multiple resources for efficient execution. For example, such applications may require both large compute and storage resources; however, very few supercomputing centers can provide large quantities of both. Thus, data generated at the compute site oftentimes has to be moved to a remote storage site for either storage or visualization and analysis. Clearly, this is not an efficient model, especially when the two sites are distributed over a wide-area network. Thus, we present a framework called 'ParaMEDIC: Parallel Metadata Environment for Distributed I/O and Computing' which uses application-specific semantic information to convert the generatedmore » data to orders-of-magnitude smaller metadata at the compute site, transfer the metadata to the storage site, and re-process the metadata at the storage site to regenerate the output. Specifically, ParaMEDIC trades a small amount of additional computation (in the form of data post-processing) for a potentially significant reduction in data that needs to be transferred in distributed environments.« less

A Robust CRISPR/Cas9 System for Convenient, High-Efficiency Multiplex Genome Editing in Monocot and Dicot Plants.

PubMed

Ma, Xingliang; Zhang, Qunyu; Zhu, Qinlong; Liu, Wei; Chen, Yan; Qiu, Rong; Wang, Bin; Yang, Zhongfang; Li, Heying; Lin, Yuru; Xie, Yongyao; Shen, Rongxin; Chen, Shuifu; Wang, Zhi; Chen, Yuanling; Guo, Jingxin; Chen, Letian; Zhao, Xiucai; Dong, Zhicheng; Liu, Yao-Guang

2015-08-01

CRISPR/Cas9 genome targeting systems have been applied to a variety of species. However, most CRISPR/Cas9 systems reported for plants can only modify one or a few target sites. Here, we report a robust CRISPR/Cas9 vector system, utilizing a plant codon optimized Cas9 gene, for convenient and high-efficiency multiplex genome editing in monocot and dicot plants. We designed PCR-based procedures to rapidly generate multiple sgRNA expression cassettes, which can be assembled into the binary CRISPR/Cas9 vectors in one round of cloning by Golden Gate ligation or Gibson Assembly. With this system, we edited 46 target sites in rice with an average 85.4% rate of mutation, mostly in biallelic and homozygous status. We reasoned that about 16% of the homozygous mutations in rice were generated through the non-homologous end-joining mechanism followed by homologous recombination-based repair. We also obtained uniform biallelic, heterozygous, homozygous, and chimeric mutations in Arabidopsis T1 plants. The targeted mutations in both rice and Arabidopsis were heritable. We provide examples of loss-of-function gene mutations in T0 rice and T1 Arabidopsis plants by simultaneous targeting of multiple (up to eight) members of a gene family, multiple genes in a biosynthetic pathway, or multiple sites in a single gene. This system has provided a versatile toolbox for studying functions of multiple genes and gene families in plants for basic research and genetic improvement. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Fatigue failure of hydrogen embrittled high strength steels

NASA Technical Reports Server (NTRS)

Kim, Y. G.; Aleszka, J.

1975-01-01

Results of an experimental investigation are presented concerning the fracture behavior of cathodically charged, quenched and tempered martensitic steels under cyclic load conditions. Introduction of H2 by cathodic charging reduced fatigue life by as much as 60%. It is proposed that subsurface transverse fatigue cracks nucleate simultaneously at multiple sites, such as at microcracks, voids, or inclusions. Fatigue crack growth then occurs on planes perpendicular to the major applied stress axis in the presence of the critical combination of applied external stress and hydrogen.

True bilateral nasopharyngeal angiofibroma: report and review.

PubMed

Mishra, Anupam; Mishra, Subhash Chandra

2016-10-01

This report describes the third case of a true bilateral Juvenile nasopharyngeal angiofibroma (JNA), i.e. two separate JNA arising from both sides simultaneously. The associated multiple recurrences in such a case have not yet been reported. A 21-year-man underwent transpalatal excision and recurred twice. The last 'neo-occurrence' encountered after 2 years was at a different site and was subsequently managed by post-embolization endoscopic resection. A complete report of its clinico-radiological features and management outcome is discussed.

Kinetics of heavy metal adsorption and desorption in soil: Developing a unified model based on chemical speciation

NASA Astrophysics Data System (ADS)

Peng, Lanfang; Liu, Paiyu; Feng, Xionghan; Wang, Zimeng; Cheng, Tao; Liang, Yuzhen; Lin, Zhang; Shi, Zhenqing

2018-03-01

Predicting the kinetics of heavy metal adsorption and desorption in soil requires consideration of multiple heterogeneous soil binding sites and variations of reaction chemistry conditions. Although chemical speciation models have been developed for predicting the equilibrium of metal adsorption on soil organic matter (SOM) and important mineral phases (e.g. Fe and Al (hydr)oxides), there is still a lack of modeling tools for predicting the kinetics of metal adsorption and desorption reactions in soil. In this study, we developed a unified model for the kinetics of heavy metal adsorption and desorption in soil based on the equilibrium models WHAM 7 and CD-MUSIC, which specifically consider metal kinetic reactions with multiple binding sites of SOM and soil minerals simultaneously. For each specific binding site, metal adsorption and desorption rate coefficients were constrained by the local equilibrium partition coefficients predicted by WHAM 7 or CD-MUSIC, and, for each metal, the desorption rate coefficients of various binding sites were constrained by their metal binding constants with those sites. The model had only one fitting parameter for each soil binding phase, and all other parameters were derived from WHAM 7 and CD-MUSIC. A stirred-flow method was used to study the kinetics of Cd, Cu, Ni, Pb, and Zn adsorption and desorption in multiple soils under various pH and metal concentrations, and the model successfully reproduced most of the kinetic data. We quantitatively elucidated the significance of different soil components and important soil binding sites during the adsorption and desorption kinetic processes. Our model has provided a theoretical framework to predict metal adsorption and desorption kinetics, which can be further used to predict the dynamic behavior of heavy metals in soil under various natural conditions by coupling other important soil processes.

A distribution-oriented approach to support landscape connectivity for ecologically distinct bird species.

PubMed

Herrera, José M; Alagador, Diogo; Salgueiro, Pedro; Mira, António

2018-01-01

Managing landscape connectivity is a widely recognized overarching strategy for conserving biodiversity in human-impacted landscapes. However, planning the conservation and management of landscape connectivity of multiple and ecologically distinct species is still challenging. Here we provide a spatially-explicit framework which identifies and prioritizes connectivity conservation and restoration actions for species with distinct habitat affinities. Specifically, our study system comprised three groups of common bird species, forest-specialists, farmland-specialists, and generalists, populating a highly heterogeneous agricultural countryside in the southwestern Iberian Peninsula. We first performed a comprehensive analysis of the environmental variables underlying the distributional patterns of each bird species to reveal generalities in their guild-specific responses to landscape structure. Then, we identified sites which could be considered pivotal in maintaining current levels of landscape connectivity for the three bird guilds simultaneously, as well as the number and location of sites that need to be restored to maximize connectivity levels. Interestingly, we found that a small number of sites defined the shortest connectivity paths for the three bird guilds simultaneously, and were therefore considered key for conservation. Moreover, an even smaller number of sites were identified as critical to expand the landscape connectivity at maximum for the regional bird assemblage as a whole. Our spatially-explicit framework can provide valuable decision-making support to conservation practitioners aiming to identify key connectivity and restoration sites, a particularly urgent task in rapidly changing landscapes such as agroecosystems.

A distribution-oriented approach to support landscape connectivity for ecologically distinct bird species

PubMed Central

Salgueiro, Pedro; Mira, António

2018-01-01

Managing landscape connectivity is a widely recognized overarching strategy for conserving biodiversity in human-impacted landscapes. However, planning the conservation and management of landscape connectivity of multiple and ecologically distinct species is still challenging. Here we provide a spatially-explicit framework which identifies and prioritizes connectivity conservation and restoration actions for species with distinct habitat affinities. Specifically, our study system comprised three groups of common bird species, forest-specialists, farmland-specialists, and generalists, populating a highly heterogeneous agricultural countryside in the southwestern Iberian Peninsula. We first performed a comprehensive analysis of the environmental variables underlying the distributional patterns of each bird species to reveal generalities in their guild-specific responses to landscape structure. Then, we identified sites which could be considered pivotal in maintaining current levels of landscape connectivity for the three bird guilds simultaneously, as well as the number and location of sites that need to be restored to maximize connectivity levels. Interestingly, we found that a small number of sites defined the shortest connectivity paths for the three bird guilds simultaneously, and were therefore considered key for conservation. Moreover, an even smaller number of sites were identified as critical to expand the landscape connectivity at maximum for the regional bird assemblage as a whole. Our spatially-explicit framework can provide valuable decision-making support to conservation practitioners aiming to identify key connectivity and restoration sites, a particularly urgent task in rapidly changing landscapes such as agroecosystems. PMID:29641610

Assessing the effects of multiple stressors on the functioning of Mediterranean rivers using poplar wood breakdown.

PubMed

Aristi, Ibon; Díez, Jose Ramon; Larrañaga, Aitor; Navarro-Ortega, Alícia; Barceló, Damià; Elosegi, Arturo

2012-12-01

Mediterranean rivers in the Iberian Peninsula are being increasingly affected by human activities, which threaten their ecological status. A clear picture of how do these multiple stressors affect river ecosystem functioning is still lacking. We addressed this question by measuring a key ecosystem process, namely breakdown of organic matter, at 66 sites distributed across Mediterranean Spain. We performed breakdown experiments by measuring the mass lost by wood sticks for 54 to 106 days. Additionally, we gathered data on physico-chemical, biological and geomorphological characteristics of study sites. Study sites spanned a broad range of environmental characteristics and breakdown rates varied fiftyfold across sites. No clear geographic patterns were found between or within basins. 90th quantile regressions performed to link breakdown rates with environmental characteristics included the following 7 variables in the model, in decreasing order of importance: altitude, water content in phosphorus, catchment area, toxicity, invertebrate-based biotic index, riparian buffer width, and diatom-based quality index. Breakdown rate was systematically low in high-altitude rivers with few human impacts, but showed a high variability in areas affected by human activity. This increase in variability is the result of the influence of multiple stressors acting simultaneously, as some of these can promote whereas others slow down the breakdown of organic matter. Therefore, stick breakdown gives information on the intensity of a key ecosystem process, which would otherwise be very difficult to predict based on environmental variables. Copyright © 2012 Elsevier B.V. All rights reserved.

One-Tube-Only Standardized Site-Directed Mutagenesis: An Alternative Approach to Generate Amino Acid Substitution Collections

PubMed Central

Mingo, Janire; Erramuzpe, Asier; Luna, Sandra; Aurtenetxe, Olaia; Amo, Laura; Diez, Ibai; Schepens, Jan T. G.; Hendriks, Wiljan J. A. J.; Cortés, Jesús M.; Pulido, Rafael

2016-01-01

Site-directed mutagenesis (SDM) is a powerful tool to create defined collections of protein variants for experimental and clinical purposes, but effectiveness is compromised when a large number of mutations is required. We present here a one-tube-only standardized SDM approach that generates comprehensive collections of amino acid substitution variants, including scanning- and single site-multiple mutations. The approach combines unified mutagenic primer design with the mixing of multiple distinct primer pairs and/or plasmid templates to increase the yield of a single inverse-PCR mutagenesis reaction. Also, a user-friendly program for automatic design of standardized primers for Ala-scanning mutagenesis is made available. Experimental results were compared with a modeling approach together with stochastic simulation data. For single site-multiple mutagenesis purposes and for simultaneous mutagenesis in different plasmid backgrounds, combination of primer sets and/or plasmid templates in a single reaction tube yielded the distinct mutations in a stochastic fashion. For scanning mutagenesis, we found that a combination of overlapping primer sets in a single PCR reaction allowed the yield of different individual mutations, although this yield did not necessarily follow a stochastic trend. Double mutants were generated when the overlap of primer pairs was below 60%. Our results illustrate that one-tube-only SDM effectively reduces the number of reactions required in large-scale mutagenesis strategies, facilitating the generation of comprehensive collections of protein variants suitable for functional analysis. PMID:27548698

Development and evaluation of a real-time fluorogenic loop-mediated isothermal amplification assay integrated on a microfluidic disc chip (on-chip LAMP) for rapid and simultaneous detection of ten pathogenic bacteria in aquatic animals.

PubMed

Zhou, Qian-Jin; Wang, Lei; Chen, Jiong; Wang, Rui-Na; Shi, Yu-Hong; Li, Chang-Hong; Zhang, De-Min; Yan, Xiao-Jun; Zhang, Yan-Jun

2014-09-01

Rapid, low-cost, and user-friendly strategies are urgently needed for early disease diagnosis and timely treatment, particularly for on-site screening of pathogens in aquaculture. In this study, we successfully developed a real-time fluorogenic loop-mediated isothermal amplification assay integrated on a microfluidic disc chip (on-chip LAMP), which was capable of simultaneously detecting 10 pathogenic bacteria in aquatic animals, i.e., Nocardia seriolae, Pseudomonas putida, Streptococcus iniae, Vibrio alginolyticus, Vibrio anguillarum, Vibrio fluvialis, Vibrio harveyi, Vibrio parahaemolyticus, Vibrio rotiferianus, and Vibrio vulnificus. The assay provided a nearly-automated approach, with only a single pipetting step per chip for sample dispensing. This technique could achieve limits of detection (LOD) ranging from 0.40 to 6.42pg per 1.414μL reaction in less than 30 min. The robust reproducibility was demonstrated by a little variation among duplications for each bacterium with the coefficient of variation (CV) for time to positive (Tp) value less than 0.10. The clinical sensitivity and specificity of this on-chip LAMP assay in detecting field samples were 96.2% and 93.8% by comparison with conventional microbiological methods. Compared with other well-known techniques, on-chip LAMP assay provides low sample and reagent consumption, ease-of-use, accelerated analysis, multiple bacteria and on-site detection, and high reproducibility, indicating that such a technique would be applicable for on-site detection and routine monitoring of multiple pathogens in aquaculture. Copyright © 2014 Elsevier B.V. All rights reserved.

Flexible multielectrodes can resolve multiple muscles in an insect appendage.

PubMed

Spence, Andrew J; Neeves, Keith B; Murphy, Devon; Sponberg, Simon; Land, Bruce R; Hoy, Ronald R; Isaacson, Michael S

2007-01-15

Research into the neuromechanical basis of behavior, either in biomechanics, neuroethology, or neuroscience, is frequently limited by methods of data collection. Two of the most pressing needs are for methods with which to (1) record from multiple neurons or muscles simultaneously and (2) perform this recording in intact, behaving animals. In this paper we present the fabrication and testing of flexible multielectrode arrays (fMEAs) that move us significantly towards these goals. The fMEAs were used to record the activity of several distinct units in the coxa of the cockroach Blaberus discoidalis. The devices fabricated here address the first goal in two ways: (1) their flexibility allows them to be inserted into an animal and guided through internal tissues in order to access distinct groups of neurons and muscles and (2) their recording site geometry has been tuned to suit the anatomy under study, yielding multichannel spike waveforms that are easily separable under conditions of spike overlap. The flexible nature of the devices simultaneously addresses the second goal, in that it is less likely to interfere with the natural movement of the animal.

Multifunctional magnetic-optical nanoparticle probes for simultaneous detection, separation, and thermal ablation of multiple pathogens.

PubMed

Wang, Chungang; Irudayaraj, Joseph

2010-01-01

Multifunctional nanoparticles possessing magnetization and near-infrared (NIR) absorption have warranted interest due to their significant applications in magnetic resonance imaging, diagnosis, bioseparation, target delivery, and NIR photothermal ablation. Herein, the site-selective assembly of magnetic nanoparticles onto the ends or ends and sides of gold nanorods with different aspect ratios (ARs) to create multifunctional nanorods decorated with varying numbers of magnetic particles is described for the first time. The resulting hybrid nanoparticles are designated as Fe(3)O(4)-Au(rod)-Fe(3)O(4) nanodumbbells and Fe(3)O(4)-Au(rod) necklacelike constructs with tunable optical and magnetic properties, respectively. These hybrid nanomaterials can be used for multiplex detection and separation because of their tunable magnetic and plasmonic functionality. More specifically, Fe(3)O(4)-Au(rod) necklacelike probes of different ARs are utilized for simultaneous optical detection based on their plasmon properties, magnetic separation, and photokilling of multiple pathogens from a single sample at one time. The combined functionalities of the synthesized probes will open up many exciting opportunities in dual imaging for targeted delivery and photothermal therapy.

Direct duplex real-time loop mediated isothermal amplification assay for the simultaneous detection of cow and goat species origin of milk and yogurt products for field use.

PubMed

Kim, Mi-Ju; Kim, Hae-Yeong

2018-04-25

A multiple loop-mediated isothermal amplification (LAMP) method was developed to detect cow and goat milk in the field using a portable fluorescence device. For rapid on-site detection, this duplex LAMP assay was used in combination with direct amplification, without DNA extraction. The cow- and goat-specific LAMP primer sets were designed based on the mitochondrial cytochrome b gene, and showed specificity against 13 other animal species in the reactions. The sensitivity of the duplex LAMP assay for cow and goat was 0.1 and 1 pg, respectively. The detection limit for both target species in milk mixtures was 2%. This assay successfully amplified and identified the two target species in 24 samples of commercial milk and yogurt products, with 30 min sampling-to-result analysis time. Therefore, this direct duplex real-time LAMP assay is useful for on-site simultaneous detection of cow and goat milk in commercial products, a capability needed to confirm accurate labeling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Observations of the Ion Signatures of Double Merging and the Formation of Newly Closed Field Lines

NASA Technical Reports Server (NTRS)

Chandler, Michael O.; Avanov, Levon A.; Craven, Paul D.

2007-01-01

Observations from the Polar spacecraft, taken during a period of northward interplanetary magnetic field (IMF) show magnetosheath ions within the magnetosphere with velocity distributions resulting from multiple merging sites along the same field line. The observations from the TIDE instrument show two separate ion energy-time dispersions that are attributed to two widely separated (-20Re) merging sites. Estimates of the initial merging times show that they occurred nearly simultaneously (within 5 minutes.) Along with these populations, cold, ionospheric ions were observed counterstreaming along the field lines. The presence of such ions is evidence that these field lines are connected to the ionosphere on both ends. These results are consistent with the hypothesis that double merging can produce closed field lines populated by solar wind plasma. While the merging sites cannot be unambiguously located, the observations and analyses favor one site poleward of the northern cusp and a second site at low latitudes.

Tetramerization and interdomain flexibility of the replication initiation controller YabA enables simultaneous binding to multiple partners

PubMed Central

Felicori, Liza; Jameson, Katie H.; Roblin, Pierre; Fogg, Mark J.; Garcia-Garcia, Transito; Ventroux, Magali; Cherrier, Mickaël V.; Bazin, Alexandre; Noirot, Philippe; Wilkinson, Anthony J.; Molina, Franck; Terradot, Laurent; Noirot-Gros, Marie-Françoise

2016-01-01

YabA negatively regulates initiation of DNA replication in low-GC Gram-positive bacteria. The protein exerts its control through interactions with the initiator protein DnaA and the sliding clamp DnaN. Here, we combined X-ray crystallography, X-ray scattering (SAXS), modeling and biophysical approaches, with in vivo experimental data to gain insight into YabA function. The crystal structure of the N-terminal domain (NTD) of YabA solved at 2.7 Å resolution reveals an extended α-helix that contributes to an intermolecular four-helix bundle. Homology modeling and biochemical analysis indicates that the C-terminal domain (CTD) of YabA is a small Zn-binding domain. Multi-angle light scattering and SAXS demonstrate that YabA is a tetramer in which the CTDs are independent and connected to the N-terminal four-helix bundle via flexible linkers. While YabA can simultaneously interact with both DnaA and DnaN, we found that an isolated CTD can bind to either DnaA or DnaN, individually. Site-directed mutagenesis and yeast-two hybrid assays identified DnaA and DnaN binding sites on the YabA CTD that partially overlap and point to a mutually exclusive mode of interaction. Our study defines YabA as a novel structural hub and explains how the protein tetramer uses independent CTDs to bind multiple partners to orchestrate replication initiation in the bacterial cell. PMID:26615189

Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe

PubMed Central

Fiáth, Richárd; Beregszászi, Patrícia; Horváth, Domonkos; Wittner, Lucia; Aarts, Arno A. A.; Ruther, Patrick; Neves, Hercules P.; Bokor, Hajnalka; Acsády, László

2016-01-01

Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study. PMID:27535370

Correlation between skin-prick testing, individual specific IgE tests, and a multiallergen IgE assay for allergy detection in patients with chronic rhinitis.

PubMed

Cho, Jae Hoon; Suh, Jeffrey D; Kim, Jin Kook; Hong, Seok-Chan; Park, Il-Ho; Lee, Heung-Man

2014-01-01

Allergy test results can differ based on the method used. The most common tests include skin-prick testing (SPT) and in vitro tests to detect allergen-specific IgE. This study was designed to assess allergy test results using SPT, individual specific IgE tests, and a multiallergen IgE assay (multiple allergen simultaneous test) in patients with chronic rhinitis and controls. One hundred forty total patients were prospectively enrolled in the study, including 100 patients with chronic rhinitis and 40 control patients without atopy. All eligible patients underwent SPT, serum analysis using individual specific IgE test, and multiple allergen simultaneous test against 10 common allergens. Allergy test results were then compared to identify correlation and interest agreement. There was an 81-97% agreement between SPT and individual specific IgE test in allergen detection and an 80-98% agreement between SPT and multiple allergen simultaneous test. Individual specific IgE test and multiple allergen simultaneous test allergy detection prevalence was generally similar to SPT in patients with chronic rhinitis. All control patients had negative SPT (0/40), but low positive results were found with both individual specific IgE test (5-12.5%) and multiple allergen simultaneous test (2.5-7.5%) to some allergens, especially cockroach, Dermatophagoides farina, and ragweed. Agreement and correlation between individual specific IgE test and multiple allergen simultaneous test were good to excellent for a majority of tested allergens. This study shows good agreement and correlation between SPT with individual specific IgE test and multiple allergen simultaneous test on a majority of the tested allergens for patients with chronic rhinitis. Comparing the two in vitro tests, individual specific IgE test agrees with SPT better than multiple allergen simultaneous test.

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

PubMed Central

Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

2014-01-01

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

Multi-Site λ-dynamics for simulated Structure-Activity Relationship studies

PubMed Central

Knight, Jennifer L.; Brooks, Charles L.

2011-01-01

Multi-Site λ-dynamics (MSλD) is a new free energy simulation method that is based on λ-dynamics. It has been developed to enable multiple substituents at multiple sites on a common ligand core to be modeled simultaneously and their free energies assessed. The efficacy of MSλD for estimating relative hydration free energies and relative binding affinties is demonstrated using three test systems. Model compounds representing multiple identical benzene, dihydroxybenzene and dimethoxybenzene molecules show total combined MSλD trajectory lengths of ~1.5 ns are sufficient to reliably achieve relative hydration free energy estimates within 0.2 kcal/mol and are less sensitive to the number of trajectories that are used to generate these estimates for hybrid ligands that contain up to ten substituents modeled at a single site or five substituents modeled at each of two sites. Relative hydration free energies among six benzene derivatives calculated from MSλD simulations are in very good agreement with those from alchemical free energy simulations (with average unsigned differences of 0.23 kcal/mol and R2=0.991) and experiment (with average unsigned errors of 1.8 kcal/mol and R2=0.959). Estimates of the relative binding affinities among 14 inhibitors of HIV-1 reverse transcriptase obtained from MSλD simulations are in reasonable agreement with those from traditional free energy simulations and experiment (average unsigned errors of 0.9 kcal/mol and R2=0.402). For the same level of accuracy and precision MSλD simulations are achieved ~20–50 times faster than traditional free energy simulations and thus with reliable force field parameters can be used effectively to screen tens to hundreds of compounds in structure-based drug design applications. PMID:22125476

Hybrid-Lambda: simulation of multiple merger and Kingman gene genealogies in species networks and species trees.

PubMed

Zhu, Sha; Degnan, James H; Goldstien, Sharyn J; Eldon, Bjarki

2015-09-15

There has been increasing interest in coalescent models which admit multiple mergers of ancestral lineages; and to model hybridization and coalescence simultaneously. Hybrid-Lambda is a software package that simulates gene genealogies under multiple merger and Kingman's coalescent processes within species networks or species trees. Hybrid-Lambda allows different coalescent processes to be specified for different populations, and allows for time to be converted between generations and coalescent units, by specifying a population size for each population. In addition, Hybrid-Lambda can generate simulated datasets, assuming the infinitely many sites mutation model, and compute the F ST statistic. As an illustration, we apply Hybrid-Lambda to infer the time of subdivision of certain marine invertebrates under different coalescent processes. Hybrid-Lambda makes it possible to investigate biogeographic concordance among high fecundity species exhibiting skewed offspring distribution.

Multiple-electrode radiofrequency ablation: simultaneous production of separate zones of coagulation in an in vivo porcine liver model.

PubMed

Laeseke, Paul F; Sampson, Lisa A; Haemmerich, Dieter; Brace, Chris L; Fine, Jason P; Frey, Tina M; Winter, Thomas C; Lee, Fred T

2005-12-01

A multiple-electrode radiofrequency (RF) system was developed based on switching between electrodes that allows for the simultaneous use of as many as three electrically independent electrodes. The purpose of this study was to determine if each multiple-electrode ablation zone is identical to an ablation zone created with conventional single-electrode mode. Nine female domestic pigs (mean weight, 90 kg) were used for this study. A prototype monopolar multiple-electrode RF ablation system was created with use of an RF generator and an electronic switching algorithm. A maximum of three electrodes can be used simultaneously by switching between electrodes at each impedance spike (30 omega greater than baseline levels). A total of 39 zones of ablation were created at open laparotomy in pig livers with use of a conventional single electrode (n = 9), two single electrodes simultaneously (n = 6 ablations; 12 ablation zones), or three single electrodes simultaneously (n = 6 ablations; 18 ablation zones). RF electrodes were spaced in separate lobes of the liver when multiple zones of coagulation were created simultaneously. Animals were euthanized after RF ablation, livers were removed, and ablation zones were sectioned and measured. Zones of coagulation created simultaneously with two or three electrodes were equivalent to ablation zones created with use of conventional single-electrode ablation. No significant differences were observed among control animals treated with a single electrode, those with two separate zones of ablation created simultaneously, and those with three simultaneously created ablation zones in terms of mean (+/-SD) minimum diameter (1.6 cm +/- 0.6, 1.6 cm +/- 0.5, and 1.7 cm +/- 0.4, respectively), maximum diameter (2.0 cm +/- 0.5, 2.3 cm +/- 0.5, 2.2 cm +/- 0.5, respectively), and volume (6.7 cm3 +/- 3.7, 7.4 cm3 +/- 3.8, and 7.8 cm3 +/- 3.9; P > .30, analysis of variance, pairwise t-test comparisons). A rapid-switching multiple-electrode RF system was able to simultaneously create as many as three separate ablation zones of equivalent size compared with single-electrode controls. This system would allow physicians to simultaneously treat multiple tumors, substantially reducing procedure time and anesthesia risk.

Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions

DOEpatents

Beattie, Kenneth L.

1998-01-01

An improved microfabricated apparatus for conducting a multiplicity of individual and simultaneous binding reactions is described. The apparatus comprises a substrate on which are located discrete and isolated sites for binding reactions. The apparatus is characterized by discrete and isolated regions that extend through said substrate and terminate on a second surface thereof such that when a test sample is allowed to the substrate, it is capable of penetrating through each such region during the course of said binding reaction. The apparatus is especially useful for sequencing by hybridization of DNA molecules.

Simultaneous multiple non-crossing quantile regression estimation using kernel constraints

PubMed Central

Liu, Yufeng; Wu, Yichao

2011-01-01

Quantile regression (QR) is a very useful statistical tool for learning the relationship between the response variable and covariates. For many applications, one often needs to estimate multiple conditional quantile functions of the response variable given covariates. Although one can estimate multiple quantiles separately, it is of great interest to estimate them simultaneously. One advantage of simultaneous estimation is that multiple quantiles can share strength among them to gain better estimation accuracy than individually estimated quantile functions. Another important advantage of joint estimation is the feasibility of incorporating simultaneous non-crossing constraints of QR functions. In this paper, we propose a new kernel-based multiple QR estimation technique, namely simultaneous non-crossing quantile regression (SNQR). We use kernel representations for QR functions and apply constraints on the kernel coefficients to avoid crossing. Both unregularised and regularised SNQR techniques are considered. Asymptotic properties such as asymptotic normality of linear SNQR and oracle properties of the sparse linear SNQR are developed. Our numerical results demonstrate the competitive performance of our SNQR over the original individual QR estimation. PMID:22190842

Analytic hierarchy process-based approach for selecting a Pareto-optimal solution of a multi-objective, multi-site supply-chain planning problem

NASA Astrophysics Data System (ADS)

Ayadi, Omar; Felfel, Houssem; Masmoudi, Faouzi

2017-07-01

The current manufacturing environment has changed from traditional single-plant to multi-site supply chain where multiple plants are serving customer demands. In this article, a tactical multi-objective, multi-period, multi-product, multi-site supply-chain planning problem is proposed. A corresponding optimization model aiming to simultaneously minimize the total cost, maximize product quality and maximize the customer satisfaction demand level is developed. The proposed solution approach yields to a front of Pareto-optimal solutions that represents the trade-offs among the different objectives. Subsequently, the analytic hierarchy process method is applied to select the best Pareto-optimal solution according to the preferences of the decision maker. The robustness of the solutions and the proposed approach are discussed based on a sensitivity analysis and an application to a real case from the textile and apparel industry.

Detritus in K/T boundary clays of western North America - Evidence against a single oceanic impact

NASA Technical Reports Server (NTRS)

Sharpton, V. L.; Schuraytz, B. C.; Burke, K.; Murali, A. V.; Ryder, G.

1990-01-01

Understanding the crustal signature of impact ejecta contained in the Cretaceous/Tertiary (K/T) boundary layer is crucial to constraining the possible site(s) of the postulated K/T impact event. The relatively unaltered clastic constituents of the boundary layer at widely separated outcrops within the western interior of North America are not compatible with a single oceanic impact but require instead an impact site on a continent or continental margin. On the other hand, chemical compositions of highly altered K/T boundary layer components in some marine sections have suggested to others an impact into oceanic crust. We suspect that post-depositional alteration within the marine setting accounts for this apparent oceanic affinity. If, however, this is not the case, multiple simultaneous impacts, striking continent as well as ocean floor, would seem to be required.

Euk-mPLoc: a fusion classifier for large-scale eukaryotic protein subcellular location prediction by incorporating multiple sites.

PubMed

Chou, Kuo-Chen; Shen, Hong-Bin

2007-05-01

One of the critical challenges in predicting protein subcellular localization is how to deal with the case of multiple location sites. Unfortunately, so far, no efforts have been made in this regard except for the one focused on the proteins in budding yeast only. For most existing predictors, the multiple-site proteins are either excluded from consideration or assumed even not existing. Actually, proteins may simultaneously exist at, or move between, two or more different subcellular locations. For instance, according to the Swiss-Prot database (version 50.7, released 19-Sept-2006), among the 33,925 eukaryotic protein entries that have experimentally observed subcellular location annotations, 2715 have multiple location sites, meaning about 8% bearing the multiplex feature. Proteins with multiple locations or dynamic feature of this kind are particularly interesting because they may have some very special biological functions intriguing to investigators in both basic research and drug discovery. Meanwhile, according to the same Swiss-Prot database, the number of total eukaryotic protein entries (except those annotated with "fragment" or those with less than 50 amino acids) is 90,909, meaning a gap of (90,909-33,925) = 56,984 entries for which no knowledge is available about their subcellular locations. Although one can use the computational approach to predict the desired information for the blank, so far, all the existing methods for predicting eukaryotic protein subcellular localization are limited in the case of single location site only. To overcome such a barrier, a new ensemble classifier, named Euk-mPLoc, was developed that can be used to deal with the case of multiple location sites as well. Euk-mPLoc is freely accessible to the public as a Web server at http://202.120.37.186/bioinf/euk-multi. Meanwhile, to support the people working in the relevant areas, Euk-mPLoc has been used to identify all eukaryotic protein entries in the Swiss-Prot database that do not have subcellular location annotations or are annotated as being uncertain. The large-scale results thus obtained have been deposited at the same Web site via a downloadable file prepared with Microsoft Excel and named "Tab_Euk-mPLoc.xls". Furthermore, to include new entries of eukaryotic proteins and reflect the continuous development of Euk-mPLoc in both the coverage scope and prediction accuracy, we will timely update the downloadable file as well as the predictor, and keep users informed by publishing a short note in the Journal and making an announcement in the Web Page.

76 FR 1158 - Auction of 700 MHz Band Licenses Scheduled for July 19, 2011; Comment Sought on Competitive...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-07

... relating to Auction 92. A. Auction Structure i. Simultaneous Multiple-Round Auction Design 7. The Bureau proposes to auction all licenses included in Auction 92 using the Commission's standard simultaneous... competitiveness and economic efficiency of a simultaneous multiple-round auction may be enhanced if such...

Self-calibrated multiple-echo acquisition with radial trajectories using the conjugate gradient method (SMART-CG).

PubMed

Jung, Youngkyoo; Samsonov, Alexey A; Bydder, Mark; Block, Walter F

2011-04-01

To remove phase inconsistencies between multiple echoes, an algorithm using a radial acquisition to provide inherent phase and magnitude information for self correction was developed. The information also allows simultaneous support for parallel imaging for multiple coil acquisitions. Without a separate field map acquisition, a phase estimate from each echo in multiple echo train was generated. When using a multiple channel coil, magnitude and phase estimates from each echo provide in vivo coil sensitivities. An algorithm based on the conjugate gradient method uses these estimates to simultaneously remove phase inconsistencies between echoes, and in the case of multiple coil acquisition, simultaneously provides parallel imaging benefits. The algorithm is demonstrated on single channel, multiple channel, and undersampled data. Substantial image quality improvements were demonstrated. Signal dropouts were completely removed and undersampling artifacts were well suppressed. The suggested algorithm is able to remove phase cancellation and undersampling artifacts simultaneously and to improve image quality of multiecho radial imaging, the important technique for fast three-dimensional MRI data acquisition. Copyright © 2011 Wiley-Liss, Inc.

Self-calibrated Multiple-echo Acquisition with Radial Trajectories using the Conjugate Gradient Method (SMART-CG)

PubMed Central

Jung, Youngkyoo; Samsonov, Alexey A; Bydder, Mark; Block, Walter F.

2011-01-01

Purpose To remove phase inconsistencies between multiple echoes, an algorithm using a radial acquisition to provide inherent phase and magnitude information for self correction was developed. The information also allows simultaneous support for parallel imaging for multiple coil acquisitions. Materials and Methods Without a separate field map acquisition, a phase estimate from each echo in multiple echo train was generated. When using a multiple channel coil, magnitude and phase estimates from each echo provide in-vivo coil sensitivities. An algorithm based on the conjugate gradient method uses these estimates to simultaneously remove phase inconsistencies between echoes, and in the case of multiple coil acquisition, simultaneously provides parallel imaging benefits. The algorithm is demonstrated on single channel, multiple channel, and undersampled data. Results Substantial image quality improvements were demonstrated. Signal dropouts were completely removed and undersampling artifacts were well suppressed. Conclusion The suggested algorithm is able to remove phase cancellation and undersampling artifacts simultaneously and to improve image quality of multiecho radial imaging, the important technique for fast 3D MRI data acquisition. PMID:21448967

Field Trials of the Multi-Source Approach for Resistivity and Induced Polarization Data Acquisition

NASA Astrophysics Data System (ADS)

LaBrecque, D. J.; Morelli, G.; Fischanger, F.; Lamoureux, P.; Brigham, R.

2013-12-01

Implementing systems of distributed receivers and transmitters for resistivity and induced polarization data is an almost inevitable result of the availability of wireless data communication modules and GPS modules offering precise timing and instrument locations. Such systems have a number of advantages; for example, they can be deployed around obstacles such as rivers, canyons, or mountains which would be difficult with traditional 'hard-wired' systems. However, deploying a system of identical, small, battery powered, transceivers, each capable of injecting a known current and measuring the induced potential has an additional and less obvious advantage in that multiple units can inject current simultaneously. The original purpose for using multiple simultaneous current sources (multi-source) was to increase signal levels. In traditional systems, to double the received signal you inject twice the current which requires you to apply twice the voltage and thus four times the power. Alternatively, one approach to increasing signal levels for large-scale surveys collected using small, battery powered transceivers is it to allow multiple units to transmit in parallel. In theory, using four 400 watt transmitters on separate, parallel dipoles yields roughly the same signal as a single 6400 watt transmitter. Furthermore, implementing the multi-source approach creates the opportunity to apply more complex current flow patterns than simple, parallel dipoles. For a perfect, noise-free system, multi-sources adds no new information to a data set that contains a comprehensive set of data collected using single sources. However, for realistic, noisy systems, it appears that multi-source data can substantially impact survey results. In preliminary model studies, the multi-source data produced such startling improvements in subsurface images that even the authors questioned their veracity. Between December of 2012 and July of 2013, we completed multi-source surveys at five sites with depths of exploration ranging from 150 to 450 m. The sites included shallow geothermal sites near Reno Nevada, Pomarance Italy, and Volterra Italy; a mineral exploration site near Timmins Quebec; and a landslide investigation near Vajont Dam in northern Italy. These sites provided a series of challenges in survey design and deployment including some extremely difficult terrain and a broad range of background resistivity and induced values. Despite these challenges, comparison of multi-source results to resistivity and induced polarization data collection with more traditional methods support the thesis that the multi-source approach is capable of providing substantial improvements in both depth of penetration and resolution over conventional approaches.

Simultaneity, Sequentiality, and Speed: Organizational Messages about Multiple-Task Completion

ERIC Educational Resources Information Center

Stephens, Keri K.; Cho, Jaehee K.; Ballard, Dawna I.

2012-01-01

Workplace norms for task completion increasingly value speed and the ability to accomplish multiple tasks at once. This study situates this popularized issue of multitasking within the context of chronemics scholarship by addressing related issues of simultaneity, sequentiality, and speed. Ultimately, we consider 2 multiple-task completion…

Group specific internal standard technology (GSIST) for simultaneous identification and quantification of small molecules

DOEpatents

Adamec, Jiri; Yang, Wen-Chu; Regnier, Fred E

2014-01-14

Reagents and methods are provided that permit simultaneous analysis of multiple diverse small molecule analytes present in a complex mixture. Samples are labeled with chemically identical but isotopically distince forms of the labeling reagent, and analyzed using mass spectrometry. A single reagent simultaneously derivatizes multiple small molecule analytes having different reactive functional groups.

A multicolor panel of novel lentiviral "gene ontology" (LeGO) vectors for functional gene analysis.

PubMed

Weber, Kristoffer; Bartsch, Udo; Stocking, Carol; Fehse, Boris

2008-04-01

Functional gene analysis requires the possibility of overexpression, as well as downregulation of one, or ideally several, potentially interacting genes. Lentiviral vectors are well suited for this purpose as they ensure stable expression of complementary DNAs (cDNAs), as well as short-hairpin RNAs (shRNAs), and can efficiently transduce a wide spectrum of cell targets when packaged within the coat proteins of other viruses. Here we introduce a multicolor panel of novel lentiviral "gene ontology" (LeGO) vectors designed according to the "building blocks" principle. Using a wide spectrum of different fluorescent markers, including drug-selectable enhanced green fluorescent protein (eGFP)- and dTomato-blasticidin-S resistance fusion proteins, LeGO vectors allow simultaneous analysis of multiple genes and shRNAs of interest within single, easily identifiable cells. Furthermore, each functional module is flanked by unique cloning sites, ensuring flexibility and individual optimization. The efficacy of these vectors for analyzing multiple genes in a single cell was demonstrated in several different cell types, including hematopoietic, endothelial, and neural stem and progenitor cells, as well as hepatocytes. LeGO vectors thus represent a valuable tool for investigating gene networks using conditional ectopic expression and knock-down approaches simultaneously.

76 FR 18769 - Prospective Grant of Exclusive License: Device and System for Two Dimensional Analysis of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-05

..., 2004, now expired, entitled ``Method And Apparatus for Performing Multiple Simultaneous Manipulations..., 2006 entitled ``Method And Apparatus for Performing Multiple Simultaneous Manipulations of Biomolecules...

Shared worlds: multi-sited ethnography and nursing research.

PubMed

Molloy, Luke; Walker, Kim; Lakeman, Richard

2017-03-22

Background Ethnography, originally developed for the study of supposedly small-scale societies, is now faced with an increasingly mobile, changing and globalised world. Cultural identities can exist without reference to a specific location and extend beyond regional and national boundaries. It is therefore no longer imperative that the sole object of the ethnographer's practice should be a geographically bounded site. Aim To present a critical methodological review of multi-sited ethnography. Discussion Understanding that it can no longer be taken with any certainty that location alone determines culture, multi-sited ethnography provides a method of contextualising multi-sited social phenomena. The method enables researchers to examine social phenomena that are simultaneously produced in different locations. It has been used to undertake cultural analysis of diverse areas such as organ trafficking, global organisations, technologies and anorexia. Conclusion The authors contend that multi-sited ethnography is particularly suited to nursing research as it provides researchers with an ethnographic method that is more relevant to the interconnected world of health and healthcare services. Implications for practice Multi-sited ethnography provides nurse researchers with an approach to cultural analysis in areas such as the social determinants of health, healthcare services and the effects of health policies across multiple locations.

A Multifunctional Surface That Simultaneously Balances Hydrophilic Enzyme Catalysis and Hydrophobic Water Repellency.

PubMed

Lawton, Timothy J; Uzarski, Joshua R; Filocamo, Shaun F

2016-08-16

The compatibility of multiple functions at a single interface is difficult to achieve, but is even more challenging when the functions directly counteract one another. This study provides insight into the creation of a simultaneously multifunctional surface formed by balancing two orthogonal functions; water repellency and enzyme catalysis. A partially fluorinated thiol is used to impart bulk hydrophobicity on the surface, and an N-hydroxysuccinimide ester-terminated thiol provides a specific anchoring sites for the covalent enzyme attachment. Different ratios of the two thiols are mixed together to form amphiphilic self-assembled monolayers, which are characterized with polarization-modulation infrared reflection-absorption spectroscopy and contact angle goniometry. The enzyme activity is measured by a fluorescence assay. With the results collected here, specific surface compositions are identified at which the orthogonal functions of water repellency and enzyme catalysis are balanced and exist simultaneously. An understanding of how to effectively balance orthogonal functions at surfaces can be extended to a number of higher-scale applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A simple procedure for parallel sequence analysis of both strands of 5'-labeled DNA.

PubMed

Razvi, F; Gargiulo, G; Worcel, A

1983-08-01

Ligation of a 5'-labeled DNA restriction fragment results in a circular DNA molecule carrying the two 32Ps at the reformed restriction site. Double digestions of the circular DNA with the original enzyme and a second restriction enzyme cleavage near the labeled site allows direct chemical sequencing of one 5'-labeled DNA strand. Similar double digestions, using an isoschizomer that cleaves differently at the 32P-labeled site, allows direct sequencing of the now 3'-labeled complementary DNA strand. It is possible to directly sequence both strands of cloned DNA inserts by using the above protocol and a multiple cloning site vector that provides the necessary restriction sites. The simultaneous and parallel visualization of both DNA strands eliminates sequence ambiguities. In addition, the labeled circular molecules are particularly useful for single-hit DNA cleavage studies and DNA footprint analysis. As an example, we show here an analysis of the micrococcal nuclease-induced breaks on the two strands of the somatic 5S RNA gene of Xenopus borealis, which suggests that the enzyme may recognize and cleave small AT-containing palindromes along the DNA helix.

Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe.

PubMed

Fiáth, Richárd; Beregszászi, Patrícia; Horváth, Domonkos; Wittner, Lucia; Aarts, Arno A A; Ruther, Patrick; Neves, Hercules P; Bokor, Hajnalka; Acsády, László; Ulbert, István

2016-11-01

Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study. Copyright © 2016 the American Physiological Society.

Remote observing environment using a KVM-over-IP for the OAO 188 cm telescope

NASA Astrophysics Data System (ADS)

Yanagisawa, Kenshi; Inoue, Goki; Kuroda, Daisuke; Ukita, Nobuharu; Mizumoto, Yoshihiko; Izumiura, Hideyuki

2016-08-01

We have prepared remote observing environment for the 188 cm telescope at Okayama Astrophysical Observatory. A KVM-over-IP and a VPN gateway are employed as core devices, which offer reliable, secure and fast link between on site and remote sites. We have confirmed the KVM-over-IP has ideal characteristics for serving the remote observing environment; the use is simple for both users and maintainer; access from any platform is available; multiple and simultaneous access is possible; and maintenance load is small. We also demonstrated that the degradation of observing efficiency specific to the remote observing is negligibly small. The remote observing environment has fully opened since the semester 2016A, about 30% of the total observing time in the last semester was occupied by remote observing.

Simultaneous detection of multiple chemical residues in milk using broad-specifity antibodies in a hybrid immunosorbent assay

USDA-ARS?s Scientific Manuscript database

The wide array of applications using quantum dots (QDs) for detection of multiple analytes reflects the versatility of the technology. In this study, a novel immunoassay using 2 types of sensors (QDs and an enzyme) were simultaneously used for detecting multiple structurally different low-molecular...

78 FR 45524 - Auction of H Block Licenses in the 1915-1920 MHz and 1995-2000 MHz Bands; Comment Sought on...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... issues relating to the conduct of Auction 96. A. Auction Design i. Simultaneous Multiple-Round Auction--With or Without Package Bidding 14. The Bureau proposes to conduct Auction 96 using a simultaneous... incorporate provisions for a simple form of package bidding into the simultaneous multiple-round auction. In...

Imaging of enzyme activity using bio-LSI system enables simultaneous immunosensing of different analytes in multiple specimens.

PubMed

Hokuto, Toshiki; Yasukawa, Tomoyuki; Kunikata, Ryota; Suda, Atsushi; Inoue, Kumi Y; Ino, Kosuke; Matsue, Tomokazu; Mizutani, Fumio

2016-06-01

Electrochemical imaging is an excellent technique to characterize an activity of biomaterials, such as enzymes and cells. Large scale integration-based amperometric sensor (Bio-LSI) has been developed for the simultaneous and continuous detection of the concentration distribution of redox species generated by reactions of biomolecules. In this study, the Bio-LSI system was demonstrated to be applicable for simultaneous detection of different anaytes in multiple specimens. The multiple specimens containing human immunoglobulin G (hIgG) and mouse IgG (mIgG) were introduced into each channel of the upper substrate across the antibody lines for hIgG and mIgG on the lower substrate. Hydrogen peroxide generated by the enzyme reaction of glucose oxidase captured at intersections was simultaneously detected by 400 microelectrodes of Bio-LSI chip. The oxidation current increased with increasing the concentrations of hIgG, which can be detected in the range of 0.01-1.0 µg mL(-1) . Simultaneous detection of hIgG and mIgG in multiple specimens was achieved by using line pattern of both antibodies. Therefore, the presence of different target molecules in the multiple samples would be quantitatively and simultaneously visualized as a current image by the Bio-LSI system. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temperature dependent CO2 behavior in microporous 1-D channels of a metal-organic framework with multiple interaction sites

PubMed Central

Kim, Dongwook; Park, Jaehun; Kim, Yung Sam; Lah, Myoung Soo

2017-01-01

The MOF with the encapsulated CO2 molecule shows that the CO2 molecule is ligated to the unsaturated Cu(II) sites in the cage using its Lewis basic oxygen atom via an angular η1-(OA) coordination mode and also interacts with Lewis basic nitrogen atoms of the tetrazole ligands using its Lewis acidic carbon atom. Temperature dependent structure analyses indicate the simultaneous weakening of both interactions as temperature increases. Infrared spectroscopy of the MOF confirmed that the CO2 interaction with the framework is temperature dependent. The strength of the interaction is correlated to the separation of the two bending peaks of the bound CO2 rather than the frequency shift of the asymmetric stretching peak from that of free CO2. The encapsulated CO2 in the cage is weakly interacting with the framework at around ambient temperatures and can have proper orientation for wiggling out of the cage through the narrow portals so that the reversible uptake can take place. On the other hand, the CO2 in the cage is restrained at a specific orientation at 195 K since it interacts with the framework strong enough using the multiple interaction sites so that adsorption process is slightly restricted and desorption process is almost clogged. PMID:28128298

Evaluating the Effects of Emission Reductions on Multiple Pollutants Simultaneously

EPA Science Inventory

Modeling studies over the Philadelphia metropolitan area have examined how emission control strategies might affect several types of air pollutants simultaneously. This study supports considering effects of multiple pollutants in determining optimum pollution control strategies. ...

Polycistronic tRNA and CRISPR guide-RNA enables highly efficient multiplexed genome engineering in human cells

PubMed Central

Dong, Fengping; Xie, Kabin; Chen, Yueying; Yang, Yinong; Mao, Yingwei

2016-01-01

CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides a potential tool to introduce multiple mutations in a genome. To mimic complicated genomic variants in human diseases, such as multiple gene deletions or mutations, two or more small guide RNAs (sgRNAs) need to be introduced all together. This can be achieved by separate Pol III promoters in a construct. However, limited enzyme sites and increased insertion size lower the efficiency to make a construct. Here, we report a strategy to quickly assembly multiple sgRNAs in one construct using a polycistronic-tRNA-gRNA (PTG) strategy. Taking advantage of the endogenous tRNA processing system in mammalian cells, we efficiently express multiple sgRNAs driven using only one Pol III promoter. Using an all-in-one construct carrying PTG, we disrupt the deacetylase domain in multiple histone deacetylases (HDACs) in human cells simultaneously. We demonstrate that multiple HDAC deletions significantly affect the activation of the Wnt-signaling pathway. Thus, this method enables to efficiently target multiple genes and provide a useful tool to establish mutated cells mimicking human diseases. PMID:27890617

Polycistronic tRNA and CRISPR guide-RNA enables highly efficient multiplexed genome engineering in human cells.

PubMed

Dong, Fengping; Xie, Kabin; Chen, Yueying; Yang, Yinong; Mao, Yingwei

2017-01-22

CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides a potential tool to introduce multiple mutations in a genome. To mimic complicated genomic variants in human diseases, such as multiple gene deletions or mutations, two or more small guide RNAs (sgRNAs) need to be introduced all together. This can be achieved by separate Pol III promoters in a construct. However, limited enzyme sites and increased insertion size lower the efficiency to make a construct. Here, we report a strategy to quickly assembly multiple sgRNAs in one construct using a polycistronic-tRNA-gRNA (PTG) strategy. Taking advantage of the endogenous tRNA processing system in mammalian cells, we efficiently express multiple sgRNAs driven using only one Pol III promoter. Using an all-in-one construct carrying PTG, we disrupt the deacetylase domain in multiple histone deacetylases (HDACs) in human cells simultaneously. We demonstrate that multiple HDAC deletions significantly affect the activation of the Wnt-signaling pathway. Thus, this method enables to efficiently target multiple genes and provide a useful tool to establish mutated cells mimicking human diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Blends of Pheromones, With and Without Host Plant Volatiles, Can Attract Multiple Species of Cerambycid Beetles Simultaneously

Treesearch

L.M. Hanks; J.A. Mongold-Diers; T.H. Atkinson; M.K. Fierke; M.D. Ginzel; E.E. Graham; T.M. Poland; A.B. Richards; M.L. Richardson; J.G. Millar

2018-01-01

Pheromone components of cerambycid beetles are often conserved, with a given compound serving as a pheromone component for multiple related species, including species native to different continents. Consequently, a single synthesized compound may attract multiple species to a trap simultaneously. Furthermore, our previous research in east-central Illinois had...

Unsupervised learning of contextual constraints in neural networks for simultaneous visual processing of multiple objects

NASA Astrophysics Data System (ADS)

Marshall, Jonathan A.

1992-12-01

A simple self-organizing neural network model, called an EXIN network, that learns to process sensory information in a context-sensitive manner, is described. EXIN networks develop efficient representation structures for higher-level visual tasks such as segmentation, grouping, transparency, depth perception, and size perception. Exposure to a perceptual environment during a developmental period serves to configure the network to perform appropriate organization of sensory data. A new anti-Hebbian inhibitory learning rule permits superposition of multiple simultaneous neural activations (multiple winners), while maintaining contextual consistency constraints, instead of forcing winner-take-all pattern classifications. The activations can represent multiple patterns simultaneously and can represent uncertainty. The network performs parallel parsing, credit attribution, and simultaneous constraint satisfaction. EXIN networks can learn to represent multiple oriented edges even where they intersect and can learn to represent multiple transparently overlaid surfaces defined by stereo or motion cues. In the case of stereo transparency, the inhibitory learning implements both a uniqueness constraint and permits coactivation of cells representing multiple disparities at the same image location. Thus two or more disparities can be active simultaneously without interference. This behavior is analogous to that of Prazdny's stereo vision algorithm, with the bonus that each binocular point is assigned a unique disparity. In a large implementation, such a NN would also be able to represent effectively the disparities of a cloud of points at random depths, like human observers, and unlike Prazdny's method

Hum-mPLoc: an ensemble classifier for large-scale human protein subcellular location prediction by incorporating samples with multiple sites.

PubMed

Shen, Hong-Bin; Chou, Kuo-Chen

2007-04-20

Proteins may simultaneously exist at, or move between, two or more different subcellular locations. Proteins with multiple locations or dynamic feature of this kind are particularly interesting because they may have some very special biological functions intriguing to investigators in both basic research and drug discovery. For instance, among the 6408 human protein entries that have experimentally observed subcellular location annotations in the Swiss-Prot database (version 50.7, released 19-Sept-2006), 973 ( approximately 15%) have multiple location sites. The number of total human protein entries (except those annotated with "fragment" or those with less than 50 amino acids) in the same database is 14,370, meaning a gap of (14,370-6408)=7962 entries for which no knowledge is available about their subcellular locations. Although one can use the computational approach to predict the desired information for the gap, so far all the existing methods for predicting human protein subcellular localization are limited in the case of single location site only. To overcome such a barrier, a new ensemble classifier, named Hum-mPLoc, was developed that can be used to deal with the case of multiple location sites as well. Hum-mPLoc is freely accessible to the public as a web server at http://202.120.37.186/bioinf/hum-multi. Meanwhile, for the convenience of people working in the relevant areas, Hum-mPLoc has been used to identify all human protein entries in the Swiss-Prot database that do not have subcellular location annotations or are annotated as being uncertain. The large-scale results thus obtained have been deposited in a downloadable file prepared with Microsoft Excel and named "Tab_Hum-mPLoc.xls". This file is available at the same website and will be updated twice a year to include new entries of human proteins and reflect the continuous development of Hum-mPLoc.

A Virtual Mixture Approach to the Study of Multistate Equilibrium: Application to Constant pH Simulation in Explicit Water

PubMed Central

Wu, Xiongwu; Brooks, Bernard R.

2015-01-01

Chemical and thermodynamic equilibrium of multiple states is a fundamental phenomenon in biology systems and has been the focus of many experimental and computational studies. This work presents a simulation method to directly study the equilibrium of multiple states. This method constructs a virtual mixture of multiple states (VMMS) to sample the conformational space of all chemical states simultaneously. The VMMS system consists of multiple subsystems, one for each state. The subsystem contains a solute and a solvent environment. The solute molecules in all subsystems share the same conformation but have their own solvent environments. Transition between states is implicated by the change of their molar fractions. Simulation of a VMMS system allows efficient calculation of relative free energies of all states, which in turn determine their equilibrium molar fractions. For systems with a large number of state transition sites, an implicit site approximation is introduced to minimize the cost of simulation. A direct application of the VMMS method is for constant pH simulation to study protonation equilibrium. Applying the VMMS method to a heptapeptide of 3 ionizable residues, we calculated the pKas of those residues both with all explicit states and with implicit sites and obtained consistent results. For mouse epidermal growth factor of 9 ionizable groups, our VMMS simulations with implicit sites produced pKas of all 9 ionizable groups and the results agree qualitatively with NMR measurement. This example demonstrates the VMMS method can be applied to systems of a large number of ionizable groups and the computational cost scales linearly with the number of ionizable groups. For one of the most challenging systems in constant pH calculation, SNase Δ+PHS/V66K, our VMMS simulation shows that it is the state-dependent water penetration that causes the large deviation in lysine66’s pKa. PMID:26506245

A Virtual Mixture Approach to the Study of Multistate Equilibrium: Application to Constant pH Simulation in Explicit Water.

PubMed

Wu, Xiongwu; Brooks, Bernard R

2015-10-01

Chemical and thermodynamic equilibrium of multiple states is a fundamental phenomenon in biology systems and has been the focus of many experimental and computational studies. This work presents a simulation method to directly study the equilibrium of multiple states. This method constructs a virtual mixture of multiple states (VMMS) to sample the conformational space of all chemical states simultaneously. The VMMS system consists of multiple subsystems, one for each state. The subsystem contains a solute and a solvent environment. The solute molecules in all subsystems share the same conformation but have their own solvent environments. Transition between states is implicated by the change of their molar fractions. Simulation of a VMMS system allows efficient calculation of relative free energies of all states, which in turn determine their equilibrium molar fractions. For systems with a large number of state transition sites, an implicit site approximation is introduced to minimize the cost of simulation. A direct application of the VMMS method is for constant pH simulation to study protonation equilibrium. Applying the VMMS method to a heptapeptide of 3 ionizable residues, we calculated the pKas of those residues both with all explicit states and with implicit sites and obtained consistent results. For mouse epidermal growth factor of 9 ionizable groups, our VMMS simulations with implicit sites produced pKas of all 9 ionizable groups and the results agree qualitatively with NMR measurement. This example demonstrates the VMMS method can be applied to systems of a large number of ionizable groups and the computational cost scales linearly with the number of ionizable groups. For one of the most challenging systems in constant pH calculation, SNase Δ+PHS/V66K, our VMMS simulation shows that it is the state-dependent water penetration that causes the large deviation in lysine66's pKa.

Better dual-task processing in simultaneous interpreters

PubMed Central

Strobach, Tilo; Becker, Maxi; Schubert, Torsten; Kühn, Simone

2015-01-01

Simultaneous interpreting (SI) is a highly complex activity and requires the performance and coordination of multiple, simultaneous tasks: analysis and understanding of the discourse in a first language, reformulating linguistic material, storing of intermediate processing steps, and language production in a second language among others. It is, however, an open issue whether persons with experience in SI possess superior skills in coordination of multiple tasks and whether they are able to transfer these skills to lab-based dual-task situations. Within the present study, we set out to explore whether interpreting experience is associated with related higher-order executive functioning in the context of dual-task situations of the Psychological Refractory Period (PRP) type. In this PRP situation, we found faster reactions times in participants with experience in simultaneous interpretation in contrast to control participants without such experience. Thus, simultaneous interpreters possess superior skills in coordination of multiple tasks in lab-based dual-task situations. PMID:26528232

Golden Gate Assembly of CRISPR gRNA expression array for simultaneously targeting multiple genes.

PubMed

Vad-Nielsen, Johan; Lin, Lin; Bolund, Lars; Nielsen, Anders Lade; Luo, Yonglun

2016-11-01

The engineered CRISPR/Cas9 technology has developed as the most efficient and broadly used genome editing tool. However, simultaneously targeting multiple genes (or genomic loci) in the same individual cells using CRISPR/Cas9 remain one technical challenge. In this article, we have developed a Golden Gate Assembly method for the generation of CRISPR gRNA expression arrays, thus enabling simultaneous gene targeting. Using this method, the generation of CRISPR gRNA expression array can be accomplished in 2 weeks, and contains up to 30 gRNA expression cassettes. We demonstrated in the study that simultaneously targeting 10 genomic loci or simultaneously inhibition of multiple endogenous genes could be achieved using the multiplexed gRNA expression array vector in human cells. The complete set of plasmids is available through the non-profit plasmid repository Addgene.

Ropizine concurrently enhances and inhibits ( sup 3 H) dextromethorpan binding to different structures of the guinea pig brain: Autoradiographic evidence for multiple binding sites

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

Canoll, P.D.; Smith, P.R.; and Musacchio, J.M.

1990-01-01

Ropizine produces a simultaneous enhancement and inhibition of ({sup 3}H) dextromethorphan (DM) high-affinity binding to different areas of the guinea pig brain. These results imply that there are two distinct types of high-affinity ({sup 3}H)DM binding sites, which are present in variable proportions in different brain structures. The ropizine-enhances ({sup 3}H)DM binding type was preferentially inhibited by (+)-pentazocine. This is consistent with the presumption that the (+)-pentazocine-sensitive site is identical with the common site for DM and 3-(-3-Hydroxphenyl)-N-(1-propyl)piperidine ((+)-3-PPP). The second binding type, which is inhibited by ropizine and is not so sensitive to (+){minus} pentazocine, has not been fullymore » characterized. This study demonstrates that the biphasic effects to ropizine are due, at least in part, to the effects of ropizine on two different types of ({sup 3}H)DM binding sites. However, this study does not rule out that the common DM/(+)-3-PPP site also might be inhibited by higher concentrations of ropizine.« less

Integrated Optoelectronics for Parallel Microbioanalysis

NASA Technical Reports Server (NTRS)

Stirbl, Robert; Moynihan, Philip; Bearman, Gregory; Lane, Arthur

2003-01-01

Miniature, relatively inexpensive microbioanalytical systems ("laboratory-on-achip" devices) have been proposed for the detection of hazardous microbes and toxic chemicals. Each system of this type would include optoelectronic sensors and sensor-output-processing circuitry that would simultaneously look for the optical change, fluorescence, delayed fluorescence, or phosphorescence signatures from multiple redundant sites that have interacted with the test biomolecules in order to detect which one(s) was present in a given situation. These systems could be used in a variety of settings that could include doctors offices, hospitals, hazardous-material laboratories, biological-research laboratories, military operations, and chemical-processing plants.

Electron bifurcation.

PubMed

Peters, John W; Miller, Anne-Frances; Jones, Anne K; King, Paul W; Adams, Michael Ww

2016-04-01

Electron bifurcation is the recently recognized third mechanism of biological energy conservation. It simultaneously couples exergonic and endergonic oxidation-reduction reactions to circumvent thermodynamic barriers and minimize free energy loss. Little is known about the details of how electron bifurcating enzymes function, but specifics are beginning to emerge for several bifurcating enzymes. To date, those characterized contain a collection of redox cofactors including flavins and iron-sulfur clusters. Here we discuss the current understanding of bifurcating enzymes and the mechanistic features required to reversibly partition multiple electrons from a single redox site into exergonic and endergonic electron transfer paths. Copyright © 2016. Published by Elsevier Ltd.

A Comparative Analysis of Three Monocular Passive Ranging Methods on Real Infrared Sequences

NASA Astrophysics Data System (ADS)

Bondžulić, Boban P.; Mitrović, Srđan T.; Barbarić, Žarko P.; Andrić, Milenko S.

2013-09-01

Three monocular passive ranging methods are analyzed and tested on the real infrared sequences. The first method exploits scale changes of an object in successive frames, while other two use Beer-Lambert's Law. Ranging methods are evaluated by comparing with simultaneously obtained reference data at the test site. Research is addressed on scenarios where multiple sensor views or active measurements are not possible. The results show that these methods for range estimation can provide the fidelity required for object tracking. Maximum values of relative distance estimation errors in near-ideal conditions are less than 8%.

Fully coupled simulation of multiple hydraulic fractures to propagate simultaneously from a perforated horizontal wellbore

NASA Astrophysics Data System (ADS)

Zeng, Qinglei; Liu, Zhanli; Wang, Tao; Gao, Yue; Zhuang, Zhuo

2018-02-01

In hydraulic fracturing process in shale rock, multiple fractures perpendicular to a horizontal wellbore are usually driven to propagate simultaneously by the pumping operation. In this paper, a numerical method is developed for the propagation of multiple hydraulic fractures (HFs) by fully coupling the deformation and fracturing of solid formation, fluid flow in fractures, fluid partitioning through a horizontal wellbore and perforation entry loss effect. The extended finite element method (XFEM) is adopted to model arbitrary growth of the fractures. Newton's iteration is proposed to solve these fully coupled nonlinear equations, which is more efficient comparing to the widely adopted fixed-point iteration in the literatures and avoids the need to impose fluid pressure boundary condition when solving flow equations. A secant iterative method based on the stress intensity factor (SIF) is proposed to capture different propagation velocities of multiple fractures. The numerical results are compared with theoretical solutions in literatures to verify the accuracy of the method. The simultaneous propagation of multiple HFs is simulated by the newly proposed algorithm. The coupled influences of propagation regime, stress interaction, wellbore pressure loss and perforation entry loss on simultaneous propagation of multiple HFs are investigated.

Phenotypic diversification by enhanced genome restructuring after induction of multiple DNA double-strand breaks.

PubMed

Muramoto, Nobuhiko; Oda, Arisa; Tanaka, Hidenori; Nakamura, Takahiro; Kugou, Kazuto; Suda, Kazuki; Kobayashi, Aki; Yoneda, Shiori; Ikeuchi, Akinori; Sugimoto, Hiroki; Kondo, Satoshi; Ohto, Chikara; Shibata, Takehiko; Mitsukawa, Norihiro; Ohta, Kunihiro

2018-05-18

DNA double-strand break (DSB)-mediated genome rearrangements are assumed to provide diverse raw genetic materials enabling accelerated adaptive evolution; however, it remains unclear about the consequences of massive simultaneous DSB formation in cells and their resulting phenotypic impact. Here, we establish an artificial genome-restructuring technology by conditionally introducing multiple genomic DSBs in vivo using a temperature-dependent endonuclease TaqI. Application in yeast and Arabidopsis thaliana generates strains with phenotypes, including improved ethanol production from xylose at higher temperature and increased plant biomass, that are stably inherited to offspring after multiple passages. High-throughput genome resequencing revealed that these strains harbor diverse rearrangements, including copy number variations, translocations in retrotransposons, and direct end-joinings at TaqI-cleavage sites. Furthermore, large-scale rearrangements occur frequently in diploid yeasts (28.1%) and tetraploid plants (46.3%), whereas haploid yeasts and diploid plants undergo minimal rearrangement. This genome-restructuring system (TAQing system) will enable rapid genome breeding and aid genome-evolution studies.

Collective Care: Multiple Caregivers and Multiple Care Recipients in Mexican American Families

PubMed Central

Evans, Bronwynne C.; Coon, David W.; Belyea, Michael J.; Ume, Ebere

2016-01-01

Purpose Specific stressors associated with caregiving in Mexican-American (MA) families are not well documented, yet caregiving issues are paramount because informal care for parents is central to their culture. Although MA families who band together to provide care for one member are not unique, the literature does not describe the phenomenon of collective caregiving, which may be widespread but unrecognized. Such families are both understudied and poorly served by contemporary health systems because their characteristics are unknown. Design Descriptive, multi-site, longitudinal mixed-methods study of MA caregiving families. Findings We identified three types of collective caregivers: those providing care for multiple family members simultaneously; those providing care successively to several family members, and/or those finding themselves obliged to accept care during their caregiving of others. Discussion and Conclusions Collective caregiving of MA elders warrants further investigation. Implications for Practice Exploration of collective caregiving may provide a foundation for tailored family interventions. PMID:27389911

Simultaneous Exposure to Multiple Air Pollutants Influences Alveolar Epithelial Cell Ion Transport

EPA Science Inventory

Purpose. Air pollution sources generally release multiple pollutants simultaneously and yet, research has historically focused on the source-to-health linkages of individual air pollutants. We recently showed that exposure of alveolar epithelial cells to a combination of particul...

Neurons in cat V1 show significant clustering by degree of tuning

PubMed Central

Ziskind, Avi J.; Emondi, Al A.; Kurgansky, Andrei V.; Rebrik, Sergei P.

2015-01-01

Neighboring neurons in cat primary visual cortex (V1) have similar preferred orientation, direction, and spatial frequency. How diverse is their degree of tuning for these properties? To address this, we used single-tetrode recordings to simultaneously isolate multiple cells at single recording sites and record their responses to flashed and drifting gratings of multiple orientations, spatial frequencies, and, for drifting gratings, directions. Orientation tuning width, spatial frequency tuning width, and direction selectivity index (DSI) all showed significant clustering: pairs of neurons recorded at a single site were significantly more similar in each of these properties than pairs of neurons from different recording sites. The strength of the clustering was generally modest. The percent decrease in the median difference between pairs from the same site, relative to pairs from different sites, was as follows: for different measures of orientation tuning width, 29–35% (drifting gratings) or 15–25% (flashed gratings); for DSI, 24%; and for spatial frequency tuning width measured in octaves, 8% (drifting gratings). The clusterings of all of these measures were much weaker than for preferred orientation (68% decrease) but comparable to that seen for preferred spatial frequency in response to drifting gratings (26%). For the above properties, little difference in clustering was seen between simple and complex cells. In studies of spatial frequency tuning to flashed gratings, strong clustering was seen among simple-cell pairs for tuning width (70% decrease) and preferred frequency (71% decrease), whereas no clustering was seen for simple-complex or complex-complex cell pairs. PMID:25652921

Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein.

PubMed

Li, Huameng; Li, Chenglong

2010-07-30

Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein-ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl-xL complex with ABT-737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single-ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively. 2010 Wiley Periodicals, Inc.

Molecular-Scale Features that Govern the Effects of O-Glycosylation on a Carbohydrate-Binding Module

DOE PAGES

Guan, Xiaoyang; Chaffey, Patrick K.; Zeng, Chen; ...

2015-09-21

The protein glycosylation is a ubiquitous post-translational modification in all kingdoms of life. Despite its importance in molecular and cellular biology, the molecular-level ramifications of O-glycosylation on biomolecular structure and function remain elusive. Here, we took a small model glycoprotein and changed the glycan structure and size, amino acid residues near the glycosylation site, and glycosidic linkage while monitoring any corresponding changes to physical stability and cellulose binding affinity. The results of this study reveal the collective importance of all the studied features in controlling the most pronounced effects of O-glycosylation in this system. This study suggests the possibility ofmore » designing proteins with multiple improved properties by simultaneously varying the structures of O-glycans and amino acids local to the glycosylation site.« less

A universal mini-vector and an annealing of PCR products (APP)-based cloning strategy for convenient molecular biological manipulations.

PubMed

Liu, Xia; Li, Tuoping; Hart, Darren J; Gao, Song; Wang, Hongling; Gao, Herui; Xu, Shumin; Zhang, Yifeng; Liu, Yifei; An, Yingfeng

2018-03-18

Currently, the most widely used strategies for molecular cloning are sticky-end ligation-based cloning, TA cloning, blunt-end ligation-based cloning and ligase-independent cloning. In this study we have developed a novel mini-vector pANY1 which can simultaneously meet the requirements of all these cloning strategies. In addition, the selection of appropriate restriction digestion sites is difficult in some cases because of the presence of internal sites. In this study, an annealing of PCR products (APP)-based sticky-end cloning strategy was introduced to avoid this issue. Additionally, false positives occur during molecular cloning, which increases the workload of isolating positive clones. The plasmid pANY1 contains a ccdB cassette between multiple cloning sites, which efficiently avoids these false positives. Therefore, this mini-vector should serve as a useful tool with wide applications in biosciences, agriculture, food technologies, etc. Copyright © 2018 Elsevier Inc. All rights reserved.

The Impacts of Multiple Simultaneous Climate Variations

DTIC Science & Technology

2016-12-01

MULTIPLE SIMULTANEOUS CLIMATE VARIATIONS by Richard E. Ilczuk Jr. December 2016 Thesis Advisor: Tom Murphree Co-Advisor: Megan Hutchins......13. ABSTRACT (maximum 200 words) Climate variations—such as El Niño–La Niña (ENLN), the Madden–Julian Oscillation (MJO), and the Arctic

Investigating the biogeochemical interactions involved in simultaneous TCE and Arsenic in situ bioremediation

NASA Astrophysics Data System (ADS)

Cook, E.; Troyer, E.; Keren, R.; Liu, T.; Alvarez-Cohen, L.

2016-12-01

The in situ bioremediation of contaminated sediment and groundwater is often focused on one toxin, even though many of these sites contain multiple contaminants. This reductionist approach neglects how other toxins may affect the biological and chemical conditions, or vice versa. Therefore, it is of high value to investigate the concurrent bioremediation of multiple contaminants while studying the microbial activities affected by biogeochemical factors. A prevalent example is the bioremediation of arsenic at sites co-contaminated with trichloroethene (TCE). The conditions used to promote a microbial community to dechlorinate TCE often has the adverse effect of inducing the release of previously sequestered arsenic. The overarching goal of our study is to simultaneously evaluate the bioremediation of arsenic and TCE. Although TCE bioremediation is a well-understood process, there is still a lack of thorough understanding of the conditions necessary for effective and stable arsenic bioremediation in the presence of TCE. The objective of this study is to promote bacterial activity that stimulates the precipitation of stable arsenic-bearing minerals while providing anaerobic, non-extreme conditions necessary for TCE dechlorination. To that end, endemic microbial communities were examined under various conditions to attempt successful sequestration of arsenic in addition to complete TCE dechlorination. Tested conditions included variations of substrates, carbon source, arsenate and sulfate concentrations, and the presence or absence of TCE. Initial arsenic-reducing enrichments were unable to achieve TCE dechlorination, probably due to low abundance of dechlorinating bacteria in the culture. However, favorable conditions for arsenic precipitation in the presence of TCE were eventually discovered. This study will contribute to the understanding of the key species in arsenic cycling, how they are affected by various concentrations of TCE, and how they interact with the key species in a dechlorinating community.

Acoustic and higher-level representations of naturalistic auditory scenes in human auditory and frontal cortex.

PubMed

Hausfeld, Lars; Riecke, Lars; Formisano, Elia

2018-06-01

Often, in everyday life, we encounter auditory scenes comprising multiple simultaneous sounds and succeed to selectively attend to only one sound, typically the most relevant for ongoing behavior. Studies using basic sounds and two-talker stimuli have shown that auditory selective attention aids this by enhancing the neural representations of the attended sound in auditory cortex. It remains unknown, however, whether and how this selective attention mechanism operates on representations of auditory scenes containing natural sounds of different categories. In this high-field fMRI study we presented participants with simultaneous voices and musical instruments while manipulating their focus of attention. We found an attentional enhancement of neural sound representations in temporal cortex - as defined by spatial activation patterns - at locations that depended on the attended category (i.e., voices or instruments). In contrast, we found that in frontal cortex the site of enhancement was independent of the attended category and the same regions could flexibly represent any attended sound regardless of its category. These results are relevant to elucidate the interacting mechanisms of bottom-up and top-down processing when listening to real-life scenes comprised of multiple sound categories. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Volatile aromatic hydrocarbons and dicarboxylic acid concentrations in air at an urban site in the Southwestern US

NASA Astrophysics Data System (ADS)

Tran, Ngoc K.; Steinberg, Spencer M.; Johnson, Brian J.

Concentrations of benzene, toluene, ethylbenzene, o-xylene, and m- and p-xylene were measured at an urban sampling site in Las Vegas, NV by sorbent sampling followed by thermal desorption and determination by GC-PID. Simultaneously, measurements of oxalic, malonic, succinic, and adipic acids were made at the same site by collection on quartz filters, extraction, esterification, and determination by GC-FID. For the period from April 7, 1997 to June 11, 1997, 201 sets of hydrocarbon measurements and 99 sets of acid measurements were made. Additional measurements of dicarboxylic acids were made on samples that represented potential direct sources, e.g. green plants and road dust. Correlations between the hydrocarbon and CO concentrations (measured by the Clark County Health District at a nearby site) were highly significant and a strong negative correlation of hydrocarbon concentration with ozone concentration (also from the county site) was observed under quiescent atmospheric conditions. In general, dicarboxylic acid concentrations were well correlated with one another (with the exception of adipic acid) but not well correlated with hydrocarbon, CO, and ozone concentrations. Multiple sources and complex formation processes are indicated for the dicarboxylic acids.

Simultaneous addition of two ligands: a potential strategy for estimating divalent ion affinities in EF-hand proteins by isothermal titration calorimetry.

PubMed

Henzl, Michael T; Markus, Lindsey A; Davis, Meredith E; McMillan, Andrew T

2013-03-01

Capable of providing a detailed thermodynamic picture of noncovalent association reactions, isothermal titration calorimetry (ITC) has become a popular method for studying protein-ligand interactions. We routinely employ the technique to study divalent ion-binding by two-site EF-hand proteins from the parvalbumin- and polcalcin lineages. The combination of high Ca(2+) affinity and relatively low Mg(2+) affinity, and the attendant complication of parameter correlation, conspire to make the simultaneous extraction of binding constants and -enthalpies for both ions challenging. Although global analysis of multiple ITC experiments can overcome these hurdles, our current experimental protocol includes upwards of 10 titrations - requiring a substantial investment in labor, machine time, and material. This paper explores the potential for using a smaller suite of experiments that includes simultaneous titrations with Ca(2+) and Mg(2+) at different ratios of the two ions. The results obtained for four proteins, differing substantially in their divalent ion-binding properties, suggest that the approach has merit. The Ca(2+)- and Mg(2+)-binding constants afforded by the streamlined analysis are in reasonable agreement with those obtained from the standard analysis protocol. Likewise, the abbreviated analysis provides comparable values for the Ca(2+)-binding enthalpies. However, the streamlined analysis can yield divergent values for the Mg(2+)-binding enthalpies - particularly those for lower affinity sites. This shortcoming can be remedied, in large measure, by including data from a direct Ca(2+) titration in the presence of a high, fixed Mg(2+) concentration. Copyright © 2013. Published by Elsevier Inc.

Private E-Mail Requests and the Diffusion of Responsibility.

ERIC Educational Resources Information Center

Barron, Greg; Yechiam, Eldad

2002-01-01

Discussion of e-mail technology and requesting information from multiple sources simultaneously focuses on an experiment demonstrating that addressing e-mails simultaneously to multiple recipients may actually reduce the number of helpful responses. Discusses diffusion of responsibility and implications for the application of social cueing theory…

Simultaneous Detection of Electronic Structure Changes from Two Elements of a Bifunctional Catalyst Using Wavelength-Dispersive X-ray Emission Spectroscopy and in situ Electrochemistry

PubMed Central

Gul, Sheraz; Desmond Ng, Jia Wei; Alonso-Mori, Roberto; Kern, Jan; Sokaras, Dimosthenis; Anzenberg, Eitan; Lassalle-Kaiser, Benedikt; Gorlin, Yelena; Weng, Tsu-Chien; Zwart, Petrus H.; Zhang, Jin Z.; Bergmann, Uwe; Yachandra, Vittal K.; Jaramillo, Thomas F.; Yano, Junko

2015-01-01

Multielectron catalytic reactions, such as water oxidation, nitrogen reduction, or hydrogen production in enzymes and inorganic catalysts often involve multimetallic clusters. In these systems, the reaction takes place between metals or metals and ligands to facilitate charge transfer, bond formation/breaking, substrate binding, and release of products. In this study, we present a method to detect X-ray emission signals from multiple elements simultaneously, which allows for the study of charge transfer and the sequential chemistry occurring between elements. Kβ X-ray emission spectroscopy (XES) probes charge and spin states of metals as well as their ligand environment. A wavelength-dispersive spectrometer based on the von Hamos geometry was used to disperse Kβ signals of multiple elements onto a position detector, enabling an XES spectrum to be measured in a single-shot mode. This overcomes the scanning needs of the scanning spectrometers, providing data free from temporal and normalization errors and therefore ideal to follow sequential chemistry at multiple sites. We have applied this method to study MnOx-based bifunctional electrocatalysts for the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR). In particular, we investigated the effects of adding a secondary element, Ni, to form MnNiOx and its impact on the chemical states and catalytic activity, by tracking the redox characteristics of each element upon sweeping the electrode potential. The detection scheme we describe here is general and can be applied to time-resolved studies of materials consisting of multiple elements, to follow the dynamics of catalytic and electron transfer reactions. PMID:25747045

Simultaneous detection of electronic structure changes from two elements of a bifunctional catalyst using wavelength-dispersive X-ray emission spectroscopy and in situ electrochemistry.

PubMed

Gul, Sheraz; Ng, Jia Wei Desmond; Alonso-Mori, Roberto; Kern, Jan; Sokaras, Dimosthenis; Anzenberg, Eitan; Lassalle-Kaiser, Benedikt; Gorlin, Yelena; Weng, Tsu-Chien; Zwart, Petrus H; Zhang, Jin Z; Bergmann, Uwe; Yachandra, Vittal K; Jaramillo, Thomas F; Yano, Junko

2015-04-14

Multielectron catalytic reactions, such as water oxidation, nitrogen reduction, or hydrogen production in enzymes and inorganic catalysts often involve multimetallic clusters. In these systems, the reaction takes place between metals or metals and ligands to facilitate charge transfer, bond formation/breaking, substrate binding, and release of products. In this study, we present a method to detect X-ray emission signals from multiple elements simultaneously, which allows for the study of charge transfer and the sequential chemistry occurring between elements. Kβ X-ray emission spectroscopy (XES) probes charge and spin states of metals as well as their ligand environment. A wavelength-dispersive spectrometer based on the von Hamos geometry was used to disperse Kβ signals of multiple elements onto a position detector, enabling an XES spectrum to be measured in a single-shot mode. This overcomes the scanning needs of the scanning spectrometers, providing data free from temporal and normalization errors and therefore ideal to follow sequential chemistry at multiple sites. We have applied this method to study MnOx-based bifunctional electrocatalysts for the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR). In particular, we investigated the effects of adding a secondary element, Ni, to form MnNiOx and its impact on the chemical states and catalytic activity, by tracking the redox characteristics of each element upon sweeping the electrode potential. The detection scheme we describe here is general and can be applied to time-resolved studies of materials consisting of multiple elements, to follow the dynamics of catalytic and electron transfer reactions.

Simultaneous detection of electronic structure changes from two elements of a bifunctional catalyst using wavelength-dispersive X-ray emission spectroscopy and in situ electrochemistry

DOE PAGES

Gul, Sheraz; Ng, Jia Wei Desmond; Alonso-Mori, Roberto; ...

2015-02-25

Multielectron catalytic reactions, such as water oxidation, nitrogen reduction, or hydrogen production in enzymes and inorganic catalysts often involve multimetallic clusters. In these systems, the reaction takes place between metals or metals and ligands to facilitate charge transfer, bond formation/breaking, substrate binding, and release of products. In this study, we present a method to detect X-ray emission signals from multiple elements simultaneously, which allows for the study of charge transfer and the sequential chemistry occurring between elements. Kβ X-ray emission spectroscopy (XES) probes charge and spin states of metals as well as their ligand environment. A wavelength-dispersive spectrometer based onmore » the von Hamos geometry was used to disperse Kβ signals of multiple elements onto a position detector, enabling an XES spectrum to be measured in a single-shot mode. This overcomes the scanning needs of the scanning spectrometers, providing data free from temporal and normalization errors and therefore ideal to follow sequential chemistry at multiple sites. We have applied this method to study MnOx-based bifunctional electrocatalysts for the oxygen evolution reaction (OER) and the oxygen reduction reaction (ORR). In particular, we investigated the effects of adding a secondary element, Ni, to form MnNiOx and its impact on the chemical states and catalytic activity, by tracking the redox characteristics of each element upon sweeping the electrode potential. In conclusion, the detection scheme we describe here is general and can be applied to time-resolved studies of materials consisting of multiple elements, to follow the dynamics of catalytic and electron transfer reactions.« less

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

PubMed

Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

2015-10-01

The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with the consensus model of the resting state VSD and the spin-spin distance histograms from ESR/DEER experiments on T4 lysozyme are accurately reproduced.

Competitive Reporter Monitored Amplification (CMA) - Quantification of Molecular Targets by Real Time Monitoring of Competitive Reporter Hybridization

PubMed Central

Ullrich, Thomas; Ermantraut, Eugen; Schulz, Torsten; Steinmetzer, Katrin

2012-01-01

Background State of the art molecular diagnostic tests are based on the sensitive detection and quantification of nucleic acids. However, currently established diagnostic tests are characterized by elaborate and expensive technical solutions hindering the development of simple, affordable and compact point-of-care molecular tests. Methodology and Principal Findings The described competitive reporter monitored amplification allows the simultaneous amplification and quantification of multiple nucleic acid targets by polymerase chain reaction. Target quantification is accomplished by real-time detection of amplified nucleic acids utilizing a capture probe array and specific reporter probes. The reporter probes are fluorescently labeled oligonucleotides that are complementary to the respective capture probes on the array and to the respective sites of the target nucleic acids in solution. Capture probes and amplified target compete for reporter probes. Increasing amplicon concentration leads to decreased fluorescence signal at the respective capture probe position on the array which is measured after each cycle of amplification. In order to observe reporter probe hybridization in real-time without any additional washing steps, we have developed a mechanical fluorescence background displacement technique. Conclusions and Significance The system presented in this paper enables simultaneous detection and quantification of multiple targets. Moreover, the presented fluorescence background displacement technique provides a generic solution for real time monitoring of binding events of fluorescently labelled ligands to surface immobilized probes. With the model assay for the detection of human immunodeficiency virus type 1 and 2 (HIV 1/2), we have been able to observe the amplification kinetics of five targets simultaneously and accommodate two additional hybridization controls with a simple instrument set-up. The ability to accommodate multiple controls and targets into a single assay and to perform the assay on simple and robust instrumentation is a prerequisite for the development of novel molecular point of care tests. PMID:22539973

Phylo-mLogo: an interactive and hierarchical multiple-logo visualization tool for alignment of many sequences

PubMed Central

Shih, Arthur Chun-Chieh; Lee, DT; Peng, Chin-Lin; Wu, Yu-Wei

2007-01-01

Background When aligning several hundreds or thousands of sequences, such as epidemic virus sequences or homologous/orthologous sequences of some big gene families, to reconstruct the epidemiological history or their phylogenies, how to analyze and visualize the alignment results of many sequences has become a new challenge for computational biologists. Although there are several tools available for visualization of very long sequence alignments, few of them are applicable to the alignments of many sequences. Results A multiple-logo alignment visualization tool, called Phylo-mLogo, is presented in this paper. Phylo-mLogo calculates the variabilities and homogeneities of alignment sequences by base frequencies or entropies. Different from the traditional representations of sequence logos, Phylo-mLogo not only displays the global logo patterns of the whole alignment of multiple sequences, but also demonstrates their local homologous logos for each clade hierarchically. In addition, Phylo-mLogo also allows the user to focus only on the analysis of some important, structurally or functionally constrained sites in the alignment selected by the user or by built-in automatic calculation. Conclusion With Phylo-mLogo, the user can symbolically and hierarchically visualize hundreds of aligned sequences simultaneously and easily check the changes of their amino acid sites when analyzing many homologous/orthologous or influenza virus sequences. More information of Phylo-mLogo can be found at URL . PMID:17319966

Simultaneous detection of multiple adulterants in dry milk using macro-scale Raman chemical imaging

USDA-ARS?s Scientific Manuscript database

The potential of Raman chemical imaging for simultaneously detecting multiple adulterants in milk powder was investigated. Potential chemical adulterants, including ammonium sulfate, dicyandiamide, melamine, and urea, were mixed together into skim dry milk in the concentration range of 0.1–5.0% for ...

Teaching Students with Cognitive Impairment Chained Mathematical Task of Decimal Subtraction Using Simultaneous Prompting

ERIC Educational Resources Information Center

Rao, Shaila; Kane, Martha T.

2009-01-01

This study assessed effectiveness of simultaneous prompting procedure in teaching two middle school students with cognitive impairment decimal subtraction using regrouping. A multiple baseline, multiple probe design replicated across subjects successfully taught two students with cognitive impairment at middle school level decimal subtraction…

MODi: a powerful and convenient web server for identifying multiple post-translational peptide modifications from tandem mass spectra.

PubMed

Kim, Sangtae; Na, Seungjin; Sim, Ji Woong; Park, Heejin; Jeong, Jaeho; Kim, Hokeun; Seo, Younghwan; Seo, Jawon; Lee, Kong-Joo; Paek, Eunok

2006-07-01

MOD(i) (http://modi.uos.ac.kr/modi/) is a powerful and convenient web service that facilitates the interpretation of tandem mass spectra for identifying post-translational modifications (PTMs) in a peptide. It is powerful in that it can interpret a tandem mass spectrum even when hundreds of modification types are considered and the number of potential PTMs in a peptide is large, in contrast to most of the methods currently available for spectra interpretation that limit the number of PTM sites and types being used for PTM analysis. For example, using MOD(i), one can consider for analysis both the entire PTM list published on the unimod webpage (http://www.unimod.org) and user-defined PTMs simultaneously, and one can also identify multiple PTM sites in a spectrum. MOD(i) is convenient in that it can take various input file formats such as .mzXML, .dta, .pkl and .mgf files, and it is equipped with a graphical tool called MassPective developed to display MOD(i)'s output in a user-friendly manner and helps users understand MOD(i)'s output quickly. In addition, one can perform manual de novo sequencing using MassPective.

Dendrimer-Linked Antifreeze Proteins Have Superior Activity and Thermal Recovery.

PubMed

Stevens, Corey A; Drori, Ran; Zalis, Shiran; Braslavsky, Ido; Davies, Peter L

2015-09-16

By binding to ice, antifreeze proteins (AFPs) depress the freezing point of a solution and inhibit ice recrystallization if freezing does occur. Previous work showed that the activity of an AFP was incrementally increased by fusing it to another protein. Even larger increases in activity were achieved by doubling the number of ice-binding sites by dimerization. Here, we have combined the two strategies by linking multiple outward-facing AFPs to a dendrimer to significantly increase both the size of the molecule and the number of ice-binding sites. Using a heterobifunctional cross-linker, we attached between 6 and 11 type III AFPs to a second-generation polyamidoamine (G2-PAMAM) dendrimer with 16 reactive termini. This heterogeneous sample of dendrimer-linked type III constructs showed a greater than 4-fold increase in freezing point depression over that of monomeric type III AFP. This multimerized AFP was particularly effective at ice recrystallization inhibition activity, likely because it can simultaneously bind multiple ice surfaces. Additionally, attachment to the dendrimer has afforded the AFP superior recovery from heat denaturation. Linking AFPs together via polymers can generate novel reagents for controlling ice growth and recrystallization.

Multiple well-shutdown tests and site-scale flow simulation in fractured rocks

USGS Publications Warehouse

Tiedeman, Claire; Lacombe, Pierre J.; Goode, Daniel J.

2010-01-01

A new method was developed for conducting aquifer tests in fractured-rock flow systems that have a pump-and-treat (P&T) operation for containing and removing groundwater contaminants. The method involves temporary shutdown of individual pumps in wells of the P&T system. Conducting aquifer tests in this manner has several advantages, including (1) no additional contaminated water is withdrawn, and (2) hydraulic containment of contaminants remains largely intact because pumping continues at most wells. The well-shutdown test method was applied at the former Naval Air Warfare Center (NAWC), West Trenton, New Jersey, where a P&T operation is designed to contain and remove trichloroethene and its daughter products in the dipping fractured sedimentary rocks underlying the site. The detailed site-scale subsurface geologic stratigraphy, a three-dimensional MODFLOW model, and inverse methods in UCODE_2005 were used to analyze the shutdown tests. In the model, a deterministic method was used for representing the highly heterogeneous hydraulic conductivity distribution and simulations were conducted using an equivalent porous media method. This approach was very successful for simulating the shutdown tests, contrary to a common perception that flow in fractured rocks must be simulated using a stochastic or discrete fracture representation of heterogeneity. Use of inverse methods to simultaneously calibrate the model to the multiple shutdown tests was integral to the effectiveness of the approach.

Co-delivery of chemotherapeutics and proteins for synergistic therapy.

PubMed

He, Chaoliang; Tang, Zhaohui; Tian, Huayu; Chen, Xuesi

2016-03-01

Combination therapy with chemotherapeutics and protein therapeutics, typically cytokines and antibodies, has been a type of crucial approaches for synergistic cancer treatment. However, conventional approaches by simultaneous administration of free chemotherapeutic drugs and proteins lead to limitations for further optimizing the synergistic effects, due to the distinct in vivo pharmacokinetics and distribution of small drugs and proteins, insufficient tumor selectivity and tumor accumulation, unpredictable drug/protein ratios at tumor sites, short half-lives, and serious systemic adverse effects. Consequently, to obtain optimal synergistic anti-tumor efficacy, considerable efforts have been devoted to develop the co-delivery systems for co-incorporating chemotherapeutics and proteins into a single carrier system and subsequently releasing the dual or multiple payloads at desired target sites in a more controllable manner. The co-delivery systems result in markedly enhanced blood stability and in vivo half-lives of the small drugs and proteins, elevated tumor accumulation, as well as the capability of delivering the multiple agents to the same target sites with rational drug/protein ratios, which may facilitate maximizing the synergistic effects and therefore lead to optimal antitumor efficacy. This review emphasizes the recent advances in the co-delivery systems for chemotherapeutics and proteins, typically cytokines and antibodies, for systemic or localized synergistic cancer treatment. Moreover, the proposed mechanisms responsible for the synergy of chemotherapeutic drugs and proteins are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Modelling multi-hazard hurricane damages on an urbanized coast with a Bayesian Network approach

USGS Publications Warehouse

van Verseveld, H.C.W.; Van Dongeren, A. R.; Plant, Nathaniel G.; Jäger, W.S.; den Heijer, C.

2015-01-01

Hurricane flood impacts to residential buildings in coastal zones are caused by a number of hazards, such as inundation, overflow currents, erosion, and wave attack. However, traditional hurricane damage models typically make use of stage-damage functions, where the stage is related to flooding depth only. Moreover, these models are deterministic and do not consider the large amount of uncertainty associated with both the processes themselves and with the predictions. This uncertainty becomes increasingly important when multiple hazards (flooding, wave attack, erosion, etc.) are considered simultaneously. This paper focusses on establishing relationships between observed damage and multiple hazard indicators in order to make better probabilistic predictions. The concept consists of (1) determining Local Hazard Indicators (LHIs) from a hindcasted storm with use of a nearshore morphodynamic model, XBeach, and (2) coupling these LHIs and building characteristics to the observed damages. We chose a Bayesian Network approach in order to make this coupling and used the LHIs ‘Inundation depth’, ‘Flow velocity’, ‘Wave attack’, and ‘Scour depth’ to represent flooding, current, wave impacts, and erosion related hazards.The coupled hazard model was tested against four thousand damage observations from a case site at the Rockaway Peninsula, NY, that was impacted by Hurricane Sandy in late October, 2012. The model was able to accurately distinguish ‘Minor damage’ from all other outcomes 95% of the time and could distinguish areas that were affected by the storm, but not severely damaged, 68% of the time. For the most heavily damaged buildings (‘Major Damage’ and ‘Destroyed’), projections of the expected damage underestimated the observed damage. The model demonstrated that including multiple hazards doubled the prediction skill, with Log-Likelihood Ratio test (a measure of improved accuracy and reduction in uncertainty) scores between 0.02 and 0.17 when only one hazard is considered and a score of 0.37 when multiple hazards are considered simultaneously. The LHIs with the most predictive skill were ‘Inundation depth’ and ‘Wave attack’. The Bayesian Network approach has several advantages over the market-standard stage-damage functions: the predictive capacity of multiple indicators can be combined; probabilistic predictions can be obtained, which include uncertainty; and quantitative as well as descriptive information can be used simultaneously.

JADOPPT: java based AutoDock preparing and processing tool.

PubMed

García-Pérez, Carlos; Peláez, Rafael; Therón, Roberto; Luis López-Pérez, José

2017-02-15

AutoDock is a very popular software package for docking and virtual screening. However, currently it is hard work to visualize more than one result from the virtual screening at a time. To overcome this limitation we have designed JADOPPT, a tool for automatically preparing and processing multiple ligand-protein docked poses obtained from AutoDock. It allows the simultaneous visual assessment and comparison of multiple poses through clustering methods. Moreover, it permits the representation of reference ligands with known binding modes, binding site residues, highly scoring regions for the ligand, and the calculated binding energy of the best ranked results. JADOPPT, supplementary material (Case Studies 1 and 2) and video tutorials are available at http://visualanalytics.land/cgarcia/JADOPPT.html. carlosgarcia@usal.es or pelaez@usal.es. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Detection of Multiple Pathogens in Serum Using Silica-Encapsulated Nanotags in a Surface-Enhanced Raman Scattering-Based Immunoassay.

PubMed

Neng, Jing; Li, Yina; Driscoll, Ashley J; Wilson, William C; Johnson, Patrick A

2018-06-06

A robust immunoassay based on surface-enhanced Raman scattering (SERS) has been developed to simultaneously detect trace quantities of multiple pathogenic antigens from West Nile virus, Rift Valley fever virus, and Yersinia pestis in fetal bovine serum. Antigens were detected by capture with silica-encapsulated nanotags and magnetic nanoparticles conjugated with polyclonal antibodies. The magnetic pull-down resulted in aggregation of the immune complexes, and the silica-encapsulated nanotags provided distinct spectra corresponding to each antigen captured. The limit of detection was ∼10 pg/mL in 20% fetal bovine serum, a significant improvement over previous studies in terms of sensitivity, level of multiplexing, and medium complexity. This highly sensitive multiplex immunoassay platform provides a promising method to detect various antigens directly in crude serum samples without the tedious process of sample preparation, which is desirable for on-site diagnostic testing and real-time disease monitoring.

Passive Localization of Multiple Sources Using Widely-Spaced Arrays with Application to Marine Mammals

DTIC Science & Technology

2007-09-30

the behavioral ecology of marine mammals by simultaneously tracking multiple vocalizing individuals in space and time. OBJECTIVES The ...goal is to contribute to the behavioral ecology of marine mammals by simultaneously tracking multiple vocalizing individuals in space and time. 15...OA Graduate Traineeship for E-M Nosal) LONG-TERM GOALS The goal of our research is to develop systems that use a widely spaced hydrophone array

Mirrored pyramidal wells for simultaneous multiple vantage point microscopy.

PubMed

Seale, K T; Reiserer, R S; Markov, D A; Ges, I A; Wright, C; Janetopoulos, C; Wikswo, J P

2008-10-01

We report a novel method for obtaining simultaneous images from multiple vantage points of a microscopic specimen using size-matched microscopic mirrors created from anisotropically etched silicon. The resulting pyramidal wells enable bright-field and fluorescent side-view images, and when combined with z-sectioning, provide additional information for 3D reconstructions of the specimen. We have demonstrated the 3D localization and tracking over time of the centrosome of a live Dictyostelium discoideum. The simultaneous acquisition of images from multiple perspectives also provides a five-fold increase in the theoretical collection efficiency of emitted photons, a property which may be useful for low-light imaging modalities such as bioluminescence, or low abundance surface-marker labelling.

In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR-dCas9-activator transgenic mice.

PubMed

Zhou, Haibo; Liu, Junlai; Zhou, Changyang; Gao, Ni; Rao, Zhiping; Li, He; Hu, Xinde; Li, Changlin; Yao, Xuan; Shen, Xiaowen; Sun, Yidi; Wei, Yu; Liu, Fei; Ying, Wenqin; Zhang, Junming; Tang, Cheng; Zhang, Xu; Xu, Huatai; Shi, Linyu; Cheng, Leping; Huang, Pengyu; Yang, Hui

2018-03-01

Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.

Multiple Antibiotic Resistance Plasmids Allow Scalable,
PCR-Mediated DNA Manipulation and Near-Zero Background Cloning

PubMed Central

Arnak, Remigiusz; Altun, Burcin; Tosato, Valentina

2016-01-01

Summary We have constructed two plasmids that can be used for cloning as templates for PCR- -based gene disruption, mutagenesis and the construction of DNA chromosome translocation cassettes. To our knowledge, these plasmids are the first vectors that confer resistance to ampicillin, kanamycin and hygromycin B in bacteria, and to geneticin (G418) and hygromycin B in Saccharomyces cerevisiae simultaneously. The option of simultaneously using up to three resistance markers provides a highly stringent control of recombinant selection and the almost complete elimination of background resistance, while unique restriction sites allow easy cloning of chosen genetic material. Moreover, we successfully used these new vectors as PCR templates for the induction of chromosome translocation in budding yeast by the bridge-induced translocation system. Cells in which translocation was induced carried chromosomal rearrangements as expected and exhibited resistance to both, G418 and hygromycin B. These features make our constructs very handy tools for many molecular biology applications. PMID:27956856

Cisplatin Cross-Linked Multifunctional Nanodrugplexes for Combination Therapy.

PubMed

Zhang, Weiqi; Tung, Ching-Hsuan

2017-03-15

Combination therapy efficiently tackles cancer by hitting multiple action mechanisms. However, drugs administered, simultaneously or sequentially, may not reach the targeted sites with the desired dose and ratio. The outcomes of combination therapy could be improved with a polymeric nanoparticle, which can simultaneously transport an optimal combination of drugs. We have demonstrated a simple one-pot strategy to formulate nanomedicines based on platinum coordination and the noncovalent interactions of the drugs. A naturally occurring polymer, hyaluronan (HA), was chosen as the building scaffold to form a nanodrugplex with cisplatin and aromatic-cationic drugs. The platinum coordination between cisplatin and HA induces the formation of a nanocomplex. The aromatic-cationic drugs are tightly packed by an electrostatic interaction and π-π stacking. The nanodrugplex bears excellent flexibility in drug combination and size control. It is stable in storage and has favorable release kinetics and targeting capabilities toward CD44, a receptor for HA that is highly expressed on many types of cancer cells.

Delivery of Cancer Therapeutics Using Nanotechnology

PubMed Central

Lim, Eun-Kyung; Jang, Eunji; Lee, Kwangyeol; Haam, Seungjoo; Huh, Yong-Min

2013-01-01

Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems. PMID:24300452

A simultaneous multichannel monophasic action potential electrode array for in vivo epicardial repolarization mapping.

PubMed

Sahakian, A V; Peterson, M S; Shkurovich, S; Hamer, M; Votapka, T; Ji, T; Swiryn, S

2001-03-01

While the recording of extracellular monophasic action potentials (MAPs) from single epicardial or endocardial sites has been performed for over a century, we are unaware of any previous successful attempt to record MAPs simultaneously from a large number of sites in vivo. We report here the design and validation of an array of MAP electrodes which records both depolarization and repolarization simultaneously at up to 16 epicardial sites in a square array on the heart in vivo. The array consists of 16 sintered Ag-AgCl electrodes mounted in a common housing with individual suspensions allowing each electrode to exert a controlled pressure on the epicardial surface. The electrodes are arranged in a square array, with each quadrant of four having an additional recessed sintered Ag-AgCl reference electrode at its center. A saline-soaked sponge establishes ionic contact between the reference electrodes and the tissue. The array was tested on six anesthetized open-chested pigs. Simultaneous diagnostic-quality MAP recordings were obtained from up to 13 out of 16 ventricular sites. Ventricular MAPs had amplitudes of 10-40 mV with uniform morphologies and stable baselines for up to 30 min. MAP duration at 90% repolarization was measured and shown to vary as expected with cycle length during sustained pacing. The relationship between MAP duration and effective refractory period was also confirmed. The ability of the array to detect local differences in repolarization was tested in two ways. Placement of the array straddling the atrioventricular (AV) junction yielded simultaneous atrial or ventricular recordings at corresponding sites during 1:1 and 2:1 AV conduction. Localized ischemia via constriction of a coronary artery branch resulted in shortening of the repolarization phase at the ischemic, but not the nonischemic, sites. In conclusion, these results indicate that the simultaneous multichannel MAP electrode array is a viable method for in vivo epicardial repolarization mapping. The array has the potential to be expanded to increase the number of sites and spatial resolution.

Rapid analytical methods for on-site triage for traumatic brain injury.

PubMed

North, Stella H; Shriver-Lake, Lisa C; Taitt, Chris R; Ligler, Frances S

2012-01-01

Traumatic brain injury (TBI) results from an event that causes rapid acceleration and deceleration of the brain or penetration of the skull with an object. Responses to stimuli and questions, loss of consciousness, and altered behavior are symptoms currently used to justify brain imaging for diagnosis and therapeutic guidance. Tests based on such symptoms are susceptible to false-positive and false-negative results due to stress, fatigue, and medications. Biochemical markers of neuronal damage and the physiological response to that damage are being identified. Biosensors capable of rapid measurement of such markers in the circulation offer a solution for on-site triage, as long as three criteria are met: (a) Recognition reagents can be identified that are sufficiently sensitive and specific, (b) the biosensor can provide quantitative assessment of multiple markers rapidly and simultaneously, and (c) both the sensor and reagents are designed for use outside the laboratory.

Quantifying Genome Editing Outcomes at Endogenous Loci using SMRT Sequencing

PubMed Central

Clark, Joseph; Punjya, Niraj; Sebastiano, Vittorio; Bao, Gang; Porteus, Matthew H

2014-01-01

SUMMARY Targeted genome editing with engineered nucleases has transformed the ability to introduce precise sequence modifications at almost any site within the genome. A major obstacle to probing the efficiency and consequences of genome editing is that no existing method enables the frequency of different editing events to be simultaneously measured across a cell population at any endogenous genomic locus. We have developed a novel method for quantifying individual genome editing outcomes at any site of interest using single molecule real time (SMRT) DNA sequencing. We show that this approach can be applied at various loci, using multiple engineered nuclease platforms including TALENs, RNA guided endonucleases (CRISPR/Cas9), and ZFNs, and in different cell lines to identify conditions and strategies in which the desired engineering outcome has occurred. This approach facilitates the evaluation of new gene editing technologies and permits sensitive quantification of editing outcomes in almost every experimental system used. PMID:24685129

Copper bioavailability and toxicity to Mytilus galloprovincialis in Shelter Island Yacht Basin, San Diego, CA.

PubMed

Bosse, Casey; Rosen, Gunther; Colvin, Marienne; Earley, Patrick; Santore, Robert; Rivera-Duarte, Ignacio

2014-08-15

The bioavailability and toxicity of copper (Cu) in Shelter Island Yacht Basin (SIYB), San Diego, CA, USA, was assessed with simultaneous toxicological, chemical, and modeling approaches. Toxicological measurements included laboratory toxicity testing with Mytilus galloprovincialis (Mediterranean mussel) embryos added to both site water (ambient) and site water spiked with multiple Cu concentrations. Chemical assessment of ambient samples included total and dissolved Cu concentrations, and Cu complexation capacity measurements. Modeling was based on chemical speciation and predictions of bioavailability and toxicity using a marine Biotic Ligand Model (BLM). Cumulatively, these methods assessed the natural buffering capacity of Cu in SIYB during singular wet and dry season sampling events. Overall, the three approaches suggested negligible bioavailability, and isolated observed or predicted toxicity, despite an observed gradient of increasing Cu concentration, both horizontally and vertically within the water body, exceeding current water quality criteria for saltwater. Published by Elsevier Ltd.

Rapid Analytical Methods for On-Site Triage for Traumatic Brain Injury

NASA Astrophysics Data System (ADS)

North, Stella H.; Shriver-Lake, Lisa C.; Taitt, Chris R.; Ligler, Frances S.

2012-07-01

Traumatic brain injury (TBI) results from an event that causes rapid acceleration and deceleration of the brain or penetration of the skull with an object. Responses to stimuli and questions, loss of consciousness, and altered behavior are symptoms currently used to justify brain imaging for diagnosis and therapeutic guidance. Tests based on such symptoms are susceptible to false-positive and false-negative results due to stress, fatigue, and medications. Biochemical markers of neuronal damage and the physiological response to that damage are being identified. Biosensors capable of rapid measurement of such markers in the circulation offer a solution for on-site triage, as long as three criteria are met: (a) Recognition reagents can be identified that are sufficiently sensitive and specific, (b) the biosensor can provide quantitative assessment of multiple markers rapidly and simultaneously, and (c) both the sensor and reagents are designed for use outside the laboratory.

The theory of maximally and minimally even sets, the one- dimensional antiferromagnetic Ising model, and the continued fraction compromise of musical scales

NASA Astrophysics Data System (ADS)

Douthett, Elwood (Jack) Moser, Jr.

1999-10-01

Cyclic configurations of white and black sites, together with convex (concave) functions used to weight path length, are investigated. The weights of the white set and black set are the sums of the weights of the paths connecting the white sites and black sites, respectively, and the weight between sets is the sum of the weights of the paths that connect sites opposite in color. It is shown that when the weights of all configurations of a fixed number of white and a fixed number of black sites are compared, minimum (maximum) weight of a white set, minimum (maximum) weight of the a black set, and maximum (minimum) weight between sets occur simultaneously. Such configurations are called maximally even configurations. Similarly, the configurations whose weights are the opposite extremes occur simultaneously and are called minimally even configurations. Algorithms that generate these configurations are constructed and applied to the one- dimensional antiferromagnetic spin-1/2 Ising model. Next the goodness of continued fractions as applied to musical intervals (frequency ratios and their base 2 logarithms) is explored. It is shown that, for the intermediate convergents between two consecutive principal convergents of an irrational number, the first half of the intermediate convergents are poorer approximations than the preceding principal convergent while the second half are better approximations; the goodness of a middle intermediate convergent can only be determined by calculation. These convergents are used to determine what equal-tempered systems have intervals that most closely approximate the musical fifth (pn/ qn = log2(3/2)). The goodness of exponentiated convergents ( 2pn/qn~3/2 ) is also investigated. It is shown that, with the exception of a middle convergent, the goodness of the exponential form agrees with that of its logarithmic Counterpart As in the case of the logarithmic form, the goodness of a middle intermediate convergent in the exponential form can only be determined by calculation. A Desirability Function is constructed that simultaneously measures how well multiple intervals fit in a given equal-tempered system. These measurements are made for octave (base 2) and tritave systems (base 3). Combinatorial properties important to music modulation are considered. These considerations lead These considerations lead to the construction of maximally even scales as partitions of an equal-tempered system.

Structured plant metabolomics for the simultaneous exploration of multiple factors.

PubMed

Vasilev, Nikolay; Boccard, Julien; Lang, Gerhard; Grömping, Ulrike; Fischer, Rainer; Goepfert, Simon; Rudaz, Serge; Schillberg, Stefan

2016-11-17

Multiple factors act simultaneously on plants to establish complex interaction networks involving nutrients, elicitors and metabolites. Metabolomics offers a better understanding of complex biological systems, but evaluating the simultaneous impact of different parameters on metabolic pathways that have many components is a challenging task. We therefore developed a novel approach that combines experimental design, untargeted metabolic profiling based on multiple chromatography systems and ionization modes, and multiblock data analysis, facilitating the systematic analysis of metabolic changes in plants caused by different factors acting at the same time. Using this method, target geraniol compounds produced in transgenic tobacco cell cultures were grouped into clusters based on their response to different factors. We hypothesized that our novel approach may provide more robust data for process optimization in plant cell cultures producing any target secondary metabolite, based on the simultaneous exploration of multiple factors rather than varying one factor each time. The suitability of our approach was verified by confirming several previously reported examples of elicitor-metabolite crosstalk. However, unravelling all factor-metabolite networks remains challenging because it requires the identification of all biochemically significant metabolites in the metabolomics dataset.

Disruption of the microbiota across multiple body sites in critically ill children.

PubMed

Rogers, Matthew B; Firek, Brian; Shi, Min; Yeh, Andrew; Brower-Sinning, Rachel; Aveson, Victoria; Kohl, Brittany L; Fabio, Anthony; Carcillo, Joseph A; Morowitz, Michael J

2016-12-29

Despite intense interest in the links between the microbiome and human health, little has been written about dysbiosis among ICU patients. We characterized microbial diversity in samples from 37 children in a pediatric ICU (PICU). Standard measures of alpha and beta diversity were calculated, and results were compared with data from adult and pediatric reference datasets. Bacterial 16S rRNA gene sequences were analyzed from 71 total tongue swabs, 50 skin swabs, and 77 stool samples or rectal swabs. The mean age of the PICU patients was 2.9 years (range 1-9 years), and many were chronically ill children that had previously been hospitalized in the PICU. Relative to healthy adults and children, alpha diversity was decreased in PICU GI and tongue but not skin samples. Measures of beta diversity indicated differences in community membership at each body site between PICU, adult, and pediatric groups. Taxonomic alterations in the PICU included enrichment of gut pathogens such as Enterococcus and Staphylococcus at multiple body sites and depletion of commensals such as Faecalibacterium and Ruminococcus from GI samples. Alpha and beta diversity were unstable over time in patients followed longitudinally. We observed the frequent presence of "dominant" pathogens in PICU samples at relative abundance >50%. PICU samples were characterized by loss of site specificity, with individual taxa commonly present simultaneously at three sample sites on a single individual. Some pathogens identified by culture of tracheal aspirates were commonly observed in skin samples from the same patient. We conclude that the microbiota in critically ill children differs sharply from the microbiota of healthy children and adults. Acknowledgement of dysbiosis associated with critical illness could provide opportunities to modulate the microbiota with precision and thereby improve patient outcomes.

Comparison of procedures for correction of matrix interferences in the analysis of soils by ICP-OES with CCD detection

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

Sadler, D.A.; Sun, F.; Littlejohn, D.

1995-12-31

ICP-OES is a useful technique for multi-element analysis of soils. However, as a number of elements are present in relatively high concentrations, matrix interferences can occur and examples have been widely reported. The availability of CCD detectors has increased the opportunities for rapid multi-element, multi-wave-length determination of elemental concentrations in soils and other environmental samples. As the composition of soils from industrial sites can vary considerably, especially when taken from different pit horizons, procedures are required to assess the extent of interferences and correct the effects, on a simultaneous multi-element basis. In single element analysis, plasma operating conditions can sometimesmore » be varied to minimize or even remove multiplicative interferences. In simultaneous multi-element analysis, the scope for this approach may be limited, depending on the spectrochemical characteristics of the emitting analyte species. Matrix matching, by addition of major sample components to the analyte calibrant solutions, can be used to minimize inaccuracies. However, there are also limitations to this procedure, when the sample composition varies significantly. Multiplicative interference effects can also be assessed by a {open_quotes}single standard addition{close_quotes} of each analyte to the sample solution and the information obtained may be used to correct the analyte concentrations determined directly. Each of these approaches has been evaluated to ascertain the best procedure for multi-element analysis of industrial soils by ICP-OES with CCD detection at multiple wavelengths. Standard reference materials and field samples have been analyzed to illustrate the efficacy of each procedure.« less

Multiple Frequency Contrast Source Inversion Method for Vertical Electromagnetic Profiling: 2D Simulation Results and Analyses

NASA Astrophysics Data System (ADS)

Li, Jinghe; Song, Linping; Liu, Qing Huo

2016-02-01

A simultaneous multiple frequency contrast source inversion (CSI) method is applied to reconstructing hydrocarbon reservoir targets in a complex multilayered medium in two dimensions. It simulates the effects of a salt dome sedimentary formation in the context of reservoir monitoring. In this method, the stabilized biconjugate-gradient fast Fourier transform (BCGS-FFT) algorithm is applied as a fast solver for the 2D volume integral equation for the forward computation. The inversion technique with CSI combines the efficient FFT algorithm to speed up the matrix-vector multiplication and the stable convergence of the simultaneous multiple frequency CSI in the iteration process. As a result, this method is capable of making quantitative conductivity image reconstruction effectively for large-scale electromagnetic oil exploration problems, including the vertical electromagnetic profiling (VEP) survey investigated here. A number of numerical examples have been demonstrated to validate the effectiveness and capacity of the simultaneous multiple frequency CSI method for a limited array view in VEP.

End of FY10 report - used fuel disposition technical bases and lessons learned : legal and regulatory framework for high-level waste disposition in the United States.

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

Weiner, Ruth F.; Blink, James A.; Rechard, Robert Paul

This report examines the current policy, legal, and regulatory framework pertaining to used nuclear fuel and high level waste management in the United States. The goal is to identify potential changes that if made could add flexibility and possibly improve the chances of successfully implementing technical aspects of a nuclear waste policy. Experience suggests that the regulatory framework should be established prior to initiating future repository development. Concerning specifics of the regulatory framework, reasonable expectation as the standard of proof was successfully implemented and could be retained in the future; yet, the current classification system for radioactive waste, including hazardousmore » constituents, warrants reexamination. Whether or not consideration of multiple sites are considered simultaneously in the future, inclusion of mechanisms such as deliberate use of performance assessment to manage site characterization would be wise. Because of experience gained here and abroad, diversity of geologic media is not particularly necessary as a criterion in site selection guidelines for multiple sites. Stepwise development of the repository program that includes flexibility also warrants serious consideration. Furthermore, integration of the waste management system from storage, transportation, and disposition, should be examined and would be facilitated by integration of the legal and regulatory framework. Finally, in order to enhance acceptability of future repository development, the national policy should be cognizant of those policy and technical attributes that enhance initial acceptance, and those policy and technical attributes that maintain and broaden credibility.« less

Comparative efficacy of simultaneous versus sequential multiple health behavior change interventions among adults: A systematic review of randomised trials.

PubMed

James, Erica; Freund, Megan; Booth, Angela; Duncan, Mitch J; Johnson, Natalie; Short, Camille E; Wolfenden, Luke; Stacey, Fiona G; Kay-Lambkin, Frances; Vandelanotte, Corneel

2016-08-01

Growing evidence points to the benefits of addressing multiple health behaviors rather than single behaviors. This review evaluates the relative effectiveness of simultaneous and sequentially delivered multiple health behavior change (MHBC) interventions. Secondary aims were to identify: a) the most effective spacing of sequentially delivered components; b) differences in efficacy of MHBC interventions for adoption/cessation behaviors and lifestyle/addictive behaviors, and; c) differences in trial retention between simultaneously and sequentially delivered interventions. MHBC intervention trials published up to October 2015 were identified through a systematic search. Eligible trials were randomised controlled trials that directly compared simultaneous and sequential delivery of a MHBC intervention. A narrative synthesis was undertaken. Six trials met the inclusion criteria and across these trials the behaviors targeted were smoking, diet, physical activity, and alcohol consumption. Three trials reported a difference in intervention effect between a sequential and simultaneous approach in at least one behavioral outcome. Of these, two trials favoured a sequential approach on smoking. One trial favoured a simultaneous approach on fat intake. There was no difference in retention between sequential and simultaneous approaches. There is limited evidence regarding the relative effectiveness of sequential and simultaneous approaches. Given only three of the six trials observed a difference in intervention effectiveness for one health behavior outcome, and the relatively consistent finding that the sequential and simultaneous approaches were more effective than a usual/minimal care control condition, it appears that both approaches should be considered equally efficacious. PROSPERO registration number: CRD42015027876. Copyright © 2016 Elsevier Inc. All rights reserved.

Automated simultaneous multiple feature classification of MTI data

NASA Astrophysics Data System (ADS)

Harvey, Neal R.; Theiler, James P.; Balick, Lee K.; Pope, Paul A.; Szymanski, John J.; Perkins, Simon J.; Porter, Reid B.; Brumby, Steven P.; Bloch, Jeffrey J.; David, Nancy A.; Galassi, Mark C.

2002-08-01

Los Alamos National Laboratory has developed and demonstrated a highly capable system, GENIE, for the two-class problem of detecting a single feature against a background of non-feature. In addition to the two-class case, however, a commonly encountered remote sensing task is the segmentation of multispectral image data into a larger number of distinct feature classes or land cover types. To this end we have extended our existing system to allow the simultaneous classification of multiple features/classes from multispectral data. The technique builds on previous work and its core continues to utilize a hybrid evolutionary-algorithm-based system capable of searching for image processing pipelines optimized for specific image feature extraction tasks. We describe the improvements made to the GENIE software to allow multiple-feature classification and describe the application of this system to the automatic simultaneous classification of multiple features from MTI image data. We show the application of the multiple-feature classification technique to the problem of classifying lava flows on Mauna Loa volcano, Hawaii, using MTI image data and compare the classification results with standard supervised multiple-feature classification techniques.

Bivalent phenethylamines as novel dopamine transporter inhibitors: evidence for multiple substrate-binding sites in a single transporter.

PubMed

Schmitt, Kyle C; Mamidyala, Sreeman; Biswas, Swati; Dutta, Aloke K; Reith, Maarten E A

2010-03-01

Bivalent ligands--compounds incorporating two receptor-interacting moieties linked by a flexible chain--often exhibit profoundly enhanced binding affinity compared with their monovalent components, implying concurrent binding to multiple sites on the target protein. It is generally assumed that neurotransmitter sodium symporter (NSS) proteins, such as the dopamine transporter (DAT), contain a single domain responsible for recognition of substrate molecules. In this report, we show that molecules possessing two substrate-like phenylalkylamine moieties linked by a progressively longer aliphatic spacer act as progressively more potent DAT inhibitors (rather than substrates). One compound bearing two dopamine (DA)-like pharmacophoric 'heads' separated by an 8-carbon linker achieved an 82-fold gain in inhibition of [(3)H] 2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane (CFT) binding compared with DA itself; bivalent compounds with a 6-carbon linker and heterologous combinations of DA-, amphetamine- and beta-phenethylamine-like heads all resulted in considerable and comparable gains in DAT affinity. A series of short-chain bivalent-like compounds with a single N-linkage was also identified, the most potent of which displayed a 74-fold gain in binding affinity. Computational modelling of the DAT protein and docking of the two most potent bivalent (-like) ligands suggested simultaneous occupancy of two discrete substrate-binding domains. Assays with the DAT mutants W84L and D313N--previously employed by our laboratory to probe conformation-specific binding of different structural classes of DAT inhibitors--indicated a bias of the bivalent ligands for inward-facing transporters. Our results strongly indicate the existence of multiple DAT substrate-interaction sites, implying that it is possible to design novel types of DAT inhibitors based upon the 'multivalent ligand' strategy.

Hydraulic characterization of volcanic rocks in Pahute Mesa using an integrated analysis of 16 multiple-well aquifer tests, Nevada National Security Site, 2009–14

USGS Publications Warehouse

Garcia, C. Amanda; Jackson, Tracie R.; Halford, Keith J.; Sweetkind, Donald S.; Damar, Nancy A.; Fenelon, Joseph M.; Reiner, Steven R.

2017-01-20

An improved understanding of groundwater flow and radionuclide migration downgradient from underground nuclear-testing areas at Pahute Mesa, Nevada National Security Site, requires accurate subsurface hydraulic characterization. To improve conceptual models of flow and transport in the complex hydrogeologic system beneath Pahute Mesa, the U.S. Geological Survey characterized bulk hydraulic properties of volcanic rocks using an integrated analysis of 16 multiple-well aquifer tests. Single-well aquifer-test analyses provided transmissivity estimates at pumped wells. Transmissivity estimates ranged from less than 1 to about 100,000 square feet per day in Pahute Mesa and the vicinity. Drawdown from multiple-well aquifer testing was estimated and distinguished from natural fluctuations in more than 200 pumping and observation wells using analytical water-level models. Drawdown was detected at distances greater than 3 miles from pumping wells and propagated across hydrostratigraphic units and major structures, indicating that neither faults nor structural blocks noticeably impede or divert groundwater flow in the study area.Consistent hydraulic properties were estimated by simultaneously interpreting drawdown from the 16 multiple-well aquifer tests with an integrated groundwater-flow model composed of 11 well-site models—1 for each aquifer test site. Hydraulic properties were distributed across volcanic rocks with the Phase II Pahute Mesa-Oasis Valley Hydrostratigraphic Framework Model. Estimated hydraulic-conductivity distributions spanned more than two orders of magnitude in hydrostratigraphic units. Overlapping hydraulic conductivity ranges among units indicated that most Phase II Hydrostratigraphic Framework Model units were not hydraulically distinct. Simulated total transmissivity ranged from 1,600 to 68,000 square feet per day for all pumping wells analyzed. High-transmissivity zones exceeding 10,000 square feet per day exist near caldera margins and extend along the northern and eastern Pahute Mesa study area and near the southwestern edge of the study area. The estimated hydraulic-property distributions and observed hydraulic connections among geologic structures improved the characterization and representation of groundwater flow at Pahute Mesa.

Seeing the forest through the trees: Considering roost-site selection at multiple spatial scales

USGS Publications Warehouse

Jachowski, David S.; Rota, Christopher T.; Dobony, Christopher A.; Ford, W. Mark; Edwards, John W.

2016-01-01

Conservation of bat species is one of the most daunting wildlife conservation challenges in North America, requiring detailed knowledge about their ecology to guide conservation efforts. Outside of the hibernating season, bats in temperate forest environments spend their diurnal time in day-roosts. In addition to simple shelter, summer roost availability is as critical as maternity sites and maintaining social group contact. To date, a major focus of bat conservation has concentrated on conserving individual roost sites, with comparatively less focus on the role that broader habitat conditions contribute towards roost-site selection. We evaluated roost-site selection by a northern population of federally-endangered Indiana bats (Myotis sodalis) at Fort Drum Military Installation in New York, USA at three different spatial scales: landscape, forest stand, and individual tree level. During 2007–2011, we radiotracked 33 Indiana bats (10 males, 23 females) and located 348 roosting events in 116 unique roost trees. At the landscape scale, bat roost-site selection was positively associated with northern mixed forest, increased slope, and greater distance from human development. At the stand scale, we observed subtle differences in roost site selection based on sex and season, but roost selection was generally positively associated with larger stands with a higher basal area, larger tree diameter, and a greater sugar maple (Acer saccharum) component. We observed no distinct trends of roosts being near high-quality foraging areas of water and forest edges. At the tree scale, roosts were typically in American elm (Ulmus americana) or sugar maple of large diameter (>30 cm) of moderate decay with loose bark. Collectively, our results highlight the importance of considering day roost needs simultaneously across multiple spatial scales. Size and decay class of individual roosts are key ecological attributes for the Indiana bat, however, larger-scale stand structural components that are products of past and current land use interacting with environmental aspects such as landform also are important factors influencing roost-tree selection patterns.

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

Bevelhimer, Mark S.; Adams, Marshall; Fortner, Allison M.

The effect of coal ash exposure on fish health in freshwater communities is largely unknown. Given the large number of possible pathways of effects (e.g., toxicological effect of exposure to multiple metals, physical effects from ash exposure, and food web effects), measurement of only a few health metrics is not likely to give a complete picture. The authors measured a suite of 20 health metrics from 1100+ fish collected from 5 sites (3 affected and 2 reference) near a coal ash spill in east Tennessee over a 4.5-yr period. The metrics represented a wide range of physiological and energetic responsesmore » and were evaluated simultaneously using 2 multivariate techniques. Results from both hierarchical clustering and canonical discriminant analyses suggested that for most speciesXseason combinations, the suite of fish health indicators varied more among years than between spill and reference sites within a year. In a few cases, spill sites from early years in the investigation stood alone or clustered together separate from reference sites and later year spill sites. Outlier groups of fish with relatively unique health profiles were most often from spill sites, suggesting that some response to the ash exposure may have occurred. Results from the 2 multivariate methods suggest that any change in the health status of fish at the spill sites was small and appears to have diminished since the first 2 to 3 yr after the spill.« less

Solute-specific patterns and drivers of urban stream chemistry revealed by long-term monitoring in Baltimore, Maryland

NASA Astrophysics Data System (ADS)

Reisinger, A. J.; Woytowitz, E.; Majcher, E.; Rosi, E. J.; Groffman, P.

2017-12-01

Urban streams receive a myriad of chemical inputs from the surrounding landscape due to altered lithology (asphalt, concrete), leaky sewage infrastructure, and other human activities (road salt, fertilizer, industrial wastes, wastewater effluent), potentially leading to multiple chemical stressors occurring simultaneously. To evaluate potential drivers of water chemistry change, we used approximately 20 years of weekly water chemistry monitoring data from streams in the Baltimore Ecosystem Study (BES) to quantify trends of annual loads and flow-weighted concentrations for multiple solutes of interest, including nitrate (NO3-), phosphate (PO43-), total nitrogen (TN), total phosphorus (TP), chloride (Cl-), and sulfate (SO42-) and subsequently examined various gray and green infrastructure characteristics at the watershed scale. For example, we quantified annual volume and duration of reported sanitary sewer overflows (SSO) and cumulative storage volume and area of various best management practices (BMPs). Site- and solute-specific trends differed, but across our monitoring network we found evidence for decreasing annual export for multiple solutes. Additionally, we found that changes in gray- and green-infrastructure characteristics were related to changes in water quality at our most downstream (most urban) monitoring site. For example, annual NO3- loads increased with longer cumulative SSO duration, whereas annual PO43- and TP loads decreased with a cumulative BMP area in the watershed. Further, we used same long-term water chemistry data and multivariate analyses to investigate whether urban streams have unique water chemistry fingerprints representing the multiple chemical stressors at a given site, which could provide insight into sources and impacts of water-quality impairment. These analyses and results illustrate the major role gray and green infrastructure play in influencing water quality in urban environments, and illustrate that focusing on a variety of chemical stressors is necessary to gain a broader understanding of the issues affecting urban water quality.

A molecular and antigenic survey of H5N1 highly pathogenic avian influenza virus isolates from smallholder duck farms in Central Java, Indonesia during 2007-2008.

PubMed

Wibawa, Hendra; Henning, Joerg; Wong, Frank; Selleck, Paul; Junaidi, Akhmad; Bingham, John; Daniels, Peter; Meers, Joanne

2011-09-07

Indonesia is one of the countries most severely affected by H5N1 highly pathogenic avian influenza (HPAI) virus in terms of poultry and human health. However, there is little information on the diversity of H5N1 viruses circulating in backyard farms, where chickens and ducks often intermingle. In this study, H5N1 virus infection occurring in 96 smallholder duck farms in central Java, Indonesia from 2007-2008 was investigated and the molecular and antigenic characteristics of H5N1 viruses isolated from these farms were analysed. All 84 characterised viruses belonged to H5N1 clade 2.1 with three virus sublineages being identified: clade 2.1.1 (1), clade 2.1.3 (80), and IDN/6/05-like viruses (3) that did not belong to any of the present clades. All three clades were found in ducks, while only clade 2.1.3 was isolated from chickens. There were no significant amino acid mutations of the hemagglutinin (HA) and neuraminidase (NA) sites of the viruses, including the receptor binding, glycosylation, antigenic and catalytic sites and NA inhibitor targets. All the viruses had polybasic amino acids at the HA cleavage site. No evidence of major antigenic variants was detected. Based on the HA gene, identical virus variants could be found on different farms across the study sites and multiple genetic variants could be isolated from HPAI outbreaks simultaneously or at different time points from single farms. HPAI virus was isolated from both ducks and chickens; however, the proportion of surviving duck cases was considerably higher than in chickens. The 2.1.3 clade was the most common lineage found in this study. All the viruses had sequence characteristic of HPAI, but negligible variations in other recognized amino acids at the HA and NA proteins which determine virus phenotypes. Multiple genetic variants appeared to be circulating simultaneously within poultry communities. The high proportion of live duck cases compared to chickens over the study period suggests that ducks are more likely to survive infection and they may better suit the role of long-term maintenance host for H5N1. As some viruses were isolated from dead birds, there was no clear correlation between genetic variations and pathogenicity of these viruses.

Tracking Multiple Statistics: Simultaneous Learning of Object Names and Categories in English and Mandarin Speakers

ERIC Educational Resources Information Center

Chen, Chi-hsin; Gershkoff-Stowe, Lisa; Wu, Chih-Yi; Cheung, Hintat; Yu, Chen

2017-01-01

Two experiments were conducted to examine adult learners' ability to extract multiple statistics in simultaneously presented visual and auditory input. Experiment 1 used a cross-situational learning paradigm to test whether English speakers were able to use co-occurrences to learn word-to-object mappings and concurrently form object categories…

Acoustic classification of multiple simultaneous bird species: a multi-instance multi-label approach

Treesearch

F. Briggs; B. Lakshminarayanan; L. Neal; X.Z. Fern; R. Raich; S.F. Hadley; A.S. Hadley; M.G. Betts

2012-01-01

Although field-collected recordings typically contain multiple simultaneously vocalizing birds of different species, acoustic species classification in this setting has received little study so far. This work formulates the problem of classifying the set of species present in an audio recording using the multi-instance multi-label (MIML) framework for machine learning...

Predicting Final GPA of Graduate School Students: Comparing Artificial Neural Networking and Simultaneous Multiple Regression

ERIC Educational Resources Information Center

Anderson, Joan L.

2006-01-01

Data from graduate student applications at a large Western university were used to determine which factors were the best predictors of success in graduate school, as defined by cumulative graduate grade point average. Two statistical models were employed and compared: artificial neural networking and simultaneous multiple regression. Both models…

Mirrored pyramidal wells for simultaneous multiple vantage point microscopy

PubMed Central

Seale, K.T.; Reiserer, R.S.; Markov, D.A.; Ges, I.A.; Wright, C.; Janetopoulos, C.; Wikswo, J.P.

2013-01-01

Summary We report a novel method for obtaining simultaneous images from multiple vantage points of a microscopic specimen using size-matched microscopic mirrors created from anisotropically etched silicon. The resulting pyramidal wells enable bright-field and fluorescent side-view images, and when combined with z-sectioning, provide additional information for 3D reconstructions of the specimen. We have demonstrated the 3D localization and tracking over time of the centrosome of a live Dictyostelium discoideum. The simultaneous acquisition of images from multiple perspectives also provides a five-fold increase in the theoretical collection efficiency of emitted photons, a property which may be useful for low-light imaging modalities such as bioluminescence, or low abundance surface-marker labelling. PMID:19017196

Simultaneously measuring multiple protein interactions and their correlations in a cell by Protein-interactome Footprinting

PubMed Central

Luo, Si-Wei; Liang, Zhi; Wu, Jia-Rui

2017-01-01

Quantitatively detecting correlations of multiple protein-protein interactions (PPIs) in vivo is a big challenge. Here we introduce a novel method, termed Protein-interactome Footprinting (PiF), to simultaneously measure multiple PPIs in one cell. The principle of PiF is that each target physical PPI in the interactome is simultaneously transcoded into a specific DNA sequence based on dimerization of the target proteins fused with DNA-binding domains. The interaction intensity of each target protein is quantified as the copy number of the specific DNA sequences bound by each fusion protein dimers. Using PiF, we quantitatively reveal dynamic patterns of PPIs and their correlation network in E. coli two-component systems. PMID:28338015

The influence of vegetation and soil characteristics on active-layer thickness of permafrost soils in boreal forest.

PubMed

Fisher, James P; Estop-Aragonés, Cristian; Thierry, Aaron; Charman, Dan J; Wolfe, Stephen A; Hartley, Iain P; Murton, Julian B; Williams, Mathew; Phoenix, Gareth K

2016-09-01

Carbon release from thawing permafrost soils could significantly exacerbate global warming as the active-layer deepens, exposing more carbon to decay. Plant community and soil properties provide a major control on this by influencing the maximum depth of thaw each summer (active-layer thickness; ALT), but a quantitative understanding of the relative importance of plant and soil characteristics, and their interactions in determine ALTs, is currently lacking. To address this, we undertook an extensive survey of multiple vegetation and edaphic characteristics and ALTs across multiple plots in four field sites within boreal forest in the discontinuous permafrost zone (NWT, Canada). Our sites included mature black spruce, burned black spruce and paper birch, allowing us to determine vegetation and edaphic drivers that emerge as the most important and broadly applicable across these key vegetation and disturbance gradients, as well as providing insight into site-specific differences. Across sites, the most important vegetation characteristics limiting thaw (shallower ALTs) were tree leaf area index (LAI), moss layer thickness and understory LAI in that order. Thicker soil organic layers also reduced ALTs, though were less influential than moss thickness. Surface moisture (0-6 cm) promoted increased ALTs, whereas deeper soil moisture (11-16 cm) acted to modify the impact of the vegetation, in particular increasing the importance of understory or tree canopy shading in reducing thaw. These direct and indirect effects of moisture indicate that future changes in precipitation and evapotranspiration may have large influences on ALTs. Our work also suggests that forest fires cause greater ALTs by simultaneously decreasing multiple ecosystem characteristics which otherwise protect permafrost. Given that vegetation and edaphic characteristics have such clear and large influences on ALTs, our data provide a key benchmark against which to evaluate process models used to predict future impacts of climate warming on permafrost degradation and subsequent feedback to climate. © 2016 The Authors. Global Change Biology Published by John Wiley & Sons Ltd.

Pointright: a system to redirect mouse and keyboard control among multiple machines

DOEpatents

Johanson, Bradley E [Palo Alto, CA; Winograd, Terry A [Stanford, CA; Hutchins, Gregory M [Mountain View, CA

2008-09-30

The present invention provides a software system, PointRight, that allows for smooth and effortless control of pointing and input devices among multiple displays. With PointRight, a single free-floating mouse and keyboard can be used to control multiple screens. When the cursor reaches the edge of a screen it seamlessly moves to the adjacent screen and keyboard control is simultaneously redirected to the appropriate machine. Laptops may also redirect their keyboard and pointing device, and multiple pointers are supported simultaneously. The system automatically reconfigures itself as displays go on, go off, or change the machine they display.

The Curious Case of the Camelthorn: Competition, Coexistence, and Nest-Site Limitation in a Multispecies Mutualism.

PubMed

Campbell, Heather; Fellowes, Mark D E; Cook, James M

2015-12-01

Myrmecophyte plants house ants within domatia in exchange for protection against herbivores. Ant-myrmecophyte mutualisms exhibit two general patterns due to competition between ants for plant occupancy: (i) domatia nest sites are a limiting resource and (ii) each individual plant hosts one ant species at a time. However, individual camelthorn trees (Vachellia erioloba) typically host two to four ant species simultaneously, often coexisting in adjacent domatia on the same branch. Such fine-grain spatial coexistence brings into question the conventional wisdom on ant-myrmecophyte mutualisms. Camelthorn ants appear not to be nest-site limited, despite low abundance of suitable domatia, and have random distributions of nest sites within and across trees. These patterns suggest a lack of competition between ants for domatia and contrast strongly with other ant-myrmecophyte systems. Comparison of this unusual case with others suggests that spatial scale is crucial to coexistence or competitive exclusion involving multiple ant species. Furthermore, coexistence may be facilitated when co-occurring ant species diverge strongly on at least one niche axis. Our conclusions provide recommendations for future ant-myrmecophyte research, particularly in utilizing multispecies systems to further our understanding of mutualism biology.

CRISPR-Cas9-Edited Site Sequencing (CRES-Seq): An Efficient and High-Throughput Method for the Selection of CRISPR-Cas9-Edited Clones.

PubMed

Veeranagouda, Yaligara; Debono-Lagneaux, Delphine; Fournet, Hamida; Thill, Gilbert; Didier, Michel

2018-01-16

The emergence of clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-Cas9) gene editing systems has enabled the creation of specific mutants at low cost, in a short time and with high efficiency, in eukaryotic cells. Since a CRISPR-Cas9 system typically creates an array of mutations in targeted sites, a successful gene editing project requires careful selection of edited clones. This process can be very challenging, especially when working with multiallelic genes and/or polyploid cells (such as cancer and plants cells). Here we described a next-generation sequencing method called CRISPR-Cas9 Edited Site Sequencing (CRES-Seq) for the efficient and high-throughput screening of CRISPR-Cas9-edited clones. CRES-Seq facilitates the precise genotyping up to 96 CRISPR-Cas9-edited sites (CRES) in a single MiniSeq (Illumina) run with an approximate sequencing cost of $6/clone. CRES-Seq is particularly useful when multiple genes are simultaneously targeted by CRISPR-Cas9, and also for screening of clones generated from multiallelic genes/polyploid cells. © 2018 by John Wiley & Sons, Inc. Copyright © 2018 John Wiley & Sons, Inc.

Focused intracochlear electric stimulation with phased array channels.

PubMed

van den Honert, Chris; Kelsall, David C

2007-06-01

A method is described for producing focused intracochlear electric stimulation using an array of N electrodes. For each electrode site, N weights are computed that define the ratios of positive and negative electrode currents required to produce cancellation of the voltage within scala tympani at all of the N-1 other sites. Multiple sites can be stimulated simultaneously by superposition of their respective current vectors. The method allows N independent stimulus waveforms to be delivered to each of the N electrode sites without spatial overlap. Channel interaction from current spread associated with monopolar stimulation is substantially eliminated. The method operates by inverting the spread functions of individual monopoles as measured with the other electrodes. The method was implemented and validated with data from three human subjects implanted with 22-electrode perimodiolar arrays. Results indicate that (1) focusing is realizable with realistic precision; (2) focusing comes at the cost of increased total stimulation current; (3) uncanceled voltages that arise beyond the ends of the array are weak except when stimulating the two end channels; and (4) close perimodiolar positioning of the electrodes may be important for minimizing stimulation current and sensitivity to measurement errors.

Modeling Particle Exposure in US Trucking Terminals

PubMed Central

Davis, ME; Smith, TJ; Laden, F; Hart, JE; Ryan, LM; Garshick, E

2007-01-01

Multi-tiered sampling approaches are common in environmental and occupational exposure assessment, where exposures for a given individual are often modeled based on simultaneous measurements taken at multiple indoor and outdoor sites. The monitoring data from such studies is hierarchical by design, imposing a complex covariance structure that must be accounted for in order to obtain unbiased estimates of exposure. Statistical methods such as structural equation modeling (SEM) represent a useful alternative to simple linear regression in these cases, providing simultaneous and unbiased predictions of each level of exposure based on a set of covariates specific to the exposure setting. We test the SEM approach using data from a large exposure assessment of diesel and combustion particles in the US trucking industry. The exposure assessment includes data from 36 different trucking terminals across the United States sampled between 2001 and 2005, measuring PM2.5 and its elemental carbon (EC), organic carbon (OC) components, by personal monitoring, and sampling at two indoor work locations and an outdoor “background” location. Using the SEM method, we predict: 1) personal exposures as a function of work related exposure and smoking status; 2) work related exposure as a function of terminal characteristics, indoor ventilation, job location, and background exposure conditions; and 3) background exposure conditions as a function of weather, nearby source pollution, and other regional differences across terminal sites. The primary advantage of SEMs in this setting is the ability to simultaneously predict exposures at each of the sampling locations, while accounting for the complex covariance structure among the measurements and descriptive variables. The statistically significant results and high R2 values observed from the trucking industry application supports the broader use of this approach in exposure assessment modeling. PMID:16856739

CRISPR/Cas9-Based Multiplex Genome Editing in Monocot and Dicot Plants.

PubMed

Ma, Xingliang; Liu, Yao-Guang

2016-07-01

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated genome targeting system has been applied to a variety of organisms, including plants. Compared to other genome-targeting technologies such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), the CRISPR/Cas9 system is easier to use and has much higher editing efficiency. In addition, multiple "single guide RNAs" (sgRNAs) with different target sequences can be designed to direct the Cas9 protein to multiple genomic sites for simultaneous multiplex editing. Here, we present a procedure for highly efficient multiplex genome targeting in monocot and dicot plants using a versatile and robust CRISPR/Cas9 vector system, emphasizing the construction of binary constructs with multiple sgRNA expression cassettes in one round of cloning using Golden Gate ligation. We also describe the genotyping of targeted mutations in transgenic plants by direct Sanger sequencing followed by decoding of superimposed sequencing chromatograms containing biallelic or heterozygous mutations using the Web-based tool DSDecode. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Injection System for Multi-Well Injection Using a Single Pump

PubMed Central

Wovkulich, Karen; Stute, Martin; Protus, Thomas J.; Mailloux, Brian J.; Chillrud, Steven N.

2015-01-01

Many hydrological and geochemical studies rely on data resulting from injection of tracers and chemicals into groundwater wells. The even distribution of liquids to multiple injection points can be challenging or expensive, especially when using multiple pumps. An injection system was designed using one chemical metering pump to evenly distribute the desired influent simultaneously to 15 individual injection points through an injection manifold. The system was constructed with only one metal part contacting the fluid due to the low pH of the injection solutions. The injection manifold system was used during a three-month pilot scale injection experiment at the Vineland Chemical Company Superfund site. During the two injection phases of the experiment (Phase I = 0.27 L/min total flow, Phase II = 0.56 L/min total flow), flow measurements were made 20 times over three months; an even distribution of flow to each injection well was maintained (RSD <4%). This durable system is expandable to at least 16 injection points and should be adaptable to other injection experiments that require distribution of air-stable liquids to multiple injection points with a single pump. PMID:26140014

A portable fluorescent sensing system using multiple LEDs

NASA Astrophysics Data System (ADS)

Shin, Young-Ho; Barnett, Jonathan Z.; Gutierrez-Wing, M. Teresa; Rusch, Kelly A.; Choi, Jin-Woo

2017-02-01

This paper presents a portable fluorescent sensing system that utilizes different light emitting diode (LED) excitation lights for multiple target detection. In order to identify different analytes, three different wavelengths (385 nm, 448 nm, and 590 nm) of excitation light emitting diodes were used to selectively stimulate the target analytes. A highly sensitive silicon photomultiplier (SiPM) was used to detect corresponding fluorescent signals from each analyte. Based on the unique fluorescent response of each analyte, it is possible to simultaneously differentiate one analyte from the other in a mixture of target analytes. A portable system was designed and fabricated consisting of a display module, battery, data storage card, and sample loading tray into a compact 3D-printed jig. The portable sensor system was demonstrated for quantification and differentiation of microalgae (Chlorella vulgaris) and cyanobacteria (Spirulina) by measuring fluorescent responses of chlorophyll a in microalgae and phycocyanin in cyanobacteria. Obtained results suggest that the developed portable sensor system could be used as a generic fluorescence sensor platform for on-site detection of multiple analytes of interest.

Microcomputer-assisted transmission of disaster data by cellular telephone.

PubMed

Wigder, H N; Fligner, D J; Rivers, D; Hotch, D

1989-01-01

Voice communication of information during disasters is often inadequate. In particular, simultaneous transmission by multiple callers on the same frequency can result in blocked transmissions and miscommunications. In contrast, nonvoice transmission of data requires less time than does voice communication of the same data, and may be more accurate. We conducted a pilot study to test the feasibility of a microcomputer assisted communication (MAC) network linking the disaster scene and the command hospital. The radio chosen to transmit data from the field disaster site to the command hospital was a cellular telephone connected to the microcomputer by modem. Typed communications between the microcomputer operators enabled dialogue between the disaster site and the hospitals. A computer program using commercially available software (Symphony by Lotus, Inc.) was written to allow for data entry, data transmission, and reports. Patient data, including age, sex, severity of injury, identification number, major injuries, and hospital destination were successfully transmitted from the disaster site command post to the command hospital. This pilot test demonstrated the potential applicability of MAC for facilitating transmission of patient data during a disaster.

Site-Specific Three-Color Labeling of α-Synuclein via Conjugation to Uniquely Reactive Cysteines during Assembly by Native Chemical Ligation.

PubMed

Lee, Taehyung C; Moran, Crystal R; Cistrone, Philip A; Dawson, Philip E; Deniz, Ashok A

2018-04-12

Single-molecule fluorescence is widely used to study conformational complexity in proteins, and has proven especially valuable with intrinsically disordered proteins (IDPs). Protein studies using dual-color single-molecule Förster resonance energy transfer (smFRET) are now quite common, but many could benefit from simultaneous measurement of multiple distances through multi-color labeling. Such studies, however, have suffered from limitations in site-specific incorporation of more than two dyes per polypeptide. Here we present a fully site-specific three-color labeling scheme for α-synuclein, an IDP with important putative functions and links to Parkinson disease. The convergent synthesis combines native chemical ligation with regiospecific cysteine protection of expressed protein fragments to permit highly controlled labeling via standard cysteine-maleimide chemistry, enabling more global smFRET studies. Furthermore, this modular approach is generally compatible with recombinant proteins and expandable to accommodate even more complex experiments, such as by labeling with additional colors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions

PubMed Central

Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping. PMID:28700619

A brief review on the history of human functional near-infrared spectroscopy (fNIRS) development and fields of application.

PubMed

Ferrari, Marco; Quaresima, Valentina

2012-11-01

This review is aimed at celebrating the upcoming 20th anniversary of the birth of human functional near-infrared spectroscopy (fNIRS). After the discovery in 1992 that the functional activation of the human cerebral cortex (due to oxygenation and hemodynamic changes) can be explored by NIRS, human functional brain mapping research has gained a new dimension. fNIRS or optical topography, or near-infrared imaging or diffuse optical imaging is used mainly to detect simultaneous changes in optical properties of the human cortex from multiple measurement sites and displays the results in the form of a map or image over a specific area. In order to place current fNIRS research in its proper context, this paper presents a brief historical overview of the events that have shaped the present status of fNIRS. In particular, technological progresses of fNIRS are highlighted (i.e., from single-site to multi-site functional cortical measurements (images)), introduction of the commercial multi-channel systems, recent commercial wireless instrumentation and more advanced prototypes. Copyright © 2012 Elsevier Inc. All rights reserved.

Mto2 multisite phosphorylation inactivates non-spindle microtubule nucleation complexes during mitosis

PubMed Central

Borek, Weronika E.; Groocock, Lynda M.; Samejima, Itaru; Zou, Juan; de Lima Alves, Flavia; Rappsilber, Juri; Sawin, Kenneth E.

2015-01-01

Microtubule nucleation is highly regulated during the eukaryotic cell cycle, but the underlying molecular mechanisms are largely unknown. During mitosis in fission yeast Schizosaccharomyces pombe, cytoplasmic microtubule nucleation ceases simultaneously with intranuclear mitotic spindle assembly. Cytoplasmic nucleation depends on the Mto1/2 complex, which binds and activates the γ-tubulin complex and also recruits the γ-tubulin complex to both centrosomal (spindle pole body) and non-centrosomal sites. Here we show that the Mto1/2 complex disassembles during mitosis, coincident with hyperphosphorylation of Mto2 protein. By mapping and mutating multiple Mto2 phosphorylation sites, we generate mto2-phosphomutant strains with enhanced Mto1/2 complex stability, interaction with the γ-tubulin complex and microtubule nucleation activity. A mutant with 24 phosphorylation sites mutated to alanine, mto2[24A], retains interphase-like behaviour even in mitotic cells. This provides a molecular-level understanding of how phosphorylation ‘switches off' microtubule nucleation complexes during the cell cycle and, more broadly, illuminates mechanisms regulating non-centrosomal microtubule nucleation. PMID:26243668

Intra-operative multi-site stimulation: Expanding methodology for cortical brain mapping of language functions.

PubMed

Gonen, Tal; Gazit, Tomer; Korn, Akiva; Kirschner, Adi; Perry, Daniella; Hendler, Talma; Ram, Zvi

2017-01-01

Direct cortical stimulation (DCS) is considered the gold-standard for functional cortical mapping during awake surgery for brain tumor resection. DCS is performed by stimulating one local cortical area at a time. We present a feasibility study using an intra-operative technique aimed at improving our ability to map brain functions which rely on activity in distributed cortical regions. Following standard DCS, Multi-Site Stimulation (MSS) was performed in 15 patients by applying simultaneous cortical stimulations at multiple locations. Language functioning was chosen as a case-cognitive domain due to its relatively well-known cortical organization. MSS, performed at sites that did not produce disruption when applied in a single stimulation point, revealed additional language dysfunction in 73% of the patients. Functional regions identified by this technique were presumed to be significant to language circuitry and were spared during surgery. No new neurological deficits were observed in any of the patients following surgery. Though the neuro-electrical effects of MSS need further investigation, this feasibility study may provide a first step towards sophistication of intra-operative cortical mapping.

SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes

PubMed Central

Shen, Yue; Stracquadanio, Giovanni; Wang, Yun; Yang, Kun; Mitchell, Leslie A.; Xue, Yaxin; Cai, Yizhi; Chen, Tai; Dymond, Jessica S.; Kang, Kang; Gong, Jianhui; Zeng, Xiaofan; Zhang, Yongfen; Li, Yingrui; Feng, Qiang; Xu, Xun; Wang, Jun; Wang, Jian; Yang, Huanming; Boeke, Jef D.; Bader, Joel S.

2016-01-01

Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3′ UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes. PMID:26566658

Simultaneous nano-tracking of multiple motor proteins via spectral discrimination of quantum dots.

PubMed

Kakizuka, Taishi; Ikezaki, Keigo; Kaneshiro, Junichi; Fujita, Hideaki; Watanabe, Tomonobu M; Ichimura, Taro

2016-07-01

Simultaneous nanometric tracking of multiple motor proteins was achieved by combining multicolor fluorescent labeling of target proteins and imaging spectroscopy, revealing dynamic behaviors of multiple motor proteins at the sub-diffraction-limit scale. Using quantum dot probes of distinct colors, we experimentally verified the localization precision to be a few nanometers at temporal resolution of 30 ms or faster. One-dimensional processive movement of two heads of a single myosin molecule and multiple myosin molecules was successfully traced. Furthermore, the system was modified for two-dimensional measurement and applied to tracking of multiple myosin molecules. Our approach is useful for investigating cooperative movement of proteins in supramolecular nanomachinery.

Simultaneous nano-tracking of multiple motor proteins via spectral discrimination of quantum dots

PubMed Central

Kakizuka, Taishi; Ikezaki, Keigo; Kaneshiro, Junichi; Fujita, Hideaki; Watanabe, Tomonobu M.; Ichimura, Taro

2016-01-01

Simultaneous nanometric tracking of multiple motor proteins was achieved by combining multicolor fluorescent labeling of target proteins and imaging spectroscopy, revealing dynamic behaviors of multiple motor proteins at the sub-diffraction-limit scale. Using quantum dot probes of distinct colors, we experimentally verified the localization precision to be a few nanometers at temporal resolution of 30 ms or faster. One-dimensional processive movement of two heads of a single myosin molecule and multiple myosin molecules was successfully traced. Furthermore, the system was modified for two-dimensional measurement and applied to tracking of multiple myosin molecules. Our approach is useful for investigating cooperative movement of proteins in supramolecular nanomachinery. PMID:27446684

Surface-modified CMOS IC electrochemical sensor array targeting single chromaffin cells for highly parallel amperometry measurements.

PubMed

Huang, Meng; Delacruz, Joannalyn B; Ruelas, John C; Rathore, Shailendra S; Lindau, Manfred

2018-01-01

Amperometry is a powerful method to record quantal release events from chromaffin cells and is widely used to assess how specific drugs modify quantal size, kinetics of release, and early fusion pore properties. Surface-modified CMOS-based electrochemical sensor arrays allow simultaneous recordings from multiple cells. A reliable, low-cost technique is presented here for efficient targeting of single cells specifically to the electrode sites. An SU-8 microwell structure is patterned on the chip surface to provide insulation for the circuitry as well as cell trapping at the electrode sites. A shifted electrode design is also incorporated to increase the flexibility of the dimension and shape of the microwells. The sensitivity of the electrodes is validated by a dopamine injection experiment. Microwells with dimensions slightly larger than the cells to be trapped ensure excellent single-cell targeting efficiency, increasing the reliability and efficiency for on-chip single-cell amperometry measurements. The surface-modified device was validated with parallel recordings of live chromaffin cells trapped in the microwells. Rapid amperometric spikes with no diffusional broadening were observed, indicating that the trapped and recorded cells were in very close contact with the electrodes. The live cell recording confirms in a single experiment that spike parameters vary significantly from cell to cell but the large number of cells recorded simultaneously provides the statistical significance.

Simultaneous detection of multiple DNA targets by integrating dual-color graphene quantum dot nanoprobes and carbon nanotubes.

PubMed

Qian, Zhaosheng; Shan, Xiaoyue; Chai, Lujing; Chen, Jianrong; Feng, Hui

2014-12-01

Simultaneous detection of multiple DNA targets was achieved based on a biocompatible graphene quantum dots (GQDs) and carbon nanotubes (CNTs) platform through spontaneous assembly between dual-color GQD-based probes and CNTs and subsequently self-recognition between DNA probes and targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scatter characterization and correction for simultaneous multiple small-animal PET imaging.

PubMed

Prasad, Rameshwar; Zaidi, Habib

2014-04-01

The rapid growth and usage of small-animal positron emission tomography (PET) in molecular imaging research has led to increased demand on PET scanner's time. One potential solution to increase throughput is to scan multiple rodents simultaneously. However, this is achieved at the expense of deterioration of image quality and loss of quantitative accuracy owing to enhanced effects of photon attenuation and Compton scattering. The purpose of this work is, first, to characterize the magnitude and spatial distribution of the scatter component in small-animal PET imaging when scanning single and multiple rodents simultaneously and, second, to assess the relevance and evaluate the performance of scatter correction under similar conditions. The LabPET™-8 scanner was modelled as realistically as possible using Geant4 Application for Tomographic Emission Monte Carlo simulation platform. Monte Carlo simulations allow the separation of unscattered and scattered coincidences and as such enable detailed assessment of the scatter component and its origin. Simple shape-based and more realistic voxel-based phantoms were used to simulate single and multiple PET imaging studies. The modelled scatter component using the single-scatter simulation technique was compared to Monte Carlo simulation results. PET images were also corrected for attenuation and the combined effect of attenuation and scatter on single and multiple small-animal PET imaging evaluated in terms of image quality and quantitative accuracy. A good agreement was observed between calculated and Monte Carlo simulated scatter profiles for single- and multiple-subject imaging. In the LabPET™-8 scanner, the detector covering material (kovar) contributed the maximum amount of scatter events while the scatter contribution due to lead shielding is negligible. The out-of field-of-view (FOV) scatter fraction (SF) is 1.70, 0.76, and 0.11% for lower energy thresholds of 250, 350, and 400 keV, respectively. The increase in SF ranged between 25 and 64% when imaging multiple subjects (three to five) of different size simultaneously in comparison to imaging a single subject. The spill-over ratio (SOR) increases with increasing the number of subjects in the FOV. Scatter correction improved the SOR for both water and air cold compartments of single and multiple imaging studies. The recovery coefficients for different body parts of the mouse whole-body and rat whole-body anatomical models were improved for multiple imaging studies following scatter correction. The magnitude and spatial distribution of the scatter component in small-animal PET imaging of single and multiple subjects simultaneously were characterized, and its impact was evaluated in different situations. Scatter correction improves PET image quality and quantitative accuracy for single rat and simultaneous multiple mice and rat imaging studies, whereas its impact is insignificant in single mouse imaging.

Urban-air-toxics Monitoring Program, 1990

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

Not Available

1991-06-01

From March 1990 through February 1991 samples of ambient air were collected at 12 sites in the eastern part of the U.S. Every 12 days, air was integrated over 24-hour periods into passivated stainless steel canisters. Simultaneously, air was drawn through cartridges containing dinitrophenylhydrazine to collect carbonyl compounds. The samples were analyzed at a central laboratory for a total of 37 halogenated and aromatic hydrocarbons, formaldehyde, acetaldehyde, and other oxygenated species. The hydrocarbon species were analyzed by gas chromatography/multiple detectors and gas chromatography/mass spectrometry, while the carbonyl species were analyzed by liquid chromatography. Complete data for all the hydrocarbon samplesmore » are presented in the report.« less

Changes to CMS Reimbursement Rules for Intraoperative Neurophysiological Monitoring: Implications for Telemedicine

PubMed Central

2013-01-01

Abstract Intraoperative neurophysiological monitoring (IONM) is used as an adjunct for surgeries that pose risk to nervous system structures. IONM is performed by a technologist in the operating room and is overseen by a highly trained fellowship-trained physician clinical neurophysiologist. Telemedicine has allowed the professional oversight component to be done remotely, with reimbursement for multiple simultaneous cases. Recent changes to Current Procedure Terminology coding and Medicare reimbursement policies provide options only for exclusive 1:1 technologist:oversight physician billing. This policy change may create profound repercussions in the practice of telemedicine by actively discouraging the leveraging of highly specialized and scarce expertise through on-site physician extenders. PMID:23952785

Simultaneous site-directed mutagenesis of duplicated loci in soybean using a single guide RNA.

PubMed

Kanazashi, Yuhei; Hirose, Aya; Takahashi, Ippei; Mikami, Masafumi; Endo, Masaki; Hirose, Sakiko; Toki, Seiichi; Kaga, Akito; Naito, Ken; Ishimoto, Masao; Abe, Jun; Yamada, Tetsuya

2018-03-01

Using a gRNA and Agrobacterium-mediated transformation, we performed simultaneous site-directed mutagenesis of two GmPPD loci in soybean. Mutations in GmPPD loci were confirmed in at least 33% of T 2 seeds. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated endonuclease 9 (Cas9) system is a powerful tool for site-directed mutagenesis in crops. Using a single guide RNA (gRNA) and Agrobacterium-mediated transformation, we performed simultaneous site-directed mutagenesis of two homoeologous loci in soybean (Glycine max), GmPPD1 and GmPPD2, which encode the orthologs of Arabidopsis thaliana PEAPOD (PPD). Most of the T 1 plants had heterozygous and/or chimeric mutations for the targeted loci. The sequencing analysis of T 1 and T 2 generations indicates that putative mutation induced in the T 0 plant is transmitted to the T 1 generation. The inheritable mutation induced in the T 1 plant was also detected. This result indicates that continuous induction of mutations during T 1 plant development increases the occurrence of mutations in germ cells, which ensures the transmission of mutations to the next generation. Simultaneous site-directed mutagenesis in both GmPPD loci was confirmed in at least 33% of T 2 seeds examined. Approximately 19% of double mutants did not contain the Cas9/gRNA expression construct. Double mutants with frameshift mutations in both GmPPD1 and GmPPD2 had dome-shaped trifoliate leaves, extremely twisted pods, and produced few seeds. Taken together, our data indicate that continuous induction of mutations in the whole plant and advancing generations of transgenic plants enable efficient simultaneous site-directed mutagenesis in duplicated loci in soybean.

Simultaneously extracting multiple parameters via multi-distance and multi-exposure diffuse speckle contrast analysis

PubMed Central

Liu, Jialin; Zhang, Hongchao; Lu, Jian; Ni, Xiaowu; Shen, Zhonghua

2017-01-01

Recent advancements in diffuse speckle contrast analysis (DSCA) have opened the path for noninvasive acquisition of deep tissue microvasculature blood flow. In fact, in addition to blood flow index αDB, the variations of tissue optical absorption μa, reduced scattering coefficients μs′, as well as coherence factor β can modulate temporal fluctuations of speckle patterns. In this study, we use multi-distance and multi-exposure DSCA (MDME-DSCA) to simultaneously extract multiple parameters such as μa, μs′, αDB, and β. The validity of MDME-DSCA has been validated by the simulated data and phantoms experiments. Moreover, as a comparison, the results also show that it is impractical to simultaneously obtain multiple parameters by multi-exposure DSCA (ME-DSCA). PMID:29082083

Simultaneous assay of multiple antibiotics in human plasma by LC-MS/MS: importance of optimizing formic acid concentration.

PubMed

Chen, Feng; Hu, Zhe-Yi; Laizure, S Casey; Hudson, Joanna Q

2017-03-01

Optimal dosing of antibiotics in critically ill patients is complicated by the development of resistant organisms requiring treatment with multiple antibiotics and alterations in systemic exposure due to diseases and extracorporeal drug removal. Developing guidelines for optimal antibiotic dosing is an important therapeutic goal requiring robust analytical methods to simultaneously measure multiple antibiotics. An LC-MS/MS assay using protein precipitation for cleanup followed by a 6-min gradient separation was developed to simultaneously determine five antibiotics in human plasma. The precision and accuracy were within the 15% acceptance range. The formic acid concentration was an important determinant of signal intensity, peak shape and matrix effects. The method was designed to be simple and successfully applied to a clinical pharmacokinetic study.

Simple method for assembly of CRISPR synergistic activation mediator gRNA expression array.

PubMed

Vad-Nielsen, Johan; Nielsen, Anders Lade; Luo, Yonglun

2018-05-20

When studying complex interconnected regulatory networks, effective methods for simultaneously manipulating multiple genes expression are paramount. Previously, we have developed a simple method for generation of an all-in-one CRISPR gRNA expression array. We here present a Golden Gate Assembly-based system of synergistic activation mediator (SAM) compatible CRISPR/dCas9 gRNA expression array for the simultaneous activation of multiple genes. Using this system, we demonstrated the simultaneous activation of the transcription factors, TWIST, SNAIL, SLUG, and ZEB1 a human breast cancer cell line. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous Excitation of Multiple-Input Multiple-Output CFD-Based Unsteady Aerodynamic Systems

NASA Technical Reports Server (NTRS)

Silva, Walter A.

2008-01-01

A significant improvement to the development of CFD-based unsteady aerodynamic reduced-order models (ROMs) is presented. This improvement involves the simultaneous excitation of the structural modes of the CFD-based unsteady aerodynamic system that enables the computation of the unsteady aerodynamic state-space model using a single CFD execution, independent of the number of structural modes. Four different types of inputs are presented that can be used for the simultaneous excitation of the structural modes. Results are presented for a flexible, supersonic semi-span configuration using the CFL3Dv6.4 code.

Simultaneous Excitation of Multiple-Input Multiple-Output CFD-Based Unsteady Aerodynamic Systems

NASA Technical Reports Server (NTRS)

Silva, Walter A.

2007-01-01

A significant improvement to the development of CFD-based unsteady aerodynamic reduced-order models (ROMs) is presented. This improvement involves the simultaneous excitation of the structural modes of the CFD-based unsteady aerodynamic system that enables the computation of the unsteady aerodynamic state-space model using a single CFD execution, independent of the number of structural modes. Four different types of inputs are presented that can be used for the simultaneous excitation of the structural modes. Results are presented for a flexible, supersonic semi-span configuration using the CFL3Dv6.4 code.

Equalization filters for multiple-channel electromyogram arrays

PubMed Central

Clancy, Edward A.; Xia, Hongfang; Christie, Anita; Kamen, Gary

2007-01-01

Multiple channels of electromyogram activity are frequently transduced via electrodes, then combined electronically to form one electrophysiologic recording, e.g. bipolar, linear double difference and Laplacian montages. For high quality recordings, precise gain and frequency response matching of the individual electrode potentials is achieved in hardware (e.g., an instrumentation amplifier for bipolar recordings). This technique works well when the number of derived signals is small and the montages are pre-determined. However, for array electrodes employing a variety of montages, hardware channel matching can be expensive and tedious, and limits the number of derived signals monitored. This report describes a method for channel matching based on the concept of equalization filters. Monopolar potentials are recorded from each site without precise hardware matching. During a calibration phase, a time-varying linear chirp voltage is applied simultaneously to each site and recorded. Based on the calibration recording, each monopolar channel is digitally filtered to “correct” for (equalize) differences in the individual channels, and then any derived montages subsequently created. In a hardware demonstration system, the common mode rejection ratio (at 60 Hz) of bipolar montages improved from 35.2 ± 5.0 dB (prior to channel equalization) to 69.0 ± 5.0 dB (after equalization). PMID:17614134

Stable long-term blood formation by stem cells in murine steady-state hematopoiesis.

PubMed

Zavidij, Oksana; Ball, Claudia R; Herbst, Friederike; Oppel, Felix; Fessler, Sylvia; Schmidt, Manfred; von Kalle, Christof; Glimm, Hanno

2012-09-01

Hematopoietic stem cells (HSCs) generate all mature blood cells during the whole lifespan of an individual. However, the clonal contribution of individual HSC and progenitor cells in steady-state hematopoiesis is poorly understood. To investigate the activity of HSCs under steady-state conditions, murine HSC and progenitor cells were genetically marked in vivo by integrating lentiviral vectors (LVs) encoding green fluorescent protein (GFP). Hematopoietic contribution of individual marked clones was monitored by determination of lentiviral integration sites using highly sensitive linear amplification-mediated-polymerase chain reaction. A remarkably stable small proportion of hematopoietic cells expressed GFP in LV-injected animals for up to 24 months, indicating stable marking of murine steady-state hematopoiesis. Analysis of the lentiviral integration sites revealed that multiple hematopoietic clones with both myeloid and lymphoid differentiation potential contributed to long-term hematopoiesis. In contrast to intrafemoral vector injection, intravenous administration of LV preferentially targeted short-lived progenitor cells. Myelosuppressive treatment of mice prior to LV-injection did not affect the marking efficiency. Our study represents the first continuous analysis of clonal behavior of genetically marked hematopoietic cells in an unmanipulated system, providing evidence that multiple clones are simultaneously active in murine steady-state hematopoiesis. Copyright © 2012 AlphaMed Press.

Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector

PubMed Central

Kabadi, Ami M.; Ousterout, David G.; Hilton, Isaac B.; Gersbach, Charles A.

2014-01-01

Engineered DNA-binding proteins that manipulate the human genome and transcriptome have enabled rapid advances in biomedical research. In particular, the RNA-guided CRISPR/Cas9 system has recently been engineered to create site-specific double-strand breaks for genome editing or to direct targeted transcriptional regulation. A unique capability of the CRISPR/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide RNAs (sgRNAs) targeted to distinct genomic sites. This approach can be used to simultaneously create multiple DNA breaks or to target multiple transcriptional activators to a single promoter for synergistic enhancement of gene induction. To address the need for uniform and sustained delivery of multiplex CRISPR/Cas9-based genome engineering tools, we developed a single lentiviral system to express a Cas9 variant, a reporter gene and up to four sgRNAs from independent RNA polymerase III promoters that are incorporated into the vector by a convenient Golden Gate cloning method. Each sgRNA is efficiently expressed and can mediate multiplex gene editing and sustained transcriptional activation in immortalized and primary human cells. This delivery system will be significant to enabling the potential of CRISPR/Cas9-based multiplex genome engineering in diverse cell types. PMID:25122746

A comparison of the real-time controllability of pattern recognition to conventional myoelectric control for discrete and simultaneous movements

PubMed Central

2014-01-01

Myoelectric control has been used for decades to control powered upper limb prostheses. Conventional, amplitude-based control has been employed to control a single prosthesis degree of freedom (DOF) such as closing and opening of the hand. Within the last decade, new and advanced arm and hand prostheses have been constructed that are capable of actuating numerous DOFs. Pattern recognition control has been proposed to control a greater number of DOFs than conventional control, but has traditionally been limited to sequentially controlling DOFs one at a time. However, able-bodied individuals use multiple DOFs simultaneously, and it may be beneficial to provide amputees the ability to perform simultaneous movements. In this study, four amputees who had undergone targeted motor reinnervation (TMR) surgery with previous training using myoelectric prostheses were configured to use three control strategies: 1) conventional amplitude-based myoelectric control, 2) sequential (one-DOF) pattern recognition control, 3) simultaneous pattern recognition control. Simultaneous pattern recognition was enabled by having amputees train each simultaneous movement as a separate motion class. For tasks that required control over just one DOF, sequential pattern recognition based control performed the best with the lowest average completion times, completion rates and length error. For tasks that required control over 2 DOFs, the simultaneous pattern recognition controller performed the best with the lowest average completion times, completion rates and length error compared to the other control strategies. In the two strategies in which users could employ simultaneous movements (conventional and simultaneous pattern recognition), amputees chose to use simultaneous movements 78% of the time with simultaneous pattern recognition and 64% of the time with conventional control for tasks that required two DOF motions to reach the target. These results suggest that when amputees are given the ability to control multiple DOFs simultaneously, they choose to perform tasks that utilize multiple DOFs with simultaneous movements. Additionally, they were able to perform these tasks with higher performance (faster speed, lower length error and higher completion rates) without losing substantial performance in 1 DOF tasks. PMID:24410948

Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

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

Wang, Ying; Li, Zhaohui; Liu, Misha

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeledmore » single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.« less

LuciPHOr: Algorithm for Phosphorylation Site Localization with False Localization Rate Estimation Using Modified Target-Decoy Approach*

PubMed Central

Fermin, Damian; Walmsley, Scott J.; Gingras, Anne-Claude; Choi, Hyungwon; Nesvizhskii, Alexey I.

2013-01-01

The localization of phosphorylation sites in peptide sequences is a challenging problem in large-scale phosphoproteomics analysis. The intense neutral loss peaks and the coexistence of multiple serine/threonine and/or tyrosine residues are limiting factors for objectively scoring site patterns across thousands of peptides. Various computational approaches for phosphorylation site localization have been proposed, including Ascore, Mascot Delta score, and ProteinProspector, yet few address direct estimation of the false localization rate (FLR) in each experiment. Here we propose LuciPHOr, a modified target-decoy-based approach that uses mass accuracy and peak intensities for site localization scoring and FLR estimation. Accurate estimation of the FLR is a difficult task at the individual-site level because the degree of uncertainty in localization varies significantly across different peptides. LuciPHOr carries out simultaneous localization on all candidate sites in each peptide and estimates the FLR based on the target-decoy framework, where decoy phosphopeptides generated by placing artificial phosphorylation(s) on non-candidate residues compete with the non-decoy phosphopeptides. LuciPHOr also reports approximate site-level confidence scores for all candidate sites as a means to localize additional sites from multiphosphorylated peptides in which localization can be partially achieved. Unlike the existing tools, LuciPHOr is compatible with any search engine output processed through the Trans-Proteomic Pipeline. We evaluated the performance of LuciPHOr in terms of the sensitivity and accuracy of FLR estimates using two synthetic phosphopeptide libraries and a phosphoproteomic dataset generated from complex mouse brain samples. PMID:23918812

Multi-scale occupancy estimation and modelling using multiple detection methods

USGS Publications Warehouse

Nichols, James D.; Bailey, Larissa L.; O'Connell, Allan F.; Talancy, Neil W.; Grant, Evan H. Campbell; Gilbert, Andrew T.; Annand, Elizabeth M.; Husband, Thomas P.; Hines, James E.

2008-01-01

Occupancy estimation and modelling based on detection–nondetection data provide an effective way of exploring change in a species’ distribution across time and space in cases where the species is not always detected with certainty. Today, many monitoring programmes target multiple species, or life stages within a species, requiring the use of multiple detection methods. When multiple methods or devices are used at the same sample sites, animals can be detected by more than one method.We develop occupancy models for multiple detection methods that permit simultaneous use of data from all methods for inference about method-specific detection probabilities. Moreover, the approach permits estimation of occupancy at two spatial scales: the larger scale corresponds to species’ use of a sample unit, whereas the smaller scale corresponds to presence of the species at the local sample station or site.We apply the models to data collected on two different vertebrate species: striped skunks Mephitis mephitis and red salamanders Pseudotriton ruber. For striped skunks, large-scale occupancy estimates were consistent between two sampling seasons. Small-scale occupancy probabilities were slightly lower in the late winter/spring when skunks tend to conserve energy, and movements are limited to males in search of females for breeding. There was strong evidence of method-specific detection probabilities for skunks. As anticipated, large- and small-scale occupancy areas completely overlapped for red salamanders. The analyses provided weak evidence of method-specific detection probabilities for this species.Synthesis and applications. Increasingly, many studies are utilizing multiple detection methods at sampling locations. The modelling approach presented here makes efficient use of detections from multiple methods to estimate occupancy probabilities at two spatial scales and to compare detection probabilities associated with different detection methods. The models can be viewed as another variation of Pollock's robust design and may be applicable to a wide variety of scenarios where species occur in an area but are not always near the sampled locations. The estimation approach is likely to be especially useful in multispecies conservation programmes by providing efficient estimates using multiple detection devices and by providing device-specific detection probability estimates for use in survey design.

Untangling the Diverse Interior and Multiple Exterior Guest Interactions of a Supramolecular Host by the Simultaneous Analysis of Complementary Observables.

PubMed

Sgarlata, Carmelo; Raymond, Kenneth N

2016-07-05

The entropic and enthalpic driving forces for encapsulation versus sequential exterior guest binding to the [Ga4L6](12-) supramolecular host in solution are very different, which significantly complicates the determination of these thermodynamic parameters. The simultaneous use of complementary techniques, such as NMR, UV-vis, and isothermal titration calorimetry, enables the disentanglement of such multiple host-guest interactions. Indeed, data collected by each technique measure different components of the host-guest equilibria and together provide a complete picture of the solution thermodynamics. Unfortunately, commercially available programs do not allow for global analysis of different physical observables. We thus resorted to a novel procedure for the simultaneous refinement of multiple parameters (ΔG°, ΔH°, and ΔS°) by treating different observables through a weighted nonlinear least-squares analysis of a constrained model. The refinement procedure is discussed for the multiple binding of the Et4N(+) guest, but it is broadly applicable to the deconvolution of other intricate host-guest equilibria.

Retrospective Evaluation of Safety, Efficacy and Risk Factors for Pneumothorax in Simultaneous Localizations of Multiple Pulmonary Nodules Using Hook Wire System.

PubMed

Zhong, Yan; Xu, Xiao-Quan; Pan, Xiang-Long; Zhang, Wei; Xu, Hai; Yuan, Mei; Kong, Ling-Yan; Pu, Xue-Hui; Chen, Liang; Yu, Tong-Fu

2017-09-01

To evaluate the safety and efficacy of the hook wire system in the simultaneous localizations for multiple pulmonary nodules (PNs) before video-assisted thoracoscopic surgery (VATS), and to clarify the risk factors for pneumothorax associated with the localization procedure. Between January 2010 and February 2016, 67 patients (147 nodules, Group A) underwent simultaneous localizations for multiple PNs using a hook wire system. The demographic, localization procedure-related information and the occurrence rate of pneumothorax were assessed and compared with a control group (349 patients, 349 nodules, Group B). Multivariate logistic regression analyses were used to determine the risk factors for pneumothorax during the localization procedure. All the 147 nodules were successfully localized. Four (2.7%) hook wires dislodged before VATS procedure, but all these four lesions were successfully resected according to the insertion route of hook wire. Pathological diagnoses were acquired for all 147 nodules. Compared with Group B, Group A demonstrated significantly longer procedure time (p < 0.001) and higher occurrence rate of pneumothorax (p = 0.019). Multivariate logistic regression analysis indicated that position change during localization procedure (OR 2.675, p = 0.021) and the nodules located in the ipsilateral lung (OR 9.404, p < 0.001) were independent risk factors for pneumothorax. Simultaneous localizations for multiple PNs using a hook wire system before VATS procedure were safe and effective. Compared with localization for single PN, simultaneous localizations for multiple PNs were prone to the occurrence of pneumothorax. Position change during localization procedure and the nodules located in the ipsilateral lung were independent risk factors for pneumothorax.

Pacific Circulation and the Resilience of its Equatorial Reefs

NASA Astrophysics Data System (ADS)

Cohen, A. L.; Drenkard, E.

2012-12-01

High rates of calcification by tropical reef-building corals are paramount to the maintenance of healthy reefs. Investigations of the impact of ocean acidification in both laboratory and field studies demonstrate unequivocally the dependence of coral and coral reef calcification on the carbonate ion concentration of seawater, a dependence predicted by fundamental laws of physical chemistry. Nevertheless, results from a new generation of experiments that exploit the biology of coral calcification, suggest that effects of ocean acidification can - in some instances - be mitigated with simultaneous manipulation of multiple factors. These laboratory results imply that coral reefs in regions projected to experience changes in, for example, nutrient delivery, light and flow, in addition to pH and carbonate ion concentration, may be more resilient (or vulnerable) to the effects of ocean acidification alone. If demonstrated to be true, these observations have profound implications for the conservation and management of coral reefs in the 21st century. We quantified spatial and temporal variability in rates of calcification of a dominant Indo-Pacific reef building coral across sites where changes in ocean circulation patterns drive variability in multiple physical, chemical and biological parameters. Such changes are occurring against a background of variability and trends in carbonate system chemistry. Our field data provide support for hypotheses based on laboratory observations, and show that impacts of ocean acidification on coral calcification can be partially and in some cases, fully, offset by simultaneous changes in multiple factors. Our results imply that projected changes in oceanic and atmospheric circulation patterns, driven by global warming, must be considered when predicting coral reef resilience, or vulnerability, to 21st century ocean acidification.

Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins and Cas9 mRNA for Genome Editing in Zebrafish

PubMed Central

Hu, Peinan; Zhao, Xueying; Zhang, Qinghua; Li, Weiming; Zu, Yao

2018-01-01

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS) fused to different termini and Cas9 mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N-, C-, or both the N- and C-termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the tyr gene and two sites in the gol gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7 Endonuclease I (T7E1) assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that a high frequency of indels occurred in the target sites (tyr1 > 66%, tyr2 > 73%, gol1 > 50%, and gol2 > 35%), as well as various types (more than six) of indel mutations observed in all four types of Cas9-injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and Cas9 mRNAs have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on guide RNAs (gRNAs) and gene loci. These findings may help to simplify the selection of Cas9 for gene editing using the CRISPR/Cas9 system. PMID:29295818

Three-dimensional fluorescent microscopy via simultaneous illumination and detection at multiple planes.

PubMed

Ma, Qian; Khademhosseinieh, Bahar; Huang, Eric; Qian, Haoliang; Bakowski, Malina A; Troemel, Emily R; Liu, Zhaowei

2016-08-16

The conventional optical microscope is an inherently two-dimensional (2D) imaging tool. The objective lens, eyepiece and image sensor are all designed to capture light emitted from a 2D 'object plane'. Existing technologies, such as confocal or light sheet fluorescence microscopy have to utilize mechanical scanning, a time-multiplexing process, to capture a 3D image. In this paper, we present a 3D optical microscopy method based upon simultaneously illuminating and detecting multiple focal planes. This is implemented by adding two diffractive optical elements to modify the illumination and detection optics. We demonstrate that the image quality of this technique is comparable to conventional light sheet fluorescent microscopy with the advantage of the simultaneous imaging of multiple axial planes and reduced number of scans required to image the whole sample volume.

Overlapping reactivations of herpes simplex virus type 2 in the genital and perianal mucosa.

PubMed

Tata, Sunitha; Johnston, Christine; Huang, Meei-Li; Selke, Stacy; Magaret, Amalia; Corey, Lawrence; Wald, Anna

2010-02-15

Genital shedding of herpes simplex virus (HSV) type 2 occurs frequently. Anatomic patterns of genital HSV-2 reactivation have not been intensively studied. Four HSV-2-seropositive women with symptomatic genital herpes attended a clinic daily during a 30-day period. Daily samples were collected from 7 separate genital sites. Swab samples were assayed for HSV DNA by quantitative polymerase chain reaction. Anatomic sites of clinical HSV-2 recurrences were recorded. HSV was detected on 44 (37%) of 120 days and from 136 (16%) of 840 swab samples. Lesions were documented on 35 (29%) of 120 days. HSV was detected at >1 anatomic site on 25 (57%) of 44 days with HSV shedding (median, 2 sites; range, 1-7), with HSV detected bilaterally on 20 (80%) of the 25 days. The presence of a lesion was significantly associated with detectable HSV from any genital site (incident rate ratio [IRR], 5.41; 95% confidence interval [CI], 1.24-23.50; P= .02) and with the number of positive sites (IRR, 1.19; 95% CI, 1. 01-1.40; P=.03). The maximum HSV copy number detected was associated with the number of positive sites (IRR, 1.62; 95% CI, 1.44-1.82; P<.001). HSV-2 reactivation occurs frequently at widely spaced regions throughout the genital tract. To prevent HSV-2 reactivation, suppressive HSV-2 therapy must control simultaneous viral reactivations from multiple sacral ganglia.

Double-label immunofluorescence method for simultaneous detection of adenovirus and herpes simplex virus from the eye.

PubMed

Walpita, P; Darougar, S

1989-07-01

The development and application of a double-label immunofluorescence method which has the potential to screen for single or dual infections from any site, in single shell vial cultures, is described. In this study, a total of 1,141 ocular specimens were inoculated in shell vials, centrifuged at 15,000 X g for 1 h, incubated at 37 degrees C for 48 h, and fixed in methanol at room temperature for 15 min. The virus inclusions were detected by staining with a double-label indirect immunofluorescence procedure using mixtures of appropriate first antibodies, followed by fluorescein- and rhodamine-conjugated second antibodies. Each specimen was also inoculated in parallel by the conventional virus isolation method. The sensitivity and specificity of the double-label shell vial procedure were comparable to those with the conventional method, and the former test took only 48 h to complete. The test offers a rapid and simple single-vial procedure which allows for individual or simultaneous detection of multiple pathogens. It results in savings in time and cost over the conventional virus isolation method and other shell vial procedures.

General Anesthetics Have Additive Actions on Three Ligand-Gated Ion Channels

PubMed Central

Jenkins, Andrew; Lobo, Ingrid A.; Gong, Diane; Trudell, James R.; Solt, Ken; Harris, R. Adron; Eger, Edmond I

2008-01-01

Background The purpose of this study was to determine whether pairs of compounds, including general anesthetics, could simultaneously modulate receptor function in a synergistic manner, thus demonstrating the existence of multiple intra-protein anesthetic binding sites. Methods Using standard electrophysiologic methods, we measured the effects of at least one combination of benzene, isoflurane, halothane, chloroform, flunitrazepam, zinc and pentobarbital on at least one of the following ligand gated ion channels: N-methyl-D-aspartate receptors (NMDARs), glycine receptors (GlyRs) and γ-aminobutyric acid type A receptors (GABAARs). Results All drug-drug-receptor combinations were found to exhibit additive, not synergistic modulation. Isoflurane with benzene additively depressed NMDAR function. Isoflurane with halothane additively enhanced GlyR function, as did isoflurane with zinc. Isoflurane with halothane additively enhanced GABAAR function as did all of the following: halothane with chloroform, pentobarbital with isoflurane, and flunitrazepam with isoflurane. Conclusions The simultaneous allosteric modulation of ligand gated ion channels by general anesthetics is entirely additive. Where pairs of general anesthetic drugs interact synergistically to produce general anesthesia, they must do so on systems more complex than a single receptor. PMID:18633027

Towards multifocal ultrasonic neural stimulation: pattern generation algorithms

NASA Astrophysics Data System (ADS)

Hertzberg, Yoni; Naor, Omer; Volovick, Alexander; Shoham, Shy

2010-10-01

Focused ultrasound (FUS) waves directed onto neural structures have been shown to dynamically modulate neural activity and excitability, opening up a range of possible systems and applications where the non-invasiveness, safety, mm-range resolution and other characteristics of FUS are advantageous. As in other neuro-stimulation and modulation modalities, the highly distributed and parallel nature of neural systems and neural information processing call for the development of appropriately patterned stimulation strategies which could simultaneously address multiple sites in flexible patterns. Here, we study the generation of sparse multi-focal ultrasonic distributions using phase-only modulation in ultrasonic phased arrays. We analyse the relative performance of an existing algorithm for generating multifocal ultrasonic distributions and new algorithms that we adapt from the field of optical digital holography, and find that generally the weighted Gerchberg-Saxton algorithm leads to overall superior efficiency and uniformity in the focal spots, without significantly increasing the computational burden. By combining phased-array FUS and magnetic-resonance thermometry we experimentally demonstrate the simultaneous generation of tightly focused multifocal distributions in a tissue phantom, a first step towards patterned FUS neuro-modulation systems and devices.

A Simplified Approach for Simultaneous Measurements of Wavefront Velocity and Curvature in the Heart Using Activation Times.

PubMed

Mazeh, Nachaat; Haines, David E; Kay, Matthew W; Roth, Bradley J

2013-12-01

The velocity and curvature of a wave front are important factors governing the propagation of electrical activity through cardiac tissue, particularly during heart arrhythmias of clinical importance such as fibrillation. Presently, no simple computational model exists to determine these values simultaneously. The proposed model uses the arrival times at four or five sites to determine the wave front speed ( v ), direction (θ), and radius of curvature (ROC) ( r 0 ). If the arrival times are measured, then v , θ, and r 0 can be found from differences in arrival times and the distance between these sites. During isotropic conduction, we found good correlation between measured values of the ROC r 0 and the distance from the unipolar stimulus ( r = 0.9043 and p < 0.0001). The conduction velocity (m/s) was correlated ( r = 0.998, p < 0.0001) using our method (mean = 0.2403, SD = 0.0533) and an empirical method (mean = 0.2352, SD = 0.0560). The model was applied to a condition of anisotropy and a complex case of reentry with a high voltage extra stimulus. Again, results show good correlation between our simplified approach and established methods for multiple wavefront morphologies. In conclusion, insignificant measurement errors were observed between this simplified approach and an approach that was more computationally demanding. Accuracy was maintained when the requirement that ε (ε = b/r 0 , ratio of recording site spacing over wave fronts ROC) was between 0.001 and 0.5. The present simplified model can be applied to a variety of clinical conditions to predict behavior of planar, elliptical, and reentrant wave fronts. It may be used to study the genesis and propagation of rotors in human arrhythmias and could lead to rotor mapping using low density endocardial recording electrodes.

Non-targeted, high resolution mass spectrometry strategy for simultaneous monitoring of xenobiotics and endogenous compounds in green sea turtles on the Great Barrier Reef.

PubMed

Heffernan, Amy L; Gómez-Ramos, Maria M; Gaus, Caroline; Vijayasarathy, Soumini; Bell, Ian; Hof, Christine; Mueller, Jochen F; Gómez-Ramos, Maria J

2017-12-01

Chemical contamination poses a threat to ecosystem, biota and human health, and identifying these hazards is a complex challenge. Traditional hazard identification relies on a priori-defined targets of limited chemical scope, and is generally inappropriate for exploratory studies such as explaining toxicological effects in environmental systems. Here we present a non-target high resolution mass spectrometry environmental monitoring study with multivariate statistical analysis to simultaneously detect biomarkers of exposure (e.g. xenobiotics) and biomarkers of effect in whole turtle blood. Borrowing the concept from clinical chemistry, a case-control sampling approach was used to investigate the potential influence of xenobiotics of anthropogenic origin on free-ranging green sea turtles (Chelonia mydas) from a remote, offshore 'control' site; and two coastal 'case' sites influenced by urban/industrial and agricultural activities, respectively, on the Great Barrier Reef in North Queensland, Australia. Multiple biomarkers of exposure, including sulfonic acids (n=9), a carbamate insecticide metabolite, and other industrial chemicals; and five biomarkers of effect (lipid peroxidation products), were detected in case sites. Additionally, two endogenous biomarkers of neuroinflammation and oxidative stress were identified, and showed moderate-to-strong correlations with clinical measures of inflammation and liver dysfunction. Our data filtering strategy overcomes limitations of traditional a priori selection of target compounds, and adds to the limited environmental xenobiotic metabolomics literature. To our knowledge this is the first case-control study of xenobiotics in marine megafauna, and demonstrates the utility of green sea turtles to link internal and external exposure, to explain potential toxicological effects in environmental systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics.

PubMed

Hirsch, B; Endris, V; Lassmann, S; Weichert, W; Pfarr, N; Schirmacher, P; Kovaleva, V; Werner, M; Bonzheim, I; Fend, F; Sperveslage, J; Kaulich, K; Zacher, A; Reifenberger, G; Köhrer, K; Stepanow, S; Lerke, S; Mayr, T; Aust, D E; Baretton, G; Weidner, S; Jung, A; Kirchner, T; Hansmann, M L; Burbat, L; von der Wall, E; Dietel, M; Hummel, M

2018-04-01

The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.

GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation.

PubMed

Hess, Berk; Kutzner, Carsten; van der Spoel, David; Lindahl, Erik

2008-03-01

Molecular simulation is an extremely useful, but computationally very expensive tool for studies of chemical and biomolecular systems. Here, we present a new implementation of our molecular simulation toolkit GROMACS which now both achieves extremely high performance on single processors from algorithmic optimizations and hand-coded routines and simultaneously scales very well on parallel machines. The code encompasses a minimal-communication domain decomposition algorithm, full dynamic load balancing, a state-of-the-art parallel constraint solver, and efficient virtual site algorithms that allow removal of hydrogen atom degrees of freedom to enable integration time steps up to 5 fs for atomistic simulations also in parallel. To improve the scaling properties of the common particle mesh Ewald electrostatics algorithms, we have in addition used a Multiple-Program, Multiple-Data approach, with separate node domains responsible for direct and reciprocal space interactions. Not only does this combination of algorithms enable extremely long simulations of large systems but also it provides that simulation performance on quite modest numbers of standard cluster nodes.

Mesoscopic Modeling of Blood Clotting: Coagulation Cascade and Platelets Adhesion

NASA Astrophysics Data System (ADS)

Yazdani, Alireza; Li, Zhen; Karniadakis, George

2015-11-01

The process of clot formation and growth at a site on a blood vessel wall involve a number of multi-scale simultaneous processes including: multiple chemical reactions in the coagulation cascade, species transport and flow. To model these processes we have incorporated advection-diffusion-reaction (ADR) of multiple species into an extended version of Dissipative Particle Dynamics (DPD) method which is considered as a coarse-grained Molecular Dynamics method. At the continuum level this is equivalent to the Navier-Stokes equation plus one advection-diffusion equation for each specie. The chemistry of clot formation is now understood to be determined by mechanisms involving reactions among many species in dilute solution, where reaction rate constants and species diffusion coefficients in plasma are known. The role of blood particulates, i.e. red cells and platelets, in the clotting process is studied by including them separately and together in the simulations. An agonist-induced platelet activation mechanism is presented, while platelets adhesive dynamics based on a stochastic bond formation/dissociation process is included in the model.

Screening Mixtures of Small Molecules for Binding to Multiple Sites on the Surface Tetanus Toxin C Fragment by Bioaffinity NMR

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

Cosman, M; Zeller, L; Lightstone, F C

2002-01-01

The clostridial neurotoxins include the closely related tetanus (TeNT) and botulinum (BoNT) toxins. Botulinum toxin is used to treat severe muscle disorders and as a cosmetic wrinkle reducer. Large quantities of botulinum toxin have also been produced by terrorists for use as a biological weapon. Because there are no known antidotes for these toxins, they thus pose a potential threat to human health whether by an accidental overdose or by a hostile deployment. Thus, the discovery of high specificity and affinity compounds that can inhibit their binding to neural cells can be used as antidotes or in the design ofmore » chemical detectors. Using the crystal structure of the C fragment of the tetanus toxin (TetC), which is the cell recognition and cell surface binding domain, and the computational program DOCK, sets of small molecules have been predicted to bind to two different sites located on the surface of this protein. While Site-1 is common to the TeNT and BoNTs, Site-2 is unique to TeNT. Pairs of these molecules from each site can then be linked together synthetically to thereby increase the specificity and affinity for this toxin. Electrospray ionization mass spectroscopy was used to experimentally screen each compound for binding. Mixtures containing binders were further screened for activity under biologically relevant conditions using nuclear magnetic resonance (NMR) methods. The screening of mixtures of compounds offers increased efficiency and throughput as compared to testing single compounds and can also evaluate how possible structural changes induced by the binding of one ligand can influence the binding of the second ligand. In addition, competitive binding experiments with mixtures containing ligands predicted to bind the same site could identify the best binder for that site. NMR transfer nuclear Overhauser effect (trNOE) confirm that TetC binds doxorubicin but that this molecule is displaced by N-acetylneuraminic acid (sialic acid) in a mixture that also contains 3-sialyllactose (another predicted site 1 binder) and bisbenzimide 33342 (non-binder). A series of five predicted Site-2 binders were then screened sequentially in the presence of the Site-1 binder doxorubicin. These experiments showed that the compounds lavendustin A and naphthofluorescein-di-({beta}-D-galactopyranoside) binds along with doxorubicin to TetC. Further experiments indicate that doxorubicin and lavendustin are potential candidates to use in preparing a bidendate inhibitor specific for TetC. The simultaneous binding of two different predicted Site-2 ligands to TetC suggests that they may bind multiple sites. Another possibility is that the conformations of the binding sites are dynamic and can bind multiple diverse ligands at a single site depending on the pre-existing conformation of the protein, especially when doxorubicin is already bound.« less

Establishing versus preserving impressions: Predicting success in the multiple audience problem.

PubMed

Nichols, Austin Lee; Cottrell, Catherine A

2015-12-01

People sometimes seek to convey discrepant impressions of themselves to different audiences simultaneously. Research suggests people are generally successful in this "multiple audience problem." Adding to previous research, the current research sought to examine factors that may limit this success by measuring social anxiety and placing participants into situations requiring them to either establish or preserve multiple impressions simultaneously. In general, participants were more successful when preserving previously conveyed impressions than when establishing impressions for the first time. In contrast, social anxiety did not affect multiple audience success. In all, this research offers valuable insight into potential challenges that people face in many social situations. © 2015 International Union of Psychological Science.

Management of Globally Distributed Software Development Projects in Multiple-Vendor Constellations

NASA Astrophysics Data System (ADS)

Schott, Katharina; Beck, Roman; Gregory, Robert Wayne

Global information systems development outsourcing is an apparent trend that is expected to continue in the foreseeable future. Thereby, IS-related services are not only increasingly provided from different geographical sites simultaneously but beyond that from multiple service providers based in different countries. The purpose of this paper is to understand how the involvement of multiple service providers affects the management of the globally distributed information systems development projects. As research on this topic is scarce, we applied an exploratory in-depth single-case study design as research approach. The case we analyzed comprises a global software development outsourcing project initiated by a German bank together with several globally distributed vendors. For data collection and data analysis we have adopted techniques suggested by the grounded theory method. Whereas the extant literature points out the increased management overhead associated with multi-sourcing, the analysis of our case suggests that the required effort for managing global outsourcing projects with multiple vendors depends among other things on the maturation level of the cooperation within the vendor portfolio. Furthermore, our data indicate that this interplay maturity is positively impacted through knowledge about the client that has been derived based on already existing client-vendor relationships. The paper concludes by offering theoretical and practical implications.

Where in the world are my field plots? Using GPS effectively in environmental field studies

USGS Publications Warehouse

Johnson, Chris E.; Barton, Christopher C.

2004-01-01

Global positioning system (GPS) technology is rapidly replacing tape, compass, and traditional surveying instruments as the preferred tool for estimating the positions of environmental research sites. One important problem, however, is that it can be difficult to estimate the uncertainty of GPS-derived positions. Sources of error include various satellite- and site-related factors, such as forest canopy and topographic obstructions. In a case study from the Hubbard Brook Experimental Forest in New Hampshire, hand-held, mapping-grade GPS receivers generally estimated positions with 1–5 m precision in open, unobstructed settings, and 20–30 m precision under forest canopy. Surveying-grade receivers achieved precisions of 10 cm or less, even in challenging terrain. Users can maximize the quality of their GPS measurements by “mission planning” to take advantage of high-quality satellite conditions. Repeated measurements and simultaneous data collection at multiple points can be used to assess accuracy and precision.

Stochastic simulation of uranium migration at the Hanford 300 Area.

PubMed

Hammond, Glenn E; Lichtner, Peter C; Rockhold, Mark L

2011-03-01

This work focuses on the quantification of groundwater flow and subsequent U(VI) transport uncertainty due to heterogeneity in the sediment permeability at the Hanford 300 Area. U(VI) migration at the site is simulated with multiple realizations of stochastically-generated high resolution permeability fields and comparisons are made of cumulative water and U(VI) flux to the Columbia River. The massively parallel reactive flow and transport code PFLOTRAN is employed utilizing 40,960 processor cores on DOE's petascale Jaguar supercomputer to simultaneously execute 10 transient, variably-saturated groundwater flow and U(VI) transport simulations within 3D heterogeneous permeability fields using the code's multi-realization simulation capability. Simulation results demonstrate that the cumulative U(VI) flux to the Columbia River is less responsive to fine scale heterogeneity in permeability and more sensitive to the distribution of permeability within the river hyporheic zone and mean permeability of larger-scale geologic structures at the site. Copyright © 2010 Elsevier B.V. All rights reserved.

Flexibility or Inexactitude? The "Lab 60" at Karolinska Institutet: From Medical Disciplines towards the Modern Biomedical Complex.

PubMed

Normark, Daniel

2015-05-01

In 1960, a new laboratory ("Lab 60") was built on the premises of Karolinska Institutet, Stockholm. This paper describes how the laboratory was envisioned. While planners and builders strove to optimise a generic laboratory, researchers argued for specialisation. The compromise was to enhance the reorganisation capability of the interior (flexibility) while simultaneously creating a "movable" institution consisting of researchers temporarily working in the laboratory for periods of three to five years, regardless of their disciplinary affiliation. Even though flexibility was not a novelty, the building succeeded as an organisational experiment and encouraged the abandonment of the model of one discipline, one professor, and one building in favour of a "movable" institution conducting temporary research. While the credibility of laboratories was established by their "placelessness" (anywhere), Lab 60 imitated multiple, heterogeneous sites (anything) in order to maintain credibility. As such, the lab embodied many sites between the disciplines of chemistry and medicine.

Multiple feature extraction by using simultaneous wavelet transforms

NASA Astrophysics Data System (ADS)

Mazzaferri, Javier; Ledesma, Silvia; Iemmi, Claudio

2003-07-01

We propose here a method to optically perform multiple feature extraction by using wavelet transforms. The method is based on obtaining the optical correlation by means of a Vander Lugt architecture, where the scene and the filter are displayed on spatial light modulators (SLMs). Multiple phase filters containing the information about the features that we are interested in extracting are designed and then displayed on an SLM working in phase mostly mode. We have designed filters to simultaneously detect edges and corners or different characteristic frequencies contained in the input scene. Simulated and experimental results are shown.

Wafer hotspot prevention using etch aware OPC correction

NASA Astrophysics Data System (ADS)

Hamouda, Ayman; Power, Dave; Salama, Mohamed; Chen, Ao

2016-03-01

As technology development advances into deep-sub-wavelength nodes, multiple patterning is becoming more essential to achieve the technology shrink requirements. Recently, Optical Proximity Correction (OPC) technology has proposed simultaneous correction of multiple mask-patterns to enable multiple patterning awareness during OPC correction. This is essential to prevent inter-layer hot-spots during the final pattern transfer. In state-of-art literature, multi-layer awareness is achieved using simultaneous resist-contour simulations to predict and correct for hot-spots during mask generation. However, this approach assumes a uniform etch shrink response for all patterns independent of their proximity, which isn't sufficient for the full prevention of inter-exposure hot-spot, for example different color space violations post etch or via coverage/enclosure post etch. In this paper, we explain the need to include the etch component during multiple patterning OPC. We also introduce a novel approach for Etch-aware simultaneous Multiple-patterning OPC, where we calibrate and verify a lumped model that includes the combined resist and etch responses. Adding this extra simulation condition during OPC is suitable for full chip processing from a computation intensity point of view. Also, using this model during OPC to predict and correct inter-exposures hot-spots is similar to previously proposed multiple-patterning OPC, yet our proposed approach more accurately corrects post-etch defects too.

Information extraction during simultaneous motion processing.

PubMed

Rideaux, Reuben; Edwards, Mark

2014-02-01

When confronted with multiple moving objects the visual system can process them in two stages: an initial stage in which a limited number of signals are processed in parallel (i.e. simultaneously) followed by a sequential stage. We previously demonstrated that during the simultaneous stage, observers could discriminate between presentations containing up to 5 vs. 6 spatially localized motion signals (Edwards & Rideaux, 2013). Here we investigate what information is actually extracted during the simultaneous stage and whether the simultaneous limit varies with the detail of information extracted. This was achieved by measuring the ability of observers to extract varied information from low detail, i.e. the number of signals presented, to high detail, i.e. the actual directions present and the direction of a specific element, during the simultaneous stage. The results indicate that the resolution of simultaneous processing varies as a function of the information which is extracted, i.e. as the information extraction becomes more detailed, from the number of moving elements to the direction of a specific element, the capacity to process multiple signals is reduced. Thus, when assigning a capacity to simultaneous motion processing, this must be qualified by designating the degree of information extraction. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Edge-Driven Block Rotations Interpreted From New GPS Results: Papua New Guinea

NASA Astrophysics Data System (ADS)

Wallace, L.

2001-12-01

An ongoing discussion in plate tectonics involves whether microplate motions are driven by plate edge forces or by flow at the base of the lithosphere. We present results from a GPS network of 40 sites spanning much of the mainland of Papua New Guinea (PNG). Most of the sites are concentrated in the region of the active Finisterre arc-continent collision and have been observed on multiple campaigns from 1993-2001. Significant portions of the Ramu-Markham fault are locked, which has implications for seismic hazard assessment in the Markham Valley region. Additionally, we find that out-of-sequence thrusting is important in emplacement of the Finisterre arc terrane onto the PNG mainland. Site velocities derived from these GPS data have helped to delineate the major tectonic blocks in the region. We model site velocities by simultaneously dealing with rigid block rotation and elastic strain. We find that the mainland of PNG consists of four distinct tectonic plates: the Australian, South Bismarck and Woodlark plates (in agreement with previous studies), and a previously unrecognized New Guinea Highlands plate. The relative rotation poles for at least two of these plate pairs plot on their respective boundaries, indicating that microplate motion in PNG may be dominantly edge-driven, as predicted for this region by Schouten and Benes (1993).

In situ experimental assessment of lake whitefish development following a freshwater oil spill.

PubMed

Debruyn, Adrian M H; Wernick, Barbara G; Stefura, Corey; McDonald, Blair G; Rudolph, Barri-Lynn; Patterson, Luanne; Chapman, Peter M

2007-10-15

Wabamun Lake (Alberta, Canada) has been subject to ongoing contamination with polycyclic aromatic hydrocarbons (PAHs) from multiple sources for decades and in August 2005 was exposed to ca. 149 500 L of bunker C oil following a train derailment. We compared the pattern, frequency, and severity of deformity in larvae of lake whitefish (Coregonus clupeaformis) incubated in situ in areas of Wabamun Lake exposed only to "background" PAH contamination and in areas additionally exposed to PAHs from the oil. All sites in the lake (including reference areas) showed incidences of deformity higher than are typically observed in laboratory studies. A small number of oil-exposed sites showed higher incidences of some teratogenic deformities and a tendency to exhibit deformities of higher severity than sites not exposed to oil. The frequency of moderate to severe deformities in 8 of 16 classes was correlated with PAH exposure. Nonmetric multivariate ordination of deformity data revealed a general pattern of increasing incidence and severity of several skeletal (lordosis, scoliosis) and craniofacial (ocular, jaw) deformities at sites with relatively high exposure to oil-derived PAHs. A simultaneous consideration of incidence, severity, and pattern of deformity enabled us to detect a consistent (overall approximately 5% above background) response to the oil despite high variability and high background deformity rates in this historically contaminated environment.

Intracortical microstimulation induced changes in spectral and temporal response properties in cat auditory cortex.

PubMed

Valentine, Pamela A; Eggermont, Jos J

2003-09-01

Intracortical microstimulation (ICMS), consisting of a 40 ms burst (rate 300 Hz) of 10 microA pulses, repetitively administered once per second, for a total duration of 1 h, induced cortical reorganization in the primary auditory cortical field of the anesthetized cat. Multiple single-unit activity was simultaneously recorded from three to nine microelectrodes. Spiking activity was recorded from the same units prior to and following the application of ICMS in conjunction with tone pips at the characteristic frequency (CF) of the stimulus electrode. ICMS produced a significant increase in the mean firing rate, and in the occurrence of burst activity. There was an increase in the cross-correlation coefficient (R) for unit pairs recorded from sites distant from the ICMS site, and a decrease in R for unit pairs that were recorded at the stimulation site. ICMS induced a shift in the CF, dependent on the difference between the baseline CF and the ICMS-paired tone pip frequency. ICMS also resulted in broader tuning curves, increased driven peak firing rate and reduced response latency. This suggests a lasting reduction in inhibition in a small region surrounding the ICMS site that allows expansion of the frequency range normally represented in the vicinity of the stimulation electrode.

Single cell visualization of transcription kinetics variance of highly mobile identical genes using 3D nanoimaging

PubMed Central

Annibale, Paolo; Gratton, Enrico

2015-01-01

Multi-cell biochemical assays and single cell fluorescence measurements revealed that the elongation rate of Polymerase II (PolII) in eukaryotes varies largely across different cell types and genes. However, there is not yet a consensus whether intrinsic factors such as the position, local mobility or the engagement by an active molecular mechanism of a genetic locus could be the determinants of the observed heterogeneity. Here by employing high-speed 3D fluorescence nanoimaging techniques we resolve and track at the single cell level multiple, distinct regions of mRNA synthesis within the model system of a large transgene array. We demonstrate that these regions are active transcription sites that release mRNA molecules in the nucleoplasm. Using fluctuation spectroscopy and the phasor analysis approach we were able to extract the local PolII elongation rate at each site as a function of time. We measured a four-fold variation in the average elongation between identical copies of the same gene measured simultaneously within the same cell, demonstrating a correlation between local transcription kinetics and the movement of the transcription site. Together these observations demonstrate that local factors, such as chromatin local mobility and the microenvironment of the transcription site, are an important source of transcription kinetics variability. PMID:25788248

REDO: RNA Editing Detection in Plant Organelles Based on Variant Calling Results.

PubMed

Wu, Shuangyang; Liu, Wanfei; Aljohi, Hasan Awad; Alromaih, Sarah A; Alanazi, Ibrahim O; Lin, Qiang; Yu, Jun; Hu, Songnian

2018-05-01

RNA editing is a post-transcriptional or cotranscriptional process that changes the sequence of the precursor transcript by substitutions, insertions, or deletions. Almost all of the land plants undergo RNA editing in organelles (plastids and mitochondria). Although several software tools have been developed to identify RNA editing events, there has been a great challenge to distinguish true RNA editing events from genome variation, sequencing errors, and other factors. Here we introduce REDO, a comprehensive application tool for identifying RNA editing events in plant organelles based on variant call format files from RNA-sequencing data. REDO is a suite of Perl scripts that illustrate a bunch of attributes of RNA editing events in figures and tables. REDO can also detect RNA editing events in multiple samples simultaneously and identify the significant differential proportion of RNA editing loci. Comparing with similar tools, such as REDItools, REDO runs faster with higher accuracy, and more specificity at the cost of slightly lower sensitivity. Moreover, REDO annotates each RNA editing site in RNAs, whereas REDItools reports only possible RNA editing sites in genome, which need additional steps to obtain RNA editing profiles for RNAs. Overall, REDO can identify potential RNA editing sites easily and provide several functions such as detailed annotations, statistics, figures, and significantly differential proportion of RNA editing sites among different samples.

Statistical technique for analysing functional connectivity of multiple spike trains.

PubMed

Masud, Mohammad Shahed; Borisyuk, Roman

2011-03-15

A new statistical technique, the Cox method, used for analysing functional connectivity of simultaneously recorded multiple spike trains is presented. This method is based on the theory of modulated renewal processes and it estimates a vector of influence strengths from multiple spike trains (called reference trains) to the selected (target) spike train. Selecting another target spike train and repeating the calculation of the influence strengths from the reference spike trains enables researchers to find all functional connections among multiple spike trains. In order to study functional connectivity an "influence function" is identified. This function recognises the specificity of neuronal interactions and reflects the dynamics of postsynaptic potential. In comparison to existing techniques, the Cox method has the following advantages: it does not use bins (binless method); it is applicable to cases where the sample size is small; it is sufficiently sensitive such that it estimates weak influences; it supports the simultaneous analysis of multiple influences; it is able to identify a correct connectivity scheme in difficult cases of "common source" or "indirect" connectivity. The Cox method has been thoroughly tested using multiple sets of data generated by the neural network model of the leaky integrate and fire neurons with a prescribed architecture of connections. The results suggest that this method is highly successful for analysing functional connectivity of simultaneously recorded multiple spike trains. Copyright © 2011 Elsevier B.V. All rights reserved.

Synergistic activation of NF-{kappa}B by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKK{beta}-I{kappa}B{alpha}, and p38 MAPK

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

Kweon, Soo-Mi; Wang, Beinan; Rixter, Davida

2006-12-15

In review of the past studies on NF-{kappa}B regulation, most of them have focused on investigating how NF-{kappa}B is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-{kappa}B and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-{kappa}B-dependent inflammatory response via activation of multiple signaling pathways in vitromore » and in vivo. The classical IKK{beta}-I{kappa}B{alpha} and p38 MAPK pathways are involved in synergistic activation of NF-{kappa}B via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-{kappa}B via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-{kappa}B-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases.« less

New nonlinear control algorithms for multiple robot arms

NASA Technical Reports Server (NTRS)

Tarn, T. J.; Bejczy, A. K.; Yun, X.

1988-01-01

Multiple coordinated robot arms are modeled by considering the arms as closed kinematic chains and as a force-constrained mechanical system working on the same object simultaneously. In both formulations, a novel dynamic control method is discussed. It is based on feedback linearization and simultaneous output decoupling technique. By applying a nonlinear feedback and a nonlinear coordinate transformation, the complicated model of the multiple robot arms in either formulation is converted into a linear and output decoupled system. The linear system control theory and optimal control theory are used to design robust controllers in the task space. The first formulation has the advantage of automatically handling the coordination and load distribution among the robot arms. In the second formulation, it was found that by choosing a general output equation it became possible simultaneously to superimpose the position and velocity error feedback with the force-torque error feedback in the task space.

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents.

PubMed

Anderson, Christian E; Donnola, Shannon B; Jiang, Yun; Batesole, Joshua; Darrah, Rebecca; Drumm, Mitchell L; Brady-Kalnay, Susann M; Steinmetz, Nicole F; Yu, Xin; Griswold, Mark A; Flask, Chris A

2017-08-16

Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI's ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast - Magnetic Resonance Fingerprinting (DC - MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This "multi-color" MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.

Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis.

PubMed

Martinez, Andres W; Phillips, Scott T; Carrilho, Emanuel; Thomas, Samuel W; Sindi, Hayat; Whitesides, George M

2008-05-15

This article describes a prototype system for quantifying bioassays and for exchanging the results of the assays digitally with physicians located off-site. The system uses paper-based microfluidic devices for running multiple assays simultaneously, camera phones or portable scanners for digitizing the intensity of color associated with each colorimetric assay, and established communications infrastructure for transferring the digital information from the assay site to an off-site laboratory for analysis by a trained medical professional; the diagnosis then can be returned directly to the healthcare provider in the field. The microfluidic devices were fabricated in paper using photolithography and were functionalized with reagents for colorimetric assays. The results of the assays were quantified by comparing the intensities of the color developed in each assay with those of calibration curves. An example of this system quantified clinically relevant concentrations of glucose and protein in artificial urine. The combination of patterned paper, a portable method for obtaining digital images, and a method for exchanging results of the assays with off-site diagnosticians offers new opportunities for inexpensive monitoring of health, especially in situations that require physicians to travel to patients (e.g., in the developing world, in emergency management, and during field operations by the military) to obtain diagnostic information that might be obtained more effectively by less valuable personnel.

Urban Air Toxics Monitoring Program, 1989

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

McAllister, R.A.; Moore, W.H.; Rice, J.

1990-10-01

From January 1989 through January 1990 samples of ambient air were collected at 14 sites in the eastern part of the U.S. Every 12 days, air was integrated over 24-hour periods into passivated stainless steel canisters. Simultaneously, air was drawn through cartridges containing dinitrophenylhydrazine to collect carbonyl compounds. The samples were analyzed at a central laboratory for a total of 37 halogenated and aromatic hydrocarbons, formaldehyde, acetaldehyde, and other oxygenated species. The hydrocarbon species were analyzed by gas chromatography/multiple detectors and gas chromatography/mass spectrometry, while the carbonyl species were analyzed by liquid chromatography. An extensive quality assurance program was carriedmore » on to secure high quality data. Complete data for all the carbonyl samples are presented in the report.« less

Sensitivity of decomposition rates of soil organic matter with respect to simultaneous changes in temperature and moisture

NASA Astrophysics Data System (ADS)

Sierra, Carlos A.; Trumbore, Susan E.; Davidson, Eric A.; Vicca, Sara; Janssens, I.

2015-03-01

The sensitivity of soil organic matter decomposition to global environmental change is a topic of prominent relevance for the global carbon cycle. Decomposition depends on multiple factors that are being altered simultaneously as a result of global environmental change; therefore, it is important to study the sensitivity of the rates of soil organic matter decomposition with respect to multiple and interacting drivers. In this manuscript, we present an analysis of the potential response of decomposition rates to simultaneous changes in temperature and moisture. To address this problem, we first present a theoretical framework to study the sensitivity of soil organic matter decomposition when multiple driving factors change simultaneously. We then apply this framework to models and data at different levels of abstraction: (1) to a mechanistic model that addresses the limitation of enzyme activity by simultaneous effects of temperature and soil water content, the latter controlling substrate supply and oxygen concentration for microbial activity; (2) to different mathematical functions used to represent temperature and moisture effects on decomposition in biogeochemical models. To contrast model predictions at these two levels of organization, we compiled different data sets of observed responses in field and laboratory studies. Then we applied our conceptual framework to: (3) observations of heterotrophic respiration at the ecosystem level; (4) laboratory experiments looking at the response of heterotrophic respiration to independent changes in moisture and temperature; and (5) ecosystem-level experiments manipulating soil temperature and water content simultaneously.

A Single Multiplex crRNA Array for FnCpf1-Mediated Human Genome Editing.

PubMed

Sun, Huihui; Li, Fanfan; Liu, Jie; Yang, Fayu; Zeng, Zhenhai; Lv, Xiujuan; Tu, Mengjun; Liu, Yeqing; Ge, Xianglian; Liu, Changbao; Zhao, Junzhao; Zhang, Zongduan; Qu, Jia; Song, Zongming; Gu, Feng

2018-06-15

Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy. However, there are no reports at present that show FnCpf1-mediated multiplex genome editing via a single customized CRISPR RNA (crRNA) array. In the present study, we utilize a single customized crRNA array to simultaneously target multiple genes in human cells. In addition, we also demonstrate that a single customized crRNA array to target multiple sites in one gene could be achieved. Collectively, FnCpf1, a powerful genome-editing tool for multiple genomic targets, can be harnessed for effective manipulation of the human genome. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Evidence for Spiral Magnetic Structures at the Magnetopause: A Case for Multiple Reconnections

NASA Technical Reports Server (NTRS)

Vaisberg, O. L.; Smirnov, V. N.; Avanov, L. A.; Moore, T. E.

2003-01-01

We analyze plasma structures within the low latitude boundary layer (LLBL) observed by the lnterball Tail spacecraft under southward interplanetary magnetic field. Ion velocity distributions observed in the LLBL under these conditions fall into three categories: (a) D-shaped distributions, (b) ion velocity distributions consisting of two counterstreaming magnetosheath-type, and (c) distributions with three components where one of them has nearly zero velocity parallel to magnetic field (VlI), while the other two are counter-streaming components. D-shaped ion velocity distributions (a) correspond to magnetosheath plasma injections into reconnected flux tubes, as influenced by spacecraft location relative to the reconnection site. Simultaneous counter-streaming injections (b) suggest multiple reconnections. Three-component ion velocity distributions (c) and theii evolution with decreasing number density in the LLBL are consistent v behavior expected on long spiral flux tube islands at the magnetopaus as has been proposed and found to occur in magnetopause simulatior We interpret these distributions as a natural consequence of the formation of spiral magnetic flux tubes consisting of a mixture of alternating segments originating from the magnetosheath and magnetospheric plasmas. We suggest that multiple reconnections pla! an important role in the formation of the LLBL.

A ROle-Oriented Filtering (ROOF) approach for collaborative recommendation

NASA Astrophysics Data System (ADS)

Ghani, Imran; Jeong, Seung Ryul

2016-09-01

In collaborative filtering (CF) recommender systems, existing techniques frequently focus on determining similarities among users' historical interests. This generally refers to situations in which each user normally plays a single role and his/her taste remains consistent over the long term. However, we note that existing techniques have not been significantly employed in a role-oriented context. This is especially so in situations where users may change their roles over time or play multiple roles simultaneously, while still expecting to access relevant information resources accordingly. Such systems include enterprise architecture management systems, e-commerce sites or journal management systems. In scenarios involving existing techniques, each user needs to build up very different profiles (preferences and interests) based on multiple roles which change over time. Should this not occur to a satisfactory degree, their previous information will either be lost or not utilised at all. To limit the occurrence of such issues, we propose a ROle-Oriented Filtering (ROOF) approach focusing on the manner in which multiple user profiles are obtained and maintained over time. We conducted a number of experiments using an enterprise architecture management scenario. In so doing, we observed that the ROOF approach performs better in comparison with other existing collaborative filtering-based techniques.

Striatal and Hippocampal Entropy and Recognition Signals in Category Learning: Simultaneous Processes Revealed by Model-Based fMRI

PubMed Central

Davis, Tyler; Love, Bradley C.; Preston, Alison R.

2012-01-01

Category learning is a complex phenomenon that engages multiple cognitive processes, many of which occur simultaneously and unfold dynamically over time. For example, as people encounter objects in the world, they simultaneously engage processes to determine their fit with current knowledge structures, gather new information about the objects, and adjust their representations to support behavior in future encounters. Many techniques that are available to understand the neural basis of category learning assume that the multiple processes that subserve it can be neatly separated between different trials of an experiment. Model-based functional magnetic resonance imaging offers a promising tool to separate multiple, simultaneously occurring processes and bring the analysis of neuroimaging data more in line with category learning’s dynamic and multifaceted nature. We use model-based imaging to explore the neural basis of recognition and entropy signals in the medial temporal lobe and striatum that are engaged while participants learn to categorize novel stimuli. Consistent with theories suggesting a role for the anterior hippocampus and ventral striatum in motivated learning in response to uncertainty, we find that activation in both regions correlates with a model-based measure of entropy. Simultaneously, separate subregions of the hippocampus and striatum exhibit activation correlated with a model-based recognition strength measure. Our results suggest that model-based analyses are exceptionally useful for extracting information about cognitive processes from neuroimaging data. Models provide a basis for identifying the multiple neural processes that contribute to behavior, and neuroimaging data can provide a powerful test bed for constraining and testing model predictions. PMID:22746951

Site-level progression of periodontal disease during a follow-up period

PubMed Central

Morozumi, Toshiya; Nakagawa, Taneaki; Sugaya, Tsutomu; Kawanami, Masamitsu; Suzuki, Fumihiko; Takahashi, Keiso; Abe, Yuzo; Sato, Soh; Makino-Oi, Asako; Saito, Atsushi; Takano, Satomi; Minabe, Masato; Nakayama, Yohei; Ogata, Yorimasa; Kobayashi, Hiroaki; Izumi, Yuichi; Sugano, Naoyuki; Ito, Koichi; Sekino, Satoshi; Numabe, Yukihiro; Fukaya, Chie; Yoshinari, Nobuo; Fukuda, Mitsuo; Noguchi, Toshihide; Kono, Tomoo; Umeda, Makoto; Fujise, Osamu; Nishimura, Fusanori; Yoshimura, Atsutoshi; Hara, Yoshitaka; Nakamura, Toshiaki; Noguchi, Kazuyuki; Kakuta, Erika; Hanada, Nobuhiro; Takashiba, Shogo; Amitani, Yasuharu; Yoshie, Hiromasa

2017-01-01

Periodontal disease is assessed and its progression is determined via observations on a site-by-site basis. Periodontal data are complex and structured in multiple levels; thus, applying a summary statistical approach (i.e., the mean) for site-level evaluations results in loss of information. Previous studies have shown the availability of mixed effects modeling. However, clinically beneficial information on the progression of periodontal disease during the follow-up period is not available. We conducted a multicenter prospective cohort study. Using mixed effects modeling, we analyzed 18,834 sites distributed on 3,139 teeth in 124 patients, and data were collected 5 times over a 24-month follow-up period. The change in the clinical attachment level (CAL) was used as the outcome variable. The CAL at baseline was an important determinant of the CAL changes, which varied widely according to the tooth surface. The salivary levels of periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, were affected by CAL progression. “Linear”- and “burst”-type patterns of CAL progression occurred simultaneously within the same patient. More than half of the teeth that presented burst-type progression sites also presented linear-type progression sites, and most of the progressions were of the linear type. Maxillary premolars and anterior teeth tended to show burst-type progression. The parameters identified in this study may guide practitioners in determining the type and extent of treatment needed at the site and patient levels. In addition, these results show that prior hypotheses concerning "burst" and "linear" theories are not valid. PMID:29206238

Multiple binding sites for transcriptional repressors can produce regular bursting and enhance noise suppression

NASA Astrophysics Data System (ADS)

Lengyel, Iván M.; Morelli, Luis G.

2017-04-01

Cells may control fluctuations in protein levels by means of negative autoregulation, where transcription factors bind DNA sites to repress their own production. Theoretical studies have assumed a single binding site for the repressor, while in most species it is found that multiple binding sites are arranged in clusters. We study a stochastic description of negative autoregulation with multiple binding sites for the repressor. We find that increasing the number of binding sites induces regular bursting of gene products. By tuning the threshold for repression, we show that multiple binding sites can also suppress fluctuations. Our results highlight possible roles for the presence of multiple binding sites of negative autoregulators.

Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue

PubMed Central

Gizzi, Alessio; Cherry, Elizabeth M.; Gilmour, Robert F.; Luther, Stefan; Filippi, Simonetta; Fenton, Flavio H.

2013-01-01

Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events. PMID:23637684

Unmanned Aircraft Systems (UAS) Traffic Management (UTM) National Campaign II

NASA Technical Reports Server (NTRS)

Aweiss, Arwa S.; Owens, Brandon D.; Rios, Joseph L.; Homola, Jeffrey R.; Mohlenbrink, Christoph P.

2018-01-01

The Unmanned Aircraft System (UAS) Traffic Management (UTM) effort at NASA aims to enable access to low-altitude airspace for small UAS. This goal is being pursued partly through partnerships that NASA has developed with the UAS stakeholder community, the FAA, other government agencies, and the designated FAA UAS Test Sites. By partnering with the FAA UAS Test Sites, NASA's UTM project has performed a geographically diverse, simultaneous set of UAS operations at locations in six states. The demonstrations used an architecture that was developed by NASA in partnership with the FAA to safely coordinate such operations. These demonstrations-the second or 'Technical Capability Level (TCL 2)' National Campaign of UTM testing-was performed from May 15 through June 9, 2017. Multiple UAS operations occurred during the testing at sites located in Alaska, Nevada, Texas, North Dakota, Virginia, and New York with multiple organizations serving as UAS Service Suppliers and/or UAS Operators per the specifications provided by NASA. By engaging various members of the UAS community in development and operational roles, this campaign provided initial validation of different aspects of the UTM concept including: UAS Service Supplier technologies and procedures; geofencing technologies/conformance monitoring; ground-based surveillance/sense and avoid; airborne sense and avoid; communication, navigation, surveillance; and human factors related to UTM data creation and display. Additionally, measures of performance were defined and calculated from the flight data to establish quantitative bases for comparing flight test activities and to provide potential metrics that might be routinely monitored in future operational UTM systems.

The effect of an integrated multisector model for achieving the Millennium Development Goals and improving child survival in rural sub-Saharan Africa: a non-randomised controlled assessment.

PubMed

Pronyk, Paul M; Muniz, Maria; Nemser, Ben; Somers, Marie-Andrée; McClellan, Lucy; Palm, Cheryl A; Huynh, Uyen Kim; Ben Amor, Yanis; Begashaw, Belay; McArthur, John W; Niang, Amadou; Sachs, Sonia Ehrlich; Singh, Prabhjot; Teklehaimanot, Awash; Sachs, Jeffrey D

2012-06-09

Simultaneously addressing multiple Millennium Development Goals (MDGs) has the potential to complement essential health interventions to accelerate gains in child survival. The Millennium Villages project is an integrated multisector approach to rural development operating across diverse sub-Saharan African sites. Our aim was to assess the effects of the project on MDG-related outcomes including child mortality 3 years after implementation and compare these changes to local comparison data. Village sites averaging 35,000 people were selected from rural areas across diverse agroecological zones with high baseline levels of poverty and undernutrition. Starting in 2006, simultaneous investments were made in agriculture, the environment, business development, education, infrastructure, and health in partnership with communities and local governments at an annual projected cost of US$120 per person. We assessed MDG-related progress by monitoring changes 3 years after implementation across Millenium Village sites in nine countries. The primary outcome was the mortality rate of children younger than 5 years of age. To assess plausibility and attribution, we compared changes to reference data gathered from matched randomly selected comparison sites for the mortality rate of children younger than 5 years of age. Analyses were done on a per-protocol basis. This trial is registered with ClinicalTrials.gov, number NCT01125618. Baseline levels of MDG-related spending averaged $27 per head, increasing to $116 by year 3 of which $25 was spent on health. After 3 years, reductions in poverty, food insecurity, stunting, and malaria parasitaemia were reported across nine Millennium Village sites. Access to improved water and sanitation increased, along with coverage for many maternal-child health interventions. Mortality rates in children younger than 5 years of age decreased by 22% in Millennium Village sites relative to baseline (absolute decrease 25 deaths per 1000 livebirths, p=0·015) and 32% relative to matched comparison sites (30 deaths per 1000 livebirths, p=0·033). An integrated multisector approach for addressing the MDGs can produce rapid declines in child mortality in the first 3 years of a long-term effort in rural sub-Saharan Africa. UN Human Security Trust Fund, the Lenfest Foundation, Bill & Melinda Gates Foundation, and Becton Dickinson. Copyright © 2012 Elsevier Ltd. All rights reserved.

A molecular and antigenic survey of H5N1 highly pathogenic avian influenza virus isolates from smallholder duck farms in Central Java, Indonesia during 2007-2008

PubMed Central

2011-01-01

Background Indonesia is one of the countries most severely affected by H5N1 highly pathogenic avian influenza (HPAI) virus in terms of poultry and human health. However, there is little information on the diversity of H5N1 viruses circulating in backyard farms, where chickens and ducks often intermingle. In this study, H5N1 virus infection occurring in 96 smallholder duck farms in central Java, Indonesia from 2007-2008 was investigated and the molecular and antigenic characteristics of H5N1 viruses isolated from these farms were analysed. Results All 84 characterised viruses belonged to H5N1 clade 2.1 with three virus sublineages being identified: clade 2.1.1 (1), clade 2.1.3 (80), and IDN/6/05-like viruses (3) that did not belong to any of the present clades. All three clades were found in ducks, while only clade 2.1.3 was isolated from chickens. There were no significant amino acid mutations of the hemagglutinin (HA) and neuraminidase (NA) sites of the viruses, including the receptor binding, glycosylation, antigenic and catalytic sites and NA inhibitor targets. All the viruses had polybasic amino acids at the HA cleavage site. No evidence of major antigenic variants was detected. Based on the HA gene, identical virus variants could be found on different farms across the study sites and multiple genetic variants could be isolated from HPAI outbreaks simultaneously or at different time points from single farms. HPAI virus was isolated from both ducks and chickens; however, the proportion of surviving duck cases was considerably higher than in chickens. Conclusions The 2.1.3 clade was the most common lineage found in this study. All the viruses had sequence characteristic of HPAI, but negligible variations in other recognized amino acids at the HA and NA proteins which determine virus phenotypes. Multiple genetic variants appeared to be circulating simultaneously within poultry communities. The high proportion of live duck cases compared to chickens over the study period suggests that ducks are more likely to survive infection and they may better suit the role of long-term maintenance host for H5N1. As some viruses were isolated from dead birds, there was no clear correlation between genetic variations and pathogenicity of these viruses. PMID:21896207

Radiofrequency catheter ablation of idiopathic ventricular arrhythmias originating from intramural foci in the left ventricular outflow tract: efficacy of sequential versus simultaneous unipolar catheter ablation.

PubMed

Yamada, Takumi; Maddox, William R; McElderry, H Thomas; Doppalapudi, Harish; Plumb, Vance J; Kay, G Neal

2015-04-01

Idiopathic ventricular arrhythmias (VAs) originating from the left ventricular outflow tract (LVOT) sometimes require catheter ablation from the endocardial and epicardial sides for their elimination, suggesting the presence of intramural VA foci. This study investigated the efficacy of sequential and simultaneous unipolar radiofrequency catheter ablation from the endocardial and epicardial sides in treating intramural LVOT VAs. Fourteen consecutive LVOT VAs, which required sequential or simultaneous irrigated unipolar radiofrequency ablation from the endocardial and epicardial sides for their elimination, were studied. The first ablation was performed at the site with the earliest local ventricular activation and best pace map on the endocardial or epicardial side. When the first ablation was unsuccessful, the second ablation was delivered on the other surface. If this sequential unipolar ablation failed, simultaneous unipolar ablation from both sides was performed. The first ablation was performed on the epicardial side in 9 VAs and endocardial side in 5 VAs. The intramural LVOT VAs were successfully eliminated by the sequential (n=9) or simultaneous (n=5) unipolar catheter ablation. Simultaneous ablation was most likely to be required for the elimination of the VAs when the distance between the endocardial and epicardial ablation sites was >8 mm and the earliest local ventricular activation time relative to the QRS onset during the VAs of <-30 ms was recorded at those ablation sites. LVOT VAs originating from intramural foci could usually be eliminated by sequential unipolar radiofrequency ablation and sometimes required simultaneous ablation from both the endocardial and epicardial sides. © 2015 American Heart Association, Inc.

Dual-track CCS stakeholder engagement: Lessons learned from FutureGen in Illinois

USGS Publications Warehouse

Hund, G.; Greenberg, S.E.

2011-01-01

FutureGen, as originally planned, was to be the world's first coal-fueled, near-zero emissions power plant with fully integrated, 90% carbon capture and storage (CCS). From conception through siting and design, it enjoyed strong support from multiple stakeholder groups, which benefited the overall project. Understanding the stakeholder engagement process for this project provides valuable insights into the design of stakeholder programs for future CCS projects. FutureGen is one of few projects worldwide that used open competition for siting both the power plant and storage reservoir. Most site proposals were coordinated by State governments. It was unique in this and other respects relative to the site selection method used on other DOE-supported projects. At the time of site selection, FutureGen was the largest proposed facility designed to combine an integrated gasification combined cycle (IGCC) coal-fueled power plant with a CCS system. Stakeholder engagement by states and the industry consortium responsible for siting, designing, building, and operating the facility took place simultaneously and on parallel tracks. On one track were states spearheading state-wide site assessments to identify candidate sites that they wanted to propose for consideration. On the other track was a public-private partnership between an industry consortium of thirteen coal companies and electric utilities that comprised the FutureGen Alliance (Alliance) and the U.S. Department of Energy (DOE). The partnership was based on a cooperative agreement signed by both parties, which assigned the lead for siting to the Alliance. This paper describes the stakeholder engagement strategies used on both of these tracks and provides examples from the engagement process using the Illinois semi-finalist sites. ?? 2011 Published by Elsevier Ltd.

Modes of Interaction of Pleckstrin Homology Domains with Membranes: Toward a Computational Biochemistry of Membrane Recognition.

PubMed

Naughton, Fiona B; Kalli, Antreas C; Sansom, Mark S P

2018-02-02

Pleckstrin homology (PH) domains mediate protein-membrane interactions by binding to phosphatidylinositol phosphate (PIP) molecules. The structural and energetic basis of selective PH-PIP interactions is central to understanding many cellular processes, yet the molecular complexities of the PH-PIP interactions are largely unknown. Molecular dynamics simulations using a coarse-grained model enables estimation of free-energy landscapes for the interactions of 12 different PH domains with membranes containing PIP 2 or PIP 3 , allowing us to obtain a detailed molecular energetic understanding of the complexities of the interactions of the PH domains with PIP molecules in membranes. Distinct binding modes, corresponding to different distributions of cationic residues on the PH domain, were observed, involving PIP interactions at either the "canonical" (C) and/or "alternate" (A) sites. PH domains can be grouped by the relative strength of their C- and A-site interactions, revealing that a higher affinity correlates with increased C-site interactions. These simulations demonstrate that simultaneous binding of multiple PIP molecules by PH domains contributes to high-affinity membrane interactions, informing our understanding of membrane recognition by PH domains in vivo. Copyright © 2017. Published by Elsevier Ltd.

Submarine groundwater discharge and nutrient addition to the coastal zone and coral reefs of leeward Hawai'i

USGS Publications Warehouse

Street, J.H.; Knee, K.L.; Grossman, E.E.; Paytan, A.

2008-01-01

Multiple tracers of groundwater input (salinity, Si, 223Ra, 224Ra, and 226Ra) were used together to determine the magnitude, character (meteoric versus seawater), and nutrient contribution associated with submarine groundwater discharge across the leeward shores of the Hawai'ian Islands Maui, Moloka'i, and Hawai'i. Tracer abundances were elevated in the unconfined coastal aquifer and the nearshore zone, decreasing to low levels offshore, indicative of groundwater discharge (near-fresh, brackish, or saline) at all locations. At several sites, we detected evidence of fresh and saline SGD occurring simultaneously. Conservative estimates of SGD fluxes ranged widely, from 0.02-0.65??m3??m- 2 d- 1at the various sites. Groundwater nutrient fluxes of 0.04-40??mmol N m- 2 d- 1 and 0.01-1.6??mmol P m- 2 d- 1 represent a major source of new nutrients to coastal ecosystems along these coasts. Nutrient additions were typically greatest at locations with a substantial meteoric component in groundwater, but the recirculation of seawater through the aquifer may provide a means of transferring terrestrially-derived nutrients to the coastal zone at several sites. ?? 2007 Elsevier B.V. All rights reserved.

CMS Readiness for Multi-Core Workload Scheduling

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

Perez-Calero Yzquierdo, A.; Balcas, J.; Hernandez, J.

In the present run of the LHC, CMS data reconstruction and simulation algorithms benefit greatly from being executed as multiple threads running on several processor cores. The complexity of the Run 2 events requires parallelization of the code to reduce the memory-per- core footprint constraining serial execution programs, thus optimizing the exploitation of present multi-core processor architectures. The allocation of computing resources for multi-core tasks, however, becomes a complex problem in itself. The CMS workload submission infrastructure employs multi-slot partitionable pilots, built on HTCondor and GlideinWMS native features, to enable scheduling of single and multi-core jobs simultaneously. This provides amore » solution for the scheduling problem in a uniform way across grid sites running a diversity of gateways to compute resources and batch system technologies. This paper presents this strategy and the tools on which it has been implemented. The experience of managing multi-core resources at the Tier-0 and Tier-1 sites during 2015, along with the deployment phase to Tier-2 sites during early 2016 is reported. The process of performance monitoring and optimization to achieve efficient and flexible use of the resources is also described.« less

Earth Observing System Data Gateway

NASA Technical Reports Server (NTRS)

Pfister, Robin; McMahon, Joe; Amrhein, James; Sefert, Ed; Marsans, Lorena; Solomon, Mark; Nestler, Mark

2006-01-01

The Earth Observing System Data Gateway (EDG) software provides a "one-stop-shopping" standard interface for exploring and ordering Earth-science data stored at geographically distributed sites. EDG enables a user to do the following: 1) Search for data according to high-level criteria (e.g., geographic location, time, or satellite that acquired the data); 2) Browse the results of a search, viewing thumbnail sketches of data that satisfy the user s criteria; and 3) Order selected data for delivery to a specified address on a chosen medium (e.g., compact disk or magnetic tape). EDG consists of (1) a component that implements a high-level client/server protocol, and (2) a collection of C-language libraries that implement the passing of protocol messages between an EDG client and one or more EDG servers. EDG servers are located at sites usually called "Distributed Active Archive Centers" (DAACs). Each DAAC may allow access to many individual data items, called "granules" (e.g., single Landsat images). Related granules are grouped into collections called "data sets." EDG enables a user to send a search query to multiple DAACs simultaneously, inspect the resulting information, select browseable granules, and then order selected data from the different sites in a seamless fashion.

Range discrimination in ultrasonic vibrometry: theory and experiment.

PubMed

Martin, J S; Rogers, P H; Gray, M D

2011-09-01

A technique has been developed to demodulate periodic broadband ultrasonic interrogation signals that are returned from multiple scattering sites to simultaneously determine the low-frequency displacement time histories of each individual site. The technique employs a broadband periodic transmit signal. The motions of scattering sites are separately determined from the echoed receive signal by an algorithm involving comb filtering and pulse synthesis. This algorithm permits spatial resolution comparable to pulse-echo techniques and displacement sensitivities comparable to pure-tone techniques. A system based on this technique was used to image transient audio-frequency displacements on the order of 1-10 μm peak (≥ 50 nm/√Hz) that were produced by propagating shear waves in a tissue phantom. The system used concentric transmitting and receiving transducers and a carrier signal centered at 2.5 MHz with an 800 kHz bandwidth. The system was self-noise-limited and capable of detecting motions of strongly reflecting regions on the order of 1 nm/√Hz. System performance is limited by several factors including signal selection, component hardware, and ultrasonic propagation within the media of interest. © 2011 Acoustical Society of America

CMS readiness for multi-core workload scheduling

NASA Astrophysics Data System (ADS)

Perez-Calero Yzquierdo, A.; Balcas, J.; Hernandez, J.; Aftab Khan, F.; Letts, J.; Mason, D.; Verguilov, V.

2017-10-01

In the present run of the LHC, CMS data reconstruction and simulation algorithms benefit greatly from being executed as multiple threads running on several processor cores. The complexity of the Run 2 events requires parallelization of the code to reduce the memory-per- core footprint constraining serial execution programs, thus optimizing the exploitation of present multi-core processor architectures. The allocation of computing resources for multi-core tasks, however, becomes a complex problem in itself. The CMS workload submission infrastructure employs multi-slot partitionable pilots, built on HTCondor and GlideinWMS native features, to enable scheduling of single and multi-core jobs simultaneously. This provides a solution for the scheduling problem in a uniform way across grid sites running a diversity of gateways to compute resources and batch system technologies. This paper presents this strategy and the tools on which it has been implemented. The experience of managing multi-core resources at the Tier-0 and Tier-1 sites during 2015, along with the deployment phase to Tier-2 sites during early 2016 is reported. The process of performance monitoring and optimization to achieve efficient and flexible use of the resources is also described.

Emergent Neutrality in Adaptive Asexual Evolution

PubMed Central

Schiffels, Stephan; Szöllősi, Gergely J.; Mustonen, Ville; Lässig, Michael

2011-01-01

In nonrecombining genomes, genetic linkage can be an important evolutionary force. Linkage generates interference interactions, by which simultaneously occurring mutations affect each other’s chance of fixation. Here, we develop a comprehensive model of adaptive evolution in linked genomes, which integrates interference interactions between multiple beneficial and deleterious mutations into a unified framework. By an approximate analytical solution, we predict the fixation rates of these mutations, as well as the probabilities of beneficial and deleterious alleles at fixed genomic sites. We find that interference interactions generate a regime of emergent neutrality: all genomic sites with selection coefficients smaller in magnitude than a characteristic threshold have nearly random fixed alleles, and both beneficial and deleterious mutations at these sites have nearly neutral fixation rates. We show that this dynamic limits not only the speed of adaptation, but also a population’s degree of adaptation in its current environment. We apply the model to different scenarios: stationary adaptation in a time-dependent environment and approach to equilibrium in a fixed environment. In both cases, the analytical predictions are in good agreement with numerical simulations. Our results suggest that interference can severely compromise biological functions in an adapting population, which sets viability limits on adaptive evolution under linkage. PMID:21926305

SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes.

PubMed

Shen, Yue; Stracquadanio, Giovanni; Wang, Yun; Yang, Kun; Mitchell, Leslie A; Xue, Yaxin; Cai, Yizhi; Chen, Tai; Dymond, Jessica S; Kang, Kang; Gong, Jianhui; Zeng, Xiaofan; Zhang, Yongfen; Li, Yingrui; Feng, Qiang; Xu, Xun; Wang, Jun; Wang, Jian; Yang, Huanming; Boeke, Jef D; Bader, Joel S

2016-01-01

Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3' UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes. © 2016 Shen et al.; Published by Cold Spring Harbor Laboratory Press.

Localization Performance of Multiple Vibrotactile Cues on Both Arms.

PubMed

Wang, Dangxiao; Peng, Cong; Afzal, Naqash; Li, Weiang; Wu, Dong; Zhang, Yuru

2018-01-01

To present information using vibrotactile stimuli in wearable devices, it is fundamental to understand human performance of localizing vibrotactile cues across the skin surface. In this paper, we studied human ability to identify locations of multiple vibrotactile cues activated simultaneously on both arms. Two haptic bands were mounted in proximity to the elbow and shoulder joints on each arm, and two vibrotactile motors were mounted on each band to provide vibration cues to the dorsal and palmar side of the arm. The localization performance under four conditions were compared, with the number of the simultaneously activated cues varying from one to four in each condition. Experimental results illustrate that the rate of correct localization decreases linearly with the increase in the number of activated cues. It was 27.8 percent for three activated cues, and became even lower for four activated cues. An analysis of the correct rate and error patterns show that the layout of vibrotactile cues can have significant effects on the localization performance of multiple vibrotactile cues. These findings might provide guidelines for using vibrotactile cues to guide the simultaneous motion of multiple joints on both arms.

Investigation of glucose binding sites on insulin.

PubMed

Zoete, Vincent; Meuwly, Markus; Karplus, Martin

2004-05-15

Possible insulin binding sites for D-glucose have been investigated theoretically by docking and molecular dynamics (MD) simulations. Two different docking programs for small molecules were used; Multiple Copy Simultaneous Search (MCSS) and Solvation Energy for Exhaustive Docking (SEED) programs. The configurations resulting from the MCSS search were evaluated with a scoring function developed to estimate the binding free energy. SEED calculations were performed using various values for the dielectric constant of the solute. It is found that scores emphasizing non-polar interactions gave a preferential binding site in agreement with that inferred from recent fluorescence and NMR NOESY experiments. The calculated binding affinity of -1.4 to -3.5 kcal/mol is within the measured range of -2.0 +/- 0.5 kcal/mol. The validity of the binding site is suggested by the dynamical stability of the bound glucose when examined with MD simulations with explicit solvent. Alternative binding sites were found in the simulations and their relative stabilities were estimated. The motions of the bound glucose during molecular dynamics simulations are correlated with the motions of the insulin side chains that are in contact with it and with larger scale insulin motions. These results raise the question of whether glucose binding to insulin could play a role in its activity. The results establish the complementarity of molecular dynamics simulations and normal mode analyses with the search for binding sites proposed with small molecule docking programs. Copyright 2004 Wiley-Liss, Inc.

Striatal and Hippocampal Entropy and Recognition Signals in Category Learning: Simultaneous Processes Revealed by Model-Based fMRI

ERIC Educational Resources Information Center

Davis, Tyler; Love, Bradley C.; Preston, Alison R.

2012-01-01

Category learning is a complex phenomenon that engages multiple cognitive processes, many of which occur simultaneously and unfold dynamically over time. For example, as people encounter objects in the world, they simultaneously engage processes to determine their fit with current knowledge structures, gather new information about the objects, and…

75 FR 32773 - Auction of 218-219 MHz Service and Phase II 220 MHz Service Licenses Scheduled for December 7...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-09

... licenses included in Auction 89 using the Commission's standard simultaneous multiple-round auction format... sequential bidding rounds. The initial bidding schedule will be announced in a public notice to be released.... For Auction 89, the Bureau proposes to employ a simultaneous stopping rule approach. A simultaneous...

A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes.

PubMed

Kuan, Da-Han; Wang, I-Shun; Lin, Jiun-Rue; Yang, Chao-Han; Huang, Chi-Hsien; Lin, Yen-Hung; Lin, Chih-Ting; Huang, Nien-Tsu

2016-08-02

The hemoglobin-A1c test, measuring the ratio of glycated hemoglobin (HbA1c) to hemoglobin (Hb) levels, has been a standard assay in diabetes diagnosis that removes the day-to-day glucose level variation. Currently, the HbA1c test is restricted to hospitals and central laboratories due to the laborious, time-consuming whole blood processing and bulky instruments. In this paper, we have developed a microfluidic device integrating dual CMOS polysilicon nanowire sensors (MINS) for on-chip whole blood processing and simultaneous detection of multiple analytes. The micromachined polymethylmethacrylate (PMMA) microfluidic device consisted of a serpentine microchannel with multiple dam structures designed for non-lysed cells or debris trapping, uniform plasma/buffer mixing and dilution. The CMOS-fabricated polysilicon nanowire sensors integrated with the microfluidic device were designed for the simultaneous, label-free electrical detection of multiple analytes. Our study first measured the Hb and HbA1c levels in 11 clinical samples via these nanowire sensors. The results were compared with those of standard Hb and HbA1c measurement methods (Hb: the sodium lauryl sulfate hemoglobin detection method; HbA1c: cation-exchange high-performance liquid chromatography) and showed comparable outcomes. Finally, we successfully demonstrated the efficacy of the MINS device's on-chip whole blood processing followed by simultaneous Hb and HbA1c measurement in a clinical sample. Compared to current Hb and HbA1c sensing instruments, the MINS platform is compact and can simultaneously detect two analytes with only 5 μL of whole blood, which corresponds to a 300-fold blood volume reduction. The total assay time, including the in situ sample processing and analyte detection, was just 30 minutes. Based on its on-chip whole blood processing and simultaneous multiple analyte detection functionalities with a lower sample volume requirement and shorter process time, the MINS device can be effectively applied to real-time diabetes diagnostics and monitoring in point-of-care settings.

Data Reduction of Laser Ablation Split-Stream (LASS) Analyses Using Newly Developed Features Within Iolite: With Applications to Lu-Hf + U-Pb in Detrital Zircon and Sm-Nd +U-Pb in Igneous Monazite

NASA Astrophysics Data System (ADS)

Fisher, Christopher M.; Paton, Chad; Pearson, D. Graham; Sarkar, Chiranjeeb; Luo, Yan; Tersmette, Daniel B.; Chacko, Thomas

2017-12-01

A robust platform to view and integrate multiple data sets collected simultaneously is required to realize the utility and potential of the Laser Ablation Split-Stream (LASS) method. This capability, until now, has been unavailable and practitioners have had to laboriously process each data set separately, making it challenging to take full advantage of the benefits of LASS. We describe a new program for handling multiple mass spectrometric data sets collected simultaneously, designed specifically for the LASS technique, by which a laser aerosol is been split into two or more separate "streams" to be measured on separate mass spectrometers. New features within Iolite (https://iolite-software.com) enable the capability of loading, synchronizing, viewing, and reducing two or more data sets acquired simultaneously, as multiple DRSs (data reduction schemes) can be run concurrently. While this version of Iolite accommodates any combination of simultaneously collected mass spectrometer data, we demonstrate the utility using case studies where U-Pb and Lu-Hf isotope composition of zircon, and U-Pb and Sm-Nd isotope composition of monazite were analyzed simultaneously, in crystals showing complex isotopic zonation. These studies demonstrate the importance of being able to view and integrate simultaneously acquired data sets, especially for samples with complicated zoning and decoupled isotope systematics, in order to extract accurate and geologically meaningful isotopic and compositional data. This contribution provides instructions and examples for handling simultaneously collected laser ablation data. An instructional video is also provided. The updated Iolite software will help to fully develop the applications of both LASS and multi-instrument mass spectrometric measurement capabilities.

Part 2. Development of Enhanced Statistical Methods for Assessing Health Effects Associated with an Unknown Number of Major Sources of Multiple Air Pollutants.

PubMed

Park, Eun Sug; Symanski, Elaine; Han, Daikwon; Spiegelman, Clifford

2015-06-01

A major difficulty with assessing source-specific health effects is that source-specific exposures cannot be measured directly; rather, they need to be estimated by a source-apportionment method such as multivariate receptor modeling. The uncertainty in source apportionment (uncertainty in source-specific exposure estimates and model uncertainty due to the unknown number of sources and identifiability conditions) has been largely ignored in previous studies. Also, spatial dependence of multipollutant data collected from multiple monitoring sites has not yet been incorporated into multivariate receptor modeling. The objectives of this project are (1) to develop a multipollutant approach that incorporates both sources of uncertainty in source-apportionment into the assessment of source-specific health effects and (2) to develop enhanced multivariate receptor models that can account for spatial correlations in the multipollutant data collected from multiple sites. We employed a Bayesian hierarchical modeling framework consisting of multivariate receptor models, health-effects models, and a hierarchical model on latent source contributions. For the health model, we focused on the time-series design in this project. Each combination of number of sources and identifiability conditions (additional constraints on model parameters) defines a different model. We built a set of plausible models with extensive exploratory data analyses and with information from previous studies, and then computed posterior model probability to estimate model uncertainty. Parameter estimation and model uncertainty estimation were implemented simultaneously by Markov chain Monte Carlo (MCMC*) methods. We validated the methods using simulated data. We illustrated the methods using PM2.5 (particulate matter ≤ 2.5 μm in aerodynamic diameter) speciation data and mortality data from Phoenix, Arizona, and Houston, Texas. The Phoenix data included counts of cardiovascular deaths and daily PM2.5 speciation data from 1995-1997. The Houston data included respiratory mortality data and 24-hour PM2.5 speciation data sampled every six days from a region near the Houston Ship Channel in years 2002-2005. We also developed a Bayesian spatial multivariate receptor modeling approach that, while simultaneously dealing with the unknown number of sources and identifiability conditions, incorporated spatial correlations in the multipollutant data collected from multiple sites into the estimation of source profiles and contributions based on the discrete process convolution model for multivariate spatial processes. This new modeling approach was applied to 24-hour ambient air concentrations of 17 volatile organic compounds (VOCs) measured at nine monitoring sites in Harris County, Texas, during years 2000 to 2005. Simulation results indicated that our methods were accurate in identifying the true model and estimated parameters were close to the true values. The results from our methods agreed in general with previous studies on the source apportionment of the Phoenix data in terms of estimated source profiles and contributions. However, we had a greater number of statistically insignificant findings, which was likely a natural consequence of incorporating uncertainty in the estimated source contributions into the health-effects parameter estimation. For the Houston data, a model with five sources (that seemed to be Sulfate-Rich Secondary Aerosol, Motor Vehicles, Industrial Combustion, Soil/Crustal Matter, and Sea Salt) showed the highest posterior model probability among the candidate models considered when fitted simultaneously to the PM2.5 and mortality data. There was a statistically significant positive association between respiratory mortality and same-day PM2.5 concentrations attributed to one of the sources (probably industrial combustion). The Bayesian spatial multivariate receptor modeling approach applied to the VOC data led to a highest posterior model probability for a model with five sources (that seemed to be refinery, petrochemical production, gasoline evaporation, natural gas, and vehicular exhaust) among several candidate models, with the number of sources varying between three and seven and with different identifiability conditions. Our multipollutant approach assessing source-specific health effects is more advantageous than a single-pollutant approach in that it can estimate total health effects from multiple pollutants and can also identify emission sources that are responsible for adverse health effects. Our Bayesian approach can incorporate not only uncertainty in the estimated source contributions, but also model uncertainty that has not been addressed in previous studies on assessing source-specific health effects. The new Bayesian spatial multivariate receptor modeling approach enables predictions of source contributions at unmonitored sites, minimizing exposure misclassification and providing improved exposure estimates along with their uncertainty estimates, as well as accounting for uncertainty in the number of sources and identifiability conditions.

Herbicide volatilization trumps runoff losses, a multi-year investigation

USDA-ARS?s Scientific Manuscript database

Surface runoff and volatilization are two processes critical to herbicide off-site transport. To determine the relevance of these off-site transport mechanisms, runoff and turbulent vapor fluxes were simultaneously monitored on the same site for eight years. Site location, herbicide formulations, ...

Enhancement of juvenile Caribbean spiny lobsters: an evaluation of changes in multiple response variables with the addition of large artificial shelters.

PubMed

Briones-Fourzán, Patricia; Lozano-Alvarez, Enrique; Negrete-Soto, Fernando; Barradas-Ortiz, Cecilia

2007-03-01

Shortage of natural crevice shelters may produce population bottlenecks in juvenile Caribbean spiny lobsters (Panulirus argus), a socially gregarious species. We conducted a field experiment to test enhancement of a local population of juvenile P. argus with the addition of artificial shelters ("casitas") that mimic large crevices (1.1 m(2) in surface area and 3.8 cm in height). Changes in density and biomass of juvenile lobsters 15-50 mm carapace length (CL) were assessed with a multiple before-after control-impact (MBACI) analysis. Separate analyses were also conducted on small (15-35 mm CL) and large (35.1-50 mm CL) juveniles to assess size-related effects. First, we carried out 13 lobster surveys on nine fixed 1-ha sites over a shallow reef lagoon ("before" period). Then, we deployed ten casitas in each of five sites and left four sites as controls, and conducted 22 further surveys ("after" period). Deployment of casitas resulted in a sixfold increase in juvenile density (76% contributed by small and 24% by large juveniles) and a sevenfold increase in biomass (40 and 60%, respectively). Capture-recapture results revealed that enhancement was achieved not by promoting individual growth but by increasing survival, persistence, and foraging ranges of small and large juveniles. Casitas both mitigated shortage of natural shelter and increased sociality, allowing for cohabitation of smaller, more vulnerable juveniles with larger conspecifics that have greater defensive abilities. Casitas may help enhance local populations of juvenile P. argus in Caribbean seagrass habitats, typically poor in natural crevice shelters. The use of MBACI and the simultaneous assessment of multiple interrelated response variables may be a powerful analytical approach to test shelter limitation in other species and to examine the function of structural habitat in other systems.

Bilateral Video-Assisted Thoracoscopic Surgery Resection for Multiple Mediastinal Myelolipoma: Report of a Case

PubMed Central

Kohno, Tadasu; Mun, Mingyon; Yoshiya, Tomoharu

2014-01-01

Myelolipoma in the mediastinum is an extremely rare entity. In this report, we present the case of a 79-year-old asymptomatic man who had three bilateral paravertebral mediastinal tumors. The three tumors were resected simultaneously using bilateral three-port video-assisted thoracoscopic surgery (VATS). There has been no evidence of recurrence within four years after the operation. Multiple bilateral mediastinal myelolipomas are extremely rare. There are no reports in the English literature of multiple bilateral thoracic myelolipomas that were resected simultaneously using bilateral VATS. We also present characteristic features of myelolipomas, which are helpful for diagnosis. PMID:24782978

Spatial dependence and correlation of rainfall in the Danube catchment and its role in flood risk assessment.

NASA Astrophysics Data System (ADS)

Martina, M. L. V.; Vitolo, R.; Todini, E.; Stephenson, D. B.; Cook, I. M.

2009-04-01

The possibility that multiple catastrophic events occur within a given timespan and affect the same portfolio of insured properties may induce enhanced risk. For this reason, in the insurance industry it is of interest to characterise not only the point probability of catastrophic events, but also their spatial structure. As far as floods are concerned it is important to determine the probability of having multiple simultaneous events in different parts of the same basin: in this case, indeed, the loss in a portfolio can be significantly different. Understanding the spatial structure of the precipitation field is a necessary step for the proper modelling of the spatial dependence and correlation of river discharge. Several stochastic models are available in the scientific literature for the multi-site generation of precipitation. Although most models achieve good performance in modelling mean values, temporal variability and inter-site dependence of extremes are still delicate issues. In this work we aim at identifying the main spatial characteristics of the precipitation structure and then at analysing them in a real case. We consider data from a large network of raingauges in the Danube catchment. This catchment is a good example of a large-scale catchment where the spatial correlation of flood events can radically change the effect in term of flood damage.

Simultaneous fits in ISIS on the example of GRO J1008-57

NASA Astrophysics Data System (ADS)

Kühnel, Matthias; Müller, Sebastian; Kreykenbohm, Ingo; Schwarm, Fritz-Walter; Grossberger, Christoph; Dauser, Thomas; Pottschmidt, Katja; Ferrigno, Carlo; Rothschild, Richard E.; Klochkov, Dmitry; Staubert, Rüdiger; Wilms, Joern

2015-04-01

Parallel computing and steadily increasing computation speed have led to a new tool for analyzing multiple datasets and datatypes: fitting several datasets simultaneously. With this technique, physically connected parameters of individual data can be treated as a single parameter by implementing this connection into the fit directly. We discuss the terminology, implementation, and possible issues of simultaneous fits based on the X-ray data analysis tool Interactive Spectral Interpretation System (ISIS). While all data modeling tools in X-ray astronomy allow in principle fitting data from multiple data sets individually, the syntax used in these tools is not often well suited for this task. Applying simultaneous fits to the transient X-ray binary GRO J1008-57, we find that the spectral shape is only dependent on X-ray flux. We determine time independent parameters such as, e.g., the folding energy E_fold, with unprecedented precision.

Simultaneous Profiling of DNA Mutation and Methylation by Melting Analysis Using Magnetoresistive Biosensor Array.

PubMed

Rizzi, Giovanni; Lee, Jung-Rok; Dahl, Christina; Guldberg, Per; Dufva, Martin; Wang, Shan X; Hansen, Mikkel F

2017-09-26

Epigenetic modifications, in particular DNA methylation, are gaining increasing interest as complementary information to DNA mutations for cancer diagnostics and prognostics. We introduce a method to simultaneously profile DNA mutation and methylation events for an array of sites with single site specificity. Genomic (mutation) or bisulphite-treated (methylation) DNA is amplified using nondiscriminatory primers, and the amplicons are then hybridized to a giant magnetoresistive (GMR) biosensor array followed by melting curve measurements. The GMR biosensor platform offers scalable multiplexed detection of DNA hybridization, which is insensitive to temperature variation. The melting curve approach further enhances the assay specificity and tolerance to variations in probe length. We demonstrate the utility of this method by simultaneously profiling five mutation and four methylation sites in human melanoma cell lines. The method correctly identified all mutation and methylation events and further provided quantitative assessment of methylation density validated by bisulphite pyrosequencing.

Exploring Cognitive Flexibility With a Noninvasive BCI Using Simultaneous Steady-State Visual Evoked Potentials and Sensorimotor Rhythms.

PubMed

Edelman, Bradley J; Meng, Jianjun; Gulachek, Nicholas; Cline, Christopher C; He, Bin

2018-05-01

EEG-based brain-computer interface (BCI) technology creates non-biological pathways for conveying a user's mental intent solely through noninvasively measured neural signals. While optimizing the performance of a single task has long been the focus of BCI research, in order to translate this technology into everyday life, realistic situations, in which multiple tasks are performed simultaneously, must be investigated. In this paper, we explore the concept of cognitive flexibility, or multitasking, within the BCI framework by utilizing a 2-D cursor control task, using sensorimotor rhythms (SMRs), and a four-target visual attention task, using steady-state visual evoked potentials (SSVEPs), both individually and simultaneously. We found no significant difference between the accuracy of the tasks when executing them alone (SMR-57.9% ± 15.4% and SSVEP-59.0% ± 14.2%) and simultaneously (SMR-54.9% ± 17.2% and SSVEP-57.5% ± 15.4%). These modest decreases in performance were supported by similar, non-significant changes in the electrophysiology of the SSVEP and SMR signals. In this sense, we report that multiple BCI tasks can be performed simultaneously without a significant deterioration in performance; this finding will help drive these systems toward realistic daily use in which a user's cognition will need to be involved in multiple tasks at once.

Modeling the evolution of regulatory elements by simultaneous detection and alignment with phylogenetic pair HMMs.

PubMed

Majoros, William H; Ohler, Uwe

2010-12-16

The computational detection of regulatory elements in DNA is a difficult but important problem impacting our progress in understanding the complex nature of eukaryotic gene regulation. Attempts to utilize cross-species conservation for this task have been hampered both by evolutionary changes of functional sites and poor performance of general-purpose alignment programs when applied to non-coding sequence. We describe a new and flexible framework for modeling binding site evolution in multiple related genomes, based on phylogenetic pair hidden Markov models which explicitly model the gain and loss of binding sites along a phylogeny. We demonstrate the value of this framework for both the alignment of regulatory regions and the inference of precise binding-site locations within those regions. As the underlying formalism is a stochastic, generative model, it can also be used to simulate the evolution of regulatory elements. Our implementation is scalable in terms of numbers of species and sequence lengths and can produce alignments and binding-site predictions with accuracy rivaling or exceeding current systems that specialize in only alignment or only binding-site prediction. We demonstrate the validity and power of various model components on extensive simulations of realistic sequence data and apply a specific model to study Drosophila enhancers in as many as ten related genomes and in the presence of gain and loss of binding sites. Different models and modeling assumptions can be easily specified, thus providing an invaluable tool for the exploration of biological hypotheses that can drive improvements in our understanding of the mechanisms and evolution of gene regulation.

Regional Evapotranspiration Estimation by Using Wireless Sap Flow and Soil Moisture Measurement Systems

NASA Astrophysics Data System (ADS)

Kuo, C.; Yu, P.; Yang, T.; Davis, T. W.; Liang, X.; Tseng, C.; Cheng, C.

2011-12-01

The objective of this study proposed herein is to estimate regional evapotranspiration via sap flow and soil moisture measurements associated with wireless sensor network in the field. Evapotranspiration is one of the important factors in water balance computation. Pan evaporation collected from the meteorological station can only be accounted as a single-point scale measurement rather than the water loss of the entire region. Thus, we need a multiple-site measurement for understanding the regional evapotranspiration. Applying sap flow method with self-made probes, we could calculate transpiration. Soil moisture measurement was used to monitor the daily soil moisture variety for evaporation. Sap flow and soil moisture measurements in multiple sites are integrated by using wireless sensor network (WSN). Then, the measurement results of each site were scaled up and combined into the regional evapotranspiration. This study used thermal dissipation method to measure sap flow in trees to represent the plant transpiration. Sap flow was measured by using the self-made sap probes which needed to be calibrated before setting up at the observation field. Regional transpiration was scaled up through the Leaf Area Index (LAI). The LAI of regional scale was from the MODIS image calculated at 1km X 1km grid size. The soil moistures collected from areas outside the distributing area of tree roots and tree canopy were used to represent the evaporation. The observation was undertaken to collect soil moisture variety from five different soil depths of 10, 20, 30, 40 and 50 cm respectively. The regional evaporation can be estimated by averaging the variation of soil moisture from each site within the region. The result data measured by both sap flow and soil moisture measurements of each site were collected through the wireless sensor network. The WSN performs the functions of P2P and mesh networking. That can collect data in multiple locations simultaneously and has less power consumption. WSN is the best way for collecting sap flow and soil moisture data in this study. Since the data were collected through the radio in the field, there may have some noise randomly. The weighted least-squares method was used to filter the raw data. Through collecting the observation data by WSN and transferring them into regional scale, we could get regional evapotranspiration.

The DDN (Defense Data Network) Course,

DTIC Science & Technology

1986-04-01

devices will share the same node-to-node channels. * Simultaneous availability of source and destination is not required. * Speed and code conversion can...address multiple addresses simultaneously 3) Disadvantages of Message Switching Systems Not suited to real time or interactive use * Long and highly...transmission b) Unlike message switching, packet switching requires the -. simultaneous availability of source and destination. 64 -4 ) ..xa...e s

K-edge ratio method for identification of multiple nanoparticulate contrast agents by spectral CT imaging

PubMed Central

Ghadiri, H; Ay, M R; Shiran, M B; Soltanian-Zadeh, H

2013-01-01

Objective: Recently introduced energy-sensitive X-ray CT makes it feasible to discriminate different nanoparticulate contrast materials. The purpose of this work is to present a K-edge ratio method for differentiating multiple simultaneous contrast agents using spectral CT. Methods: The ratio of two images relevant to energy bins straddling the K-edge of the materials is calculated using an analytic CT simulator. In the resulting parametric map, the selected contrast agent regions can be identified using a thresholding algorithm. The K-edge ratio algorithm is applied to spectral images of simulated phantoms to identify and differentiate up to four simultaneous and targeted CT contrast agents. Results: We show that different combinations of simultaneous CT contrast agents can be identified by the proposed K-edge ratio method when energy-sensitive CT is used. In the K-edge parametric maps, the pixel values for biological tissues and contrast agents reach a maximum of 0.95, whereas for the selected contrast agents, the pixel values are larger than 1.10. The number of contrast agents that can be discriminated is limited owing to photon starvation. For reliable material discrimination, minimum photon counts corresponding to 140 kVp, 100 mAs and 5-mm slice thickness must be used. Conclusion: The proposed K-edge ratio method is a straightforward and fast method for identification and discrimination of multiple simultaneous CT contrast agents. Advances in knowledge: A new spectral CT-based algorithm is proposed which provides a new concept of molecular CT imaging by non-iteratively identifying multiple contrast agents when they are simultaneously targeting different organs. PMID:23934964

GroEL-GroES assisted folding of multiple recombinant proteins simultaneously over-expressed in Escherichia coli.

PubMed

Goyal, Megha; Chaudhuri, Tapan K

2015-07-01

Folding of aggregation prone recombinant proteins through co-expression of chaperonin GroEL and GroES has been a popular practice in the effort to optimize preparation of functional protein in Escherichia coli. Considering the demand for functional recombinant protein products, it is desirable to apply the chaperone assisted protein folding strategy for enhancing the yield of properly folded protein. Toward the same direction, it is also worth attempting folding of multiple recombinant proteins simultaneously over-expressed in E. coli through the assistance of co-expressed GroEL-ES. The genesis of this thinking was originated from the fact that cellular GroEL and GroES assist in the folding of several endogenous proteins expressed in the bacterial cell. Here we present the experimental findings from our study on co-expressed GroEL-GroES assisted folding of simultaneously over-expressed proteins maltodextrin glucosidase (MalZ) and yeast mitochondrial aconitase (mAco). Both proteins mentioned here are relatively larger and aggregation prone, mostly form inclusion bodies, and undergo GroEL-ES assisted folding in E. coli cells during over-expression. It has been reported that the relative yield of properly folded functional forms of MalZ and mAco with the exogenous GroEL-ES assistance were comparable with the results when these proteins were overexpressed alone. This observation is quite promising and highlights the fact that GroEL and GroES can assist in the folding of multiple substrate proteins simultaneously when over-expressed in E. coli. This method might be a potential tool for enhanced production of multiple functional recombinant proteins simultaneously in E. coli. Copyright © 2015 Elsevier Ltd. All rights reserved.

Passive radio frequency peak power multiplier

DOEpatents

Farkas, Zoltan D.; Wilson, Perry B.

1977-01-01

Peak power multiplication of a radio frequency source by simultaneous charging of two high-Q resonant microwave cavities by applying the source output through a directional coupler to the cavities and then reversing the phase of the source power to the coupler, thereby permitting the power in the cavities to simultaneously discharge through the coupler to the load in combination with power from the source to apply a peak power to the load that is a multiplication of the source peak power.

Orthogonal Cas9 proteins for RNA-guided gene regulation and editing

DOEpatents

Church, George M.; Esvelt, Kevin; Mali, Prashant

2017-03-07

Methods of modulating expression of a target nucleic acid in a cell are provided including use of multiple orthogonal Cas9 proteins to simultaneously and independently regulate corresponding genes or simultaneously and independently edit corresponding genes.

Cognitive Development and Reading: The Relation of Reading-Specific Multiple Classification Skill to Reading Comprehension in Elementary School Children.

ERIC Educational Resources Information Center

Cartwright, Kelly B.

2002-01-01

A reading-specific multiple classification task was designed that required children to classify printed words along phonological and semantic dimensions simultaneously. Reading-specific multiple classification skill made a unique contribution to children's reading comprehension over contributions made by age, domain-general multiple classification…

Modeling Polytomous Item Responses Using Simultaneously Estimated Multinomial Logistic Regression Models

ERIC Educational Resources Information Center

Anderson, Carolyn J.; Verkuilen, Jay; Peyton, Buddy L.

2010-01-01

Survey items with multiple response categories and multiple-choice test questions are ubiquitous in psychological and educational research. We illustrate the use of log-multiplicative association (LMA) models that are extensions of the well-known multinomial logistic regression model for multiple dependent outcome variables to reanalyze a set of…

A Multiple Items EPQ/EOQ Model for a Vendor and Multiple Buyers System with Considering Continuous and Discrete Demand Simultaneously

NASA Astrophysics Data System (ADS)

Jonrinaldi; Rahman, T.; Henmaidi; Wirdianto, E.; Zhang, D. Z.

2018-03-01

This paper proposed a mathematical model for multiple items Economic Production and Order Quantity (EPQ/EOQ) with considering continuous and discrete demand simultaneously in a system consisting of a vendor and multiple buyers. This model is used to investigate the optimal production lot size of the vendor and the number of shipments policy of orders to multiple buyers. The model considers the multiple buyers’ holding cost as well as transportation cost, which minimize the total production and inventory costs of the system. The continuous demand from any other customers can be fulfilled anytime by the vendor while the discrete demand from multiple buyers can be fulfilled by the vendor using the multiple delivery policy with a number of shipments of items in the production cycle time. A mathematical model is developed to illustrate the system based on EPQ and EOQ model. Solution procedures are proposed to solve the model using a Mixed Integer Non Linear Programming (MINLP) and algorithm methods. Then, the numerical example is provided to illustrate the system and results are discussed.

Method and apparatus for the simultaneous display and correlation of independently generated images

DOEpatents

Vaitekunas, Jeffrey J.; Roberts, Ronald A.

1991-01-01

An apparatus and method for location by location correlation of multiple images from Non-Destructive Evaluation (NDE) and other sources. Multiple images of a material specimen are displayed on one or more monitors of an interactive graphics system. Specimen landmarks are located in each image and mapping functions from a reference image to each other image are calcuated using the landmark locations. A location selected by positioning a cursor in the reference image is mapped to the other images and location identifiers are simultaneously displayed in those images. Movement of the cursor in the reference image causes simultaneous movement of the location identifiers in the other images to positions corresponding to the location of the reference image cursor.

Sent packing: protein engineering generates a new crystal form of Pseudomonas aeruginosa DsbA1 with increased catalytic surface accessibility

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

McMahon, Roisin M., E-mail: r.mcmahon1@uq.edu.au; Coinçon, Mathieu; Tay, Stephanie

The crystal structure of a P. aeruginosa DsbA1 variant is more suitable for fragment-based lead discovery efforts to identify inhibitors of this antimicrobial drug target. In the reported structures the active site of the protein can simultaneously bind multiple ligands introduced in the crystallization solution or via soaking. Pseudomonas aeruginosa is an opportunistic human pathogen for which new antimicrobial drug options are urgently sought. P. aeruginosa disulfide-bond protein A1 (PaDsbA1) plays a pivotal role in catalyzing the oxidative folding of multiple virulence proteins and as such holds great promise as a drug target. As part of a fragment-based lead discoverymore » approach to PaDsbA1 inhibitor development, the identification of a crystal form of PaDsbA1 that was more suitable for fragment-soaking experiments was sought. A previously identified crystallization condition for this protein was unsuitable, as in this crystal form of PaDsbA1 the active-site surface loops are engaged in the crystal packing, occluding access to the target site. A single residue involved in crystal-packing interactions was substituted with an amino acid commonly found at this position in closely related enzymes, and this variant was successfully used to generate a new crystal form of PaDsbA1 in which the active-site surface is more accessible for soaking experiments. The PaDsbA1 variant displays identical redox character and in vitro activity to wild-type PaDsbA1 and is structurally highly similar. Two crystal structures of the PaDsbA1 variant were determined in complex with small molecules bound to the protein active site. These small molecules (MES, glycerol and ethylene glycol) were derived from the crystallization or cryoprotectant solutions and provide a proof of principle that the reported crystal form will be amenable to co-crystallization and soaking with small molecules designed to target the protein active-site surface.« less

Technical note: Simultaneous fully dynamic characterization of multiple input–output relationships in climate models

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

Kravitz, Ben; MacMartin, Douglas G.; Rasch, Philip J.

We introduce system identification techniques to climate science wherein multiple dynamic input–output relationships can be simultaneously characterized in a single simulation. This method, involving multiple small perturbations (in space and time) of an input field while monitoring output fields to quantify responses, allows for identification of different timescales of climate response to forcing without substantially pushing the climate far away from a steady state. We use this technique to determine the steady-state responses of low cloud fraction and latent heat flux to heating perturbations over 22 regions spanning Earth's oceans. We show that the response characteristics are similar to thosemore » of step-change simulations, but in this new method the responses for 22 regions can be characterized simultaneously. Moreover, we can estimate the timescale over which the steady-state response emerges. The proposed methodology could be useful for a wide variety of purposes in climate science, including characterization of teleconnections and uncertainty quantification to identify the effects of climate model tuning parameters.« less

Technical note: Simultaneous fully dynamic characterization of multiple input–output relationships in climate models

DOE PAGES

Kravitz, Ben; MacMartin, Douglas G.; Rasch, Philip J.; ...

2017-02-17

We introduce system identification techniques to climate science wherein multiple dynamic input–output relationships can be simultaneously characterized in a single simulation. This method, involving multiple small perturbations (in space and time) of an input field while monitoring output fields to quantify responses, allows for identification of different timescales of climate response to forcing without substantially pushing the climate far away from a steady state. We use this technique to determine the steady-state responses of low cloud fraction and latent heat flux to heating perturbations over 22 regions spanning Earth's oceans. We show that the response characteristics are similar to thosemore » of step-change simulations, but in this new method the responses for 22 regions can be characterized simultaneously. Moreover, we can estimate the timescale over which the steady-state response emerges. The proposed methodology could be useful for a wide variety of purposes in climate science, including characterization of teleconnections and uncertainty quantification to identify the effects of climate model tuning parameters.« less

Simultaneous and Sequential MS/MS Scan Combinations and Permutations in a Linear Quadrupole Ion Trap.

PubMed

Snyder, Dalton T; Szalwinski, Lucas J; Cooks, R Graham

2017-10-17

Methods of performing precursor ion scans as well as neutral loss scans in a single linear quadrupole ion trap have recently been described. In this paper we report methodology for performing permutations of MS/MS scan modes, that is, ordered combinations of precursor, product, and neutral loss scans following a single ion injection event. Only particular permutations are allowed; the sequences demonstrated here are (1) multiple precursor ion scans, (2) precursor ion scans followed by a single neutral loss scan, (3) precursor ion scans followed by product ion scans, and (4) segmented neutral loss scans. (5) The common product ion scan can be performed earlier in these sequences, under certain conditions. Simultaneous scans can also be performed. These include multiple precursor ion scans, precursor ion scans with an accompanying neutral loss scan, and multiple neutral loss scans. We argue that the new capability to perform complex simultaneous and sequential MS n operations on single ion populations represents a significant step in increasing the selectivity of mass spectrometry.

Tracking Multiple Statistics: Simultaneous Learning of Object Names and Categories in English and Mandarin Speakers.

PubMed

Chen, Chi-Hsin; Gershkoff-Stowe, Lisa; Wu, Chih-Yi; Cheung, Hintat; Yu, Chen

2017-08-01

Two experiments were conducted to examine adult learners' ability to extract multiple statistics in simultaneously presented visual and auditory input. Experiment 1 used a cross-situational learning paradigm to test whether English speakers were able to use co-occurrences to learn word-to-object mappings and concurrently form object categories based on the commonalities across training stimuli. Experiment 2 replicated the first experiment and further examined whether speakers of Mandarin, a language in which final syllables of object names are more predictive of category membership than English, were able to learn words and form object categories when trained with the same type of structures. The results indicate that both groups of learners successfully extracted multiple levels of co-occurrence and used them to learn words and object categories simultaneously. However, marked individual differences in performance were also found, suggesting possible interference and competition in processing the two concurrent streams of regularities. Copyright © 2016 Cognitive Science Society, Inc.

High-efficiency CRISPR/Cas9 multiplex gene editing using the glycine tRNA-processing system-based strategy in maize.

PubMed

Qi, Weiwei; Zhu, Tong; Tian, Zhongrui; Li, Chaobin; Zhang, Wei; Song, Rentao

2016-08-11

CRISPR/Cas9 genome editing strategy has been applied to a variety of species and the tRNA-processing system has been used to compact multiple gRNAs into one synthetic gene for manipulating multiple genes in rice. We optimized and introduced the multiplex gene editing strategy based on the tRNA-processing system into maize. Maize glycine-tRNA was selected to design multiple tRNA-gRNA units for the simultaneous production of numerous gRNAs under the control of one maize U6 promoter. We designed three gRNAs for simplex editing and three multiple tRNA-gRNA units for multiplex editing. The results indicate that this system not only increased the number of targeted sites but also enhanced mutagenesis efficiency in maize. Additionally, we propose an advanced sequence selection of gRNA spacers for relatively more efficient and accurate chromosomal fragment deletion, which is important for complete abolishment of gene function especially long non-coding RNAs (lncRNAs). Our results also indicated that up to four tRNA-gRNA units in one expression cassette design can still work in maize. The examples reported here demonstrate the utility of the tRNA-processing system-based strategy as an efficient multiplex genome editing tool to enhance maize genetic research and breeding.

Chemical characterization and source identification of PM2.5 at multiple sites in the Beijing-Tianjin-Hebei region, China

NASA Astrophysics Data System (ADS)

Huang, Xiaojuan; Liu, Zirui; Liu, Jingyun; Hu, Bo; Wen, Tianxue; Tang, Guiqian; Zhang, Junke; Wu, Fangkun; Ji, Dongsheng; Wang, Lili; Wang, Yuesi

2017-11-01

The simultaneous observation and analysis of atmospheric fine particles (PM2.5) on a regional scale is an important approach to develop control strategies for haze pollution. In this study, samples of filtered PM2.5 were collected simultaneously at three urban sites (Beijing, Tianjin, and Shijiazhuang) and at a regional background site (Xinglong) in the Beijing-Tianjin-Hebei (BTH) region from June 2014 to April 2015. The PM2.5 at the four sites was mainly comprised of organic matter, secondary inorganic ions, and mineral dust. Positive matrix factorization (PMF) demonstrated that, on an annual basis, secondary inorganic aerosol was the largest PM2.5 source in this region, accounting for 29.2-40.5 % of the PM2.5 mass at the urban sites; the second-largest PM2.5 source was motor vehicle exhaust, particularly in Beijing (24.9 %), whereas coal combustion was also a large source in Tianjin (12.4 %) and Shijiazhuang (15.5 %), with particular dominance in winter. Secondary inorganic aerosol plays a vital role in the haze process, with the exception of the spring haze in Shijiazhuang and Tianjin, for which the dust source was crucial. In addition to secondary transformations, local direct emissions (coal combustion and motor vehicle exhaust) significantly contribute to the winter haze at the urban sites. Moreover, with the aggravation of haze pollution, the OC / EC mass ratio of PM2.5 decreased considerably and the nitrate-rich secondary aerosol increased during all four seasons in Beijing, both of which indicate that local motor vehicle emissions significantly contribute to the severe haze episodes in Beijing. To assess the impacts of regional transport on haze pollution, the PMF results were further processed with backward-trajectory cluster analysis, revealing that haze pollution usually occurred when air masses originating from polluted industrial regions in the south prevailed and is characterized by high PM2.5 loadings with considerable contributions from secondary aerosols. This study suggests that control strategies to mitigate haze pollution in the BTH region should focus on the reduction of gaseous precursor emissions from fossil fuel combustion (motor vehicle emissions in Beijing and coal combustion in Tianjin, Hebei, and nearby provinces).

STATISTICAL METHODOLOGY FOR THE SIMULTANEOUS ANALYSIS OF MULTIPLE TYPES OF OUTCOMES IN NONLINEAR THRESHOLD MODELS.

EPA Science Inventory

Multiple outcomes are often measured on each experimental unit in toxicology experiments. These multiple observations typically imply the existence of correlation between endpoints, and a statistical analysis that incorporates it may result in improved inference. When both disc...

A Large-scale Dissemination and Implementation Model for Evidence-based Treatment and Continuing Care

PubMed Central

Garner, Bryan R.; Smith, Jane Ellen; Meyers, Robert J.; Godley, Mark D.

2010-01-01

Multiple evidence-based treatments for adolescents with substance use disorders are available; however, the diffusion of these treatments in practice remains minimal. A dissemination and implementation model incorporating research-based training components for simultaneous implementation across 33 dispersed sites and over 200 clinical staff is described. Key elements for the diffusion of the Adolescent Community Reinforcement Approach and Assertive Continuing Care were: (a) three years of funding to support local implementation; (b) comprehensive training, including a 3.5 day workshop, bi-weekly coaching calls, and ongoing performance feedback facilitated by a web tool; (c) a clinician certification process; (d) a supervisor certification process to promote long-term sustainability; and (e) random fidelity reviews after certification. Process data are summarized for 167 clinicians and 64 supervisors. PMID:21547241

Recent Advances of Cocktail Chemotherapy by Combination Drug Delivery Systems

PubMed Central

Hu, Quanyin; Sun, Wujin; Wang, Chao; Gu, Zhen

2016-01-01

Combination chemotherapy is widely exploited for enhanced cancer treatment in clinic. However, the traditional cocktail administration of combination regimens often suffers from varying pharmacokinetics among different drugs. The emergence of nanotechnology offers an unparalleled opportunity for developing advanced combination drug delivery strategies with the ability to encapsulate various drugs simultaneously and unify the pharmacokinetics of each drug. This review surveys the most recent advances in combination delivery of multiple small molecule chemotherapeutics using nanocarriers. The mechanisms underlying combination chemotherapy, including the synergistic, additive and potentiation effects, are also discussed with typical examples. We further highlight the sequential and site-specific co-delivery strategies, which provide new guidelines for development of programmable combination drug delivery systems. Clinical outlook and challenges are also discussed in the end. PMID:26546751

Nonmethane organic compound monitoring program. Final report 1988. Volume 2. Urban air toxics monitoring program

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

McAllister, R.A.; Moore, W.H.; Rice, J.

1989-04-01

From October, 1987 to October, 1988 samples of ambient air were collected at 19 sites in the eastern part of the U.S. Every 12 days, air was integrated over 24-hour periods into passivated stainless steel canisters. Simultaneously, air was drawn through cartridges containing dinitrophenylhydrazine to collect carbonyl compounds. The samples were analyzed at a central laboratory for a total of 37 halogenated and aromatic hydrocarbons, formaldehyde, acetaldehyde, and other oxygenated species. The hydrocarbon species were analyzed by gas chromatography/multiple detectors and gas chromatography/mass spectrometry, while the carbonyl species were analyzed by liquid chromatography. An extensive quality assurance program was carriedmore » on to secure high quality data. Complete data for all the hydrocarbon samples are presented in the report.« less

Multicolour Multilevel STED nanoscopy of Actin/Spectrin Organization at Synapses

PubMed Central

Sidenstein, Sven C.; D’Este, Elisa; Böhm, Marvin J.; Danzl, Johann G.; Belov, Vladimir N.; Hell, Stefan W.

2016-01-01

Superresolution fluorescence microscopy of multiple fluorophores still requires development. Here we present simultaneous three-colour stimulated emission depletion (STED) nanoscopy relying on a single STED beam at 620 nm. Toggling the STED beam between two or more power levels (“multilevelSTED”) optimizes resolution and contrast in all colour channels, which are intrinsically co-aligned and well separated. Three-colour recording is demonstrated by imaging the nanoscale cytoskeletal organization in cultured hippocampal neurons. The down to ~35 nm resolution identified periodic actin/betaII spectrin lattices along dendrites and spines; however, at presynaptic and postsynaptic sites, these patterns were found to be absent. Both our multicolour scheme and the 620 nm STED line should be attractive for routine STED microscopy applications. PMID:27220554

A novel fiber-free technique for brain activity imaging in multiple freely behaving mice

NASA Astrophysics Data System (ADS)

Inagaki, Shigenori; Agetsuma, Masakazu; Nagai, Takeharu

2018-02-01

Brain functions and related psychiatric disorders have been investigated by recording electrophysiological field potential. When recording it, a conventional method requires fiber-based apparatus connected to the brain, which however hampers the simultaneous measurement in multiple animals (e.g. by a tangle of fibers). Here, we propose a fiber-free recording technique in conjunction with a ratiometric bioluminescent voltage indicator. Our method allows investigation of electrophysiological filed potential dynamics in multiple freely behaving animals simultaneously over a long time period. Therefore, this fiber-free technique opens up the way to investigate a new mechanism of brain function that governs social behaviors and animal-to-animal interaction.

Dual-Functional Ultrafiltration Membrane for Simultaneous Removal of Multiple Pollutants with High Performance.

PubMed

Pan, Shunlong; Li, Jiansheng; Noonan, Owen; Fang, Xiaofeng; Wan, Gaojie; Yu, Chengzhong; Wang, Lianjun

2017-05-02

Simultaneous removal of multiple pollutants from aqueous solution with less energy consumption is crucial in water purification. Here, a novel concept of dual-functional ultrafiltration (DFUF) membrane is demonstrated by entrapment of nanostructured adsorbents into the finger-like pores of ultrafiltration (UF) membrane rather than in the membrane matrix in previous reports of blend membranes, resulting in an exceptionally high active content and simultaneous removal of multiple pollutants from water due to the dual functions of rejection and adsorption. As a demonstration, hollow porous Zr(OH) x nanospheres (HPZNs) were immobilized in poly(ether sulfone) (PES) UF membranes through polydopamine coating with a high content of 68.9 wt %. The decontamination capacity of DFUF membranes toward multiple model pollutants (colloidal gold, polyethylene glycol (PEG), Pb(II)) was evaluated against a blend membrane. Compared to the blend membrane, the DFUF membranes showed 2.1-fold increase in the effective treatment volume for the treatment of Pb(II) contaminated water from 100 ppb to below 10 ppb (WHO drinking water standard). Simultaneously, the DFUF membranes effectively removed the colloidal gold and PEG below instrument detection limit, however the blend membrane only achieved 97.6% and 96.8% rejection for colloidal gold and PEG, respectively. Moreover, the DFUF membranes showed negligible leakage of nanoadsorbents during testing; and the membrane can be easily regenerated and reused. This study sheds new light on the design of high performance multifunction membranes for drinking water purification.

Tumor suppressor miR-1 inhibits tumor growth and metastasis by simultaneously targeting multiple genes

PubMed Central

Liu, Cuilian; Zhang, Song; Wang, Qizhi; Zhang, Xiaobo

2017-01-01

Cancer progression depends on tumor growth and metastasis, which are activated or suppressed by multiple genes. An individual microRNA may target multiple genes, suggesting that a miRNA may suppress tumor growth and metastasis via simultaneously targeting different genes. However, thus far, this issue has not been explored. In the present study, the findings showed that miR-1 could simultaneously inhibit tumor growth and metastasis of gastric and breast cancers by targeting multiple genes. The results indicated that miR-1 was significantly downregulated in cancer tissues compared with normal tissues. The miR-1 overexpression led to cell cycle arrest in the G1 phase in gastric and breast cancer cells but not in normal cells. Furthermore, the miR-1 overexpression significantly inhibited the metastasis of gastric and breast cancer cells. An analysis of the underlying mechanism revealed that the simultaneous inhibition of tumor growth and metastasis mediated by miR-1 was due to the synchronous targeting of 6 miR-1 target genes encoding cyclin dependent kinase 4, twinfilin actin binding protein 1, calponin 3, coronin 1C, WAS protein family member 2 and thymosin beta 4, X-linked. In vivo assays demonstrated that miR-1 efficiently inhibited tumor growth and metastasis of gastric and breast cancers in nude mice. Therefore, our study contributed novel insights into the miR-1′s roles in tumorigenesis of gastric and breast cancers. PMID:28159933

Tumor suppressor miR-1 inhibits tumor growth and metastasis by simultaneously targeting multiple genes.

PubMed

Liu, Cuilian; Zhang, Song; Wang, Qizhi; Zhang, Xiaobo

2017-06-27

Cancer progression depends on tumor growth and metastasis, which are activated or suppressed by multiple genes. An individual microRNA may target multiple genes, suggesting that a miRNA may suppress tumor growth and metastasis via simultaneously targeting different genes. However, thus far, this issue has not been explored. In the present study, the findings showed that miR-1 could simultaneously inhibit tumor growth and metastasis of gastric and breast cancers by targeting multiple genes. The results indicated that miR-1 was significantly downregulated in cancer tissues compared with normal tissues. The miR-1 overexpression led to cell cycle arrest in the G1 phase in gastric and breast cancer cells but not in normal cells. Furthermore, the miR-1 overexpression significantly inhibited the metastasis of gastric and breast cancer cells. An analysis of the underlying mechanism revealed that the simultaneous inhibition of tumor growth and metastasis mediated by miR-1 was due to the synchronous targeting of 6 miR-1 target genes encoding cyclin dependent kinase 4, twinfilin actin binding protein 1, calponin 3, coronin 1C, WAS protein family member 2 and thymosin beta 4, X-linked. In vivo assays demonstrated that miR-1 efficiently inhibited tumor growth and metastasis of gastric and breast cancers in nude mice. Therefore, our study contributed novel insights into the miR-1's roles in tumorigenesis of gastric and breast cancers.

A simple cage-autonomous method for the maintenance of the barrier status of germ-free mice during experimentation.

PubMed

Hecht, G; Bar-Nathan, C; Milite, G; Alon, I; Moshe, Y; Greenfeld, L; Dotsenko, N; Suez, J; Levy, M; Thaiss, C A; Dafni, H; Elinav, E; Harmelin, A

2014-10-01

The use of germ-free (GF) isolators for microbiome-related research is exponentially increasing, yet limited by its cost, isolator size and potential for trans-contamination. As such, current isolator technology is highly limiting to researchers engaged in short period experiments involving multiple mouse strains and employing a variety of mono-inoculated microorganisms. In this study, we evaluate the use of positive pressure Isocages as a solution for short period studies (days to 2-3 weeks) of experimentation with GF mice at multiple simultaneous conditions. We demonstrate that this new Isocage technology is cost-effective and room-sparing, and enables maintenance of multiple simultaneous groups of GF mice. Using this technology, transferring GF mice from isolators to Isocage racks for experimentation, where they are kept under fully germ-free conditions, enables parallel inoculation with different bacterial strains and simultaneous experimentation with multiple research conditions. Altogether, the new GF Isocage technology enables the expansion of GF capabilities in a safe and cost-effective manner that can facilitate the growth, elaboration and flexibility of microbiome research. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Solution-based analysis of multiple analytes by a sensor array: toward the development of an electronic tongue

NASA Astrophysics Data System (ADS)

Savoy, Steven M.; Lavigne, John J.; Yoo, J. S.; Wright, John; Rodriguez, Marc; Goodey, Adrian; McDoniel, Bridget; McDevitt, John T.; Anslyn, Eric V.; Shear, Jason B.; Ellington, Andrew D.; Neikirk, Dean P.

1998-12-01

A micromachined sensor array has been developed for the rapid characterization of multi-component mixtures in aqueous media. The sensor functions in a manner analogous to that of the mammalian tongue, using an array composed of individually immobilized polystyrene-polyethylene glycol composite microspheres selectively arranged in micromachined etch cavities localized o n silicon wafers. Sensing occurs via colorimetric or fluorometric changes to indicator molecules that are covalently bound to amine termination sites on the polymeric microspheres. The hybrid micromachined structure has been interfaced directly to a charged-coupled-device that is used for the simultaneous acquisition of the optical data from the individually addressable `taste bud' elements. With the miniature sensor array, acquisition of data streams composed of red, green, and blue color patterns distinctive for the analytes in the solution are rapidly acquired. The unique combination of carefully chosen reporter molecules with water permeable microspheres allows for the simultaneous detection and quantification of a variety of analytes. The fabrication of the sensor structures and the initial colorimetric and fluorescent responses for pH, Ca+2, Ce+3, and sugar are reported. Interface to microfluidic components should also be possible, producing a complete sampling/sensing system.

Simultaneous antegrade/retrograde upper urinary tract access: Bart's modified lateral position for complex upper tract endourologic pathologic features.

PubMed

Moraitis, Konstantinos; Philippou, Prodromos; El-Husseiny, Tamer; Wazait, Hassan; Masood, Junaid; Buchholz, Noor

2012-02-01

To determine whether the Bart's modified lateral position is safe and effective for achieving simultaneous anterograde and retrograde access in complex upper urinary tract pathologic features. From November 2006 to September 2010, 45 procedures were performed, with the patients in the modified lateral position. The indication for these procedures was the presence of complex unilateral upper urinary tract pathologic features. The patients with muscular and/or skeletal abnormalities were excluded. All procedures were performed using simultaneous anterograde and retrograde access with the patient under general anesthesia. The preoperative investigation protocol included assessment of the stone burden and location using enhanced abdominal computed tomography. The patients were routinely examined 6 weeks after the procedure with a combination of plain abdominal radiography and renal ultrasonography. For patients treated for conditions causing upper urinary tract obstruction (pelviureteral junction obstruction and/or ureteral strictures), a mercaptoacetyltriglycine renography was performed at 4, 12, and 24 months postoperatively. The mean patient age was 51.2 years (range 17-79). Stone clearance was achieved by a single combined procedure in 36 patients (80%). Successful recanalization was achieved in all patients with pelviureteral junction obstruction and ureteral strictures. In 4 patients (8.8%), persistent hematuria was noted, and 2 patients (4.4%) developed postoperative urinary sepsis and were treated conservatively. Modification to the lateral position compares equally with contemporary percutaneous nephrolithotomy series. It provides wide exposure of the flank, allowing the choice of multiple access sites, enhanced control, and a wide angle for handling of the antegrade instruments. Two surgeons can work simultaneously, addressing complex endourologic pathologic features in high-risk patients. Copyright © 2012. Published by Elsevier Inc.

Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression

PubMed Central

He, Xin; Samee, Md. Abul Hassan; Blatti, Charles; Sinha, Saurabh

2010-01-01

Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled, or heuristic approximations of the underlying regulatory mechanisms. We have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence, as a function of transcription factor concentrations and their DNA-binding specificities. It uses statistical thermodynamics theory to model not only protein-DNA interaction, but also the effect of DNA-bound activators and repressors on gene expression. In addition, the model incorporates mechanistic features such as synergistic effect of multiple activators, short range repression, and cooperativity in transcription factor-DNA binding, allowing us to systematically evaluate the significance of these features in the context of available expression data. Using this model on segmentation-related enhancers in Drosophila, we find that transcriptional synergy due to simultaneous action of multiple activators helps explain the data beyond what can be explained by cooperative DNA-binding alone. We find clear support for the phenomenon of short-range repression, where repressors do not directly interact with the basal transcriptional machinery. We also find that the binding sites contributing to an enhancer's function may not be conserved during evolution, and a noticeable fraction of these undergo lineage-specific changes. Our implementation of the model, called GEMSTAT, is the first publicly available program for simultaneously modeling the regulatory activities of a given set of sequences. PMID:20862354

Role of the AP2 β-Appendage Hub in Recruiting Partners for Clathrin-Coated Vesicle Assembly

PubMed Central

Burtey, Anne; Praefcke, Gerrit J. K; Peak-Chew, Sew-Yeu; Mills, Ian G; Benmerah, Alexandre; McMahon, Harvey T

2006-01-01

Adaptor protein complex 2 α and β-appendage domains act as hubs for the assembly of accessory protein networks involved in clathrin-coated vesicle formation. We identify a large repertoire of β-appendage interactors by mass spectrometry. These interact with two distinct ligand interaction sites on the β-appendage (the “top” and “side” sites) that bind motifs distinct from those previously identified on the α-appendage. We solved the structure of the β-appendage with a peptide from the accessory protein Eps15 bound to the side site and with a peptide from the accessory cargo adaptor β-arrestin bound to the top site. We show that accessory proteins can bind simultaneously to multiple appendages, allowing these to cooperate in enhancing ligand avidities that appear to be irreversible in vitro. We now propose that clathrin, which interacts with the β-appendage, achieves ligand displacement in vivo by self-polymerisation as the coated pit matures. This changes the interaction environment from liquid-phase, affinity-driven interactions, to interactions driven by solid-phase stability (“matricity”). Accessory proteins that interact solely with the appendages are thereby displaced to areas of the coated pit where clathrin has not yet polymerised. However, proteins such as β-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors. PMID:16903783

Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems.

PubMed

Harari, Colin M; Magagna, Michelle; Bedoya, Mariajose; Lee, Fred T; Lubner, Meghan G; Hinshaw, J Louis; Ziemlewicz, Timothy; Brace, Christopher L

2016-01-01

To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. © RSNA, 2015.

Autonomous Magnetic Microrobots by Navigating Gates for Multiple Biomolecules Delivery.

PubMed

Hu, Xinghao; Lim, Byeonghwa; Torati, Sri Ramulu; Ding, Junjia; Novosad, Valentine; Im, Mi-Young; Reddy, Venu; Kim, Kunwoo; Jung, Eunjoo; Shawl, Asif Iqbal; Kim, Eunjoo; Kim, CheolGi

2018-05-08

The precise delivery of biofunctionalized matters is of great interest from the fundamental and applied viewpoints. In spite of significant progress achieved during the last decade, a parallel and automated isolation and manipulation of rare analyte, and their simultaneous on-chip separation and trapping, still remain challenging. Here, a universal micromagnet junction for self-navigating gates of microrobotic particles to deliver the biomolecules to specific sites using a remote magnetic field is described. In the proposed concept, the nonmagnetic gap between the lithographically defined donor and acceptor micromagnets creates a crucial energy barrier to restrict particle gating. It is shown that by carefully designing the geometry of the junctions, it becomes possible to deliver multiple protein-functionalized carriers in high resolution, as well as MCF-7 and THP-1 cells from the mixture, with high fidelity and trap them in individual apartments. Integration of such junctions with magnetophoretic circuitry elements could lead to novel platforms without retrieving for the synchronous digital manipulation of particles/biomolecules in microfluidic multiplex arrays for next-generation biochips. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental and Numerical Investigations on Colloid-facilitated Plutonium Reactive Transport in Fractured Tuffaceous Rocks

NASA Astrophysics Data System (ADS)

Dai, Z.; Wolfsberg, A. V.; Zhu, L.; Reimus, P. W.

2017-12-01

Colloids have the potential to enhance mobility of strongly sorbing radionuclide contaminants in fractured rocks at underground nuclear test sites. This study presents an experimental and numerical investigation of colloid-facilitated plutonium reactive transport in fractured porous media for identifying plutonium sorption/filtration processes. The transport parameters for dispersion, diffusion, sorption, and filtration are estimated with inverse modeling for minimizing the least squares objective function of multicomponent concentration data from multiple transport experiments with the Shuffled Complex Evolution Metropolis (SCEM). Capitalizing on an unplanned experimental artifact that led to colloid formation and migration, we adopt a stepwise strategy to first interpret the data from each experiment separately and then to incorporate multiple experiments simultaneously to identify a suite of plutonium-colloid transport processes. Nonequilibrium or kinetic attachment and detachment of plutonium-colloid in fractures was clearly demonstrated and captured in the inverted modeling parameters along with estimates of the source plutonium fraction that formed plutonium-colloids. The results from this study provide valuable insights for understanding the transport mechanisms and environmental impacts of plutonium in fractured formations and groundwater aquifers.

The microassay on a card: A rugged, portable immunoassay

NASA Technical Reports Server (NTRS)

Kidwell, David

1991-01-01

The Microassay on a Card (MAC) is a portable, hand-held, non-instrumental immunoassay that can test for the presence of a wide variety of substances in the environment. The MAC is a simple device to use. A drop of test solution is placed on one side of the card and within five minutes a color is developed on the other side in proportion to the amount of substance in the test solution, with sensitivity approaching 10 ng/ml. The MAC is self-contained and self-timed; no reagents or timing is necessary. The MAC may be configured with multiple wells to provide simultaneous testing for multiple species. As envisioned, the MAC will be employed first as an on-site screen for drugs of abuse in urine or saliva. If the MAC can be used as a screen of saliva for drugs of abuse, it could be applied to driving while intoxicated, use of drugs on the job, or testing of the identity of seized materials. With appropriate modifications, the MAC also could be used to test for environmental toxins or pollutants.

Design of ligand-targeted nanoparticles for enhanced cancer targeting

NASA Astrophysics Data System (ADS)

Stefanick, Jared F.

Ligand-targeted nanoparticles are increasingly used as drug delivery vehicles for cancer therapy, yet have not consistently produced successful clinical outcomes. Although these inconsistencies may arise from differences in disease models and target receptors, nanoparticle design parameters can significantly influence therapeutic efficacy. By employing a multifaceted synthetic strategy to prepare peptide-targeted nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, this work evaluates the roles of polyethylene glycol (PEG) coating, ethylene glycol (EG) peptide-linker length, peptide hydrophilicity, peptide density, and nanoparticle size on tumor targeting in a systematic manner. These parameters were analyzed in multiple disease models by targeting human epidermal growth factor receptor 2 (HER2) in breast cancer and very late antigen-4 (VLA-4) in multiple myeloma to demonstrate the widespread applicability of this approach. By increasing the hydrophilicity of the targeting peptide sequence and simultaneously optimizing the EG peptide-linker length, the in vitro cellular uptake of targeted liposomes was significantly enhanced. Specifically, including a short oligolysine chain adjacent to the targeting peptide sequence effectively increased cellular uptake ~80-fold using an EG6 peptide-linker compared to ~10-fold using an EG45 linker. In vivo, targeted liposomes prepared in a traditional manner lacking the oligolysine chain demonstrated similar biodistribution and tumor uptake to non-targeted liposomes. However, by including the oligolysine chain, targeted liposomes using an EG45 linker significantly improved tumor uptake ~8-fold over non-targeted liposomes, while the use of an EG6 linker decreased tumor accumulation and uptake, owing to differences in cellular uptake kinetics, clearance mechanisms, and binding site barrier effects. To further improve tumor targeting and enhance the selectivity of targeted nanoparticles, a dual-receptor targeted approach was evaluated by targeting multiple cell surface receptors simultaneously. Liposomes functionalized with two distinct peptide antagonists to target VLA-4 and Leukocyte Peyer's Patch Adhesion Molecule-1 (LPAM-1) demonstrated synergistically enhanced cellular uptake by cells overexpressing both target receptors and negligible uptake by cells that do not simultaneously express both receptors, providing a strategy to improve selectivity over conventional single receptor-targeted designs. Taken together, this process of systematic optimization of well-defined nanoparticle drug delivery systems has the potential to improve cancer therapy for a broader patient population.

Characterization of Candida isolates from pediatric burn patients.

PubMed Central

Neely, A N; Odds, F C; Basatia, B K; Holder, I A

1988-01-01

To provide more detailed information about Candida epidemiology and pathogenesis in pediatric burn patients, Candida isolates from 113 patients collected over 3 years were identified at the species level and the serotypes and biotypes of the C. albicans isolates were determined. A total of 85% of the patients were colonized or infected by C. albicans, 18% by C. tropicalis, and 11% by C. parapsilosis. Although colonization or infection often was found at multiple sites and times, 87% of the patients were colonized or infected by only one Candida species or strain; the other 13% showed multiple colonizations or infections, some of which occurred simultaneously at the same site. C. albicans biotyping determined the tolerance of the isolates to pH (pH 1.4) and salt; flucytosine, borate, and safranine resistance; and ability to produce proteinase and assimilate urea, sorbose, and citrate; results are expressed as three-digit numbers. For isolates from three different anatomical sites, the distribution of the nine biotype characteristics was similar in all cases but one. Significantly more fecal than wound or throat isolates were resistant to safranine. Sixty-four different serotype-biotype combinations were found in the 96 patients with C. albicans infections or colonizations. Twenty-nine percent of all C. albicans isolates had the partial biotype -57, while 20 of the 96 patients had specifically serotype B, biotype 557 colonizations or infections. Eleven patients had the B557 infection when admitted; nine patients acquired the yeast in-house. Thirty percent of the C. albicans isolated from 23 adult patients at a nearby hospital also showed the -57 biotype pattern, suggesting that C. albicans isolates expressing this biotype are either extremely prevalent in nature or are more virulent than other C. albicans isolates. PMID:3053771

Multiple stressors and amphibian declines: dual impacts of pesticides and fish on yellow-legged frogs.

PubMed

Davidson, Carlos; Knapp, Roland A

2007-03-01

More than 40% of Earth's 5700+ amphibian species have undergone recent declines. Despite the likely involvement of multiple factors in driving these declines, most studies continue to focus on single stressors. In California (USA), separate studies have implicated either introduced fish or pesticides as causal agents. To date, however, no study has simultaneously evaluated the respective roles of these two potential stressors nor attempted to assess their relative importance, information critical for the development of effective conservation efforts and environmental policies. We examined the role and relative effect of fish and pesticides on the mountain yellow-legged frog (Rana muscosa) using unusually detailed data sets for a large portion of R. muscosa's historic range in California's Sierra Nevada. Habitat characteristics and presence/absence of R. muscosa and fish were quantified at each of 6831 sites during field surveys. Pesticide use upwind of each site was calculated from pesticide application records and predominant wind directions. Using generalized additive models, we found that, after accounting for habitat effects, the probability of R. muscosa presence was significantly reduced by both fish and pesticides, with the landscape-scale effect of pesticides much stronger than that of fish. The degree to which a site was sheltered from the predominant wind (and associated pesticides) was also a significant predictor of R. muscosa presence. Taken together, these results represent the strongest evidence to date that windborne pesticides are contributing to amphibian declines in pristine locations. Our results suggest that amphibian declines may have complex multi-factorial causes, and caution that single-factor studies that demonstrate the importance of one factor should not be used as evidence against the importance of other factors.

One-step formation of w/o/w multiple emulsions stabilized by single amphiphilic block copolymers.

PubMed

Hong, Liangzhi; Sun, Guanqing; Cai, Jinge; Ngai, To

2012-02-07

Multiple emulsions are complex polydispersed systems in which both oil-in-water (O/W) and water-in-oil (W/O) emulsion exists simultaneously. They are often prepared accroding to a two-step process and commonly stabilized using a combination of hydrophilic and hydrophobic surfactants. Recently, some reports have shown that multiple emulsions can also be produced through one-step method with simultaneous occurrence of catastrophic and transitional phase inversions. However, these reported multiple emulsions need surfactant blends and are usually described as transitory or temporary systems. Herein, we report a one-step phase inversion process to produce water-in-oil-in-water (W/O/W) multiple emulsions stabilized solely by a synthetic diblock copolymer. Unlike the use of small molecule surfactant combinations, block copolymer stabilized multiple emulsions are remarkably stable and show the ability to separately encapsulate both polar and nonpolar cargos. The importance of the conformation of the copolymer surfactant at the interfaces with regards to the stability of the multiple emulsions using the one-step method is discussed.

PrimerDesign-M: A multiple-alignment based multiple-primer design tool for walking across variable genomes

DOE PAGES

Yoon, Hyejin; Leitner, Thomas

2014-12-17

Analyses of entire viral genomes or mtDNA requires comprehensive design of many primers across their genomes. In addition, simultaneous optimization of several DNA primer design criteria may improve overall experimental efficiency and downstream bioinformatic processing. To achieve these goals, we developed PrimerDesign-M. It includes several options for multiple-primer design, allowing researchers to efficiently design walking primers that cover long DNA targets, such as entire HIV-1 genomes, and that optimizes primers simultaneously informed by genetic diversity in multiple alignments and experimental design constraints given by the user. PrimerDesign-M can also design primers that include DNA barcodes and minimize primer dimerization. PrimerDesign-Mmore » finds optimal primers for highly variable DNA targets and facilitates design flexibility by suggesting alternative designs to adapt to experimental conditions.« less

Sensory mediation of stimulus-driven attentional capture in multiple-cue displays.

PubMed

Wright, Richard D; Richard, Christian M

2003-08-01

Three location-cuing experiments were conducted in order to examine the stimulus-driven control of attentional capture in multiple-cue displays. These displays consisted of one to four simultaneously presented direct location cues. The results indicated that direct location cuing can produce cue effects that are mediated, in part, by nonattentional processing that occurs simultaneously at multiple locations. When single cues were presented in isolation, however, the resulting cue effect appeared to be due to a combination of sensory processing and attentional capture by the cue. This suggests that the faster responses produced by direct cues may be associated with two different components: an attention-related component that can be modulated by goal-driven factors and a nonattentional component that occurs in parallel at multiple direct-cue locations and is minimally affected by goal-driven factors.

Hamming and Accumulator Codes Concatenated with MPSK or QAM

NASA Technical Reports Server (NTRS)

Divsalar, Dariush; Dolinar, Samuel

2009-01-01

In a proposed coding-and-modulation scheme, a high-rate binary data stream would be processed as follows: 1. The input bit stream would be demultiplexed into multiple bit streams. 2. The multiple bit streams would be processed simultaneously into a high-rate outer Hamming code that would comprise multiple short constituent Hamming codes a distinct constituent Hamming code for each stream. 3. The streams would be interleaved. The interleaver would have a block structure that would facilitate parallelization for high-speed decoding. 4. The interleaved streams would be further processed simultaneously into an inner two-state, rate-1 accumulator code that would comprise multiple constituent accumulator codes - a distinct accumulator code for each stream. 5. The resulting bit streams would be mapped into symbols to be transmitted by use of a higher-order modulation - for example, M-ary phase-shift keying (MPSK) or quadrature amplitude modulation (QAM). The novelty of the scheme lies in the concatenation of the multiple-constituent Hamming and accumulator codes and the corresponding parallel architectures of the encoder and decoder circuitry (see figure) needed to process the multiple bit streams simultaneously. As in the cases of other parallel-processing schemes, one advantage of this scheme is that the overall data rate could be much greater than the data rate of each encoder and decoder stream and, hence, the encoder and decoder could handle data at an overall rate beyond the capability of the individual encoder and decoder circuits.

Detection of Acoustic/Infrasonic/Seismic Waves Generated by Hypersonic Re-Entry of the HAYABUSA Capsule and Fragmented Parts of the Spacecraft

NASA Astrophysics Data System (ADS)

Yamamoto, Masa-Yuki; Ishihara, Yoshiaki; Hiramatsu, Yoshihiro; Kitamura, Kazuki; Ueda, Masayoshi; Shiba, Yasuo; Furumoto, Muneyoshi; Fujita, Kazuhisa

2011-10-01

Acoustic/infrasonic/seismic waves were observed during the re-entry of the Japanese asteroid explorer ``HAYABUSA'' at 6 ground sites in Woomera, Australia, on 2010 June 13. Overpressure values of infrasound waves were detected at 3 ground sites in a range from 1.3 Pa, 1.0 Pa, and 0.7 Pa with each distance of 36.9 km, 54.9 km, and 67.8 km, respectively, apart from the SRC trajectory. Seismic waveforms through air-to-ground coupling processes were also detected at 6 sites, showing a one-to-one correspondence to infrasound waves at all simultaneous observation sites. Audible sound up to 1 kHz was recorded at one site with a distance of 67.8 km. The mother spacecraft was fragmented from 75 km down to 38 km with a few explosive enhancements of emissions. A persistent train of HAYABUSA re-entry was confirmed at an altitude range of between 92 km down to 82 km for about 3 minutes. Light curves of 136 fragmented parts of the spacecraft were analyzed in detail based on video observations taken at multiple ground sites, being classified into three types of fragmentations, i.e., melting, explosive, and re-fragmented types. In a comparison between infrasonic waves and video-image analyses, regarding the generation of sonic-boom type shock waves by hypersonically moving artificial meteors, both the sample return capsule and fragmented parts of the mother spacecraft, at an altitude of 40 ± 1 km were confirmed with a one-to-one correspondence with each other.

Homology modeling and molecular dynamics simulation of N-myristoyltransferase from protozoan parasites: active site characterization and insights into rational inhibitor design

NASA Astrophysics Data System (ADS)

Sheng, Chunquan; Ji, Haitao; Miao, Zhenyuan; Che, Xiaoyin; Yao, Jianzhong; Wang, Wenya; Dong, Guoqiang; Guo, Wei; Lü, Jiaguo; Zhang, Wannian

2009-06-01

Myristoyl-CoA:protein N-myristoyltransferase (NMT) is a cytosolic monomeric enzyme that catalyzes the transfer of the myristoyl group from myristoyl-CoA to the N-terminal glycine of a number of eukaryotic cellular and viral proteins. Recent experimental data suggest NMT from parasites could be a promising new target for the design of novel antiparasitic agents with new mode of action. However, the active site topology and inhibitor specificity of these enzymes remain unclear. In this study, three-dimensional models of NMT from Plasmodium falciparum (PfNMT), Leishmania major (LmNMT) and Trypanosoma brucei (TbNMT) were constructed on the basis of the crystal structures of fungal NMTs using homology modeling method. The models were further refined by energy minimization and molecular dynamics simulations. The active sites of PfNMT, LmNMT and TbNMT were characterized by multiple copy simultaneous search (MCSS). MCSS functional maps reveal that PfNMT, LmNMT and TbNMT share a similar active site topology, which is defined by two hydrophobic pockets, a hydrogen-bonding (HB) pocket, a negatively-charged HB pocket and a positively-charged HB pocket. Flexible docking approaches were then employed to dock known inhibitors into the active site of PfNMT. The binding mode, structure-activity relationships and selectivity of inhibitors were investigated in detail. From the results of molecular modeling, the active site architecture and certain key residues responsible for inhibitor binding were identified, which provided insights for the design of novel inhibitors of parasitic NMTs.

Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord

NASA Astrophysics Data System (ADS)

Sharpe, Abigail N.; Jackson, Andrew

2014-02-01

Objective. Electrical stimulation of the spinal cord has potential applications following spinal cord injury for reanimating paralysed limbs and promoting neuroplastic changes that may facilitate motor rehabilitation. Here we systematically compare the efficacy, selectivity and frequency-dependence of different stimulation methods in the cervical enlargement of anaesthetized monkeys. Approach. Stimulating electrodes were positioned at multiple epidural and subdural sites on both dorsal and ventral surfaces, as well as at different depths within the spinal cord. Motor responses were recorded from arm, forearm and hand muscles. Main results. Stimulation efficacy increased from dorsal to ventral stimulation sites, with the exception of ventral epidural electrodes which had the highest recruitment thresholds. Compared to epidural and intraspinal methods, responses to subdural stimulation were more selective but also more similar between adjacent sites. Trains of stimuli delivered to ventral sites elicited consistent responses at all frequencies whereas from dorsal sites we observed a mixture of short-latency facilitation and long-latency suppression. Finally, paired stimuli delivered to dorsal surface and intraspinal sites exhibited symmetric facilitatory interactions at interstimulus intervals between 2-5 ms whereas on the ventral side interactions tended to be suppressive for near-simultaneous stimuli. Significance. We interpret these results in the context of differential activation of afferent and efferent roots and intraspinal circuit elements. In particular, we propose that distinct direct and indirect actions of spinal cord stimulation on motoneurons may be advantageous for different applications, and this should be taken into consideration when designing neuroprostheses for upper-limb function.

Global Mapping of Transcription Factor Binding Sites by Sequencing Chromatin Surrogates: a Perspective on Experimental Design, Data Analysis, and Open Problems.

PubMed

Wei, Yingying; Wu, George; Ji, Hongkai

2013-05-01

Mapping genome-wide binding sites of all transcription factors (TFs) in all biological contexts is a critical step toward understanding gene regulation. The state-of-the-art technologies for mapping transcription factor binding sites (TFBSs) couple chromatin immunoprecipitation (ChIP) with high-throughput sequencing (ChIP-seq) or tiling array hybridization (ChIP-chip). These technologies have limitations: they are low-throughput with respect to surveying many TFs. Recent advances in genome-wide chromatin profiling, including development of technologies such as DNase-seq, FAIRE-seq and ChIP-seq for histone modifications, make it possible to predict in vivo TFBSs by analyzing chromatin features at computationally determined DNA motif sites. This promising new approach may allow researchers to monitor the genome-wide binding sites of many TFs simultaneously. In this article, we discuss various experimental design and data analysis issues that arise when applying this approach. Through a systematic analysis of the data from the Encyclopedia Of DNA Elements (ENCODE) project, we compare the predictive power of individual and combinations of chromatin marks using supervised and unsupervised learning methods, and evaluate the value of integrating information from public ChIP and gene expression data. We also highlight the challenges and opportunities for developing novel analytical methods, such as resolving the one-motif-multiple-TF ambiguity and distinguishing functional and non-functional TF binding targets from the predicted binding sites. The online version of this article (doi:10.1007/s12561-012-9066-5) contains supplementary material, which is available to authorized users.

Trace elements have limited utility for studying migratory connectivity in shorebirds that winter in Argentina

USGS Publications Warehouse

Torres-Dowdall, J.; Farmer, A.H.; Abril, M.; Bucher, E.H.; Ridley, I.

2010-01-01

Trace-element analysis has been suggested as a tool for the study of migratory connectivity because (1) trace-element abundance varies spatially in the environment, (2) trace elements are assimilated into animals' tissues through the diet, and (3) current technology permits the analysis of multiple trace elements in a small tissue sample, allowing the simultaneous exploration of several elements. We explored the potential of trace elements (B, Na, Mg, Al, Si, P, S, K, Ca, Ti, Cr, Mn, Ni, Cu, Zn, As, Sr, Cs, Hg, Tl, Pb, Bi, Th, and U) to clarify the migratory connectivity of shorebirds that breed in North America and winter in southern South America. We collected 66 recently replaced secondary feathers from Red Knots (Calidris canutus) at three sites in Patagonia and 76 from White-rumped Sandpipers (C. fuscicollis) at nine sites across Argentina. There were significant differences in trace-element abundance in shorebird feathers grown at different nonbreeding sites, and annual variability within a site was small compared to variability among sites. Across Argentina, there was no large-scale gradient in trace elements. The lack of such a gradient restricts the application of this technique to questions concerning the origin of shorebirds to a small number of discrete sites. Furthermore, our results including three additional species, the Pectoral Sandpiper (C. melanotos), Wilson's Phalarope (Phalaropus tricolor), and Collared Plover (Charadrius collaris), suggest that trace-element profiles change as feathers age. Temporal instability of trace-element values could undermine their application to the study of migratory connectivity in shorebirds. ?? The Cooper Ornithological Society 2010.

Improved Chemical Control of Chagas Disease Vectors in the Dry Chaco Region

PubMed Central

CECERE, MARÍA CARLA; VAZQUEZ-PROKOPEC, GONZALO M.; CEBALLOS, LEONARDO A.; BORAGNO, SILVANA; ZÁRATE, JOAQUÍN E.; KITRON, URIEL; GÜRTLER, RICARDO E.

2013-01-01

The effectiveness of two doses of suspension concentrate (SC) pyrethroid insecticides in suppressing peridomestic populations of Triatoma infestans (Klug) was evaluated in 28 rural communities located in Santiago del Estero province, northwestern Argentina, including 388 houses and 1,516 identified sites. Four treatments were randomly assigned to peridomiciles within each community: 5% SC β-cypermethrin at standard (S, 50 mg active ingredient [AI]/m2) and double dose (2S), and 2.5% SC deltamethrin at standard (D, 25 mg [AI]/m2) and double dose (2D). Simultaneously, we assessed the effects of both pyrethroids applied at standard doses against domestic infestations. Bug infestation at the site level was assessed by timed manual collections with a dislodging agent at baseline, 13 and 21 mo postspraying (MPS). In domiciles, D and S nearly suppressed all T. infestans infestations up to 21 MPS. In peridomestic sites infested before interventions, multiple logistic regression analysis showed that site-level reinfestation at 13 MPS was significantly lower for treatment 2D (1%) than for other treatments, whereas 2S (6%), D (5%), and S (14%) did not differ significantly between them. The risk of reinfestation after spraying was significantly greater in goat or pig corrals than in other peridomestic ecotopes (in which treatments did not differ significantly), and in sites infested before interventions than in uninfested sites. The application of SC deltamethrin at double dose in goat or pig corrals may suppress T. infestans foci and achieve more sustained effects in the dry Chaco. PMID:23540129

Usefulness of esophagogastroduodenoscopy and 18F-fluorodeoxyglucose positron-emission tomography in detecting synchronous multiple primary cancers with oral cancer.

PubMed

Ishibashi-Kanno, Naomi; Yamagata, Kenji; Uchida, Fumihiko; Hasegawa, Shogo; Yanagawa, Toru; Bukawa, Hiroki

2017-12-01

The purpose of this study is to compare the value of screening for synchronous multiple primary cancers in other organs by esophagogastroduodenoscopy (EGD) or 18 F-fluorodeoxyglucose positron-emission tomography (PET-CT) in patients newly diagnosed with oral cancer. We retrospectively examined consecutive Japanese patients who were diagnosed with oral squamous cell carcinoma (OSCC) and were screened for synchronous multiple primary cancers in other organs by EGD and/or PET-CT between January 2010 and December 2015 at our institution. The study included 190 patients (106 males and 84 females) from 36 to 93 years of age (median age 68.8 years). The patients were screened by EGD, PET-CT, or both before beginning treatment for OSCC. Of 190 Japanese patients with OSCC, 15 had multiple primary cancers: 13 patients had double cancer and two had triple cancers. The sites of the 17 multiple primary cancers were gastric (6), esophageal (4), and lung (3), and ovarian, colon, liver, and thyroid (1 each). All of the gastric and esophageal cancers were found by EGD and were not detected by PET-CT. For three patients, the detection of multiple cancers affected the treatment modality or order of treatment selected for the OSCC. In two cases, the oral cancer and multiple primary cancer(s) in another organ were resected simultaneously by joint surgical teams. PET-CT for oral cancer patients is an effective supporting diagnostic tool. However, the ability of PET-CT has some limitations. Especially for early detection of the upper gastrointestinal cancers, it is necessary to be supplemented by EGD.

Multifocal laser surgery: cutting enhancement by hydrodynamic interactions between cavitation bubbles.

PubMed

Toytman, I; Silbergleit, A; Simanovski, D; Palanker, D

2010-10-01

Transparent biological tissues can be precisely dissected with ultrafast lasers using optical breakdown in the tight focal zone. Typically, tissues are cut by sequential application of pulses, each of which produces a single cavitation bubble. We investigate the hydrodynamic interactions between simultaneous cavitation bubbles originating from multiple laser foci. Simultaneous expansion and collapse of cavitation bubbles can enhance the cutting efficiency, by increasing the resulting deformations in tissue, and the associated rupture zone. An analytical model of the flow induced by the bubbles is presented and experimentally verified. The threshold strain of the material rupture is measured in a model tissue. Using the computational model and the experimental value of the threshold strain one can compute the shape of the rupture zone in tissue resulting from application of multiple bubbles. With the threshold strain of 0.7 two simultaneous bubbles produce a continuous cut when applied at the distance 1.35 times greater than that required in sequential approach. Simultaneous focusing of the laser in multiple spots along the line of intended cut can extend this ratio to 1.7. Counterpropagating jets forming during collapse of two bubbles in materials with low viscosity can further extend the cutting zone-up to approximately a factor of 1.5.

LSST Operations Simulator

NASA Astrophysics Data System (ADS)

Cook, K. H.; Delgado, F.; Miller, M.; Saha, A.; Allsman, R.; Pinto, P.; Gee, P. A.

2005-12-01

We have developed an operations simulator for LSST and used it to explore design and operations parameter space for this large etendue telescope and its ten year survey mission. The design is modular, with separate science programs coded in separate modules. There is a sophisticated telescope module with all motions parametrized for ease of testing different telescope capabilities, e.g. effect of acceleration capabilities of various motors on science output. Sky brightness is calculated as a function of moon phase and separation. A sophisticated exposure time calculator has been developed for LSST which is being incorporated into the simulator to allow specification of S/N requirements. All important parameters for the telescope, the site and the science programs are easily accessible in configuration files. Seeing and cloud data from the three candidate LSST sites are used for our simulations. The simulator has two broad categories of science proposals: sky coverage and transient events. Sky coverage proposals base their observing priorities on a required number of observations for each field in a particular filter with specified conditions (maximum seeing, sky brightness, etc) and one is used for a weak lensing investigation. Transient proposals are highly configurable. A transient proposal can require sequential, multiple exposures in various filters with a specified sequence of filters, and require a particular cadence for multiple revisits to complete an observation sequence. Each science proposal ranks potential observations based upon the internal logic of that proposal. We present the results of a variety of mixed science program observing simulations, showing how varied programs can be carried out simultaneously, with many observations serving multiple science goals. The simulator has shown that LSST can carry out its multiple missions under a variety of conditions. KHC's work was performed under the auspices of the US DOE, NNSA by the Univ. of California, LLNL under contract No. W-7405-Eng-48.

mCAL: A New Approach for Versatile Multiplex Action of Cas9 Using One sgRNA and Loci Flanked by a Programmed Target Sequence.

PubMed

Finnigan, Gregory C; Thorner, Jeremy

2016-07-07

Genome editing exploiting CRISPR/Cas9 has been adopted widely in academia and in the biotechnology industry to manipulate DNA sequences in diverse organisms. Molecular engineering of Cas9 itself and its guide RNA, and the strategies for using them, have increased efficiency, optimized specificity, reduced inappropriate off-target effects, and introduced modifications for performing other functions (transcriptional regulation, high-resolution imaging, protein recruitment, and high-throughput screening). Moreover, Cas9 has the ability to multiplex, i.e., to act at different genomic targets within the same nucleus. Currently, however, introducing concurrent changes at multiple loci involves: (i) identification of appropriate genomic sites, especially the availability of suitable PAM sequences; (ii) the design, construction, and expression of multiple sgRNA directed against those sites; (iii) potential difficulties in altering essential genes; and (iv) lingering concerns about "off-target" effects. We have devised a new approach that circumvents these drawbacks, as we demonstrate here using the yeast Saccharomyces cerevisiae First, any gene(s) of interest are flanked upstream and downstream with a single unique target sequence that does not normally exist in the genome. Thereafter, expression of one sgRNA and cotransformation with appropriate PCR fragments permits concomitant Cas9-mediated alteration of multiple genes (both essential and nonessential). The system we developed also allows for maintenance of the integrated, inducible Cas9-expression cassette or its simultaneous scarless excision. Our scheme-dubbed mCAL for " M: ultiplexing of C: as9 at A: rtificial L: oci"-can be applied to any organism in which the CRISPR/Cas9 methodology is currently being utilized. In principle, it can be applied to install synthetic sequences into the genome, to generate genomic libraries, and to program strains or cell lines so that they can be conveniently (and repeatedly) manipulated at multiple loci with extremely high efficiency. Copyright © 2016 Finnigan and Thorner.

Geotechnical Site Investigation Using S-waves with Implications for Ground Motion Analysis

NASA Astrophysics Data System (ADS)

Hassan, Bilal; Butt, Stephen D.; Hurich, Charles A.

2017-12-01

Evaluation results of shear wave attenuation-based ground motion restricted by fracture orientation and rheology, from among those of an extended experimental study, are presented herein. The issues of competence of fractured bedrock dynamically disturbed multilaterally are assessed. Disturbance is primarily modelled by Sh and Sv stimulation, given fracture orientation, while subjected to direct fracture stress regime conditions varying in time. Hence, directionalities of polarisation and stress are taken into consideration simultaneously following simple site-specific non-erodetic approach. Comparison of spectral curves and spectral ratio curves of attenuation with respect to variations of direction and stress emphasise the amplification of the `seismic response' in one direction compared to the other, i.e. vertical vs. horizontal, in terms of weighing possibilities of or predicting structural integrity against failure. The composite analyses of multiple spectral curves not only enable determination of the orientation of the fracture set/s in space but also allow inferring the nature of more amplified response perpendicular to the crack surface compared to that of a response parallel to the crack surface.

Human papillomavirus-32-associated focal epithelial hyperplasia accompanying HPV-16-positive papilloma-like lesions in oral mucosa.

PubMed

Liu, Na; Wang, Jiayi; Lei, Lei; Li, Yanzhong; Zhou, Min; Dan, Hongxia; Zeng, Xin; Chen, Qianming

2013-05-01

Human papillomavirus infection can cause a variety of benign or malignant oral lesions, and the various genotypes can cause distinct types of lesions. To our best knowledge, there has been no report of 2 different human papillomavirus-related oral lesions in different oral sites in the same patient before. This paper reported a patient with 2 different oral lesions which were clinically and histologically in accord with focal epithelial hyperplasia and oral papilloma, respectively. Using DNA extracted from these 2 different lesions, tissue blocks were tested for presence of human papillomavirus followed by specific polymerase chain reaction testing for 6, 11, 13, 16, 18, and 32 subtypes in order to confirm the clinical diagnosis. Finally, human papillomavirus-32-positive focal epithelial hyperplasia accompanying human papillomavirus-16-positive oral papilloma-like lesions were detected in different sites of the oral mucosa. Nucleotide sequence sequencing further confirmed the results. So in our clinical work, if the simultaneous occurrences of different human papillomavirus associated lesions are suspected, the multiple biopsies from different lesions and detection of human papillomavirus genotype are needed to confirm the diagnosis.

Thoracic Unilateral Spinal Cord Injury After Spinal Anaesthesia for Total Hip Replacement: Fate or Mistake?

PubMed Central

Fabio, Costa; Romualdo, Del Buono; Eugenio, Agrò Felice; Vittoradolfo, Tambone; Massimiliano, Vitali Andrea; Giovanna, Ricci

2017-01-01

Spinal anaesthesia is the most preffered anesthesia technique for total hip replacement, and its complications range from low entity (insignificant) to life threatening. The incidence of neurologic complications after neuraxial anaesthesia is not perfectly clear, although there are several described cases of spinal cord ischaemia. We present a case of unilateral T8–T11 spinal cord ischaemia following L2–L3 spinal anaesthesia for total hip replacement. Magnetic resonance imaging showed a hyperintense T8–T11 signal alteration on the leftside of paramedian spinal cord. A temporal epidemiologic linkage between the damage and the surgery seems to be present. The injury occurred without anatomical proximity between the injury site and the spinal needle entry site. This may be due to multiple contributing factors, each of them is probably not enough to determine the damage by itself; however, acting simultaneously, they could have been responsible for the complication. The result was unpredictable and unavoidable and was caused by unforeseeable circumstances and not by inadequate medical practice. PMID:28439446

Frequency multiplexed long range swept source optical coherence tomography

PubMed Central

Zurauskas, Mantas; Bradu, Adrian; Podoleanu, Adrian Gh.

2013-01-01

We present a novel swept source optical coherence tomography configuration, equipped with acousto-optic deflectors that can be used to simultaneously acquire multiple B-scans originating from different depths. The sensitivity range of the configuration is evaluated while acquiring five simultaneous B-scans. Then the configuration is employed to demonstrate long range B-scan imaging by combining two simultaneous B-scans from a mouse head sample. PMID:23760762

Methods for simultaneous control of lignin content and composition, and cellulose content in plants

DOEpatents

Chiang, Vincent Lee C.; Li, Laigeng

2005-02-15

The present invention relates to a method of concurrently introducing multiple genes into plants and trees is provided. The method includes simultaneous transformation of plants with multiple genes from the phenylpropanoid pathways including 4CL, CAld5H, AldOMT, SAD and CAD genes and combinations thereof to produce various lines of transgenic plants displaying altered agronomic traits. The agronomic traits of the plants are regulated by the orientation of the specific genes and the selected gene combinations, which are incorporated into the plant genome.

Large area silicon sheet by EFG

NASA Technical Reports Server (NTRS)

1981-01-01

A multiple growth run with three 10 cm cartridges was carried out with the best throughput rates and time percentage of simultaneous three ribbon growth achieved to date in this system. Growth speeds were between 3.2 and 3.6 cm/minute on all three cartridges and simultaneous full width growth of three ribbons was achieved 47 percent of the time over the eight hour duration of the experiment. Improvements in instrumentation and in the main zone temperature uniformity were two factors that have led to more reproducible growth conditions in the multiple ribbon furnace.

Targeted Multiplex Imaging Mass Spectrometry with Single Chain Fragment Variable (scfv) Recombinant Antibodies

NASA Astrophysics Data System (ADS)

Thiery, Gwendoline; Mernaugh, Ray L.; Yan, Heping; Spraggins, Jeffrey M.; Yang, Junhai; Parl, Fritz F.; Caprioli, Richard M.

2012-10-01

Recombinant scfv antibodies specific for CYP1A1 and CYP1B1 P450 enzymes were combined with targeted imaging mass spectrometry to simultaneously detect the P450 enzymes present in archived, paraffin-embedded, human breast cancer tissue sections. By using CYP1A1 and CYP1B1 specific scfv, each coupled to a unique reporter molecule (i.e., a mass tag) it was possible to simultaneously detect multiple antigens within a single tissue sample with high sensitivity and specificity using mass spectrometry. The capability of imaging multiple antigens at the same time is a significant advance that overcomes technical barriers encountered when using present day approaches to develop assays that can simultaneously detect more than a single antigen in the same tissue sample.

Using Infrared Thermography to Assess Emotional Responses to Infants

ERIC Educational Resources Information Center

Esposito, Gianluca; Nakazawa, Jun; Ogawa, Shota; Stival, Rita; Putnick, Diane L.; Bornstein, Marc H.

2015-01-01

Adult-infant interactions operate simultaneously across multiple domains and at multiple levels -- from physiology to behaviour. Unpackaging and understanding them, therefore, involve analysis of multiple data streams. In this study, we tested physiological responses and cognitive preferences for infant and adult faces in adult females and males.…

Simultaneous Two-Way Clustering of Multiple Correspondence Analysis

ERIC Educational Resources Information Center

Hwang, Heungsun; Dillon, William R.

2010-01-01

A 2-way clustering approach to multiple correspondence analysis is proposed to account for cluster-level heterogeneity of both respondents and variable categories in multivariate categorical data. Specifically, in the proposed method, multiple correspondence analysis is combined with k-means in a unified framework in which "k"-means is…

Assessing Spurious Interaction Effects in Structural Equation Modeling

ERIC Educational Resources Information Center

Harring, Jeffrey R.; Weiss, Brandi A.; Li, Ming

2015-01-01

Several studies have stressed the importance of simultaneously estimating interaction and quadratic effects in multiple regression analyses, even if theory only suggests an interaction effect should be present. Specifically, past studies suggested that failing to simultaneously include quadratic effects when testing for interaction effects could…

Roman Brunecky | NREL

Science.gov Websites

barriers, both at the level of the biomass chip and the structure of the cell wall. There are multiple ) based on simultaneous saccharification and fermentation (SSF). Diagram of the traditional biomass to ) based on simultaneous saccharification and fermentation (SSF). Recently we have discovered that

Simultaneous fluorescent detection of multiple metal ions based on the DNAzymes and graphene oxide.

PubMed

Yun, Wen; Wu, Hong; Liu, Xingyan; Fu, Min; Jiang, Jiaolai; Du, Yunfeng; Yang, Lizhu; Huang, Yu

2017-09-15

A novel fluorescent detection strategy for simultaneous detection of Cu 2+ , Pb 2+ and Mg 2+ based on DNAzyme branched junction structure with three kinds of DNAzymes and graphene oxide (GO) was presented. Three fluorophores labeled DNA sequences consisted with enzyme-strand (E-DNA) and substrate strand (S-DNA) were annealed to form DNAzyme branched junction structure. In the presence of target metal ion, the DNAzyme was activated to cleave the fluorophore labeled S-DNA. The S-DNA fragments were released and adsorbed onto GO surface to quench the fluorescent signal. The detection limit was calculated to be 1 nM for Cu 2+ , 200 nM for Mg 2+ , and 0.3 nM for Pb 2+ , respectively. This strategy was successfully used for simultaneous detection of Cu 2+ , Mg 2+ and Pb 2+ in human serum. Moreover, it had potential application for simultaneous detection of multiple metal ions in environmental and biological samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Simultaneous homicide-suicide: a case report of double drowning.

PubMed

Melez, İpek Esen; Avşar, Abdullah; Başpınar, Bünyamin; Melez, Deniz Oğuzhan; Şahin, Fatih; Özdeş, Taşkın

2014-09-01

Homicide-suicide is a tragic phenomenon which typically does not result in a criminal charge or trial. However, correct diagnosis and classification of homicide-suicide cases are important to determine the perpetrators and dynamics of each category properly. The deaths in the homicide-suicide acts can be divided into two categories with respect to the number of involved individuals: dyadic deaths and triple or multiple deaths. These two categories can also be divided into two subgroups according to the chronology of the incidents: simultaneous deaths and consecutive deaths. Herein, a simultaneous homicide-suicide case of a father and daughter where both deaths occurred through drowning which was not found in the selected literature review and where the victim was a child is presented. The article aims to clarify the term discrepancies about multiple death cases in the literature and to discuss the pathological and psychosocial characteristics of the simultaneous dyadic death cases. © 2014 American Academy of Forensic Sciences.

A pulse coding and decoding strategy to perform Lamb wave inspections using simultaneously multiple actuators

NASA Astrophysics Data System (ADS)

De Marchi, Luca; Marzani, Alessandro; Moll, Jochen; Kudela, Paweł; Radzieński, Maciej; Ostachowicz, Wiesław

2017-07-01

The performance of Lamb wave based monitoring systems, both in terms of diagnosis time and data complexity, can be enhanced by increasing the number of transducers used to actuate simultaneously the guided waves in the inspected medium. However, in case of multiple simultaneously-operated actuators the interference among the excited wave modes within the acquired signals has to be considered for the further processing. To this aim, in this work a code division strategy based on the Warped Frequency Transform is presented. At first, the proposed procedure encodes actuation pulses using Gold sequences. Next, for each considered actuator the acquired signals are compensated from dispersion by cross correlating the warped version of the actuated and received signals. Compensated signals form the base for a final wavenumber imaging meant at emphasizing defects and or anomalies by removing incident wavefield and edge reflections. The proposed strategy is tested numerically, and validated through an experiment in which guided waves are actuated in a plate by four piezoelectric transducers operating simultaneously.

Comparison of Various Nuclear Localization Signal-Fused Cas9 Proteins and Cas9 mRNA for Genome Editing in Zebrafish.

PubMed

Hu, Peinan; Zhao, Xueying; Zhang, Qinghua; Li, Weiming; Zu, Yao

2018-03-02

The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has been proven to be an efficient and precise genome editing technology in various organisms. However, the gene editing efficiencies of Cas9 proteins with a nuclear localization signal (NLS) fused to different termini and Cas9 mRNA have not been systematically compared. Here, we compared the ability of Cas9 proteins with NLS fused to the N-, C-, or both the N- and C-termini and N-NLS-Cas9-NLS-C mRNA to target two sites in the tyr gene and two sites in the gol gene related to pigmentation in zebrafish. Phenotypic analysis revealed that all types of Cas9 led to hypopigmentation in similar proportions of injected embryos. Genome analysis by T7 Endonuclease I (T7E1) assays demonstrated that all types of Cas9 similarly induced mutagenesis in four target sites. Sequencing results further confirmed that a high frequency of indels occurred in the target sites ( tyr1 > 66%, tyr2 > 73%, gol1 > 50%, and gol2 > 35%), as well as various types (more than six) of indel mutations observed in all four types of Cas9-injected embryos. Furthermore, all types of Cas9 showed efficient targeted mutagenesis on multiplex genome editing, resulting in multiple phenotypes simultaneously. Collectively, we conclude that various NLS-fused Cas9 proteins and Cas9 mRNAs have similar genome editing efficiencies on targeting single or multiple genes, suggesting that the efficiency of CRISPR/Cas9 genome editing is highly dependent on guide RNAs (gRNAs) and gene loci. These findings may help to simplify the selection of Cas9 for gene editing using the CRISPR/Cas9 system. Copyright © 2018 Hu et al.

Non-additive benefit or cost? Disentangling the indirect effects that occur when plants bearing extrafloral nectaries and honeydew-producing insects share exotic ant mutualists.

PubMed

Savage, Amy M; Rudgers, Jennifer A

2013-06-01

In complex communities, organisms often form mutualisms with multiple different partners simultaneously. Non-additive effects may emerge among species linked by these positive interactions. Ants commonly participate in mutualisms with both honeydew-producing insects (HPI) and their extrafloral nectary (EFN)-bearing host plants. Consequently, HPI and EFN-bearing plants may experience non-additive benefits or costs when these groups co-occur. The outcomes of these interactions are likely to be influenced by variation in preferences among ants for honeydew vs. nectar. In this study, a test was made for non-additive effects on HPI and EFN-bearing plants resulting from sharing exotic ant guards. Preferences of the dominant exotic ant species for nectar vs. honeydew resources were also examined. Ant access, HPI and nectar availability were manipulated on the EFN-bearing shrub, Morinda citrifolia, and ant and HPI abundances, herbivory and plant growth were assessed. Ant-tending behaviours toward HPI across an experimental gradient of nectar availability were also tracked in order to investigate mechanisms underlying ant responses. The dominant ant species, Anoplolepis gracilipes, differed from less invasive ants in response to multiple mutualists, with reductions in plot-wide abundances when nectar was reduced, but no response to HPI reduction. Conversely, at sites where A. gracilipes was absent or rare, abundances of less invasive ants increased when nectar was reduced, but declined when HPI were reduced. Non-additive benefits were found at sites dominated by A. gracilipes, but only for M. citrifolia plants. Responses of HPI at these sites supported predictions of the non-additive cost model. Interestingly, the opposite non-additive patterns emerged at sites dominated by other ants. It was demonstrated that strong non-additive benefits and costs can both occur when a plant and herbivore share mutualist partners. These findings suggest that broadening the community context of mutualism studies can reveal important non-additive effects and increase understanding of the dynamics of species interactions.

Force Mapping during the Formation and Maturation of Cell Adhesion Sites with Multiple Optical Tweezers

PubMed Central

Schwingel, Melanie; Bastmeyer, Martin

2013-01-01

Focal contacts act as mechanosensors allowing cells to respond to their biomechanical environment. Force transmission through newly formed contact sites is a highly dynamic process requiring a stable link between the intracellular cytoskeleton and the extracellular environment. To simultaneously investigate cellular traction forces in several individual maturing adhesion sites within the same cell, we established a custom-built multiple trap optical tweezers setup. Beads functionalized with fibronectin or RGD-peptides were placed onto the apical surface of a cell and trapped with a maximum force of 160 pN. Cells form adhesion contacts around the beads as demonstrated by vinculin accumulation and start to apply traction forces after 30 seconds. Force transmission was found to strongly depend on bead size, surface density of integrin ligands and bead location on the cell surface. Highest traction forces were measured for beads positioned on the leading edge. For mouse embryonic fibroblasts, traction forces acting on single beads are in the range of 80 pN after 5 minutes. If two beads were positioned parallel to the leading edge and with a center-to-center distance less than 10 µm, traction forces acting on single beads were reduced by 40%. This indicates a spatial and temporal coordination of force development in closely related adhesion sites. We also used our setup to compare traction forces, retrograde transport velocities, and migration velocities between two cell lines (mouse melanoma and fibroblasts) and primary chick fibroblasts. We find that maximal force development differs considerably between the three cell types with the primary cells being the strongest. In addition, we observe a linear relation between force and retrograde transport velocity: a high retrograde transport velocity is associated with strong cellular traction forces. In contrast, migration velocity is inversely related to traction forces and retrograde transport velocity. PMID:23372781

Use of giant-sized flow-through venous flap for simultaneous reconstruction of dual or multiple major arteries in salvage therapy for complex upper limb traumatic injury.

PubMed

Zheng, Da-Wei; Li, Zhang-Can; Shi, Rong-Jian; Sun, Feng; Xu, Li; Shou, Kui-Shui

2016-02-01

Salvage repair after complex upper limb traumatic injury is surgically challenging due to underlying major arterial impairment with complicating a large-sized soft tissue defect. The purpose of this study was to evaluate the effectiveness and safety of using a giant-sized (≥100 cm(2)) flow-through venous flap for reconstruction of dual or multiple forearm, metacarpal, or digital arteries after complex upper limb traumatic injury. Seven patients were consecutively hospitalized for emergency salvage repair after complex upper limb traumatic injury between March 2012 and May 2014. The forearm and palmar artery defects were repaired using the calf great saphenous vein flap and the volar forearm venous flap, respectively. The flow-through venous flap ranged from 9.5 cm × 12.0 cm to 12.0 cm × 20.0 cm (mean, 158.4 cm(2)) in size. The flaps and affected limbs survived uneventfully in five patients, with one patient experiencing distal flap marginal necrosis and a second patient requiring amputation of the affected limb. Computed tomography angiography showed patent vessels in all patients. The mean total active motion of the repaired fingers was 199.5° versus 258.8° for the contralateral counterpart (77.1%). The sensory return was determined to be S2 in 2 patients, S3 in 3 patients and S3+ in 1 patient. The disability scores for the arm, shoulder, and hand ranged from 4.6-18.2 (mean, 11.3), and the mean Michigan hand outcomes questionnaire score was 7.8 ± 0.9. The flow-through venous flap is an effective and safe treatment alternative for salvage therapy of a ≥100-cm(2) complex upper limb traumatic injury with dual or multiple major arterial impairment. This technique allows simultaneous reconstruction of dual or multiple artery injuries and an extensive soft tissue defect. Serious surgical site infection remains a major safety concern and necessitates radical debridement in complicating cases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous real-time monitoring of multiple cortical systems.

PubMed

Gupta, Disha; Jeremy Hill, N; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L; Schalk, Gerwin

2014-10-01

Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. We study these questions using electrocorticographic signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (six for offline parameter optimization, six for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main Results: Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelopes. These decoders were trained separately and executed simultaneously in real time. This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic.

Simultaneous Real-Time Monitoring of Multiple Cortical Systems

PubMed Central

Gupta, Disha; Hill, N. Jeremy; Brunner, Peter; Gunduz, Aysegul; Ritaccio, Anthony L.; Schalk, Gerwin

2014-01-01

Objective Real-time monitoring of the brain is potentially valuable for performance monitoring, communication, training or rehabilitation. In natural situations, the brain performs a complex mix of various sensory, motor, or cognitive functions. Thus, real-time brain monitoring would be most valuable if (a) it could decode information from multiple brain systems simultaneously, and (b) this decoding of each brain system were robust to variations in the activity of other (unrelated) brain systems. Previous studies showed that it is possible to decode some information from different brain systems in retrospect and/or in isolation. In our study, we set out to determine whether it is possible to simultaneously decode important information about a user from different brain systems in real time, and to evaluate the impact of concurrent activity in different brain systems on decoding performance. Approach We study these questions using electrocorticographic (ECoG) signals recorded in humans. We first document procedures for generating stable decoding models given little training data, and then report their use for offline and for real-time decoding from 12 subjects (6 for offline parameter optimization, 6 for online experimentation). The subjects engage in tasks that involve movement intention, movement execution and auditory functions, separately, and then simultaneously. Main results Our real-time results demonstrate that our system can identify intention and movement periods in single trials with an accuracy of 80.4% and 86.8%, respectively (where 50% would be expected by chance). Simultaneously, the decoding of the power envelope of an auditory stimulus resulted in an average correlation coefficient of 0.37 between the actual and decoded power envelope. These decoders were trained separately and executed simultaneously in real time. Significance This study yielded the first demonstration that it is possible to decode simultaneously the functional activity of multiple independent brain systems. Our comparison of univariate and multivariate decoding strategies, and our analysis of the influence of their decoding parameters, provides benchmarks and guidelines for future research on this topic. PMID:25080161

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning.

PubMed

Happel, Max F K; Deliano, Matthias; Ohl, Frank W

2015-10-22

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species. Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Lethal control of an apex predator has unintended cascading effects on forest mammal assemblages.

PubMed

Colman, N J; Gordon, C E; Crowther, M S; Letnic, M

2014-05-07

Disruption to species-interaction networks caused by irruptions of herbivores and mesopredators following extirpation of apex predators is a global driver of ecosystem reorganization and biodiversity loss. Most studies of apex predators' ecological roles focus on effects arising from their interactions with herbivores or mesopredators in isolation, but rarely consider how the effects of herbivores and mesopredators interact. Here, we provide evidence that multiple cascade pathways induced by lethal control of an apex predator, the dingo, drive unintended shifts in forest ecosystem structure. We compared mammal assemblages and understorey structure at seven sites in southern Australia. Each site comprised an area where dingoes were poisoned and an area without control. The effects of dingo control on mammals scaled with body size. Activity of herbivorous macropods, arboreal mammals and a mesopredator, the red fox, were greater, but understorey vegetation sparser and abundances of small mammals lower, where dingoes were controlled. Structural equation modelling suggested that both predation by foxes and depletion of understorey vegetation by macropods were related to small mammal decline at poisoned sites. Our study suggests that apex predators' suppressive effects on herbivores and mesopredators occur simultaneously and should be considered in tandem in order to appreciate the extent of apex predators' indirect effects.

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

PubMed Central

Happel, Max F.K.

2015-01-01

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species. Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning). PMID:26556300

Lethal control of an apex predator has unintended cascading effects on forest mammal assemblages

PubMed Central

Colman, N. J.; Gordon, C. E.; Crowther, M. S.; Letnic, M.

2014-01-01

Disruption to species-interaction networks caused by irruptions of herbivores and mesopredators following extirpation of apex predators is a global driver of ecosystem reorganization and biodiversity loss. Most studies of apex predators' ecological roles focus on effects arising from their interactions with herbivores or mesopredators in isolation, but rarely consider how the effects of herbivores and mesopredators interact. Here, we provide evidence that multiple cascade pathways induced by lethal control of an apex predator, the dingo, drive unintended shifts in forest ecosystem structure. We compared mammal assemblages and understorey structure at seven sites in southern Australia. Each site comprised an area where dingoes were poisoned and an area without control. The effects of dingo control on mammals scaled with body size. Activity of herbivorous macropods, arboreal mammals and a mesopredator, the red fox, were greater, but understorey vegetation sparser and abundances of small mammals lower, where dingoes were controlled. Structural equation modelling suggested that both predation by foxes and depletion of understorey vegetation by macropods were related to small mammal decline at poisoned sites. Our study suggests that apex predators’ suppressive effects on herbivores and mesopredators occur simultaneously and should be considered in tandem in order to appreciate the extent of apex predators’ indirect effects. PMID:24619441

Under What Assumptions Do Site-by-Treatment Instruments Identify Average Causal Effects?

ERIC Educational Resources Information Center

Reardon, Sean F.; Raudenbush, Stephen W.

2011-01-01

The purpose of this paper is to clarify the assumptions that must be met if this--multiple site, multiple mediator--strategy, hereafter referred to as "MSMM," is to identify the average causal effects (ATE) in the populations of interest. The authors' investigation of the assumptions of the multiple-mediator, multiple-site IV model demonstrates…

Simultaneous Detection of c-Fos Activation from Mesolimbic and Mesocortical Dopamine Reward Sites Following Naive Sugar and Fat Ingestion in Rats.

PubMed

Dela Cruz, Julie A D; Coke, Tricia; Bodnar, Richard J

2016-08-24

This study uses cellular c-fos activation to assess effects of novel ingestion of fat and sugar on brain dopamine (DA) pathways in rats. Intakes of sugars and fats are mediated by their innate attractions as well as learned preferences. Brain dopamine, especially meso-limbic and meso-cortical projections from the ventral tegmental area (VTA), has been implicated in both of these unlearned and learned responses. The concept of distributed brain networks, wherein several sites and transmitter/peptide systems interact, has been proposed to mediate palatable food intake, but there is limited evidence empirically demonstrating such actions. Thus, sugar intake elicits DA release and increases c-fos-like immunoreactivity (FLI) from individual VTA DA projection zones including the nucleus accumbens (NAC), amygdala (AMY) and medial prefrontal cortex (mPFC) as well as the dorsal striatum. Further, central administration of selective DA receptor antagonists into these sites differentially reduce acquisition and expression of conditioned flavor preferences elicited by sugars or fats. One approach by which to determine whether these sites interacted as a distributed brain network in response to sugar or fat intake would be to simultaneous evaluate whether the VTA and its major mesotelencephalic DA projection zones (prelimbic and infralimbic mPFC, core and shell of the NAc, basolateral and central-cortico-medial AMY) as well as the dorsal striatum would display coordinated and simultaneous FLI activation after oral, unconditioned intake of corn oil (3.5%), glucose (8%), fructose (8%) and saccharin (0.2%) solutions. This approach is a successful first step in identifying the feasibility of using cellular c-fos activation simultaneously across relevant brain sites to study reward-related learning in ingestion of palatable food in rodents.

LITERATURE REVIEW OF MOLECULAR METHODS FOR SIMULTANEOUS DETECTION OF PATHOGENS IN WATER

EPA Science Inventory

This literature search is a review of molecular technologies (qPCR, microarray, microfluidics and lab-on-a-chip) for simultaneous detection of multiple waterborne pathogens in order to understand the state of the technology. The search content focuses on: pathogen detection witho...

Population responses in primary auditory cortex simultaneously represent the temporal envelope and periodicity features in natural speech.

PubMed

Abrams, Daniel A; Nicol, Trent; White-Schwoch, Travis; Zecker, Steven; Kraus, Nina

2017-05-01

Speech perception relies on a listener's ability to simultaneously resolve multiple temporal features in the speech signal. Little is known regarding neural mechanisms that enable the simultaneous coding of concurrent temporal features in speech. Here we show that two categories of temporal features in speech, the low-frequency speech envelope and periodicity cues, are processed by distinct neural mechanisms within the same population of cortical neurons. We measured population activity in primary auditory cortex of anesthetized guinea pig in response to three variants of a naturally produced sentence. Results show that the envelope of population responses closely tracks the speech envelope, and this cortical activity more closely reflects wider bandwidths of the speech envelope compared to narrow bands. Additionally, neuronal populations represent the fundamental frequency of speech robustly with phase-locked responses. Importantly, these two temporal features of speech are simultaneously observed within neuronal ensembles in auditory cortex in response to clear, conversation, and compressed speech exemplars. Results show that auditory cortical neurons are adept at simultaneously resolving multiple temporal features in extended speech sentences using discrete coding mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Micro-optics for simultaneous multi-spectral imaging applied to chemical/biological and IED detection

NASA Astrophysics Data System (ADS)

Hinnrichs, Michele

2012-06-01

Using diffractive micro-lenses configured in an array and placed in close proximity to the focal plane array will enable a small compact simultaneous multispectral imaging camera. This approach can be applied to spectral regions from the ultraviolet (UV) to the long-wave infrared (LWIR). The number of simultaneously imaged spectral bands is determined by the number of individually configured diffractive optical micro-lenses (lenslet) in the array. Each lenslet images at a different wavelength determined by the blaze and set at the time of manufacturing based on application. In addition, modulation of the focal length of the lenslet array with piezoelectric or electro-static actuation will enable spectral band fill-in allowing hyperspectral imaging. Using the lenslet array with dual-band detectors will increase the number of simultaneous spectral images by a factor of two when utilizing multiple diffraction orders. Configurations and concept designs will be presented for detection application for biological/chemical agents, buried IED's and reconnaissance. The simultaneous detection of multiple spectral images in a single frame of data enhances the image processing capability by eliminating temporal differences between colors and enabling a handheld instrument that is insensitive to motion.

Case report: multifocal subchondral stress fractures of the femoral heads and tibial condyles in a young military recruit.

PubMed

Yoon, Pil Whan; Yoo, Jeong Joon; Yoon, Kang Sup; Kim, Hee Joong

2012-03-01

Subchondral stress fractures of the femoral head may be either of the insufficiency-type with poor quality bone or the fatigue-type with normal quality bone but subject to high repetitive stresses. Unlike osteonecrosis, multiple site involvement rarely has been reported for subchondral stress fractures. We describe a case of multifocal subchondral stress fractures involving femoral heads and medial tibial condyles bilaterally within 2 weeks. A 27-year-old military recruit began having left knee pain after 2 weeks of basic training, without any injury. Subsequently, right knee, right hip, and left hip pain developed sequentially within 2 weeks. The diagnosis of multifocal subchondral stress fracture was confirmed by plain radiographs and MR images. Nonoperative treatment of the subchondral stress fractures of both medial tibial condyles and the left uncollapsed femoral head resulted in resolution of symptoms. The collapsed right femoral head was treated with a fibular strut allograft to restore congruity and healed without further collapse. There has been one case report in which an insufficiency-type subchondral stress fracture of the femoral head and medial femoral condyle occurred within a 2-year interval. Because the incidence of bilateral subchondral stress fractures of the femoral head is low and multifocal involvement has not been reported, multifocal subchondral stress fractures can be confused with multifocal osteonecrosis. Our case shows that subchondral stress fractures can occur in multiple sites almost simultaneously.

Temporal dynamics of direct N2O fluxes from agro-ecosystems in cold climates: importance of year-round measurements in multiple cropping systems

NASA Astrophysics Data System (ADS)

Wagner-Riddle, C.; Tenuta, M.

2014-12-01

Soil N2O fluxes (direct emissions) are highly variable in time and space due to soil, weather and management drivers. In cold climates, freeze/thaw cycles and short growing seasons can enhance soil N2O production contributing to the temporal variability of fluxes. Year-round measurements of N2O fluxes in multiple cropping systems are needed to decrease the uncertainty of annual emission estimates and to devise mitigation practices for emission reduction in cold climates. We have deployed a micrometeorological flux-gradient approach coupled to a tunable diode laser absorption spectroscopy system at two long-term sites in Canada: Elora, Ontario (2000-2014) and Glenlea, Manitoba (2006-2014). Quasi-simultaneous half-hourly flux measurements on four 4-ha fields within a level and aerodynamically homogeneous landscape were obtained allowing for comparison of crop type and/or management practices within and between years. Annual crops such as corn, soybeans, wheat, and barley received typical inorganic fertilizer and/or manure applications, and best management practices such as timing of application and reduced tillage were studied. Perennial grass-alfalfa hayfields were compared to annual crops during selected time periods. Here we synthesize the long-term datasets from these two sites, and quantify the overall contribution of non-growing season (mainly freeze/thaw cycles) and growing season (mainly nitrogen application) to annual emission totals. Uncertainties of regional estimates for cold-climates will be assessed using these long-term datasets.

Quantum-enhanced metrology for multiple phase estimation with noise

PubMed Central

Yue, Jie-Dong; Zhang, Yu-Ran; Fan, Heng

2014-01-01

We present a general quantum metrology framework to study the simultaneous estimation of multiple phases in the presence of noise as a discretized model for phase imaging. This approach can lead to nontrivial bounds of the precision for multiphase estimation. Our results show that simultaneous estimation (SE) of multiple phases is always better than individual estimation (IE) of each phase even in noisy environment. The utility of the bounds of multiple phase estimation for photon loss channels is exemplified explicitly. When noise is low, those bounds possess the Heisenberg scale showing quantum-enhanced precision with the O(d) advantage for SE, where d is the number of phases. However, this O(d) advantage of SE scheme in the variance of the estimation may disappear asymptotically when photon loss becomes significant and then only a constant advantage over that of IE scheme demonstrates. Potential application of those results is presented. PMID:25090445

Realization of multiple orbital angular momentum modes simultaneously through four-dimensional antenna arrays.

PubMed

Sun, Chao; Yang, Shiwen; Chen, Yikai; Guo, Jixin; Qu, Shiwei

2018-01-09

Electromagnetic waves carrying orbital angular momentum (OAM) in radio frequency range have drawn great attention owing to its potential applications in increasing communication capacity. In this paper, both single-pole single-throw (SPST) switches and single-pole double-throw (SPDT) switches are designed and implemented. Optimal time sequence allows four-dimensional (4-D) circular antenna array to generate multiple OAM-carrying waves as well as enhance the field intensity of each OAM-carrying wave. A novel experimental platform is developed to measure the phase distribution when the transmitting antenna and the receiving antenna operate at different frequencies. The good agreement between the measurement and simulation results demonstrate that 4-D circular antenna array is able to generate multiple OAM modes simultaneously. Furthermore, the superiority of the 4-D circular antenna array in receiving and demodulating multiple OAM-carrying signals is validated through the filter and bit error rate (BER) simulations.

Multiple-mouse MRI with multiple arrays of receive coils.

PubMed

Ramirez, Marc S; Esparza-Coss, Emilio; Bankson, James A

2010-03-01

Compared to traditional single-animal imaging methods, multiple-mouse MRI has been shown to dramatically improve imaging throughput and reduce the potentially prohibitive cost for instrument access. To date, up to a single radiofrequency coil has been dedicated to each animal being simultaneously scanned, thus limiting the sensitivity, flexibility, and ultimate throughput. The purpose of this study was to investigate the feasibility of multiple-mouse MRI with a phased-array coil dedicated to each animal. A dual-mouse imaging system, consisting of a pair of two-element phased-array coils, was developed and used to achieve acceleration factors greater than the number of animals scanned at once. By simultaneously scanning two mice with a retrospectively gated cardiac cine MRI sequence, a 3-fold acceleration was achieved with signal-to-noise ratio in the heart that is equivalent to that achieved with an unaccelerated scan using a commercial mouse birdcage coil. (c) 2010 Wiley-Liss, Inc.

Multi-pixel high-resolution three-dimensional imaging radar

NASA Technical Reports Server (NTRS)

Cooper, Ken B. (Inventor); Dengler, Robert J. (Inventor); Siegel, Peter H. (Inventor); Chattopadhyay, Goutam (Inventor); Ward, John S. (Inventor); Juan, Nuria Llombart (Inventor); Bryllert, Tomas E. (Inventor); Mehdi, Imran (Inventor); Tarsala, Jan A. (Inventor)

2012-01-01

A three-dimensional imaging radar operating at high frequency e.g., 670 GHz radar using low phase-noise synthesizers and a fast chirper to generate a frequency-modulated continuous-wave (FMCW) waveform, is disclosed that operates with a multiplexed beam to obtain range information simultaneously on multiple pixels of a target. A source transmit beam may be divided by a hybrid coupler into multiple transmit beams multiplexed together and directed to be reflected off a target and return as a single receive beam which is demultiplexed and processed to reveal range information of separate pixels of the target associated with each transmit beam simultaneously. The multiple transmit beams may be developed with appropriate optics to be temporally and spatially differentiated before being directed to the target. Temporal differentiation corresponds to a different intermediate frequencies separating the range information of the multiple pixels. Collinear transmit beams having differentiated polarizations may also be implemented.

Functional profiles reveal unique ecological roles of various biological soil crust organisms

USGS Publications Warehouse

Bowker, M.A.; Mau, R.L.; Maestre, F.T.; Escolar, C.; Castillo-Monroy, A. P.

2011-01-01

1. At the heart of the body of research on biodiversity effects on ecosystem function is the debate over whether different species tend to be functionally singular or redundant. When we consider ecosystem multi-function, the provision of multiple ecosystem functions simultaneously, we may find that seemingly redundant species may in fact play unique roles in ecosystems. 2. Over the last few decades, the significance of biological soil crusts (BSCs) as ecological boundaries and ecosystem engineers, and their multi-functional nature, has become increasingly well documented. We compiled 'functional profiles' of the organisms in this understudied community, to determine whether functional singularity emerges when multiple ecosystem functions are considered. 3. In two data sets, one representing multiple sites around the semi-arid regions of Spain (regional scale), and another from a single site in central Spain (local scale), we examined correlations between the abundance or frequency of BSC species in a community, and multiple surrogates of ecosystem functioning. There was a wide array of apparent effects of species on specific functions. 4. Notably, in gypsiferous soils and at regional scale, we found that indicators of carbon (C) and phosphorus cycling were apparently suppressed and promoted by the lichens Diploschistes diacapsis and Squamarina lentigera, respectively. The moss Pleurochaete squarrosa appears to promote C cycling in calcareous soils at this spatial scale. At the local scale in gypsiferous soils, D. diacapsis positively correlated with carbon cycling, but negatively with nitrogen cycling, whereas numerous lichens exhibited the opposite profile. 5. We found a high degree of functional singularity, i.e. that species were highly individualistic in their effects on multiple functions. Many functional attributes were not easily predictable from existing functional grouping systems based primarily on morphology. 6. Our results suggest that maintaining species-rich BSC communities is crucial to maintain the overall functionality of ecosystems dominated by these organisms, and that dominance and the outcome of competition could be highly influential in the determination of such functionality. ?? 2011 The Authors. Functional Ecology ?? 2011 British Ecological Society.

Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems

PubMed Central

Harari, Colin M.; Magagna, Michelle; Bedoya, Mariajose; Lee, Fred T.; Lubner, Meghan G.; Hinshaw, J. Louis; Ziemlewicz, Timothy

2016-01-01

Purpose To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. Materials and Methods All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. Results On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. Conclusion The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. © RSNA, 2015 PMID:26133361

Development of Multiple-Element Flame Emission Spectrometer Using CCD Detection

ERIC Educational Resources Information Center

Seney, Caryn S.; Sinclair, Karen V.; Bright, Robin M.; Momoh, Paul O.; Bozeman, Amelia D.

2005-01-01

The full wavelength coverage of charge coupled device (CCD) detector when coupled with an echelle spectrography, the system allows for simultaneously multiple element spectroscopy to be performed. The multiple-element flame spectrometer was built and characterized through the analysis of environmentally significant elements such as Ca, K, Na, Cu,…

Endogenous Task Shift Processes in Relapsing-Remitting Multiple Sclerosis

ERIC Educational Resources Information Center

Stablum, F.; Meligrana, L.; Sgaramella, T.; Bortolon, F.; Toso, V.

2004-01-01

This paper reports a study that was aimed to evaluate executive functions in relapsing-remitting multiple sclerosis patients. The groups tested comprised 22 relapsing-remitting multiple sclerosis patients, and 22 non-brain damaged controls. When one is engaged in two speeded tasks, not simultaneously but with some form of alternation, it is slower…

15 CFR 921.33 - Boundary changes, amendments to the management plan, and addition of multiple-site components.

Code of Federal Regulations, 2010 CFR

2010-01-01

... management plan, and addition of multiple-site components. 921.33 Section 921.33 Commerce and Foreign Trade... management plan, and addition of multiple-site components. (a) Changes in the boundary of a Reserve and major... management plan shall address goals and objectives for all components of the multi-site Reserve and the...

Web Transfer Over Satellites Being Improved

NASA Technical Reports Server (NTRS)

Allman, Mark

1999-01-01

Extensive research conducted by NASA Lewis Research Center's Satellite Networks and Architectures Branch and the Ohio University has demonstrated performance improvements in World Wide Web transfers over satellite-based networks. The use of a new version of the Hypertext Transfer Protocol (HTTP) reduced the time required to load web pages over a single Transmission Control Protocol (TCP) connection traversing a satellite channel. However, an older technique of simultaneously making multiple requests of a given server has been shown to provide even faster transfer time. Unfortunately, the use of multiple simultaneous requests has been shown to be harmful to the network in general. Therefore, we are developing new mechanisms for the HTTP protocol which may allow a single request at any given time to perform as well as, or better than, multiple simultaneous requests. In the course of study, we also demonstrated that the time for web pages to load is at least as short via a satellite link as it is via a standard 28.8-kbps dialup modem channel. This demonstrates that satellites are a viable means of accessing the Internet.

SATCHMO-JS: a webserver for simultaneous protein multiple sequence alignment and phylogenetic tree construction.

PubMed

Hagopian, Raffi; Davidson, John R; Datta, Ruchira S; Samad, Bushra; Jarvis, Glen R; Sjölander, Kimmen

2010-07-01

We present the jump-start simultaneous alignment and tree construction using hidden Markov models (SATCHMO-JS) web server for simultaneous estimation of protein multiple sequence alignments (MSAs) and phylogenetic trees. The server takes as input a set of sequences in FASTA format, and outputs a phylogenetic tree and MSA; these can be viewed online or downloaded from the website. SATCHMO-JS is an extension of the SATCHMO algorithm, and employs a divide-and-conquer strategy to jump-start SATCHMO at a higher point in the phylogenetic tree, reducing the computational complexity of the progressive all-versus-all HMM-HMM scoring and alignment. Results on a benchmark dataset of 983 structurally aligned pairs from the PREFAB benchmark dataset show that SATCHMO-JS provides a statistically significant improvement in alignment accuracy over MUSCLE, Multiple Alignment using Fast Fourier Transform (MAFFT), ClustalW and the original SATCHMO algorithm. The SATCHMO-JS webserver is available at http://phylogenomics.berkeley.edu/satchmo-js. The datasets used in these experiments are available for download at http://phylogenomics.berkeley.edu/satchmo-js/supplementary/.

Simultaneous acquisition of multiple auditory-motor transformations in speech

PubMed Central

Rochet-Capellan, Amelie; Ostry, David J.

2011-01-01

The brain easily generates the movement that is needed in a given situation. Yet surprisingly, the results of experimental studies suggest that it is difficult to acquire more than one skill at a time. To do so, it has generally been necessary to link the required movement to arbitrary cues. In the present study, we show that speech motor learning provides an informative model for the acquisition of multiple sensorimotor skills. During training, subjects are required to repeat aloud individual words in random order while auditory feedback is altered in real-time in different ways for the different words. We find that subjects can quite readily and simultaneously modify their speech movements to correct for these different auditory transformations. This multiple learning occurs effortlessly without explicit cues and without any apparent awareness of the perturbation. The ability to simultaneously learn several different auditory-motor transformations is consistent with the idea that in speech motor learning, the brain acquires instance specific memories. The results support the hypothesis that speech motor learning is fundamentally local. PMID:21325534

Homology-integrated CRISPR-Cas (HI-CRISPR) system for one-step multigene disruption in Saccharomyces cerevisiae.

PubMed

Bao, Zehua; Xiao, Han; Liang, Jing; Zhang, Lu; Xiong, Xiong; Sun, Ning; Si, Tong; Zhao, Huimin

2015-05-15

One-step multiple gene disruption in the model organism Saccharomyces cerevisiae is a highly useful tool for both basic and applied research, but it remains a challenge. Here, we report a rapid, efficient, and potentially scalable strategy based on the type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated proteins (Cas) system to generate multiple gene disruptions simultaneously in S. cerevisiae. A 100 bp dsDNA mutagenizing homologous recombination donor is inserted between two direct repeats for each target gene in a CRISPR array consisting of multiple donor and guide sequence pairs. An ultrahigh copy number plasmid carrying iCas9, a variant of wild-type Cas9, trans-encoded RNA (tracrRNA), and a homology-integrated crRNA cassette is designed to greatly increase the gene disruption efficiency. As proof of concept, three genes, CAN1, ADE2, and LYP1, were simultaneously disrupted in 4 days with an efficiency ranging from 27 to 87%. Another three genes involved in an artificial hydrocortisone biosynthetic pathway, ATF2, GCY1, and YPR1, were simultaneously disrupted in 6 days with 100% efficiency. This homology-integrated CRISPR (HI-CRISPR) strategy represents a powerful tool for creating yeast strains with multiple gene knockouts.

Simultaneous Inference Procedures for Means.

ERIC Educational Resources Information Center

Krishnaiah, P. R.

Some aspects of simultaneous tests for means are reviewed. Specifically, the comparison of univariate or multivariate normal populations based on the values of the means or mean vectors when the variances or covariance matrices are equal is discussed. Tukey's and Dunnett's tests for multiple comparisons of means, Scheffe's method of examining…

Effects of Condensation on Peri-implant Bone Density and Remodeling

PubMed Central

Wang, L.; Wu, Y.; Perez, K.C.; Hyman, S.; Brunski, J.B.; Tulu, U.; Bao, C.; Salmon, B.; Helms, J.A.

2017-01-01

Bone condensation is thought to densify interfacial bone and thus improve implant primary stability, but scant data substantiate either claim. We developed a murine oral implant model to test these hypotheses. Osteotomies were created in healed maxillary extraction sites 1) by drilling or 2) by drilling followed by stepwise condensation with tapered osteotomes. Condensation increased interfacial bone density, as measured by a significant change in bone volume/total volume and trabecular spacing, but it simultaneously damaged the bone. On postimplant day 1, the condensed bone interface exhibited microfractures and osteoclast activity. Finite element modeling, mechanical testing, and immunohistochemical analyses at multiple time points throughout the osseointegration period demonstrated that condensation caused very high interfacial strains, marginal bone resorption, and no improvement in implant stability. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability. PMID:28048963

Effects of Condensation on Peri-implant Bone Density and Remodeling.

PubMed

Wang, L; Wu, Y; Perez, K C; Hyman, S; Brunski, J B; Tulu, U; Bao, C; Salmon, B; Helms, J A

2017-04-01

Bone condensation is thought to densify interfacial bone and thus improve implant primary stability, but scant data substantiate either claim. We developed a murine oral implant model to test these hypotheses. Osteotomies were created in healed maxillary extraction sites 1) by drilling or 2) by drilling followed by stepwise condensation with tapered osteotomes. Condensation increased interfacial bone density, as measured by a significant change in bone volume/total volume and trabecular spacing, but it simultaneously damaged the bone. On postimplant day 1, the condensed bone interface exhibited microfractures and osteoclast activity. Finite element modeling, mechanical testing, and immunohistochemical analyses at multiple time points throughout the osseointegration period demonstrated that condensation caused very high interfacial strains, marginal bone resorption, and no improvement in implant stability. Collectively, these multiscale analyses demonstrate that condensation does not positively contribute to implant stability.

A Web Based Collaborative Design Environment for Spacecraft

NASA Technical Reports Server (NTRS)

Dunphy, Julia

1998-01-01

In this era of shrinking federal budgets in the USA we need to dramatically improve our efficiency in the spacecraft engineering design process. We have come up with a method which captures much of the experts' expertise in a dataflow design graph: Seamlessly connectable set of local and remote design tools; Seamlessly connectable web based design tools; and Web browser interface to the developing spacecraft design. We have recently completed our first web browser interface and demonstrated its utility in the design of an aeroshell using design tools located at web sites at three NASA facilities. Multiple design engineers and managers are now able to interrogate the design engine simultaneously and find out what the design looks like at any point in the design cycle, what its parameters are, and how it reacts to adverse space environments.

[Analysis of H2S/PH3/NH3/AsH3/Cl2 by Full-Spectral Flame Photometric Detector].

PubMed

Ding, Zhi-jun; Wang, Pu-hong; Li, Zhi-jun; Du, Bin; Guo, Lei; Yu, Jian-hua

2015-07-01

Flame photometric analysis technology has been proven to be a rapid and sensitive method for sulfur and phosphorus detection. It has been widely used in environmental inspections, pesticide detection, industrial and agricultural production. By improving the design of the traditional flame photometric detector, using grating and CCD sensor array as a photoelectric conversion device, the types of compounds that can be detected were expanded. Instead of a single point of characteristic spectral lines, full spectral information has been used for qualitative and quantitative analysis of H2S, PH3, NH3, AsH3 and Cl2. Combined with chemometric method, flame photometric analysis technology is expected to become an alternative fast, real-time on-site detection technology to simultaneously detect multiple toxic and harmful gases.

Integrated Magneto-Electrochemical Sensor for Exosome Analysis.

PubMed

Jeong, Sangmoo; Park, Jongmin; Pathania, Divya; Castro, Cesar M; Weissleder, Ralph; Lee, Hakho

2016-02-23

Extracellular vesicles, including exosomes, are nanoscale membrane particles that carry molecular information on parental cells. They are being pursued as biomarkers of cancers that are difficult to detect or serially follow. Here we present a compact sensor technology for rapid, on-site exosome screening. The sensor is based on an integrated magneto-electrochemical assay: exosomes are immunomagnetically captured from patient samples and profiled through electrochemical reaction. By combining magnetic enrichment and enzymatic amplification, the approach enables (i) highly sensitive, cell-specific exosome detection and (ii) sensor miniaturization and scale-up for high-throughput measurements. As a proof-of-concept, we implemented a portable, eight-channel device and applied it to screen extracellular vesicles in plasma samples from ovarian cancer patients. The sensor allowed for the simultaneous profiling of multiple protein markers within an hour, outperforming conventional methods in assay sensitivity and speed.

Integrated Magneto-Electrochemical Sensor for Exosome Analysis

PubMed Central

Jeong, Sangmoo; Park, Jongmin; Pathania, Divya; Castro, Cesar M.; Weissleder, Ralph; Lee, Hakho

2016-01-01

Extracellular vesicles, including exosomes, are nanoscale vesicles that carry molecular information of parental cells. They are being pursued as biomarkers of cancers that are difficult to detect or serially follow. Here we present a compact sensor technology for rapid, on-site exosome screening. The sensor is based on an integrated magnetic-electrochemical assay: exosomes are immunomagnetically captured from patient samples, and profiled through electrochemical reaction. By combining magnetic enrichment and enzymatic amplification, the approach enables i) highly sensitive, cell-specific exosome detection, and ii) sensor miniaturization and scale-up for high throughput measurements. As a proof-of-concept, we implemented a portable, eight-channel device, and applied it to screen extracellular vesicles in plasma samples from ovarian cancer patients. The sensor allowed for the profiling of multiple protein markers simultaneously within an hour, outperforming conventional methods in assay sensitivity and speed. PMID:26808216

Modeling Environment for Total Risk-4M

EPA Science Inventory

MENTOR-4M uses an integrated, mechanistically consistent, source-to-dose modeling framework to quantify simultaneous exposures and doses of individuals and populations to multiple contaminants. It is an implementation of the MENTOR system for exposures to Multiple contaminants fr...

Multiple environmental contexts and preterm birth risks

EPA Science Inventory

Human health is affected by simultaneous exposure to numerous stressors and amenities, but research often focuses on single exposure models. To address this, a United States county-level Multiple Environmental Domain Index (MEDI) was constructed with data representing five envir...

Deblending of simultaneous-source data using iterative seislet frame thresholding based on a robust slope estimation

NASA Astrophysics Data System (ADS)

Zhou, Yatong; Han, Chunying; Chi, Yue

2018-06-01

In a simultaneous source survey, no limitation is required for the shot scheduling of nearby sources and thus a huge acquisition efficiency can be obtained but at the same time making the recorded seismic data contaminated by strong blending interference. In this paper, we propose a multi-dip seislet frame based sparse inversion algorithm to iteratively separate simultaneous sources. We overcome two inherent drawbacks of traditional seislet transform. For the multi-dip problem, we propose to apply a multi-dip seislet frame thresholding strategy instead of the traditional seislet transform for deblending simultaneous-source data that contains multiple dips, e.g., containing multiple reflections. The multi-dip seislet frame strategy solves the conflicting dip problem that degrades the performance of the traditional seislet transform. For the noise issue, we propose to use a robust dip estimation algorithm that is based on velocity-slope transformation. Instead of calculating the local slope directly using the plane-wave destruction (PWD) based method, we first apply NMO-based velocity analysis and obtain NMO velocities for multi-dip components that correspond to multiples of different orders, then a fairly accurate slope estimation can be obtained using the velocity-slope conversion equation. An iterative deblending framework is given and validated through a comprehensive analysis over both numerical synthetic and field data examples.

integIRTy: a method to identify genes altered in cancer by accounting for multiple mechanisms of regulation using item response theory.

PubMed

Tong, Pan; Coombes, Kevin R

2012-11-15

Identifying genes altered in cancer plays a crucial role in both understanding the mechanism of carcinogenesis and developing novel therapeutics. It is known that there are various mechanisms of regulation that can lead to gene dysfunction, including copy number change, methylation, abnormal expression, mutation and so on. Nowadays, all these types of alterations can be simultaneously interrogated by different types of assays. Although many methods have been proposed to identify altered genes from a single assay, there is no method that can deal with multiple assays accounting for different alteration types systematically. In this article, we propose a novel method, integration using item response theory (integIRTy), to identify altered genes by using item response theory that allows integrated analysis of multiple high-throughput assays. When applied to a single assay, the proposed method is more robust and reliable than conventional methods such as Student's t-test or the Wilcoxon rank-sum test. When used to integrate multiple assays, integIRTy can identify novel-altered genes that cannot be found by looking at individual assay separately. We applied integIRTy to three public cancer datasets (ovarian carcinoma, breast cancer, glioblastoma) for cross-assay type integration which all show encouraging results. The R package integIRTy is available at the web site http://bioinformatics.mdanderson.org/main/OOMPA:Overview. kcoombes@mdanderson.org. Supplementary data are available at Bioinformatics online.

Simultaneous single-shot readout of multi-qubit circuits using a traveling-wave parametric amplifier

NASA Astrophysics Data System (ADS)

O'Brien, Kevin

Observing and controlling the state of ever larger quantum systems is critical for advancing quantum computation. Utilizing a Josephson traveling wave parametric amplifier (JTWPA), we demonstrate simultaneous multiplexed single shot readout of 10 transmon qubits in a planar architecture. We employ digital image sideband rejection to eliminate noise at the image frequencies. We quantify crosstalk and infidelity due to simultaneous readout and control of multiple qubits. Based on current amplifier technology, this approach can scale to simultaneous readout of at least 20 qubits. This work was supported by the Army Research Office.

The ultrasound brain helmet: early human feasibility study of multiple simultaneous 3D scans of cerebral vasculature

NASA Astrophysics Data System (ADS)

Lindsey, Brooks D.; Ivancevich, Nikolas M.; Whitman, John; Light, Edward; Fronheiser, Matthew; Nicoletto, Heather A.; Laskowitz, Daniel T.; Smith, Stephen W.

2009-02-01

We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple simultaneous real-time 3D scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the skull. The transducer hardware and software of the Volumetrics Medical Imaging real-time 3D scanner were modified to support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous 64° pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128° sector, two simultaneous parasagittal images merged into a 128° × 64° C-mode plane, and a simultaneous 64° axial image. Real-time 3D color Doppler images acquired in initial clinical studies after contrast injection demonstrate flow in several representative blood vessels. An offline Doppler rendering of data from two transducers simultaneously scanning via the temporal windows provides an early visualization of the flow in vessels on both sides of the brain. The long-term goal is to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet transmission, thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.

SITEQUAL--A User's Guide: Computerized Site Evaluation for 14 Southern Hardwood Species

Treesearch

Constance A. Harrington; Bettina M. Casson

1986-01-01

An interactive computer program, SITEQUAL, has been developed from the widely-used Baker and Broadfoot field guides, which evaluate site quality for 14 southern hardwood tree species. The SITEQUAL program calculates site index for all species simultaneously and provides a breakdown of site index into the component contributions by each of the four major soil factors...

Flight Test Evaluation of an Unmanned Aircraft System Traffic Management (UTM) Concept for Multiple Beyond-Visual-Line-of-Sight (BVLOS) Operations

NASA Technical Reports Server (NTRS)

Johnson, Marcus; Jung, Jaewoo; Rios, Joseph; Mercer, Joey; Homola, Jeffrey; Prevot, Thomas; Mulfinger, Daniel; Kopardekar, Parimal

2017-01-01

This study evaluates a traffic management concept designed to enable simultaneous operations of multiple small unmanned aircraft systems (UAS) in the national airspace system (NAS). A five-day flight-test activity is described that examined the feasibility of operating multiple UAS beyond visual line of sight (BVLOS) of their respective operators in the same airspace. Over the five-day campaign, three groups of five flight crews operated a total of eleven different aircraft. Each group participated in four flight scenarios involving five simultaneous missions. Each vehicle was operated BVLOS up to 1.5 miles from the pilot in command. Findings and recommendations are presented to support the feasibility and safety of routine BVLOS operations for small UAS.

Flight Test Evaluation of an Unmanned Aircraft System Traffic Management (UTM) Concept for Multiple Beyond-Visual-Line-of-Sight Operations

NASA Technical Reports Server (NTRS)

Johnson, Marcus; Jung, Jaewoo; Rios, Joseph; Mercer, Joey; Homola, Jeffrey; Prevot, Thomas; Mulfinger, Daniel; Kopardekar, Parimal

2017-01-01

This study evaluates a traffic management concept designed to enable simultaneous operations of multiple small unmanned aircraft systems (UAS) in the national airspace system (NAS). A five-day flight-test activity is described that examined the feasibility of operating multiple UAS beyond visual line of sight (BVLOS) of their respective operators in the same airspace. Over the five-day campaign, three groups of five flight crews operated a total of eleven different aircraft. Each group participated in four flight scenarios involving five simultaneous missions. Each vehicle was operated BVLOS up to 1.5 miles from the pilot in command. Findings and recommendations are presented to support the feasibility and safety of routine BVLOS operations for small UAS.

Novel microbial fuel cell design to operate with different wastewaters simultaneously.

PubMed

Mathuriya, Abhilasha Singh

2016-04-01

A novel single cathode chamber and multiple anode chamber microbial fuel cell design (MAC-MFC) was developed by incorporating multiple anode chambers into a single unit and its performance was checked. During 60 days of operation, performance of MAC-MFC was assessed and compared with standard single anode/cathode chamber microbial fuel cell (SC-MFC). The tests showed that MAC-MFC generated stable and higher power outputs compared with SC-MFC and each anode chamber contributed efficiently. Further, MAC-MFCs were incorporated with different wastewaters in different anode chambers and their behavior in MFC performance was observed. MAC-MFC efficiently treated multiple wastewaters simultaneously at low cost and small space, which claims its candidature for future possible scale-up applications. Copyright © 2015. Published by Elsevier B.V.

Global Proteome Analyses of Lysine Acetylation and Succinylation Reveal the Widespread Involvement of both Modification in Metabolism in the Embryo of Germinating Rice Seed.

PubMed

He, Dongli; Wang, Qiong; Li, Ming; Damaris, Rebecca Njeri; Yi, Xingling; Cheng, Zhongyi; Yang, Pingfang

2016-03-04

Regulation of rice seed germination has been shown to mainly occur at post-transcriptional levels, of which the changes on proteome status is a major one. Lysine acetylation and succinylation are two prevalent protein post-translational modifications (PTMs) involved in multiple biological processes, especially for metabolism regulation. To investigate the potential mechanism controlling metabolism regulation in rice seed germination, we performed the lysine acetylation and succinylation analyses simultaneously. Using high-accuracy nano-LC-MS/MS in combination with the enrichment of lysine acetylated or succinylated peptides from digested embryonic proteins of 24 h after imbibition (HAI) rice seed, a total of 699 acetylated sites from 389 proteins and 665 succinylated sites from 261 proteins were identified. Among these modified lysine sites, 133 sites on 78 proteins were commonly modified by two PTMs. The overlapped PTM sites were more likely to be in polar acidic/basic amino acid regions and exposed on the protein surface. Both of the acetylated and succinylated proteins cover nearly all aspects of cellular functions. Ribosome complex and glycolysis/gluconeogenesis-related proteins were significantly enriched in both acetylated and succinylated protein profiles through KEGG enrichment and protein-protein interaction network analyses. The acetyl-CoA and succinyl-CoA metabolism-related enzymes were found to be extensively modified by both modifications, implying the functional interaction between the two PTMs. This study provides a rich resource to examine the modulation of the two PTMs on the metabolism pathway and other biological processes in germinating rice seed.

mTORC1 promotes T-bet phosphorylation to regulate Th1 differentiation

PubMed Central

Chornoguz, Olesya; Hagan, Robert S.; Haile, Azeb; Arwood, Matthew L.; Gamper, Christopher J.; Banerjee, Arnob; Powell, Jonathan D.

2017-01-01

CD4+ T cells lacking the mTORC1 activator Rheb fail to secrete IFNγ under Th1 polarizing conditions. We hypothesized that this phenotype is due to defects in regulation of the canonical Th1 transcription factor T-bet at the level of protein phosphorylation downstream of mTORC1. To test this hypothesis, we employed targeted mass-spectrometry proteomic analysis – multiple reaction monitoring mass spectrometry (MRM-MS). We used MRM-MS to detect and quantify predicted phospho-peptides derived from T-bet. By analyzing activated murine WT and Rheb deficient CD4+ T cells, as well as murine CD4+ T cells activated in the presence of rapamycin, a pharmacologic inhibitor of mTORC1, we were able to identify 6 T-bet phosphorylation sites. Five of these are novel, and 4 sites are consistently dephosphorylated in both Rheb deficient CD4+ T-cells and T-cells treated with rapamycin, suggesting mTORC1 signaling controls their phosphorylation. Alanine mutagenesis of each of the 6 phosphorylation sites was tested for the ability to impair IFNγ expression. Single phosphorylation site mutants still support induction of IFNγ expression, however simultaneous mutation of 3 of the mTORC1-dependent sites results in significantly reduced IFNγ expression. The reduced activity of the triple mutant T-bet is associated with its failure to recruit chromatin remodeling complexes to the Ifng gene promoter. These results establish a novel mechanism by which mTORC1 regulates Th1 differentiation, through control of T-bet phosphorylation. PMID:28424242

Detection and clonal analysis of anaerobic bacteria associated to endodontic-periodontal lesions.

PubMed

Pereira, Cássio V; Stipp, Rafael N; Fonseca, Douglas C; Pereira, Luciano J; Höfling, José F

2011-12-01

Microbial agents in root canal systems can induce periodontal inflammation. The aims of this study are to detect anaerobic microorganisms in endodontic-periodontal lesions, determine the genetic diversity among them, and assess the simultaneous colonization of the pulp and periodontal microenvironments by a single clone. Twenty-seven teeth of patients with endodontic-periodontal lesions were selected. Samples were spread on an agar-blood medium, the detection of each species was performed using a polymerase chain reaction, and the determination of the simultaneous presence of the same species in the microenvironments by one or more clones was determined using arbitrarily primed PCR. Prevotella intermedia (Pi) was the most prevalent species of the colonies in periodontal pockets, whereas Porphyromonas gingivalis (Pg) and Pi were the more prevalent in root canals. Isolates of Pi and Pg were simultaneously identified in root canals and periodontal pockets. Eighteen percent of teeth exhibited the simultaneous colonization by Pg, Tannerella forsythia (previously T. forsythensis), and Porphyromonas endodontalis in the pulp and periodontal microenvironments. The presence of these species was noted even in niches from which no colonies were isolated. Seventeen different genotypes were found in periodontal and pulp sites, with the majority of sites colonized by one or two different genotypes. A high degree of genotype similarity was found for samples of Pg isolated from only one site as well as for those isolated from both microenvironments. Different clones of Pi and Pg with a high intraspecific genotype similarity were found to colonize the same anatomic sites in endodontic-periodontal infections.

Generation of mammalian cells stably expressing multiple genes at predetermined levels.

PubMed

Liu, X; Constantinescu, S N; Sun, Y; Bogan, J S; Hirsch, D; Weinberg, R A; Lodish, H F

2000-04-10

Expression of cloned genes at desired levels in cultured mammalian cells is essential for studying protein function. Controlled levels of expression have been difficult to achieve, especially for cell lines with low transfection efficiency or when expression of multiple genes is required. An internal ribosomal entry site (IRES) has been incorporated into many types of expression vectors to allow simultaneous expression of two genes. However, there has been no systematic quantitative analysis of expression levels in individual cells of genes linked by an IRES, and thus the broad use of these vectors in functional analysis has been limited. We constructed a set of retroviral expression vectors containing an IRES followed by a quantitative selectable marker such as green fluorescent protein (GFP) or truncated cell surface proteins CD2 or CD4. The gene of interest is placed in a multiple cloning site 5' of the IRES sequence under the control of the retroviral long terminal repeat (LTR) promoter. These vectors exploit the approximately 100-fold differences in levels of expression of a retrovirus vector depending on its site of insertion in the host chromosome. We show that the level of expression of the gene downstream of the IRES and the expression level and functional activity of the gene cloned upstream of the IRES are highly correlated in stably infected target cells. This feature makes our vectors extremely useful for the rapid generation of stably transfected cell populations or clonal cell lines expressing specific amounts of a desired protein simply by fluorescent activated cell sorting (FACS) based on the level of expression of the gene downstream of the IRES. We show how these vectors can be used to generate cells expressing high levels of the erythropoietin receptor (EpoR) or a dominant negative Smad3 protein and to generate cells expressing two different cloned proteins, Ski and Smad4. Correlation of a biologic effect with the level of expression of the protein downstream of the IRES provides strong evidence for the function of the protein placed upstream of the IRES.

The Multiple-Use of Accountability Assessments: Implications for the Process of Validation

ERIC Educational Resources Information Center

Koch, Martha J.

2014-01-01

Implications of the multiple-use of accountability assessments for the process of validation are examined. Multiple-use refers to the simultaneous use of results from a single administration of an assessment for its intended use and for one or more additional uses. A theoretical discussion of the issues for validation which emerge from…

Novel technique for repair of severed peripheral nerves in rats using polyurea crosslinked silica aerogel scaffold.

PubMed

Sabri, Firouzeh; Gerth, David; Tamula, George-Rudolph M; Phung, Thien-Chuong N; Lynch, Kyle J; Boughter, John D

2014-10-01

To design, synthesize, and test in vivo an aerogel-based top-open peripheral nerve scaffold to simultaneously support and guide multiple completely severed peripheral nerves in a rat model. Also, to explore options for immobilizing severed nerves on the aerogel material without the use of sutures resulting in reduced surgical time. A novel material and approach was developed for the reattachment of severed peripheral nerves. Nerve confinement and alignment in this case relies on the surface properties of a lightweight, highly porous, polyurea crosslinked silica aerogel scaffold. The distal and proximal ends of completely transected nerve terminals were positioned inside prefabricated "top-open" corrugated channels that cradled approximately two thirds of the circumference of the nerve trunk and connectivity of the severed nerves was evaluated using sciatic function index (SFI) technique for five months post-surgery on 10 female Sprague-Dawley rats then compared with the gold standard for peripheral nerve repair. The interaction of nerves with the surface of the scaffold was investigated also. Multichannel aerogel-based nerve support scaffold showed similar SFI recovery trend as the case suture repair technique. Usage of an adhesion-promoting coating reduced the friction between the nerve and the scaffold leading to slippage and lack of attachment between nerve and surface. The aerogel scaffold used in this study did not collapse under pressure during the incubation period and allowed for a rapid and non-invasive peripheral nerve repair approach without the demands of microsurgery on both time and surgical expertise. This technique may allow for simultaneous repair and reconnection of multiple severed nerves particularly relevant to nerve branching sites.

Determining the relative importance of the mechanisms of behavior change within Alcoholics Anonymous: a multiple mediator analysis.

PubMed

Kelly, John F; Hoeppner, Bettina; Stout, Robert L; Pagano, Maria

2012-02-01

Evidence indicates that Alcoholics Anonymous (AA) participation reduces relapse risk but less is known about the mechanisms through which AA confers this benefit. Initial studies indicate self-efficacy, negative affect, adaptive social networks and spiritual practices are mediators of this effect, but because these have been tested in isolation, their relative importance remains elusive. This study tested multiple mediators simultaneously to help determine the most influential pathways. Prospective, statistically controlled, naturalistic investigation examined the extent to which these previously identified mechanisms mediated AA attendance effects on alcohol outcomes controlling for baseline outcome values, mediators, treatment, and other confounders. Nine clinical sites within the United States. Adults (n = 1726) suffering from alcohol use disorder (AUD) initially enrolled in a randomized study with two arms: aftercare (n = 774); and out-patient (n = 952) comparing three out-patient treatments (Project MATCH). AA attendance during treatment; mediators at 9 months; and outcomes [percentage of days abstinent (PDA) and drinks per drinking day (DDD)] at 15 months. Among out-patients the effect of AA attendance on alcohol outcomes was explained primarily by adaptive social network changes and increases in social abstinence self-efficacy. Among more impaired aftercare patients, in addition to mediation through adaptive network changes and increases in social self-efficacy, AA lead to better outcomes through increasing spirituality/religiosity and by reducing negative affect. The degree to which mediators explained the relationship between AA and outcomes ranged from 43% to 67%. While Alcoholics Anonymous facilitates recovery by mobilizing several processes simultaneously, it is changes in social factors which appear to be of primary importance. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

PubMed

Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

2017-03-09

It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

Catalytic efficiency and thermostability improvement of Suc2 invertase through rational site-directed mutagenesis.

PubMed

Mohandesi, Nooshin; Haghbeen, Kamahldin; Ranaei, Omid; Arab, Seyed Shahriar; Hassani, Sorour

2017-01-01

Engineering of invertases has come to attention because of increasing demand for possible applications of invertases in various industrial processes. Due to the known physicochemical properties, invertases from micro-organisms such as Saccharomyces cerevisiae carrying SUC2 gene are considered as primary models. To improve thermostability and catalytic efficiency of SUC2 invertase (SInv), six influential residues with Relative Solvent Accessibility<5% were selected through multiple-sequence alignments, molecular modelling, structural and computational analyses. Consequently, SInv and 5 mutants including three mutants with single point substitution [Mut1=P152V, Mut2=S85V and Mut3=K153F)], one mutant with two points [Mut4=S305V-N463V] and one mutant with three points [Mut5=S85V-K153F-T271V] were developed via site-directed mutagenesis and produced using Pichia pastoris as the host. Physicochemical studies on these enzymes indicated that the selected amino acids which were located in the active site region mainly influenced catalytic efficiency. The best improvement belonged to Mut1 (54% increase in K cat /K m ) and Mut3 exhibited the worst effect (90% increase in K m ). These results suggest that Pro152 and Lys153 play key role in preparation of the right substrate lodging in the active site of SInv. The best thermostability improvement (16%) was observed for Mut4 in which two hydrophilic residues located on the loops, far from the active site, were replaced by Valines. These results suggest that tactful simultaneous substitution of influential hydrophilic residues in both active site region and peripheral loops with hydrophobic amino acids could result in more thermostable invertases with enhanced catalytic efficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

One ligand, two regulators and three binding sites: How KDPG controls primary carbon metabolism in Pseudomonas

PubMed Central

Fung, Rowena K. Y.; Grenga, Lucia; Trampari, Eleftheria; Pepe, Simona

2017-01-01

Effective regulation of primary carbon metabolism is critically important for bacteria to successfully adapt to different environments. We have identified an uncharacterised transcriptional regulator; RccR, that controls this process in response to carbon source availability. Disruption of rccR in the plant-associated microbe Pseudomonas fluorescens inhibits growth in defined media, and compromises its ability to colonise the wheat rhizosphere. Structurally, RccR is almost identical to the Entner-Doudoroff (ED) pathway regulator HexR, and both proteins are controlled by the same ED-intermediate; 2-keto-3-deoxy-6-phosphogluconate (KDPG). Despite these similarities, HexR and RccR control entirely different aspects of primary metabolism, with RccR regulating pyruvate metabolism (aceEF), the glyoxylate shunt (aceA, glcB, pntAA) and gluconeogenesis (pckA, gap). RccR displays complex and unusual regulatory behaviour; switching repression between the pyruvate metabolism and glyoxylate shunt/gluconeogenesis loci depending on the available carbon source. This regulatory complexity is enabled by two distinct pseudo-palindromic binding sites, differing only in the length of their linker regions, with KDPG binding increasing affinity for the 28 bp aceA binding site but decreasing affinity for the 15 bp aceE site. Thus, RccR is able to simultaneously suppress and activate gene expression in response to carbon source availability. Together, the RccR and HexR regulators enable the rapid coordination of multiple aspects of primary carbon metabolism, in response to levels of a single key intermediate. PMID:28658302

Searching for statistically significant regulatory modules.

PubMed

Bailey, Timothy L; Noble, William Stafford

2003-10-01

The regulatory machinery controlling gene expression is complex, frequently requiring multiple, simultaneous DNA-protein interactions. The rate at which a gene is transcribed may depend upon the presence or absence of a collection of transcription factors bound to the DNA near the gene. Locating transcription factor binding sites in genomic DNA is difficult because the individual sites are small and tend to occur frequently by chance. True binding sites may be identified by their tendency to occur in clusters, sometimes known as regulatory modules. We describe an algorithm for detecting occurrences of regulatory modules in genomic DNA. The algorithm, called mcast, takes as input a DNA database and a collection of binding site motifs that are known to operate in concert. mcast uses a motif-based hidden Markov model with several novel features. The model incorporates motif-specific p-values, thereby allowing scores from motifs of different widths and specificities to be compared directly. The p-value scoring also allows mcast to only accept motif occurrences with significance below a user-specified threshold, while still assigning better scores to motif occurrences with lower p-values. mcast can search long DNA sequences, modeling length distributions between motifs within a regulatory module, but ignoring length distributions between modules. The algorithm produces a list of predicted regulatory modules, ranked by E-value. We validate the algorithm using simulated data as well as real data sets from fruitfly and human. http://meme.sdsc.edu/MCAST/paper

Development of a High Throughput Assay for Rapid and Accurate 10-Plex Detection of Citrus Pathogens

USDA-ARS?s Scientific Manuscript database

The need to reliably detect and identify multiple plant pathogens simultaneously, especially in woody perennial hosts, has led to development of new molecular diagnostic approaches. In this study, a Luminex-based system was developed that provided a robust and sensitive test for simultaneous detect...

A case of triple volvulus.

PubMed

Elsharif, M; Basu, I; Phillips, D

2012-03-01

Situs inversus is a rare congenital anomaly that has reportedly been associated with caecal volvulus. We describe a case of partial situs inversus complicated by intestinal obstruction secondary to three simultaneously occurring volvuli of the stomach, caecum and sigmoid colon. To our knowledge, this is the first documented case in the literature of multiple, simultaneously occurring volvuli.

Using a Simultaneous Prompting Procedure to Embed Core Content When Teaching a Potential Employment Skill

ERIC Educational Resources Information Center

Collins, Belva C.; Terrell, Misty; Test, David W.

2017-01-01

This investigation used a multiple-probe-across-participants design to examine the effects of using a simultaneous prompting procedure to teach four secondary students with mild intellectual disabilities the employment task of caring for plants in a greenhouse. The instructor also embedded photosynthesis science content as nontargeted information…

A Comparison of Simultaneous Prompting and Constant Time Delay Procedures in Teaching State Capitals

ERIC Educational Resources Information Center

Head, Kenneth David; Collins, Belva C.; Schuster, John W.; Ault, Melinda Jones

2011-01-01

This investigation compared the effectiveness and efficiency of constant time delay (CTD) and simultaneous prompting (SP) procedures in teaching discrete social studies facts to 4 high school students with learning and behavior disorders using an adapted alternating treatments design nested within a multiple probe design. The results indicated…

Simultaneous Determination of Oxysterols, Cholesterol and 25-Hydroxy-Vitamin D3 in Human Plasma by LC-UV-MS

PubMed Central

Narayanaswamy, Rohini; Iyer, Vignesh; Khare, Prachi; Bodziak, Mary Lou; Badgett, Darlene; Zivadinov, Robert; Weinstock-Guttman, Bianca; Rideout, Todd C.; Ramanathan, Murali; Browne, Richard W.

2015-01-01

Background Oxysterols are promising biomarkers of neurodegenerative diseases that are linked with cholesterol and vitamin D metabolism. There is an unmet need for methods capable of sensitive, and simultaneous quantitation of multiple oxysterols, vitamin D and cholesterol pathway biomarkers. Methods A method for simultaneous determination of 5 major oxysterols, 25-hydroxy vitamin D3 and cholesterol in human plasma was developed. Total oxysterols were prepared by room temperature saponification followed by solid phase extraction from plasma spiked with deuterated internal standards. Oxysterols were resolved by reverse phase HPLC using a methanol/water/0.1% formic acid gradient. Oxysterols and 25-hydroxy vitamin D3 were detected with atmospheric pressure chemical ionization mass spectrometry in positive ion mode; in-series photodiode array detection at 204nm was used for cholesterol. Method validation studies were performed. Oxysterol levels in 220 plasma samples from healthy control subjects, multiple sclerosis and other neurological disorders patients were quantitated. Results Our method quantitated 5 oxysterols, cholesterol and 25-hydroxy vitamin D3 from 200 μL plasma in 35 minutes. Recoveries were >85% for all analytes and internal standards. The limits of detection were 3-10 ng/mL for oxysterols and 25-hydroxy vitamin D3 and 1 μg/mL for simultaneous detection of cholesterol. Analytical imprecision was <10 %CV for 24(S)-, 25-, 27-, 7α-hydroxycholesterol (HC) and cholesterol and ≤15 % for 7-keto-cholesterol. Multiple Sclerosis and other neurological disorder patients had lower 27-hydroxycholesterol levels compared to controls whereas 7α-hydroxycholesterol was lower specifically in Multiple Sclerosis. Conclusion The method is suitable for measuring plasma oxysterols levels in human health and disease. Analysis of human plasma indicates that the oxysterol, bile acid precursors 7α-hydroxycholesterol and 27-hydroxycholesterol are lower in Multiple Sclerosis and may serve as potential biomarkers of disease. PMID:25875771

Simultaneous spawning by female stream goby Rhinogobius sp. and the association with brood cannibalism by nesting males.

PubMed

Ito, S; Iwao, H; Sakata, J; Inoue, M; Omori, K; Yanagisawa, Y

2016-09-01

A laboratory experiment was conducted by varying the undersurface area of nesting substratum and the number of females in an experimental tank to elucidate the determinants of the mating pattern in the stream goby, Rhinogobius sp. cross-band type. Males with larger nests tended to attract two or more females to their nest in a tank. Moreover, males spawned simultaneously with multiple females and entire brood cannibalism by males was rarely observed under a female-biased sex ratio. When males spawned with a single female with low fecundity, however, entire brood cannibalism occurred at a high frequency, suggesting that a male guarding a nest with fewer eggs consumes the brood. Therefore, spawning behaviour of females that leads to a large egg mass would decrease the risk of entire brood cannibalism. In this species, simultaneous spawning by multiple females in a nest serves as a female counter-measure against entire brood cannibalism. These results suggest that a conflict of interest between the sexes through brood cannibalism is a major determinant of simultaneous spawning. © 2016 The Fisheries Society of the British Isles.

SU-F-T-349: Dosimetric Comparison of Three Different Simultaneous Integrated Boost Irradiation Techniques for Multiple Brain Metastases: Intensity-Modulatedradiotherapy, Hybrid Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

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

Lin, X; Sun, T; Yin, Y

Purpose: To study the dosimetric impact of intensity-modulated radiotherapy (IMRT), hybrid intensity-modulated radiotherapy (h-IMRT) and volumetric modulated arc therapy(VMAT) for whole-brain radiotherapy (WBRT) with simultaneous integrated boost in patients with multiple brain metastases. Methods: Ten patients with multiple brain metastases were included in this analysis. The prescribed dose was 45 Gy to the whole brain (PTVWBRT) and 55 Gy to individual brain metastases (PTVboost) delivered simultaneously in 25 fractions. Three treatment techniques were designed: the 7 equal spaced fields IMRT plan, hybrid IMRT plan and VMAT with two 358°arcs. In hybrid IMRT plan, two fields(90°and 270°) were planned to themore » whole brain. This was used as a base dose plan. Then 5 fields IMRT plan was optimized based on the two fields plan. The dose distribution in the target, the dose to the organs at risk and total MU in three techniques were compared. Results: For the target dose, conformity and homogeneity in PTV, no statistically differences were observed in the three techniques. For the maximum dose in bilateral lens and the mean dose in bilateral eyes, IMRT and h-IMRT plans showed the highest and lowest value respectively. No statistically significant differences were observed in the dose of optic nerve and brainstem. For the monitor units, IMRT and VMAT plans showed the highest and lowest value respectively. Conclusion: For WBRT with simultaneous integrated boost in patients with multiple brain metastases, hybrid IMRT could reduce the doses to lens and eyes. It is feasible for patients with brain metastases.« less

Element-specific spectral imaging of multiple contrast agents: a phantom study

NASA Astrophysics Data System (ADS)

Panta, R. K.; Bell, S. T.; Healy, J. L.; Aamir, R.; Bateman, C. J.; Moghiseh, M.; Butler, A. P. H.; Anderson, N. G.

2018-02-01

This work demonstrates the feasibility of simultaneous discrimination of multiple contrast agents based on their element-specific and energy-dependent X-ray attenuation properties using a pre-clinical photon-counting spectral CT. We used a photon-counting based pre-clinical spectral CT scanner with four energy thresholds to measure the X-ray attenuation properties of various concentrations of iodine (9, 18 and 36 mg/ml), gadolinium (2, 4 and 8 mg/ml) and gold (2, 4 and 8 mg/ml) based contrast agents, calcium chloride (140 and 280 mg/ml) and water. We evaluated the spectral imaging performances of different energy threshold schemes between 25 to 82 keV at 118 kVp, based on K-factor and signal-to-noise ratio and ranked them. K-factor was defined as the X-ray attenuation in the K-edge containing energy range divided by the X-ray attenuation in the preceding energy range, expressed as a percentage. We evaluated the effectiveness of the optimised energy selection to discriminate all three contrast agents in a phantom of 33 mm diameter. A photon-counting spectral CT using four energy thresholds of 27, 33, 49 and 81 keV at 118 kVp simultaneously discriminated three contrast agents based on iodine, gadolinium and gold at various concentrations using their K-edge and energy-dependent X-ray attenuation features in a single scan. A ranking method to evaluate spectral imaging performance enabled energy thresholds to be optimised to discriminate iodine, gadolinium and gold contrast agents in a single spectral CT scan. Simultaneous discrimination of multiple contrast agents in a single scan is likely to open up new possibilities of improving the accuracy of disease diagnosis by simultaneously imaging multiple bio-markers each labelled with a nano-contrast agent.

The 2010 California Research at the Nexus of Air Quality and Climate Change (CalNex) field study

NASA Astrophysics Data System (ADS)

Ryerson, T. B.; Andrews, A. E.; Angevine, W. M.; Bates, T. S.; Brock, C. A.; Cairns, B.; Cohen, R. C.; Cooper, O. R.; de Gouw, J. A.; Fehsenfeld, F. C.; Ferrare, R. A.; Fischer, M. L.; Flagan, R. C.; Goldstein, A. H.; Hair, J. W.; Hardesty, R. M.; Hostetler, C. A.; Jimenez, J. L.; Langford, A. O.; McCauley, E.; McKeen, S. A.; Molina, L. T.; Nenes, A.; Oltmans, S. J.; Parrish, D. D.; Pederson, J. R.; Pierce, R. B.; Prather, K.; Quinn, P. K.; Seinfeld, J. H.; Senff, C. J.; Sorooshian, A.; Stutz, J.; Surratt, J. D.; Trainer, M.; Volkamer, R.; Williams, E. J.; Wofsy, S. C.

2013-06-01

The California Research at the Nexus of Air Quality and Climate Change (CalNex) field study was conducted throughout California in May, June, and July of 2010. The study was organized to address issues simultaneously relevant to atmospheric pollution and climate change, including (1) emission inventory assessment, (2) atmospheric transport and dispersion, (3) atmospheric chemical processing, and (4) cloud-aerosol interactions and aerosol radiative effects. Measurements from networks of ground sites, a research ship, tall towers, balloon-borne ozonesondes, multiple aircraft, and satellites provided in situ and remotely sensed data on trace pollutant and greenhouse gas concentrations, aerosol chemical composition and microphysical properties, cloud microphysics, and meteorological parameters. This overview report provides operational information for the variety of sites, platforms, and measurements, their joint deployment strategy, and summarizes findings that have resulted from the collaborative analyses of the CalNex field study. Climate-relevant findings from CalNex include that leakage from natural gas infrastructure may account for the excess of observed methane over emission estimates in Los Angeles. Air-quality relevant findings include the following: mobile fleet VOC significantly declines, and NOx emissions continue to have an impact on ozone in the Los Angeles basin; the relative contributions of diesel and gasoline emission to secondary organic aerosol are not fully understood; and nighttime NO3 chemistry contributes significantly to secondary organic aerosol mass in the San Joaquin Valley. Findings simultaneously relevant to climate and air quality include the following: marine vessel emissions changes due to fuel sulfur and speed controls result in a net warming effect but have substantial positive impacts on local air quality.

Characteristics of formation and growth of atmospheric nanoparticles observed at four regional background sites in Korea

NASA Astrophysics Data System (ADS)

Kim, Yumi; Kim, Sang-Woo; Yoon, Soon-Chang; Park, Jin-Soo; Lim, Jae-Hyun; Hong, Jihyung; Lim, Han-Cheol; Ryu, Jegyu; Lee, Chul-Kyu; Heo, Bok-Haeng

2016-02-01

Measurements of the number concentration and size distribution of atmospheric nanoparticles were conducted at four sites on the west coast of the Korean Peninsula by using identical scanning mobility particle sizers (SMPSs) in October 2012. The new particle formation and subsequent growth (NPF) of atmospheric nanoparticles, which were identified by the cyclostationary empirical orthogonal function (CSEOF) analysis technique, was observed on 11 out of 21 days at the Baengnyeong-do Comprehensive Monitoring Observatory (BCMO); and on 10 out of 21 days at the Korea Global Atmosphere Watch Center (KGAWC) from October 9 to 29, 2012. We also observed NPF events for 9 out of 21 days at both the Gosan Climate Observatory (GCO) and the Jeju Comprehensive Monitoring Observatory (JCMO). During the study period, NPF was simultaneously observed for five days at all four sites, which indicates that the NPF event had a spatial extent of at least 540 km. A cold, dry and cloud-free continental air mass originated from northern China, formed favorable environmental conditions (e.g., increasing solar insolation at the surface) on simultaneous NPF at the four sites. These synoptic weather patterns were closely associated with an extraordinary typhoon passing over the south of Japan. The mean values of particle formation rates at BCMO (1.26 cm- 3 s- 1) and KGAWC (1.49 cm- 3 s- 1) were relatively higher than those at GCO (0.39 cm- 3 s- 1) and JCMO (0.74 cm- 3 s- 1), however, the growth rate showed a similar level among four sites. An increase in the spatial homogeneity and inter-site correlation of atmospheric particles among the four sites was apparent for small particles (diameter < 30 nm) on simultaneous NPF event days.

Simultaneous estimation of local-scale and flow path-scale dual-domain mass transfer parameters using geoelectrical monitoring

USGS Publications Warehouse

Briggs, Martin A.; Day-Lewis, Frederick D.; Ong, John B.; Curtis, Gary P.; Lane, John W.

2013-01-01

Anomalous solute transport, modeled as rate-limited mass transfer, has an observable geoelectrical signature that can be exploited to infer the controlling parameters. Previous experiments indicate the combination of time-lapse geoelectrical and fluid conductivity measurements collected during ionic tracer experiments provides valuable insight into the exchange of solute between mobile and immobile porosity. Here, we use geoelectrical measurements to monitor tracer experiments at a former uranium mill tailings site in Naturita, Colorado. We use nonlinear regression to calibrate dual-domain mass transfer solute-transport models to field data. This method differs from previous approaches by calibrating the model simultaneously to observed fluid conductivity and geoelectrical tracer signals using two parameter scales: effective parameters for the flow path upgradient of the monitoring point and the parameters local to the monitoring point. We use regression statistics to rigorously evaluate the information content and sensitivity of fluid conductivity and geophysical data, demonstrating multiple scales of mass transfer parameters can simultaneously be estimated. Our results show, for the first time, field-scale spatial variability of mass transfer parameters (i.e., exchange-rate coefficient, porosity) between local and upgradient effective parameters; hence our approach provides insight into spatial variability and scaling behavior. Additional synthetic modeling is used to evaluate the scope of applicability of our approach, indicating greater range than earlier work using temporal moments and a Lagrangian-based Damköhler number. The introduced Eulerian-based Damköhler is useful for estimating tracer injection duration needed to evaluate mass transfer exchange rates that range over several orders of magnitude.

Quantitative comparison of tumor delivery for multiple targeted nanoparticles simultaneously by multiplex ICP-MS.

PubMed

Elias, Andrew; Crayton, Samuel H; Warden-Rothman, Robert; Tsourkas, Andrew

2014-07-28

Given the rapidly expanding library of disease biomarkers and targeting agents, the number of unique targeted nanoparticles is growing exponentially. The high variability and expense of animal testing often makes it unfeasible to examine this large number of nanoparticles in vivo. This often leads to the investigation of a single formulation that performed best in vitro. However, nanoparticle performance in vivo depends on many variables, many of which cannot be adequately assessed with cell-based assays. To address this issue, we developed a lanthanide-doped nanoparticle method that allows quantitative comparison of multiple targeted nanoparticles simultaneously. Specifically, superparamagnetic iron oxide (SPIO) nanoparticles with different targeting ligands were created, each with a unique lanthanide dopant. Following the simultaneous injection of the various SPIO compositions into tumor-bearing mice, inductively coupled plasma mass spectroscopy was used to quantitatively and orthogonally assess the concentration of each SPIO composition in serial blood and resected tumor samples.

Simultaneous measurement of multiple radiation-induced protein expression profiles using the Luminex(TM) system

NASA Technical Reports Server (NTRS)

Desai, N.; Wu, H.; George, K.; Gonda, S. R.; Cucinotta, F. A.; Cucniotta, F. A. (Principal Investigator)

2004-01-01

Space flight results in the exposure of astronauts to a mixed field of radiation composed of energetic particles of varying energies, and biological indicators of space radiation exposure provides a better understanding of the associated long-term health risks. Current methods of biodosimetry have employed the use of cytogenetic analysis for biodosimetry, and more recently the advent of technological progression has led to advanced research in the use of genomic and proteomic expression profiling to simultaneously assess biomarkers of radiation exposure. We describe here the technical advantages of the Luminex(TM) 100 system relative to traditional methods and its potential as a tool to simultaneously profile multiple proteins induced by ionizing radiation. The development of such a bioassay would provide more relevant post-translational dynamics of stress response and will impart important implications in the advancement of space and other radiation contact monitoring. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

Simultaneous multicolor imaging of wide-field epi-fluorescence microscopy with four-bucket detection

PubMed Central

Park, Kwan Seob; Kim, Dong Uk; Lee, Jooran; Kim, Geon Hee; Chang, Ki Soo

2016-01-01

We demonstrate simultaneous imaging of multiple fluorophores using wide-field epi-fluorescence microscopy with a monochrome camera. The intensities of the three lasers are modulated by a sinusoidal waveform in order to excite each fluorophore with the same modulation frequency and a different time-delay. Then, the modulated fluorescence emissions are simultaneously detected by a camera operating at four times the excitation frequency. We show that two different fluorescence beads having crosstalk can be clearly separated using digital processing based on the phase information. In addition, multiple organelles within multi-stained single cells are shown with the phase mapping method, demonstrating an improved dynamic range and contrast compared to the conventional fluorescence image. These findings suggest that wide-field epi-fluorescence microscopy with four-bucket detection could be utilized for high-contrast multicolor imaging applications such as drug delivery and fluorescence in situ hybridization. PMID:27375944

Multiple delivery cesium oven system for negative ion sources

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

Bansal, G.; Bhartiya, S.; Pandya, K.

2012-02-15

Distribution of cesium in large negative ion beam sources to be operational in ITER, is presently based on the use of three or more cesium ovens, which operate simultaneously and are controlled remotely. However, use of multiple Cs ovens simultaneously is likely to pose difficulties in operation and maintenance of the ovens. An alternate method of Cs delivery, based on a single oven distribution system is proposed as one which could reduce the need of simultaneous operation of many ovens. A proof of principle experiment verifying the concept of a multinozzle distributor based Cs oven has been carried out atmore » Institute for Plasma Research. It is also observed that the Cs flux is not controlled by Cs reservoir temperature after few hours of operation but by the temperature of the distributor which starts behaving as a Cs reservoir.« less

Re-designing the PhEDEx Security Model

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

Huang, C.-H.; Wildish, T.; Zhang, X.

2014-01-01

PhEDEx, the data-placement tool used by the CMS experiment at the LHC, was conceived in a more trusting time. The security model provided a safe environment for site agents and operators, but offerred little more protection than that. Data was not sufficiently protected against loss caused by operator error or software bugs or by deliberate manipulation of the database. Operators were given high levels of access to the database, beyond what was actually needed to accomplish their tasks. This exposed them to the risk of suspicion should an incident occur. Multiple implementations of the security model led to difficulties maintainingmore » code, which can lead to degredation of security over time. In order to meet the simultaneous goals of protecting CMS data, protecting the operators from undue exposure to risk, increasing monitoring capabilities and improving maintainability of the security model, the PhEDEx security model was redesigned and re-implemented. Security was moved from the application layer into the database itself, fine-grained access roles were established, and tools and procedures created to control the evolution of the security model over time. In this paper we describe this work, we describe the deployment of the new security model, and we show how these enhancements improve security on several fronts simultaneously.« less

Re-designing the PhEDEx Security Model

NASA Astrophysics Data System (ADS)

C-H, Huang; Wildish, T.; X, Zhang

2014-06-01

PhEDEx, the data-placement tool used by the CMS experiment at the LHC, was conceived in a more trusting time. The security model provided a safe environment for site agents and operators, but offerred little more protection than that. Data was not sufficiently protected against loss caused by operator error or software bugs or by deliberate manipulation of the database. Operators were given high levels of access to the database, beyond what was actually needed to accomplish their tasks. This exposed them to the risk of suspicion should an incident occur. Multiple implementations of the security model led to difficulties maintaining code, which can lead to degredation of security over time. In order to meet the simultaneous goals of protecting CMS data, protecting the operators from undue exposure to risk, increasing monitoring capabilities and improving maintainability of the security model, the PhEDEx security model was redesigned and re-implemented. Security was moved from the application layer into the database itself, fine-grained access roles were established, and tools and procedures created to control the evolution of the security model over time. In this paper we describe this work, we describe the deployment of the new security model, and we show how these enhancements improve security on several fronts simultaneously.

Site Features

EPA Pesticide Factsheets

This dataset consists of various site features from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times and were combined into one region-wide layer.

The ultrasound brain helmet: feasibility study of multiple simultaneous 3D scans of cerebral vasculature.

PubMed

Smith, Stephen W; Ivancevich, Nikolas M; Lindsey, Brooks D; Whitman, John; Light, Edward; Fronheiser, Matthew; Nicoletto, Heather A; Laskowitz, Daniel T

2009-02-01

We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple simultaneous real-time three-dimensional (3D) scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the skull. The transducer hardware and software of the Volumetrics Medical Imaging (Durham, NC, USA) real-time 3D scanner were modified to support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous 64 degrees pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128 degrees sector, two simultaneous parasagittal images merged into a 128 degrees x 64 degrees C-mode plane and a simultaneous 64 degrees axial image. Real-time 3D color Doppler scans from a skull phantom with latex blood vessel were obtained after contrast agent injection as a proof of concept. The long-term goal is to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet transmission thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.

A gas sensor array for the simultaneous detection of multiple VOCs.

PubMed

Zhang, Yumin; Zhao, Jianhong; Du, Tengfei; Zhu, Zhongqi; Zhang, Jin; Liu, Qingju

2017-05-16

Air quality around the globe is declining and public health is seriously threatened by indoor air pollution. Typically, indoor air pollutants are composed of a series of volatile organic compounds (VOCs) that are generally harmful to the human body, especially VOCs with low molecular weights (less than 100 Da). Moreover, in some situations, more than one type of VOC is present; thus, a device that can detect one or more VOCs simultaneously would be most beneficial. Here, we synthesized a sensor array with 4 units to detect 4 VOCs: acetone (unit 1), benzene (unit 2), methanol (unit 3) and formaldehyde (unit 4) simultaneously. All units were simultaneously exposed to 2.5 ppm of all four VOCs. The sensitivity of unit 1 was 14.67 for acetone and less than 2.54 for the other VOCs. The sensitivities of units 2, 3 and 4 to benzene, methanol and formaldehyde were 2 18.64, 20.98 and 17.26, respectively, and less than 4.01 for the other VOCs. These results indicated that the sensor array exhibited good selectivity and could be used for the real-time monitoring of indoor air quality. Thus, this device will be useful in situations requiring the simultaneous detection of multiple VOCs.

Time-jittered marine seismic data acquisition via compressed sensing and sparsity-promoting wavefield reconstruction

NASA Astrophysics Data System (ADS)

Wason, H.; Herrmann, F. J.; Kumar, R.

2016-12-01

Current efforts towards dense shot (or receiver) sampling and full azimuthal coverage to produce high resolution images have led to the deployment of multiple source vessels (or streamers) across marine survey areas. Densely sampled marine seismic data acquisition, however, is expensive, and hence necessitates the adoption of sampling schemes that save acquisition costs and time. Compressed sensing is a sampling paradigm that aims to reconstruct a signal--that is sparse or compressible in some transform domain--from relatively fewer measurements than required by the Nyquist sampling criteria. Leveraging ideas from the field of compressed sensing, we show how marine seismic acquisition can be setup as a compressed sensing problem. A step ahead from multi-source seismic acquisition is simultaneous source acquisition--an emerging technology that is stimulating both geophysical research and commercial efforts--where multiple source arrays/vessels fire shots simultaneously resulting in better coverage in marine surveys. Following the design principles of compressed sensing, we propose a pragmatic simultaneous time-jittered time-compressed marine acquisition scheme where single or multiple source vessels sail across an ocean-bottom array firing airguns at jittered times and source locations, resulting in better spatial sampling and speedup acquisition. Our acquisition is low cost since our measurements are subsampled. Simultaneous source acquisition generates data with overlapping shot records, which need to be separated for further processing. We can significantly impact the reconstruction quality of conventional seismic data from jittered data and demonstrate successful recovery by sparsity promotion. In contrast to random (sub)sampling, acquisition via jittered (sub)sampling helps in controlling the maximum gap size, which is a practical requirement of wavefield reconstruction with localized sparsifying transforms. We illustrate our results with simulations of simultaneous time-jittered marine acquisition for 2D and 3D ocean-bottom cable survey.

Quantification of multiple simultaneously occurring nitrogen flows in the euphotic ocean

NASA Astrophysics Data System (ADS)

Xu, Min Nina; Wu, Yanhua; Zheng, Li Wei; Zheng, Zhenzhen; Zhao, Huade; Laws, Edward A.; Kao, Shuh-Ji

2017-03-01

The general features of the N cycle in the sunlit region of the ocean are well known, but methodological difficulties have previously confounded simultaneous quantification of transformation rates among the many different forms of N, e.g., ammonium (NH4+), nitrite (NO2-), nitrate (NO3-), and particulate/dissolved organic nitrogen (PN/DON). However, recent advances in analytical methodology have made it possible to employ a convenient isotope labeling technique to quantify in situ fluxes among oft-measured nitrogen species within the euphotic zone. Addition of a single 15N-labeled NH4+ tracer and monitoring of the changes in the concentrations and isotopic compositions of the total dissolved nitrogen (TDN), PN, NH4+, NO2-, and NO3- pools allowed us to quantify the 15N and 14N fluxes simultaneously. Constraints expressing the balance of 15N and 14N fluxes between the different N pools were expressed in the form of simultaneous equations, the unique solution of which via matrix inversion yielded the relevant N fluxes, including rates of NH4+, NO2-, and NO3- uptake; ammonia oxidation; nitrite oxidation; DON release; and NH4+ uptake by bacteria. The matrix inversion methodology that we used was designed specifically to analyze the results of incubations under simulated in situ conditions in the euphotic zone. By taking into consideration simultaneous fluxes among multiple N pools, we minimized potential artifacts caused by non-targeted processes in traditional source-product methods. The proposed isotope matrix method facilitates post hoc analysis of data from on-deck incubation experiments and can be used to probe effects of environmental factors (e.g., pH, temperature, and light) on multiple processes under controlled conditions.

Electromagnetic sounding of the moon using Apollo 16 and Lunokhod 2 surface magnetometer observations /preliminary results/

NASA Technical Reports Server (NTRS)

Vanian, L. L.; Vnutchokova, T. A.; Fainberg, E. B.; Eroschenko, E. A.; Dyal, P.; Parkin, C. W.; Daily, W. D.

1977-01-01

A technique of deep electromagnetic sounding of the moon using simultaneous magnetic-field measurements at two lunar surface sites is described. The method, used with the assumption that deep electrical conductivity is a function only of lunar radius, has the advantage of allowing calculation of the external driving field from two surface-site measurements only and therefore does not require data from a lunar orbiting satellite. A transient-response calculation is presented for the example of a magnetic-field discontinuity, measured simultaneously by Apollo 16 and Lunokhod 2 surface magnetometers.

Electromagnetic Sounding of the Moon Using Apollo 16 and Lunokhod 2 Surface Magnetometer Observations (Preliminary Results)

NASA Technical Reports Server (NTRS)

Vanyan, L. L.; Vnutchokova, T. A.; Fainberg, E. B.; Eroschenko, E. A.; Dyal, P.; Parkin, C. W.; Parkin, C. W.

1977-01-01

A new technique of deep electromagnetic sounding of the Moon using simultaneous magnetic field measurements at two lunar surface sites is described. The method, used with the assumption that deep electrical conductivity is a function only of lunar radius, has the advantage of allowing calculation of the external driving field from two surface site measurements only, and therefore does not require data from a lunar orbiting satellite. A transient response calculation is presented for the example of a magnetic field discontinuity of February 13, 1973, measured simultaneously by Apollo 16 and Lunokhod 2 surface magnetometers.

The 2011 Eco3D Flight Campaign: Vegetation Structure and Biomass Estimation from Simultaneous SAR, Lidar and Radiometer Measurements

NASA Technical Reports Server (NTRS)

Fatoyinbo, Temilola; Rincon, Rafael; Harding, David; Gatebe, Charles; Ranson, Kenneth Jon; Sun, Guoqing; Dabney, Phillip; Roman, Miguel

2012-01-01

The Eco3D campaign was conducted in the Summer of 2011. As part of the campaign three unique and innovative NASA Goddard Space Flight Center airborne sensors were flown simultaneously: The Digital Beamforming Synthetic Aperture Radar (DBSAR), the Slope Imaging Multi-polarization Photon-counting Lidar (SIMPL) and the Cloud Absorption Radiometer (CAR). The campaign covered sites from Quebec to Southern Florida and thereby acquired data over forests ranging from Boreal to tropical wetlands. This paper describes the instruments and sites covered and presents the first images resulting from the campaign.

Multiple pathways from three types of sugar receptor sites to metabotropic transduction pathways of the blowfly: study by the whole cell-clamp experiments.

PubMed

Kan, Hideko; Kataoka-Shirasugi, Naoko; Amakawa, Taisaku

2011-09-01

Multiple pathways from three types of multiple receptor sites to three types of metabotropic signal transduction pathways were investigated in the whole cell-clamp experiments using isolated labellar sugar receptor neurons (cells) of the adult blowfly, Phormia regina. First, the concentration-response curves of three types of sweet taste components specialized to multiple receptor sites were obtained: sucrose for the pyranose sites (P-sites), fructose for the furanose sites (F-sites), and l-valine for the alkyl sites (R-sites). Next, the effects of inhibitors such as 2', 5'-dideoxyadenosine on adenylyl cyclase in the cAMP pathway, LY 83583 on guanylyl cyclase in the cGMP pathway, and U-73122 on phospholipase C in the IP₃ pathway were examined. The results showed that all of the inhibitors affected each specific target in the second-messenger transduction pathways. The obtained results verified that the P-site corresponded to the cAMP, the F-site to the cGMP, and the R-site to the IP₃ transduction pathway, and that these three signal pathways did not have crossing points. Copyright © 2011 Elsevier Inc. All rights reserved.

The simultaneous occurrence of multiple myeloma and JAK2 positive myeloproliferative neoplasms - Report on two cases

PubMed Central

Badelita, S; Dobrea, C; Colita, A; Dogaru, M; Dragomir, M; Jardan, C; Coriu, D

2015-01-01

Multiple myeloma and JAK2 positive chronic myeloproliferative neoplasms are hematologic malignancies with a completely different cellular origin. Two cases of simultaneous occurrence of multiple myeloma, one with primary myelofibrosis and another one with essential thrombocythemia are reported in this article. In such cases, an accurate diagnosis requires a molecular testing, including gene sequencing and differential diagnosis of pancytosis associated with splenic amyloidosis. In general, in such cases, of two coexisting malignant hematologic diseases, the treatment of the most aggressive one is recommended. For our two cases, it was decided to start a Velcade based therapy. The main concern was the medullar toxicity, especially when a multiple myeloma was associated with a primary myelofibrosis. Abbreviations:JAK2 = Janus kinase 2 gene, PMF = primary myelofibrosis, MPNs = myeloproliferative neoplasms, ET = essential thrombocythemia, PV = polycythemia vera, MM = multiple myeloma, WBC = white blood cells, Hb = haemoglobin, Ht = haematocrit, Plt = platelets, BMB = bone marrow biopsy, CBC = blood cell count, CT = computerized tomography, LAP = leukocyte alkaline phosphatase, MGUS = monoclonal gammopathy of undetermined significance. PMID:25914740

Multi-Population Invariance with Dichotomous Measures: Combining Multi-Group and MIMIC Methodologies in Evaluating the General Aptitude Test in the Arabic Language

ERIC Educational Resources Information Center

Sideridis, Georgios D.; Tsaousis, Ioannis; Al-harbi, Khaleel A.

2015-01-01

The purpose of the present study was to extend the model of measurement invariance by simultaneously estimating invariance across multiple populations in the dichotomous instrument case using multi-group confirmatory factor analytic and multiple indicator multiple causes (MIMIC) methodologies. Using the Arabic version of the General Aptitude Test…

From Lucy to Kadanuumuu: balanced analyses of Australopithecus afarensis assemblages confirm only moderate skeletal dimorphism.

PubMed

Reno, Philip L; Lovejoy, C Owen

2015-01-01

Sexual dimorphism in body size is often used as a correlate of social and reproductive behavior in Australopithecus afarensis. In addition to a number of isolated specimens, the sample for this species includes two small associated skeletons (A.L. 288-1 or "Lucy" and A.L. 128/129) and a geologically contemporaneous death assemblage of several larger individuals (A.L. 333). These have driven both perceptions and quantitative analyses concluding that Au. afarensis was markedly dimorphic. The Template Method enables simultaneous evaluation of multiple skeletal sites, thereby greatly expanding sample size, and reveals that A. afarensis dimorphism was similar to that of modern humans. A new very large partial skeleton (KSD-VP-1/1 or "Kadanuumuu") can now also be used, like Lucy, as a template specimen. In addition, the recently developed Geometric Mean Method has been used to argue that Au. afarensis was equally or even more dimorphic than gorillas. However, in its previous application Lucy and A.L. 128/129 accounted for 10 of 11 estimates of female size. Here we directly compare the two methods and demonstrate that including multiple measurements from the same partial skeleton that falls at the margin of the species size range dramatically inflates dimorphism estimates. Prevention of the dominance of a single specimen's contribution to calculations of multiple dimorphism estimates confirms that Au. afarensis was only moderately dimorphic.

From Lucy to Kadanuumuu: balanced analyses of Australopithecus afarensis assemblages confirm only moderate skeletal dimorphism

PubMed Central

Lovejoy, C. Owen

2015-01-01

Sexual dimorphism in body size is often used as a correlate of social and reproductive behavior in Australopithecus afarensis. In addition to a number of isolated specimens, the sample for this species includes two small associated skeletons (A.L. 288-1 or “Lucy” and A.L. 128/129) and a geologically contemporaneous death assemblage of several larger individuals (A.L. 333). These have driven both perceptions and quantitative analyses concluding that Au. afarensis was markedly dimorphic. The Template Method enables simultaneous evaluation of multiple skeletal sites, thereby greatly expanding sample size, and reveals that A. afarensis dimorphism was similar to that of modern humans. A new very large partial skeleton (KSD-VP-1/1 or “Kadanuumuu”) can now also be used, like Lucy, as a template specimen. In addition, the recently developed Geometric Mean Method has been used to argue that Au. afarensis was equally or even more dimorphic than gorillas. However, in its previous application Lucy and A.L. 128/129 accounted for 10 of 11 estimates of female size. Here we directly compare the two methods and demonstrate that including multiple measurements from the same partial skeleton that falls at the margin of the species size range dramatically inflates dimorphism estimates. Prevention of the dominance of a single specimen’s contribution to calculations of multiple dimorphism estimates confirms that Au. afarensis was only moderately dimorphic. PMID:25945314

Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria.

PubMed

Lehouritis, Panos; Stanton, Michael; McCarthy, Florence O; Jeavons, Matthieu; Tangney, Mark

2016-01-28

Some chemotherapeutic drugs (prodrugs) require activation by an enzyme for efficacy. We and others have demonstrated the ability of probiotic bacteria to grow specifically within solid tumours following systemic administration, and we hypothesised that the natural enzymatic activity of these tumour-localised bacteria may be suitable for activation of certain such chemotherapeutic drugs. Several wild-type probiotic bacteria; Escherichia coli Nissle, Bifidobacterium breve, Lactococcus lactis and Lactobacillus species, were screened against a panel of popular prodrugs. All strains were capable of activating at least one prodrug. E. coli Nissle 1917 was selected for further studies because of its ability to activate numerous prodrugs and its resistance to prodrug toxicity. HPLC data confirmed biochemical transformation of prodrugs to their toxic counterparts. Further analysis demonstrated that different enzymes can complement prodrug activation, while simultaneous activation of multiple prodrugs (CB1954, 5-FC, AQ4N and Fludarabine phosphate) by E. coli was confirmed, resulting in significant efficacy improvement. Experiments in mice harbouring murine tumours validated in vitro findings, with significant reduction in tumour growth and increase in survival of mice treated with probiotic bacteria and a combination of prodrugs. These findings demonstrate the ability of probiotic bacteria, without the requirement for genetic modification, to enable high-level activation of multiple prodrugs specifically at the site of action. Copyright © 2015 Elsevier B.V. All rights reserved.

Equatorial late-afternoon periodic TEC fluctuations observed by multiple GPS receivers

NASA Astrophysics Data System (ADS)

Tsugawa, T.; Maruyama, T.; Saito, S.; Ishii, M.

2009-12-01

We report, for the first time, equatorial periodic total electron content (TEC) fluctuations observed in the late afternoon by multiple GPS receivers. As a part of Southeast Asia low-latitude ionospheric network (SEALION), GPS receivers at Chiang Mai and Chumphon, Thailand, have been operated since 2005. We found that periodic TEC fluctuations (PTF) with the periods of 15-30 minutes are often observed at these two sites in the spring (Apr-May) late afternoon. Further investigations using multiple GPS receivers in Southeast Asia revealed that the PTFs propagate at 150-200 m/s away from the equator and their amplitudes depend on the satellite azimuth angle. Statistical study of the PTF activity at different latitudes and longitudes clarified that the PTFs are not observed at mid-latitudes, and their seasonal variations are different at different longitudes and at geomagnetically conjugate regions. These observational results indicate that the PTFs are caused by the atmospheric gravity waves (AGW) which are generated in the equatorial lower atmosphere and propagate away from the equator. Simultaneous GPS-TEC and ionosonde observations at Chumphon revealed that the day-to-day variations of PTF activities are well correlated with those of the rate of TEC change index (ROTI) and the occurrence of equatorial spread F (ESF) after the sunset, indicating the PTFs may be related with the onset of the ESF and plasma bubbles.

Innovations in Clinical Trial Design in the Era of Molecular Profiling.

PubMed

Wulfkuhle, Julia D; Spira, Alexander; Edmiston, Kirsten H; Petricoin, Emanuel F

2017-01-01

Historically, cancer has been studied, and therapeutic agents have been evaluated based on organ site, clinical staging, and histology. The science of molecular profiling has expanded our knowledge of cancer at the cellular and molecular level such that numerous subtypes are being described based on biomarker expression and genetic mutations rather than traditional classifications of the disease. Drug development has experienced a concomitant revolution in response to this knowledge with many new targeted therapeutic agents becoming available, and this has necessitated an evolution in clinical trial design. The traditional, large phase II and phase III adjuvant trial models need to be replaced with smaller, shorter, and more focused trials. These trials need to be more efficient and adaptive in order to quickly assess the efficacy of new agents and develop new companion diagnostics. We are now seeing a substantial shift from the traditional multiphase trial model to an increase in phase II adjuvant and neoadjuvant trials in earlier-stage disease incorporating surrogate endpoints for long-term survival to assess efficacy of therapeutic agents in shorter time frames. New trial designs have emerged with capabilities to assess more efficiently multiple disease types, multiple molecular subtypes, and multiple agents simultaneously, and regulatory agencies have responded by outlining new pathways for accelerated drug approval that can help bring effective targeted therapeutic agents to the clinic more quickly for patients in need.

Dual-tail approach to discovery of novel carbonic anhydrase IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site.

PubMed

Hou, Zhuang; Lin, Bin; Bao, Yu; Yan, Hai-Ning; Zhang, Miao; Chang, Xiao-Wei; Zhang, Xin-Xin; Wang, Zi-Jie; Wei, Gao-Fei; Cheng, Mao-Sheng; Liu, Yang; Guo, Chun

2017-05-26

Dual-tail approach was employed to design novel Carbonic Anhydrase (CA) IX inhibitors by simultaneously matching the hydrophobic and hydrophilic halves of the active site, which also contains a zinc ion as part of the catalytic center. The classic sulfanilamide moiety was used as the zinc binding group. An amino glucosamine fragment was chosen as the hydrophilic part and a cinnamamide fragment as the hydrophobic part in order to draw favorable interactions with the corresponding halves of the active site. In comparison with sulfanilamide which is largely devoid of the hydrophilic and hydrophobic interactions with the two halves of the active site, the compounds so designed and synthesized in this study showed 1000-fold improvement in binding affinity. Most of the compounds inhibited the CA effectively with IC 50 values in the range of 7-152 nM. Compound 14e (IC 50 : 7 nM) was more effective than the reference drug acetazolamide (IC 50 : 30 nM). The results proved that the dual-tail approach to simultaneously matching the hydrophobic and hydrophilic halves of the active site by linking hydrophobic and hydrophilic fragments was useful for designing novel CA inhibitors. The effectiveness of those compounds was elucidated by both the experimental data and molecular docking simulations. This work laid a solid foundation for further development of novel CA IX inhibitors for cancer treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Instrumentation for simultaneous kinetic imaging of multiple fluorophores in single living cells

NASA Astrophysics Data System (ADS)

Morris, Stephen J.; Beatty, Diane M.; Welling, Larry W.; Wiegmann, Thomas B.

1991-05-01

Low-light fluorescence video microscopy has established itself as an excellent method for investigations of cell dynamics. There is a growing interest in resolving multiple images of 'ratio' fluorophores like indo or BCECF or the emission from multiple dyes placed in the same cell system. For rapid kinetic studies, the problems of photodynamic damage and photobleaching on one hand and the need for good spatial and temporal resolution on the other, press the resolution of the instrumentation. Rapid resolution of multiple probes at multiple wavelengths presents a third set of problems of exciting the probes and appropriately imaging the emitted light. The authors have designed a new real-time low-light fluorescence video microscope for capturing intensified images of up to four dyes contained in the same cell system. These can be two dual-emission wavelength 'ratio' dyes or multiple dyes. The optics allow simultaneous excitation of up to four fluorophores and the real-time (30 frames/second) capture of four separate fluorescence emission images. Each emission wavelength is imaged simultaneously by one of four cameras, then digitized and appropriately combined at standard video frame rates to be stored at high resolution on tape or video disk for further off-line correction and analysis. The design has no moving parts in its optical train, which overcomes a number of technical difficulties encountered in filter wheel or mechanical shutter designs for multiple imaging. The instrument can be assembled form off-the-shelf components. Coupled to compatible image processing software utilizing PC-AT computers, it can be realized for relatively low cost. Two examples of simultaneous multi-parameter imaging are presented. Synchronous observations of calcium and pH distribution in kidney epithelial cells, loaded with both indo-1 and SNARF-1TM, show that both are altered in response to ionomycin treatment; however, the kinetics for the two changes are quite different. Intracellular calcium increases rapidly when the bath Ca2+ is raised. The pH remains stable for several seconds, then suddenly collapses. The second example concerns fusion of human red blood cells (RBC) to fibroblasts expressing influenza hemagglutinin. Movement of soluble and membrane-bound dyes follow different kinetics, depending upon the molecular weight of the soluble dye. Furthermore, the swelling of the RBC occurs after the onset of fusion, and therefore cannot provide the driving force.

Strategies and Challenges in Simultaneous Augmentation Mastopexy.

PubMed

Spring, Michelle A; Hartmann, Emily C; Stevens, W Grant

2015-10-01

Simultaneous breast augmentation and mastopexy is a common procedure often considered to be one of the most difficult cosmetic breast surgeries. One-stage augmentation mastopexy was initially described more than 50 years ago. The challenge lies in the fact that the surgery has multiple opposing goals: to increasing the volume of a breast, enhance the shape, and simultaneously decrease the skin envelope. Successful outcomes in augmentation can be expected with proper planning, technique, and patient education. This article focuses on common indications for simultaneous augmentation mastopexy, techniques for safe and effective combined procedures, challenges of the procedure, and potential complications. Copyright © 2015 Elsevier Inc. All rights reserved.

Bayesian source tracking via focalization and marginalization in an uncertain Mediterranean Sea environment.

PubMed

Dosso, Stan E; Wilmut, Michael J; Nielsen, Peter L

2010-07-01

This paper applies Bayesian source tracking in an uncertain environment to Mediterranean Sea data, and investigates the resulting tracks and track uncertainties as a function of data information content (number of data time-segments, number of frequencies, and signal-to-noise ratio) and of prior information (environmental uncertainties and source-velocity constraints). To track low-level sources, acoustic data recorded for multiple time segments (corresponding to multiple source positions along the track) are inverted simultaneously. Environmental uncertainty is addressed by including unknown water-column and seabed properties as nuisance parameters in an augmented inversion. Two approaches are considered: Focalization-tracking maximizes the posterior probability density (PPD) over the unknown source and environmental parameters. Marginalization-tracking integrates the PPD over environmental parameters to obtain a sequence of joint marginal probability distributions over source coordinates, from which the most-probable track and track uncertainties can be extracted. Both approaches apply track constraints on the maximum allowable vertical and radial source velocity. The two approaches are applied for towed-source acoustic data recorded at a vertical line array at a shallow-water test site in the Mediterranean Sea where previous geoacoustic studies have been carried out.

3D indoor modeling using a hand-held embedded system with multiple laser range scanners

NASA Astrophysics Data System (ADS)

Hu, Shaoxing; Wang, Duhu; Xu, Shike

2016-10-01

Accurate three-dimensional perception is a key technology for many engineering applications, including mobile mapping, obstacle detection and virtual reality. In this article, we present a hand-held embedded system designed for constructing 3D representation of structured indoor environments. Different from traditional vehicle-borne mobile mapping methods, the system presented here is capable of efficiently acquiring 3D data while an operator carrying the device traverses through the site. It consists of a simultaneous localization and mapping(SLAM) module, a 3D attitude estimate module and a point cloud processing module. The SLAM is based on a scan matching approach using a modern LIDAR system, and the 3D attitude estimate is generated by a navigation filter using inertial sensors. The hardware comprises three 2D time-flight laser range finders and an inertial measurement unit(IMU). All the sensors are rigidly mounted on a body frame. The algorithms are developed on the frame of robot operating system(ROS). The 3D model is constructed using the point cloud library(PCL). Multiple datasets have shown robust performance of the presented system in indoor scenarios.

Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer.

PubMed

Wei, Shuo; Kozono, Shingo; Kats, Lev; Nechama, Morris; Li, Wenzong; Guarnerio, Jlenia; Luo, Manli; You, Mi-Hyeon; Yao, Yandan; Kondo, Asami; Hu, Hai; Bozkurt, Gunes; Moerke, Nathan J; Cao, Shugeng; Reschke, Markus; Chen, Chun-Hau; Rego, Eduardo M; Lo-Coco, Francesco; Cantley, Lewis C; Lee, Tae Ho; Wu, Hao; Zhang, Yan; Pandolfi, Pier Paolo; Zhou, Xiao Zhen; Lu, Kun Ping

2015-05-01

A common key regulator of oncogenic signaling pathways in multiple tumor types is the unique isomerase Pin1. However, available Pin1 inhibitors lack the required specificity and potency for inhibiting Pin1 function in vivo. By using mechanism-based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for acute promyelocytic leukemia (APL) that is considered the first example of targeted therapy in cancer, but whose drug target remains elusive--inhibits and degrades active Pin1 selectively in cancer cells by directly binding to the substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA-induced Pin1 ablation degrades the protein encoded by the fusion oncogene PML-RARA and treats APL in APL cell and animal models as well as in human patients. ATRA-induced Pin1 ablation also potently inhibits triple-negative breast cancer cell growth in human cells and in animal models by acting on many Pin1 substrate oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1-regulated cancer-driving pathways, an attractive property for treating aggressive and drug-resistant tumors.

Genealogies of rapidly adapting populations

PubMed Central

Neher, Richard A.; Hallatschek, Oskar

2013-01-01

The genetic diversity of a species is shaped by its recent evolutionary history and can be used to infer demographic events or selective sweeps. Most inference methods are based on the null hypothesis that natural selection is a weak or infrequent evolutionary force. However, many species, particularly pathogens, are under continuous pressure to adapt in response to changing environments. A statistical framework for inference from diversity data of such populations is currently lacking. Towards this goal, we explore the properties of genealogies in a model of continual adaptation in asexual populations. We show that lineages trace back to a small pool of highly fit ancestors, in which almost simultaneous coalescence of more than two lineages frequently occurs. Whereas such multiple mergers are unlikely under the neutral coalescent, they create a unique genetic footprint in adapting populations. The site frequency spectrum of derived neutral alleles, for example, is nonmonotonic and has a peak at high frequencies, whereas Tajima’s D becomes more and more negative with increasing sample size. Because multiple merger coalescents emerge in many models of rapid adaptation, we argue that they should be considered as a null model for adapting populations. PMID:23269838

On Identifiability of Bias-Type Actuator-Sensor Faults in Multiple-Model-Based Fault Detection and Identification

NASA Technical Reports Server (NTRS)

Joshi, Suresh M.

2012-01-01

This paper explores a class of multiple-model-based fault detection and identification (FDI) methods for bias-type faults in actuators and sensors. These methods employ banks of Kalman-Bucy filters to detect the faults, determine the fault pattern, and estimate the fault values, wherein each Kalman-Bucy filter is tuned to a different failure pattern. Necessary and sufficient conditions are presented for identifiability of actuator faults, sensor faults, and simultaneous actuator and sensor faults. It is shown that FDI of simultaneous actuator and sensor faults is not possible using these methods when all sensors have biases.

Full-band TDM-OPDMA for OBI-reduced simultaneous multiple access in a single-wavelength optical access network.

PubMed

Jung, Sun-Young; Kim, Chang-Hun; Han, Sang-Kook

2018-05-14

Simultaneous multiple access (MA) within a single wavelength can increase the data rate and split ratio in a passive optical network while optical beat interference (OBI) becomes serious in the uplink. Previous techniques to reduce OBI were limited by their complexity and lack of extendibility; as well, bandwidth allocation among MA signals is needed for single photo diode (PD) detection. We proposed and experimentally demonstrated full-band optical pulse division multiplexing-based MA (OPDMA) in an optical access network, which can effectively reduce OBI with extendibility and fully utilize frequency resources of optical modulator without bandwidth allocation in a single-wavelength MA.

Simultaneous entanglement swapping of multiple orbital angular momentum states of light.

PubMed

Zhang, Yingwen; Agnew, Megan; Roger, Thomas; Roux, Filippus S; Konrad, Thomas; Faccio, Daniele; Leach, Jonathan; Forbes, Andrew

2017-09-21

High-bit-rate long-distance quantum communication is a proposed technology for future communication networks and relies on high-dimensional quantum entanglement as a core resource. While it is known that spatial modes of light provide an avenue for high-dimensional entanglement, the ability to transport such quantum states robustly over long distances remains challenging. To overcome this, entanglement swapping may be used to generate remote quantum correlations between particles that have not interacted; this is the core ingredient of a quantum repeater, akin to repeaters in optical fibre networks. Here we demonstrate entanglement swapping of multiple orbital angular momentum states of light. Our approach does not distinguish between different anti-symmetric states, and thus entanglement swapping occurs for several thousand pairs of spatial light modes simultaneously. This work represents the first step towards a quantum network for high-dimensional entangled states and provides a test bed for fundamental tests of quantum science.Entanglement swapping in high dimensions requires large numbers of entangled photons and consequently suffers from low photon flux. Here the authors demonstrate entanglement swapping of multiple spatial modes of light simultaneously, without the need for increasing the photon numbers with dimension.

Improving detection of copy-number variation by simultaneous bias correction and read-depth segmentation.

PubMed

Szatkiewicz, Jin P; Wang, WeiBo; Sullivan, Patrick F; Wang, Wei; Sun, Wei

2013-02-01

Structural variation is an important class of genetic variation in mammals. High-throughput sequencing (HTS) technologies promise to revolutionize copy-number variation (CNV) detection but present substantial analytic challenges. Converging evidence suggests that multiple types of CNV-informative data (e.g. read-depth, read-pair, split-read) need be considered, and that sophisticated methods are needed for more accurate CNV detection. We observed that various sources of experimental biases in HTS confound read-depth estimation, and note that bias correction has not been adequately addressed by existing methods. We present a novel read-depth-based method, GENSENG, which uses a hidden Markov model and negative binomial regression framework to identify regions of discrete copy-number changes while simultaneously accounting for the effects of multiple confounders. Based on extensive calibration using multiple HTS data sets, we conclude that our method outperforms existing read-depth-based CNV detection algorithms. The concept of simultaneous bias correction and CNV detection can serve as a basis for combining read-depth with other types of information such as read-pair or split-read in a single analysis. A user-friendly and computationally efficient implementation of our method is freely available.

Monte Carlo based method for fluorescence tomographic imaging with lifetime multiplexing using time gates

PubMed Central

Chen, Jin; Venugopal, Vivek; Intes, Xavier

2011-01-01

Time-resolved fluorescence optical tomography allows 3-dimensional localization of multiple fluorophores based on lifetime contrast while providing a unique data set for improved resolution. However, to employ the full fluorescence time measurements, a light propagation model that accurately simulates weakly diffused and multiple scattered photons is required. In this article, we derive a computationally efficient Monte Carlo based method to compute time-gated fluorescence Jacobians for the simultaneous imaging of two fluorophores with lifetime contrast. The Monte Carlo based formulation is validated on a synthetic murine model simulating the uptake in the kidneys of two distinct fluorophores with lifetime contrast. Experimentally, the method is validated using capillaries filled with 2.5nmol of ICG and IRDye™800CW respectively embedded in a diffuse media mimicking the average optical properties of mice. Combining multiple time gates in one inverse problem allows the simultaneous reconstruction of multiple fluorophores with increased resolution and minimal crosstalk using the proposed formulation. PMID:21483610

Simple-MSSM: a simple and efficient method for simultaneous multi-site saturation mutagenesis.

PubMed

Cheng, Feng; Xu, Jian-Miao; Xiang, Chao; Liu, Zhi-Qiang; Zhao, Li-Qing; Zheng, Yu-Guo

2017-04-01

To develop a practically simple and robust multi-site saturation mutagenesis (MSSM) method that enables simultaneously recombination of amino acid positions for focused mutant library generation. A general restriction enzyme-free and ligase-free MSSM method (Simple-MSSM) based on prolonged overlap extension PCR (POE-PCR) and Simple Cloning techniques. As a proof of principle of Simple-MSSM, the gene of eGFP (enhanced green fluorescent protein) was used as a template gene for simultaneous mutagenesis of five codons. Forty-eight randomly selected clones were sequenced. Sequencing revealed that all the 48 clones showed at least one mutant codon (mutation efficiency = 100%), and 46 out of the 48 clones had mutations at all the five codons. The obtained diversities at these five codons are 27, 24, 26, 26 and 22, respectively, which correspond to 84, 75, 81, 81, 69% of the theoretical diversity offered by NNK-degeneration (32 codons; NNK, K = T or G). The enzyme-free Simple-MSSM method can simultaneously and efficiently saturate five codons within one day, and therefore avoid missing interactions between residues in interacting amino acid networks.

A case of triple volvulus

PubMed Central

Basu, I; Phillips, D

2012-01-01

Situs inversus is a rare congenital anomaly that has reportedly been associated with caecal volvulus. We describe a case of partial situs inversus complicated by intestinal obstruction secondary to three simultaneously occurring volvuli of the stomach, caecum and sigmoid colon. To our knowledge, this is the first documented case in the literature of multiple, simultaneously occurring volvuli. PMID:22391352

Using Simultaneous Prompting and Computer-Assisted Instruction to Teach Story Writing to Students with Autism

ERIC Educational Resources Information Center

Pennington, Robert C.; Ault, Melinda Jones; Schuster, John W.; Sanders, Ann

2011-01-01

In the current study, the researchers evaluated the effects of simultaneous prompting and computer-assisted instruction on the story-writing responses of 3 males with autism, 7 to 10 ears of age. Classroom teachers conducted all probe and training sessions. The researchers used a multiple baseline across participants design to evaluate the…

Extending the Simultaneous-Sequential Paradigm to Measure Perceptual Capacity for Features and Words

ERIC Educational Resources Information Center

Scharff, Alec; Palmer, John; Moore, Cathleen M.

2011-01-01

In perception, divided attention refers to conditions in which multiple stimuli are relevant to an observer. To measure the effect of divided attention in terms of perceptual capacity, we introduce an extension of the simultaneous-sequential paradigm. The extension makes predictions for fixed-capacity models as well as for unlimited-capacity…

APPLICATIONS ANALYSIS REPORT: AWD TECHNOLOGIES, INC AQUADETOX®/SVE TECHNOLOGY

EPA Science Inventory

In support of the U.S. Environmental Protection Agency’s (EPA) Superfund Innovative Technology Evaluation (SITE) Program, this report evaluates the AWD Technologies, Inc., integrated AquaDetox®/SVE treatment system for simultaneous on-site treatment of contaminated groundwater an...

A dual-learning paradigm can simultaneously train multiple characteristics of walking

PubMed Central

Toliver, Alexis; Bastian, Amy J.

2016-01-01

Impairments in human motor patterns are complex: what is often observed as a single global deficit (e.g., limping when walking) is actually the sum of several distinct abnormalities. Motor adaptation can be useful to teach patients more normal motor patterns, yet conventional training paradigms focus on individual features of a movement, leaving others unaddressed. It is known that under certain conditions, distinct movement components can be simultaneously adapted without interference. These previous “dual-learning” studies focused solely on short, planar reaching movements, yet it is unknown whether these findings can generalize to a more complex behavior like walking. Here we asked whether a dual-learning paradigm, incorporating two distinct motor adaptation tasks, can be used to simultaneously train multiple components of the walking pattern. We developed a joint-angle learning task that provided biased visual feedback of sagittal joint angles to increase peak knee or hip flexion during the swing phase of walking. Healthy, young participants performed this task independently or concurrently with another locomotor adaptation task, split-belt treadmill adaptation, where subjects adapted their step length symmetry. We found that participants were able to successfully adapt both components of the walking pattern simultaneously, without interference, and at the same rate as adapting either component independently. This leads us to the interesting possibility that combining rehabilitation modalities within a single training session could be used to help alleviate multiple deficits at once in patients with complex gait impairments. PMID:26961100

Development of a simultaneous multiple solid-phase microextraction-single shot-gas chromatography/mass spectrometry method and application to aroma profile analysis of commercial coffee.

PubMed

Lee, Changgook; Lee, Younghoon; Lee, Jae-Gon; Buglass, Alan J

2013-06-21

A simultaneous multiple solid-phase microextraction-single shot-gas chromatography mass spectrometry (smSPME-ss-GC/MS) method has been developed for headspace analysis. Up to four fibers (50/30 μm DVB/CAR/PDMS) were used simultaneously for the extraction of aroma components from the headspace of a single sample chamber in order to increase sensitivity of aroma extraction. To avoid peak broadening and to maximize resolution, a simple cryofocusing technique was adopted during sequential thermal desorption of multiple SPME fibers prior to a 'single shot' chromatographic run. The method was developed and validated on a model flavor mixture, containing 81 known pure components. With the conditions of 10 min of incubation and 30 min of extraction at 50 °C, single, dual, triple and quadruple SPME extractions were compared. The increase in total peak area with increase in the number of fibers showed good linearity (R(2)=0.9917) and the mean precision was 12.0% (RSD) for the total peak sum, with quadruple simultaneous SPME extraction. Using a real sample such as commercial coffee granules, aroma profile analysis was conducted using single, dual, triple and quadruple SPME fibers. The increase in total peak intensity again showed good linearity with increase in the number of SPME fibers used (R(2)=0.9992) and the precision of quadruple SPME extraction was 9.9% (RSD) for the total peak sum. Copyright © 2013 Elsevier B.V. All rights reserved.

Characterization of the interactions of PARP-1 with UV-damaged DNA in vivo and in vitro

PubMed Central

Purohit, Nupur K.; Robu, Mihaela; Shah, Rashmi G.; Geacintov, Nicholas E.; Shah, Girish M.

2016-01-01

The existing methodologies for studying robust responses of poly (ADP-ribose) polymerase-1 (PARP-1) to DNA damage with strand breaks are often not suitable for examining its subtle responses to altered DNA without strand breaks, such as UV-damaged DNA. Here we describe two novel assays with which we characterized the interaction of PARP-1 with UV-damaged DNA in vivo and in vitro. Using an in situ fractionation technique to selectively remove free PARP-1 while retaining the DNA-bound PARP-1, we demonstrate a direct recruitment of the endogenous or exogenous PARP-1 to the UV-lesion site in vivo after local irradiation. In addition, using the model oligonucleotides with single UV lesion surrounded by multiple restriction enzyme sites, we demonstrate in vitro that DDB2 and PARP-1 can simultaneously bind to UV-damaged DNA and that PARP-1 casts a bilateral asymmetric footprint from −12 to +9 nucleotides on either side of the UV-lesion. These techniques will permit characterization of different roles of PARP-1 in the repair of UV-damaged DNA and also allow the study of normal housekeeping roles of PARP-1 with undamaged DNA. PMID:26753915

Affordances and Limitations of Immersive Participatory Augmented Reality Simulations for Teaching and Learning

NASA Astrophysics Data System (ADS)

Dunleavy, Matt; Dede, Chris; Mitchell, Rebecca

2009-02-01

The purpose of this study was to document how teachers and students describe and comprehend the ways in which participating in an augmented reality (AR) simulation aids or hinders teaching and learning. Like the multi-user virtual environment (MUVE) interface that underlies Internet games, AR is a good medium for immersive collaborative simulation, but has different strengths and limitations than MUVEs. Within a design-based research project, the researchers conducted multiple qualitative case studies across two middle schools (6th and 7th grade) and one high school (10th grade) in the northeastern United States to document the affordances and limitations of AR simulations from the student and teacher perspective. The researchers collected data through formal and informal interviews, direct observations, web site posts, and site documents. Teachers and students reported that the technology-mediated narrative and the interactive, situated, collaborative problem solving affordances of the AR simulation were highly engaging, especially among students who had previously presented behavioral and academic challenges for the teachers. However, while the AR simulation provided potentially transformative added value, it simultaneously presented unique technological, managerial, and cognitive challenges to teaching and learning.

Improved rate of substrate oxidation catalyzed by genetically-engineered myoglobin.

PubMed

Chand, Subhash; Ray, Sriparna; Wanigasekara, Eranda; Yadav, Poonam; Crawford, Joshua A; Armstrong, Daniel W; Rajeshwar, Krishnan; Pierce, Brad S

2018-02-01

This study showcases the potential of unnatural amino acids to enable non-natural functions when incorporated in the protein scaffold of heme metalloproteins. For this purpose, a genetically-engineered myoglobin (Mb) mutant was created by incorporating redox-active 3-amino-l-tyrosine (NH 2 Tyr) into its active site, replacing the distal histidine (H64) with NH 2 Tyr. In peroxide-shunt assays, this variant exhibits an increased rate of turnover for thioanisole and benzaldehyde oxidation as compared to the wild-type (WT) Mb. Indeed, in the presence of excess hydrogen peroxide (H 2 O 2 ), a 9-fold and 81-fold increase in activity was observed over multiple turnovers for thioanisole sulfoxidation and benzoic acid formation, respectively. The increased oxidation activity in the H64NH 2 Tyr Mb mutant underlined the role of NH 2 Tyr in the distal active-site scaffold in peroxide activation. Kinetic, electrochemical, and EPR spectroscopic experiments were performed. On the basis of these studies, it is argued that the single NH 2 Tyr residue within the Mb variant simultaneously serves the role of the conserved His/Arg-pair within the distal pocket of horseradish peroxidase. Copyright © 2018 Elsevier Inc. All rights reserved.

Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility.

PubMed

Chen, Zhongwen; Oh, Dongmyung; Biswas, Kabir H; Yu, Cheng-Han; Zaidel-Bar, Ronen; Groves, Jay T

2018-06-19

Recent studies have revealed pronounced effects of the spatial distribution of EphA2 receptors on cellular response to receptor activation. However, little is known about molecular mechanisms underlying this spatial sensitivity, in part due to lack of experimental systems. Here, we introduce a hybrid live-cell patterned supported lipid bilayer experimental platform in which the sites of EphA2 activation and integrin adhesion are spatially controlled. Using a series of live-cell imaging and single-molecule tracking experiments, we map the transmission of signals from ephrinA1:EphA2 complexes. Results show that ligand-dependent EphA2 activation induces localized myosin-dependent contractions while simultaneously increasing focal adhesion dynamics throughout the cell. Mechanistically, Src kinase is activated at sites of ephrinA1:EphA2 clustering and subsequently diffuses on the membrane to focal adhesions, where it up-regulates FAK and paxillin tyrosine phosphorylation. EphrinA1:EphA2 signaling triggers multiple cellular responses with differing spatial dependencies to enable a directed migratory response to spatially resolved contact with ephrinA1 ligands.

The Carboxy-Terminal Domain of Hsc70 Provides Binding Sites for a Distinct Set of Chaperone Cofactors

PubMed Central

Demand, Jens; Lüders, Jens; Höhfeld, Jörg

1998-01-01

The modulation of the chaperone activity of the heat shock cognate Hsc70 protein in mammalian cells involves cooperation with chaperone cofactors, such as Hsp40; BAG-1; the Hsc70-interacting protein, Hip; and the Hsc70-Hsp90-organizing protein, Hop. By employing the yeast two-hybrid system and in vitro interaction assays, we have provided insight into the structural basis that underlies Hsc70’s cooperation with different cofactors. The carboxy-terminal domain of Hsc70, previously shown to form a lid over the peptide binding pocket of the chaperone protein, mediates the interaction of Hsc70 with Hsp40 and Hop. Remarkably, the two cofactors bind to the carboxy terminus of Hsc70 in a noncompetitive manner, revealing the existence of distinct binding sites for Hsp40 and Hop within this domain. In contrast, Hip interacts exclusively with the amino-terminal ATPase domain of Hsc70. Hence, Hsc70 possesses separate nonoverlapping binding sites for Hsp40, Hip, and Hop. This appears to enable the chaperone protein to cooperate simultaneously with multiple cofactors. On the other hand, BAG-1 and Hip have recently been shown to compete in binding to the ATPase domain. Our data thus establish the existence of a network of cooperating and competing cofactors regulating the chaperone activity of Hsc70 in the mammalian cell. PMID:9528774

Spatial distribution of errors associated with multistatic meteor radar

NASA Astrophysics Data System (ADS)

Hocking, W. K.

2018-06-01

With the recent increase in numbers of small and versatile low-power meteor radars, the opportunity exists to benefit from simultaneous application of multiple systems spaced by only a few hundred km and less. Transmissions from one site can be recorded at adjacent receiving sites using various degrees of forward scatter, potentially allowing atmospheric conditions in the mesopause regions between stations to be diagnosed. This can allow a better spatial overview of the atmospheric conditions at any time. Such studies have been carried out using a small version of such so-called multistatic meteor radars, e.g. Chau et al. (Radio Sci 52:811-828, 2017, https://doi.org/10.1002/2016rs006225 ). These authors were able to also make measurements of vorticity and divergence. However, measurement uncertainties arise which need to be considered in any application of such techniques. Some errors are so severe that they prohibit useful application of the technique in certain locations, particularly for zones at the midpoints of the radars sites. In this paper, software is developed to allow these errors to be determined, and examples of typical errors involved are discussed. The software should be of value to others who wish to optimize their own MMR systems.

Improving the Fit of a Land-Surface Model to Data Using its Adjoint

NASA Astrophysics Data System (ADS)

Raoult, Nina; Jupp, Tim; Cox, Peter; Luke, Catherine

2016-04-01

Land-surface models (LSMs) are crucial components of the Earth System Models (ESMs) which are used to make coupled climate-carbon cycle projections for the 21st century. The Joint UK Land Environment Simulator (JULES) is the land-surface model used in the climate and weather forecast models of the UK Met Office. In this study, JULES is automatically differentiated using commercial software from FastOpt, resulting in an analytical gradient, or adjoint, of the model. Using this adjoint, the adJULES parameter estimation system has been developed, to search for locally optimum parameter sets by calibrating against observations. We present an introduction to the adJULES system and demonstrate its ability to improve the model-data fit using eddy covariance measurements of gross primary production (GPP) and latent heat (LE) fluxes. adJULES also has the ability to calibrate over multiple sites simultaneously. This feature is used to define new optimised parameter values for the 5 Plant Functional Types (PFTS) in JULES. The optimised PFT-specific parameters improve the performance of JULES over 90% of the FLUXNET sites used in the study. These reductions in error are shown and compared to reductions found due to site-specific optimisations. Finally, we show that calculation of the 2nd derivative of JULES allows us to produce posterior probability density functions of the parameters and how knowledge of parameter values is constrained by observations.

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

Iguchi, Toshihiro, E-mail: iguchi@ba2.so-net.ne.jp; Hiraki, Takao, E-mail: takaoh@tc4.so-net.ne.jp; Gobara, Hideo, E-mail: gobara@cc.okayama-u.ac.jp

PurposeThe aim of the study was to retrospectively evaluate simultaneous multiple hook wire placement outcomes before video-assisted thoracoscopic surgery (VATS).Materials and MethodsThirty-eight procedures were performed on 35 patients (13 men and 22 women; mean age, 59.9 years) with 80 lung lesions (mean diameter 7.9 mm) who underwent simultaneous multiple hook wire placements for preoperative localizations. The primary endpoints were technical success, complications, procedure duration, and VATS outcome; secondary endpoints included comparisons between technical success rates, complication rates, and procedure durations of the 238 single-placement procedures performed. Complications were also evaluated.ResultsIn 35 procedures including 74 lesions, multiple hook wire placements were technically successful;more » in the remaining three procedures, the second target placement was aborted because of massive pneumothorax after the first placement. Although complications occurred in 34 procedures, no grade 3 or above adverse event was observed. The mean procedure duration was 36.4 ± 11.8 min. Three hook wires dislodged during patient transport to the surgical suite. Seventy-four successfully marked lesions were resected. Six lesions without hook wires were successfully resected after detection by palpation with an additional mini-thoracotomy or using subtle pleural changes as a guide. The complication rates and procedure durations of multiple-placement procedures were significantly higher (P = 0.04) and longer (P < 0.001) than those in the single-placement group, respectively, while the technical success rate was not significantly different (P = 0.051).ConclusionsSimultaneous multiple hook wire placements before VATS were clinically feasible, but increased the complication rate and lengthened the procedure time.« less

The comparison between several robust ridge regression estimators in the presence of multicollinearity and multiple outliers

NASA Astrophysics Data System (ADS)

Zahari, Siti Meriam; Ramli, Norazan Mohamed; Moktar, Balkiah; Zainol, Mohammad Said

2014-09-01

In the presence of multicollinearity and multiple outliers, statistical inference of linear regression model using ordinary least squares (OLS) estimators would be severely affected and produces misleading results. To overcome this, many approaches have been investigated. These include robust methods which were reported to be less sensitive to the presence of outliers. In addition, ridge regression technique was employed to tackle multicollinearity problem. In order to mitigate both problems, a combination of ridge regression and robust methods was discussed in this study. The superiority of this approach was examined when simultaneous presence of multicollinearity and multiple outliers occurred in multiple linear regression. This study aimed to look at the performance of several well-known robust estimators; M, MM, RIDGE and robust ridge regression estimators, namely Weighted Ridge M-estimator (WRM), Weighted Ridge MM (WRMM), Ridge MM (RMM), in such a situation. Results of the study showed that in the presence of simultaneous multicollinearity and multiple outliers (in both x and y-direction), the RMM and RIDGE are more or less similar in terms of superiority over the other estimators, regardless of the number of observation, level of collinearity and percentage of outliers used. However, when outliers occurred in only single direction (y-direction), the WRMM estimator is the most superior among the robust ridge regression estimators, by producing the least variance. In conclusion, the robust ridge regression is the best alternative as compared to robust and conventional least squares estimators when dealing with simultaneous presence of multicollinearity and outliers.

High-resolution non-contact measurement of the electrical activity of plants in situ using optical recording

PubMed Central

Zhao, Dong-Jie; Chen, Yang; Wang, Zi-Yang; Xue, Lin; Mao, Tong-Lin; Liu, Yi-Min; Wang, Zhong-Yi; Huang, Lan

2015-01-01

The limitations of conventional extracellular recording and intracellular recording make high-resolution multisite recording of plant bioelectrical activity in situ challenging. By combining a cooled charge-coupled device camera with a voltage-sensitive dye, we recorded the action potentials in the stem of Helianthus annuus and variation potentials at multiple sites simultaneously with high spatial resolution. The method of signal processing using coherence analysis was used to determine the synchronization of the selected signals. Our results provide direct visualization of the phloem, which is the distribution region of the electrical activities in the stem and leaf of H. annuus, and verify that the phloem is the main action potential transmission route in the stems of higher plants. Finally, the method of optical recording offers a unique opportunity to map the dynamic bioelectrical activity and provides an insight into the mechanisms of long-distance electrical signal transmission in higher plants. PMID:26333536

Spontaneous Trait Inferences on Social Media.

PubMed

Levordashka, Ana; Utz, Sonja

2017-01-01

The present research investigates whether spontaneous trait inferences occur under conditions characteristic of social media and networking sites: nonextreme, ostensibly self-generated content, simultaneous presentation of multiple cues, and self-paced browsing. We used an established measure of trait inferences (false recognition paradigm) and a direct assessment of impressions. Without being asked to do so, participants spontaneously formed impressions of people whose status updates they saw. Our results suggest that trait inferences occurred from nonextreme self-generated content, which is commonly found in social media updates (Experiment 1) and when nine status updates from different people were presented in parallel (Experiment 2). Although inferences did occur during free browsing, the results suggest that participants did not necessarily associate the traits with the corresponding status update authors (Experiment 3). Overall, the findings suggest that spontaneous trait inferences occur on social media. We discuss implications for online communication and research on spontaneous trait inferences.

The 150 most important questions in cancer research and clinical oncology series: Questions 25-30 : Edited by Chinese Journal of Cancer.

PubMed

2017-05-04

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 6 more questions are presented as followed. Question 25: Does imprinting of immune responses to infections early in life predict future risk of childhood and adult cancers? Question 26: How to induce homogeneous tumor antigen expression in a heterogeneous tumor mass to enhance the efficacy of cancer immunotherapy? Question 27: Could we enhance the therapeutic effects of immunotherapy by targeting multiple tumor antigens simultaneously or sequentially? Question 28: Can immuno-targeting to cytokines halt cancer metastasis? Question 29: How can we dynamically and less-invasively monitor the activity of CD8 + T killer cells at tumor sites and draining lymph nodes? Question 30: How can the immune system destroy the niches for cancer initiation?

Pharmacokinetics of topically applied pilocarpine in the albino rabbit eye.

PubMed

Makoid, M C; Robinson, J R

1979-04-01

The temporal and spatial pattern of [3H]-pilocarpine nitrate distribution in the albino rabbit eye following topical administration was determined. A four-compartment caternary chain model describing this disposition corresponds to the precorneal area, the cornea, the aqueous humor, and the lens and vitreous. Simultaneous computer fitting of data from tissue corresponding to some compartments in the model supported the proposed model. Additional support was provided by the excellent correlation between predicted and observed values in multiple-dosing studies. Several important aspects of ocular drug disposition are evident from the model. The extensive parallel elimination at the absorption site gives rise to an apparent absorption rate constant that is one to two orders of magnitude larger than the true absorption rate constant. In addition, aqueous flow accounts for most of the drug removal. Thus, major effects on absorption and elimination, independent of the drug structure, suggest the possibility of similar pharmacokinetics for vastly different drugs.

Posttransplantation lymphoproliferative disease involving the pituitary gland.

PubMed

Meriden, Zina; Bullock, Grant C; Bagg, Adam; Bonatti, Hugo; Cousar, John B; Lopes, M Beatriz; Robbins, Mark K; Cathro, Helen P

2010-11-01

Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD. Copyright © 2010 Elsevier Inc. All rights reserved.

A digital underwater video camera system for aquatic research in regulated rivers

USGS Publications Warehouse

Martin, Benjamin M.; Irwin, Elise R.

2010-01-01

We designed a digital underwater video camera system to monitor nesting centrarchid behavior in the Tallapoosa River, Alabama, 20 km below a peaking hydropower dam with a highly variable flow regime. Major components of the system included a digital video recorder, multiple underwater cameras, and specially fabricated substrate stakes. The innovative design of the substrate stakes allowed us to effectively observe nesting redbreast sunfish Lepomis auritus in a highly regulated river. Substrate stakes, which were constructed for the specific substratum complex (i.e., sand, gravel, and cobble) identified at our study site, were able to withstand a discharge level of approximately 300 m3/s and allowed us to simultaneously record 10 active nests before and during water releases from the dam. We believe our technique will be valuable for other researchers that work in regulated rivers to quantify behavior of aquatic fauna in response to a discharge disturbance.

Multinuclear Detection of Nuclear Spin Optical Rotation at Low Field.

PubMed

Zhu, Yue; Gao, Yuheng; Rodocker, Shane; Savukov, Igor; Hilty, Christian

2018-06-06

We describe the multinuclear detection of nuclear spin optical rotation (NSOR), an effect dependent on the hyperfine interaction between nuclear spins and electrons. Signals of 1 H and 19 F are discriminated by frequency in a single spectrum acquired at sub-millitesla field. The simultaneously acquired optical signal along with the nuclear magnetic resonance signal allows the calculation of the relative magnitude of the NSOR constants corresponding to different nuclei within the sample molecules. This is illustrated by a larger NSOR signal measured at the 19 F frequency despite a smaller corresponding spin concentration. Second, it is shown that heteronuclear J-coupling is observable in the NSOR signal, which can be used to retrieve chemical information. Multinuclear frequency and J resolution can localize optical signals in the molecule. Properties of electronic states at multiple sites in a molecule may therefore ultimately be determined by frequency-resolved NSOR spectroscopy at low field.

Manipulating multiple order parameters via oxygen vacancies: The case of E u0.5B a0.5Ti O3 -δ

NASA Astrophysics Data System (ADS)

Li, Weiwei; He, Qian; Wang, Le; Zeng, Huizhong; Bowlan, John; Ling, Langsheng; Yarotski, Dmitry A.; Zhang, Wenrui; Zhao, Run; Dai, Jiahong; Gu, Junxing; Shen, Shipeng; Guo, Haizhong; Pi, Li; Wang, Haiyan; Wang, Yongqiang; Velasco-Davalos, Ivan A.; Wu, Yangjiang; Hu, Zhijun; Chen, Bin; Li, Run-Wei; Sun, Young; Jin, Kuijuan; Zhang, Yuheng; Chen, Hou-Tong; Ju, Sheng; Ruediger, Andreas; Shi, Daning; Borisevich, Albina Y.; Yang, Hao

2017-09-01

Controlling functionalities, such as magnetism or ferroelectricity, by means of oxygen vacancies (VO) is a key issue for the future development of transition-metal oxides. Progress in this field is currently addressed through VO variations and their impact on mainly one order parameter. Here we reveal a mechanism for tuning both magnetism and ferroelectricity simultaneously by using VO. Combining experimental and density-functional theory studies of E u0.5B a0.5Ti O3 -δ , we demonstrate that oxygen vacancies create T i3 +3 d1 defect states, mediating the ferromagnetic coupling between the localized Eu 4 f7 spins, and increase an off-center displacement of Ti ions, enhancing the ferroelectric Curie temperature. The dual function of Ti sites also promises a magnetoelectric coupling in the E u0.5B a0.5Ti O3 -δ .

Large-scale, high-density (up to 512 channels) recording of local circuits in behaving animals

PubMed Central

Berényi, Antal; Somogyvári, Zoltán; Nagy, Anett J.; Roux, Lisa; Long, John D.; Fujisawa, Shigeyoshi; Stark, Eran; Leonardo, Anthony; Harris, Timothy D.

2013-01-01

Monitoring representative fractions of neurons from multiple brain circuits in behaving animals is necessary for understanding neuronal computation. Here, we describe a system that allows high-channel-count recordings from a small volume of neuronal tissue using a lightweight signal multiplexing headstage that permits free behavior of small rodents. The system integrates multishank, high-density recording silicon probes, ultraflexible interconnects, and a miniaturized microdrive. These improvements allowed for simultaneous recordings of local field potentials and unit activity from hundreds of sites without confining free movements of the animal. The advantages of large-scale recordings are illustrated by determining the electroanatomic boundaries of layers and regions in the hippocampus and neocortex and constructing a circuit diagram of functional connections among neurons in real anatomic space. These methods will allow the investigation of circuit operations and behavior-dependent interregional interactions for testing hypotheses of neural networks and brain function. PMID:24353300

Multidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli.

PubMed

Zhang, Congqiang; Seow, Vui Yin; Chen, Xixian; Too, Heng-Phon

2018-05-11

Optimization of metabolic pathways consisting of large number of genes is challenging. Multivariate modular methods (MMMs) are currently available solutions, in which reduced regulatory complexities are achieved by grouping multiple genes into modules. However, these methods work well for balancing the inter-modules but not intra-modules. In addition, application of MMMs to the 15-step heterologous route of astaxanthin biosynthesis has met with limited success. Here, we expand the solution space of MMMs and develop a multidimensional heuristic process (MHP). MHP can simultaneously balance different modules by varying promoter strength and coordinating intra-module activities by using ribosome binding sites (RBSs) and enzyme variants. Consequently, MHP increases enantiopure 3S,3'S-astaxanthin production to 184 mg l -1 day -1 or 320 mg l -1 . Similarly, MHP improves the yields of nerolidol and linalool. MHP may be useful for optimizing other complex biochemical pathways.

Integrated optimization of planetary rover layout and exploration routes

NASA Astrophysics Data System (ADS)

Lee, Dongoo; Ahn, Jaemyung

2018-01-01

This article introduces an optimization framework for the integrated design of a planetary surface rover and its exploration route that is applicable to the initial phase of a planetary exploration campaign composed of multiple surface missions. The scientific capability and the mobility of a rover are modelled as functions of the science weight fraction, a key parameter characterizing the rover. The proposed problem is formulated as a mixed-integer nonlinear program that maximizes the sum of profits obtained through a planetary surface exploration mission by simultaneously determining the science weight fraction of the rover, the sites to visit and their visiting sequences under resource consumption constraints imposed on each route and collectively on a mission. A solution procedure for the proposed problem composed of two loops (the outer loop and the inner loop) is developed. The results of test cases demonstrating the effectiveness of the proposed framework are presented.

Combining atomic force and fluorescence microscopy for analysis of quantum-dot labeled protein–DNA complexes

PubMed Central

Ebenstein, Yuval; Gassman, Natalie; Kim, Soohong; Weiss, Shimon

2011-01-01

Atomic force microscopy (AFM) and fluorescence microscopy are widely used for the study of protein-DNA interactions. While AFM excels in its ability to elucidate structural detail and spatial arrangement, it lacks the ability to distinguish between similarly sized objects in a complex system. This information is readily accessible to optical imaging techniques via site-specific fluorescent labels, which enable the direct detection and identification of multiple components simultaneously. Here, we show how the utilization of semiconductor quantum dots (QDs), serving as contrast agents for both AFM topography and fluorescence imaging, facilitates the combination of both imaging techniques, and with the addition of a flow based DNA extension method for sample deposition, results in a powerful tool for the study of protein-DNA complexes. We demonstrate the inherent advantages of this novel combination of techniques by imaging individual RNA polymerases (RNAP) on T7 genomic DNA. PMID:19452448

Multiple Testing in the Context of Gene Discovery in Sickle Cell Disease Using Genome-Wide Association Studies.

PubMed

Kuo, Kevin H M

2017-01-01

The issue of multiple testing, also termed multiplicity, is ubiquitous in studies where multiple hypotheses are tested simultaneously. Genome-wide association study (GWAS), a type of genetic association study that has gained popularity in the past decade, is most susceptible to the issue of multiple testing. Different methodologies have been employed to address the issue of multiple testing in GWAS. The purpose of the review is to examine the methodologies employed in dealing with multiple testing in the context of gene discovery using GWAS in sickle cell disease complications.

Geospatial optimization of siting large-scale solar projects

USGS Publications Warehouse

Macknick, Jordan; Quinby, Ted; Caulfield, Emmet; Gerritsen, Margot; Diffendorfer, James E.; Haines, Seth S.

2014-01-01

guidelines by being user-driven, transparent, interactive, capable of incorporating multiple criteria, and flexible. This work provides the foundation for a dynamic siting assistance tool that can greatly facilitate siting decisions among multiple stakeholders.

Multiple-Use Site Demand Analysis: An Application to the Boundary Waters Canoe Area Wilderness.

ERIC Educational Resources Information Center

Peterson, George L.; And Others

1982-01-01

A single-site, multiple-use model for analyzing trip demand is derived from a multiple site regional model based on utility maximizing choice theory. The model is used to analyze and compare trips to the Boundary Waters Canoe Area Wilderness for several types of use. Travel cost elasticities of demand are compared and discussed. (Authors/JN)

Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid

PubMed Central

Kwon, Inchan; Choi, Eun Sil

2016-01-01

Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation. PMID:27028506

Forced Ambiguity of the Leucine Codons for Multiple-Site-Specific Incorporation of a Noncanonical Amino Acid.

PubMed

Kwon, Inchan; Choi, Eun Sil

2016-01-01

Multiple-site-specific incorporation of a noncanonical amino acid into a recombinant protein would be a very useful technique to generate multiple chemical handles for bioconjugation and multivalent binding sites for the enhanced interaction. Previously combination of a mutant yeast phenylalanyl-tRNA synthetase variant and the yeast phenylalanyl-tRNA containing the AAA anticodon was used to incorporate a noncanonical amino acid into multiple UUU phenylalanine (Phe) codons in a site-specific manner. However, due to the less selective codon recognition of the AAA anticodon, there was significant misincorporation of a noncanonical amino acid into unwanted UUC Phe codons. To enhance codon selectivity, we explored degenerate leucine (Leu) codons instead of Phe degenerate codons. Combined use of the mutant yeast phenylalanyl-tRNA containing the CAA anticodon and the yPheRS_naph variant allowed incorporation of a phenylalanine analog, 2-naphthylalanine, into murine dihydrofolate reductase in response to multiple UUG Leu codons, but not to other Leu codon sites. Despite the moderate UUG codon occupancy by 2-naphthylalaine, these results successfully demonstrated that the concept of forced ambiguity of the genetic code can be achieved for the Leu codons, available for multiple-site-specific incorporation.

Spontaneous nasal cerebrospinal fluid leaks and empty sella syndrome: a clinical association.

PubMed

Schlosser, Rodney J; Bolger, William E

2003-01-01

Spontaneous, idiopathic nasal meningoencephaloceles are herniations of arachnoid/dura and cerebrospinal fluid (CSF) through anatomically fragile sites within the skull base. Empty sella syndrome occurs when intracranial contents herniate through the sellar diaphragm filling the sella turcica with CSF and giving the radiographic appearance of an absent pituitary gland. The objective of this study was to examine the association between spontaneous encephaloceles/CSF leaks and empty sella syndrome because of their similar clinical features and potential common pathophysiology. Retrospective. Sixteen patients were treated for spontaneous encephaloceles between 1996 and 2001. All 16 patients had associated CSF leaks. Five patients had multiple simultaneous encephaloceles. Fifteen patients with imaging of the sella turcica had empty (10 patients) or partially empty (5 patients) sellas. One patient did not have complete imaging of the sella. Three patients had lumbar punctures with measurement of CSF pressure during computed tomography cisternograms because of multiple skull base defects. Mean CSF pressure was 28.3 cm of water (range, 19-34 cm; normal, 0-15 cm). Thirteen of 16 patients (81%) were obese women (mean body mass index 35.9 kg/m2; normal, <25 kg/m2). Mean follow-up was 14.2 months with 100% success in closure of the defects after one procedure. Spontaneous meningoencephaloceles and CSF leaks are strongly associated with radiographic findings of an empty sella and suggest a common pathophysiology. The underlying condition probably represents a form of intracranial hypertension that exerts hydrostatic pressure at anatomically weakened sites within the skull base. Otolaryngologists should be familiar with this disease entity and the implications intracranial hypertension has on patient management.

Non-peristaltic patterns of motor activity in the guinea-pig proximal colon.

PubMed

Hennig, G W; Gregory, S; Brookes, S J H; Costa, M

2010-06-01

The guinea-pig proximal colon contains semi-solid feces which are propelled by intermittent neural peristaltic waves to the distal colon, where solid pellets are formed. Between propulsive periods, complex motor patterns underlie fluid re-absorption and mixing of contents. Spatio-temporal analysis of video recordings were used to investigate neural and myogenic patterns of non-peristaltic motor activity. At low distension (6 cmH(2)O), two major motor patterns were seen. Narrow rings of constriction (abrupt contractions) occurred at 19 cpm. These previously undescribed contractions occurred, almost simultaneously, at many points along the preparation, with a calculated propagation velocity of 110 mm s(-1). They were abolished by hexamethonium and by tetrodotoxin, indicating they were neurally mediated. Inhibition of nitric oxide synthase resulted in increased frequency of 'abrupt contractions' suggesting ongoing inhibitory modulation by endogenous nitric oxide. After tetrodotoxin, another distinct motor pattern was revealed; 'ripples'(1) consisted of shallow rings of contraction, occurring at 18 cpm and propagating at 2.7-2.9 mm s(-1) orally or aborally from multiple initiation sites. The frequency of 'ripples' increased as intraluminal pressure was raised, becoming very irregular at high distensions. L-type calcium channel blockers and openers affected the amplitude of 'ripples'. No frequency gradient of 'ripples' along the proximal colon was detected. This absence explains the multiple initiation sites which often shifted over time, and the oral and aboral propagation of 'ripples'. The interaction of myogenic 'ripples' with neurogenic 'abrupt contractions' generates localized alternating rings of contractions and dilatation, well suited to effective mixing of contents.

Multiple ligand-binding modes in bacterial R67 dihydrofolate reductase

NASA Astrophysics Data System (ADS)

Alonso, Hernán; Gillies, Malcolm B.; Cummins, Peter L.; Bliznyuk, Andrey A.; Gready, Jill E.

2005-03-01

R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central active-site pore. Two reactants (dihydrofolate, DHF), two cofactors (NADPH) or one of each (R67•DHF•NADPH) can be found simultaneously within the active site, the last one being the reactive ternary complex. As the positioning of the ligands has proven elusive to empirical determination, we addressed the problem from a theoretical perspective. Several potential structures of the ternary complex were generated using the docking programs AutoDock and FlexX. The variability among the final poses, many of which conformed to experimental data, prompted us to perform a comparative scoring analysis and molecular dynamics simulations to assess the stability of the complexes. Analysis of ligand-ligand and ligand-protein interactions along the 4 ns trajectories of eight different structures allowed us to identify important inter-ligand contacts and key protein residues. Our results, combined with published empirical data, clearly suggest that multipe binding modes of the ligands are possible within R67 DHFR. While the pterin ring of DHF and the nicotinamide ring of NADPH assume a stacked endo-conformation at the centre of the pore, probably assisted by V66, Q67 and I68, the tails of the molecules extend towards opposite ends of the cavity, adopting multiple configurations in a solvent rich-environment where hydrogen-bond interactions with K32 and Y69 may play important roles.