Two-photon holographic optogenetics of neural circuits (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yang, Weijian; Carrillo-Reid, Luis; Peterka, Darcy S.; Yuste, Rafael

2016-03-01

Optical manipulation of in vivo neural circuits with cellular resolution could be important for understanding cortical function. Despite recent progress, simultaneous optogenetic activation with cellular precision has either been limited to 2D planes, or a very small numbers of neurons over a limited volume. Here we demonstrate a novel paradigm for simultaneous 3D activation using a low repetition rate pulse-amplified fiber laser system and a spatial light modulator (SLM) to project 3D holographic excitation patterns on the cortex of mice in vivo for targeted volumetric 3D photoactivation. This method is compatible with two-photon imaging, and enables the simultaneous activation of multiple cells in 3D, using red-shifted opsins, such as C1V1 or ReaChR, while simultaneously imaging GFP-based sensors such as GCaMP6. This all-optical imaging and 3D manipulation approach achieves simultaneous reading and writing of cortical activity, and should be a powerful tool for the study of neuronal circuits.

Multirate delivery of multiple therapeutic agents from metal-organic frameworks

DOE PAGES

McKinlay, Alistair C.; Allan, Phoebe K.; Renouf, Catherine L.; ...

2014-12-01

The highly porous nature of metal-organic frameworks (MOFs) offers great potential for the delivery of therapeutic agents. Here, we show that highly porous metal-organic frameworks can be used to deliver multiple therapeutic agents—a biologically active gas, an antibiotic drug molecule, and an active metal ion—simultaneously but at different rates. The possibilities offered by delivery of multiple agents with different mechanisms of action and, in particular, variable timescales may allow new therapy approaches. Here, we show that the loaded MOFs are highly active against various strains of bacteria.

Single cell multiplexed assay for proteolytic activity using droplet microfluidics.

PubMed

Ng, Ee Xien; Miller, Miles A; Jing, Tengyang; Chen, Chia-Hung

2016-07-15

Cellular enzymes interact in a post-translationally regulated fashion to govern individual cell behaviors, yet current platform technologies are limited in their ability to measure multiple enzyme activities simultaneously in single cells. Here, we developed multi-color Förster resonance energy transfer (FRET)-based enzymatic substrates and use them in a microfluidics platform to simultaneously measure multiple specific protease activities from water-in-oil droplets that contain single cells. By integrating the microfluidic platform with a computational analytical method, Proteolytic Activity Matrix Analysis (PrAMA), we are able to infer six different protease activity signals from individual cells in a high throughput manner (~100 cells/experimental run). We characterized protease activity profiles at single cell resolution for several cancer cell lines including breast cancer cell line MDA-MB-231, lung cancer cell line PC-9, and leukemia cell line K-562 using both live-cell and in-situ cell lysis assay formats, with special focus on metalloproteinases important in metastasis. The ability to measure multiple proteases secreted from or expressed in individual cells allows us to characterize cell heterogeneity and has potential applications including systems biology, pharmacology, cancer diagnosis and stem cell biology. Copyright © 2016 Elsevier B.V. All rights reserved.

Spectrally Resolved Fiber Photometry for Multi-component Analysis of Brain Circuits.

PubMed

Meng, Chengbo; Zhou, Jingheng; Papaneri, Amy; Peddada, Teja; Xu, Karen; Cui, Guohong

2018-04-25

To achieve simultaneous measurement of multiple cellular events in molecularly defined groups of neurons in vivo, we designed a spectrometer-based fiber photometry system that allows for spectral unmixing of multiple fluorescence signals recorded from deep brain structures in behaving animals. Using green and red Ca 2+ indicators differentially expressed in striatal direct- and indirect-pathway neurons, we were able to simultaneously monitor the neural activity in these two pathways in freely moving animals. We found that the activities were highly synchronized between the direct and indirect pathways within one hemisphere and were desynchronized between the two hemispheres. We further analyzed the relationship between the movement patterns and the magnitude of activation in direct- and indirect-pathway neurons and found that the striatal direct and indirect pathways coordinately control the dynamics and fate of movement. Published by Elsevier Inc.

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.

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.

Integration of silicon-based neural probes and micro-drive arrays for chronic recording of large populations of neurons in behaving animals

NASA Astrophysics Data System (ADS)

Michon, Frédéric; Aarts, Arno; Holzhammer, Tobias; Ruther, Patrick; Borghs, Gustaaf; McNaughton, Bruce; Kloosterman, Fabian

2016-08-01

Objective. Understanding how neuronal assemblies underlie cognitive function is a fundamental question in system neuroscience. It poses the technical challenge to monitor the activity of populations of neurons, potentially widely separated, in relation to behaviour. In this paper, we present a new system which aims at simultaneously recording from a large population of neurons from multiple separated brain regions in freely behaving animals. Approach. The concept of the new device is to combine the benefits of two existing electrophysiological techniques, i.e. the flexibility and modularity of micro-drive arrays and the high sampling ability of electrode-dense silicon probes. Main results. Newly engineered long bendable silicon probes were integrated into a micro-drive array. The resulting device can carry up to 16 independently movable silicon probes, each carrying 16 recording sites. Populations of neurons were recorded simultaneously in multiple cortical and/or hippocampal sites in two freely behaving implanted rats. Significance. Current approaches to monitor neuronal activity either allow to flexibly record from multiple widely separated brain regions (micro-drive arrays) but with a limited sampling density or to provide denser sampling at the expense of a flexible placement in multiple brain regions (neural probes). By combining these two approaches and their benefits, we present an alternative solution for flexible and simultaneous recordings from widely distributed populations of neurons in freely behaving rats.

Multifunctional RNA Nanoparticles

PubMed Central

2015-01-01

Our recent advancements in RNA nanotechnology introduced novel nanoscaffolds (nanorings); however, the potential of their use for biomedical applications was never fully revealed. As presented here, besides functionalization with multiple different short interfering RNAs for combinatorial RNA interference (e.g., against multiple HIV-1 genes), nanorings also allow simultaneous embedment of assorted RNA aptamers, fluorescent dyes, proteins, as well as recently developed RNA–DNA hybrids aimed to conditionally activate multiple split functionalities inside cells. PMID:25267559

Learning multiple relative attributes with humans in the loop.

PubMed

Qian, Buyue; Wang, Xiang; Cao, Nan; Jiang, Yu-Gang; Davidson, Ian

2014-12-01

Semantic attributes have been recognized as a more spontaneous manner to describe and annotate image content. It is widely accepted that image annotation using semantic attributes is a significant improvement to the traditional binary or multiclass annotation due to its naturally continuous and relative properties. Though useful, existing approaches rely on an abundant supervision and high-quality training data, which limit their applicability. Two standard methods to overcome small amounts of guidance and low-quality training data are transfer and active learning. In the context of relative attributes, this would entail learning multiple relative attributes simultaneously and actively querying a human for additional information. This paper addresses the two main limitations in existing work: 1) it actively adds humans to the learning loop so that minimal additional guidance can be given and 2) it learns multiple relative attributes simultaneously and thereby leverages dependence amongst them. In this paper, we formulate a joint active learning to rank framework with pairwise supervision to achieve these two aims, which also has other benefits such as the ability to be kernelized. The proposed framework optimizes over a set of ranking functions (measuring the strength of the presence of attributes) simultaneously and dependently on each other. The proposed pairwise queries take the form of which one of these two pictures is more natural? These queries can be easily answered by humans. Extensive empirical study on real image data sets shows that our proposed method, compared with several state-of-the-art methods, achieves superior retrieval performance while requires significantly less human inputs.

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.

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…

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.

Simultaneous determination of multiple soil enzyme activities for soil health-biogeochemical indexes

USDA-ARS?s Scientific Manuscript database

Enzyme activities (EAs) are soil health indicators of changes in decomposition processes due to management and the crop(s) affecting the quantity and quality of plant residues and nutrients entering the soil. More commonly assessed soil EAs can provide information of reactions where plant available ...

Tracking the Continuity of Language Comprehension: Computer Mouse Trajectories Suggest Parallel Syntactic Processing

ERIC Educational Resources Information Center

Farmer, Thomas A.; Cargill, Sarah A.; Hindy, Nicholas C.; Dale, Rick; Spivey, Michael J.

2007-01-01

Although several theories of online syntactic processing assume the parallel activation of multiple syntactic representations, evidence supporting simultaneous activation has been inconclusive. Here, the continuous and non-ballistic properties of computer mouse movements are exploited, by recording their streaming x, y coordinates to procure…

Multiple-generator errors are unavoidable under model misspecification.

PubMed

Jewett, D L; Zhang, Z

1995-08-01

Model misspecification poses a major problem for dipole source localization (DSL) because it causes insidious multiple-generator errors (MulGenErrs) to occur in the fitted dipole parameters. This paper describes how and why this occurs, based upon simple algebraic considerations. MulGenErrs must occur, to some degree, in any DSL analysis of real data because there is model misspecification and mathematically the equations used for the simultaneously active generators must be of a different form than the equations for each generator active alone.

Determining heterogeneous slip activity on multiple slip systems from single crystal orientation pole figures

DOE PAGES

Pagan, Darren C.; Miller, Matthew P.

2016-09-01

A new experimental method to determine heterogeneity of shear strains associated with crystallographic slip in the bulk of ductile, crystalline materials is outlined. The method quantifies the time resolved evolution of misorientation within plastically deforming crystals using single crystal orientation pole figures (SCPFs) measured in-situ with X-ray diffraction. A multiplicative decomposition of the crystal kinematics is used to interpret the distributions of lattice plane orientation observed on the SCPFs in terms of heterogeneous slip activity (shear strains) on multiple slip systems. Here, to show the method’s utility, the evolution of heterogeneous slip is quantified in a silicon single crystal plasticallymore » deformed at high temperature at multiple load steps, with slip activity in sub-volumes of the crystal analyzed simultaneously.« less

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).

Multi-neuron intracellular recording in vivo via interacting autopatching robots

PubMed Central

Holst, Gregory L; Singer, Annabelle C; Han, Xue; Brown, Emery N

2018-01-01

The activities of groups of neurons in a circuit or brain region are important for neuronal computations that contribute to behaviors and disease states. Traditional extracellular recordings have been powerful and scalable, but much less is known about the intracellular processes that lead to spiking activity. We present a robotic system, the multipatcher, capable of automatically obtaining blind whole-cell patch clamp recordings from multiple neurons simultaneously. The multipatcher significantly extends automated patch clamping, or 'autopatching’, to guide four interacting electrodes in a coordinated fashion, avoiding mechanical coupling in the brain. We demonstrate its performance in the cortex of anesthetized and awake mice. A multipatcher with four electrodes took an average of 10 min to obtain dual or triple recordings in 29% of trials in anesthetized mice, and in 18% of the trials in awake mice, thus illustrating practical yield and throughput to obtain multiple, simultaneous whole-cell recordings in vivo. PMID:29297466

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.

Wide field-of-view, multi-region two-photon imaging of neuronal activity in the mammalian brain

PubMed Central

Stirman, Jeffrey N.; Smith, Ikuko T.; Kudenov, Michael W.; Smith, Spencer L.

2016-01-01

Two-photon calcium imaging provides an optical readout of neuronal activity in populations of neurons with subcellular resolution. However, conventional two-photon imaging systems are limited in their field of view to ~1 mm2, precluding the visualization of multiple cortical areas simultaneously. Here, we demonstrate a two-photon microscope with an expanded field of view (>9.5 mm2) for rapidly reconfigurable simultaneous scanning of widely separated populations of neurons. We custom designed and assembled an optimized scan engine, objective, and two independently positionable, temporally multiplexed excitation pathways. We used this new microscope to measure activity correlations between two cortical visual areas in mice during visual processing. PMID:27347754

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.

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.

Simultaneous EUV and radio observations of bidirectional plasmoids ejection during magnetic reconnection

NASA Astrophysics Data System (ADS)

Kumar, Pankaj; Cho, Kyung-Suk

2013-09-01

We present a multiwavelength study of the X-class flare, which occurred in active region (AR) NOAA 11339 on 3 November 2011. The extreme ultraviolet (EUV) images recorded by SDO/AIA show the activation of a remote filament (located north of the AR) with footpoint brightenings about 50 min prior to the flare's occurrence. The kinked filament rises up slowly, and after reaching a projected height of ~49 Mm, it bends and falls freely near the AR, where the X-class flare was triggered. Dynamic radio spectrum from the Green Bank Solar Radio Burst Spectrometer (GBSRBS) shows simultaneous detection of both positive and negative drifting pulsating structures (DPSs) in the decimetric radio frequencies (500-1200 MHz) during the impulsive phase of the flare. The global negative DPSs in solar flares are generally interpreted as a signature of electron acceleration related to the upward-moving plasmoids in the solar corona. The EUV images from AIA 94 Å reveal the ejection of multiple plasmoids, which move simultaneously upward and downward in the corona during the magnetic reconnection. The estimated speeds of the upward- and downward-moving plasmoids are ~152-362 and ~83-254 km s-1, respectively. These observations strongly support the recent numerical simulations of the formation and interaction of multiple plasmoids due to tearing of the current-sheet structure. On the basis of our analysis, we suggest that the simultaneous detection of both the negative and positive DPSs is most likely generated by the interaction or coalescence of the multiple plasmoids moving upward and downward along the current-sheet structure during the magnetic reconnection process. Moreover, the differential emission measure (DEM) analysis of the active region reveals a hot flux-rope structure (visible in AIA 131 and 94 Å) prior to the flare initiation and ejection of the multitemperature plasmoids during the flare impulsive phase. Movie is available in electronic form at http://www.aanda.org

Memory: Ironing Out a Wrinkle in Time.

PubMed

Miller, Adam M P; Frankland, Paul W; Josselyn, Sheena A

2018-05-21

Individual hippocampal neurons encode time over seconds, whereas large-scale changes in population activity of hippocampal neurons encode time over minutes and days. New research shows how the hippocampus represents these multiple timescales simultaneously. Copyright © 2018 Elsevier Ltd. All rights reserved.

Continuous and simultaneous estimation of finger kinematics using inputs from an EMG-to-muscle activation model.

PubMed

Ngeo, Jimson G; Tamei, Tomoya; Shibata, Tomohiro

2014-08-14

Surface electromyography (EMG) signals are often used in many robot and rehabilitation applications because these reflect motor intentions of users very well. However, very few studies have focused on the accurate and proportional control of the human hand using EMG signals. Many have focused on discrete gesture classification and some have encountered inherent problems such as electro-mechanical delays (EMD). Here, we present a new method for estimating simultaneous and multiple finger kinematics from multi-channel surface EMG signals. In this study, surface EMG signals from the forearm and finger kinematic data were extracted from ten able-bodied subjects while they were tasked to do individual and simultaneous multiple finger flexion and extension movements in free space. Instead of using traditional time-domain features of EMG, an EMG-to-Muscle Activation model that parameterizes EMD was used and shown to give better estimation performance. A fast feed forward artificial neural network (ANN) and a nonparametric Gaussian Process (GP) regressor were both used and evaluated to estimate complex finger kinematics, with the latter rarely used in the other related literature. The estimation accuracies, in terms of mean correlation coefficient, were 0.85 ± 0.07, 0.78 ± 0.06 and 0.73 ± 0.04 for the metacarpophalangeal (MCP), proximal interphalangeal (PIP) and the distal interphalangeal (DIP) finger joint DOFs, respectively. The mean root-mean-square error in each individual DOF ranged from 5 to 15%. We show that estimation improved using the proposed muscle activation inputs compared to other features, and that using GP regression gave better estimation results when using fewer training samples. The proposed method provides a viable means of capturing the general trend of finger movements and shows a good way of estimating finger joint kinematics using a muscle activation model that parameterizes EMD. The results from this study demonstrates a potential control strategy based on EMG that can be applied for simultaneous and continuous control of multiple DOF(s) devices such as robotic hand/finger prostheses or exoskeletons.

Note on simultaneous inferences about non-inferiority and superiority for a primary and a secondary endpoint.

PubMed

Guilbaud, Olivier

2011-11-01

In their review of challenges to multiple testing in clinical trials, Hung and Wang (2010) considered the situation where a treatment is to be compared with an active comparator and the aim is to show non-inferiority and (if possible) superiority with respect to a primary and a secondary endpoint. This note extends their discussion of this particular situation, taking the sequentially rejective procedure they used for illustration as a starting point. Some alternative multiple testing procedures (MTPs) are considered, and corresponding simultaneous confidence regions are discussed that provide additional information "for free". The choice may then be based on the properties of these MTPs and corresponding confidence regions. 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Space-Time Processing for Tactical Mobile Ad Hoc Networks

DTIC Science & Technology

2007-08-01

rates in mobile ad hoc networks. In addition, he has considered the design of a cross-layer multi-user resource allocation framework using a... framework for many-to-one communication. In this context, multiple nodes cooperate to transmit their packets simultaneously to a single node using multi...spatially multiplexed signals transmitted from multiple nodes. Our goal is to form a framework that activates different sets of communication links

Parallel Object Activation and Attentional Gating of Information: Evidence from Eye Movements in the Multiple Object Naming Paradigm

ERIC Educational Resources Information Center

Schotter, Elizabeth R.; Ferreira, Victor S.; Rayner, Keith

2013-01-01

Do we access information from any object we can see, or do we access information only from objects that we intend to name? In 3 experiments using a modified multiple object naming paradigm, subjects were required to name several objects in succession when previews appeared briefly and simultaneously in the same location as the target as well as at…

A novel clinical multimodal multiphoton tomograph for AF, SHG, CARS imaging, and FLIM

NASA Astrophysics Data System (ADS)

Weinigel, Martin; Breunig, Hans Georg; König, Karsten

2014-02-01

We report on a flexible nonlinear medical tomograph with multiple miniaturized detectors for simultaneous acquisition of two-photon autofluorescence (AF), second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) images. The simultaneous visualization of the distribution of endogenous fluorophores NAD(P)H, melanin and elastin, SHG-active collagen and as well as non-fluorescent lipids within human skin in vivo is possible. Furthermore, fluorescence lifetime images (FLIM) can be generated using time-correlated single photon counting.

Holographic imaging and photostimulation of neural activity.

PubMed

Yang, Weijian; Yuste, Rafael

2018-06-01

Optical imaging methods are powerful tools in neuroscience as they can systematically monitor the activity of neuronal populations with high spatiotemporal resolution using calcium or voltage indicators. Moreover, caged compounds and optogenetic actuators enable to optically manipulate neural activity. Among optical methods, computer-generated holography offers an enormous flexibility to sculpt the excitation light in three-dimensions (3D), particularly when combined with two-photon light sources. By projecting holographic light patterns on the sample, the activity of multiple neurons across a 3D brain volume can be simultaneously imaged or optically manipulated with single-cell precision. This flexibility makes two-photon holographic microscopy an ideal all-optical platform to simultaneously read and write activity in neuronal populations in vivo in 3D, a critical ability to dissect the function of neural circuits. Copyright © 2018 Elsevier Ltd. All rights reserved.

A multiplexed fluorescent assay for independent second-messenger systems: decoding GPCR activation in living cells.

PubMed

Tewson, Paul H; Quinn, Anne Marie; Hughes, Thomas E

2013-08-01

There is a growing need in drug discovery and basic research to measure multiple second-messenger components of cell signaling pathways in real time and in relevant tissues and cell types. Many G-protein-coupled receptors activate the heterotrimeric protein, Gq, which in turn activates phospholipase C (PLC). PLC cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) to produce two second messengers: diacylglycerol (DAG), which remains in the plasma membrane, and inositol triphosphate (IP3), which diffuses through the cytosol to release stores of intracellular calcium ions (Ca(2+)). Our goal was to create a series of multiplex sensors that would make it possible to simultaneously measure two different components of the Gq pathway in living cells. Here we describe new fluorescent sensors for DAG and PIP2 that produce robust changes in green or red fluorescence and can be combined with one another, or with existing Ca(2+) sensors, in a live-cell assay. These assays can detect multiple components of Gq signaling, simultaneously in real time, on standard fluorescent plate readers or live-cell imaging systems.

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

Simultaneous quantification of alternatively spliced transcripts in a single droplet digital PCR reaction.

PubMed

Sun, Bing; Tao, Lian; Zheng, Yun-Ling

2014-06-01

Human telomerase reverse transcriptase (hTERT) is an essential component required for telomerase activity and telomere maintenance. Several alternatively spliced forms of hTERT mRNA have been reported in human primary and tumor cells. Currently, however, there is no sensitive and accurate method for the simultaneous quantification of multiple alternatively spliced RNA transcripts, such as in the case of hTERT. Here we show droplet digital PCR (ddPCR) provides sensitive, simultaneous digital quantification in a single reaction of two alternatively spliced single deletion hTERT transcripts (α-/β+ and α+/β-) as well as the opportunity to manually quantify non-deletion (α+/β+) and double deletion (α-/β-) transcripts. Our ddPCR method enables direct comparison among four alternatively spliced mRNAs without the need for internal standards or multiple primer pairs specific for each variant as real-time PCR (qPCR) requires, thus eliminating potential variation due to differences in PCR amplification efficiency.

Effects of Shared Active Surface Technology on the Communication and Speech of Two Preschool Children with Disabilities

ERIC Educational Resources Information Center

Travers, Jason C.; Fefer, Sarah A.

2017-01-01

Shared active surface (SAS) technology can be described as a supersized tablet computer for multiple simultaneous users. SAS technology has the potential to resolve issues historically associated with learning via single-user computer technology. This study reports findings of a SAS on the social communication and nonsocial speech of two preschool…

Multicolor Super-Resolution Fluorescence Imaging via Multi-Parameter Fluorophore Detection

PubMed Central

Bates, Mark; Dempsey, Graham T; Chen, Kok Hao; Zhuang, Xiaowei

2012-01-01

Understanding the complexity of the cellular environment will benefit from the ability to unambiguously resolve multiple cellular components, simultaneously and with nanometer-scale spatial resolution. Multicolor super-resolution fluorescence microscopy techniques have been developed to achieve this goal, yet challenges remain in terms of the number of targets that can be simultaneously imaged and the crosstalk between color channels. Herein, we demonstrate multicolor stochastic optical reconstruction microscopy (STORM) based on a multi-parameter detection strategy, which uses both the fluorescence activation wavelength and the emission color to discriminate between photo-activatable fluorescent probes. First, we obtained two-color super-resolution images using the near-infrared cyanine dye Alexa 750 in conjunction with a red cyanine dye Alexa 647, and quantified color crosstalk levels and image registration accuracy. Combinatorial pairing of these two switchable dyes with fluorophores which enhance photo-activation enabled multi-parameter detection of six different probes. Using this approach, we obtained six-color super-resolution fluorescence images of a model sample. The combination of multiple fluorescence detection parameters for improved fluorophore discrimination promises to substantially enhance our ability to visualize multiple cellular targets with sub-diffraction-limit resolution. PMID:22213647

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.

Simultaneous profiling of activity patterns in multiple neuronal subclasses.

PubMed

Parrish, R Ryley; Grady, John; Codadu, Neela K; Trevelyan, Andrew J; Racca, Claudia

2018-06-01

Neuronal networks typically comprise heterogeneous populations of neurons. A core objective when seeking to understand such networks, therefore, is to identify what roles these different neuronal classes play. Acquiring single cell electrophysiology data for multiple cell classes can prove to be a large and daunting task. Alternatively, Ca 2+ network imaging provides activity profiles of large numbers of neurons simultaneously, but without distinguishing between cell classes. We therefore developed a strategy for combining cellular electrophysiology, Ca 2+ network imaging, and immunohistochemistry to provide activity profiles for multiple cell classes at once. This involves cross-referencing easily identifiable landmarks between imaging of the live and fixed tissue, and then using custom MATLAB functions to realign the two imaging data sets, to correct for distortions of the tissue introduced by the fixation or immunohistochemical processing. We illustrate the methodology for analyses of activity profiles during epileptiform events recorded in mouse brain slices. We further demonstrate the activity profile of a population of parvalbumin-positive interneurons prior, during, and following a seizure-like event. Current approaches to Ca 2+ network imaging analyses are severely limited in their ability to subclassify neurons, and often rely on transgenic approaches to identify cell classes. In contrast, our methodology is a generic, affordable, and flexible technique to characterize neuronal behaviour with respect to classification based on morphological and neurochemical identity. We present a new approach for analysing Ca 2+ network imaging datasets, and use this to explore the parvalbumin-positive interneuron activity during epileptiform events. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous Top-down Modulation of the Primary Somatosensory Cortex and Thalamic Nuclei during Active Tactile Discrimination

PubMed Central

Pais-Vieira, Miguel; Lebedev, Mikhail A.; Wiest, Michael C.; Nicolelis, Miguel A.L.

2013-01-01

The rat somatosensory system contains multiple thalamocortical loops (TCL) that altogether process, in fundamentally different ways, tactile stimuli delivered passively or actively sampled. To elucidate potential top-down mechanisms that govern TCL processing in awake, behaving animals, we simultaneously recorded neuronal ensemble activity across multiple cortical and thalamic areas while rats performed an active aperture discrimination task. Single neurons located in the primary somatosensory cortex (S1), the ventroposterior medial (VPM) and the posterior medial (POM) thalamic nuclei of the trigeminal somatosensory pathways exhibited prominent anticipatory firing modulations prior to the whiskers touching the aperture edges. This cortical and thalamic anticipatory firing could not be explained by whisker movements or whisker stimulation, because neither trigeminal ganglion sensory-evoked responses nor EMG activity were detected during the same period. Both thalamic and S1 anticipatory activity were predictive of the animal’s discrimination accuracy. Inactivation of the primary motor cortex (M1) with muscimol affected anticipatory patterns in S1 and the thalamus, and impaired the ability to predict the animal’s performance accuracy based on thalamocortical anticipatory activity. These findings suggest that neural processing in TCLs is launched in anticipation of whisker contact with objects, depends on top-down effects generated in part by M1 activity, and cannot be explained by the classical feedforward model of the rat trigeminal system. PMID:23447616

Robust extraction of basis functions for simultaneous and proportional myoelectric control via sparse non-negative matrix factorization

NASA Astrophysics Data System (ADS)

Lin, Chuang; Wang, Binghui; Jiang, Ning; Farina, Dario

2018-04-01

Objective. This paper proposes a novel simultaneous and proportional multiple degree of freedom (DOF) myoelectric control method for active prostheses. Approach. The approach is based on non-negative matrix factorization (NMF) of surface EMG signals with the inclusion of sparseness constraints. By applying a sparseness constraint to the control signal matrix, it is possible to extract the basis information from arbitrary movements (quasi-unsupervised approach) for multiple DOFs concurrently. Main Results. In online testing based on target hitting, able-bodied subjects reached a greater throughput (TP) when using sparse NMF (SNMF) than with classic NMF or with linear regression (LR). Accordingly, the completion time (CT) was shorter for SNMF than NMF or LR. The same observations were made in two patients with unilateral limb deficiencies. Significance. The addition of sparseness constraints to NMF allows for a quasi-unsupervised approach to myoelectric control with superior results with respect to previous methods for the simultaneous and proportional control of multi-DOF. The proposed factorization algorithm allows robust simultaneous and proportional control, is superior to previous supervised algorithms, and, because of minimal supervision, paves the way to online adaptation in myoelectric control.

Designing Digital Environments for Art Education/Exploration.

ERIC Educational Resources Information Center

Milekic, Slavko

2000-01-01

Examines the role of digital technology in the context of art education and art exploration. Discusses the development of digital environments as the next step in the evolution of traditional computers, whose main characteristic is support for simultaneous multiple-user interactions and for social and collaborative activities. (LRW)

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.

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.

Optogenetic micro-electrocorticography for modulating and localizing cerebral cortex activity

PubMed Central

Richner, Thomas J.; Thongpang, Sanitta; Brodnick, Sarah K.; Schendel, Amelia A.; Falk, Ryan W.; Krugner-Higby, Lisa A.; Pashaie, Ramin; Williams, Justin C.

2014-01-01

Objective Spatial localization of neural activity from within the brain with electrocorticography (ECoG) and electroencephalography (EEG) remains a challenge in clinical and research settings, and while microfabricated ECoG (micro-ECoG) array technology continues to improve, complimentary methods to simultaneously modulate cortical activity while recording are needed. Approach We developed a neural interface utilizing optogenetics, cranial windowing, and micro-ECoG arrays fabricated on a transparent polymer. This approach enabled us to directly modulate neural activity at known locations around micro-ECoG arrays in mice expressing Channelrhodopsin-2 (ChR2). We applied photostimuli varying in time, space and frequency to the cortical surface, and we targeted multiple depths within the cortex using an optical fiber while recording micro-ECoG signals. Main Results Negative potentials of up to 1.5 mV were evoked by photostimuli applied to the entire cortical window, while focally applied photostimuli evoked spatially localized micro-ECoG potentials. Two simultaneously applied focal stimuli could be separated, depending on the distance between them. Photostimuli applied within the cortex with an optical fiber evoked more complex micro-ECoG potentials with multiple positive and negative peaks whose relative amplitudes depended on the depth of the fiber. Significance Optogenetic ECoG has potential applications in the study of epilepsy, cortical dynamics, and neuroprostheses. PMID:24445482

Neural basis for dynamic updating of object representation in visual working memory.

PubMed

Takahama, Sachiko; Miyauchi, Satoru; Saiki, Jun

2010-02-15

In real world, objects have multiple features and change dynamically. Thus, object representations must satisfy dynamic updating and feature binding. Previous studies have investigated the neural activity of dynamic updating or feature binding alone, but not both simultaneously. We investigated the neural basis of feature-bound object representation in a dynamically updating situation by conducting a multiple object permanence tracking task, which required observers to simultaneously process both the maintenance and dynamic updating of feature-bound objects. Using an event-related design, we separated activities during memory maintenance and change detection. In the search for regions showing selective activation in dynamic updating of feature-bound objects, we identified a network during memory maintenance that was comprised of the inferior precentral sulcus, superior parietal lobule, and middle frontal gyrus. In the change detection period, various prefrontal regions, including the anterior prefrontal cortex, were activated. In updating object representation of dynamically moving objects, the inferior precentral sulcus closely cooperates with a so-called "frontoparietal network", and subregions of the frontoparietal network can be decomposed into those sensitive to spatial updating and feature binding. The anterior prefrontal cortex identifies changes in object representation by comparing memory and perceptual representations rather than maintaining object representations per se, as previously suggested. Copyright 2009 Elsevier Inc. All rights reserved.

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

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

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.

Holding multiple items in short term memory: a neural mechanism.

PubMed

Rolls, Edmund T; Dempere-Marco, Laura; Deco, Gustavo

2013-01-01

Human short term memory has a capacity of several items maintained simultaneously. We show how the number of short term memory representations that an attractor network modeling a cortical local network can simultaneously maintain active is increased by using synaptic facilitation of the type found in the prefrontal cortex. We have been able to maintain 9 short term memories active simultaneously in integrate-and-fire simulations where the proportion of neurons in each population, the sparseness, is 0.1, and have confirmed the stability of such a system with mean field analyses. Without synaptic facilitation the system can maintain many fewer memories active in the same network. The system operates because of the effectively increased synaptic strengths formed by the synaptic facilitation just for those pools to which the cue is applied, and then maintenance of this synaptic facilitation in just those pools when the cue is removed by the continuing neuronal firing in those pools. The findings have implications for understanding how several items can be maintained simultaneously in short term memory, how this may be relevant to the implementation of language in the brain, and suggest new approaches to understanding and treating the decline in short term memory that can occur with normal aging.

Holding Multiple Items in Short Term Memory: A Neural Mechanism

PubMed Central

Rolls, Edmund T.; Dempere-Marco, Laura; Deco, Gustavo

2013-01-01

Human short term memory has a capacity of several items maintained simultaneously. We show how the number of short term memory representations that an attractor network modeling a cortical local network can simultaneously maintain active is increased by using synaptic facilitation of the type found in the prefrontal cortex. We have been able to maintain 9 short term memories active simultaneously in integrate-and-fire simulations where the proportion of neurons in each population, the sparseness, is 0.1, and have confirmed the stability of such a system with mean field analyses. Without synaptic facilitation the system can maintain many fewer memories active in the same network. The system operates because of the effectively increased synaptic strengths formed by the synaptic facilitation just for those pools to which the cue is applied, and then maintenance of this synaptic facilitation in just those pools when the cue is removed by the continuing neuronal firing in those pools. The findings have implications for understanding how several items can be maintained simultaneously in short term memory, how this may be relevant to the implementation of language in the brain, and suggest new approaches to understanding and treating the decline in short term memory that can occur with normal aging. PMID:23613789

Transitions in Learning: Evidence for Simultaneously Activated Strategies.

ERIC Educational Resources Information Center

Goldin-Meadow, Susan; And Others

Children rarely cite more than one strategy when asked to explain how they solved a particular arithmetic problem, hence their verbal explanations will not necessarily reveal whether they have considered multiple strategies on that problem. However, previous work has shown that, when asked to explain their performance on a task, children often use…

Electrochemical camera chip for simultaneous imaging of multiple metabolites in biofilms

PubMed Central

Bellin, Daniel L.; Sakhtah, Hassan; Zhang, Yihan; Price-Whelan, Alexa; Dietrich, Lars E. P.; Shepard, Kenneth L.

2016-01-01

Monitoring spatial distribution of metabolites in multicellular structures can enhance understanding of the biochemical processes and regulation involved in cellular community development. Here we report on an electrochemical camera chip capable of simultaneous spatial imaging of multiple redox-active phenazine metabolites produced by Pseudomonas aeruginosa PA14 colony biofilms. The chip features an 8 mm × 8 mm array of 1,824 electrodes multiplexed to 38 parallel output channels. Using this chip, we demonstrate potential-sweep-based electrochemical imaging of whole-biofilms at measurement rates in excess of 0.2 s per electrode. Analysis of mutants with various capacities for phenazine production reveals distribution of phenazine-1-carboxylic acid (PCA) throughout the colony, with 5-methylphenazine-1-carboxylic acid (5-MCA) and pyocyanin (PYO) localized to the colony edge. Anaerobic growth on nitrate confirms the O2-dependence of PYO production and indicates an effect of O2 availability on 5-MCA synthesis. This integrated-circuit-based technique promises wide applicability in detecting redox-active species from diverse biological samples. PMID:26813638

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…

Linear summation of outputs in a balanced network model of motor cortex.

PubMed

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis.

Functional Magnetic Resonance Imaging with Concurrent Urodynamic Testing Identifies Brain Structures Involved in Micturition Cycle in Patients with Multiple Sclerosis.

PubMed

Khavari, Rose; Karmonik, Christof; Shy, Michael; Fletcher, Sophie; Boone, Timothy

2017-02-01

Neurogenic lower urinary tract dysfunction, which is common in patients with multiple sclerosis, has a significant impact on quality of life. In this study we sought to determine brain activity processes during the micturition cycle in female patients with multiple sclerosis and neurogenic lower urinary tract dysfunction. We report brain activity on functional magnetic resonance imaging and simultaneous urodynamic testing in 23 ambulatory female patients with multiple sclerosis. Individual functional magnetic resonance imaging activation maps at strong desire to void and at initiation of voiding were calculated and averaged at Montreal Neuroimaging Institute. Areas of significant activation were identified in these average maps. Subgroup analysis was performed in patients with elicitable neurogenic detrusor overactivity or detrusor-sphincter dyssynergia. Group analysis of all patients at strong desire to void yielded areas of activation in regions associated with executive function (frontal gyrus), emotional regulation (cingulate gyrus) and motor control (putamen, cerebellum and precuneus). Comparison of the average change in activation between previously reported healthy controls and patients with multiple sclerosis showed predominantly stronger, more focal activation in the former and lower, more diffused activation in the latter. Patients with multiple sclerosis who had demonstrable neurogenic detrusor overactivity and detrusor-sphincter dyssynergia showed a trend toward distinct brain activation at full urge and at initiation of voiding respectively. We successfully studied brain activation during the entire micturition cycle in female patients with neurogenic lower urinary tract dysfunction and multiple sclerosis using a concurrent functional magnetic resonance imaging/urodynamic testing platform. Understanding the central neural processes involved in specific parts of micturition in patients with neurogenic lower urinary tract dysfunction may identify areas of interest for future intervention. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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 Low Power, Parallel Wearable Multi-Sensor System for Human Activity Evaluation.

PubMed

Li, Yuecheng; Jia, Wenyan; Yu, Tianjian; Luan, Bo; Mao, Zhi-Hong; Zhang, Hong; Sun, Mingui

2015-04-01

In this paper, the design of a low power heterogeneous wearable multi-sensor system, built with Zynq System-on-Chip (SoC), for human activity evaluation is presented. The powerful data processing capability and flexibility of this SoC represent significant improvements over our previous ARM based system designs. The new system captures and compresses multiple color images and sensor data simultaneously. Several strategies are adopted to minimize power consumption. Our wearable system provides a new tool for the evaluation of human activity, including diet, physical activity and lifestyle.

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...

Hyperspectral imaging for simultaneous measurements of two FRET biosensors in pancreatic β-cells.

PubMed

Elliott, Amicia D; Bedard, Noah; Ustione, Alessandro; Baird, Michelle A; Davidson, Michael W; Tkaczyk, Tomasz; Piston, David W

2017-01-01

Fluorescent protein (FP) biosensors based on Förster resonance energy transfer (FRET) are commonly used to study molecular processes in living cells. There are FP-FRET biosensors for many cellular molecules, but it remains difficult to perform simultaneous measurements of multiple biosensors. The overlapping emission spectra of the commonly used FPs, including CFP/YFP and GFP/RFP make dual FRET measurements challenging. In addition, a snapshot imaging modality is required for simultaneous imaging. The Image Mapping Spectrometer (IMS) is a snapshot hyperspectral imaging system that collects high resolution spectral data and can be used to overcome these challenges. We have previously demonstrated the IMS's capabilities for simultaneously imaging GFP and CFP/YFP-based biosensors in pancreatic β-cells. Here, we demonstrate a further capability of the IMS to image simultaneously two FRET biosensors with a single excitation band, one for cAMP and the other for Caspase-3. We use these measurements to measure simultaneously cAMP signaling and Caspase-3 activation in pancreatic β-cells during oxidative stress and hyperglycemia, which are essential components in the pathology of diabetes.

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...

An active acoustic tripwire for simultaneous detection and localization of multiple underwater intruders.

PubMed

Folegot, Thomas; Martinelli, Giovanna; Guerrini, Piero; Stevenson, J Mark

2008-11-01

An algorithm allowing simultaneous detection and localization of multiple submerged targets crossing an acoustic tripwire based on forward scattering is described and then evaluated based upon data collected at sea. This paper quantifies the agreement between the theoretical performance and the results obtained from processing data gathered at sea for crossings at several depths and ranges. Targets crossing the acoustic field produce shadows on each side of the barrier, for specific sensors and for specific acoustic paths. In post-processing, a model is invoked to associate expected paths with the observed shadows. This process allows triangulation of the target's position inside the acoustic field. Precise localization is achieved by taking advantage of the multipath propagation structure of the received signal, together with the diversity of the source and receiver locations. Environmental robustness is demonstrated using simulations and can be explained by the use of an array of sources spatially distributed through the water column.

The antimicrobial activity of nanoparticles: present situation and prospects for the future

PubMed Central

Wang, Linlin; Hu, Chen; Shao, Longquan

2017-01-01

Nanoparticles (NPs) are increasingly used to target bacteria as an alternative to antibiotics. Nanotechnology may be particularly advantageous in treating bacterial infections. Examples include the utilization of NPs in antibacterial coatings for implantable devices and medicinal materials to prevent infection and promote wound healing, in antibiotic delivery systems to treat disease, in bacterial detection systems to generate microbial diagnostics, and in antibacterial vaccines to control bacterial infections. The antibacterial mechanisms of NPs are poorly understood, but the currently accepted mechanisms include oxidative stress induction, metal ion release, and non-oxidative mechanisms. The multiple simultaneous mechanisms of action against microbes would require multiple simultaneous gene mutations in the same bacterial cell for antibacterial resistance to develop; therefore, it is difficult for bacterial cells to become resistant to NPs. In this review, we discuss the antibacterial mechanisms of NPs against bacteria and the factors that are involved. The limitations of current research are also discussed. PMID:28243086

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...

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.

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. ...

Simultaneous quantitative determination of multiple bioactive markers in Ocimum sanctum obtained from different locations and its marketed herbal formulations using UPLC-ESI-MS/MS combined with principal component analysis.

PubMed

Pandey, Renu; Chandra, Preeti; Srivastava, Mukesh; Mishra, D K; Kumar, Brijesh

2015-01-01

Ocimum sanctum L., with phenolic acids, flavonoids, propenyl phenols and terpenoids as active pharmacological constituents, is a popular medicinal herb and is present as an ingredient in many herbal formulations. Therefore, development of a reliable analytical method for simultaneous determination of the pharmacologically active constituents of O. sanctum is of high importance. To develop and validate a new, rapid, sensitive and selective UPLC-ESI/MS/MS method for simultaneous determination of 23 bioactive markers including phenolic acids, flavonoids, propenyl phenol and terpenoid in the leaf extract and marketed herbal formulations of O. sanctum. An UPLC-ESI/MS/MS method using negative electrospray ionisation (ESI) in multiple-reaction-monitoring (MRM) mode was used for simultaneous determination. Chromatographic separation was achieved on an Acquity UPLC BEH C18 -column using a gradient elution with 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Principal component analysis (PCA) was applied to correlate and discriminate eight geographical collections of O. sanctum based on quantitative data of the analytes. The developed method was validated as per International Conference on Harmonization guidelines and found to be accurate, with overall recovery in the range 95.09-104.84% (RSD ≤ 1.85%), precise (RSD ≤ 1.98%) and linear (r(2)  ≥ 0.9971) over the concentration range of 0.5-1000 ng/mL. Ursolic acid was found to be the most abundant marker in all the samples investigated, except for the marketed tablet. The method established is simple, rapid and sensitive, hence it can be reliably utilised for the quality control of O. sanctum and derived herbal formulations. Copyright © 2015 John Wiley & Sons, Ltd.

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...

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.

Shrimp miR-12 Suppresses White Spot Syndrome Virus Infection by Synchronously Triggering Antiviral Phagocytosis and Apoptosis Pathways

PubMed Central

Shu, Le; Zhang, Xiaobo

2017-01-01

Growing evidence has indicated that the innate immune system can be regulated by microRNAs (miRNAs). However, the mechanism underlying miRNA-mediated simultaneous activation of multiple immune pathways remains unknown. To address this issue, the role of host miR-12 in shrimp (Marsupenaeus japonicus) antiviral immune responses was characterized in the present study. The results indicated that miR-12 participated in virus infection, host phagocytosis, and apoptosis in defense against white spot syndrome virus invasion. miR-12 could simultaneously trigger phagocytosis, apoptosis, and antiviral immunity through the synchronous downregulation of the expression of shrimp genes [PTEN (phosphatase and tensin homolog) and BI-1(transmembrane BAX inhibitor motif containing 6)] and the viral gene (wsv024). Further analysis showed that miR-12 could synchronously mediate the 5′–3′ exonucleolytic degradation of its target mRNAs, and this degradation terminated in the vicinity of the 3′ untranslated region sequence complementary to the seed sequence of miR-12. Therefore, the present study showed novel aspects of the miRNA-mediated simultaneous regulation of multiple immune pathways. PMID:28824612

Linear summation of outputs in a balanced network model of motor cortex

PubMed Central

Capaday, Charles; van Vreeswijk, Carl

2015-01-01

Given the non-linearities of the neural circuitry's elements, we would expect cortical circuits to respond non-linearly when activated. Surprisingly, when two points in the motor cortex are activated simultaneously, the EMG responses are the linear sum of the responses evoked by each of the points activated separately. Additionally, the corticospinal transfer function is close to linear, implying that the synaptic interactions in motor cortex must be effectively linear. To account for this, here we develop a model of motor cortex composed of multiple interconnected points, each comprised of reciprocally connected excitatory and inhibitory neurons. We show how non-linearities in neuronal transfer functions are eschewed by strong synaptic interactions within each point. Consequently, the simultaneous activation of multiple points results in a linear summation of their respective outputs. We also consider the effects of reduction of inhibition at a cortical point when one or more surrounding points are active. The network response in this condition is linear over an approximately two- to three-fold decrease of inhibitory feedback strength. This result supports the idea that focal disinhibition allows linear coupling of motor cortical points to generate movement related muscle activation patterns; albeit with a limitation on gain control. The model also explains why neural activity does not spread as far out as the axonal connectivity allows, whilst also explaining why distant cortical points can be, nonetheless, functionally coupled by focal disinhibition. Finally, we discuss the advantages that linear interactions at the cortical level afford to motor command synthesis. PMID:26097452

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.

Measuring specificity in multi-substrate/product systems as a tool to investigate selectivity in vivo.

PubMed

Kuo, Yin-Ming; Henry, Ryan A; Andrews, Andrew J

2016-01-01

Multiple substrate enzymes present a particular challenge when it comes to understanding their activity in a complex system. Although a single target may be easy to model, it does not always present an accurate representation of what that enzyme will do in the presence of multiple substrates simultaneously. Therefore, there is a need to find better ways to both study these enzymes in complicated systems, as well as accurately describe the interactions through kinetic parameters. This review looks at different methods for studying multiple substrate enzymes, as well as explores options on how to most accurately describe an enzyme's activity within these multi-substrate systems. Identifying and defining this enzymatic activity should help clear the way to using in vitro systems to accurately predicting the behavior of multi-substrate enzymes in vivo. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions. Copyright © 2015. Published by Elsevier B.V.

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

Seizure entrainment with polarizing low-frequency electric fields in a chronic animal epilepsy model

NASA Astrophysics Data System (ADS)

Sunderam, Sridhar; Chernyy, Nick; Peixoto, Nathalia; Mason, Jonathan P.; Weinstein, Steven L.; Schiff, Steven J.; Gluckman, Bruce J.

2009-08-01

Neural activity can be modulated by applying a polarizing low-frequency (Lt100 Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF stimulation has a graded, modulatory effect on neuronal excitability, and permits the simultaneous recording of neuronal activity during stimulation suitable for continuous feedback control. We tested a prototype system that allows for simultaneous PLEF stimulation with minimal recording artifact in a chronic tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous seizures. Depth electrode local field potentials recorded during seizures revealed a characteristic pattern of field postsynaptic potentials (fPSPs). Sinusoidal voltage-controlled PLEF stimulation (0.5-25 Hz) was applied in open-loop cycles radially across the CA3 of ventral hippocampus. For stimulated seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical significance of entrainment was assessed with Thomson's harmonic F-test, with 45/132 stimulated seizures in four animals individually demonstrating significant entrainment (p < 0.04). Significant entrainment for multiple presentations at the same frequency (p < 0.01) was observed in three of four animals in 42/64 stimulated seizures. This is the first demonstration in chronically implanted freely behaving animals of PLEF modulation of neural activity with simultaneous recording.

Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

PubMed

Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

2018-06-01

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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...

Simultaneous water activation and glucose metabolic rate imaging with PET

NASA Astrophysics Data System (ADS)

Verhaeghe, Jeroen; Reader, Andrew J.

2013-02-01

A novel imaging and signal separation strategy is proposed to be able to separate [18F]FDG and multiple [15O]H2O signals from a simultaneously acquired dynamic PET acquisition of the two tracers. The technique is based on the fact that the dynamics of the two tracers are very distinct. By adopting an appropriate bolus injection strategy and by defining tailored sets of basis functions that model either the FDG or water component, it is possible to separate the FDG and water signal. The basis functions are inspired from the spectral analysis description of dynamic PET studies and are defined as the convolution of estimated generating functions (GFs) with a set of decaying exponential functions. The GFs are estimated from the overall measured head curve, while the decaying exponential functions are pre-determined. In this work, the time activity curves (TACs) are modelled post-reconstruction but the model can be incorporated in a global 4D reconstruction strategy. Extensive PET simulation studies are performed considering single [18F]FDG and 6 [15O]H2O bolus injections for a total acquisition time of 75 min. The proposed method is evaluated at multiple noise levels and different parameters were estimated such as [18F]FDG uptake and blood flow estimated from the [15O]H2O component, requiring a full dynamic analysis of the two components, static images of [18F]FDG and the water components as well as [15O]H2O activation. It is shown that the resulting images and parametric values in ROIs are comparable to images obtained from separate imaging, illustrating the feasibility of simultaneous imaging of [18F]FDG and [15O]H2O components. For more information on this article, see medicalphysicsweb.org

A highly tunable system for the simultaneous expression of multiple enzymes in Saccharomyces cerevisiae.

PubMed

Ito, Yoichiro; Yamanishi, Mamoru; Ikeuchi, Akinori; Matsuyama, Takashi

2015-01-16

Control of the expression levels of multiple enzymes in transgenic yeasts is essential for the effective production of complex molecules through fermentation. Here, we propose a tunable strategy for the control of expression levels based on the design of terminator regions and other gene-expression control elements in Saccharomyces cerevisiae. Our genome-integrated system, which is capable of producing high expression levels over a wide dynamic range, will broadly enable metabolic engineering and synthetic biology. We demonstrated that the activities of multiple cellulases and the production of ethanol were doubled in a transgenic yeast constructed with our system compared with those achieved with a standard expression system.

Potentiometric Dye Imaging for Pheochromocytoma and Cortical Neurons with a Novel Measurement System Using an Integrated Complementary Metal-Oxide-Semiconductor Imaging Device

NASA Astrophysics Data System (ADS)

Kobayashi, Takuma; Tagawa, Ayato; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Hatanaka, Yumiko; Tamura, Hideki; Ishikawa, Yasuyuki; Shiosaka, Sadao; Ohta, Jun

2010-11-01

The combination of optical imaging with voltage-sensitive dyes is a powerful tool for studying the spatiotemporal patterns of neural activity and understanding the neural networks of the brain. To visualize the potential status of multiple neurons simultaneously using a compact instrument with high density and a wide range, we present a novel measurement system using an implantable biomedical photonic LSI device with a red absorptive light filter for voltage-sensitive dye imaging (BpLSI-red). The BpLSI-red was developed for sensing fluorescence by the on-chip LSI, which was designed by using complementary metal-oxide-semiconductor (CMOS) technology. A micro-electro-mechanical system (MEMS) microfabrication technique was used to postprocess the CMOS sensor chip; light-emitting diodes (LEDs) were integrated for illumination and to enable long-term cell culture. Using the device, we succeeded in visualizing the membrane potential of 2000-3000 cells and the process of depolarization of pheochromocytoma cells (PC12 cells) and mouse cerebral cortical neurons in a primary culture with cellular resolution. Therefore, our measurement application enables the detection of multiple neural activities simultaneously.

Will a category cue attract you? Motor output reveals dynamic competition across person construal.

PubMed

Freeman, Jonathan B; Ambady, Nalini; Rule, Nicholas O; Johnson, Kerri L

2008-11-01

People use social categories to perceive others, extracting category cues to glean membership. Growing evidence for continuous dynamics in real-time cognition suggests, contrary to prevailing social psychological accounts, that person construal may involve dynamic competition between simultaneously active representations. To test this, the authors examined social categorization in real-time by streaming the x, y coordinates of hand movements as participants categorized typical and atypical faces by sex. Though judgments of atypical targets were largely accurate, online motor output exhibited a continuous spatial attraction toward the opposite sex category, indicating dynamic competition between multiple social category alternatives. The authors offer a dynamic continuity account of social categorization and provide converging evidence across categorizations of real male and female faces (containing a typical or an atypical sex-specifying cue) and categorizations of computer-generated male and female faces (with subtly morphed sex-typical or sex-atypical features). In 3 studies, online motor output revealed continuous dynamics underlying person construal, in which multiple simultaneously and partially active category representations gradually cascade into social categorical judgments. Such evidence is challenging for discrete stage-based accounts. (c) 2008 APA, 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

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

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

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…

A novel tetrode microdrive for simultaneous multi-neuron recording from different regions of primate brain.

PubMed

Santos, Lucas; Opris, Ioan; Fuqua, Joshua; Hampson, Robert E; Deadwyler, Sam A

2012-04-15

A unique custom-made tetrode microdrive for recording from large numbers of neurons in several areas of primate brain is described as a means for assessing simultaneous neural activity in cortical and subcortical structures in nonhuman primates (NHPs) performing behavioral tasks. The microdrive device utilizes tetrode technology with up to six ultra-thin microprobe guide tubes (0.1mm) that can be independently positioned, each containing reduced diameter tetrode and/or hexatrode microwires (0.02 mm) for recording and isolating single neuron activity. The microdrive device is mounted within the standard NHP cranial well and allows traversal of brain depths up to 40.0 mm. The advantages of this technology are demonstrated via simultaneously recorded large populations of neurons with tetrode type probes during task performance from a) primary motor cortex and deep brain structures (caudate-putamen and hippocampus) and b) multiple layers within the prefrontal cortex. The means to characterize interactions of well-isolated ensembles of neurons recorded simultaneously from different regions, as shown with this device, has not been previously available for application in primate brain. The device has extensive application to primate models for the detection and study of inoperative or maladaptive neural circuits related to human neurological disorders. Published by Elsevier B.V.

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…

A Phytochemical-Sensing Strategy Based on Mass Spectrometry Imaging and Metabolic Profiling for Understanding the Functionality of the Medicinal Herb Green Tea.

PubMed

Fujimura, Yoshinori; Miura, Daisuke; Tachibana, Hirofumi

2017-09-27

Low-molecular-weight phytochemicals have health benefits and reduce the risk of diseases, but the mechanisms underlying their activities have remained elusive because of the lack of a methodology that can easily visualize the exact behavior of such small molecules. Recently, we developed an in situ label-free imaging technique, called mass spectrometry imaging, for visualizing spatially-resolved biotransformations based on simultaneous mapping of the major bioactive green tea polyphenol and its phase II metabolites. In addition, we established a mass spectrometry-based metabolic profiling technique capable of evaluating the bioactivities of diverse green tea extracts, which contain multiple phytochemicals, by focusing on their compositional balances. This methodology allowed us to simultaneously evaluate the relative contributions of the multiple compounds present in a multicomponent system to its bioactivity. This review highlights small molecule-sensing techniques for visualizing the complex behaviors of herbal components and linking such information to an enhanced understanding of the functionalities of multicomponent medicinal herbs.

Inference in a Synchronization Game with Social Interactions *

PubMed Central

de Paula, Áureo

2009-01-01

This paper studies inference in a continuous time game where an agent's decision to quit an activity depends on the participation of other players. In equilibrium, similar actions can be explained not only by direct influences but also by correlated factors. Our model can be seen as a simultaneous duration model with multiple decision makers and interdependent durations. We study the problem of determining the existence and uniqueness of equilibrium stopping strategies in this setting. This paper provides results and conditions for the detection of these endogenous effects. First, we show that the presence of such effects is a necessary and sufficient condition for simultaneous exits. This allows us to set up a nonparametric test for the presence of such influences which is robust to multiple equilibria. Second, we provide conditions under which parameters in the game are identified. Finally, we apply the model to data on desertion in the Union Army during the American Civil War and find evidence of endogenous influences. PMID:20046804

Combinatorial Screening for Transgenic Yeasts with High Cellulase Activities in Combination with a Tunable Expression System

PubMed Central

Ito, Yoichiro; Yamanishi, Mamoru; Ikeuchi, Akinori; Imamura, Chie; Matsuyama, Takashi

2015-01-01

Combinatorial screening used together with a broad library of gene expression cassettes is expected to produce a powerful tool for the optimization of the simultaneous expression of multiple enzymes. Recently, we proposed a highly tunable protein expression system that utilized multiple genome-integrated target genes to fine-tune enzyme expression in yeast cells. This tunable system included a library of expression cassettes each composed of three gene-expression control elements that in different combinations produced a wide range of protein expression levels. In this study, four gene expression cassettes with graded protein expression levels were applied to the expression of three cellulases: cellobiohydrolase 1, cellobiohydrolase 2, and endoglucanase 2. After combinatorial screening for transgenic yeasts simultaneously secreting these three cellulases, we obtained strains with higher cellulase expressions than a strain harboring three cellulase-expression constructs within one high-performance gene expression cassette. These results show that our method will be of broad use throughout the field of metabolic engineering. PMID:26692026

Theta and Alpha Oscillations in Attentional Interaction during Distracted Driving

PubMed Central

Wang, Yu-Kai; Jung, Tzyy-Ping; Lin, Chin-Teng

2018-01-01

Performing multiple tasks simultaneously usually affects the behavioral performance as compared with executing the single task. Moreover, processing multiple tasks simultaneously often involve more cognitive demands. Two visual tasks, lane-keeping task and mental calculation, were utilized to assess the brain dynamics through 32-channel electroencephalogram (EEG) recorded from 14 participants. A 400-ms stimulus onset asynchrony (SOA) factor was used to induce distinct levels of attentional requirements. In the dual-task conditions, the deteriorated behavior reflected the divided attention and the overlapping brain resources used. The frontal, parietal and occipital components were decomposed by independent component analysis (ICA) algorithm. The event- and response-related theta and alpha oscillations in selected brain regions were investigated first. The increased theta oscillation in frontal component and decreased alpha oscillations in parietal and occipital components reflect the cognitive demands and attentional requirements as executing the designed tasks. Furthermore, time-varying interactive over-additive (O-Add), additive (Add) and under-additive (U-Add) activations were explored and summarized through the comparison between the summation of the elicited spectral perturbations in two single-task conditions and the spectral perturbations in the dual task. Add and U-Add activations were observed while executing the dual tasks. U-Add theta and alpha activations dominated the posterior region in dual-task situations. Our results show that both deteriorated behaviors and interactive brain activations should be comprehensively considered for evaluating workload or attentional interaction precisely. PMID:29479310

Program Completion of a Web-Based Tailored Lifestyle Intervention for Adults: Differences between a Sequential and a Simultaneous Approach

PubMed Central

Schneider, Francine; de Vries, Hein; van Osch, Liesbeth ADM; van Nierop, Peter WM; Kremers, Stef PJ

2012-01-01

Background Unhealthy lifestyle behaviors often co-occur and are related to chronic diseases. One effective method to change multiple lifestyle behaviors is web-based computer tailoring. Dropout from Internet interventions, however, is rather high, and it is challenging to retain participants in web-based tailored programs, especially programs targeting multiple behaviors. To date, it is unknown how much information people can handle in one session while taking part in a multiple behavior change intervention, which could be presented either sequentially (one behavior at a time) or simultaneously (all behaviors at once). Objectives The first objective was to compare dropout rates of 2 computer-tailored interventions: a sequential and a simultaneous strategy. The second objective was to assess which personal characteristics are associated with completion rates of the 2 interventions. Methods Using an RCT design, demographics, health status, physical activity, vegetable consumption, fruit consumption, alcohol intake, and smoking were self-assessed through web-based questionnaires among 3473 adults, recruited through Regional Health Authorities in the Netherlands in the autumn of 2009. First, a health risk appraisal was offered, indicating whether respondents were meeting the 5 national health guidelines. Second, psychosocial determinants of the lifestyle behaviors were assessed and personal advice was provided, about one or more lifestyle behaviors. Results Our findings indicate a high non-completion rate for both types of intervention (71.0%; n = 2167), with more incompletes in the simultaneous intervention (77.1%; n = 1169) than in the sequential intervention (65.0%; n = 998). In both conditions, discontinuation was predicted by a lower age (sequential condition: OR = 1.04; P < .001; CI = 1.02-1.05; simultaneous condition: OR = 1.04; P < .001; CI = 1.02-1.05) and an unhealthy lifestyle (sequential condition: OR = 0.86; P = .01; CI = 0.76-0.97; simultaneous condition: OR = 0.49; P < .001; CI = 0.42-0.58). In the sequential intervention, being male (OR = 1.27; P = .04; CI = 1.01-1.59) also predicted dropout. When respondents failed to adhere to at least 2 of the guidelines, those receiving the simultaneous intervention were more inclined to drop out than were those receiving the sequential intervention. Conclusion Possible reasons for the higher dropout rate in our simultaneous intervention may be the amount of time required and information overload. Strategies to optimize program completion as well as continued use of computer-tailored interventions should be studied. Trial Registration Dutch Trial Register NTR2168 PMID:22403770

Program completion of a web-based tailored lifestyle intervention for adults: differences between a sequential and a simultaneous approach.

PubMed

Schulz, Daniela N; Schneider, Francine; de Vries, Hein; van Osch, Liesbeth A D M; van Nierop, Peter W M; Kremers, Stef P J

2012-03-08

Unhealthy lifestyle behaviors often co-occur and are related to chronic diseases. One effective method to change multiple lifestyle behaviors is web-based computer tailoring. Dropout from Internet interventions, however, is rather high, and it is challenging to retain participants in web-based tailored programs, especially programs targeting multiple behaviors. To date, it is unknown how much information people can handle in one session while taking part in a multiple behavior change intervention, which could be presented either sequentially (one behavior at a time) or simultaneously (all behaviors at once). The first objective was to compare dropout rates of 2 computer-tailored interventions: a sequential and a simultaneous strategy. The second objective was to assess which personal characteristics are associated with completion rates of the 2 interventions. Using an RCT design, demographics, health status, physical activity, vegetable consumption, fruit consumption, alcohol intake, and smoking were self-assessed through web-based questionnaires among 3473 adults, recruited through Regional Health Authorities in the Netherlands in the autumn of 2009. First, a health risk appraisal was offered, indicating whether respondents were meeting the 5 national health guidelines. Second, psychosocial determinants of the lifestyle behaviors were assessed and personal advice was provided, about one or more lifestyle behaviors. Our findings indicate a high non-completion rate for both types of intervention (71.0%; n = 2167), with more incompletes in the simultaneous intervention (77.1%; n = 1169) than in the sequential intervention (65.0%; n = 998). In both conditions, discontinuation was predicted by a lower age (sequential condition: OR = 1.04; P < .001; CI = 1.02-1.05; simultaneous condition: OR = 1.04; P < .001; CI = 1.02-1.05) and an unhealthy lifestyle (sequential condition: OR = 0.86; P = .01; CI = 0.76-0.97; simultaneous condition: OR = 0.49; P < .001; CI = 0.42-0.58). In the sequential intervention, being male (OR = 1.27; P = .04; CI = 1.01-1.59) also predicted dropout. When respondents failed to adhere to at least 2 of the guidelines, those receiving the simultaneous intervention were more inclined to drop out than were those receiving the sequential intervention. Possible reasons for the higher dropout rate in our simultaneous intervention may be the amount of time required and information overload. Strategies to optimize program completion as well as continued use of computer-tailored interventions should be studied. Dutch Trial Register NTR2168.

A new parameter to simultaneously assess antioxidant activity for multiple phenolic compounds present in food products.

PubMed

Yang, Hong; Xue, Xuejia; Li, Huan; Tay-Chan, Su Chin; Ong, Seng Poon; Tian, Edmund Feng

2017-08-15

In this work, we established a new methodology to simultaneously assess the relative reaction rates of multiple antioxidant compounds in one experimental set-up. This new methodology hypothesizes that the competition among antioxidant compounds towards limiting amount of free radical (in this article, DPPH) would reflect their relative reaction rates. In contrast with the conventional detection of DPPH decrease at 515nm on a spectrophotometer, depletion of antioxidant compounds treated by a series of DPPH concentrations was monitored instead using liquid chromatography coupled with quadrupole time-of-flight (LC-QTOF). A new parameter, namely relative antioxidant activity (RAA), has been proposed to rank these antioxidants according to their reaction rate constants. We have investigated the applicability of RAA using pre-mixed standard phenolic compounds, and also extended this application to two food products, i.e. red wine and green tea. It has been found that RAA correlates well with the reported k values. This new parameter, RAA, provides a new perspective in evaluating antioxidant compounds present in food and herbal matrices. It not only realistically reflects the antioxidant activity of compounds when co-existing with competitive constituents; and it could also quicken up the discovery process in the search for potent yet rare antioxidants from many herbs of food/medicinal origins. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and application of a quantitative multiplexed small GTPase activity assay using targeted proteomics.

PubMed

Zhang, Cheng-Cheng; Li, Ru; Jiang, Honghui; Lin, Shujun; Rogalski, Jason C; Liu, Kate; Kast, Juergen

2015-02-06

Small GTPases are a family of key signaling molecules that are ubiquitously expressed in various types of cells. Their activity is often analyzed by western blot, which is limited by its multiplexing capability, the quality of isoform-specific antibodies, and the accuracy of quantification. To overcome these issues, a quantitative multiplexed small GTPase activity assay has been developed. Using four different binding domains, this assay allows the binding of up to 12 active small GTPase isoforms simultaneously in a single experiment. To accurately quantify the closely related small GTPase isoforms, a targeted proteomic approach, i.e., selected/multiple reaction monitoring, was developed, and its functionality and reproducibility were validated. This assay was successfully applied to human platelets and revealed time-resolved coactivation of multiple small GTPase isoforms in response to agonists and differential activation of these isoforms in response to inhibitor treatment. This widely applicable approach can be used for signaling pathway studies and inhibitor screening in many cellular systems.

Small molecule SIRT1 activators for the treatment of aging and age-related diseases

PubMed Central

Hubbard, Basil P.; Sinclair, David A.

2014-01-01

Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, significantly extending healthy years of life. In this review we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD+-dependent deacylases that are central to the body’s response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that the two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs. PMID:24439680

Development of Light-Activated CRISPR Using Guide RNAs with Photocleavable Protectors.

PubMed

Jain, Piyush K; Ramanan, Vyas; Schepers, Arnout G; Dalvie, Nisha S; Panda, Apekshya; Fleming, Heather E; Bhatia, Sangeeta N

2016-09-26

The ability to remotely trigger CRISPR/Cas9 activity would enable new strategies to study cellular events with greater precision and complexity. In this work, we have developed a method to photocage the activity of the guide RNA called "CRISPR-plus" (CRISPR-precise light-mediated unveiling of sgRNAs). The photoactivation capability of our CRISPR-plus method is compatible with the simultaneous targeting of multiple DNA sequences and supports numerous modifications that can enable guide RNA labeling for use in imaging and mechanistic investigations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chronic, Wireless Recordings of Large Scale Brain Activity in Freely Moving Rhesus Monkeys

PubMed Central

Schwarz, David A.; Lebedev, Mikhail A.; Hanson, Timothy L.; Dimitrov, Dragan F.; Lehew, Gary; Meloy, Jim; Rajangam, Sankaranarayani; Subramanian, Vivek; Ifft, Peter J.; Li, Zheng; Ramakrishnan, Arjun; Tate, Andrew; Zhuang, Katie; Nicolelis, Miguel A.L.

2014-01-01

Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 units per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years), and recording of a broad range of behaviors, e.g. social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research, while providing a framework for the development and testing of clinically relevant neuroprostheses. PMID:24776634

Empower multiplex cell and tissue-specific CRISPR-mediated gene manipulation with self-cleaving ribozymes and tRNA.

PubMed

Xu, Li; Zhao, Lixia; Gao, Yandi; Xu, Jing; Han, Renzhi

2017-03-17

Clustered regularly interspaced short palindromic repeat/Cas9 (CRISPR/Cas9) system has emerged in recent years as a highly efficient RNA-guided gene manipulation platform. Simultaneous editing or transcriptional activation/suppression of different genes becomes feasible with the co-delivery of multiple guide RNAs (gRNAs). Here, we report that multiple gRNAs linked with self-cleaving ribozymes and/or tRNA could be simultaneously expressed from a single U6 promoter to exert genome editing of dystrophin and myosin binding protein C3 in human and mouse cells. Moreover, this strategy allows the expression of multiple gRNAs for synergistic transcription activation of follistatin when used with catalytically inactive dCas9-VP64 or dCas9-p300core fusions. Finally, the gRNAs linked by the self-cleaving ribozymes and tRNA could be expressed from RNA polymerase type II (pol II) promoters such as generic CMV and muscle/heart-specific MHCK7. This is particularly useful for in vivo applications when the packaging capacity of recombinant adeno-associated virus is limited while tissue-specific delivery of gRNAs and Cas9 is desired. Taken together, this study provides a novel strategy to enable tissue-specific expression of more than one gRNAs for multiplex gene editing from a single pol II promoter. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Move to learn: Integrating spatial information from multiple viewpoints.

PubMed

Holmes, Corinne A; Newcombe, Nora S; Shipley, Thomas F

2018-05-11

Recalling a spatial layout from multiple orientations - spatial flexibility - is challenging, even when the global configuration can be viewed from a single vantage point, but more so when it must be viewed piecemeal. In the current study, we examined whether experiencing the transition between multiple viewpoints enhances spatial memory and flexible recall for a spatial configuration viewed simultaneously (Exp. 1) and sequentially (Exp. 2), whether the type of transition matters, and whether action provides an additional advantage over passive experience. In Experiment 1, participants viewed an array of dollhouse furniture from four viewpoints, but with all furniture simultaneously visible. In Experiment 2, participants viewed the same array piecemeal, from four partitioned viewpoints that allowed for viewing only a segment at a time. The transition between viewpoints involved rotation of the array or participant movement around it. Rotation and participant movement were passively experienced or actively generated. The control condition presented the dollhouse as a series of static views. Across both experiments, participant movement significantly enhanced spatial memory relative to array rotation or static views. However, in Exp. 2, there was a further advantage for actively walking around the array compared to being passively pushed. These findings suggest that movement around a stable environment is key to spatial memory and flexible recall, with action providing an additional boost to the integration of temporally segmented spatial events. Thus, spatial memory may be more flexible than prior data indicate, when studied under more natural acquisition conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

STATS: a unique high speed, multiple channel, real-time data acquisition system

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

Ross, F.A.; O'Connell, L.; Trellue, R.

1980-01-01

A Stand Alone Test System, called STATS, was developd to acquire and analyze data from as many as 120 analog channels. STATS is used in testing weapon systems under simulated environments at a laboratory in Texas. Some analog channels are sampled every 10 microseconds, but most are digitized every 100 microseconds. STATS features hardware data compression and a first-in-first-out buffer for each channel. It has also provided a way for the test configuration to be controlled by the diskette files that contain the test specifications. The analysis specifications are also predefined in diskette files keyed to the particular test type.more » The techniques used are applicable when many channels must be monitored simultaneously, channel activity comes in spurts separated by long quiet periods, and more than a few channels experience nearly simultaneous bursts of activity.« less

Calcium neuroimaging in behaving zebrafish larvae using a turn-key light field camera

NASA Astrophysics Data System (ADS)

Cruz Perez, Carlos; Lauri, Antonella; Symvoulidis, Panagiotis; Cappetta, Michele; Erdmann, Arne; Westmeyer, Gil Gregor

2015-09-01

Reconstructing a three-dimensional scene from multiple simultaneously acquired perspectives (the light field) is an elegant scanless imaging concept that can exceed the temporal resolution of currently available scanning-based imaging methods for capturing fast cellular processes. We tested the performance of commercially available light field cameras on a fluorescent microscopy setup for monitoring calcium activity in the brain of awake and behaving reporter zebrafish larvae. The plenoptic imaging system could volumetrically resolve diverse neuronal response profiles throughout the zebrafish brain upon stimulation with an aversive odorant. Behavioral responses of the reporter fish could be captured simultaneously together with depth-resolved neuronal activity. Overall, our assessment showed that with some optimizations for fluorescence microscopy applications, commercial light field cameras have the potential of becoming an attractive alternative to custom-built systems to accelerate molecular imaging research on cellular dynamics.

Calcium neuroimaging in behaving zebrafish larvae using a turn-key light field camera.

PubMed

Perez, Carlos Cruz; Lauri, Antonella; Symvoulidis, Panagiotis; Cappetta, Michele; Erdmann, Arne; Westmeyer, Gil Gregor

2015-09-01

Reconstructing a three-dimensional scene from multiple simultaneously acquired perspectives (the light field) is an elegant scanless imaging concept that can exceed the temporal resolution of currently available scanning-based imaging methods for capturing fast cellular processes. We tested the performance of commercially available light field cameras on a fluorescent microscopy setup for monitoring calcium activity in the brain of awake and behaving reporter zebrafish larvae. The plenoptic imaging system could volumetrically resolve diverse neuronal response profiles throughout the zebrafish brain upon stimulation with an aversive odorant. Behavioral responses of the reporter fish could be captured simultaneously together with depth-resolved neuronal activity. Overall, our assessment showed that with some optimizations for fluorescence microscopy applications, commercial light field cameras have the potential of becoming an attractive alternative to custom-built systems to accelerate molecular imaging research on cellular dynamics.

Competition in saccade target selection reveals attentional guidance by simultaneously active working memory representations.

PubMed

Beck, Valerie M; Hollingworth, Andrew

2017-02-01

The content of visual working memory (VWM) guides attention, but whether this interaction is limited to a single VWM representation or functional for multiple VWM representations is under debate. To test this issue, we developed a gaze-contingent search paradigm to directly manipulate selection history and examine the competition between multiple cue-matching saccade target objects. Participants first saw a dual-color cue followed by two pairs of colored objects presented sequentially. For each pair, participants selectively fixated an object that matched one of the cued colors. Critically, for the second pair, the cued color from the first pair was presented either with a new distractor color or with the second cued color. In the latter case, if two cued colors in VWM interact with selection simultaneously, we expected the second cued color object to generate substantial competition for selection, even though the first cued color was used to guide attention in the immediately previous pair. Indeed, in the second pair, selection probability of the first cued color was substantially reduced in the presence of the second cued color. This competition between cue-matching objects provides strong evidence that both VWM representations interacted simultaneously with selection. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Multiple-channel detection of cellular activities by ion-sensitive transistors

NASA Astrophysics Data System (ADS)

Machida, Satoru; Shimada, Hideto; Motoyama, Yumi

2018-04-01

An ion-sensitive field-effect transistor to record cellular activities was demonstrated. This field-effect transistor (bio transistor) includes cultured cells on the gate insulator instead of gate electrode. The bio transistor converts a change in potential underneath the cells into variation of the drain current when ion channels open. The bio transistor has high detection sensitivity to even minute variations in potential utilizing a subthreshold swing region. To open ion channels, a reagent solution (acetylcholine) was added to a human-originating cell cultured on the bio transistor. The drain current was successfully decreased with the addition of acetylcholine. Moreover, we attempted to detect the opening of ion channels using a multiple-channel measurement circuit containing several bio transistors. As a consequence, the drain current distinctly decreased only after the addition of acetylcholine. We confirmed that this measurement system including bio transistors enables to observation of cellular activities sensitively and simultaneously.

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.

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

Seizure entrainment with polarizing low frequency electric fields in a chronic animal epilepsy model

PubMed Central

Sunderam, Sridhar; Chernyy, Nick; Peixoto, Nathalia; Mason, Jonathan P.; Weinstein, Steven L.; Schiff, Steven J.; Gluckman, Bruce J.

2009-01-01

Neural activity can be modulated by applying a polarizing low frequency (≪ 100 Hz) electric field (PLEF). Unlike conventional pulsed stimulation, PLEF stimulation has a graded, modulatory effect on neuronal excitability, and permits the simultaneous recording of neuronal activity during stimulation suitable for continuous feedback control. We tested a prototype system that allows for simultaneous PLEF stimulation with minimal recording artifact in a chronic tetanus toxin animal model (rat) of hippocampal epilepsy with spontaneous seizures. Depth electrode local field potentials recorded during seizures revealed a characteristic pattern of field postsynaptic potentials (fPSPs). Sinusoidal voltage-controlled PLEF stimulation (0.5–25 Hz) was applied in open-loop cycles radially across the CA3 of ventral hippocampus. For stimulated seizures, fPSPs were transiently entrained with the PLEF waveform. Statistical significance of entrainment was assessed with Thomson’s harmonic F-test, with 45/132 stimulated seizures in 4 animals individually demonstrating significant entrainment (p < 0.04). Significant entrainment for multiple presentations at the same frequency (p < 0.01) was observed in 3 of 4 animals in 42/64 stimulated seizures. This is the first demonstration in chronically implanted freely behaving animals of PLEF modulation of neural activity with simultaneous recording. PMID:19602730

Synchronous Spike Patterns in Macaque Motor Cortex during an Instructed-Delay Reach-to-Grasp Task

PubMed Central

Torre, Emiliano; Quaglio, Pietro; Denker, Michael; Brochier, Thomas; Riehle, Alexa

2016-01-01

The computational role of spike time synchronization at millisecond precision among neurons in the cerebral cortex is hotly debated. Studies performed on data of limited size provided experimental evidence that low-order correlations occur in relation to behavior. Advances in electrophysiological technology to record from hundreds of neurons simultaneously provide the opportunity to observe coordinated spiking activity of larger populations of cells. We recently published a method that combines data mining and statistical evaluation to search for significant patterns of synchronous spikes in massively parallel spike trains (Torre et al., 2013). The method solves the computational and multiple testing problems raised by the high dimensionality of the data. In the current study, we used our method on simultaneous recordings from two macaque monkeys engaged in an instructed-delay reach-to-grasp task to determine the emergence of spike synchronization in relation to behavior. We found a multitude of synchronous spike patterns aligned in both monkeys along a preferential mediolateral orientation in brain space. The occurrence of the patterns is highly specific to behavior, indicating that different behaviors are associated with the synchronization of different groups of neurons (“cell assemblies”). However, pooled patterns that overlap in neuronal composition exhibit no specificity, suggesting that exclusive cell assemblies become active during different behaviors, but can recruit partly identical neurons. These findings are consistent across multiple recording sessions analyzed across the two monkeys. SIGNIFICANCE STATEMENT Neurons in the brain communicate via electrical impulses called spikes. How spikes are coordinated to process information is still largely unknown. Synchronous spikes are effective in triggering a spike emission in receiving neurons and have been shown to occur in relation to behavior in a number of studies on simultaneous recordings of few neurons. We recently published a method to extend this type of investigation to larger data. Here, we apply it to simultaneous recordings of hundreds of neurons from the motor cortex of macaque monkeys performing a motor task. Our analysis reveals groups of neurons selectively synchronizing their activity in relation to behavior, which sheds new light on the role of synchrony in information processing in the cerebral cortex. PMID:27511007

Synchronous Spike Patterns in Macaque Motor Cortex during an Instructed-Delay Reach-to-Grasp Task.

PubMed

Torre, Emiliano; Quaglio, Pietro; Denker, Michael; Brochier, Thomas; Riehle, Alexa; Grün, Sonja

2016-08-10

The computational role of spike time synchronization at millisecond precision among neurons in the cerebral cortex is hotly debated. Studies performed on data of limited size provided experimental evidence that low-order correlations occur in relation to behavior. Advances in electrophysiological technology to record from hundreds of neurons simultaneously provide the opportunity to observe coordinated spiking activity of larger populations of cells. We recently published a method that combines data mining and statistical evaluation to search for significant patterns of synchronous spikes in massively parallel spike trains (Torre et al., 2013). The method solves the computational and multiple testing problems raised by the high dimensionality of the data. In the current study, we used our method on simultaneous recordings from two macaque monkeys engaged in an instructed-delay reach-to-grasp task to determine the emergence of spike synchronization in relation to behavior. We found a multitude of synchronous spike patterns aligned in both monkeys along a preferential mediolateral orientation in brain space. The occurrence of the patterns is highly specific to behavior, indicating that different behaviors are associated with the synchronization of different groups of neurons ("cell assemblies"). However, pooled patterns that overlap in neuronal composition exhibit no specificity, suggesting that exclusive cell assemblies become active during different behaviors, but can recruit partly identical neurons. These findings are consistent across multiple recording sessions analyzed across the two monkeys. Neurons in the brain communicate via electrical impulses called spikes. How spikes are coordinated to process information is still largely unknown. Synchronous spikes are effective in triggering a spike emission in receiving neurons and have been shown to occur in relation to behavior in a number of studies on simultaneous recordings of few neurons. We recently published a method to extend this type of investigation to larger data. Here, we apply it to simultaneous recordings of hundreds of neurons from the motor cortex of macaque monkeys performing a motor task. Our analysis reveals groups of neurons selectively synchronizing their activity in relation to behavior, which sheds new light on the role of synchrony in information processing in the cerebral cortex. Copyright © 2016 Torre, et al.

A Facile Stable-Isotope Dilution Method for Determination of Sphingosine Phosphate Lyase Activity

PubMed Central

Suh, Jung H.; Eltanawy, Abeer; Rangan, Apoorva; Saba, Julie D.

2015-01-01

A new technique for quantifying sphingosine phosphate lyase activity in biological samples is described. In this procedure, 2-hydrazinoquinoline is used to convert (2E)-hexadecenal into the corresponding hydrazone derivative to improve ionization efficiency and selectivity of detection. Combined utilization of liquid chromatographic separation and multiple reaction monitoring-mass spectrometry allows for simultaneous quantification of the substrate S1P and product (2E)-hexadecenal. Incorporation of (2E)-d5-hexadecenal as an internal standard improves detection accuracy and precision. A simple one-step derivatization procedure eliminates the need for further extractions. Limits of quantification for (2E)-hexadecenal and sphingosine-1-phosphate are 100 and 50 fmol, respectively. The assay displays a wide dynamic detection range useful for detection of low basal sphingosine phosphate lyase activity in wild type cells, SPL-overexpressing cell lines, and wild type mouse tissues. Compared to current methods, the capacity for simultaneous detection of sphingosine-1-phosphate and (2E)-hexadecenal greatly improves the accuracy of results and shows excellent sensitivity and specificity for sphingosine phosphate lyase activity detection. PMID:26408264

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.

Relationships of multitasking, physicians' strain, and performance: an observational study in ward physicians.

PubMed

Weigl, Matthias; Müller, Andreas; Sevdalis, Nick; Angerer, Peter

2013-03-01

Simultaneous task performance ("multitasking") is common in hospital physicians' work and is implicated as a major determinant for enhanced strain and detrimental performance. The aim was to determine the impact of multitasking by hospital physicians on their self reported strain and performance. A prospective observational time-and-motion study in a Community Hospital was conducted. Twenty-seven hospital physicians (surgical and internal specialties) were observed in 40 full-shift observations. Observed physicians reported twice on their self-monitored strain and performance during the observation time. Associations of observed multitasking events and subsequent strain and performance appraisals were calculated. About 21% of the working time physicians were engaged in simultaneous activities. The average time spent in multitasking activities correlated significantly with subsequently reported strain (r = 0.27, P = 0.018). The number of instances of multitasking activities correlated with self-monitored performance to a marginally significant level (r = 0.19, P = 0.098). Physicians who engage in multitasking activities tend to self-report better performance but at the cost of enhanced psychophysical strain. Hence, physicians do not perceive their own multitasking activities as a source for deficient performance, for example, medical errors. Readjustment of workload, improved organization of work for hospital physicians, and training programs to improve physicians' skills in dealing with multiple clinical demands, prioritization, and efficient task allocation may be useful avenues to explore to reduce the potentially negative impact of simultaneous task performance in clinical settings.

Survey of selected seaweeds for simultaneous photoproduction of hydrogen and oxygen

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

Greenbaum, E.; Ramus, J.

1983-03-01

Then seaweed species were surveyed for simultaneous photoevolution of hydrogen and oxygen. In an attempt to induce hydrogenase activity (as measured by hydrogen photoproduction) the seaweeds were maintained under anaerobiosis in CO/sub 2/-free seawater for varying lengths of time. Although oxygen evolution was observed in every alga studied, hydrogen evolution was not observed. One conclusion of this research is that, in contrast to the microscopic algae, there is not a single example of a macroscopic alga for which the photoevolution of hydrogen has been observed, in spite of the fact that there are now at least nine macroscopic algal speciesmore » known for which hydrogenase activity has been reported (either by dark hydrogen evolution or light-activated hydrogen uptake). These results are in conflict with the conventional view that algal hydrogenase can catalyze a multiplicity of reactions, one of which is the photoproduction of molecular hydrogen. Two possible explanations for the lack of hydrogen photoproduction in macroscopic algae are presented. It is postulated that electron acceptors other than carbon dioxide can take up reducing equivalents from Photosystem I to the measurable exclusion of hydrogen photoproduction. Alternatively, the hydrogenase system in macroscopic algae may be primarily a hydrogen-uptake system with respect to light-activated reactions. A simple kinetic argument based on recent measurements of the photosynthetic turnover times of simultaneous light-activated hydrogen and oxygen production is presented that supports the second explanation. 25 references, 3 figures, 1 table.« 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.

Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation.

PubMed

Normann, R A; Dowden, B R; Frankel, M A; Wilder, A M; Hiatt, S D; Ledbetter, N M; Warren, D A; Clark, G A

2012-04-01

The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation

NASA Astrophysics Data System (ADS)

Normann, R. A.; Dowden, B. R.; Frankel, M. A.; Wilder, A. M.; Hiatt, S. D.; Ledbetter, N. M.; Warren, D. A.; Clark, G. A.

2012-04-01

The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

A 3D interactive multi-object segmentation tool using local robust statistics driven active contours.

PubMed

Gao, Yi; Kikinis, Ron; Bouix, Sylvain; Shenton, Martha; Tannenbaum, Allen

2012-08-01

Extracting anatomical and functional significant structures renders one of the important tasks for both the theoretical study of the medical image analysis, and the clinical and practical community. In the past, much work has been dedicated only to the algorithmic development. Nevertheless, for clinical end users, a well designed algorithm with an interactive software is necessary for an algorithm to be utilized in their daily work. Furthermore, the software would better be open sourced in order to be used and validated by not only the authors but also the entire community. Therefore, the contribution of the present work is twofolds: first, we propose a new robust statistics based conformal metric and the conformal area driven multiple active contour framework, to simultaneously extract multiple targets from MR and CT medical imagery in 3D. Second, an open source graphically interactive 3D segmentation tool based on the aforementioned contour evolution is implemented and is publicly available for end users on multiple platforms. In using this software for the segmentation task, the process is initiated by the user drawn strokes (seeds) in the target region in the image. Then, the local robust statistics are used to describe the object features, and such features are learned adaptively from the seeds under a non-parametric estimation scheme. Subsequently, several active contours evolve simultaneously with their interactions being motivated by the principles of action and reaction-this not only guarantees mutual exclusiveness among the contours, but also no longer relies upon the assumption that the multiple objects fill the entire image domain, which was tacitly or explicitly assumed in many previous works. In doing so, the contours interact and converge to equilibrium at the desired positions of the desired multiple objects. Furthermore, with the aim of not only validating the algorithm and the software, but also demonstrating how the tool is to be used, we provide the reader reproducible experiments that demonstrate the capability of the proposed segmentation tool on several public available data sets. Copyright © 2012 Elsevier B.V. All rights reserved.

A 3D Interactive Multi-object Segmentation Tool using Local Robust Statistics Driven Active Contours

PubMed Central

Gao, Yi; Kikinis, Ron; Bouix, Sylvain; Shenton, Martha; Tannenbaum, Allen

2012-01-01

Extracting anatomical and functional significant structures renders one of the important tasks for both the theoretical study of the medical image analysis, and the clinical and practical community. In the past, much work has been dedicated only to the algorithmic development. Nevertheless, for clinical end users, a well designed algorithm with an interactive software is necessary for an algorithm to be utilized in their daily work. Furthermore, the software would better be open sourced in order to be used and validated by not only the authors but also the entire community. Therefore, the contribution of the present work is twofolds: First, we propose a new robust statistics based conformal metric and the conformal area driven multiple active contour framework, to simultaneously extract multiple targets from MR and CT medical imagery in 3D. Second, an open source graphically interactive 3D segmentation tool based on the aforementioned contour evolution is implemented and is publicly available for end users on multiple platforms. In using this software for the segmentation task, the process is initiated by the user drawn strokes (seeds) in the target region in the image. Then, the local robust statistics are used to describe the object features, and such features are learned adaptively from the seeds under a non-parametric estimation scheme. Subsequently, several active contours evolve simultaneously with their interactions being motivated by the principles of action and reaction — This not only guarantees mutual exclusiveness among the contours, but also no longer relies upon the assumption that the multiple objects fill the entire image domain, which was tacitly or explicitly assumed in many previous works. In doing so, the contours interact and converge to equilibrium at the desired positions of the desired multiple objects. Furthermore, with the aim of not only validating the algorithm and the software, but also demonstrating how the tool is to be used, we provide the reader reproducible experiments that demonstrate the capability of the proposed segmentation tool on several public available data sets. PMID:22831773

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.

Finding Multiple Lanes in Urban Road Networks with Vision and Lidar

DTIC Science & Technology

2009-03-24

drawbacks. First, the cost of updating and main- taining millions of kilometers of roadway is prohibitive. Second, the danger of autonomous vehicles perceiving... autonomous vehicles . We propose that a data infrastructure is useful for topological information and sparse geometry, but reject relying upon it for dense...Throughout the race, approximately 50 human- driven and autonomous vehicles were simultaneously active, thus providing realistic traffic scenarios. Our most

Simultaneous Activation of Multiple Memory Systems during Learning: Insights from Electrophysiology and Modeling

DTIC Science & Technology

2010-06-01

autonomic and pain functions, and facilitating/inhibiting voluntary movements. The external segment of the globus pallidus (globus pallidus externa, GPe...or less responsive to pain stimuli. 1.2.4. Other cortico-basal ganglia loops Alexander, Strick and colleagues have additionally defined a number of... orofacial loop and loops through inferotemporal and posterior parietal cortical areas have also been defined. 1.2.5. Interactions between loops Once

Deducing multiple interfacial dynamics during polymeric foaming.

PubMed

Chandan, Mohammed Rehaan; Naskar, Nilanjon; Das, Anuja; Mukherjee, Rabibrata; Harikrishnan, Gopalakrishna Pillai

2018-06-15

Several interfacial phenomena are active during polymeric foaming, the dynamics of which significantly influence terminal stability, cell structure and in turn the thermo-mechanical properties of temporally evolved foam. Understanding these dynamics is important in achieving desired foam properties. Here, we introduce a method to simultaneously portray the time evolution of bubble growth, lamella thinning and Plateau border drainage, occurring during reactive polymeric foaming. In this method, we initially conduct bulk and surface shear rheology under polymerizing and non-foaming conditions. In a subsequent step, foaming experiments were conducted in a rheometer. The microscopic structural dimensions pertaining to the terminal values of the dynamics of each interfacial phenomena are then measured using a combination of scanning electron microscopy, optical microscopy and imaging ellipsometry, after the foaming is over. The measured surface and bulk rheological parameters are incorporated in time evolution equations that are derived from mass and momentum transport occurring when a model viscoelastic fluid is foamed by gas dispersion. Analytical and numerical solutions to these equations portray the dynamics. We demonstrate this method for a series of reactive polyurethane foams generated from different chemical sources. The effectiveness of our method is in simultaneously obtaining these dynamics that are difficult to directly monitor due to short active durations over multiple length scales.

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

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.

Exogenous ascorbic acid improves defence responses of sunflower (Helianthus annuus) exposed to multiple stresses.

PubMed

Kaya, Armagan

2017-09-01

Ascorbic acid is an important antioxidant that plays role both on growth and development and also stress response of the plant. The purpose of this study was to determine the effect of ascorbate on physiological and biochemical changes of sunflower that was exposed to multiple stresses. Chlorophyll and carotenoid contents decreased and glutathione, ascorbate and malondialdehyde contents as well as antioxidant enzyme activities increased for sunflower plant that was exposed to 50 mM NaCl and pendimethalin at different concentrations. These changes were found to be more significant in groups simultaneously exposed to both stress factors. While malondialdehyde content decreased, chlorophyll, carotenoid, ascorbate, glutathione contents and antioxidant enzyme activities increased in plants treated exogenously with ascorbate, compared to the untreated samples. According to the findings of our study; compared to individual stress, the effect of stress is more pronounced in sunflower exposed to multiple stresses, and treatment with exogenous ascorbate reduces the negative effects of stress.

Evaluation of effects of shellfish aquaculture and capture fishery on a semi-closed bay ecosystem

NASA Astrophysics Data System (ADS)

Han, Dongyan; Chen, Yong; Zhang, Chongliang; Ren, Yiping; Xu, Binduo; Xue, Ying

2018-07-01

Coastal waters in the world are suffering from multiple anthropogenic disturbances, including capture fisheries and aquaculture. Ignoring possible interactions between multiple disturbances may cause serious consequences in our understanding of ecosystem dynamics. This study simulates individual and combined effects of fishing activities and shellfish cultivation on a semi-closed bay ecosystem using Ecopath with Ecosim (EwE). The changes of biomass and ecosystem structure were examined for three scenarios of having fishing alone, shellfish cultivation alone and both fishing and aquaculture. We found considerable impacts of shellfish aquaculture but minor impacts from fishing, suggesting shellfish aquaculture had dominated impacts on the study ecosystem. In addition, the effects of fishing and shellfish aquaculture were not additive on species biomass, rather showing a combined effect with synergy. Given the same loss in fisheries yield, controlling fishing and shellfish aquaculture simultaneously was more efficient for increasing nekton biomass compared to the control of either activity. We highlight the necessity for integrating management of multiple human stressors for an ecosystem-based management.

More than child's play: variable- and pattern-centered approaches for examining effects of sports participation on youth development.

PubMed

Zarrett, Nicole; Fay, Kristen; Li, Yibing; Carrano, Jennifer; Phelps, Erin; Lerner, Richard M

2009-03-01

The authors used data from Grades 5 through 7 of the longitudinal 4-H Study of Positive Youth Development to assess relations among sports participation, other out-of-school-time (OST) activities, and indicators of youth development. They used a mixture of variable- and pattern-centered analyses aimed at disentangling different features of participation (i.e., intensity, breadth). The benefits of sports participation were found to depend, in part, on specific combinations of multiple activities in which youths participated along with sports. In particular, participation in a combination of sports and youth development programs was related to positive youth development and youth contribution, even after controlling for the total time youths spent in OST activities and their sports participation duration. Adolescents' total time spent participating in OST activities, duration of participation in sports, and activity participation pattern each explained a unique part of the variance in some of the indicators of youth functioning. These findings suggest the need for future research to simultaneously assess multiple indices of OST activity participation.

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

Gender, Religiosity, Sexual Activity, Sexual Knowledge, and Attitudes Toward Controversial Aspects of Sexuality.

PubMed

Sümer, Zeynep Hatipoğlu

2015-12-01

The purpose of this study is to examine the role of gender, religiosity, sexual activity, and sexual knowledge in predicting attitudes toward controversial aspects of sexuality among Turkish university students. Participants were 162 female and 135 male undergraduate students who were recruited on a volunteer basis from an urban state university in Turkey. The SKAT-A Attitude Scale along with background information form, sexual activities inventory, and sexual knowledge scale were administered to the participants. Simultaneous multiple regression analyses revealed that religiosity, particularly attendance to religious services was the most significant predictor in explaining university students' attitudes toward masturbation, abortion, homosexuality, pornography, and sexual coercion.

Probing the function of neuronal populations: combining micromirror-based optogenetic photostimulation with voltage-sensitive dye imaging

PubMed Central

Tsuda, Sachiko; Kee, Michelle Z.L.; Cunha, Catarina; Kim, Jinsook; Yan, Ping; Loew, Leslie M.; Augustine, George J.

2013-01-01

Recent advances in our understanding of brain function have come from using light to either control or image neuronal activity. Here we describe an approach that combines both techniques: a micromirror array is used to photostimulate populations of presynaptic neurons expressing channelrhodopsin-2, while a red-shifted voltage-sensitive dye allows optical detection of resulting postsynaptic activity. Such technology allowed us to control the activity of cerebellar interneurons while simultaneously recording inhibitory responses in multiple Purkinje neurons, their postsynaptic targets. This approach should substantially accelerate our understanding of information processing by populations of neurons within brain circuits. PMID:23254260

Using Infrared Thermography to Assess Emotional Responses to Infants.

PubMed

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 behavior. Unpackaging and understanding them, therefore, involves 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. Infrared thermography was used to assess facial temperature changes as a measure of emotional valence, and we used a behavioral rating system to assess adults' expressed preferences. We found greater physiological activation in response to infant stimuli in females than males. As for cognitive preferences, we found greater responses to adult stimuli than to infant stimuli, both in males and females. The results are discuss in light of the Life History Theory. Finally, we discuss the importance of integrating the two data streams on our conclusions.

A longitudinal examination of the interrelationship of multiple health behaviors.

PubMed

deRuiter, Wayne K; Cairney, John; Leatherdale, Scott T; Faulkner, Guy E J

2014-09-01

Evaluating the interrelationship of health behaviors could assist in the development of effective public health interventions. Furthermore, the ability to identify cognitive mediators that may influence multiple behavioral changes requires evaluation. To evaluate covariation among health behaviors, specifically alcohol consumption, leisure-time physical activity, and smoking, and examine whether mastery acts as a mediating social-cognitive mechanism that facilitates multiple health behavior change in a longitudinal analysis. In 2010, secondary data analysis was conducted on the first seven cycles of the Canadian National Population Health Survey. Data collection began in 1994-1995 and has continued biennially. At the time of this analysis, only seven cycles of data (2006-2007) were available. Parallel process growth curve models were used to analyze covariation between health behaviors and the potential mediating effects of perceived mastery. Increases in leisure-time physical activity were associated with reductions in tobacco use, whereas declines in alcohol consumption were associated with decreases in tobacco use. Covariation between alcohol consumption and leisure-time physical activity did not reach statistical significance. For the most part, mastery was unsuccessful in mediating the interrelationship of multiple behavioral changes. Health behaviors are not independent but rather interrelated. In order to optimize limited prevention resources, these results suggest that population-level intervention efforts targeting multiple modifiable behavioral risk factors may not need to occur simultaneously. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

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.

Differentially Variable Component Analysis (dVCA): Identifying Multiple Evoked Components using Trial-to-Trial Variability

NASA Technical Reports Server (NTRS)

Knuth, Kevin H.; Shah, Ankoor S.; Truccolo, Wilson; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.

2003-01-01

Electric potentials and magnetic fields generated by ensembles of synchronously active neurons in response to external stimuli provide information essential to understanding the processes underlying cognitive and sensorimotor activity. Interpreting recordings of these potentials and fields is difficult as each detector records signals simultaneously generated by various regions throughout the brain. We introduce the differentially Variable Component Analysis (dVCA) algorithm, which relies on trial-to-trial variability in response amplitude and latency to identify multiple components. Using simulations we evaluate the importance of response variability to component identification, the robustness of dVCA to noise, and its ability to characterize single-trial data. Finally, we evaluate the technique using visually evoked field potentials recorded at incremental depths across the layers of cortical area VI, in an awake, behaving macaque monkey.

Simultaneous determination of multiple active components in rat plasma using ultra-fast liquid chromatography with tandem mass spectrometry and application to a comparative pharmacokinetic study after oral administration of Suan-Zao-Ren decoction and Suan-Zao-Ren granule.

PubMed

Du, Yiyang; He, Bosai; Li, Qing; He, Jiao; Wang, Di; Bi, Kaishun

2017-05-01

Suan-Zao-Ren decoction has been used to treat insomnia for many years. In this work, a rapid and sensitive ultra-fast liquid chromatography with tandem mass spectrometry method was first developed and fully validated for the simultaneous quantification of seven main active components, spinosin, mangiferin, neomangiferin, ferulic acid, liquiritin, isoliquiritin, and liquiritin apioside in rat plasma. The method was also successfully applied to compare the pharmacokinetics of these active ingredients after oral administration of Suan-Zao-Ren decoction and Suan-Zao-Ren granule. The separation was achieved on a Venusil MP C 18 column and the detection was conducted by the multiple reaction monitoring mode using negative ion mode. Each calibration curve had good linearity over a wide concentration range. The precision of intra- and interday were all within 15%, and the extraction recoveries at different analyte concentrations were all above 82.0%. The established method was successfully applied to compare the pharmacokinetic profiles of the analytes between Suan-Zao-Ren decoction and Suan-Zao-Ren granule groups. The results indicated that all the analytes had similar mean concentration-time curves trend between two groups. No significant differences were observed in pharmacokinetic parameters of mangiferin, while the others had significant differences. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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.

Conflict effects without conflict in anterior cingulate cortex: multiple response effects and context specific representations

PubMed Central

Brown, Joshua W.

2009-01-01

The error likelihood computational model of anterior cingulate cortex (ACC) (Brown & Braver, 2005) has successfully predicted error likelihood effects, risk prediction effects, and how individual differences in conflict and error likelihood effects vary with trait differences in risk aversion. The same computational model now makes a further prediction that apparent conflict effects in ACC may result in part from an increasing number of simultaneously active responses, regardless of whether or not the cued responses are mutually incompatible. In Experiment 1, the model prediction was tested with a modification of the Eriksen flanker task, in which some task conditions require two otherwise mutually incompatible responses to be generated simultaneously. In that case, the two response processes are no longer in conflict with each other. The results showed small but significant medial PFC effects in the incongruent vs. congruent contrast, despite the absence of response conflict, consistent with model predictions. This is the multiple response effect. Nonetheless, actual response conflict led to greater ACC activation, suggesting that conflict effects are specific to particular task contexts. In Experiment 2, results from a change signal task suggested that the context dependence of conflict signals does not depend on error likelihood effects. Instead, inputs to ACC may reflect complex and task specific representations of motor acts, such as bimanual responses. Overall, the results suggest the existence of a richer set of motor signals monitored by medial PFC and are consistent with distinct effects of multiple responses, conflict, and error likelihood in medial PFC. PMID:19375509

Simultaneous knockdown of six non-family genes using a single synthetic RNAi fragment in Arabidopsis thaliana

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

Czarnecki, Olaf; Bryan, Anthony C.; Jawdy, Sara S.

Genetic engineering of plants that results in successful establishment of new biochemical or regulatory pathways requires stable introduction of one or more genes into the plant genome. It might also be necessary to down-regulate or turn off expression of endogenous genes in order to reduce activity of competing pathways. An established way to knockdown gene expression in plants is expressing a hairpin-RNAi construct, eventually leading to degradation of a specifically targeted mRNA. Knockdown of multiple genes that do not share homologous sequences is still challenging and involves either sophisticated cloning strategies to create vectors with different serial expression constructs ormore » multiple transformation events that is often restricted by a lack of available transformation markers. Synthetic RNAi fragments were assembled in yeast carrying homologous sequences to six or seven non-family genes and introduced into pAGRIKOLA. Transformation of Arabidopsis thaliana and subsequent expression analysis of targeted genes proved efficient knockdown of all target genes. In conclusion, we present a simple and cost-effective method to create constructs to simultaneously knockdown multiple non-family genes or genes that do not share sequence homology. The presented method can be applied in plant and animal synthetic biology as well as traditional plant and animal genetic engineering.« less

Simultaneous knockdown of six non-family genes using a single synthetic RNAi fragment in Arabidopsis thaliana

DOE PAGES

Czarnecki, Olaf; Bryan, Anthony C.; Jawdy, Sara S.; ...

2016-02-17

Genetic engineering of plants that results in successful establishment of new biochemical or regulatory pathways requires stable introduction of one or more genes into the plant genome. It might also be necessary to down-regulate or turn off expression of endogenous genes in order to reduce activity of competing pathways. An established way to knockdown gene expression in plants is expressing a hairpin-RNAi construct, eventually leading to degradation of a specifically targeted mRNA. Knockdown of multiple genes that do not share homologous sequences is still challenging and involves either sophisticated cloning strategies to create vectors with different serial expression constructs ormore » multiple transformation events that is often restricted by a lack of available transformation markers. Synthetic RNAi fragments were assembled in yeast carrying homologous sequences to six or seven non-family genes and introduced into pAGRIKOLA. Transformation of Arabidopsis thaliana and subsequent expression analysis of targeted genes proved efficient knockdown of all target genes. In conclusion, we present a simple and cost-effective method to create constructs to simultaneously knockdown multiple non-family genes or genes that do not share sequence homology. The presented method can be applied in plant and animal synthetic biology as well as traditional plant and animal genetic engineering.« less

Two women with multiple disabilities sharing an acoustic orientation system and traveling together to indoor destinations.

PubMed

Lancioni, G E; Mantini, M

1998-12-01

This study assessed whether two women with total blindness and profound intellectual disability could share an acoustic orientation system and travel together simultaneously to common indoor destinations to perform occupational and vocational activities. The orientation system provided acoustic cues which indicated the direction to the destinations. Analysis of data indicated that the women were successful in sharing the system and could reach the destinations independently.

Effects of a web-based tailored multiple-lifestyle intervention for adults: a two-year randomized controlled trial comparing sequential and simultaneous delivery modes.

PubMed

Schulz, Daniela N; Kremers, Stef P J; Vandelanotte, Corneel; van Adrichem, Mathieu J G; Schneider, Francine; Candel, Math J J M; de Vries, Hein

2014-01-27

Web-based computer-tailored interventions for multiple health behaviors can have a significant public health impact. Yet, few randomized controlled trials have tested this assumption. The objective of this paper was to test the effects of a sequential and simultaneous Web-based tailored intervention on multiple lifestyle behaviors. A randomized controlled trial was conducted with 3 tailoring conditions (ie, sequential, simultaneous, and control conditions) in the Netherlands in 2009-2012. Follow-up measurements took place after 12 and 24 months. The intervention content was based on the I-Change model. In a health risk appraisal, all respondents (N=5055) received feedback on their lifestyle behaviors that indicated whether they complied with the Dutch guidelines for physical activity, vegetable consumption, fruit consumption, alcohol intake, and smoking. Participants in the sequential (n=1736) and simultaneous (n=1638) conditions received tailored motivational feedback to change unhealthy behaviors one at a time (sequential) or all at the same time (simultaneous). Mixed model analyses were performed as primary analyses; regression analyses were done as sensitivity analyses. An overall risk score was used as outcome measure, then effects on the 5 individual lifestyle behaviors were assessed and a process evaluation was performed regarding exposure to and appreciation of the intervention. Both tailoring strategies were associated with small self-reported behavioral changes. The sequential condition had the most significant effects compared to the control condition after 12 months (T1, effect size=0.28). After 24 months (T2), the simultaneous condition was most effective (effect size=0.18). All 5 individual lifestyle behaviors changed over time, but few effects differed significantly between the conditions. At both follow-ups, the sequential condition had significant changes in smoking abstinence compared to the simultaneous condition (T1 effect size=0.31; T2 effect size=0.41). The sequential condition was more effective in decreasing alcohol consumption than the control condition at 24 months (effect size=0.27). Change was predicted by the amount of exposure to the intervention (total visiting time: beta=-.06; P=.01; total number of visits: beta=-.11; P<.001). Both interventions were appreciated well by respondents without significant differences between conditions. Although evidence was found for the effectiveness of both programs, no simple conclusive finding could be drawn about which intervention mode was more effective. The best kind of intervention may depend on the behavior that is targeted or on personal preferences and motivation. Further research is needed to identify moderators of intervention effectiveness. The results need to be interpreted in view of the high and selective dropout rates, multiple comparisons, and modest effect sizes. However, a large number of people were reached at low cost and behavioral change was achieved after 2 years. Nederlands Trial Register: NTR 2168; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2168 (Archived by WebCite at http://www.webcitation.org/6MbUqttYB).

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.

Fast automated segmentation of multiple objects via spatially weighted shape learning

NASA Astrophysics Data System (ADS)

Chandra, Shekhar S.; Dowling, Jason A.; Greer, Peter B.; Martin, Jarad; Wratten, Chris; Pichler, Peter; Fripp, Jurgen; Crozier, Stuart

2016-11-01

Active shape models (ASMs) have proved successful in automatic segmentation by using shape and appearance priors in a number of areas such as prostate segmentation, where accurate contouring is important in treatment planning for prostate cancer. The ASM approach however, is heavily reliant on a good initialisation for achieving high segmentation quality. This initialisation often requires algorithms with high computational complexity, such as three dimensional (3D) image registration. In this work, we present a fast, self-initialised ASM approach that simultaneously fits multiple objects hierarchically controlled by spatially weighted shape learning. Prominent objects are targeted initially and spatial weights are progressively adjusted so that the next (more difficult, less visible) object is simultaneously initialised using a series of weighted shape models. The scheme was validated and compared to a multi-atlas approach on 3D magnetic resonance (MR) images of 38 cancer patients and had the same (mean, median, inter-rater) Dice’s similarity coefficients of (0.79, 0.81, 0.85), while having no registration error and a computational time of 12-15 min, nearly an order of magnitude faster than the multi-atlas approach.

Fast automated segmentation of multiple objects via spatially weighted shape learning.

PubMed

Chandra, Shekhar S; Dowling, Jason A; Greer, Peter B; Martin, Jarad; Wratten, Chris; Pichler, Peter; Fripp, Jurgen; Crozier, Stuart

2016-11-21

Active shape models (ASMs) have proved successful in automatic segmentation by using shape and appearance priors in a number of areas such as prostate segmentation, where accurate contouring is important in treatment planning for prostate cancer. The ASM approach however, is heavily reliant on a good initialisation for achieving high segmentation quality. This initialisation often requires algorithms with high computational complexity, such as three dimensional (3D) image registration. In this work, we present a fast, self-initialised ASM approach that simultaneously fits multiple objects hierarchically controlled by spatially weighted shape learning. Prominent objects are targeted initially and spatial weights are progressively adjusted so that the next (more difficult, less visible) object is simultaneously initialised using a series of weighted shape models. The scheme was validated and compared to a multi-atlas approach on 3D magnetic resonance (MR) images of 38 cancer patients and had the same (mean, median, inter-rater) Dice's similarity coefficients of (0.79, 0.81, 0.85), while having no registration error and a computational time of 12-15 min, nearly an order of magnitude faster than the multi-atlas approach.

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.

Evolution of defence cocktails: Antimicrobial peptide combinations reduce mortality and persistent infection.

PubMed

Zanchi, Caroline; Johnston, Paul R; Rolff, Jens

2017-10-01

The simultaneous expression of costly immune effectors such as multiple antimicrobial peptides is a hallmark of innate immunity of multicellular organisms, yet the adaptive advantage remains unresolved. Here, we test current hypotheses on the evolution of such defence cocktails. We use RNAi gene knock-down to explore, the effects of three highly expressed antimicrobial peptides, displaying different degrees of activity in vitro against Staphylococcus aureus, during an infection in the beetle Tenebrio molitor. We find that a defensin confers no survival benefit but reduces bacterial loads. A coleoptericin contributes to host survival without affecting bacterial loads. An attacin has no individual effect. Simultaneous knock-down of the defensin with the other AMPs results in increased mortality and elevated bacterial loads. Contrary to common expectations, the effects on host survival and bacterial load can be independent. The expression of multiple AMPs increases host survival and contributes to the control of persisting infections and tolerance. This is an emerging property that explains the adaptive benefit of defence cocktails. © 2017 John Wiley & Sons Ltd.

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.

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

Context-Dependent Upper Limb Prosthesis Control for Natural and Robust Use.

PubMed

Amsuess, Sebastian; Vujaklija, Ivan; Goebel, Peter; Roche, Aidan D; Graimann, Bernhard; Aszmann, Oskar C; Farina, Dario

2016-07-01

Pattern recognition and regression methods applied to the surface EMG have been used for estimating the user intended motor tasks across multiple degrees of freedom (DOF), for prosthetic control. While these methods are effective in several conditions, they are still characterized by some shortcomings. In this study we propose a methodology that combines these two approaches for mutually alleviating their limitations. This resulted in a control method capable of context-dependent movement estimation that switched automatically between sequential (one DOF at a time) or simultaneous (multiple DOF) prosthesis control, based on an online estimation of signal dimensionality. The proposed method was evaluated in scenarios close to real-life situations, with the control of a physical prosthesis in applied tasks of varying difficulties. Test prostheses were individually manufactured for both able-bodied and transradial amputee subjects. With these prostheses, two amputees performed the Southampton Hand Assessment Procedure test with scores of 58 and 71 points. The five able-bodied individuals performed standardized tests, such as the box&block and clothes pin test, reducing the completion times by up to 30%, with respect to using a state-of-the-art pure sequential control algorithm. Apart from facilitating fast simultaneous movements, the proposed control scheme was also more intuitive to use, since human movements are predominated by simultaneous activations across joints. The proposed method thus represents a significant step towards intelligent, intuitive and natural control of upper limb prostheses.

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

QSAR modeling of cumulative environmental end-points for the prioritization of hazardous chemicals.

PubMed

Gramatica, Paola; Papa, Ester; Sangion, Alessandro

2018-01-24

The hazard of chemicals in the environment is inherently related to the molecular structure and derives simultaneously from various chemical properties/activities/reactivities. Models based on Quantitative Structure Activity Relationships (QSARs) are useful to screen, rank and prioritize chemicals that may have an adverse impact on humans and the environment. This paper reviews a selection of QSAR models (based on theoretical molecular descriptors) developed for cumulative multivariate endpoints, which were derived by mathematical combination of multiple effects and properties. The cumulative end-points provide an integrated holistic point of view to address environmentally relevant properties of chemicals.

Lessons Learned from Coordinating Relay Activities at Mars

NASA Technical Reports Server (NTRS)

Gladden, Roy E.; Hwang, Pauline; Waggoner, Bruce; McLaughlin, Bruce; Fieseler, Paul; Thomas, Reid; Bigwood, Maria; Herrera, Paul

2005-01-01

The Mission Management Office at the Jet Propulsion Laboratory was tasked with coordinating the relay of data between multiple spacecraft at Mars in support of the Mars Exploration Rover Missions in early 2004. The confluence of three orbiters (Mars Global Surveyor, Mars Odyssey, and Mars Express), two rovers (Spirit and Opportunity), and one lander (Beagle 2) has provided a challenging operational scenario that required careful coordination between missions to provide the necessary support and to avoid potential interference during simultaneous relay sessions. As these coordination efforts progressed, several important lessons were learned that should be applied to future Mars relay activities.

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.

Sorption studies of nickel ions onto activated carbon

NASA Astrophysics Data System (ADS)

Joshi, Parth; Vyas, Meet; Patel, Chirag

2018-05-01

Activated porous carbons are made through pyrolysis and activation of carbonaceous natural as well as synthetic precursors. The use of low-cost activated carbon derived from azadirachta indica, an agricultural waste material, has been investigated as a replacement for the current expensive methods of removing nickel ions from wastewater. The temperature variation study showed that the nickel ions adsorption is endothermic and spontaneous with increased randomness at the solid solution interface. Significant effect on adsorption was observed on varying the pH of the nickel ion solutions. Therefore, this study revealed that azadirachta indica can serve as a good source of activated carbon with multiple and simultaneous metal ions removing potentials and may serve as a better replacement for commercial activated carbons in applications that warrant their use.

Real-time separation of multineuron recordings with a DSP32C signal processor.

PubMed

Gädicke, R; Albus, K

1995-04-01

We have developed a hardware and software package for real-time discrimination of multiple-unit activities recorded simultaneously from multiple microelectrodes using a VME-Bus system. Compared with other systems cited in literature or commercially available, our system has the following advantages. (1) Each electrode is served by its own preprocessor (DSP32C); (2) On-line spike discrimination is performed independently for each electrode. (3) The VME-bus allows processing of data received from 16 electrodes. The digitized (62.5 kHz) spike form is itself used as the model spike; the algorithm allows for comparing and sorting complete wave forms in real time into 8 different models per electrode.

Development of a real-time radon monitoring system for simultaneous measurements in multiple sites

NASA Astrophysics Data System (ADS)

Yamamoto, S.; Yamasoto, K.; Iida, T.

1999-12-01

A real-time radon monitoring system that can simultaneously measure radon concentrations in multiple sites was developed and tested. The system consists of maximum of four radon detectors, optical fiber cables and a data acquisition personal computer. The radon detector uses a plastic scintillation counter that collects radon daughters in the chamber electrostatically. The applied voltage on the photocathode for the photomultiplier tube (PMT) acts as an electrode for radon daughters. The thickness of the plastic scintillator was thin, 50 /spl mu/m, so as to minimize the background counts due to the environmental gamma rays or beta particles. The energy discriminated signals from the radon detectors are fed to the data acquisition personal computer via optical fiber cables. The system made it possible to measure the radon concentrations in multiple sites simultaneously.

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.

Motor unit activity within the depth of the masseter characterized by an adapted scanning EMG technique.

PubMed

van Dijk, J P; Eiglsperger, U; Hellmann, D; Giannakopoulos, N N; McGill, K C; Schindler, H J; Lapatki, B G

2016-09-01

To study motor unit activity in the medio-lateral extension of the masseter using an adapted scanning EMG technique that allows studying the territories of multiple motor units (MUs) in one scan. We studied the m. masseter of 10 healthy volunteers in whom two scans were performed. A monopolar scanning needle and two pairs of fine-wire electrodes were inserted into the belly of the muscle. The signals of the fine wire electrodes were decomposed into the contribution of single MUs and used as a trigger for the scanning needle. In this manner multiple MU territory scans were obtained simultaneously. We determined 161 MU territories. The maximum number of territories obtained in one scan was 15. The median territory size was 4.0mm. Larger and smaller MU territories were found throughout the muscle. The presented technique showed its feasibility in obtaining multiple MU territories in one scan. MUs were active throughout the depth of the muscle. The distribution of electrical and anatomical size of MUs substantiates the heterogeneous distribution of MUs throughout the muscle volume. This distributed activity may be of functional significance for the stabilization of the muscle during force generation. Copyright © 2016 International Federation of Clinical Neurophysiology. All rights reserved.

Gas-phase broadband spectroscopy using active sources: progress, status, and applications

PubMed Central

Cossel, Kevin C.; Waxman, Eleanor M.; Finneran, Ian A.; Blake, Geoffrey A.; Ye, Jun; Newbury, Nathan R.

2017-01-01

Broadband spectroscopy is an invaluable tool for measuring multiple gas-phase species simultaneously. In this work we review basic techniques, implementations, and current applications for broadband spectroscopy. We discuss components of broad-band spectroscopy including light sources, absorption cells, and detection methods and then discuss specific combinations of these components in commonly-used techniques. We finish this review by discussing potential future advances in techniques and applications of broad-band spectroscopy. PMID:28630530

A novel GMO biosensor for rapid ultrasensitive and simultaneous detection of multiple DNA components in GMO products.

PubMed

Huang, Lin; Zheng, Lei; Chen, Yinji; Xue, Feng; Cheng, Lin; Adeloju, Samuel B; Chen, Wei

2015-04-15

Since the introduction of genetically modified organisms (GMOs), there has been on-going and continuous concern and debates on the commercialization of products derived from GMOs. There is an urgent need for development of highly efficient analytical methods for rapid and high throughput screening of GMOs components, as required for appropriate labeling of GMO-derived foods, as well as for on-site inspection and import/export quarantine. In this study, we describe, for the first time, a multi-labeling based electrochemical biosensor for simultaneous detection of multiple DNA components of GMO products on the same sensing interface. Two-round signal amplification was applied by using both an exonuclease enzyme catalytic reaction and gold nanoparticle-based bio-barcode related strategies, respectively. Simultaneous multiple detections of different DNA components of GMOs were successfully achieved with satisfied sensitivity using this electrochemical biosensor. Furthermore, the robustness and effectiveness of the proposed approach was successfully demonstrated by application to various GMO products, including locally obtained and confirmed commercial GMO seeds and transgenetic plants. The proposed electrochemical biosensor demonstrated unique merits that promise to gain more interest in its use for rapid and on-site simultaneous multiple screening of different components of GMO products. Copyright © 2014 Elsevier B.V. All rights reserved.

A task analysis of emergency physician activities in academic and community settings.

PubMed

Chisholm, Carey D; Weaver, Christopher S; Whenmouth, Laura; Giles, Beverly

2011-08-01

We characterize and compare the work activities, including peak patient loads, associated with the workplace in the academic and community emergency department (ED) settings. This allows assessment of the effect of future ED system operational changes and identifies potential sources contributing to medical error. This was an observational, time-motion study. Trained observers shadowed physicians, recording activities. Data included total interactions, distances walked, time sitting, patients concurrently treated, interruptions, break in tasks, physical contact with patients, hand washing, diagnostic tests ordered, and therapies rendered. Activities were classified as direct patient care, indirect patient care, or personal time with a priori definitions. There were 203 2-hour observation periods of 85 physicians at 2 academic EDs with 100,000 visits per year at each (N=160) and 2 community EDs with annual visits of 19,000 and 21,000 (N=43). Reported data present the median and minimum-maximum values per 2-hour period. Emergency physicians spent the majority of time on indirect care activities (academic 64 minutes, 29 to 91 minutes; community 55 min, 25 to 95 minutes), followed by direct care activities (academic 36 minutes, 6 to 79 minutes; community 41 minutes, 5 to 60 minutes). Personal time differed by location type (academic 6 minutes, 0 to 66 minutes; community 13 minutes, 0 to 69 minutes). All physicians simultaneously cared for multiple patients, with a median number of patients greater than 5 (academic 7 patients, 2 to 16 patients; community 6 patients, 2 to 12 patients). Emergency physicians spend the majority of their time involved in indirect patient care activities. They are frequently interrupted and interact with a large number of individuals. They care for a wide range of patients simultaneously, with surges in multiple patient care responsibilities. Physicians working in academic settings are interrupted at twice the rate of their community counterparts. Copyright © 2010 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.

Testing the Feasibility of a Passive and Active Case Ascertainment System for Multiple Rare Conditions Simultaneously: The Experience in Three US States

PubMed Central

McDermott, Suzanne; Ruttenber, Margaret; Mann, Joshua; Smith, Michael G; Royer, Julie; Valdez, Rodolfo

2016-01-01

Background Owing to their low prevalence, single rare conditions are difficult to monitor through current state passive and active case ascertainment systems. However, such monitoring is important because, as a group, rare conditions have great impact on the health of affected individuals and the well-being of their caregivers. A viable approach could be to conduct passive and active case ascertainment of several rare conditions simultaneously. This is a report about the feasibility of such an approach. Objective To test the feasibility of a case ascertainment system with passive and active components aimed at monitoring 3 rare conditions simultaneously in 3 states of the United States (Colorado, Kansas, and South Carolina). The 3 conditions are spina bifida, muscular dystrophy, and fragile X syndrome. Methods Teams from each state evaluated the possibility of using current or modified versions of their local passive and active case ascertainment systems and datasets to monitor the 3 conditions. Together, these teams established the case definitions and selected the variables and the abstraction tools for the active case ascertainment approach. After testing the ability of their local passive and active case ascertainment system to capture all 3 conditions, the next steps were to report the number of cases detected actively and passively for each condition, to list the local barriers against the combined passive and active case ascertainment system, and to describe the experiences in trying to overcome these barriers. Results During the test period, the team from South Carolina was able to collect data on all 3 conditions simultaneously for all ages. The Colorado team was also able to collect data on all 3 conditions but, because of age restrictions in its passive and active case ascertainment system, it was able to report few cases of fragile X syndrome. The team from Kansas was able to collect data only on spina bifida. For all states, the implementation of an active component of the ascertainment system was problematic. The passive component appears viable with minor modifications. Conclusions Despite evident barriers, the joint passive and active case ascertainment of rare disorders using modified existing surveillance systems and datasets seems feasible, especially for systems that rely on passive case ascertainment. PMID:27574026

Balancing focused combinatorial libraries based on multiple GPCR ligands

NASA Astrophysics Data System (ADS)

Soltanshahi, Farhad; Mansley, Tamsin E.; Choi, Sun; Clark, Robert D.

2006-08-01

G-Protein coupled receptors (GPCRs) are important targets for drug discovery, and combinatorial chemistry is an important tool for pharmaceutical development. The absence of detailed structural information, however, limits the kinds of combinatorial design techniques that can be applied to GPCR targets. This is particularly problematic given the current emphasis on focused combinatorial libraries. By linking an incremental construction method (OptDesign) to the very fast shape-matching capability of ChemSpace, we have created an efficient method for designing targeted sublibraries that are topomerically similar to known actives. Multi-objective scoring allows consideration of multiple queries (actives) simultaneously. This can lead to a distribution of products skewed towards one particular query structure, however, particularly when the ligands of interest are quite dissimilar to one another. A novel pivoting technique is described which makes it possible to generate promising designs even under those circumstances. The approach is illustrated by application to some serotonergic agonists and chemokine antagonists.

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.

Probing the function of neuronal populations: combining micromirror-based optogenetic photostimulation with voltage-sensitive dye imaging.

PubMed

Tsuda, Sachiko; Kee, Michelle Z L; Cunha, Catarina; Kim, Jinsook; Yan, Ping; Loew, Leslie M; Augustine, George J

2013-01-01

Recent advances in our understanding of brain function have come from using light to either control or image neuronal activity. Here we describe an approach that combines both techniques: a micromirror array is used to photostimulate populations of presynaptic neurons expressing channelrhodopsin-2, while a red-shifted voltage-sensitive dye allows optical detection of resulting postsynaptic activity. Such technology allowed us to control the activity of cerebellar interneurons while simultaneously recording inhibitory responses in multiple Purkinje neurons, their postsynaptic targets. This approach should substantially accelerate our understanding of information processing by populations of neurons within brain circuits. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Influence of Al³⁺ addition on the flocculation and sedimentation of activated sludge: comparison of single and multiple dosing patterns.

PubMed

Wen, Yue; Zheng, Wanlin; Yang, Yundi; Cao, Asheng; Zhou, Qi

2015-05-15

In this study, the flocculation and sedimentation performance of activated sludge (AS) with single and multiple dosing of trivalent aluminum (Al(3+)) were studied. The AS samples were cultivated in sequencing batch reactors at 22 °C. The dosages of Al(3+) were 0.00, 0.125, 0.5, 1.0, and 1.5 meq/L for single dosing, and 0.1 meq/L for multiple dosing. Under single dosing conditions, as Al(3+) dosage increased, the zeta potential, total interaction energy, and effluent turbidity decreased, whereas the sludge volume index (SVI) increased, indicating that single Al(3+) dosing could enhance sludge flocculation, but deteriorate sedimentation. By comparison, adding an equal amount of Al(3+) through multiple dosing achieved a similar reduction in turbidity, but the zeta potential was higher, while the loosely bound extracellular polymeric substances (LB-EPS) content and SVI remarkably declined. Although the difference in the flocculation performances between the two dosing patterns was not significant, the underlying mechanisms were quite distinct: the interaction energy played a more important role under single dosing conditions, whereas multiple dosing was more effective in reducing the EPS content. Multiple dosing, which allows sufficient time for sludge restructuring and floc aggregation, could simultaneously optimize sludge flocculation and sedimentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bispecific single-chain diabody-immunoliposomes targeting endoglin (CD105) and fibroblast activation protein (FAP) simultaneously.

PubMed

Rabenhold, Markus; Steiniger, Frank; Fahr, Alfred; Kontermann, Roland E; Rüger, Ronny

2015-03-10

Liposomes are well-established drug delivery systems with cancer chemotherapy as main focus. To increase the cellular drug delivery, liposomes can be endowed with ligands, e.g. recombinant antibody fragments, which ensure specific cell interaction. Multispecific immunoliposomes can be prepared to improve the liposome to cell interaction by targeting multiple different targets at the same time, for instance by coupling two or more different ligands to the liposomal surface, resulting in a synergistic or additive increase in binding. An alternative approach is the use of bispecific ligands to address at least two different targets. For this purpose we cloned a single-chain diabody fragment (scDb`), a bispecific molecule targeting two antigens, endoglin (CD105) and fibroblast activation protein (FAP), expressed on cells of the tumor microenvironment. As model cell system, a human fibrosarcoma cell line was used expressing endoglin and FAP simultaneously. Monospecific immunoliposomes directed either against endoglin or FAP were compared in vitro for cell binding and cytotoxic activity with bispecific dual-targeted scFv`-IL (bispecific scFv`FAP/CD105-IL) and bispecific single-chain diabody`-IL (scDb`CD105/FAP-IL) targeting endoglin and FAP simultaneously. In the underlying study, bispecific scFv`FAP/CD105-IL interacted stronger with cells expressing FAP and endoglin (both targets simultaneously) compared to the monospecific immunoliposomes. Furthermore, bispecific scDb`-immunoliposomes increased the cell interaction massively and showed enhanced cytotoxicity against target cells using doxorubicin-loaded immunoliposomes. The use of recombinant bispecific ligands as scDb`-molecules facilitates the generation of bispecific immunoliposomes by using the established post-insertion technique, enabling an extension of the ligand specificity spectrum via genetic modification. Copyright © 2015 Elsevier B.V. All rights reserved.

Diverse expected gradient active learning for relative attributes.

PubMed

You, Xinge; Wang, Ruxin; Tao, Dacheng

2014-07-01

The use of relative attributes for semantic understanding of images and videos is a promising way to improve communication between humans and machines. However, it is extremely labor- and time-consuming to define multiple attributes for each instance in large amount of data. One option is to incorporate active learning, so that the informative samples can be actively discovered and then labeled. However, most existing active-learning methods select samples one at a time (serial mode), and may therefore lose efficiency when learning multiple attributes. In this paper, we propose a batch-mode active-learning method, called diverse expected gradient active learning. This method integrates an informativeness analysis and a diversity analysis to form a diverse batch of queries. Specifically, the informativeness analysis employs the expected pairwise gradient length as a measure of informativeness, while the diversity analysis forces a constraint on the proposed diverse gradient angle. Since simultaneous optimization of these two parts is intractable, we utilize a two-step procedure to obtain the diverse batch of queries. A heuristic method is also introduced to suppress imbalanced multiclass distributions. Empirical evaluations of three different databases demonstrate the effectiveness and efficiency of the proposed approach.

Diverse Expected Gradient Active Learning for Relative Attributes.

PubMed

You, Xinge; Wang, Ruxin; Tao, Dacheng

2014-06-02

The use of relative attributes for semantic understanding of images and videos is a promising way to improve communication between humans and machines. However, it is extremely labor- and time-consuming to define multiple attributes for each instance in large amount of data. One option is to incorporate active learning, so that the informative samples can be actively discovered and then labeled. However, most existing active-learning methods select samples one at a time (serial mode), and may therefore lose efficiency when learning multiple attributes. In this paper, we propose a batch-mode active-learning method, called Diverse Expected Gradient Active Learning (DEGAL). This method integrates an informativeness analysis and a diversity analysis to form a diverse batch of queries. Specifically, the informativeness analysis employs the expected pairwise gradient length as a measure of informativeness, while the diversity analysis forces a constraint on the proposed diverse gradient angle. Since simultaneous optimization of these two parts is intractable, we utilize a two-step procedure to obtain the diverse batch of queries. A heuristic method is also introduced to suppress imbalanced multi-class distributions. Empirical evaluations of three different databases demonstrate the effectiveness and efficiency of the proposed approach.

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.

A novel multi-hyphenated analytical method to simultaneously determine xanthine oxidase inhibitors and superoxide anion scavengers in natural products.

PubMed

Qi, Jin; Sun, Li-Qiong; Qian, Steven Y; Yu, Bo-Yang

2017-09-01

Natural products, such as rosmarinic acid and apigenin, can act as xanthine oxidase inhibitors (XOIs) as well as superoxide anion scavengers, and have potential for treatment of diseases associated with high uric acid levels and oxidative stress. However, efficient simultaneous screening of these two bioactivities in natural products has been challenging. We have developed a novel method by assembling a multi-hyphenated high performance liquid chromatography (HPLC) system that combines a photo-diode array, chemiluminescence detector and a HPLC system with a variable wavelength detector, to simultaneously detect components that act as both XOIs and superoxide anion scavengers in natural products. Superoxide anion scavenging activity in the analyte was measured by on-line chemiluminescence chromatography based on pyrogallol-luminol oxidation, while xanthine oxidase inhibitory activity was determined by semi-on-line HPLC analysis. After optimizing multiple elements, including chromatographic conditions (e.g., organic solvent concentration and mobile phase pH), concentrations of xanthine/xanthine oxidase and reaction temperature, our validated analytical method was capable of mixed sample analysis. The final results from our method are presented in an easily understood visual format including comprehensive bioactivity data of natural products. Copyright © 2017. Published by Elsevier B.V.

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.

Static calibration of the RSRA active-isolator rotor balance system

NASA Technical Reports Server (NTRS)

Acree, C. W., Jr.

1987-01-01

The Rotor Systems Research Aircraft (RSRA) active-isolator system is designed to reduce rotor vibrations transmitted to the airframe and to simultaneously measure all six forces and moments generated by the rotor. These loads are measured by using a combination of load cells, strain gages, and hydropneumatic active isolators with built-in pressure gages. The first static calibration of the complete active-isolator rotor balance system was performed in l983 to verify its load-measurement capabilities. Analysis of the data included the use of multiple linear regressions to determine calibration matrices for different data sets and a hysteresis-removal algorithm to estimate in-flight measurement errors. Results showed that the active-isolator system can fulfill most performance predictions. The results also suggested several possible improvements to the system.

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.

Nonlinear convergence active vibration absorber for single and multiple frequency vibration control

NASA Astrophysics Data System (ADS)

Wang, Xi; Yang, Bintang; Guo, Shufeng; Zhao, Wenqiang

2017-12-01

This paper presents a nonlinear convergence algorithm for active dynamic undamped vibration absorber (ADUVA). The damping of absorber is ignored in this algorithm to strengthen the vibration suppressing effect and simplify the algorithm at the same time. The simulation and experimental results indicate that this nonlinear convergence ADUVA can help significantly suppress vibration caused by excitation of both single and multiple frequency. The proposed nonlinear algorithm is composed of equivalent dynamic modeling equations and frequency estimator. Both the single and multiple frequency ADUVA are mathematically imitated by the same mechanical structure with a mass body and a voice coil motor (VCM). The nonlinear convergence estimator is applied to simultaneously satisfy the requirements of fast convergence rate and small steady state frequency error, which are incompatible for linear convergence estimator. The convergence of the nonlinear algorithm is mathematically proofed, and its non-divergent characteristic is theoretically guaranteed. The vibration suppressing experiments demonstrate that the nonlinear ADUVA can accelerate the convergence rate of vibration suppressing and achieve more decrement of oscillation attenuation than the linear ADUVA.

Many si/shRNAs can kill cancer cells by targeting multiple survival genes through an off-target mechanism

PubMed Central

van Dongen, Stijn; Haluck-Kangas, Ashley; Sarshad, Aishe A; Bartom, Elizabeth T; Kim, Kwang-Youn A; Scholtens, Denise M; Hafner, Markus; Zhao, Jonathan C; Murmann, Andrea E

2017-01-01

Over 80% of multiple-tested siRNAs and shRNAs targeting CD95 or CD95 ligand (CD95L) induce a form of cell death characterized by simultaneous activation of multiple cell death pathways preferentially killing transformed and cancer stem cells. We now show these si/shRNAs kill cancer cells through canonical RNAi by targeting the 3’UTR of critical survival genes in a unique form of off-target effect we call DISE (death induced by survival gene elimination). Drosha and Dicer-deficient cells, devoid of most miRNAs, are hypersensitive to DISE, suggesting cellular miRNAs protect cells from this form of cell death. By testing 4666 shRNAs derived from the CD95 and CD95L mRNA sequences and an unrelated control gene, Venus, we have identified many toxic sequences - most of them located in the open reading frame of CD95L. We propose that specific toxic RNAi-active sequences present in the genome can kill cancer cells. PMID:29063830

Control of thermal therapies with moving power deposition field.

PubMed

Arora, Dhiraj; Minor, Mark A; Skliar, Mikhail; Roemer, Robert B

2006-03-07

A thermal therapy feedback control approach to control thermal dose using a moving power deposition field is developed and evaluated using simulations. A normal tissue safety objective is incorporated in the controller design by imposing constraints on temperature elevations at selected normal tissue locations. The proposed control technique consists of two stages. The first stage uses a model-based sliding mode controller that dynamically generates an 'ideal' power deposition profile which is generally unrealizable with available heating modalities. Subsequently, in order to approximately realize this spatially distributed idealized power deposition, a constrained quadratic optimizer is implemented to compute intensities and dwell times for a set of pre-selected power deposition fields created by a scanned focused transducer. The dwell times for various power deposition profiles are dynamically generated online as opposed to the commonly employed a priori-decided heating strategies. Dynamic intensity and trajectory generation safeguards the treatment outcome against modelling uncertainties and unknown disturbances. The controller is designed to enforce simultaneous activation of multiple normal tissue temperature constraints by rapidly switching between various power deposition profiles. The hypothesis behind the controller design is that the simultaneous activation of multiple constraints substantially reduces treatment time without compromising normal tissue safety. The controller performance and robustness with respect to parameter uncertainties is evaluated using simulations. The results demonstrate that the proposed controller can successfully deliver the desired thermal dose to the target while maintaining the temperatures at the user-specified normal tissue locations at or below the maximum allowable values. Although demonstrated for the case of a scanned focused ultrasound transducer, the developed approach can be extended to other heating modalities with moving deposition fields, such as external and interstitial ultrasound phased arrays, multiple radiofrequency needle applicators and microwave antennae.

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.

Multi-object segmentation framework using deformable models for medical imaging analysis.

PubMed

Namías, Rafael; D'Amato, Juan Pablo; Del Fresno, Mariana; Vénere, Marcelo; Pirró, Nicola; Bellemare, Marc-Emmanuel

2016-08-01

Segmenting structures of interest in medical images is an important step in different tasks such as visualization, quantitative analysis, simulation, and image-guided surgery, among several other clinical applications. Numerous segmentation methods have been developed in the past three decades for extraction of anatomical or functional structures on medical imaging. Deformable models, which include the active contour models or snakes, are among the most popular methods for image segmentation combining several desirable features such as inherent connectivity and smoothness. Even though different approaches have been proposed and significant work has been dedicated to the improvement of such algorithms, there are still challenging research directions as the simultaneous extraction of multiple objects and the integration of individual techniques. This paper presents a novel open-source framework called deformable model array (DMA) for the segmentation of multiple and complex structures of interest in different imaging modalities. While most active contour algorithms can extract one region at a time, DMA allows integrating several deformable models to deal with multiple segmentation scenarios. Moreover, it is possible to consider any existing explicit deformable model formulation and even to incorporate new active contour methods, allowing to select a suitable combination in different conditions. The framework also introduces a control module that coordinates the cooperative evolution of the snakes and is able to solve interaction issues toward the segmentation goal. Thus, DMA can implement complex object and multi-object segmentations in both 2D and 3D using the contextual information derived from the model interaction. These are important features for several medical image analysis tasks in which different but related objects need to be simultaneously extracted. Experimental results on both computed tomography and magnetic resonance imaging show that the proposed framework has a wide range of applications especially in the presence of adjacent structures of interest or under intra-structure inhomogeneities giving excellent quantitative results.

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.

Effects of a Web-Based Tailored Multiple-Lifestyle Intervention for Adults: A Two-Year Randomized Controlled Trial Comparing Sequential and Simultaneous Delivery Modes

PubMed Central

Kremers, Stef PJ; Vandelanotte, Corneel; van Adrichem, Mathieu JG; Schneider, Francine; Candel, Math JJM; de Vries, Hein

2014-01-01

Background Web-based computer-tailored interventions for multiple health behaviors can have a significant public health impact. Yet, few randomized controlled trials have tested this assumption. Objective The objective of this paper was to test the effects of a sequential and simultaneous Web-based tailored intervention on multiple lifestyle behaviors. Methods A randomized controlled trial was conducted with 3 tailoring conditions (ie, sequential, simultaneous, and control conditions) in the Netherlands in 2009-2012. Follow-up measurements took place after 12 and 24 months. The intervention content was based on the I-Change model. In a health risk appraisal, all respondents (N=5055) received feedback on their lifestyle behaviors that indicated whether they complied with the Dutch guidelines for physical activity, vegetable consumption, fruit consumption, alcohol intake, and smoking. Participants in the sequential (n=1736) and simultaneous (n=1638) conditions received tailored motivational feedback to change unhealthy behaviors one at a time (sequential) or all at the same time (simultaneous). Mixed model analyses were performed as primary analyses; regression analyses were done as sensitivity analyses. An overall risk score was used as outcome measure, then effects on the 5 individual lifestyle behaviors were assessed and a process evaluation was performed regarding exposure to and appreciation of the intervention. Results Both tailoring strategies were associated with small self-reported behavioral changes. The sequential condition had the most significant effects compared to the control condition after 12 months (T1, effect size=0.28). After 24 months (T2), the simultaneous condition was most effective (effect size=0.18). All 5 individual lifestyle behaviors changed over time, but few effects differed significantly between the conditions. At both follow-ups, the sequential condition had significant changes in smoking abstinence compared to the simultaneous condition (T1 effect size=0.31; T2 effect size=0.41). The sequential condition was more effective in decreasing alcohol consumption than the control condition at 24 months (effect size=0.27). Change was predicted by the amount of exposure to the intervention (total visiting time: beta=–.06; P=.01; total number of visits: beta=–.11; P<.001). Both interventions were appreciated well by respondents without significant differences between conditions. Conclusions Although evidence was found for the effectiveness of both programs, no simple conclusive finding could be drawn about which intervention mode was more effective. The best kind of intervention may depend on the behavior that is targeted or on personal preferences and motivation. Further research is needed to identify moderators of intervention effectiveness. The results need to be interpreted in view of the high and selective dropout rates, multiple comparisons, and modest effect sizes. However, a large number of people were reached at low cost and behavioral change was achieved after 2 years. Trial Registration Nederlands Trial Register: NTR 2168; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2168 (Archived by WebCite at http://www.webcitation.org/6MbUqttYB). PMID:24472854

A brief description of the Medical Information Computer System (MEDICS). [real time minicomputer system

NASA Technical Reports Server (NTRS)

Moseley, E. C.

1974-01-01

The Medical Information Computer System (MEDICS) is a time shared, disk oriented minicomputer system capable of meeting storage and retrieval needs for the space- or non-space-related applications of at least 16 simultaneous users. At the various commercially available low cost terminals, the simple command and control mechanism and the generalized communication activity of the system permit multiple form inputs, real-time updating, and instantaneous retrieval capability with a full range of options.

Terrorism Information Sharing and the Nationwide Suspicious Activity Report Initiative: Background and Issues for Congress

DTIC Science & Technology

2009-11-05

December_23_2008_Final.pdf. 46 Ibid. 47 Federated search is the process of performing a simultaneous real-time search of multiple diverse and distributed...sources from a single search page, with the federated search engine acting as intermediary. See Sol Lederman, “A Federated Search Primer, Part II...at http://www.altsearchengines.com/2009/01/12/a- federated - search -primer-part-ii-of- iii/ 48 Examples of this controversy can be found at Alice

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.

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...

Simultaneous Measurement of Multiple Mechanical Properties of Single Cells Using AFM by Indentation and Vibration.

PubMed

Zhang, Chuang; Shi, Jialin; Wang, Wenxue; Xi, Ning; Wang, Yuechao; Liu, Lianqing

2017-12-01

The mechanical properties of cells, which are the main characteristics determining their physical performance and physiological functions, have been actively studied in the fields of cytobiology and biomedical engineering and for the development of medicines. In this study, an indentation-vibration-based method is proposed to simultaneously measure the mechanical properties of cells in situ, including cellular mass (m), elasticity (k), and viscosity (c). The proposed measurement method is implemented based on the principle of forced vibration stimulated by simple harmonic force using an atomic force microscope (AFM) system integrated with a piezoelectric transducer as the substrate vibrator. The corresponding theoretical model containing the three mechanical properties is derived and used to perform simulations and calculations. Living and fixed human embryonic kidney 293 (HEK 293) cells were subjected to indentation and vibration to measure and compare their mechanical parameters and verify the proposed approach. The results that the fixed sample cells are more viscous and elastic than the living sample cells and the measured mechanical properties of cell are consistent within, but not outside of the central region of the cell, are in accordance with the previous studies. This work provides an approach to simultaneous measurement of the multiple mechanical properties of single cells using an integrated AFM system based on the principle force vibration and thickness-corrected Hertz model. This study should contribute to progress in biomedical engineering, cytobiology, medicine, early diagnosis, specific therapy and cell-powered robots.

Magnetic molecularly imprinted polymers based on silica modified by deep eutectic solvents for the rapid simultaneous magnetic-based solid-phase extraction of Salvia miltiorrhiza bunge, Glycine max (Linn.) Merr and green tea.

PubMed

Li, Guizhen; Wang, Xiaoqin; Row, Kyung Ho

2018-04-01

Novel magnetic molecularly imprinted polymers (MMIPs) with multiple-template based on silica were modified by four types of deep eutectic solvents (DESs) for the rapid simultaneous magnetic solid-phase extraction (MSPE) of tanshinone Ⅰ, tanshinone ⅡA, and cryptotanshinone from Salvia miltiorrhiza bunge; glycitein, genistein, and daidzein from Glycine max (Linn.) Merr; and epicatechin, epigallocatechin gallate, and epicatechin gallate from green tea, respectively. The synthesized materials were characterized by Fourier transform infrared spectroscopy and field emission scanning electron microscopy. Single factor experiments were to explore the relationship between the extraction efficiency and four factors (the sample solution pH, amount of DESs for modification, amount of adsorbent, and extraction time). It was showed that the DES4-MMIPs have better extraction ability than the MMIPs without DESs and the other three DESs-modified MMIPs. The best extraction recoveries with DES4-MMIP were tanshinone Ⅰ (85.57%), tanshinone ⅡA (80.58%), cryptotanshinone (92.12%), glycitein (81.65%), genistein (87.72%), daidzein (92.24%), epicatechin (86.43%), epigallocatechin gallate (80.92%), and epicatechin gallate (93.64%), respectively. The novel multiple-template MMIPs materials modified by DES for the rapid simultaneous MSPE of active compounds were proved to reduce the experimental steps than single-template technique, and increase the extraction efficiency. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Simple Method to Simultaneously Detect and Identify Spikes from Raw Extracellular Recordings.

PubMed

Petrantonakis, Panagiotis C; Poirazi, Panayiota

2015-01-01

The ability to track when and which neurons fire in the vicinity of an electrode, in an efficient and reliable manner can revolutionize the neuroscience field. The current bottleneck lies in spike sorting algorithms; existing methods for detecting and discriminating the activity of multiple neurons rely on inefficient, multi-step processing of extracellular recordings. In this work, we show that a single-step processing of raw (unfiltered) extracellular signals is sufficient for both the detection and identification of active neurons, thus greatly simplifying and optimizing the spike sorting approach. The efficiency and reliability of our method is demonstrated in both real and simulated data.

Transmedia Storytelling in Science Communication: One Subject, Multiple Media, Multiple Stories

NASA Astrophysics Data System (ADS)

Unger, M.; Moloney, K.

2012-12-01

Each communication medium has particular storytelling strengths. For example, video is particularly good at illustrating a progression of events, text at background and context, and games at describing systems. In what USC's Prof. Henry Jenkins described as "transmedia storytelling," multiple media are used simultaneously, in an expansive rather than repetitive way, to better tell a single, complex story. The audience is given multiple entry points to the story, and the story is exposed to diverse and dispersed audiences, ultimately engaging a broader public. We will examine the effectiveness of a transmedia approach to communicating scientific and other complex concepts to a broad and diverse audience. Using the recently developed Educational Visitor Center at the NCAR-Wyoming Supercomputing Center as a case study, we will evaluate the reach of various means of presenting information about the geosciences, climate change and computational science. These will include an assessment of video, mechanical and digital interactive elements, animated movie segments, web-based content, photography, scientific visualizations, printed material and docent-led activities.

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.

Online evaluation of novel choices by simultaneous representation of multiple memories

PubMed Central

Barron, Helen C; Dolan, Raymond J; Behrens, Timothy E J

2014-01-01

Prior experience plays a critical role in decision making. It enables explicit representation of potential outcomes and provides training to valuation mechanisms. However, we can also make choices in the absence of prior experience, by merely imagining the consequences of a new experience. Here, using fMRI repetition suppression in humans, we show how neuronal representations of novel rewards can be constructed and evaluated. A likely novel experience is constructed by invoking multiple independent memories within hippocampus and medial prefrontal cortex. This construction persists for only a short time period, during which new associations are observed between the memories for component items. Together these findings suggest that in the absence of direct experience, co-activation of multiple relevant memories can provide a training signal to the valuation system which allows the consequences of new experiences to be imagined and acted upon. PMID:24013592

What have we been priming all these years? On the development, mechanisms, and ecology of nonconscious social behavior

PubMed Central

BARGH, JOHN A.

2009-01-01

Priming or nonconscious activation of social knowledge structures has produced a plethora of rather amazing findings over the past 25 years: priming a single social concept such as aggressive can have multiple effects across a wide array of psychological systems, such as perception, motivation, behavior, and evaluation. But we may have reached childhood’s end, so to speak, and need now to move on to research questions such as how these multiple effects of single primes occur (the generation problem); next, how these multiple simultaneous priming influences in the environment get distilled into nonconscious social action that has to happen serially, in real time (the reduction problem). It is suggested that models of complex conceptual structures (Lakoff & Johnson, 1980), language use in real-life conversational settings (Clark, 1996), and speech production (Dell, 1986) might hold the key for solving these two important ‘second-generation’ research problems. PMID:19844598

TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer Immunotherapy

PubMed Central

Grada, Zakaria; Hegde, Meenakshi; Byrd, Tiara; Shaffer, Donald R; Ghazi, Alexia; Brawley, Vita S; Corder, Amanda; Schönfeld, Kurt; Koch, Joachim; Dotti, Gianpietro; Heslop, Helen E; Gottschalk, Stephen; Wels, Winfried S; Baker, Matthew L; Ahmed, Nabil

2013-01-01

Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen receptor—the TanCAR, a novel artificial molecule that mediates bispecific activation and targeting of T cells. We demonstrate the feasibility of cumulative integration of structure and docking simulation data using computational tools to interrogate the design and predict the functionality of such a complex bispecific molecule. Our prototype TanCAR induced distinct T cell reactivity against each of two tumor restricted antigens, and produced synergistic enhancement of effector functions when both antigens were simultaneously encountered. Furthermore, the TanCAR preserved the cytolytic ability of T cells upon loss of one of the target molecules and better controlled established experimental tumors by recognition of both targets in an animal disease model. This proof-of-concept approach can be used to increase the specificity of effector cells for malignant versus normal target cells, to offset antigen escape or to allow for targeting the tumor and its microenvironment. PMID:23839099

Demonstration of optically controlled data routing with the use of multiple-quantum-well bistable and electro-optical devices.

PubMed

Koppa, P; Chavel, P; Oudar, J L; Kuszelewicz, R; Schnell, J P; Pocholle, J P

1997-08-10

We present experimental results on a 1-to-64-channel free-space photonic switching demonstration system based on GaAs/GaAlAs multiple-quantum-well active device arrays. Two control schemes are demonstrated: data transparent optical self-routing usable in a packet-switching environment and direct optical control with potential signal amplification for circuit switching. The self-routing operation relies on the optical recognition of the binary destination address coded in each packet header. Address decoding is implemented with elementary optical bistable devices and modulator pixels as all-optical latches and electro-optical and gates, respectively. All 60 defect-free channels of the system could be operated one by one, but the simultaneous operation of only three channels could be achieved mainly because of the spatial nonhomogeneities of the devices. Direct-control operation is based on directly setting the bistable device reflectivity with a variable-control beam power. This working mode turned out to be much more tolerant of spatial noises: 37 channels of the system could be operated simultaneously. Further development of the system to a crossbar of N inputs and M outputs and system miniaturization are also considered.

Activation of concurrent apoptosis and necroptosis by SMAC mimetics for the treatment of refractory and relapsed ALL.

PubMed

McComb, Scott; Aguadé-Gorgorió, Júlia; Harder, Lena; Marovca, Blerim; Cario, Gunnar; Eckert, Cornelia; Schrappe, Martin; Stanulla, Martin; von Stackelberg, Arend; Bourquin, Jean-Pierre; Bornhauser, Beat C

2016-05-18

More precise treatment strategies are urgently needed to decrease toxicity and improve outcomes for treatment-refractory leukemia. We used ex vivo drug response profiling of high-risk, relapsed, or refractory acute lymphoblastic leukemia (ALL) cases and identified a subset with exquisite sensitivity to small-molecule mimetics of the second mitochondria-derived activator of caspases (SMAC) protein. Potent ex vivo activity of the SMAC mimetic (SM) birinapant correlated with marked in vivo antileukemic effects, as indicated by delayed engraftment, decreased leukemia burden, and prolonged survival of xenografted mice. Antileukemic activity was dependent on simultaneous execution of apoptosis and necroptosis, as demonstrated by functional genomic dissection with a multicolored lentiCRISPR approach to simultaneously disrupt multiple genes in patient-derived ALL. SM specifically targeted receptor-interacting protein kinase 1 (RIP1)-dependent death, and CRISPR-mediated disruption of RIP1 completely blocked SM-induced death yet had no impact on the response to standard antileukemic agents. Thus, SM compounds such as birinapant circumvent escape from apoptosis in leukemia by activating a potent dual RIP1-dependent apoptotic and necroptotic cell death, which is not exploited by current therapy. Ex vivo drug activity profiling could provide important functional diagnostic information to identify patients who may benefit from targeted treatment with birinapant in early clinical trials. Copyright © 2016, American Association for the Advancement of Science.

Imaging Voltage in Genetically Defined Neuronal Subpopulations with a Cre Recombinase-Targeted Hybrid Voltage Sensor.

PubMed

Bayguinov, Peter O; Ma, Yihe; Gao, Yu; Zhao, Xinyu; Jackson, Meyer B

2017-09-20

Genetically encoded voltage indicators create an opportunity to monitor electrical activity in defined sets of neurons as they participate in the complex patterns of coordinated electrical activity that underlie nervous system function. Taking full advantage of genetically encoded voltage indicators requires a generalized strategy for targeting the probe to genetically defined populations of cells. To this end, we have generated a mouse line with an optimized hybrid voltage sensor (hVOS) probe within a locus designed for efficient Cre recombinase-dependent expression. Crossing this mouse with Cre drivers generated double transgenics expressing hVOS probe in GABAergic, parvalbumin, and calretinin interneurons, as well as hilar mossy cells, new adult-born neurons, and recently active neurons. In each case, imaging in brain slices from male or female animals revealed electrically evoked optical signals from multiple individual neurons in single trials. These imaging experiments revealed action potentials, dynamic aspects of dendritic integration, and trial-to-trial fluctuations in response latency. The rapid time response of hVOS imaging revealed action potentials with high temporal fidelity, and enabled accurate measurements of spike half-widths characteristic of each cell type. Simultaneous recording of rapid voltage changes in multiple neurons with a common genetic signature offers a powerful approach to the study of neural circuit function and the investigation of how neural networks encode, process, and store information. SIGNIFICANCE STATEMENT Genetically encoded voltage indicators hold great promise in the study of neural circuitry, but realizing their full potential depends on targeting the sensor to distinct cell types. Here we present a new mouse line that expresses a hybrid optical voltage sensor under the control of Cre recombinase. Crossing this line with Cre drivers generated double-transgenic mice, which express this sensor in targeted cell types. In brain slices from these animals, single-trial hybrid optical voltage sensor recordings revealed voltage changes with submillisecond resolution in multiple neurons simultaneously. This imaging tool will allow for the study of the emergent properties of neural circuits and permit experimental tests of the roles of specific types of neurons in complex circuit activity. Copyright © 2017 the authors 0270-6474/17/379305-15$15.00/0.

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

Combined rule extraction and feature elimination in supervised classification.

PubMed

Liu, Sheng; Patel, Ronak Y; Daga, Pankaj R; Liu, Haining; Fu, Gang; Doerksen, Robert J; Chen, Yixin; Wilkins, Dawn E

2012-09-01

There are a vast number of biology related research problems involving a combination of multiple sources of data to achieve a better understanding of the underlying problems. It is important to select and interpret the most important information from these sources. Thus it will be beneficial to have a good algorithm to simultaneously extract rules and select features for better interpretation of the predictive model. We propose an efficient algorithm, Combined Rule Extraction and Feature Elimination (CRF), based on 1-norm regularized random forests. CRF simultaneously extracts a small number of rules generated by random forests and selects important features. We applied CRF to several drug activity prediction and microarray data sets. CRF is capable of producing performance comparable with state-of-the-art prediction algorithms using a small number of decision rules. Some of the decision rules are biologically significant.

Multiple homologous genes knockout (KO) by CRISPR/Cas9 system in rabbit.

PubMed

Liu, Huan; Sui, Tingting; Liu, Di; Liu, Tingjun; Chen, Mao; Deng, Jichao; Xu, Yuanyuan; Li, Zhanjun

2018-03-20

The CRISPR/Cas9 system is a highly efficient and convenient genome editing tool, which has been widely used for single or multiple gene mutation in a variety of organisms. Disruption of multiple homologous genes, which have similar DNA sequences and gene function, is required for the study of the desired phenotype. In this study, to test whether the CRISPR/Cas9 system works on the mutation of multiple homologous genes, a single guide RNA (sgRNA) targeting three fucosyltransferases encoding genes (FUT1, FUT2 and SEC1) was designed. As expected, triple gene mutation of FUT1, FUT2 and SEC1 could be achieved simultaneously via a sgRNA mediated CRISPR/Cas9 system. Besides, significantly reduced serum fucosyltransferases enzymes activity was also determined in those triple gene mutation rabbits. Thus, we provide the first evidence that multiple homologous genes knockout (KO) could be achieved efficiently by a sgRNA mediated CRISPR/Cas9 system in mammals, which could facilitate the genotype to phenotype studies of homologous genes in future. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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.

A Convenient Cas9-based Conditional Knockout Strategy for Simultaneously Targeting Multiple Genes in Mouse.

PubMed

Chen, Jiang; Du, Yinan; He, Xueyan; Huang, Xingxu; Shi, Yun S

2017-03-31

The most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.

Changes in Cortical Activity During Real and Imagined Movements: an ERP Study

PubMed Central

Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Ribeiro, Pedro; Cagy, Mauricio; Piedade, Roberto; Almada, Leonardo Ferreira; Anghinah, Renato; Basile, Luis; Moro, Maria Francesca; Orsini, Marco; Silva, Julio Guilherme; Silva, Adriana Cardoso; Nardi, Antonio E.

2013-01-01

This study aims to compare the topographic distribution of cortical activation between real and imagined movement through event-related potential (ERP). We are specifically interested in identifying, the topographic distribution of activated areas, the intensity of activated areas, and the temporal occurrence of these activations on preparation and motor response phases. Twelve healthy and right handed subjects were instructed to perform a task under real and imagery conditions. The task was performed simultaneously to electroencephalographic (EEG) recording. When compared the conditions, we found a statistically significant difference in favor of real condition revealed by performing an unpaired t-test with multiple corrections of Bonferroni, demonstrating negative activity on electrode C3 and positive activity on the electrode C4 only in motor response phase. These findings revealed similar functional connections established during real and imagery conditions, suggesting that there are common neural substrate and similar properties of functional integration shared by conditions. PMID:24358049

Changes in Cortical Activity During Real and Imagined Movements: an ERP Study.

PubMed

Machado, Sergio; Arias-Carrión, Oscar; Paes, Flávia; Ribeiro, Pedro; Cagy, Mauricio; Piedade, Roberto; Almada, Leonardo Ferreira; Anghinah, Renato; Basile, Luis; Moro, Maria Francesca; Orsini, Marco; Silva, Julio Guilherme; Silva, Adriana Cardoso; Nardi, Antonio E

2013-11-15

This study aims to compare the topographic distribution of cortical activation between real and imagined movement through event-related potential (ERP). We are specifically interested in identifying, the topographic distribution of activated areas, the intensity of activated areas, and the temporal occurrence of these activations on preparation and motor response phases. Twelve healthy and right handed subjects were instructed to perform a task under real and imagery conditions. The task was performed simultaneously to electroencephalographic (EEG) recording. When compared the conditions, we found a statistically significant difference in favor of real condition revealed by performing an unpaired t-test with multiple corrections of Bonferroni, demonstrating negative activity on electrode C3 and positive activity on the electrode C4 only in motor response phase. These findings revealed similar functional connections established during real and imagery conditions, suggesting that there are common neural substrate and similar properties of functional integration shared by conditions.

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.

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.

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.

Integration of Teaching Processes and Learning Assessment in the Prefrontal Cortex during a Video Game Teaching–learning Task

PubMed Central

Takeuchi, Naoyuki; Mori, Takayuki; Suzukamo, Yoshimi; Izumi, Shin-Ichi

2017-01-01

Human teaching is a social interaction that supports reciprocal and dynamical feedback between the teacher and the student. The prefrontal cortex (PFC) is a region of particular interest due to its demonstrated role in social interaction. In the present study, we evaluated the PFC activity simultaneously in two individuals playing the role of a teacher and student in a video game teaching–learning task. For that, we used two wearable near-infrared spectroscopy (NIRS) devices in order to elucidate the neural mechanisms underlying cognitive interactions between teachers and students. Fifteen teacher–student pairs in total (N = 30) participated in this study. Each teacher was instructed to teach the video game to their student partner, without speaking. The PFC activity was simultaneously evaluated in both participants using a wearable 16-channel NIRS system during the video game teaching–learning task. Two sessions, each including a triplet of a 30-s teaching–learning task, were performed in order to evaluate changes in PFC activity after advancement of teaching–learning state. Changes in the teachers’ left PFC activity between the first and second session positively correlated with those observed in students (r = 0.694, p = 0.004). Moreover, among teachers, multiple regression analysis revealed a correlation between the left PFC activity and the assessment gap between one’s own teaching and the student’s understanding (β = 0.649, p = 0.009). Activity in the left PFC changed synchronously in both teachers and students after advancement of the teaching–learning state. The left PFC of teachers may be involved in integrating information regarding one’s own teaching process and the student’s learning state. The present observations indicate that simultaneous recording and analysis of brain activity data during teacher–student interactions may be useful in the field of educational neuroscience. PMID:28119650

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.

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.

Low DPP4 expression and activity in multiple sclerosis.

PubMed

Tejera-Alhambra, Marta; Casrouge, Armanda; de Andrés, Clara; Ramos-Medina, Rocío; Alonso, Bárbara; Vega, Janet; Albert, Matthew L; Sánchez-Ramón, Silvia

2014-02-01

Multiple sclerosis (MS) is a prototypic Th1/Th17 chronic autoimmune disease of the central nervous system. Dipeptidyl peptidase 4 (DPP4 or CD26) is a multifunctional molecule involved in autoimmune diseases' pathophysiology. We sought to integrate disparate pieces of data and analyze the plasma levels of sDPP4, DPP activity and DPP4 surface expression on T-cells in 129 MS patients with different clinical forms and 53 healthy controls, across two independent cohorts. Herein, we provide new evidence that sDPP4 concentration and DPP activity are significantly lower in MS patients than controls (p < 0.0001 and p < 0.01, respectively). In contrast, the frequency of circulating CD8(+)DPP4(hi) T-cells (p = 0.02) was increased in MS patients. This is the first study that simultaneously analyzes DPP4 expression and function in a large cohort of MS patients. Our data indicate a putative role for DPP4 in MS pathophysiology and suggest that a deeper understanding of surface versus shed DPP4 biology is warranted. Copyright © 2013 Elsevier Inc. All rights reserved.

[Inter-rater concordance of the "Nursing Activities Score" in intensive care].

PubMed

Valls-Matarín, Josefa; Salamero-Amorós, Maria; Roldán-Gil, Carmen; Quintana-Riera, Salvador

2015-01-01

To evaluate inter-rater concordance in the valuation of the "Nursing Activities Score". Cross-sectional descriptive study conducted from December 2012 until June 2013 in a general intensive care unit with twelve beds. Three evaluator nurses, simultaneously and independently, through the patient daily charts, scored the nursing workload using Nursing Activities Score scale in all patients admitted over 18 years old. Three hundreds and thirty-nine records were collected. The intra-class correlation coefficient (ICC) between evaluators was 0.92 (0.89-0.94). A perfect concordance was obtained in 39.1% of the items, with 52.2% having a high, and 8.7% having lower concordance, corresponding to two of the items with multiple scoring options. Significant differences between two of the evaluators (P=.049) were found. Although the inter-rater concordance was high, more accurate records are needed to reduce the variability of the items with multiple options and to allow more accuracy in the interpretation and measurement of the data regarding nursing workload. Copyright © 2015 Elsevier España, S.L.U. 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.

Changes in monosaccharides, organic acids and amino acids during Cabernet Sauvignon wine ageing based on a simultaneous analysis using gas chromatography-mass spectrometry.

PubMed

Zhang, Xin-Ke; Lan, Yi-Bin; Zhu, Bao-Qing; Xiang, Xiao-Feng; Duan, Chang-Qing; Shi, Ying

2018-01-01

Monosaccharides, organic acids and amino acids are the important flavour-related components in wines. The aim of this article is to develop and validate a method that could simultaneously analyse these compounds in wine based on silylation derivatisation and gas chromatography-mass spectrometry (GC-MS), and apply this method to the investigation of the changes of these compounds and speculate upon their related influences on Cabernet Sauvignon wine flavour during wine ageing. This work presented a new approach for wine analysis and provided more information concerning red wine ageing. This method could simultaneously quantitatively analyse 2 monosaccharides, 8 organic acids and 13 amino acids in wine. A validation experiment showed good linearity, sensitivity, reproducibility and recovery. Multiple derivatives of five amino acids have been found but their effects on quantitative analysis were negligible, except for methionine. The evolution pattern of each category was different, and we speculated that the corresponding mechanisms involving microorganism activities, physical interactions and chemical reactions had a great correlation with red wine flavours during ageing. Simultaneously quantitative analysis of monosaccharides, organic acids and amino acids in wine was feasible and reliable and this method has extensive application prospects. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Investigation of the effect of EEG-BCI on the simultaneous execution of flight simulation and attentional tasks.

PubMed

Vecchiato, Giovanni; Borghini, Gianluca; Aricò, Pietro; Graziani, Ilenia; Maglione, Anton Giulio; Cherubino, Patrizia; Babiloni, Fabio

2016-10-01

Brain-computer interfaces (BCIs) are widely used for clinical applications and exploited to design robotic and interactive systems for healthy people. We provide evidence to control a sensorimotor electroencephalographic (EEG) BCI system while piloting a flight simulator and attending a double attentional task simultaneously. Ten healthy subjects were trained to learn how to manage a flight simulator, use the BCI system, and answer to the attentional tasks independently. Afterward, the EEG activity was collected during a first flight where subjects were required to concurrently use the BCI, and a second flight where they were required to simultaneously use the BCI and answer to the attentional tasks. Results showed that the concurrent use of the BCI system during the flight simulation does not affect the flight performances. However, BCI performances decrease from the 83 to 63 % while attending additional alertness and vigilance tasks. This work shows that it is possible to successfully control a BCI system during the execution of multiple tasks such as piloting a flight simulator with an extra cognitive load induced by attentional tasks. Such framework aims to foster the knowledge on BCI systems embedded into vehicles and robotic devices to allow the simultaneous execution of secondary tasks.

Simultaneous and Continuous Estimation of Shoulder and Elbow Kinematics from Surface EMG Signals

PubMed Central

Zhang, Qin; Liu, Runfeng; Chen, Wenbin; Xiong, Caihua

2017-01-01

In this paper, we present a simultaneous and continuous kinematics estimation method for multiple DoFs across shoulder and elbow joint. Although simultaneous and continuous kinematics estimation from surface electromyography (EMG) is a feasible way to achieve natural and intuitive human-machine interaction, few works investigated multi-DoF estimation across the significant joints of upper limb, shoulder and elbow joints. This paper evaluates the feasibility to estimate 4-DoF kinematics at shoulder and elbow during coordinated arm movements. Considering the potential applications of this method in exoskeleton, prosthetics and other arm rehabilitation techniques, the estimation performance is presented with different muscle activity decomposition and learning strategies. Principle component analysis (PCA) and independent component analysis (ICA) are respectively employed for EMG mode decomposition with artificial neural network (ANN) for learning the electromechanical association. Four joint angles across shoulder and elbow are simultaneously and continuously estimated from EMG in four coordinated arm movements. By using ICA (PCA) and single ANN, the average estimation accuracy 91.12% (90.23%) is obtained in 70-s intra-cross validation and 87.00% (86.30%) is obtained in 2-min inter-cross validation. This result suggests it is feasible and effective to use ICA (PCA) with single ANN for multi-joint kinematics estimation in variant application conditions. PMID:28611573

Synergistic anti-tumor therapy by a comb-like multifunctional antibody nanoarray with exceptionally potent activity

NASA Astrophysics Data System (ADS)

Li, Huafei; Sun, Yun; Chen, Di; Zhao, He; Zhao, Mengxin; Zhu, Xiandi; Ke, Changhong; Zhang, Ge; Jiang, Cheng; Zhang, Li; Zhang, Fulei; Wei, Huafeng; Li, Wei

2015-10-01

Simultaneously blocking multiple mediators offers new hope for the treatment of complex diseases. However, the curative potential of current combination therapy by chronological administration of separate monoclonal antibodies (mAbs) or multi-specific mAbs is still moderate due to inconvenient manipulation, low cooperative effectors, poor pharmacokinetics and insufficient tumor accumulation. Here, we describe a facile strategy that arms distinct mAbs with cooperative effectors onto a long chain to form a multicomponent comb-like nano mAb. Unlike dissociative parental mAbs, the multifunctional mAb nanoarray (PL-RB) constructed from type I/II anti-CD20 mAbs shows good pharmacokinetics. This PL-RB simultaneously targets distinct epitopes on a single antigen (Ag) and neighboring Ags on different lymphocytes. This unique intra- and intercellular Ag cross-linking endows the multifunctional mAb nanoarray with potent apoptosis activity. The exceptional apoptosis, complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) that are synchronously evoked by the nano PL-RB are further synergistically promoted via enhanced permeability and retention (EPR), which resulted in high intratumor accumulation and excellent anti-lymphoma efficiency.

Synergistic anti-tumor therapy by a comb-like multifunctional antibody nanoarray with exceptionally potent activity.

PubMed

Li, Huafei; Sun, Yun; Chen, Di; Zhao, He; Zhao, Mengxin; Zhu, Xiandi; Ke, Changhong; Zhang, Ge; Jiang, Cheng; Zhang, Li; Zhang, Fulei; Wei, Huafeng; Li, Wei

2015-10-28

Simultaneously blocking multiple mediators offers new hope for the treatment of complex diseases. However, the curative potential of current combination therapy by chronological administration of separate monoclonal antibodies (mAbs) or multi-specific mAbs is still moderate due to inconvenient manipulation, low cooperative effectors, poor pharmacokinetics and insufficient tumor accumulation. Here, we describe a facile strategy that arms distinct mAbs with cooperative effectors onto a long chain to form a multicomponent comb-like nano mAb. Unlike dissociative parental mAbs, the multifunctional mAb nanoarray (PL-RB) constructed from type I/II anti-CD20 mAbs shows good pharmacokinetics. This PL-RB simultaneously targets distinct epitopes on a single antigen (Ag) and neighboring Ags on different lymphocytes. This unique intra- and intercellular Ag cross-linking endows the multifunctional mAb nanoarray with potent apoptosis activity. The exceptional apoptosis, complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) that are synchronously evoked by the nano PL-RB are further synergistically promoted via enhanced permeability and retention (EPR), which resulted in high intratumor accumulation and excellent anti-lymphoma efficiency.

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.

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...

Stretching of Active Muscle Elicits Chronic Changes in Multiple Strain Risk Factors.

PubMed

Kay, Anthony David; Richmond, Dominic; Talbot, Chris; Mina, Minas; Baross, Anthony William; Blazevich, Anthony John

2016-07-01

The muscle stretch intensity imposed during "flexibility" training influences the magnitude of joint range of motion (ROM) adaptation. Thus, stretching while the muscle is voluntarily activated was hypothesized to provide a greater stimulus than passive stretching. The effect of a 6-wk program of stretch imposed on an isometrically contracting muscle (i.e., qualitatively similar to isokinetic eccentric training) on muscle-tendon mechanics was therefore studied in 13 healthy human volunteers. Before and after the training program, dorsiflexion ROM, passive joint moment, and maximal isometric plantarflexor moment were recorded on an isokinetic dynamometer. Simultaneous real-time motion analysis and ultrasound imaging recorded gastrocnemius medialis muscle and Achilles tendon elongation. Training was performed twice weekly and consisted of five sets of 12 maximal isokinetic eccentric contractions at 10°·s. Significant increases (P < 0.01) in ROM (92.7% [14.7°]), peak passive moment (i.e., stretch tolerance; 136.2%), area under the passive moment curve (i.e., energy storage; 302.6%), and maximal isometric plantarflexor moment (51.3%) were observed after training. Although no change in the slope of the passive moment curve (muscle-tendon stiffness) was detected (-1.5%, P > 0.05), a significant increase in tendon stiffness (31.2%, P < 0.01) and a decrease in passive muscle stiffness (-14.6%, P < 0.05) were observed. The substantial positive adaptation in multiple functional and physiological variables that are cited within the primary etiology of muscle strain injury, including strength, ROM, muscle stiffness, and maximal energy storage, indicate that the stretching of active muscle might influence injury risk in addition to muscle function. The lack of change in muscle-tendon stiffness simultaneous with significant increases in tendon stiffness and decreases in passive muscle stiffness indicates that tissue-specific effects were elicited.

Working memory load-dependent spatio-temporal activity of single-trial P3 response detected with an adaptive wavelet denoiser.

PubMed

Zhang, Qiushi; Yang, Xueqian; Yao, Li; Zhao, Xiaojie

2017-03-27

Working memory (WM) refers to the holding and manipulation of information during cognitive tasks. Its underlying neural mechanisms have been explored through both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Trial-by-trial coupling of simultaneously collected EEG and fMRI signals has become an important and promising approach to study the spatio-temporal dynamics of such cognitive processes. Previous studies have demonstrated a modulation effect of the WM load on both the BOLD response in certain brain areas and the amplitude of P3. However, much remains to be explored regarding the WM load-dependent relationship between the amplitude of ERP components and cortical activities, and the low signal-to-noise ratio (SNR) of the EEG signal still poses a challenge to performing single-trial analyses. In this paper, we investigated the spatio-temporal activities of P3 during an n-back verbal WM task by introducing an adaptive wavelet denoiser into the extraction of single-trial P3 features and using general linear model (GLM) to integrate simultaneously collected EEG and fMRI data. Our results replicated the modulation effect of the WM load on the P3 amplitude. Additionally, the activation of single-trial P3 amplitudes was detected in multiple brain regions, including the insula, the cuneus, the lingual gyrus (LG), and the middle occipital gyrus (MOG). Moreover, we found significant correlations between P3 features and behavioral performance. These findings suggest that the single-trial integration of simultaneous EEG and fMRI signals may provide new insights into classical cognitive functions. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

Semantic-based surveillance video retrieval.

PubMed

Hu, Weiming; Xie, Dan; Fu, Zhouyu; Zeng, Wenrong; Maybank, Steve

2007-04-01

Visual surveillance produces large amounts of video data. Effective indexing and retrieval from surveillance video databases are very important. Although there are many ways to represent the content of video clips in current video retrieval algorithms, there still exists a semantic gap between users and retrieval systems. Visual surveillance systems supply a platform for investigating semantic-based video retrieval. In this paper, a semantic-based video retrieval framework for visual surveillance is proposed. A cluster-based tracking algorithm is developed to acquire motion trajectories. The trajectories are then clustered hierarchically using the spatial and temporal information, to learn activity models. A hierarchical structure of semantic indexing and retrieval of object activities, where each individual activity automatically inherits all the semantic descriptions of the activity model to which it belongs, is proposed for accessing video clips and individual objects at the semantic level. The proposed retrieval framework supports various queries including queries by keywords, multiple object queries, and queries by sketch. For multiple object queries, succession and simultaneity restrictions, together with depth and breadth first orders, are considered. For sketch-based queries, a method for matching trajectories drawn by users to spatial trajectories is proposed. The effectiveness and efficiency of our framework are tested in a crowded traffic scene.

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.

Object Perception Impairments Predict Instrumental Activities of Daily Living Dependence in Alzheimer's Disease

PubMed Central

JEFFERSON, ANGELA L.; BARAKAT, LAMIA P.; GIOVANNETTI, TANIA; PAUL, ROBERT H.; GLOSSER, GUILA

2009-01-01

This study examined the contribution of object perception and spatial localization to functional dependence among Alzheimer's disease (AD) patients. Forty patients with probable AD completed measures assessing verbal recognition memory, working memory, object perception, spatial localization, semantic knowledge, and global cognition. Primary caregivers completed a measure of activities of daily living (ADLs) that included instrumental and basic self-care subscales (i.e., IADLs and BADLs, respectively). Stepwise multiple regressions revealed that global cognition accounted for significant portions of variance among the ADL total, IADL, and BADL scores. However, when global cognition was removed from the model, object perception was the only significant cognitive predictor of the ADL total and IADL subscale scores, accounting for 18.5% and 19.3% of the variance, respectively. When considering multiple cognitive components simultaneously, object perception and the integrity of the inferotemporal cortex is important in the completion of functional abilities in general and IADLs in particular among AD patients. PMID:16822730

Multimode drug inducible CRISPR/Cas9 devices for transcriptional activation and genome editing

PubMed Central

Lu, Jia; Zhao, Chen; Zhao, Yingze; Zhang, Jingfang; Zhang, Yue; Chen, Li; Han, Qiyuan; Ying, Yue; Peng, Shuai; Ai, Runna; Wang, Yu

2018-01-01

Abstract Precise investigation and manipulation of dynamic biological processes often requires molecular modulation in a controlled inducible manner. The clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) has emerged as a versatile tool for targeted gene editing and transcriptional programming. Here, we designed and vigorously optimized a series of Hybrid drug Inducible CRISPR/Cas9 Technologies (HIT) for transcriptional activation by grafting a mutated human estrogen receptor (ERT2) to multiple CRISPR/Cas9 systems, which renders them 4-hydroxytamoxifen (4-OHT) inducible for the access of genome. Further, extra functionality of simultaneous genome editing was achieved with one device we named HIT2. Optimized terminal devices herein delivered advantageous performances in comparison with several existing designs. They exerted selective, titratable, rapid and reversible response to drug induction. In addition, these designs were successfully adapted to an orthogonal Cas9. HIT systems developed in this study can be applied for controlled modulation of potentially any genomic loci in multiple modes. PMID:29237052

Different effects of religion and God on prosociality with the ingroup and outgroup.

PubMed

Preston, Jesse Lee; Ritter, Ryan S

2013-11-01

Recent studies have found that activating religious cognition by priming techniques can enhance prosocial behavior, arguably because religious concepts carry prosocial associations. But many of these studies have primed multiple concepts simultaneously related to the sacred. We argue here that religion and God are distinct concepts that activate distinct associations. In particular, we examine the effect of God and religion on prosociality toward the ingroup and outgroup. In three studies, we found that religion primes enhanced prosociality toward ingroup members, consistent with ingroup affiliation, whereas, God primes enhanced prosociality toward outgroup member, consistent with concerns of moral impression management. Implications for theory and methodology in religious cognition are discussed.

Development and Application of a Virtual Screening Protocol for the Identification of Multitarget Fragments.

PubMed

Bottegoni, Giovanni; Veronesi, Marina; Bisignano, Paola; Kacker, Puneet; Favia, Angelo D; Cavalli, Andrea

2016-06-20

In this study, we report on a virtual ligand screening protocol optimized to identify fragments endowed with activity at multiple targets. Thanks to this protocol, we were able to identify a fragment that displays activity in the low-micromolar range at both β-secretase 1 (BACE-1) and glycogen synthase kinase 3β (GSK-3β). These two structurally and physiologically unrelated enzymes likely contribute, through different pathways, to the onset of Alzheimer's disease (AD). Therefore, their simultaneous inhibition holds great potential in exerting a profound effect on AD. In perspective, the strategy outlined herein can be adapted to other target combinations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Neural feedback for instantaneous spatiotemporal modulation of afferent pathways in bi-directional brain-machine interfaces.

PubMed

Liu, Jianbo; Khalil, Hassan K; Oweiss, Karim G

2011-10-01

In bi-directional brain-machine interfaces (BMIs), precisely controlling the delivery of microstimulation, both in space and in time, is critical to continuously modulate the neural activity patterns that carry information about the state of the brain-actuated device to sensory areas in the brain. In this paper, we investigate the use of neural feedback to control the spatiotemporal firing patterns of neural ensembles in a model of the thalamocortical pathway. Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is achieved based on microstimulation of thalamic relay cells through multiple-input multiple-output (MIMO) feedback controllers. This closed loop feedback control mechanism is achieved by simultaneously varying the stimulation parameters across multiple stimulation electrodes in the thalamic circuit based on continuous monitoring of the difference between reference patterns and the evoked responses of the cortical PY cells. We demonstrate that it is feasible to achieve a desired level of performance by controlling the firing activity pattern of a few "key" neural elements in the network. Our results suggest that neural feedback could be an effective method to facilitate the delivery of information to the cortex to substitute lost sensory inputs in cortically controlled BMIs.

Cyclic phosphatidic acid treatment suppress cuprizone-induced demyelination and motor dysfunction in mice.

PubMed

Yamamoto, Shinji; Gotoh, Mari; Kawamura, Yuuki; Yamashina, Kota; Yagishita, Sosuke; Awaji, Takeo; Tanaka, Motomu; Maruyama, Kei; Murakami-Murofushi, Kimiko; Yoshikawa, Keisuke

2014-10-15

Multiple sclerosis is a chronic demyelinating disease of the central nervous system leading to progressive cognitive and motor dysfunction, which is characterized by neuroinflammation, demyelination, astrogliosis, loss of oligodendrocytes, and axonal pathologies. Cyclic phosphatidic acid (cPA) is a naturally occurring phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death. In this study, we investigated the effects of cPA on cuprizone-induced demyelination, which is a model of multiple sclerosis. Mice were fed a diet containing 0.2% cuprizone for 5 weeks, which induces severe demyelination, astrocyte and microglial activation, and motor dysfunction. Simultaneous administration of cPA effectively attenuated cuprizone-induced demyelination, glial activation, and motor dysfunction. These data indicate that cPA may be a useful treatment to reduce the extent of demyelination and the severity of motor dysfunction in multiple sclerosis. cPA is a potential lead compound in the development of drugs for the treatment of this devastating disease. Copyright © 2014 Elsevier B.V. All rights reserved.

The multiple-function multi-input/multi-output digital controller system for the AFW wind-tunnel model

NASA Technical Reports Server (NTRS)

Hoadley, Sherwood T.; Mcgraw, Sandra M.

1992-01-01

A real time multiple-function digital controller system was developed for the Active Flexible Wing (AFW) Program. The digital controller system (DCS) allowed simultaneous execution of two control laws: flutter suppression and either roll trim or a rolling maneuver load control. The DCS operated within, but independently of, a slower host operating system environment, at regulated speeds up to 200 Hz. It also coordinated the acquisition, storage, and transfer of data for near real time controller performance evaluation and both open- and closed-loop plant estimation. It synchronized the operation of four different processing units, allowing flexibility in the number, form, functionality, and order of control laws, and variability in the selection of the sensors and actuators employed. Most importantly, the DCS allowed for the successful demonstration of active flutter suppression to conditions approximately 26 percent (in dynamic pressure) above the open-loop boundary in cases when the model was fixed in roll and up to 23 percent when it was free to roll. Aggressive roll maneuvers with load control were achieved above the flutter boundary. The purpose here is to present the development, validation, and wind tunnel testing of this multiple-function digital controller system.

Retrospective forecasting of the 2010-2014 Melbourne influenza seasons using multiple surveillance systems.

PubMed

Moss, R; Zarebski, A; Dawson, P; McCAW, J M

2017-01-01

Accurate forecasting of seasonal influenza epidemics is of great concern to healthcare providers in temperate climates, since these epidemics vary substantially in their size, timing and duration from year to year, making it a challenge to deliver timely and proportionate responses. Previous studies have shown that Bayesian estimation techniques can accurately predict when an influenza epidemic will peak many weeks in advance, and we have previously tailored these methods for metropolitan Melbourne (Australia) and Google Flu Trends data. Here we extend these methods to clinical observation and laboratory-confirmation data for Melbourne, on the grounds that these data sources provide more accurate characterizations of influenza activity. We show that from each of these data sources we can accurately predict the timing of the epidemic peak 4-6 weeks in advance. We also show that making simultaneous use of multiple surveillance systems to improve forecast skill remains a fundamental challenge. Disparate systems provide complementary characterizations of disease activity, which may or may not be comparable, and it is unclear how a 'ground truth' for evaluating forecasts against these multiple characterizations might be defined. These findings are a significant step towards making optimal use of routine surveillance data for outbreak forecasting.

Single-sensor system for spatially resolved, continuous, and multiparametric optical mapping of cardiac tissue

PubMed Central

Lee, Peter; Bollensdorff, Christian; Quinn, T. Alexander; Wuskell, Joseph P.; Loew, Leslie M.; Kohl, Peter

2011-01-01

Background Simultaneous optical mapping of multiple electrophysiologically relevant parameters in living myocardium is desirable for integrative exploration of mechanisms underlying heart rhythm generation under normal and pathophysiologic conditions. Current multiparametric methods are technically challenging, usually involving multiple sensors and moving parts, which contributes to high logistic and economic thresholds that prevent easy application of the technique. Objective The purpose of this study was to develop a simple, affordable, and effective method for spatially resolved, continuous, simultaneous, and multiparametric optical mapping of the heart, using a single camera. Methods We present a new method to simultaneously monitor multiple parameters using inexpensive off-the-shelf electronic components and no moving parts. The system comprises a single camera, commercially available optical filters, and light-emitting diodes (LEDs), integrated via microcontroller-based electronics for frame-accurate illumination of the tissue. For proof of principle, we illustrate measurement of four parameters, suitable for ratiometric mapping of membrane potential (di-4-ANBDQPQ) and intracellular free calcium (fura-2), in an isolated Langendorff-perfused rat heart during sinus rhythm and ectopy, induced by local electrical or mechanical stimulation. Results The pilot application demonstrates suitability of this imaging approach for heart rhythm research in the isolated heart. In addition, locally induced excitation, whether stimulated electrically or mechanically, gives rise to similar ventricular propagation patterns. Conclusion Combining an affordable camera with suitable optical filters and microprocessor-controlled LEDs, single-sensor multiparametric optical mapping can be practically implemented in a simple yet powerful configuration and applied to heart rhythm research. The moderate system complexity and component cost is destined to lower the threshold to broader application of functional imaging and to ease implementation of more complex optical mapping approaches, such as multiparametric panoramic imaging. A proof-of-principle application confirmed that although electrically and mechanically induced excitation occur by different mechanisms, their electrophysiologic consequences downstream from the point of activation are not dissimilar. PMID:21459161

PET Imaging Stability Measurements During Simultaneous Pulsing of Aggressive MR Sequences on the SIGNA PET/MR System.

PubMed

Deller, Timothy W; Khalighi, Mohammad Mehdi; Jansen, Floris P; Glover, Gary H

2018-01-01

The recent introduction of simultaneous whole-body PET/MR scanners has enabled new research taking advantage of the complementary information obtainable with PET and MRI. One such application is kinetic modeling, which requires high levels of PET quantitative stability. To accomplish the required PET stability levels, the PET subsystem must be sufficiently isolated from the effects of MR activity. Performance measurements have previously been published, demonstrating sufficient PET stability in the presence of MR pulsing for typical clinical use; however, PET stability during radiofrequency (RF)-intensive and gradient-intensive sequences has not previously been evaluated for a clinical whole-body scanner. In this work, PET stability of the GE SIGNA PET/MR was examined during simultaneous scanning of aggressive MR pulse sequences. Methods: PET performance tests were acquired with MR idle and during simultaneous MR pulsing. Recent system improvements mitigating RF interference and gain variation were used. A fast recovery fast spin echo MR sequence was selected for high RF power, and an echo planar imaging sequence was selected for its high heat-inducing gradients. Measurements were performed to determine PET stability under varying MR conditions using the following metrics: sensitivity, scatter fraction, contrast recovery, uniformity, count rate performance, and image quantitation. A final PET quantitative stability assessment for simultaneous PET scanning during functional MRI studies was performed with a spiral in-and-out gradient echo sequence. Results: Quantitation stability of a 68 Ge flood phantom was demonstrated within 0.34%. Normalized sensitivity was stable during simultaneous scanning within 0.3%. Scatter fraction measured with a 68 Ge line source in the scatter phantom was stable within the range of 40.4%-40.6%. Contrast recovery and uniformity were comparable for PET images acquired simultaneously with multiple MR conditions. Peak noise equivalent count rate was 224 kcps at an effective activity concentration of 18.6 kBq/mL, and the count rate curves and scatter fraction curve were consistent for the alternating MR pulsing states. A final test demonstrated quantitative stability during a spiral functional MRI sequence. Conclusion: PET stability metrics demonstrated that PET quantitation was not affected during simultaneous aggressive MRI. This stability enables demanding applications such as kinetic modeling. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Simultaneous and quasi-independent strain and temperature sensor based on microstructured optical fiber

NASA Astrophysics Data System (ADS)

Lopez-Aldaba, A.; Auguste, J.-L.; Jamier, R.; Roy, P.; Lopez-Amo, M.

2017-04-01

In this paper, a new sensor system for simultaneous and quasi-independent strain and temperature measurements is presented. The interrogation of the sensing head has been carried out by monitoring the FFT phase variations of two of the microstructured optical fiber (MOF) cavity interference frequencies. This method is independent of the signal amplitude and also avoids the need to track the wavelength evolution in the spectrum, which can be a handicap when there are multiple interference frequency components with different sensitivities. The sensor is operated within a range of temperature of 30°C-75°C, and 380μɛ of maximum strain were applied; being the sensitivities achieved of 127.5pm/°C and -19.1pm/μɛ respectively. Because the system uses an optical interrogator as unique active element, the system presents a cost-effective feature.

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.

A sensitive and rapid ultra HPLC-MS/MS method for the simultaneous detection of clopidogrel and its derivatized active thiol metabolite in human plasma.

PubMed

Peer, Cody J; Spencer, Shawn D; VanDenBerg, Dustin A H; Pacanowski, Michael A; Horenstein, Richard B; Figg, William D

2012-01-01

A sensitive, selective, and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (uHPLC-MS/MS) was developed for the simultaneous quantification of clopidogrel (Plavix(®)) and its derivatized active metabolite (CAMD) in human plasma. Derivatization of the active metabolite in blood with 2-bromo-3'-methoxy acetophenone (MPB) immediately after collection ensured metabolite stability during sample handling and storage. Following addition of ticlopidine as an internal standard and simple protein precipitation, the analytes were separated on a Waters Acquity UPLC™ sub-2 μm-C(18) column via gradient elution before detection on a triple-quadrupole MS with multiple-reaction-monitoring via electrospray ionization. The method was validated across the clinically relevant concentration range of 0.01-50 ng/mL for parent clopidogrel and 0.1-150 ng/mL (r(2)=0.99) for CAMD, with a fast run time of 1.5 min to support pharmacokinetic studies using 75, 150, or 300 mg oral doses of clopidogrel. The analytical method measured concentrations of clopidogrel and CAMD with accuracy (%DEV) <±12% and precision (%CV) of <±6%. The method was successfully applied to measure the plasma concentrations of clopidogrel and CAMD in three subjects administered single oral doses of 75, 150, and 300 mg clopidogrel. It was further demonstrated that the derivatizing agent (MPB) does not affect clopidogrel levels, thus from one aliquot of blood drawn clinically, this method can simultaneously quantify both clopidogrel and CAMD with sensitivity in the picogram per mL range. Published by Elsevier B.V.

A Sensitive and Rapid Ultra HPLC-MS/MS Method for the Simultaneous Detection of Clopidogrel and its Derivatized Active Thiol Metabolite in Human Plasma

PubMed Central

Peer, Cody J.; Spencer, Shawn D.; VanDenBerg, Dustin A. H.; Pacanowski, Michael A.; Horenstein, Richard B.; Figg, William D.

2011-01-01

A sensitive, selective, and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (uHPLC-MS/MS) was developed for the simultaneous quantification of clopidogrel (Plavix®) and its derivatized active metabolite (CAMD) in human plasma. Derivatization of the active metabolite in blood with 2-bromo-3’-methoxy acetophenone (MPB) immediately after collection ensured metabolite stability during sample handling and storage. Following addition of ticlopidine as an internal standard and simple protein precipitation, the analytes were separated on a Waters Acquity UPLC™ sub-2µm-C18 column via gradient elution before detection on a triple-quadrupole MS with multiple-reaction-monitoring via electrospray ionization. The method was validated across the clinically-relevant concentration range of 0.01–50 ng/mL for parent clopidogrel and 0.1–150 ng/mL (r2= 0.99) for CAMD, with a fast run time of 1.5 min to support pharmacokinetic studies using 75, 150, or 300 mg oral doses of clopidogrel. The analytical method measured concentrations of clopidogrel and CAMD with accuracy (%DEV) < ±12% and precision (%CV) of < ±6%. The method was successfully applied to measure the plasma concentrations of clopidogrel and CAMD in three subjects administered single oral doses of 75, 150, and 300 mg clopidogrel. It was further demonstrated that the derivatizing agent (MPB) does not affect clopidogrel levels, thus from one aliquot of blood drawn clinically, this method can simultaneously quantify both clopidogrel and CAMD with sensitivity in the picogram per mL range. PMID:22169056

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.

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.

A Novel System for Simultaneous or Sequential Integration of Multiple Gene-Loading Vectors into a Defined Site of a Human Artificial Chromosome

PubMed Central

Suzuki, Teruhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo; Hara, Takahiko

2014-01-01

Human artificial chromosomes (HACs) are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV) into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system) via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming. PMID:25303219

A novel system for simultaneous or sequential integration of multiple gene-loading vectors into a defined site of a human artificial chromosome.

PubMed

Suzuki, Teruhiko; Kazuki, Yasuhiro; Oshimura, Mitsuo; Hara, Takahiko

2014-01-01

Human artificial chromosomes (HACs) are gene-delivery vectors suitable for introducing large DNA fragments into mammalian cells. Although a HAC theoretically incorporates multiple gene expression cassettes of unlimited DNA size, its application has been limited because the conventional gene-loading system accepts only one gene-loading vector (GLV) into a HAC. We report a novel method for the simultaneous or sequential integration of multiple GLVs into a HAC vector (designated as the SIM system) via combined usage of Cre, FLP, Bxb1, and φC31 recombinase/integrase. As a proof of principle, we first attempted simultaneous integration of three GLVs encoding EGFP, Venus, and TdTomato into a gene-loading site of a HAC in CHO cells. These cells successfully expressed all three fluorescent proteins. Furthermore, microcell-mediated transfer of HACs enabled the expression of those fluorescent proteins in recipient cells. We next demonstrated that GLVs could be introduced into a HAC one-by-one via reciprocal usage of recombinase/integrase. Lastly, we introduced a fourth GLV into a HAC after simultaneous integration of three GLVs by FLP-mediated DNA recombination. The SIM system expands the applicability of HAC vectors and is useful for various biomedical studies, including cell reprogramming.

Multiple behavior changes in diet and activity: a randomized controlled trial using mobile technology.

PubMed

Spring, Bonnie; Schneider, Kristin; McFadden, H Gene; Vaughn, Jocelyn; Kozak, Andrea T; Smith, Malaina; Moller, Arlen C; Epstein, Leonard H; Demott, Andrew; Hedeker, Donald; Siddique, Juned; Lloyd-Jones, Donald M

2012-05-28

Many patients exhibit multiple chronic disease risk behaviors. Research provides little information about advice that can maximize simultaneous health behavior changes. To test which combination of diet and activity advice maximizes healthy change, we randomized 204 adults with elevated saturated fat and low fruit and vegetable intake, high sedentary leisure time, and low physical activity to 1 of 4 treatments: increase fruit/vegetable intake and physical activity, decrease fat and sedentary leisure, decrease fat and increase physical activity, and increase fruit/vegetable intake and decrease sedentary leisure. Treatments provided 3 weeks of remote coaching supported by mobile decision support technology and financial incentives. During treatment, incentives were contingent on using the mobile device to self-monitor and attain behavioral targets; during follow-up, incentives were contingent only on recording. The outcome was standardized, composite improvement on the 4 diet and activity behaviors at the end of treatment and at 5-month follow-up. Of the 204 individuals randomized, 200 (98.0%) completed follow-up. The increase fruits/vegetables and decrease sedentary leisure treatments improved more than the other 3 treatments (P < .001). Specifically, daily fruit/vegetable intake increased from 1.2 servings to 5.5 servings, sedentary leisure decreased from 219.2 minutes to 89.3 minutes, and saturated fat decreased from 12.0% to 9.5% of calories consumed. Differences between treatment groups were maintained through follow-up. Traditional dieting (decrease fat and increase physical activity) improved less than the other 3 treatments (P < .001). Remote coaching supported by mobile technology and financial incentives holds promise to improve diet and activity. Targeting fruits/vegetables and sedentary leisure together maximizes overall adoption and maintenance of multiple healthy behavior changes.

Multiple Behavior Change in Diet and Activity: A Randomized Controlled Trial Using Mobile Technology

PubMed Central

Spring, Bonnie; Schneider, Kristin; McFadden, H.G.; Vaughn, Jocelyn; Kozak, Andrea T.; Smith, Malaina; Moller, Arlen C.; Epstein, Leonard H.; DeMott, Andrew; Hedeker, Donald; Siddique, Juned; Lloyd-Jones, Donald M.

2012-01-01

Background Many patients exhibit multiple chronic disease risk behaviors. Research provides little information about advice that can maximize simultaneous health behavior changes. Methods To test which combination of diet and activity advice maximizes healthy change, we randomized 204 adults with elevated saturated fat and low fruit/vegetable intakes, high sedentary leisure time and low physical activity to one of four treatments: increase fruit/vegetable and physical activity; decrease fat and sedentary leisure; decrease fat and increase physical activity; increase fruit/vegetable and decrease sedentary leisure. Treatments provided three weeks of remote coaching supported by mobile decision support technology and financial incentives. During treatment, incentives were contingent on using the mobile device to self-monitor and attain behavioral targets; during follow-up they were contingent only on recording. The outcome was standardized, composite improvement on the four diet and activity behaviors at end of treatment and five month follow-up. Results Of those randomized, 200 (98%) completed follow-up. The increase fruit/vegetable and decrease sedentary leisure treatment improved more than the other 3 treatments (p<.001). Specifically, fruit/vegetables increased from 1.2 servings/day to 5.5; sedentary leisure decreased from 219.2 minutes/day to 89.3; saturated fat decreased from 12.0% of calories consumed to 9.5%. Differences between treatment groups were maintained through follow-up. Traditional dieting (decrease fat and increase physical activity) improved less than the other 3 treatments (p<.001). Conclusions Remote coaching supported by mobile technology and financial incentives holds promise to improve diet and activity. Targeting fruits/vegetables and sedentary leisure together maximizes overall adoption and maintenance of multiple healthy behavior changes. PMID:22636824

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

Multiple Ships and Multiple Media: A Flexible Telepresence Program

NASA Astrophysics Data System (ADS)

Pelz, M.; Hoeberechts, M.; Riddell, D. J.; Ewing, N.

2016-02-01

Ocean Networks Canada (ONC) uses a number of research and exploration vessels equipped with remotely operated vehicles (ROVs) to maintain the NEPTUNE and VENUS cabled ocean observatories off the west coast of British Columbia, Canada. Maintenance expeditions range from several days to multiple weeks and encompass a range of activities including deploying new instruments, laying cable, recovering platforms, scientific sampling and conducting multibeam and visual surveys. In order to engage the widest possible participation in at-sea work, ONC uses telepresence technology to communicate from ship to shore and back with scientists, students, teachers and online viewers. In this presentation, we explore the challenge of designing a sustainable and flexible telepresence program which can be supported across multiple ship and ROV platforms, sometimes simultaneously. To meet outreach and education objectives, onboard educators conduct presentations to K-12 and post-secondary classrooms, museums and science centres on a daily basis. Online commentary by the educators, dive chief and ROV pilots accompanies the ROV dive footage and is streamed online 24/7 during underwater operations. Sharing the sights and sounds of the expeditions with students and educators ashore, including those in remote and inland communities, creates a unique learning environment for both formal and informal education audiences. As space is always a limiting factor on expeditions, the use of telepresence and other communication media enables ONC to simultaneously achieve engineering and science priorities at sea while communicating the successes and challenges of the expedition back to shore. Scientists and engineers provide guidance for operations from shore using a variety of communication technologies. We give examples from Ocean Networks Canada's most recent expedition, Fall 2015, which involved co-ordinated operations with three vessels - the R/V Thompson, the E/V Nautilus and the C/S Wave Venture.

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

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…

Chemical inhibition of a subset of Arabidopsis thaliana GSK3-like kinases activates brassinosteroid signaling.

PubMed

De Rybel, Bert; Audenaert, Dominique; Vert, Grégory; Rozhon, Wilfried; Mayerhofer, Juliane; Peelman, Frank; Coutuer, Silvie; Denayer, Tinneke; Jansen, Leentje; Nguyen, Long; Vanhoutte, Isabelle; Beemster, Gerrit T S; Vleminckx, Kris; Jonak, Claudia; Chory, Joanne; Inzé, Dirk; Russinova, Eugenia; Beeckman, Tom

2009-06-26

Glycogen synthase kinase 3 (GSK3) is a key regulator in signaling pathways in both animals and plants. Three Arabidopsis thaliana GSK3s are shown to be related to brassinosteroid (BR) signaling. In a phenotype-based compound screen we identified bikinin, a small molecule that activates BR signaling downstream of the BR receptor. Bikinin directly binds the GSK3 BIN2 and acts as an ATP competitor. Furthermore, bikinin inhibits the activity of six other Arabidopsis GSK3s. Genome-wide transcript analyses demonstrate that simultaneous inhibition of seven GSK3s is sufficient to activate BR responses. Our data suggest that GSK3 inhibition is the sole activation mode of BR signaling and argues against GSK3-independent BR responses in Arabidopsis. The opportunity to generate multiple and conditional knockouts in key regulators in the BR signaling pathway by bikinin represents a useful tool to further unravel regulatory mechanisms.

Compact, Energy-Efficient High-Frequency Switched Capacitor Neural Stimulator With Active Charge Balancing.

PubMed

Hsu, Wen-Yang; Schmid, Alexandre

2017-08-01

Safety and energy efficiency are two major concerns for implantable neural stimulators. This paper presents a novel high-frequency, switched capacitor (HFSC) stimulation and active charge balancing scheme, which achieves high energy efficiency and well-controlled stimulation charge in the presence of large electrode impedance variations. Furthermore, the HFSC can be implemented in a compact size without any external component to simultaneously enable multichannel stimulation by deploying multiple stimulators. The theoretical analysis shows significant benefits over the constant-current and voltage-mode stimulation methods. The proposed solution was fabricated using a 0.18 μm high-voltage technology, and occupies only 0.035 mm 2 for a single stimulator. The measurement result shows 50% peak energy efficiency and confirms the effectiveness of active charge balancing to prevent the electrode dissolution.

Synchronous activity in cat visual cortex encodes collinear and cocircular contours.

PubMed

Samonds, Jason M; Zhou, Zhiyi; Bernard, Melanie R; Bonds, A B

2006-04-01

We explored how contour information in primary visual cortex might be embedded in the simultaneous activity of multiple cells recorded with a 100-electrode array. Synchronous activity in cat visual cortex was more selective and predictable in discriminating between drifting grating and concentric ring stimuli than changes in firing rate. Synchrony was found even between cells with wholly different orientation preferences when their receptive fields were circularly aligned, and membership in synchronous groups was orientation and curvature dependent. The existence of synchrony between cocircular cells reinforces its role as a general mechanism for contour integration and shape detection as predicted by association field concepts. Our data suggest that cortical synchrony results from common and synchronous input from earlier visual areas and that it could serve to shape extrastriate response selectivity.

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 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.

Multi-isotope SPECT imaging of the 225Ac decay chain: feasibility studies

NASA Astrophysics Data System (ADS)

Robertson, A. K. H.; Ramogida, C. F.; Rodríguez-Rodríguez, C.; Blinder, Stephan; Kunz, Peter; Sossi, Vesna; Schaffer, Paul

2017-06-01

Effective use of the {}225Ac decay chain in targeted internal radioimmunotherapy requires the retention of both {}225Ac and progeny isotopes at the target site. Imaging-based pharmacokinetic tests of these pharmaceuticals must therefore separately yet simultaneously image multiple isotopes that may not be colocalized despite being part of the same decay chain. This work presents feasibility studies demonstrating the ability of a microSPECT/CT scanner equipped with a high energy collimator to simultaneously image two components of the {}225Ac decay chain: {}221Fr (218 keV) and {}213Bi (440 keV). Image quality phantoms were used to assess the performance of two collimators for simultaneous {}221Fr and {}213Bi imaging in terms of contrast and noise. A hotrod resolution phantom containing clusters of thin rods with diameters ranging between 0.85 and 1.70 mm was used to assess resolution. To demonstrate ability to simultaneously image dynamic {}221Fr and {}213Bi activity distributions, a phantom containing a {}213Bi generator from {}225Ac was imaged. These tests were performed with two collimators, a high-energy ultra-high resolution (HEUHR) collimator and an ultra-high sensitivity (UHS) collimator. Values consistent with activity concentrations determined independently via gamma spectroscopy were observed in high activity regions of the images. In hotrod phantom images, the HEUHR collimator resolved all rods for both {}221Fr and {}213Bi images. With the UHS collimator, no rods were resolvable in {}213Bi images and only rods  ⩾1.3 mm were resolved in {}221Fr images. After eluting the {}213Bi generator, images accurately visualized the reestablishment of transient equilibrium of the {}225Ac decay chain. The feasibility of evaluating the pharmacokinetics of the {}225Ac decay chain in vivo has been demonstrated. This presented method requires the use of a high-performance high-energy collimator.

A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets

PubMed Central

Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

2014-01-01

Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways. PMID:25475013

A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets.

PubMed

Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

2014-12-05

Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways.

The validity of activity monitors for measuring sleep in elite athletes.

PubMed

Sargent, Charli; Lastella, Michele; Halson, Shona L; Roach, Gregory D

2016-10-01

There is a growing interest in monitoring the sleep of elite athletes. Polysomnography is considered the gold standard for measuring sleep, however this technique is impractical if the aim is to collect data simultaneously with multiple athletes over consecutive nights. Activity monitors may be a suitable alternative for monitoring sleep, but these devices have not been validated against polysomnography in a population of elite athletes. Participants (n=16) were endurance-trained cyclists participating in a 6-week training camp. A total of 122 nights of sleep were recorded with polysomnography and activity monitors simultaneously. Agreement, sensitivity, and specificity were calculated from epoch-for-epoch comparisons of polysomnography and activity monitor data. Sleep variables derived from polysomnography and activity monitors were compared using paired t-tests. Activity monitor data were analysed using low, medium, and high sleep-wake thresholds. Epoch-for-epoch comparisons showed good agreement between activity monitors and polysomnography for each sleep-wake threshold (81-90%). Activity monitors were sensitive to sleep (81-92%), but specificity differed depending on the threshold applied (67-82%). Activity monitors underestimated sleep duration (18-90min) and overestimated wake duration (4-77min) depending on the threshold applied. Applying the correct sleep-wake threshold is important when using activity monitors to measure the sleep of elite athletes. For example, the default sleep-wake threshold (>40 activity counts=wake) underestimates sleep duration by ∼50min and overestimates wake duration by ∼40min. In contrast, sleep-wake thresholds that have a high sensitivity to sleep (>80 activity counts=wake) yield the best combination of agreement, sensitivity, and specificity. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Cognitive context determines dorsal premotor cortical activity during hand movement in patients after stroke.

PubMed

Dennis, Andrea; Bosnell, Rose; Dawes, Helen; Howells, Ken; Cockburn, Janet; Kischka, Udo; Matthews, Paul; Johansen-Berg, Heidi

2011-04-01

Stroke patients often have difficulties in simultaneously performing a motor and cognitive task. Functional imaging studies have shown that movement of an affected hand after stroke is associated with increased activity in multiple cortical areas, particularly in the contralesional hemisphere. We hypothesized patients for whom executing simple movements demands greater selective attention will show greater brain activity during movement. Eight chronic stroke patients performed a behavioral interference test using a visuo-motor tracking with and without a simultaneous cognitive task. The magnitude of behavioral task decrement under cognitive motor interference (CMI) conditions was calculated for each subject. Functional MRI was used to assess brain activity in the same patients during performance of a visuo-motor tracking task alone; correlations between CMI score and movement-related brain activation were then explored. Movement-related activation in the dorsal precentral gyrus of the contralesional hemisphere correlated strongly and positively with CMI score (r(2) at peak voxel=0.92; P<0.05). Similar but weaker relationships were observed in the ventral precentral and middle frontal gyrus. There was no independent relationship between hand motor impairment and CMI. Results suggest that variations in the degree to which a cognitive task interferes with performance of a concurrent motor task explains a substantial proportion of the variations in movement-related brain activity in patients after stroke. The results emphasize the importance of considering cognitive context when interpreting brain activity patterns and provide a rationale for further evaluation of integrated cognitive and movement interventions for rehabilitation in stroke.

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...

In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters.

PubMed

Hama, Kotaro; Provost, Elayne; Baranowski, Timothy C; Rubinstein, Amy L; Anderson, Jennifer L; Leach, Steven D; Farber, Steven A

2009-02-01

Optical clarity of larvae makes the zebrafish ideal for real-time analyses of vertebrate organ function through the use of fluorescent reporters of enzymatic activities. A key function of digestive organs is to couple the generation of enzymes with mechanical processes that enable nutrient availability and absorption. However, it has been extremely difficult, and in many cases not possible, to directly observe digestive processes in a live vertebrate. Here we describe a new method to visualize intestinal protein and lipid processing simultaneously in live zebrafish larvae using a quenched fluorescent protein (EnzChek) and phospholipid (PED6). By employing these reagents, we found that wild-type larvae exhibit significant variation in intestinal phospholipase and protease activities within a group but display a strong correlation between the activities within individuals. Furthermore, we found that pancreas function is essential for larval digestive protease activity but not for larval intestinal phospholipase activity. Although fat-free (ffr) mutant larvae were previously described to exhibit impaired lipid processes, we found they also had significantly reduced protease activity. Finally, we selected and evaluated compounds that were previously suggested to have altered phospholipase activity and are known or suspected to have inflammatory effects in the intestinal tract including nonsteroidal anti-inflammatory drugs, and identified a compound that significantly increases intestinal phospholipid processing. Thus the multiple fluorescent reporter-based methodology facilitates the rapid analysis of digestive organ function in live zebrafish larvae.

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.

Preparation of a dual-enzyme co-immobilized capillary microreactor and simultaneous screening of multiple enzyme inhibitors by capillary electrophoresis.

PubMed

Lin, Pingtan; Zhao, Shulin; Lu, Xin; Ye, Fanggui; Wang, Hengshan

2013-08-01

A CE method based on a dual-enzyme co-immobilized capillary microreactor was developed for the simultaneous screening of multiple enzyme inhibitors. The capillary microreactor was prepared by co-immobilizing adenosine deaminase and xanthine oxidase on the inner wall at the inlet end of the separation capillary. The enzymes were first immobilized on gold nanoparticles, and the functionalized gold nanoparticles were then assembled on the inner wall at the inlet end of the separation capillary treated with polyethyleneimine. With the developed CE method, the substrates and products were baseline separated within 3 min. The activity of the immobilized enzyme can be directly detected by measuring the peak height of the products. A statistical parameter Z' factor was recommended for evaluation of the accuracy of a drug screening system. In the present study, it was calculated to be larger than 0.5, implying a good accuracy. Finally, screening a small compound library containing two known enzyme inhibitors and 20 natural extracts by the proposed method was demonstrated. The known inhibitors were identified, and some natural extracts were found to be positive for two-enzyme inhibition by the present method. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A generic minimization random allocation and blinding system on web.

PubMed

Cai, Hongwei; Xia, Jielai; Xu, Dezhong; Gao, Donghuai; Yan, Yongping

2006-12-01

Minimization is a dynamic randomization method for clinical trials. Although recommended by many researchers, the utilization of minimization has been seldom reported in randomized trials mainly because of the controversy surrounding the validity of conventional analyses and its complexity in implementation. However, both the statistical and clinical validity of minimization were demonstrated in recent studies. Minimization random allocation system integrated with blinding function that could facilitate the implementation of this method in general clinical trials has not been reported. SYSTEM OVERVIEW: The system is a web-based random allocation system using Pocock and Simon minimization method. It also supports multiple treatment arms within a trial, multiple simultaneous trials, and blinding without further programming. This system was constructed with generic database schema design method, Pocock and Simon minimization method and blinding method. It was coded with Microsoft Visual Basic and Active Server Pages (ASP) programming languages. And all dataset were managed with a Microsoft SQL Server database. Some critical programming codes were also provided. SIMULATIONS AND RESULTS: Two clinical trials were simulated simultaneously to test the system's applicability. Not only balanced groups but also blinded allocation results were achieved in both trials. Practical considerations for minimization method, the benefits, general applicability and drawbacks of the technique implemented in this system are discussed. Promising features of the proposed system are also summarized.

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits

PubMed Central

Cox, Daniel T. C.; Shanahan, Danielle F.; Hudson, Hannah L.; Fuller, Richard A.; Anderson, Karen; Hancock, Steven; Gaston, Kevin J.

2017-01-01

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare. PMID:28208789

Doses of Nearby Nature Simultaneously Associated with Multiple Health Benefits.

PubMed

Cox, Daniel T C; Shanahan, Danielle F; Hudson, Hannah L; Fuller, Richard A; Anderson, Karen; Hancock, Steven; Gaston, Kevin J

2017-02-09

Exposure to nature provides a wide range of health benefits. A significant proportion of these are delivered close to home, because this offers an immediate and easily accessible opportunity for people to experience nature. However, there is limited information to guide recommendations on its management and appropriate use. We apply a nature dose-response framework to quantify the simultaneous association between exposure to nearby nature and multiple health benefits. We surveyed ca. 1000 respondents in Southern England, UK, to determine relationships between (a) nature dose type, that is the frequency and duration (time spent in private green space) and intensity (quantity of neighbourhood vegetation cover) of nature exposure and (b) health outcomes, including mental, physical and social health, physical behaviour and nature orientation. We then modelled dose-response relationships between dose type and self-reported depression. We demonstrate positive relationships between nature dose and mental and social health, increased physical activity and nature orientation. Dose-response analysis showed that lower levels of depression were associated with minimum thresholds of weekly nature dose. Nearby nature is associated with quantifiable health benefits, with potential for lowering the human and financial costs of ill health. Dose-response analysis has the potential to guide minimum and optimum recommendations on the management and use of nearby nature for preventative healthcare.

Selective attention to temporal features on nested time scales.

PubMed

Henry, Molly J; Herrmann, Björn; Obleser, Jonas

2015-02-01

Meaningful auditory stimuli such as speech and music often vary simultaneously along multiple time scales. Thus, listeners must selectively attend to, and selectively ignore, separate but intertwined temporal features. The current study aimed to identify and characterize the neural network specifically involved in this feature-selective attention to time. We used a novel paradigm where listeners judged either the duration or modulation rate of auditory stimuli, and in which the stimulation, working memory demands, response requirements, and task difficulty were held constant. A first analysis identified all brain regions where individual brain activation patterns were correlated with individual behavioral performance patterns, which thus supported temporal judgments generically. A second analysis then isolated those brain regions that specifically regulated selective attention to temporal features: Neural responses in a bilateral fronto-parietal network including insular cortex and basal ganglia decreased with degree of change of the attended temporal feature. Critically, response patterns in these regions were inverted when the task required selectively ignoring this feature. The results demonstrate how the neural analysis of complex acoustic stimuli with multiple temporal features depends on a fronto-parietal network that simultaneously regulates the selective gain for attended and ignored temporal features. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Adaption of Ulva pertusa to multiple-contamination of heavy metals and nutrients: Biological mechanism of outbreak of Ulva sp. green tide.

PubMed

Ge, Changzi; Yu, Xiru; Kan, Manman; Qu, Chunfeng

2017-12-15

The multiple-contamination of heavy metals and nutrients worsens increasingly and Ulva sp. green tide occurs almost simultaneously. To reveal the biological mechanism for outbreak of the green tide, Ulva pertusa was exposed to seven-day-multiple-contamination. The relation between pH variation (V pH ), Chl a content, ratio of (Chl a content)/(Chl b content) (R chla/chlb ), SOD activity of U. pertusa (A SOD ) and contamination concentration is [Formula: see text] (p<0.05), C chla =0.88 ±0.09 -0.01 ±0.00 ×C Cd (p<0.05), [Formula: see text] (p<0.05), and [Formula: see text] (p<0.05), respectively. C ammonia , C Cd and C Zn is concentration of ammonia, Cd 2+ and Zn 2+ , respectively. Comparing the contamination concentrations of seawaters where Ulva sp. green tide occurred and the contamination concentrations set in the present work, U. pertusa can adapt to multiple-contaminations in these waters. Thus, the adaption to multiple-contamination may be one biological mechanism for the outbreak of Ulva sp. green tide. Copyright © 2017 Elsevier Ltd. 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.

Identification of hydrophobic amino acids required for lipid activation of C. elegans CTP:phosphocholine cytidylyltransferase.

PubMed

Braker, Jay D; Hodel, Kevin J; Mullins, David R; Friesen, Jon A

2009-12-01

CTP:phosphocholine cytidylyltransferase (CCT), critical for phosphatidylcholine biosynthesis, is activated by translocation to the membrane surface. The lipid activation region of Caenorhabditis elegans CCT is between residues 246 and 266 of the 347 amino acid polypeptide, a region proposed to form an amphipathic alpha helix. When leucine 246, tryptophan 249, isoleucine 256, isoleucine 257, or phenylalanine 260, on the hydrophobic face of the helix, were changed individually to serine low activity was observed in the absence of lipid vesicles, similar to wild-type CCT, while lipid stimulated activity was reduced compared to wild-type CCT. Mutational analysis of phenylalanine 260 implicated this residue as a contributor to auto-inhibition of CCT while mutation of L246, W249, I256, and I257 simultaneously to serine resulted in significantly higher activity in the absence of lipid vesicles and an enzyme that was not lipid activated. These results support a concerted mechanism of lipid activation that requires multiple residues on the hydrophobic face of the putative amphipathic alpha helix.

Multiscale decoding for reliable brain-machine interface performance over time.

PubMed

Han-Lin Hsieh; Wong, Yan T; Pesaran, Bijan; Shanechi, Maryam M

2017-07-01

Recordings from invasive implants can degrade over time, resulting in a loss of spiking activity for some electrodes. For brain-machine interfaces (BMI), such a signal degradation lowers control performance. Achieving reliable performance over time is critical for BMI clinical viability. One approach to improve BMI longevity is to simultaneously use spikes and other recording modalities such as local field potentials (LFP), which are more robust to signal degradation over time. We have developed a multiscale decoder that can simultaneously model the different statistical profiles of multi-scale spike/LFP activity (discrete spikes vs. continuous LFP). This decoder can also run at multiple time-scales (millisecond for spikes vs. tens of milliseconds for LFP). Here, we validate the multiscale decoder for estimating the movement of 7 major upper-arm joint angles in a non-human primate (NHP) during a 3D reach-to-grasp task. The multiscale decoder uses motor cortical spike/LFP recordings as its input. We show that the multiscale decoder can improve decoding accuracy by adding information from LFP to spikes, while running at the fast millisecond time-scale of the spiking activity. Moreover, this improvement is achieved using relatively few LFP channels, demonstrating the robustness of the approach. These results suggest that using multiscale decoders has the potential to improve the reliability and longevity of BMIs.

Multiple foci of spatial attention in multimodal working memory.

PubMed

Katus, Tobias; Eimer, Martin

2016-11-15

The maintenance of sensory information in working memory (WM) is mediated by the attentional activation of stimulus representations that are stored in perceptual brain regions. Using event-related potentials (ERPs), we measured tactile and visual contralateral delay activity (tCDA/CDA components) in a bimodal WM task to concurrently track the attention-based maintenance of information stored in anatomically segregated (somatosensory and visual) brain areas. Participants received tactile and visual sample stimuli on both sides, and in different blocks, memorized these samples on the same side or on opposite sides. After a retention delay, memory was unpredictably tested for touch or vision. In the same side blocks, tCDA and CDA components simultaneously emerged over the same hemisphere, contralateral to the memorized tactile/visual sample set. In opposite side blocks, these two components emerged over different hemispheres, but had the same sizes and onset latencies as in the same side condition. Our results reveal distinct foci of tactile and visual spatial attention that were concurrently maintained on task-relevant stimulus representations in WM. The independence of spatially-specific biasing mechanisms for tactile and visual WM content suggests that multimodal information is stored in distributed perceptual brain areas that are activated through modality-specific processes that can operate simultaneously and largely independently of each other. Copyright © 2016 Elsevier Inc. All rights reserved.

Fast-pulverization enabled simultaneous enhancement on cycling stability and rate capability of C@NiFe2O4 hierarchical fibrous bundle

NASA Astrophysics Data System (ADS)

Chen, Zerui; Zhang, Yu; Wang, Xiaoling; Sun, Wenping; Dou, Shixue; Huang, Xin; Shi, Bi

2017-09-01

Electrochemical-grinding induced pulverization is the origin of capacity fading in NiFe2O4. Increasing current density normally accelerates the pulverization that deteriorates lithium storage properties of NiFe2O4. Here we show that the high current induced fast-pulverization can serve as an efficient activation strategy for quick and simultaneous enhancement on cycling stability and rate capability of NiFe2O4 nanoparticles (NPs) that are densely packed on the hierarchically structured carbon nanofiber strand. At a high current density, the pulverization of NiFe2O4 NPs can be accomplished in a few cycles exposing more active surface. During the fast-pulverization, the hierarchically structured carbon nanofiber strand maintains conductive contact for the densely packed NiFe2O4 NPs regardless of charge or discharge, which also effectively suppresses the repetitive breaks and growths of solid-electrolyte-interphase (SEI) via multiple-level structural adaption that favourites the quick formation of a thin and dense SEI, thus providing strong interparticle connectivity with enhancement on cycling stability and rate capability (e.g. doubled capacity). Our findings demonstrate the potential importance of high current induced fast-pulverization as an efficient activation strategy for achieving durable electrode materials suffering from electrochemical-grinding effects.

Th17 cells and CD4(+) multifunctional T cells in patients with systemic lupus erythematosus.

PubMed

Araújo, Júlio Antônio Pereira; Mesquita, Danilo; de Melo Cruvinel, Wilson; Salmazi, Karina Inácio; Kallás, Esper Georges; Andrade, Luis Eduardo Coelho

2016-01-01

Recent evidence suggests that abnormalities involving Th17 lymphocytes are associated with the pathophysiology of systemic lupus erythematosus (SLE). In addition, multifunctional T cells (MFT), i.e., those producing multiple cytokines simultaneously, are present in the inflammatory milieu and may be implicated in the autoimmune process observed in SLE. In the present study, we aimed to characterize the functional status of CD4(+) T cells in SLE by simultaneously determining the concentration of IL-2, IFN-γ and IL-17 in lymphocyte cultures under exogenous and self-antigenic stimuli. Eighteen patients with active disease, 18 with inactive disease, and 14 healthy controls had functional status of CD4(+) T cells analyzed. We found that SLE patients presented a decreased number of total CD4(+) cells, an increased number of activated T cells, and an increased frequency of Th17 cells compared to healthy controls (HC). MFT cells had increased frequency in SLE patients and there was an increased frequency of tri-functional MFT in patients with active SLE compared with those with inactive SLE. Interestingly, MTF cells produced larger amounts of IFNγ than mono-functional T cells in patients and controls. Taken together these data indicate the participation of recently activated Th17 cells and MTF cells in the SLE pathophysiology. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Multivalent Display of Antifreeze Proteins by Fusion to Self-Assembling Protein Cages Enhances Ice-Binding Activities.

PubMed

Phippen, Sean W; Stevens, Corey A; Vance, Tyler D R; King, Neil P; Baker, David; Davies, Peter L

2016-12-13

Antifreeze proteins (AFPs) are small monomeric proteins that adsorb to the surface of ice to inhibit ice crystal growth and impart freeze resistance to the organisms producing them. Previously, monomeric AFPs have been conjugated to the termini of branched polymers to increase their activity through the simultaneous binding of more than one AFP to ice. Here, we describe a superior approach to increasing AFP activity through oligomerization that eliminates the need for conjugation reactions with varying levels of efficiency. A moderately active AFP from a fish and a hyperactive AFP from an Antarctic bacterium were genetically fused to the C-termini of one component of the 24-subunit protein cage T33-21, resulting in protein nanoparticles that multivalently display exactly 12 AFPs. The resulting nanoparticles exhibited freezing point depression >50-fold greater than that seen with the same concentration of monomeric AFP and a similar increase in the level of ice-recrystallization inhibition. These results support the anchored clathrate mechanism of binding of AFP to ice. The enhanced freezing point depression could be due to the difficulty of overgrowing a larger AFP on the ice surface and the improved ice-recrystallization inhibition to the ability of the nanoparticle to simultaneously bind multiple ice grains. Oligomerization of these proteins using self-assembling protein cages will be useful in a variety of biotechnology and cryobiology applications.

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.

Simultaneous control of multiple instruments at the Advanced Technology Solar Telescope

NASA Astrophysics Data System (ADS)

Johansson, Erik M.; Goodrich, Bret

2012-09-01

The Advanced Technology Solar Telescope (ATST) is a 4-meter solar observatory under construction at Haleakala, Hawaii. The simultaneous use of multiple instruments is one of the unique capabilities that makes the ATST a premier ground based solar observatory. Control of the instrument suite is accomplished by the Instrument Control System (ICS), a layer of software between the Observatory Control System (OCS) and the instruments. The ICS presents a single narrow interface to the OCS and provides a standard interface for the instruments to be controlled. It is built upon the ATST Common Services Framework (CSF), an infrastructure for the implementation of a distributed control system. The ICS responds to OCS commands and events, coordinating and distributing them to the various instruments while monitoring their progress and reporting the status back to the OCS. The ICS requires no specific knowledge about the instruments. All information about the instruments used in an experiment is passed by the OCS to the ICS, which extracts and forwards the parameters to the appropriate instrument controllers. The instruments participating in an experiment define the active instrument set. A subset of those instruments must complete their observing activities in order for the experiment to be considered complete and are referred to as the must-complete instrument set. In addition, instruments may participate in eavesdrop mode, outside of the control of the ICS. All instrument controllers use the same standard narrow interface, which allows new instruments to be added without having to modify the interface or any existing instrument controllers.

Multiple protocol fluorometer and method

DOEpatents

Kolber, Zbigniew S.; Falkowski, Paul G.

2000-09-19

A multiple protocol fluorometer measures photosynthetic parameters of phytoplankton and higher plants using actively stimulated fluorescence protocols. The measured parameters include spectrally-resolved functional and optical absorption cross sections of PSII, extent of energy transfer between reaction centers of PSII, F.sub.0 (minimal), F.sub.m (maximal) and F.sub.v (variable) components of PSII fluorescence, photochemical and non-photochemical quenching, size of the plastoquinone (PQ) pool, and the kinetics of electron transport between Q.sub.a and PQ pool and between PQ pool and PSI. The multiple protocol fluorometer, in one embodiment, is equipped with an excitation source having a controlled spectral output range between 420 nm and 555 nm and capable of generating flashlets having a duration of 0.125-32 .mu.s, an interval between 0.5 .mu.s and 2 seconds, and peak optical power of up to 2 W/cm.sup.2. The excitation source is also capable of generating, simultaneous with the flashlets, a controlled continuous, background illumination.

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…

THE ABSENCE OF RADIO EMISSION FROM THE GLOBULAR CLUSTER G1

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

Miller-Jones, J. C. A.; Wrobel, J. M.; Sivakoff, G. R.

2012-08-10

The detections of both X-ray and radio emission from the cluster G1 in M31 have provided strong support for existing dynamical evidence for an intermediate-mass black hole (IMBH) of mass (1.8 {+-} 0.5) Multiplication-Sign 10{sup 4} M{sub Sun} at the cluster center. However, given the relatively low significance and astrometric accuracy of the radio detection, and the non-simultaneity of the X-ray and radio measurements, this identification required further confirmation. Here we present deep, high angular resolution, strictly simultaneous X-ray and radio observations of G1. While the X-ray emission (L{sub X} = 1.74{sup +0.53}{sub -0.44} Multiplication-Sign 10{sup 36} (d/750 kpc){sup 2}more » erg s{sup -1} in the 0.5-10 keV band) remained fully consistent with previous observations, we detected no radio emission from the cluster center down to a 3{sigma} upper limit of 4.7 {mu}Jy beam{sup -1}. Our favored explanation for the previous radio detection is flaring activity from a black hole low-mass X-ray binary (LMXB). We performed a new regression of the 'Fundamental Plane' of black hole activity, valid for determining black hole mass from radio and X-ray observations of sub-Eddington black holes, finding log M{sub BH} = (1.638 {+-} 0.070)log L{sub R} - (1.136 {+-} 0.077)log L{sub X} - (6.863 {+-} 0.790), with an empirically determined uncertainty of 0.44 dex. This constrains the mass of the X-ray source in G1, if a black hole, to be <9.7 Multiplication-Sign 10{sup 3} M{sub Sun} at 95% confidence, suggesting that it is a persistent LMXB. This annuls what was previously the most convincing evidence from radiation for an IMBH in the Local Group, though the evidence for an IMBH in G1 from velocity dispersion measurements remains unaffected by these results.« less

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…

Participant observation of time allocation, direct patient contact and simultaneous activities in hospital physicians.

PubMed

Weigl, Matthias; Müller, Andreas; Zupanc, Andrea; Angerer, Peter

2009-06-29

Hospital physicians' time is a critical resource in medical care. Two aspects are of interest. First, the time spent in direct patient contact - a key principle of effective medical care. Second, simultaneous task performance ('multitasking') which may contribute to medical error, impaired safety behaviour, and stress. There is a call for instruments to assess these aspects. A preliminary study to gain insight into activity patterns, time allocation and simultaneous activities of hospital physicians was carried out. Therefore an observation instrument for time-motion-studies in hospital settings was developed and tested. 35 participant observations of internists and surgeons of a German municipal 300-bed hospital were conducted. Complete day shifts of hospital physicians on wards, emergency ward, intensive care unit, and operating room were continuously observed. Assessed variables of interest were time allocation, share of direct patient contact, and simultaneous activities. Inter-rater agreement of Kappa = .71 points to good reliability of the instrument. Hospital physicians spent 25.5% of their time at work in direct contact with patients. Most time was allocated to documentation and conversation with colleagues and nursing staff. Physicians performed parallel simultaneous activities for 17-20% of their work time. Communication with patients, documentation, and conversation with colleagues and nursing staff were the most frequently observed simultaneous activities. Applying logit-linear analyses, specific primary activities increase the probability of particular simultaneous activities. Patient-related working time in hospitals is limited. The potential detrimental effects of frequently observed simultaneous activities on performance outcomes need further consideration.

Towards a Reconceptualization of Striatal Interactions Between Glutamatergic and Dopaminergic Neurotransmission and Their Contribution to the Production of Movements

PubMed Central

David, Hélène N

2009-01-01

According to the current model of the basal ganglia organization, simultaneous activation of the striato-nigral direct pathway by glutamatergic and dopaminergic neurotransmission should lead to a synergistic facilitatory action on locomotor activity, while in contrast activation of the indirect pathway by these two neurotransmittions should lead to antagonistic effects on locomotor activity. Based on published data, as a break with the current thinking, we propose a reconceptualization of functional interactions between dopaminergic and glutamatergic neurotransmission. In this model, dopaminergic neurotransmission is seen as a motor pacemaker responsible for the basal and primary activation of striatal output neurons and glutamate as a driver providing a multiple combination of tonic, phasic, facilitatory and inhibitory influxes resulting from the processing of environmental, emotional and mnesic stimuli. Thus, in the model, glutamate-coded inputs would allow tuning the intrinsic motor-activating properties of dopamine to adjust the production of locomotor activity into goal-oriented movements. PMID:19949572

Spontaneous default network activity reflects behavioral variability independent of mind-wandering.

PubMed

Kucyi, Aaron; Esterman, Michael; Riley, Clay S; Valera, Eve M

2016-11-29

The brain's default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain-behavior-experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report.

Spontaneous default network activity reflects behavioral variability independent of mind-wandering

PubMed Central

Kucyi, Aaron; Esterman, Michael; Riley, Clay S.; Valera, Eve M.

2016-01-01

The brain’s default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain–behavior–experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report. PMID:27856733

Catabolic regulation analysis of Escherichia coli and its crp, mlc, mgsA, pgi and ptsG mutants

PubMed Central

2011-01-01

Background Most bacteria can use various compounds as carbon sources. These carbon sources can be either co-metabolized or sequentially metabolized, where the latter phenomenon typically occurs as catabolite repression. From the practical application point of view of utilizing lignocellulose for the production of biofuels etc., it is strongly desirable to ferment all sugars obtained by hydrolysis from lignocellulosic materials, where simultaneous consumption of sugars would benefit the formation of bioproducts. However, most organisms consume glucose prior to consumption of other carbon sources, and exhibit diauxic growth. It has been shown by fermentation experiments that simultaneous consumption of sugars can be attained by ptsG, mgsA mutants etc., but its mechanism has not been well understood. It is strongly desirable to understand the mechanism of metabolic regulation for catabolite regulation to improve the performance of fermentation. Results In order to make clear the catabolic regulation mechanism, several continuous cultures were conducted at different dilution rates of 0.2, 0.4, 0.6 and 0.7 h-1 using wild type Escherichia coli. The result indicates that the transcript levels of global regulators such as crp, cra, mlc and rpoS decreased, while those of fadR, iclR, soxR/S increased as the dilution rate increased. These affected the metabolic pathway genes, which in turn affected fermentation result where the specific glucose uptake rate, the specific acetate formation rate, and the specific CO2 evolution rate (CER) were increased as the dilution rate was increased. This was confirmed by the 13C-flux analysis. In order to make clear the catabolite regulation, the effect of crp gene knockout (Δcrp) and crp enhancement (crp+) as well as mlc, mgsA, pgi and ptsG gene knockout on the metabolism was then investigated by the continuous culture at the dilution rate of 0.2 h-1 and by some batch cultures. In the case of Δcrp (and also Δmlc) mutant, TCA cycle and glyoxylate were repressed, which caused acetate accumulation. In the case of crp+ mutant, glycolysis, TCA cycle, and gluconeogenesis were activated, and simultaneous consumption of multiple carbon sources can be attained, but the glucose consumption rate became less due to repression of ptsG and ptsH by the activation of Mlc. Simultaneous consumption of multiple carbon sources could be attained by mgsA, pgi, and ptsG mutants due to increase in crp as well as cyaA, while glucose consumption rate became lower. Conclusions The transcriptional catabolite regulation mechanism was made clear for the wild type E. coli, and its crp, mlc, ptsG, pgi, and mgsA gene knockout mutants. The results indicate that catabolite repression can be relaxed and crp as well as cyaA can be increased by crp+, mgsA, pgi, and ptsG mutants, and thus simultaneous consumption of multiple carbon sources including glucose can be made, whereas the glucose uptake rate became lower as compared to wild type due to inactivation of ptsG in all the mutants considered. PMID:21831320

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...

From Molecules to Cells to Organisms: Understanding Health and Disease with Multidimensional Single-Cell Methods

NASA Astrophysics Data System (ADS)

Candia, Julián

2013-03-01

The multidimensional nature of many single-cell measurements (e.g. multiple markers measured simultaneously using Fluorescence-Activated Cell Sorting (FACS) technologies) offers unprecedented opportunities to unravel emergent phenomena that are governed by the cooperative action of multiple elements across different scales, from molecules and proteins to cells and organisms. We will discuss an integrated analysis framework to investigate multicolor FACS data from different perspectives: Singular Value Decomposition to achieve an effective dimensional reduction in the data representation, machine learning techniques to separate different patient classes and improve diagnosis, as well as a novel cell-similarity network analysis method to identify cell subpopulations in an unbiased manner. Besides FACS data, this framework is versatile: in this vein, we will demonstrate an application to the multidimensional single-cell shape analysis of healthy and prematurely aged cells.

Model misspecification detection by means of multiple generator errors, using the observed potential map.

PubMed

Zhang, Z; Jewett, D L

1994-01-01

Due to model misspecification, currently-used Dipole Source Localization (DSL) methods may contain Multiple-Generator Errors (MulGenErrs) when fitting simultaneously-active dipoles. The size of the MulGenErr is a function of both the model used, and the dipole parameters, including the dipoles' waveforms (time-varying magnitudes). For a given fitting model, by examining the variation of the MulGenErrs (or the fit parameters) under different waveforms for the same generating-dipoles, the accuracy of the fitting model for this set of dipoles can be determined. This method of testing model misspecification can be applied to evoked potential maps even when the parameters of the generating-dipoles are unknown. The dipole parameters fitted in a model should only be accepted if the model can be shown to be sufficiently accurate.

Optimisation of a Generic Ionic Model of Cardiac Myocyte Electrical Activity

PubMed Central

Guo, Tianruo; Al Abed, Amr; Lovell, Nigel H.; Dokos, Socrates

2013-01-01

A generic cardiomyocyte ionic model, whose complexity lies between a simple phenomenological formulation and a biophysically detailed ionic membrane current description, is presented. The model provides a user-defined number of ionic currents, employing two-gate Hodgkin-Huxley type kinetics. Its generic nature allows accurate reconstruction of action potential waveforms recorded experimentally from a range of cardiac myocytes. Using a multiobjective optimisation approach, the generic ionic model was optimised to accurately reproduce multiple action potential waveforms recorded from central and peripheral sinoatrial nodes and right atrial and left atrial myocytes from rabbit cardiac tissue preparations, under different electrical stimulus protocols and pharmacological conditions. When fitted simultaneously to multiple datasets, the time course of several physiologically realistic ionic currents could be reconstructed. Model behaviours tend to be well identified when extra experimental information is incorporated into the optimisation. PMID:23710254

CRAVE: a database, middleware and visualization system for phenotype ontologies.

PubMed

Gkoutos, Georgios V; Green, Eain C J; Greenaway, Simon; Blake, Andrew; Mallon, Ann-Marie; Hancock, John M

2005-04-01

A major challenge in modern biology is to link genome sequence information to organismal function. In many organisms this is being done by characterizing phenotypes resulting from mutations. Efficiently expressing phenotypic information requires combinatorial use of ontologies. However tools are not currently available to visualize combinations of ontologies. Here we describe CRAVE (Concept Relation Assay Value Explorer), a package allowing storage, active updating and visualization of multiple ontologies. CRAVE is a web-accessible JAVA application that accesses an underlying MySQL database of ontologies via a JAVA persistent middleware layer (Chameleon). This maps the database tables into discrete JAVA classes and creates memory resident, interlinked objects corresponding to the ontology data. These JAVA objects are accessed via calls through the middleware's application programming interface. CRAVE allows simultaneous display and linking of multiple ontologies and searching using Boolean and advanced searches.

Multi-angle VECSEL cavities for dispersion control and multi-color operation

NASA Astrophysics Data System (ADS)

Baker, Caleb; Scheller, Maik; Laurain, Alexandre; Yang, Hwang-Jye; Ruiz Perez, Antje; Stolz, Wolfgang; Addamane, Sadhvikas J.; Balakrishnan, Ganesh; Jones, R. Jason; Moloney, Jerome V.

2017-02-01

We present a novel Vertical External Cavity Surface Emitting Laser (VECSEL) cavity design which makes use of multiple interactions with the gain region under different angles of incidence in a single round trip. This design allows for optimization of the net, round-trip Group Delay Dispersion (GDD) by shifting the GDD of the gain via cavity fold angle while still maintaining the high gain of resonant structures. The effectiveness of this scheme is demonstrated with femtosecond-regime pulses from a resonant structure and record pulse energies for the VECSEL gain medium. In addition, we show that the interference pattern of the intracavity mode within the active region, resulting from the double-angle multifold, is advantageous for operating the laser in CW on multiple wavelengths simultaneously. Power, noise, and mode competition characterization is presented.

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

Thompson, M. C., E-mail: mthompson@trialphaenergy.com; Gota, H.; Putvinski, S.

The C-2U experiment at Tri Alpha Energy studies the evolution of field-reversed configuration (FRC) plasmas sustained by neutral beam injection. Data on the FRC plasma performance are provided by a comprehensive suite of diagnostics that includes magnetic sensors, interferometry, Thomson scattering, spectroscopy, bolometry, reflectometry, neutral particle analyzers, and fusion product detectors. While many of these diagnostic systems were inherited from the preceding experiment C-2, C-2U has a variety of new and upgraded diagnostic systems: multi-chord far-infrared polarimetry, multiple fast imaging cameras with selectable atomic line filters, proton detector arrays, and 100 channel bolometer units capable of observing multiple regions ofmore » the spectrum simultaneously. In addition, extensive ongoing work focuses on advanced methods of measuring separatrix shape and plasma current profile that will facilitate equilibrium reconstruction and active control of the FRC plasma.« less

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

Nicotine Inhibits Memory CTL Programming

PubMed Central

Sun, Zhifeng; Smyth, Kendra; Garcia, Karla; Mattson, Elliot; Li, Lei; Xiao, Zhengguo

2013-01-01

Nicotine is the main tobacco component responsible for tobacco addiction and is used extensively in smoking and smoking cessation therapies. However, little is known about its effects on the immune system. We confirmed that multiple nicotinic receptors are expressed on mouse and human cytotoxic T lymphocytes (CTLs) and demonstrated that nicotinic receptors on mouse CTLs are regulated during activation. Acute nicotine presence during activation increases primary CTL expansion in vitro, but impairs in vivo expansion after transfer and subsequent memory CTL differentiation, which reduces protection against subsequent pathogen challenges. Furthermore, nicotine abolishes the regulatory effect of rapamycin on memory CTL programming, which can be attributed to the fact that rapamycin enhances expression of nicotinic receptors. Interestingly, naïve CTLs from chronic nicotine-treated mice have normal memory programming, which is impaired by nicotine during activation in vitro. In conclusion, simultaneous exposure to nicotine and antigen during CTL activation negatively affects memory development. PMID:23844169

Rotation of endosomes demonstrates coordination of molecular motors during axonal transport.

PubMed

Kaplan, Luke; Ierokomos, Athena; Chowdary, Praveen; Bryant, Zev; Cui, Bianxiao

2018-03-01

Long-distance axonal transport is critical to the maintenance and function of neurons. Robust transport is ensured by the coordinated activities of multiple molecular motors acting in a team. Conventional live-cell imaging techniques used in axonal transport studies detect this activity by visualizing the translational dynamics of a cargo. However, translational measurements are insensitive to torques induced by motor activities. By using gold nanorods and multichannel polarization microscopy, we simultaneously measure the rotational and translational dynamics for thousands of axonally transported endosomes. We find that the rotational dynamics of an endosome provide complementary information regarding molecular motor activities to the conventionally tracked translational dynamics. Rotational dynamics correlate with translational dynamics, particularly in cases of increased rotation after switches between kinesin- and dynein-mediated transport. Furthermore, unambiguous measurement of nanorod angle shows that endosome-contained nanorods align with the orientation of microtubules, suggesting a direct mechanical linkage between the ligand-receptor complex and the microtubule motors.

Extracellular wire tetrode recording in brain of freely walking insects.

PubMed

Guo, Peiyuan; Pollack, Alan J; Varga, Adrienn G; Martin, Joshua P; Ritzmann, Roy E

2014-04-01

Increasing interest in the role of brain activity in insect motor control requires that we be able to monitor neural activity while insects perform natural behavior. We previously developed a technique for implanting tetrode wires into the central complex of cockroach brains that allowed us to record activity from multiple neurons simultaneously while a tethered cockroach turned or altered walking speed. While a major advance, tethered preparations provide access to limited behaviors and often lack feedback processes that occur in freely moving animals. We now present a modified version of that technique that allows us to record from the central complex of freely moving cockroaches as they walk in an arena and deal with barriers by turning, climbing or tunneling. Coupled with high speed video and cluster cutting, we can now relate brain activity to various parameters of the movement of freely behaving insects.

Sensory and Repetitive Behaviors among Children with Autism Spectrum Disorder at Home

PubMed Central

Kirby, Anne V.; Boyd, Brian A.; Williams, Kathryn; Faldowski, Richard A.; Baranek, Grace T.

2017-01-01

Atypical sensory and repetitive behaviors are defining features of autism spectrum disorder (ASD) and are thought to be influenced by environmental factors; however, there is a lack of naturalistic research exploring contexts surrounding these behaviors. The current study involved video recording observations of 32 children with ASD (2 – 12 years of age) engaging in sensory and repetitive behaviors during home activities. Behavioral coding was used to determine what activity contexts, sensory modalities, and stimulus characteristics were associated with specific behavior types: hyperresponsive, hyporesponsive, sensory seeking, and repetitive/stereotypic. Results indicated that hyperresponsive behaviors were most associated with activities of daily living and family-initiated stimuli, whereas sensory seeking behaviors were associated with free play activities and child-initiated stimuli. Behaviors associated with multiple sensory modalities simultaneously were common, emphasizing the multi-sensory nature of children’s behaviors in natural contexts. Implications for future research more explicitly considering context are discussed. PMID:27091950

A multiplexable TALE-based binary expression system for in vivo cellular interaction studies.

PubMed

Toegel, Markus; Azzam, Ghows; Lee, Eunice Y; Knapp, David J H F; Tan, Ying; Fa, Ming; Fulga, Tudor A

2017-11-21

Binary expression systems have revolutionised genetic research by enabling delivery of loss-of-function and gain-of-function transgenes with precise spatial-temporal resolution in vivo. However, at present, each existing platform relies on a defined exogenous transcription activator capable of binding a unique recognition sequence. Consequently, none of these technologies alone can be used to simultaneously target different tissues or cell types in the same organism. Here, we report a modular system based on programmable transcription activator-like effector (TALE) proteins, which enables parallel expression of multiple transgenes in spatially distinct tissues in vivo. Using endogenous enhancers coupled to TALE drivers, we demonstrate multiplexed orthogonal activation of several transgenes carrying cognate variable activating sequences (VAS) in distinct neighbouring cell types of the Drosophila central nervous system. Since the number of combinatorial TALE-VAS pairs is virtually unlimited, this platform provides an experimental framework for highly complex genetic manipulation studies in vivo.

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.

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.

Spatial location influences vocal interactions in bullfrog choruses

PubMed Central

Bates, Mary E.; Cropp, Brett F.; Gonchar, Marina; Knowles, Jeffrey; Simmons, James A.; Simmons, Andrea Megela

2010-01-01

A multiple sensor array was employed to identify the spatial locations of all vocalizing male bullfrogs (Rana catesbeiana) in five natural choruses. Patterns of vocal activity collected with this array were compared with computer simulations of chorus activity. Bullfrogs were not randomly spaced within choruses, but tended to cluster into closely spaced groups of two to five vocalizing males. There were nonrandom, differing patterns of vocal interactions within clusters of closely spaced males and between different clusters. Bullfrogs located within the same cluster tended to overlap or alternate call notes with two or more other males in that cluster. These near-simultaneous calling bouts produced advertisement calls with more pronounced amplitude modulation than occurred in nonoverlapping notes or calls. Bullfrogs located in different clusters more often alternated entire calls or overlapped only small segments of their calls. They also tended to respond sequentially to calls of their farther neighbors compared to their nearer neighbors. Results of computational analyses showed that the observed patterns of vocal interactions were significantly different than expected based on random activity. The use of a multiple sensor array provides a richer view of the dynamics of choruses than available based on single microphone techniques. PMID:20370047

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.

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.

Epigenetic polypharmacology: from combination therapy to multitargeted drugs.

PubMed

de Lera, Angel R; Ganesan, A

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. However, the use of cocktails or multicomponent drugs to address several targets simultaneously is also popular to treat multifactorial diseases such as cancer and neurological disorders. We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. Epigenetic drug discovery is a rapidly advancing field, and drugs targeting epigenetic enzymes are in the clinic for the treatment of hematological cancers. Approved and experimental epigenetic drugs are undergoing clinical trials in combination with other therapeutic agents via fused or linked pharmacophores in order to benefit from synergistic effects of polypharmacology. In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). These multiple ligands should in principle have a lower risk of drug-drug interactions and drug resistance compared to cocktails or multicomponent drugs. This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed.

Higher-efficiency photoelectrochemical electrodes of titanium dioxide-based nanoarrays sensitized simultaneously with plasmonic silver nanoparticles and multiple metal sulfides photosensitizers

NASA Astrophysics Data System (ADS)

Guo, Keying; Liu, Zhifeng; Han, Jianhua; Zhang, Xueqi; Li, Yajun; Hong, Tiantian; Zhou, Cailou

2015-07-01

This paper describes a novel design of high-efficiency photoelectrochemical water splitting electrode, i.e., ordered TiO2 nanorod arrays (NRs) sensitized simultaneously with noble metal (Ag), binary metal sulfides (Ag2S) and ternary metal sulfides (Ag3CuS2) multiple photosensitizers for the first time. The TiO2/Ag/Ag2S/Ag3CuS2 NRs heterostructure is successfully synthesized through successive ion layer adsorption and reaction (SILAR) and a simple ion-exchange process based on ionic reaction mechanism. On the basis of an optimal quantity of Ag, Ag2S and Ag3CuS2 nanoparticles, such TiO2/Ag/Ag2S/Ag3CuS2 NRs exhibit a higher photoelectrochemical activity ever reported for TiO2-based nanoarrays in PEC water splitting, the photocurrent density is up to 9.82 mA cm-2 at 0.47 V versus Ag/AgCl, respectively. This novel architecture is able to increase electron collection efficiency and suppress carrier recombination via (i) a higher efficiency of light-harvesting through these multiple photosensitizers (Ag, Ag2S and Ag3CuS2); (ii) the efficient separation of photo-induced electrons and holes due to the direct electrical pathways; (iii) the surface plasmon resonance (SPR) effect of Ag nanoparticles, which enhances the efficient charge separation and high carrier mobility. This work is useful to explore feasible routes to further enhance the performance of oxide semiconductors for PEC water splitting to produce clean H2 energy.

Facile route to versatile nanoplatforms for drug delivery by one-pot self-assembly.

PubMed

Zhou, Xing; Che, Ling; Wei, Yanling; Dou, Yin; Chen, Sha; He, Hongmei; Gong, Hao; Li, Xiaohui; Zhang, Jianxiang

2014-06-01

There is still unmet demand for developing powerful approaches to produce polymeric nanoplatforms with versatile functions and broad applications, which are essential for the successful bench-to-bedside translation of polymeric nanotherapeutics developed in the laboratory. We have discovered a facile, convenient, cost-effective and easily scalable one-pot strategy to assemble various lipophilic therapeutics bearing carboxyl groups into nanomedicines, through which highly effective cargo loading and nanoparticle formation can be achieved simultaneously. Besides dramatically improving water solubility, the assembled nanopharmaceuticals showed significantly higher bioavailability and much better therapeutic activity. These one-pot assemblies may also serve as nanocontainers to effectively accommodate other highly hydrophobic drugs such as paclitaxel (PTX). PTX nanomedicines thus formulated display strikingly enhanced in vitro antitumor activity and can reverse the multidrug resistance of tumor cells to PTX therapy. The special surface chemistry offers these assembled entities the additional capability of efficiently packaging and efficaciously transfecting plasmid DNA, with a transfection efficiency markedly higher than that of commonly used positive controls. Consequently, this one-pot assembly approach provides a facile route to multifunctional nanoplatforms for simultaneous delivery of multiple therapeutics with improved therapeutic significance. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Layered Systems Engineering Engines

NASA Technical Reports Server (NTRS)

Breidenthal, Julian C.; Overman, Marvin J.

2009-01-01

A notation is described for depicting the relationships between multiple, contemporaneous systems engineering efforts undertaken within a multi-layer system-of-systems hierarchy. We combined the concepts of remoteness of activity from the end customer, depiction of activity on a timeline, and data flow to create a new kind of diagram which we call a "Layered Vee Diagram." This notation is an advance over previous notations because it is able to be simultaneously precise about activity, level of granularity, product exchanges, and timing; these advances provide systems engineering managers a significantly improved ability to express and understand the relationships between many systems engineering efforts. Using the new notation, we obtain a key insight into the relationship between project duration and the strategy selected for chaining the systems engineering effort between layers, as well as insights into the costs, opportunities, and risks associated with alternate chaining strategies.

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…

Facing Challenges in Differential Classical Conditioning Research: Benefits of a Hybrid Design for Simultaneous Electrodermal and Electroencephalographic Recording.

PubMed

Pastor, M Carmen; Rehbein, Maimu Alissa; Junghöfer, Markus; Poy, Rosario; López, Raul; Moltó, Javier

2015-01-01

Several challenges make it difficult to simultaneously investigate central and autonomous nervous system correlates of conditioned stimulus (CS) processing in classical conditioning paradigms. Such challenges include, for example, the discrepant requirements of electroencephalography (EEG) and electrodermal activity (EDA) recordings with regard to multiple repetitions of conditions and sufficient trial duration. Here, we propose a MultiCS conditioning set-up, in which we increased the number of CSs, decreased the number of learning trials, and used trials of short and long durations for meeting requirements of simultaneous EEG-EDA recording in a differential aversive conditioning task. Forty-eight participants underwent MultiCS conditioning, in which four neutral faces (CS+) were paired four times each with aversive electric stimulation (unconditioned stimulus) during acquisition, while four different neutral faces (CS-) remained unpaired. When comparing after relative to before learning measurements, EEG revealed an enhanced centro-posterior positivity to CS+ vs. CS- during 368-600 ms, and subjective ratings indicated CS+ to be less pleasant and more arousing than CS-. Furthermore, changes in CS valence and arousal were strong enough to bias subjective ratings when faces of CS+/CS- identity were displayed with different emotional expression (happy, angry) in a post-experimental behavioral task. In contrast to a persistent neural and evaluative CS+/CS- differentiation that sustained multiple unreinforced CS presentations, electrodermal differentiation was rapidly extinguished. Current results suggest that MultiCS conditioning provides a promising paradigm for investigating pre-post-learning changes under minimal influences of extinction and overlearning of simple stimulus features. Our data also revealed methodological pitfalls, such as the possibility of occurring artifacts when combining different acquisition systems for central and peripheral psychophysiological measures.

Facing Challenges in Differential Classical Conditioning Research: Benefits of a Hybrid Design for Simultaneous Electrodermal and Electroencephalographic Recording

PubMed Central

Pastor, M. Carmen; Rehbein, Maimu Alissa; Junghöfer, Markus; Poy, Rosario; López, Raul; Moltó, Javier

2015-01-01

Several challenges make it difficult to simultaneously investigate central and autonomous nervous system correlates of conditioned stimulus (CS) processing in classical conditioning paradigms. Such challenges include, for example, the discrepant requirements of electroencephalography (EEG) and electrodermal activity (EDA) recordings with regard to multiple repetitions of conditions and sufficient trial duration. Here, we propose a MultiCS conditioning set-up, in which we increased the number of CSs, decreased the number of learning trials, and used trials of short and long durations for meeting requirements of simultaneous EEG–EDA recording in a differential aversive conditioning task. Forty-eight participants underwent MultiCS conditioning, in which four neutral faces (CS+) were paired four times each with aversive electric stimulation (unconditioned stimulus) during acquisition, while four different neutral faces (CS−) remained unpaired. When comparing after relative to before learning measurements, EEG revealed an enhanced centro-posterior positivity to CS+ vs. CS− during 368–600 ms, and subjective ratings indicated CS+ to be less pleasant and more arousing than CS−. Furthermore, changes in CS valence and arousal were strong enough to bias subjective ratings when faces of CS+/CS− identity were displayed with different emotional expression (happy, angry) in a post-experimental behavioral task. In contrast to a persistent neural and evaluative CS+/CS− differentiation that sustained multiple unreinforced CS presentations, electrodermal differentiation was rapidly extinguished. Current results suggest that MultiCS conditioning provides a promising paradigm for investigating pre–post-learning changes under minimal influences of extinction and overlearning of simple stimulus features. Our data also revealed methodological pitfalls, such as the possibility of occurring artifacts when combining different acquisition systems for central and peripheral psychophysiological measures. PMID:26106318

Three dimensional two-photon brain imaging in freely moving mice using a miniature fiber coupled microscope with active axial-scanning.

PubMed

Ozbay, Baris N; Futia, Gregory L; Ma, Ming; Bright, Victor M; Gopinath, Juliet T; Hughes, Ethan G; Restrepo, Diego; Gibson, Emily A

2018-05-25

We present a miniature head mounted two-photon fiber-coupled microscope (2P-FCM) for neuronal imaging with active axial focusing enabled using a miniature electrowetting lens. We show three-dimensional two-photon imaging of neuronal structure and record neuronal activity from GCaMP6s fluorescence from multiple focal planes in a freely-moving mouse. Two-color simultaneous imaging of GFP and tdTomato fluorescence is also demonstrated. Additionally, dynamic control of the axial scanning of the electrowetting lens allows tilting of the focal plane enabling neurons in multiple depths to be imaged in a single plane. Two-photon imaging allows increased penetration depth in tissue yielding a working distance of 450 μm with an additional 180 μm of active axial focusing. The objective NA is 0.45 with a lateral resolution of 1.8 μm, an axial resolution of 10 μm, and a field-of-view of 240 μm diameter. The 2P-FCM has a weight of only ~2.5 g and is capable of repeatable and stable head-attachment. The 2P-FCM with dynamic axial scanning provides a new capability to record from functionally distinct neuronal layers, opening new opportunities in neuroscience research.

The mitogen-activated protein kinase (MAPK) cascade controls phosphatase and tensin homolog (PTEN) expression through multiple mechanisms.

PubMed

Ciuffreda, Ludovica; Di Sanza, Cristina; Cesta Incani, Ursula; Eramo, Adriana; Desideri, Marianna; Biagioni, Francesca; Passeri, Daniela; Falcone, Italia; Sette, Giovanni; Bergamo, Paola; Anichini, Andrea; Sabapathy, Kanaga; McCubrey, James A; Ricciardi, Maria Rosaria; Tafuri, Agostino; Blandino, Giovanni; Orlandi, Augusto; De Maria, Ruggero; Cognetti, Francesco; Del Bufalo, Donatella; Milella, Michele

2012-06-01

The mitogen-activated protein kinase (MAPK) and PI3K pathways are regulated by extensive crosstalk, occurring at different levels. In tumors, transactivation of the alternate pathway is a frequent "escape" mechanism, suggesting that combined inhibition of both pathways may achieve synergistic antitumor activity. Here we show that, in the M14 melanoma model, simultaneous inhibition of both MEK and mammalian target of rapamycin (mTOR) achieves synergistic effects at suboptimal concentrations, but becomes frankly antagonistic in the presence of relatively high concentrations of MEK inhibitors. This observation led to the identification of a novel crosstalk mechanism, by which either pharmacologic or genetic inhibition of constitutive MEK signaling restores phosphatase and tensin homolog (PTEN) expression, both in vitro and in vivo, and inhibits downstream signaling through AKT and mTOR, thus bypassing the need for double pathway blockade. This appears to be a general regulatory mechanism and is mediated by multiple mechanisms, such as MAPK-dependent c-Jun and miR-25 regulation. Finally, PTEN upregulation appears to be a major effector of MEK inhibitors' antitumor activity, as cancer cells in which PTEN is inactivated are consistently more resistant to the growth inhibitory and anti-angiogenic effects of MEK blockade.

Economic Impacts of Infrastructure Damages on Industrial Sector

NASA Astrophysics Data System (ADS)

Kajitani, Yoshio

This paper proposes a basic model for evaluating economic impacts on industrial sectors under the conditions that multiple infrastructures are simultaneously damaged during the earthquake disasters. Especially, focusing on the available economic data developed in the smallest spatial scale in Japan (small area statistics), economic loss estimation model based on the small area statistics and its applicability are investigated on. In the detail, a loss estimation framework, utilizing survey results on firms' activities under electricity, water and gas disruptions, and route choice models in Transportation Engineering, are applied to the case of 2004 Mid-Niigata Earthquake.

The Nitrosocarbonyl Hetero-Diels–Alder Reaction as a Useful Tool for Organic Syntheses

PubMed Central

Bodnar, Brian S.

2014-01-01

Organic transformations that result in the formation of multiple covalent bonds within the same reaction are some of the most powerful tools in synthetic organic chemistry. Nitrosocarbonyl hetero-Diels–Alder (HDA) reactions allow for the simultaneous stereospecific introduction of carbon–nitrogen and carbon–oxygen bonds in one synthetic step, and provide direct access to 3,6-dihydro-1,2-oxazines. This Review describes the development of the nitrosocarbonyl HDA reaction and the utility of the resulting oxazine ring in the synthesis of a variety of important, biologically active molecules. PMID:21520360

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%.

Development of flight experiments for remote measurement of pollution

NASA Technical Reports Server (NTRS)

Keafer, L. S., Jr.; Kopia, L. P.

1973-01-01

The status as of February 1973 of several NASA-sponsored development projects is reported concerning flight experiments for remote measurement of pollution. Eight passive multispectral instruments for remotely sensing air and water pollutants are described, as well as two active (laser radar) measuring techniques. These techniques are expected to add some new dimensions to the remote sensing of water quality, oceanographic parameters, and earth resources. Multiple applications in these fields are generally possible. Successful completion of the flight demonstration tests and comparisons with simultaneously obtained surface truth measurements may establish these techniques as valid water quality monitoring tools.

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.

Temporal Sequence of Ictal discharges Propagation in the Corticolimbic Basal Ganglia System during Amygdala Kindled Seizures in Freely Moving Rats

PubMed Central

Shi, Li-Hong; Luo, Fei; Woodward, Donald J.; McIntyre, Dan C.; Chang, Jing-Yu

2007-01-01

We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures. PMID:17049434

Differential Encoding of Time by Prefrontal and Striatal Network Dynamics.

PubMed

Bakhurin, Konstantin I; Goudar, Vishwa; Shobe, Justin L; Claar, Leslie D; Buonomano, Dean V; Masmanidis, Sotiris C

2017-01-25

Telling time is fundamental to many forms of learning and behavior, including the anticipation of rewarding events. Although the neural mechanisms underlying timing remain unknown, computational models have proposed that the brain represents time in the dynamics of neural networks. Consistent with this hypothesis, changing patterns of neural activity dynamically in a number of brain areas-including the striatum and cortex-has been shown to encode elapsed time. To date, however, no studies have explicitly quantified and contrasted how well different areas encode time by recording large numbers of units simultaneously from more than one area. Here, we performed large-scale extracellular recordings in the striatum and orbitofrontal cortex of mice that learned the temporal relationship between a stimulus and a reward and reported their response with anticipatory licking. We used a machine-learning algorithm to quantify how well populations of neurons encoded elapsed time from stimulus onset. Both the striatal and cortical networks encoded time, but the striatal network outperformed the orbitofrontal cortex, a finding replicated both in simultaneously and nonsimultaneously recorded corticostriatal datasets. The striatal network was also more reliable in predicting when the animals would lick up to ∼1 s before the actual lick occurred. Our results are consistent with the hypothesis that temporal information is encoded in a widely distributed manner throughout multiple brain areas, but that the striatum may have a privileged role in timing because it has a more accurate "clock" as it integrates information across multiple cortical areas. The neural representation of time is thought to be distributed across multiple functionally specialized brain structures, including the striatum and cortex. However, until now, the neural code for time has not been compared quantitatively between these areas. Here, we performed large-scale recordings in the striatum and orbitofrontal cortex of mice trained on a stimulus-reward association task involving a delay period and used a machine-learning algorithm to quantify how well populations of simultaneously recorded neurons encoded elapsed time from stimulus onset. We found that, although both areas encoded time, the striatum consistently outperformed the orbitofrontal cortex. These results suggest that the striatum may refine the code for time by integrating information from multiple inputs. Copyright © 2017 the authors 0270-6474/17/370854-17$15.00/0.

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

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.

Cellular Decision Making by Non-Integrative Processing of TLR Inputs.

PubMed

Kellogg, Ryan A; Tian, Chengzhe; Etzrodt, Martin; Tay, Savaş

2017-04-04

Cells receive a multitude of signals from the environment, but how they process simultaneous signaling inputs is not well understood. Response to infection, for example, involves parallel activation of multiple Toll-like receptors (TLRs) that converge on the nuclear factor κB (NF-κB) pathway. Although we increasingly understand inflammatory responses for isolated signals, it is not clear how cells process multiple signals that co-occur in physiological settings. We therefore examined a bacterial infection scenario involving co-stimulation of TLR4 and TLR2. Independent stimulation of these receptors induced distinct NF-κB dynamic profiles, although surprisingly, under co-stimulation, single cells continued to show ligand-specific dynamic responses characteristic of TLR2 or TLR4 signaling rather than a mixed response, comprising a cellular decision that we term "non-integrative" processing. Iterating modeling and microfluidic experiments revealed that non-integrative processing occurred through interaction of switch-like NF-κB activation, receptor-specific processing timescales, cell-to-cell variability, and TLR cross-tolerance mediated by multilayer negative feedback. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Distinct encoding of risk and value in economic choice between multiple risky options☆

PubMed Central

Wright, Nicholas D.; Symmonds, Mkael; Dolan, Raymond J.

2013-01-01

Neural encoding of value-based stimuli is suggested to involve representations of summary statistics, including risk and expected value (EV). A more complex, but ecologically more common, context is when multiple risky options are evaluated together. However, it is unknown whether encoding related to option evaluation in these situations involves similar principles. Here we employed fMRI during a task that parametrically manipulated EV and risk in two simultaneously presented lotteries, both of which contained either gains or losses. We found representations of EV in medial prefrontal cortex and anterior insula, an encoding that was dependent on which option was chosen (i.e. chosen and unchosen EV) and whether the choice was over gains or losses. Parietal activity reflected whether the riskier or surer option was selected, whilst activity in a network of regions that also included parietal cortex reflected both combined risk and difference in risk for the two options. Our findings provide support for the idea that summary statistics underpin a representation of value-based stimuli, and further that these summary statistics undergo distinct forms of encoding. PMID:23684860

Multichannel optical mapping: investigation of depth information

NASA Astrophysics Data System (ADS)

Sase, Ichiro; Eda, Hideo; Seiyama, Akitoshi; Tanabe, Hiroki C.; Takatsuki, Akira; Yanagida, Toshio

2001-06-01

Near infrared (NIR) light has become a powerful tool for non-invasive imaging of human brain activity. Many systems have been developed to capture the changes in regional brain blood flow and hemoglobin oxygenation, which occur in the human cortex in response to neural activity. We have developed a multi-channel reflectance imaging system, which can be used as a `mapping device' and also as a `multi-channel spectrophotometer'. In the present study, we visualized changes in the hemodynamics of the human occipital region in multiple ways. (1) Stimulating left and right primary visual cortex independently by showing sector shaped checkerboards sequentially over the contralateral visual field, resulted in corresponding changes in the hemodynamics observed by `mapping' measurement. (2) Simultaneous measurement of functional-MRI and NIR (changes in total hemoglobin) during visual stimulation showed good spatial and temporal correlation with each other. (3) Placing multiple channels densely over the occipital region demonstrated spatial patterns more precisely, and depth information was also acquired by placing each pair of illumination and detection fibers at various distances. These results indicate that optical method can provide data for 3D analysis of human brain functions.

High-resolution Identification and Separation of Living Cell Types by Multiple microRNA-responsive Synthetic mRNAs.

PubMed

Endo, Kei; Hayashi, Karin; Saito, Hirohide

2016-02-23

The precise identification and separation of living cell types is critical to both study cell function and prepare cells for medical applications. However, intracellular information to distinguish live cells remains largely inaccessible. Here, we develop a method for high-resolution identification and separation of cell types by quantifying multiple microRNA (miRNA) activities in live cell populations. We found that a set of miRNA-responsive, in vitro synthesized mRNAs identify a specific cell population as a sharp peak and clearly separate different cell types based on less than two-fold differences in miRNA activities. Increasing the number of miRNA-responsive mRNAs enhanced the capability for cell identification and separation, as we precisely and simultaneously distinguished different cell types with similar miRNA profiles. In addition, the set of synthetic mRNAs separated HeLa cells into subgroups, uncovering heterogeneity of the cells and the level of resolution achievable. Our method could identify target live cells and improve the efficiency of cell purification from heterogeneous populations.

Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

PubMed

Hofman, Zonne L M; Relan, Anurag; Hack, C Erik

2016-02-01

Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed.

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

SET1A/COMPASS and shadow enhancers in the regulation of homeotic gene expression

PubMed Central

Cao, Kaixiang; Collings, Clayton K.; Marshall, Stacy A.; Morgan, Marc A.; Rendleman, Emily J.; Wang, Lu; Sze, Christie C.; Sun, Tianjiao; Bartom, Elizabeth T.; Shilatifard, Ali

2017-01-01

The homeotic (Hox) genes are highly conserved in metazoans, where they are required for various processes in development, and misregulation of their expression is associated with human cancer. In the developing embryo, Hox genes are activated sequentially in time and space according to their genomic position within Hox gene clusters. Accumulating evidence implicates both enhancer elements and noncoding RNAs in controlling this spatiotemporal expression of Hox genes, but disentangling their relative contributions is challenging. Here, we identify two cis-regulatory elements (E1 and E2) functioning as shadow enhancers to regulate the early expression of the HoxA genes. Simultaneous deletion of these shadow enhancers in embryonic stem cells leads to impaired activation of HoxA genes upon differentiation, while knockdown of a long noncoding RNA overlapping E1 has no detectable effect on their expression. Although MLL/COMPASS (complex of proteins associated with Set1) family of histone methyltransferases is known to activate transcription of Hox genes in other contexts, we found that individual inactivation of the MLL1-4/COMPASS family members has little effect on early Hox gene activation. Instead, we demonstrate that SET1A/COMPASS is required for full transcriptional activation of multiple Hox genes but functions independently of the E1 and E2 cis-regulatory elements. Our results reveal multiple regulatory layers for Hox genes to fine-tune transcriptional programs essential for development. PMID:28487406

How does spatial extent of fMRI datasets affect independent component analysis decomposition?

PubMed

Aragri, Adriana; Scarabino, Tommaso; Seifritz, Erich; Comani, Silvia; Cirillo, Sossio; Tedeschi, Gioacchino; Esposito, Fabrizio; Di Salle, Francesco

2006-09-01

Spatial independent component analysis (sICA) of functional magnetic resonance imaging (fMRI) time series can generate meaningful activation maps and associated descriptive signals, which are useful to evaluate datasets of the entire brain or selected portions of it. Besides computational implications, variations in the input dataset combined with the multivariate nature of ICA may lead to different spatial or temporal readouts of brain activation phenomena. By reducing and increasing a volume of interest (VOI), we applied sICA to different datasets from real activation experiments with multislice acquisition and single or multiple sensory-motor task-induced blood oxygenation level-dependent (BOLD) signal sources with different spatial and temporal structure. Using receiver operating characteristics (ROC) methodology for accuracy evaluation and multiple regression analysis as benchmark, we compared sICA decompositions of reduced and increased VOI fMRI time-series containing auditory, motor and hemifield visual activation occurring separately or simultaneously in time. Both approaches yielded valid results; however, the results of the increased VOI approach were spatially more accurate compared to the results of the decreased VOI approach. This is consistent with the capability of sICA to take advantage of extended samples of statistical observations and suggests that sICA is more powerful with extended rather than reduced VOI datasets to delineate brain activity. (c) 2006 Wiley-Liss, Inc.

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…

Attentional priorities and access to short-term memory: parietal interactions.

PubMed

Gillebert, Céline R; Dyrholm, Mads; Vangkilde, Signe; Kyllingsbæk, Søren; Peeters, Ronald; Vandenberghe, Rik

2012-09-01

The intraparietal sulcus (IPS) has been implicated in selective attention as well as visual short-term memory (VSTM). To contrast mechanisms of target selection, distracter filtering, and access to VSTM, we combined behavioral testing, computational modeling and functional magnetic resonance imaging. Sixteen healthy subjects participated in a change detection task in which we manipulated both target and distracter set sizes. We directly compared the IPS response as a function of the number of targets and distracters in the display and in VSTM. When distracters were not present, the posterior and middle segments of IPS showed the predicted asymptotic activity increase with an increasing target set size. When distracters were added to a single target, activity also increased as predicted. However, the addition of distracters to multiple targets suppressed both middle and posterior IPS activities, thereby displaying a significant interaction between the two factors. The interaction between target and distracter set size in IPS could not be accounted for by a simple explanation in terms of number of items accessing VSTM. Instead, it led us to a model where items accessing VSTM receive differential weights depending on their behavioral relevance, and secondly, a suppressive effect originates during the selection phase when multiple targets and multiple distracters are simultaneously present. The reverse interaction between target and distracter set size was significant in the right temporoparietal junction (TPJ), where activity was highest for a single target compared to any other condition. Our study reconciles the role of middle IPS in attentional selection and biased competition with its role in VSTM access. Copyright © 2012 Elsevier Inc. All rights reserved.

In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters

PubMed Central

Hama, Kotaro; Provost, Elayne; Baranowski, Timothy C.; Rubinstein, Amy L.; Anderson, Jennifer L.; Leach, Steven D.; Farber, Steven A.

2009-01-01

Optical clarity of larvae makes the zebrafish ideal for real-time analyses of vertebrate organ function through the use of fluorescent reporters of enzymatic activities. A key function of digestive organs is to couple the generation of enzymes with mechanical processes that enable nutrient availability and absorption. However, it has been extremely difficult, and in many cases not possible, to directly observe digestive processes in a live vertebrate. Here we describe a new method to visualize intestinal protein and lipid processing simultaneously in live zebrafish larvae using a quenched fluorescent protein (EnzChek) and phospholipid (PED6). By employing these reagents, we found that wild-type larvae exhibit significant variation in intestinal phospholipase and protease activities within a group but display a strong correlation between the activities within individuals. Furthermore, we found that pancreas function is essential for larval digestive protease activity but not for larval intestinal phospholipase activity. Although fat-free (ffr) mutant larvae were previously described to exhibit impaired lipid processes, we found they also had significantly reduced protease activity. Finally, we selected and evaluated compounds that were previously suggested to have altered phospholipase activity and are known or suspected to have inflammatory effects in the intestinal tract including nonsteroidal anti-inflammatory drugs, and identified a compound that significantly increases intestinal phospholipid processing. Thus the multiple fluorescent reporter-based methodology facilitates the rapid analysis of digestive organ function in live zebrafish larvae. PMID:19056761

Diverse ways of perturbing the human arachidonic acid metabolic network to control inflammation.

PubMed

Meng, Hu; Liu, Ying; Lai, Luhua

2015-08-18

Inflammation and other common disorders including diabetes, cardiovascular disease, and cancer are often the result of several molecular abnormalities and are not likely to be resolved by a traditional single-target drug discovery approach. Though inflammation is a normal bodily reaction, uncontrolled and misdirected inflammation can cause inflammatory diseases such as rheumatoid arthritis and asthma. Nonsteroidal anti-inflammatory drugs including aspirin, ibuprofen, naproxen, or celecoxib are commonly used to relieve aches and pains, but often these drugs have undesirable and sometimes even fatal side effects. To facilitate safer and more effective anti-inflammatory drug discovery, a balanced treatment strategy should be developed at the biological network level. In this Account, we focus on our recent progress in modeling the inflammation-related arachidonic acid (AA) metabolic network and subsequent multiple drug design. We first constructed a mathematical model of inflammation based on experimental data and then applied the model to simulate the effects of commonly used anti-inflammatory drugs. Our results indicated that the model correctly reproduced the established bleeding and cardiovascular side effects. Multitarget optimal intervention (MTOI), a Monte Carlo simulated annealing based computational scheme, was then developed to identify key targets and optimal solutions for controlling inflammation. A number of optimal multitarget strategies were discovered that were both effective and safe and had minimal associated side effects. Experimental studies were performed to evaluate these multitarget control solutions further using different combinations of inhibitors to perturb the network. Consequently, simultaneous control of cyclooxygenase-1 and -2 and leukotriene A4 hydrolase, as well as 5-lipoxygenase and prostaglandin E2 synthase were found to be among the best solutions. A single compound that can bind multiple targets presents advantages including low risk of drug-drug interactions and robustness regarding concentration fluctuations. Thus, we developed strategies for multiple-target drug design and successfully discovered several series of multiple-target inhibitors. Optimal solutions for a disease network often involve mild but simultaneous interventions of multiple targets, which is in accord with the philosophy of traditional Chinese medicine (TCM). To this end, our AA network model can aptly explain TCM anti-inflammatory herbs and formulas at the molecular level. We also aimed to identify activators for several enzymes that appeared to have increased activity based on MTOI outcomes. Strategies were then developed to predict potential allosteric sites and to discover enzyme activators based on our hypothesis that combined treatment with the projected activators and inhibitors could balance different AA network pathways, control inflammation, and reduce associated adverse effects. Our work demonstrates that the integration of network modeling and drug discovery can provide novel solutions for disease control, which also calls for new developments in drug design concepts and methodologies. With the rapid accumulation of quantitative data and knowledge of the molecular networks of disease, we can expect an increase in the development and use of quantitative disease models to facilitate efficient and safe drug discovery.

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.

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.

Langerhans cell histiocytosis manifesting as recurrent simultaneous bilateral spontaneous pneumothorax in early infancy.

PubMed

Alavi, Samin; Ashena, Zahra; Paydar, Afshin; Hemmati, Nadereh

2007-12-01

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by infiltration of either single or multiple organs by a distinct cell type that is S-100 and CD1a positive and contains ultrastructural Birbeck granules on electron microscopy. Historically, LCH included four main clinical forms: Letter-Siwe disease, Hand-Schuller-Christian disease, eosinophilic granuloma (together grouped as histiocytosis) and Hashimoto-Pritzker disease. The writing group of the Histiocytotic Society in 1987 proposed the uniform term of 'Langerhans cell histiocytosis' to encompass all the aforementioned eponymous forms. Lung involvement occurs in up to half of all children with multisystem disease and usually parallels overall disease activity. Spontaneous pneumothorax (SP) occurs in approximately 10% of children with pulmonary disease and may be a fatal complication. Patients with pulmonary LCH are likely predisposed to the development of pneumothorax based on destructive changes in the lung parenchyma. Here, we report a case of multisystem LCH in which the patient presented at 2 months of age because of simultaneous bilateral pneumothorax.

Active multiple plasmon-induced transparencies with detuned asymmetric multi-rectangle resonators

NASA Astrophysics Data System (ADS)

Liu, Dongdong; Wang, Jicheng; Lu, Jian

2016-11-01

The phenomenon of plasmon-induced transparency (PIT) is realized in surface plasmon polariton waveguide at the visible and near-infrared ranges. By adding one and two resonant cavities, the PIT peak(s) was (were) achieved due to destructive interference between the side-coupled rectangle cavity and the bus waveguide. The proposed structures were demonstrated by the finite element method. The simulation results showed that for three rectangle resonators system, not only can we manipulate each single PIT window, but also the double PIT windows simultaneously by adjusting one of the geometrical parameters of the system; for four rectangle resonators system, by changing the widths, the lengths and the refractive index of three cavities simultaneously, we would realize treble PIT peaks and induce an off-to-on PIT optical response. Our novel plasmonic structures and the findings pave the way for new design and engineering of highly integrated optical circuit such as nanoscale optical switching, nanosensor and wavelength-selecting nanostructure.

Drug-Eluting Fibers for HIV-1 Inhibition and Contraception

PubMed Central

Ball, Cameron; Krogstad, Emily; Chaowanachan, Thanyanan; Woodrow, Kim A.

2012-01-01

Multipurpose prevention technologies (MPTs) that simultaneously prevent sexually transmitted infections (STIs) and unintended pregnancy are a global health priority. Combining chemical and physical barriers offers the greatest potential to design effective MPTs, but integrating both functional modalities into a single device has been challenging. Here we show that drug-eluting fiber meshes designed for topical drug delivery can function as a combination chemical and physical barrier MPT. Using FDA-approved polymers, we fabricated nanofiber meshes with tunable fiber size and controlled degradation kinetics that facilitate simultaneous release of multiple agents against HIV-1, HSV-2, and sperm. We observed that drug-loaded meshes inhibited HIV-1 infection in vitro and physically obstructed sperm penetration. Furthermore, we report on a previously unknown activity of glycerol monolaurate (GML) to potently inhibit sperm motility and viability. The application of drug-eluting nanofibers for HIV-1 prevention and sperm inhibition may serve as an innovative platform technology for drug delivery to the lower female reproductive tract. PMID:23209601

Simultaneous and rapid determination of multiple component concentrations in a Kraft liquor process stream

DOEpatents

Li, Jian [Marietta, GA; Chai, Xin Sheng [Atlanta, GA; Zhu, Junyoung [Marietta, GA

2008-06-24

The present invention is a rapid method of determining the concentration of the major components in a chemical stream. The present invention is also a simple, low cost, device of determining the in-situ concentration of the major components in a chemical stream. In particular, the present invention provides a useful method for simultaneously determining the concentrations of sodium hydroxide, sodium sulfide and sodium carbonate in aqueous kraft pulping liquors through use of an attenuated total reflectance (ATR) tunnel flow cell or optical probe capable of producing a ultraviolet absorbency spectrum over a wavelength of 190 to 300 nm. In addition, the present invention eliminates the need for manual sampling and dilution previously required to generate analyzable samples. The inventive method can be used in Kraft pulping operations to control white liquor causticizing efficiency, sulfate reduction efficiency in green liquor, oxidation efficiency for oxidized white liquor and the active and effective alkali charge to kraft pulping operations.

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

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…

Developing a multi-joint upper limb exoskeleton robot for diagnosis, therapy, and outcome evaluation in neurorehabilitation.

PubMed

Ren, Yupeng; Kang, Sang Hoon; Park, Hyung-Soon; Wu, Yi-Ning; Zhang, Li-Qun

2013-05-01

Arm impairments in patients post stroke involve the shoulder, elbow and wrist simultaneously. It is not very clear how patients develop spasticity and reduced range of motion (ROM) at the multiple joints and the abnormal couplings among the multiple joints and the multiple degrees-of-freedom (DOF) during passive movement. It is also not clear how they lose independent control of individual joints/DOFs and coordination among the joints/DOFs during voluntary movement. An upper limb exoskeleton robot, the IntelliArm, which can control the shoulder, elbow, and wrist, was developed, aiming to support clinicians and patients with the following integrated capabilities: 1) quantitative, objective, and comprehensive multi-joint neuromechanical pre-evaluation capabilities aiding multi-joint/DOF diagnosis for individual patients; 2) strenuous and safe passive stretching of hypertonic/deformed arm for loosening up muscles/joints based on the robot-aided diagnosis; 3) (assistive/resistive) active reaching training after passive stretching for regaining/improving motor control ability; and 4) quantitative, objective, and comprehensive neuromechanical outcome evaluation at the level of individual joints/DOFs, multiple joints, and whole arm. Feasibility of the integrated capabilities was demonstrated through experiments with stroke survivors and healthy subjects.

FIA: An Open Forensic Integration Architecture for Composing Digital Evidence

NASA Astrophysics Data System (ADS)

Raghavan, Sriram; Clark, Andrew; Mohay, George

The analysis and value of digital evidence in an investigation has been the domain of discourse in the digital forensic community for several years. While many works have considered different approaches to model digital evidence, a comprehensive understanding of the process of merging different evidence items recovered during a forensic analysis is still a distant dream. With the advent of modern technologies, pro-active measures are integral to keeping abreast of all forms of cyber crimes and attacks. This paper motivates the need to formalize the process of analyzing digital evidence from multiple sources simultaneously. In this paper, we present the forensic integration architecture (FIA) which provides a framework for abstracting the evidence source and storage format information from digital evidence and explores the concept of integrating evidence information from multiple sources. The FIA architecture identifies evidence information from multiple sources that enables an investigator to build theories to reconstruct the past. FIA is hierarchically composed of multiple layers and adopts a technology independent approach. FIA is also open and extensible making it simple to adapt to technological changes. We present a case study using a hypothetical car theft case to demonstrate the concepts and illustrate the value it brings into the field.

Parallel updating and weighting of multiple spatial maps for visual stability during whole body motion

PubMed Central

Medendorp, W. P.

2015-01-01

It is known that the brain uses multiple reference frames to code spatial information, including eye-centered and body-centered frames. When we move our body in space, these internal representations are no longer in register with external space, unless they are actively updated. Whether the brain updates multiple spatial representations in parallel, or whether it restricts its updating mechanisms to a single reference frame from which other representations are constructed, remains an open question. We developed an optimal integration model to simulate the updating of visual space across body motion in multiple or single reference frames. To test this model, we designed an experiment in which participants had to remember the location of a briefly presented target while being translated sideways. The behavioral responses were in agreement with a model that uses a combination of eye- and body-centered representations, weighted according to the reliability in which the target location is stored and updated in each reference frame. Our findings suggest that the brain simultaneously updates multiple spatial representations across body motion. Because both representations are kept in sync, they can be optimally combined to provide a more precise estimate of visual locations in space than based on single-frame updating mechanisms. PMID:26490289

3-D CSEM data inversion algorithm based on simultaneously active multiple transmitters concept

NASA Astrophysics Data System (ADS)

Dehiya, Rahul; Singh, Arun; Gupta, Pravin Kumar; Israil, Mohammad

2017-05-01

We present an algorithm for efficient 3-D inversion of marine controlled-source electromagnetic data. The efficiency is achieved by exploiting the redundancy in data. The data redundancy is reduced by compressing the data through stacking of the response of transmitters which are in close proximity. This stacking is equivalent to synthesizing the data as if the multiple transmitters are simultaneously active. The redundancy in data, arising due to close transmitter spacing, has been studied through singular value analysis of the Jacobian formed in 1-D inversion. This study reveals that the transmitter spacing of 100 m, typically used in marine data acquisition, does result in redundancy in the data. In the proposed algorithm, the data are compressed through stacking which leads to both computational advantage and reduction in noise. The performance of the algorithm for noisy data is demonstrated through the studies on two types of noise, viz., uncorrelated additive noise and correlated non-additive noise. It is observed that in case of uncorrelated additive noise, up to a moderately high (10 percent) noise level the algorithm addresses the noise as effectively as the traditional full data inversion. However, when the noise level in the data is high (20 percent), the algorithm outperforms the traditional full data inversion in terms of data misfit. Similar results are obtained in case of correlated non-additive noise and the algorithm performs better if the level of noise is high. The inversion results of a real field data set are also presented to demonstrate the robustness of the algorithm. The significant computational advantage in all cases presented makes this algorithm a better choice.

Older adults' transportation walking: a cross-sectional study on the cumulative influence of physical environmental factors.

PubMed

Van Cauwenberg, Jelle; Clarys, Peter; De Bourdeaudhuij, Ilse; Van Holle, Veerle; Verté, Dominique; De Witte, Nico; De Donder, Liesbeth; Buffel, Tine; Dury, Sarah; Deforche, Benedicte

2013-08-14

The physical environment may play a crucial role in promoting older adults' walking for transportation. However, previous studies on relationships between the physical environment and older adults' physical activity behaviors have reported inconsistent findings. A possible explanation for these inconsistencies is the focus upon studying environmental factors separately rather than simultaneously. The current study aimed to investigate the cumulative influence of perceived favorable environmental factors on older adults' walking for transportation. Additionally, the moderating effect of perceived distance to destinations on this relationship was studied. The sample was comprised of 50,685 non-institutionalized older adults residing in Flanders (Belgium). Cross-sectional data on demographics, environmental perceptions and frequency of walking for transportation were collected by self-administered questionnaires in the period 2004-2010. Perceived distance to destinations was categorized into short, medium, and large distance to destinations. An environmental index (=a sum of favorable environmental factors, ranging from 0 to 7) was constructed to investigate the cumulative influence of favorable environmental factors. Multilevel logistic regression analyses were applied to predict probabilities of daily walking for transportation. For short distance to destinations, probability of daily walking for transportation was significantly higher when seven compared to three, four or five favorable environmental factors were present. For medium distance to destinations, probabilities significantly increased for an increase from zero to four favorable environmental factors. For large distance to destinations, no relationship between the environmental index and walking for transportation was observed. Our findings suggest that the presence of multiple favorable environmental factors can motivate older adults to walk medium distances to facilities. Future research should focus upon the relationship between older adults' physical activity and multiple environmental factors simultaneously instead of separately.

Interactions between Meteorus pulchricornis and Spodoptera exigua Multiple Nucleopolyhedrovirus

PubMed Central

Guo, Hui-Fang; Fang, Ji-Chao; Zhong, Wan-Fang; Liu, Bao-Sheng

2013-01-01

Baculoviruses may interact with parasitoids in the same host. A previous study has shown that infection of larvae with Spodoptera litura nucleopolyhedrovirus (SpltNPV) was deleterious to the survival and development of Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae). In this paper, the interactions between M. pulchricornis and Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) in Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), a permissive host of the virus and parasitoid, were investigated. The results showed that the effect of M. pulchricornis on SeMNPV and the effect of the virus on the parasitoid both depended on the concentration of the virus and the interval between viral infection and parasitism. Whether S. exigua was treated with the parasitoid and virus simultaneously or 1 day apart, the biological activities of 105, 106, and 107 OBs/mL SeMNPV were all significantly improved by M. pulchricornis. In contrast, the biological activity of 103 OBs/mL SeMNPV was significantly decreased when the host was exposed to the virus and parasitoid simultaneously. Regarding the impact of SeMNPV on M. pulchricornis, exposing the host to the parasitoid and SeMNPV with concentrations lower than 106 occlusion bodies (OBs)/mL produced no negative effects on the parasitoid. The results also showed that ingestion of SeMNPV by adult stage M. pulchricornis significantly increased the number of parasitoid offspring that successfully emerged from the host. Furthermore, M. pulchricornis was found to transmit SeMNPV among populations of S. exigua. Taken together, these findings indicate that M. pulchricornis integrated with an appropriate concentration of SeMNPV has the potential to improve the efficacy of biological control against S. exigua. PMID:23885801

Interactions between Meteorus pulchricornis and Spodoptera exigua multiple nucleopolyhedrovirus.

PubMed

Guo, Hui-Fang; Fang, Ji-Chao; Zhong, Wan-Fang; Liu, Bao-Sheng

2013-01-01

Baculoviruses may interact with parasitoids in the same host. A previous study has shown that infection of larvae with Spodoptera litura nucleopolyhedrovirus (SpltNPV) was deleterious to the survival and development of Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae). In this paper, the interactions between M. pulchricornis and Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) in Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), a permissive host of the virus and parasitoid, were investigated. The results showed that the effect of M. pulchricornis on SeMNPV and the effect of the virus on the parasitoid both depended on the concentration of the virus and the interval between viral infection and parasitism. Whether S. exigua was treated with the parasitoid and virus simultaneously or 1 day apart, the biological activities of 10(5), 10(6), and 10(7) OBs/mL SeMNPV were all significantly improved by M. pulchricornis. In contrast, the biological activity of 10(3) OBs/mL SeMNPV was significantly decreased when the host was exposed to the virus and parasitoid simultaneously. Regarding the impact of SeMNPV on M. pulchricornis, exposing the host to the parasitoid and SeMNPV with concentrations lower than 10(6) occlusion bodies (OBs)/mL produced no negative effects on the parasitoid. The results also showed that ingestion of SeMNPV by adult stage M. pulchricornis significantly increased the number of parasitoid offspring that successfully emerged from the host. Furthermore, M. pulchricornis was found to transmit SeMNPV among populations of S. exigua. Taken together, these findings indicate that M. pulchricornis integrated with an appropriate concentration of SeMNPV has the potential to improve the efficacy of biological control against S. exigua.

Validation of a patch clamp screening protocol that simultaneously measures compound activity in multiple states of the voltage-gated sodium channel Nav1.2.

PubMed

Liu, Yi; Beck, Edward J; Flores, Christopher M

2011-12-01

Hyperactivity of voltage-gated sodium channels underlies, at least in part, a range of pathological states, including pain and epilepsy. Selective blockers of these channels may offer effective treatment of such disorders. Currently employed methods to screen for sodium channel blockers, however, are inadequate to rationally identify mechanistically diverse blockers, limiting the potential range of indications that may be treated by such agents. Here, we describe an improved patch clamp screening assay that increases the mechanistic diversity of sodium channel blockers being identified. Using QPatch HT, a medium-throughput, automated patch clamp system, we tested three common sodium channel blockers (phenytoin, lidocaine, and tetrodotoxin) with distinct mechanistic profiles at Nav1.2. The single-voltage protocol employed in this assay simultaneously measured the compound activity in multiple states, including the slow inactivated state, of the channel. A long compound incubation period (10 s) was introduced during channel inactivation to increase the probability of identifying "slow binders." As such, phenytoin, which preferentially binds with slow kinetics to the fast inactivated state, exhibited significantly higher potency than that obtained from a brief exposure (100 ms) used in typical assays. This assay also successfully detected the use-dependent block of tetrodotoxin, a well-documented property of this molecule yet unobserved in typical patch clamp protocols. These results indicate that the assay described here can increase the likelihood of identification and mechanistic diversity of sodium channel blockers from a primary screen. It can also be used to efficiently guide the in vitro optimization of leads that retain the desired mechanistic properties. © MARY ANN LIEBERT, INC.

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.

Older adults’ transportation walking: a cross-sectional study on the cumulative influence of physical environmental factors

PubMed Central

2013-01-01

Background The physical environment may play a crucial role in promoting older adults’ walking for transportation. However, previous studies on relationships between the physical environment and older adults’ physical activity behaviors have reported inconsistent findings. A possible explanation for these inconsistencies is the focus upon studying environmental factors separately rather than simultaneously. The current study aimed to investigate the cumulative influence of perceived favorable environmental factors on older adults’ walking for transportation. Additionally, the moderating effect of perceived distance to destinations on this relationship was studied. Methods The sample was comprised of 50,685 non-institutionalized older adults residing in Flanders (Belgium). Cross-sectional data on demographics, environmental perceptions and frequency of walking for transportation were collected by self-administered questionnaires in the period 2004-2010. Perceived distance to destinations was categorized into short, medium, and large distance to destinations. An environmental index (=a sum of favorable environmental factors, ranging from 0 to 7) was constructed to investigate the cumulative influence of favorable environmental factors. Multilevel logistic regression analyses were applied to predict probabilities of daily walking for transportation. Results For short distance to destinations, probability of daily walking for transportation was significantly higher when seven compared to three, four or five favorable environmental factors were present. For medium distance to destinations, probabilities significantly increased for an increase from zero to four favorable environmental factors. For large distance to destinations, no relationship between the environmental index and walking for transportation was observed. Conclusions Our findings suggest that the presence of multiple favorable environmental factors can motivate older adults to walk medium distances to facilities. Future research should focus upon the relationship between older adults’ physical activity and multiple environmental factors simultaneously instead of separately. PMID:23945285

Cytokinetically quiescent (G0/G1) human multiple myeloma cells are susceptible to simultaneous inhibition of Chk1 and MEK1/2

PubMed Central

Pei, Xin-Yan; Dai, Yun; Youssefian, Leena E.; Chen, Shuang; Bodie, Wesley W.; Takabatake, Yukie; Felthousen, Jessica; Almenara, Jorge A.; Kramer, Lora B.; Dent, Paul

2011-01-01

Effects of Chk1 and MEK1/2 inhibition were investigated in cytokinetically quiescent multiple myeloma (MM) and primary CD138+ cells. Coexposure to the Chk1 and MEK1/2 inhibitors AZD7762 and selumetinib (AZD6244) robustly induced apoptosis in various MM cells and CD138+ primary samples, but spared normal CD138− and CD34+ cells. Furthermore, Chk1/MEK1/2 inhibitor treatment of asynchronized cells induced G0/G1 arrest and increased apoptosis in all cell-cycle phases, including G0/G1. To determine whether this regimen is active against quiescent G0/G1 MM cells, cells were cultured in low-serum medium to enrich the G0/G1 population. G0/G1–enriched cells exhibited diminished sensitivity to conventional agents (eg, Taxol and VP-16) but significantly increased susceptibility to Chk1 ± MEK1/2 inhibitors or Chk1 shRNA knock-down. These events were associated with increased γH2A.X expression/foci formation and Bim up-regulation, whereas Bim shRNA knock-down markedly attenuated lethality. Immunofluorescent analysis of G0/G1–enriched or primary MM cells demonstrated colocalization of activated caspase-3 and the quiescent (G0) marker statin, a nuclear envelope protein. Finally, Chk1/MEK1/2 inhibition increased cell death in the Hoechst-positive (Hst+), low pyronin Y (PY)–staining (2N Hst+/PY−) G0 population and in sorted small side-population (SSP) MM cells. These findings provide evidence that cytokinetically quiescent MM cells are highly susceptible to simultaneous Chk1 and MEK1/2 inhibition. PMID:21911831

Cytokinetically quiescent (G0/G1) human multiple myeloma cells are susceptible to simultaneous inhibition of Chk1 and MEK1/2.

PubMed

Pei, Xin-Yan; Dai, Yun; Youssefian, Leena E; Chen, Shuang; Bodie, Wesley W; Takabatake, Yukie; Felthousen, Jessica; Almenara, Jorge A; Kramer, Lora B; Dent, Paul; Grant, Steven

2011-11-10

Effects of Chk1 and MEK1/2 inhibition were investigated in cytokinetically quiescent multiple myeloma (MM) and primary CD138(+) cells. Coexposure to the Chk1 and MEK1/2 inhibitors AZD7762 and selumetinib (AZD6244) robustly induced apoptosis in various MM cells and CD138(+) primary samples, but spared normal CD138(-) and CD34(+) cells. Furthermore, Chk1/MEK1/2 inhibitor treatment of asynchronized cells induced G(0)/G(1) arrest and increased apoptosis in all cell-cycle phases, including G(0)/G(1). To determine whether this regimen is active against quiescent G(0)/G(1) MM cells, cells were cultured in low-serum medium to enrich the G(0)/G(1) population. G(0)/G(1)-enriched cells exhibited diminished sensitivity to conventional agents (eg, Taxol and VP-16) but significantly increased susceptibility to Chk1 ± MEK1/2 inhibitors or Chk1 shRNA knock-down. These events were associated with increased γH2A.X expression/foci formation and Bim up-regulation, whereas Bim shRNA knock-down markedly attenuated lethality. Immunofluorescent analysis of G(0)/G(1)-enriched or primary MM cells demonstrated colocalization of activated caspase-3 and the quiescent (G(0)) marker statin, a nuclear envelope protein. Finally, Chk1/MEK1/2 inhibition increased cell death in the Hoechst-positive (Hst(+)), low pyronin Y (PY)-staining (2N Hst(+)/PY(-)) G(0) population and in sorted small side-population (SSP) MM cells. These findings provide evidence that cytokinetically quiescent MM cells are highly susceptible to simultaneous Chk1 and MEK1/2 inhibition.

Long-range dismount activity classification: LODAC

NASA Astrophysics Data System (ADS)

Garagic, Denis; Peskoe, Jacob; Liu, Fang; Cuevas, Manuel; Freeman, Andrew M.; Rhodes, Bradley J.

2014-06-01

Continuous classification of dismount types (including gender, age, ethnicity) and their activities (such as walking, running) evolving over space and time is challenging. Limited sensor resolution (often exacerbated as a function of platform standoff distance) and clutter from shadows in dense target environments, unfavorable environmental conditions, and the normal properties of real data all contribute to the challenge. The unique and innovative aspect of our approach is a synthesis of multimodal signal processing with incremental non-parametric, hierarchical Bayesian machine learning methods to create a new kind of target classification architecture. This architecture is designed from the ground up to optimally exploit correlations among the multiple sensing modalities (multimodal data fusion) and rapidly and continuously learns (online self-tuning) patterns of distinct classes of dismounts given little a priori information. This increases classification performance in the presence of challenges posed by anti-access/area denial (A2/AD) sensing. To fuse multimodal features, Long-range Dismount Activity Classification (LODAC) develops a novel statistical information theoretic approach for multimodal data fusion that jointly models multimodal data (i.e., a probabilistic model for cross-modal signal generation) and discovers the critical cross-modal correlations by identifying components (features) with maximal mutual information (MI) which is efficiently estimated using non-parametric entropy models. LODAC develops a generic probabilistic pattern learning and classification framework based on a new class of hierarchical Bayesian learning algorithms for efficiently discovering recurring patterns (classes of dismounts) in multiple simultaneous time series (sensor modalities) at multiple levels of feature granularity.

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.

Current State of Overlapping, Concurrent, and Multiple-Room Surgery in Otolaryngology: A National Survey.

PubMed

Cognetti, David M; Nussenbaum, Brian; Brenner, Michael J; Chi, David H; McCormick, Michael E; Venkatraman, Giri; Zhan, Tingting; McKinlay, Alex J

2017-12-01

Objective Multiple-room surgery has gained attention due to reports in the lay press scrutinizing the activity, with hospitals and the government collecting data on current practice. We studied practices and attitudes toward multiple-room surgery in otolaryngology. Methods A survey was developed by members of the Patient Safety and Quality Improvement Committee of the American Academy of Otolaryngology-Head and Neck Surgery. The survey was distributed to members of the Academy and included questions on demographics, current practices, and opinions regarding multiple-room surgery. The survey was designed to capture the spectrum of multidisciplinary, overlapping, and simultaneous/concurrent surgery practices. Data were collected via SurveyMonkey. Results A total of 907 of 9520 members completed the survey. Of the respondents, 40.4% reported performing some form of multiple-room surgery. Multiple-room surgery is more common amongst subspecialists than general otolaryngologists. Most believed that regulations disallowing multiple-room surgery would result in an increase in late starts (73.5%), an increase in the time to schedule surgery (84.5%), a detriment to residency training (63.1%), and no improvement in patient safety (60%.) Discussion Multiple-room surgery is common among responding otolaryngologists. Most respondents consider the practice to serve a role in facilitating access, efficiency, and training. Implications for Practice Due to recent attention placed on multiple-room surgery, institutions are reviewing policies regarding the practice. This survey suggests that policy changes that restrict multiple-room surgery must consider a potential unintended negative impact on patient care and access.

Physicochemical compatibility of mixtures of dornase alfa and tobramycin containing nebulizer solutions.

PubMed

Krämer, Irene; Schwabe, Astrid; Lichtinghagen, Ralf; Kamin, Wolfgang

2009-02-01

Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of the nebulizer solution dornase alfa (Pulmozyme) with tobramycin nebulizer solutions (TOBI and GERNEBCIN 80 mg) are physico-chemically compatible. Drug combinations were prepared by mixing the content of one respule Pulmozyme with either one respule TOBI or one ampoule GERNEBCIN 80 mg. Test solutions were stored at room temperature and exposed to light. Dornase alfa activity and tobramycin concentrations were determined by using a kinetic colorimetric DNase activity assay and a fluorescence immunoassay, respectively. Physical compatibility was determined by visual inspection and measurements of pH and osmolality. Tobramycin concentration was not affected by mixing the drug products. In spite of the high variability of the dornase alfa potency assay, it is obvious that activity is especially affected by sodium metabisulfite, used as excipient in GERNEBCIN. Patients should be advised, not to mix Pulmozyme with GERNEBCIN because of the incompatibility reaction. Further analytical studies are needed in order to determine the integrity and activity of dornase alfa in mixtures of Pulmozyme with TOBI. Finally clinical studies are necessary in order to demonstrate equivalent efficacy and safety of simultaneous inhalation in comparison to consecutive inhalation of both drugs. (c) 2008 Wiley-Liss, Inc.

Chemical Inhibition of a Subset of Arabidopsis thaliana GSK3-like Kinases Activates Brassinosteroid Signaling

PubMed Central

De Rybel, Bert; Audenaert, Dominique; Vert, Grégory; Rozhon, Wilfried; Mayerhofer, Juliane; Peelman, Frank; Coutuer, Silvie; Denayer, Tinneke; Jansen, Leentje; Nguyen, Long; Vanhoutte, Isabelle; Beemster, Gerrit T.S.; Vleminckx, Kris; Jonak, Claudia; Chory, Joanne; Inzé, Dirk; Russinova, Eugenia; Beeckman, Tom

2016-01-01

SUMMARY Glycogen synthase kinase 3 (GSK3) is a key regulator in signaling pathways in both animals and plants. Three Arabidopsis thaliana GSK3s are shown to be related to brassinosteroid (BR) signaling. In a phenotype-based compound screen we identified bikinin, a small molecule that activates BR signaling downstream of the BR receptor. Bikinin directly binds the GSK3 BIN2 and acts as an ATP competitor. Furthermore, bikinin inhibits the activity of six other Arabidopsis GSK3s. Genome-wide transcript analyses demonstrate that simultaneous inhibition of seven GSK3s is sufficient to activate BR responses. Our data suggest that GSK3 inhibition is the sole activation mode of BR signaling and argues against GSK3-independent BR responses in Arabidopsis. The opportunity to generate multiple and conditional knockouts in key regulators in the BR signaling pathway by bikinin represents a useful tool to further unravel regulatory mechanisms. PMID:19549598

Design of activated serine-containing catalytic triads with atomic level accuracy

PubMed Central

Rajagopalan, Sridharan; Wang, Chu; Yu, Kai; Kuzin, Alexandre P.; Richter, Florian; Lew, Scott; Miklos, Aleksandr E.; Matthews, Megan L.; Seetharaman, Jayaraman; Su, Min; Hunt, John. F.; Cravatt, Benjamin F.; Baker, David

2014-01-01

A challenge in the computational design of enzymes is that multiple properties must be simultaneously optimized -- substrate-binding, transition state stabilization, and product release -- and this has limited the absolute activity of successful designs. Here, we focus on a single critical property of many enzymes: the nucleophilicity of an active site residue that initiates catalysis. We design proteins with idealized serine-containing catalytic triads, and assess their nucleophilicity directly in native biological systems using activity-based organophosphate probes. Crystal structures of the most successful designs show unprecedented agreement with computational models, including extensive hydrogen bonding networks between the catalytic triad (or quartet) residues, and mutagenesis experiments demonstrate that these networks are critical for serine activation and organophosphate-reactivity. Following optimization by yeast-display, the designs react with organophosphate probes at rates comparable to natural serine hydrolases. Co-crystal structures with diisopropyl fluorophosphate bound to the serine nucleophile suggest the designs could provide the basis for a new class of organophosphate captures agents. PMID:24705591

Rural Residents’ Perspectives on Multiple Morbidity Management and Disease Prevention

PubMed Central

Bardach, Shoshana H.; Schoenberg, Nancy E.; Tarasenko, Yelena N.; Fleming, Steven T.

2013-01-01

Middle-aged and older adults often experience several simultaneously occurring chronic conditions or “multiple morbidity” (MM). The task of both managing MM and preventing chronic conditions can be overwhelming, particularly in populations with high disease burdens, low socioeconomic status, and health care provider shortages. This article sought to understand Appalachian residents’ perspectives on MM management and prevention. Forty-one rural Appalachian residents aged 50 and above with MM were interviewed about disease management and colorectal cancer (CRC) prevention. Transcripts were examined for overall analytic categories and coded using techniques to enhance transferability and rigor. Participants indicate facing various challenges to prevention due, in part, to conditions within their rural environment. Patients and providers spend significant time and energy on MM management, often precluding prevention activities. This article discusses implications of MM management for CRC prevention and strategies to increase disease prevention among this rural, vulnerable population burdened by MM. PMID:23833393

Using Priced Options to Solve the Exposure Problem in Sequential Auctions

NASA Astrophysics Data System (ADS)

Mous, Lonneke; Robu, Valentin; La Poutré, Han

This paper studies the benefits of using priced options for solving the exposure problem that bidders with valuation synergies face when participating in multiple, sequential auctions. We consider a model in which complementary-valued items are auctioned sequentially by different sellers, who have the choice of either selling their good directly or through a priced option, after fixing its exercise price. We analyze this model from a decision-theoretic perspective and we show, for a setting where the competition is formed by local bidders, that using options can increase the expected profit for both buyers and sellers. Furthermore, we derive the equations that provide minimum and maximum bounds between which a synergy buyer's bids should fall in order for both sides to have an incentive to use the options mechanism. Next, we perform an experimental analysis of a market in which multiple synergy bidders are active simultaneously.

A Mechanistic Model for Cooperative Behavior of Co-transcribing RNA Polymerases

PubMed Central

Heberling, Tamra; Davis, Lisa; Gedeon, Jakub; Morgan, Charles; Gedeon, Tomáš

2016-01-01

In fast-transcribing prokaryotic genes, such as an rrn gene in Escherichia coli, many RNA polymerases (RNAPs) transcribe the DNA simultaneously. Active elongation of RNAPs is often interrupted by pauses, which has been observed to cause RNAP traffic jams; yet some studies indicate that elongation seems to be faster in the presence of multiple RNAPs than elongation by a single RNAP. We propose that an interaction between RNAPs via the torque produced by RNAP motion on helically twisted DNA can explain this apparent paradox. We have incorporated the torque mechanism into a stochastic model and simulated transcription both with and without torque. Simulation results illustrate that the torque causes shorter pause durations and fewer collisions between polymerases. Our results suggest that the torsional interaction of RNAPs is an important mechanism in maintaining fast transcription times, and that transcription should be viewed as a cooperative group effort by multiple polymerases. PMID:27517607

Multivariate Autoregressive Modeling and Granger Causality Analysis of Multiple Spike Trains

PubMed Central

Krumin, Michael; Shoham, Shy

2010-01-01

Recent years have seen the emergence of microelectrode arrays and optical methods allowing simultaneous recording of spiking activity from populations of neurons in various parts of the nervous system. The analysis of multiple neural spike train data could benefit significantly from existing methods for multivariate time-series analysis which have proven to be very powerful in the modeling and analysis of continuous neural signals like EEG signals. However, those methods have not generally been well adapted to point processes. Here, we use our recent results on correlation distortions in multivariate Linear-Nonlinear-Poisson spiking neuron models to derive generalized Yule-Walker-type equations for fitting ‘‘hidden” Multivariate Autoregressive models. We use this new framework to perform Granger causality analysis in order to extract the directed information flow pattern in networks of simulated spiking neurons. We discuss the relative merits and limitations of the new method. PMID:20454705

Three-dimensional imaging and photostimulation by remote-focusing and holographic light patterning

PubMed Central

Anselmi, Francesca; Ventalon, Cathie; Bègue, Aurélien; Ogden, David; Emiliani, Valentina

2011-01-01

Access to three-dimensional structures in the brain is fundamental to probe signal processing at multiple levels, from integration of synaptic inputs to network activity mapping. Here, we present an optical method for independent three-dimensional photoactivation and imaging by combination of digital holography with remote-focusing. We experimentally demonstrate compensation of spherical aberration for out-of-focus imaging in a range of at least 300 μm, as well as scanless imaging along oblique planes. We apply this method to perform functional imaging along tilted dendrites of hippocampal pyramidal neurons in brain slices, after photostimulation by multiple spots glutamate uncaging. By bringing extended portions of tilted dendrites simultaneously in-focus, we monitor the spatial extent of dendritic calcium signals, showing a shift from a widespread to a spatially confined response upon blockage of voltage-gated Na+ channels. PMID:22074779

Software-defined networking control plane for seamless integration of multiple silicon photonic switches in Datacom networks.

PubMed

Shen, Yiwen; Hattink, Maarten H N; Samadi, Payman; Cheng, Qixiang; Hu, Ziyiz; Gazman, Alexander; Bergman, Keren

2018-04-16

Silicon photonics based switches offer an effective option for the delivery of dynamic bandwidth for future large-scale Datacom systems while maintaining scalable energy efficiency. The integration of a silicon photonics-based optical switching fabric within electronic Datacom architectures requires novel network topologies and arbitration strategies to effectively manage the active elements in the network. We present a scalable software-defined networking control plane to integrate silicon photonic based switches with conventional Ethernet or InfiniBand networks. Our software-defined control plane manages both electronic packet switches and multiple silicon photonic switches for simultaneous packet and circuit switching. We built an experimental Dragonfly network testbed with 16 electronic packet switches and 2 silicon photonic switches to evaluate our control plane. Observed latencies occupied by each step of the switching procedure demonstrate a total of 344 µs control plane latency for data-center and high performance computing platforms.

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.

Simultaneous quantification of 25 active constituents in the total flavonoids extract from Herba Desmodii Styracifolii by high-performance liquid chromatography with electrospray ionization tandem mass spectrometry.

PubMed

Guo, Panpan; Yan, Wenying; Han, Qingjie; Wang, Chunying; Zhang, Zijian

2015-04-01

A sensitive and selective high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry method has been developed and validated for the simultaneous determination of 25 active constituents, including 21 flavonoids and four phenolic acids in the total flavonoids extract from Herba Desmodii Styracifolii for the first time. Among the 25 compounds, seven compounds including caffeic acid, acacetin, genistein, genistin, diosmetin, diosmin and hesperidin were identified and quantified for the first time in Herba Desmodii Styracifolii. Chromatographic separation was accomplished on a ZORBAX SB-C18 (250 mm×4.6 mm, 5.0 μm) column using gradient elution of methanol and 0.1‰ acetic acid v/v at a flow rate of 1.0 mL/min. The identification and quantification of the analytes were achieved using negative electrospray ionization mass spectrometry in multiple-reaction monitoring mode. The method was fully validated in terms of limits of detection and quantification, linearity, precision and accuracy. The results indicated that the developed method is simple, rapid, specific and reliable. Furthermore, the developed method was successfully applied to quantify the 25 active components in six batches of total flavonoids extract from Herba Desmodii Styracifolii. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiobjective optimization of combinatorial libraries.

PubMed

Agrafiotis, D K

2002-01-01

Combinatorial chemistry and high-throughput screening have caused a fundamental shift in the way chemists contemplate experiments. Designing a combinatorial library is a controversial art that involves a heterogeneous mix of chemistry, mathematics, economics, experience, and intuition. Although there seems to be little agreement as to what constitutes an ideal library, one thing is certain: only one property or measure seldom defines the quality of the design. In most real-world applications, a good experiment requires the simultaneous optimization of several, often conflicting, design objectives, some of which may be vague and uncertain. In this paper, we discuss a class of algorithms for subset selection rooted in the principles of multiobjective optimization. Our approach is to employ an objective function that encodes all of the desired selection criteria, and then use a simulated annealing or evolutionary approach to identify the optimal (or a nearly optimal) subset from among the vast number of possibilities. Many design criteria can be accommodated, including diversity, similarity to known actives, predicted activity and/or selectivity determined by quantitative structure-activity relationship (QSAR) models or receptor binding models, enforcement of certain property distributions, reagent cost and availability, and many others. The method is robust, convergent, and extensible, offers the user full control over the relative significance of the various objectives in the final design, and permits the simultaneous selection of compounds from multiple libraries in full- or sparse-array format.

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.

Simultaneous imaging of neural activity in three dimensions

PubMed Central

Quirin, Sean; Jackson, Jesse; Peterka, Darcy S.; Yuste, Rafael

2014-01-01

We introduce a scanless optical method to image neuronal activity in three dimensions simultaneously. Using a spatial light modulator and a custom-designed phase mask, we illuminate and collect light simultaneously from different focal planes and perform calcium imaging of neuronal activity in vitro and in vivo. This method, combining structured illumination with volume projection imaging, could be used as a technological platform for brain activity mapping. PMID:24772066

Ultrasonic waste activated sludge disintegration for recovering multiple nutrients for biofuel production.

PubMed

Xie, Guo-Jun; Liu, Bing-Feng; Wang, Qilin; Ding, Jie; Ren, Nan-Qi

2016-04-15

Waste activated sludge is a valuable resource containing multiple nutrients, but is currently treated and disposed of as an important source of pollution. In this work, waste activated sludge after ultrasound pretreatment was reused as multiple nutrients for biofuel production. The nutrients trapped in sludge floc were transferred into liquid medium by ultrasonic disintegration during first 30 min, while further increase of pretreatment time only resulted in slight increase of nutrients release. Hydrogen production by Ethanoligenens harbinense B49 from glucose significantly increased with the concentration of ultrasonic sludge, and reached maximum yield of 1.97 mol H2/mol glucose at sludge concentration of 7.75 g volatile suspended solids/l. Without addition of any other chemicals, waste molasses rich in carbohydrate was efficiently turned into hydrogen with yield of 189.34 ml H2/g total sugar by E. harbinense B49 using ultrasonic sludge as nutrients. The results also showed that hydrogen production using pretreated sludge as multiple nutrients was higher than those using standard nutrients. Acetic acid produced by E. harbinense B49 together with the residual nutrients in the liquid medium were further converted into hydrogen (271.36 ml H2/g total sugar) by Rhodopseudomonas faecalis RLD-53 through photo fermentation, while ethanol was the sole end product with yield of 220.26 mg/g total sugar. Thus, pretreated sludge was an efficient nutrients source for biofuel production, which could replace the standard nutrients. This research provided a novel strategy to achieve environmental friendly sludge disposal and simultaneous efficient biofuel recovery from organic waste. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dual Target Search is Neither Purely Simultaneous nor Purely Successive.

PubMed

Cave, Kyle R; Menneer, Tamaryn; Nomani, Mohammad S; Stroud, Michael J; Donnelly, Nick

2017-08-31

Previous research shows that visual search for two different targets is less efficient than search for a single target. Stroud, Menneer, Cave and Donnelly (2012) concluded that two target colours are represented separately based on modeling the fixation patterns. Although those analyses provide evidence for two separate target representations, they do not show whether participants search simultaneously for both targets, or first search for one target and then the other. Some studies suggest that multiple target representations are simultaneously active, while others indicate that search can be voluntarily simultaneous, or switching, or a mixture of both. Stroud et al.'s participants were not explicitly instructed to use any particular strategy. These data were revisited to determine which strategy was employed. Each fixated item was categorised according to whether its colour was more similar to one target or the other. Once an item similar to one target is fixated, the next fixated item is more likely to be similar to that target than the other, showing that at a given moment during search, one target is generally favoured. However, the search for one target is not completed before search for the other begins. Instead, there are often short runs of one or two fixations to distractors similar to one target, with each run followed by a switch to the other target. Thus, the results suggest that one target is more highly weighted than the other at any given time, but not to the extent that search is purely successive.

The relationship of social support with treatment adherence and weight loss in Latinos with type 2 diabetes.

PubMed

Marquez, Becky; Anderson, Andrea; Wing, Rena R; West, Delia S; Newton, Robert L; Meacham, Maria; Hazuda, Helen P; Peters, Anne; Montez, Maria G; Broyles, Stephanie T; Walker, Martha; Evans-Hudsnall, Gina

2016-03-01

Little is known about the effects of social support on weight loss in Latinos. This study determined whether sex moderated and treatment adherence mediated the association between social support and weight loss. Data from 278 Latino males and females with type 2 diabetes in the Intensive Lifestyle Intervention of the Look AHEAD trial were analyzed. Multivariable modeling tested for moderation and parallel multiple mediator modeling simultaneously tested the mediating effects of adherence to physical activity, diet, and session attendance on the relationship between baseline social support and percent weight loss at 1 year. Social support for physical activity (having family and friends join in physical activity) was related to weight loss. Adherence to physical activity was related to both social support for physical activity and weight loss. Sex did not moderate these relationships. Adherence to physical activity completely mediated the relationship between social support for physical activity and weight loss. Increasing companionship for physical activity may be an effective intervention strategy to promote behaviors important for weight loss among Latinos. © 2016 The Obesity Society.

The relationship of social support with treatment adherence and weight loss in Latinos with type 2 diabetes

PubMed Central

Marquez, Becky; Anderson, Andrea; Wing, Rena R.; West, Delia S.; Newton, Robert L.; Meacham, Maria; Hazuda, Helen P.; Peters, Anne; Montez, Maria G.; Broyles, Stephanie T.; Walker, Martha; Evans-Hudsnall, Gina

2016-01-01

Objective Little is known about the effects of social support on weight loss in Latinos. This study determined whether sex moderated and treatment adherence mediated the association between social support and weight loss. Methods Data from 278 Latino males and females with type 2 diabetes in the Intensive Lifestyle Intervention of the Look AHEAD trial were analyzed. Multivariable modeling tested for moderation and parallel multiple mediator modeling simultaneously tested the mediating effects of adherence to physical activity, diet, and session attendance on the relationship between baseline social support and percent weight loss at 1 year. Results Social support for physical activity (having family and friends join in physical activity) was related to weight loss. Adherence to physical activity was related to both social support for physical activity and weight loss. Sex did not moderate these relationships. Adherence to physical activity completely mediated the relationship between social support for physical activity and weight loss. Conclusion Increasing companionship for physical activity may be an effective intervention strategy to promote behaviors important for weight loss among Latinos. PMID:26833676

Myoelectric control system and task-specific characteristics affect voluntary use of simultaneous control

PubMed Central

Smith, Lauren H.; Kuiken, Todd A.; Hargrove, Levi J.

2015-01-01

Clinically available myoelectric control does not enable simultaneous proportional control of prosthetic degrees of freedom. Multiple studies have proposed systems that provide simultaneous control, though few have investigated whether subjects voluntarily use simultaneous control or how they implement it. Additionally, few studies have explicitly evaluated the effect of providing proportional velocity control. The objective of this study was to evaluate factors influencing when and how subjects use simultaneous myoelectric control, including the ability to proportionally control the velocity and the required task precision. Five able-bodied subjects used simultaneous myoelectric control systems with and without proportional velocity control in a virtual Fitts’ Law task. Though subjects used simultaneous control to a substantial degree when proportional velocity control was present, they used very little simultaneous control when using constant-velocity control. Furthermore, use of simultaneous control varied significantly with target distance and width, reflecting a strategy of using simultaneous control for gross cursor positioning and sequential control for fine corrective movements. These results provide insight into how users take advantage of simultaneous control and highlight the need for real-time evaluation of simultaneous control algorithms, as the potential benefit of providing simultaneous control may be affected by other characteristics of the myoelectric control system. PMID:25769167

Long-term synchronized electrophysiological and behavioral wireless monitoring of freely moving animals

PubMed Central

Grand, Laszlo; Ftomov, Sergiu; Timofeev, Igor

2012-01-01

Parallel electrophysiological recording and behavioral monitoring of freely moving animals is essential for a better understanding of the neural mechanisms underlying behavior. In this paper we describe a novel wireless recording technique, which is capable of synchronously recording in vivo multichannel electrophysiological (LFP, MUA, EOG, EMG) and activity data (accelerometer, video) from freely moving cats. The method is based on the integration of commercially available components into a simple monitoring system and is complete with accelerometers and the needed signal processing tools. LFP activities of freely moving group-housed cats were recorded from multiple intracortical areas and from the hippocampus. EMG, EOG, accelerometer and video were simultaneously acquired with LFP activities 24-h a day for 3 months. These recordings confirm the possibility of using our wireless method for 24-h long-term monitoring of neurophysiological and behavioral data of freely moving experimental animals such as cats, ferrets, rabbits and other large animals. PMID:23099345

The 120-S minute: using analysis of work activity to prevent psychological distress among elementary school teachers.

PubMed

Messing, K; Seifert, A M; Escalona, E

1997-01-01

Primary school teachers in Québec suffer psychological distress, as shown by the Québec Health Survey (M. Gervais, 1993; Santè Québec, 1995). The authors applied and extended the French model (F. Guérin, A. Laville, F. Daniellou, J. Duraffourg, & A. Kerguelen, 1991) of analysis of work activity to observing classroom teaching (14 women in 10 classrooms for a total of 48 hr 24 min) to identify stressful elements. The authors observed a rapid sequence of actions, eye fixations of short duration, little physical or mental relaxation, multiple simultaneous activities, and uncomfortable temperature and humidity levels. Teachers use many strategies to teach, to create a learning environment, and to maintain attention in classrooms under adverse conditions. Examination of these strategies led to recommendations to improve relations between the teachers and their supervisors and to make the classroom an easier place to teach.

Simultaneous reduction and nitrogen functionalization of graphene oxide using lemon for metal-free oxygen reduction reaction

NASA Astrophysics Data System (ADS)

Begum, Halima; Ahmed, Mohammad Shamsuddin; Cho, Sung; Jeon, Seungwon

2017-12-01

Inspire by the vision of finding a simple and green method for simultaneous reduction and nitrogen (N)-functionalization of graphene oxide (GO), a N-rich reduced graphene oxide (rGO) has been synthesized through a facile and ecofriendly hydrothermal strategy while most of the existing methods are involving with multiple steps and highly toxic reducing agents that are harmful to human health and environment. In this paper, the simultaneous reduction and N-functionalization of GO using as available lemon juice (denoted as Lem-rGO) for metal-free electrocatalysis towards oxygen reduction reaction (ORR) is described. The proposed method is based on the reduction of GO using of the reducing and the N-precursor capability of ascorbic acid and citric acid as well as the nitrogenous compounds, respectively, that containing in lemon juice. The resultant Lem-rGO has higher reduction degree, higher specific surface area and better crystalline nature with N-incorporation than that of well investigated ascorbic acid and citric acid treated rGO. As a result, it shows better ORR electrocatalytic activity in respect to the improved onset potential, electron transfer rate and kinetics than those typical rGO catalysts. Moreover, it shows a significant tolerance to the anodic fuels and durability than the Pt/C during ORR.

Understanding dynamic pattern and process across spatial scales in river systems using simultaneous deployments of in situ sensors

NASA Astrophysics Data System (ADS)

Wollheim, W. M.; Mulukutla, G.; Cook, C.; Carey, R. O.

2014-12-01

Biogeochemical conditions throughout aquatic landscapes are spatially varied and temporally dynamic due to interactions of upstream land use, climate, hydrologic responses, and internal aquatic processes. One of the key goals in aquatic ecosystem ecology is to parse the upstream influences of terrestrial and aquatic processes on local conditions, which becomes progressively more difficult as watershed size increases and as processes are altered by diverse human activities. Simultaneous deployments of high frequency, in situ aquatic sensors for multiple constituents (e.g. NO3-N, CDOM, turbidity, conductivity, D.O., water temperature, along with flow) offer a new approach for understanding patterns along the aquatic continuum. For this talk, we explore strategies for deployments within single watersheds to improve understanding of terrestrial and aquatic processes. We address applications regarding mobilization of non-point nutrient sources across temporal scales, interactions with land use and watershed size, and the importance of aquatic processes. We also explore ways in which simultaneous sensor deployments can be designed to improve parameterization and testing of river network biogeochemical models. We will provide several specific examples using conductivity, nitrate and carbon from ongoing sensor deployments in New England, USA. We expect that improved deployments of sensors and sensor networks will benefit the management of critical freshwater resources.

A novel dual luciferase assay for the simultaneous monitoring of HIV infection and cell viability.

PubMed

Mitsuki, Yu-Ya; Yamamoto, Takuya; Mizukoshi, Fuminori; Momota, Masatoshi; Terahara, Kazutaka; Yoshimura, Kazuhisa; Harada, Shigeyoshi; Tsunetsugu-Yokota, Yasuko

2016-05-01

Human immunodeficiency virus type 1 (HIV-1) reporter cell lines are critical tools for drug development. However, one disadvantage of HIV-1 reporter cell lines is that reductions in reporter gene activity need to be normalized to cytotoxicity, i.e., live cell numbers. Here, we developed a dual luciferase assay based on a R. reniformis luciferase (hRLuc)-expressing R5-type HIV-1 (NLAD8-hRLuc) and a CEM cell line expressing CCR5 and firefly luciferase (R5CEM-FiLuc). The NLAD8-hRLuc reporter virus was replication competent in peripheral blood mononuclear cells. The level of hRLuc was correlated with p24 antigen levels (p<0.001, R=0.862). The target cell line, R5CEM-FiLuc, stably expressed the firefly luciferase (FiLuc) reporter gene and allowed the simultaneous monitoring of compound cytotoxicity. The dual reporter assay combining a NLAD8-hRLuc virus with R5CEM-FiLuc cells permitted the accurate determination of drug susceptibility for entry, reverse transcriptase, integrase, and protease inhibitors at different multiplicities of infection. This dual reporter assay provides a rapid and direct method for the simultaneous monitoring of HIV infection and cell viability. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Simultaneous extraction of acetylsalicylic acid and salicylic acid from human plasma and simultaneous estimation by liquid chromatography and atmospheric pressure chemical ionization/tandem mass spectrometry detection. Application to a pharmacokinetic study.

PubMed

Nirogi, Ramakrishna; Kandikere, Vishwottam; Mudigonda, Koteshwara; Ajjala, Devender; Suraneni, Ramakrishna; Thoddi, Parthasarathi

2011-01-01

A simple analytical method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in atmospheric chemical ionization mode (APCI) for the simultaneous estimation of acetylsalicylic acid (ASA, CAS 50-78-2) and its active metabolite salicylic acid (SA, CAS 69-72-7) in human plasma has been developed and validated. ASA and SA were analyzed simultaneously despite differences in plasma concentration ranges of ASA and SA after oral administration of ASA. In spite of having different chemical, ionization and chromatographic properties, ASA and SA were extracted simultaneously from the plasma sample using acetonitrile protein precipitation followed by liquid-liquid extraction. The analytes were separated on a reversed phase column with rapid gradient program using mobile phase consisting of ammonium acetate buffer and methanol. The structural analogue diclofenac was used as an internal standard. The multiple reaction monitoring (MRM) transitions m/z 179 --> 137 for ASA, m/z 137 --> 65 for SA and m/z 294 --> 250 for IS were used. The assay exhibited a linear dynamic range of 0.02-10 microg/mL for ASA and 0.1-50 microg/mL for SA. The between-batch precision (%CV) ranged from 2.1 to 7.9% for ASA and from 0.2 to 5.2% for SA. The between-batch accuracy ranged from 95.4 to 96.7% for ASA and from 94.6 to 111.3% for SA. The validated method was successfully applied for the evaluation of pharmacokinetics of ASA after single oral administration of 650 mg test formulation versus two 325 mg reference formulations of ASA in human subjects.

Sonochemical assisted hydrothermal synthesis of ZnO: Cr nanoparticles loaded activated carbon for simultaneous ultrasound-assisted adsorption of ternary toxic organic dye: Derivative spectrophotometric, optimization, kinetic and isotherm study.

PubMed

Jamshidi, M; Ghaedi, M; Dashtian, K; Hajati, S; Bazrafshan, A A

2016-09-01

Chromium doped zinc oxide nanoparticles (ZnO: Cr-NPs) was synthesized by ultrasonically assisted hydrothermal method and characterized by FE-SEM, XRD and TEM analysis. Subsequently, this composite ultrasonically assisted was deposited on activated carbon (ZnO: Cr-NPs-AC) and used for simultaneous ultrasound-assisted removal of three toxic organic dye namely of malachite green (MG), eosin yellow (EY) and Auramine O (AO). Dyes spectra overlap in mixture (major problem for simultaneous investigation) of this systems was extensively resolved by derivative spectrophotometric method. The magnitude of variables like initial dyes concentration, adsorbent mass and sonication time influence on dyes removal was optimized using small central composite design (CCD) combined with desirability function (DF) approach, while pH was studied by one-a-time approach. The maximized removal percentages at desirability of 0.9740 was set as follow: pH 6.0, 0.019g ZnO: Cr-NPs-AC, 3.9min sonication at 4.5, 4.8 and 4.7mgL(-1) of MG, EY and AO, respectively. Above optimized points lead to achievement of removal percentage of 98.36%, 97.24%, and 99.26% correspond to MG, EY and AO, respectively. ANOVA for each dyes based p-value less than (<0.0001) suggest highly efficiency of CCD model for prediction of data concern to simultaneous removal of these dyes within 95% confidence interval, while their F-value for MG, EY and AO is 935, 800.2, and 551.3, respectively, that confirm low participation of this them in signal. The value of multiple correlation coefficient R(2), adjusted and predicted R(2) for simultaneous removal of MG is 0.9982, 0.9972 and 0.9940, EY is 0.9979, 0.9967 and 0.9930 and for AO is 0.9970, 0.9952 and 0.9939. The adsorption rate well fitted by pseudo second-order and Langmuir model via high, economic and profitable adsorption capacity of 214.0, 189.7 and 211.6mgg(-1) for MG, EY and AO, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Ultra-performance liquid chromatography tandem mass-spectrometry (uplc-ms/ms) for the rapid, simultaneous analysis of thiamin, riboflavin, flavin adenine dinucleotide, nicotinamide and pyridoxal in human milk

USDA-ARS?s Scientific Manuscript database

A novel, rapid and sensitive Ultra Performance Liquid-Chromatography tandem Mass-Spectrometry (UPLC-MS/MS) method for the simultaneous determination of several B-vitamins in human milk was developed. Resolution by retention time or multiple reaction monitoring (MRM) for thiamin, riboflavin, flavin a...

Ingot slicing machine and method

NASA Technical Reports Server (NTRS)

Kuo, Y. S. (Inventor)

1984-01-01

An improved method for simultaneously slicing one or a multiplicity of boules of silicon into silicon wafers is described. A plurality of vertical stacks of horizontal saw blades of circular configuration are arranged in juxtaposed coaxial alignment. Each blade is characterized by having a cutting diameter slightly greater than the cutting diameter of the blade arranged immediately above, imparting a simultaneous rotation to the blades.

Increasing Instructional Efficiency When Using Simultaneous Prompting Procedure in Teaching Academic Skills to Students with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Tekin-Iftar, Elif; Olcay-Gul, Seray

2016-01-01

A multiple probe design across behaviors replicated across participants was used to examine the effects of a simultaneous prompting procedure delivered along with instructive feedback and observational learning stimuli when teaching academic skills to a small group of students with ASD. Different target skills were taught to each student in the…

Method and apparatus for simultaneous detection and measurement of charged particles at one or more levels of particle flux for analysis of same

DOEpatents

Denton, M Bonner [Tucson, AZ; Sperline, Roger , Koppenaal, David W. , Barinaga, Charles J. , Hieftje, Gary , Barnes, IV, James H.; Atlas, Eugene [Irvine, CA

2009-03-03

A charged particle detector and method are disclosed providing for simultaneous detection and measurement of charged particles at one or more levels of particle flux in a measurement cycle. The detector provides multiple and independently selectable levels of integration and/or gain in a fully addressable readout manner.

Simultaneous spectrophotometric determination of salbutamol and bromhexine in tablets.

PubMed

Habib, I H I; Hassouna, M E M; Zaki, G A

2005-03-01

Typical anti-mucolytic drugs called salbutamol hydrochloride and bromhexine sulfate encountered in tablets were determined simultaneously either by using linear regression at zero-crossing wavelengths of the first derivation of UV-spectra or by application of multiple linear partial least squares regression method. The results obtained by the two proposed mathematical methods were compared with those obtained by the HPLC technique.

One Mouse per Child: Interpersonal Computer for Individual Arithmetic Practice

ERIC Educational Resources Information Center

Alcoholado, C.; Nussbaum, M.; Tagle, A.; Gomez, F.; Denardin, F.; Susaeta, H.; Villalta, M.; Toyama, K.

2012-01-01

Single Display Groupware (SDG) allows multiple people in the same physical space to interact simultaneously over a single communal display through individual input devices that work on the same machine. The aim of this paper is to show how SDG can be used to improve the way resources are used in schools, allowing students to work simultaneously on…

Using a Constant Time Delay Procedure to Teach Support Personnel to Use a Simultaneous Prompting Procedure

ERIC Educational Resources Information Center

Britton, Nicole Scott; Collins, Belva C.; Ault, Melinda Jones; Bausch, Margaret E.

2017-01-01

Within the context of a multiple baseline design, the researchers in this investigation used a constant time delay (CTD) procedure to teach two classroom support personnel (i.e., paraprofessional, peer tutor) to use a simultaneous prompting (SP) procedure when teaching a high school student with a moderate intellectual disability to (a) identify…

Optimal graph search segmentation using arc-weighted graph for simultaneous surface detection of bladder and prostate.

PubMed

Song, Qi; Wu, Xiaodong; Liu, Yunlong; Smith, Mark; Buatti, John; Sonka, Milan

2009-01-01

We present a novel method for globally optimal surface segmentation of multiple mutually interacting objects, incorporating both edge and shape knowledge in a 3-D graph-theoretic approach. Hard surface interacting constraints are enforced in the interacting regions, preserving the geometric relationship of those partially interacting surfaces. The soft smoothness a priori shape compliance is introduced into the energy functional to provide shape guidance. The globally optimal surfaces can be simultaneously achieved by solving a maximum flow problem based on an arc-weighted graph representation. Representing the segmentation problem in an arc-weighted graph, one can incorporate a wider spectrum of constraints into the formulation, thus increasing segmentation accuracy and robustness in volumetric image data. To the best of our knowledge, our method is the first attempt to introduce the arc-weighted graph representation into the graph-searching approach for simultaneous segmentation of multiple partially interacting objects, which admits a globally optimal solution in a low-order polynomial time. Our new approach was applied to the simultaneous surface detection of bladder and prostate. The result was quite encouraging in spite of the low saliency of the bladder and prostate in CT images.

Visual brain activity patterns classification with simultaneous EEG-fMRI: A multimodal approach.

PubMed

Ahmad, Rana Fayyaz; Malik, Aamir Saeed; Kamel, Nidal; Reza, Faruque; Amin, Hafeez Ullah; Hussain, Muhammad

2017-01-01

Classification of the visual information from the brain activity data is a challenging task. Many studies reported in the literature are based on the brain activity patterns using either fMRI or EEG/MEG only. EEG and fMRI considered as two complementary neuroimaging modalities in terms of their temporal and spatial resolution to map the brain activity. For getting a high spatial and temporal resolution of the brain at the same time, simultaneous EEG-fMRI seems to be fruitful. In this article, we propose a new method based on simultaneous EEG-fMRI data and machine learning approach to classify the visual brain activity patterns. We acquired EEG-fMRI data simultaneously on the ten healthy human participants by showing them visual stimuli. Data fusion approach is used to merge EEG and fMRI data. Machine learning classifier is used for the classification purposes. Results showed that superior classification performance has been achieved with simultaneous EEG-fMRI data as compared to the EEG and fMRI data standalone. This shows that multimodal approach improved the classification accuracy results as compared with other approaches reported in the literature. The proposed simultaneous EEG-fMRI approach for classifying the brain activity patterns can be helpful to predict or fully decode the brain activity patterns.

Multiple-Object Tracking in Children: The "Catch the Spies" Task

ERIC Educational Resources Information Center

Trick, L.M.; Jaspers-Fayer, F.; Sethi, N.

2005-01-01

Multiple-object tracking involves simultaneously tracking positions of a number of target-items as they move among distractors. The standard version of the task poses special challenges for children, demanding extended concentration and the ability to distinguish targets from identical-looking distractors, and may thus underestimate children's…

Changing Multiple Adolescent Health Behaviors through School-Based Interventions: A Review of the Literature

ERIC Educational Resources Information Center

Busch, Vincent; de Leeuw, Johannes Rob Josephus; de Harder, Alinda; Schrijvers, Augustinus Jacobus Petrus

2013-01-01

Background: In approaches to health promotion in adolescents, unhealthy behaviors are no longer regarded as independent processes, but as interrelated. This article presents a systematic literature review of school-based interventions targeting multiple adolescent behaviors simultaneously. Methods: A systematic literature search was performed…

Planarian shows decision-making behavior in response to multiple stimuli by integrative brain function.

PubMed

Inoue, Takeshi; Hoshino, Hajime; Yamashita, Taiga; Shimoyama, Seira; Agata, Kiyokazu

2015-01-01

Planarians belong to an evolutionarily early group of organisms that possess a central nervous system including a well-organized brain with a simple architecture but many types of neurons. Planarians display a number of behaviors, such as phototaxis and thermotaxis, in response to external stimuli, and it has been shown that various molecules and neural pathways in the brain are involved in controlling these behaviors. However, due to the lack of combinatorial assay methods, it remains obscure whether planarians possess higher brain functions, including integration in the brain, in which multiple signals coming from outside are coordinated and used in determining behavioral strategies. In the present study, we designed chemotaxis and thigmotaxis/kinesis tracking assays to measure several planarian behaviors in addition to those measured by phototaxis and thermotaxis assays previously established by our group, and used these tests to analyze planarian chemotactic and thigmotactic/kinetic behaviors. We found that headless planarian body fragments and planarians that had specifically lost neural activity following regeneration-dependent conditional gene knockdown (Readyknock) of synaptotagmin in the brain lost both chemotactic and thigmotactic behaviors, suggesting that neural activity in the brain is required for the planarian's chemotactic and thigmotactic behaviors. Furthermore, we compared the strength of phototaxis, chemotaxis, thigmotaxis/kinesis, and thermotaxis by presenting simultaneous binary stimuli to planarians. We found that planarians showed a clear order of predominance of these behaviors. For example, when planarians were simultaneously exposed to 400 lux of light and a chemoattractant, they showed chemoattractive behavior irrespective of the direction of the light source, although exposure to light of this intensity alone induces evasive behavior away from the light source. In contrast, when the light intensity was increased to 800 or 1600 lux and the same dose of chemoattractant was presented, planarian behaviors were gradually shifted to negative phototaxis rather than chemoattraction. These results suggest that planarians may be capable of selecting behavioral strategies via the integration of discrete brain functions when exposed to multiple stimuli. The planarian brain processes external signals received through the respective sensory neurons, thereby resulting in the production of appropriate behaviors. In addition, planarians can adjust behavioral features in response to stimulus conditions by integrating multiple external signals in the brain.

Dyspraxia in ASD: Impaired coordination of movement elements.

PubMed

McAuliffe, Danielle; Pillai, Ajay S; Tiedemann, Alyssa; Mostofsky, Stewart H; Ewen, Joshua B

2017-04-01

Children with autism spectrum disorders (ASD) have long been known to have deficits in the performance of praxis gestures; these motor deficits also correlate with social and communicative deficits. To date, the precise nature of the errors involved in praxis has not been clearly mapped out. Based on observations of individuals with ASD performing gestures, we hypothesized that the simultaneous execution of multiple movement elements is especially impaired in affected children. We examined 25 school-aged participants with ASD and 25 age-matched controls performing seven simultaneous gestures that required the concurrent performance of movement elements and nine serial gestures, in which all elements were performed serially. There was indeed a group × gesture-type interaction (P < 0.001). Whereas both groups had greater difficulty performing simultaneous than serial gestures, children with ASD had a 2.6-times greater performance decrement with simultaneous (vs. serial) gestures than controls. These results point to a potential deficit in the simultaneous processing of multiple inputs and outputs in ASD. Such deficits could relate to models of social interaction that highlight the parallel-processing nature of social communication. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 648-652. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Negotiating for more: the multiple equivalent simultaneous offer.

PubMed

Heller, Richard E

2014-02-01

Whether a doctor, professional baseball manager, or a politician, having successful negotiation skills is a critical part of being a leader. Building upon prior journal articles on negotiation strategy, the author presents the concept of the multiple equivalent simultaneous offer (MESO). The concept of a MESO is straightforward: as opposed to making a single offer, make multiple offers with several variables. Each offer alters the different variables, such that the end result of each offer is equivalent from the perspective of the party making the offer. Research has found several advantages to the use of MESOs. For example, using MESOs, an offer was more likely to be accepted, and the counterparty was more likely to be satisfied with the negotiated deal. Additional benefits have been documented as well, underscoring why a prepared radiology business leader should understand the theory and practice of MESO. Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.

KCNQ channels determine serotonergic modulation of ventral surface chemoreceptors and respiratory drive

PubMed Central

Hawryluk, Joanna M.; Moreira, Thiago S.; Takakura, Ana C.; Wenker, Ian C.; Tzingounis, Anastasios V.; Mulkey, Daniel K.

2012-01-01

Chemosensitive neurons in the retrotrapezoid nucleus (RTN) regulate breathing in response to CO2/H+ changes. Their activity is also sensitive to neuromodulatory inputs from multiple respiratory centers, and thus they serve as a key nexus of respiratory control. However, molecular mechanisms that control their activity and susceptibility to neuromodulation are unknown. Here, we show in vitro and in vivo that KCNQ channels are critical determinants of RTN neural activity. In particular, we find that pharmacological block of KCNQ channels (XE991, 10 μM) increased basal activity and CO2-responsivness of RTN neurons in rat brain slices; whereas KCNQ channel activation (retigabine 2–40 μM) silenced these neurons. Interestingly, we also find that KCNQ and apamin sensitive SK channels act synergistically to regulate firing rate of RTN chemoreceptors; simultaneous blockade of both channels led to a increase in CO2-responsivness. Furthermore, we also show that KCNQ channels but not SK channels are downstream effectors of serotonin modulation of RTN activity in vitro. In contrast, inhibition of KCNQ channel did not prevent modulation of RTN activity by Substance P or TRH; previously identified neuromodulators of RTN chemoreception. Importantly, we also show that KCNQ channels are critical for RTN activity in vivo. Inhibition of KCNQ channels lowered the CO2 threshold for phrenic nerve discharge in anesthetized rats and decreased the ventilatory response to serotonin in awake and anesthetized animals. Given that serotonergic dysfunction may contribute to respiratory failure, our findings suggest KCNQ channels as a new therapeutic avenue for respiratory complications associated with multiple neurological disorders. PMID:23175845

PPAR agonists as therapeutics for CNS trauma and neurological diseases

PubMed Central

Mandrekar-Colucci, Shweta; Sauerbeck, Andrew; Popovich, Phillip G.; McTigue, Dana M.

2013-01-01

Traumatic injury or disease of the spinal cord and brain elicits multiple cellular and biochemical reactions that together cause or are associated with neuropathology. Specifically, injury or disease elicits acute infiltration and activation of immune cells, death of neurons and glia, mitochondrial dysfunction, and the secretion of substrates that inhibit axon regeneration. In some diseases, inflammation is chronic or non-resolving. Ligands that target PPARs (peroxisome proliferator-activated receptors), a group of ligand-activated transcription factors, are promising therapeutics for neurologic disease and CNS injury because their activation affects many, if not all, of these interrelated pathologic mechanisms. PPAR activation can simultaneously weaken or reprogram the immune response, stimulate metabolic and mitochondrial function, promote axon growth and induce progenitor cells to differentiate into myelinating oligodendrocytes. PPAR activation has beneficial effects in many pre-clinical models of neurodegenerative diseases and CNS injury; however, the mechanisms through which PPARs exert these effects have yet to be fully elucidated. In this review we discuss current literature supporting the role of PPAR activation as a therapeutic target for treating traumatic injury and degenerative diseases of the CNS. PMID:24215544

The nitrosocarbonyl hetero-Diels-Alder reaction as a useful tool for organic syntheses.

PubMed

Bodnar, Brian S; Miller, Marvin J

2011-06-14

Organic transformations that result in the formation of multiple covalent bonds within the same reaction are some of the most powerful tools in synthetic organic chemistry. Nitrosocarbonyl hetero-Diels-Alder (HDA) reactions allow for the simultaneous stereospecific introduction of carbon-nitrogen and carbon-oxygen bonds in one synthetic step, and provide direct access to 3,6-dihydro-1,2-oxazines. This Review describes the development of the nitrosocarbonyl HDA reaction and the utility of the resulting oxazine ring in the synthesis of a variety of important, biologically active molecules. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Intrinsic optical signal imaging of glucose-stimulated physiological responses in the insulin secreting INS-1 β-cell line

NASA Astrophysics Data System (ADS)

Li, Yi-Chao; Cui, Wan-Xing; Wang, Xu-Jing; Amthor, Franklin; Yao, Xin-Cheng

2011-03-01

Intrinsic optical signal (IOS) imaging has been established for noninvasive monitoring of stimulus-evoked physiological responses in the retina and other neural tissues. Recently, we extended the IOS imaging technology for functional evaluation of insulin secreting INS-1 cells. INS-1 cells provide a popular model for investigating β-cell dysfunction and diabetes. Our experiments indicate that IOS imaging allows simultaneous monitoring of glucose-stimulated physiological responses in multiple cells with high spatial (sub-cellular) and temporal (sub-second) resolution. Rapid image sequences reveal transient optical responses that have time courses comparable to glucose-evoked β-cell electrical activities.

The Fragility of Healing

PubMed Central

Mattingly, Cheryl; Lawlor, Mary

2010-01-01

This article explores a paradox—the simultaneous cultivation and suppression of “healing dramas” by pediatric rehabilitation therapists. Dramatic moments are defined as ones in which the routine exercises and treatment activities of therapeutic practice are transformed into narrative plots. These improvisational plots involve multiple characters, risks, suspense, and above all, a heightened sense that something is at stake. Experience itself becomes the focus of attention for the patient. Based upon ethnographic research in Chicago and Los Angeles, this article offers an anatomy of two such moments, investigating not only how healing dramas are constructed between patients and healers but how and why institutional discourses and practices invite their abandonment. PMID:20930950

Simultaneous two-photon imaging and two-photon optogenetics of cortical circuits in three dimensions

PubMed Central

Carrillo-Reid, Luis; Bando, Yuki; Peterka, Darcy S

2018-01-01

The simultaneous imaging and manipulating of neural activity could enable the functional dissection of neural circuits. Here we have combined two-photon optogenetics with simultaneous volumetric two-photon calcium imaging to measure and manipulate neural activity in mouse neocortex in vivo in three-dimensions (3D) with cellular resolution. Using a hybrid holographic approach, we simultaneously photostimulate more than 80 neurons over 150 μm in depth in layer 2/3 of the mouse visual cortex, while simultaneously imaging the activity of the surrounding neurons. We validate the usefulness of the method by photoactivating in 3D selected groups of interneurons, suppressing the response of nearby pyramidal neurons to visual stimuli in awake animals. Our all-optical approach could be used as a general platform to read and write neuronal activity. PMID:29412138

Multiplicity: discussion points from the Statisticians in the Pharmaceutical Industry multiplicity expert group.

PubMed

Phillips, Alan; Fletcher, Chrissie; Atkinson, Gary; Channon, Eddie; Douiri, Abdel; Jaki, Thomas; Maca, Jeff; Morgan, David; Roger, James Henry; Terrill, Paul

2013-01-01

In May 2012, the Committee of Health and Medicinal Products issued a concept paper on the need to review the points to consider document on multiplicity issues in clinical trials. In preparation for the release of the updated guidance document, Statisticians in the Pharmaceutical Industry held a one-day expert group meeting in January 2013. Topics debated included multiplicity and the drug development process, the usefulness and limitations of newly developed strategies to deal with multiplicity, multiplicity issues arising from interim decisions and multiregional development, and the need for simultaneous confidence intervals (CIs) corresponding to multiple test procedures. A clear message from the meeting was that multiplicity adjustments need to be considered when the intention is to make a formal statement about efficacy or safety based on hypothesis tests. Statisticians have a key role when designing studies to assess what adjustment really means in the context of the research being conducted. More thought during the planning phase needs to be given to multiplicity adjustments for secondary endpoints given these are increasing in importance in differentiating products in the market place. No consensus was reached on the role of simultaneous CIs in the context of superiority trials. It was argued that unadjusted intervals should be employed as the primary purpose of the intervals is estimation, while the purpose of hypothesis testing is to formally establish an effect. The opposing view was that CIs should correspond to the test decision whenever possible. Copyright © 2013 John Wiley & Sons, Ltd.

A centralized audio presentation manager

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

Papp, A.L. III; Blattner, M.M.

1994-05-16

The centralized audio presentation manager addresses the problems which occur when multiple programs running simultaneously attempt to use the audio output of a computer system. Time dependence of sound means that certain auditory messages must be scheduled simultaneously, which can lead to perceptual problems due to psychoacoustic phenomena. Furthermore, the combination of speech and nonspeech audio is examined; each presents its own problems of perceptibility in an acoustic environment composed of multiple auditory streams. The centralized audio presentation manager receives abstract parameterized message requests from the currently running programs, and attempts to create and present a sonic representation in themore » most perceptible manner through the use of a theoretically and empirically designed rule set.« less