Analyzing multistep homogeneous nucleation in vapor-to-solid transitions using molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Tanaka, Kyoko K.; Diemand, Jürg; Tanaka, Hidekazu; Angélil, Raymond

2017-08-01

In this paper, we present multistep homogeneous nucleations in vapor-to-solid transitions as revealed by molecular dynamics simulations on Lennard-Jones molecules, where liquidlike clusters are created and crystallized. During a long, direct N V E (constant volume, energy, and number of molecules) involving the integration of (1.9 -15 )× 106 molecules in up to 200 million steps (=4.3 μ s ), crystallization in many large, supercooled nanoclusters is observed once the liquid clusters grow to a certain size (˜800 molecules for the case of T ≃0.5 ɛ /k ). In the simulations, we discovered an interesting process associated with crystallization: the solid clusters lost 2-5 % of their mass during crystallization at low temperatures below their melting temperatures. Although the crystallized clusters were heated by latent heat, they were stabilized by cooling due to evaporation. The clusters crystallized quickly and completely except at surface layers. However, they did not have stable crystal structures, rather they had metastable structures such as icosahedral, decahedral, face-centered-cubic-rich (fcc-rich), and hexagonal-close-packed-rich (hcp-rich). Several kinds of cluster structures coexisted in the same size range of ˜1000 -5000 molecules. Our results imply that multistep nucleation is a common first stage of condensation from vapor to solid.

Multi-Step Deep Reactive Ion Etching Fabrication Process for Silicon-Based Terahertz Components

NASA Technical Reports Server (NTRS)

Reck, Theodore (Inventor); Perez, Jose Vicente Siles (Inventor); Lee, Choonsup (Inventor); Cooper, Ken B. (Inventor); Jung-Kubiak, Cecile (Inventor); Mehdi, Imran (Inventor); Chattopadhyay, Goutam (Inventor); Lin, Robert H. (Inventor); Peralta, Alejandro (Inventor)

2016-01-01

A multi-step silicon etching process has been developed to fabricate silicon-based terahertz (THz) waveguide components. This technique provides precise dimensional control across multiple etch depths with batch processing capabilities. Nonlinear and passive components such as mixers and multipliers waveguides, hybrids, OMTs and twists have been fabricated and integrated into a small silicon package. This fabrication technique enables a wafer-stacking architecture to provide ultra-compact multi-pixel receiver front-ends in the THz range.

INDES User's guide multistep input design with nonlinear rotorcraft modeling

NASA Technical Reports Server (NTRS)

1979-01-01

The INDES computer program, a multistep input design program used as part of a data processing technique for rotorcraft systems identification, is described. Flight test inputs base on INDES improve the accuracy of parameter estimates. The input design algorithm, program input, and program output are presented.

Frontal and Parietal Cortices Show Different Spatiotemporal Dynamics across Problem-solving Stages.

PubMed

Tschentscher, Nadja; Hauk, Olaf

2016-08-01

Arithmetic problem-solving can be conceptualized as a multistage process ranging from task encoding over rule and strategy selection to step-wise task execution. Previous fMRI research suggested a frontal-parietal network involved in the execution of complex numerical and nonnumerical tasks, but evidence is lacking on the particular contributions of frontal and parietal cortices across time. In an arithmetic task paradigm, we evaluated individual participants' "retrieval" and "multistep procedural" strategies on a trial-by-trial basis and contrasted those in time-resolved analyses using combined EEG and MEG. Retrieval strategies relied on direct retrieval of arithmetic facts (e.g., 2 + 3 = 5). Procedural strategies required multiple solution steps (e.g., 12 + 23 = 12 + 20 + 3 or 23 + 10 + 2). Evoked source analyses revealed independent activation dynamics within the first second of problem-solving in brain areas previously described as one network, such as the frontal-parietal cognitive control network: The right frontal cortex showed earliest effects of strategy selection for multistep procedural strategies around 300 msec, before parietal cortex activated around 700 msec. In time-frequency source power analyses, memory retrieval and multistep procedural strategies were differentially reflected in theta, alpha, and beta frequencies: Stronger beta and alpha desynchronizations emerged for procedural strategies in right frontal, parietal, and temporal regions as function of executive demands. Arithmetic fact retrieval was reflected in right prefrontal increases in theta power. Our results demonstrate differential brain dynamics within frontal-parietal networks across the time course of a problem-solving process, and analyses of different frequency bands allowed us to disentangle cortical regions supporting the underlying memory and executive functions.

Online Analysis Enhances Use of NASA Earth Science Data

NASA Technical Reports Server (NTRS)

Acker, James G.; Leptoukh, Gregory

2007-01-01

Giovanni, the Goddard Earth Sciences Data and Information Services Center (GES DISC) Interactive Online Visualization and Analysis Infrastructure, has provided researchers with advanced capabilities to perform data exploration and analysis with observational data from NASA Earth observation satellites. In the past 5-10 years, examining geophysical events and processes with remote-sensing data required a multistep process of data discovery, data acquisition, data management, and ultimately data analysis. Giovanni accelerates this process by enabling basic visualization and analysis directly on the World Wide Web. In the last two years, Giovanni has added new data acquisition functions and expanded analysis options to increase its usefulness to the Earth science research community.

Applying flow chemistry: methods, materials, and multistep synthesis.

PubMed

McQuade, D Tyler; Seeberger, Peter H

2013-07-05

The synthesis of complex molecules requires control over both chemical reactivity and reaction conditions. While reactivity drives the majority of chemical discovery, advances in reaction condition control have accelerated method development/discovery. Recent tools include automated synthesizers and flow reactors. In this Synopsis, we describe how flow reactors have enabled chemical advances in our groups in the areas of single-stage reactions, materials synthesis, and multistep reactions. In each section, we detail the lessons learned and propose future directions.

Glucose and phytohormone interplay in controlling root directional growth in Arabidopsis.

PubMed

Singh, Manjul; Gupta, Aditi; Laxmi, Ashverya

2014-01-01

Sensing and responding toward gravity vector is a complicated and multistep process. Gravity is a constant factor feeding plants with reliable information for the spatial orientation of their organs. Auxin, cytokinin, ethylene and BRs have been the most explored hormones in relation to gravitropism. We have previously shown that glucose (Glc) could promote brassinosteroid (BR) signaling thereby inducing changes in root directional growth. Auxin signaling and polar transport components are also involved in Glc induced changes in root directional growth. Here, we provide evidence for involvement of cytokinin and ethylene signaling components in regulation of root directional growth downstream to Glc and BR. Altogether, Glc mediated change in root direction is an adaptive feature which is a result of a collaborative effort integrating phytohormonal signaling cues.

Abundance and composition of indigenous bacterial communities in a multi-step biofiltration-based drinking water treatment plant.

PubMed

Lautenschlager, Karin; Hwang, Chiachi; Ling, Fangqiong; Liu, Wen-Tso; Boon, Nico; Köster, Oliver; Egli, Thomas; Hammes, Frederik

2014-10-01

Indigenous bacterial communities are essential for biofiltration processes in drinking water treatment systems. In this study, we examined the microbial community composition and abundance of three different biofilter types (rapid sand, granular activated carbon, and slow sand filters) and their respective effluents in a full-scale, multi-step treatment plant (Zürich, CH). Detailed analysis of organic carbon degradation underpinned biodegradation as the primary function of the biofilter biomass. The biomass was present in concentrations ranging between 2-5 × 10(15) cells/m(3) in all filters but was phylogenetically, enzymatically and metabolically diverse. Based on 16S rRNA gene-based 454 pyrosequencing analysis for microbial community composition, similar microbial taxa (predominantly Proteobacteria, Planctomycetes, Acidobacteria, Bacteriodetes, Nitrospira and Chloroflexi) were present in all biofilters and in their respective effluents, but the ratio of microbial taxa was different in each filter type. This change was also reflected in the cluster analysis, which revealed a change of 50-60% in microbial community composition between the different filter types. This study documents the direct influence of the filter biomass on the microbial community composition of the final drinking water, particularly when the water is distributed without post-disinfection. The results provide new insights on the complexity of indigenous bacteria colonizing drinking water systems, especially in different biofilters of a multi-step treatment plant. Copyright © 2014 Elsevier Ltd. All rights reserved.

Numerical simulation of machining distortions on a forged aerospace component following a one and a multi-step approaches

NASA Astrophysics Data System (ADS)

Prete, Antonio Del; Franchi, Rodolfo; Antermite, Fabrizio; Donatiello, Iolanda

2018-05-01

Residual stresses appear in a component as a consequence of thermo-mechanical processes (e.g. ring rolling process) casting and heat treatments. When machining these kinds of components, distortions arise due to the redistribution of residual stresses due to the foregoing process history inside the material. If distortions are excessive, they can lead to a large number of scrap parts. Since dimensional accuracy can affect directly the engines efficiency, the dimensional control for aerospace components is a non-trivial issue. In this paper, the problem related to the distortions of large thin walled aeroengines components in nickel superalloys has been addressed. In order to estimate distortions on inner diameters after internal turning operations, a 3D Finite Element Method (FEM) analysis has been developed on a real industrial test case. All the process history, has been taken into account by developing FEM models of ring rolling process and heat treatments. Three different strategies of ring rolling process have been studied and the combination of related parameters which allows to obtain the best dimensional accuracy has been found. Furthermore, grain size evolution and recrystallization phenomena during manufacturing process has been numerically investigated using a semi empirical Johnson-Mehl-Avrami-Kohnogorov (JMAK) model. The volume subtractions have been simulated by boolean trimming: a one step and a multi step analysis have been performed. The multi-step procedure has allowed to choose the best material removal sequence in order to reduce machining distortions.

Multistep translation and cultural adaptation of the Penn acoustic neuroma quality-of-life scale for German-speaking patients.

PubMed

Kristin, Julia; Glaas, Marcel Fabian; Stenin, Igor; Albrecht, Angelika; Klenzner, Thomas; Schipper, Jörg; Eysel-Gosepath, Katrin

2017-11-01

Monitoring the health-related quality of life (HRQOL) for patients with vestibular schwannoma (VS) has garnered increasing interest. In German-speaking countries, there is no disease-specific questionnaire available similar to the "Penn Acoustic Neuroma Quality-of-life Scale" (PANQOL). We translated the PANQOL for German-speaking patients based on a multistep protocol that included not only a forward-backward translation but also linguistic and sociocultural adaptations. The process consists of translation, synthesis, back translation, review by an expert committee, administration of the prefinal version to our patients, submission and appraisal of all written documents by our research team. The required multidisciplinary team for translation comprised head and neck surgeons, language professionals (German and English), a professional translator, and bilingual participants. A total of 123 patients with VS underwent microsurgical procedures via different approaches at our clinic between January 2007 and January 2017. Among these, 72 patients who underwent the translabyrinthine approach participated in the testing of the German-translated PANQOL. The first German version of the PANQOL questionnaire was created by a multistep translation process. The responses indicate that the questionnaire is simple to administer and applicable to our patients. The use of a multistep process to translate quality-of-life questionnaires is complex and time-consuming. However, this process was performed properly and resulted in a version of the PANQOL for assessing the quality of life of German-speaking patients with VS.

A Multistep Algorithm for the Radiation Hydrodynamical Transport of Cosmological Ionization Fronts and Ionized Flows

NASA Astrophysics Data System (ADS)

Whalen, Daniel; Norman, Michael L.

2006-02-01

Radiation hydrodynamical transport of ionization fronts (I-fronts) in the next generation of cosmological reionization simulations holds the promise of predicting UV escape fractions from first principles as well as investigating the role of photoionization in feedback processes and structure formation. We present a multistep integration scheme for radiative transfer and hydrodynamics for accurate propagation of I-fronts and ionized flows from a point source in cosmological simulations. The algorithm is a photon-conserving method that correctly tracks the position of I-fronts at much lower resolutions than nonconservative techniques. The method applies direct hierarchical updates to the ionic species, bypassing the need for the costly matrix solutions required by implicit methods while retaining sufficient accuracy to capture the true evolution of the fronts. We review the physics of ionization fronts in power-law density gradients, whose analytical solutions provide excellent validation tests for radiation coupling schemes. The advantages and potential drawbacks of direct and implicit schemes are also considered, with particular focus on problem time-stepping, which if not properly implemented can lead to morphologically plausible I-front behavior that nonetheless departs from theory. We also examine the effect of radiation pressure from very luminous central sources on the evolution of I-fronts and flows.

Numerical computation of linear instability of detonations

NASA Astrophysics Data System (ADS)

Kabanov, Dmitry; Kasimov, Aslan

2017-11-01

We propose a method to study linear stability of detonations by direct numerical computation. The linearized governing equations together with the shock-evolution equation are solved in the shock-attached frame using a high-resolution numerical algorithm. The computed results are processed by the Dynamic Mode Decomposition technique to generate dispersion relations. The method is applied to the reactive Euler equations with simple-depletion chemistry as well as more complex multistep chemistry. The results are compared with those known from normal-mode analysis. We acknowledge financial support from King Abdullah University of Science and Technology.

A Systems Approach towards an Intelligent and Self-Controlling Platform for Integrated Continuous Reaction Sequences**

PubMed Central

Ingham, Richard J; Battilocchio, Claudio; Fitzpatrick, Daniel E; Sliwinski, Eric; Hawkins, Joel M; Ley, Steven V

2015-01-01

Performing reactions in flow can offer major advantages over batch methods. However, laboratory flow chemistry processes are currently often limited to single steps or short sequences due to the complexity involved with operating a multi-step process. Using new modular components for downstream processing, coupled with control technologies, more advanced multi-step flow sequences can be realized. These tools are applied to the synthesis of 2-aminoadamantane-2-carboxylic acid. A system comprising three chemistry steps and three workup steps was developed, having sufficient autonomy and self-regulation to be managed by a single operator. PMID:25377747

Using the Binary Phase-Field Crystal Model to Describe Non-Classical Nucleation Pathways in Gold Nanoparticles

NASA Astrophysics Data System (ADS)

Smith, Nathan; Provatas, Nikolas

Recent experimental work has shown that gold nanoparticles can precipitate from an aqueous solution through a non-classical, multi-step nucleation process. This multi-step process begins with spinodal decomposition into solute-rich and solute-poor liquid domains followed by nucleation from within the solute-rich domains. We present a binary phase-field crystal theory that shows the same phenomology and examine various cross-over regimes in the growth and coarsening of liquid and solid domains. We'd like to the thank Canada Research Chairs (CRC) program for funding this work.

Optimal generalized multistep integration formulae for real-time digital simulation

NASA Technical Reports Server (NTRS)

Moerder, D. D.; Halyo, N.

1985-01-01

The problem of discretizing a dynamical system for real-time digital simulation is considered. Treating the system and its simulation as stochastic processes leads to a statistical characterization of simulator fidelity. A plant discretization procedure based on an efficient matrix generalization of explicit linear multistep discrete integration formulae is introduced, which minimizes a weighted sum of the mean squared steady-state and transient error between the system and simulator outputs.

Microarc oxidation coating covered Ti implants with micro-scale gouges formed by a multi-step treatment for improving osseointegration.

PubMed

Bai, Yixin; Zhou, Rui; Cao, Jianyun; Wei, Daqing; Du, Qing; Li, Baoqiang; Wang, Yaming; Jia, Dechang; Zhou, Yu

2017-07-01

The sub-microporous microarc oxidation (MAO) coating covered Ti implant with micro-scale gouges has been fabricated via a multi-step MAO process to overcome the compromised bone-implant integration. The as-prepared implant has been further mediated by post-heat treatment to compare the effects of -OH functional group and the nano-scale orange peel-like morphology on osseointegration. The bone regeneration, bone-implant contact interface, and biomechanical push-out force of the modified Ti implant have been discussed thoroughly in this work. The greatly improved push-out force for the MAO coated Ti implants with micro-scale gouges could be attributed to the excellent mechanical interlocking effect between implants and biologically meshed bone tissues. Attributed to the -OH functional group which promotes synostosis between the biologically meshed bone and the gouge surface of implant, the multi-step MAO process could be an effective strategy to improve the osseointegration of Ti implant. Copyright © 2017 Elsevier B.V. All rights reserved.

Round-off error in long-term orbital integrations using multistep methods

NASA Technical Reports Server (NTRS)

Quinlan, Gerald D.

1994-01-01

Techniques for reducing roundoff error are compared by testing them on high-order Stormer and summetric multistep methods. The best technique for most applications is to write the equation in summed, function-evaluation form and to store the coefficients as rational numbers. A larger error reduction can be achieved by writing the equation in backward-difference form and performing some of the additions in extended precision, but this entails a larger central processing unit (cpu) cost.

PSO-MISMO modeling strategy for multistep-ahead time series prediction.

PubMed

Bao, Yukun; Xiong, Tao; Hu, Zhongyi

2014-05-01

Multistep-ahead time series prediction is one of the most challenging research topics in the field of time series modeling and prediction, and is continually under research. Recently, the multiple-input several multiple-outputs (MISMO) modeling strategy has been proposed as a promising alternative for multistep-ahead time series prediction, exhibiting advantages compared with the two currently dominating strategies, the iterated and the direct strategies. Built on the established MISMO strategy, this paper proposes a particle swarm optimization (PSO)-based MISMO modeling strategy, which is capable of determining the number of sub-models in a self-adaptive mode, with varying prediction horizons. Rather than deriving crisp divides with equal-size s prediction horizons from the established MISMO, the proposed PSO-MISMO strategy, implemented with neural networks, employs a heuristic to create flexible divides with varying sizes of prediction horizons and to generate corresponding sub-models, providing considerable flexibility in model construction, which has been validated with simulated and real datasets.

GREEN CHEMISTRY. Shape-selective zeolite catalysis for bioplastics production.

PubMed

Dusselier, Michiel; Van Wouwe, Pieter; Dewaele, Annelies; Jacobs, Pierre A; Sels, Bert F

2015-07-03

Biodegradable and renewable polymers, such as polylactic acid, are benign alternatives for petrochemical-based plastics. Current production of polylactic acid via its key building block lactide, the cyclic dimer of lactic acid, is inefficient in terms of energy, time, and feedstock use. We present a direct zeolite-based catalytic process, which converts lactic acid into lactide. The shape-selective properties of zeolites are essential to attain record lactide yields, outperforming those of the current multistep process by avoiding both racemization and side-product formation. The highly productive process is strengthened by facile recovery and practical reactivation of the catalyst, which remains structurally fit during at least six consecutive reactions, and by the ease of solvent and side-product recycling. Copyright © 2015, American Association for the Advancement of Science.

Multistep Ionization of Argon Clusters in Intense Femtosecond Extreme Ultraviolet Pulses

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

Bostedt, C.; Thomas, H.; Hoener, M.

The interaction of intense extreme ultraviolet femtosecond laser pulses ({lambda}=32.8 nm) from the FLASH free electron laser (FEL) with clusters has been investigated by means of photoelectron spectroscopy and modeled by Monte Carlo simulations. For laser intensities up to 5x10{sup 13} W/cm{sup 2}, we find that the cluster ionization process is a sequence of direct electron emission events in a developing Coulomb field. A nanoplasma is formed only at the highest investigated power densities where ionization is frustrated due to the deep cluster potential. In contrast with earlier studies in the IR and vacuum ultraviolet spectral regime, we find nomore » evidence for electron emission from plasma heating processes.« less

Quantum molecular dynamics and multistep-direct analyses of multiple preequilibrium emission

NASA Astrophysics Data System (ADS)

Chadwick, M. B.; Chiba, S.; Niita, K.; Maruyama, T.; Iwamoto, A.

1995-11-01

We study multiple preequilibrium emission in nucleon induced reactions at intermediate energies, and compare quantum molecular dynamics (QMD) calculations with multistep-direct Feshbach-Kerman-Koonin results [M. B. Chadwick, P. G. Young, D. C. George, and Y. Watanabe, Phys. Rev. C 50, 996 (1994)]. When the theoretical expressions of this reference are reformulated so that the definitions of primary and multiple emission correspond to those used in QMD, the two theories yield similar results for primary and multiple preequilibrium emission. We use QMD as a tool to determine the multiplicities of fast preequilibrium nucleons as a function of incident energy. For fast particle cross sections to exceed 5% of the inclusive preequilibrium emission cross sections we find that two particles should be included in reactions above 50 MeV, three above about 180 MeV, and four are only needed when the incident energy exceeds about 400 MeV.

Direct coal liquefaction process

DOEpatents

Rindt, John R.; Hetland, Melanie D.

1993-01-01

An improved multistep liquefaction process for organic carbonaceous mater which produces a virtually completely solvent-soluble carbonaceous liquid product. The solubilized product may be more amenable to further processing than liquid products produced by current methods. In the initial processing step, the finely divided organic carbonaceous material is treated with a hydrocarbonaceous pasting solvent containing from 10% and 100% by weight process-derived phenolic species at a temperature within the range of 300.degree. C. to 400.degree. C. for typically from 2 minutes to 120 minutes in the presence of a carbon monoxide reductant and an optional hydrogen sulfide reaction promoter in an amount ranging from 0 to 10% by weight of the moisture- and ash-free organic carbonaceous material fed to the system. As a result, hydrogen is generated via the water/gas shift reaction at a rate necessary to prevent condensation reactions. In a second step, the reaction product of the first step is hydrogenated.

Direct coal liquefaction process

DOEpatents

Rindt, J.R.; Hetland, M.D.

1993-10-26

An improved multistep liquefaction process for organic carbonaceous mater which produces a virtually completely solvent-soluble carbonaceous liquid product. The solubilized product may be more amenable to further processing than liquid products produced by current methods. In the initial processing step, the finely divided organic carbonaceous material is treated with a hydrocarbonaceous pasting solvent containing from 10% and 100% by weight process-derived phenolic species at a temperature within the range of 300 C to 400 C for typically from 2 minutes to 120 minutes in the presence of a carbon monoxide reductant and an optional hydrogen sulfide reaction promoter in an amount ranging from 0 to 10% by weight of the moisture- and ash-free organic carbonaceous material fed to the system. As a result, hydrogen is generated via the water/gas shift reaction at a rate necessary to prevent condensation reactions. In a second step, the reaction product of the first step is hydrogenated.

Application of the quality by design approach to the drug substance manufacturing process of an Fc fusion protein: towards a global multi-step design space.

PubMed

Eon-duval, Alex; Valax, Pascal; Solacroup, Thomas; Broly, Hervé; Gleixner, Ralf; Strat, Claire L E; Sutter, James

2012-10-01

The article describes how Quality by Design principles can be applied to the drug substance manufacturing process of an Fc fusion protein. First, the quality attributes of the product were evaluated for their potential impact on safety and efficacy using risk management tools. Similarly, process parameters that have a potential impact on critical quality attributes (CQAs) were also identified through a risk assessment. Critical process parameters were then evaluated for their impact on CQAs, individually and in interaction with each other, using multivariate design of experiment techniques during the process characterisation phase. The global multi-step Design Space, defining operational limits for the entire drug substance manufacturing process so as to ensure that the drug substance quality targets are met, was devised using predictive statistical models developed during the characterisation study. The validity of the global multi-step Design Space was then confirmed by performing the entire process, from cell bank thawing to final drug substance, at its limits during the robustness study: the quality of the final drug substance produced under different conditions was verified against predefined targets. An adaptive strategy was devised whereby the Design Space can be adjusted to the quality of the input material to ensure reliable drug substance quality. Finally, all the data obtained during the process described above, together with data generated during additional validation studies as well as manufacturing data, were used to define the control strategy for the drug substance manufacturing process using a risk assessment methodology. Copyright © 2012 Wiley-Liss, Inc.

A study of increasing radical density and etch rate using remote plasma generator system

NASA Astrophysics Data System (ADS)

Lee, Jaewon; Kim, Kyunghyun; Cho, Sung-Won; Chung, Chin-Wook

2013-09-01

To improve radical density without changing electron temperature, remote plasma generator (RPG) is applied. Multistep dissociation of the polyatomic molecule was performed using RPG system. RPG is installed to inductively coupled type processing reactor; electrons, positive ions, radicals and polyatomic molecule generated in RPG and they diffused to processing reactor. The processing reactor dissociates the polyatomic molecules with inductively coupled power. The polyatomic molecules are dissociated by the processing reactor that is operated by inductively coupled power. Therefore, the multistep dissociation system generates more radicals than single-step system. The RPG was composed with two cylinder type inductively coupled plasma (ICP) using 400 kHz RF power and nitrogen gas. The processing reactor composed with two turn antenna with 13.56 MHz RF power. Plasma density, electron temperature and radical density were measured with electrical probe and optical methods.

Personalized multistep cognitive behavioral therapy for obesity

PubMed Central

Dalle Grave, Riccardo; Sartirana, Massimiliano; El Ghoch, Marwan; Calugi, Simona

2017-01-01

Multistep cognitive behavioral therapy for obesity (CBT-OB) is a treatment that may be delivered at three levels of care (outpatient, day hospital, and residential). In a stepped-care approach, CBT-OB associates the traditional procedures of weight-loss lifestyle modification, ie, physical activity and dietary recommendations, with specific cognitive behavioral strategies that have been indicated by recent research to influence weight loss and maintenance by addressing specific cognitive processes. The treatment program as a whole is delivered in six modules. These are introduced according to the individual patient’s needs in a flexible and personalized fashion. A recent randomized controlled trial has found that 88 patients suffering from morbid obesity treated with multistep residential CBT-OB achieved a mean weight loss of 15% after 12 months, with no tendency to regain weight between months 6 and 12. The treatment has also shown promising long-term results in the management of obesity associated with binge-eating disorder. If these encouraging findings are confirmed by the two ongoing outpatient studies (one delivered individually and one in a group setting), this will provide evidence-based support for the potential of multistep CBT-OB to provide a more effective alternative to standard weight-loss lifestyle-modification programs. PMID:28615960

Identification of Steady and Non-Steady Gait of Humanexoskeleton Walking System

NASA Astrophysics Data System (ADS)

Żur, K. K.

2013-08-01

In this paper a method of analysis of exoskeleton multistep locomotion was presented by using a computer with the preinstalled DChC program. The paper also presents a way to analytically calculate the ",motion indicator", as well as the algorithm calculating its two derivatives. The algorithm developed by the author processes data collected from the investigation and then a program presents the obtained final results. Research into steady and non-steady multistep locomotion can be used to design two-legged robots of DAR type and exoskeleton control system

A Novel WA-BPM Based on the Generalized Multistep Scheme in the Propagation Direction in the Waveguide

NASA Astrophysics Data System (ADS)

Ji, Yang; Chen, Hong; Tang, Hongwu

2017-06-01

A highly accurate wide-angle scheme, based on the generalized mutistep scheme in the propagation direction, is developed for the finite difference beam propagation method (FD-BPM). Comparing with the previously presented method, the simulation shows that our method results in a more accurate solution, and the step size can be much larger

Multi-step high-throughput conjugation platform for the development of antibody-drug conjugates.

PubMed

Andris, Sebastian; Wendeler, Michaela; Wang, Xiangyang; Hubbuch, Jürgen

2018-07-20

Antibody-drug conjugates (ADCs) form a rapidly growing class of biopharmaceuticals which attracts a lot of attention throughout the industry due to its high potential for cancer therapy. They combine the specificity of a monoclonal antibody (mAb) and the cell-killing capacity of highly cytotoxic small molecule drugs. Site-specific conjugation approaches involve a multi-step process for covalent linkage of antibody and drug via a linker. Despite the range of parameters that have to be investigated, high-throughput methods are scarcely used so far in ADC development. In this work an automated high-throughput platform for a site-specific multi-step conjugation process on a liquid-handling station is presented by use of a model conjugation system. A high-throughput solid-phase buffer exchange was successfully incorporated for reagent removal by utilization of a batch cation exchange step. To ensure accurate screening of conjugation parameters, an intermediate UV/Vis-based concentration determination was established including feedback to the process. For conjugate characterization, a high-throughput compatible reversed-phase chromatography method with a runtime of 7 min and no sample preparation was developed. Two case studies illustrate the efficient use for mapping the operating space of a conjugation process. Due to the degree of automation and parallelization, the platform is capable of significantly reducing process development efforts and material demands and shorten development timelines for antibody-drug conjugates. Copyright © 2018 Elsevier B.V. All rights reserved.

Syntactic processing in the absence of awareness and semantics.

PubMed

Hung, Shao-Min; Hsieh, Po-Jang

2015-10-01

The classical view that multistep rule-based operations require consciousness has recently been challenged by findings that both multiword semantic processing and multistep arithmetic equations can be processed unconsciously. It remains unclear, however, whether pure rule-based cognitive processes can occur unconsciously in the absence of semantics. Here, after presenting 2 words consciously, we suppressed the third with continuous flash suppression. First, we showed that the third word in the subject-verb-verb format (syntactically incongruent) broke suppression significantly faster than the third word in the subject-verb-object format (syntactically congruent). Crucially, the same effect was observed even with sentences composed of pseudowords (pseudo subject-verb-adjective vs. pseudo subject-verb-object) without any semantic information. This is the first study to show that syntactic congruency can be processed unconsciously in the complete absence of semantics. Our findings illustrate how abstract rule-based processing (e.g., syntactic categories) can occur in the absence of visual awareness, even when deprived of semantics. (c) 2015 APA, all rights reserved).

Controllable 3D architectures of aligned carbon nanotube arrays by multi-step processes

NASA Astrophysics Data System (ADS)

Huang, Shaoming

2003-06-01

An effective way to fabricate large area three-dimensional (3D) aligned CNTs pattern based on pyrolysis of iron(II) phthalocyanine (FePc) by two-step processes is reported. The controllable generation of different lengths and selective growth of the aligned CNT arrays on metal-patterned (e.g., Ag and Au) substrate are the bases for generating such 3D aligned CNTs architectures. By controlling experimental conditions 3D aligned CNT arrays with different lengths/densities and morphologies/structures as well as multi-layered architectures can be fabricated in large scale by multi-step pyrolysis of FePc. These 3D architectures could have interesting properties and be applied for developing novel nanotube-based devices.

Considerations In The Design And Specifications Of An Automatic Inspection System

NASA Astrophysics Data System (ADS)

Lee, David T.

1980-05-01

Considerable activities have been centered around the automation of manufacturing quality control and inspection functions. Several reasons can be cited for this development. The continuous pressure of direct and indirect labor cost increase is only one of the obvious motivations. With the drive for electronics miniaturization come more and more complex processes where control parameters are critical and the yield is highly susceptible to inadequate process monitor and inspection. With multi-step, multi-layer process for substrate fabrication, process defects that are not detected and corrected at certain critical points may render the entire subassembly useless. As a process becomes more complex, the time required to test the product increases significantly in the total build cycle. The urgency to reduce test time brings more pressure to improve in-process control and inspection. The advances and improvements of components, assemblies and systems such as micro-processors, micro-computers, programmable controllers, and other intelligent devices, have made the automation of quality control much more cost effective and justifiable.

Variation of nanopore diameter along porous anodic alumina channels by multi-step anodization.

PubMed

Lee, Kwang Hong; Lim, Xin Yuan; Wai, Kah Wing; Romanato, Filippo; Wong, Chee Cheong

2011-02-01

In order to form tapered nanocapillaries, we investigated a method to vary the nanopore diameter along the porous anodic alumina (PAA) channels using multi-step anodization. By anodizing the aluminum in either single acid (H3PO4) or multi-acid (H2SO4, oxalic acid and H3PO4) with increasing or decreasing voltage, the diameter of the nanopore along the PAA channel can be varied systematically corresponding to the applied voltages. The pore size along the channel can be enlarged or shrunken in the range of 20 nm to 200 nm. Structural engineering of the template along the film growth direction can be achieved by deliberately designing a suitable voltage and electrolyte together with anodization time.

Adaptation to Vocal Expressions Reveals Multistep Perception of Auditory Emotion

PubMed Central

Maurage, Pierre; Rouger, Julien; Latinus, Marianne; Belin, Pascal

2014-01-01

The human voice carries speech as well as important nonlinguistic signals that influence our social interactions. Among these cues that impact our behavior and communication with other people is the perceived emotional state of the speaker. A theoretical framework for the neural processing stages of emotional prosody has suggested that auditory emotion is perceived in multiple steps (Schirmer and Kotz, 2006) involving low-level auditory analysis and integration of the acoustic information followed by higher-level cognition. Empirical evidence for this multistep processing chain, however, is still sparse. We examined this question using functional magnetic resonance imaging and a continuous carry-over design (Aguirre, 2007) to measure brain activity while volunteers listened to non-speech-affective vocalizations morphed on a continuum between anger and fear. Analyses dissociated neuronal adaptation effects induced by similarity in perceived emotional content between consecutive stimuli from those induced by their acoustic similarity. We found that bilateral voice-sensitive auditory regions as well as right amygdala coded the physical difference between consecutive stimuli. In contrast, activity in bilateral anterior insulae, medial superior frontal cortex, precuneus, and subcortical regions such as bilateral hippocampi depended predominantly on the perceptual difference between morphs. Our results suggest that the processing of vocal affect recognition is a multistep process involving largely distinct neural networks. Amygdala and auditory areas predominantly code emotion-related acoustic information while more anterior insular and prefrontal regions respond to the abstract, cognitive representation of vocal affect. PMID:24920615

Adaptation to vocal expressions reveals multistep perception of auditory emotion.

PubMed

Bestelmeyer, Patricia E G; Maurage, Pierre; Rouger, Julien; Latinus, Marianne; Belin, Pascal

2014-06-11

The human voice carries speech as well as important nonlinguistic signals that influence our social interactions. Among these cues that impact our behavior and communication with other people is the perceived emotional state of the speaker. A theoretical framework for the neural processing stages of emotional prosody has suggested that auditory emotion is perceived in multiple steps (Schirmer and Kotz, 2006) involving low-level auditory analysis and integration of the acoustic information followed by higher-level cognition. Empirical evidence for this multistep processing chain, however, is still sparse. We examined this question using functional magnetic resonance imaging and a continuous carry-over design (Aguirre, 2007) to measure brain activity while volunteers listened to non-speech-affective vocalizations morphed on a continuum between anger and fear. Analyses dissociated neuronal adaptation effects induced by similarity in perceived emotional content between consecutive stimuli from those induced by their acoustic similarity. We found that bilateral voice-sensitive auditory regions as well as right amygdala coded the physical difference between consecutive stimuli. In contrast, activity in bilateral anterior insulae, medial superior frontal cortex, precuneus, and subcortical regions such as bilateral hippocampi depended predominantly on the perceptual difference between morphs. Our results suggest that the processing of vocal affect recognition is a multistep process involving largely distinct neural networks. Amygdala and auditory areas predominantly code emotion-related acoustic information while more anterior insular and prefrontal regions respond to the abstract, cognitive representation of vocal affect. Copyright © 2014 Bestelmeyer et al.

Star sub-pixel centroid calculation based on multi-step minimum energy difference method

NASA Astrophysics Data System (ADS)

Wang, Duo; Han, YanLi; Sun, Tengfei

2013-09-01

The star's centroid plays a vital role in celestial navigation, star images which be gotten during daytime, due to the strong sky background, have a low SNR, and the star objectives are nearly submerged in the background, takes a great trouble to the centroid localization. Traditional methods, such as a moment method, weighted centroid calculation method is simple but has a big error, especially in the condition of a low SNR. Gaussian method has a high positioning accuracy, but the computational complexity. Analysis of the energy distribution in star image, a location method for star target centroids based on multi-step minimum energy difference is proposed. This method uses the linear superposition to narrow the centroid area, in the certain narrow area uses a certain number of interpolation to pixels for the pixels' segmentation, and then using the symmetry of the stellar energy distribution, tentatively to get the centroid position: assume that the current pixel is the star centroid position, and then calculates and gets the difference of the sum of the energy which in the symmetric direction(in this paper we take the two directions of transverse and longitudinal) and the equal step length(which can be decided through different conditions, the paper takes 9 as the step length) of the current pixel, and obtain the centroid position in this direction when the minimum difference appears, and so do the other directions, then the validation comparison of simulated star images, and compare with several traditional methods, experiments shows that the positioning accuracy of the method up to 0.001 pixel, has good effect to calculate the centroid of low SNR conditions; at the same time, uses this method on a star map which got at the fixed observation site during daytime in near-infrared band, compare the results of the paper's method with the position messages which were known of the star, it shows that :the multi-step minimum energy difference method achieves a better effect.

Progress in the development of paper-based diagnostics for low-resource point-of-care settings

PubMed Central

Byrnes, Samantha; Thiessen, Gregory; Fu, Elain

2014-01-01

This Review focuses on recent work in the field of paper microfluidics that specifically addresses the goal of translating the multistep processes that are characteristic of gold-standard laboratory tests to low-resource point-of-care settings. A major challenge is to implement multistep processes with the robust fluid control required to achieve the necessary sensitivity and specificity of a given application in a user-friendly package that minimizes equipment. We review key work in the areas of fluidic controls for automation in paper-based devices, readout methods that minimize dedicated equipment, and power and heating methods that are compatible with low-resource point-of-care settings. We also highlight a focused set of recent applications and discuss future challenges. PMID:24256361

Heat shield characterization: Outer planet atmospheric entry probe

NASA Technical Reports Server (NTRS)

Mezines, S. A.; Rusert, E. L.; Disser, E. F.

1976-01-01

A full scale carbon phenolic heat shield was fabricated for the Outer Planet Probe in order to demonstrate the feasibility of molding large carbon phenolic parts with a new fabrication processing method (multistep). The sphere-cone heat shield was molded as an integral unit with the nose cap plies configured into a double inverse chevron shape to achieve the desired ply orientation. The fabrication activity was successful and the feasibility of the multistep processing technology was established. Delaminations or unbonded plies were visible on the heat shield and resulted from excessive loss of resin and lack of sufficient pressure applied on the part during the curing cycle. A comprehensive heat shield characterization test program was conducted, including: nondestructive tests with the full scale heat shield and thermal and mechanical property tests with small test specimen.

Formation of Stone-Wales edge: Multistep reconstruction and growth mechanisms of zigzag nanographene.

PubMed

Dang, Jing-Shuang; Wang, Wei-Wei; Zheng, Jia-Jia; Nagase, Shigeru; Zhao, Xiang

2017-10-05

Although the existence of Stone-Wales (5-7) defect at graphene edge has been clarified experimentally, theoretical study on the formation mechanism is still imperfect. In particular, the regioselectivity of multistep reactions at edge (self-reconstruction and growth with foreign carbon feedstock) is essential to understand the kinetic behavior of reactive boundaries but investigations are still lacking. Herein, by using finite-sized models, multistep reconstructions and carbon dimer additions of a bared zigzag edge are introduced using density functional theory calculations. The zigzag to 5-7 transformation is proved as a site-selective process to generate alternating 5-7 pairs sequentially and the first step with largest barrier is suggested as the rate-determining step. Conversely, successive C 2 insertions on the active edge are calculated to elucidate the formation of 5-7 edge during graphene growth. A metastable intermediate with a triple sequentially fused pentagon fragment is proved as the key structure for 5-7 edge formation. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

NONE

ARCTECH has developed a novel process (MicGAS) for direct, anaerobic biomethanation of coals. Biomethanation potential of coals of different ranks (Anthracite, bitumious, sub-bitumious, and lignites of different types), by various microbial consortia, was investigated. Studies on biogasification of Texas Lignite (TxL) were conducted with a proprietary microbial consortium, Mic-1, isolated from hind guts of soil eating termites (Zootermopsis and Nasutitermes sp.) and further improved at ARCTECH. Various microbial populations of the Mic-1 consortium carry out the multi-step MicGAS Process. First, the primary coal degraders, or hydrolytic microbes, degrade the coal to high molecular weight (MW) compounds. Then acedogens ferment themore » high MW compounds to low MW volatile fatty acids. The volatile fatty acids are converted to acetate by acetogens, and the methanogens complete the biomethanation by converting acetate and CO{sub 2} to methane.« less

Data-based control of a multi-step forming process

NASA Astrophysics Data System (ADS)

Schulte, R.; Frey, P.; Hildenbrand, P.; Vogel, M.; Betz, C.; Lechner, M.; Merklein, M.

2017-09-01

The fourth industrial revolution represents a new stage in the organization and management of the entire value chain. However, concerning the field of forming technology, the fourth industrial revolution has only arrived gradually until now. In order to make a valuable contribution to the digital factory the controlling of a multistage forming process was investigated. Within the framework of the investigation, an abstracted and transferable model is used to outline which data have to be collected, how an interface between the different forming machines can be designed tangible and which control tasks must be fulfilled. The goal of this investigation was to control the subsequent process step based on the data recorded in the first step. The investigated process chain links various metal forming processes, which are typical elements of a multi-step forming process. Data recorded in the first step of the process chain is analyzed and processed for an improved process control of the subsequent process. On the basis of the gained scientific knowledge, it is possible to make forming operations more robust and at the same time more flexible, and thus create the fundament for linking various production processes in an efficient way.

Continuous In Vitro Evolution of a Ribozyme that Catalyzes Three Successive Nucleotidyl Addition Reactions

NASA Technical Reports Server (NTRS)

McGinness, Kathleen E.; Wright, Martin C.; Joyce, Gerald F.

2002-01-01

Variants of the class I ligase ribozyme, which catalyzes joining of the 3' end of a template bound oligonucleotide to its own 5' end, have been made to evolve in a continuous manner by a simple serial transfer procedure that can be carried out indefinitely. This process was expanded to allow the evolution of ribozymes that catalyze three successive nucleotidyl addition reactions, two template-directed mononucleotide additions followed by RNA ligation. During the development of this behavior, a population of ribozymes was maintained against an overall dilution of more than 10(exp 406). The resulting ribozymes were capable of catalyzing the three-step reaction pathway, with nucleotide addition occurring in either a 5' yieldig 3' or a 3' yielding 5' direction. This purely chemical system provides a functional model of a multi-step reaction pathway that is undergoing Darwinian evolution.

The role of Myc-induced protein synthesis in cancer

PubMed Central

Ruggero, Davide

2009-01-01

Deregulation in different steps of translational control is an emerging mechanism for cancer formation. One example of an oncogene with a direct role in control of translation is the Myc transcription factor. Myc directly increases protein synthesis rates by controlling the expression of multiple components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, Pol III and rDNA. However, the contribution of Myc-dependent increases in protein synthesis towards the multi-step process leading to cancer has remained unknown. Recent evidence strongly suggests that Myc oncogenic signaling may monopolize the translational machinery to elicit cooperative effects on cell growth, cell cycle progression, and genome instability as a mechanism for cancer initiation. Moreover, new genetic tools to restore aberrant increases in protein synthesis control are now available, which should enable the dissection of important mechanisms in cancer that rely on the translational machinery. PMID:19934336

Down- and up-conversion luminescent carbon dot fluid: inkjet printing and gel glass fabrication

NASA Astrophysics Data System (ADS)

Wang, Fu; Xie, Zheng; Zhang, Bing; Liu, Yun; Yang, Wendong; Liu, Chun-Yan

2014-03-01

Room temperature liquid-like nanoparticles have emerged as an exciting new research and development area, because their properties could be tailored over a broad range by manipulating geometric and chemical characteristics of the inorganic core and organic canopy. However, related applications are rarely reported due to the multi-step synthesis process and potential toxicity of cadmium based nanomaterials. In this study, we prepared inexpensive and eco-friendly carbon dot fluid by the direct thermal decomposition method. The carbon dot fluid can be excited from UV to near infrared light, and can be prepared as highly concentrated luminescent ink or incorporated into sol-gel derived organically modified silicate glass, suggesting that it has great application potential in the field of printable electronics, solid state lighting and so on.Room temperature liquid-like nanoparticles have emerged as an exciting new research and development area, because their properties could be tailored over a broad range by manipulating geometric and chemical characteristics of the inorganic core and organic canopy. However, related applications are rarely reported due to the multi-step synthesis process and potential toxicity of cadmium based nanomaterials. In this study, we prepared inexpensive and eco-friendly carbon dot fluid by the direct thermal decomposition method. The carbon dot fluid can be excited from UV to near infrared light, and can be prepared as highly concentrated luminescent ink or incorporated into sol-gel derived organically modified silicate glass, suggesting that it has great application potential in the field of printable electronics, solid state lighting and so on. Electronic supplementary information (ESI) available: Details of FTIR, XRD and DLS of CDF, optical properties of CDF, TEM images of other obtained products, luminescent spectra of CDF at different temperatures, and the optical photographs of CDF inks and silica glasses with different concentrations under normal, UV and 800 nm light. See DOI: 10.1039/c3nr05869g

Deciphering the Possible Role of Strain Path on the Evolution of Microstructure, Texture, and Magnetic Properties in a Fe-Cr-Ni Alloy

NASA Astrophysics Data System (ADS)

Kumar, Amit; Khatirkar, Rajesh Kisni; Gupta, Aman; Shekhawat, Satish K.; Suwas, Satyam

2018-06-01

In the present work, the influence of strain path on the evolution of microstructure, crystallographic texture, and magnetic properties of a two-phase Fe-Cr-Ni alloy was investigated. The Fe-Cr-Ni alloy had nearly equal proportion of austenite and ferrite and was cold rolled up to a true strain of 1.6 (thickness reduction) using two different strain paths—unidirectional rolling and multi-step cross rolling. The microstructures were characterized by scanning electron microscopy (SEM) and electron backscattered diffraction (EBSD), while crystallographic textures were determined using X-ray diffraction. For magnetic characterization, B-H loops and M-H curves were measured and magnetic force microscopy was performed. After unidirectional rolling, ferrite showed the presence of strong α-fiber (rolling direction, RD//<110>) and austenite showed strong brass type texture (consisting of Brass (Bs) ({110}<112>), Goss ({110}<001>), and S ({123}<634>)). After multi-step cross rolling, strong rotated cube ({100}<110>) was developed in ferrite, while austenite showed ND (normal direction) rotated brass ( 10 deg) texture. The strain-induced martensite (SIM) was found to be higher in unidirectionally rolled samples than multi-step cross-rolled samples. The coherently diffracting domain size, micro-strain, coercivity, and core loss also showed a strong correlation with strain and strain path. More strain was partitioned into austenite than ferrite during deformation (unidirectional as well as cross rolling). Further, the strain partitioning (in both austenite and ferrite) was found to be higher in unidirectionally rolled samples.

A Multistep Equilibria-Redox-Complexation Demonstration to Illustrate Le Chatelier's Principle.

ERIC Educational Resources Information Center

Berger, Tomas G.; Mellon, Edward K.

1996-01-01

Describes a process that can be used to illustrate a number of chemical principles including Le Chatelier's principle, redox chemistry, equilibria versus steady state situations, and solubility of species. (JRH)

Genetics Home Reference: tyrosinemia

MedlinePlus

... in the multistep process that breaks down the amino acid tyrosine, a building block of most proteins. If ... Resources MedlinePlus (4 links) Encyclopedia: Aminoaciduria Health Topic: Amino Acid Metabolism Disorders Health Topic: Liver Diseases Health Topic: ...

No-Cook Process for Ethanol Production Using Indian Broken Rice and Pearl Millet

PubMed Central

Gohel, Vipul; Duan, Gang

2012-01-01

No-cook process using granular starch hydrolyzing enzyme (GSHE) was evaluated for Indian broken rice and pearl millet. One-factor-at-a-time optimization method was used in ethanol production to identify optimum concentration of GSHE, under yeast fermentation conditions using broken rice and pearl millet as fermentation feedstocks. An acid fungal protease at a concentration of 0.2 kg per metric ton of grain was used along with various dosages of GSHE under yeast fermentation conditions to degrade the grain proteins into free amino nitrogen for yeast growth. To measure the efficacy of GSHE to hydrolyze no-cook broken rice and pearl millet, the chemical composition, fermentation efficiency, and ethanol recovery were determined. In both feedstocks, fermentation efficiency and ethanol recovery obtained through single-step no-cook process were higher than conventional multistep high-temperature process, currently considered the ideal industrial process. Furthermore, the no-cook process can directly impact energy consumption through steam saving and reducing the water cooling capacity needs, compared to conventional high-temperature process. PMID:22518148

Effects of pretanning processes on collagen structure and reactivity

USDA-ARS?s Scientific Manuscript database

The cattle hide, a major byproduct of the US meat industry, is the tanner’s substrate, and also the source of collagen for the food and biomaterials industries. Conversion of animal hides into leather is a multistep process that continually evolves in response to economic and environmental concerns...

Powdered hide for research on tanning mechanisms

USDA-ARS?s Scientific Manuscript database

The conversion of animal hides into leather, the most valuable coproduct of the US meat industry, is a multistep process that has evolved more as art form than as science. A variety of dehairing and other hide preparation processes have been adopted without an understanding of how they affect the c...

Meta-Analysis: An Introduction Using Regression Models

ERIC Educational Resources Information Center

Rhodes, William

2012-01-01

Research synthesis of evaluation findings is a multistep process. An investigator identifies a research question, acquires the relevant literature, codes findings from that literature, and analyzes the coded data to estimate the average treatment effect and its distribution in a population of interest. The process of estimating the average…

Predicting synergy in atomic layer etching

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

Kanarik, Keren J.; Tan, Samantha; Yang, Wenbing

2017-03-27

Atomic layer etching (ALE) is a multistep process used today in manufacturing for removing ultrathin layers of material. In this article, the authors report on ALE of Si, Ge, C, W, GaN, and SiO 2 using a directional (anisotropic) plasma-enhanced approach. The authors analyze these systems by defining an “ALE synergy” parameter which quantifies the degree to which a process approaches the ideal ALE regime. This parameter is inspired by the ion-neutral synergy concept introduced in the 1979 paper by Coburn and Winters. ALE synergy is related to the energetics of underlying surface interactions and is understood in terms ofmore » energy criteria for the energy barriers involved in the reactions. Synergistic behavior is observed for all of the systems studied, with each exhibiting behavior unique to the reactant–material combination. By systematically studying atomic layer etching of a group of materials, the authors show that ALE synergy scales with the surface binding energy of the bulk material. This insight explains why some materials are more or less amenable to the directional ALE approach. Furthermore, they conclude that ALE is both simpler to understand than conventional plasma etch processing and is applicable to metals, semiconductors, and dielectrics.« less

75 FR 42378 - Fisheries of the South Atlantic; Southeast Data, Assessment, and Review (SEDAR); South Atlantic...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-21

... (SEDAR) process, a multi-step method for determining the status of fish stocks in the Southeast Region. SEDAR includes a Data Workshop, a Stock Assessment Process and a Review Workshop. The product of the... datasets are appropriate for assessment analyses. The product of the Stock Assessment Process is a stock...

Optimizing the deposition of hydrogen evolution sites on suspended semiconductor particles using on-line photocatalytic reforming of aqueous methanol solutions.

PubMed

Busser, G Wilma; Mei, Bastian; Muhler, Martin

2012-11-01

The deposition of hydrogen evolution sites on photocatalysts is a crucial step in the multistep process of synthesizing a catalyst that is active for overall photocatalytic water splitting. An alternative approach to conventional photodeposition was developed, applying the photocatalytic reforming of aqueous methanol solutions to deposit metal particles on semiconductor materials such as Ga₂O₃ and (Ga₀.₆ Zn₀.₄)(N₀.₆O₀.₄). The method allows optimizing the loading of the co-catalysts based on the stepwise addition of their precursors and the continuous online monitoring of the evolved hydrogen. Moreover, a synergetic effect between different co-catalysts can be directly established. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

1D GAS-DYNAMIC SIMULATION OF SHOCK-WAVE PROCESSES VIA INTERNET

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

Khishchenko, K. V.; Levashov, P. R.; Povarnitsyn, M. E.

2009-12-28

We present a Web-interface for 1D simulation of different shock-wave experiments. The choosing of initial parameters, the modeling itself and output data treatment can be made directly via the Internet. The interface is based upon the expert system on shock-wave data and equations of state and contains both the Eulerian and Lagrangian Godunov hydrocodes. The availability of equations of state for a broad set of substances makes this system a useful tool for planning and interpretation of shock-wave experiments. As an example of simulation with the system, results of modeling of multistep shock loading of potassium between polytetrafluoroethylene and stainlessmore » steel plates are presented in comparison with experimental data from Shakhray et al.(2005).« less

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

Hou, Kun; Gao, Ziwei, E-mail: zwgao@snnu.edu.cn; Da, Min

Highlights: Black-Right-Pointing-Pointer Highly oriented and well-defined ZnO urchin-like crystals were successfully fabricated by a facile and effective hydrotherm method. Black-Right-Pointing-Pointer Polyvinylpyrrolidone- and hydrogen peroxide-assisted synthesis of ZnO could optimize its crystalline quality and the obtained ZnO have smooth surface, radial growth of morphology, obvious crystal edges and decreased defects. Black-Right-Pointing-Pointer The physicochemical properties of samples were studied by analysis of its structure, morphology, surface and optical properties. Black-Right-Pointing-Pointer This study represented a multistep mechanism based on [Zn(OH){sub 4}]{sup 2-} growth units about formation such urchin-like structure. -- Abstract: The urchin-like ZnO microcrystals with high crystallinity decomposed from [Zn(OH){sub 4}]{sup 2-}more » directly were obtained via a hydrothermal method. The morphology, particle size, crystalline structure and fluorescence of the as-prepared ZnO were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and photoluminescence (PL) analyses. The results demonstrated that the urchin-like ZnO crystals with wurtzite structure had a narrow distribution in size, which could be adjusted in the range of 30-80 {mu}m by varying reaction time. Broad visible light emission peak was also observed in the PL spectra of the synthesized ZnO products. A multistep growth process about how to form such a structure was proposed.« less

Multi-step approach for comparing the local air pollution contributions of conventional and innovative MSW thermo-chemical treatments.

PubMed

Ragazzi, M; Rada, E C

2012-10-01

In the sector of municipal solid waste management the debate on the performances of conventional and novel thermo-chemical technologies is still relevant. When a plant must be constructed, decision makers often select a technology prior to analyzing the local environmental impact of the available options, as this type of study is generally developed when the design of the plant has been carried out. Additionally, in the literature there is a lack of comparative analyses of the contributions to local air pollution from different technologies. The present study offers a multi-step approach, based on pollutant emission factors and atmospheric dilution coefficients, for a local comparative analysis. With this approach it is possible to check if some assumptions related to the advantages of the novel thermochemical technologies, in terms of local direct impact on air quality, can be applied to municipal solid waste treatment. The selected processes concern combustion, gasification and pyrolysis, alone or in combination. The pollutants considered are both carcinogenic and non-carcinogenic. A case study is presented concerning the location of a plant in an alpine region and its contribution to the local air pollution. Results show that differences among technologies are less than expected. Performances of each technology are discussed in details. Copyright © 2012 Elsevier Ltd. All rights reserved.

(n,{gamma}) Experiments on tin isotopes

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

Baramsai, B.; Mitchell, G. E.; Walker, C. L.

2013-04-19

Neutron capture experiments on highly enriched {sup 117,119}Sn isotopes were performed with the DANCE detector array located at the Los Alamos Neutron Science Center. The DANCE detector provides detailed information about the multi-step {gamma}-ray cascade following neutron capture. Analysis of the experimental data provides important information to improve understanding of the neutron capture reaction, including a test of the statistical model, the assignment of spins and parities of neutron resonances, and information concerning the Photon Strength Function (PSF) and Level Density (LD) below the neutron separation energy. Preliminary results for the (n,{gamma}) reaction on {sup 117,119}Sn are presented. Resonance spinsmore » of the odd-A tin isotopes were almost completely unknown. Resonance spins and parities have been assigned via analysis of the multi-step {gamma}-ray spectra and directional correlations.« less

Continuous-Time Random Walk with multi-step memory: an application to market dynamics

NASA Astrophysics Data System (ADS)

Gubiec, Tomasz; Kutner, Ryszard

2017-11-01

An extended version of the Continuous-Time Random Walk (CTRW) model with memory is herein developed. This memory involves the dependence between arbitrary number of successive jumps of the process while waiting times between jumps are considered as i.i.d. random variables. This dependence was established analyzing empirical histograms for the stochastic process of a single share price on a market within the high frequency time scale. Then, it was justified theoretically by considering bid-ask bounce mechanism containing some delay characteristic for any double-auction market. Our model appeared exactly analytically solvable. Therefore, it enables a direct comparison of its predictions with their empirical counterparts, for instance, with empirical velocity autocorrelation function. Thus, the present research significantly extends capabilities of the CTRW formalism. Contribution to the Topical Issue "Continuous Time Random Walk Still Trendy: Fifty-year History, Current State and Outlook", edited by Ryszard Kutner and Jaume Masoliver.

45-110 GHz Quad-Ridge Horn With Stable Gain and Symmetric Beam

NASA Astrophysics Data System (ADS)

Manafi, Sara; Al-Tarifi, Muhannad; Filipovic, Dejan S.

2017-09-01

A quad-ridge horn antenna with stabilized gain and minimum difference between Eand H-plane half-power beamwidths (HPBWs) is demonstrated for operation over 45-110 GHz bandwidth. Multistep flaring and corrugations on a finite ground plane are applied to obtain stable radiation patterns with 16-dBi minimum gain over the entire range. The computational studies are validated through measurements of a 3-D printed prototype using the direct metal laser sintering (DMLS) process. Accurate fabrication with achieved surface roughness of < 1.7 μm of the fabricated antenna is verified with digital microscope. The obtained gain variation, VSWR, and HPBW variation with rotation and over 45-110 GHz bandwidth are below 1.7 dB, 1.7:1, and 9°, respectively. This work demonstrates that the DMLS is a viable fabrication process for wideband horn antennas at millimeter-wave frequencies.

Evidence integration in model-based tree search

PubMed Central

Solway, Alec; Botvinick, Matthew M.

2015-01-01

Research on the dynamics of reward-based, goal-directed decision making has largely focused on simple choice, where participants decide among a set of unitary, mutually exclusive options. Recent work suggests that the deliberation process underlying simple choice can be understood in terms of evidence integration: Noisy evidence in favor of each option accrues over time, until the evidence in favor of one option is significantly greater than the rest. However, real-life decisions often involve not one, but several steps of action, requiring a consideration of cumulative rewards and a sensitivity to recursive decision structure. We present results from two experiments that leveraged techniques previously applied to simple choice to shed light on the deliberation process underlying multistep choice. We interpret the results from these experiments in terms of a new computational model, which extends the evidence accumulation perspective to multiple steps of action. PMID:26324932

Flow chemistry vs. flow analysis.

PubMed

Trojanowicz, Marek

2016-01-01

The flow mode of conducting chemical syntheses facilitates chemical processes through the use of on-line analytical monitoring of occurring reactions, the application of solid-supported reagents to minimize downstream processing and computerized control systems to perform multi-step sequences. They are exactly the same attributes as those of flow analysis, which has solid place in modern analytical chemistry in several last decades. The following review paper, based on 131 references to original papers as well as pre-selected reviews, presents basic aspects, selected instrumental achievements and developmental directions of a rapidly growing field of continuous flow chemical synthesis. Interestingly, many of them might be potentially employed in the development of new methods in flow analysis too. In this paper, examples of application of flow analytical measurements for on-line monitoring of flow syntheses have been indicated and perspectives for a wider application of real-time analytical measurements have been discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Implementing a Structured Reporting Initiative Using a Collaborative Multistep Approach.

PubMed

Goldberg-Stein, Shlomit; Walter, William R; Amis, E Stephen; Scheinfeld, Meir H

To describe the successful implementation of a structured reporting initiative in a large urban academic radiology department. We describe our process, compromises, and top 10 lessons learned in overhauling traditional reporting practices and comprehensively implementing structured reporting at our institution. To achieve our goals, we took deliberate steps toward consensus building, undertook multistep template refinement, and achieved close collaboration with the technical staff, department coders, and hospital information technologists. Following institutional review board exemption, we audited radiologist compliance by evaluating 100 consecutive cases of 12 common examination types. Fisher exact test was applied to determine significance of association between trainee initial report drafting and template compliance. We produced and implemented structured reporting templates for 95% of all departmental computed tomography, magnetic resonance, and ultrasound examinations. Structured templates include specialized reports adhering to the American College of Radiology's Reporting and Data Systems (ACR's RADS) recommendations (eg, Lung-RADS and Li-RADS). We attained 94% radiologist compliance within 2 years, without any financial incentives. We provide a blueprint of how to successfully achieve structured reporting using a collaborative multistep approach. Copyright © 2017 Elsevier Inc. All rights reserved.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics.

PubMed

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-07-21

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format.

Dissolvable fluidic time delays for programming multi-step assays in instrument-free paper diagnostics

PubMed Central

Lutz, Barry; Liang, Tinny; Fu, Elain; Ramachandran, Sujatha; Kauffman, Peter; Yager, Paul

2013-01-01

Lateral flow tests (LFTs) are an ingenious format for rapid and easy-to-use diagnostics, but they are fundamentally limited to assay chemistries that can be reduced to a single chemical step. In contrast, most laboratory diagnostic assays rely on multiple timed steps carried out by a human or a machine. Here, we use dissolvable sugar applied to paper to create programmable flow delays and present a paper network topology that uses these time delays to program automated multi-step fluidic protocols. Solutions of sucrose at different concentrations (10-70% of saturation) were added to paper strips and dried to create fluidic time delays spanning minutes to nearly an hour. A simple folding card format employing sugar delays was shown to automate a four-step fluidic process initiated by a single user activation step (folding the card); this device was used to perform a signal-amplified sandwich immunoassay for a diagnostic biomarker for malaria. The cards are capable of automating multi-step assay protocols normally used in laboratories, but in a rapid, low-cost, and easy-to-use format. PMID:23685876

Multistep cascade annihilations of dark matter and the Galactic Center excess

DOE PAGES

Elor, Gilly; Rodd, Nicholas L.; Slatyer, Tracy R.

2015-05-26

If dark matter is embedded in a non-trivial dark sector, it may annihilate and decay to lighter dark-sector states which subsequently decay to the Standard Model. Such scenarios - with annihilation followed by cascading dark-sector decays - can explain the apparent excess GeV gamma-rays identified in the central Milky Way, while evading bounds from dark matter direct detection experiments. Each 'step' in the cascade will modify the observable signatures of dark matter annihilation and decay, shifting the resulting photons and other final state particles to lower energies and broadening their spectra. We explore, in a model-independent way, the effect ofmore » multi-step dark-sector cascades on the preferred regions of parameter space to explain the GeV excess. We find that the broadening effects of multi-step cascades can admit final states dominated by particles that would usually produce too sharply peaked photon spectra; in general, if the cascades are hierarchical (each particle decays to substantially lighter particles), the preferred mass range for the dark matter is in all cases 20-150 GeV. Decay chains that have nearly-degenerate steps, where the products are close to half the mass of the progenitor, can admit much higher DM masses. We map out the region of mass/cross-section parameter space where cascades (degenerate, hierarchical or a combination) can fit the signal, for a range of final states. In the current paper, we study multi-step cascades in the context of explaining the GeV excess, but many aspects of our results are general and can be extended to other applications.« less

Lessons from the synthetic chemist nature.

PubMed

Jürjens, Gerrit; Kirschning, Andreas; Candito, David A

2015-05-01

This conceptual review examines the ideal multistep synthesis from the perspective of nature. We suggest that besides step- and redox economies, one other key to efficiency is steady state processing with intermediates that are immediately transformed to the next intermediate when formed. We discuss four of nature's strategies (multicatalysis, domino reactions, iteration and compartmentation) that commonly proceed via short-lived intermediates and show that these strategies are also part of the chemist's portfolio. We particularly focus on compartmentation which in nature is found microscopically within cells (organelles) and between cells and on a molecular level on multiprotein scaffolds (e.g. in polyketide synthases) and demonstrate how compartmentation is manifested in modern multistep flow synthesis.

78 FR 15707 - Fisheries of the Atlantic and Gulf of Mexico; Southeast Data, Assessment, and Review (SEDAR...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-12

... Southeast Data, Assessment and Review (SEDAR) process, a multi-step method for determining the status of... Center. Participants include: data collectors and database managers; stock assessment scientists...

Cold-in-place recycling in New York State.

DOT National Transportation Integrated Search

2010-07-01

Cold in-place recycling (CIPR) is a continuous multi-step process in which the existing asphalt pavement is : recycled using specialized equipment that cold mills the asphaltic pavement and blends asphalt emulsion and : aggregate (if necessary) with ...

78 FR 13868 - New England Fishery Management Council; Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-01

.... It is an important early step in what will be a multi-step process to develop the policy. The agenda... opportunity for communications between participants about management and science issues that relate to the ABC...

Multi-Step Lithiation of Tin Sulfide: An Investigation Using In Situ Electron Microscopy

DOE PAGES

Hwang, Sooyeon; Yao, Zhenpeng; Zhang, Lei; ...

2018-04-03

Two-dimensional metal sulfides have been widely explored as promising electrodes for lithium ion batteries since their two-dimensional layered structure allows lithium ions to intercalate between layers. For tin disulfide, the lithiation process proceeds via a sequence of three different types of reactions: intercalation, conversion, and alloying but the full scenario of reaction dynamics remains nebulous. In this paper, we investigate the dynamical process of the multi-step reactions using in situ electron microscopy and discover an intermediate rock-salt phase with the disordering of Li and Sn cations, after the initial 2-dimensional intercalation. The disordered cations occupy all the octahedral sites andmore » block the channels for intercalation, which alter the reaction pathways during further lithiation. Our first principles calculations of the non-equilibrium lithiation of SnS2 corroborate the energetic preference of the disordered rock-salt structure over known layered polymorphs. The in situ observations and calculations suggest a two-phase reaction nature for intercalation, disordering, and following conversion reactions. In addition, in situ de-lithiation observation confirms that the alloying reaction is reversible while the conversion reaction is not, which is consistent to the ex situ analysis. This work reveals the full lithiation characteristic of SnS2 and sheds light on the understanding of complex multistep reactions in two-dimensional materials.« less

Multi-Step Lithiation of Tin Sulfide: An Investigation Using In Situ Electron Microscopy

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

Hwang, Sooyeon; Yao, Zhenpeng; Zhang, Lei

Two-dimensional metal sulfides have been widely explored as promising electrodes for lithium ion batteries since their two-dimensional layered structure allows lithium ions to intercalate between layers. For tin disulfide, the lithiation process proceeds via a sequence of three different types of reactions: intercalation, conversion, and alloying but the full scenario of reaction dynamics remains nebulous. In this paper, we investigate the dynamical process of the multi-step reactions using in situ electron microscopy and discover an intermediate rock-salt phase with the disordering of Li and Sn cations, after the initial 2-dimensional intercalation. The disordered cations occupy all the octahedral sites andmore » block the channels for intercalation, which alter the reaction pathways during further lithiation. Our first principles calculations of the non-equilibrium lithiation of SnS2 corroborate the energetic preference of the disordered rock-salt structure over known layered polymorphs. The in situ observations and calculations suggest a two-phase reaction nature for intercalation, disordering, and following conversion reactions. In addition, in situ de-lithiation observation confirms that the alloying reaction is reversible while the conversion reaction is not, which is consistent to the ex situ analysis. This work reveals the full lithiation characteristic of SnS2 and sheds light on the understanding of complex multistep reactions in two-dimensional materials.« less

A new theory for multistep discretizations of stiff ordinary differential equations: Stability with large step sizes

NASA Technical Reports Server (NTRS)

Majda, G.

1985-01-01

A large set of variable coefficient linear systems of ordinary differential equations which possess two different time scales, a slow one and a fast one is considered. A small parameter epsilon characterizes the stiffness of these systems. A system of o.d.e.s. in this set is approximated by a general class of multistep discretizations which includes both one-leg and linear multistep methods. Sufficient conditions are determined under which each solution of a multistep method is uniformly bounded, with a bound which is independent of the stiffness of the system of o.d.e.s., when the step size resolves the slow time scale, but not the fast one. This property is called stability with large step sizes. The theory presented lets one compare properties of one-leg methods and linear multistep methods when they approximate variable coefficient systems of stiff o.d.e.s. In particular, it is shown that one-leg methods have better stability properties with large step sizes than their linear multistep counter parts. The theory also allows one to relate the concept of D-stability to the usual notions of stability and stability domains and to the propagation of errors for multistep methods which use large step sizes.

A dynamic integrated fault diagnosis method for power transformers.

PubMed

Gao, Wensheng; Bai, Cuifen; Liu, Tong

2015-01-01

In order to diagnose transformer fault efficiently and accurately, a dynamic integrated fault diagnosis method based on Bayesian network is proposed in this paper. First, an integrated fault diagnosis model is established based on the causal relationship among abnormal working conditions, failure modes, and failure symptoms of transformers, aimed at obtaining the most possible failure mode. And then considering the evidence input into the diagnosis model is gradually acquired and the fault diagnosis process in reality is multistep, a dynamic fault diagnosis mechanism is proposed based on the integrated fault diagnosis model. Different from the existing one-step diagnosis mechanism, it includes a multistep evidence-selection process, which gives the most effective diagnostic test to be performed in next step. Therefore, it can reduce unnecessary diagnostic tests and improve the accuracy and efficiency of diagnosis. Finally, the dynamic integrated fault diagnosis method is applied to actual cases, and the validity of this method is verified.

A Dynamic Integrated Fault Diagnosis Method for Power Transformers

PubMed Central

Gao, Wensheng; Liu, Tong

2015-01-01

In order to diagnose transformer fault efficiently and accurately, a dynamic integrated fault diagnosis method based on Bayesian network is proposed in this paper. First, an integrated fault diagnosis model is established based on the causal relationship among abnormal working conditions, failure modes, and failure symptoms of transformers, aimed at obtaining the most possible failure mode. And then considering the evidence input into the diagnosis model is gradually acquired and the fault diagnosis process in reality is multistep, a dynamic fault diagnosis mechanism is proposed based on the integrated fault diagnosis model. Different from the existing one-step diagnosis mechanism, it includes a multistep evidence-selection process, which gives the most effective diagnostic test to be performed in next step. Therefore, it can reduce unnecessary diagnostic tests and improve the accuracy and efficiency of diagnosis. Finally, the dynamic integrated fault diagnosis method is applied to actual cases, and the validity of this method is verified. PMID:25685841

TALE transcription factors during early development of the vertebrate brain and eye.

PubMed

Schulte, Dorothea; Frank, Dale

2014-01-01

Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification. Copyright © 2013 Wiley Periodicals, Inc.

Designing a Likert-Type Scale to Predict Environmentally Responsible Behavior in Undergraduate Students: A Multistep Process.

ERIC Educational Resources Information Center

Smith-Sebasto, N. J.; D'Costa, Ayres

1995-01-01

Describes an attempt to develop a reliable and valid instrument to assess the relationship between locus of control of reinforcement and environmentally responsible behavior. Presents a six-step psychometric process used to develop the Environmental Action Internal Control Index (EAICI) for undergraduate students. Contains 54 references. (JRH)

75 FR 59226 - Fisheries of the South Atlantic, Gulf of Mexico, and Caribbean; Southeastern Data, Assessment...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... the Southeast Data, Assessment and Review (SEDAR) process, a multi-step method for determining the... the South Atlantic, Gulf of Mexico, and Caribbean; Southeastern Data, Assessment, and Review (SEDAR... Committee will meet to discuss the SEDAR assessment schedule, budget, and the SEDAR process. See...

Capturing Problem-Solving Processes Using Critical Rationalism

ERIC Educational Resources Information Center

Chitpin, Stephanie; Simon, Marielle

2012-01-01

The examination of problem-solving processes continues to be a current research topic in education. Knowing how to solve problems is not only a key aspect of learning mathematics but is also at the heart of cognitive theories, linguistics, artificial intelligence, and computers sciences. Problem solving is a multistep, higher-order cognitive task…

Fully chip-embedded automation of a multi-step lab-on-a-chip process using a modularized timer circuit.

PubMed

Kang, Junsu; Lee, Donghyeon; Heo, Young Jin; Chung, Wan Kyun

2017-11-07

For highly-integrated microfluidic systems, an actuation system is necessary to control the flow; however, the bulk of actuation devices including pumps or valves has impeded the broad application of integrated microfluidic systems. Here, we suggest a microfluidic process control method based on built-in microfluidic circuits. The circuit is composed of a fluidic timer circuit and a pneumatic logic circuit. The fluidic timer circuit is a serial connection of modularized timer units, which sequentially pass high pressure to the pneumatic logic circuit. The pneumatic logic circuit is a NOR gate array designed to control the liquid-controlling process. By using the timer circuit as a built-in signal generator, multi-step processes could be done totally inside the microchip without any external controller. The timer circuit uses only two valves per unit, and the number of process steps can be extended without limitation by adding timer units. As a demonstration, an automation chip has been designed for a six-step droplet treatment, which entails 1) loading, 2) separation, 3) reagent injection, 4) incubation, 5) clearing and 6) unloading. Each process was successfully performed for a pre-defined step-time without any external control device.

Process for Making Single-Domain Magnetite Crystals

NASA Technical Reports Server (NTRS)

Golden, D. C.; Ming, Douglas W.; Morris, Richard V.; Lofgren, Gary E.; McKay, Gordan A.; Schwandt, Craig S.; Lauer, Howard V., Jr.; Socki, Richard A.

2004-01-01

A process for making chemically pure, single-domain magnetite crystals substantially free of structural defects has been invented as a byproduct of research into the origin of globules in a meteorite found in Antarctica and believed to have originated on Mars. The globules in the meteorite comprise layers of mixed (Mg, Fe, and Ca) carbonates, magnetite, and iron sulfides. Since the discovery of the meteorite was announced in August 1996, scientists have debated whether the globules are of biological origin or were formed from inorganic materials by processes that could have taken place on Mars. While the research that led to the present invention has not provided a definitive conclusion concerning the origin of the globules, it has shown that globules of a different but related chemically layered structure can be grown from inorganic ingredients in a multistep precipitation process. As described in more detail below, the present invention comprises the multistep precipitation process plus a subsequent heat treatment. The multistep precipitation process was demonstrated in a laboratory experiment on the growth of submicron ankerite crystals, overgrown by submicron siderite and pyrite crystals, overgrown by submicron magnesite crystals, overgrown by submicron siderite and pyrite. In each step, chloride salts of appropriate cations (Ca, Fe, and Mg) were dissolved in deoxygenated, CO2- saturated water. NaHCO3 was added as a pH buffer while CO2 was passed continuously through the solution. A 15-mL aliquot of the resulting solution was transferred into each of several 20 mL, poly(tetrafluoroethylene)-lined hydrothermal pressure vessels. The vessels were closed in a CO2 atmosphere, then transferred into an oven at a temperature of 150 C. After a predetermined time, the hydrothermal vessels were removed from the oven and quenched in a freezer. Supernatant solutions were decanted, and carbonate precipitates were washed free of soluble salts by repeated decantations with deionized water.

TEACH-M: A pilot study evaluating an instructional sequence for persons with impaired memory and executive functions.

PubMed

Ehlhardt, L A; Sohlberg, M M; Glang, A; Albin, R

2005-08-10

The purpose of this pilot study was to evaluate an instructional package that facilitates learning and retention of multi-step procedures for persons with severe memory and executive function impairments resulting from traumatic brain injury. The study used a multiple baseline across participants design. Four participants, two males and two females, ranging in age from 36-58 years, were taught a 7-step e-mail task. The instructional package (TEACH-M) was the experimental intervention and the number of correct e-mail steps learned was the dependent variable. Treatment effects were replicated across the four participants and maintained at 30 days post-treatment. Generalization and social validity data further supported the treatment programme. The results suggest that individuals with severe cognitive impairments are capable of learning new skills. Directions for future research include application of the instructional package to other multi-step procedures.

Ultra-fast consensus of discrete-time multi-agent systems with multi-step predictive output feedback

NASA Astrophysics Data System (ADS)

Zhang, Wenle; Liu, Jianchang

2016-04-01

This article addresses the ultra-fast consensus problem of high-order discrete-time multi-agent systems based on a unified consensus framework. A novel multi-step predictive output mechanism is proposed under a directed communication topology containing a spanning tree. By predicting the outputs of a network several steps ahead and adding this information into the consensus protocol, it is shown that the asymptotic convergence factor is improved by a power of q + 1 compared to the routine consensus. The difficult problem of selecting the optimal control gain is solved well by introducing a variable called convergence step. In addition, the ultra-fast formation achievement is studied on the basis of this new consensus protocol. Finally, the ultra-fast consensus with respect to a reference model and robust consensus is discussed. Some simulations are performed to illustrate the effectiveness of the theoretical results.

Down- and up-conversion luminescent carbon dot fluid: inkjet printing and gel glass fabrication.

PubMed

Wang, Fu; Xie, Zheng; Zhang, Bing; Liu, Yun; Yang, Wendong; Liu, Chun-yan

2014-04-07

Room temperature liquid-like nanoparticles have emerged as an exciting new research and development area, because their properties could be tailored over a broad range by manipulating geometric and chemical characteristics of the inorganic core and organic canopy. However, related applications are rarely reported due to the multi-step synthesis process and potential toxicity of cadmium based nanomaterials. In this study, we prepared inexpensive and eco-friendly carbon dot fluid by the direct thermal decomposition method. The carbon dot fluid can be excited from UV to near infrared light, and can be prepared as highly concentrated luminescent ink or incorporated into sol-gel derived organically modified silicate glass, suggesting that it has great application potential in the field of printable electronics, solid state lighting and so on.

ARSENIC (+3 OXIDATION STATE) METHYLTRANSFERASE AND THE METHYLATION OF ARSENICALS

EPA Science Inventory

Metabolic conversion of inorganic arsenic into methylated products is a multistep process that yields mono, di, and trimethylated arsenicals. In recent years, it has become apparent that formation of methylated metabolites of inorganic arsenic is not necessarily a detoxification...

Characterization of the proteome of cytoplasmic lipid droplets in mouse enterocytes after a dietary fat challenge

USDA-ARS?s Scientific Manuscript database

Dietary fat absorption by the small intestine is a multistep process that regulates the uptake and delivery of essential nutrients and energy. One step of this process is the temporary storage of dietary fat in cytoplasmic lipid droplets (CLDs). The storage and mobilization of dietary fat is thought...

The route from problem to solution in multistep continuous flow synthesis of pharmaceutical compounds.

PubMed

Bana, Péter; Örkényi, Róbert; Lövei, Klára; Lakó, Ágnes; Túrós, György István; Éles, János; Faigl, Ferenc; Greiner, István

2017-12-01

Recent advances in the field of continuous flow chemistry allow the multistep preparation of complex molecules such as APIs (Active Pharmaceutical Ingredients) in a telescoped manner. Numerous examples of laboratory-scale applications are described, which are pointing towards novel manufacturing processes of pharmaceutical compounds, in accordance with recent regulatory, economical and quality guidances. The chemical and technical knowledge gained during these studies is considerable; nevertheless, connecting several individual chemical transformations and the attached analytics and purification holds hidden traps. In this review, we summarize innovative solutions for these challenges, in order to benefit chemists aiming to exploit flow chemistry systems for the synthesis of biologically active molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bone Talk: Activated Osteoblasts Promote Lung Cancer Growth.

PubMed

Bružas, Emilis; Egeblad, Mikala

2018-03-01

Cancer cells can directly stimulate the generation and recruitment of tumor-supportive bone marrow-derived cells (BMDCs), including neutrophils, via secreted factors. A new study demonstrates that lung tumors also remotely activate bone-residing osteoblasts, which in turn promote neutrophil production. This is a multistep mechanism of establishing a supportive tumor microenvironment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Computational comparison of quantum-mechanical models for multistep direct reactions

NASA Astrophysics Data System (ADS)

Koning, A. J.; Akkermans, J. M.

1993-02-01

We have carried out a computational comparison of all existing quantum-mechanical models for multistep direct (MSD) reactions. The various MSD models, including the so-called Feshbach-Kerman-Koonin, Tamura-Udagawa-Lenske and Nishioka-Yoshida-Weidenmüller models, have been implemented in a single computer system. All model calculations thus use the same set of parameters and the same numerical techniques; only one adjustable parameter is employed. The computational results have been compared with experimental energy spectra and angular distributions for several nuclear reactions, namely, 90Zr(p,p') at 80 MeV, 209Bi(p,p') at 62 MeV, and 93Nb(n,n') at 25.7 MeV. In addition, the results have been compared with the Kalbach systematics and with semiclassical exciton model calculations. All quantum MSD models provide a good fit to the experimental data. In addition, they reproduce the systematics very well and are clearly better than semiclassical model calculations. We furthermore show that the calculated predictions do not differ very strongly between the various quantum MSD models, leading to the conclusion that the simplest MSD model (the Feshbach-Kerman-Koonin model) is adequate for the analysis of experimental data.

Evaluation of accuracy in implant site preparation performed in single- or multi-step drilling procedures.

PubMed

Marheineke, Nadine; Scherer, Uta; Rücker, Martin; von See, Constantin; Rahlf, Björn; Gellrich, Nils-Claudius; Stoetzer, Marcus

2018-06-01

Dental implant failure and insufficient osseointegration are proven results of mechanical and thermal damage during the surgery process. We herein performed a comparative study of a less invasive single-step drilling preparation protocol and a conventional multiple drilling sequence. Accuracy of drilling holes was precisely analyzed and the influence of different levels of expertise of the handlers and additional use of drill template guidance was evaluated. Six experimental groups, deployed in an osseous study model, were representing template-guided and freehanded drilling actions in a stepwise drilling procedure in comparison to a single-drill protocol. Each experimental condition was studied by the drilling actions of respectively three persons without surgical knowledge as well as three highly experienced oral surgeons. Drilling actions were performed and diameters were recorded with a precision measuring instrument. Less experienced operators were able to significantly increase the drilling accuracy using a guiding template, especially when multi-step preparations are performed. Improved accuracy without template guidance was observed when experienced operators were executing single-step versus multi-step technique. Single-step drilling protocols have shown to produce more accurate results than multi-step procedures. The outcome of any protocol can be further improved by use of guiding templates. Operator experience can be a contributing factor. Single-step preparations are less invasive and are promoting osseointegration. Even highly experienced surgeons are achieving higher levels of accuracy by combining this technique with template guidance. Hereby template guidance enables a reduction of hands-on time and side effects during surgery and lead to a more predictable clinical diameter.

Multi-step splicing of sphingomyelin synthase linear and circular RNAs.

PubMed

Filippenkov, Ivan B; Sudarkina, Olga Yu; Limborska, Svetlana A; Dergunova, Lyudmila V

2018-05-15

The SGMS1 gene encodes the enzyme sphingomyelin synthase 1 (SMS1), which is involved in the regulation of lipid metabolism, apoptosis, intracellular vesicular transport and other significant processes. The SGMS1 gene is located on chromosome 10 and has a size of 320 kb. Previously, we showed that dozens of alternative transcripts of the SGMS1 gene are present in various human tissues. In addition to mRNAs that provide synthesis of the SMS1 protein, this gene participates in the synthesis of non-coding transcripts, including circular RNAs (circRNAs), which include exons of the 5'-untranslated region (5'-UTR) and are highly represented in the brain. In this study, using the high-throughput technology RNA-CaptureSeq, many new SGMS1 transcripts were identified, including both intronic unspliced RNAs (premature RNAs) and RNAs formed via alternative splicing. Recursive exons (RS-exons) that can participate in the multi-step splicing of long introns of the gene were also identified. These exons participate in the formation of circRNAs. Thus, multi-step splicing may provide a variety of linear and circular RNAs of eukaryotic genes in tissues. Copyright © 2018 Elsevier B.V. All rights reserved.

Lignocellulose hydrolysis by multienzyme complexes

USDA-ARS?s Scientific Manuscript database

Lignocellulosic biomass is the most abundant renewable resource on the planet. Converting this material into a usable fuel is a multi-step process, the rate-limiting step being enzymatic hydrolysis of organic polymers into monomeric sugars. While the substrate can be complex and require a multitud...

GIST Clinic Application 2018 | Center for Cancer Research

Cancer.gov

Clinic date: June 20-22, 2018 This Application is the first step in a multi-step process for being considered for participation in our upcoming Pediatric and wild-type GIST clinic. Please review all 3 pages and complete all questions in full.

Counting the peaks in the excitation function for precompound processes

NASA Astrophysics Data System (ADS)

Bonetti, R.; Hussein, M. S.; Mello, P. A.

1983-08-01

The "counting of maxima" method of Brink and Stephen, conventionally used for the extraction of the correlation width of statistical (compound nucleus) reactions, is generalized to include precompound processes as well. It is found that this method supplies an important independent check of the results obtained from autocorrelation studies. An application is made to the reaction 25Mg(3He,p). NUCLEAR REACTIONS Statistical multistep compound processes discussed.

Setting the Scope of Concept Inventories for Introductory Computing Subjects

ERIC Educational Resources Information Center

Goldman, Ken; Gross, Paul; Heeren, Cinda; Herman, Geoffrey L.; Kaczmarczyk, Lisa; Loui, Michael C.; Zilles, Craig

2010-01-01

A concept inventory is a standardized assessment tool intended to evaluate a student's understanding of the core concepts of a topic. In order to create a concept inventory it is necessary to accurately identify these core concepts. A Delphi process is a structured multi-step process that uses a group of experts to achieve a consensus opinion. We…

Batch and multi-step fed-batch enzymatic saccharification of Formiline-pretreated sugarcane bagasse at high solid loadings for high sugar and ethanol titers.

PubMed

Zhao, Xuebing; Dong, Lei; Chen, Liang; Liu, Dehua

2013-05-01

Formiline pretreatment pertains to a biomass fractionation process. In the present work, Formiline-pretreated sugarcane bagasse was hydrolyzed with cellulases by batch and multi-step fed-batch processes at 20% solid loading. For wet pulp, after 144 h incubation with cellulase loading of 10 FPU/g dry solid, fed-batch process obtained ~150 g/L glucose and ~80% glucan conversion, while batch process obtained ~130 g/L glucose with corresponding ~70% glucan conversion. Solid loading could be further increased to 30% for the acetone-dried pulp. By fed-batch hydrolysis of the dried pulp in pH 4.8 buffer solution, glucose concentration could be 247.3±1.6 g/L with corresponding 86.1±0.6% glucan conversion. The enzymatic hydrolyzates could be well converted to ethanol by a subsequent fermentation using Saccharomices cerevisiae with ethanol titer of 60-70 g/L. Batch and fed-batch SSF indicated that Formiline-pretreated substrate showed excellent fermentability. The final ethanol concentration was 80 g/L with corresponding 82.7% of theoretical yield. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Neural Basis of Aversive Pavlovian Guidance during Planning

PubMed Central

Faulkner, Paul

2017-01-01

Important real-world decisions are often arduous as they frequently involve sequences of choices, with initial selections affecting future options. Evaluating every possible combination of choices is computationally intractable, particularly for longer multistep decisions. Therefore, humans frequently use heuristics to reduce the complexity of decisions. We recently used a goal-directed planning task to demonstrate the profound behavioral influence and ubiquity of one such shortcut, namely aversive pruning, a reflexive Pavlovian process that involves neglecting parts of the decision space residing beyond salient negative outcomes. However, how the brain implements this important decision heuristic and what underlies individual differences have hitherto remained unanswered. Therefore, we administered an adapted version of the same planning task to healthy male and female volunteers undergoing functional magnetic resonance imaging (fMRI) to determine the neural basis of aversive pruning. Through both computational and standard categorical fMRI analyses, we show that when planning was influenced by aversive pruning, the subgenual cingulate cortex was robustly recruited. This neural signature was distinct from those associated with general planning and valuation, two fundamental cognitive components elicited by our task but which are complementary to aversive pruning. Furthermore, we found that individual variation in levels of aversive pruning was associated with the responses of insula and dorsolateral prefrontal cortices to the receipt of large monetary losses, and also with subclinical levels of anxiety. In summary, our data reveal the neural signatures of an important reflexive Pavlovian process that shapes goal-directed evaluations and thereby determines the outcome of high-level sequential cognitive processes. SIGNIFICANCE STATEMENT Multistep decisions are complex because initial choices constrain future options. Evaluating every path for long decision sequences is often impractical; thus, cognitive shortcuts are often essential. One pervasive and powerful heuristic is aversive pruning, in which potential decision-making avenues are curtailed at immediate negative outcomes. We used neuroimaging to examine how humans implement such pruning. We found it to be associated with activity in the subgenual cingulate cortex, with neural signatures that were distinguishable from those covarying with planning and valuation. Individual variations in aversive pruning levels related to subclinical anxiety levels and insular cortex activation. These findings reveal the neural mechanisms by which basic negative Pavlovian influences guide decision-making during planning, with implications for disrupted decision-making in psychiatric disorders. PMID:28924006

The Neural Basis of Aversive Pavlovian Guidance during Planning.

PubMed

Lally, Níall; Huys, Quentin J M; Eshel, Neir; Faulkner, Paul; Dayan, Peter; Roiser, Jonathan P

2017-10-18

Important real-world decisions are often arduous as they frequently involve sequences of choices, with initial selections affecting future options. Evaluating every possible combination of choices is computationally intractable, particularly for longer multistep decisions. Therefore, humans frequently use heuristics to reduce the complexity of decisions. We recently used a goal-directed planning task to demonstrate the profound behavioral influence and ubiquity of one such shortcut, namely aversive pruning, a reflexive Pavlovian process that involves neglecting parts of the decision space residing beyond salient negative outcomes. However, how the brain implements this important decision heuristic and what underlies individual differences have hitherto remained unanswered. Therefore, we administered an adapted version of the same planning task to healthy male and female volunteers undergoing functional magnetic resonance imaging (fMRI) to determine the neural basis of aversive pruning. Through both computational and standard categorical fMRI analyses, we show that when planning was influenced by aversive pruning, the subgenual cingulate cortex was robustly recruited. This neural signature was distinct from those associated with general planning and valuation, two fundamental cognitive components elicited by our task but which are complementary to aversive pruning. Furthermore, we found that individual variation in levels of aversive pruning was associated with the responses of insula and dorsolateral prefrontal cortices to the receipt of large monetary losses, and also with subclinical levels of anxiety. In summary, our data reveal the neural signatures of an important reflexive Pavlovian process that shapes goal-directed evaluations and thereby determines the outcome of high-level sequential cognitive processes. SIGNIFICANCE STATEMENT Multistep decisions are complex because initial choices constrain future options. Evaluating every path for long decision sequences is often impractical; thus, cognitive shortcuts are often essential. One pervasive and powerful heuristic is aversive pruning, in which potential decision-making avenues are curtailed at immediate negative outcomes. We used neuroimaging to examine how humans implement such pruning. We found it to be associated with activity in the subgenual cingulate cortex, with neural signatures that were distinguishable from those covarying with planning and valuation. Individual variations in aversive pruning levels related to subclinical anxiety levels and insular cortex activation. These findings reveal the neural mechanisms by which basic negative Pavlovian influences guide decision-making during planning, with implications for disrupted decision-making in psychiatric disorders. Copyright © 2017 the authors 0270-6474/17/3710216-15$15.00/0.

Solar thermochemical splitting of water to generate hydrogen

PubMed Central

Rao, C. N. R.; Dey, Sunita

2017-01-01

Solar photochemical means of splitting water (artificial photosynthesis) to generate hydrogen is emerging as a viable process. The solar thermochemical route also promises to be an attractive means of achieving this objective. In this paper we present different types of thermochemical cycles that one can use for the purpose. These include the low-temperature multistep process as well as the high-temperature two-step process. It is noteworthy that the multistep process based on the Mn(II)/Mn(III) oxide system can be carried out at 700 °C or 750 °C. The two-step process has been achieved at 1,300 °C/900 °C by using yttrium-based rare earth manganites. It seems possible to render this high-temperature process as an isothermal process. Thermodynamics and kinetics of H2O splitting are largely controlled by the inherent redox properties of the materials. Interestingly, under the conditions of H2O splitting in the high-temperature process CO2 can also be decomposed to CO, providing a feasible method for generating the industrially important syngas (CO+H2). Although carbonate formation can be addressed as a hurdle during CO2 splitting, the problem can be avoided by a suitable choice of experimental conditions. The choice of the solar reactor holds the key for the commercialization of thermochemical fuel production. PMID:28522461

Characterization and multi-step transketolase-ω-transaminase bioconversions in an immobilized enzyme microreactor (IEMR) with packed tube.

PubMed

Halim, Amanatuzzakiah Abdul; Szita, Nicolas; Baganz, Frank

2013-12-01

The concept of de novo metabolic engineering through novel synthetic pathways offers new directions for multi-step enzymatic synthesis of complex molecules. This has been complemented by recent progress in performing enzymatic reactions using immobilized enzyme microreactors (IEMR). This work is concerned with the construction of de novo designed enzyme pathways in a microreactor synthesizing chiral molecules. An interesting compound, commonly used as the building block in several pharmaceutical syntheses, is a single diastereoisomer of 2-amino-1,3,4-butanetriol (ABT). This chiral amino alcohol can be synthesized from simple achiral substrates using two enzymes, transketolase (TK) and transaminase (TAm). Here we describe the development of an IEMR using His6-tagged TK and TAm immobilized onto Ni-NTA agarose beads and packed into tubes to enable multi-step enzyme reactions. The kinetic parameters of both enzymes were first determined using single IEMRs evaluated by a kinetic model developed for packed bed reactors. The Km(app) for both enzymes appeared to be flow rate dependent, while the turnover number kcat was reduced 3 fold compared to solution-phase TK and TAm reactions. For the multi-step enzyme reaction, single IEMRs were cascaded in series, whereby the first enzyme, TK, catalyzed a model reaction of lithium-hydroxypyruvate (HPA) and glycolaldehyde (GA) to L-erythrulose (ERY), and the second unit of the IEMR with immobilized TAm converted ERY into ABT using (S)-α-methylbenzylamine (MBA) as amine donor. With initial 60mM (HPA and GA each) and 6mM (MBA) substrate concentration mixture, the coupled reaction reached approximately 83% conversion in 20 min at the lowest flow rate. The ability to synthesize a chiral pharmaceutical intermediate, ABT in relatively short time proves this IEMR system as a powerful tool for construction and evaluation of de novo pathways as well as for determination of enzyme kinetics. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Examination of Wildland Fire Spread at Small Scales Using Direct Numerical Simulations and High-Speed Laser Diagnostics

NASA Astrophysics Data System (ADS)

Wimer, N. T.; Mackoweicki, A. S.; Poludnenko, A. Y.; Hoffman, C.; Daily, J. W.; Rieker, G. B.; Hamlington, P.

2017-12-01

Results are presented from a joint computational and experimental research effort focused on understanding and characterizing wildland fire spread at small scales (roughly 1m-1mm) using direct numerical simulations (DNS) with chemical kinetics mechanisms that have been calibrated using data from high-speed laser diagnostics. The simulations are intended to directly resolve, with high physical accuracy, all small-scale fluid dynamic and chemical processes relevant to wildland fire spread. The high fidelity of the simulations is enabled by the calibration and validation of DNS sub-models using data from high-speed laser diagnostics. These diagnostics have the capability to measure temperature and chemical species concentrations, and are used here to characterize evaporation and pyrolysis processes in wildland fuels subjected to an external radiation source. The chemical kinetics code CHEMKIN-PRO is used to study and reduce complex reaction mechanisms for water removal, pyrolysis, and gas phase combustion during solid biomass burning. Simulations are then presented for a gaseous pool fire coupled with the resulting multi-step chemical reaction mechanisms, and the results are connected to the fundamental structure and spread of wildland fires. It is anticipated that the combined computational and experimental approach of this research effort will provide unprecedented access to information about chemical species, temperature, and turbulence during the entire pyrolysis, evaporation, ignition, and combustion process, thereby permitting more complete understanding of the physics that must be represented by coarse-scale numerical models of wildland fire spread.

A novel method for a multi-level hierarchical composite with brick-and-mortar structure

PubMed Central

Brandt, Kristina; Wolff, Michael F. H.; Salikov, Vitalij; Heinrich, Stefan; Schneider, Gerold A.

2013-01-01

The fascination for hierarchically structured hard tissues such as enamel or nacre arises from their unique structure-properties-relationship. During the last decades this numerously motivated the synthesis of composites, mimicking the brick-and-mortar structure of nacre. However, there is still a lack in synthetic engineering materials displaying a true hierarchical structure. Here, we present a novel multi-step processing route for anisotropic 2-level hierarchical composites by combining different coating techniques on different length scales. It comprises polymer-encapsulated ceramic particles as building blocks for the first level, followed by spouted bed spray granulation for a second level, and finally directional hot pressing to anisotropically consolidate the composite. The microstructure achieved reveals a brick-and-mortar hierarchical structure with distinct, however not yet optimized mechanical properties on each level. It opens up a completely new processing route for the synthesis of multi-level hierarchically structured composites, giving prospects to multi-functional structure-properties relationships. PMID:23900554

A novel method for a multi-level hierarchical composite with brick-and-mortar structure.

PubMed

Brandt, Kristina; Wolff, Michael F H; Salikov, Vitalij; Heinrich, Stefan; Schneider, Gerold A

2013-01-01

The fascination for hierarchically structured hard tissues such as enamel or nacre arises from their unique structure-properties-relationship. During the last decades this numerously motivated the synthesis of composites, mimicking the brick-and-mortar structure of nacre. However, there is still a lack in synthetic engineering materials displaying a true hierarchical structure. Here, we present a novel multi-step processing route for anisotropic 2-level hierarchical composites by combining different coating techniques on different length scales. It comprises polymer-encapsulated ceramic particles as building blocks for the first level, followed by spouted bed spray granulation for a second level, and finally directional hot pressing to anisotropically consolidate the composite. The microstructure achieved reveals a brick-and-mortar hierarchical structure with distinct, however not yet optimized mechanical properties on each level. It opens up a completely new processing route for the synthesis of multi-level hierarchically structured composites, giving prospects to multi-functional structure-properties relationships.

A novel method for a multi-level hierarchical composite with brick-and-mortar structure

NASA Astrophysics Data System (ADS)

Brandt, Kristina; Wolff, Michael F. H.; Salikov, Vitalij; Heinrich, Stefan; Schneider, Gerold A.

2013-07-01

The fascination for hierarchically structured hard tissues such as enamel or nacre arises from their unique structure-properties-relationship. During the last decades this numerously motivated the synthesis of composites, mimicking the brick-and-mortar structure of nacre. However, there is still a lack in synthetic engineering materials displaying a true hierarchical structure. Here, we present a novel multi-step processing route for anisotropic 2-level hierarchical composites by combining different coating techniques on different length scales. It comprises polymer-encapsulated ceramic particles as building blocks for the first level, followed by spouted bed spray granulation for a second level, and finally directional hot pressing to anisotropically consolidate the composite. The microstructure achieved reveals a brick-and-mortar hierarchical structure with distinct, however not yet optimized mechanical properties on each level. It opens up a completely new processing route for the synthesis of multi-level hierarchically structured composites, giving prospects to multi-functional structure-properties relationships.

CFD analysis of a solid oxide fuel cell with internal reforming: Coupled interactions of transport, heterogeneous catalysis and electrochemical processes

NASA Astrophysics Data System (ADS)

Janardhanan, Vinod M.; Deutschmann, Olaf

Direct internal reforming in solid oxide fuel cell (SOFC) results in increased overall efficiency of the system. Present study focus on the chemical and electrochemical process in an internally reforming anode supported SOFC button cell running on humidified CH 4 (3% H 2 O). The computational approach employs a detailed multi-step model for heterogeneous chemistry in the anode, modified Butler-Volmer formalism for the electrochemistry and Dusty Gas Model (DGM) for the porous media transport. Two-dimensional elliptic model equations are solved for a button cell configuration. The electrochemical model assumes hydrogen as the only electrochemically active species. The predicted cell performances are compared with experimental reports. The results show that model predictions are in good agreement with experimental observation except the open circuit potentials. Furthermore, the steam content in the anode feed stream is found to have remarkable effect on the resulting overpotential losses and surface coverages of various species at the three-phase boundary.

Magnetization switching behavior with competing anisotropies in epitaxial Co3FeN /MnN exchange-coupled bilayers

NASA Astrophysics Data System (ADS)

Hajiri, T.; Yoshida, T.; Jaiswal, S.; Filianina, M.; Borie, B.; Ando, H.; Asano, H.; Zabel, H.; Kläui, M.

2016-11-01

We report unusual magnetization switching processes and angular-dependent exchange bias effects in fully epitaxial Co3FeN /MnN bilayers, where magnetocrystalline anisotropy and exchange coupling compete, probed by longitudinal and transverse magneto-optic Kerr effect (MOKE) magnetometry. The MOKE loops show multistep jumps corresponding to the nucleation and propagation of 90∘ domain walls in as-grown bilayers. By inducing exchange coupling, we confirm changes of the magnetization switching process due to the unidirectional anisotropy field of the exchange coupling. Taking into account the experimentally obtained values of the fourfold magnetocrystalline anisotropy, the unidirectional anisotropy field, the exchange-coupling constant, and the uniaxial anisotropy including its direction, the calculated angular-dependent exchange bias reproduces the experimental results. These results demonstrate the essential role of the competition between magnetocrystalline anisotropy and exchange coupling for understanding and tailoring exchange-coupling phenomena usable for engineering switching in fully epitaxial bilayers made of tailored materials.

Effects of pretanning processes on bovine hide collagen structure

USDA-ARS?s Scientific Manuscript database

The US meat industry currently produces approximately 35 million cattle hides annually as its most valuable coproduct. These hides serve as raw material, first for the leather industry, and then for the gelatin, and biomaterials industries. The conversion of animal hides into leather is a multistep...

Stability with large step sizes for multistep discretizations of stiff ordinary differential equations

NASA Technical Reports Server (NTRS)

Majda, George

1986-01-01

One-leg and multistep discretizations of variable-coefficient linear systems of ODEs having both slow and fast time scales are investigated analytically. The stability properties of these discretizations are obtained independent of ODE stiffness and compared. The results of numerical computations are presented in tables, and it is shown that for large step sizes the stability of one-leg methods is better than that of the corresponding linear multistep methods.

Event-triggered logical flow control for comprehensive process integration of multi-step assays on centrifugal microfluidic platforms.

PubMed

Kinahan, David J; Kearney, Sinéad M; Dimov, Nikolay; Glynn, Macdara T; Ducrée, Jens

2014-07-07

The centrifugal "lab-on-a-disc" concept has proven to have great potential for process integration of bioanalytical assays, in particular where ease-of-use, ruggedness, portability, fast turn-around time and cost efficiency are of paramount importance. Yet, as all liquids residing on the disc are exposed to the same centrifugal field, an inherent challenge of these systems remains the automation of multi-step, multi-liquid sample processing and subsequent detection. In order to orchestrate the underlying bioanalytical protocols, an ample palette of rotationally and externally actuated valving schemes has been developed. While excelling with the level of flow control, externally actuated valves require interaction with peripheral instrumentation, thus compromising the conceptual simplicity of the centrifugal platform. In turn, for rotationally controlled schemes, such as common capillary burst valves, typical manufacturing tolerances tend to limit the number of consecutive laboratory unit operations (LUOs) that can be automated on a single disc. In this paper, a major advancement on recently established dissolvable film (DF) valving is presented; for the very first time, a liquid handling sequence can be controlled in response to completion of preceding liquid transfer event, i.e. completely independent of external stimulus or changes in speed of disc rotation. The basic, event-triggered valve configuration is further adapted to leverage conditional, large-scale process integration. First, we demonstrate a fluidic network on a disc encompassing 10 discrete valving steps including logical relationships such as an AND-conditional as well as serial and parallel flow control. Then we present a disc which is capable of implementing common laboratory unit operations such as metering and selective routing of flows. Finally, as a pilot study, these functions are integrated on a single disc to automate a common, multi-step lab protocol for the extraction of total RNA from mammalian cell homogenate.

Architecture of Eph receptor clusters

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

Himanen, Juha P.; Yermekbayeva, Laila; Janes, Peter W.

2010-10-04

Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation during normal and oncogenic development. Signaling of Ephs is initiated in a multistep process leading to the assembly of higher-order signaling clusters that set off bidirectional signaling in interacting cells. However, the structural and mechanistic details of this assembly remained undefined. Here we present high-resolution structures of the complete EphA2 ectodomain and complexes with ephrin-A1 and A5 as the base unit of an Eph cluster. The structures reveal an elongated architecture with novel Eph/Eph interactions, both within and outside of the Eph ligand-binding domain, that suggest the molecular mechanismmore » underlying Eph/ephrin clustering. Structure-function analysis, by using site-directed mutagenesis and cell-based signaling assays, confirms the importance of the identified oligomerization interfaces for Eph clustering.« less

The limits to biocatalysis: pushing the envelope.

PubMed

Sheldon, Roger A; Brady, Dean

2018-06-12

In the period 1985 to 1995 applications of biocatalysis, driven by the need for more sustainable manufacture of chemicals and catalytic, (enantio)selective methods for the synthesis of pharmaceutical intermediates, largely involved the available hydrolases. This was followed, in the next two decades, by revolutionary developments in protein engineering and directed evolution for the optimisation of enzyme function and performance that totally changed the biocatalysis landscape. In the same period, metabolic engineering and synthetic biology revolutionised the use of whole cell biocatalysis in the synthesis of commodity chemicals by fermentation. In particular, developments in the enzymatic enantioselective synthesis of chiral alcohols and amines are highlighted. Progress in enzyme immobilisation facilitated applications under harsh industrial conditions, such as in organic solvents. The emergence of biocatalytic or chemoenzymatic cascade processes, often with co-immobilised enzymes, has enabled telescoping of multi-step processes. Discovering and inventing new biocatalytic processes, based on (meta)genomic sequencing, evolving enzyme promiscuity, chemomimetic biocatalysis, artificial metalloenzymes, and the introduction of non-canonical amino acids into proteins, are pushing back the limits of biocatalysis function. Finally, the integral role of biocatalysis in developing a biobased carbon-neutral economy is discussed.

Complex supramolecular interfacial tessellation through convergent multi-step reaction of a dissymmetric simple organic precursor

NASA Astrophysics Data System (ADS)

Zhang, Yi-Qi; Paszkiewicz, Mateusz; Du, Ping; Zhang, Liding; Lin, Tao; Chen, Zhi; Klyatskaya, Svetlana; Ruben, Mario; Seitsonen, Ari P.; Barth, Johannes V.; Klappenberger, Florian

2018-03-01

Interfacial supramolecular self-assembly represents a powerful tool for constructing regular and quasicrystalline materials. In particular, complex two-dimensional molecular tessellations, such as semi-regular Archimedean tilings with regular polygons, promise unique properties related to their nontrivial structures. However, their formation is challenging, because current methods are largely limited to the direct assembly of precursors, that is, where structure formation relies on molecular interactions without using chemical transformations. Here, we have chosen ethynyl-iodophenanthrene (which features dissymmetry in both geometry and reactivity) as a single starting precursor to generate the rare semi-regular (3.4.6.4) Archimedean tiling with long-range order on an atomically flat substrate through a multi-step reaction. Intriguingly, the individual chemical transformations converge to form a symmetric alkynyl-Ag-alkynyl complex as the new tecton in high yields. Using a combination of microscopy and X-ray spectroscopy tools, as well as computational modelling, we show that in situ generated catalytic Ag complexes mediate the tecton conversion.

Developing a Mind-Body Exercise Programme for Stressed Children

ERIC Educational Resources Information Center

Wang, Claudia; Seo, Dong-Chul; Geib, Roy W

2017-01-01

Objective: To describe the process of developing a Health Qigong programme for stressed children using a formative evaluation approach. Methods: A multi-step formative evaluation method was utilised. These steps included (1) identifying programme content and drafting the curriculum, (2) synthesising effective and age-appropriate pedagogies, (3)…

A Quantitative Tunneling/Desorption Model for the Exchange Current at the Porous Electrode/Beta - Alumina/Alkali Metal Gas Three Phase Zone at 700-1300K

NASA Technical Reports Server (NTRS)

Williams, R. M.; Ryan, M. A.; Saipetch, C.; LeDuc, H. G.

1996-01-01

The exchange current observed at porous metal electrodes on sodium or potassium beta -alumina solid electrolytes in alkali metal vapor is quantitatively modeled with a multi-step process with good agreement with experimental results.

Thermally Stable Ni-rich Austenite Formed Utilizing Multistep Intercritical Heat Treatment in a Low-Carbon 10 Wt Pct Ni Martensitic Steel

NASA Astrophysics Data System (ADS)

Jain, Divya; Isheim, Dieter; Zhang, Xian J.; Ghosh, Gautam; Seidman, David N.

2017-08-01

Austenite reversion and its thermal stability attained during the transformation is key to enhanced toughness and blast resistance in transformation-induced-plasticity martensitic steels. We demonstrate that the thermal stability of Ni-stabilized austenite and kinetics of the transformation can be controlled by forming Ni-rich regions in proximity of pre-existing (retained) austenite. Atom probe tomography (APT) in conjunction with thermodynamic and kinetic modeling elucidates the role of Ni-rich regions in enhancing growth kinetics of thermally stable austenite, formed utilizing a multistep intercritical ( Quench- Lamellarization- Tempering (QLT)-type) heat treatment for a low-carbon 10 wt pct Ni steel. Direct evidence of austenite formation is provided by dilatometry, and the volume fraction is quantified by synchrotron X-ray diffraction. The results indicate the growth of nm-thick austenite layers during the second intercritical tempering treatment (T-step) at 863 K (590 °C), with austenite retained from first intercritical treatment (L-step) at 923 K (650 °C) acting as a nucleation template. For the first time, the thermal stability of austenite is quantified with respect to its compositional evolution during the multistep intercritical treatment of these steels. Austenite compositions measured by APT are used in combination with the thermodynamic and kinetic approach formulated by Ghosh and Olson to assess thermal stability and predict the martensite-start temperature. This approach is particularly useful as empirical relations cannot be extrapolated for the highly Ni-enriched austenite investigated in the present study.

Multistep fluorescence gated proportional counters

NASA Technical Reports Server (NTRS)

Ramsey, Brian D.; Weisskopf, Martin C.

1990-01-01

A proportional counter is introduced in which the levels of energy and spatial resolutions and background rejection permit the application of the device to X-ray astronomy. A multistep approach is employed in which photons cause a signal that triggers the system and measures the energy of the incident photon. The multistep approach permits good energy resolution from parallel geometry and from the imaging stage due to coupling of the imaging and amplification stages. The design also employs fluorescence gating to reduce background, a method that is compatible with the multistep technique. Use of the proportional counter is reported for NASA's supernova campaign, and the pair background is below 0.0001 counts/sq cm sec keV at the xenon k-edge. Potential improvements and applications are listed including the CASES, POF, and EXOSS mission programs.

The MSFC large-area imaging multistep proportional counter

NASA Technical Reports Server (NTRS)

Ramsey, B. D.; Weisskopf, M. C.; Joy, M. K.

1989-01-01

A large-area multistep imaging proportional counter that is being currently developed at the Marshall Space Flight Center is described. The device, known as a multistep fluorescence gated detector, consists of a multiwire proportional counter (MWPC) with a preamplification region. The MWCP features superior spatial resolution with a very high degree of background rejection. It is ideally suited for use in X-ray astronomy in 20-100 keV energy range. The paper includes the MWPC schematic and a list of instrument specifications.

An analysis of hydrogen production via closed-cycle schemes. [thermochemical processings from water

NASA Technical Reports Server (NTRS)

Chao, R. E.; Cox, K. E.

1975-01-01

A thermodynamic analysis and state-of-the-art review of three basic schemes for production of hydrogen from water: electrolysis, thermal water-splitting, and multi-step thermochemical closed cycles is presented. Criteria for work-saving thermochemical closed-cycle processes are established, and several schemes are reviewed in light of such criteria. An economic analysis is also presented in the context of energy costs.

Synthesis of 2-Azulenyltetrathiafulvalenes by Palladium-Catalyzed Direct Arylation of 2-Chloroazulenes with Tetrathiafulvalene and Their Optical and Electrochemical Properties.

PubMed

Shoji, Taku; Araki, Takanori; Sugiyama, Shuhei; Ohta, Akira; Sekiguchi, Ryuta; Ito, Shunji; Okujima, Tetsuo; Toyota, Kozo

2017-02-03

Tetrathiafulvalene (TTF) derivatives with 2-azulenyl substituents 5-11 were prepared by the palladium-catalyzed direct arylation reaction of 2-chloroazulenes with TTF in good yield. Photophysical properties of these compounds were investigated by UV-vis spectroscopy and theoretical calculations. Redox behavior of the novel azulene-substituted TTFs was examined by using cyclic voltammetry and differential pulse voltammetry, which revealed their multistep electrochemical oxidation and/or reduction properties. Moreover, these TTF derivatives showed significant spectral change in the visible region under the redox conditions.

Comparison of microbial community shifts in two parallel multi-step drinking water treatment processes.

PubMed

Xu, Jiajiong; Tang, Wei; Ma, Jun; Wang, Hong

2017-07-01

Drinking water treatment processes remove undesirable chemicals and microorganisms from source water, which is vital to public health protection. The purpose of this study was to investigate the effects of treatment processes and configuration on the microbiome by comparing microbial community shifts in two series of different treatment processes operated in parallel within a full-scale drinking water treatment plant (DWTP) in Southeast China. Illumina sequencing of 16S rRNA genes of water samples demonstrated little effect of coagulation/sedimentation and pre-oxidation steps on bacterial communities, in contrast to dramatic and concurrent microbial community shifts during ozonation, granular activated carbon treatment, sand filtration, and disinfection for both series. A large number of unique operational taxonomic units (OTUs) at these four treatment steps further illustrated their strong shaping power towards the drinking water microbial communities. Interestingly, multidimensional scaling analysis revealed tight clustering of biofilm samples collected from different treatment steps, with Nitrospira, the nitrite-oxidizing bacteria, noted at higher relative abundances in biofilm compared to water samples. Overall, this study provides a snapshot of step-to-step microbial evolvement in multi-step drinking water treatment systems, and the results provide insight to control and manipulation of the drinking water microbiome via optimization of DWTP design and operation.

Interfacing to the brain’s motor decisions

PubMed Central

2017-01-01

It has been long known that neural activity, recorded with electrophysiological methods, contains rich information about a subject’s motor intentions, sensory experiences, allocation of attention, action planning, and even abstract thoughts. All these functions have been the subject of neurophysiological investigations, with the goal of understanding how neuronal activity represents behavioral parameters, sensory inputs, and cognitive functions. The field of brain-machine interfaces (BMIs) strives for a somewhat different goal: it endeavors to extract information from neural modulations to create a communication link between the brain and external devices. Although many remarkable successes have been already achieved in the BMI field, questions remain regarding the possibility of decoding high-order neural representations, such as decision making. Could BMIs be employed to decode the neural representations of decisions underlying goal-directed actions? In this review we lay out a framework that describes the computations underlying goal-directed actions as a multistep process performed by multiple cortical and subcortical areas. We then discuss how BMIs could connect to different decision-making steps and decode the neural processing ongoing before movements are initiated. Such decision-making BMIs could operate as a system with prediction that offers many advantages, such as shorter reaction time, better error processing, and improved unsupervised learning. To present the current state of the art, we review several recent BMIs incorporating decision-making components. PMID:28003406

Laser direct-write for fabrication of three-dimensional paper-based devices.

PubMed

He, P J W; Katis, I N; Eason, R W; Sones, C L

2016-08-16

We report the use of a laser-based direct-write (LDW) technique that allows the design and fabrication of three-dimensional (3D) structures within a paper substrate that enables implementation of multi-step analytical assays via a 3D protocol. The technique is based on laser-induced photo-polymerisation, and through adjustment of the laser writing parameters such as the laser power and scan speed we can control the depths of hydrophobic barriers that are formed within a substrate which, when carefully designed and integrated, produce 3D flow paths. So far, we have successfully used this depth-variable patterning protocol for stacking and sealing of multi-layer substrates, for assembly of backing layers for two-dimensional (2D) lateral flow devices and finally for fabrication of 3D devices. Since the 3D flow paths can also be formed via a single laser-writing process by controlling the patterning parameters, this is a distinct improvement over other methods that require multiple complicated and repetitive assembly procedures. This technique is therefore suitable for cheap, rapid and large-scale fabrication of 3D paper-based microfluidic devices.

Expression of metastasis suppressor BRMS1 in breast cancer cells results in a marked delay in cellular adhesion to matrix

USDA-ARS?s Scientific Manuscript database

Metastatic dissemination is a multi-step process that depends on cancer cells’ ability to respond to microenvironmental cues by adapting adhesion abilities and undergoing cytoskeletal rearrangement. Breast Cancer Metastasis Suppressor 1 (BRMS1) affects several steps of the metastatic cascade: it dec...

Proteases in Fas-mediated apoptosis.

PubMed

Zhivotovsky, B; Burgess, D H; Schlegel, J; Pörn, M I; Vanags, D; Orrenius, S

1997-01-01

Involvement of a unique family of cysteine proteases in the multistep apoptotic process has been documented. Cloning of several mammalian genes identifies some components of this cellular response. However, it is currently unclear which protease plays a role as a signal and/or effector of apoptosis. We summarize contributions to the data concerning proteases in Fas-mediated apoptosis.

Development of Active Learning with Simulations and Games

ERIC Educational Resources Information Center

Zapalska, Alina; Brozik, Dallas; Rudd, Denis

2012-01-01

Educational games and simulations are excellent active learning tools that offer students hands-on experience. Little research is available on developing games and simulations and how teachers can be assisted in making their own games and simulations. In this context, the paper presents a multi-step process of how to develop games and simulations…

Chemical Research Writing: A Preparatory Course for Student Capstone Research

ERIC Educational Resources Information Center

Schepmann, Hala G.; Hughes, Laura A.

2006-01-01

A research writing course was developed to prepare chemistry majors to conduct and report on their capstone research projects. The course guides students through a multistep process of preparing a literature review and research proposal. Students learn how to identify and avoid plagiarism, critically read and summarize a scientific article,…

Home Language Survey Data Quality Self-Assessment. REL 2017-198

ERIC Educational Resources Information Center

Henry, Susan F.; Mello, Dan; Avery, Maria-Paz; Parker, Caroline; Stafford, Erin

2017-01-01

Most state departments of education across the United States recommend or require that districts use a home language survey as the first step in a multistep process of identifying students who qualify for English learner student services. School districts typically administer the home language survey to parents and guardians during a student's…

Scholastic Audits. Research Brief

ERIC Educational Resources Information Center

Walker, Karen

2009-01-01

What is a scholastic audit? The purpose of the audit is to assist individual schools and districts improve. The focus is on gathering data and preparing recommendations that can be used to guide school improvement initiatives. Scholastic audits use a multi-step approach and include: (1) Preparing for the Audit; (2) Audit process; (3) Audit report;…

78 FR 36525 - Fisheries of the Atlantic and the Gulf of Mexico; Southeast Data, Assessment, and Review (SEDAR...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

...) Atlantic Sharpnose (Rhizoprionodon terraenovae) and Bonnethead (Sphyrna tiburo) sharks. SUMMARY: The SEDAR 34 assessment of HMS Atlantic Sharpnose and Bonnethead sharks will consist of an in-person workshop... for determining the status of fish stocks in the Southeast Region. SEDAR is a multi-step process...

Protoparvovirus Knocking at the Nuclear Door.

PubMed

Mäntylä, Elina; Kann, Michael; Vihinen-Ranta, Maija

2017-10-02

Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes. The capsids are transported actively across the nuclear pore complexes using nuclear import receptors. The nuclear import is sometimes accompanied by structural changes in the nuclear envelope, and is completed by intranuclear disassembly of capsids and chromatinization of the viral genome. This review discusses the nuclear import strategies of protoparvoviruses and describes its dynamics comprising active and passive movement, and directed and diffusive motion of capsids in the molecularly crowded environment of the cell.

Evaluating the Veterans Health Administration's Staffing Methodology Model: A Reliable Approach.

PubMed

Taylor, Beth; Yankey, Nicholas; Robinson, Claire; Annis, Ann; Haddock, Kathleen S; Alt-White, Anna; Krein, Sarah L; Sales, Anne

2015-01-01

All Veterans Health Administration facilities have been mandated to use a standardized method of determining appropriate direct-care staffing by nursing personnel. A multi-step process was designed to lead to projection of full-time equivalent employees required for safe and effective care across all inpatient units. These projections were intended to develop appropriate budgets for each facility. While staffing levels can be increased, even in facilities subject to budget and personnel caps, doing so requires considerable commitment at all levels of the facility. This commitment must come from front-line nursing personnel to senior leadership, not only in nursing and patient care services, but throughout the hospital. Learning to interpret and rely on data requires a considerable shift in thinking for many facilities, which have relied on historical levels to budget for staffing, but which does not take into account the dynamic character of nursing units and patient need.

Cross-cultural adaptation of instruments assessing breastfeeding determinants: a multi-step approach

PubMed Central

2014-01-01

Background Cross-cultural adaptation is a necessary process to effectively use existing instruments in other cultural and language settings. The process of cross-culturally adapting, including translation, of existing instruments is considered a critical set to establishing a meaningful instrument for use in another setting. Using a multi-step approach is considered best practice in achieving cultural and semantic equivalence of the adapted version. We aimed to ensure the content validity of our instruments in the cultural context of KwaZulu-Natal, South Africa. Methods The Iowa Infant Feeding Attitudes Scale, Breastfeeding Self-Efficacy Scale-Short Form and additional items comprise our consolidated instrument, which was cross-culturally adapted utilizing a multi-step approach during August 2012. Cross-cultural adaptation was achieved through steps to maintain content validity and attain semantic equivalence in the target version. Specifically, Lynn’s recommendation to apply an item-level content validity index score was followed. The revised instrument was translated and back-translated. To ensure semantic equivalence, Brislin’s back-translation approach was utilized followed by the committee review to address any discrepancies that emerged from translation. Results Our consolidated instrument was adapted to be culturally relevant and translated to yield more reliable and valid results for use in our larger research study to measure infant feeding determinants effectively in our target cultural context. Conclusions Undertaking rigorous steps to effectively ensure cross-cultural adaptation increases our confidence that the conclusions we make based on our self-report instrument(s) will be stronger. In this way, our aim to achieve strong cross-cultural adaptation of our consolidated instruments was achieved while also providing a clear framework for other researchers choosing to utilize existing instruments for work in other cultural, geographic and population settings. PMID:25285151

Progress on BN and Doped-BN Coatings on Woven Fabrics

NASA Technical Reports Server (NTRS)

Hurwitz, Frances I.; Scott, John M.; Chayka, Paul V.

2001-01-01

A novel, multistep process for applying interface coatings to woven structures using a pulsed CVD process is being evaluated. Borazine (B3N3H6), a neat liquid, and several Si precursors are used in the process to produce BN and SiBN coatings on Hi- Nicalon fabrics and preforms. A three variable, two level, full factorial matrix is proposed to define the influence of processing parameters. Coating morphology, uniformity and chemistry are characterized by field emission scanning electron microscopy (FESEM), energy dispersive (EDS) and Auger spectroscopies.

Multi-step rhodopsin inactivation schemes can account for the size variability of single photon responses in Limulus ventral photoreceptors

PubMed Central

1994-01-01

Limulus ventral photoreceptors generate highly variable responses to the absorption of single photons. We have obtained data on the size distribution of these responses, derived the distribution predicted from simple transduction cascade models and compared the theory and data. In the simplest of models, the active state of the visual pigment (defined by its ability to activate G protein) is turned off in a single reaction. The output of such a cascade is predicted to be highly variable, largely because of stochastic variation in the number of G proteins activated. The exact distribution predicted is exponential, but we find that an exponential does not adequately account for the data. The data agree much better with the predictions of a cascade model in which the active state of the visual pigment is turned off by a multi-step process. PMID:8057085

Integration of living cells into nanostructures using non-conventional self-assembly

NASA Astrophysics Data System (ADS)

Carnes, Eric C.

Patternable cell immobilization is an essential feature of any solid-state device designed for interrogating or exploiting living cells. Immobilized cells must remain viable in a robust matrix that promotes fluidic connectivity between the cells and their environment while retaining the ability to establish and maintain necessary chemical gradients. A suitable inorganic matrix can be constructed via evaporation-induced self-assembly of nanostructured silica, in which phospholipids are used in place of traditional surfactant structure-directing agents in order to enhance cell viability and to create a coherent interface between the cell and the surrounding three-dimensional nanostructure. We have used this technique to develop two distinct cell encapsulation processes: cell-directed assembly and cell-directed integration. Cell-directed assembly is a one-step procedure that provides superior viability of immobilized cells by encouraging cells to interact with the developing host matrix. Limitations of this system include low viability for some cell types due to exposure to solvents and stresses, as well as a lack of control over the developing host nanostructure. Cell-directed integration addresses these shortcomings by introducing a two-step process in which cells become encapsulated in a pre-formed silica matrix. The validity of each encapsulation method has been demonstrated with Gram-positive and Gram-negative bacteria, yeast, and mammalian cells. The ability of the immobilized cells to establish relevant gradients of ions or signaling molecules, a key feature of these systems, has been characterized. Additionally, extension of cell encapsulation to address lingering questions in cell biology is addressed. We have also adapted these immobilization processes to be compatible with a variety of patterning strategies having tailorable properties. Widely available photolithography techniques, as well as direct aerosol deposition, have been adapted to provide methods for obtaining both positive and negative transfer of desired cell patterns. Multi-step lithography is also used to create a highly functional system allowing spatial control of not only cells but also media and other molecules of interest.

Focused-electron-beam-induced processing (FEBIP) for emerging applications in carbon nanoelectronics

NASA Astrophysics Data System (ADS)

Fedorov, Andrei G.; Kim, Songkil; Henry, Mathias; Kulkarni, Dhaval; Tsukruk, Vladimir V.

2014-12-01

Focused-electron-beam-induced processing (FEBIP), a resist-free additive nanomanufacturing technique, is an actively researched method for "direct-write" processing of a wide range of structural and functional nanomaterials, with high degree of spatial and time-domain control. This article attempts to critically assess the FEBIP capabilities and unique value proposition in the context of processing of electronics materials, with a particular emphasis on emerging carbon (i.e., based on graphene and carbon nanotubes) devices and interconnect structures. One of the major hurdles in advancing the carbon-based electronic materials and device fabrication is a disjoint nature of various processing steps involved in making a functional device from the precursor graphene/CNT materials. Not only this multi-step sequence severely limits the throughput and increases the cost, but also dramatically reduces the processing reproducibility and negatively impacts the quality because of possible between-the-step contamination, especially for impurity-susceptible materials such as graphene. The FEBIP provides a unique opportunity to address many challenges of carbon nanoelectronics, especially when it is employed as part of an integrated processing environment based on multiple "beams" of energetic particles, including electrons, photons, and molecules. This avenue is promising from the applications' prospective, as such a multi-functional (electron/photon/molecule beam) enables one to define shapes (patterning), form structures (deposition/etching), and modify (cleaning/doping/annealing) properties with locally resolved control on nanoscale using the same tool without ever changing the processing environment. It thus will have a direct positive impact on enhancing functionality, improving quality and reducing fabrication costs for electronic devices, based on both conventional CMOS and emerging carbon (CNT/graphene) materials.

A multi-step approach for testing non-toxic amphiphilic antifouling coatings against marine microfouling at different levels of biological complexity.

PubMed

Zecher, Karsten; Aitha, Vishwa Prasad; Heuer, Kirsten; Ahlers, Herbert; Roland, Katrin; Fiedel, Michael; Philipp, Bodo

2018-03-01

Marine biofouling on artificial surfaces such as ship hulls or fish farming nets causes enormous economic damage. The time for the developmental process of antifouling coatings can be shortened by reliable laboratory assays. For designing such test systems, it is important that toxic effects can be excluded, that multiple parameters can be addressed simultaneously and that mechanistic aspects can be included. In this study, a multi-step approach for testing antifouling coatings was established employing photoautotrophic biofilm formation of marine microorganisms in micro- and mesoscoms. Degree and pattern of biofilm formation was determined by quantification of chlorophyll fluorescence. For the microcosms, co-cultures of diatoms and a heterotrophic bacterium were exposed to fouling-release coatings. For the mesocosms, a novel device was developed that permits parallel quantification of a multitude of coatings under defined conditions with varying degrees of shear stress. Additionally, the antifouling coatings were tested for leaching of potential compounds and finally tested in sea trials. This multistep-approach revealed that the individual steps led to consistent results regarding antifouling activity of the coatings. Furthermore, the novel mesocosm system can be employed for advanced antifouling analysis including metagenomic approaches for determination of microbial diversity attaching to different coatings under changing shear forces. Copyright © 2018 Elsevier B.V. All rights reserved.

The Reality of Welfare-to-Work: Employment Opportunities for Women Affected by Welfare Time Limits in Texas.

ERIC Educational Resources Information Center

Lawson, Leslie O.; King, Christopher T.

Researchers assembled a database of current and projected information on the following: welfare recipients; other female participants in the labor market; employment, occupational availability, and job openings; and occupational characteristics. The database was used in a multistep process to project the number of women forced to leave welfare…

76 FR 103 - Fisheries of the Gulf of Mexico; Southeast Data, Assessment, and Review (SEDAR); Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-03

... have implemented the Southeast Data, Assessment and Review (SEDAR) process, a multi-step method for... Workshop Schedule February 14-17, 2011; SEDAR 22 Review Workshop February 14, 2010: 1 p.m.-8 p.m.; February... the Gulf of Mexico; Southeast Data, Assessment, and Review (SEDAR); Public Meeting AGENCY: National...

77 FR 16812 - Fisheries of the Gulf of Mexico; Southeast Data, Assessment, and Review (SEDAR); Public Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-22

...: Notice of SEDAR 29 assessment webinars for Highly Migratory Species (HMS) blacktip shark (Carcharhinus limbatus). SUMMARY: The SEDAR 29 assessment of HMS blacktip shark will consist of a workshop and series of... Review (SEDAR) process, a multi-step method for determining the status of fish stocks in the Southeast...

78 FR 34046 - Fisheries of the Gulf of Mexico; Southeast Data, Assessment, and Review (SEDAR); Public Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... Bonnethead sharks. SUMMARY: The SEDAR assessment of the HMS stocks of Atlantic Sharpnose and Bonnethead sharks will consist of one workshop and a series of Webinars. See SUPPLEMENTARY INFORMATION. DATES: The... status of fish stocks in the Southeast Region. SEDAR is a multi-step process including: (1) Data...

Research to Go: Taking an Information Literacy Credit Course Online

ERIC Educational Resources Information Center

Long, Jessica; Burke, John J.; Tumbleson, Beth

2012-01-01

Adapting an existing face-to-face information literacy course that teaches undergraduates how to successfully conduct research and creating an online or hybrid version is a multi-step process. It begins with a desire to reach more students and help them achieve academic success. The primary learning outcomes for any information literacy course are…

Multistep process to produce fermentable sugars and lignosulfonates from softwood enzymolysis residues

Treesearch

Yalan Liu; Jinwu Wang; Michael P. Wolcott

2016-01-01

The residual solids from enzymatic hydrolysis are usually burned to produce energy and have been explored as a feedstock for various products including activated carbon and lignin based polymers. These products require additional procedures unrelated to the existing biorefinery equipment. In the current study, we proposed successive sulfite treatments to utilize the...

Description of bioremediation of soils using the model of a multistep system of microorganisms

NASA Astrophysics Data System (ADS)

Lubysheva, A. I.; Potashev, K. A.; Sofinskaya, O. A.

2018-01-01

The paper deals with the development of a mathematical model describing the interaction of a multi-step system of microorganisms in soil polluted with oil products. Each step in this system uses products of vital activity of the previous step to feed. Six different models of the multi-step system are considered. The equipping of the models with coefficients was carried out from the condition of minimizing the residual of the calculated and experimental data using an original algorithm based on the Levenberg-Marquardt method in combination with the Monte Carlo method for the initial approximation finding.

Error behavior of multistep methods applied to unstable differential systems

NASA Technical Reports Server (NTRS)

Brown, R. L.

1977-01-01

The problem of modeling a dynamic system described by a system of ordinary differential equations which has unstable components for limited periods of time is discussed. It is shown that the global error in a multistep numerical method is the solution to a difference equation initial value problem, and the approximate solution is given for several popular multistep integration formulas. Inspection of the solution leads to the formulation of four criteria for integrators appropriate to unstable problems. A sample problem is solved numerically using three popular formulas and two different stepsizes to illustrate the appropriateness of the criteria.

Multistep estimators of the between-study variance: The relationship with the Paule-Mandel estimator.

PubMed

van Aert, Robbie C M; Jackson, Dan

2018-04-26

A wide variety of estimators of the between-study variance are available in random-effects meta-analysis. Many, but not all, of these estimators are based on the method of moments. The DerSimonian-Laird estimator is widely used in applications, but the Paule-Mandel estimator is an alternative that is now recommended. Recently, DerSimonian and Kacker have developed two-step moment-based estimators of the between-study variance. We extend these two-step estimators so that multiple (more than two) steps are used. We establish the surprising result that the multistep estimator tends towards the Paule-Mandel estimator as the number of steps becomes large. Hence, the iterative scheme underlying our new multistep estimator provides a hitherto unknown relationship between two-step estimators and Paule-Mandel estimator. Our analysis suggests that two-step estimators are not necessarily distinct estimators in their own right; instead, they are quantities that are closely related to the usual iterative scheme that is used to calculate the Paule-Mandel estimate. The relationship that we establish between the multistep and Paule-Mandel estimator is another justification for the use of the latter estimator. Two-step and multistep estimators are perhaps best conceptualized as approximate Paule-Mandel estimators. © 2018 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Multi-step routes of capuchin monkeys in a laser pointer traveling salesman task.

PubMed

Howard, Allison M; Fragaszy, Dorothy M

2014-09-01

Prior studies have claimed that nonhuman primates plan their routes multiple steps in advance. However, a recent reexamination of multi-step route planning in nonhuman primates indicated that there is no evidence for planning more than one step ahead. We tested multi-step route planning in capuchin monkeys using a pointing device to "travel" to distal targets while stationary. This device enabled us to determine whether capuchins distinguish the spatial relationship between goals and themselves and spatial relationships between goals and the laser dot, allocentrically. In Experiment 1, two subjects were presented with identical food items in Near-Far (one item nearer to subject) and Equidistant (both items equidistant from subject) conditions with a laser dot visible between the items. Subjects moved the laser dot to the items using a joystick. In the Near-Far condition, one subject demonstrated a bias for items closest to self but the other subject chose efficiently. In the second experiment, subjects retrieved three food items in similar Near-Far and Equidistant arrangements. Both subjects preferred food items nearest the laser dot and showed no evidence of multi-step route planning. We conclude that these capuchins do not make choices on the basis of multi-step look ahead strategies. © 2014 Wiley Periodicals, Inc.

Digital Image Correlation of 2D X-ray Powder Diffraction Data for Lattice Strain Evaluation

PubMed Central

Zhang, Hongjia; Sui, Tan; Daisenberger, Dominik; Fong, Kai Soon

2018-01-01

High energy 2D X-ray powder diffraction experiments are widely used for lattice strain measurement. The 2D to 1D conversion of diffraction patterns is a necessary step used to prepare the data for full pattern refinement, but is inefficient when only peak centre position information is required for lattice strain evaluation. The multi-step conversion process is likely to lead to increased errors associated with the ‘caking’ (radial binning) or fitting procedures. A new method is proposed here that relies on direct Digital Image Correlation analysis of 2D X-ray powder diffraction patterns (XRD-DIC, for short). As an example of using XRD-DIC, residual strain values along the central line in a Mg AZ31B alloy bar after 3-point bending are calculated by using both XRD-DIC and the conventional ‘caking’ with fitting procedures. Comparison of the results for strain values in different azimuthal angles demonstrates excellent agreement between the two methods. The principal strains and directions are calculated using multiple direction strain data, leading to full in-plane strain evaluation. It is therefore concluded that XRD-DIC provides a reliable and robust method for strain evaluation from 2D powder diffraction data. The XRD-DIC approach simplifies the analysis process by skipping 2D to 1D conversion, and opens new possibilities for robust 2D powder diffraction data analysis for full in-plane strain evaluation. PMID:29543728

Distributed-observer-based cooperative control for synchronization of linear discrete-time multi-agent systems.

PubMed

Liang, Hongjing; Zhang, Huaguang; Wang, Zhanshan

2015-11-01

This paper considers output synchronization of discrete-time multi-agent systems with directed communication topologies. The directed communication graph contains a spanning tree and the exosystem as its root. Distributed observer-based consensus protocols are proposed, based on the relative outputs of neighboring agents. A multi-step algorithm is presented to construct the observer-based protocols. In light of the discrete-time algebraic Riccati equation and internal model principle, synchronization problem is completed. At last, numerical simulation is provided to verify the effectiveness of the theoretical results. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Direct C-H Arylation Meets Perovskite Solar Cells: Sn-Free Synthesis Shortcut to High Performance Hole-Transporting Materials.

PubMed

Chang, Yu-Chieh; Lee, Kun-Mu; Lai, Chia-Hsin; Liu, Ching-Yuan

2018-03-30

In contrast to the traditional multistep synthesis, we demonstrate herein a two-step synthesis-shortcut to triphenylamine-based hole-transporting materials (HTMs) through sequential direct C-H arylations. These hole-transporting molecules are fabricated in perovskite-based solar cells (PSCs), exhibiting promising efficiencies up to 17.69%, which is comparable to PSCs utilizing the commercially available spiro-OMeTAD as HTM. This is the first report describing the use of step-saving C-H activations/arylations in the facile synthesis of small-molecule HTMs for perovskite solar cells. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Poly(vinylpyrrolidone)-Free Multistep Synthesis of Silver Nanoplates with Plasmon Resonance in the Near Infrared Range.

PubMed

Khan, Assad U; Zhou, Zhengping; Krause, Joseph; Liu, Guoliang

2017-11-01

Herein, a poly(vinylpyrrolidone) (PVP)-free method is described for synthesizing Ag nanoplates that have localized surface plasmon resonance in the near-infrared (NIR) range. Citrate-capped Ag spherical nanoparticles are first grown into small Ag nanoplates that resonate in the range of 500-800 nm. The small Ag nanoplates are used as seeds to further grow into large Ag nanoplates with a lateral dimension of 100-600 nm and a plasmon resonance wavelength of 800-1660 nm and above. The number of growth steps can be increased as desired. Without introducing additional citrate into the solutions of small Ag nanoplate seeds, large Ag nanoplates can be synthesized within minutes. The entire synthesis is completely PVP free, which promotes the nanoparticle growth along the lateral direction to form large Ag nanoplates. The multistep growth and the minimum usage of citrate are essential for the fast growth of high-aspect-ratio Ag nanoplates resonating in the NIR range. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Maskless Lithography and in situ Visualization of Conductivity of Graphene using Helium Ion Microscopy

DOE PAGES

Iberi, Vighter O.; Vlassiouk, Ivan V.; Zhang, X. -G.; ...

2015-07-07

The remarkable mechanical and electronic properties of graphene make it an ideal candidate for next generation nanoelectronics. With the recent development of commercial-level single-crystal graphene layers, the potential for manufacturing household graphene-based devices has improved, but significant challenges still remain with regards to patterning the graphene into devices. In the case of graphene supported on a substrate, traditional nanofabrication techniques such as e-beam lithography (EBL) are often used in fabricating graphene nanoribbons but the multi-step processes they require can result in contamination of the graphene with resists and solvents. In this letter, we report the utility of scanning helium ionmore » lithography for fabricating functional graphene nanoconductors that are supported directly on a silicon dioxide layer, and we measure the minimum feature size achievable due to limitations imposed by thermal fluctuations and ion scattering during the milling process. Further we demonstrate that ion beams, due to their positive charging nature, may be used to observe and test the conductivity of graphene-based nanoelectronic devices in situ.« less

Energy harvesting: an integrated view of materials, devices and applications.

PubMed

Radousky, H B; Liang, H

2012-12-21

Energy harvesting refers to the set of processes by which useful energy is captured from waste, environmental, or mechanical sources and is converted into a usable form. The discipline of energy harvesting is a broad topic that includes established methods and materials such as photovoltaics and thermoelectrics, as well as more recent technologies that convert mechanical energy, magnetic energy and waste heat to electricity. This article will review various state-of-the-art materials and devices for direct energy conversion and in particular will include multistep energy conversion approaches. The article will highlight the nano-materials science underlying energy harvesting principles and devices, but also include more traditional bulk processes and devices as appropriate and synergistic. Emphasis is placed on device-design innovations that lead to higher efficiency energy harvesting or conversion technologies ranging from the cm/mm-scale down to MEMS/NEMS (micro- and nano-electromechanical systems) devices. Theoretical studies are reviewed, which address transport properties, crystal chemistry, thermodynamic analysis, energy transfer, system efficiency and device operation. New developments in experimental methods; device design and fabrication; nanostructured materials fabrication; materials properties; and device performance measurement techniques are discussed.

Energy harvesting: an integrated view of materials, devices and applications

NASA Astrophysics Data System (ADS)

Radousky, H. B.; Liang, H.

2012-12-01

Energy harvesting refers to the set of processes by which useful energy is captured from waste, environmental, or mechanical sources and is converted into a usable form. The discipline of energy harvesting is a broad topic that includes established methods and materials such as photovoltaics and thermoelectrics, as well as more recent technologies that convert mechanical energy, magnetic energy and waste heat to electricity. This article will review various state-of-the-art materials and devices for direct energy conversion and in particular will include multistep energy conversion approaches. The article will highlight the nano-materials science underlying energy harvesting principles and devices, but also include more traditional bulk processes and devices as appropriate and synergistic. Emphasis is placed on device-design innovations that lead to higher efficiency energy harvesting or conversion technologies ranging from the cm/mm-scale down to MEMS/NEMS (micro- and nano-electromechanical systems) devices. Theoretical studies are reviewed, which address transport properties, crystal chemistry, thermodynamic analysis, energy transfer, system efficiency and device operation. New developments in experimental methods; device design and fabrication; nanostructured materials fabrication; materials properties; and device performance measurement techniques are discussed.

Aub and Ago3 are recruited to nuage through two mechanisms to form a ping-pong complex assembled by Krimper

PubMed Central

Webster, Alexandre; Li, Sisi; Hur, Junho K.; Wachsmuth, Malte; Bois, Justin S.; Perkins, Edward M.; Patel, Dinshaw J.; Aravin, Alexei A.

2015-01-01

In Drosophila, two Piwi proteins, Aubergine (Aub) and Argonaute-3 (Ago3) localize to perinuclear ‘nuage’ granules and use guide piRNAs to target and destroy transposable element transcripts. We find that Aub and Ago3 are recruited to nuage by two different mechanisms. Aub requires a piRNA guide for nuage recruitment, indicating that its localization depends on recognition of RNA targets. Ago3 is recruited to nuage independently of a piRNA cargo and relies on interaction with Krimper, a stable component of nuage that is able to aggregate in the absence of other nuage proteins. We show that Krimper interacts directly with Aub and Ago3 to coordinate the assembly of the ping-pong piRNA processing (4P) complex. Symmetrical dimethylated arginines are required for Aub to interact with Krimper, but are dispensable for Ago3 to bind Krimper. Our study reveals a multi-step process responsible for the assembly and function of nuage complexes in piRNA-guided transposon repression. PMID:26295961

A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.

PubMed

Velasco, Silvia; Ibrahim, Mahmoud M; Kakumanu, Akshay; Garipler, Görkem; Aydin, Begüm; Al-Sayegh, Mohamed Ahmed; Hirsekorn, Antje; Abdul-Rahman, Farah; Satija, Rahul; Ohler, Uwe; Mahony, Shaun; Mazzoni, Esteban O

2017-02-02

Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions. Subsequently, Isl1/Lhx3 binding shifts from one set of targets to another, controlling regulatory region activity and gene expression as cell differentiation progresses. Binding of Isl1/Lhx3 to later motor neuron enhancers depends on the Ebf and Onecut TFs, which are induced by Ngn2 during the programming process. Thus, motor neuron programming is the product of two initially independent transcriptional modules that converge with a feedforward transcriptional logic. Copyright © 2017 Elsevier Inc. All rights reserved.

Recent progress on understanding the mechanisms of amyloid nucleation.

PubMed

Chatani, Eri; Yamamoto, Naoki

2018-04-01

Amyloid fibrils are supramolecular protein assemblies with a fibrous morphology and cross-β structure. The formation of amyloid fibrils typically follows a nucleation-dependent polymerization mechanism, in which a one-step nucleation scheme has widely been accepted. However, a variety of oligomers have been identified in early stages of fibrillation, and a nucleated conformational conversion (NCC) mechanism, in which oligomers serve as a precursor of amyloid nucleation and convert to amyloid nuclei, has been proposed. This development has raised the need to consider more complicated multi-step nucleation processes in addition to the simplest one-step process, and evidence for the direct involvement of oligomers as nucleation precursors has been obtained both experimentally and theoretically. Interestingly, the NCC mechanism has some analogy with the two-step nucleation mechanism proposed for inorganic and organic crystals and protein crystals, although a more dramatic conformational conversion of proteins should be considered in amyloid nucleation. Clarifying the properties of the nucleation precursors of amyloid fibrils in detail, in comparison with those of crystals, will allow a better understanding of the nucleation of amyloid fibrils and pave the way to develop techniques to regulate it.

Apoptotic Cell Clearance in Development.

PubMed

Shklover, Jeny; Levy-Adam, Flonia; Kurant, Estee

2015-01-01

Programmed cell death and its specific form apoptosis play an important role during development of multicellular organisms. They are crucial for morphogenesis and organ sculpting as well as for adjusting cell number in different systems. Removal of apoptotic cells is the last critical step of apoptosis. Apoptotic cells are properly and efficiently recognized and eliminated through phagocytosis, which is performed by professional and nonprofessional phagocytes. Phagocytosis of apoptotic cells or apoptotic cell clearance is a dynamic multistep process, involving interactions between phagocytic receptors and ligands on apoptotic cells, which are highly conserved in evolution. However, this process is extremely redundant in mammals, containing multiple factors playing similar roles in the process. Using model organisms such as Caenorhabditis elegans, Drosophila melanogaster, zebrafish, and mouse permits addressing fundamental questions in developmental cell clearance by a comprehensive approach including powerful genetics and cell biological tools enriched by live imaging. Recent studies in model organisms have enhanced significantly our understanding of the molecular and cellular basis of apoptotic cell clearance during development. Here, we review the current knowledge and illuminate the great potential of the research performed in genetic models, which opens new directions in developmental biology. © 2015 Elsevier Inc. All rights reserved.

Cultural and linguistic adaptation of a multimedia colorectal cancer screening decision aid for Spanish-speaking Latinos.

PubMed

Ko, Linda K; Reuland, Daniel; Jolles, Monica; Clay, Rebecca; Pignone, Michael

2014-01-01

As the United States becomes more linguistically and culturally diverse, there is a need for effective health communication interventions that target diverse, vulnerable populations, including Latinos. To address such disparities, health communication interventionists often face the challenge to adapt existing interventions from English into Spanish in a way that retains essential elements of the original intervention while also addressing the linguistic needs and cultural perspectives of the target population. The authors describe the conceptual framework, context, rationale, methods, and findings of a formative research process used in creating a Spanish-language version of an evidence-based (English language) multimedia colorectal cancer screening decision aid. The multistep process included identification of essential elements of the existing intervention, literature review, assessment of the regional context and engagement of key stakeholders, and solicitation of direct input from target population. The authors integrated these findings in the creation of the new adapted intervention. They describe how they used this process to identify and integrate sociocultural themes such as personalism (personalismo), familism (familismo), fear (miedo), embarrassment (verguenza), power distance (respeto), machismo, and trust (confianza) into the Spanish-language decision aid.

A transition from using multi-step procedures to a fully integrated system for performing extracorporeal photopheresis: A comparison of costs and efficiencies.

PubMed

Azar, Nabih; Leblond, Veronique; Ouzegdouh, Maya; Button, Paul

2017-12-01

The Pitié Salpêtrière Hospital Hemobiotherapy Department, Paris, France, has been providing extracorporeal photopheresis (ECP) since November 2011, and started using the Therakos ® CELLEX ® fully integrated system in 2012. This report summarizes our single-center experience of transitioning from the use of multi-step ECP procedures to the fully integrated ECP system, considering the capacity and cost implications. The total number of ECP procedures performed 2011-2015 was derived from department records. The time taken to complete a single ECP treatment using a multi-step technique and the fully integrated system at our department was assessed. Resource costs (2014€) were obtained for materials and calculated for personnel time required. Time-driven activity-based costing methods were applied to provide a cost comparison. The number of ECP treatments per year increased from 225 (2012) to 727 (2015). The single multi-step procedure took 270 min compared to 120 min for the fully integrated system. The total calculated per-session cost of performing ECP using the multi-step procedure was greater than with the CELLEX ® system (€1,429.37 and €1,264.70 per treatment, respectively). For hospitals considering a transition from multi-step procedures to fully integrated methods for ECP where cost may be a barrier, time-driven activity-based costing should be utilized to gain a more comprehensive understanding the full benefit that such a transition offers. The example from our department confirmed that there were not just cost and time savings, but that the time efficiencies gained with CELLEX ® allow for more patient treatments per year. © 2017 The Authors Journal of Clinical Apheresis Published by Wiley Periodicals, Inc.

Separation of Zirconium and Hafnium: A Review

NASA Astrophysics Data System (ADS)

Xu, L.; Xiao, Y.; van Sandwijk, A.; Xu, Q.; Yang, Y.

Zirconium is an ideal material for nuclear reactors due to its low absorption cross-section for thermal neutrons, whereas the typically contained hafnium with strong neutron-absorption is very harmful for zirconium. This paper provides an overview of the processes for separating hafnium from zirconium. The separation processes are roughly classified into hydro- and pyrometallurgical routes. The current dominant zirconium production route involves pyrometallurgical ore cracking, multi-step hydrometallurgical liquid-liquid extraction for hafnium removal and the reduction of zirconium tetrachloride to the pure metal by the Kroll process. The lengthy hydrometallurgical Zr-Hf separation operations leads to high production cost, intensive labour and heavy environmental burden. Using a compact pyrometallurgical separation method can simplify the whole production flowsheet with a higher process efficiency. The known separation methods are discussed based on the following reaction features: redox characteristics, volatility, electrochemical properties and molten salt extraction. The commercially operating extractive distillation process is a significant advance in Zr-Hf separation technology but it suffers from high process maintenance cost. The recently developed new process based on molten salt-metal equilibrium for Zr-Hf separation shows a great potential for industrial application, which is compact for nuclear grade zirconium production starting from crude ore. In the present paper, the available separation technologies are compared. The advantages and disadvantages as well as future directions of research and development for nuclear grade zirconium production are discussed.

Controlled growth of silica-titania hybrid functional nanoparticles through a multistep microfluidic approach.

PubMed

Shiba, K; Sugiyama, T; Takei, T; Yoshikawa, G

2015-11-11

Silica/titania-based functional nanoparticles were prepared through controlled nucleation of titania and subsequent encapsulation by silica through a multistep microfluidic approach, which was successfully applied to obtaining aminopropyl-functionalized silica/titania nanoparticles for a highly sensitive humidity sensor.

Continuous track paths reveal additive evidence integration in multistep decision making.

PubMed

Buc Calderon, Cristian; Dewulf, Myrtille; Gevers, Wim; Verguts, Tom

2017-10-03

Multistep decision making pervades daily life, but its underlying mechanisms remain obscure. We distinguish four prominent models of multistep decision making, namely serial stage, hierarchical evidence integration, hierarchical leaky competing accumulation (HLCA), and probabilistic evidence integration (PEI). To empirically disentangle these models, we design a two-step reward-based decision paradigm and implement it in a reaching task experiment. In a first step, participants choose between two potential upcoming choices, each associated with two rewards. In a second step, participants choose between the two rewards selected in the first step. Strikingly, as predicted by the HLCA and PEI models, the first-step decision dynamics were initially biased toward the choice representing the highest sum/mean before being redirected toward the choice representing the maximal reward (i.e., initial dip). Only HLCA and PEI predicted this initial dip, suggesting that first-step decision dynamics depend on additive integration of competing second-step choices. Our data suggest that potential future outcomes are progressively unraveled during multistep decision making.

The Use of Novel Camtasia Videos to Improve Performance of At-Risk Students in Undergraduate Physiology Courses

ERIC Educational Resources Information Center

Miller, Cynthia J.

2014-01-01

Students in undergraduate physiology courses often have difficulty understanding complex, multi-step processes, and these concepts consume a large portion of class time. For this pilot study, it was hypothesized that online multimedia resources may improve student performance in a high-risk population and reduce the in-class workload. A narrated…

77 FR 11066 - Fisheries of the Gulf of Mexico; Southeast Data, Assessment, and Review (SEDAR); Public Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

...: Notice of SEDAR Data/Assessment Workshop for Highly Migratory Species (HMS) blacktip sharks. SUMMARY: The SEDAR assessment of the HMS stocks of Gulf of Mexico blacktip sharks will consist of one workshop and a..., Assessment and Review (SEDAR) process, a multi-step method for determining the status of fish stocks in the...

Impedance feedback control of microfluidic valves for reliable post processing combinatorial droplet injection.

PubMed

Axt, Brant; Hsieh, Yi-Fan; Nalayanda, Divya; Wang, Tza-Huei

2017-09-01

Droplet microfluidics has found use in many biological assay applications as a means of high-throughput sample processing. One of the challenges of the technology, however, is the ability to control and merge droplets on-demand as they flow through the microdevices. It is in the interest of developing lab-on-chip devices to be able to combinatorically program additive mixing steps for more complex multistep and multiplex assays. Existing technologies to merge droplets are either passive in nature or require highly predictable droplet movement for feedforward control, making them vulnerable to errors during high throughput operation. In this paper, we describe and demonstrate a microfluidic valve-based device for the purpose of combinatorial droplet injection at any stage in a multistep assay. Microfluidic valves are used to robustly control fluid flow, droplet generation, and droplet mixing in the device on-demand, while on-chip impedance measurements taken in real time are used as feedback to accurately time the droplet injections. The presented system is contrasted to attempts without feedback, and is shown to be 100% reliable over long durations. Additionally, content detection and discretionary injections are explored and successfully executed.

The Role of Evolutive Elastic Properties in the Performance of a Sheet Formed Spring Applied in Multimedia Car Industry

NASA Astrophysics Data System (ADS)

Faria, J.; Silva, J.; Bernardo, P.; Araújo, M.; Alves, J. L.

2016-08-01

The manufacturing process and the behaviour of a spring manufactured from an aluminium sheet is described and investigated in this work considering the specifications for the in-service conditions. The spring is intended to be applied in car multimedia industry to replace bolted connections. Among others, are investigated the roles of the constitutive parameters and the hypothesis of evolutive elastic properties with the plastic work in the multistep forming process and in working conditions.

Technical note: Equivalent genomic models with a residual polygenic effect.

PubMed

Liu, Z; Goddard, M E; Hayes, B J; Reinhardt, F; Reents, R

2016-03-01

Routine genomic evaluations in animal breeding are usually based on either a BLUP with genomic relationship matrix (GBLUP) or single nucleotide polymorphism (SNP) BLUP model. For a multi-step genomic evaluation, these 2 alternative genomic models were proven to give equivalent predictions for genomic reference animals. The model equivalence was verified also for young genotyped animals without phenotypes. Due to incomplete linkage disequilibrium of SNP markers to genes or causal mutations responsible for genetic inheritance of quantitative traits, SNP markers cannot explain all the genetic variance. A residual polygenic effect is normally fitted in the genomic model to account for the incomplete linkage disequilibrium. In this study, we start by showing the proof that the multi-step GBLUP and SNP BLUP models are equivalent for the reference animals, when they have a residual polygenic effect included. Second, the equivalence of both multi-step genomic models with a residual polygenic effect was also verified for young genotyped animals without phenotypes. Additionally, we derived formulas to convert genomic estimated breeding values of the GBLUP model to its components, direct genomic values and residual polygenic effect. Third, we made a proof that the equivalence of these 2 genomic models with a residual polygenic effect holds also for single-step genomic evaluation. Both the single-step GBLUP and SNP BLUP models lead to equal prediction for genotyped animals with phenotypes (e.g., reference animals), as well as for (young) genotyped animals without phenotypes. Finally, these 2 single-step genomic models with a residual polygenic effect were proven to be equivalent for estimation of SNP effects, too. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Adaptive multi-step Full Waveform Inversion based on Waveform Mode Decomposition

NASA Astrophysics Data System (ADS)

Hu, Yong; Han, Liguo; Xu, Zhuo; Zhang, Fengjiao; Zeng, Jingwen

2017-04-01

Full Waveform Inversion (FWI) can be used to build high resolution velocity models, but there are still many challenges in seismic field data processing. The most difficult problem is about how to recover long-wavelength components of subsurface velocity models when seismic data is lacking of low frequency information and without long-offsets. To solve this problem, we propose to use Waveform Mode Decomposition (WMD) method to reconstruct low frequency information for FWI to obtain a smooth model, so that the initial model dependence of FWI can be reduced. In this paper, we use adjoint-state method to calculate the gradient for Waveform Mode Decomposition Full Waveform Inversion (WMDFWI). Through the illustrative numerical examples, we proved that the low frequency which is reconstructed by WMD method is very reliable. WMDFWI in combination with the adaptive multi-step inversion strategy can obtain more faithful and accurate final inversion results. Numerical examples show that even if the initial velocity model is far from the true model and lacking of low frequency information, we still can obtain good inversion results with WMD method. From numerical examples of anti-noise test, we see that the adaptive multi-step inversion strategy for WMDFWI has strong ability to resist Gaussian noise. WMD method is promising to be able to implement for the land seismic FWI, because it can reconstruct the low frequency information, lower the dominant frequency in the adjoint source, and has a strong ability to resist noise.

A Multistep Synthesis for an Advanced Undergraduate Organic Chemistry Laboratory

ERIC Educational Resources Information Center

Chang Ji; Peters, Dennis G.

2006-01-01

Multistep syntheses are often important components of the undergraduate organic laboratory experience and a three-step synthesis of 5-(2-sulfhydrylethyl) salicylaldehyde was described. The experiment is useful as a special project for an advanced undergraduate organic chemistry laboratory course and offers opportunities for students to master a…

"Metamagnetoelectric" effect in multiferroics

NASA Astrophysics Data System (ADS)

Fouokeng, G. C.; Fodouop, F. Kuate; Tchoffo, M.; Fai, L. C.; Randrianantoandro, N.

2018-05-01

We present a theoretical calculation of magnetoelectric properties in a quasi-two dimensional spin chain externally controlled by a static electric field in y-direction and magnetic field in z-direction. Given the diversity of properties in functional materials and their applications in physics, the multiferroic model is investigated. By using the Fermi-Dirac statistics of quantum gases and the Landau theory, we assess the effects of the Dzyaloshinskii-Moriya interaction and the electric polarization on the magnetoelectric coupling that induces at low temperature the "metamagnetoelectric" effet, and likewise affects the ferroelectricity induced through symmetry mechanisms and magnetic properties of the multiferroic system. In fact, the variation of the induced polarisation due to spin arrangement through the Dzyaloshinskii-Moriya interaction gives rise to a multistep interdependent metamagnetic and metaelectric transitions which are settled up by the corresponding Dzyaloshinskii-Moriya parameter and the system then exhibits a spin gap that results from an electric and a magnetic demagnetization field range. This metamagnetoelectric effect observed in these multiferroic materials model is seem to be highly tunable via the external electric and magnetic fields and thus can be crucial in the design of new mechanisms for the processing and storage of data and other spintronic applications.

Autophagy Driven by a Master Regulator of Hematopoiesis

PubMed Central

Kang, Yoon-A; Sanalkumar, Rajendran; O'Geen, Henriette; Linnemann, Amelia K.; Chang, Chan-Jung; Bouhassira, Eric E.; Farnham, Peggy J.; Keles, Sunduz

2012-01-01

Developmental and homeostatic remodeling of cellular organelles is mediated by a complex process termed autophagy. The cohort of proteins that constitute the autophagy machinery functions in a multistep biochemical pathway. Though components of the autophagy machinery are broadly expressed, autophagy can occur in specialized cellular contexts, and mechanisms underlying cell-type-specific autophagy are poorly understood. We demonstrate that the master regulator of hematopoiesis, GATA-1, directly activates transcription of genes encoding the essential autophagy component microtubule-associated protein 1 light chain 3B (LC3B) and its homologs (MAP1LC3A, GABARAP, GABARAPL1, and GATE-16). In addition, GATA-1 directly activates genes involved in the biogenesis/function of lysosomes, which mediate autophagic protein turnover. We demonstrate that GATA-1 utilizes the forkhead protein FoxO3 to activate select autophagy genes. GATA-1-dependent LC3B induction is tightly coupled to accumulation of the active form of LC3B and autophagosomes, which mediate mitochondrial clearance as a critical step in erythropoiesis. These results illustrate a novel mechanism by which a master regulator of development establishes a genetic network to instigate cell-type-specific autophagy. PMID:22025678

Single-step affinity purification of enzyme biotherapeutics: a platform methodology for accelerated process development.

PubMed

Brower, Kevin P; Ryakala, Venkat K; Bird, Ryan; Godawat, Rahul; Riske, Frank J; Konstantinov, Konstantin; Warikoo, Veena; Gamble, Jean

2014-01-01

Downstream sample purification for quality attribute analysis is a significant bottleneck in process development for non-antibody biologics. Multi-step chromatography process train purifications are typically required prior to many critical analytical tests. This prerequisite leads to limited throughput, long lead times to obtain purified product, and significant resource requirements. In this work, immunoaffinity purification technology has been leveraged to achieve single-step affinity purification of two different enzyme biotherapeutics (Fabrazyme® [agalsidase beta] and Enzyme 2) with polyclonal and monoclonal antibodies, respectively, as ligands. Target molecules were rapidly isolated from cell culture harvest in sufficient purity to enable analysis of critical quality attributes (CQAs). Most importantly, this is the first study that demonstrates the application of predictive analytics techniques to predict critical quality attributes of a commercial biologic. The data obtained using the affinity columns were used to generate appropriate models to predict quality attributes that would be obtained after traditional multi-step purification trains. These models empower process development decision-making with drug substance-equivalent product quality information without generation of actual drug substance. Optimization was performed to ensure maximum target recovery and minimal target protein degradation. The methodologies developed for Fabrazyme were successfully reapplied for Enzyme 2, indicating platform opportunities. The impact of the technology is significant, including reductions in time and personnel requirements, rapid product purification, and substantially increased throughput. Applications are discussed, including upstream and downstream process development support to achieve the principles of Quality by Design (QbD) as well as integration with bioprocesses as a process analytical technology (PAT). © 2014 American Institute of Chemical Engineers.

Highly durable direct hydrazine hydrate anion exchange membrane fuel cell

NASA Astrophysics Data System (ADS)

Sakamoto, Tomokazu; Serov, Alexey; Masuda, Teruyuki; Kamakura, Masaki; Yoshimoto, Koji; Omata, Takuya; Kishi, Hirofumi; Yamaguchi, Susumu; Hori, Akihiro; Horiuchi, Yousuke; Terada, Tomoaki; Artyushkova, Kateryna; Atanassov, Plamen; Tanaka, Hirohisa

2018-01-01

The factors influenced on degradation of direct hydrazine hydrate fuel cells (DHFCs) under operation conditions are analyzed by in situ soft X-ray radiography. A durability of DHFCs is significantly improved by multi-step reaction DHFCs (MSR-DHFCs) approach designed to decrease the crossover of liquid fuel. An open circuit voltage (OCV) as well as cell voltage at 5 mA cm-2 of MSR-DHFC construct with commercial anion exchange membrane (AEM) maintained for over of 3500 h at 60 °C. Furthermore, the commercial proton exchange membrane (PEM) is integrated into AEM of MSR-DHFCs resulting in stable power output of MSR-DHFCs for over than 2800 h at 80 °C.

Multistep integration formulas for the numerical integration of the satellite problem

NASA Technical Reports Server (NTRS)

Lundberg, J. B.; Tapley, B. D.

1981-01-01

The use of two Class 2/fixed mesh/fixed order/multistep integration packages of the PECE type for the numerical integration of the second order, nonlinear, ordinary differential equation of the satellite orbit problem. These two methods are referred to as the general and the second sum formulations. The derivation of the basic equations which characterize each formulation and the role of the basic equations in the PECE algorithm are discussed. Possible starting procedures are examined which may be used to supply the initial set of values required by the fixed mesh/multistep integrators. The results of the general and second sum integrators are compared to the results of various fixed step and variable step integrators.

Analysis of Time Filters in Multistep Methods

NASA Astrophysics Data System (ADS)

Hurl, Nicholas

Geophysical ow simulations have evolved sophisticated implicit-explicit time stepping methods (based on fast-slow wave splittings) followed by time filters to control any unstable models that result. Time filters are modular and parallel. Their effect on stability of the overall process has been tested in numerous simulations, but never analyzed. Stability is proven herein for the Crank-Nicolson Leapfrog (CNLF) method with the Robert-Asselin (RA) time filter and for the Crank-Nicolson Leapfrog method with the Robert-Asselin-Williams (RAW) time filter for systems by energy methods. We derive an equivalent multistep method for CNLF+RA and CNLF+RAW and stability regions are obtained. The time step restriction for energy stability of CNLF+RA is smaller than CNLF and CNLF+RAW time step restriction is even smaller. Numerical tests find that RA and RAW add numerical dissipation. This thesis also shows that all modes of the Crank-Nicolson Leap Frog (CNLF) method are asymptotically stable under the standard timestep condition.

Multistep Synthesis of a Terphenyl Derivative Showcasing the Diels-Alder Reaction

ERIC Educational Resources Information Center

Davie, Elizabeth A. Colby

2015-01-01

An adaptable multistep synthesis project designed for the culmination of a second-year organic chemistry laboratory course is described. The target compound is a terphenyl derivative that is an intermediate in the synthesis of compounds used in organic light-emitting devices. Students react a conjugated diene with dimethylacetylene dicarboxylate…

Biocatalyzed Regioselective Synthesis in Undergraduate Organic Laboratories: Multistep Synthesis of 2-Arachidonoylglycerol

ERIC Educational Resources Information Center

Johnston, Meghan R.; Makriyannis, Alexandros; Whitten, Kyle M.; Drew, Olivia C.; Best, Fiona A.

2016-01-01

In order to introduce the concepts of biocatalysis and its utility in synthesis to organic chemistry students, a multistep synthesis of endogenous cannabinergic ligand 2-arachidonoylglycerol (2-AG) was tailored for use as a laboratory exercise. Over four weeks, students successfully produced 2-AG, purifying and characterizing products at each…

Attention and Multistep Problem Solving in 24-Month-Old Children

ERIC Educational Resources Information Center

Carrico, Renee L.

2013-01-01

The current study examined the role of increased attentional load in 24 month-old children's multistep problem-solving behavior. Children solved an object-based nonspatial working-memory search task, to which a motor component of varying difficulty was added. Significant disruptions in search performance were observed with the introduction of the…

A Multistep Synthesis Incorporating a Green Bromination of an Aromatic Ring

ERIC Educational Resources Information Center

Cardinal, Pascal; Greer, Brandon; Luong, Horace; Tyagunova, Yevgeniya

2012-01-01

Electrophilic aromatic substitution is a fundamental topic taught in the undergraduate organic chemistry curriculum. A multistep synthesis that includes a safer and greener method for the bromination of an aromatic ring than traditional bromination methods is described. This experiment is multifaceted and can be used to teach students about…

A Multistep Synthesis Featuring Classic Carbonyl Chemistry for the Advanced Organic Chemistry Laboratory

ERIC Educational Resources Information Center

Duff, David B.; Abbe, Tyler G.; Goess, Brian C.

2012-01-01

A multistep synthesis of 5-isopropyl-1,3-cyclohexanedione is carried out from three commodity chemicals. The sequence involves an aldol condensation, Dieckmann-type annulation, ester hydrolysis, and decarboxylation. No purification is required until after the final step, at which point gravity column chromatography provides the desired product in…

Induction of Pectinase Hyper Production by Multistep Mutagenesis Using a Fungal Isolate--Aspergillus flavipes.

PubMed

Akbar, Sabika; Prasuna, R Gyana; Khanam, Rasheeda

2014-04-01

Aspergillus flavipes, a slow growing pectinase producing ascomycete, was isolated from soil identified and characterised in the previously done preliminary studies. Optimisation studies revealed that Citrus peel--groundnut oil cake [CG] production media is the best media for production of high levels of pectinase up to 39 U/ml using wild strain of A. flavipes. Strain improvement of this isolated strain for enhancement of pectinase production using multistep mutagenesis procedure is the endeavour of this project. For this, the wild strain of A. flavipes was treated with both physical (UV irradiation) and chemical [Colchicine, Ethidium bromide, H2O2] mutagens to obtain Ist generation mutants. The obtained mutants were assayed and differentiated basing on pectinase productivity. The better pectinase producing strains were further subjected to multistep mutagenesis to attain stability in mutants. The goal of this project was achieved by obtaining the best pectinase secreting mutant, UV80 of 45 U/ml compared to wild strain and sister mutants. This fact was confirmed by quantitatively analysing 3rd generation mutants obtained after multistep mutagenesis.

Probabilistic soil erosion modeling using the Erosion Risk Management Tool (ERMIT) after wildfires

Treesearch

P. R. Robichaud; W. J. Elliot; J. W. Wagenbrenner

2011-01-01

The decision of whether or not to apply post-fire hillslope erosion mitigation treatments, and if so, where these treatments are most needed, is a multi-step process. Land managers must assess the risk of damaging runoff and sediment delivery events occurring on the unrecovered burned hillslope. We developed the Erosion Risk Management Tool (ERMiT) to address this need...

Synthesis, antitubercular and anticancer activities of substituted furyl-quinazolin-3(4H)-ones.

PubMed

Raghavendra, Nulgulmnalli M; Thampi, Parameshwaran; Gurubasavarajaswamy, Purvarga M; Sriram, Dharmarajan

2007-12-01

Some novel substituted-3-{[(1E)-(substituted-2-furyl)-methylene]amino}quinazolin-4(3H)-one (5, 6, 7) a-f were synthesized by a multi-step process. These synthesized compounds are characterized by various spectroscopic techniques and evaluated for their antitubercular and anticancer activities. Biological activity indicated that some of the title compounds are potent antitubercular and anticancer agents.

Synchrotron x-ray study of a low roughness and high efficiency K 2 CsSb photocathode during film growth

DOE PAGES

Xie, Junqi; Demarteau, Marcel; Wagner, Robert; ...

2017-04-24

Reduction of roughness to the nm level is critical of achieving the ultimate performance from photocathodes used in high gradient fields. The thrust of this paper is to explore the evolution of roughness during sequential growth, and to show that deposition of multilayer structures consisting of very thin reacted layers results in an nm level smooth photocathode. Synchrotron x-ray methods were applied to study the multi-step growth process of a high efficiency K 2CsSb photocathode. We observed a transition point of the Sb film grown on Si at the film thickness of similar to 40 angstrom with the substrate temperaturemore » at 100 degrees C and the growth rate at 0.1 Å s -1. The final K 2CsSb photocathode exhibits a thickness of around five times that of the total deposited Sb film regardless of how the Sb film was grown. The film surface roughening process occurs first at the step when K diffuses into the crystalline Sb. Furthermore, the photocathode we obtained from the multi-step growth exhibits roughness in an order of magnitude lower than the normal sequential process. X-ray diffraction measurements show that the material goes through two structural changes of the crystalline phase during formation, from crystalline Sb to K 3Sb and finally to K 2CsSb.« less

Synchrotron x-ray study of a low roughness and high efficiency K 2 CsSb photocathode during film growth

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

Xie, Junqi; Demarteau, Marcel; Wagner, Robert

Reduction of roughness to the nm level is critical of achieving the ultimate performance from photocathodes used in high gradient fields. The thrust of this paper is to explore the evolution of roughness during sequential growth, and to show that deposition of multilayer structures consisting of very thin reacted layers results in an nm level smooth photocathode. Synchrotron x-ray methods were applied to study the multi-step growth process of a high efficiency K 2CsSb photocathode. We observed a transition point of the Sb film grown on Si at the film thickness of similar to 40 angstrom with the substrate temperaturemore » at 100 degrees C and the growth rate at 0.1 Å s -1. The final K 2CsSb photocathode exhibits a thickness of around five times that of the total deposited Sb film regardless of how the Sb film was grown. The film surface roughening process occurs first at the step when K diffuses into the crystalline Sb. Furthermore, the photocathode we obtained from the multi-step growth exhibits roughness in an order of magnitude lower than the normal sequential process. X-ray diffraction measurements show that the material goes through two structural changes of the crystalline phase during formation, from crystalline Sb to K 3Sb and finally to K 2CsSb.« less

Understanding current steam sterilization recommendations and guidelines.

PubMed

Spry, Cynthia

2008-10-01

Processing surgical instruments in preparation for surgery is a complex multistep practice. It is impractical to culture each and every item to determine sterility; therefore, the best assurance of a sterile product is careful execution of every step in the process coupled with an ongoing quality control program. Perioperative staff nurses and managers responsible for instrument processing, whether for a single instrument or multiple sets, must be knowledgeable with regard to cleaning; packaging; cycle selection; and the use of physical, chemical, and biological monitors. Nurses also should be able to resolve issues related to loaner sets, flash sterilization, and extended cycles.

VisAdapt: A Visualization Tool to Support Climate Change Adaptation.

PubMed

Johansson, Jimmy; Opach, Tomasz; Glaas, Erik; Neset, Tina-Simone; Navarra, Carlo; Linner, Bjorn-Ola; Rod, Jan Ketil

2017-01-01

The web-based visualization VisAdapt tool was developed to help laypeople in the Nordic countries assess how anticipated climate change will impact their homes. The tool guides users through a three-step visual process that helps them explore risks and identify adaptive actions specifically modified to their location and house type. This article walks through the tool's multistep, user-centered design process. Although VisAdapt's target end users are Nordic homeowners, the insights gained from the development process and the lessons learned from the project are applicable to a wide range of domains.

A Facile Route for Patterned Growth of Metal-Insulator Carbon Lateral Junction through One-Pot Synthesis.

PubMed

Park, Beomjin; Park, Jaesung; Son, Jin Gyeong; Kim, Yong-Jin; Yu, Seong Uk; Park, Hyo Ju; Chae, Dong-Hun; Byun, Jinseok; Jeon, Gumhye; Huh, Sung; Lee, Seoung-Ki; Mishchenko, Artem; Hyun, Seung; Lee, Tae Geol; Han, Sang Woo; Ahn, Jong-Hyun; Lee, Zonghoon; Hwang, Chanyong; Novoselov, Konstantin S; Kim, Kwang S; Hong, Byung Hee; Kim, Jin Kon

2015-08-25

Precise graphene patterning is of critical importance for tailor-made and sophisticated two-dimensional nanoelectronic and optical devices. However, graphene-based heterostructures have been grown by delicate multistep chemical vapor deposition methods, limiting preparation of versatile heterostructures. Here, we report one-pot synthesis of graphene/amorphous carbon (a-C) heterostructures from a solid source of polystyrene via selective photo-cross-linking process. Graphene is successfully grown from neat polystyrene regions, while patterned cross-linked polystyrene regions turn into a-C because of a large difference in their thermal stability. Since the electrical resistance of a-C is at least 2 orders of magnitude higher than that for graphene, the charge transport in graphene/a-C heterostructure occurs through the graphene region. Measurement of the quantum Hall effect in graphene/a-C lateral heterostructures clearly confirms the reliable quality of graphene and well-defined graphene/a-C interface. The direct synthesis of patterned graphene from polymer pattern could be further exploited to prepare versatile heterostructures.

Quantifying the Energy Landscape Statistics in Proteins - a Relaxation Mode Analysis

NASA Astrophysics Data System (ADS)

Cai, Zhikun; Zhang, Yang

Energy landscape, the hypersurface in the configurational space, has been a useful concept in describing complex processes that occur over a very long time scale, such as the multistep slow relaxations of supercooled liquids and folding of polypeptide chains into structured proteins. Despite extensive simulation studies, its experimental characterization still remains a challenge. To address this challenge, we developed a relaxation mode analysis (RMA) for liquids under a framework analogous to the normal mode analysis for solids. Using RMA, important statistics of the activation barriers of the energy landscape becomes accessible from experimentally measurable two-point correlation functions, e.g. using quasi-elastic and inelastic scattering experiments. We observed a prominent coarsening effect of the energy landscape. The results were further confirmed by direct sampling of the energy landscape using a metadynamics-like adaptive autonomous basin climbing computation. We first demonstrate RMA in a supercooled liquid when dynamical cooperativity emerges in the landscape-influenced regime. Then we show this framework reveals encouraging energy landscape statistics when applied to proteins.

Fast quantification of bovine milk proteins employing external cavity-quantum cascade laser spectroscopy.

PubMed

Schwaighofer, Andreas; Kuligowski, Julia; Quintás, Guillermo; Mayer, Helmut K; Lendl, Bernhard

2018-06-30

Analysis of proteins in bovine milk is usually tackled by time-consuming analytical approaches involving wet-chemical, multi-step sample clean-up procedures. The use of external cavity-quantum cascade laser (EC-QCL) based IR spectroscopy was evaluated as an alternative screening tool for direct and simultaneous quantification of individual proteins (i.e. casein and β-lactoglobulin) and total protein content in commercial bovine milk samples. Mid-IR spectra of protein standard mixtures were used for building partial least squares (PLS) regression models. A sample set comprising different milk types (pasteurized; differently processed extended shelf life, ESL; ultra-high temperature, UHT) was analysed and results were compared to reference methods. Concentration values of the QCL-IR spectroscopy approach obtained within several minutes are in good agreement with reference methods involving multiple sample preparation steps. The potential application as a fast screening method for estimating the heat load applied to liquid milk is demonstrated. Copyright © 2018 Elsevier Ltd. All rights reserved.

Discrepancy between mRNA and protein abundance: Insight from information retrieval process in computers

PubMed Central

Wang, Degeng

2008-01-01

Discrepancy between the abundance of cognate protein and RNA molecules is frequently observed. A theoretical understanding of this discrepancy remains elusive, and it is frequently described as surprises and/or technical difficulties in the literature. Protein and RNA represent different steps of the multi-stepped cellular genetic information flow process, in which they are dynamically produced and degraded. This paper explores a comparison with a similar process in computers - multi-step information flow from storage level to the execution level. Functional similarities can be found in almost every facet of the retrieval process. Firstly, common architecture is shared, as the ribonome (RNA space) and the proteome (protein space) are functionally similar to the computer primary memory and the computer cache memory respectively. Secondly, the retrieval process functions, in both systems, to support the operation of dynamic networks – biochemical regulatory networks in cells and, in computers, the virtual networks (of CPU instructions) that the CPU travels through while executing computer programs. Moreover, many regulatory techniques are implemented in computers at each step of the information retrieval process, with a goal of optimizing system performance. Cellular counterparts can be easily identified for these regulatory techniques. In other words, this comparative study attempted to utilize theoretical insight from computer system design principles as catalysis to sketch an integrative view of the gene expression process, that is, how it functions to ensure efficient operation of the overall cellular regulatory network. In context of this bird’s-eye view, discrepancy between protein and RNA abundance became a logical observation one would expect. It was suggested that this discrepancy, when interpreted in the context of system operation, serves as a potential source of information to decipher regulatory logics underneath biochemical network operation. PMID:18757239

MULTIWAVELENGTH OBSERVATIONS OF A SLOW-RISE, MULTISTEP X1.6 FLARE AND THE ASSOCIATED ERUPTION

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

Yurchyshyn, V.; Kumar, P.; Cho, K.-S.

Using multiwavelength observations, we studied a slow-rise, multistep X1.6 flare that began on 2014 November 7 as a localized eruption of core fields inside a δ-sunspot and later engulfed the entire active region (AR). This flare event was associated with formation of two systems of post-eruption arcades (PEAs) and several J-shaped flare ribbons showing extremely fine details, irreversible changes in the photospheric magnetic fields, and it was accompanied by a fast and wide coronal mass ejection. Data from the Solar Dynamics Observatory and IRIS spacecraft, along with the ground-based data from the New Solar Telescope, present evidence that (i) themore » flare and the eruption were directly triggered by a flux emergence that occurred inside a δ-sunspot at the boundary between two umbrae; (ii) this event represented an example of the formation of an unstable flux rope observed only in hot AIA channels (131 and 94 Å) and LASCO C2 coronagraph images; (iii) the global PEA spanned the entire AR and was due to global-scale reconnection occurring at heights of about one solar radius, indicating the global spatial and temporal scale of the eruption.« less

Discovery of Novel New Delhi Metallo-β-Lactamases-1 Inhibitors by Multistep Virtual Screening

PubMed Central

Wang, Xuequan; Lu, Meiling; Shi, Yang; Ou, Yu; Cheng, Xiaodong

2015-01-01

The emergence of NDM-1 containing multi-antibiotic resistant "Superbugs" necessitates the needs of developing of novel NDM-1inhibitors. In this study, we report the discovery of novel NDM-1 inhibitors by multi-step virtual screening. From a 2,800,000 virtual drug-like compound library selected from the ZINC database, we generated a focused NDM-1 inhibitor library containing 298 compounds of which 44 chemical compounds were purchased and evaluated experimentally for their ability to inhibit NDM-1 in vitro. Three novel NDM-1 inhibitors with micromolar IC50 values were validated. The most potent inhibitor, VNI-41, inhibited NDM-1 with an IC50 of 29.6 ± 1.3 μM. Molecular dynamic simulation revealed that VNI-41 interacted extensively with the active site. In particular, the sulfonamide group of VNI-41 interacts directly with the metal ion Zn1 that is critical for the catalysis. These results demonstrate the feasibility of applying virtual screening methodologies in identifying novel inhibitors for NDM-1, a metallo-β-lactamase with a malleable active site and provide a mechanism base for rational design of NDM-1 inhibitors using sulfonamide as a functional scaffold. PMID:25734558

Factors associated with the use of cognitive aids in operating room crises: a cross-sectional study of US hospitals and ambulatory surgical centers.

PubMed

Alidina, Shehnaz; Goldhaber-Fiebert, Sara N; Hannenberg, Alexander A; Hepner, David L; Singer, Sara J; Neville, Bridget A; Sachetta, James R; Lipsitz, Stuart R; Berry, William R

2018-03-26

Operating room (OR) crises are high-acuity events requiring rapid, coordinated management. Medical judgment and decision-making can be compromised in stressful situations, and clinicians may not experience a crisis for many years. A cognitive aid (e.g., checklist) for the most common types of crises in the OR may improve management during unexpected and rare events. While implementation strategies for innovations such as cognitive aids for routine use are becoming better understood, cognitive aids that are rarely used are not yet well understood. We examined organizational context and implementation process factors influencing the use of cognitive aids for OR crises. We conducted a cross-sectional study using a Web-based survey of individuals who had downloaded OR cognitive aids from the websites of Ariadne Labs or Stanford University between January 2013 and January 2016. In this paper, we report on the experience of 368 respondents from US hospitals and ambulatory surgical centers. We analyzed the relationship of more successful implementation (measured as reported regular cognitive aid use during applicable clinical events) with organizational context and with participation in a multi-step implementation process. We used multivariable logistic regression to identify significant predictors of reported, regular OR cognitive aid use during OR crises. In the multivariable logistic regression, small facility size was associated with a fourfold increase in the odds of a facility reporting more successful implementation (p = 0.0092). Completing more implementation steps was also significantly associated with more successful implementation; each implementation step completed was associated with just over 50% higher odds of more successful implementation (p ≤ 0.0001). More successful implementation was associated with leadership support (p < 0.0001) and dedicated time to train staff (p = 0.0189). Less successful implementation was associated with resistance among clinical providers to using cognitive aids (p < 0.0001), absence of an implementation champion (p = 0.0126), and unsatisfactory content or design of the cognitive aid (p = 0.0112). Successful implementation of cognitive aids in ORs was associated with a supportive organizational context and following a multi-step implementation process. Building strong organizational support and following a well-planned multi-step implementation process will likely increase the use of OR cognitive aids during intraoperative crises, which may improve patient outcomes.

Use of Chiral Oxazolidinones for a Multi-Step Synthetic Laboratory Module

ERIC Educational Resources Information Center

Betush, Matthew P.; Murphree, S. Shaun

2009-01-01

Chiral oxazolidinone chemistry is used as a framework for an advanced multi-step synthesis lab. The cost-effective and robust preparation of chiral starting materials is presented, as well as the use of chiral auxiliaries in a synthesis scheme that is appropriate for students currently in the second semester of the organic sequence. (Contains 1…

Articulating Identities and Analyzing Belonging: A Multistep Intervention That Affirms and Informs a Diversity of Students

ERIC Educational Resources Information Center

Cook-Sather, Alison; Des-Ogugua, Crystal; Bahti, Melanie

2018-01-01

This article describes a multistep intervention developed for an undergraduate course called 'Advocating Diversity in Higher Education.' The goal of the intervention was to affirm diversity and foster a sense of inclusion among students within and beyond the course. We contextualize the intervention in student protests during 2015 and 2016…

A Multistep Organocatalysis Experiment for the Undergraduate Organic Laboratory: An Enantioselective Aldol Reaction Catalyzed by Methyl Prolinamide

ERIC Educational Resources Information Center

Wade, Edmir O.; Walsh, Kenneth E.

2011-01-01

In recent years, there has been an explosion of research concerning the area of organocatalysis. A multistep capstone laboratory project that combines traditional reactions frequently found in organic laboratory curriculums with this new field of research is described. In this experiment, the students synthesize a prolinamide-based organocatalyst…

Synthesis of Frontalin, the Aggregation Pheromone of the Southern Pine Beetle: A Multistep Organic Synthesis for Undergraduate Students.

ERIC Educational Resources Information Center

Bartlett, Paul A.; And Others

1984-01-01

Background information and experimental procedures are provided for the multistep synthesis of frontalin. The experiment exposes students to a range of practical laboratory problems and important synthetic reactions and provides experiences in working on a medium-size, as well as a relatively small-size scale. (JN)

Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course

ERIC Educational Resources Information Center

Demare, Patricia; Regla, Ignacio

2012-01-01

This article describes one of the projects in the advanced undergraduate organic chemistry laboratory course concerning the synthesis of two local anesthetic drugs, prilocaine and benzocaine, with a common three-step sequence starting from toluene. Students undertake, in a several-week independent project, the multistep synthesis of a…

Synthesis of 10-Ethyl Flavin: A Multistep Synthesis Organic Chemistry Laboratory Experiment for Upper-Division Undergraduate Students

ERIC Educational Resources Information Center

Sichula, Vincent A.

2015-01-01

A multistep synthesis of 10-ethyl flavin was developed as an organic chemistry laboratory experiment for upper-division undergraduate students. Students synthesize 10-ethyl flavin as a bright yellow solid via a five-step sequence. The experiment introduces students to various hands-on experimental organic synthetic techniques, such as column…

Numerical parametric studies of spray combustion instability

NASA Technical Reports Server (NTRS)

Pindera, M. Z.

1993-01-01

A coupled numerical algorithm has been developed for studies of combustion instabilities in spray-driven liquid rocket engines. The model couples gas and liquid phase physics using the method of fractional steps. Also introduced is a novel, efficient methodology for accounting for spray formation through direct solution of liquid phase equations. Preliminary parametric studies show marked sensitivity of spray penetration and geometry to droplet diameter, considerations of liquid core, and acoustic interactions. Less sensitivity was shown to the combustion model type although more rigorous (multi-step) formulations may be needed for the differences to become apparent.

Next generation calmodulin affinity purification: Clickable calmodulin facilitates improved protein purification

PubMed Central

Kinzer-Ursem, Tamara L.

2018-01-01

As the proteomics field continues to expand, scientists are looking to integrate cross-disciplinary tools for studying protein structure, function, and interactions. Protein purification remains a key tool for many characterization studies. Calmodulin (CaM) is a calcium-binding messenger protein with over a hundred downstream binding partners, and is involved in a host of physiological processes, from learning and memory to immune and cardiac function. To facilitate biophysical studies of calmodulin, researchers have designed a site-specific labeling process for use in bioconjugation applications while maintaining high levels of protein activity. Here, we present a platform for selective conjugation of calmodulin directly from clarified cell lysates under bioorthogonal reaction conditions. Using a chemoenzymatically modified calmodulin, we employ popular click chemistry reactions for the conjugation of calmodulin to Sepharose resin, thereby streamlining a previously multi-step purification and conjugation process. We show that this “next-generation” calmodulin-Sepharose resin is not only easy to produce, but is also able to purify more calmodulin-binding proteins per volume of resin than traditional calmodulin-Sepharose resins. We expect these methods to be translatable to other proteins of interest and to other conjugation applications such as surface-based assays for the characterization of protein-protein interaction dynamics. PMID:29864125

Strategic cognitive sequencing: a computational cognitive neuroscience approach.

PubMed

Herd, Seth A; Krueger, Kai A; Kriete, Trenton E; Huang, Tsung-Ren; Hazy, Thomas E; O'Reilly, Randall C

2013-01-01

We address strategic cognitive sequencing, the "outer loop" of human cognition: how the brain decides what cognitive process to apply at a given moment to solve complex, multistep cognitive tasks. We argue that this topic has been neglected relative to its importance for systematic reasons but that recent work on how individual brain systems accomplish their computations has set the stage for productively addressing how brain regions coordinate over time to accomplish our most impressive thinking. We present four preliminary neural network models. The first addresses how the prefrontal cortex (PFC) and basal ganglia (BG) cooperate to perform trial-and-error learning of short sequences; the next, how several areas of PFC learn to make predictions of likely reward, and how this contributes to the BG making decisions at the level of strategies. The third models address how PFC, BG, parietal cortex, and hippocampus can work together to memorize sequences of cognitive actions from instruction (or "self-instruction"). The last shows how a constraint satisfaction process can find useful plans. The PFC maintains current and goal states and associates from both of these to find a "bridging" state, an abstract plan. We discuss how these processes could work together to produce strategic cognitive sequencing and discuss future directions in this area.

Cultural and Linguistic Adaptation of a Multimedia Colorectal Cancer Screening Decision Aid for Spanish Speaking Latinos

PubMed Central

Ko, Linda K.; Reuland, Daniel; Jolles, Monica; Clay, Rebecca; Pignone, Michael

2014-01-01

As the United States becomes more linguistically and culturally diverse, there is a need for effective health communication interventions that target diverse and most vulnerable populations. Latinos also have the lowest colorectal (CRC) screening rates of any ethnic group in the U.S. To address such disparities, health communication interventionists are often faced with the challenge to adapt existing interventions from English into Spanish in a way that retains essential elements of the original intervention while also addressing the linguistic needs and cultural perspectives of the target population. We describe the conceptual framework, context, rationale, methods, and findings of a formative research process used in creating a Spanish language version of an evidenced-based (English language) multimedia CRC screening decision aid. Our multi-step process included identification of essential elements of the existing intervention, literature review, assessment of the regional context and engagement of key stakeholders, and solicitation of direct input from target population. We integrated these findings in the creation of the new adapted intervention. We describe how we used this process to identify and integrate socio-cultural themes such as personalism (personalismo), familism (familismo), fear (miedo), embarrassment (verguenza), power distance (respeto), machismo, and trust (confianza) into the Spanish language decision aid. PMID:24328496

Internal motion in high vacuum systems

NASA Astrophysics Data System (ADS)

Frank, J. M.

Three transfer and positioning mechanisms have been developed for the non-air exposed, multistep processing of components in vacuum chambers. The functions to be performed in all of the systems include ultraviolet/ozone cleaning, vacuum baking, deposition of thin films, and thermocompression sealing of the enclosures. Precise positioning of the components is required during the evaporation and sealing processes. The three methods of transporting and positioning the components were developed to accommodate the design criteria and goals of each individual system. The design philosophy, goals, and operation of the three mechanisms are discussed.

Nonlinear optical and multiphoton processes for in situ manipulation and conversion of photons: applications to energy and healthcare (Conference Presentation)

NASA Astrophysics Data System (ADS)

Prasad, Paras N.

2017-02-01

Chiral control of nonlinear optical functions holds a great promise for a wide range of applications including optical signal processing, bio-sensing and chiral bio-imaging. In chiral polyfluorene thin films, we demonstrated extremely large chiral nonlinearity. The physics of manipulating excitation dynamics for photon transformation will be discussed, along with nanochemistry control of upconversion in hierarchically built organic chromophore coupled-core-multiple shell nanostructures which enable introduce new, organic-inorganic energy transfer routes for broadband light harvesting and increased upconversion efficiency via multistep cascaded energy transfer. We are pursuing the applications of photon conversion technology in IR harvesting for photovoltaics, high contrast bioimaging, photoacoustic imaging, photodynamic therapy, and optogenetics. An important application is in Brain research and Neurophotonics for functional mapping and modulation of brain activities. Another new direction pursued is magnetic field control of light in in a chiral polymer nanocomposite to achieve large magneto-optic coefficient which can enable sensing of extremely weak magnetic field due to brain waves. Finally, we will consider the thought provoking concept of utilizing photons to quantify, through magneto-optics, and augment - through nanoptogenetics, the cognitive states, thus paving the path way to a quantified human paradigm.

Single-step production of the simvastatin precursor monacolin J by engineering of an industrial strain of Aspergillus terreus.

PubMed

Huang, Xuenian; Liang, Yajing; Yang, Yong; Lu, Xuefeng

2017-07-01

Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete bioproduction of the cholesterol-lowering drug simvastatin feasible and promising. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Mitochondrial fragmentation in excitotoxicity requires ROCK activation.

PubMed

Martorell-Riera, Alejandro; Segarra-Mondejar, Marc; Reina, Manuel; Martínez-Estrada, Ofelia M; Soriano, Francesc X

2015-01-01

Mitochondria morphology constantly changes through fission and fusion processes that regulate mitochondrial function, and it therefore plays a prominent role in cellular homeostasis. Cell death progression is associated with mitochondrial fission. Fission is mediated by the mainly cytoplasmic Drp1, which is activated by different post-translational modifications and recruited to mitochondria to perform its function. Our research and other studies have shown that in the early moments of excitotoxic insult Drp1 must be nitrosylated to mediate mitochondrial fragmentation in neurons. Nonetheless, mitochondrial fission is a multistep process in which filamentous actin assembly/disassembly and myosin-mediated mitochondrial constriction play prominent roles. Here we establish that in addition to nitric oxide production, excitotoxicity-induced mitochondrial fragmentation also requires activation of the actomyosin regulator ROCK. Although ROCK1 has been shown to phosphorylate and activate Drp1, experiments using phosphor-mutant forms of Drp1 in primary cortical neurons indicate that in excitotoxic conditions, ROCK does not act directly on Drp1 to mediate fission, but may act on the actomyosin complex. Thus, these data indicate that a wider range of signaling pathways than those that target Drp1 are amenable to be inhibited to prevent mitochondrial fragmentation as therapeutic option.

Environmentally-benign conversion of biomass residues to electricity

NASA Astrophysics Data System (ADS)

Davies, Andrew

As petroleum resources are finite, it is imperative to use them wisely in energy conversion applications and, at the same time, develop alternative energy sources. Biomass is one of the renewable energy sources that can be used to partially replace fossil fuels. Biomass-based fuels can be produced domestically and can reduce dependency on fuel imports. Due to their abundant supply, and given that to an appreciable extent they can be considered carbon-neutral, their use for power generation is of technological interest. However, whereas biomasses can be directly burned in furnaces, such a conventional direct combustion technique is ill-controlled and typically produces considerable amounts of health-hazardous airborne compounds [1,2]. Thus, an alternative technology for biomass utilization is described herein to address increasing energy needs in an environmentally-benign manner. More specifically, a multi-step process/device is presented to accept granulated or pelletized biomass, and generate an easily-identifiable form of energy as a final product. To achieve low emissions of products of incomplete combustion, the biomass is gasified pyrolytically, mixed with air, ignited and, finally, burned in nominally premixed low-emission flames. Combustion is thus indirect, since the biomass is not directly burned, instead its gaseous pyrolyzates are burned upon mixing with air. Thereby, combustion is well-controlled and can be complete. A demonstration device has been constructed to convert the internal energy of plastics into "clean" thermal energy and, eventually to electricity.

Batch fabrication of polymer microfluidic cartridges for QCM sensor packaging by direct bonding

NASA Astrophysics Data System (ADS)

Sandström, Niklas; Zandi Shafagh, Reza; Gylfason, Kristinn B.; Haraldsson, Tommy; van der Wijngaart, Wouter

2017-12-01

Quartz crystal microbalance (QCM) sensing is an established technique commonly used in laboratory based life-science applications. However, the relatively complex, multi-part design and multi-step fabrication and assembly of state-of-the-art QCM cartridges make them unsuited for disposable applications such as point-of-care (PoC) diagnostics. In this work, we present the uncomplicated manufacturing of QCMs in polymer microfluidic cartridges. Our novel approach comprises two key innovations: the batch reaction injection molding of microfluidic parts; and the integration of the cartridge components by direct, unassisted bonding. We demonstrate molding of batches of 12 off-stoichiometry thiol-ene epoxy polymer (OSTE+) polymer parts in a single molding cycle using an adapted reaction injection molding process; and the direct bonding of the OSTE+  parts to other OSTE+  substrates, to printed circuit boards, and to QCMs. The microfluidic QCM OSTE+  cartridges were successfully evaluated in terms of liquid sealing as well as electrical properties, and the sensor performance characteristics are on par with those of a commercially available QCM biosensor cartridge. The simplified manufacturing of QCM sensors with maintained performance potentializes novel application areas, e.g. as disposable devices in a point of care setting. Moreover, our results can be extended to simplifying the fabrication of other microfluidic devices with multiple heterogeneously integrated components.

Chromospheric dust formation, stellar masers and mass loss

NASA Technical Reports Server (NTRS)

Stencel, R. E.

1986-01-01

A multistep scenario which describes a plausible mass loss mechanism associated with red giant and related stars is outlined. The process involves triggering a condensation instability in an extended chromosphere, leading to the formation of cool, dense clouds which are conducive to the formation of molecules and dust grains. Once formed, the dust can be driven away from the star by radiation pressure. Consistency with various observed phenomena is discussed.

Self-Regulated Strategy Development Instruction for Teaching Multi-Step Equations to Middle School Students Struggling in Math

ERIC Educational Resources Information Center

Cuenca-Carlino, Yojanna; Freeman-Green, Shaqwana; Stephenson, Grant W.; Hauth, Clara

2016-01-01

Six middle school students identified as having a specific learning disability or at risk for mathematical difficulties were taught how to solve multi-step equations by using the self-regulated strategy development (SRSD) model of instruction. A multiple-probe-across-pairs design was used to evaluate instructional effects. Instruction was provided…

The Relationship Between Non-Symbolic Multiplication and Division in Childhood

PubMed Central

McCrink, Koleen; Shafto, Patrick; Barth, Hilary

2016-01-01

Children without formal education in addition and subtraction are able to perform multi-step operations over an approximate number of objects. Further, their performance improves when solving approximate (but not exact) addition and subtraction problems that allow for inversion as a shortcut (e.g., a + b − b = a). The current study examines children’s ability to perform multi-step operations, and the potential for an inversion benefit, for the operations of approximate, non-symbolic multiplication and division. Children were trained to compute a multiplication and division scaling factor (*2 or /2, *4 or /4), and then tested on problems that combined two of these factors in a way that either allowed for an inversion shortcut (e.g., 8 * 4 / 4) or did not (e.g., 8 * 4 / 2). Children’s performance was significantly better than chance for all scaling factors during training, and they successfully computed the outcomes of the multi-step testing problems. They did not exhibit a performance benefit for problems with the a * b / b structure, suggesting they did not draw upon inversion reasoning as a logical shortcut to help them solve the multi-step test problems. PMID:26880261

Shadowing effects on multi-step Langmuir probe array on HL-2A tokamak

NASA Astrophysics Data System (ADS)

Ke, R.; Xu, M.; Nie, L.; Gao, Z.; Wu, Y.; Yuan, B.; Chen, J.; Song, X.; Yan, L.; Duan, X.

2018-05-01

Multi-step Langmuir probe arrays have been designed and installed on the HL-2A tokamak [1]–[2] to study the turbulent transport in the edge plasma, especially for the measurement of poloidal momentum flux, Reynolds stress Rs. However, except the probe tips on the top step, all other tips on lower steps are shadowed by graphite skeleton. It is necessary to estimate the shadowing effects on equilibrium and fluctuation measurement. In this paper, comparison of shadowed tips to unshadowed ones is presented. The results show that shadowing can strongly reduce the ion and electron effective collection area. However, its effect is negligible for the turbulence intensity and coherence measurement, confirming that the multi-step LP array is proper for the turbulent transport measurement.

Overview Of Dry-Etch Techniques

NASA Astrophysics Data System (ADS)

Salzer, John M.

1986-08-01

With pattern dimensions shrinking, dry methods of etching providing controllable degrees of anisotropy become a necessity. A number of different configurations of equipment - inline, hex, planar, barrel - have been offered, and within each type, there are numerous significant variations. Further, each specific type of machine must be perfected over a complex, interactive parameter space to achieve suitable removal of various materials. Among the most critical system parameters are the choice of cathode or anode to hold the wafers, the chamber pressure, the plasma excitation frequency, and the electrode and magnetron structures. Recent trends include the use of vacuum load locks, multiple chambers, multiple electrodes, downstream etching or stripping, and multistep processes. A major percentage of etches in production handle the three materials: polysilicon, oxide and aluminum. Recent process developments have targeted refractory metals, their silicides, and with increasing emphasis, silicon trenching. Indeed, with new VLSI structures, silicon trenching has become the process of greatest interest. For stripping, dry processes provide advantages other than anisotropy. Here, too, new configurations and methods have been introduced recently. While wet processes are less than desirable from a number of viewpoints (handling, safety, disposal, venting, classes of clean room, automatability), dry methods are still being perfected as a direct, universal replacement. The paper will give an overview of these machine structures and process solutions, together with examples of interest. These findings and the trends discussed are based on semiannual survey of manufacturers and users of the various types of equipment.

Facilitating Students' Review of the Chemistry of Nitrogen-Containing Heterocyclic Compounds and Their Characterization through Multistep Synthesis of Thieno[2,3-"b"]Pyridine Derivatives

ERIC Educational Resources Information Center

Liu, Hanlin; Zaplishnyy, Vladimir; Mikhaylichenko, Lana

2016-01-01

A multistep synthesis of thieno[2,3-"b"]pyridine derivatives is described that is suitable for the upper-level undergraduate organic laboratory. This experiment exposes students to various hands-on experimental techniques as well as methods of product characterization such as IR and [superscript 1]H NMR spectroscopy, and…

Coping Strategies Applied to Comprehend Multistep Arithmetic Word Problems by Students with Above-Average Numeracy Skills and Below-Average Reading Skills

ERIC Educational Resources Information Center

Nortvedt, Guri A.

2011-01-01

This article discusses how 13-year-old students with above-average numeracy skills and below-average reading skills cope with comprehending word problems. Compared to other students who are proficient in numeracy and are skilled readers, these students are more disadvantaged when solving single-step and multistep arithmetic word problems. The…

Multistep Methods for Integrating the Solar System

DTIC Science & Technology

1988-07-01

Technical Report 1055 [Multistep Methods for Integrating the Solar System 0 Panayotis A. Skordos’ MIT Artificial Intelligence Laboratory DTIC S D g8...RMA ELEENT. PROECT. TASK Artific ial Inteligence Laboratory ARE1A G WORK UNIT NUMBERS 545 Technology Square Cambridge, MA 02139 IL. CONTROLLING...describes research done at the Artificial Intelligence Laboratory of the Massachusetts Institute of Technology, supported by the Advanced Research Projects

Continuous Video Modeling to Assist with Completion of Multi-Step Home Living Tasks by Young Adults with Moderate Intellectual Disability

ERIC Educational Resources Information Center

Mechling, Linda C.; Ayres, Kevin M.; Bryant, Kathryn J.; Foster, Ashley L.

2014-01-01

The current study evaluated a relatively new video-based procedure, continuous video modeling (CVM), to teach multi-step cleaning tasks to high school students with moderate intellectual disability. CVM in contrast to video modeling and video prompting allows repetition of the video model (looping) as many times as needed while the user completes…

Immediate use steam sterilization: moving beyond current policy.

PubMed

Seavey, Rose

2013-05-01

Immediate-use steam sterilization (IUSS) is steam sterilization intended for immediate use. IUSS may cause an increased risk of infection to patients because of stress and time constraints placed on staff. When IUSS is used, it is vital to properly carry out the complete multistep process according to the manufacturer's written validated instructions for use. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

3D Microperfusion Model of ADPKD

DTIC Science & Technology

2015-10-01

Stratasys 3D printer. PDMS was cast in the negative molds in order to create permanent biocompatible plastic masters (SmoothCast 310). All goals of task...fabrication was accomplished using a custom multistep fabrication process. A negative mold of the bioreactor, designed in AutoCAD, was created using a...immortalized renal cortical epithelial cells (NKi-2). A range of doxycycline concentrations were dosed on the cells for 48 hours to test for induction of

Development of the Fray-Farthing-Chen Cambridge Process: Towards the Sustainable Production of Titanium and Its Alloys

NASA Astrophysics Data System (ADS)

Hu, Di; Dolganov, Aleksei; Ma, Mingchan; Bhattacharya, Biyash; Bishop, Matthew T.; Chen, George Z.

2018-02-01

The Kroll process has been employed for titanium extraction since the 1950s. It is a labour and energy intensive multi-step semi-batch process. The post-extraction processes for making the raw titanium into alloys and products are also excessive, including multiple remelting steps. Invented in the late 1990s, the Fray-Farthing-Chen (FFC) Cambridge process extracts titanium from solid oxides at lower energy consumption via electrochemical reduction in molten salts. Its ability to produce alloys and powders, while retaining the cathode shape also promises energy and material efficient manufacturing. Focusing on titanium and its alloys, this article reviews the recent development of the FFC-Cambridge process in two aspects, (1) resource and process sustainability and (2) advanced post-extraction processing.

Automatic Generation of Wide Dynamic Range Image without Pseudo-Edge Using Integration of Multi-Steps Exposure Images

NASA Astrophysics Data System (ADS)

Migiyama, Go; Sugimura, Atsuhiko; Osa, Atsushi; Miike, Hidetoshi

Recently, digital cameras are offering technical advantages rapidly. However, the shot image is different from the sight image generated when that scenery is seen with the naked eye. There are blown-out highlights and crushed blacks in the image that photographed the scenery of wide dynamic range. The problems are hardly generated in the sight image. These are contributory cause of difference between the shot image and the sight image. Blown-out highlights and crushed blacks are caused by the difference of dynamic range between the image sensor installed in a digital camera such as CCD and CMOS and the human visual system. Dynamic range of the shot image is narrower than dynamic range of the sight image. In order to solve the problem, we propose an automatic method to decide an effective exposure range in superposition of edges. We integrate multi-step exposure images using the method. In addition, we try to erase pseudo-edges using the process to blend exposure values. Afterwards, we get a pseudo wide dynamic range image automatically.

Enforced hematopoietic cell E- and L-selectin ligand (HCELL) expression primes transendothelial migration of human mesenchymal stem cells.

PubMed

Thankamony, Sai P; Sackstein, Robert

2011-02-08

According to the multistep model of cell migration, chemokine receptor engagement (step 2) triggers conversion of rolling interactions (step 1) into firm adhesion (step 3), yielding transendothelial migration. We recently reported that glycosyltransferase-programmed stereosubstitution (GPS) of CD44 on human mesenchymal stem cells (hMSCs) creates the E-selectin ligand HCELL (hematopoietic cell E-selectin/L-selectin ligand) and, despite absence of CXCR4, systemically administered HCELL(+)hMSCs display robust osteotropism visualized by intravital microscopy. Here we performed studies to define the molecular effectors of this process. We observed that engagement of hMSC HCELL with E-selectin triggers VLA-4 adhesiveness, resulting in shear-resistant adhesion to ligand VCAM-1. This VLA-4 activation is mediated via a Rac1/Rap1 GTPase signaling pathway, resulting in transendothelial migration on stimulated human umbilical vein endothelial cells without chemokine input. These findings indicate that hMSCs coordinately integrate CD44 ligation and integrin activation, circumventing chemokine-mediated signaling, yielding a step 2-bypass pathway of the canonical multistep paradigm of cell migration.

Micro-chemical synthesis of molecular probes on an electronic microfluidic device

PubMed Central

Keng, Pei Yuin; Chen, Supin; Ding, Huijiang; Sadeghi, Saman; Shah, Gaurav J.; Dooraghi, Alex; Phelps, Michael E.; Satyamurthy, Nagichettiar; Chatziioannou, Arion F.; Kim, Chang-Jin “CJ”; van Dam, R. Michael

2012-01-01

We have developed an all-electronic digital microfluidic device for microscale chemical synthesis in organic solvents, operated by electrowetting-on-dielectric (EWOD). As an example of the principles, we demonstrate the multistep synthesis of [18F]FDG, the most common radiotracer for positron emission tomography (PET), with high and reliable radio-fluorination efficiency of [18F]FTAG (88 ± 7%, n = 11) and quantitative hydrolysis to [18F]FDG (> 95%, n = 11). We furthermore show that batches of purified [18F]FDG can successfully be used for PET imaging in mice and that they pass typical quality control requirements for human use (including radiochemical purity, residual solvents, Kryptofix, chemical purity, and pH). We report statistical repeatability of the radiosynthesis rather than best-case results, demonstrating the robustness of the EWOD microfluidic platform. Exhibiting high compatibility with organic solvents and the ability to carry out sophisticated actuation and sensing of reaction droplets, EWOD is a unique platform for performing diverse microscale chemical syntheses in small volumes, including multistep processes with intermediate solvent-exchange steps. PMID:22210110

Construction and characterization of mismatch-containing circular DNA molecules competent for assessment of nick-directed human mismatch repair in vitro.

PubMed

Larson, Erik D; Nickens, David; Drummond, James T

2002-02-01

The ability of cell-free extracts to correct DNA mismatches has been demonstrated in both prokaryotes and eukaryotes. Such an assay requires a template containing both a mismatch and a strand discrimination signal, and the multi-step construction process can be technically difficult. We have developed a three-step procedure for preparing DNA heteroduplexes containing a site-specific nick. The mismatch composition, sequence context, distance to the strand signal, and the means for assessing repair in each strand are adjustable features built into a synthetic oligonucleotide. Controlled ligation events involving three of the four DNA strands incorporate the oligonucleotide into a circular template and generate the repair-directing nick. Mismatch correction in either strand of a prototype G.T mismatch was achieved by placing a nick 10-40 bp away from the targeted base. This proximity of nick and mismatch represents a setting where repair has not been well characterized, but the presence of a nick was shown to be essential, as was the MSH2/MSH6 heterodimer, although low levels of repair occurred in extract defective in each protein. All repair events were inhibited by a peptide that interacts with proliferating cell nuclear antigen and inhibits both mismatch repair and long-patch replication.

Direct hydride shift mechanism and stereoselectivity of P450nor confirmed by QM/MM calculations.

PubMed

Krámos, Balázs; Menyhárd, Dóra K; Oláh, Julianna

2012-01-19

Nitric oxide reductase (P450(nor)) found in Fusarium oxysporum catalyzes the reduction of nitric oxide to N(2)O in a multistep process. The reducing agent, NADH, is bound in the distal pocket of the enzyme, and direct hydride transfer occurs from NADH to the nitric oxide bound heme enzyme, forming intermediate I. Here we studied the possibility of hydride transfer from NADH to both the nitrogen and oxygen of the heme-bound nitric oxide, using quantum chemical and combined quantum mechanics/molecular mechanics (QM/MM) calculations, on two different protein models, representing both possible stereochemistries, a syn- and an anti-NADH arrangement. All calculations clearly favor hydride transfer to the nitrogen of nitric oxide, and the QM-only barrier and kinetic isotope effects are good agreement with the experimental values of intermediate I formation. We obtained higher barriers in the QM/MM calculations for both pathways, but hydride transfer to the nitrogen of nitric oxide is still clearly favored. The barriers obtained for the syn, Pro-R conformation of NADH are lower and show significantly less variation than the barriers obtained in the case of anti conformation. The effect of basis set and wide range of functionals on the obtained results are also discussed.

Region-based multi-step optic disk and cup segmentation from color fundus image

NASA Astrophysics Data System (ADS)

Xiao, Di; Lock, Jane; Manresa, Javier Moreno; Vignarajan, Janardhan; Tay-Kearney, Mei-Ling; Kanagasingam, Yogesan

2013-02-01

Retinal optic cup-disk-ratio (CDR) is a one of important indicators of glaucomatous neuropathy. In this paper, we propose a novel multi-step 4-quadrant thresholding method for optic disk segmentation and a multi-step temporal-nasal segmenting method for optic cup segmentation based on blood vessel inpainted HSL lightness images and green images. The performance of the proposed methods was evaluated on a group of color fundus images and compared with the manual outlining results from two experts. Dice scores of detected disk and cup regions between the auto and manual results were computed and compared. Vertical CDRs were also compared among the three results. The preliminary experiment has demonstrated the robustness of the method for automatic optic disk and cup segmentation and its potential value for clinical application.

Model predictive control design for polytopic uncertain systems by synthesising multi-step prediction scenarios

NASA Astrophysics Data System (ADS)

Lu, Jianbo; Xi, Yugeng; Li, Dewei; Xu, Yuli; Gan, Zhongxue

2018-01-01

A common objective of model predictive control (MPC) design is the large initial feasible region, low online computational burden as well as satisfactory control performance of the resulting algorithm. It is well known that interpolation-based MPC can achieve a favourable trade-off among these different aspects. However, the existing results are usually based on fixed prediction scenarios, which inevitably limits the performance of the obtained algorithms. So by replacing the fixed prediction scenarios with the time-varying multi-step prediction scenarios, this paper provides a new insight into improvement of the existing MPC designs. The adopted control law is a combination of predetermined multi-step feedback control laws, based on which two MPC algorithms with guaranteed recursive feasibility and asymptotic stability are presented. The efficacy of the proposed algorithms is illustrated by a numerical example.

Rethinking behavioral health processes by using design for six sigma.

PubMed

Lucas, Anthony G; Primus, Kelly; Kovach, Jamison V; Fredendall, Lawrence D

2015-02-01

Clinical evidence-based practices are strongly encouraged and commonly utilized in the behavioral health community. However, evidence-based practices that are related to quality improvement processes, such as Design for Six Sigma, are often not used in behavioral health care. This column describes the unique partnership formed between a behavioral health care provider in the greater Pittsburgh area, a nonprofit oversight and monitoring agency for behavioral health services, and academic researchers. The authors detail how the partnership used the multistep process outlined in Design for Six Sigma to completely redesign the provider's intake process. Implementation of the redesigned process increased access to care, decreased bad debt and uncollected funds, and improved cash flow--while consumer satisfaction remained high.

Synthesis of Well-Defined Copper "N"-Heterocyclic Carbene Complexes and Their Use as Catalysts for a "Click Reaction": A Multistep Experiment that Emphasizes the Role of Catalysis in Green Chemistry

ERIC Educational Resources Information Center

Ison, Elon A.; Ison, Ana

2012-01-01

A multistep experiment for an advanced synthesis lab course that incorporates topics in organic-inorganic synthesis and catalysis and highlights green chemistry principles was developed. Students synthesized two "N"-heterocyclic carbene ligands, used them to prepare two well-defined copper(I) complexes and subsequently utilized the complexes as…

Rotational paper-based electrochemiluminescence immunodevices for sensitive and multiplexed detection of cancer biomarkers.

PubMed

Sun, Xiange; Li, Bowei; Tian, Chunyuan; Yu, Fabiao; Zhou, Na; Zhan, Yinghua; Chen, Lingxin

2018-05-12

This paper describes a novel rotational paper-based analytical device (RPAD) to implement multi-step electrochemiluminescence (ECL) immunoassays. The integrated paper-based rotational valves can be easily controlled by rotating paper discs manually and this advantage makes it user-friendly to untrained users to carry out the multi-step assays. In addition, the rotational valves are reusable and the response time can be shortened to several seconds, which promotes the rotational paper-based device to have great advantages in multi-step operations. Under the control of rotational valves, multi-step ECL immunoassays were conducted on the rotational device for the multiplexed detection of carcinoembryonic antigen (CEA) and prostate specific antigen (PSA). The rotational device exhibited excellent analytical performance for CEA and PSA, and they could be detected in the linear ranges of 0.1-100 ng mL -1 and 0.1-50 ng mL -1 with detection limits down to 0.07 ng mL -1 and 0.03 ng mL -1 , respectively, which were within the ranges of clinical concentrations. We hope this technique will open a new avenue for the fabrication of paper-based valves and provide potential application in clinical diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

Long range personalized cancer treatment strategies incorporating evolutionary dynamics.

PubMed

Yeang, Chen-Hsiang; Beckman, Robert A

2016-10-22

Current cancer precision medicine strategies match therapies to static consensus molecular properties of an individual's cancer, thus determining the next therapeutic maneuver. These strategies typically maintain a constant treatment while the cancer is not worsening. However, cancers feature complicated sub-clonal structure and dynamic evolution. We have recently shown, in a comprehensive simulation of two non-cross resistant therapies across a broad parameter space representing realistic tumors, that substantial improvement in cure rates and median survival can be obtained utilizing dynamic precision medicine strategies. These dynamic strategies explicitly consider intratumoral heterogeneity and evolutionary dynamics, including predicted future drug resistance states, and reevaluate optimal therapy every 45 days. However, the optimization is performed in single 45 day steps ("single-step optimization"). Herein we evaluate analogous strategies that think multiple therapeutic maneuvers ahead, considering potential outcomes at 5 steps ahead ("multi-step optimization") or 40 steps ahead ("adaptive long term optimization (ALTO)") when recommending the optimal therapy in each 45 day block, in simulations involving both 2 and 3 non-cross resistant therapies. We also evaluate an ALTO approach for situations where simultaneous combination therapy is not feasible ("Adaptive long term optimization: serial monotherapy only (ALTO-SMO)"). Simulations utilize populations of 764,000 and 1,700,000 virtual patients for 2 and 3 drug cases, respectively. Each virtual patient represents a unique clinical presentation including sizes of major and minor tumor subclones, growth rates, evolution rates, and drug sensitivities. While multi-step optimization and ALTO provide no significant average survival benefit, cure rates are significantly increased by ALTO. Furthermore, in the subset of individual virtual patients demonstrating clinically significant difference in outcome between approaches, by far the majority show an advantage of multi-step or ALTO over single-step optimization. ALTO-SMO delivers cure rates superior or equal to those of single- or multi-step optimization, in 2 and 3 drug cases respectively. In selected virtual patients incurable by dynamic precision medicine using single-step optimization, analogous strategies that "think ahead" can deliver long-term survival and cure without any disadvantage for non-responders. When therapies require dose reduction in combination (due to toxicity), optimal strategies feature complex patterns involving rapidly interleaved pulses of combinations and high dose monotherapy. This article was reviewed by Wendy Cornell, Marek Kimmel, and Andrzej Swierniak. Wendy Cornell and Andrzej Swierniak are external reviewers (not members of the Biology Direct editorial board). Andrzej Swierniak was nominated by Marek Kimmel.

Theoretical analysis of the effects of light intensity on the photocorrosion of semiconductor electrodes

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

Benito, R.M.; Nozik, A.J.

1985-07-18

A kinetic model was developed to describe the effects of light intensity on the photocorrosion of n-type semiconductor electrodes. The model is an extension of previous work by Gomes and co-workers that includes the possibility of multiple steps for the oxidation reaction of the reducing agent in the electrolyte. Six cases are considered where the semiconductor decomposition reaction is multistep (each step involves a hole); the oxidation reaction of the reducing agent is multistep (each step after the first involves a hole or a chemical intermediate), and the first steps of the competing oxidation reactions are reversible or irreversible. Itmore » was found, contrary to previous results, that the photostability of semiconductor electrodes could increase with increased light intensity if the desired oxidation reaction of the reducing agent in the electrolyte was multistep with the first step being reversible. 14 references, 5 figures, 1 table.« less

Propagators for the Time-Dependent Kohn-Sham Equations: Multistep, Runge-Kutta, Exponential Runge-Kutta, and Commutator Free Magnus Methods.

PubMed

Gómez Pueyo, Adrián; Marques, Miguel A L; Rubio, Angel; Castro, Alberto

2018-05-09

We examine various integration schemes for the time-dependent Kohn-Sham equations. Contrary to the time-dependent Schrödinger's equation, this set of equations is nonlinear, due to the dependence of the Hamiltonian on the electronic density. We discuss some of their exact properties, and in particular their symplectic structure. Four different families of propagators are considered, specifically the linear multistep, Runge-Kutta, exponential Runge-Kutta, and the commutator-free Magnus schemes. These have been chosen because they have been largely ignored in the past for time-dependent electronic structure calculations. The performance is analyzed in terms of cost-versus-accuracy. The clear winner, in terms of robustness, simplicity, and efficiency is a simplified version of a fourth-order commutator-free Magnus integrator. However, in some specific cases, other propagators, such as some implicit versions of the multistep methods, may be useful.

Microfluidic Sample Preparation for Diagnostic Cytopathology

PubMed Central

Mach, Albert J.; Adeyiga, Oladunni B.; Di Carlo, Dino

2014-01-01

The cellular components of body fluids are routinely analyzed to identify disease and treatment approaches. While significant focus has been placed on developing cell analysis technologies, tools to automate the preparation of cellular specimens have been more limited, especially for body fluids beyond blood. Preparation steps include separating, concentrating, and exposing cells to reagents. Sample preparation continues to be routinely performed off-chip by technicians, preventing cell-based point-of-care diagnostics, increasing the cost of tests, and reducing the consistency of the final analysis following multiple manually-performed steps. Here, we review the assortment of biofluids for which suspended cells are analyzed, along with their characteristics and diagnostic value. We present an overview of the conventional sample preparation processes for cytological diagnosis. We finally discuss the challenges and opportunities in developing microfluidic devices for the purpose of automating or miniaturizing these processes, with particular emphases on preparing large or small volume samples, working with samples of high cellularity, automating multi-step processes, and obtaining high purity subpopulations of cells. We hope to convey the importance of and help identify new research directions addressing the vast biological and clinical applications in preparing and analyzing the array of available biological fluids. Successfully addressing the challenges described in this review can lead to inexpensive systems to improve diagnostic accuracy while simultaneously reducing overall systemic healthcare costs. PMID:23380972

Generation of Antibunched Light by Excited Molecules in a Microcavity Trap

NASA Technical Reports Server (NTRS)

DeMartini, F.; DiGiuseppe, G.; Marrocco, M.

1996-01-01

The active microcavity is adopted as an efficient source of non-classical light. By this device, excited by a mode-locked laser at a rate of 100 MHz, single-photons are generated over a single field mode with a nonclassical sub-poissonian distribution. The process of adiabatic recycling within a multi-step Franck-Condon molecular optical-pumping mechanism, characterized in our case by a quantum efficiency very close to one, implies a pump self-regularization process leading to a striking n-squeezing effect. By a replication of the basic single-atom excitation process a beam of quantum photon (Fock states) can be created. The new process represents a significant advance in the modern fields of basic quantum-mechanical investigation, quantum communication and quantum cryptography.

Fabrication of diamond shells

DOEpatents

Hamza, Alex V.; Biener, Juergen; Wild, Christoph; Woerner, Eckhard

2016-11-01

A novel method for fabricating diamond shells is introduced. The fabrication of such shells is a multi-step process, which involves diamond chemical vapor deposition on predetermined mandrels followed by polishing, microfabrication of holes, and removal of the mandrel by an etch process. The resultant shells of the present invention can be configured with a surface roughness at the nanometer level (e.g., on the order of down to about 10 nm RMS) on a mm length scale, and exhibit excellent hardness/strength, and good transparency in the both the infra-red and visible. Specifically, a novel process is disclosed herein, which allows coating of spherical substrates with optical-quality diamond films or nanocrystalline diamond films.

Biosimilars: Key regulatory considerations and similarity assessment tools

PubMed Central

Wang, Xiao‐Zhuo Michelle; Conlon, Hugh D.; Anderson, Scott; Ryan, Anne M.; Bose, Arindam

2017-01-01

Abstract A biosimilar drug is defined in the US Food and Drug Administration (FDA) guidance document as a biopharmaceutical that is highly similar to an already licensed biologic product (referred to as the reference product) notwithstanding minor differences in clinically inactive components and for which there are no clinically meaningful differences in purity, potency, and safety between the two products. The development of biosimilars is a challenging, multistep process. Typically, the assessment of similarity involves comprehensive structural and functional characterization throughout the development of the biosimilar in an iterative manner and, if required by the local regulatory authority, an in vivo nonclinical evaluation, all conducted with direct comparison to the reference product. In addition, comparative clinical pharmacology studies are conducted with the reference product. The approval of biosimilars is highly regulated although varied across the globe in terms of nomenclature and the precise criteria for demonstrating similarity. Despite varied regulatory requirements, differences between the proposed biosimilar and the reference product must be supported by strong scientific evidence that these differences are not clinically meaningful. This review discusses the challenges faced by pharmaceutical companies in the development of biosimilars. PMID:28842986

Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

PubMed Central

Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

2012-01-01

Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

Probiotic bacteria as biological control agents in aquaculture.

PubMed

Verschuere, L; Rombaut, G; Sorgeloos, P; Verstraete, W

2000-12-01

There is an urgent need in aquaculture to develop microbial control strategies, since disease outbreaks are recognized as important constraints to aquaculture production and trade and since the development of antibiotic resistance has become a matter of growing concern. One of the alternatives to antimicrobials in disease control could be the use of probiotic bacteria as microbial control agents. This review describes the state of the art of probiotic research in the culture of fish, crustaceans, mollusks, and live food, with an evaluation of the results obtained so far. A new definition of probiotics, also applicable to aquatic environments, is proposed, and a detailed description is given of their possible modes of action, i.e., production of compounds that are inhibitory toward pathogens, competition with harmful microorganisms for nutrients and energy, competition with deleterious species for adhesion sites, enhancement of the immune response of the animal, improvement of water quality, and interaction with phytoplankton. A rationale is proposed for the multistep and multidisciplinary process required for the development of effective and safe probiotics for commercial application in aquaculture. Finally, directions for further research are discussed.

Probiotic Bacteria as Biological Control Agents in Aquaculture

PubMed Central

Verschuere, Laurent; Rombaut, Geert; Sorgeloos, Patrick; Verstraete, Willy

2000-01-01

There is an urgent need in aquaculture to develop microbial control strategies, since disease outbreaks are recognized as important constraints to aquaculture production and trade and since the development of antibiotic resistance has become a matter of growing concern. One of the alternatives to antimicrobials in disease control could be the use of probiotic bacteria as microbial control agents. This review describes the state of the art of probiotic research in the culture of fish, crustaceans, mollusks, and live food, with an evaluation of the results obtained so far. A new definition of probiotics, also applicable to aquatic environments, is proposed, and a detailed description is given of their possible modes of action, i.e., production of compounds that are inhibitory toward pathogens, competition with harmful microorganisms for nutrients and energy, competition with deleterious species for adhesion sites, enhancement of the immune response of the animal, improvement of water quality, and interaction with phytoplankton. A rationale is proposed for the multistep and multidisciplinary process required for the development of effective and safe probiotics for commercial application in aquaculture. Finally, directions for further research are discussed. PMID:11104813

Differences in shotgun protein expression profile between superficial bladder transitional cell carcinoma and normal urothelium.

PubMed

Niu, Hai Tao; Zhang, Yi Bing; Jiang, Hai Ping; Cheng, Bo; Sun, Guang; Wang, Yi; E, Ya Jun; Pang, De Quan; Chang, Ji Wu

2009-01-01

This study was undertaken to identify differences in protein expression profiles between superficial bladder transitional cell carcinoma (BTCC) and normal urothelial cells. We used laser capture microdissection (LCM) to harvest purified cells, and used two-dimensional liquid chromatography (2D-LC) followed by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to separate and identify the peptide mixture. A total of 440/438 proteins commonly appeared in 4 paired specimens. Multi-step bioinformatic procedures were used for the analysis of identified proteins; 175/179 of the 293/287 proteins that were specific expressed in tumor/normal cells own gene ontology (GO) biological process annotation. Compared with the entire list of the international protein index (IPI), there are 52/46 GO terms exhibited as enriched and 6/10 exhibited as depleted, respectively. Significantly altered pathways between tumor and normal cells mainly include oxidative phosphorylation, focal adhesion, etc. Finally, descriptive statistics show that the shotgun proteomics strategy has practice directive significance for biomarker discovery by two-dimensional electrophoresis (2-DE) technology.

Self-Sealed Bionic Long Microchannels with Thin Walls and Designable Nanoholes Prepared by Line-Contact Capillary-Force Assembly.

PubMed

Lao, Zhao-Xin; Hu, Yan-Lei; Pan, Deng; Wang, Ren-Yan; Zhang, Chen-Chu; Ni, Jin-Cheng; Xu, Bing; Li, Jia-Wen; Wu, Dong; Chu, Jia-Ru

2017-06-01

Long microchannels with thin walls, small width, and nanoholes or irregular shaped microgaps, which are similar to capillaries or cancerous vessels, are urgently needed to simulate the physiological activities in human body. However, the fabrication of such channels remains challenging. Here, microchannels with designable holes are manufactured by combining laser printing with line-contact capillary-force assembly. Two microwalls are first printed by femtosecond laser direct-writing, and subsequently driven to collapse into a channel by the capillary force that arises in the evaporation of developer. The channel can remain stable in solvent due to the enhanced Van der Waals' force caused by the line-contact of microwalls. Microchannels with controllable nanoholes and almost arbitrary patterns can be fabricated without any bonding or multistep processes. As-prepared microchannels, with wall thicknesses less than 1 µm, widths less than 3 µm, lengths more than 1 mm, are comparable with human capillaries. In addition, the prepared channels also exhibit the ability to steer the flow of liquid without any external pump. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Laser resonance ionization spectroscopy on lutetium for the MEDICIS project

NASA Astrophysics Data System (ADS)

Gadelshin, V.; Cocolios, T.; Fedoseev, V.; Heinke, R.; Kieck, T.; Marsh, B.; Naubereit, P.; Rothe, S.; Stora, T.; Studer, D.; Van Duppen, P.; Wendt, K.

2017-11-01

The MEDICIS-PROMED Innovative Training Network under the Horizon 2020 EU program aims to establish a network of early stage researchers, involving scientific exchange and active cooperation between leading European research institutions, universities, hospitals, and industry. Primary scientific goal is the purpose of providing and testing novel radioisotopes for nuclear medical imaging and radionuclide therapy. Within a closely linked project at CERN, a dedicated electromagnetic mass separator system is presently under installation for production of innovative radiopharmaceutical isotopes at the new CERN-MEDICIS laboratory, directly adjacent to the existing CERN-ISOLDE radioactive ion beam facility. It is planned to implement a resonance ionization laser ion source (RILIS) to ensure high efficiency and unrivaled purity in the production of radioactive ions. To provide a highly efficient ionization process, identification and characterization of a specific multi-step laser ionization scheme for each individual element with isotopes of interest is required. The element lutetium is of primary relevance, and therefore was considered as first candidate. Three two-step excitation schemes for lutetium atoms are presented in this work, and spectroscopic results are compared with data of other authors.

The mechanism of Li2S activation in lithium-sulfur batteries: Can we avoid the polysulfide formation?

NASA Astrophysics Data System (ADS)

Vizintin, Alen; Chabanne, Laurent; Tchernychova, Elena; Arčon, Iztok; Stievano, Lorenzo; Aquilanti, Giuliana; Antonietti, Markus; Fellinger, Tim-Patrick; Dominko, Robert

2017-03-01

Electrochemical reactions in the Lisbnd S batteries are considered as a multistep reaction process with at least 2-3 equilibrium states. Here we report a possibility of having a conversion of Li2S into sulfur without detectible formation of polysulfides. That was confirmed by using a novel material system consisting of carbon coated Li2S particles prepared by carbothermal reduction of Li2SO4. Two independent in operando measurements showed direct oxidation of Li2S into sulfur for this system, with almost negligible formation of polysulfides at potentials above 2.5 V vs. Li/Li+. Our results link the diversity of first charge profiles in the literature to the Li2S oxidation mechanism and show the importance of ionic wiring within the material. Furthermore, we demonstrate that the Li2S oxidation mechanism depends on the relative amount of soluble sulfur in the electrolyte. By controlling the type and the amount of electrolyte within the encapsulating carbon shell, it is thereby possible to control the reaction mechanism of Li2S activation.

Non-conventional Pt-Cu alloy/carbon paper electrochemical catalyst formed by electrodeposition using hydrogen bubble as template

NASA Astrophysics Data System (ADS)

Kim, Youngkwang; Lee, Hyunjoon; Lim, Taeho; Kim, Hyun-Jong; Kwon, Oh Joong

2017-10-01

With emerging stability issues in fuel cell technology, a non-conventional catalyst not supported on carbon materials has been highlighted because it can avoid negative influences of carbon support materials on the stability, such as carbon corrosion. The nanostructured thin film catalyst is representative of non-conventional catalysts, which shows improved stability, enhanced mass specific activity, and fast mass transfer at high current densities. However, the nanostructured thin film catalyst usually requires multi-step processes for fabrication, making its mass production complex and irreproducible. We introduce a Pt-Cu alloy nanostructured thin film catalyst, which can be simply prepared by electrodeposition. By using hydrogen bubbles as a template, a three-dimensional free-standing foam of Cu was electrodeposited directly on the micro-porous layer/carbon paper and it was then displaced with Pt by simple immersion. The structure characterization revealed that a porous thin Pt-Cu alloy catalyst layer was successfully formed on the micro-porous layer/carbon paper. The synthesized Pt-Cu alloy catalyst exhibited superior durability compared to a conventional Pt/C in single cell test.

Kinetic analysis of overlapping multistep thermal decomposition comprising exothermic and endothermic processes: thermolysis of ammonium dinitramide.

PubMed

Muravyev, Nikita V; Koga, Nobuyoshi; Meerov, Dmitry B; Pivkina, Alla N

2017-01-25

This study focused on kinetic modeling of a specific type of multistep heterogeneous reaction comprising exothermic and endothermic reaction steps, as exemplified by the practical kinetic analysis of the experimental kinetic curves for the thermal decomposition of molten ammonium dinitramide (ADN). It is known that the thermal decomposition of ADN occurs as a consecutive two step mass-loss process comprising the decomposition of ADN and subsequent evaporation/decomposition of in situ generated ammonium nitrate. These reaction steps provide exothermic and endothermic contributions, respectively, to the overall thermal effect. The overall reaction process was deconvoluted into two reaction steps using simultaneously recorded thermogravimetry and differential scanning calorimetry (TG-DSC) curves by considering the different physical meanings of the kinetic data derived from TG and DSC by P value analysis. The kinetic data thus separated into exothermic and endothermic reaction steps were kinetically characterized using kinetic computation methods including isoconversional method, combined kinetic analysis, and master plot method. The overall kinetic behavior was reproduced as the sum of the kinetic equations for each reaction step considering the contributions to the rate data derived from TG and DSC. During reproduction of the kinetic behavior, the kinetic parameters and contributions of each reaction step were optimized using kinetic deconvolution analysis. As a result, the thermal decomposition of ADN was successfully modeled as partially overlapping exothermic and endothermic reaction steps. The logic of the kinetic modeling was critically examined, and the practical usefulness of phenomenological modeling for the thermal decomposition of ADN was illustrated to demonstrate the validity of the methodology and its applicability to similar complex reaction processes.

Novel examination for evaluating medical student clinical reasoning: reliability and association with patients seen.

PubMed

Hemmer, Paul A; Dong, Ting; Durning, Steven J; Pangaro, Louis N

2015-04-01

Medical students learn clinical reasoning, in part, through patient care. Although the numbers of patients seen is associated with knowledge examination scores, studies have not demonstrated an association between patient problems and an assessment of clinical reasoning. To examine the reliability of a clinical reasoning examination and investigate whether there was association between internal medicine core clerkship students' performance on this examination and the number of patients they saw with matching problems during their internal medicine clerkship. Students on the core internal medicine clerkship at the Uniformed Services University students log 11 core patient problems based on the Clerkship Directors in Internal Medicine curriculum. On a final clerkship examination (Multistep), students watch a scripted video encounter between physician and patient actors that assesses three sequential steps in clinical reasoning: Step One focuses on history and physical examination; Step Two, students write a problem list after viewing additional clinical findings; Step Three, students complete a prioritized differential diagnosis and treatment plan. Each Multistep examination has three different cases. For graduating classes 2010-2012 (n = 497), we matched the number of patients seen with the problem most represented by the Multistep cases (epigastric pain, generalized edema, monoarticular arthritis, angina, syncope, pleuritic chest pain). We report two-way Pearson correlations between the number of patients students reported with similar problems and the student's percent score on: Step One, Step Two, Step Three, and Overall Test. Multistep reliability: Step 1, 0.6 to 0.8; Step 2, 0.41 to 0.65; Step 3, 0.53 to 0.78; Overall examination (3 cases): 0.74 to 0.83. For three problems, the number of patients seen had small to modest correlations with the Multistep Examination of Analytic Ability total score (r = 0.27 for pleuritic pain, p < 0.05, n = 81 patients; r = 0.14 for epigastric pain, p < 0.05, n = 324 patients; r = 0.19 for generalized edema, p < 0.05, n = 118 patients). DISCUSSION or Although a reliable assessment, student performance on a clinical reasoning examination was weakly associated with the numbers of patients seen with similar problems. This may be as a result of transfer of knowledge between clinical and examination settings, the complexity of clinical reasoning, or the limits of reliability with patient logs and the Multistep. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Comparability of river quality assessment using macrophytes: a multi-step procedure to overcome biogeographical differences.

PubMed

Aguiar, F C; Segurado, P; Urbanič, G; Cambra, J; Chauvin, C; Ciadamidaro, S; Dörflinger, G; Ferreira, J; Germ, M; Manolaki, P; Minciardi, M R; Munné, A; Papastergiadou, E; Ferreira, M T

2014-04-01

This paper exposes a new methodological approach to solve the problem of intercalibrating river quality national methods when a common metric is lacking and most of the countries share the same Water Framework Directive (WFD) assessment method. We provide recommendations for similar works in future concerning the assessment of ecological accuracy and highlight the importance of a good common ground to make feasible the scientific work beyond the intercalibration. The approach herein presented was applied to highly seasonal rivers of the Mediterranean Geographical Intercalibration Group for the Biological Quality Element Macrophytes. The Mediterranean Group of river macrophytes involved seven countries and two assessment methods with similar acquisition data and assessment concept: the Macrophyte Biological Index for Rivers (IBMR) for Cyprus, France, Greece, Italy, Portugal and Spain, and the River Macrophyte Index (RMI) for Slovenia. Database included 318 sites of which 78 were considered as benchmarks. The boundary harmonization was performed for common WFD-assessment methods (all countries except Slovenia) using the median of the Good/Moderate and High/Good boundaries of all countries. Then, whenever possible, the Slovenian method, RMI was computed for the entire database. The IBMR was also computed for the Slovenian sites and was regressed against RMI in order to check the relatedness of methods (R(2)=0.45; p<0.00001) and to convert RMI boundaries into the IBMR scale. The boundary bias of RMI was computed using direct comparison of classification and the median boundary values following boundary harmonization. The average absolute class differences after harmonization is 26% and the percentage of classifications differing by half of a quality class is also small (16.4%). This multi-step approach to the intercalibration was endorsed by the WFD Regulatory Committee. © 2013 Elsevier B.V. All rights reserved.

Highly Sensitive Immunoassay Based on Controlled Rehydration of Patterned Reagents in a 2-Dimensional Paper Network

PubMed Central

2015-01-01

We have demonstrated a multistep 2-dimensional paper network immunoassay based on controlled rehydration of patterned, dried reagents. Previous work has shown that signal enhancement improves the limit of detection in 2-dimensional paper network assays, but until now, reagents have only been included as wet or dried in separate conjugate pads placed at the upstream end of the assay device. Wet reagents are not ideal for point-of-care because they must be refrigerated and typically limit automation and require more user steps. Conjugate pads allow drying but do not offer any control of the reagent distribution upon rehydration and can be a source of error when pads do not contact the assay membrane uniformly. Furthermore, each reagent is dried on a separate pad, increasing the fabrication complexity when implementing multistep assays that require several different reagents. Conversely, our novel method allows for consistent, controlled rehydration from patterned reagent storage depots directly within the paper membrane. In this assay demonstration, four separate reagents were patterned in different regions of the assay device: a gold-antibody conjugate used for antigen detection and three different signal enhancement components that must not be mixed until immediately before use. To show the viability of patterning and drying reagents directly onto a paper device for dry reagent storage and subsequent controlled release, we tested this device with the malaria antigen Plasmodium falciparum histidine-rich protein 2 (PfHRP2) as an example of target analyte. In this demonstration, the signal enhancement step increases the visible signal by roughly 3-fold and decreases the analytical limit of detection by 2.75-fold. PMID:24882058

Expedient antibiotics production: Final report

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

Bienkowski, P.R.; Byers, C.H.; Lee, D.D.

The literature on the manufacture, separation and purification, and clinical uses of antibiotics was reviewed, and a bibliography of the pertinent material was completed. Five antimicrobial drugs, penicillin V and G, (and amoxicillin with clavulanic acid), Cephalexin (a cephalosporin), tetracycline and oxytetracycline, Bacitracin (topical), and sulfonamide (chemically produced) were identified for emergency production. Plants that manufacture antibiotics in the continental United States, Mexico, and Puerto Rico have been identified along with potential alternate sites such as those where SCP, enzyme, and fermentation ethanol are produced. Detailed process flow sheets and process descriptions have been derived from the literature and documented.more » This investigation revealed that a typical antibiotic-manufacturing facility is composed of two main sections: (1) a highly specialized, but generic, fermentation unit and (2) a multistep, complex separation and purification unit which is specific to a particular antibiotic product. The fermentation section requires specialized equipment for operation in a sterile environment which is not usually available in other industries. The emergency production of antibiotics under austere conditions will be feasible only if a substantial reduction in the complexity and degree of separation and purity normally required can be realized. Detailed instructions were developed to assist state and federal officials who would be directing the resumption of antibiotic production after a nuclear attack. 182 refs., 54 figs., 26 tabs.« less

The role of secreted heat shock protein-90 (Hsp90) in wound healing - how could it shape future therapeutics?

PubMed

Guo, Jiacong; Chang, Cheng; Li, Wei

2017-08-01

Defects in tissue repair or wound healing pose a clinical, economic and social problem worldwide. Despite decades of studies, there have been few effective therapeutic treatments. Areas covered: We discuss the possible reasons for why growth factor therapy did not succeed. We point out the lack of human disorder-relevant animal models as another blockade for therapeutic development. We summarize the recent discovery of secreted heat shock protein-90 (Hsp90) as a novel wound healing agent. Expert commentary: Wound healing is a highly complex and multistep process that requires participations of many cell types, extracellular matrices and soluble molecules to work together in a spatial and temporal fashion within the wound microenvironment. The time that wounds remain open directly correlates with the clinical mortality associated with wounds. This time urgency makes the healing process impossible to regenerate back to the unwounded stage, rather forces it to take many shortcuts in order to protect life. Therefore, for therapeutic purpose, it is crucial to identify so-called 'driver genes' for the life-saving phase of wound closure. Keratinocyte-secreted Hsp90α was discovered in 2007 and has shown the promise by overcoming several key hurdles that have blocked the effectiveness of growth factors during wound healing.

Reducing workpieces to their base geometry for multi-step incremental forming using manifold harmonics

NASA Astrophysics Data System (ADS)

Carette, Yannick; Vanhove, Hans; Duflou, Joost

2018-05-01

Single Point Incremental Forming is a flexible process that is well-suited for small batch production and rapid prototyping of complex sheet metal parts. The distributed nature of the deformation process and the unsupported sheet imply that controlling the final accuracy of the workpiece is challenging. To improve the process limits and the accuracy of SPIF, the use of multiple forming passes has been proposed and discussed by a number of authors. Most methods use multiple intermediate models, where the previous one is strictly smaller than the next one, while gradually increasing the workpieces' wall angles. Another method that can be used is the manufacture of a smoothed-out "base geometry" in the first pass, after which more detailed features can be added in subsequent passes. In both methods, the selection of these intermediate shapes is freely decided by the user. However, their practical implementation in the production of complex freeform parts is not straightforward. The original CAD model can be manually adjusted or completely new CAD models can be created. This paper discusses an automatic method that is able to extract the base geometry from a full STL-based CAD model in an analytical way. Harmonic decomposition is used to express the final geometry as the sum of individual surface harmonics. It is then possible to filter these harmonic contributions to obtain a new CAD model with a desired level of geometric detail. This paper explains the technique and its implementation, as well as its use in the automatic generation of multi-step geometries.

Separation, Aspiration, and Fat Equalization: SAFE Liposuction Concepts for Comprehensive Body Contouring.

PubMed

Wall, Simeon H; Lee, Michael R

2016-12-01

Separation, aspiration, and fatty equilibration (SAFE) liposuction uses a process approach to body contouring and minimizes injury to surrounding structures. The multistep process allows for (1) fat separation, (2) lipoaspiration, and (3) fat equalization. The purpose of this study was to review both outcomes and complications of primary SAFE liposuction. Retrospective chart review was completed of patients undergoing SAFE liposuction from January of 2006 to January of 2011. Patient selection was limited to those undergoing liposuction alone with no adjuvant excisional procedures. Data were collected regarding demographics, body mass index, operative details, and outcomes. Seven hundred thirty-four patients were identified as having undergone SAFE liposuction. One hundred twenty-nine patients were found to have been treated with liposuction alone. Patient age ranged from 18 to 42 years and body mass index ranged from 18 to 42 kg/m (mean, 26.3 kg/m). Seven patients (5.4 percent) underwent treatment of the face and neck, six patients (4.7 percent) underwent treatment of upper extremities, 13 patients (10.1 percent) underwent treatment of the chest, 20 patients (15.5 percent) underwent treatment of lower extremities, 32 patients (24.8 percent) underwent treatment of the circumferential trunk, and 51 patients (39.5 percent) underwent treatment of circumferential trunk and additional area(s). No major complications occurred. Five of the 129 patients (3.87 percent) developed the minor complication of seroma formation. SAFE liposuction is a multistep process approach to body contouring consisting of (1) fat separation, (2) lipoaspiration, and (3) fat equalization. The results of this study show such technique to be safe and effective. Therapeutic, IV.

Single- and multistep resistance selection studies on the activity of retapamulin compared to other agents against Staphylococcus aureus and Streptococcus pyogenes.

PubMed

Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bogdanovich, Tatiana; Appelbaum, Peter C

2006-02-01

Retapamulin had the lowest rate of spontaneous mutations by single-step passaging and the lowest parent and selected mutant MICs by multistep passaging among all drugs tested for all Staphylococcus aureus strains and three Streptococcus pyogenes strains which yielded resistant clones. Retapamulin has a low potential for resistance selection in S. pyogenes, with a slow and gradual propensity for resistance development in S. aureus.

Single- and Multistep Resistance Selection Studies on the Activity of Retapamulin Compared to Other Agents against Staphylococcus aureus and Streptococcus pyogenes

PubMed Central

Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bogdanovich, Tatiana; Appelbaum, Peter C.

2006-01-01

Retapamulin had the lowest rate of spontaneous mutations by single-step passaging and the lowest parent and selected mutant MICs by multistep passaging among all drugs tested for all Staphylococcus aureus strains and three Streptococcus pyogenes strains which yielded resistant clones. Retapamulin has a low potential for resistance selection in S. pyogenes, with a slow and gradual propensity for resistance development in S. aureus. PMID:16436741

Multifunctional picoliter droplet manipulation platform and its application in single cell analysis.

PubMed

Gu, Shu-Qing; Zhang, Yun-Xia; Zhu, Ying; Du, Wen-Bin; Yao, Bo; Fang, Qun

2011-10-01

We developed an automated and multifunctional microfluidic platform based on DropLab to perform flexible generation and complex manipulations of picoliter-scale droplets. Multiple manipulations including precise droplet generation, sequential reagent merging, and multistep solid-phase extraction for picoliter-scale droplets could be achieved in the present platform. The system precision in generating picoliter-scale droplets was significantly improved by minimizing the thermo-induced fluctuation of flow rate. A novel droplet fusion technique based on the difference of droplet interfacial tensions was developed without the need of special microchannel networks or external devices. It enabled sequential addition of reagents to droplets on demand for multistep reactions. We also developed an effective picoliter-scale droplet splitting technique with magnetic actuation. The difficulty in phase separation of magnetic beads from picoliter-scale droplets due to the high interfacial tension was overcome using ferromagnetic particles to carry the magnetic beads to pass through the phase interface. With this technique, multistep solid-phase extraction was achieved among picoliter-scale droplets. The present platform had the ability to perform complex multistep manipulations to picoliter-scale droplets, which is particularly required for single cell analysis. Its utility and potentials in single cell analysis were preliminarily demonstrated in achieving high-efficiency single-cell encapsulation, enzyme activity assay at the single cell level, and especially, single cell DNA purification based on solid-phase extraction.

Finite Adaptation and Multistep Moves in the Metropolis-Hastings Algorithm for Variable Selection in Genome-Wide Association Analysis

PubMed Central

Peltola, Tomi; Marttinen, Pekka; Vehtari, Aki

2012-01-01

High-dimensional datasets with large amounts of redundant information are nowadays available for hypothesis-free exploration of scientific questions. A particular case is genome-wide association analysis, where variations in the genome are searched for effects on disease or other traits. Bayesian variable selection has been demonstrated as a possible analysis approach, which can account for the multifactorial nature of the genetic effects in a linear regression model. Yet, the computation presents a challenge and application to large-scale data is not routine. Here, we study aspects of the computation using the Metropolis-Hastings algorithm for the variable selection: finite adaptation of the proposal distributions, multistep moves for changing the inclusion state of multiple variables in a single proposal and multistep move size adaptation. We also experiment with a delayed rejection step for the multistep moves. Results on simulated and real data show increase in the sampling efficiency. We also demonstrate that with application specific proposals, the approach can overcome a specific mixing problem in real data with 3822 individuals and 1,051,811 single nucleotide polymorphisms and uncover a variant pair with synergistic effect on the studied trait. Moreover, we illustrate multimodality in the real dataset related to a restrictive prior distribution on the genetic effect sizes and advocate a more flexible alternative. PMID:23166669

Discovery of novel mGluR1 antagonists: a multistep virtual screening approach based on an SVM model and a pharmacophore hypothesis significantly increases the hit rate and enrichment factor.

PubMed

Li, Guo-Bo; Yang, Ling-Ling; Feng, Shan; Zhou, Jian-Ping; Huang, Qi; Xie, Huan-Zhang; Li, Lin-Li; Yang, Sheng-Yong

2011-03-15

Development of glutamate non-competitive antagonists of mGluR1 (Metabotropic glutamate receptor subtype 1) has increasingly attracted much attention in recent years due to their potential therapeutic application for various nervous disorders. Since there is no crystal structure reported for mGluR1, ligand-based virtual screening (VS) methods, typically pharmacophore-based VS (PB-VS), are often used for the discovery of mGluR1 antagonists. Nevertheless, PB-VS usually suffers a lower hit rate and enrichment factor. In this investigation, we established a multistep ligand-based VS approach that is based on a support vector machine (SVM) classification model and a pharmacophore model. Performance evaluation of these methods in virtual screening against a large independent test set, M-MDDR, show that the multistep VS approach significantly increases the hit rate and enrichment factor compared with the individual SB-VS and PB-VS methods. The multistep VS approach was then used to screen several large chemical libraries including PubChem, Specs, and Enamine. Finally a total of 20 compounds were selected from the top ranking compounds, and shifted to the subsequent in vitro and in vivo studies, which results will be reported in the near future. Copyright © 2011 Elsevier Ltd. All rights reserved.

Statistical Mechanics and Dynamics of the Outer Solar System.I. The Jupiter/Saturn Zone

NASA Technical Reports Server (NTRS)

Grazier, K. R.; Newman, W. I.; Kaula, W. M.; Hyman, J. M.

1996-01-01

We report on numerical simulations designed to understand how the solar system evolved through a winnowing of planetesimals accreeted from the early solar nebula. This sorting process is driven by the energy and angular momentum and continues to the present day. We reconsider the existence and importance of stable niches in the Jupiter/Saturn Zone using greatly improved numerical techniques based on high-order optimized multi-step integration schemes coupled to roundoff error minimizing methods.

Deducing the Kinetics of Protein Synthesis In Vivo from the Transition Rates Measured In Vitro

PubMed Central

Rudorf, Sophia; Thommen, Michael; Rodnina, Marina V.; Lipowsky, Reinhard

2014-01-01

The molecular machinery of life relies on complex multistep processes that involve numerous individual transitions, such as molecular association and dissociation steps, chemical reactions, and mechanical movements. The corresponding transition rates can be typically measured in vitro but not in vivo. Here, we develop a general method to deduce the in-vivo rates from their in-vitro values. The method has two basic components. First, we introduce the kinetic distance, a new concept by which we can quantitatively compare the kinetics of a multistep process in different environments. The kinetic distance depends logarithmically on the transition rates and can be interpreted in terms of the underlying free energy barriers. Second, we minimize the kinetic distance between the in-vitro and the in-vivo process, imposing the constraint that the deduced rates reproduce a known global property such as the overall in-vivo speed. In order to demonstrate the predictive power of our method, we apply it to protein synthesis by ribosomes, a key process of gene expression. We describe the latter process by a codon-specific Markov model with three reaction pathways, corresponding to the initial binding of cognate, near-cognate, and non-cognate tRNA, for which we determine all individual transition rates in vitro. We then predict the in-vivo rates by the constrained minimization procedure and validate these rates by three independent sets of in-vivo data, obtained for codon-dependent translation speeds, codon-specific translation dynamics, and missense error frequencies. In all cases, we find good agreement between theory and experiment without adjusting any fit parameter. The deduced in-vivo rates lead to smaller error frequencies than the known in-vitro rates, primarily by an improved initial selection of tRNA. The method introduced here is relatively simple from a computational point of view and can be applied to any biomolecular process, for which we have detailed information about the in-vitro kinetics. PMID:25358034

Directivity pattern of the sound radiated from axisymmetric stepped plates.

PubMed

He, Xiping; Yan, Xiuli; Li, Na

2016-08-01

For the purpose of optimal design and efficient utilization of the kind of stepped plate radiator in air, in this contribution, an approach for calculation of the directivity pattern of the sound radiated from a stepped plate in flexural vibration with a free edge is developed based on Kirchhoff-Love hypothesis and Rayleigh integral principle. Experimental tests of directivity pattern for a fabricated flat plate and two fabricated plates with one and two step radiators were carried out. It shows that the configuration of the measured directivity patterns by the proposed analytic approach is similar to those of the calculated approach. Comparison of the agreement between the calculated directivity pattern of a stepped plate and its corresponding theoretical piston show that the former radiator is equivalent to the latter, and the diffraction field generated by the unbaffled upper surface may be small. It also shows that the directivity pattern of a stepped radiator is independent of the metallic material but dependent on the thickness of base plate and resonant frequency. The thicker the thickness of base plate, the more directive the radiation is. The proposed analytic approach in this work may be adopted for any other plates with multi-steps.

Microprocessor dynamics shows co- and post-transcriptional processing of pri-miRNAs.

PubMed

Louloupi, Annita; Ntini, Evgenia; Liz, Julia; Ørom, Ulf Andersson

2017-06-01

miRNAs are small regulatory RNAs involved in the regulation of translation of target transcripts. miRNA biogenesis is a multistep process starting with the cleavage of the primary miRNA transcript in the nucleus by the Microprocessor complex. Endogenous processing of pri-miRNAs is challenging to study and the in vivo kinetics of this process is not known. Here, we present a method for determining the processing kinetics of pri-miRNAs within intact cells over time, using a pulse-chase approach to label transcribed RNA during 15 min, and follow the processing within a 1-hour window after labeling with bromouridine. We show that pri-miRNAs exhibit different processing kinetics ranging from fast over intermediate to slow processing, and we provide evidence that pri-miRNA processing can occur both cotranscriptionally and post-transcriptionally. © 2017 Louloupi et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

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.

Multistep modeling (MSM) of biomolecular structure application to the A-G mispair in the B-DNA environment

NASA Technical Reports Server (NTRS)

Srinivasan, S.; Raghunathan, G.; Shibata, M.; Rein, R.

1986-01-01

A multistep modeling procedure has been evolved to study the structural changes introduced by lesions in DNA. We report here the change in the structure of regular B-DNA geometry due to the incorporation of Ganti-Aanti mispair in place of a regular G-C pair, preserving the helix continuity. The energetics of the structure so obtained is compared with the Ganti-Asyn configuration under similar constrained conditions. We present the methodology adopted and discuss the results.

Gravitational waves from the first order electroweak phase transition in the Z3 symmetric singlet scalar model

NASA Astrophysics Data System (ADS)

Matsui, Toshinori

2018-01-01

Among various scenarios of baryon asymmetry of the Universe, electroweak baryogenesis is directly connected with physics of the Higgs sector. We discuss spectra of gravitational waves which are originated by the strongly first order phase transition at the electroweak symmetry breaking, which is required for a successful scenario of electroweak baryogenesis. In the Z3 symmetric singlet scalar model, the significant gravitational waves are caused by the multi-step phase transition. We show that the model can be tested by measuring the characteristic spectra of the gravitational waves at future interferometers such as LISA and DECIGO.

Two-Step Self-Assembly of Liposome-Multidomain Peptide Nanofiber Hydrogel for Time-Controlled Release

PubMed Central

2015-01-01

Progress in self-assembly and supramolecular chemistry has been directed toward obtaining macromolecular assemblies with higher degrees of complexity, simulating the highly structured environment in natural systems. One approach to this type of complexity are multistep, multicomponent, self-assembling systems that allow approaches comparable to traditional multistep synthetic organic chemistry; however, only a few examples of this approach have appeared in the literature. Our previous work demonstrated nanofibrous mimics of the extracellular matrix. Here we demonstrate the ability to create a unique hydrogel, developed by stepwise self-assembly of multidomain peptide fibers and liposomes. The two-component system allows for controlled release of bioactive factors at multiple time points. The individual components of the self-assembled gel and the composite hydrogel were characterized by TEM, SEM, and rheometry, demonstrating that peptide nanofibers and lipid vesicles both retain their structural integrity in the composite gel. The rheological robustness of the hydrogel is shown to be largely unaffected by the presence of liposomes. Release studies from the composite gels loaded with different growth factors EGF, MCP-1, and PlGF-1 showed delay and prolongation of release by liposomes entrapped in the hydrogel compared to more rapid release from the hydrogel alone. This bimodal release system may have utility in systems where timed cascades of biological signals may be valuable, such as in tissue regeneration. PMID:25308335

Segmenting the Femoral Head and Acetabulum in the Hip Joint Automatically Using a Multi-Step Scheme

NASA Astrophysics Data System (ADS)

Wang, Ji; Cheng, Yuanzhi; Fu, Yili; Zhou, Shengjun; Tamura, Shinichi

We describe a multi-step approach for automatic segmentation of the femoral head and the acetabulum in the hip joint from three dimensional (3D) CT images. Our segmentation method consists of the following steps: 1) construction of the valley-emphasized image by subtracting valleys from the original images; 2) initial segmentation of the bone regions by using conventional techniques including the initial threshold and binary morphological operations from the valley-emphasized image; 3) further segmentation of the bone regions by using the iterative adaptive classification with the initial segmentation result; 4) detection of the rough bone boundaries based on the segmented bone regions; 5) 3D reconstruction of the bone surface using the rough bone boundaries obtained in step 4) by a network of triangles; 6) correction of all vertices of the 3D bone surface based on the normal direction of vertices; 7) adjustment of the bone surface based on the corrected vertices. We evaluated our approach on 35 CT patient data sets. Our experimental results show that our segmentation algorithm is more accurate and robust against noise than other conventional approaches for automatic segmentation of the femoral head and the acetabulum. Average root-mean-square (RMS) distance from manual reference segmentations created by experienced users was approximately 0.68mm (in-plane resolution of the CT data).

Performance limitations of label-free sensors in molecular diagnosis using complex samples

NASA Astrophysics Data System (ADS)

Varma, Manoj

2016-03-01

Label-free biosensors promised a paradigm involving direct detection of biomarkers from complex samples such as serum without requiring multistep sample processing typical of labelled methods such as ELISA or immunofluorescence assays. Label-free sensors have witnessed decades of development with a veritable zoo of techniques available today exploiting a multitude of physical effects. It is appropriate now to critically assess whether label-free technologies have succeeded in delivering their promise with respect to diagnostic applications, particularly, ambitious goals such as early cancer detection using serum biomarkers, which require low limits of detection (LoD). Comparison of nearly 120 limits of detection (LoD) values reported by labelled and label-free sensing approaches over a wide range of detection techniques and target molecules in serum revealed that labeled techniques achieve 2-3 orders of magnitude better LoDs. Data from experiments where labelled and label-free assays were performed simultaneously using the same assay parameters also confirm that the LoD achieved by labelled techniques is 2 to 3 orders of magnitude better than that by label-free techniques. Furthermore, label-free techniques required significant signal amplification, for e.g. using nanoparticle conjugated secondary antibodies, to achieve LoDs comparable to labelled methods substantially deviating from the original "direct detection" paradigm. This finding has important implications on the practical limits of applying label-free detection methods for molecular diagnosis.

Medical hypothesis: bifunctional genetic-hormonal pathways to breast cancer.

PubMed

Davis, D L; Telang, N T; Osborne, M P; Bradlow, H L

1997-04-01

As inherited germ line mutations, such as loss of BRCA1 or AT, account for less than 5% of all breast cancer, most cases involve acquired somatic perturbations. Cumulative lifetime exposure to bioavailable estradiol links most known risk factors (except radiation) for breast cancer. Based on a series of recent experimental and epidemiologic findings, we hypothesize that the multistep process of breast carcinogenesis results from exposure to endogenous or exogenous hormones, including phytoestrogens that directly or indirectly alter estrogen metabolism. Xenohormones are defined as xenobiotic materials that modify hormonal production; they can work bifunctionally, through genetic or hormonal paths, depending on the periods and extent of exposure. As for genetic paths, xenohormones can modify DNA structure or function. As for hormonal paths, two distinct mechanisms can influence the potential for aberrant cell growth: compounds can directly bind with endogenous hormone or growth factor receptors affecting cell proliferation or compounds can modify breast cell proliferation altering the formation of hormone metabolites that influence epithelial-stromal interaction and growth regulation. Beneficial xenohormones, such as indole-3-carbinol, genistein, and other bioflavonoids, may reduce aberrant breast cell proliferation, and influence the rate of DNA repair or apoptosis and thereby influence the genetic or hormonal microenvironments. Upon validation with appropriate in vitro and in vivo studies, biologic markers of the risk for breast cancer, such as hormone metabolites, total bioavailable estradiol, and free radical generators can enhance cancer detection and prevention.

Significantly enhanced memory effect in metallic glass by multistep training

NASA Astrophysics Data System (ADS)

Li, M. X.; Luo, P.; Sun, Y. T.; Wen, P.; Bai, H. Y.; Liu, Y. H.; Wang, W. H.

2017-11-01

The state of metastable equilibrium glass can carry an imprint of the past and exhibit memory effect. As a hallmark of glassy dynamics, memory effect can affect glassy behavior as it evolves further upon time. Even though the physical picture of the memory effect has been well studied, it is unclear whether a glass can recall as many pieces of information as possible, and if so, how the glass will accordingly behave. We report that by fractionizing temperature interval, inserting multistep aging protocols, and optimizing the time of each temperature step, i.e., by imposing a multistep "training" on a prototypical P d40N i10C u30P20 metallic glass, the memory of the trained glass can be significantly strengthened, marked by a pronounced augment in potential energy. These findings provide a new guide for regulating the energy state of glass by enhancing the nonequilibrium behaviors of the memory effect and offer an opportunity to develop a clearer physical picture of glassy dynamics.

Impact of user influence on information multi-step communication in a micro-blog

NASA Astrophysics Data System (ADS)

Wu, Yue; Hu, Yong; He, Xiao-Hai; Deng, Ken

2014-06-01

User influence is generally considered as one of the most critical factors that affect information cascading spreading. Based on this common assumption, this paper proposes a theoretical model to examine user influence on the information multi-step communication in a micro-blog. The multi-steps of information communication are divided into first-step and non-first-step, and user influence is classified into five dimensions. Actual data from the Sina micro-blog is collected to construct the model by means of an approach based on structural equations that uses the Partial Least Squares (PLS) technique. Our experimental results indicate that the dimensions of the number of fans and their authority significantly impact the information of first-step communication. Leader rank has a positive impact on both first-step and non-first-step communication. Moreover, global centrality and weight of friends are positively related to the information non-first-step communication, but authority is found to have much less relation to it.

Thermodynamics and Kinetics of Prenucleation Clusters, Classical and Non-Classical Nucleation

PubMed Central

Zahn, Dirk

2015-01-01

Recent observations of prenucleation species and multi-stage crystal nucleation processes challenge the long-established view on the thermodynamics of crystal formation. Here, we review and generalize extensions to classical nucleation theory. Going beyond the conventional implementation as has been used for more than a century now, nucleation inhibitors, precursor clusters and non-classical nucleation processes are rationalized as well by analogous concepts based on competing interface and bulk energy terms. This is illustrated by recent examples of species formed prior to/instead of crystal nucleation and multi-step nucleation processes. Much of the discussed insights were obtained from molecular simulation using advanced sampling techniques, briefly summarized herein for both nucleation-controlled and diffusion-controlled aggregate formation. PMID:25914369

Tilling the soil while sowing the seeds: combining resident education with medical home transformation.

PubMed

Muench, John; Jarvis, Kelly; Boverman, Josh; Hardman, Joseph; Hayes, Meg; Winkle, Jim

2012-01-01

In order to successfully integrate screening, brief intervention, and referral to treatment (SBIRT) into primary care, education of clinicians must be paired with sustainable transformation of the clinical settings in which they practice. The SBIRT Oregon project adopted this strategy in an effort to fully integrate SBIRT into 7 primary care residency clinics. Residents were trained to assess and intervene in their patients' unhealthy substance use, whereas clinic staff personnel were trained to carry out a multistep screening process. Electronic medical record tools were created to further integrate and track SBIRT processes. This article describes how a resident training curriculum complemented and was informed by the transformation of workflow processes within the residents' home clinics.

A multi-step reaction model for ignition of fully-dense Al-CuO nanocomposite powders

NASA Astrophysics Data System (ADS)

Stamatis, D.; Ermoline, A.; Dreizin, E. L.

2012-12-01

A multi-step reaction model is developed to describe heterogeneous processes occurring upon heating of an Al-CuO nanocomposite material prepared by arrested reactive milling. The reaction model couples a previously derived Cabrera-Mott oxidation mechanism describing initial, low temperature processes and an aluminium oxidation model including formation of different alumina polymorphs at increased film thicknesses and higher temperatures. The reaction model is tuned using traces measured by differential scanning calorimetry. Ignition is studied for thin powder layers and individual particles using respectively the heated filament (heating rates of 103-104 K s-1) and laser ignition (heating rate ∼106 K s-1) experiments. The developed heterogeneous reaction model predicts a sharp temperature increase, which can be associated with ignition when the laser power approaches the experimental ignition threshold. In experiments, particles ignited by the laser beam are observed to explode, indicating a substantial gas release accompanying ignition. For the heated filament experiments, the model predicts exothermic reactions at the temperatures, at which ignition is observed experimentally; however, strong thermal contact between the metal filament and powder prevents the model from predicting the thermal runaway. It is suggested that oxygen gas release from decomposing CuO, as observed from particles exploding upon ignition in the laser beam, disrupts the thermal contact of the powder and filament; this phenomenon must be included in the filament ignition model to enable prediction of the temperature runaway.

Treatment of maladaptive aggression in youth: CERT guidelines II. Treatments and ongoing management.

PubMed

Scotto Rosato, Nancy; Correll, Christoph U; Pappadopulos, Elizabeth; Chait, Alanna; Crystal, Stephen; Jensen, Peter S

2012-06-01

To develop guidelines for management and treatment of maladaptive aggression in youth in the areas of psychosocial interventions, medication treatments, and side-effect management. Evidence was assembled and evaluated in a multistep process, including systematic reviews of published literature; an expert survey of recommended practices; a consensus conference of researchers, policymakers, clinicians, and family advocates; and review by the steering committee of successive drafts of the recommendations. The Center for Education and Research on Mental Health Therapeutics Treatment of Maladaptive Aggression in Youth guidelines reflect a synthesis of the available evidence, based on this multistep process. This article describes the content, rationale, and evidence for 11 recommendations. Key treatment principles include considering psychosocial interventions, such as evidence-based parent and child skills training as the first line of treatment; targeting the underlying disorder first following evidence-based guidelines; considering individual psychosocial and medical factors, including cardiovascular risk in the selection of agents if medication treatment (ideally with the best evidence base) is initiated; avoiding the use of multiple psychotropic medications simultaneously; and careful monitoring of treatment response, by using structured rating scales, as well as close medical monitoring for side effects, including metabolic changes. Treatment of children with maladaptive aggression is a "moving target" requiring ongoing assimilation of new evidence as it emerges. Based on the existing evidence, the Treatment of Maladaptive Aggression in Youth guidelines provide a framework for management of maladaptive aggression in youth, appropriate for use by primary care clinicians and mental health providers.

Contaminant source and release history identification in groundwater: A multi-step approach

NASA Astrophysics Data System (ADS)

Gzyl, G.; Zanini, A.; Frączek, R.; Kura, K.

2014-02-01

The paper presents a new multi-step approach aiming at source identification and release history estimation. The new approach consists of three steps: performing integral pumping tests, identifying sources, and recovering the release history by means of a geostatistical approach. The present paper shows the results obtained from the application of the approach within a complex case study in Poland in which several areal sources were identified. The investigated site is situated in the vicinity of a former chemical plant in southern Poland in the city of Jaworzno in the valley of the Wąwolnica River; the plant has been in operation since the First World War producing various chemicals. From an environmental point of view the most relevant activity was the production of pesticides, especially lindane. The application of the multi-step approach enabled a significant increase in the knowledge of contamination at the site. Some suspected contamination sources have been proven to have minor effect on the overall contamination. Other suspected sources have been proven to have key significance. Some areas not taken into consideration previously have now been identified as key sources. The method also enabled estimation of the magnitude of the sources and, a list of the priority reclamation actions will be drawn as a result. The multi-step approach has proven to be effective and may be applied to other complicated contamination cases. Moreover, the paper shows the capability of the geostatistical approach to manage a complex real case study.

Preparation of molecularly imprinted polymers for strychnine by precipitation polymerization and multistep swelling and polymerization and their application for the selective extraction of strychnine from nux-vomica extract powder.

PubMed

Nakamura, Yukari; Matsunaga, Hisami; Haginaka, Jun

2016-04-01

Monodisperse molecularly imprinted polymers for strychnine were prepared by precipitation polymerization and multistep swelling and polymerization, respectively. In precipitation polymerization, methacrylic acid and divinylbenzene were used as a functional monomer and crosslinker, respectively, while in multistep swelling and polymerization, methacrylic acid and ethylene glycol dimethacrylate were used as a functional monomer and crosslinker, respectively. The retention and molecular recognition properties of the molecularly imprinted polymers prepared by both methods for strychnine were evaluated using a mixture of sodium phosphate buffer and acetonitrile as a mobile phase by liquid chromatography. In addition to shape recognition, ionic and hydrophobic interactions could affect the retention of strychnine in low acetonitrile content. Furthermore, molecularly imprinted polymers prepared by both methods could selectively recognize strychnine among solutes tested. The retention factors and imprinting factors of strychnine on the molecularly imprinted polymer prepared by precipitation polymerization were 220 and 58, respectively, using 20 mM sodium phosphate buffer (pH 6.0)/acetonitrile (50:50, v/v) as a mobile phase, and those on the molecularly imprinted polymer prepared by multistep swelling and polymerization were 73 and 4.5. These results indicate that precipitation polymerization is suitable for the preparation of a molecularly imprinted polymer for strychnine. Furthermore, the molecularly imprinted polymer could be successfully applied for selective extraction of strychnine in nux-vomica extract powder. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effective stakeholder participation in setting research priorities using a Global Evidence Mapping approach.

PubMed

Clavisi, Ornella; Bragge, Peter; Tavender, Emma; Turner, Tari; Gruen, Russell L

2013-05-01

We present a multistep process for identifying priority research areas in rehabilitation and long-term care of traumatic brain-injured (TBI) patients. In particular, we aimed to (1) identify which stakeholders should be involved; (2) identify what methods are appropriate; (3) examine different criteria for the generation of research priority areas; and (4) test the feasibility of linkage and exchange among researchers, decision makers, and other potential users of the research. Potential research questions were identified and developed using an initial scoping meeting and preliminary literature search, followed by a facilitated mapping workshop and an online survey. Identified research questions were then prioritized against specific criteria (clinical importance, novelty, and controversy). Existing evidence was then mapped to the high-priority questions using usual processes for search, screening, and selection. A broad range of stakeholders were then brought together at a forum to identify priority research themes for future research investment. Using clinical and research leaders, smaller targeted planning workshops prioritized specific research projects for each of the identified themes. Twenty-six specific questions about TBI rehabilitation were generated, 14 of which were high priority. No one method identified all high-priority questions. Methods that relied solely on the views of clinicians and researchers identified fewer high-priority questions compared with methods that used broader stakeholder engagement. Evidence maps of these high-priority questions yielded a number of evidence gaps. Priority questions and evidence maps were then used to inform a research forum, which identified 12 priority themes for future research. Our research demonstrates the value of a multistep and multimethod process involving many different types of stakeholders for prioritizing research to improve the rehabilitation outcomes of people who have suffered TBI. Enhancing stakeholder representation can be augmented using a combination of methods and a process of linkage and exchange. This process can inform decisions about prioritization of research areas. Copyright © 2013 Elsevier Inc. All rights reserved.

Improved quality of cryopreserved cheetah (Acinonyx jubatus) spermatozoa after centrifugation through Accudenz.

PubMed

Crosier, Adrienne E; Henghali, Josephine N; Howard, Jogayle; Pukazhenthi, Budhan S; Terrell, Kimberly A; Marker, Laurie L; Wildt, David E

2009-01-01

Sperm cryopreservation, in combination with assisted reproductive techniques, is a valuable tool for the genetic management of endangered felids. However, the acrosome of the cheetah spermatozoon is especially sensitive to cryopreservation, with approximately 40% of spermatozoa experiencing acrosomal damage immediately after thawing and then another approximately 15% loss during the next 4 hours in vitro. Additionally, thawing causes a reduction in sperm motility by approximately 20% with another decrease of approximately 12% during subsequent incubation in vitro. We hypothesized that slow removal of glycerol from cryopreserved cheetah spermatozoa using an Accudenz gradient would improve acrosomal integrity, sperm motility longevity, and structural morphology. Accudenz was compared with traditional cheetah sperm processing methods for glycerol removal that involves washing, multistep resuspension, and swim-up processing. Electroejaculates (n = 21 total from 8 males) were washed in Ham F10 medium, and sperm pellets were resuspended in TEST-yolk buffer with 0% glycerol. Samples were cryopreserved in straws in 4% final glycerol, thawed, and assessed for percent intact acrosomes (% IA), percent motility (% M), and forward progressive status (FPS; scale, 0-5). Sperm motility index (SMI) was calculated as (% M + [FPS x 20]) / 2. In study 1, glycerol removal by centrifugation through an Accudenz gradient (4%, 10%) was compared with traditional sperm washing (control) and multistep resuspension protocols. At each time after centrifugation (hourly for 4 hours), % IA was improved (P < .05) for Accudenz (range, 36%-39%) compared with control (30%-33%) and multistep (29%-33%) treatments. In study 2, a modified Accudenz protocol was compared with traditional washing and was found to improve (P < .05) SMI (range, 52-64) compared with controls (range, 41-52) at each time postthaw after centrifugation. In study 3, swim-up processed sperm were compared with those treated by centrifugation through Accudenz and traditional sperm washing for improving sperm morphology. The percentage of structurally-normal sperm recovered postthawing increased (P < .05) for both the Accudenz (38%) and swim-up (33%) treatments compared with controls (21%). Percent IA and SMI also were improved (P < .05) for Accudenz (range, 39%-47% and 46-59, respectively) compared with controls (range, 26%-33% and 40-53, respectively). Results indicate that using Accudenz for glycerol removal from cryopreserved cheetah sperm mitigates the significant loss in sperm quality that occurs after freeze-thawing. This alleviation of cellular damage resulting from cryopreservation contributes to a more than 10% improvement in overall sperm motility and, more importantly, allows retention of 40% or more of sperm with intact acrosomes.

Tuning cell adhesion by direct nanostructuring silicon into cell repulsive/adhesive patterns

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

Premnath, Priyatha, E-mail: priyatha.premnath@ryerson.ca; Tavangar, Amirhossein, E-mail: atavanga@ryerson.ca; Tan, Bo, E-mail: tanbo@ryerson.ca

2015-09-10

Developing platforms that allow tuning cell functionality through incorporating physical, chemical, or mechanical cues onto the material surfaces is one of the key challenges in research in the field of biomaterials. In this respect, various approaches have been proposed and numerous structures have been developed on a variety of materials. Most of these approaches, however, demand a multistep process or post-chemical treatment. Therefore, a simple approach would be desirable to develop bio-functionalized platforms for effectively modulating cell adhesion and consequently programming cell functionality without requiring any chemical or biological surface treatment. This study introduces a versatile yet simple laser approachmore » to structure silicon (Si) chips into cytophobic/cytophilic patterns in order to modulate cell adhesion and proliferation. These patterns are fabricated on platforms through direct laser processing of Si substrates, which renders a desired computer-generated configuration into patterns. We investigate the morphology, chemistry, and wettability of the platform surfaces. Subsequently, we study the functionality of the fabricated platforms on modulating cervical cancer cells (HeLa) behaviour. The results from in vitro studies suggest that the nanostructures efficiently repel HeLa cells and drive them to migrate onto untreated sites. The study of the morphology of the cells reveals that cells evade the cytophobic area by bending and changing direction. Additionally, cell patterning, cell directionality, cell channelling, and cell trapping are achieved by developing different platforms with specific patterns. The flexibility and controllability of this approach to effectively structure Si substrates to cell-repulsive and cell-adhesive patterns offer perceptible outlook for developing bio-functionalized platforms for a variety of biomedical devices. Moreover, this approach could pave the way for developing anti-cancer platforms that selectively repel cancer cells while favoring the adhesion of normal cells. - Highlights: • Si platforms with cytophobic/philic patterns were developed to program cell growth. • Both nanotopography and chemistry contributed to the cytophobic property. • Cytophobic zones efficiently repel and drive HeLa cells to migrate to adhesive sites. • The approach enables cell patterning, directionality, channelling, and trapping. • This approach paves the way for developing anti-cancer platforms.« less

Sweeping as a multistep enrichment process in micellar electrokinetic chromatography: the retention factor gradient effect.

PubMed

El-Awady, Mohamed; Pyell, Ute

2013-07-05

The application of a new method developed for the assessment of sweeping efficiency in MEKC under homogeneous and inhomogeneous electric field conditions is extended to the general case, in which the distribution coefficient and the electric conductivity of the analyte in the sample zone and in the separation compartment are varied. As test analytes p-hydroxybenzoates (parabens), benzamide and some aromatic amines are studied under MEKC conditions with SDS as anionic surfactant. We show that in the general case - in contrast to the classical description - the obtainable enrichment factor is not only dependent on the retention factor of the analyte in the sample zone but also dependent on the retention factor in the background electrolyte (BGE). It is shown that in the general case sweeping is inherently a multistep focusing process. We describe an additional focusing/defocusing step (the retention factor gradient effect, RFGE) quantitatively by extending the classical equation employed for the description of the sweeping process with an additional focusing/defocusing factor. The validity of this equation is demonstrated experimentally (and theoretically) under variation of the organic solvent content (in the sample and/or the BGE), the type of organic solvent (in the sample and/or the BGE), the electric conductivity (in the sample), the pH (in the sample), and the concentration of surfactant (in the BGE). It is shown that very high enrichment factors can be obtained, if the pH in the sample zone makes possible to convert the analyte into a charged species that has a high distribution coefficient with respect to an oppositely charged micellar phase, while the pH in the BGE enables separation of the neutral species under moderate retention factor conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-Step Ka/Ka Dichroic Plate with Rounded Corners for NASA's 34m Beam Waveguide Antenna

NASA Technical Reports Server (NTRS)

Veruttipong, Watt; Khayatian, Behrouz; Hoppe, Daniel; Long, Ezra

2013-01-01

A multi-step Ka/Ka dichroic plate Frequency Selective Surface (FSS structure) is designed, manufactured and tested for use in NASA's Deep Space Network (DSN) 34m Beam Waveguide (BWG) antennas. The proposed design allows ease of manufacturing and ability to handle the increased transmit power (reflected off the FSS) of the DSN BWG antennas from 20kW to 100 kW. The dichroic is designed using HFSS and results agree well with measured data considering the manufacturing tolerances that could be achieved on the dichroic.

Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions.

PubMed

Cole, Kevin P; Groh, Jennifer McClary; Johnson, Martin D; Burcham, Christopher L; Campbell, Bradley M; Diseroad, William D; Heller, Michael R; Howell, John R; Kallman, Neil J; Koenig, Thomas M; May, Scott A; Miller, Richard D; Mitchell, David; Myers, David P; Myers, Steven S; Phillips, Joseph L; Polster, Christopher S; White, Timothy D; Cashman, Jim; Hurley, Declan; Moylan, Robert; Sheehan, Paul; Spencer, Richard D; Desmond, Kenneth; Desmond, Paul; Gowran, Olivia

2017-06-16

Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods. Success was enabled by advances in chemistry, engineering, analytical science, process modeling, and equipment design. Substantial technical and business drivers were identified, which merited the continuous process. The continuous process afforded improved performance and safety relative to batch processes and also improved containment of a highly potent compound. Copyright © 2017, American Association for the Advancement of Science.

Application of fuzzy logic and fuzzy AHP to mineral prospectivity mapping of porphyry and hydrothermal vein copper deposits in the Dananhu-Tousuquan island arc, Xinjiang, NW China

NASA Astrophysics Data System (ADS)

Zhang, Nannan; Zhou, Kefa; Du, Xishihui

2017-04-01

Mineral prospectivity mapping (MPM) is a multi-step process that ranks promising target areas for further exploration. Fuzzy logic and fuzzy analytical hierarchy process (AHP) are knowledge-driven MPM approaches. In this study, both approaches were used for data processing, based on which MPM was performed for porphyry and hydrothermal vein copper deposits in the Dananhu-Tousuquan island arc, Xinjiang. The results of the two methods were then compared. The two methods combined expert experience and the Studentized contrast (S(C)) values of the weights-of-evidence approach to calculate the weights of 15 layers, and these layers were then integrated by the gamma operator (γ). Through prediction-area (P-A) plot analysis, the optimal γ for fuzzy logic and fuzzy AHP was determined as 0.95 and 0.93, respectively. The thresholds corresponding to different levels of metallogenic probability were defined via concentration-area (C-A) fractal analysis. The prediction performances of the two methods were compared on this basis. The results showed that in MPM based on fuzzy logic, the area under the receiver operating characteristic (ROC) curve was 0.806 and 81.48% of the known deposits were predicted, whereas in MPM based on fuzzy AHP, the area under the ROC curve was 0.862 and 92.59% of the known deposits were predicted. Therefore, prediction based on fuzzy AHP is more accurate and can provide directions for future prospecting.

Simulations of flow induced structural transition of the β-switch region of glycoprotein Ibα.

PubMed

Han, Mengzhi; Xu, Ji; Ren, Ying; Li, Jinghai

2016-02-01

Binding of glycoprotein Ibα to von Willebrand factor induces platelet adhesion to injured vessel walls and initiates a multistep hemostatic process. It has been hypothesized that the flow condition could induce a loop to β-sheet conformational change in the β-switch region of glycoprotein Ibα, which regulates it binding to the von Willebrand factor and facilitates the blood clot formation and wound healing. In this work, direct molecular dynamics (MD), flow MD and metadynamics, were employed to investigate the mechanisms of this flow induced conformational transition process. Specifically, the free energy landscape of the whole transition process was drawn by metadynamics with the path collective variable approach. The results reveal that without flow, the free energy landscape has two main basins, including a random loop basin stabilized by large conformational entropy and a partially folded β-sheet basin. The free energy barrier separating these two basins is relatively high and the β-switch could not fold from loop to β-sheet state spontaneously. The fully β-sheet conformations located in high free energy regions, which are also unstable and gradually unfold into partially folded β-sheet state with flow. Relatively weak flow could trigger some folding of the β-switch but could not fold it into fully β-sheet state. Under strong flow conditions, the β-switch could readily overcome the high free energy barrier and fold into fully β-sheet state. Copyright © 2015 Elsevier B.V. All rights reserved.

A Bioinspired Catalytic Aerobic Oxidative C–H Functionalization of Primary Aliphatic Amines: Synthesis of 1,2-Disubstituted Benzimidazoles

PubMed Central

Nguyen, Khac Minh Huy; Largeron, Martine

2015-01-01

Aerobic oxidative C–H functionalization of primary aliphatic amines has been accomplished with a biomimetic cooperative catalytic system to furnish 1,2-disubstituted benzimidazoles that play an important role as drug discovery targets. This one-pot atom-economical multistep process, which proceeds under mild conditions, with ambient air and equimolar amounts of each coupling partner, constitutes a convenient environmentally friendly strategy to functionalize non-activated aliphatic amines that remain challenging substrates for non-enzymatic catalytic aerobic systems. PMID:26206475

Development of working hypotheses linking management of the Missouri River to population dynamics of Scaphirhynchus albus (pallid sturgeon)

USGS Publications Warehouse

Jacobson, Robert B.; Parsley, Michael J.; Annis, Mandy L.; Colvin, Michael E.; Welker, Timothy L.; James, Daniel A.

2016-01-20

The initial set of candidate hypotheses provides a useful starting point for quantitative modeling and adaptive management of the river and species. We anticipate that hypotheses will change from the set of working management hypotheses as adaptive management progresses. More importantly, hypotheses that have been filtered out of our multistep process are still being considered. These filtered hypotheses are archived and if existing hypotheses are determined to be inadequate to explain observed population dynamics, new hypotheses can be created or filtered hypotheses can be reinstated.

Analysis of the phosphorescent dye concentration dependence of triplet-triplet annihilation in organic host-guest systems

NASA Astrophysics Data System (ADS)

Zhang, L.; van Eersel, H.; Bobbert, P. A.; Coehoorn, R.

2016-10-01

Using a novel method for analyzing transient photoluminescence (PL) experiments, a microscopic description is obtained for the dye concentration dependence of triplet-triplet annihilation (TTA) in phosphorescent host-guest systems. It is demonstrated that the TTA-mechanism, which could be a single-step dominated process or a diffusion-mediated multi-step process, can be deduced for any given dye concentration from a recently proposed PL intensity analysis. A comparison with the results of kinetic Monte Carlo simulations provides the TTA-Förster radius and shows that the TTA enhancement due to triplet diffusion can be well described in a microscopic manner assuming Förster- or Dexter-type energy transfer.

Genetic control of Drosophila nerve cord development

NASA Technical Reports Server (NTRS)

Skeath, James B.; Thor, Stefan

2003-01-01

The Drosophila ventral nerve cord has been a central model system for studying the molecular genetic mechanisms that control CNS development. Studies show that the generation of neural diversity is a multistep process initiated by the patterning and segmentation of the neuroectoderm. These events act together with the process of lateral inhibition to generate precursor cells (neuroblasts) with specific identities, distinguished by the expression of unique combinations of regulatory genes. The expression of these genes in a given neuroblast restricts the fate of its progeny, by activating specific combinations of downstream genes. These genes in turn specify the identity of any given postmitotic cell, which is evident by its cellular morphology and choice of neurotransmitter.

Comparing Multi-Step IMAC and Multi-Step TiO2 Methods for Phosphopeptide Enrichment

PubMed Central

Yue, Xiaoshan; Schunter, Alissa; Hummon, Amanda B.

2016-01-01

Phosphopeptide enrichment from complicated peptide mixtures is an essential step for mass spectrometry-based phosphoproteomic studies to reduce sample complexity and ionization suppression effects. Typical methods for enriching phosphopeptides include immobilized metal affinity chromatography (IMAC) or titanium dioxide (TiO2) beads, which have selective affinity and can interact with phosphopeptides. In this study, the IMAC enrichment method was compared with the TiO2 enrichment method, using a multi-step enrichment strategy from whole cell lysate, to evaluate their abilities to enrich for different types of phosphopeptides. The peptide-to-beads ratios were optimized for both IMAC and TiO2 beads. Both IMAC and TiO2 enrichments were performed for three rounds to enable the maximum extraction of phosphopeptides from the whole cell lysates. The phosphopeptides that are unique to IMAC enrichment, unique to TiO2 enrichment, and identified with both IMAC and TiO2 enrichment were analyzed for their characteristics. Both IMAC and TiO2 enriched similar amounts of phosphopeptides with comparable enrichment efficiency. However, phosphopeptides that are unique to IMAC enrichment showed a higher percentage of multi-phosphopeptides, as well as a higher percentage of longer, basic, and hydrophilic phosphopeptides. Also, the IMAC and TiO2 procedures clearly enriched phosphopeptides with different motifs. Finally, further enriching with two rounds of TiO2 from the supernatant after IMAC enrichment, or further enriching with two rounds of IMAC from the supernatant TiO2 enrichment does not fully recover the phosphopeptides that are not identified with the corresponding multi-step enrichment. PMID:26237447

Immobilised enzyme microreactor for screening of multi-step bioconversions: characterisation of a de novo transketolase-ω-transaminase pathway to synthesise chiral amino alcohols.

PubMed

Matosevic, S; Lye, G J; Baganz, F

2011-09-20

Complex molecules are synthesised via a number of multi-step reactions in living cells. In this work, we describe the development of a continuous flow immobilized enzyme microreactor platform for use in evaluation of multi-step bioconversion pathways demonstrating a de novo transketolase/ω-transaminase-linked asymmetric amino alcohol synthesis. The prototype dual microreactor is based on the reversible attachment of His₆-tagged enzymes via Ni-NTA linkage to two surface derivatised capillaries connected in series. Kinetic parameters established for the model transketolase (TK)-catalysed conversion of lithium-hydroxypyruvate (Li-HPA) and glycolaldehyde (GA) to L-erythrulose using a continuous flow system with online monitoring of reaction output was in good agreement with kinetic parameters determined for TK in stop-flow mode. By coupling the transketolase catalysed chiral ketone forming reaction with the biocatalytic addition of an amine to the TK product using a transaminase (ω-TAm) it is possible to generate chiral amino alcohols from achiral starting compounds. We demonstrated this in a two-step configuration, where the TK reaction was followed by the ω-TAm-catalysed amination of L-erythrulose to synthesise 2-amino-1,3,4-butanetriol (ABT). Synthesis of the ABT product via the dual reaction and the on-line monitoring of each component provided a full profile of the de novo two-step bioconversion and demonstrated the utility of this microreactor system to provide in vitro multi-step pathway evaluation. Copyright © 2011 Elsevier B.V. All rights reserved.

Multi-Step Time Series Forecasting with an Ensemble of Varied Length Mixture Models.

PubMed

Ouyang, Yicun; Yin, Hujun

2018-05-01

Many real-world problems require modeling and forecasting of time series, such as weather temperature, electricity demand, stock prices and foreign exchange (FX) rates. Often, the tasks involve predicting over a long-term period, e.g. several weeks or months. Most existing time series models are inheritably for one-step prediction, that is, predicting one time point ahead. Multi-step or long-term prediction is difficult and challenging due to the lack of information and uncertainty or error accumulation. The main existing approaches, iterative and independent, either use one-step model recursively or treat the multi-step task as an independent model. They generally perform poorly in practical applications. In this paper, as an extension of the self-organizing mixture autoregressive (AR) model, the varied length mixture (VLM) models are proposed to model and forecast time series over multi-steps. The key idea is to preserve the dependencies between the time points within the prediction horizon. Training data are segmented to various lengths corresponding to various forecasting horizons, and the VLM models are trained in a self-organizing fashion on these segments to capture these dependencies in its component AR models of various predicting horizons. The VLM models form a probabilistic mixture of these varied length models. A combination of short and long VLM models and an ensemble of them are proposed to further enhance the prediction performance. The effectiveness of the proposed methods and their marked improvements over the existing methods are demonstrated through a number of experiments on synthetic data, real-world FX rates and weather temperatures.

Space station automation study: Automation requirements derived from space manufacturing concepts. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1984-01-01

The electroepitaxial process and the Very Large Scale Integration (VLSI) circuits (chips) facilities were chosen because each requires a very high degree of automation, and therefore involved extensive use of teleoperators, robotics, process mechanization, and artificial intelligence. Both cover a raw materials process and a sophisticated multi-step process and are therfore highly representative of the kinds of difficult operation, maintenance, and repair challenges which can be expected for any type of space manufacturing facility. Generic areas were identified which will require significant further study. The initial design will be based on terrestrial state-of-the-art hard automation. One hundred candidate missions were evaluated on the basis of automation portential and availability of meaning ful knowldege. The design requirements and unconstrained design concepts developed for the two missions are presented.

Approximate analytical modeling of leptospirosis infection

NASA Astrophysics Data System (ADS)

Ismail, Nur Atikah; Azmi, Amirah; Yusof, Fauzi Mohamed; Ismail, Ahmad Izani

2017-11-01

Leptospirosis is an infectious disease carried by rodents which can cause death in humans. The disease spreads directly through contact with feces, urine or through bites of infected rodents and indirectly via water contaminated with urine and droppings from them. Significant increase in the number of leptospirosis cases in Malaysia caused by the recent severe floods were recorded during heavy rainfall season. Therefore, to understand the dynamics of leptospirosis infection, a mathematical model based on fractional differential equations have been developed and analyzed. In this paper an approximate analytical method, the multi-step Laplace Adomian decomposition method, has been used to conduct numerical simulations so as to gain insight on the spread of leptospirosis infection.

Methoxy-Directed Aryl-to-Aryl 1,3-Rhodium Migration

PubMed Central

Zhang, Jing; Liu, Jun-Feng; Ugrinov, Angel; Pillai, Anthony F. X.; Sun, Zhong-Ming; Zhao, Pinjing

2015-01-01

Through-space metal/hydrogen shift is an important strategy for transition metal-catalyzed C-H bond activation. Here we describe the synthesis and characterization of a Rh(I) 2,6-dimethoxybenzoate complex that underwent stoichiometric rearrangement via a highly unusual 1,3- rhodium migration. This aryl-to-aryl 1,3-Rh/H shift was also demonstrated in a Rh(I)-catalyzed decarboxylative conjugate addition to form a C-C bond at a meta position instead of the ipso-carboxyl position. A deuterium-labeling study under the conditions of Rh(I)-catalyzed protodecarboxylation revealed the involvement of an ortho-methoxy group in a multi-step pathway of consecutive sp3 and sp2 C-H bond activations. PMID:24171626

Multiscale Relaxation Dynamics in Ultrathin Metallic Glass-Forming Films

NASA Astrophysics Data System (ADS)

Bi, Q. L.; Lü, Y. J.; Wang, W. H.

2018-04-01

The density layering phenomenon originating from a free surface gives rise to the layerlike dynamics and stress heterogeneity in ultrathin Cu-Zr glassy films, which facilitates the occurrence of multistep relaxations in the timescale of computer simulations. Taking advantage of this condition, we trace the relaxation decoupling and evolution with temperature simply via the intermediate scattering function. We show that the β relaxation hierarchically follows fast and slow modes in films, and there is a β -relaxation transition as the film is cooled close to the glass transition. We provide the direct observation of particle motions responsible for the β relaxation and reveal the dominant mechanism varying from the thermal activated to the cooperative jumps across the transition.

One-pot synthesis of 2,5-dihydropyrroles from terminal alkynes, azides, and propargylic alcohols by relay actions of copper, rhodium, and gold.

PubMed

Miura, Tomoya; Tanaka, Takamasa; Matsumoto, Kohei; Murakami, Masahiro

2014-12-01

Relay actions of copper, rhodium, and gold formulate a one-pot multistep pathway, which directly gives 2,5-dihydropyrroles starting from terminal alkynes, sulfonyl azides, and propargylic alcohols. Initially, copper-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides affords 1-sulfonyl-1,2,3-triazoles, which then react with propargylic alcohols under the catalysis of rhodium. The resulting alkenyl propargyl ethers subsequently undergo the thermal Claisen rearrangement to give α-allenyl-α-amino ketones. Finally, a gold catalyst prompts 5-endo cyclization to produce 2,5-dihydropyrroles. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Atomic Resolution in Situ Imaging of a Double-Bilayer Multistep Growth Mode in Gallium Nitride Nanowires

DOE PAGES

Gamalski, A. D.; Tersoff, J.; Stach, E. A.

2016-04-13

We study the growth of GaN nanowires from liquid Au–Ga catalysts using environmental transmission electron microscopy. GaN wires grow in either (11¯20) or (11¯00) directions, by the addition of {11¯00} double bilayers via step flow with multiple steps. Step-train growth is not typically seen with liquid catalysts, and we suggest that it results from low step mobility related to the unusual double-height step structure. Finally, the results here illustrate the surprising dynamics of catalytic GaN wire growth at the nanoscale and highlight striking differences between the growth of GaN and other III–V semiconductor nanowires.

The Unexplored Mechanisms and Regulatory Functions of Ribosomal Translocation

NASA Astrophysics Data System (ADS)

Alejo, Jose Luis

In every cell, protein synthesis is carried out by the ribosome, a complex macromolecular RNA-protein assembly. Decades of structural and kinetic studies have increased our understanding of ribosome initiation, decoding, translocation and termination. Yet, the underlying mechanism of these fundamental processes has yet to be fully delineated. Hence, the molecular basis of regulation remains obscure. Here, single-molecule fluorescence methods are applied to decipher the mechanism and regulatory roles of the multi-step process of directional substrate translocation on the ribosome that accompanies every round of protein synthesis. In Chapter 1, single-molecule fluorescence resonance energy transfer (smFRET) is introduced as a tool for studying bacterial ribosome translocation. Chapter 2 details the experimental methods. In Chapter 3, the elongation factor G(EF-G)-catalyzed movement of substrates through the ribosome is examined from several perspectives or signals reporting on various degrees of freedom of ribosome dynamics. Two ribosomal states interconvert in the presence of EF-G(GDP), displaying novel head domain motions, until relocking takes place. In Chapter 4, in order to test if the mentioned fluctuations leading to relocking are correlated to the engagement of the P-site by the peptidyl-tRNA, the translocation of miscoded tRNAs is studied. Severe defects in the relocking stages of translocation reveal the correlation between this new stage of translocation and P-site tRNA engagement.

Radar observations of density gradients, electric fields, and plasma irregularities near polar cap patches in the context of the gradient-drift instability

NASA Astrophysics Data System (ADS)

Lamarche, Leslie J.; Makarevich, Roman A.

2017-03-01

We present observations of plasma density gradients, electric fields, and small-scale plasma irregularities near a polar cap patch made by the Super Dual Auroral Radar Network radar at Rankin Inlet (RKN) and the northern face of Resolute Bay Incoherent Scatter Radar (RISR-N). RKN echo power and occurrence are analyzed in the context of gradient-drift instability (GDI) theory, with a particular focus on the previously uninvestigated 2-D dependencies on wave propagation, electric field, and gradient vectors, with the latter two quantities evaluated directly from RISR-N measurements. It is shown that higher gradient and electric field components along the wave vector generally lead to the higher observed echo occurrence, which is consistent with the expected higher GDI growth rate, but the relationship with echo power is far less straightforward. The RKN echo power increases monotonically as the predicted linear growth rate approaches zero from negative values but does not continue this trend into positive growth rate values, in contrast with GDI predictions. The observed greater consistency of echo occurrence with GDI predictions suggests that GDI operating in the linear regime can control basic plasma structuring, but measured echo strength may be affected by other processes and factors, such as multistep or nonlinear processes or a shear-driven instability.

Miscoding-induced stalling of substrate translocation on the bacterial ribosome.

PubMed

Alejo, Jose L; Blanchard, Scott C

2017-10-10

Directional transit of the ribosome along the messenger RNA (mRNA) template is a key determinant of the rate and processivity of protein synthesis. Imaging of the multistep translocation mechanism using single-molecule FRET has led to the hypothesis that substrate movements relative to the ribosome resolve through relatively long-lived late intermediates wherein peptidyl-tRNA enters the P site of the small ribosomal subunit via reversible, swivel-like motions of the small subunit head domain within the elongation factor G (GDP)-bound ribosome complex. Consistent with translocation being rate-limited by recognition and productive engagement of peptidyl-tRNA within the P site, we now show that base-pairing mismatches between the peptidyl-tRNA anticodon and the mRNA codon dramatically delay this rate-limiting, intramolecular process. This unexpected relationship between aminoacyl-tRNA decoding and translocation suggests that miscoding antibiotics may impact protein synthesis by impairing the recognition of peptidyl-tRNA in the small subunit P site during EF-G-catalyzed translocation. Strikingly, we show that elongation factor P (EF-P), traditionally known to alleviate ribosome stalling at polyproline motifs, can efficiently rescue translocation defects arising from miscoding. These findings help reveal the nature and origin of the rate-limiting steps in substrate translocation on the bacterial ribosome and indicate that EF-P can aid in resuming translation elongation stalled by miscoding errors.

Miscoding-induced stalling of substrate translocation on the bacterial ribosome

PubMed Central

Alejo, Jose L.; Blanchard, Scott C.

2017-01-01

Directional transit of the ribosome along the messenger RNA (mRNA) template is a key determinant of the rate and processivity of protein synthesis. Imaging of the multistep translocation mechanism using single-molecule FRET has led to the hypothesis that substrate movements relative to the ribosome resolve through relatively long-lived late intermediates wherein peptidyl-tRNA enters the P site of the small ribosomal subunit via reversible, swivel-like motions of the small subunit head domain within the elongation factor G (GDP)-bound ribosome complex. Consistent with translocation being rate-limited by recognition and productive engagement of peptidyl-tRNA within the P site, we now show that base-pairing mismatches between the peptidyl-tRNA anticodon and the mRNA codon dramatically delay this rate-limiting, intramolecular process. This unexpected relationship between aminoacyl-tRNA decoding and translocation suggests that miscoding antibiotics may impact protein synthesis by impairing the recognition of peptidyl-tRNA in the small subunit P site during EF-G–catalyzed translocation. Strikingly, we show that elongation factor P (EF-P), traditionally known to alleviate ribosome stalling at polyproline motifs, can efficiently rescue translocation defects arising from miscoding. These findings help reveal the nature and origin of the rate-limiting steps in substrate translocation on the bacterial ribosome and indicate that EF-P can aid in resuming translation elongation stalled by miscoding errors. PMID:28973849

RIBEYE(B)-domain binds to lipid components of synaptic vesicles in an NAD(H)-dependent, redox-sensitive manner.

PubMed

Schwarz, Karin; Schmitz, Frank

2017-03-20

Synaptic ribbons are needed for fast and continuous exocytosis in ribbon synapses. RIBEYE is a main protein component of synaptic ribbons and is necessary to build the synaptic ribbon. RIBEYE consists of a unique A-domain and a carboxyterminal B-domain, which binds NAD(H). Within the presynaptic terminal, the synaptic ribbons are in physical contact with large numbers of synaptic vesicle (SV)s. How this physical contact between ribbons and synaptic vesicles is established at a molecular level is not well understood. In the present study, we demonstrate that the RIBEYE(B)-domain can directly interact with lipid components of SVs using two different sedimentation assays with liposomes of defined chemical composition. Similar binding results were obtained with a SV-containing membrane fraction. The binding of liposomes to RIBEYE(B) depends upon the presence of a small amount of lysophospholipids present in the liposomes. Interestingly, binding of liposomes to RIBEYE(B) depends on NAD(H) in a redox-sensitive manner. The binding is enhanced by NADH, the reduced form, and is inhibited by NAD + , the oxidized form. Lipid-mediated attachment of vesicles is probably part of a multi-step process that also involves additional, protein-dependent processes. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Grouped and Multistep Nanoheteroepitaxy: Toward High-Quality GaN on Quasi-Periodic Nano-Mask.

PubMed

Feng, Xiaohui; Yu, Tongjun; Wei, Yang; Ji, Cheng; Cheng, Yutian; Zong, Hua; Wang, Kun; Yang, Zhijian; Kang, Xiangning; Zhang, Guoyi; Fan, Shoushan

2016-07-20

A novel nanoheteroepitaxy method, namely, the grouped and multistep nanoheteroepitaxy (GM-NHE), is proposed to attain a high-quality gallium nitride (GaN) epilayer by metal-organic vapor phase epitaxy. This method combines the effects of sub-100 nm nucleation and multistep lateral growth by using a low-cost but unique carbon nanotube mask, which consists of nanoscale growth windows with a quasi-periodic 2D fill factor. It is found that GM-NHE can facilely reduce threading dislocation density (TDD) and modulate residual stress on foreign substrate without any regrowth. As a result, high-quality GaN epilayer is produced with homogeneously low TDD of 4.51 × 10(7) cm(-2) and 2D-modulated stress, and the performance of the subsequent 410 nm near-ultraviolet light-emitting diode is greatly boosted. In this way, with the facile fabrication of nanomask and the one-off epitaxy procedure, GaN epilayer is prominently improved with the assistance of nanotechnology, which demonstrates great application potential for high-efficiency TDD-sensitive optoelectronic and electronic devices.

One-Pot Conversion of Carbohydrates into Furan Derivatives via Furfural and 5-Hydroxylmethylfurfural as Intermediates.

PubMed

Liu, Bing; Zhang, Zehui

2016-08-23

Recently, there has been growing interest in the transformation of renewable biomass into value-added fuels and chemicals. The catalytic conversion of naturally abundant carbohydrates can generate two-important furan chemicals: 5-hydroxymethylfurfural (HMF) from C6 carbohydrates and furfural from C5 carbohydrates. Both HMF and furfural have received great interest as precursors in the synthesis of commodity chemicals and liquid fuels. In recent years, a trend has emerged to integrate sequential catalytic processes involving multistep reactions for the direct one-pot transformation of carbohydrates into the aimed fuels and chemicals. One-pot reactions have remarkably unique and environmentally friendly benefits, including the fact that isolation and purification of intermediate compounds can be avoided. Herein, the present article aims to review recent advances in the one-pot conversion of carbohydrates into furan derivatives via furfural and HMF as intermediates. Special attention will be paid to the catalytic systems, mechanistic insight, reaction pathways, and catalyst stability. It is expected that this review will guide researchers to develop effective catalytic systems for the one-pot transformation of carbohydrates into furan derivatives. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

PubMed

Kikushige, Yoshikane; Miyamoto, Toshihiro

2015-11-01

Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

Damage initiation and propagation assessed from stress-induced microseismic events during a mine-by test in the Opalinus Clay

NASA Astrophysics Data System (ADS)

Le Gonidec, Y.; Sarout, J.; Wassermann, J.; Nussbaum, C.

2014-07-01

We report in this paper an original analysis of microseismic events (MSEs) induced by an excavation operation in the clay environment of the Mont Terri underground rock laboratory. In order to identify the MSEs with confidence, we develop a restrictive but efficient multistep method for filtering the recorded events. We deduce the spatial distribution and processes associated with the excavation-induced damage from the spatial location and focal mechanisms of the MSEs. We observe an asymmetric geometry of the excavation damaged zone around the excavated gallery, without notable microseismic activity in the sandy facies sidewall, in contrast with the shaly facies sidewall where a first burst of events is recorded, followed by two smaller bursts: one locates ahead of the excavation front and is associated with a dominant double-couple component, suggesting bedding plane reworking, that is, shear fracture mode, and the MSEs of the other cluster inside the shaly sidewall of the gallery, with a dominant compensated linear vector dipole component, suggesting extensive cracking. We identify and discuss four major factors that seem to control the MSEs source mechanisms: lithology, geometry of the geological features, gallery orientation and direction of the main compressive stress.

Biocatalytic, one-pot diterminal oxidation and esterification of n-alkanes for production of α,ω-diol and α,ω-dicarboxylic acid esters.

PubMed

van Nuland, Youri M; de Vogel, Fons A; Scott, Elinor L; Eggink, Gerrit; Weusthuis, Ruud A

2017-11-01

Direct and selective terminal oxidation of medium-chain n-alkanes is a major challenge in chemistry. Efforts to achieve this have so far resulted in low specificity and overoxidized products. Biocatalytic oxidation of medium-chain n-alkanes - with for example the alkane monooxygenase AlkB from P. putida GPo1- on the other hand is highly selective. However, it also results in overoxidation. Moreover, diterminal oxidation of medium-chain n-alkanes is inefficient. Hence, α,ω-bifunctional monomers are mostly produced from olefins using energy intensive, multi-step processes. By combining biocatalytic oxidation with esterification we drastically increased diterminal oxidation upto 92mol% and reduced overoxidation to 3% for n-hexane. This methodology allowed us to convert medium-chain n-alkanes into α,ω-diacetoxyalkanes and esterified α,ω-dicarboxylic acids. We achieved this in a one-pot reaction with resting-cell suspensions of genetically engineered Escherichia coli. The combination of terminal oxidation and esterification constitutes a versatile toolbox to produce α,ω-bifunctional monomers from n-alkanes. Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Very-short-term wind power prediction by a hybrid model with single- and multi-step approaches

NASA Astrophysics Data System (ADS)

Mohammed, E.; Wang, S.; Yu, J.

2017-05-01

Very-short-term wind power prediction (VSTWPP) has played an essential role for the operation of electric power systems. This paper aims at improving and applying a hybrid method of VSTWPP based on historical data. The hybrid method is combined by multiple linear regressions and least square (MLR&LS), which is intended for reducing prediction errors. The predicted values are obtained through two sub-processes:1) transform the time-series data of actual wind power into the power ratio, and then predict the power ratio;2) use the predicted power ratio to predict the wind power. Besides, the proposed method can include two prediction approaches: single-step prediction (SSP) and multi-step prediction (MSP). WPP is tested comparatively by auto-regressive moving average (ARMA) model from the predicted values and errors. The validity of the proposed hybrid method is confirmed in terms of error analysis by using probability density function (PDF), mean absolute percent error (MAPE) and means square error (MSE). Meanwhile, comparison of the correlation coefficients between the actual values and the predicted values for different prediction times and window has confirmed that MSP approach by using the hybrid model is the most accurate while comparing to SSP approach and ARMA. The MLR&LS is accurate and promising for solving problems in WPP.

Process Intensification for Cellulosic Biorefineries.

PubMed

Sadula, Sunitha; Athaley, Abhay; Zheng, Weiqing; Ierapetritou, Marianthi; Saha, Basudeb

2017-06-22

Utilization of renewable carbon source, especially non-food biomass is critical to address the climate change and future energy challenge. Current chemical and enzymatic processes for producing cellulosic sugars are multistep, and energy- and water-intensive. Techno-economic analysis (TEA) suggests that upstream lignocellulose processing is a major hurdle to the economic viability of the cellulosic biorefineries. Process intensification, which integrates processes and uses less water and energy, has the potential to overcome the aforementioned challenges. Here, we demonstrate a one-pot depolymerization and saccharification process of woody biomass, energy crops, and agricultural residues to produce soluble sugars with high yields. Lignin is separated as a solid for selective upgrading. Further integration of our upstream process with a reactive extraction step makes energy-efficient separation of sugars in the form of furans. TEA reveals that the process efficiency and integration enable, for the first time, economic production of feed streams that could profoundly improve process economics for downstream cellulosic bioproducts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Frederix, Marijke; Mingardon, Florence; Hu, Matthew

Biological production of chemicals and fuels using microbial transformation of sustainable carbon sources, such as pretreated and saccharified plant biomass, is a multi-step process. Typically, each segment of the workflow is optimized separately, often generating conditions that may not be suitable for integration or consolidation with the upstream or downstream steps. While significant effort has gone into developing solutions to incompatibilities at discrete steps, very few studies report the consolidation of the multi-step workflow into a single pot reactor system. Here we demonstrate a one-pot biofuel production process that uses the ionic liquid 1-ethyl-3-methylimidazolium acetate (C 2C 1Im][OAc] ) formore » pretreatment of switchgrass biomass. [C 2C 1Im][OAc] is highly effective in deconstructing lignocellulose, but nonetheless leaves behind residual reagents that are toxic to standard saccharification enzymes and the microbial production host. We report the discovery of an [C 2C 1Im]-tolerant E. coli strain, where [C 2C 1Im] tolerance is bestowed by a P7Q mutation in the transcriptional regulator encoded by rcdA. We establish that the causal impact of this mutation is the derepression of a hitherto uncharacterized major facilitator family transporter, YbjJ. To develop the strain for a one-pot process we engineered this [C 2C 1Im]-tolerant strain to express a recently reported d-limonene production pathway. We also screened previously reported [C 2C 1Im]-tolerant cellulases to select one that would function with the range of E. coli cultivation conditions and expressed it in the [C 2C 1 Im]-tolerant E. coli strain so as to secrete this [C 2C 1Im]-tolerant cellulase. The final strain digests pretreated biomass, and uses the liberated sugars to produce the bio-jet fuel candidate precursor d-limonene in a one-pot process.« less

Development of an E. coli strain for one-pot biofuel production from ionic liquid pretreated cellulose and switchgrass

DOE PAGES

Frederix, Marijke; Mingardon, Florence; Hu, Matthew; ...

2016-04-11

Biological production of chemicals and fuels using microbial transformation of sustainable carbon sources, such as pretreated and saccharified plant biomass, is a multi-step process. Typically, each segment of the workflow is optimized separately, often generating conditions that may not be suitable for integration or consolidation with the upstream or downstream steps. While significant effort has gone into developing solutions to incompatibilities at discrete steps, very few studies report the consolidation of the multi-step workflow into a single pot reactor system. Here we demonstrate a one-pot biofuel production process that uses the ionic liquid 1-ethyl-3-methylimidazolium acetate (C 2C 1Im][OAc] ) formore » pretreatment of switchgrass biomass. [C 2C 1Im][OAc] is highly effective in deconstructing lignocellulose, but nonetheless leaves behind residual reagents that are toxic to standard saccharification enzymes and the microbial production host. We report the discovery of an [C 2C 1Im]-tolerant E. coli strain, where [C 2C 1Im] tolerance is bestowed by a P7Q mutation in the transcriptional regulator encoded by rcdA. We establish that the causal impact of this mutation is the derepression of a hitherto uncharacterized major facilitator family transporter, YbjJ. To develop the strain for a one-pot process we engineered this [C 2C 1Im]-tolerant strain to express a recently reported d-limonene production pathway. We also screened previously reported [C 2C 1Im]-tolerant cellulases to select one that would function with the range of E. coli cultivation conditions and expressed it in the [C 2C 1 Im]-tolerant E. coli strain so as to secrete this [C 2C 1Im]-tolerant cellulase. The final strain digests pretreated biomass, and uses the liberated sugars to produce the bio-jet fuel candidate precursor d-limonene in a one-pot process.« less

Multistep synthesis on SU-8: combining microfabrication and solid-phase chemistry on a single material.

PubMed

Cavalli, Gabriel; Banu, Shahanara; Ranasinghe, Rohan T; Broder, Graham R; Martins, Hugo F P; Neylon, Cameron; Morgan, Hywel; Bradley, Mark; Roach, Peter L

2007-01-01

SU-8 is an epoxy-novolac resin and a well-established negative photoresist for microfabrication and microengineering. The photopolymerized resist is an extremely highly crosslinked polymer showing outstanding chemical and physical robustness with residual surface epoxy groups amenable for chemical functionalization. In this paper we describe, for the first time, the preparation and surface modification of SU-8 particles shaped as microbars, the attachment of appropriate linkers, and the successful application of these particles to multistep solid-phase synthesis leading to oligonucleotides and peptides attached in an unambiguous manner to the support surface.

Hard-X-Ray-Induced Multistep Ultrafast Dissociation

NASA Astrophysics Data System (ADS)

Travnikova, Oksana; Marchenko, Tatiana; Goldsztejn, Gildas; Jänkälä, Kari; Sisourat, Nicolas; Carniato, Stéphane; Guillemin, Renaud; Journel, Loïc; Céolin, Denis; Püttner, Ralph; Iwayama, Hiroshi; Shigemasa, Eiji; Piancastelli, Maria Novella; Simon, Marc

2016-05-01

Creation of deep core holes with very short (τ ≤1 fs ) lifetimes triggers a chain of relaxation events leading to extensive nuclear dynamics on a few-femtosecond time scale. Here we demonstrate a general multistep ultrafast dissociation on an example of HCl following Cl 1 s →σ* excitation. Intermediate states with one or multiple holes in the shallower core electron shells are generated in the course of the decay cascades. The repulsive character and large gradients of the potential energy surfaces of these intermediates enable ultrafast fragmentation after the absorption of a hard x-ray photon.

Improving site selection in clinical studies: a standardised, objective, multistep method and first experience results.

PubMed

Hurtado-Chong, Anahí; Joeris, Alexander; Hess, Denise; Blauth, Michael

2017-07-12

A considerable number of clinical studies experience delays, which result in increased duration and costs. In multicentre studies, patient recruitment is among the leading causes of delays. Poor site selection can result in low recruitment and bad data quality. Site selection is therefore crucial for study quality and completion, but currently no specific guidelines are available. Selection of sites adequate to participate in a prospective multicentre cohort study was performed through an open call using a newly developed objective multistep approach. The method is based on use of a network, definition of objective criteria and a systematic screening process. Out of 266 interested sites, 24 were shortlisted and finally 12 sites were selected to participate in the study. The steps in the process included an open call through a network, use of selection questionnaires tailored to the study, evaluation of responses using objective criteria and scripted telephone interviews. At each step, the number of candidate sites was quickly reduced leaving only the most promising candidates. Recruitment and quality of data went according to expectations in spite of the contracting problems faced with some sites. The results of our first experience with a standardised and objective method of site selection are encouraging. The site selection method described here can serve as a guideline for other researchers performing multicentre studies. ClinicalTrials.gov: NCT02297581. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cell sheet-based tissue engineering for fabricating 3-dimensional heart tissues.

PubMed

Shimizu, Tatsuya

2014-01-01

In addition to stem cell biology, tissue engineering is an essential research field for regenerative medicine. In contrast to cell injection, bioengineered tissue transplantation minimizes cell loss and has the potential to repair tissue defects. A popular approach is scaffold-based tissue engineering, which utilizes a biodegradable polymer scaffold for seeding cells; however, new techniques of cell sheet-based tissue engineering have been developed. Cell sheets are harvested from temperature-responsive culture dishes by simply lowering the temperature. Monolayer or stacked cell sheets are transplantable directly onto damaged tissues and cell sheet transplantation has already been clinically applied. Cardiac cell sheet stacking produces pulsatile heart tissue; however, lack of vasculature limits the viable tissue thickness to 3 layers. Multistep transplantation of triple-layer cardiac cell sheets cocultured with endothelial cells has been used to form thick vascularized cardiac tissue in vivo. Furthermore, in vitro functional blood vessel formation within 3-dimensional (3D) tissues has been realized by successfully imitating in vivo conditions. Triple-layer cardiac cell sheets containing endothelial cells were layered on vascular beds and the constructs were media-perfused using novel bioreactor systems. Interestingly, cocultured endothelial cells migrate into the vascular beds and form perfusable blood vessels. An in vitro multistep procedure has also enabled the fabrication of thick, vascularized heart tissues. Cell sheet-based tissue engineering has revealed great potential to fabricate 3D cardiac tissues and should contribute to future treatment of severe heart diseases and human tissue model production.

Inverting the planning gradient: adjustment of grasps to late segments of multi-step object manipulations.

PubMed

Mathew, Hanna; Kunde, Wilfried; Herbort, Oliver

2017-05-01

When someone grasps an object, the grasp depends on the intended object manipulation and usually facilitates it. If several object manipulation steps are planned, the first step has been reported to primarily determine the grasp selection. We address whether the grasp can be aligned to the second step, if the second step's requirements exceed those of the first step. Participants grasped and rotated a dial first by a small extent and then by various extents in the opposite direction, without releasing the dial. On average, when the requirements of the first and the second step were similar, participants mostly aligned the grasp to the first step. When the requirements of the second step were considerably higher, participants aligned the grasp to the second step, even though the first step still had a considerable impact. Participants employed two different strategies. One subgroup initially aligned the grasp to the first step and then ceased adjusting the grasp to either step. Another group also initially aligned the grasp to the first step and then switched to aligning it primarily to the second step. The data suggest that participants are more likely to switch to the latter strategy when they experienced more awkward arm postures. In summary, grasp selections for multi-step object manipulations can be aligned to the second object manipulation step, if the requirements of this step clearly exceed those of the first step and if participants have some experience with the task.

Postarrest stalling rather than crawling favors CD8+ over CD4+ T‐cell migration across the blood–brain barrier under flow in vitro

PubMed Central

Rudolph, Henriette; Klopstein, Armelle; Gruber, Isabelle; Blatti, Claudia; Lyck, Ruth

2016-01-01

Although CD8+ T cells have been implied in the pathogenesis of multiple sclerosis (MS), the molecular mechanisms mediating CD8+ T‐cell migration across the blood–brain barrier (BBB) into the central nervous system (CNS) are ill defined. Using in vitro live cell imaging, we directly compared the multistep extravasation of activated CD4+ and CD8+ T cells across primary mouse brain microvascular endothelial cells (pMBMECs) as a model for the BBB under physiological flow. Significantly higher numbers of CD8+ than CD4+ T cells arrested on pMBMECs under noninflammatory and inflammatory conditions. While CD4+ T cells polarized and crawled prior to their diapedesis, the majority of CD8+ T cells stalled and readily crossed the pMBMEC monolayer preferentially via a transcellular route. T‐cell arrest and crawling were independent of G‐protein‐coupled receptor signaling. Rather, absence of endothelial ICAM‐1 and ICAM‐2 abolished increased arrest of CD8+ over CD4+ T cells and abrogated T‐cell crawling, leading to the efficient reduction of CD4+, but to a lesser degree of CD8+, T‐cell diapedesis across ICAM‐1null/ICAM‐2−/− pMBMECs. Thus, cellular and molecular mechanisms mediating the multistep extravasation of activated CD8+ T cells across the BBB are distinguishable from those involved for CD4+ T cells. PMID:27338806

Direct fabrication of bio-inspired gecko-like geometries with vat polymerization additive manufacturing method

NASA Astrophysics Data System (ADS)

Davoudinejad, A.; Ribo, M. M.; Pedersen, D. B.; Islam, A.; Tosello, G.

2018-08-01

Functional surfaces have proven their potential to solve many engineering problems, attracting great interest among the scientific community. Bio-inspired multi-hierarchical micro-structures grant the surfaces with new properties, such as hydrophobicity, adhesion, unique optical properties and so on. The geometry and fabrication of these surfaces are still under research. In this study, the feasibility of using direct fabrication of microscale features by additive manufacturing (AM) processes was investigated. The investigation was carried out using a specifically designed vat photopolymerization AM machine-tool suitable for precision manufacturing at the micro dimensional scale which has previously been developed, built and validated at the Technical University of Denmark. It was shown that it was possible to replicate a simplified surface inspired by the Tokay gecko, the geometry was previously designed and replicated by a complex multi-step micromanufacturing method extracted from the literature and used as benchmark. Ultimately, the smallest printed features were analyzed by conducting a sensitivity analysis to obtain the righteous parameters in terms of layer thickness and exposure time. Moreover, two more intricate designs were fabricated with the same parameters to assess the surfaces functionality by its wettability. The surface with increased density and decreased feature size showed a water contact angle (CA) of 124°  ±  0.10°, agreeing with the Cassie–Baxter model. These results indicate the possibility of using precision AM for a rapid, easy and reliable fabrication method for functional surfaces.

Apigenin blocks IKKα activation and suppresses prostate cancer progression

PubMed Central

Shukla, Sanjeev; Kanwal, Rajnee; Shankar, Eswar; Datt, Manish; Chance, Mark R.; Fu, Pingfu; MacLennan, Gregory T.; Gupta, Sanjay

2015-01-01

IKKα has been implicated as a key regulator of oncogenesis and driver of the metastatic process; therefore is regarded as a promising therapeutic target in anticancer drug development. In spite of the progress made in the development of IKK inhibitors, no potent IKKα inhibitor(s) have been identified. Our multistep approach of molecular modeling and direct binding has led to the identification of plant flavone apigenin as a specific IKKα inhibitor. Here we report apigenin, in micro molar range, inhibits IKKα kinase activity, demonstrates anti-proliferative and anti-invasive activities in functional cell based assays and exhibits anticancer efficacy in experimental tumor model. We found that apigenin directly binds with IKKα, attenuates IKKα kinase activity and suppresses NF-ĸB/p65 activation in human prostate cancer PC-3 and 22Rv1 cells much more effectively than IKK inhibitor, PS1145. We also showed that apigenin caused cell cycle arrest similar to knockdown of IKKα in prostate cancer cells. Studies in xenograft mouse model indicate that apigenin feeding suppresses tumor growth, lowers proliferation and enhances apoptosis. These effects correlated with inhibition of p-IKKα, NF-ĸB/p65, proliferating cell nuclear antigen and increase in cleaved caspase 3 expression in a dose-dependent manner. Overall, our results suggest that inhibition of cell proliferation, invasiveness and decrease in tumor growth by apigenin are mediated by its ability to suppress IKKα and downstream targets affecting NF-ĸB signaling pathways. PMID:26435478

Apigenin blocks IKKα activation and suppresses prostate cancer progression.

PubMed

Shukla, Sanjeev; Kanwal, Rajnee; Shankar, Eswar; Datt, Manish; Chance, Mark R; Fu, Pingfu; MacLennan, Gregory T; Gupta, Sanjay

2015-10-13

IKKα has been implicated as a key regulator of oncogenesis and driver of the metastatic process; therefore is regarded as a promising therapeutic target in anticancer drug development. In spite of the progress made in the development of IKK inhibitors, no potent IKKα inhibitor(s) have been identified. Our multistep approach of molecular modeling and direct binding has led to the identification of plant flavone apigenin as a specific IKKα inhibitor. Here we report apigenin, in micro molar range, inhibits IKKα kinase activity, demonstrates anti-proliferative and anti-invasive activities in functional cell based assays and exhibits anticancer efficacy in experimental tumor model. We found that apigenin directly binds with IKKα, attenuates IKKα kinase activity and suppresses NF-ĸB/p65 activation in human prostate cancer PC-3 and 22Rv1 cells much more effectively than IKK inhibitor, PS1145. We also showed that apigenin caused cell cycle arrest similar to knockdown of IKKα in prostate cancer cells. Studies in xenograft mouse model indicate that apigenin feeding suppresses tumor growth, lowers proliferation and enhances apoptosis. These effects correlated with inhibition of p-IKKα, NF-ĸB/p65, proliferating cell nuclear antigen and increase in cleaved caspase 3 expression in a dose-dependent manner. Overall, our results suggest that inhibition of cell proliferation, invasiveness and decrease in tumor growth by apigenin are mediated by its ability to suppress IKKα and downstream targets affecting NF-ĸB signaling pathways.

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms.

PubMed

Kahvejian, Avak; Svitkin, Yuri V; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5'-end of the mRNA to promote the recruitment of the ribosome. Although the 3' poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (approximately 65% vs. approximately 35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5'-end of mRNA.

Mammalian poly(A)-binding protein is a eukaryotic translation initiation factor, which acts via multiple mechanisms

PubMed Central

Kahvejian, Avak; Svitkin, Yuri V.; Sukarieh, Rami; M'Boutchou, Marie-Noël; Sonenberg, Nahum

2005-01-01

Translation initiation is a multistep process involving several canonical translation factors, which assemble at the 5′-end of the mRNA to promote the recruitment of the ribosome. Although the 3′ poly(A) tail of eukaryotic mRNAs and its major bound protein, the poly(A)-binding protein (PABP), have been studied extensively, their mechanism of action in translation is not well understood and is confounded by differences between in vivo and in vitro systems. Here, we provide direct evidence for the involvement of PABP in key steps of the translation initiation pathway. Using a new technique to deplete PABP from mammalian cell extracts, we show that extracts lacking PABP exhibit dramatically reduced rates of translation, reduced efficiency of 48S and 80S ribosome initiation complex formation, and impaired interaction of eIF4E with the mRNA cap structure. Supplementing PABP-depleted extracts with wild-type PABP completely rectified these deficiencies, whereas a mutant of PABP, M161A, which is incapable of interacting with eIF4G, failed to restore translation. In addition, a stronger inhibition (approximately twofold) of 80S as compared to 48S ribosome complex formation (∼65% vs. ∼35%, respectively) by PABP depletion suggests that PABP plays a direct role in 60S subunit joining. PABP can thus be considered a canonical translation initiation factor, integral to initiation complex formation at the 5′-end of mRNA. PMID:15630022

Quantum information processing with a travelling wave of light

NASA Astrophysics Data System (ADS)

Serikawa, Takahiro; Shiozawa, Yu; Ogawa, Hisashi; Takanashi, Naoto; Takeda, Shuntaro; Yoshikawa, Jun-ichi; Furusawa, Akira

2018-02-01

We exploit quantum information processing on a traveling wave of light, expecting emancipation from thermal noise, easy coupling to fiber communication, and potentially high operation speed. Although optical memories are technically challenging, we have an alternative approach to apply multi-step operations on traveling light, that is, continuous-variable one-way computation. So far our achievement includes generation of a one-million-mode entangled chain in time-domain, mode engineering of nonlinear resource states, and real-time nonlinear feedforward. Although they are implemented with free space optics, we are also investigating photonic integration and performed quantum teleportation with a passive liner waveguide chip as a demonstration of entangling, measurement, and feedforward. We also suggest a loop-based architecture as another model of continuous-variable computing.

Establishment, operation and development of a donor human milk bank.

PubMed

Biasini, Augusto; Stella, Marcello; Malaigia, Laura; China, Mariachiara; Azzalli, Milena; Laguardia, Maria Chiara; Rizzo, Vittoria

2013-10-01

Human milk is very valuable in premature infant nutrition. The collection, screening, processing and distribution of donor human milk are described in this report. These activities take place in the Donor Human Milk Bank (DHMB) of the Large Romagna Area (LRA) in Italy, the development of which is also described here. Over the years, the activities of this bank, which is located in Cesena Hospital, in the center of the LRA, have developed from an informal and domestic-level activity to become a multistep controlled process designed to prevent the possibility of disease transmission. This little food-supply industry, run by a multi-disciplinary team with strict rules and diverse responsibilities, complies with the Hazards Analysis and Critical Control Points (HACCP) system. © 2013.

Harnessing Thin-Film Continuous-Flow Assembly Lines.

PubMed

Britton, Joshua; Castle, Jared W; Weiss, Gregory A; Raston, Colin L

2016-07-25

Inspired by nature's ability to construct complex molecules through sequential synthetic transformations, an assembly line synthesis of α-aminophosphonates has been developed. In this approach, simple starting materials are continuously fed through a thin-film reactor where the intermediates accrue molecular complexity as they progress through the flow system. Flow chemistry allows rapid multistep transformations to occur via reaction compartmentalization, an approach not amenable to using conventional flasks. Thin film processing can also access facile in situ solvent exchange to drive reaction efficiency, and through this method, α-aminophosphonate synthesis requires only 443 s residence time to produce 3.22 g h(-1) . Assembly-line synthesis allows unprecedented reaction flexibility and processing efficiency. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sealed-bladdered chemical processing method and apparatus

DOEpatents

Harless, D. Phillip

1999-01-01

A method and apparatus which enables a complete multi-stepped chemical treatment process to occur within a single, sealed-bladdered vessel 31. The entire chemical process occurs without interruption of the sealed-bladdered vessel 31 such as opening the sealed-bladdered vessel 31 between various steps of the process. The sealed-bladdered vessel 31 is loaded with a batch to be dissolved, treated, decanted, rinsed and/or dried. A pressure filtration step may also occur. The self-contained chemical processing apparatus 32 contains a sealed-bladder 32, a fluid pump 34, a reservoir 20, a compressed gas inlet, a vacuum pump 24, and a cold trap 23 as well as the associated piping 33, numerous valves 21,22,25,26,29,30,35,36 and other controls associated with such an apparatus. The claimed invention allows for dissolution and/or chemical treatment without the operator of the self-contained chemical processing apparatus 38 coming into contact with any of the process materials.

microRNA biogenesis and turnover in plants.

PubMed

Rogers, K; Chen, X

2012-01-01

microRNAs (miRNAs) are short RNAs that regulate gene expression in eukaryotes. The biogenesis and turnover of miRNAs determine their spatiotemporal accumulation within tissues. miRNA biogenesis is a multistep process that entails transcription, processing, nuclear export, and formation of the miRNA-ARGONAUTE complex. Factors that perform each of these steps have been identified. Generation of mature miRNAs from primary transcripts, i.e., miRNA processing, is a key step in miRNA biogenesis. Our understanding of miRNA processing has expanded beyond the enzyme that performs the reactions, as more and more additional factors that impact the efficiency and accuracy of miRNA processing are uncovered. In contrast to miRNA biogenesis, miRNA turnover is an important but poorly understood process that contributes to the steady-state levels of miRNAs. Enzymes responsible for miRNA degradation have only recently been identified. This review describes the processes of miRNA maturation and degradation in plants.

From Cocoa to Chocolate: The Impact of Processing on In Vitro Antioxidant Activity and the Effects of Chocolate on Antioxidant Markers In Vivo

PubMed Central

Di Mattia, Carla D.; Sacchetti, Giampiero; Mastrocola, Dino; Serafini, Mauro

2017-01-01

Chocolate is a product processed from cocoa rich in flavonoids, antioxidant compounds, and bioactive ingredients that have been associated with both its healthy and sensory properties. Chocolate production consists of a multistep process which, starting from cocoa beans, involves fermentation, drying, roasting, nib grinding and refining, conching, and tempering. During cocoa processing, the naturally occurring antioxidants (flavonoids) are lost, while others, such as Maillard reaction products, are formed. The final content of antioxidant compounds and the antioxidant activity of chocolate is a function of several variables, some related to the raw material and others related to processing and formulation. The aim of this mini-review is to revise the literature on the impact of full processing on the in vitro antioxidant activity of chocolate, providing a critical analysis of the implications of processing on the evaluation of the antioxidant effect of chocolate in in vivo studies in humans. PMID:29033932

From Cocoa to Chocolate: The Impact of Processing on In Vitro Antioxidant Activity and the Effects of Chocolate on Antioxidant Markers In Vivo.

PubMed

Di Mattia, Carla D; Sacchetti, Giampiero; Mastrocola, Dino; Serafini, Mauro

2017-01-01

Chocolate is a product processed from cocoa rich in flavonoids, antioxidant compounds, and bioactive ingredients that have been associated with both its healthy and sensory properties. Chocolate production consists of a multistep process which, starting from cocoa beans, involves fermentation, drying, roasting, nib grinding and refining, conching, and tempering. During cocoa processing, the naturally occurring antioxidants (flavonoids) are lost, while others, such as Maillard reaction products, are formed. The final content of antioxidant compounds and the antioxidant activity of chocolate is a function of several variables, some related to the raw material and others related to processing and formulation. The aim of this mini-review is to revise the literature on the impact of full processing on the in vitro antioxidant activity of chocolate, providing a critical analysis of the implications of processing on the evaluation of the antioxidant effect of chocolate in in vivo studies in humans.

Materials-Related Aspects of Thermochemical Water and Carbon Dioxide Splitting: A Review

PubMed Central

Roeb, Martin; Neises, Martina; Monnerie, Nathalie; Call, Friedemann; Simon, Heike; Sattler, Christian; Schmücker, Martin; Pitz-Paal, Robert

2012-01-01

Thermochemical multistep water- and CO2-splitting processes are promising options to face future energy problems. Particularly, the possible incorporation of solar power makes these processes sustainable and environmentally attractive since only water, CO2 and solar power are used; the concentrated solar energy is converted into storable and transportable fuels. One of the major barriers to technological success is the identification of suitable active materials like catalysts and redox materials exhibiting satisfactory durability, reactivity and efficiencies. Moreover, materials play an important role in the construction of key components and for the implementation in commercial solar plants. The most promising thermochemical water- and CO2-splitting processes are being described and discussed with respect to further development and future potential. The main materials-related challenges of those processes are being analyzed. Technical approaches and development progress in terms of solving them are addressed and assessed in this review.

Water evaporation on highly viscoelastic polymer surfaces.

PubMed

Pu, Gang; Severtson, Steven J

2012-07-03

Results are reported for a study on the evaporation of water droplets from a highly viscoelastic acrylic polymer surface. These are contrasted with those collected for the same measurements carried out on polydimethylsiloxane (PDMS). For PDMS, the evaporation process involves the expected multistep process including constant drop area, constant contact angle, and finally a combination of these steps until the liquid is gone. In contrast, water evaporation from the acrylic polymer shows a constant drop area mode throughout. Furthermore, during the evaporation process, the drop area actually expands on the acrylic polymer. The single mode evaporation process is consistent with formation of wetting structures, which cannot be propagated by the capillary forces. Expansion of the drop area is attributed to the influence of the drop capillary pressure. Furthermore, the rate of drop area expansion is shown to be dependent on the thickness of the polymer film.

High temperature thermochromic polydiacetylenes: Design and colorimetric properties

NASA Astrophysics Data System (ADS)

Huo, Jingpei; Hu, Zhudong; He, Guozhang; Hong, Xiaxiao; Yang, Zhihao; Luo, Shihe; Ye, Xiufang; Li, Yanli; Zhang, Yubo; Zhang, Min; Chen, Hong; Fan, Ting; Zhang, Yuyuan; Xiong, Bangyun; Wang, Zhaoyang; Zhu, Zhibo; Chen, Dongchu

2017-11-01

Three novel polydiacetylenes (PDAs) are synthesized through the self-assembly followed by the topochemical polymerization via controllable electrophoretic deposition. All the samples could undergo a multi-step thermochromic process, turning purple and red successively over a wide range from room temperature to above 250 °C. Resulting PDAs are studied by UV-vis, IR, Raman spectroscopies, and chromoisomerism by naked eye visualization; their stabilities by thermogravimetric method, and emission behavior by fluorescence spectroscopy. To study the mechanism of the thermochromic response, temperature-dependent UV-vis spectra, the results of which successfully highlighted the close relationship between chromatic transitions and the conformational changes.

Clinical relevance and biology of circulating tumor cells

PubMed Central

2011-01-01

Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

Multi-electrolyte-step anodic aluminum oxide method for the fabrication of self-organized nanochannel arrays

PubMed Central

2012-01-01

Nanochannel arrays were fabricated by the self-organized multi-electrolyte-step anodic aluminum oxide [AAO] method in this study. The anodization conditions used in the multi-electrolyte-step AAO method included a phosphoric acid solution as the electrolyte and an applied high voltage. There was a change in the phosphoric acid by the oxalic acid solution as the electrolyte and the applied low voltage. This method was used to produce self-organized nanochannel arrays with good regularity and circularity, meaning less power loss and processing time than with the multi-step AAO method. PMID:22333268

Cytoskeleton in motion: the dynamics of keratin intermediate filaments in epithelia.

PubMed

Windoffer, Reinhard; Beil, Michael; Magin, Thomas M; Leube, Rudolf E

2011-09-05

Epithelia are exposed to multiple forms of stress. Keratin intermediate filaments are abundant in epithelia and form cytoskeletal networks that contribute to cell type-specific functions, such as adhesion, migration, and metabolism. A perpetual keratin filament turnover cycle supports these functions. This multistep process keeps the cytoskeleton in motion, facilitating rapid and protein biosynthesis-independent network remodeling while maintaining an intact network. The current challenge is to unravel the molecular mechanisms underlying the regulation of the keratin cycle in relation to actin and microtubule networks and in the context of epithelial tissue function.

Cytoskeleton in motion: the dynamics of keratin intermediate filaments in epithelia

PubMed Central

Windoffer, Reinhard; Beil, Michael; Magin, Thomas M.

2011-01-01

Epithelia are exposed to multiple forms of stress. Keratin intermediate filaments are abundant in epithelia and form cytoskeletal networks that contribute to cell type–specific functions, such as adhesion, migration, and metabolism. A perpetual keratin filament turnover cycle supports these functions. This multistep process keeps the cytoskeleton in motion, facilitating rapid and protein biosynthesis–independent network remodeling while maintaining an intact network. The current challenge is to unravel the molecular mechanisms underlying the regulation of the keratin cycle in relation to actin and microtubule networks and in the context of epithelial tissue function. PMID:21893596

Cell separation and electrofusion in space

NASA Technical Reports Server (NTRS)

Morrison, D. R.; Hofmann, G. A.

1990-01-01

In microgravity, free-fluid electrophoretic methods for separating living cells and proteins are improved significantly by the absence of gravity-driven phenomena. Cell fusion, culture, and other bioprocessing steps are being investigated to understand the limits of earth-based processing. A multistep space bioprocess is described that includes electrophoretic separation of human target cells, single-cell manipulations using receptor-specific antibodies, electrofusion to produce immortal hybridomas, gentle suspension culture, and monoclonal antibody recovery using continuous-flow electrophoresis or recirculating isoelectric focusing. Improvements in several key steps already have been demonstrated by space experiments, and others will be studied on Space Station Freedom.

The role of exosomes in cancer metastasis.

PubMed

Steinbichler, Teresa Bernadette; Dudás, József; Riechelmann, Herbert; Skvortsova, Ira-Ida

2017-06-01

Exosomes are small membrane vesicles with a size ranging from 40 to 100nm. They can serve as functional mediators in cell interaction leading to cancer metastasis. Metastasis is a complex multistep process of cancer cell invasion, survival in blood vessels, attachment to and colonization of the host organ. Exosomes influence every step of this cascade and can be targeted by oncological treatment. This review highlights the role of exosomes in the various steps of the metastatic cascade and how exosome dependent pathways can be targeted as therapeutic approach or used for liquid biopsies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokinin-auxin crosstalk in cell type specification.

PubMed

Chandler, John William; Werr, Wolfgang

2015-05-01

Auxin and cytokinin affect cell fate specification transcriptionally and non-transcriptionally, and their roles have been characterised in several founder cell specification and activation contexts. Similarly to auxin, local cytokinin synthesis and response gradients are instructive, and the roles of ARABIDOPSIS RESPONSE REGULATOR 7/15 (ARR7/15) and the negative cytokinin response regulator ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN 6, as well as auxin signalling via MONOPTEROS/BODENLOS, are functionally conserved across different developmental processes. Auxin and cytokinin crosstalk is tissue- and context-specific, and may be synergistic in the shoot apical meristem (SAM) but antagonistic in the root. We review recent advances in understanding the interactions between auxin and cytokinin in pivotal developmental processes, and show that feedback complexity and the multistep nature of specification processes argue against a single morphogenetic signal. Copyright © 2015 Elsevier Ltd. All rights reserved.

GPS Satellite Orbit Prediction at User End for Real-Time PPP System.

PubMed

Yang, Hongzhou; Gao, Yang

2017-08-30

This paper proposed the high-precision satellite orbit prediction process at the user end for the real-time precise point positioning (PPP) system. Firstly, the structure of a new real-time PPP system will be briefly introduced in the paper. Then, the generation of satellite initial parameters (IP) at the sever end will be discussed, which includes the satellite position, velocity, and the solar radiation pressure (SRP) parameters for each satellite. After that, the method for orbit prediction at the user end, with dynamic models including the Earth's gravitational force, lunar gravitational force, solar gravitational force, and the SRP, are presented. For numerical integration, both the single-step Runge-Kutta and multi-step Adams-Bashforth-Moulton integrator methods are implemented. Then, the comparison between the predicted orbit and the international global navigation satellite system (GNSS) service (IGS) final products are carried out. The results show that the prediction accuracy can be maintained for several hours, and the average prediction error of the 31 satellites are 0.031, 0.032, and 0.033 m for the radial, along-track and cross-track directions over 12 h, respectively. Finally, the PPP in both static and kinematic modes are carried out to verify the accuracy of the predicted satellite orbit. The average root mean square error (RMSE) for the static PPP of the 32 globally distributed IGS stations are 0.012, 0.015, and 0.021 m for the north, east, and vertical directions, respectively; while the RMSE of the kinematic PPP with the predicted orbit are 0.031, 0.069, and 0.167 m in the north, east and vertical directions, respectively.

GPS Satellite Orbit Prediction at User End for Real-Time PPP System

PubMed Central

Yang, Hongzhou; Gao, Yang

2017-01-01

This paper proposed the high-precision satellite orbit prediction process at the user end for the real-time precise point positioning (PPP) system. Firstly, the structure of a new real-time PPP system will be briefly introduced in the paper. Then, the generation of satellite initial parameters (IP) at the sever end will be discussed, which includes the satellite position, velocity, and the solar radiation pressure (SRP) parameters for each satellite. After that, the method for orbit prediction at the user end, with dynamic models including the Earth’s gravitational force, lunar gravitational force, solar gravitational force, and the SRP, are presented. For numerical integration, both the single-step Runge–Kutta and multi-step Adams–Bashforth–Moulton integrator methods are implemented. Then, the comparison between the predicted orbit and the international global navigation satellite system (GNSS) service (IGS) final products are carried out. The results show that the prediction accuracy can be maintained for several hours, and the average prediction error of the 31 satellites are 0.031, 0.032, and 0.033 m for the radial, along-track and cross-track directions over 12 h, respectively. Finally, the PPP in both static and kinematic modes are carried out to verify the accuracy of the predicted satellite orbit. The average root mean square error (RMSE) for the static PPP of the 32 globally distributed IGS stations are 0.012, 0.015, and 0.021 m for the north, east, and vertical directions, respectively; while the RMSE of the kinematic PPP with the predicted orbit are 0.031, 0.069, and 0.167 m in the north, east and vertical directions, respectively. PMID:28867771

A study of numerical methods of solution of the equations of motion of a controlled satellite under the influence of gravity gradient torque

NASA Technical Reports Server (NTRS)

Thompson, J. F.; Mcwhorter, J. C.; Siddiqi, S. A.; Shanks, S. P.

1973-01-01

Numerical methods of integration of the equations of motion of a controlled satellite under the influence of gravity-gradient torque are considered. The results of computer experimentation using a number of Runge-Kutta, multi-step, and extrapolation methods for the numerical integration of this differential system are presented, and particularly efficient methods are noted. A large bibliography of numerical methods for initial value problems for ordinary differential equations is presented, and a compilation of Runge-Kutta and multistep formulas is given. Less common numerical integration techniques from the literature are noted for further consideration.

Model of multistep electron transfer in a single-mode polar medium

NASA Astrophysics Data System (ADS)

Feskov, S. V.; Yudanov, V. V.

2017-09-01

A mathematical model of multistep photoinduced electron transfer (PET) in a polar medium with a single relaxation time (Debye solvent) is developed. The model includes the polarization nonequilibrity formed in the vicinity of the donor-acceptor molecular system at the initial steps of photoreaction and its influence on the subsequent steps of PET. It is established that the results from numerical simulation of transient luminescence spectra of photoexcited donor-acceptor complexes (DAC) conform to calculated data obtained on the basis of the familiar experimental technique used to measure the relaxation function of solvent polarization in the vicinity of DAC in the picosecond and subpicosecond ranges.

Inverse solutions for electrical impedance tomography based on conjugate gradients methods

NASA Astrophysics Data System (ADS)

Wang, M.

2002-01-01

A multistep inverse solution for two-dimensional electric field distribution is developed to deal with the nonlinear inverse problem of electric field distribution in relation to its boundary condition and the problem of divergence due to errors introduced by the ill-conditioned sensitivity matrix and the noise produced by electrode modelling and instruments. This solution is based on a normalized linear approximation method where the change in mutual impedance is derived from the sensitivity theorem and a method of error vector decomposition. This paper presents an algebraic solution of the linear equations at each inverse step, using a generalized conjugate gradients method. Limiting the number of iterations in the generalized conjugate gradients method controls the artificial errors introduced by the assumption of linearity and the ill-conditioned sensitivity matrix. The solution of the nonlinear problem is approached using a multistep inversion. This paper also reviews the mathematical and physical definitions of the sensitivity back-projection algorithm based on the sensitivity theorem. Simulations and discussion based on the multistep algorithm, the sensitivity coefficient back-projection method and the Newton-Raphson method are given. Examples of imaging gas-liquid mixing and a human hand in brine are presented.

Influence of multi-step washing using Na2EDTA, oxalic acid and phosphoric acid on metal fractionation and spectroscopy characteristics from contaminated soil.

PubMed

Wei, Meng; Chen, Jiajun

2016-11-01

A multi-step soil washing test using a typical chelating agent (Na 2 EDTA), organic acid (oxalic acid), and inorganic weak acid (phosphoric acid) was conducted to remediate soil contaminated with heavy metals near an arsenic mining area. The aim of the test was to improve the heavy metal removal efficiency and investigate its influence on metal fractionation and the spectroscopy characteristics of contaminated soil. The results indicated that the orders of the multi-step washing were critical for the removal efficiencies of the metal fractions, bioavailability, and potential mobility due to the different dissolution levels of mineral fractions and the inter-transformation of metal fractions by XRD and FT-IR spectral analyses. The optimal soil washing options were identified as the Na 2 EDTA-phosphoric-oxalic acid (EPO) and phosphoric-oxalic acid-Na 2 EDTA (POE) sequences because of their high removal efficiencies (approximately 45 % for arsenic and 88 % for cadmium) and the minimal harmful effects that were determined by the mobility and bioavailability of the remaining heavy metals based on the metal stability (I R ) and modified redistribution index ([Formula: see text]).

On the Development of Multi-Step Inverse FEM with Shell Model

NASA Astrophysics Data System (ADS)

Huang, Y.; Du, R.

2005-08-01

The inverse or one-step finite element approach is increasingly used in the sheet metal stamping industry to predict strain distribution and the initial blank shape in the preliminary design stage. Based on the existing theory, there are two types of method: one is based on the principle of virtual work and the other is based on the principle of extreme work. Much research has been conducted to improve the accuracy of simulation results. For example, based on the virtual work principle, Batoz et al. developed a new method using triangular DKT shell elements. In this new method, the bending and unbending effects are considered. Based on the principle of extreme work, Majlessi and et al. proposed the multi-step inverse approach with membrane elements and applied it to an axis-symmetric part. Lee and et al. presented an axis-symmetric shell element model to solve the similar problem. In this paper, a new multi-step inverse method is introduced with no limitation on the workpiece shape. It is a shell element model based on the virtual work principle. The new method is validated by means of comparing to the commercial software system (PAMSTAMP®). The comparison results indicate that the accuracy is good.

Powerful Voter Selection for Making Multistep Delegate Ballot Fair

NASA Astrophysics Data System (ADS)

Yamakawa, Hiroshi

For decision by majority, each voter often exercises his right by delegating to trustable other voters. Multi-step delegates rule allows indirect delegating through more than one voter, and this helps each voter finding his delegate voters. In this paper, we propose powerful voter selection method depending on the multi-step delegate rule. This method sequentially selects voters who is most delegated indirectly. Multi-agent simulation demonstrate that we can achieve highly fair poll results from small number of vote by using proposed method. Here, fairness is prediction accuracy to sum of all voters preferences for choices. In simulation, each voter selects choices arranged on one dimensional preference axis for voting. Acquaintance relationships among voters were generated as a random network, and each voter delegates some of his acquaintances who has similar preferences. We obtained simulation results from various acquaintance networks, and then averaged these results. Firstly, if each voter has enough acquaintances in average, proposed method can help predicting sum of all voters' preferences of choices from small number of vote. Secondly, if the number of each voter's acquaintances increases corresponding to an increase in the number of voters, prediction accuracy (fairness) from small number of vote can be kept in appropriate level.

Hydrogenation of fluoroarenes: Direct access to all-cis-(multi)fluorinated cycloalkanes.

PubMed

Wiesenfeldt, Mario P; Nairoukh, Zackaria; Li, Wei; Glorius, Frank

2017-09-01

All-c is -multifluorinated cycloalkanes exhibit intriguing electronic properties. In particular, they display extremely high dipole moments perpendicular to the aliphatic ring, making them highly desired motifs in material science. Very few such motifs have been prepared, as their syntheses require multistep sequences from diastereoselectively prefunctionalized precursors. Herein we report a synthetic strategy to access these valuable materials via the rhodium-cyclic (alkyl)(amino)carbene (CAAC)-catalyzed hydrogenation of readily available fluorinated arenes in hexane. This route enables the scalable single-step preparation of an abundance of multisubstituted and multifluorinated cycloalkanes, including all- cis -1,2,3,4,5,6-hexafluorocyclohexane as well as cis-configured fluorinated aliphatic heterocycles. Copyright © 2017, American Association for the Advancement of Science.

Multi-step production of a diphoton resonance

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

Dobrescu, Bogdan A.; Fox, Patrick J.; Kearney, John

2017-04-24

Assuming that the mass peak at 750 GeV reported by the ATLAS and CMS Collaborations is due to a spin-0 particle that decays into two photons, we present two weakly-coupled renormalizable models that lead to different production mechanisms. In one model, a scalar particle produced through gluon fusion decays into the diphoton particle and a light, long-lived pseudoscalar. In another model, a $Z'$ boson produced from the annihilation of a strange-antistrange quark pair undergoes a cascade decay that leads to the diphoton particle and two sterile neutrinos. We show that various kinematic distributions may differentiate these models from the canonicalmore » model where the diphoton particle is directly produced in gluon fusion.« less

NCC-RANSAC: a fast plane extraction method for 3-D range data segmentation.

PubMed

Qian, Xiangfei; Ye, Cang

2014-12-01

This paper presents a new plane extraction (PE) method based on the random sample consensus (RANSAC) approach. The generic RANSAC-based PE algorithm may over-extract a plane, and it may fail in case of a multistep scene where the RANSAC procedure results in multiple inlier patches that form a slant plane straddling the steps. The CC-RANSAC PE algorithm successfully overcomes the latter limitation if the inlier patches are separate. However, it fails if the inlier patches are connected. A typical scenario is a stairway with a stair wall where the RANSAC plane-fitting procedure results in inliers patches in the tread, riser, and stair wall planes. They connect together and form a plane. The proposed method, called normal-coherence CC-RANSAC (NCC-RANSAC), performs a normal coherence check to all data points of the inlier patches and removes the data points whose normal directions are contradictory to that of the fitted plane. This process results in separate inlier patches, each of which is treated as a candidate plane. A recursive plane clustering process is then executed to grow each of the candidate planes until all planes are extracted in their entireties. The RANSAC plane-fitting and the recursive plane clustering processes are repeated until no more planes are found. A probabilistic model is introduced to predict the success probability of the NCC-RANSAC algorithm and validated with real data of a 3-D time-of-flight camera-SwissRanger SR4000. Experimental results demonstrate that the proposed method extracts more accurate planes with less computational time than the existing RANSAC-based methods.

NCC-RANSAC: A Fast Plane Extraction Method for 3-D Range Data Segmentation

PubMed Central

Qian, Xiangfei; Ye, Cang

2015-01-01

This paper presents a new plane extraction (PE) method based on the random sample consensus (RANSAC) approach. The generic RANSAC-based PE algorithm may over-extract a plane, and it may fail in case of a multistep scene where the RANSAC procedure results in multiple inlier patches that form a slant plane straddling the steps. The CC-RANSAC PE algorithm successfully overcomes the latter limitation if the inlier patches are separate. However, it fails if the inlier patches are connected. A typical scenario is a stairway with a stair wall where the RANSAC plane-fitting procedure results in inliers patches in the tread, riser, and stair wall planes. They connect together and form a plane. The proposed method, called normal-coherence CC-RANSAC (NCC-RANSAC), performs a normal coherence check to all data points of the inlier patches and removes the data points whose normal directions are contradictory to that of the fitted plane. This process results in separate inlier patches, each of which is treated as a candidate plane. A recursive plane clustering process is then executed to grow each of the candidate planes until all planes are extracted in their entireties. The RANSAC plane-fitting and the recursive plane clustering processes are repeated until no more planes are found. A probabilistic model is introduced to predict the success probability of the NCC-RANSAC algorithm and validated with real data of a 3-D time-of-flight camera–SwissRanger SR4000. Experimental results demonstrate that the proposed method extracts more accurate planes with less computational time than the existing RANSAC-based methods. PMID:24771605

Clinical Assessment of Risk Management: an INtegrated Approach (CARMINA).

PubMed

Tricarico, Pierfrancesco; Tardivo, Stefano; Sotgiu, Giovanni; Moretti, Francesca; Poletti, Piera; Fiore, Alberto; Monturano, Massimo; Mura, Ida; Privitera, Gaetano; Brusaferro, Silvio

2016-08-08

Purpose - The European Union recommendations for patient safety calls for shared clinical risk management (CRM) safety standards able to guide organizations in CRM implementation. The purpose of this paper is to develop a self-evaluation tool to measure healthcare organization performance on CRM and guide improvements over time. Design/methodology/approach - A multi-step approach was implemented including: a systematic literature review; consensus meetings with an expert panel from eight Italian leader organizations to get to an agreement on the first version; field testing to test instrument feasibility and flexibility; Delphi strategy with a second expert panel for content validation and balanced scoring system development. Findings - The self-assessment tool - Clinical Assessment of Risk Management: an INtegrated Approach includes seven areas (governance, communication, knowledge and skills, safe environment, care processes, adverse event management, learning from experience) and 52 standards. Each standard is evaluated according to four performance levels: minimum; monitoring; outcomes; and improvement actions, which resulted in a feasible, flexible and valid instrument to be used throughout different organizations. Practical implications - This tool allows practitioners to assess their CRM activities compared to minimum levels, monitor performance, benchmarking with other institutions and spreading results to different stakeholders. Originality/value - The multi-step approach allowed us to identify core minimum CRM levels in a field where no consensus has been reached. Most standards may be easily adopted in other countries.

Innovating Big Data Computing Geoprocessing for Analysis of Engineered-Natural Systems

NASA Astrophysics Data System (ADS)

Rose, K.; Baker, V.; Bauer, J. R.; Vasylkivska, V.

2016-12-01

Big data computing and analytical techniques offer opportunities to improve predictions about subsurface systems while quantifying and characterizing associated uncertainties from these analyses. Spatial analysis, big data and otherwise, of subsurface natural and engineered systems are based on variable resolution, discontinuous, and often point-driven data to represent continuous phenomena. We will present examples from two spatio-temporal methods that have been adapted for use with big datasets and big data geo-processing capabilities. The first approach uses regional earthquake data to evaluate spatio-temporal trends associated with natural and induced seismicity. The second algorithm, the Variable Grid Method (VGM), is a flexible approach that presents spatial trends and patterns, such as those resulting from interpolation methods, while simultaneously visualizing and quantifying uncertainty in the underlying spatial datasets. In this presentation we will show how we are utilizing Hadoop to store and perform spatial analyses to efficiently consume and utilize large geospatial data in these custom analytical algorithms through the development of custom Spark and MapReduce applications that incorporate ESRI Hadoop libraries. The team will present custom `Big Data' geospatial applications that run on the Hadoop cluster and integrate with ESRI ArcMap with the team's probabilistic VGM approach. The VGM-Hadoop tool has been specially built as a multi-step MapReduce application running on the Hadoop cluster for the purpose of data reduction. This reduction is accomplished by generating multi-resolution, non-overlapping, attributed topology that is then further processed using ESRI's geostatistical analyst to convey a probabilistic model of a chosen study region. Finally, we will share our approach for implementation of data reduction and topology generation via custom multi-step Hadoop applications, performance benchmarking comparisons, and Hadoop-centric opportunities for greater parallelization of geospatial operations.

Xerostomia Quality of Life Scale (XeQoLS) questionnaire: validation of Italian version in head and neck cancer patients.

PubMed

Lastrucci, Luciana; Bertocci, Silvia; Bini, Vittorio; Borghesi, Simona; De Majo, Roberta; Rampini, Andrea; Gennari, Pietro Giovanni; Pernici, Paola

2018-01-01

To translate the Xerostomia Quality-of-Life Scale (XeQoLS) into Italian language (XeQoLS-IT). Xerostomia is the most relevant acute and late toxicity in patients with head and neck cancer treated with radiotherapy (RT). Patient-reported outcome (PRO) instruments are subjective report on patient perception of health status. The XeQoLS consists of 15 items and measures the impact of salivary gland dysfunction and xerostomia on the four major domains of oral health-related QoL. The XeQoLS-IT was created through a linguistic validation multi-step process: forward translation (TF), backward translation (TB) and administration of the questionnaire to 35 Italian patients with head and neck cancer. Translation was independently carried out by two radiation oncologists who were Italian native speakers. The two versions were compared and adapted to obtain a reconciled version, version 1 (V1). V1 was translated back into English by an Italian pro skilled in teaching English. After review of discrepancies and choice of the most appropriate wording for clarity and similarity to the original, version 2 (V2) was reached by consensus. To evaluate version 2, patients completed the XeQoLS-IT questionnaire and also underwent a cognitive debriefing. The questionnaire was considered simple by the patients. The clarity of the instructions and the easiness to answer questions had a mean value of 4.5 (± 0.71) on a scale from 1 to 5. A valid multi-step process led to the creation of the final version of the XeQoLS-IT, a suitable instrument for the perception of xerostomia in patients treated with RT.

Exciton-exciton annihilation in a disordered molecular system by direct and multistep Förster transfer

NASA Astrophysics Data System (ADS)

Fennel, Franziska; Lochbrunner, Stefan

2015-10-01

Exciton annihilation dynamics in a disordered organic model system is investigated by ultrafast absorption spectroscopy. We show that the temporal evolution of the exciton density can be quantitatively understood by applying Förster energy transfer theory to describe the diffusion of the excitons as well as the annihilation step itself. To this end, previous formulations of Förster theory are extended to account for the inhomogeneous distribution of the S0-S1 transition energies resulting in an effective exciton diffusion constant. Two annihilation pathways are considered, the direct transfer of an exciton between two excited molecules and diffusive motion by multiple transfer steps towards a second exciton preceding the annihilation event. One pathway can be emphasized with respect to the other by tuning the exciton diffusion constant via the chromophore concentration. The investigated system allows one to extract all relevant parameters for the description and provides in this way a proof that the annihilation dynamics can be entirely understood and modeled by Förster energy transfer.

Direct evidence of octupole deformation in neutron-rich 144Ba

DOE PAGES

Bucher, B.; Zhu, S.; Wu, C. Y.; ...

2016-03-17

Here, the neutron-rich nucleus 144Ba (t 1/2 = 11.5 s) is expected to exhibit some of the strongest octupole correlations among nuclei with mass numbers A less than 200. Until now, indirect evidence for such strong correlations has been inferred from observations such as enhanced E1 transitions and interleaving positive- and negative-parity levels in the ground-state band. In this experiment, the octupole strength was measured directly by sub-barrier, multistep Coulomb excitation of a post-accelerated 650-MeV 144Ba beam on a 1.0–mg/cm 2 208Pb target. The measured value of the matrix element, < 3 1–∥M(E3)∥0 1 + >= 0.65( +17 –23) ebmore » 3/2, corresponds to a reduced B(E3) transition probability of 48( +25 –34) W.u. This result represents an unambiguous determination of the octupole collectivity, is larger than any available theoretical prediction, and is consistent with octupole deformation.« less

A new paper-based platform technology for point-of-care diagnostics.

PubMed

Gerbers, Roman; Foellscher, Wilke; Chen, Hong; Anagnostopoulos, Constantine; Faghri, Mohammad

2014-10-21

Currently, the Lateral flow Immunoassays (LFIAs) are not able to perform complex multi-step immunodetection tests because of their inability to introduce multiple reagents in a controlled manner to the detection area autonomously. In this research, a point-of-care (POC) paper-based lateral flow immunosensor was developed incorporating a novel microfluidic valve technology. Layers of paper and tape were used to create a three-dimensional structure to form the fluidic network. Unlike the existing LFIAs, multiple directional valves are embedded in the test strip layers to control the order and the timing of mixing for the sample and multiple reagents. In this paper, we report a four-valve device which autonomously directs three different fluids to flow sequentially over the detection area. As proof of concept, a three-step alkaline phosphatase based Enzyme-Linked ImmunoSorbent Assay (ELISA) protocol with Rabbit IgG as the model analyte was conducted to prove the suitability of the device for immunoassays. The detection limit of about 4.8 fm was obtained.

Bartonella henselae engages inside-out and outside-in signaling by integrin β1 and talin1 during invasome-mediated bacterial uptake.

PubMed

Truttmann, Matthias C; Misselwitz, Benjamin; Huser, Sonja; Hardt, Wolf-Dietrich; Critchley, David R; Dehio, Christoph

2011-11-01

The VirB/D4 type IV secretion system (T4SS) of the bacterial pathogen Bartonella henselae (Bhe) translocates seven effector proteins (BepA-BepG) into human cells that subvert host cellular functions. Two redundant pathways dependent on BepG or the combination of BepC and BepF trigger the formation of a bacterial uptake structure termed the invasome. Invasome formation is a multi-step process consisting of bacterial adherence, effector translocation, aggregation of bacteria on the cell surface and engulfment, and eventually, complete internalization of the bacterial aggregate occurs in an F-actin-dependent manner. In the present study, we show that Bhe-triggered invasome formation depends on integrin-β1-mediated signaling cascades that enable assembly of the F-actin invasome structure. We demonstrate that Bhe interacts with integrin β1 in a fibronectin- and VirB/D4 T4SS-independent manner and that activated integrin β1 is essential for both effector translocation and the actin rearrangements leading to invasome formation. Furthermore, we show that talin1, but not talin2, is required for inside-out activation of integrin β1 during invasome formation. Finally, integrin-β1-mediated outside-in signaling by FAK, Src, paxillin and vinculin is necessary for invasome formation. This is the first example of a bacterial entry process that fully exploits the bi-directional signaling capacity of integrin receptors in a talin1-specific manner.

Final technical report for the Center for Catalytic Hydrocarbon Functionalization (an EFRC)

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

Gunnoe, Thomas Brent

Greater than 95% of all materials produced by the chemical industry are derived from a small slate of simple hydrocarbons that are derived primarily from natural gas and petroleum, predominantly through oxygenation, C–C bond formation, halogenation or amination. Yet, current technologies for hydrocarbon conversion are typically high temperature, multi-step processes that are energy and capital intensive and result in excessive emissions (including carbon dioxide). The Center for Catalytic Hydrocarbon Functionalization (CCHF) brought together research teams with the broad coalition of skills and knowledge needed to make the fundamental advances in catalysis required for next-generation technologies to convert hydrocarbons (particularly lightmore » alkanes and methane) at high efficiency and low cost. Our new catalyst technologies offer many opportunities including enhanced utilization of natural gas in the transportation sector (via conversion to liquid fuels), more efficient generation of electricity from natural gas using direct methane fuel cells, reduced energy consumption and waste production for large petrochemical processes, and the preparation of high value molecules for use in biological/medical applications or the agricultural sector. The five year collaborative project accelerated fundamental understanding of catalyst design for the conversion of C–H bonds to functionalized products, essential to achieve the goals listed above, as evidenced by the publication of 134 manuscripts. Many of these fundamental advancements provide a foundation for potential commercialization, as evidenced by the submission of 11 patents from research support by the CCHF.« less

General Method for the Synthesis of Hollow Mesoporous Carbon Spheres with Tunable Textural Properties.

PubMed

Mezzavilla, Stefano; Baldizzone, Claudio; Mayrhofer, Karl J J; Schüth, Ferdi

2015-06-17

A versatile synthetic procedure to prepare hollow mesoporous carbon spheres (HMCS) is presented here. This approach is based on the deposition of a homogeneous hybrid polymer/silica composite shell on the outer surface of silica spheres through the surfactant-assisted simultaneous polycondensation of silica and polymer precursors in a colloidal suspension. Such composite materials can be further processed to give hollow mesoporous carbon spheres. The flexibility of this method allows for independent control of the morphological (i.e., core diameter and shell thickness) and textural features of the carbon spheres. In particular, it is demonstrated that the size of the pores within the mesoporous shell can be precisely tailored over an extended range (2-20 nm) by simply adjusting the reaction conditions. In a similar fashion, also the specific carbon surface area as well as the total shell porosity can be tuned. Most importantly, the textural features can be adjusted without affecting the dimension or the morphology of the spheres. The possibility to directly modify the shell textural properties by varying the synthetic parameters in a scalable process represents a distinct asset over the multistep hard-templating (nanocasting) routes. As an exemplary application, Pt nanoparticles were encapsulated in the mesoporous shell of HMCS. The resulting Pt@HMCS catalyst showed an enhanced stability during the oxygen reduction reaction, one of the most important reactions in electrocatalysis. This new synthetic procedure could allow the expansion, perhaps even beyond the lab-scale, of advanced carbon nanostructured supports for applications in catalysis.

Modeling the MHC class I pathway by combining predictions of proteasomal cleavage, TAP transport and MHC class I binding.

PubMed

Tenzer, S; Peters, B; Bulik, S; Schoor, O; Lemmel, C; Schatz, M M; Kloetzel, P-M; Rammensee, H-G; Schild, H; Holzhütter, H-G

2005-05-01

Epitopes presented by major histocompatibility complex (MHC) class I molecules are selected by a multi-step process. Here we present the first computational prediction of this process based on in vitro experiments characterizing proteasomal cleavage, transport by the transporter associated with antigen processing (TAP) and MHC class I binding. Our novel prediction method for proteasomal cleavages outperforms existing methods when tested on in vitro cleavage data. The analysis of our predictions for a new dataset consisting of 390 endogenously processed MHC class I ligands from cells with known proteasome composition shows that the immunological advantage of switching from constitutive to immunoproteasomes is mainly to suppress the creation of peptides in the cytosol that TAP cannot transport. Furthermore, we show that proteasomes are unlikely to generate MHC class I ligands with a C-terminal lysine residue, suggesting processing of these ligands by a different protease that may be tripeptidyl-peptidase II (TPPII).

Dynamics of scene representations in the human brain revealed by magnetoencephalography and deep neural networks

PubMed Central

Cichy, Radoslaw Martin; Khosla, Aditya; Pantazis, Dimitrios; Oliva, Aude

2017-01-01

Human scene recognition is a rapid multistep process evolving over time from single scene image to spatial layout processing. We used multivariate pattern analyses on magnetoencephalography (MEG) data to unravel the time course of this cortical process. Following an early signal for lower-level visual analysis of single scenes at ~100 ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250 ms indexing neural representations robust to changes in unrelated scene properties and viewing conditions. For a quantitative model of how scene size representations may arise in the brain, we compared MEG data to a deep neural network model trained on scene classification. Representations of scene size emerged intrinsically in the model, and resolved emerging neural scene size representation. Together our data provide a first description of an electrophysiological signal for layout processing in humans, and suggest that deep neural networks are a promising framework to investigate how spatial layout representations emerge in the human brain. PMID:27039703

Highly efficient conversion of terpenoid biomass to jet-fuel range cycloalkanes in a biphasic tandem catalytic process

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

Yang, Xiaokun; Li, Teng; Tang, Kan

2017-06-12

The demand for bio-jet fuels to reduce carbon emissions is increasing substantially in the aviation sector, while the scarcity of high-density jet fuel components limits the use of bio-jet fuels in high-performance aircrafts compared with conventional jet fuels. In this paper, we report a novel biphasic tandem catalytic process (biTCP) for synthesizing cycloalkanes from renewable terpenoid biomass, such as 1,8-cineole. Multistep tandem reactions, including C–O ring opening by hydrolysis, dehydration, and hydrogenation, were carried out in the “one-pot” biTCP. 1,8-Cineole was efficiently converted to p-menthane at high yields (>99%) in the biTCP under mild reaction conditions. Finally, the catalytic reactionmore » mechanism is discussed.« less

Adenoma–carcinoma sequence in intrahepatic cholangiocarcinoma

PubMed Central

Pinho, André Costa; Melo, Renato Bessa; Oliveira, Manuel; Almeida, Marinho; Lopes, Joanne; Graça, Luís; Costa-Maia, J.

2012-01-01

Introduction Cholangiocarcinoma is a rare tumor but recent data report a worldwide increase in incidence and mortality. There are several risk factors associated with cholangiocarcinoma, and chronic inflammation of billiary tree seems to be implied in the cholangiocarcinogenesis, but little is known about this process. Presentation of case We present a 56-year-old female with a bile duct adenoma incidentally discovered in the follow up of breast cancer that 18 months later progress to intrahepatic cholangiocarcinoma. Discussion This is a rare presentation of intrahepatic cholangiocarcinoma that suggests the classic adenoma-carcinoma sequence in cholangiocarcinogenesis. Furthermore this case gives rise to some questions about the possible common ground on intrahepatic cholangiocarcinoma and breast cancer. Conclusion Cholangiocarcinogenesis is a complex multi-step mechanism and further investigations are needed to fully understand this process. PMID:22326450

Mechanisms of autophagy and relevant small-molecule compounds for targeted cancer therapy.

PubMed

Zhang, Jin; Wang, Guan; Zhou, Yuxin; Chen, Yi; Ouyang, Liang; Liu, Bo

2018-05-01

Autophagy is an evolutionarily conserved, multi-step lysosomal degradation process for the clearance of damaged or superfluous proteins and organelles. Accumulating studies have recently revealed that autophagy is closely related to a variety of types of cancer; however, elucidation of its Janus role of either tumor-suppressive or tumor-promoting still remains to be discovered. In this review, we focus on summarizing the context-dependent role of autophagy and its complicated molecular mechanisms in different types of cancer. Moreover, we discuss a series of small-molecule compounds targeting autophagy-related proteins or the autophagic process for potential cancer therapy. Taken together, these findings would shed new light on exploiting the intricate mechanisms of autophagy and relevant small-molecule compounds as potential anti-cancer drugs to improve targeted cancer therapy.

Centrality and collision system dependence of antiproton production from p+A to Au+Au collisions at AGS energies

NASA Technical Reports Server (NTRS)

Sako, H.; Ahle, L.; Akiba, Y.; Ashktorab, K.; Baker, M. D.; Beavis, D.; Britt, H. C.; Chang, J.; Chasman, C.; Chen, Z.;

Optical Probe of the Density of Defect States in Organic Thin-Film Transistors

NASA Astrophysics Data System (ADS)

Breban, Mihaela; Romero, Danilo; Ballarotto, Vincent; Williams, Ellen

2006-03-01

We investigate the role of defect states associated with different gate dielectric materials on charge transport in organic thin film transistors. Using a modulation technique we measure the magnitude and the phase of the photocurrent^1 in pentacene thin film transistors as a function of the modulation frequency. The photocurrent generation process is modeled as exciton dissociation due to interaction with localized traps. A time domain analyses of this multi-step process allows us to extract the density of defect states. We use this technique to compare the physical mechanism underlying performances of pentacene devices fabricated with different dielectric materials. *Supported by the Laboratory for Physical Science ^1 M. Breban, et al. ``Photocurrent probe of field-dependent mobility in organic thin-film transistors'' Appl. Phys. Letts. 87, 203503 (2005)

High-throughput protein concentration and buffer exchange: comparison of ultrafiltration and ammonium sulfate precipitation.

PubMed

Moore, Priscilla A; Kery, Vladimir

2009-01-01

High-throughput protein purification is a complex, multi-step process. There are several technical challenges in the course of this process that are not experienced when purifying a single protein. Among the most challenging are the high-throughput protein concentration and buffer exchange, which are not only labor-intensive but can also result in significant losses of purified proteins. We describe two methods of high-throughput protein concentration and buffer exchange: one using ammonium sulfate precipitation and one using micro-concentrating devices based on membrane ultrafiltration. We evaluated the efficiency of both methods on a set of 18 randomly selected purified proteins from Shewanella oneidensis. While both methods provide similar yield and efficiency, the ammonium sulfate precipitation is much less labor intensive and time consuming than the ultrafiltration.

Low-loss ultracompact optical power splitter using a multistep structure.

PubMed

Huang, Zhe; Chan, Hau Ping; Afsar Uddin, Mohammad

2010-04-01

We propose a low-loss ultracompact optical power splitter for broadband passive optical network applications. The design is based on a multistep structure involving a two-material (core/cladding) system. The performance of the proposed device was evaluated through the three-dimensional finite-difference beam propagation method. By using the proposed design, an excess loss of 0.4 dB was achieved at a full branching angle of 24 degrees. The wavelength-dependent loss was found to be less than 0.3 dB, and the polarization-dependent loss was less than 0.05 dB from O to L bands. The device offers the potential of being mass-produced using low-cost polymer-based embossing techniques.

Measuring hospital care from the patients' perspective: an overview of the CAHPS Hospital Survey development process.

PubMed

Goldstein, Elizabeth; Farquhar, Marybeth; Crofton, Christine; Darby, Charles; Garfinkel, Steven

2005-12-01

To describe the developmental process for the CAHPS Hospital Survey. A pilot was conducted in three states with 19,720 hospital discharges. A rigorous, multi-step process was used to develop the CAHPS Hospital Survey. It included a public call for measures, multiple Federal Register notices soliciting public input, a review of the relevant literature, meetings with hospitals, consumers and survey vendors, cognitive interviews with consumer, a large-scale pilot test in three states and consumer testing and numerous small-scale field tests. The current version of the CAHPS Hospital Survey has survey items in seven domains, two overall ratings of the hospital and five items used for adjusting for the mix of patients across hospitals and for analytical purposes. The CAHPS Hospital Survey is a core set of questions that can be administered as a stand-alone questionnaire or combined with a broader set of hospital specific items.

Fine structuration of low-temperature co-fired ceramic (LTCC) microreactors.

PubMed

Jiang, Bo; Haber, Julien; Renken, Albert; Muralt, Paul; Kiwi-Minsker, Lioubov; Maeder, Thomas

2015-01-21

The development of microreactors that operate under harsh conditions is always of great interest for many applications. Here we present a microfabrication process based on low-temperature co-fired ceramic (LTCC) technology for producing microreactors which are able to perform chemical processes at elevated temperature (>400 °C) and against concentrated harsh chemicals such as sodium hydroxide, sulfuric acid and hydrochloric acid. Various micro-scale cavities and/or fluidic channels were successfully fabricated in these microreactors using a set of combined and optimized LTCC manufacturing processes. Among them, it has been found that laser micromachining and multi-step low-pressure lamination are particularly critical to the fabrication and quality of these microreactors. Demonstration of LTCC microreactors with various embedded fluidic structures is illustrated with a number of examples, including micro-mixers for studies of exothermic reactions, multiple-injection microreactors for ionone production, and high-temperature microreactors for portable hydrogen generation.

Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1.

PubMed

Ruthenborg, Robin J; Ban, Jae-Jun; Wazir, Anum; Takeda, Norihiko; Kim, Jung-Whan

2014-09-01

Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

Mechanisms for Ductile Rupture - FY16 ESC Progress Report

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

Boyce, Brad L.; Carroll, Jay D.; Noell, Phillip

2017-01-01

Ductile rupture in metals is generally a multi-step process of void nucleation, growth, and coalescence. Particle decohesion and particle fracture are generally invoked as the primary microstructural mechanisms for room-temperature void nucleation. However, because high-purity materials also fail by void nucleation and coalescence, other microstructural features must also act as sites for void nucleation. Early studies of void initiation in high-purity materials, which included post-mortem fracture surface characterization using scanning electron microscopy (SEM) and high-voltage electron microscopy (HVEM) and in-situ HVEM observations of fracture, established the presence of dislocation cell walls as void initiation sites in high-purity materials. Direct experimentalmore » evidence for this contention was obtained during in-situ HVEM tensile tests of Be single crystals. Voids between 0.2 and 1 μm long appeared suddenly along dislocation cell walls during tensile straining. However, subsequent attempts to replicate these results in other materials, particularly α -Fe single crystals, were unsuccessful because of the small size of the dislocation cells, and these remain the only published in-situ HVEM observations of void nucleation at dislocation cell walls in the absence of a growing macrocrack. Despite this challenge, other approaches to studying void nucleation in high-purity metals also indicate that dislocation cell walls are nucleation sites for voids.« less

Microfluidic channel-based wireless charging and communication platform for microsensors with miniaturized onboard antenna

NASA Astrophysics Data System (ADS)

Duan, G.; Zhao, X.; Seren, H. R.; Chen, C.; Li, A.; Zhang, X.

2016-12-01

A double layer spiral antenna with side length of 380 μm was fabricated by a multi-step electroplating process, and integrated with a commercialized passive RFID chip to realize the RF power harvesting and communication functions of a microsensor. To power up and communicate with the microchips, a single layer spiral reader antenna was fabricated on top of a glass substrate with side length of 1 mm. The microchips and the reader antenna were both optimized at the frequency of 915 MHz. Due to the small size of the reader antenna, the strength of the magnetic field decreased dramatically along the axial direction of the reader antenna, which limited the working distance to within 1 mm. To enclose the microchips within the reading range, a three-layer microfluidic channel was designed and fabricated. The channel and cover layers were fabricated by laser cutting of acrylic sheets, and bonded with the glass substrate to form the channel. To operate multiple microchips simultaneously, separation and focusing function units were also designed. Low loss pump oil was used to transport the microchips flowing inside the channel. Within the reading area, the microchips were powered up, and their ID information was retrieved and displayed on the computer interface successfully.

Cucurbitacin B purified from Ecballium elaterium (L.) A. Rich from Tunisia inhibits α5β1 integrin-mediated adhesion, migration, proliferation of human glioblastoma cell line and angiogenesis.

PubMed

Touihri-Barakati, Imen; Kallech-Ziri, Olfa; Ayadi, Wiem; Kovacic, Hervé; Hanchi, Belgacem; Hosni, Karim; Luis, José

2017-02-15

Integrins are essential protagonists in the complex multistep process of cancer progression and are thus attractive targets for the development of anticancer agents. Cucurbitacin B, a triterpenoid purified from the leaves of Tunisian Ecballium elaterium exhibited an anticancer effect and displayed anti-integrin activity on human glioblastoma U87 cells, without being cytotoxic at concentrations up to 500nM. Here we show that cucurbitacin B affected the adhesion and migration of U87 cells to fibronectin in a dose-dependent manner with IC50 values of 86.2nM and 84.6nM, respectively. Time-lapse videomicroscopy showed that cucurbitacin B significantly reduced U87 cells motility and affected directional persistence. Cucurbitacin B also inhibited proliferation with IC50 value of 70.1nM using Crystal Violet assay. Moreover, cucurbitacin B efficiently inhibited in vitro human microvascular endothelial cells (HMEC) angiogenesis with concentration up to 10nM. Interestingly, we demonstrate for the first time that this effect was specifically mediated by α5β1 integrins. These findings reveal a novel mechanism of action for cucurbitacin B, which displays a potential interest as a specific anti-integrin drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of Helicobacter pylori infection in gastric carcinogenesis: Current knowledge and future directions

PubMed Central

Sokic-Milutinovic, Aleksandra; Alempijevic, Tamara; Milosavljevic, Tomica

2015-01-01

Helicobacter pylori (H. pylori) plays a role in the pathogenesis of gastric cancer. The outcome of the infection depends on environmental factors and bacterial and host characteristics. Gastric carcinogenesis is a multistep process that is reversible in the early phase of mucosal damage, but the exact point of no return has not been identified. Therefore, two main therapeutic strategies could reduce gastric cancer incidence: (1) eradication of the already present infection; and (2) immunization (prior to or during the course of the infection). The success of a gastric cancer prevention strategy depends on timing because the prevention strategy must be introduced before the point of no return in gastric carcinogenesis. Although the exact point of no return has not been identified, infection should be eradicated before severe atrophy of the gastric mucosa develops. Eradication therapy rates remain suboptimal due to increasing H. pylori resistance to antibiotics and patient noncompliance. Vaccination against H. pylori would reduce the cost of eradication therapies and lower gastric cancer incidence. A vaccine against H. pylori is still a research challenge. An effective vaccine should have an adequate route of delivery, appropriate bacterial antigens and effective and safe adjuvants. Future research should focus on the development of rescue eradication therapy protocols until an efficacious vaccine against the bacterium becomes available. PMID:26556993

Morphogenesis of the fibrous sheath in the marsupial spermatozoon

PubMed Central

Ricci, M; Breed, WG

2005-01-01

The spermatozoon fibrous sheath contains longitudinal columns and circumferential ribs. It surrounds the axoneme of the principal piece of the mammalian sperm tail, and may be important in sperm stability and motility. Here we describe its assembly during spermiogenesis in a marsupial, the brush-tail possum, and compare its structural organization with that of eutherian mammals, birds and reptiles. Transmission electron microscopy showed that possum fibrous sheath assembly is a multistep process extending in a distal-to-proximal direction along the axoneme from steps 4 to 14 of spermiogenesis. For the most part, assembly of the longitudinal columns occurs before that of the circumferential ribs. Immunohistochemical and immunogold labelling showed that fibrous sheath proteins are first present in the spermatid cytoplasm; at least some of the proteins of the sheath precursors differ from those in the mature fibrous sheath. That immunoreactivity develops after initiation of chromatin condensation suggests that fibrous sheath proteins, or their mRNAs, are stored within the spermatid cytoplasmic lobule prior to their assembly along the axoneme. These findings are similar to those in laboratory rats, and thus suggests that the mode of fibrous sheath assembly evolved in a common ancestor over 125 million years ago, prior to the divergence of marsupial and eutherian lineages. PMID:16050902

Multistep Lattice-Voxel method utilizing lattice function for Monte-Carlo treatment planning with pixel based voxel model.

PubMed

Kumada, H; Saito, K; Nakamura, T; Sakae, T; Sakurai, H; Matsumura, A; Ono, K

2011-12-01

Treatment planning for boron neutron capture therapy generally utilizes Monte-Carlo methods for calculation of the dose distribution. The new treatment planning system JCDS-FX employs the multi-purpose Monte-Carlo code PHITS to calculate the dose distribution. JCDS-FX allows to build a precise voxel model consisting of pixel based voxel cells in the scale of 0.4×0.4×2.0 mm(3) voxel in order to perform high-accuracy dose estimation, e.g. for the purpose of calculating the dose distribution in a human body. However, the miniaturization of the voxel size increases calculation time considerably. The aim of this study is to investigate sophisticated modeling methods which can perform Monte-Carlo calculations for human geometry efficiently. Thus, we devised a new voxel modeling method "Multistep Lattice-Voxel method," which can configure a voxel model that combines different voxel sizes by utilizing the lattice function over and over. To verify the performance of the calculation with the modeling method, several calculations for human geometry were carried out. The results demonstrated that the Multistep Lattice-Voxel method enabled the precise voxel model to reduce calculation time substantially while keeping the high-accuracy of dose estimation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multistep Model of Cervical Cancer: Participation of miRNAs and Coding Genes

PubMed Central

López, Angelica Judith Granados; López, Jesús Adrián

2014-01-01

Aberrant miRNA expression is well recognized as an important step in the development of cancer. Close to 70 microRNAs (miRNAs) have been implicated in cervical cancer up to now, nevertheless it is unknown if aberrant miRNA expression causes the onset of cervical cancer. One of the best ways to address this issue is through a multistep model of carcinogenesis. In the progression of cervical cancer there are three well-established steps to reach cancer that we used in the model proposed here. The first step of the model comprises the gene changes that occur in normal cells to be transformed into immortal cells (CIN 1), the second comprises immortal cell changes to tumorigenic cells (CIN 2), the third step includes cell changes to increase tumorigenic capacity (CIN 3), and the final step covers tumorigenic changes to carcinogenic cells. Altered miRNAs and their target genes are located in each one of the four steps of the multistep model of carcinogenesis. miRNA expression has shown discrepancies in different works; therefore, in this model we include miRNAs recording similar results in at least two studies. The present model is a useful insight into studying potential prognostic, diagnostic, and therapeutic miRNAs. PMID:25192291

Rapid discrimination of sea buckthorn berries from different H. rhamnoides subspecies by multi-step IR spectroscopy coupled with multivariate data analysis

NASA Astrophysics Data System (ADS)

Liu, Yue; Zhang, Ying; Zhang, Jing; Fan, Gang; Tu, Ya; Sun, Suqin; Shen, Xudong; Li, Qingzhu; Zhang, Yi

2018-03-01

As an important ethnic medicine, sea buckthorn was widely used to prevent and treat various diseases due to its nutritional and medicinal properties. According to the Chinese Pharmacopoeia, sea buckthorn was originated from H. rhamnoides, which includes five subspecies distributed in China. Confusion and misidentification usually occurred due to their similar morphology, especially in dried and powdered forms. Additionally, these five subspecies have vital differences in quality and physiological efficacy. This paper focused on the quick classification and identification method of sea buckthorn berry powders from five H. rhamnoides subspecies using multi-step IR spectroscopy coupled with multivariate data analysis. The holistic chemical compositions revealed by the FT-IR spectra demonstrated that flavonoids, fatty acids and sugars were the main chemical components. Further, the differences in FT-IR spectra regarding their peaks, positions and intensities were used to identify H. rhamnoides subspecies samples. The discrimination was achieved using principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA). The results showed that the combination of multi-step IR spectroscopy and chemometric analysis offered a simple, fast and reliable method for the classification and identification of the sea buckthorn berry powders from different H. rhamnoides subspecies.

Kinetic Analysis for the Multistep Profiles of Organic Reactions: Significance of the Conformational Entropy on the Rate Constants of the Claisen Rearrangement.

PubMed

Sumiya, Yosuke; Nagahata, Yutaka; Komatsuzaki, Tamiki; Taketsugu, Tetsuya; Maeda, Satoshi

2015-12-03

The significance of kinetic analysis as a tool for understanding the reactivity and selectivity of organic reactions has recently been recognized. However, conventional simulation approaches that solve rate equations numerically are not amenable to multistep reaction profiles consisting of fast and slow elementary steps. Herein, we present an efficient and robust approach for evaluating the overall rate constants of multistep reactions via the recursive contraction of the rate equations to give the overall rate constants for the products and byproducts. This new method was applied to the Claisen rearrangement of allyl vinyl ether, as well as a substituted allyl vinyl ether. Notably, the profiles of these reactions contained 23 and 84 local minima, and 66 and 278 transition states, respectively. The overall rate constant for the Claisen rearrangement of allyl vinyl ether was consistent with the experimental value. The selectivity of the Claisen rearrangement reaction has also been assessed using a substituted allyl vinyl ether. The results of this study showed that the conformational entropy in these flexible chain molecules had a substantial impact on the overall rate constants. This new method could therefore be used to estimate the overall rate constants of various other organic reactions involving flexible molecules.

Coordinated control of active and reactive power of distribution network with distributed PV cluster via model predictive control

NASA Astrophysics Data System (ADS)

Ji, Yu; Sheng, Wanxing; Jin, Wei; Wu, Ming; Liu, Haitao; Chen, Feng

2018-02-01

A coordinated optimal control method of active and reactive power of distribution network with distributed PV cluster based on model predictive control is proposed in this paper. The method divides the control process into long-time scale optimal control and short-time scale optimal control with multi-step optimization. The models are transformed into a second-order cone programming problem due to the non-convex and nonlinear of the optimal models which are hard to be solved. An improved IEEE 33-bus distribution network system is used to analyse the feasibility and the effectiveness of the proposed control method

Nucleoside antibiotics: biosynthesis, regulation, and biotechnology.

PubMed

Niu, Guoqing; Tan, Huarong

2015-02-01

The alarming rise in antibiotic-resistant pathogens has coincided with a decline in the supply of new antibiotics. It is therefore of great importance to find and create new antibiotics. Nucleoside antibiotics are a large family of natural products with diverse biological functions. Their biosynthesis is a complex process through multistep enzymatic reactions and is subject to hierarchical regulation. Genetic and biochemical studies of the biosynthetic machinery have provided the basis for pathway engineering and combinatorial biosynthesis to create new or hybrid nucleoside antibiotics. Dissection of regulatory mechanisms is leading to strategies to increase the titer of bioactive nucleoside antibiotics. Copyright © 2014. Published by Elsevier Ltd.

Why Pull the Arrow When You Cannot See the Target? Framing Professionalism Goals in Medical Education.

PubMed

Doukas, David J; Volpe, Rebecca L

2018-04-24

Professionalism is essential for a successful physician-patient relationship and widely acknowledged as an intrinsic and important component of medical education for learners at all levels, from medical school to residency to continuing medical education. The problem is defining the educational endpoints for learners and then determining how to assess these outcomes. This Invited Commentary focuses on what medical educators can and should do to refine the vision of professionalism in medical education. The authors propose a multi-step process in which learners, educators, and the public are engaged in articulating clearly and definitively the endpoints of professionalism education.

Design of multi-body Lambert type orbits with specified departure and arrival positions

NASA Astrophysics Data System (ADS)

Ishii, Nobuaki; Kawaguchi, Jun'ichiro; Matsuo, Hiroki

1991-10-01

A new procedure for designing a multi-body Lambert type orbit comprising a multiple swingby process is developed, aiming at relieving a numerical difficulty inherent to a highly nonlinear swingby mechanism. The proposed algorithm, Recursive Multi-Step Linearization, first divides a whole orbit into several trajectory segments. Then, with a maximum use of piecewised transition matrices, a segmentized orbit is repeatedly upgraded until an approximated orbit initially based on a patched conics method eventually converges. In application to the four body earth-moon system with sun's gravitation, one of the double lunar swingby orbits including 12 lunar swingbys is successfully designed without any velocity mismatch.

The REFINEMENT Glossary of Terms: An International Terminology for Mental Health Systems Assessment.

PubMed

Montagni, Ilaria; Salvador-Carulla, Luis; Mcdaid, David; Straßmayr, Christa; Endel, Florian; Näätänen, Petri; Kalseth, Jorid; Kalseth, Birgitte; Matosevic, Tihana; Donisi, Valeria; Chevreul, Karine; Prigent, Amélie; Sfectu, Raluca; Pauna, Carmen; Gutiérrez-Colosia, Mencia R; Amaddeo, Francesco; Katschnig, Heinz

2018-03-01

Comparing mental health systems across countries is difficult because of the lack of an agreed upon terminology covering services and related financing issues. Within the European Union project REFINEMENT, international mental health care experts applied an innovative mixed "top-down" and "bottom-up" approach following a multistep design thinking strategy to compile a glossary on mental health systems, using local services as pilots. The final REFINEMENT glossary consisted of 432 terms related to service provision, service utilisation, quality of care and financing. The aim of this study was to describe the iterative process and methodology of developing this glossary.

Animal Testing

NASA Astrophysics Data System (ADS)

Moretto, Johnny; Chauffert, Bruno; Bouyer, Florence

The development of a new anticancer drug is a long, complex and multistep process which is supervised by regulatory authorities from the different countries all around the world [1]. Application of a new drug for admission to the market is supported by preclinical and clinical data, both including the determination of pharmacodynamics, toxicity, antitumour activity, therapeutic index, etc. As preclinical studies are associated with high cost, optimization of animal experiments is crucial for the overall development of a new anticancer agent. Moreover, in vivo efficacy studies remain a determinant panel for advancement of agents to human trials and thus, require cautious design and interpretation from experimental and ethical point of views.

The Akt DUBbed InAktive.

PubMed

Lin, Kui

2013-01-08

Akt is a central node in the phosphoinositide-3 kinase-Akt-mammalian target of rapamycin pathway and is activated by a multistep process in response to growth factor stimulation. An additional layer of posttranslational modification has emerged as a new paradigm in the regulation of Akt. The identification of an E3 ligase for Lys(63)-linked ubiquitination of Akt has now been complemented with the discovery of the tumor suppressor cylindromatosis as a deubiquitinating enzyme (DUB) for Akt. Thus, like phosphorylation and dephosphorylation, cycles of ubiquitination and deubiquitination provide additional on-off switches that keep Akt activity in balance, and disturbances in this balance have pathological consequences.

Flow chemistry: intelligent processing of gas-liquid transformations using a tube-in-tube reactor.

PubMed

Brzozowski, Martin; O'Brien, Matthew; Ley, Steven V; Polyzos, Anastasios

2015-02-17

CONSPECTUS: The previous decade has witnessed the expeditious uptake of flow chemistry techniques in modern synthesis laboratories, and flow-based chemistry is poised to significantly impact our approach to chemical preparation. The advantages of moving from classical batch synthesis to flow mode, in order to address the limitations of traditional approaches, particularly within the context of organic synthesis are now well established. Flow chemistry methodology has led to measurable improvements in safety and reduced energy consumption and has enabled the expansion of available reaction conditions. Contributions from our own laboratories have focused on the establishment of flow chemistry methods to address challenges associated with the assembly of complex targets through the development of multistep methods employing supported reagents and in-line monitoring of reaction intermediates to ensure the delivery of high quality target compounds. Recently, flow chemistry approaches have addressed the challenges associated with reactions utilizing reactive gases in classical batch synthesis. The small volumes of microreactors ameliorate the hazards of high-pressure gas reactions and enable improved mixing with the liquid phase. Established strategies for gas-liquid reactions in flow have relied on plug-flow (or segmented flow) regimes in which the gas plugs are introduced to a liquid stream and dissolution of gas relies on interfacial contact of the gas bubble with the liquid phase. This approach confers limited control over gas concentration within the liquid phase and is unsuitable for multistep methods requiring heterogeneous catalysis or solid supported reagents. We have identified the use of a gas-permeable fluoropolymer, Teflon AF-2400, as a simple method of achieving efficient gas-liquid contact to afford homogeneous solutions of reactive gases in flow. The membrane permits the transport of a wide range of gases with significant control of the stoichiometry of reactive gas in a given reaction mixture. We have developed a tube-in-tube reactor device consisting of a pair of concentric capillaries in which pressurized gas permeates through an inner Teflon AF-2400 tube and reacts with dissolved substrate within a liquid phase that flows within a second gas impermeable tube. This Account examines our efforts toward the development of a simple, unified methodology for the processing of gaseous reagents in flow by way of development of a tube-in-tube reactor device and applications to key C-C, C-N, and C-O bond forming and hydrogenation reactions. We further describe the application to multistep reactions using solid-supported reagents and extend the technology to processes utilizing multiple gas reagents. A key feature of our work is the development of computer-aided imaging techniques to allow automated in-line monitoring of gas concentration and stoichiometry in real time. We anticipate that this Account will illustrate the convenience and benefits of membrane tube-in-tube reactor technology to improve and concomitantly broaden the scope of gas/liquid/solid reactions in organic synthesis.

Fast 5DOF needle tracking in iOCT.

PubMed

Weiss, Jakob; Rieke, Nicola; Nasseri, Mohammad Ali; Maier, Mathias; Eslami, Abouzar; Navab, Nassir

2018-06-01

Intraoperative optical coherence tomography (iOCT) is an increasingly available imaging technique for ophthalmic microsurgery that provides high-resolution cross-sectional information of the surgical scene. We propose to build on its desirable qualities and present a method for tracking the orientation and location of a surgical needle. Thereby, we enable the direct analysis of instrument-tissue interaction directly in OCT space without complex multimodal calibration that would be required with traditional instrument tracking methods. The intersection of the needle with the iOCT scan is detected by a peculiar multistep ellipse fitting that takes advantage of the directionality of the modality. The geometric modeling allows us to use the ellipse parameters and provide them into a latency-aware estimator to infer the 5DOF pose during needle movement. Experiments on phantom data and ex vivo porcine eyes indicate that the algorithm retains angular precision especially during lateral needle movement and provides a more robust and consistent estimation than baseline methods. Using solely cross-sectional iOCT information, we are able to successfully and robustly estimate a 5DOF pose of the instrument in less than 5.4 ms on a CPU.

A time to search: finding the meaning of variable activation energy.

PubMed

Vyazovkin, Sergey

2016-07-28

This review deals with the phenomenon of variable activation energy frequently observed when studying the kinetics in the liquid or solid phase. This phenomenon commonly manifests itself through nonlinear Arrhenius plots or dependencies of the activation energy on conversion computed by isoconversional methods. Variable activation energy signifies a multi-step process and has a meaning of a collective parameter linked to the activation energies of individual steps. It is demonstrated that by using appropriate models of the processes, the link can be established in algebraic form. This allows one to analyze experimentally observed dependencies of the activation energy in a quantitative fashion and, as a result, to obtain activation energies of individual steps, to evaluate and predict other important parameters of the process, and generally to gain deeper kinetic and mechanistic insights. This review provides multiple examples of such analysis as applied to the processes of crosslinking polymerization, crystallization and melting of polymers, gelation, and solid-solid morphological and glass transitions. The use of appropriate computational techniques is discussed as well.

Process Simulation of Aluminium Sheet Metal Deep Drawing at Elevated Temperatures

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

Winklhofer, Johannes; Trattnig, Gernot; Lind, Christoph

Lightweight design is essential for an economic and environmentally friendly vehicle. Aluminium sheet metal is well known for its ability to improve the strength to weight ratio of lightweight structures. One disadvantage of aluminium is that it is less formable than steel. Therefore complex part geometries can only be realized by expensive multi-step production processes. One method for overcoming this disadvantage is deep drawing at elevated temperatures. In this way the formability of aluminium sheet metal can be improved significantly, and the number of necessary production steps can thereby be reduced. This paper introduces deep drawing of aluminium sheet metalmore » at elevated temperatures, a corresponding simulation method, a characteristic process and its optimization. The temperature and strain rate dependent material properties of a 5xxx series alloy and their modelling are discussed. A three dimensional thermomechanically coupled finite element deep drawing simulation model and its validation are presented. Based on the validated simulation model an optimised process strategy regarding formability, time and cost is introduced.« less

Treatments To Produce Stabilized Aluminum Mirrors for Cryogenic Uses

NASA Technical Reports Server (NTRS)

Zewari, Wahid; Barthelmy, Michael; Ohl, Raymond

2005-01-01

Five metallurgical treatments have been tested as means of stabilizing mirrors that are made of aluminum alloy 6061 and are intended for use in cryogenic applications. Aluminum alloy 6061 is favored as a mirror material by many scientists and engineers. Like other alloys, it shrinks upon cool-down from room temperature to cryogenic temperature. This shrinkage degrades the optical quality of the mirror surfaces. Hence, the metallurgical treatments were tested to determine which one could be most effective in minimizing the adverse optical effects of cooldown to cryogenic temperatures. Each of the five metallurgical treatments comprises a multistep process, the steps of which are interspersed with the steps of the mirror-fabrication process. The five metallurgical-treatment/fabrication.- process combinations were compared with each other and with a benchmark fabrication process, in which a mirror is made from an alloy blank by (1) symmetrical rough machining, (2) finish machining to within 0.006 in. (. 0.15 mm) of final dimensions, and finally (3) diamond turning to a mirror finish.

Hydrotreater/Distillation Column Hazard Analysis Report Rev. 2

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

Lowry, Peter P.; Wagner, Katie A.

This project Hazard and Risk Analysis Report contains the results of several hazard analyses and risk assessments. An initial assessment was conducted in 2012, which included a multi-step approach ranging from design reviews to a formal What-If hazard analysis. A second What-If hazard analysis was completed during February 2013 to evaluate the operation of the hydrotreater/distillation column processes to be installed in a process enclosure within the Process Development Laboratory West (PDL-West) facility located on the PNNL campus. The qualitative analysis included participation of project and operations personnel and applicable subject matter experts. The analysis identified potential hazardous scenarios, eachmore » based on an initiating event coupled with a postulated upset condition. The unmitigated consequences of each hazardous scenario were generally characterized as a process upset; the exposure of personnel to steam, vapors or hazardous material; a spray or spill of hazardous material; the creation of a flammable atmosphere; or an energetic release from a pressure boundary.« less

Multi-step resistive switching behavior of Li-doped ZnO resistance random access memory device controlled by compliance current

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

Lin, Chun-Cheng; Department of Mathematic and Physical Sciences, R.O.C. Air Force Academy, Kaohsiung 820, Taiwan; Tang, Jian-Fu

2016-06-28

The multi-step resistive switching (RS) behavior of a unipolar Pt/Li{sub 0.06}Zn{sub 0.94}O/Pt resistive random access memory (RRAM) device is investigated. It is found that the RRAM device exhibits normal, 2-, 3-, and 4-step RESET behaviors under different compliance currents. The transport mechanism within the device is investigated by means of current-voltage curves, in-situ transmission electron microscopy, and electrochemical impedance spectroscopy. It is shown that the ion transport mechanism is dominated by Ohmic behavior under low electric fields and the Poole-Frenkel emission effect (normal RS behavior) or Li{sup +} ion diffusion (2-, 3-, and 4-step RESET behaviors) under high electric fields.

Multistep Cylindrical Structure Analysis at Normal Incidence Based on Water-Substrate Broadband Metamaterial Absorbers

NASA Astrophysics Data System (ADS)

Fang, Chonghua

2018-01-01

A new multistep cylindrical structure based on water-substrate broadband metamaterial absorbers is designed to reduce the traditional radar cross-section (RCS) of a rod-shaped object. The proposed configuration consists of two distinct parts. One of these components is formed by a four-step cylindrical metal structure, whereas the other one is formed by a new water-substrate broadband metamaterial absorber. The designed structure can significantly reduce the radar cross section more than 10 dB from 4.58 to 18.42 GHz which is the 86.5 % bandwidth of from C-band to 20 GHz. The results of measurement show reasonably good accordance with the simulated ones, which verifies the ability and effect of the proposed design.

Fast dye salts provide fast access to azidoarene synthons in multi-step one-pot tandem click transformations

PubMed Central

Fletcher, James T.; Reilly, Jacquelline E.

2012-01-01

This study examined whether commercially available diazonium salts could be used as efficient aromatic azide precursors in one-pot multi-step click transformations. Seven different diazonium salts, including Fast Red RC, Fast Blue B, Fast Corinth V and Variamine Blue B were surveyed under aqueous click reaction conditions of CuSO4/Na ascorbate catalyst with 1:1 t-BuOH:H2O solvent. Two-step tandem reactions with terminal alkyne and diyne co-reactants led to 1,2,3-triazole products in 66%-88% yields, while three-step tandem reactions with trimethylsilyl-protected alkyne and diyne co-reactants led to 1,2,3-triazole products in 61%-78% yields. PMID:22368306

Cellulose Biosynthesis: Current Views and Evolving Concepts

PubMed Central

SAXENA, INDER M.; BROWN, R. MALCOLM

2005-01-01

• Aims To outline the current state of knowledge and discuss the evolution of various viewpoints put forth to explain the mechanism of cellulose biosynthesis. • Scope Understanding the mechanism of cellulose biosynthesis is one of the major challenges in plant biology. The simplicity in the chemical structure of cellulose belies the complexities that are associated with the synthesis and assembly of this polysaccharide. Assembly of cellulose microfibrils in most organisms is visualized as a multi-step process involving a number of proteins with the key protein being the cellulose synthase catalytic sub-unit. Although genes encoding this protein have been identified in almost all cellulose synthesizing organisms, it has been a challenge in general, and more specifically in vascular plants, to demonstrate cellulose synthase activity in vitro. The assembly of glucan chains into cellulose microfibrils of specific dimensions, viewed as a spontaneous process, necessitates the assembly of synthesizing sites unique to most groups of organisms. The steps of polymerization (requiring the specific arrangement and activity of the cellulose synthase catalytic sub-units) and crystallization (directed self-assembly of glucan chains) are certainly interlinked in the formation of cellulose microfibrils. Mutants affected in cellulose biosynthesis have been identified in vascular plants. Studies on these mutants and herbicide-treated plants suggest an interesting link between the steps of polymerization and crystallization during cellulose biosynthesis. • Conclusions With the identification of a large number of genes encoding cellulose synthases and cellulose synthase-like proteins in vascular plants and the supposed role of a number of other proteins in cellulose biosynthesis, a complete understanding of this process will necessitate a wider variety of research tools and approaches than was thought to be required a few years back. PMID:15894551

Cellulose biosynthesis: current views and evolving concepts.

PubMed

Saxena, Inder M; Brown, R Malcolm

2005-07-01

To outline the current state of knowledge and discuss the evolution of various viewpoints put forth to explain the mechanism of cellulose biosynthesis. * Understanding the mechanism of cellulose biosynthesis is one of the major challenges in plant biology. The simplicity in the chemical structure of cellulose belies the complexities that are associated with the synthesis and assembly of this polysaccharide. Assembly of cellulose microfibrils in most organisms is visualized as a multi-step process involving a number of proteins with the key protein being the cellulose synthase catalytic sub-unit. Although genes encoding this protein have been identified in almost all cellulose synthesizing organisms, it has been a challenge in general, and more specifically in vascular plants, to demonstrate cellulose synthase activity in vitro. The assembly of glucan chains into cellulose microfibrils of specific dimensions, viewed as a spontaneous process, necessitates the assembly of synthesizing sites unique to most groups of organisms. The steps of polymerization (requiring the specific arrangement and activity of the cellulose synthase catalytic sub-units) and crystallization (directed self-assembly of glucan chains) are certainly interlinked in the formation of cellulose microfibrils. Mutants affected in cellulose biosynthesis have been identified in vascular plants. Studies on these mutants and herbicide-treated plants suggest an interesting link between the steps of polymerization and crystallization during cellulose biosynthesis. * With the identification of a large number of genes encoding cellulose synthases and cellulose synthase-like proteins in vascular plants and the supposed role of a number of other proteins in cellulose biosynthesis, a complete understanding of this process will necessitate a wider variety of research tools and approaches than was thought to be required a few years back.

Density functional theory and RRKM calculations of decompositions of the metastable E-2,4-pentadienal molecular ions.

PubMed

Solano Espinoza, Eduardo A; Vallejo Narváez, Wilmer E

2010-07-01

The potential energy profiles for the fragmentations that lead to [C(5)H(5)O](+) and [C(4)H(6)](+*) ions from the molecular ions [C(5)H(6)O](+*) of E-2,4-pentadienal were obtained from calculations at the UB3LYP/6-311G + + (3df,3pd)//UB3LYP/6-31G(d,p) level of theory. Kinetic barriers and harmonic frequencies obtained by the density functional method were then employed in Rice-Ramsperger-Kassel-Marcus calculations of individual rate coefficients for a large number of reaction steps. The pre-equilibrium and rate-controlling step approximations were applied to different regions of the complex potential energy surface, allowing the overall rate of decomposition to be calculated and discriminated between three rival pathways: C-H bond cleavage, decarbonylation and cyclization. These processes should have to compete for an equilibrated mixture of four conformers of the E-2,4-pentadienal ions. The direct dissociation, however, can only become important in the high-energy regime. In contrast, loss of CO and cyclization are observable processes in the metastable kinetic window. The former involves a slow 1,2-hydrogen shift from the carbonyl group that is immediately followed by the formation of an ion-neutral complex which, in turn, decomposes rapidly to the s-trans-1,3-butadiene ion [C(4)H(6)](+*). The predominating metastable channel is the second one, that is, a multi-step ring closure which starts with a rate-limiting cis-trans isomerization. This process yields a mixture of interconverting pyran ions that dissociates to the pyrylium ions [C(5)H(5)O](+). These results can be used to rationalize the CID mass spectrum of E-2,4-pentadienal in a low-energy regime. 2010 John Wiley & Sons, Ltd.

Protection of scaffold protein Isu from degradation by the Lon protease Pim1 as a component of Fe-S cluster biogenesis regulation.

PubMed

Ciesielski, Szymon J; Schilke, Brenda; Marszalek, Jaroslaw; Craig, Elizabeth A

2016-04-01

Iron-sulfur (Fe-S) clusters, essential protein cofactors, are assembled on the mitochondrial scaffold protein Isu and then transferred to recipient proteins via a multistep process in which Isu interacts sequentially with multiple protein factors. This pathway is in part regulated posttranslationally by modulation of the degradation of Isu, whose abundance increases >10-fold upon perturbation of the biogenesis process. We tested a model in which direct interaction with protein partners protects Isu from degradation by the mitochondrial Lon-type protease. Using purified components, we demonstrated that Isu is indeed a substrate of the Lon-type protease and that it is protected from degradation by Nfs1, the sulfur donor for Fe-S cluster assembly, as well as by Jac1, the J-protein Hsp70 cochaperone that functions in cluster transfer from Isu. Nfs1 and Jac1 variants known to be defective in interaction with Isu were also defective in protecting Isu from degradation. Furthermore, overproduction of Jac1 protected Isu from degradation in vivo, as did Nfs1. Taken together, our results lead to a model of dynamic interplay between a protease and protein factors throughout the Fe-S cluster assembly and transfer process, leading to up-regulation of Isu levels under conditions when Fe-S cluster biogenesis does not meet cellular demands. © 2016 Ciesielski et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The Use of Lean Six Sigma Methodology in Increasing Capacity of a Chemical Production Facility at DSM.

PubMed

Meeuwse, Marco

2018-03-30

Lean Six Sigma is an improvement method, combining Lean, which focuses on removing 'waste' from a process, with Six Sigma, which is a data-driven approach, making use of statistical tools. Traditionally it is used to improve the quality of products (reducing defects), or processes (reducing variability). However, it can also be used as a tool to increase the productivity or capacity of a production plant. The Lean Six Sigma methodology is therefore an important pillar of continuous improvement within DSM. In the example shown here a multistep batch process is improved, by analyzing the duration of the relevant process steps, and optimizing the procedures. Process steps were performed in parallel instead of sequential, and some steps were made shorter. The variability was reduced, giving the opportunity to make a tighter planning, and thereby reducing waiting times. Without any investment in new equipment or technical modifications, the productivity of the plant was improved by more than 20%; only by changing procedures and the programming of the process control system.

Effects of protein and phosphate buffer concentrations on thermal denaturation of lysozyme analyzed by isoconversional method.

PubMed

Cao, X M; Tian, Y; Wang, Z Y; Liu, Y W; Wang, C X

2016-07-03

Thermal denaturation of lysozymes was studied as a function of protein concentration, phosphate buffer concentration, and scan rate using differential scanning calorimetry (DSC), which was then analyzed by the isoconversional method. The results showed that lysozyme thermal denaturation was only slightly affected by the protein concentration and scan rate. When the protein concentration and scan rate increased, the denaturation temperature (Tm) also increased accordingly. On the contrary, the Tm decreased with the increase of phosphate buffer concentration. The denaturation process of lysozymes was accelatated and the thermal stability was reduced with the increase of phosphate concentration. One part of degeneration process was not reversible where the aggregation occurred. The other part was reversible. The apparent activation energy (Ea) was computed by the isoconversional method. It decreased with the increase of the conversion ratio (α). The observed denaturation process could not be described by a simple reaction mechanism. It was not a process involving 2 standard reversible states, but a multi-step process. The new opportunities for investigating the kinetics process of protein denaturation can be supplied by this novel isoconversional method.

Science to Manage a Very Rare Fish in a Very Large River - Pallid Sturgeon in the Missouri River, U.S.A.

NASA Astrophysics Data System (ADS)

Jacobson, R. B.; Colvin, M. E.; Marmorek, D.; Randall, M.

2017-12-01

The Missouri River Recovery Program (MRRP) seeks to revise river-management strategies to avoid jeopardizing the existence of three species: pallid sturgeon (Scaphirhynchus albus), interior least tern (Sterna antillarum)), and piping plover (Charadrius melodus). Managing the river to maintain populations of the two birds (terns and plovers) is relatively straightforward: reproductive success can be modeled with some certainty as a direct, increasing function of exposed sandbar area. In contrast, the pallid sturgeon inhabits the benthic zone of a deep, turbid river and many parts of its complex life history are not directly observable. Hence, pervasive uncertainties exist about what factors are limiting population growth and what management actions may reverse population declines. These uncertainties are being addressed by the MRRP through a multi-step process. The first step was an Effects Analysis (EA), which: documented what is known and unknown about the river and the species; documented quality and quantity of existing information; used an expert-driven process to develop conceptual ecological models and to prioritize management hypotheses; and developed quantitative models linking management actions (flows, channel reconfigurations, and stocking) to population responses. The EA led to development of a science and adaptive-management plan with prioritized allocation of investment among 4 levels of effort ranging from fundamental research to full implementation. The plan includes learning from robust, hypothesis-driven effectiveness monitoring for all actions, with statistically sound experimental designs, multiple metrics, and explicit decision criteria to guide management. Finally, the science plan has been fully integrated with a new adaptive-management structure that links science to decision makers. The reinvigorated investment in science stems from the understanding that costly river-management decisions are not socially or politically supportable without better understanding of how this endangered fish will respond. While some hypotheses can be evaluated without actually implementing management actions in the river, assessing the effectiveness of other forms of habitat restoration requires in-river implementation within a rigorous experimental design.

Toward Exploring the Structure of Monolayer to Few-layer TaS2 by Efficient Ultrasound-free Exfoliation

NASA Astrophysics Data System (ADS)

Hu, Yiwei; Hao, Qiaoyan; Zhu, Baichuan; Li, Biao; Gao, Zhan; Wang, Yan; Tang, Kaibin

2018-01-01

Tantalum disulfide nanosheets have attracted great interest due to its electronic properties and device applications. Traditional solution-ased ultrasonic process is limited by ultrasound which may cause the disintegration into submicron-sized flake. Here, an efficient multi-step intercalation and ultrasound-free process has been successfully used to exfoliate 1T-TaS2. The obtained TaS2 nanosheets reveal an average thickness of 3 nm and several micrometers in size. The formation of few-layer TaS2 nanosheets as well as monolayer TaS2 sheets is further confirmed by atomic force microscopy images. The few-layer TaS2 nanosheets remain the 1T structure, whereas monolayer TaS2 sheets show lattice distortion and may adopt the 1H-like structure with trigonal prism coordination.

Network design and analysis for multi-enzyme biocatalysis.

PubMed

Blaß, Lisa Katharina; Weyler, Christian; Heinzle, Elmar

2017-08-10

As more and more biological reaction data become available, the full exploration of the enzymatic potential for the synthesis of valuable products opens up exciting new opportunities but is becoming increasingly complex. The manual design of multi-step biosynthesis routes involving enzymes from different organisms is very challenging. To harness the full enzymatic potential, we developed a computational tool for the directed design of biosynthetic production pathways for multi-step catalysis with in vitro enzyme cascades, cell hydrolysates and permeabilized cells. We present a method which encompasses the reconstruction of a genome-scale pan-organism metabolic network, path-finding and the ranking of the resulting pathway candidates for proposing suitable synthesis pathways. The network is based on reaction and reaction pair data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the thermodynamics calculator eQuilibrator. The pan-organism network is especially useful for finding the most suitable pathway to a target metabolite from a thermodynamic or economic standpoint. However, our method can be used with any network reconstruction, e.g. for a specific organism. We implemented a path-finding algorithm based on a mixed-integer linear program (MILP) which takes into account both topology and stoichiometry of the underlying network. Unlike other methods we do not specify a single starting metabolite, but our algorithm searches for pathways starting from arbitrary start metabolites to a target product of interest. Using a set of biochemical ranking criteria including pathway length, thermodynamics and other biological characteristics such as number of heterologous enzymes or cofactor requirement, it is possible to obtain well-designed meaningful pathway alternatives. In addition, a thermodynamic profile, the overall reactant balance and potential side reactions as well as an SBML file for visualization are generated for each pathway alternative. We present an in silico tool for the design of multi-enzyme biosynthetic production pathways starting from a pan-organism network. The method is highly customizable and each module can be adapted to the focus of the project at hand. This method is directly applicable for (i) in vitro enzyme cascades, (ii) cell hydrolysates and (iii) permeabilized cells.

Robust model predictive control for multi-step short range spacecraft rendezvous

NASA Astrophysics Data System (ADS)

Zhu, Shuyi; Sun, Ran; Wang, Jiaolong; Wang, Jihe; Shao, Xiaowei

2018-07-01

This work presents a robust model predictive control (MPC) approach for the multi-step short range spacecraft rendezvous problem. During the specific short range phase concerned, the chaser is supposed to be initially outside the line-of-sight (LOS) cone. Therefore, the rendezvous process naturally includes two steps: the first step is to transfer the chaser into the LOS cone and the second step is to transfer the chaser into the aimed region with its motion confined within the LOS cone. A novel MPC framework named after Mixed MPC (M-MPC) is proposed, which is the combination of the Variable-Horizon MPC (VH-MPC) framework and the Fixed-Instant MPC (FI-MPC) framework. The M-MPC framework enables the optimization for the two steps to be implemented jointly rather than to be separated factitiously, and its computation workload is acceptable for the usually low-power processors onboard spacecraft. Then considering that disturbances including modeling error, sensor noise and thrust uncertainty may induce undesired constraint violations, a robust technique is developed and it is attached to the above M-MPC framework to form a robust M-MPC approach. The robust technique is based on the chance-constrained idea, which ensures that constraints can be satisfied with a prescribed probability. It improves the robust technique proposed by Gavilan et al., because it eliminates the unnecessary conservativeness by explicitly incorporating known statistical properties of the navigation uncertainty. The efficacy of the robust M-MPC approach is shown in a simulation study.

Multi-step cure kinetic model of ultra-thin glass fiber epoxy prepreg exhibiting both autocatalytic and diffusion-controlled regimes under isothermal and dynamic-heating conditions

NASA Astrophysics Data System (ADS)

Kim, Ye Chan; Min, Hyunsung; Hong, Sungyong; Wang, Mei; Sun, Hanna; Park, In-Kyung; Choi, Hyouk Ryeol; Koo, Ja Choon; Moon, Hyungpil; Kim, Kwang J.; Suhr, Jonghwan; Nam, Jae-Do

2017-08-01

As packaging technologies are demanded that reduce the assembly area of substrate, thin composite laminate substrates require the utmost high performance in such material properties as the coefficient of thermal expansion (CTE), and stiffness. Accordingly, thermosetting resin systems, which consist of multiple fillers, monomers and/or catalysts in thermoset-based glass fiber prepregs, are extremely complicated and closely associated with rheological properties, which depend on the temperature cycles for cure. For the process control of these complex systems, it is usually required to obtain a reliable kinetic model that could be used for the complex thermal cycles, which usually includes both the isothermal and dynamic-heating segments. In this study, an ultra-thin prepreg with highly loaded silica beads and glass fibers in the epoxy/amine resin system was investigated as a model system by isothermal/dynamic heating experiments. The maximum degree of cure was obtained as a function of temperature. The curing kinetics of the model prepreg system exhibited a multi-step reaction and a limited conversion as a function of isothermal curing temperatures, which are often observed in epoxy cure system because of the rate-determining diffusion of polymer chain growth. The modified kinetic equation accurately described the isothermal behavior and the beginning of the dynamic-heating behavior by integrating the obtained maximum degree of cure into the kinetic model development.

Preclinical good laboratory practice-compliant safety study to evaluate biodistribution and tumorigenicity of a cartilage advanced therapy medicinal product (ATMP).

PubMed

Zscharnack, Matthias; Krause, Christoph; Aust, Gabriela; Thümmler, Christian; Peinemann, Frank; Keller, Thomas; Smink, Jeske J; Holland, Heidrun; Somerson, Jeremy S; Knauer, Jens; Schulz, Ronny M; Lehmann, Jörg

2015-05-20

The clinical development of advanced therapy medicinal products (ATMPs), a new class of drugs, requires initial safety studies that deviate from standard non-clinical safety protocols. The study provides a strategy to address the safety aspects of biodistribution and tumorigenicity of ATMPs under good laboratory practice (GLP) conditions avoiding cell product manipulation. Moreover, the strategy was applied on a human ATMP for cartilage repair. The testing strategy addresses biodistribution and tumorigenicity using a multi-step analysis without any cell manipulation to exclude changes of test item characteristics. As a safeguard measurement for meeting regulatory expectations, the project design and goals were discussed continuously with the regulatory authority using a staggered scientific advice concept. Subsequently, the strategy was applied to co.don chondrosphere® (huChon spheroid), a tissue-engineered matrix-free ATMP of human normal chondrocytes. In both the biodistribution and tumorigenicity studies, huChon spheroids were implanted subcutaneously into 40 immunodeficient mice. Biodistribution was studied 1 month after implantation. A skin disc containing the huChon spheroid, two surrounding skin rings and selected organs were analyzed by validated, gender-specific, highly-sensitive triplex qPCR and by immunohistochemistry (IHC). No human DNA was detected in distant skin rings and analyzed organs. IHC revealed no direct or indirect indications of cell migration. Tumorigenicity was assessed 6 months after huChon spheroid implantation by palpation, macroscopic inspection, histology and IHC. No mice from the huChon spheroid group developed a tumor at the implantation site. In two mice, benign tumors were detected that were negative for HLA-ABC, suggesting that they were of spontaneous murine origin. In summary, the presented strategy using a multi-step analysis was confirmed to be suitable for safety studies of ATMPs.

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

Kadmensky, S. G., E-mail: kadmensky@phys.vsu.ru; Kostryukov, P. V.

It is shown that a quantum system whose Hamiltonian is independent of time is T -invariant if this Hamiltonian contains only those terms that do not change sign upon time reversal. It is also shown that the coincidence of the amplitudes for multistep direct and statistical nuclear reactions with the timereversed amplitudes for the reactions being studied is a condition that ensures the T -invariance of the amplitudes in question, the transition from the original amplitudes to their time-reversed counterparts being accomplished, first, upon introducing the inverse-reactionmatrices T instead of the original-reaction matrix T and, second, upon replacing the wavemore » functions for the initial, final, and intermediate states of the system by the respective time-reversed functions. It is found that the T -even (T -odd) asymmetries in cross sections for nuclear reactions stem from the interference between the amplitudes characterizing these reactions and having identical (opposite) T -parities. It is shown that the T -invariance condition for the above T -even (T -odd) asymmetries is related to the conservation of (change in) the sign of these asymmetries upon going over from original to inverse nuclear reactions. Mechanisms underlying the appearance of possible T -even and T-odd asymmetries in the cross sections for the cold-polarizedneutron- induced binary and ternary fission of oriented target nuclei are analyzed for the case of employing T -invariant Hamiltonians for the systems under study. It is also shown that the asymmetries in question satisfy the T -invariance condition if the reactions being considered have a sequential multistep statistical character. It is concluded that T -invariance is violated in the limiting case where, in ternary nuclear fission, the emission of a light third particle froma fissile compound nucleus formed upon incident-neutron capture by a target nucleus and its separation to two fission fragments are simultaneous events.« less

Multi-step aberrant CpG island hyper-methylation is associated with the progression of adult T-cell leukemia/lymphoma.

PubMed

Sato, Hiaki; Oka, Takashi; Shinnou, Yoko; Kondo, Takami; Washio, Kana; Takano, Masayuki; Takata, Katsuyoshi; Morito, Toshiaki; Huang, Xingang; Tamura, Maiko; Kitamura, Yuta; Ohara, Nobuya; Ouchida, Mamoru; Ohshima, Koichi; Shimizu, Kenji; Tanimoto, Mitsune; Takahashi, Kiyoshi; Matsuoka, Masao; Utsunomiya, Atae; Yoshino, Tadashi

2010-01-01

Aberrant CpG island methylation contributes to the pathogenesis of various malignancies. However, little is known about the association of epigenetic abnormalities with multistep tumorigenic events in adult T cell leukemia/lymphoma (ATLL). To determine whether epigenetic abnormalities induce the progression of ATLL, we analyzed the methylation profiles of the SHP1, p15, p16, p73, HCAD, DAPK, hMLH-1, and MGMT genes by methylation specific PCR assay in 65 cases with ATLL patients. The number of CpG island methylated genes increased with disease progression and aberrant hypermethylation in specific genes was detected even in HTLV-1 carriers and correlated with progression to ATLL. The CpG island methylator phenotype (CIMP) was observed most frequently in lymphoma type ATLL and was also closely associated with the progression and crisis of ATLL. The high number of methylated genes and increase of CIMP incidence were shown to be unfavorable prognostic factors and correlated with a shorter overall survival by Kaplan-Meyer analysis. The present findings strongly suggest that the multistep accumulation of aberrant CpG methylation in specific target genes and the presence of CIMP are deeply involved in the crisis, progression, and prognosis of ATLL, as well as indicate the value of CpG methylation and CIMP for new diagnostic and prognostic biomarkers.

Multi-Step Aberrant CpG Island Hyper-Methylation Is Associated with the Progression of Adult T–Cell Leukemia/Lymphoma

PubMed Central

Sato, Hiaki; Oka, Takashi; Shinnou, Yoko; Kondo, Takami; Washio, Kana; Takano, Masayuki; Takata, Katsuyoshi; Morito, Toshiaki; Huang, Xingang; Tamura, Maiko; Kitamura, Yuta; Ohara, Nobuya; Ouchida, Mamoru; Ohshima, Koichi; Shimizu, Kenji; Tanimoto, Mitsune; Takahashi, Kiyoshi; Matsuoka, Masao; Utsunomiya, Atae; Yoshino, Tadashi

2010-01-01

Aberrant CpG island methylation contributes to the pathogenesis of various malignancies. However, little is known about the association of epigenetic abnormalities with multistep tumorigenic events in adult T cell leukemia/lymphoma (ATLL). To determine whether epigenetic abnormalities induce the progression of ATLL, we analyzed the methylation profiles of the SHP1, p15, p16, p73, HCAD, DAPK, hMLH-1, and MGMT genes by methylation specific PCR assay in 65 cases with ATLL patients. The number of CpG island methylated genes increased with disease progression and aberrant hypermethylation in specific genes was detected even in HTLV-1 carriers and correlated with progression to ATLL. The CpG island methylator phenotype (CIMP) was observed most frequently in lymphoma type ATLL and was also closely associated with the progression and crisis of ATLL. The high number of methylated genes and increase of CIMP incidence were shown to be unfavorable prognostic factors and correlated with a shorter overall survival by Kaplan-Meyer analysis. The present findings strongly suggest that the multistep accumulation of aberrant CpG methylation in specific target genes and the presence of CIMP are deeply involved in the crisis, progression, and prognosis of ATLL, as well as indicate the value of CpG methylation and CIMP for new diagnostic and prognostic biomarkers. PMID:20019193

Guest Programmable Multistep Spin Crossover in a Porous 2-D Hofmann-Type Material.

PubMed

Murphy, Michael J; Zenere, Katrina A; Ragon, Florence; Southon, Peter D; Kepert, Cameron J; Neville, Suzanne M

2017-01-25

The spin crossover (SCO) phenomenon defines an elegant class of switchable materials that can show cooperative transitions when long-range elastic interactions are present. Such materials can show multistepped transitions, targeted both fundamentally and for expanded data storage applications, when antagonistic interactions (i.e., competing ferro- and antiferro-elastic interactions) drive concerted lattice distortions. To this end, a new SCO framework scaffold, [Fe II (bztrz) 2 (Pd II (CN) 4 )]·n(guest) (bztrz = (E)-1-phenyl-N-(1,2,4-triazol-4-yl)methanimine, 1·n(guest)), has been prepared that supports a variety of antagonistic solid state interactions alongside a distinct dual guest pore system. In this 2-D Hofmann-type material we find that inbuilt competition between ferro- and antiferro-elastic interactions provides a SCO behavior that is intrinsically frustrated. This frustration is harnessed by guest exchange to yield a very broad array of spin transition characters in the one framework lattice (one- (1·(H 2 O,EtOH)), two- (1·3H 2 O) and three-stepped (1·∼2H 2 O) transitions and SCO-deactivation (1)). This variety of behaviors illustrates that the degree of elastic frustration can be manipulated by molecular guests, which suggests that the structural features that contribute to multistep switching may be more subtle than previously anticipated.

Analysis, design, fabrication, and performance of three-dimensional braided composites

NASA Astrophysics Data System (ADS)

Kostar, Timothy D.

1998-11-01

Cartesian 3-D (track and column) braiding as a method of composite preforming has been investigated. A complete analysis of the process was conducted to understand the limitations and potentials of the process. Knowledge of the process was enhanced through development of a computer simulation, and it was discovered that individual control of each track and column and multiple-step braid cycles greatly increases possible braid architectures. Derived geometric constraints coupled with the fundamental principles of Cartesian braiding resulted in an algorithm to optimize preform geometry in relation to processing parameters. The design of complex and unusual 3-D braids was investigated in three parts: grouping of yarns to form hybrid composites via an iterative simulation; design of composite cross-sectional shape through implementation of the Universal Method; and a computer algorithm developed to determine the braid plan based on specified cross-sectional shape. Several 3-D braids, which are the result of variations or extensions to Cartesian braiding, are presented. An automated four-step braiding machine with axial yarn insertion has been constructed and used to fabricate two-step, double two-step, four-step, and four-step with axial and transverse yarn insertion braids. A working prototype of a multi-step braiding machine was used to fabricate four-step braids with surrogate material insertion, unique hybrid structures from multiple track and column displacement and multi-step cycles, and complex-shaped structures with constant or varying cross-sections. Braid materials include colored polyester yarn to study the yarn grouping phenomena, Kevlar, glass, and graphite for structural reinforcement, and polystyrene, silicone rubber, and fasteners for surrogate material insertion. A verification study for predicted yarn orientation and volume fraction was conducted, and a topological model of 3-D braids was developed. The solid model utilizes architectural parameters, generated from the process simulation, to determine the composite elastic properties. Methods of preform consolidation are investigated and the results documented. The extent of yarn deformation (packing) resulting from preform consolidation was investigated through cross-sectional micrographs. The fiber volume fraction of select hybrid composites was measured and representative unit cells are suggested. Finally, a comparison study of the elastic performance of Kevlar/epoxy and carbon/Kevlar hybrid composites was conducted.

Cauliflower-derived porous carbon without activation for electrochemical capacitor and CO2 capture applications

NASA Astrophysics Data System (ADS)

Du, Juan; Yu, Yifeng; Lv, Haijun; Chen, Chunlin; Zhang, Jian; Chen, Aibing

2018-01-01

Carbon materials have attracted great attention in CO2 capture and energy storage due to their excellent characteristics such as tunable pore structure, modulated surface properties and superior bulk conductivities, etc. Biomass, provided by nature with non-toxic, widespread, abundant, and sustainable advantages, is considered to be a very promising precursor of carbons for the view of economic, environmental, and societal issues. However, the preparation of high-performance biomass-derived carbons is still a big challenge because of the multistep process for their synthesis and subsequent activation. Herein, hierarchically porous structured carbon materials have been prepared by directly carbonizing dried cauliflowers without any addition of agents and activation process, featuring with large specific surface area, hierarchically porous structure and improved pore volume, as well as suitable nitrogen content. Being used as a solid-state CO2 adsorbent, the obtained product exhibited a high CO2 adsorption capacity of 3.1 mmol g-1 under 1 bar and 25 °C and a remarkable reusability of 96.7% retention after 20 adsorption/regeneration cycles. Our study reveals that choosing a good biomass source was significant as the unique structure of precursor endows the carbonized product with abundant pores without the need of any post-treatment. Used as an electrode material in electrochemical capacitor, the non-activated porous carbon displayed a fairly high specific capacitance of 228.9 F g-1 at 0.5 A g-1 and an outstanding stability of 99.2% retention after 5000 cycles at 5 A g-1. [Figure not available: see fulltext.

Initial development of the recovery-oriented services assessment: A collaboration with peer-provider consultants.

PubMed

Lodge, Amy C; Kuhn, Wendy; Earley, Juli; Stevens Manser, Stacey

2018-06-01

The Recovery Self-Assessment (RSA) is a reliable and valid tool used to measure recovery-oriented services. Recent studies, however, suggest that the length and reading level of the RSA makes its routine use in service settings difficult. Recognizing the importance of including people with lived experience of a mental health challenge in research processes and the need to enhance the utility of tools that measure recovery-oriented services, this paper describes an innovative researcher-peer provider consultant multistep process used to revise the provider version of the RSA to create a new instrument-the Recovery-Oriented Services Assessment (ROSA). The authors conducted an exploratory factor analysis (EFA) with principal axis factoring extraction and direct oblimin rotation to evaluate the underlying structure of the provider RSA using data from mental health employees (n = 323). To triangulate the findings of the EFA, quantitative and qualitative data were collected from peer provider consultants (n = 9) on the importance of and language of RSA items. EFA results indicated that a 1-factor solution provided the best fit and explained 48% of the total variance. Consultants triangulated EFA results and recommended the addition of 2 items and language revisions. These results were used to develop the ROSA-a 15-item instrument measuring recovery-oriented services with accessible language. Two versions of the ROSA were developed: a staff version and a people-in-services version. The ROSA may provide organizations with a more accessible way to measure the extent to which their services are recovery oriented. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The SDM 3 Circle Model: A Literature Synthesis and Adaptation for Shared Decision Making in the Hospital.

PubMed

Rennke, Stephanie; Yuan, Patrick; Monash, Brad; Blankenburg, Rebecca; Chua, Ian; Harman, Stephanie; Sakai, Debbie S; Khan, Adeena; Hilton, Joan F; Shieh, Lisa; Satterfield, Jason

2017-12-01

Patient engagement through shared decision-making (SDM) is increasingly seen as a key component for patient safety, patient satisfaction, and quality of care. Current SDM models do not adequately account for medical and environmental contexts, which may influence medical decisions in the hospital. We identified leading SDM models and reviews to inductively construct a novel SDM model appropriate for the inpatient setting. A team of medicine and pediatric hospitalists reviewed the literature to integrate core SDM concepts and processes and iteratively constructed a synthesized draft model. We then solicited broad SDM expert feedback on the draft model for validation and further refinement. The SDM 3 Circle Model identifies 3 core categories of variables that dynamically interact within an "environmental frame." The resulting Venn diagram includes overlapping circles for (1) patient/family, (2) provider/team, and (3) medical context. The environmental frame includes all external, contextual factors that may influence any of the 3 circles. Existing multistep SDM process models were then rearticulated and contextualized to illustrate how a shared decision might be made. The SDM 3 Circle Model accounts for important environmental and contextual characteristics that vary across settings. The visual emphasis generated by each "circle" and by the environmental frame direct attention to often overlooked interactive forces and has the potential to more precisely define, promote, and improve SDM. This model provides a framework to develop interventions to improve quality and patient safety through SDM and patient engagement for hospitalists. © 2017 Society of Hospital Medicine.

UML as a cell and biochemistry modeling language.

PubMed

Webb, Ken; White, Tony

2005-06-01

The systems biology community is building increasingly complex models and simulations of cells and other biological entities, and are beginning to look at alternatives to traditional representations such as those provided by ordinary differential equations (ODE). The lessons learned over the years by the software development community in designing and building increasingly complex telecommunication and other commercial real-time reactive systems, can be advantageously applied to the problems of modeling in the biology domain. Making use of the object-oriented (OO) paradigm, the unified modeling language (UML) and Real-Time Object-Oriented Modeling (ROOM) visual formalisms, and the Rational Rose RealTime (RRT) visual modeling tool, we describe a multi-step process we have used to construct top-down models of cells and cell aggregates. The simple example model described in this paper includes membranes with lipid bilayers, multiple compartments including a variable number of mitochondria, substrate molecules, enzymes with reaction rules, and metabolic pathways. We demonstrate the relevance of abstraction, reuse, objects, classes, component and inheritance hierarchies, multiplicity, visual modeling, and other current software development best practices. We show how it is possible to start with a direct diagrammatic representation of a biological structure such as a cell, using terminology familiar to biologists, and by following a process of gradually adding more and more detail, arrive at a system with structure and behavior of arbitrary complexity that can run and be observed on a computer. We discuss our CellAK (Cell Assembly Kit) approach in terms of features found in SBML, CellML, E-CELL, Gepasi, Jarnac, StochSim, Virtual Cell, and membrane computing systems.

If we build it, will they come? Curation and use of the ESO telescope bibliography

NASA Astrophysics Data System (ADS)

Grothkopf, Uta; Meakins, Silvia; Bordelon, Dominic

2015-12-01

The ESO Telescope Bibliography (telbib) is a database of refereed papers published by the ESO users community. It links data in the ESO Science Archive with the published literature, and vice versa. Developed and maintained by the ESO library, telbib also provides insights into the organization's research output and impact as measured through bibliometric studies. Curating telbib is a multi-step process that involves extensive tagging of the database records. Based on selected use cases, this talk will explain how the rich metadata provide parameters for reports and statistics in order to investigate the performance of ESO's facilities and to understand trends and developments in the publishing behaviour of the user community.

Notch3 is required for arterial identity and maturation of vascular smooth muscle cells

PubMed Central

Domenga, Valérie; Fardoux, Peggy; Lacombe, Pierre; Monet, Marie; Maciazek, Jacqueline; Krebs, Luke T.; Klonjkowski, Bernard; Berrou, Eliane; Mericskay, Matthias; Li, Zhen; Tournier-Lasserve, Elisabeth; Gridley, Thomas; Joutel, Anne

2004-01-01

Formation of a fully functional artery proceeds through a multistep process. Here we show that Notch3 is required to generate functional arteries in mice by regulating arterial differentiation and maturation of vascular smooth muscle cells (vSMC). In adult Notch3–/– mice distal arteries exhibit structural defects and arterial myogenic responses are defective. The postnatal maturation stage of vSMC is deficient in Notch3–/– mice. We further show that Notch3 is required for arterial specification of vSMC but not of endothelial cells. Our data reveal Notch3 to be the first cell-autonomous regulator of arterial differentiation and maturation of vSMC. PMID:15545631

Regulation of floral stem cell termination in Arabidopsis

PubMed Central

Sun, Bo; Ito, Toshiro

2015-01-01

In Arabidopsis, floral stem cells are maintained only at the initial stages of flower development, and they are terminated at a specific time to ensure proper development of the reproductive organs. Floral stem cell termination is a dynamic and multi-step process involving many transcription factors, chromatin remodeling factors and signaling pathways. In this review, we discuss the mechanisms involved in floral stem cell maintenance and termination, highlighting the interplay between transcriptional regulation and epigenetic machinery in the control of specific floral developmental genes. In addition, we discuss additional factors involved in floral stem cell regulation, with the goal of untangling the complexity of the floral stem cell regulatory network. PMID:25699061

Malignant Transformation and Stromal Invasion from Normal or Hyperplastic Tissues: True or False?

PubMed Central

Man, Yan-gao; Grinkemeyer, Michael; Izadjoo, Mina; Stojadinovic, Alexander

2011-01-01

Carcinogenesis is believed to be a multi-step process, progressing sequentially from normal to hyperplastic, to in situ, and to invasive stages. A number of studies, however, have detected malignancy-associated alterations in normal or hyperplastic tissues. As the molecular profile and clinical features of these tissues have not been defined, the authors invited several well-recognized pathologist, oncologists, biologist, surgeons, and molecular biologist to offer their opinion on: (1) whether these tissues belong to a previously unrevealed malignant entity or focal alterations with no significant consequence? (2) whether these alterations are linked to early onset of cancer or cancer of unknown primary site, and (3) how to further define these lesions? PMID:21811519

Chemical Control over T-Cell Activation in Vivo Using Deprotection of trans-Cyclooctene-Modified Epitopes.

PubMed

van der Gracht, Anouk M F; de Geus, Mark A R; Camps, Marcel G M; Ruckwardt, Tracy J; Sarris, Alexi J C; Bremmers, Jessica; Maurits, Elmer; Pawlak, Joanna B; Posthoorn, Michelle M; Bonger, Kimberly M; Filippov, Dmitri V; Overkleeft, Herman S; Robillard, Marc S; Ossendorp, Ferry; van Kasteren, Sander I

2018-06-15

Activation of a cytotoxic T-cell is a complex multistep process, and tools to study the molecular events and their dynamics that result in T-cell activation in situ and in vivo are scarce. Here, we report the design and use of conditional epitopes for time-controlled T-cell activation in vivo. We show that trans-cyclooctene-protected SIINFEKL (with the lysine amine masked) is unable to elicit the T-cell response characteristic for the free SIINFEKL epitope. Epitope uncaging by means of an inverse-electron demand Diels-Alder (IEDDA) event restored T-cell activation and provided temporal control of T-cell proliferation in vivo.

How Messenger RNA and Nascent Chain Sequences Regulate Translation Elongation.

PubMed

Choi, Junhong; Grosely, Rosslyn; Prabhakar, Arjun; Lapointe, Christopher P; Wang, Jinfan; Puglisi, Joseph D

2018-06-20

Translation elongation is a highly coordinated, multistep, multifactor process that ensures accurate and efficient addition of amino acids to a growing nascent-peptide chain encoded in the sequence of translated messenger RNA (mRNA). Although translation elongation is heavily regulated by external factors, there is clear evidence that mRNA and nascent-peptide sequences control elongation dynamics, determining both the sequence and structure of synthesized proteins. Advances in methods have driven experiments that revealed the basic mechanisms of elongation as well as the mechanisms of regulation by mRNA and nascent-peptide sequences. In this review, we highlight how mRNA and nascent-peptide elements manipulate the translation machinery to alter the dynamics and pathway of elongation.

Terahertz carpet cloak based on ultrathin metasurface

NASA Astrophysics Data System (ADS)

Wei, Minggui; Yang, Quanlong; Zhang, Xueqian; Li, Yanfeng; Gu, Jianqiang; Han, Jiaguang; Zhang, Weili

2018-01-01

Ultrathin metasurfaces with local phase compensation deliver new schemes to cloaking devices. We demonstrate a remarkable large size carpet cloak realized by an ultrathin metasurface at terahertz frequencies. The metasurface cloak is constructed by periodically arranging 12 different elements. The reflected wave front is perfectly reconstructed by an ultrathin metasurface cloak, which perform well under both intensity-sensitive and phase-sensitive detectors. The invisibility is verified when the cloak is placed on a reflecting triangular surface (bump). The multi-step discrete phase design method would greatly simplify the design process and is probable to achieve large-dimension cloaks, for applications in radar and antenna systems as a thin and easy-to-fabricate solution for radio and terahertz frequencies.

Procongopain from Trypanosoma congolense is processed at basic pH: an unusual feature among cathepsin L-like cysteine proteases.

PubMed

Serveau, Carole; Boulangé, Alain; Lecaille, Fabien; Gauthier, Francis; Authié, Edith; Lalmanach, Gilles

2003-06-01

Congopain, the major cysteine protease from Trypanosoma congolense, is synthesized as an inactive zymogen, and further converted into its active form after removal of the proregion, most probably via an autocatalytic mechanism. Processing of recombinant procongopain occurs via an apparent one-step or a multistep mechanism depending on the ionic strength. The auto-activation is pH-dependent, with an optimum at pH 4.0, and no activation observed at pH 6.0. After addition of dextran sulfate (10 microg/ml), an approx. 20-fold increase of processing (expressed as enzymatic activity) is observed. Furthermore, in the presence of dextran sulfate, procongopain can be processed at pH 8.0, an unusual feature among papain-like enzymes. Detection of procongopain and trypanosomal enzymatic activity in the plasma of T. congolense-infected cattle, together with the capacity of procongopain to be activated at weakly basic pH, suggest that procongopain may be extracellularly processed in the presence of blood vessel glycosaminoglycans, supporting the hypothesis that congopain acts as a pathogenic factor in host-parasite relationships.

Dynamics of scene representations in the human brain revealed by magnetoencephalography and deep neural networks.

PubMed

Martin Cichy, Radoslaw; Khosla, Aditya; Pantazis, Dimitrios; Oliva, Aude

2017-06-01

Human scene recognition is a rapid multistep process evolving over time from single scene image to spatial layout processing. We used multivariate pattern analyses on magnetoencephalography (MEG) data to unravel the time course of this cortical process. Following an early signal for lower-level visual analysis of single scenes at ~100ms, we found a marker of real-world scene size, i.e. spatial layout processing, at ~250ms indexing neural representations robust to changes in unrelated scene properties and viewing conditions. For a quantitative model of how scene size representations may arise in the brain, we compared MEG data to a deep neural network model trained on scene classification. Representations of scene size emerged intrinsically in the model, and resolved emerging neural scene size representation. Together our data provide a first description of an electrophysiological signal for layout processing in humans, and suggest that deep neural networks are a promising framework to investigate how spatial layout representations emerge in the human brain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multi-step production of a diphoton resonance

NASA Astrophysics Data System (ADS)

Dobrescu, Bogdan A.; Fox, Patrick J.; Kearney, John

2017-06-01

Among the questions that would be raised by the observation of a new resonance at the LHC, particularly pressing are those concerning the production mechanism: What is the initial state? Is the resonance produced independently or in association with other particles? Here we present two weakly-coupled renormalizable models for production of a diphoton resonance that differ in both their initial and final states. In one model, a scalar particle produced through gluon fusion decays into a diphoton particle and a light, long-lived pseudoscalar. In another model, a {Z}\\prime boson produced from the annihilation of a strange-antistrange quark pair undergoes a cascade decay that leads to a diphoton particle and two sterile neutrinos. Various kinematic distributions may differentiate these models from the canonical model where a diphoton particle is directly produced in gluon fusion.

Design optimization and tolerance analysis of a spot-size converter for the taper-assisted vertical integration platform in InP.

PubMed

Tolstikhin, Valery; Saeidi, Shayan; Dolgaleva, Ksenia

2018-05-01

We report on the design optimization and tolerance analysis of a multistep lateral-taper spot-size converter based on indium phosphide (InP), performed using the Monte Carlo method. Being a natural fit to (and a key building block of) the regrowth-free taper-assisted vertical integration platform, such a spot-size converter enables efficient and displacement-tolerant fiber coupling to InP-based photonic integrated circuits at a wavelength of 1.31 μm. An exemplary four-step lateral-taper design featuring 0.35 dB coupling loss at optimal alignment of a standard single-mode fiber; ≥7  μm 1 dB displacement tolerance in any direction in a facet plane; and great stability against manufacturing variances is demonstrated.

Single step transformation of sulphur to Li2S2/Li2S in Li-S batteries

PubMed Central

Helen, M.; Reddy, M. Anji; Diemant, Thomas; Golla-Schindler, Ute; Behm, R. Jürgen; Kaiser, Ute; Fichtner, Maximilian

2015-01-01

Lithium-sulphur batteries have generated tremendous research interest due to their high theoretical energy density and potential cost-effectiveness. The commercial realization of Li-S batteries is still hampered by reduced cycle life associated with the formation of electrolyte soluble higher-order polysulphide (Li2Sx, x = 4–8) intermediates, leading to capacity fading, self-discharge, and a multistep voltage profile. Herein, we have realized a practical approach towards a direct transformation of sulphur to Li2S2/Li2S in lithium-sulphur batteries by alteration of the reaction pathway. A coconut shell derived ultramicroporous carbon-sulphur composite cathode has been used as reaction directing template for the sulphur. The lithiation/delithiation and capacity fading mechanism of microporous carbon confined sulphur composite was revealed by analyzing the subsurface using X-ray photoelectron spectroscopy. No higher-order polysulphides were detected in the electrolyte, on the surface, and in the subsurface of the cathode composite. The altered reaction pathway is reflected by a single-step profile in the discharge/charge of a lithium-sulphur cell. PMID:26173723

A genetically optimized kinetic model for ethanol electro-oxidation on Pt-based binary catalysts used in direct ethanol fuel cells

NASA Astrophysics Data System (ADS)

Sánchez-Monreal, Juan; García-Salaberri, Pablo A.; Vera, Marcos

2017-09-01

A one-dimensional model is proposed for the anode of a liquid-feed direct ethanol fuel cell. The complex kinetics of the ethanol electro-oxidation reaction is described using a multi-step reaction mechanism that considers free and adsorbed intermediate species on Pt-based binary catalysts. The adsorbed species are modeled using coverage factors to account for the blockage of the active reaction sites on the catalyst surface. The reaction rates are described by Butler-Volmer equations that are coupled to a one-dimensional mass transport model, which incorporates the effect of ethanol and acetaldehyde crossover. The proposed kinetic model circumvents the acetaldehyde bottleneck effect observed in previous studies by incorporating CH3CHOHads among the adsorbed intermediates. A multi-objetive genetic algorithm is used to determine the reaction constants using anode polarization and product selectivity data obtained from the literature. By adjusting the reaction constants using the methodology developed here, different catalyst layers could be modeled and their selectivities could be successfully reproduced.

Direct numerical simulations of premixed autoignition in compressible uniformly-sheared turbulence

NASA Astrophysics Data System (ADS)

Towery, Colin; Darragh, Ryan; Poludnenko, Alexei; Hamlington, Peter

2017-11-01

High-speed combustion systems, such as scramjet engines, operate at high temperatures and pressures, extremely short combustor residence times, very high rates of shear stress, and intense turbulent mixing. As a result, the reacting flow can be premixed and have highly-compressible turbulence fluctuations. We investigate the effects of compressible turbulence on the ignition delay time, heat-release-rate (HRR) intermittency, and mode of autoignition of premixed Hydrogen-air fuel in uniformly-sheared turbulence using new three-dimensional direct numerical simulations with a multi-step chemistry mechanism. We analyze autoignition in both the Eulerian and Lagrangian reference frames at eight different turbulence Mach numbers, Mat , spanning the quasi-isentropic, linear thermodynamic, and nonlinear compressibility regimes, with eddy shocklets appearing in the nonlinear regime. Results are compared to our previous study of premixed autoignition in isotropic turbulence at the same Mat and with a single-step reaction mechanism. This previous study found large decreases in delay times and large increases in HRR intermittency between the linear and nonlinear compressibility regimes and that detonation waves could form in both regimes.

A directed-overflow and damage-control N -glycosidase in riboflavin biosynthesis

DOE PAGES

Frelin, Océane; Huang, Lili; Hasnain, Ghulam; ...

2015-02-15

Plants and bacteria synthesize the essential human micronutrient riboflavin (vitamin B2) via the same multistep pathway. The early intermediates of this pathway are notoriously reactive, and may be overproduced in vivo because riboflavin biosynthesis enzymes lack feedback controls. Here we demonstrate disposal of riboflavin intermediates by COG3236 (DUF1768), a protein of previously unknown function that is fused to two different riboflavin pathway enzymes in plants and bacteria (RIBR and RibA, respectively). We present cheminformatic, biochemical, genetic, and genomic evidence to show that: (i) plant and bacterial COG3236 proteins cleave the N-glycosidic bond of the first two intermediates of riboflavin biosynthesis,more » yielding relatively innocuous products; (ii) certain COG3236 proteins are in a multienzyme riboflavin biosynthesis complex that gives them privileged access to riboflavin intermediates; and (iii) COG3236 action in Arabidopsis thaliana and Escherichia coli helps maintain flavin levels. We find COG3236 proteins thus illustrate two emerging principles in chemical biology: directed overflow metabolism, in which excess flux is diverted out of a pathway, and the pre-emption of damage from reactive metabolites.« less

Reversing the conventional leather processing sequence for cleaner leather production.

PubMed

Saravanabhavan, Subramani; Thanikaivelan, Palanisamy; Rao, Jonnalagadda Raghava; Nair, Balachandran Unni; Ramasami, Thirumalachari

2006-02-01

Conventional leather processing generally involves a combination of single and multistep processes that employs as well as expels various biological, inorganic, and organic materials. It involves nearly 14-15 steps and discharges a huge amount of pollutants. This is primarily due to the fact that conventional leather processing employs a "do-undo" process logic. In this study, the conventional leather processing steps have been reversed to overcome the problems associated with the conventional method. The charges of the skin matrix and of the chemicals and pH profiles of the process have been judiciously used for reversing the process steps. This reversed process eventually avoids several acidification and basification/neutralization steps used in conventional leather processing. The developed process has been validated through various analyses such as chromium content, shrinkage temperature, softness measurements, scanning electron microscopy, and physical testing of the leathers. Further, the performance of the leathers is shown to be on par with conventionally processed leathers through bulk property evaluation. The process enjoys a significant reduction in COD and TS by 53 and 79%, respectively. Water consumption and discharge is reduced by 65 and 64%, respectively. Also, the process benefits from significant reduction in chemicals, time, power, and cost compared to the conventional process.

Incorporating evolution of transcription factor binding sites into annotated alignments.

PubMed

Bais, Abha S; Grossmann, Stefen; Vingron, Martin

2007-08-01

Identifying transcription factor binding sites (TFBSs) is essential to elucidate putative regulatory mechanisms. A common strategy is to combine cross-species conservation with single sequence TFBS annotation to yield "conserved TFBSs". Most current methods in this field adopt a multi-step approach that segregates the two aspects. Again, it is widely accepted that the evolutionary dynamics of binding sites differ from those of the surrounding sequence. Hence, it is desirable to have an approach that explicitly takes this factor into account. Although a plethora of approaches have been proposed for the prediction of conserved TFBSs, very few explicitly model TFBS evolutionary properties, while additionally being multi-step. Recently, we introduced a novel approach to simultaneously align and annotate conserved TFBSs in a pair of sequences. Building upon the standard Smith-Waterman algorithm for local alignments, SimAnn introduces additional states for profiles to output extended alignments or annotated alignments. That is, alignments with parts annotated as gaplessly aligned TFBSs (pair-profile hits)are generated. Moreover,the pair- profile related parameters are derived in a sound statistical framework. In this article, we extend this approach to explicitly incorporate evolution of binding sites in the SimAnn framework. We demonstrate the extension in the theoretical derivations through two position-specific evolutionary models, previously used for modelling TFBS evolution. In a simulated setting, we provide a proof of concept that the approach works given the underlying assumptions,as compared to the original work. Finally, using a real dataset of experimentally verified binding sites in human-mouse sequence pairs,we compare the new approach (eSimAnn) to an existing multi-step tool that also considers TFBS evolution. Although it is widely accepted that binding sites evolve differently from the surrounding sequences, most comparative TFBS identification methods do not explicitly consider this.Additionally, prediction of conserved binding sites is carried out in a multi-step approach that segregates alignment from TFBS annotation. In this paper, we demonstrate how the simultaneous alignment and annotation approach of SimAnn can be further extended to incorporate TFBS evolutionary relationships. We study how alignments and binding site predictions interplay at varying evolutionary distances and for various profile qualities.

Free-energy landscape of protein oligomerization from atomistic simulations

PubMed Central

Barducci, Alessandro; Bonomi, Massimiliano; Prakash, Meher K.; Parrinello, Michele

2013-01-01

In the realm of protein–protein interactions, the assembly process of homooligomers plays a fundamental role because the majority of proteins fall into this category. A comprehensive understanding of this multistep process requires the characterization of the driving molecular interactions and the transient intermediate species. The latter are often short-lived and thus remain elusive to most experimental investigations. Molecular simulations provide a unique tool to shed light onto these complex processes complementing experimental data. Here we combine advanced sampling techniques, such as metadynamics and parallel tempering, to characterize the oligomerization landscape of fibritin foldon domain. This system is an evolutionarily optimized trimerization motif that represents an ideal model for experimental and computational mechanistic studies. Our results are fully consistent with previous experimental nuclear magnetic resonance and kinetic data, but they provide a unique insight into fibritin foldon assembly. In particular, our simulations unveil the role of nonspecific interactions and suggest that an interplay between thermodynamic bias toward native structure and residual conformational disorder may provide a kinetic advantage. PMID:24248370

Characteristics of lipid micro- and nanoparticles based on supercritical formation for potential pharmaceutical application

PubMed Central

2013-01-01

The interest of the pharmaceutical industry in lipid drug delivery systems due to their prolonged release profile, biocompatibility, reduction of side effects, and so on is already known. However, conventional methods of preparation of these structures for their use and production in the pharmaceutical industry are difficult since these methods are usually multi-step and involve high amount of organic solvent. Furthermore, some processes need extreme conditions, which can lead to an increase of heterogeneity of particle size and degradation of the drug. An alternative for drug delivery system production is the utilization of supercritical fluid technique. Lipid particles produced by supercritical fluid have shown different physicochemical properties in comparison to lipid particles produced by classical methods. Such particles have shown more physical stability and narrower size distribution. So, in this paper, a critical overview of supercritical fluid-based processes for the production of lipid micro- and nanoparticles is given and the most important characteristics of each process are highlighted. PMID:24034341

Receptor-mediated cell mechanosensing

PubMed Central

Chen, Yunfeng; Ju, Lining; Rushdi, Muaz; Ge, Chenghao; Zhu, Cheng

2017-01-01

Mechanosensing describes the ability of a cell to sense mechanical cues of its microenvironment, including not only all components of force, stress, and strain but also substrate rigidity, topology, and adhesiveness. This ability is crucial for the cell to respond to the surrounding mechanical cues and adapt to the changing environment. Examples of responses and adaptation include (de)activation, proliferation/apoptosis, and (de)differentiation. Receptor-mediated cell mechanosensing is a multistep process that is initiated by binding of cell surface receptors to their ligands on the extracellular matrix or the surface of adjacent cells. Mechanical cues are presented by the ligand and received by the receptor at the binding interface; but their transmission over space and time and their conversion into biochemical signals may involve other domains and additional molecules. In this review, a four-step model is described for the receptor-mediated cell mechanosensing process. Platelet glycoprotein Ib, T-cell receptor, and integrins are used as examples to illustrate the key concepts and players in this process. PMID:28954860

Conversion of Lignocellulosic Biomass to Nanocellulose: Structure and Chemical Process

PubMed Central

Lee, H. V.; Hamid, S. B. A.; Zain, S. K.

2014-01-01

Lignocellulosic biomass is a complex biopolymer that is primary composed of cellulose, hemicellulose, and lignin. The presence of cellulose in biomass is able to depolymerise into nanodimension biomaterial, with exceptional mechanical properties for biocomposites, pharmaceutical carriers, and electronic substrate's application. However, the entangled biomass ultrastructure consists of inherent properties, such as strong lignin layers, low cellulose accessibility to chemicals, and high cellulose crystallinity, which inhibit the digestibility of the biomass for cellulose extraction. This situation offers both challenges and promises for the biomass biorefinery development to utilize the cellulose from lignocellulosic biomass. Thus, multistep biorefinery processes are necessary to ensure the deconstruction of noncellulosic content in lignocellulosic biomass, while maintaining cellulose product for further hydrolysis into nanocellulose material. In this review, we discuss the molecular structure basis for biomass recalcitrance, reengineering process of lignocellulosic biomass into nanocellulose via chemical, and novel catalytic approaches. Furthermore, review on catalyst design to overcome key barriers regarding the natural resistance of biomass will be presented herein. PMID:25247208

Degradable and porous Fe-Mn-C alloy for biomaterials candidate

NASA Astrophysics Data System (ADS)

Pratesa, Yudha; Harjanto, Sri; Larasati, Almira; Suharno, Bambang; Ariati, Myrna

2018-02-01

Nowadays, degradable implants attract attention to be developed because it can improve the quality of life of patients. The degradable implant is expected to degrade easily in the body until the bone healing process already achieved. However, there is limited material that could be used as a degradable implant, polymer, magnesium, and iron. In the previous study, Fe-Mn-C alloys had succesfully produced austenitic phase. However, the weakness of the alloy is degradation rate of materials was considered below the expectation. This study aimed to produce porous Fe-Mn-C materials to improve degradation rate and reduce the density of alloy without losing it non-magnetic properties. Potassium carbonate (K2CO3) were chosen as filler material to produce foam structure by sintering and dissolution process. Multisteps sintering process under argon gas environment was performed to generate austenite phase. The product showed an increment of the degradation rate of the foamed Fe-Mn-C alloy compared with the solid Fe-Mn-C alloy without losing the Austenitic Structure

Introductory Biology Textbooks Under-Represent Scientific Process

PubMed Central

Duncan, Dara B.; Lubman, Alexandra; Hoskins, Sally G.

2011-01-01

Attrition of undergraduates from Biology majors is a long-standing problem. Introductory courses that fail to engage students or spark their curiosity by emphasizing the open-ended and creative nature of biological investigation and discovery could contribute to student detachment from the field. Our hypothesis was that introductory biology books devote relatively few figures to illustration of the design and interpretation of experiments or field studies, thereby de-emphasizing the scientific process. To investigate this possibility, we examined figures in six Introductory Biology textbooks published in 2008. On average, multistep scientific investigations were presented in fewer than 5% of the hundreds of figures in each book. Devoting such a small percentage of figures to the processes by which discoveries are made discourages an emphasis on scientific thinking. We suggest that by increasing significantly the illustration of scientific investigations, textbooks could support undergraduates’ early interest in biology, stimulate the development of design and analytical skills, and inspire some students to participate in investigations of their own. PMID:23653758

Copper indium gallium selenide (CIGS) photovoltaic devices made using multistep selenization of nanocrystal films.

PubMed

Harvey, Taylor B; Mori, Isao; Stolle, C Jackson; Bogart, Timothy D; Ostrowski, David P; Glaz, Micah S; Du, Jiang; Pernik, Douglas R; Akhavan, Vahid A; Kesrouani, Hady; Vanden Bout, David A; Korgel, Brian A

2013-09-25

The power conversion efficiency of photovoltaic devices made with ink-deposited Cu(InxGa1-x)Se2 (CIGS) nanocrystal layers can be enhanced by sintering the nanocrystals with a high temperature selenization process. This process, however, can be challenging to control. Here, we report that ink deposition followed by annealing under inert gas and then selenization can provide better control over CIGS nanocrystal sintering and yield generally improved device efficiency. Annealing under argon at 525 °C removes organic ligands and diffuses sodium from the underlying soda lime glass into the Mo back contact to improve the rate and quality of nanocrystal sintering during selenization at 500 °C. Shorter selenization time alleviates excessive MoSe2 formation at the Mo back contact that leads to film delamination, which in turn enables multiple cycles of nanocrystal deposition and selenization to create thicker, more uniform absorber films. Devices with power conversion efficiency greater than 7% are fabricated using the multiple step nanocrystal deposition and sintering process.

Light-induced electronic non-equilibrium in plasmonic particles.

PubMed

Kornbluth, Mordechai; Nitzan, Abraham; Seideman, Tamar

2013-05-07

We consider the transient non-equilibrium electronic distribution that is created in a metal nanoparticle upon plasmon excitation. Following light absorption, the created plasmons decohere within a few femtoseconds, producing uncorrelated electron-hole pairs. The corresponding non-thermal electronic distribution evolves in response to the photo-exciting pulse and to subsequent relaxation processes. First, on the femtosecond timescale, the electronic subsystem relaxes to a Fermi-Dirac distribution characterized by an electronic temperature. Next, within picoseconds, thermalization with the underlying lattice phonons leads to a hot particle in internal equilibrium that subsequently equilibrates with the environment. Here we focus on the early stage of this multistep relaxation process, and on the properties of the ensuing non-equilibrium electronic distribution. We consider the form of this distribution as derived from the balance between the optical absorption and the subsequent relaxation processes, and discuss its implication for (a) heating of illuminated plasmonic particles, (b) the possibility to optically induce current in junctions, and (c) the prospect for experimental observation of such light-driven transport phenomena.

Rodent Zic Genes in Neural Network Wiring.

PubMed

Herrera, Eloísa

2018-01-01

The formation of the nervous system is a multistep process that yields a mature brain. Failure in any of the steps of this process may cause brain malfunction. In the early stages of embryonic development, neural progenitors quickly proliferate and then, at a specific moment, differentiate into neurons or glia. Once they become postmitotic neurons, they migrate to their final destinations and begin to extend their axons to connect with other neurons, sometimes located in quite distant regions, to establish different neural circuits. During the last decade, it has become evident that Zic genes, in addition to playing important roles in early development (e.g., gastrulation and neural tube closure), are involved in different processes of late brain development, such as neuronal migration, axon guidance, and refinement of axon terminals. ZIC proteins are therefore essential for the proper wiring and connectivity of the brain. In this chapter, we review our current knowledge of the role of Zic genes in the late stages of neural circuit formation.

Free-energy landscape of protein oligomerization from atomistic simulations.

PubMed

Barducci, Alessandro; Bonomi, Massimiliano; Prakash, Meher K; Parrinello, Michele

2013-12-03

In the realm of protein-protein interactions, the assembly process of homooligomers plays a fundamental role because the majority of proteins fall into this category. A comprehensive understanding of this multistep process requires the characterization of the driving molecular interactions and the transient intermediate species. The latter are often short-lived and thus remain elusive to most experimental investigations. Molecular simulations provide a unique tool to shed light onto these complex processes complementing experimental data. Here we combine advanced sampling techniques, such as metadynamics and parallel tempering, to characterize the oligomerization landscape of fibritin foldon domain. This system is an evolutionarily optimized trimerization motif that represents an ideal model for experimental and computational mechanistic studies. Our results are fully consistent with previous experimental nuclear magnetic resonance and kinetic data, but they provide a unique insight into fibritin foldon assembly. In particular, our simulations unveil the role of nonspecific interactions and suggest that an interplay between thermodynamic bias toward native structure and residual conformational disorder may provide a kinetic advantage.

Anaerobic Digestion.

PubMed

Liebetrau, Jan; Sträuber, Heike; Kretzschmar, Jörg; Denysenko, Velina; Nelles, Michael

2017-04-09

The term anaerobic digestion usually refers to the microbial conversion of organic material to biogas, which mainly consists of methane and carbon dioxide. The technical application of the naturally-occurring process is used to provide a renewable energy carrier and - as the substrate is often waste material - to reduce the organic matter content of the substrate prior to disposal.Applications can be found in sewage sludge treatment, the treatment of industrial and municipal solid wastes and wastewaters (including landfill gas utilization), and the conversion of agricultural residues and energy crops.For biorefinery concepts, the anaerobic digestion (AD) process is, on the one hand, an option to treat organic residues from other production processes. Concomitant effects are the reduction of organic carbon within the treated substance, the conversion of nitrogen and sulfur components, and the production of an energy-rich gas - the biogas. On the other hand, the multistep conversion of complex organic material offers the possibility of interrupting the conversion chain and locking out intermediates for utilization as basic material within the chemical industry.

Factors controlling beryllium-7 at Jungfraujoch in Switzerland

NASA Astrophysics Data System (ADS)

Zanis, P.; Schuepbach, E.; Gäggeler, H. W.; Hübener, S.; Tobler, L.

1999-09-01

7Be activity concentrations were measured at the alpine research station at Jungfraujoch (JFJ), Switzerland (07°59' E/46°32'N/3580 m asl) from 4 April 1996 to 1 January 1997 with a time resolution of 2days using gamma spectroscopy. The data were analysed in relation to meteorological parameters (potential temperature at tropopause level, relative humidity, potential temperature at JFJ), and total ozone at Arosa in eastern Switzerland. Composite 500 hPa geopotential height maps were computed for days with high and low 7Be activity concentrations. It was found that downward transport associated with an upper ridge and a high tropopause is a significant controlling mechanism for high 7Be activity concentrations at JFJ. In addition, wet scavenging is also important. A multiple linear regression model using potential temperature at tropopause level and relative humidity at JFJ as predictors explained 60% of the variability in the 7Be activity concentrations over the investigated period. The results indicate that the indirect influence of stratosphere troposphere exchange (STE) to the 7Be activity concentrations at JFJ may be more important than the direct one during the period under investigation. The vigorous downward transport of stratospheric air to JFJ may be considered as the direct influence from STE, whereas a multistep transport process with a longer tropospheric age of the stratospheric air masses may be considered as the indirect one. The indirect influence of stratosphere troposphere exchange is investigated in a case study in which the highest 7Be concentration, occurring from 16 to 23 July at JFJ, is associated with stratosphere troposphere transport above northern Europe and strong southward advection with subsequent subsidence.

Ultra-selective high-flux membranes from directly synthesized zeolite nanosheets

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

Jeon, Mi Young; Kim, Donghun; Kumar, Prashant

A zeolite with structure type MFI is an aluminosilicate or silicate material that has a three-dimensionally connected pore network, which enables molecular recognition in the size range 0.5-0.6 nm. These micropore dimensions are relevant for many valuable chemical intermediates, and therefore MFI-type zeolites are widely used in the chemical industry as selective catalysts or adsorbents. As with all zeolites, strategies to tailor them for specific applications include controlling their crystal size and shape. Nanometre-thick MFI crystals (nanosheets) have been introduced in pillared and self-pillared (intergrown) architectures, offering improved mass-transfer characteristics for certain adsorption and catalysis applications. Moreover, single (non-intergrown andmore » nonlayered) nanosheets have been used to prepare thin membranes that could be used to improve the energy efficiency of separation processes. However, until now, single MFI nanosheets have been prepared using a multi-step approach based on the exfoliation of layered MFI9,15, followed by centrifugation to remove non-exfoliated particles. This top-down method is time-consuming, costly and low-yield and it produces fragmented nanosheets with submicrometre lateral dimensions. Alternatively, direct (bottom-up) synthesis could produce high-aspect-ratio zeolite nanosheets, with improved yield and at lower cost. Here we use a nanocrystal-seeded growth method triggered by a single rotational intergrowth to synthesize high-aspect-ratio MFI nanosheets with a thickness of 5 nanometres (2.5 unit cells). These high-aspect-ratio nanosheets allow the fabrication of thin and defect-free coatings that effectively cover porous substrates. Finally, these coatings can be intergrown to produce high-flux and ultra-selective MFI membranes that compare favourably with other MFI membranes prepared from existing MFI materials (such as exfoliated nanosheets or nanocrystals).« less

Ultra-selective high-flux membranes from directly synthesized zeolite nanosheets

DOE PAGES

Jeon, Mi Young; Kim, Donghun; Kumar, Prashant; ...

2017-03-15

A zeolite with structure type MFI is an aluminosilicate or silicate material that has a three-dimensionally connected pore network, which enables molecular recognition in the size range 0.5-0.6 nm. These micropore dimensions are relevant for many valuable chemical intermediates, and therefore MFI-type zeolites are widely used in the chemical industry as selective catalysts or adsorbents. As with all zeolites, strategies to tailor them for specific applications include controlling their crystal size and shape. Nanometre-thick MFI crystals (nanosheets) have been introduced in pillared and self-pillared (intergrown) architectures, offering improved mass-transfer characteristics for certain adsorption and catalysis applications. Moreover, single (non-intergrown andmore » nonlayered) nanosheets have been used to prepare thin membranes that could be used to improve the energy efficiency of separation processes. However, until now, single MFI nanosheets have been prepared using a multi-step approach based on the exfoliation of layered MFI9,15, followed by centrifugation to remove non-exfoliated particles. This top-down method is time-consuming, costly and low-yield and it produces fragmented nanosheets with submicrometre lateral dimensions. Alternatively, direct (bottom-up) synthesis could produce high-aspect-ratio zeolite nanosheets, with improved yield and at lower cost. Here we use a nanocrystal-seeded growth method triggered by a single rotational intergrowth to synthesize high-aspect-ratio MFI nanosheets with a thickness of 5 nanometres (2.5 unit cells). These high-aspect-ratio nanosheets allow the fabrication of thin and defect-free coatings that effectively cover porous substrates. Finally, these coatings can be intergrown to produce high-flux and ultra-selective MFI membranes that compare favourably with other MFI membranes prepared from existing MFI materials (such as exfoliated nanosheets or nanocrystals).« less

Immunotherapy in ovarian cancer.

PubMed

Odunsi, K

2017-11-01

Immunological destruction of tumors is a multistep, coordinated process that can be modulated or targeted at several critical points to elicit tumor rejection. These steps in the cancer immunity cycle include: (i) generation of sufficient numbers of effector T cells with high avidity recognition of tumor antigens in vivo; (ii) trafficking and infiltration into the tumor; (iii) overcoming inhibitory networks in the tumor microenvironment; (iv) direct recognition of tumor antigens and generation of an effector anti-tumor response; and (v) persistence of the anti-tumor T cells. In an effort to understand whether the immune system plays a role in controlling ovarian cancer, our group and others demonstrated that the presence of tumor infiltrating lymphocytes (TILs) is associated with improved clinical outcome in ovarian cancer patients. Recently, we hypothesized that the quality of infiltrating T cells could also be a critical determinant of outcome in ovarian cancer patients. In the past decade, several immune-based interventions have gained regulatory approval in many solid tumors and hematologic malignancies. These interventions include immune checkpoint blockade, cancer vaccines, and adoptive cell therapy. There are currently no approved immune therapies for ovarian cancer. Immunotherapy in ovarian cancer will have to consider the immune suppressive networks within the ovarian tumor microenvironment; therefore, a major direction is to develop biomarkers that would predict responsiveness to different types of immunotherapies, and allow for treatment selection based on the results. Moreover, such biomarkers would allow rational combination of immunotherapies, while minimizing toxicities. In this review, the current understanding of the host immune response in ovarian cancer patients will be briefly reviewed, progress in immune therapies, and future directions for exploiting immune based strategies for long lasting durable cure. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Synthesis of nano-sized lithium cobalt oxide via a sol-gel method

NASA Astrophysics Data System (ADS)

Li, Guangfen; Zhang, Jing

2012-07-01

In this study, nano-structured LiCoO2 thin film were synthesized by coupling a sol-gel process with a spin-coating method using polyacrylic acid (PAA) as chelating agent. The optimized conditions for obtaining a better gel formulation and subsequent homogenous dense film were investigated by varying the calcination temperature, the molar mass of PAA, and the precursor's molar ratios of PAA, lithium, and cobalt ions. The gel films on the silicon substrate surfaces were deposited by multi-step spin-coating process for either increasing the density of the gel film or adjusting the quantity of PAA in the film. The gel film was calcined by an optimized two-step heating procedure in order to obtain regular nano-structured LiCoO2 materials. Both atomic force microscopy (AFM) and scanning electron microscopy (SEM) were utilized to analyze the crystalline and the morphology of the films, respectively.

SERS- and Electrochemically Active 3D Plasmonic Liquid Marbles for Molecular-Level Spectroelectrochemical Investigation of Microliter Reactions.

PubMed

Koh, Charlynn Sher Lin; Lee, Hiang Kwee; Phan-Quang, Gia Chuong; Han, Xuemei; Lee, Mian Rong; Yang, Zhe; Ling, Xing Yi

2017-07-17

Liquid marbles are emergent microreactors owing to their isolated environment and the flexibility of materials used. Plasmonic liquid marbles (PLMs) are demonstrated as the smallest spectroelectrochemical microliter-scale reactor for concurrent spectro- and electrochemical analyses. The three-dimensional Ag shell of PLMs are exploited as a bifunctional surface-enhanced Raman scattering (SERS) platform and working electrode for redox process modulation. The combination of SERS and electrochemistry (EC) capabilities enables in situ molecular read-out of transient electrochemical species, and elucidate the potential-dependent and multi-step reaction dynamics. The 3D configuration of our PLM-based EC-SERS system exhibits 2-fold and 10-fold superior electrochemical and SERS performance than conventional 2D platforms. The rich molecular-level electrochemical insights and excellent EC-SERS capabilities offered by our 3D spectroelectrochemical system are pertinent in charge transfer processes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immunotoxins: magic bullets or misguided missiles?

PubMed

Vitetta, E S; Thorpe, P E; Uhr, J W

1993-05-01

Thirteen years have passed since specific in vitro and in vivo killing of tumour cells by immunotoxins was first described. Why, then, has it taken so long to determine whether these drugs will have a major impact on the treatment of cancer, AIDS and autoimmune disease? The answer is that the transfer of basic discoveries to the clinic is a slow, multistep, interdisciplinary process. Thus, immunotoxin molecules must be designed and redesigned by the basic scientist depending on the efficacy and toxicity shown in vitro and in relevant experimental models. Next, each version must be evaluated by clinicians in humans through a lengthy process (1-3 years) in which the dose regimen is optimized and in which new problems and issues frequently emerge. These problems must again be modelled and studied in animals before additional clinical trials are initiated. In this article, Ellen Vitetta and colleagues discuss both basic and clinical aspects of the development of immunotoxin therapy.

Further Development of Scaffolds for Regeneration of Nerves

NASA Technical Reports Server (NTRS)

Sakamoto, Jeffrey; Tuszynski, Mark

2009-01-01

Progress has been made in continuing research on scaffolds for the guided growth of nerves to replace damaged ones. The scaffolds contain pores that are approximately cylindrical and parallel, with nearly uniform widths ranging from tens to hundreds of microns. At the earlier stage of development, experimental scaffolds had been made from agarose hydrogel. Such a scaffold was made in a multistep process in which poly(methyl methacrylate) [PMMA] fibers were used as templates for the pores. The process included placement of a bundle of the PMMA fibers in a tube, filling the interstices in the tube with a hot agarose solution, cooling to turn the solution into a gel, and then immersion in acetone to dissolve the PMMA fibers. The scaffolds were typically limited to about 25 pores per scaffold, square cross sections of no more than about 1.5 by 1.5 mm, and lengths of no more than about 2 mm.

Self-constructed tree-shape high thermal conductivity nanosilver networks in epoxy.

PubMed

Pashayi, Kamyar; Fard, Hafez Raeisi; Lai, Fengyuan; Iruvanti, Sushumna; Plawsky, Joel; Borca-Tasciuc, Theodorian

2014-04-21

We report the formation of high aspect ratio nanoscale tree-shape silver networks in epoxy, at low temperatures (<150 °C) and atmospheric pressures, that are correlated to a ∼200 fold enhancement of thermal conductivity (κ) of the nanocomposite compared to the polymer matrix. The networks form through a three-step process comprising of self-assembly by diffusion limited aggregation of polyvinylpyrrolidone (PVP) coated nanoparticles, removal of PVP coating from the surface, and sintering of silver nanoparticles in high aspect ratio networked structures. Controlling self-assembly and sintering by carefully designed multistep temperature and time processing leads to κ of our silver nanocomposites that are up to 300% of the present state of the art polymer nanocomposites at similar volume fractions. Our investigation of the κ enhancements enabled by tree-shaped network nanocomposites provides a basis for the development of new polymer nanocomposites for thermal transport and storage applications.

Anti-apoptotic effect of hyperglycemia can allow survival of potentially autoreactive T cells.

PubMed

Ramakrishnan, P; Kahn, D A; Baltimore, D

2011-04-01

Thymocyte development is a tightly controlled multi-step process involving selective elimination of self-reactive and non-functional T cells by apoptosis. This developmental process depends on signaling by Notch, IL-7 and active glucose metabolism. In this study, we explored the requirement of glucose for thymocyte survival and found that in addition to metabolic regulation, glucose leads to the expression of anti-apoptotic genes. Under hyperglycemic conditions, both mouse and human thymocytes demonstrate enhanced survival. We show that glucose-induced anti-apoptotic genes are dependent on NF-κB p65 because high glucose is unable to attenuate normal ongoing apoptosis of thymocytes isolated from p65 knockout mice. Furthermore, we demonstrate that in vivo hyperglycemia decreases apoptosis of thymocytes allowing for survival of potentially self-reactive thymocytes. These results imply that hyperglycemic conditions could contribute to the development of autoimmunity through dysregulated thymic selection. © 2011 Macmillan Publishers Limited

Natural history of hepatic metastases from colorectal cancer--pathobiological pathways with clinical significance.

PubMed

Paschos, Konstantinos A; Majeed, Ali W; Bird, Nigel C

2014-04-14

Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

Health promotion and disease prevention through sanitation education in South African Zulu and Xhosa women.

PubMed

Smith, Maria A; Garbharran, Hari; Edwards, M Jo; O'Hara-Murdock, Peggy

2004-01-01

Poor sanitation and hygiene facilitate transmission of environmental diseases and pose a threat to the health of South African residents. This study focused on identifying sanitation needs from the perspective of informal community residents, addressing need related issues, and empowering Zulu and Xhosa women. The study used a multistep approach to identify and access communities of interest, reflexive critique during data collection from 300 heads of households, and a reiterative process to identify major themes. A process, which impacted 1,467 residents, was developed; it included culturally sensitive presentation styles and educational materials that facilitated understanding of sanitation concepts. Main sanitation themes were health knowledge and community role models. Educational sessions incorporated women. Using women as educators elevated their status and validated their community importance. Project participation added to the educational background of the Zulu and Xhosa women. It empowered them and provided an opportunity for them to articulate community needs.

Structural basis for the recognition and cleavage of abasic DNA in Neisseria meningitidis

PubMed Central

Lu, Duo; Silhan, Jan; MacDonald, James T.; Carpenter, Elisabeth P.; Jensen, Kirsten; Tang, Christoph M.; Baldwin, Geoff S.; Freemont, Paul S.

2012-01-01

Base excision repair (BER) is a highly conserved DNA repair pathway throughout all kingdoms from bacteria to humans. Whereas several enzymes are required to complete the multistep repair process of damaged bases, apurinic-apyrimidic (AP) endonucleases play an essential role in enabling the repair process by recognizing intermediary abasic sites cleaving the phosphodiester backbone 5′ to the abasic site. Despite extensive study, there is no structure of a bacterial AP endonuclease bound to substrate DNA. Furthermore, the structural mechanism for AP-site cleavage is incomplete. Here we report a detailed structural and biochemical study of the AP endonuclease from Neisseria meningitidis that has allowed us to capture structural intermediates providing more complete snapshots of the catalytic mechanism. Our data reveal subtle differences in AP-site recognition and kinetics between the human and bacterial enzymes that may reflect different evolutionary pressures. PMID:23035246

Epigenetic effects of green tea polyphenols in cancer

PubMed Central

Henning, Susanne M; Wang, Piwen; Carpenter, Catherine L; Heber, David

2014-01-01

Epigenetics describes heritable alterations of gene expression and chromatin organization without changes in DNA sequence. Both hypermethylation and hypomethylation of DNA can affect gene expression and the multistep process of carcinogenesis. Epigenetic changes are reversible and may be targeted by dietary interventions. Bioactive compounds from green tea (GT) such as (–)-epigallocatechin gallate have been shown to alter DNA methyltransferase activity in studies of esophageal, oral, skin, Tregs, lung, breast and prostate cancer cells, which may contribute to the chemopreventive effect of GT. Three out of four mouse model studies have confirmed the inhibitory effect of (–)-epigallocatechin gallate on DNA methylation. A human study demonstrated that decreased methylation of CDX2 and BMP-2 in gastric carcinoma was associated with higher GT consumption. It is the goal of this review to summarize our current knowledge of the potential of GT to alter epigenetic processes, which may be useful in chemoprevention. PMID:24283885

Improved fuzzy PID controller design using predictive functional control structure.

PubMed

Wang, Yuzhong; Jin, Qibing; Zhang, Ridong

2017-11-01

In conventional PID scheme, the ensemble control performance may be unsatisfactory due to limited degrees of freedom under various kinds of uncertainty. To overcome this disadvantage, a novel PID control method that inherits the advantages of fuzzy PID control and the predictive functional control (PFC) is presented and further verified on the temperature model of a coke furnace. Based on the framework of PFC, the prediction of the future process behavior is first obtained using the current process input signal. Then, the fuzzy PID control based on the multi-step prediction is introduced to acquire the optimal control law. Finally, the case study on a temperature model of a coke furnace shows the effectiveness of the fuzzy PID control scheme when compared with conventional PID control and fuzzy self-adaptive PID control. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Influence of the artificial saliva storage on 3-D surface texture characteristics of contemporary dental nanocomposites.

PubMed

Ţălu, Ştefan; Bramowicz, Miroslaw; Kulesza, Slawomir; Lainović, Tijana; Vilotić, Marko; Blažić, Larisa

2016-11-01

The aim of this study was to analyse the influence of the artificial saliva on a three-dimensional (3-D) surface texture of contemporary dental composites. The representatives of four composites types were tested: nanofilled (Filtek Ultimate Body, FUB), nanohybrid (Filtek Z550, FZ550), microfilled (Gradia Direct, GD) and microhybrid (Filtek Z250, FZ250). The specimens were polymerised and polished by the multistep protocol (SuperSnap, Shofu). Their surface was examined, before and after 3 weeks' exposure to artificial saliva storage. The surface texture was analysed using the atomic force microscope (AFM). The obtained images were processed to calculate the areal autocorrelation function (AACF), anisotropy ratio S tr (texture aspect ratio), and structure function (SF). The log-log plots of SF were used to calculate fractal properties, such as fractal dimension D, and pseudo-topothesy K. The analysis showed changes in surface anisotropy ratio S tr values, which became higher, whereas the S q roughness (root-mean-square) reduced after the artificial saliva storage. All the samples exhibited bifractal structure before the saliva treatment, but only half of them remained bifractal afterwards (GD, FZ250), whereas the other half turned into a monofractal (FUB, FZ550). The cube-count fractal dimension D cc was found to be material- and treatment-insensitive. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

A three-dimensional in vitro model to demonstrate the haptotactic effect of monocyte chemoattractant protein-1 on atherosclerosis-associated monocyte migration

PubMed Central

Ghousifam, Neda; Mortazavian, Seyyed Hamid; Bhowmick, Rudra; Vasquez, Yolanda; Blum, Frank D.; Gappa-Fahlenkamp, Heather

2017-01-01

Monocyte transendothelial migration is a multi-step process critical for the initiation and development of atherosclerosis. The chemokine monocyte chemoattractant protein-1 (MCP-1) is overexpressed during atheroma and its concentration gradients in the extracellular matrix (ECM) is critical for the transendothelial recruitment of monocytes. Based on prior observations, we hypothesize that both free and bound gradients of MCP-1 within the ECM are involved in directing monocyte migration. The interaction between a three-dimensional (3D), cell-free, collagen matrix and MCP-1; and its effect on monocyte migration was measured in this study. Our results showed such an interaction existed between MCP-1 and collagen, as 26% of the total MCP-1 added to the collagen matrix was bound to the matrix after extensive washes. We also characterized the collagen-MCP-1 interaction using biophysical techniques. The treatment of the collagen matrix with MCP-1 lead to increased monocyte migration, and this phenotype was abrogated by treating the matrix with an anti-MCP-1 antibody. Thus, our results indicate a binding interaction between MCP-1 and the collagen matrix, which could elicit a haptotactic effect on monocyte migration. A better understanding of such mechanisms controlling monocyte migration will help identify target cytokines and lead to the development of better anti-inflammatory therapeutic strategies. PMID:28041913

Modeling dynamics for oncogenesis encompassing mutations and genetic instability.

PubMed

Fassoni, Artur C; Yang, Hyun M

2018-06-27

Tumorigenesis has been described as a multistep process, where each step is associated with a genetic alteration, in the direction to progressively transform a normal cell and its descendants into a malignant tumour. Into this work, we propose a mathematical model for cancer onset and development, considering three populations: normal, premalignant and cancer cells. The model takes into account three hallmarks of cancer: self-sufficiency on growth signals, insensibility to anti-growth signals and evading apoptosis. By using a nonlinear expression to describe the mutation from premalignant to cancer cells, the model includes genetic instability as an enabling characteristic of tumour progression. Mathematical analysis was performed in detail. Results indicate that apoptosis and tissue repair system are the first barriers against tumour progression. One of these mechanisms must be corrupted for cancer to develop from a single mutant cell. The results also show that the presence of aggressive cancer cells opens way to survival of less adapted premalignant cells. Numerical simulations were performed with parameter values based on experimental data of breast cancer, and the necessary time taken for cancer to reach a detectable size from a single mutant cell was estimated with respect to some parameters. We find that the rates of apoptosis and mutations have a large influence on the pace of tumour progression and on the time it takes to become clinically detectable.

Atomic features of an autoantigen in heparin-induced thrombocytopenia (HIT).

PubMed

Cai, Zheng; Zhu, Zhiqiang; Greene, Mark I; Cines, Douglas B

2016-07-01

Autoantigen development is poorly understood at the atomic level. Heparin-induced thrombocytopenia (HIT) is an autoimmune thrombotic disorder caused by antibodies to an antigen composed of platelet factor 4 (PF4) and heparin or cellular glycosaminoglycans (GAGs). In solution, PF4 exists as an equilibrium among monomers, dimers and tetramers. Structural studies of these interacting components helped delineate a multi-step process involved in the pathogenesis of HIT. First, heparin binds to the 'closed' end of the PF4 tetramer and stabilizes its conformation; exposing the 'open' end. Second, PF4 arrays along heparin/GAG chains, which approximate tetramers, form large antigenic complexes that enhance antibody avidity. Third, pathogenic HIT antibodies bind to the 'open' end of stabilized PF4 tetramers to form an IgG/PF4/heparin ternary immune complex and also to propagate the formation of 'ultralarge immune complexes' (ULCs) that contain multiple IgG antibodies. Fourth, ULCs signal through FcγRIIA receptors, activating platelets and monocytes directly and generating thrombin, which transactivates hematopoietic and endothelial cells. A non-pathogenic anti-PF4 antibody prevents tetramer formation, binding of pathogenic antibody, platelet activation and thrombosis, providing a new approach to manage HIT. An improved understanding of the pathogenesis of HIT may lead to novel diagnostics and therapeutics for this autoimmune disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Modular Self-Assembly of Protein Cage Lattices for Multistep Catalysis

DOE PAGES

Uchida, Masaki; McCoy, Kimberly; Fukuto, Masafumi; ...

2017-11-13

The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here, we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy: the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from anmore » amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme-packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. As a result, this study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales and exhibits properties and function that arise from the interaction between individual building blocks.« less

Modular Self-Assembly of Protein Cage Lattices for Multistep Catalysis

PubMed Central

Uchida, Masaki; McCoy, Kimberly; Fukuto, Masafumi; Yang, Lin; Yoshimura, Hideyuki; Miettinen, Heini M.; LaFrance, Ben; Patterson, Dustin P.; Schwarz, Benjamin; Karty, Jonathan A.; Prevelige, Peter E.; Lee, Byeongdu; Douglas, Trevor

2018-01-01

The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy; the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from an amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles, and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. This study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales, and exhibits properties and function that arise from the interaction between individual building blocks. PMID:29131580

Evolution of atomic structure during nanoparticle formation

DOE PAGES

Tyrsted, Christoffer; Lock, Nina; Jensen, Kirsten M. Ø.; ...

2014-04-14

Understanding the mechanism of nanoparticle formation during synthesis is a key prerequisite for the rational design and engineering of desirable materials properties, yet remains elusive due to the difficulty of studying structures at the nanoscale under real conditions. Here, the first comprehensive structural description of the formation of a nanoparticle, yttria-stabilized zirconia (YSZ), all the way from its ionic constituents in solution to the final crystal, is presented. The transformation is a complicated multi-step sequence of atomic reorganizations as the material follows the reaction pathway towards the equilibrium product. Prior to nanoparticle nucleation, reagents reorganize into polymeric species whose structuremore » is incompatible with the final product. Instead of direct nucleation of clusters into the final product lattice, a highly disordered intermediate precipitate forms with a local bonding environment similar to the product yet lacking the correct topology. During maturation, bond reforming occurs by nucleation and growth of distinct domains within the amorphous intermediary. The present study moves beyond kinetic modeling by providing detailed real-time structural insight, and it is demonstrated that YSZ nanoparticle formation and growth is a more complex chemical process than accounted for in conventional models. This level of mechanistic understanding of the nanoparticle formation is the first step towards more rational control over nanoparticle synthesis through control of both solution precursors and reaction intermediaries.« less

An integrated one-step system to extract, analyze and annotate all relevant information from image-based cell screening of chemical libraries.

PubMed

Rabal, Obdulia; Link, Wolfgang; Serelde, Beatriz G; Bischoff, James R; Oyarzabal, Julen

2010-04-01

Here we report the development and validation of a complete solution to manage and analyze the data produced by image-based phenotypic screening campaigns of small-molecule libraries. In one step initial crude images are analyzed for multiple cytological features, statistical analysis is performed and molecules that produce the desired phenotypic profile are identified. A naïve Bayes classifier, integrating chemical and phenotypic spaces, is built and utilized during the process to assess those images initially classified as "fuzzy"-an automated iterative feedback tuning. Simultaneously, all this information is directly annotated in a relational database containing the chemical data. This novel fully automated method was validated by conducting a re-analysis of results from a high-content screening campaign involving 33 992 molecules used to identify inhibitors of the PI3K/Akt signaling pathway. Ninety-two percent of confirmed hits identified by the conventional multistep analysis method were identified using this integrated one-step system as well as 40 new hits, 14.9% of the total, originally false negatives. Ninety-six percent of true negatives were properly recognized too. A web-based access to the database, with customizable data retrieval and visualization tools, facilitates the posterior analysis of annotated cytological features which allows identification of additional phenotypic profiles; thus, further analysis of original crude images is not required.

Modular Self-Assembly of Protein Cage Lattices for Multistep Catalysis

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

Uchida, Masaki; McCoy, Kimberly; Fukuto, Masafumi

The assembly of individual molecules into hierarchical structures is a promising strategy for developing three-dimensional materials with properties arising from interaction between the individual building blocks. Virus capsids are elegant examples of biomolecular nanostructures, which are themselves hierarchically assembled from a limited number of protein subunits. Here, we demonstrate the bio-inspired modular construction of materials with two levels of hierarchy: the formation of catalytically active individual virus-like particles (VLPs) through directed self-assembly of capsid subunits with enzyme encapsulation, and the assembly of these VLP building blocks into three-dimensional arrays. The structure of the assembled arrays was successfully altered from anmore » amorphous aggregate to an ordered structure, with a face-centered cubic lattice, by modifying the exterior surface of the VLP without changing its overall morphology, to modulate interparticle interactions. The assembly behavior and resultant lattice structure was a consequence of interparticle interaction between exterior surfaces of individual particles and thus independent of the enzyme cargos encapsulated within the VLPs. These superlattice materials, composed of two populations of enzyme-packaged VLP modules, retained the coupled catalytic activity in a two-step reaction for isobutanol synthesis. As a result, this study demonstrates a significant step toward the bottom-up fabrication of functional superlattice materials using a self-assembly process across multiple length scales and exhibits properties and function that arise from the interaction between individual building blocks.« less

A multicontext approach to promoting transfer of strategy use and self regulation after brain injury: An exploratory study.

PubMed

Toglia, Joan; Johnston, Mark V; Goverover, Yael; Dain, Barry

2010-01-01

Persons with brain injury frequently demonstrate decreased ability to monitor and apply strategies learned in treatment to everyday situations. The aim of this study is to refine, explore and provide preliminary testing of the multicontext approach in promoting strategy use across situations and increasing self-regulation, awareness and functional performance. This study used a single-subject design with repeated measures pre- and post-intervention, with data analysed descriptively and graphically. Four persons with difficulty following multi-step directions, 3-5 years post-TBI, received a nine session intervention programme. Outcome measures included the Awareness Questionnaire, Self-Regulation Skills Interview, Behavior Rating Inventory of Executive Function, Multiple Errands Test and an Executive Function Performance Test sub-task. The process of change within each treatment session was examined with strategy and awareness ratings. All participants demonstrated positive changes in self-regulatory skills and strategy use that was observed across tasks. As expected, general awareness of deficits remained unchanged. Examination of individual participants revealed important, varying patterns of change in strategy use, learning transfer and self-awareness across intervention. Results provide preliminary support for the feasibility and efficacy of the multicontext approach in promoting transfer of strategy use to enhance functional performance and selective aspects of awareness. Further investigation, including a larger controlled study, is needed to confirm or limit these observations.

Neural Differentiation of Embryonic Stem Cells In Vitro: A Road Map to Neurogenesis in the Embryo

PubMed Central

Abranches, Elsa; Silva, Margarida; Pradier, Laurent; Schulz, Herbert; Hummel, Oliver; Henrique, Domingos; Bekman, Evguenia

2009-01-01

Background The in vitro generation of neurons from embryonic stem (ES) cells is a promising approach to produce cells suitable for neural tissue repair and cell-based replacement therapies of the nervous system. Available methods to promote ES cell differentiation towards neural lineages attempt to replicate, in different ways, the multistep process of embryonic neural development. However, to achieve this aim in an efficient and reproducible way, a better knowledge of the cellular and molecular events that are involved in the process, from the initial specification of neuroepithelial progenitors to their terminal differentiation into neurons and glial cells, is required. Methodology/Principal Findings In this work, we characterize the main stages and transitions that occur when ES cells are driven into a neural fate, using an adherent monolayer culture system. We established improved conditions to routinely produce highly homogeneous cultures of neuroepithelial progenitors, which organize into neural tube-like rosettes when they acquire competence for neuronal production. Within rosettes, neuroepithelial progenitors display morphological and functional characteristics of their embryonic counterparts, namely, apico-basal polarity, active Notch signalling, and proper timing of production of neurons and glia. In order to characterize the global gene activity correlated with each particular stage of neural development, the full transcriptome of different cell populations that arise during the in vitro differentiation protocol was determined by microarray analysis. By using embryo-oriented criteria to cluster the differentially expressed genes, we define five gene expression signatures that correlate with successive stages in the path from ES cells to neurons. These include a gene signature for a primitive ectoderm-like stage that appears after ES cells enter differentiation, and three gene signatures for subsequent stages of neural progenitor development, from an early stage that follows neural induction to a final stage preceding terminal differentiation. Conclusions/Significance Overall, our work confirms and extends the cellular and molecular parallels between monolayer ES cell neural differentiation and embryonic neural development, revealing in addition novel aspects of the genetic network underlying the multistep process that leads from uncommitted cells to differentiated neurons. PMID:19621087

Numerical integration of ordinary differential equations of various orders

NASA Technical Reports Server (NTRS)

Gear, C. W.

1969-01-01

Report describes techniques for the numerical integration of differential equations of various orders. Modified multistep predictor-corrector methods for general initial-value problems are discussed and new methods are introduced.

1,5-Diamido-9,10-anthraquinone, a Centrosymmetric Redox-Active Bridge with Two Coupled β-Ketiminato Chelate Functions: Symmetric and Asymmetric Diruthenium Complexes.

PubMed

Ansari, Mohd Asif; Mandal, Abhishek; Paretzki, Alexa; Beyer, Katharina; Fiedler, Jan; Kaim, Wolfgang; Lahiri, Goutam Kumar

2016-06-06

The dinuclear complexes {(μ-H2L)[Ru(bpy)2]2}(ClO4)2 ([3](ClO4)2), {(μ-H2L)[Ru(pap)2]2}(ClO4)2 ([4](ClO4)2), and the asymmetric [(bpy)2Ru(μ-H2L)Ru(pap)2](ClO4)2 ([5](ClO4)2) were synthesized via the mononuclear species [Ru(H3L)(bpy)2]ClO4 ([1]ClO4) and [Ru(H3L)(pap)2]ClO4 ([2]ClO4), where H4L is the centrosymmetric 1,5-diamino-9,10-anthraquinone, bpy is 2,2'-bipyridine, and pap is 2-phenylazopyridine. Electrochemistry of the structurally characterized [1]ClO4, [2]ClO4, [3](ClO4)2, [4](ClO4)2, and [5](ClO4)2 reveals multistep oxidation and reduction processes, which were analyzed by electron paramagnetic resonance (EPR) of paramagnetic intermediates and by UV-vis-NIR spectro-electrochemistry. With support by time-dependent density functional theory (DFT) calculations the redox processes could be assigned. Significant results include the dimetal/bridging ligand mixed spin distribution in 3(3+) versus largely bridge-centered spin in 4(3+)-a result of the presence of Ru(II)-stabilizig pap coligands. In addition to the metal/ligand alternative for electron transfer and spin location, the dinuclear systems allow for the observation of ligand/ligand and metal/metal site differentiation within the multistep redox series. DFT-supported EPR and NIR absorption spectroscopy of the latter case revealed class II mixed-valence behavior of the oxidized asymmetric system 5(3+) with about equal contributions from a radical bridge formulation. In comparison to the analogues with the deprotonated 1,4-diaminoanthraquinone isomer the centrosymmetric H2L(2-) bridge shows anodically shifted redox potentials and weaker electronic coupling between the chelate sites.

Development of pseudo-linear gradient elution for high-throughput resin selectivity screening in RoboColumn® Format.

PubMed

Kiesewetter, André; Menstell, Peter; Peeck, Lars H; Stein, Andreas

2016-11-01

Rapid development of chromatographic processes relies on effective high-throughput screening (HTS) methods. This article describes the development of pseudo-linear gradient elution for resin selectivity screening using RoboColumns ® . It gives guidelines for the implementation of this HTS method on a Tecan Freedom EVO ® robotic platform, addressing fundamental aspects of scale down and liquid handling. The creation of a flexible script for buffer preparation and column operation plus efficient data processing provided the basis for this work. Based on the concept of discretization, linear gradient elution was transformed into multistep gradients. The impact of column size, flow rate, multistep gradient design, and fractionation scheme on separation efficiency was systematically investigated, using a ternary model protein mixture. We identified key parameters and defined optimal settings for effective column performance. For proof of concept, we examined the selectivity of several cation exchange resins using various buffer conditions. The final protocol enabled a clear differentiation of resin selectivity on miniature chromatography column (MCC) scale. Distinct differences in separation behavior of individual resins and the influence of buffer conditions could be demonstrated. Results obtained with the robotic platform were representative and consistent with data generated on a conventional chromatography system. A study on antibody monomer/high molecular weight separation comparing MCC and lab scale under higher loading conditions provided evidence of the applicability of the miniaturized approach to practically relevant feedstocks with challenging separation tasks as well as of the predictive quality for larger scale. A comparison of varying degrees of robotic method complexity with corresponding effort (analysis time and labware consumption) and output quality highlights tradeoffs to select a method appropriate for a given separation challenge or analytical constraints. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1503-1519, 2016. © 2016 American Institute of Chemical Engineers.

Multistep modeling of protein structure: application towards refinement of tyr-tRNA synthetase

NASA Technical Reports Server (NTRS)

Srinivasan, S.; Shibata, M.; Roychoudhury, M.; Rein, R.

1987-01-01

The scope of multistep modeling (MSM) is expanding by adding a least-squares minimization step in the procedure to fit backbone reconstruction consistent with a set of C-alpha coordinates. The analytical solution of Phi and Psi angles, that fits a C-alpha x-ray coordinate is used for tyr-tRNA synthetase. Phi and Psi angles for the region where the above mentioned method fails, are obtained by minimizing the difference in C-alpha distances between the computed model and the crystal structure in a least-squares sense. We present a stepwise application of this part of MSM to the determination of the complete backbone geometry of the 321 N terminal residues of tyrosine tRNA synthetase to a root mean square deviation of 0.47 angstroms from the crystallographic C-alpha coordinates.