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

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.

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.

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;…

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.

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.

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.

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...

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...

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.

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.

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 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

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

Purification of crude glycerol from transesterification reaction of palm oil using direct method and multistep method

NASA Astrophysics Data System (ADS)

Nasir, N. F.; Mirus, M. F.; Ismail, M.

2017-09-01

Crude glycerol which produced from transesterification reaction has limited usage if it does not undergo purification process. It also contains excess methanol, catalyst and soap. Conventionally, purification method of the crude glycerol involves high cost and complex processes. This study aimed to determine the effects of using different purification methods which are direct method (comprises of ion exchange and methanol removal steps) and multistep method (comprises of neutralization, filtration, ion exchange and methanol removal steps). Two crude glycerol samples were investigated; the self-produced sample through the transesterification process of palm oil and the sample obtained from biodiesel plant. Samples were analysed using Fourier Transform Infrared Spectroscopy, Gas Chromatography and High Performance Liquid Chromatography. The results of this study for both samples after purification have showed that the pure glycerol was successfully produced and fatty acid salts were eliminated. Also, the results indicated the absence of methanol in both samples after purification process. In short, the combination of 4 purification steps has contributed to a higher quality of glycerol. Multistep purification method gave a better result compared to the direct method as neutralization and filtration steps helped in removing most excess salt, fatty acid and catalyst.

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.

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.

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.

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

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.

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.

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.

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.

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

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

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.

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.

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.

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.

Multistep-Ahead Air Passengers Traffic Prediction with Hybrid ARIMA-SVMs Models

PubMed Central

Ming, Wei; Xiong, Tao

2014-01-01

The hybrid ARIMA-SVMs prediction models have been established recently, which take advantage of the unique strength of ARIMA and SVMs models in linear and nonlinear modeling, respectively. Built upon this hybrid ARIMA-SVMs models alike, this study goes further to extend them into the case of multistep-ahead prediction for air passengers traffic with the two most commonly used multistep-ahead prediction strategies, that is, iterated strategy and direct strategy. Additionally, the effectiveness of data preprocessing approaches, such as deseasonalization and detrending, is investigated and proofed along with the two strategies. Real data sets including four selected airlines' monthly series were collected to justify the effectiveness of the proposed approach. Empirical results demonstrate that the direct strategy performs better than iterative one in long term prediction case while iterative one performs better in the case of short term prediction. Furthermore, both deseasonalization and detrending can significantly improve the prediction accuracy for both strategies, indicating the necessity of data preprocessing. As such, this study contributes as a full reference to the planners from air transportation industries on how to tackle multistep-ahead prediction tasks in the implementation of either prediction strategy. PMID:24723814

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.

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

Long-term memory-based control of attention in multi-step tasks requires working memory: evidence from domain-specific interference

PubMed Central

Foerster, Rebecca M.; Carbone, Elena; Schneider, Werner X.

2014-01-01

Evidence for long-term memory (LTM)-based control of attention has been found during the execution of highly practiced multi-step tasks. However, does LTM directly control for attention or are working memory (WM) processes involved? In the present study, this question was investigated with a dual-task paradigm. Participants executed either a highly practiced visuospatial sensorimotor task (speed stacking) or a verbal task (high-speed poem reciting), while maintaining visuospatial or verbal information in WM. Results revealed unidirectional and domain-specific interference. Neither speed stacking nor high-speed poem reciting was influenced by WM retention. Stacking disrupted the retention of visuospatial locations, but did not modify memory performance of verbal material (letters). Reciting reduced the retention of verbal material substantially whereas it affected the memory performance of visuospatial locations to a smaller degree. We suggest that the selection of task-relevant information from LTM for the execution of overlearned multi-step tasks recruits domain-specific WM. PMID:24847304

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.

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

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.

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: ...

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…

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

Macro-fingerprint analysis-through-separation of licorice based on FT-IR and 2DCOS-IR

NASA Astrophysics Data System (ADS)

Wang, Yang; Wang, Ping; Xu, Changhua; Yang, Yan; Li, Jin; Chen, Tao; Li, Zheng; Cui, Weili; Zhou, Qun; Sun, Suqin; Li, Huifen

2014-07-01

In this paper, a step-by-step analysis-through-separation method under the navigation of multi-step IR macro-fingerprint (FT-IR integrated with second derivative IR (SD-IR) and 2DCOS-IR) was developed for comprehensively characterizing the hierarchical chemical fingerprints of licorice from entirety to single active components. Subsequently, the chemical profile variation rules of three parts (flavonoids, saponins and saccharides) in the separation process were holistically revealed and the number of matching peaks and correlation coefficients with standards of pure compounds was increasing along the extracting directions. The findings were supported by UPLC results and a verification experiment of aqueous separation process. It has been demonstrated that the developed multi-step IR macro-fingerprint analysis-through-separation approach could be a rapid, effective and integrated method not only for objectively providing comprehensive chemical characterization of licorice and all its separated parts, but also for rapidly revealing the global enrichment trend of the active components in licorice separation process.

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.

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

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…

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.

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.

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

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.

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.

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

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.

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

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.

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.

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...

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.

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.

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.

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.

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.

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.

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

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.

A Bias and Variance Analysis for Multistep-Ahead Time Series Forecasting.

PubMed

Ben Taieb, Souhaib; Atiya, Amir F

2016-01-01

Multistep-ahead forecasts can either be produced recursively by iterating a one-step-ahead time series model or directly by estimating a separate model for each forecast horizon. In addition, there are other strategies; some of them combine aspects of both aforementioned concepts. In this paper, we present a comprehensive investigation into the bias and variance behavior of multistep-ahead forecasting strategies. We provide a detailed review of the different multistep-ahead strategies. Subsequently, we perform a theoretical study that derives the bias and variance for a number of forecasting strategies. Finally, we conduct a Monte Carlo experimental study that compares and evaluates the bias and variance performance of the different strategies. From the theoretical and the simulation studies, we analyze the effect of different factors, such as the forecast horizon and the time series length, on the bias and variance components, and on the different multistep-ahead strategies. Several lessons are learned, and recommendations are given concerning the advantages, disadvantages, and best conditions of use of each strategy.

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.

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.

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.

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.

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...

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

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.

Multi-step process for concentrating magnetic particles in waste sludges

DOEpatents

Watson, John L.

1990-01-01

This invention involves a multi-step, multi-force process for dewatering sludges which have high concentrations of magnetic particles, such as waste sludges generated during steelmaking. This series of processing steps involves (1) mixing a chemical flocculating agent with the sludge; (2) allowing the particles to aggregate under non-turbulent conditions; (3) subjecting the mixture to a magnetic field which will pull the magnetic aggregates in a selected direction, causing them to form a compacted sludge; (4) preferably, decanting the clarified liquid from the compacted sludge; and (5) using filtration to convert the compacted sludge into a cake having a very high solids content. Steps 2 and 3 should be performed simultaneously. This reduces the treatment time and increases the extent of flocculation and the effectiveness of the process. As partially formed aggregates with active flocculating groups are pulled through the mixture by the magnetic field, they will contact other particles and form larger aggregates. This process can increase the solids concentration of steelmaking sludges in an efficient and economic manner, thereby accomplishing either of two goals: (a) it can convert hazardous wastes into economic resources for recycling as furnace feed material, or (b) it can dramatically reduce the volume of waste material which must be disposed.

Multi-step process for concentrating magnetic particles in waste sludges

DOEpatents

Watson, J.L.

1990-07-10

This invention involves a multi-step, multi-force process for dewatering sludges which have high concentrations of magnetic particles, such as waste sludges generated during steelmaking. This series of processing steps involves (1) mixing a chemical flocculating agent with the sludge; (2) allowing the particles to aggregate under non-turbulent conditions; (3) subjecting the mixture to a magnetic field which will pull the magnetic aggregates in a selected direction, causing them to form a compacted sludge; (4) preferably, decanting the clarified liquid from the compacted sludge; and (5) using filtration to convert the compacted sludge into a cake having a very high solids content. Steps 2 and 3 should be performed simultaneously. This reduces the treatment time and increases the extent of flocculation and the effectiveness of the process. As partially formed aggregates with active flocculating groups are pulled through the mixture by the magnetic field, they will contact other particles and form larger aggregates. This process can increase the solids concentration of steelmaking sludges in an efficient and economic manner, thereby accomplishing either of two goals: (a) it can convert hazardous wastes into economic resources for recycling as furnace feed material, or (b) it can dramatically reduce the volume of waste material which must be disposed. 7 figs.

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.

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

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.

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.

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.

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

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.

Whole body MRI, including diffusion-weighted imaging in follow-up of patients with testicular cancer.

PubMed

Mosavi, Firas; Laurell, Anna; Ahlström, Håkan

2015-11-01

Whole body (WB) magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) has become increasingly utilized in cancer imaging, yet the clinical utility of these techniques in follow-up of testicular cancer patients has not been evaluated. The purpose of this study was to evaluate the feasibility of WB MRI with continuous table movement (CTM) technique, including multistep DWI in follow-up of patients with testicular cancer. WB MRI including DWI was performed in follow-up of 71 consecutive patients (median age, 37 years; range 19-84) with histologically confirmed testicular cancer. WB MRI protocol included axial T1-Dixon and T2-BLADE sequences using CTM technique. Furthermore, multi-step DWI was performed using b-value 50 and 1000 s/mm(2). One criterion for feasibility was patient tolerance and satisfactory image quality. Another criterion was the accuracy in detection of any pathological mass, compared to standard of reference. Signal intensity in DWI was used for evaluation of residual mass activity. Clinical, laboratory and imaging follow-up were applied as standard of reference for the evaluation of WB MRI. WB MRI was tolerated in nearly all patients (69/71 patients, 97%) and the image quality was satisfactory. Metal artifacts deteriorated the image quality in six patients, but it did not influence the overall results. No case of clinical relapse was observed during the follow-up time. There was a good agreement between conventional WB MRI and standard of reference in all patients. Three patients showed residual masses and DWI signal was not restricted in these patients. Furthermore, DWI showed abnormally high signal intensity in a normal-sized retroperitoneal lymph node indicating metastasis. The subsequent (18)F-FDG PET/CT could verify the finding. WB MRI with CTM technique including multi-step DWI is feasible in follow-up of patients with testicular cancer. DWI may contribute to important added-value data to conventional MRI sequences regarding the activity of residual masses.

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.

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.

Application of best practice approaches for designing decision support tools: The preparatory education about clinical trials (PRE-ACT) study

PubMed Central

Fleisher, Linda; Ruggieri, Dominique G.; Miller, Suzanne M.; Manne, Sharon; Albrecht, Terrance; Buzaglo, Joanne; Collins, Michael A.; Katz, Michael; Kinzy, Tyler G.; Liu, Tasnuva; Manning, Cheri; Charap, Ellen Specker; Millard, Jennifer; Miller, Dawn M.; Poole, David; Raivitch, Stephanie; Roach, Nancy; Ross, Eric A.; Meropol, Neal J.

2014-01-01

Objective This article describes the rigorous development process and initial feedback of the PRE-ACT (Preparatory Education About Clinical Trials) web-based- intervention designed to improve preparation for decision making in cancer clinical trials. Methods The multi-step process included stakeholder input, formative research, user testing and feedback. Diverse teams (researchers, advocates and developers) participated including content refinement, identification of actors, and development of video scripts. Patient feedback was provided in the final production period and through a vanguard group (N = 100) from the randomized trial. Results Patients/advocates confirmed barriers to cancer clinical trial participation, including lack of awareness and knowledge, fear of side effects, logistical concerns, and mistrust. Patients indicated they liked the tool’s user-friendly nature, the organized and comprehensive presentation of the subject matter, and the clarity of the videos. Conclusion The development process serves as an example of operationalizing best practice approaches and highlights the value of a multi-disciplinary team to develop a theory-based, sophisticated tool that patients found useful in their decision making process. Practice implications Best practice approaches can be addressed and are important to ensure evidence-based tools that are of value to patients and supports the usefulness of a process map in the development of e-health tools. PMID:24813474

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…

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...

Role of novel histone modifications in cancer

PubMed Central

Shanmugam, Muthu K.; Arfuso, Frank; Arumugam, Surendar; Chinnathambi, Arunachalam; Jinsong, Bian; Warrier, Sudha; Wang, Ling Zhi; Kumar, Alan Prem; Ahn, Kwang Seok; Sethi, Gautam; Lakshmanan, Manikandan

2018-01-01

Oncogenesis is a multistep process mediated by a variety of factors including epigenetic modifications. Global epigenetic post-translational modifications have been detected in almost all cancers types. Epigenetic changes appear briefly and do not involve permanent changes to the primary DNA sequence. These epigenetic modifications occur in key oncogenes, tumor suppressor genes, and transcription factors, leading to cancer initiation and progression. The most commonly observed epigenetic changes include DNA methylation, histone lysine methylation and demethylation, histone lysine acetylation and deacetylation. However, there are several other novel post-translational modifications that have been observed in recent times such as neddylation, sumoylation, glycosylation, phosphorylation, poly-ADP ribosylation, ubiquitination as well as transcriptional regulation and these have been briefly discussed in this article. We have also highlighted the diverse epigenetic changes that occur during the process of tumorigenesis and described the role of histone modifications that can occur on tumor suppressor genes as well as oncogenes, which regulate tumorigenesis and can thus form the basis of novel strategies for cancer therapy. PMID:29541423

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.

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

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.

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.

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.

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...

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…

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.

Solvent recyclability in a multistep direct liquefaction process

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

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

1995-12-31

Direct liquefaction research at the Energy & Environmental Research Center (EERC) has, for a number of years, concentrated on developing a direct liquefaction process specifically for low-rank coals (LRCs) through the use of hydrogen-donating solvents and solvents similar to coal-derived liquids, the water/gas shift reaction, and lower-severity reaction conditions. The underlying assumption of all of the research was that advantage could be taken of the reactivity and specific qualities of LRCs to produce a tetrahydrofuran (THF)-soluble material that might be easier to upgrade than the soluble residuum produced during direct liquefaction of high-rank coals. A multistep approach was taken tomore » produce the THF-soluble material, consisting of (1) preconversion treatment to prepare the coal for solubilization, (2) solubilization of the coal in the solvent, and (3) polishing to complete solubilization of the remaining material. The product of these three steps can then be upgraded during a traditional hydrotreatment step. The results of the EERC`s research indicated that additional studies to develop this process more fully were justified. Two areas were targeted for further research: (1) determination of the recyclability of the solvent used during solubilization and (2) determination of the minimum severity required for hydrotreatment of the liquid product. The current project was funded to investigate these two areas.« less

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.

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.

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.

(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

The development of clinical practice guidelines and guidance statements of the American College of Physicians: summary of methods.

PubMed

Qaseem, Amir; Snow, Vincenza; Owens, Douglas K; Shekelle, Paul

2010-08-03

The American College of Physicians (ACP) established its evidence-based clinical practice guidelines program in 1981. The ACP's Guidelines Committee and the staff of the Clinical Programs and Quality of Care Department develop the clinical recommendations. The ACP develops 2 different types of clinical recommendations: clinical practice guidelines and clinical guidance statements. The ACP clinical practice guidelines and guidance statements follow a multistep development process that includes a systematic review of the evidence, deliberation of the evidence by the committee, summary recommendations, and evidence and recommendation grading. All ACP clinical practice guidelines and clinical guidance statements, if not updated, are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.

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.

Curriculum Integration = Course Disintegration: What Does This Mean for Anatomy?

ERIC Educational Resources Information Center

Bolender, David L.; Ettarh, Rajunor; Jerrett, David P.; Laherty, Richard F.

2013-01-01

Many basic scientists including anatomists are currently involved in decisions related to revisions of the undergraduate medical curriculum. Integration is a common theme in many of these decisions. As described by Harden, integration can occur along a multistep continuum from independent, discipline-based courses to a completely interdisciplinary…

PURIFICATION OF RAT LEYDIG CELLS: INCREASED YIELDS AFTER UNIT-GRAVITY SEDIMENTATION OF COLLAGENASE-DISPERSED INTERSTITIAL CELLS

EPA Science Inventory

Abstract

Procedures for purification of Leydig cells have facilitated studies of their regulatory biology. A multistep procedure, that includes a filtration with nylon mesh (100 micron pore size) to separate interstitial cells from the seminiferous tubules, combining centr...

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.

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.

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.

All-Sky Census of Variable Stars from the ATLAS Survey

NASA Astrophysics Data System (ADS)

Heinze, Aren Nathaniel; Tonry, John; Denneau, Larry; Stalder, Brian

2018-01-01

The Asteroid Terrestrial-Impact Last Alert Survey uses two custom-built 0.5 meter telescopes to scan the whole accessible sky down to magnitude 19.5 every two nights, with a cadence optimized to detect small asteroids on their 'final plunge' toward impact with Earth. This cadence is also well suited to the detection of variable stars with a huge range of periods and properties, while ATLAS' use of two filters provides additional scientific depth. From the first two years of ATLAS data we have constructed a catalog of several hundred thousand variable objects with periods from one hour to hundreds of days. These include RR Lyrae stars, Cepheids, eclipsing binaries, spotted stars, ellipsoidal variables, Miras; and other objects both regular and irregular. We describe the construction of this catalog, including our multi-step confirmation process for genuine variables; some big-picture scientific conclusions; and prospects for more detailed results.

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…

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.

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.

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.

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.

Parallel Implicit Runge-Kutta Methods Applied to Coupled Orbit/Attitude Propagation

NASA Astrophysics Data System (ADS)

Hatten, Noble; Russell, Ryan P.

2017-12-01

A variable-step Gauss-Legendre implicit Runge-Kutta (GLIRK) propagator is applied to coupled orbit/attitude propagation. Concepts previously shown to improve efficiency in 3DOF propagation are modified and extended to the 6DOF problem, including the use of variable-fidelity dynamics models. The impact of computing the stage dynamics of a single step in parallel is examined using up to 23 threads and 22 associated GLIRK stages; one thread is reserved for an extra dynamics function evaluation used in the estimation of the local truncation error. Efficiency is found to peak for typical examples when using approximately 8 to 12 stages for both serial and parallel implementations. Accuracy and efficiency compare favorably to explicit Runge-Kutta and linear-multistep solvers for representative scenarios. However, linear-multistep methods are found to be more efficient for some applications, particularly in a serial computing environment, or when parallelism can be applied across multiple trajectories.

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.

The fusion of biology, computer science, and engineering: towards efficient and successful synthetic biology.

PubMed

Linshiz, Gregory; Goldberg, Alex; Konry, Tania; Hillson, Nathan J

2012-01-01

Synthetic biology is a nascent field that emerged in earnest only around the turn of the millennium. It aims to engineer new biological systems and impart new biological functionality, often through genetic modifications. The design and construction of new biological systems is a complex, multistep process, requiring multidisciplinary collaborative efforts from "fusion" scientists who have formal training in computer science or engineering, as well as hands-on biological expertise. The public has high expectations for synthetic biology and eagerly anticipates the development of solutions to the major challenges facing humanity. This article discusses laboratory practices and the conduct of research in synthetic biology. It argues that the fusion science approach, which integrates biology with computer science and engineering best practices, including standardization, process optimization, computer-aided design and laboratory automation, miniaturization, and systematic management, will increase the predictability and reproducibility of experiments and lead to breakthroughs in the construction of new biological systems. The article also discusses several successful fusion projects, including the development of software tools for DNA construction design automation, recursive DNA construction, and the development of integrated microfluidics systems.

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.

Characterization of the Proteome of Cytoplasmic Lipid Droplets in Mouse Enterocytes after a Dietary Fat Challenge

PubMed Central

D’Aquila, Theresa; Sirohi, Devika; Grabowski, Jeffrey M.; Hedrick, Victoria E.; Paul, Lake N.; Greenberg, Andrew S.; Kuhn, Richard J.; Buhman, Kimberly K.

2015-01-01

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 to be regulated by proteins that associate with the CLD; however, mechanistic details of this process are currently unknown. In this study we analyzed the proteome of CLDs isolated from enterocytes harvested from the small intestine of mice following a dietary fat challenge. In this analysis we identified 181 proteins associated with the CLD fraction, of which 37 are associated with known lipid related metabolic pathways. We confirmed the localization of several of these proteins on or around the CLD through confocal and electron microscopy, including perilipin 3, apolipoprotein A-IV, and acyl-CoA synthetase long-chain family member 5. The identification of the enterocyte CLD proteome provides new insight into potential regulators of CLD metabolism and the process of dietary fat absorption. PMID:25992653

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 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

Microfluidic large-scale integration: the evolution of design rules for biological automation.

PubMed

Melin, Jessica; Quake, Stephen R

2007-01-01

Microfluidic large-scale integration (mLSI) refers to the development of microfluidic chips with thousands of integrated micromechanical valves and control components. This technology is utilized in many areas of biology and chemistry and is a candidate to replace today's conventional automation paradigm, which consists of fluid-handling robots. We review the basic development of mLSI and then discuss design principles of mLSI to assess the capabilities and limitations of the current state of the art and to facilitate the application of mLSI to areas of biology. Many design and practical issues, including economies of scale, parallelization strategies, multiplexing, and multistep biochemical processing, are discussed. Several microfluidic components used as building blocks to create effective, complex, and highly integrated microfluidic networks are also highlighted.

Recent Advances in Voltammetry

PubMed Central

Batchelor-McAuley, Christopher; Kätelhön, Enno; Barnes, Edward O; Compton, Richard G; Laborda, Eduardo; Molina, Angela

2015-01-01

Recent progress in the theory and practice of voltammetry is surveyed and evaluated. The transformation over the last decade of the level of modelling and simulation of experiments has realised major advances such that electrochemical techniques can be fully developed and applied to real chemical problems of distinct complexity. This review focuses on the topic areas of: multistep electrochemical processes, voltammetry in ionic liquids, the development and interpretation of theories of electron transfer (Butler–Volmer and Marcus–Hush), advances in voltammetric pulse techniques, stochastic random walk models of diffusion, the influence of migration under conditions of low support, voltammetry at rough and porous electrodes, and nanoparticle electrochemistry. The review of the latter field encompasses both the study of nanoparticle-modified electrodes, including stripping voltammetry and the new technique of ‘nano-impacts’. PMID:26246984

Development of a Peer Teaching-Assessment Program and a Peer Observation and Evaluation Tool

PubMed Central

Trujillo, Jennifer M.; Barr, Judith; Gonyeau, Michael; Van Amburgh, Jenny A.; Matthews, S. James; Qualters, Donna

2008-01-01

Objectives To develop a formalized, comprehensive, peer-driven teaching assessment program and a valid and reliable assessment tool. Methods A volunteer taskforce was formed and a peer-assessment program was developed using a multistep, sequential approach and the Peer Observation and Evaluation Tool (POET). A pilot study was conducted to evaluate the efficiency and practicality of the process and to establish interrater reliability of the tool. Intra-class correlation coefficients (ICC) were calculated. Results ICCs for 8 separate lectures evaluated by 2-3 observers ranged from 0.66 to 0.97, indicating good interrater reliability of the tool. Conclusion Our peer assessment program for large classroom teaching, which includes a valid and reliable evaluation tool, is comprehensive, feasible, and can be adopted by other schools of pharmacy. PMID:19325963

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.

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

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…

Research on operation mode of abrasive grain during grinding

NASA Astrophysics Data System (ADS)

Ivanova, T. N.; Dement’ev, V. B.; Nikitina, O. V.

2018-03-01

The processing of materials by cutting with an abrasive tool is carried out by means of thousands of grains bonded together as a single whole. The quality of the abrasive tool is defined by cutting properties of abrasive grains and depends on features of spreading the temperature field in time and in the abrasive grain volume. Grains are exposed to heating and cooling during work. It leads to undesired effects such as a decrease of durability of grain retention in the binder, hardness, intensification of diffusion and oxidation processes between the binder and the grain, the occurrence of considerable temperature stresses in the grain itself. The obtained equation which allows calculation of temperature field of grain for one rotation of grinding wheel shows that the temperature of the wheel depends on grinding modes and thermophysical properties of abrasive material. Thus, as the time of contact of grain with processed material increases, the temperature in the cutting area rises. As thermophysical properties increase, the temperature in cutting area decreases. Thermal working conditions are determined to be different from each other depending on contact time of the grain and the material. For example, in case of creep-feed grinding, the peak value of temperature is higher than during multistep grinding; the depth of expansion is greater. While the speed of the thermal process in creep-feed grinding is 2-3 times lower than in multistep grinding, the gradient reduces 3-4 times. The analysis of machining methods shows that creep-feed grinding ensures greater depth of grain heating, a smaller heating rate and a reduced velocity gradient. It causes a decrease of probable allotropic modifications and prevents from occurring of heat strokes - cracking of grains due to high temperature falls. Consequently, it is necessary to employ creep-feed grinding to increase the efficiency of abrasive tool employing. Three operation modes of grinding wheel including blunting, full self-sharpening, emergency wear and tear are determined as the result of the research on evaluation of cutting ability of grinding wheels. Recommendations for working capacity of grinding wheels in each operation mode and with a transition from one mode to another are given. As a result of the research, different dependencies were determined. They include dependencies, governing the extent of influence of granularity, difference in height and concentration of grains, geometry parameters of the detail to be machined and the grinding wheel on machining modes and the thickness of the layer cutoff by one grain. They have an influence on the grinding process.

The Synthesis of 2-acetyl-1,4-naphthoquinone: A Multi-step Synthesis.

ERIC Educational Resources Information Center

Green, Ivan R.

1982-01-01

Outlines 2 procedures for synthesizing 2-acetyl-1,4-naphthoquinone to compare relative merits of the two pathways. The major objective of the exercise is to demonstrate that certain factors should be considered when selecting a pathway for synthesis including availability of starting materials, cost of reagents, number of steps involved,…

A Design Science Research Methodology for Developing a Computer-Aided Assessment Approach Using Method Marking Concept

ERIC Educational Resources Information Center

Genemo, Hussein; Miah, Shah Jahan; McAndrew, Alasdair

2016-01-01

Assessment has been defined as an authentic method that plays an important role in evaluating students' learning attitude in acquiring lifelong knowledge. Traditional methods of assessment including the Computer-Aided Assessment (CAA) for mathematics show limited ability to assess students' full work unless multi-step questions are sub-divided…

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

Anti-Urokinase Receptor Antisense Oligonucleotide (uPAR-aODN) to Prevent and Cure Long-Term Space Exploration-Related Retinal Pathological Angiogenesis

NASA Astrophysics Data System (ADS)

Lazzarano, Stefano; Lulli, Matteo; Fibbi, Gabriella; Margheri, Francesca; Papucci, Laura; Serrati, Simona; Witort, Ewa; Chilla, Anastasia; Lapucci, Andrea; Donnini, Martino; Quaglierini, Paolo; Romiti, Alice; Specogna, Rebecca; Del Rosso, Mario; Capaccioli, Sergio

2008-06-01

Angiogenesis underlies a variety of physiological processes and its possible deregulation during long term space exploration needs to be investigated. Angiogenesis is a multistep process of new blood capillary formation, where degradation of the extracellular matrix (ECM) by proteolytic enzymes, including uPA (urokinase plasminogen activator) and opening the way to migration of endothelial cells (EC), is critical. Plasminogen activation system regulates angiogenesis by both uPA-driven ECM degradation and uPA receptor (uPAR). Microgravity and low dose irradiations promote tissue neoangiogeenesis and neovascularization is often common occurence in ophthalmologic pathologies. We have designed and patented the uPAR antisense oligonucleotide (aODN) and evaluated its antiangiogenetic activity by EC cellular migration and capillary morphogenesis assays. The uPAR aODN treatment caused a 75% inhibition of human microvascular EC migration and a complete inhibition of capillary morphogenesis, suggesting its therapeutic application to prevent neoangiogenesis-related ophthalmologic pathologies during space exploration.

High-content screening for the discovery of pharmacological compounds: advantages, challenges and potential benefits of recent technological developments.

PubMed

Soleilhac, Emmanuelle; Nadon, Robert; Lafanechere, Laurence

2010-02-01

Screening compounds with cell-based assays and microscopy image-based analysis is an approach currently favored for drug discovery. Because of its high information yield, the strategy is called high-content screening (HCS). This review covers the application of HCS in drug discovery and also in basic research of potential new pathways that can be targeted for treatment of pathophysiological diseases. HCS faces several challenges, however, including the extraction of pertinent information from the massive amount of data generated from images. Several proposed approaches to HCS data acquisition and analysis are reviewed. Different solutions from the fields of mathematics, bioinformatics and biotechnology are presented. Potential applications and limits of these recent technical developments are also discussed. HCS is a multidisciplinary and multistep approach for understanding the effects of compounds on biological processes at the cellular level. Reliable results depend on the quality of the overall process and require strong interdisciplinary collaborations.

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.

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.

HIPPOCAMPAL CONTRIBUTIONS TO THE PROCESSING OF SOCIAL EMOTIONS

PubMed Central

Immordino-Yang, Mary Helen; Singh, Vanessa

2012-01-01

Inducing and experiencing emotions about others’ mental and physical circumstances is thought to involve self-relevant processing and personal memories of similar experiences. The hippocampus is important for self-referential processing during recall and prospection; however, its contributions during social emotions have not been systematically investigated. We use event-related averaging and Granger causal connectivity mapping to investigate hippocampal contributions during the processing of varieties of admiration and compassion pertaining to protagonists’ mental versus physical circumstances (admiration for virtue, AV, versus for skill; compassion for social/psychological pain, CSP, versus for physical pain). Data were collected using a multistep emotion induction paradigm that included psychosocial interviews, BOLD fMRI and simultaneous psychophysiological recording. Given that mnemonic demands were equivalent among conditions, we tested whether: (1) the hippocampi would be recruited more strongly and for a longer duration during the processing of AV and CSP; (2) connectivity between the hippocampi and cortical systems involved in visceral somatosensation/emotional feeling, social cognitive, and self-related processing would be more extensive during AV and CSP. Results elucidate the hippocampus’ facilitative role in inducing and sustaining appropriate emotional reactions, the importance of self-related processing during social emotions, and corroborate the conception that varieties of emotional processing pertaining to others’ mental and physical situations engage at least partially distinct neural mechanisms. PMID:22012639

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.

Degenerate variational integrators for magnetic field line flow and guiding center trajectories

NASA Astrophysics Data System (ADS)

Ellison, C. L.; Finn, J. M.; Burby, J. W.; Kraus, M.; Qin, H.; Tang, W. M.

2018-05-01

Symplectic integrators offer many benefits for numerically approximating solutions to Hamiltonian differential equations, including bounded energy error and the preservation of invariant sets. Two important Hamiltonian systems encountered in plasma physics—the flow of magnetic field lines and the guiding center motion of magnetized charged particles—resist symplectic integration by conventional means because the dynamics are most naturally formulated in non-canonical coordinates. New algorithms were recently developed using the variational integration formalism; however, those integrators were found to admit parasitic mode instabilities due to their multistep character. This work eliminates the multistep character, and therefore the parasitic mode instabilities via an adaptation of the variational integration formalism that we deem "degenerate variational integration." Both the magnetic field line and guiding center Lagrangians are degenerate in the sense that the resultant Euler-Lagrange equations are systems of first-order ordinary differential equations. We show that retaining the same degree of degeneracy when constructing discrete Lagrangians yields one-step variational integrators preserving a non-canonical symplectic structure. Numerical examples demonstrate the benefits of the new algorithms, including superior stability relative to the existing variational integrators for these systems and superior qualitative behavior relative to non-conservative algorithms.

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.

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…

New Radiotracers for Imaging of Vascular Targets in Angiogenesis-related Diseases

PubMed Central

Hong, Hao; Chen, Feng; Zhang, Yin; Cai, Weibo

2014-01-01

Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients. PMID:25086372

Probability-based constrained MPC for structured uncertain systems with state and random input delays

NASA Astrophysics Data System (ADS)

Lu, Jianbo; Li, Dewei; Xi, Yugeng

2013-07-01

This article is concerned with probability-based constrained model predictive control (MPC) for systems with both structured uncertainties and time delays, where a random input delay and multiple fixed state delays are included. The process of input delay is governed by a discrete-time finite-state Markov chain. By invoking an appropriate augmented state, the system is transformed into a standard structured uncertain time-delay Markov jump linear system (MJLS). For the resulting system, a multi-step feedback control law is utilised to minimise an upper bound on the expected value of performance objective. The proposed design has been proved to stabilise the closed-loop system in the mean square sense and to guarantee constraints on control inputs and system states. Finally, a numerical example is given to illustrate the proposed results.

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

Nuclear transport adapts to varying heat stress in a multistep mechanism.

PubMed

Ogawa, Yutaka; Imamoto, Naoko

2018-05-10

Appropriate cell growth conditions are limited to a narrow temperature range. Once the temperature is out of this range, cells respond to protect themselves, but temperature thresholds at which various intracellular responses occur, including nuclear transport systems, remain unclear. Using a newly developed precise temperature shift assay, we found that individual transport pathways have different sensitivities to a rise in temperature. Nuclear translocations of molecular chaperone HSP70s occur at a much lower temperature than the inhibition of Ran-dependent transport. Subsequently, importin (Imp) α/β-dependent import ceases at a lower temperature than other Ran-dependent transport, suggesting that these are controlled by independent mechanisms. In vitro research revealed that the inhibition of Imp α/β-dependent import is caused by the dysfunction of Imp α1 specifically at lower temperature. Thus, the thermosensitivity of Imp α1 modulates transport balances and enables the multistep shutdown of Ran-dependent transport systems according to the degree of heat stress. © 2018 Ogawa and Imamoto.

Anthocyanin and flavonoid production from Perilla frutescens: pilot plant scale processing including cross-flow microfiltration and reverse osmosis.

PubMed

Meng, Linghua; Lozano, Yves; Bombarda, Isabelle; Gaydou, Emile; Li, Bin

2006-06-14

Extraction and concentration at a pilot plant scale of anthocyanins and flavonoids from Perilla frutescens var. frutescens harvested in the Guangzhou area of China were investigated. The study of extraction efficiency using mineral acids and organic acids showed that 0.01 mol/L nitric acid was the most suitable to extract flavonoids from this slightly red leaf cultivar. The red extract contained 12 mg/L (as cyanidin equivalent) anthocyanins and other flavones. The multistep process included cross-flow microfiltration (CFM) with a ceramic type membrane, reverse osmosis (RO), and rotating evaporation (RE). The filtration fluxes were high and constant for CFM (150 L/h/m2 at 0.6 b) and for RO (22 L/h/m2 at 40 b). The red extract was concentrated 9.4 times by RO and then 5.4 times by RE. It contained 422 mg/L anthocyanins, representing 77% of the total extracted anthocyanin. The proportion of flavonoids was found unchanged during processing. The concentrated extract showed a pH of 2.7, and its free acidity was found to be 46% of the acidity added for extraction, because of the buffering capacity of the extract. At the concentration level reached, a crystallized deposit occurred and was identified as tartrate.

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.

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.

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.

Engineering fluidic delays in paper-based devices using laser direct-writing.

PubMed

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

2015-10-21

We report the use of a new laser-based direct-write technique that allows programmable and timed fluid delivery in channels within a paper substrate which enables implementation of multi-step analytical assays. 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 depth and/or the porosity of hydrophobic barriers which, when fabricated in the fluid path, produce controllable fluid delay. We have patterned these flow delaying barriers at pre-defined locations in the fluidic channels using either a continuous wave laser at 405 nm, or a pulsed laser operating at 266 nm. Using this delay patterning protocol we generated flow delays spanning from a few minutes to over half an hour. Since the channels and flow delay barriers can be written via a common laser-writing process, this is a distinct improvement over other methods that require specialist operating environments, or custom-designed equipment. This technique can therefore be used for rapid fabrication of paper-based microfluidic devices that can perform single or multistep analytical assays.

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.

Measuring NMHC and NMOG emissions from motor vehicles via FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Gierczak, Christine A.; Kralik, Lora L.; Mauti, Adolfo; Harwell, Amy L.; Maricq, M. Matti

2017-02-01

The determination of non-methane organic gases (NMOG) emissions according to United States Environmental Protection Agency (EPA) regulations is currently a multi-step process requiring separate measurement of various emissions components by a number of independent on-line and off-line techniques. The Fourier transform infrared spectroscopy (FTIR) method described in this paper records all required components using a single instrument. It gives data consistent with the regulatory method, greatly simplifies the process, and provides second by second time resolution. Non-methane hydrocarbons (NMHCs) are measured by identifying a group of hydrocarbons, including oxygenated species, that serve as a surrogate for this class, the members of which are dynamically included if they are present in the exhaust above predetermined threshold levels. This yields an FTIR equivalent measure of NMHC that correlates within 5% to the regulatory flame ionization detection (FID) method. NMOG is then determined per regulatory calculation solely from FTIR recorded emissions of NMHC, ethanol, acetaldehyde, and formaldehyde, yielding emission rates that also correlate within 5% with the reference method. Examples are presented to show how the resulting time resolved data benefit aftertreatment development for light duty vehicles.

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

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.

ISPE: A knowledge-based system for fluidization studies

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

Reddy, S.

1991-01-01

Chemical engineers use mathematical simulators to design, model, optimize and refine various engineering plants/processes. This procedure requires the following steps: (1) preparation of an input data file according to the format required by the target simulator; (2) excecuting the simulation; and (3) analyzing the results of the simulation to determine if all specified goals'' are satisfied. If the goals are not met, the input data file must be modified and the simulation repeated. This multistep process is continued until satisfactory results are obtained. This research was undertaken to develop a knowledge based system, IPSE (Intelligent Process Simulation Environment), that canmore » enhance the productivity of chemical engineers/modelers by serving as an intelligent assistant to perform a variety tasks related to process simulation. ASPEN, a widely used simulator by the US Department of Energy (DOE) at Morgantown Energy Technology Center (METC) was selected as the target process simulator in the project. IPSE, written in the C language, was developed using a number of knowledge-based programming paradigms: object-oriented knowledge representation that uses inheritance and methods, rulebased inferencing (includes processing and propagation of probabilistic information) and data-driven programming using demons. It was implemented using the knowledge based environment LASER. The relationship of IPSE with the user, ASPEN, LASER and the C language is shown in Figure 1.« less

[Cytogenetics, cytogenomics and cancer].

PubMed

Bernheim, Alain

2002-02-01

Chromosomal study in malignancy has demonstrated the pivotal role of somatic chromosomal rearrangements in oncogenesis and tumoral progression. Structural or quantitative these abnormalities can now be studied in great details with the various Fish techniques, including CGH on chromosomes or in a near future on micro arrays. The multistep pattern of most solid tumors is characterized and their genomic abnormalities more and more used for the diagnosis and the prognosis.

12-hour shifts: an ethical dilemma for the nurse executive.

PubMed

Lorenz, Susan G

2008-06-01

Flexible work hours, including 12-hour shifts, have become a common scheduling option for nurses. The author explores whether 12-hour shifts are an ethical scheduling option for nurses because recent research suggests that 12-hour shifts are a potential hazard to patients. A multistep model for ethical decision making, reflecting the concept of procedural justice, is used to examine this issue.

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.

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.

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.

Experiences Building Globus Genomics: A Next-Generation Sequencing Analysis Service using Galaxy, Globus, and Amazon Web Services

PubMed Central

Madduri, Ravi K.; Sulakhe, Dinanath; Lacinski, Lukasz; Liu, Bo; Rodriguez, Alex; Chard, Kyle; Dave, Utpal J.; Foster, Ian T.

2014-01-01

We describe Globus Genomics, a system that we have developed for rapid analysis of large quantities of next-generation sequencing (NGS) genomic data. This system achieves a high degree of end-to-end automation that encompasses every stage of data analysis including initial data retrieval from remote sequencing centers or storage (via the Globus file transfer system); specification, configuration, and reuse of multi-step processing pipelines (via the Galaxy workflow system); creation of custom Amazon Machine Images and on-demand resource acquisition via a specialized elastic provisioner (on Amazon EC2); and efficient scheduling of these pipelines over many processors (via the HTCondor scheduler). The system allows biomedical researchers to perform rapid analysis of large NGS datasets in a fully automated manner, without software installation or a need for any local computing infrastructure. We report performance and cost results for some representative workloads. PMID:25342933

Experiences Building Globus Genomics: A Next-Generation Sequencing Analysis Service using Galaxy, Globus, and Amazon Web Services.

PubMed

Madduri, Ravi K; Sulakhe, Dinanath; Lacinski, Lukasz; Liu, Bo; Rodriguez, Alex; Chard, Kyle; Dave, Utpal J; Foster, Ian T

2014-09-10

We describe Globus Genomics, a system that we have developed for rapid analysis of large quantities of next-generation sequencing (NGS) genomic data. This system achieves a high degree of end-to-end automation that encompasses every stage of data analysis including initial data retrieval from remote sequencing centers or storage (via the Globus file transfer system); specification, configuration, and reuse of multi-step processing pipelines (via the Galaxy workflow system); creation of custom Amazon Machine Images and on-demand resource acquisition via a specialized elastic provisioner (on Amazon EC2); and efficient scheduling of these pipelines over many processors (via the HTCondor scheduler). The system allows biomedical researchers to perform rapid analysis of large NGS datasets in a fully automated manner, without software installation or a need for any local computing infrastructure. We report performance and cost results for some representative workloads.

Practical considerations of image analysis and quantification of signal transduction IHC staining.

PubMed

Grunkin, Michael; Raundahl, Jakob; Foged, Niels T

2011-01-01

The dramatic increase in computer processing power in combination with the availability of high-quality digital cameras during the last 10 years has fertilized the grounds for quantitative microscopy based on digital image analysis. With the present introduction of robust scanners for whole slide imaging in both research and routine, the benefits of automation and objectivity in the analysis of tissue sections will be even more obvious. For in situ studies of signal transduction, the combination of tissue microarrays, immunohistochemistry, digital imaging, and quantitative image analysis will be central operations. However, immunohistochemistry is a multistep procedure including a lot of technical pitfalls leading to intra- and interlaboratory variability of its outcome. The resulting variations in staining intensity and disruption of original morphology are an extra challenge for the image analysis software, which therefore preferably should be dedicated to the detection and quantification of histomorphometrical end points.

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

Improving clinical trials in the critically ill.

PubMed

Angus, Derek C; Mira, Jean-Paul; Vincent, Jean-Louis

2010-02-01

To propose ways in which clinical trials in intensive care can be improved. An international roundtable conference was convened focused on improvement in three broad areas: translation of new knowledge from bench to bedside; design and conduct of clinical trials; and clinical trial infrastructure and environment. The roundtable recommendations were: improvement in clinical trials is a multistep process from better preclinical studies to better clinical trial methodology; new technologies should be used to improve models of critical illness; diseasomes and theragnostics will aid inpatient population selection and more appropriate targeting of interventions; broader study end points should include morbidity as well as mortality; more multicenter studies should be conducted by national and international networks or clinical trials groups; and better collaboration is needed with the industry. There was broad agreement among the roundtable participants regarding a number of explicit opportunities for the improvement of clinical trials in critical care.

Controlled droplet microfluidic systems for multistep chemical and biological assays.

PubMed

Kaminski, T S; Garstecki, P

2017-10-16

Droplet microfluidics is a relatively new and rapidly evolving field of science focused on studying the hydrodynamics and properties of biphasic flows at the microscale, and on the development of systems for practical applications in chemistry, biology and materials science. Microdroplets present several unique characteristics of interest to a broader research community. The main distinguishing features include (i) large numbers of isolated compartments of tiny volumes that are ideal for single cell or single molecule assays, (ii) rapid mixing and negligible thermal inertia that all provide excellent control over reaction conditions, and (iii) the presence of two immiscible liquids and the interface between them that enables new or exotic processes (the synthesis of new functional materials and structures that are otherwise difficult to obtain, studies of the functions and properties of lipid and polymer membranes and execution of reactions at liquid-liquid interfaces). The most frequent application of droplet microfluidics relies on the generation of large numbers of compartments either for ultrahigh throughput screens or for the synthesis of functional materials composed of millions of droplets or particles. Droplet microfluidics has already evolved into a complex field. In this review we focus on 'controlled droplet microfluidics' - a portfolio of techniques that provide convenient platforms for multistep complex reaction protocols and that take advantage of automated and passive methods of fluid handling on a chip. 'Controlled droplet microfluidics' can be regarded as a group of methods capable of addressing and manipulating droplets in series. The functionality and complexity of controlled droplet microfluidic systems can be positioned between digital microfluidics (DMF) addressing each droplet individually using 2D arrays of electrodes and ultrahigh throughput droplet microfluidics focused on the generation of hundreds of thousands or even millions of picoliter droplets that cannot be individually addressed by their location on a chip.

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

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

The p27Kip1 Tumor Suppressor and Multi-Step Tumorigenesis

DTIC Science & Technology

2001-08-01

Breast Cancer , Cell cycle, tumor suppressor 33 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19. SECURITY CLASSIFICATION 20...in many cancers , including carcinomas of the breast , colon, lung and prostate, and lymphoma. Although these studies of p27 expression in primary...of DMBA-induced pituitary tumors in p27-/- mice precluded determination of breast cancer risk in these mice. Nevertheless, the extensive mammary tissue

Multi-step contrast sensitivity gauge

DOEpatents

Quintana, Enrico C; Thompson, Kyle R; Moore, David G; Heister, Jack D; Poland, Richard W; Ellegood, John P; Hodges, George K; Prindville, James E

2014-10-14

An X-ray contrast sensitivity gauge is described herein. The contrast sensitivity gauge comprises a plurality of steps of varying thicknesses. Each step in the gauge includes a plurality of recesses of differing depths, wherein the depths are a function of the thickness of their respective step. An X-ray image of the gauge is analyzed to determine a contrast-to-noise ratio of a detector employed to generate the image.

Multi-step heater deployment in a subsurface formation

DOEpatents

Mason, Stanley Leroy [Allen, TX

2012-04-03

A method for installing a horizontal or inclined subsurface heater includes placing a heating section of a heater in a horizontal or inclined section of a wellbore with an installation tool. The tool is uncoupled from the heating section. A lead in section is mechanically and electrically coupled to the heating section of the heater. The lead-in section is located in an angled or vertical section of the wellbore.

Exact free vibration of multi-step Timoshenko beam system with several attachments

NASA Astrophysics Data System (ADS)

Farghaly, S. H.; El-Sayed, T. A.

2016-05-01

This paper deals with the analysis of the natural frequencies, mode shapes of an axially loaded multi-step Timoshenko beam combined system carrying several attachments. The influence of system design and the proposed sub-system non-dimensional parameters on the combined system characteristics are the major part of this investigation. The effect of material properties, rotary inertia and shear deformation of the beam system for each span are included. The end masses are elastically supported against rotation and translation at an offset point from the point of attachment. A sub-system having two degrees of freedom is located at the beam ends and at any of the intermediate stations and acts as a support and/or a suspension. The boundary conditions of the ordinary differential equation governing the lateral deflections and slope due to bending of the beam system including the shear force term, due to the sub-system, have been formulated. Exact global coefficient matrices for the combined modal frequencies, the modal shape and for the discrete sub-system have been derived. Based on these formulae, detailed parametric studies of the combined system are carried out. The applied mathematical model is valid for wide range of applications especially in mechanical, naval and structural engineering fields.

JobCenter: an open source, cross-platform, and distributed job queue management system optimized for scalability and versatility.

PubMed

Jaschob, Daniel; Riffle, Michael

2012-07-30

Laboratories engaged in computational biology or bioinformatics frequently need to run lengthy, multistep, and user-driven computational jobs. Each job can tie up a computer for a few minutes to several days, and many laboratories lack the expertise or resources to build and maintain a dedicated computer cluster. JobCenter is a client-server application and framework for job management and distributed job execution. The client and server components are both written in Java and are cross-platform and relatively easy to install. All communication with the server is client-driven, which allows worker nodes to run anywhere (even behind external firewalls or "in the cloud") and provides inherent load balancing. Adding a worker node to the worker pool is as simple as dropping the JobCenter client files onto any computer and performing basic configuration, which provides tremendous ease-of-use, flexibility, and limitless horizontal scalability. Each worker installation may be independently configured, including the types of jobs it is able to run. Executed jobs may be written in any language and may include multistep workflows. JobCenter is a versatile and scalable distributed job management system that allows laboratories to very efficiently distribute all computational work among available resources. JobCenter is freely available at http://code.google.com/p/jobcenter/.

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

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.

Artificial concurrent catalytic processes involving enzymes.

PubMed

Köhler, Valentin; Turner, Nicholas J

2015-01-11

The concurrent operation of multiple catalysts can lead to enhanced reaction features including (i) simultaneous linear multi-step transformations in a single reaction flask (ii) the control of intermediate equilibria (iii) stereoconvergent transformations (iv) rapid processing of labile reaction products. Enzymes occupy a prominent position for the development of such processes, due to their high potential compatibility with other biocatalysts. Genes for different enzymes can be co-expressed to reconstruct natural or construct artificial pathways and applied in the form of engineered whole cell biocatalysts to carry out complex transformations or, alternatively, the enzymes can be combined in vitro after isolation. Moreover, enzyme variants provide a wider substrate scope for a given reaction and often display altered selectivities and specificities. Man-made transition metal catalysts and engineered or artificial metalloenzymes also widen the range of reactivities and catalysed reactions that are potentially employable. Cascades for simultaneous cofactor or co-substrate regeneration or co-product removal are now firmly established. Many applications of more ambitious concurrent cascade catalysis are only just beginning to appear in the literature. The current review presents some of the most recent examples, with an emphasis on the combination of transition metal with enzymatic catalysis and aims to encourage researchers to contribute to this emerging field.

Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

PubMed

McCue, Justin; Kshirsagar, Rashmi; Selvitelli, Keith; Lu, Qi; Zhang, Mingxuan; Mei, Baisong; Peters, Robert; Pierce, Glenn F; Dumont, Jennifer; Raso, Stephen; Reichert, Heidi

2015-07-01

Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8-15 log10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc. Copyright © 2015 Biogen. Published by Elsevier Ltd.. All rights reserved.

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.

A quarter-long exercise that introduces general education students to neurophysiology and scientific writing.

PubMed

Krilowicz, B I; Henter, H; Kamhi-Stein, L

1997-06-01

Providing large numbers of general education students with an introduction to science is a challenge. To meet this challenge, a quarter-long neurophysiology project was developed for use in an introductory biology course. The primary goals of this multistep project were to introduce students to the scientific method, scientific writing, on-line scientific bibliographic databases, and the scientific literature, while improving their academic literacy skills. Students began by collecting data on their own circadian rhythms in autonomic, motor, and cognitive function, reliably demonstrating the predicted circadian changes in heart rate, eye-hand coordination, and adding speed. Students wrote a journal-style article using pooled class data. Students were prepared to write the paper by several methods that were designed to improve academic language skills, including a library training exercise, "modeling" of the writing assignment, and drafting of subsections of the paper. This multistep neurophysiology project represents a significant commitment of time by both students and instructors, but produces a valuable finished product and ideally gives introductory students a positive first experience with science.

Update of KDBI: Kinetic Data of Bio-molecular Interaction database

PubMed Central

Kumar, Pankaj; Han, B. C.; Shi, Z.; Jia, J.; Wang, Y. P.; Zhang, Y. T.; Liang, L.; Liu, Q. F.; Ji, Z. L.; Chen, Y. Z.

2009-01-01

Knowledge of the kinetics of biomolecular interactions is important for facilitating the study of cellular processes and underlying molecular events, and is essential for quantitative study and simulation of biological systems. Kinetic Data of Bio-molecular Interaction database (KDBI) has been developed to provide information about experimentally determined kinetic data of protein–protein, protein–nucleic acid, protein–ligand, nucleic acid–ligand binding or reaction events described in the literature. To accommodate increasing demand for studying and simulating biological systems, numerous improvements and updates have been made to KDBI, including new ways to access data by pathway and molecule names, data file in System Biology Markup Language format, more efficient search engine, access to published parameter sets of simulation models of 63 pathways, and 2.3-fold increase of data (19 263 entries of 10 532 distinctive biomolecular binding and 11 954 interaction events, involving 2635 proteins/protein complexes, 847 nucleic acids, 1603 small molecules and 45 multi-step processes). KDBI is publically available at http://bidd.nus.edu.sg/group/kdbi/kdbi.asp. PMID:18971255

Spatial effect of new municipal solid waste landfill siting using different guidelines.

PubMed

Ahmad, Siti Zubaidah; Ahamad, Mohd Sanusi S; Yusoff, Mohd Suffian

2014-01-01

Proper implementation of landfill siting with the right regulations and constraints can prevent undesirable long-term effects. Different countries have respective guidelines on criteria for new landfill sites. In this article, we perform a comparative study of municipal solid waste landfill siting criteria stated in the policies and guidelines of eight different constitutional bodies from Malaysia, Australia, India, U.S.A., Europe, China and the Middle East, and the World Bank. Subsequently, a geographic information system (GIS) multi-criteria evaluation model was applied to determine new suitable landfill sites using different criterion parameters using a constraint mapping technique and weighted linear combination. Application of Macro Modeler provided in the GIS-IDRISI Andes software helps in building and executing multi-step models. In addition, the analytic hierarchy process technique was included to determine the criterion weight of the decision maker's preferences as part of the weighted linear combination procedure. The differences in spatial results of suitable sites obtained signifies that dissimilarity in guideline specifications and requirements will have an effect on the decision-making process.

Viruses and Human Cancers: a Long Road of Discovery of Molecular Paradigms

PubMed Central

White, Martyn K.; Pagano, Joseph S.

2014-01-01

SUMMARY About a fifth of all human cancers worldwide are caused by infectious agents. In 12% of cancers, seven different viruses have been causally linked to human oncogenesis: Epstein-Barr virus, hepatitis B virus, human papillomavirus, human T-cell lymphotropic virus, hepatitis C virus, Kaposi's sarcoma herpesvirus, and Merkel cell polyomavirus. Here, we review the many molecular mechanisms of oncogenesis that have been discovered over the decades of study of these viruses. We discuss how viruses can act at different stages in the complex multistep process of carcinogenesis. Early events include their involvement in mutagenic events associated with tumor initiation such as viral integration and insertional mutagenesis as well as viral promotion of DNA damage. Also involved in tumor progression is the dysregulation of cellular processes by viral proteins, and we describe how this has been investigated by studies in cell culture and in experimental animals and by molecular cellular approaches. Also important are the molecular mechanisms whereby viruses interact with the immune system and the immune evasion strategies that have evolved. PMID:24982317

Long non-coding RNA regulation of epithelial–mesenchymal transition in cancer metastasis

PubMed Central

Xu, Q; Deng, F; Qin, Y; Zhao, Z; Wu, Z; Xing, Z; Ji, A; Wang, Q J

2016-01-01

Metastasis is a multistep process starting with the dissemination of tumor cells from a primary site and ending with secondary tumor development in an anatomically distant location. The epithelial–mesenchymal transition (EMT), a process that endows epithelial tumor cells with mesenchymal properties including reduced adhesion and increased motility, is considered a critical step driving the early phase of cancer metastasis. Although significant progress has been made in understanding the molecular characteristics of EMT, the intracellular mechanisms driving transition through the various stages of EMT remain unclear. In recent years, an increasing number of studies have demonstrated the involvement of long non-coding RNAs (lncRNAs) in tumor metastasis through modulating EMT. LncRNAs and their associated signaling networks have now emerged as new players in the induction and regulation of EMT during metastasis. Here we summarize the recent findings and characterizations of several known lncRNAs involved in the regulation of EMT. We will also discuss the potential use of these lncRNAs as diagnostic and prognostic biomarkers as well as therapeutic targets to slow down or prevent metastatic spread of malignant tumors. PMID:27277676

Enhancement and Validation of an Arab Surname Database

PubMed Central

Schwartz, Kendra; Beebani, Ganj; Sedki, Mai; Tahhan, Mamon; Ruterbusch, Julie J.

2015-01-01

Objectives Arab Americans constitute a large, heterogeneous, and quickly growing subpopulation in the United States. Health statistics for this group are difficult to find because US governmental offices do not recognize Arab as separate from white. The development and validation of an Arab- and Chaldean-American name database will enhance research efforts in this population subgroup. Methods A previously validated name database was supplemented with newly identified names gathered primarily from vital statistic records and then evaluated using a multistep process. This process included 1) review by 4 Arabic- and Chaldean-speaking reviewers, 2) ethnicity assessment by social media searches, and 3) self-report of ancestry obtained from a telephone survey. Results Our Arab- and Chaldean-American name algorithm has a positive predictive value of 91% and a negative predictive value of 100%. Conclusions This enhanced name database and algorithm can be used to identify Arab Americans in health statistics data, such as cancer and hospital registries, where they are often coded as white, to determine the extent of health disparities in this population. PMID:24625771

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.

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.

Unmanned Aerial Vehicle - A Tool for Acquiring Spatial Data for Research and Commercial Purposes. New Course in the Geography and Cartography Curriculum in Higher Education

NASA Astrophysics Data System (ADS)

Jeziorska, J.

2014-04-01

This paper describes the syllabus for the innovative course "Unmanned aerial observations of Terrain" introduced to the curriculum by the Department of Geoinformatics and Cartography of the University of Wroclaw (Poland). It indicates the objectives of the new subject, its didactic purpose, methods used in the teaching process, specifications of teaching materials, and the knowledge and skills that students are expected to acquire. Finally, it presents the content of the course and description of lesson units. The subject will be obligatory for graduate students majoring in Geography, who are participants in the Geoinformatics and Cartography Master's program. Thirty-eight hours in a summer semester has been earmarked for the course. That includes 30 hours of instructor-guided laboratory and fieldtrip work, and 8 hours of individual work. The course aims to prepare future geographers to conduct a multi-step process that includes defining the purpose of using UAV in light of the chosen research problem, preparation of the mission, flight execution; geoprocessing of acquired aerial imagery; generation of cartomertic final products, and analysis of outcomes in order to answer the initially asked research question. This comprehensive approach will allow students, future experts in the field of geoinformatics and cartography, to gain the skills needed to acquire spatial data using an UAV, process them, and apply the results of their analysis in practice.

Capabilities and constraints of NASA's ground-based reduced gravity facilities

NASA Technical Reports Server (NTRS)

Lekan, Jack; Neumann, Eric S.; Sotos, Raymond G.

1993-01-01

The ground-based reduced gravity facilities of NASA have been utilized to support numerous investigations addressing various processes and phenomina in several disciplines for the past 30 years. These facilities, which include drop towers, drop tubes, aircraft, and sounding rockets are able to provide a low gravity environment (gravitational levels that range from 10(exp -2)g to 10(exp -6)g) by creating a free fall or semi-free fall condition where the force of gravity on an experiment is offset by its linear acceleration during the 'fall' (drop or parabola). The low gravity condition obtained on the ground is the same as that of an orbiting spacecraft which is in a state of perpetual free fall. The gravitational levels and associated duration times associated with the full spectrum of reduced gravity facilities including spaced-based facilities are summarized. Even though ground-based facilities offer a relatively short experiment time, this available test time has been found to be sufficient to advance the scientific understanding of many phenomena and to provide meaningful hardware tests during the flight experiment development process. Also, since experiments can be quickly repeated in these facilities, multistep phenomena that have longer characteristic times associated with them can sometimes be examined in a step-by-step process. There is a large body of literature which has reported the study results achieved through using reduced-gravity data obtained from the facilities.

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.

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.

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.

ISPE: A knowledge-based system for fluidization studies. 1990 Annual report

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

Reddy, S.

1991-01-01

Chemical engineers use mathematical simulators to design, model, optimize and refine various engineering plants/processes. This procedure requires the following steps: (1) preparation of an input data file according to the format required by the target simulator; (2) excecuting the simulation; and (3) analyzing the results of the simulation to determine if all ``specified goals`` are satisfied. If the goals are not met, the input data file must be modified and the simulation repeated. This multistep process is continued until satisfactory results are obtained. This research was undertaken to develop a knowledge based system, IPSE (Intelligent Process Simulation Environment), that canmore » enhance the productivity of chemical engineers/modelers by serving as an intelligent assistant to perform a variety tasks related to process simulation. ASPEN, a widely used simulator by the US Department of Energy (DOE) at Morgantown Energy Technology Center (METC) was selected as the target process simulator in the project. IPSE, written in the C language, was developed using a number of knowledge-based programming paradigms: object-oriented knowledge representation that uses inheritance and methods, rulebased inferencing (includes processing and propagation of probabilistic information) and data-driven programming using demons. It was implemented using the knowledge based environment LASER. The relationship of IPSE with the user, ASPEN, LASER and the C language is shown in Figure 1.« less

Enhancing molecular logic through modulation of temporal and spatial constraints with quantum dot-based systems that use fluorescent (Förster) resonance energy transfer

NASA Astrophysics Data System (ADS)

Claussen, Jonathan C.; Algar, W. Russ; Hildebrandt, Niko; Susumu, Kimihiro; Ancona, Mario G.; Medintz, Igor L.

2013-10-01

Luminescent semiconductor nanocrystals or quantum dots (QDs) contain favorable photonic properties (e.g., resistance to photobleaching, size-tunable PL, and large effective Stokes shifts) that make them well-suited for fluorescence (Förster) resonance energy transfer (FRET) based applications including monitoring proteolytic activity, elucidating the effects of nanoparticles-mediated drug delivery, and analyzing the spatial and temporal dynamics of cellular biochemical processes. Herein, we demonstrate how unique considerations of temporal and spatial constraints can be used in conjunction with QD-FRET systems to open up new avenues of scientific discovery in information processing and molecular logic circuitry. For example, by conjugating both long lifetime luminescent terbium(III) complexes (Tb) and fluorescent dyes (A647) to a single QD, we can create multiple FRET lanes that change temporally as the QD acts as both an acceptor and donor at distinct time intervals. Such temporal FRET modulation creates multi-step FRET cascades that produce a wealth of unique photoluminescence (PL) spectra that are well-suited for the construction of a photonic alphabet and photonic logic circuits. These research advances in bio-based molecular logic open the door to future applications including multiplexed biosensing and drug delivery for disease diagnostics and treatment.

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.

High-performance liquid chromatography with fluorescence detection for the rapid analysis of pheophytins and pyropheophytins in virgin olive oil.

PubMed

Li, Xueqi; Woodman, Michael; Wang, Selina C

2015-08-01

Pheophytins and pyropheophytin are degradation products of chlorophyll pigments, and their ratios can be used as a sensitive indicator of stress during the manufacturing and storage of olive oil. They increase over time depending on the storage condition and if the oil is exposed to heat treatments during the refining process. The traditional analysis method includes solvent- and time-consuming steps of solid-phase extraction followed by analysis by high-performance liquid chromatography with ultraviolet detection. We developed an improved dilute/fluorescence method where multi-step sample preparation was replaced by a simple isopropanol dilution before the high-performance liquid chromatography injection. A quaternary solvent gradient method was used to include a fourth strong solvent wash on a quaternary gradient pump, which avoided the need to premix any solvents and greatly reduced the oil residues on the column from previous analysis. This new method not only reduces analysis cost and time but shows reliability, repeatability, and improved sensitivity, especially important for low-level samples. © 2015 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.

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.

Development of Multistep and Degenerate Variational Integrators for Applications in Plasma Physics

NASA Astrophysics Data System (ADS)

Ellison, Charles Leland

Geometric integrators yield high-fidelity numerical results by retaining conservation laws in the time advance. A particularly powerful class of geometric integrators is symplectic integrators, which are widely used in orbital mechanics and accelerator physics. An important application presently lacking symplectic integrators is the guiding center motion of magnetized particles represented by non-canonical coordinates. Because guiding center trajectories are foundational to many simulations of magnetically confined plasmas, geometric guiding center algorithms have high potential for impact. The motivation is compounded by the need to simulate long-pulse fusion devices, including ITER, and opportunities in high performance computing, including the use of petascale resources and beyond. This dissertation uses a systematic procedure for constructing geometric integrators --- known as variational integration --- to deliver new algorithms for guiding center trajectories and other plasma-relevant dynamical systems. These variational integrators are non-trivial because the Lagrangians of interest are degenerate - the Euler-Lagrange equations are first-order differential equations and the Legendre transform is not invertible. The first contribution of this dissertation is that variational integrators for degenerate Lagrangian systems are typically multistep methods. Multistep methods admit parasitic mode instabilities that can ruin the numerical results. These instabilities motivate the second major contribution: degenerate variational integrators. By replicating the degeneracy of the continuous system, degenerate variational integrators avoid parasitic mode instabilities. The new methods are therefore robust geometric integrators for degenerate Lagrangian systems. These developments in variational integration theory culminate in one-step degenerate variational integrators for non-canonical magnetic field line flow and guiding center dynamics. The guiding center integrator assumes coordinates such that one component of the magnetic field is zero; it is shown how to construct such coordinates for nested magnetic surface configurations. Additionally, collisional drag effects are incorporated in the variational guiding center algorithm for the first time, allowing simulation of energetic particle thermalization. Advantages relative to existing canonical-symplectic and non-geometric algorithms are numerically demonstrated. All algorithms have been implemented as part of a modern, parallel, ODE-solving library, suitable for use in high-performance simulations.

A Multi-Step Pathway Connecting Short Sleep Duration to Daytime Somnolence, Reduced Attention, and Poor Academic Performance: An Exploratory Cross-Sectional Study in Teenagers

PubMed Central

Perez-Lloret, Santiago; Videla, Alejandro J.; Richaudeau, Alba; Vigo, Daniel; Rossi, Malco; Cardinali, Daniel P.; Perez-Chada, Daniel

2013-01-01

Background: A multi-step causality pathway connecting short sleep duration to daytime somnolence and sleepiness leading to reduced attention and poor academic performance as the final result can be envisaged. However this hypothesis has never been explored. Objective: To explore consecutive correlations between sleep duration, daytime somnolence, attention levels, and academic performance in a sample of school-aged teenagers. Methods: We carried out a survey assessing sleep duration and daytime somnolence using the Pediatric Daytime Sleepiness Scale (PDSS). Sleep duration variables included week-days' total sleep time, usual bedtimes, and absolute weekdayto-weekend sleep time difference. Attention was assessed by d2 test and by the coding subtest from the WISC-IV scale. Academic performance was obtained from literature and math grades. Structural equation modeling was used to assess the independent relationships between these variables, while controlling for confounding effects of other variables, in one single model. Standardized regression weights (SWR) for relationships between these variables are reported. Results: Study sample included 1,194 teenagers (mean age: 15 years; range: 13-17 y). Sleep duration was inversely associated with daytime somnolence (SWR = -0.36, p < 0.01) while sleepiness was negatively associated with attention (SWR = -0.13, p < 0.01). Attention scores correlated positively with academic results (SWR = 0.18, p < 0.01). Daytime somnolence correlated negatively with academic achievements (SWR = -0.16, p < 0.01). The model offered an acceptable fit according to usual measures (RMSEA = 0.0548, CFI = 0.874, NFI = 0.838). A Sobel test confirmed that short sleep duration influenced attention through daytime somnolence (p < 0.02), which in turn influenced academic achievements through reduced attention (p < 0.002). Conclusions: Poor academic achievements correlated with reduced attention, which in turn was related to daytime somnolence. Somnolence correlated with short sleep duration. Citation: Perez-Lloret S; Videla AJ; Richaudeau A; Vigo D; Rossi M; Cardinali DP; Perez-Chada D. A multi-step pathway connecting short sleep duration to daytime somnolence, reduced attention, and poor academic performance: an exploratory cross-sectional study in teenagers. J Clin Sleep Med 2013;9(5):469-473. PMID:23674938

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.

JobCenter: an open source, cross-platform, and distributed job queue management system optimized for scalability and versatility

PubMed Central

2012-01-01

Background Laboratories engaged in computational biology or bioinformatics frequently need to run lengthy, multistep, and user-driven computational jobs. Each job can tie up a computer for a few minutes to several days, and many laboratories lack the expertise or resources to build and maintain a dedicated computer cluster. Results JobCenter is a client–server application and framework for job management and distributed job execution. The client and server components are both written in Java and are cross-platform and relatively easy to install. All communication with the server is client-driven, which allows worker nodes to run anywhere (even behind external firewalls or “in the cloud”) and provides inherent load balancing. Adding a worker node to the worker pool is as simple as dropping the JobCenter client files onto any computer and performing basic configuration, which provides tremendous ease-of-use, flexibility, and limitless horizontal scalability. Each worker installation may be independently configured, including the types of jobs it is able to run. Executed jobs may be written in any language and may include multistep workflows. Conclusions JobCenter is a versatile and scalable distributed job management system that allows laboratories to very efficiently distribute all computational work among available resources. JobCenter is freely available at http://code.google.com/p/jobcenter/. PMID:22846423

Telephone-based Assessments to Minimize Missing Data in Longitudinal Depression Trials: A Project IMPACTS Study Report

PubMed Central

Claassen, Cindy; Kurian, Ben; Trivedi, Madhukar H.; Grannemann, Bruce D.; Tuli, Ekta; Pipes, Ronny; Preston, Anne Marie; Flood, Ariell

2012-01-01

Purpose Missing data in clinical efficacy and effectiveness trials continue to be a major threat to the validity of study findings. The purpose of this report is to describe methods developed to ensure completion of outcome assessments with public mental health sector subjects participating in a longitudinal, repeated measures study for the treatment of major depressive disorder. We developed longitudinal assessment procedures that included telephone-based clinician interviews in order to minimize missing data commonly encountered with face-to-face assessment procedures. Methods A pre-planned, multi-step strategy was developed to ensure completeness of data collection. The procedure included obtaining multiple pieces of patient contact information at baseline, careful education of both staff and patients concerning the purpose of assessments, establishing good patient rapport, and finally being flexible and persistent with phone appointments to ensure the completion of telephone-based follow-up assessments. A well-developed administrative and organizational structure was also put in place prior to study implementation. Results The assessment completion rate for the primary outcome for 310 of 504 subjects who enrolled and completed 52 weeks (at the time of manuscript) of telephone-based follow-up assessments was 96.8%. Conclusion By utilizing telephone-based follow-up procedures and adapting our easy-to-use pre-defined multi-step approach, researchers can maximize patient data retention in longitudinal studies. PMID:18761427

Influence of excitation frequency on the metastable atoms and electron energy distribution function in a capacitively coupled argon discharge

NASA Astrophysics Data System (ADS)

Sharma, S.; Sirse, N.; Turner, M. M.; Ellingboe, A. R.

2018-06-01

One-dimensional particle-in-cell simulation is used to simulate the capacitively coupled argon plasma for a range of excitation frequency from 13.56 MHz to 100 MHz. The argon chemistry set can, selectively, include two metastable levels enabling multi-step ionization and metastable pooling. The results show that the plasma density decreases when metastable atoms are included with higher discrepancy at a higher excitation frequency. The contribution of multistep ionization to the overall density increases with the excitation frequency. The electron temperature increases with the inclusion of metastable atoms and decreases with the excitation frequency. At a lower excitation frequency, the density of Ar** (3p5 4p, 13.1 eV) is higher than that of Ar* (3p5 4s, 11.6 eV), whereas at higher excitation frequencies, the Ar* (3p5 4s, 11.6 eV) is the dominant metastable atom. The metastable and electron temperature profile evolve from a parabolic profile at a lower excitation frequency to a saddle type profile at a higher excitation frequency. With metastable, the electron energy distribution function (EEDF) changes its shape from Druyvesteyn type, at a low excitation frequency, to bi-Maxwellian, at a high frequency plasma excitation; however, a three-temperature EEDF is observed without metastable atoms.

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

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.

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.

The process of adopting and incorporating simulation into undergraduate nursing curricula: a grounded theory study.

PubMed

Taplay, Karyn; Jack, Susan M; Baxter, Pamela; Eva, Kevin; Martin, Lynn

2015-01-01

The aim of this study is to explain the process of adopting and incorporating simulation as a teaching strategy in undergraduate nursing programs, define uptake, and discuss potential outcomes. In many countries, simulation is increasingly adopted as a common teaching strategy. However, there is a dearth of knowledge related to the process of adoption and incorporation. We used an interpretive, constructivist approach to grounded theory to guide this research study. We conducted the study was in Ontario, Canada, during 2011-2012. Using multiple data sources, we informed the development of this theory including in-depth interviews (n = 43) and a review of key organizational documents, such as mission and vision statements (n = 67) from multiple nursing programs (n = 13). The adoption and uptake of mid- to high-fidelity simulation equipment is a multistep iterative process involving various organizational levels within the institution that entails a seven-phase process: (a) securing resources, (b) nursing leaders working in tandem, (c) getting it out of the box, (d) learning about simulation and its potential for teaching, (e) finding a fit, (f) trialing the equipment, and (g) integrating into the curriculum. These findings could assist nursing programs in Canada and internationally that wish to adopt or further incorporate simulation into their curricula and highlight potential organizational and program level outcomes. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

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.

Reporting Items for Updated Clinical Guidelines: Checklist for the Reporting of Updated Guidelines (CheckUp)

PubMed Central

Vernooij, Robin W. M.; Alonso-Coello, Pablo; Brouwers, Melissa

2017-01-01

Background Scientific knowledge is in constant development. Consequently, regular review to assure the trustworthiness of clinical guidelines is required. However, there is still a lack of preferred reporting items of the updating process in updated clinical guidelines. The present article describes the development process of the Checklist for the Reporting of Updated Guidelines (CheckUp). Methods and Findings We developed an initial list of items based on an overview of research evidence on clinical guideline updating, the Appraisal of Guidelines for Research and Evaluation (AGREE) II Instrument, and the advice of the CheckUp panel (n = 33 professionals). A multistep process was used to refine this list, including an assessment of ten existing updated clinical guidelines, interviews with key informants (response rate: 54.2%; 13/24), a three-round Delphi consensus survey with the CheckUp panel (33 participants), and an external review with clinical guideline methodologists (response rate: 90%; 53/59) and users (response rate: 55.6%; 10/18). CheckUp includes 16 items that address (1) the presentation of an updated guideline, (2) editorial independence, and (3) the methodology of the updating process. In this article, we present the methodology to develop CheckUp and include as a supplementary file an explanation and elaboration document. Conclusions CheckUp can be used to evaluate the completeness of reporting in updated guidelines and as a tool to inform guideline developers about reporting requirements. Editors may request its completion from guideline authors when submitting updated guidelines for publication. Adherence to CheckUp will likely enhance the comprehensiveness and transparency of clinical guideline updating for the benefit of patients and the public, health care professionals, and other relevant stakeholders. PMID:28072838

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.

Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein

PubMed Central

McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

2014-01-01

Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. PMID:24811361

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.

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.

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.

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.

Hybrid Method for Power Control Simulation of a Single Fluid Plasma Thruster

NASA Astrophysics Data System (ADS)

Jaisankar, S.; Sheshadri, T. S.

2018-05-01

Propulsive plasma flow through a cylindrical-conical diverging thruster is simulated by a power controlled hybrid method to obtain the basic flow, thermodynamic and electromagnetic variables. Simulation is based on a single fluid model with electromagnetics being described by the equations of potential Poisson, Maxwell and the Ohm's law while the compressible fluid dynamics by the Navier Stokes in cylindrical form. The proposed method solved the electromagnetics and fluid dynamics separately, both to segregate the two prominent scales for an efficient computation and for the delivery of voltage controlled rated power. The magnetic transport is solved for steady state while fluid dynamics is allowed to evolve in time along with an electromagnetic source using schemes based on generalized finite difference discretization. The multistep methodology with power control is employed for simulating fully ionized propulsive flow of argon plasma through the thruster. Numerical solution shows convergence of every part of the solver including grid stability causing the multistep hybrid method to converge for a rated power delivery. Simulation results are reasonably in agreement with the reported physics of plasma flow in the thruster thus indicating the potential utility of this hybrid computational framework, especially when single fluid approximation of plasma is relevant.

Municipal solid waste incineration plant: A multi-step approach to the evaluation of an energy-recovery configuration.

PubMed

Panepinto, D; Zanetti, M C

2018-03-01

This study proposes a multi-step approach to evaluating the environmental and economic aspects of a thermal treatment plant with an energy-recovery configuration. In order to validate the proposed approach, the Turin incineration plant was analyzed, and the potential of the incinerator and several different possible connections to the district heating network were then considered. Both local and global environmental balances were defined. The global-scale results provided information on carbon dioxide emissions, while the local-scale results were used as reference values for the implementation of a Gaussian model that could evaluate the actual concentrations of pollutants released into the atmosphere. The economic aspects were then analyzed, and a correspondence between the environmental and economic advantages defined. The results showed a high energy efficiency for the combined production of heat and electricity, and the opportunity to minimize environmental impacts by including cogeneration in a district heating scheme. This scheme showed an environmental advantage, whereas the electricity-only configuration showed an economic advantage. A change in the thermal energy price (specifically, to 40 €/MWh), however, would make it possible to obtain both environmental and economic advantages. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sample injection and electrophoretic separation on a simple laminated paper based analytical device.

PubMed

Xu, Chunxiu; Zhong, Minghua; Cai, Longfei; Zheng, Qingyu; Zhang, Xiaojun

2016-02-01

We described a strategy to perform multistep operations on a simple laminated paper-based separation device by using electrokinetic flow to manipulate the fluids. A laminated crossed-channel paper-based separation device was fabricated by cutting a filter paper sheet followed by lamination. Multiple function units including sample loading, sample injection, and electrophoretic separation were integrated on a single paper based analytical device for the first time, by applying potential at different reservoirs for sample, sample waste, buffer, and buffer waste. As a proof-of-concept demonstration, mixed sample solution containing carmine and sunset yellow were loaded in the sampling channel, and then injected into separation channel followed by electrophoretic separation, by adjusting the potentials applied at the four terminals of sampling and separation channel. The effects of buffer pH, buffer concentration, channel width, and separation time on resolution of electrophoretic separation were studied. This strategy may be used to perform multistep operations such as reagent dilution, sample injection, mixing, reaction, and separation on a single microfluidic paper based analytical device, which is very attractive for building micro total analysis systems on microfluidic paper based analytical devices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

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.

Neural network-based multiple robot simultaneous localization and mapping.

PubMed

Saeedi, Sajad; Paull, Liam; Trentini, Michael; Li, Howard

2011-12-01

In this paper, a decentralized platform for simultaneous localization and mapping (SLAM) with multiple robots is developed. Each robot performs single robot view-based SLAM using an extended Kalman filter to fuse data from two encoders and a laser ranger. To extend this approach to multiple robot SLAM, a novel occupancy grid map fusion algorithm is proposed. Map fusion is achieved through a multistep process that includes image preprocessing, map learning (clustering) using neural networks, relative orientation extraction using norm histogram cross correlation and a Radon transform, relative translation extraction using matching norm vectors, and then verification of the results. The proposed map learning method is a process based on the self-organizing map. In the learning phase, the obstacles of the map are learned by clustering the occupied cells of the map into clusters. The learning is an unsupervised process which can be done on the fly without any need to have output training patterns. The clusters represent the spatial form of the map and make further analyses of the map easier and faster. Also, clusters can be interpreted as features extracted from the occupancy grid map so the map fusion problem becomes a task of matching features. Results of the experiments from tests performed on a real environment with multiple robots prove the effectiveness of the proposed solution.

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

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.

Enzyme Engineering for In Situ Immobilization.

PubMed

Rehm, Fabian B H; Chen, Shuxiong; Rehm, Bernd H A

2016-10-14

Enzymes are used as biocatalysts in a vast range of industrial applications. Immobilization of enzymes to solid supports or their self-assembly into insoluble particles enhances their applicability by strongly improving properties such as stability in changing environments, re-usability and applicability in continuous biocatalytic processes. The possibility of co-immobilizing various functionally related enzymes involved in multistep synthesis, conversion or degradation reactions enables the design of multifunctional biocatalyst with enhanced performance compared to their soluble counterparts. This review provides a brief overview of up-to-date in vitro immobilization strategies while focusing on recent advances in enzyme engineering towards in situ self-assembly into insoluble particles. In situ self-assembly approaches include the bioengineering of bacteria to abundantly form enzymatically active inclusion bodies such as enzyme inclusions or enzyme-coated polyhydroxyalkanoate granules. These one-step production strategies for immobilized enzymes avoid prefabrication of the carrier as well as chemical cross-linking or attachment to a support material while the controlled oriented display strongly enhances the fraction of accessible catalytic sites and hence functional enzymes.

One-pot preparation of mRNA/cDNA display by a novel and versatile puromycin-linker DNA.

PubMed

Mochizuki, Yuki; Biyani, Manish; Tsuji-Ueno, Sachika; Suzuki, Miho; Nishigaki, Koichi; Husimi, Yuzuru; Nemoto, Naoto

2011-09-12

A rapid, easy, and robust preparation method for mRNA/cDNA display using a newly designed puromycin-linker DNA is presented. The new linker is structurally simple, easy to synthesize, and cost-effective for use in "in vitro peptide and protein selection". An introduction of RNase T1 nuclease site to the new linker facilitates the easy recovery of mRNA/cDNA displayed protein by an improvement of the efficiency of ligating the linker to mRNAs and efficient release of mRNA/cDNA displayed protein from the solid-phase (magnetic bead). For application demonstration, affinity selections were successfully performed. Furthermore, we introduced a "one-pot" preparation protocol to perform mRNA display easy. Unlike conventional approaches that require tedious and downstream multistep process including purification, this protocol will make the mRNA/cDNA display methods more practical and convenient and also facilitate the development of next-generation, high-throughput mRNA/cDNA display systems amenable to automation.

Test systems of the STS-XYTER2 ASIC: from wafer-level to in-system verification

NASA Astrophysics Data System (ADS)

Kasinski, Krzysztof; Zubrzycka, Weronika

2016-09-01

The STS/MUCH-XYTER2 ASIC is a full-size prototype chip for the Silicon Tracking System (STS) and Muon Chamber (MUCH) detectors in the new fixed-target experiment Compressed Baryonic Matter (CBM) at FAIR-center, Darmstadt, Germany. The STS assembly includes more than 14000 ASICs. The complicated, time-consuming, multi-step assembly process of the detector building blocks and tight quality assurance requirements impose several intermediate testing to be performed for verifying crucial assembly steps (e.g. custom microcable tab-bonding before wire-bonding to the PCB) and - if necessary - identifying channels or modules for rework. The chip supports the multi-level testing with different probing / contact methods (wafer probe-card, pogo-probes, in-system tests). A huge number of ASICs to be tested restricts the number and kind of tests possible to be performed within a reasonable time. The proposed architectures of test stand equipment and a brief summary of methodologies are presented in this paper.

Highly oriented diamond films on Si: growth, characterization, and devices

NASA Astrophysics Data System (ADS)

Stoner, Brian R.; Malta, D. M.; Tessmer, A. J.; Holmes, J.; Dreifus, David L.; Glass, R. C.; Sowers, A.; Nemanich, Robert J.

1994-04-01

Highly oriented, (100) textured diamond films have been grown on single-crystal Si substrates via microwave plasma enhanced chemical vapor deposition. A multistep deposition process including bias-enhanced nucleation and textured growth was used to obtain smooth films consisting of epitaxial grains with only low-angle grain boundaries. Boron-doped layers were selectively deposited onto the surface of these oriented films and temperature-dependent Hall effect measurements indicated a 3 to 5 times improvement in hole mobility over polycrystalline films grown under similar conditions. Room temperature hole mobilities between 135 and 278 cm2/V-s were measured for the highly oriented samples as compared to 2 to 50 cm2/V-s for typical polycrystalline films. Grain size effects and a comparison between the transport properties of polycrystalline, highly oriented and homoepitaxial films will be discussed. Metal-oxide- semiconductor field-effect transistors were then fabricated on the highly oriented films and exhibited saturation and pinch-off of the channel current.

Stochastic modelling of animal movement.

PubMed

Smouse, Peter E; Focardi, Stefano; Moorcroft, Paul R; Kie, John G; Forester, James D; Morales, Juan M

2010-07-27

Modern animal movement modelling derives from two traditions. Lagrangian models, based on random walk behaviour, are useful for multi-step trajectories of single animals. Continuous Eulerian models describe expected behaviour, averaged over stochastic realizations, and are usefully applied to ensembles of individuals. We illustrate three modern research arenas. (i) Models of home-range formation describe the process of an animal 'settling down', accomplished by including one or more focal points that attract the animal's movements. (ii) Memory-based models are used to predict how accumulated experience translates into biased movement choices, employing reinforced random walk behaviour, with previous visitation increasing or decreasing the probability of repetition. (iii) Lévy movement involves a step-length distribution that is over-dispersed, relative to standard probability distributions, and adaptive in exploring new environments or searching for rare targets. Each of these modelling arenas implies more detail in the movement pattern than general models of movement can accommodate, but realistic empiric evaluation of their predictions requires dense locational data, both in time and space, only available with modern GPS telemetry.

Multiple myeloma: a clinical overview.

PubMed

Anderson, Kenneth C

2011-11-15

Multiple myeloma (MM) is the second most common hematologic malignancy in the United States, affecting slightly more men than women and twice as many African Americans as Caucasians. Older age is the primary risk factor for MM, but obesity also increases risk. MM is incurable, but treatment advances in the past decade have more than doubled the duration of survival. MM is a progressive plasma cell tumor in which an initially stable clone becomes malignant via a multistep process. Causative factors implicated in this process include radiation, environmental toxins, chronic antigen stimulation, and genetics. The malignant plasma cells interact with other hematopoietic and stromal cells within the bone marrow microenvironment to disrupt homeostasis among cells and within the extracellular matrix. These tumor-host interactions lead to MM cell proliferation and migration, angiogenesis, osteolysis, immunodeficiency, and anemia. As a result, patients often present with osteolytic bone lesions, recurrent infections, renal insufficiency, and fatigue. The Durie-Salmon and International Staging Systems are used to stage MM, with the latter providing prognostic information based on readily available laboratory data. However, a number of cytogenetic markers are emerging as prognostic indicators, introducing the possibility of more refined disease staging systems and tailored treatment strategies based on genetic profiles.

HARV ANSER Flight Test Data Retrieval and Processing Procedures

NASA Technical Reports Server (NTRS)

Yeager, Jessie C.

1997-01-01

Under the NASA High-Alpha Technology Program the High Alpha Research Vehicle (HARV) was used to conduct flight tests of advanced control effectors, advanced control laws, and high-alpha design guidelines for future super-maneuverable fighters. The High-Alpha Research Vehicle is a pre-production F/A-18 airplane modified with a multi-axis thrust-vectoring system for augmented pitch and yaw control power and Actuated Nose Strakes for Enhanced Rolling (ANSER) to augment body-axis yaw control power. Flight testing at the Dryden Flight Research Center (DFRC) began in July 1995 and continued until May 1996. Flight data will be utilized to evaluate control law performance and aircraft dynamics, determine aircraft control and stability derivatives using parameter identification techniques, and validate design guidelines. To accomplish these purposes, essential flight data parameters were retrieved from the DFRC data system and stored on the Dynamics and Control Branch (DCB) computer complex at Langley. This report describes the multi-step task used to retrieve and process this data and documents the results of these tasks. Documentation includes software listings, flight information, maneuver information, time intervals for which data were retrieved, lists of data parameters and definitions, and example data plots.

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.

Synthesis of metal-doped Mn-Zn ferrite from the leaching solutions of vanadium slag using hydrothermal method

NASA Astrophysics Data System (ADS)

Liu, Shiyuan; Wang, Lijun; Chou, Kuochih

2018-03-01

Using vanadium slag as raw material, Metal-doped Mn-Zn ferrites were synthesized by multi-step processes including chlorination of iron and manganese by NH4Cl, selective oxidation of Fe cation, and hydrothermal synthesis. The phase composition and magnetic properties of synthesized metal-doped Mn-Zn ferrite were characterized by X-ray powder diffraction, Raman spectroscopy, transmission electron microscopy (TEM), X-ray photon spectra (XPS) and physical property measurement. It was found that Mn/Zn mole ratio significantly affected the magnetic properties and ZnCl2 content significantly influenced the purity of the phase of ferrite. Synthesized metal-doped Mn-Zn ferrite, exhibiting a larger saturation magnetization (Ms = 60.01 emu/g) and lower coercivity (Hc = 8.9 Oe), was obtained when the hydrothermal temperature was controlled at 200 °C for 12 h with a Mn/Zn mole ratio of 4. The effect of ZnCl2 content, Mn/Zn mole ratio and temperature on magnetic properties of the synthesized metal-doped Mn-Zn ferrite were systemically investigated. This process provided a new insight to utilize resources in the aim of obtaining functional materials.

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.

Live imaging of mitosis in the developing mouse embryonic cortex.

PubMed

Pilaz, Louis-Jan; Silver, Debra L

2014-06-04

Although of short duration, mitosis is a complex and dynamic multi-step process fundamental for development of organs including the brain. In the developing cerebral cortex, abnormal mitosis of neural progenitors can cause defects in brain size and function. Hence, there is a critical need for tools to understand the mechanisms of neural progenitor mitosis. Cortical development in rodents is an outstanding model for studying this process. Neural progenitor mitosis is commonly examined in fixed brain sections. This protocol will describe in detail an approach for live imaging of mitosis in ex vivo embryonic brain slices. We will describe the critical steps for this procedure, which include: brain extraction, brain embedding, vibratome sectioning of brain slices, staining and culturing of slices, and time-lapse imaging. We will then demonstrate and describe in detail how to perform post-acquisition analysis of mitosis. We include representative results from this assay using the vital dye Syto11, transgenic mice (histone H2B-EGFP and centrin-EGFP), and in utero electroporation (mCherry-α-tubulin). We will discuss how this procedure can be best optimized and how it can be modified for study of genetic regulation of mitosis. Live imaging of mitosis in brain slices is a flexible approach to assess the impact of age, anatomy, and genetic perturbation in a controlled environment, and to generate a large amount of data with high temporal and spatial resolution. Hence this protocol will complement existing tools for analysis of neural progenitor mitosis.

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

Contributions of dopamine-related genes and environmental factors to highly sensitive personality: a multi-step neuronal system-level approach.

PubMed

Chen, Chunhui; Chen, Chuansheng; Moyzis, Robert; Stern, Hal; He, Qinghua; Li, He; Li, Jin; Zhu, Bi; Dong, Qi

2011-01-01

Traditional behavioral genetic studies (e.g., twin, adoption studies) have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL) with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation) to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system) genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP). 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth) that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphism's main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001). Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional behavioral genetics and the lack of reproducible genetic effects observed currently from molecular genetic studies.

Contributions of Dopamine-Related Genes and Environmental Factors to Highly Sensitive Personality: A Multi-Step Neuronal System-Level Approach

PubMed Central

Chen, Chunhui; Chen, Chuansheng; Moyzis, Robert; Stern, Hal; He, Qinghua; Li, He; Li, Jin; Zhu, Bi; Dong, Qi

2011-01-01

Traditional behavioral genetic studies (e.g., twin, adoption studies) have shown that human personality has moderate to high heritability, but recent molecular behavioral genetic studies have failed to identify quantitative trait loci (QTL) with consistent effects. The current study adopted a multi-step approach (ANOVA followed by multiple regression and permutation) to assess the cumulative effects of multiple QTLs. Using a system-level (dopamine system) genetic approach, we investigated a personality trait deeply rooted in the nervous system (the Highly Sensitive Personality, HSP). 480 healthy Chinese college students were given the HSP scale and genotyped for 98 representative polymorphisms in all major dopamine neurotransmitter genes. In addition, two environment factors (stressful life events and parental warmth) that have been implicated for their contributions to personality development were included to investigate their relative contributions as compared to genetic factors. In Step 1, using ANOVA, we identified 10 polymorphisms that made statistically significant contributions to HSP. In Step 2, these polymorphism's main effects and interactions were assessed using multiple regression. This model accounted for 15% of the variance of HSP (p<0.001). Recent stressful life events accounted for an additional 2% of the variance. Finally, permutation analyses ascertained the probability of obtaining these findings by chance to be very low, p ranging from 0.001 to 0.006. Dividing these loci by the subsystems of dopamine synthesis, degradation/transport, receptor and modulation, we found that the modulation and receptor subsystems made the most significant contribution to HSP. The results of this study demonstrate the utility of a multi-step neuronal system-level approach in assessing genetic contributions to individual differences in human behavior. It can potentially bridge the gap between the high heritability estimates based on traditional behavioral genetics and the lack of reproducible genetic effects observed currently from molecular genetic studies. PMID:21765900

PredPPCrys: accurate prediction of sequence cloning, protein production, purification and crystallization propensity from protein sequences using multi-step heterogeneous feature fusion and selection.

PubMed

Wang, Huilin; Wang, Mingjun; Tan, Hao; Li, Yuan; Zhang, Ziding; Song, Jiangning

2014-01-01

X-ray crystallography is the primary approach to solve the three-dimensional structure of a protein. However, a major bottleneck of this method is the failure of multi-step experimental procedures to yield diffraction-quality crystals, including sequence cloning, protein material production, purification, crystallization and ultimately, structural determination. Accordingly, prediction of the propensity of a protein to successfully undergo these experimental procedures based on the protein sequence may help narrow down laborious experimental efforts and facilitate target selection. A number of bioinformatics methods based on protein sequence information have been developed for this purpose. However, our knowledge on the important determinants of propensity for a protein sequence to produce high diffraction-quality crystals remains largely incomplete. In practice, most of the existing methods display poorer performance when evaluated on larger and updated datasets. To address this problem, we constructed an up-to-date dataset as the benchmark, and subsequently developed a new approach termed 'PredPPCrys' using the support vector machine (SVM). Using a comprehensive set of multifaceted sequence-derived features in combination with a novel multi-step feature selection strategy, we identified and characterized the relative importance and contribution of each feature type to the prediction performance of five individual experimental steps required for successful crystallization. The resulting optimal candidate features were used as inputs to build the first-level SVM predictor (PredPPCrys I). Next, prediction outputs of PredPPCrys I were used as the input to build second-level SVM classifiers (PredPPCrys II), which led to significantly enhanced prediction performance. Benchmarking experiments indicated that our PredPPCrys method outperforms most existing procedures on both up-to-date and previous datasets. In addition, the predicted crystallization targets of currently non-crystallizable proteins were provided as compendium data, which are anticipated to facilitate target selection and design for the worldwide structural genomics consortium. PredPPCrys is freely available at http://www.structbioinfor.org/PredPPCrys.

A common monitoring framework for ending preventable maternal mortality, 2015-2030: phase I of a multi-step process.

PubMed

Moran, Allisyn C; Jolivet, R Rima; Chou, Doris; Dalglish, Sarah L; Hill, Kathleen; Ramsey, Kate; Rawlins, Barbara; Say, Lale

2016-08-26

While global maternal mortality declined 44 % between 1990 and 2015, the majority of countries fell short of attaining Millennium Development Goal targets. The Sustainable Development Goals (SDGs), adopted in late 2015, include a target to reduce national maternal mortality ratios (MMR) to achieve a global average of 70 per 100,000 live births by 2030. A comprehensive paper outlining Strategies toward Ending Preventable Maternal Mortality (EPMM) was launched in February 2015 to support achievement of the SDG global targets. To date, there has not been consensus on a set of core metrics to track progress toward the overall global maternal mortality target, which has made it difficult to systematically monitor maternal health status and programs over time. The World Health Organization (WHO), Maternal Health Taskforce (MHTF), and the US Agency for International Development (USAID) along with its flagship Maternal and Child Survival Program (MCSP), facilitated a consultative process to seek consensus on maternal health indicators for global monitoring and reporting by all countries. Consensus was reached on 12 indicators and four priority areas for further indicator development and testing. These indicators are being harmonized with the Every Newborn Action Plan core metrics for a joint global maternal newborn monitoring framework. Next steps include a similar process to agree upon indicators to monitor social, political and economic determinants of maternal health and survival highlighted in the EPMM strategies. This process provides a foundation for the maternal health community to work collaboratively to track progress on core global indicators. It is important that actors continue to work together through transparent and participatory processes to track progress to end preventable maternal mortality and achieve the SDG maternal mortality targets.

Defining Neighborhood Boundaries for Urban Health Research

PubMed Central

Weiss, Linda; Ompad, Danielle; Galea, Sandro; Vlahov, David

2008-01-01

The body of literature exploring neighborhood effects on health has increased rapidly in recent years, yet a number of methodological concerns remain, including preferred methods for identification and delineation of study neighborhoods. In research combining census or other publicly available data with surveys of residents and/or street-level observations, questions regarding neighborhood definition take on added significance. Neighborhoods must be identified and delineated in such a way as to optimize quality and availability of data from each of these sources. IMPACT, a multi-level study examining associations between features of the urban environment and mental health, drug use, and sexual behavior, utilized a multi-step neighborhood definition process including development of census block group maps, review of land use and census tract data, and field visits and observation in each of the targeted communities. Field observations were guided by a pre-identified list of environmental features focused on the potential for recruitment (e.g. pedestrian volume); characteristics commonly used to define neighborhood boundaries (e.g. obstructions to pedestrian traffic, changes in land use), and characteristics that have been associated in the literature with health behaviors and health outcomes (such as housing type, maintenance and use of open spaces). This process, implemented in February through July 2005, proved feasible and offered the opportunity to identify neighborhoods appropriate to study objectives and to collect descriptive information that can be used as a context for understanding study results. PMID:17543706

Trash-to-Gas: Converting Space Trash into Useful Products

NASA Technical Reports Server (NTRS)

Caraccio, Anne J.; Hintze, Paul E.

2013-01-01

NASA's Logistical Reduction and Repurposing (LRR) project is a collaborative effort in which NASA is determined to reduce total logistical mass through reduction, reuse and recycling of various wastes and components of long duration space missions and habitats. LRR is focusing on four distinct advanced areas of study: Advanced Clothing System, Logistics-to-Living, Heat Melt Compactor and Trash to Supply Gas (TtSG). The objective of TtSG is to develop technologies that convert material waste, human waste and food waste into high-value products. High-value products include life support oxygen and water, rocket fuels, raw material production feedstocks, and other energy sources. There are multiple pathways for converting waste to products involving single or multi-step processes. This paper discusses thermal oxidation methods of converting waste to methane. Different wastes, including food, food packaging, Maximum Absorbent Garments (MAGs), human waste simulants, and cotton washcloths have been evaluated in a thermal degradation reactor under conditions promoting pyrolysis, gasification or incineration. The goal was to evaluate the degradation processes at varying temperatures and ramp cycles and to maximize production of desirable products and minimize high molecular weight hydrocarbon (tar) production. Catalytic cracking was also evaluated to minimize tar production. The quantities of CO2, CO, CH4, and H2O were measured under the different thermal degradation conditions. The conversion efficiencies of these products were used to determine the best methods for producing desired products.

Trash to Gas: Converting Space Trash into Useful Products

NASA Technical Reports Server (NTRS)

Nur, Mononita

2013-01-01

NASA's Logistical Reduction and Repurposing (LRR) project is a collaborative effort in which NASA is determined to reduce total logistical mass through reduction, reuse and recycling of various wastes and components of long duration space missions and habitats. LRR is focusing on four distinct advanced areas of study: Advanced Clothing System, Logistics-to-Living, Heat Melt Compactor and Trash to Supply Gas (TtSG). The objective of TtSG is to develop technologies that convert material waste, human waste and food waste into high-value products. High-value products include life support oxygen and water, rocket fuels, raw material production feedstocks, and other energy sources. There are multiple pathways for converting waste to products involving single or multi-step processes. This paper discusses thermal oxidation methods of converting waste to methane. Different wastes, including food, food packaging, Maximum Absorbent Garments (MAGs), human waste simulants, and cotton washcloths have been evaluated in a thermal degradation reactor under conditions promoting pyrolysis, gasification or incineration. The goal was to evaluate the degradation processes at varying temperatures and ramp cycles and to maximize production of desirable products and minimize high molecular weight hydrocarbon (tar) production. Catalytic cracking was also evaluated to minimize tar production. The quantities of C02, CO, CH4, and H20 were measured under the different thermal degradation conditions. The conversion efficiencies of these products were used to determine the best methods for producing desired products.

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

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.

Effects of low energy E-beam irradiation on graphene and graphene field effect transistors and raman metrology of graphene on split gate test structures

NASA Astrophysics Data System (ADS)

Rao, Gayathri S.

2011-12-01

Apart from its compelling performance in conventional nanoelectronic device geometries, graphene is an appropriate candidate to study certain interesting phenomenon (e.g. the Veselago lens effect) predicted on the basis of its linear electron dispersion relation. A key requirement for the observation of such phenomenon in graphene and for its use in conventional field-effect transistor (FET) devices is the need to minimize defects such as consisting of -- or resulting from -- adsorbates and lattice non-uniformities, and reduce deleterious substrate effects. Consequently the investigation of the origin and interaction of defects in the graphene lattice is essential to improve and tailor graphene-based device performance. In this thesis, optical spectroscopic studies on the influence of low-energy electron irradiation on adsorbate-induced defectivity and doping for substrate supported and suspended graphene were carried out along with spectroscopic and transport measurements on graphene FETs. A comparative investigation of the effects of single-step versus multi-step, low-energy electron irradiation (500 eV) on suspended, substrate supported graphene and on graphene FETs is reported. E-beam irradiation (single-step and multi-step) of substrate-supported graphene resulted in an increase in the Raman ID/IG ratio largely from hydrogenation due to radiolysis of the interfacial water layer between the graphene and the SiO2 substrate and from irradiated surface adsorbates. GFETs subjected to single and multi-step irradiation showed n-doping from CNP (charge neutrality point) shift of ˜ -8 and ˜ -16 V respectively. Correlation of this data with Raman analysis of suspended and supported graphene samples implied a strong role of the substrate and irradiation sequence in determining the level of doping. A correspondingly higher reduction in mobility per incident electron was also observed for GFETs subjected to multi-step irradiation compared to single step, in line with measured Raman ID/IG ratios. Additionally, the Raman G-band DeltaFWHM variation was strongly dependent on the nature of the e-beam irradiation and the presence of the substrate. Single-step irradiated, substrate-supported graphene exhibited substantial broadening while multi-step irradiation resulted in G-band narrowing. This behavior was not observed for suspended graphene which indicated the addition or elimination of substrate-induced phonon-relaxation mechanisms in response to each type of irradiation. The narrowing of the FWHM (G) in the multi-step case is attributed to doping consistent with the Dirac point shift of ˜ -16V and the removal of Landau phonon damping above Ef > ℏwG2 . In strong contrast, single step irradiation of substrate supported graphene yielded a broadening of the FWHM (G) accompanied by a CNP shift of ˜ -8V indicating appreciable n-doping. This reveals the presence of alternate phonon decay channels even when Landau damping above Ef > ℏwG2 is removed. It is proposed in this dissertation that this phenomenon is linked to hybridization of silicon oxide defect states (induced by single-step e-beam irradiation) and graphene electron states. This hybridization promotes a graphene phonon decay channel distinct from Landau damping, the latter being forbidden under sufficient doping. It is proposed that the alternate phonon decay channel involves two-component inelastic scattering, wherein the graphene phonons transfer energy to the carriers in the lattice which in turn couple to the polar phonons of the substrate resulting in mobility reduction. Furthermore, it is proposed that this defect-induced, graphene phonon decay channel is inhibited in multi-step e-beam irradiation due to the presence of adsorbates on the graphene introduced during ambient exposure between radiation cycles. On e-beam irradiation the adsorbates induce polar orientation of water dipoles at the graphene/SiO2 interface. This polar layer shifts the hybridized defect bands closer to the graphene Dirac bands thereby reducing the inelastic scattering and inhibiting the phonon decay medicated by SiO2 surface polar phonons (SPP). This model also explains the enhancement of n-type doping in GFETS observed for multi-step irradiation. These results highlight the impact of substrate defects and interaction of induced defectivity with the e-beam along with the role of interfacial water in impacting graphene device performance. The thesis also presents data on Raman-based characterization of graphene including layer number determination and carrier concentration measurement. Determination of layer number for graphene exfoliates focused on the splitting of the 2D Raman band. In addition, an alternate Raman-based thickness metrology was evaluated for CVD-based, polycrystalline graphene. Both were carried out on split gate test structures as a method for monolayer or bilayer confirmation in device geometries. In addition, carrier concentration measurements of exfoliates on 300nm SiO2 and split-gate test structure substrate have also been characterized with back gate biasing. These measurements made use of the stiffening of the Raman G-band with doping and the narrowing of the G-band FWHM. These results were important for validating conclusions from the e-beam irradiation experiments mentioned above regarding carrier doping.

Implementing a Continuous Quality Improvement Program in a High-Volume Clinical Echocardiography Laboratory: Improving Care for Patients With Aortic Stenosis.

PubMed

Samad, Zainab; Minter, Stephanie; Armour, Alicia; Tinnemore, Amanda; Sivak, Joseph A; Sedberry, Brenda; Strub, Karen; Horan, Seanna M; Harrison, J Kevin; Kisslo, Joseph; Douglas, Pamela S; Velazquez, Eric J

2016-03-01

The management of aortic stenosis rests on accurate echocardiographic diagnosis. Hence, it was chosen as a test case to examine the utility of continuous quality improvement (CQI) approaches to increase echocardiographic data accuracy and reliability. A novel, multistep CQI program was designed and prospectively used to investigate whether it could minimize the difference in aortic valve mean gradients reported by echocardiography when compared with cardiac catheterization. The Duke Echo Laboratory compiled a multidisciplinary CQI team including 4 senior sonographers and MD faculty to develop a mapped CQI process that incorporated Intersocietal Accreditation Commission standards. Quarterly, the CQI team reviewed all moderate- or greater-severity aortic stenosis echocardiography studies with concomitant catheterization data, and deidentified individual and group results were shared at meetings attended by cardiologists and sonographers. After review of 2011 data, the CQI team proposed specific amendments implemented over 2012: the use of nontraditional imaging and Doppler windows as well as evaluation of aortic gradients by a second sonographer. The primary outcome measure was agreement between catheterization- and echocardiography-derived mean gradients calculated by using the coverage probability index with a prespecified acceptable echocardiography-catheterization difference of <10 mm Hg in mean gradient. Between January 2011 and January 2014, 2093 echocardiograms reported moderate or greater aortic stenosis. Among cases with available catheterization data pre- and post-CQI, the coverage probability index increased from 54% to 70% (P=0.03; 98 cases, year 2011; 70 cases, year 2013). The proportion of patients referred for invasive valve hemodynamics decreased from 47% pre-CQI to 19% post-CQI (P<0.001). A laboratory practice pattern that was amenable to reform was identified, and a multistep modification was designed and implemented that produced clinically valuable performance improvements. The new protocol improved aortic stenosis mean gradient agreement between echocardiography and catheterization and was associated with a measurable decrease in referrals of patients for invasive studies. © 2016 American Heart Association, Inc.

A land classification protocol for pollinator ecology research: An urbanization case study.

PubMed

Samuelson, Ash E; Leadbeater, Ellouise

2018-06-01

Land-use change is one of the most important drivers of widespread declines in pollinator populations. Comprehensive quantitative methods for land classification are critical to understanding these effects, but co-option of existing human-focussed land classifications is often inappropriate for pollinator research. Here, we present a flexible GIS-based land classification protocol for pollinator research using a bottom-up approach driven by reference to pollinator ecology, with urbanization as a case study. Our multistep method involves manually generating land cover maps at multiple biologically relevant radii surrounding study sites using GIS, with a focus on identifying land cover types that have a specific relevance to pollinators. This is followed by a three-step refinement process using statistical tools: (i) definition of land-use categories, (ii) principal components analysis on the categories, and (iii) cluster analysis to generate a categorical land-use variable for use in subsequent analysis. Model selection is then used to determine the appropriate spatial scale for analysis. We demonstrate an application of our protocol using a case study of 38 sites across a gradient of urbanization in South-East England. In our case study, the land classification generated a categorical land-use variable at each of four radii based on the clustering of sites with different degrees of urbanization, open land, and flower-rich habitat. Studies of land-use effects on pollinators have historically employed a wide array of land classification techniques from descriptive and qualitative to complex and quantitative. We suggest that land-use studies in pollinator ecology should broadly adopt GIS-based multistep land classification techniques to enable robust analysis and aid comparative research. Our protocol offers a customizable approach that combines specific relevance to pollinator research with the potential for application to a wide range of ecological questions, including agroecological studies of pest control.

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.

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

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

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.

Multi-step infrared macro-fingerprint features of ethanol extracts from different Cistanche species in China combined with HPLC fingerprint

NASA Astrophysics Data System (ADS)

Xu, Rong; Sun, Suqin; Zhu, Weicheng; Xu, Changhua; Liu, Yougang; Shen, Liang; Shi, Yue; Chen, Jun

2014-07-01

The genus Cistanche generally has four species in China, including C. deserticola (CD), C. tubulosa (CT), C. salsa (CS) and C. sinensis (CSN), among which CD and CT are official herbal sources of Cistanche Herba (CH). To clarify the sources of CH and ensure the clinical efficacy and safety, a multi-step IR macro-fingerprint method was developed to analyze and evaluate the ethanol extracts of the four species. Through this method, the four species were distinctively distinguished, and the main active components phenylethanoid glycosides (PhGs) were estimated rapidly according to the fingerprint features in the original IR spectra, second derivative spectra, correlation coefficients and 2D-IR correlation spectra. The exclusive IR fingerprints in the spectra including the positions, shapes and numbers of peaks indicated that constitutes of CD were the most abundant, and CT had the highest level of PhGs. The results deduced by some macroscopic features in IR fingerprint were in agreement with the HPLC fingerprint of PhGs from the four species, but it should be noted that the IR provided more chemical information than HPLC. In conclusion, with the advantages of high resolution, cost effective and speediness, the macroscopic IR fingerprint method should be a promising analytical technique for discriminating extremely similar herbal medicine, monitoring and tracing the constituents of different extracts and even for quality control of the complex systems such as TCM.

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.

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.

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.

Bridging the gap

PubMed Central

Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

2011-01-01

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base. PMID:21822050

Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

PubMed

Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

2011-01-01

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.

Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.

PubMed

McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

2014-07-01

Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

An update on coating/manufacturing techniques of microneedles.

PubMed

Tarbox, Tamara N; Watts, Alan B; Cui, Zhengrong; Williams, Robert O

2017-12-29

Recently, results have been published for the first successful phase I human clinical trial investigating the use of dissolving polymeric microneedles… Even so, further clinical development represents an important hurdle that remains in the translation of microneedle technology to approved products. Specifically, the potential for accumulation of polymer within the skin upon repeated application of dissolving and coated microneedles, combined with a lack of safety data in humans, predicates a need for further clinical investigation. Polymers are an important consideration for microneedle technology-from both manufacturing and drug delivery perspectives. The use of polymers enables a tunable delivery strategy, but the scalability of conventional manufacturing techniques could arguably benefit from further optimization. Micromolding has been suggested in the literature as a commercially viable means to mass production of both dissolving and swellable microneedles. However, the reliance on master molds, which are commonly manufactured using resource intensive microelectronics industry-derived processes, imparts notable material and design limitations. Further, the inherently multi-step filling and handling processes associated with micromolding are typically batch processes, which can be challenging to scale up. Similarly, conventional microneedle coating processes often follow step-wise batch processing. Recent developments in microneedle coating and manufacturing techniques are highlighted, including micromilling, atomized spraying, inkjet printing, drawing lithography, droplet-born air blowing, electro-drawing, continuous liquid interface production, 3D printing, and polyelectrolyte multilayer coating. This review provides an analysis of papers reporting on potentially scalable production techniques for the coating and manufacturing of microneedles.

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.

Biointervention makes leather processing greener: an integrated cleansing and tanning system.

PubMed

Thanikaivelan, Palanisamy; Rao, Jonnalagadda Raghava; Nair, Balachandran Unni; Ramasami, Thirumalachari

2003-06-01

The do-undo methods adopted in conventional leather processing generate huge amounts of pollutants. In other words, conventional methods employed in leather processing subject the skin/hide to wide variations in pH. Pretanning and tanning processes alone contribute more than 90% of the total pollution from leather processing. Included in this is a great deal of solid wastes such as lime and chrome sludge. In the approach described here, the hair and flesh removal as well as fiber opening have been achieved using biocatalysts at pH 8.0 for cow hides. This was followed by a pickle-free chrome tanning, which does not require a basification step. Hence, this tanning technique involves primarily three steps, namely, dehairing, fiber opening, and tanning. It has been found that the extent of hair removal, opening up of fiber bundles, and penetration and distribution of chromium are comparable to that produced by traditional methods. This has been substantiated through scanning electron microscopic, stratigraphic chrome distribution analysis, and softness measurements. Performance of the leathers is shown to be on par with conventionally processed leathers through physical and hand evaluation. Importantly, softness of the leathers is numerically proven to be comparable with that of control. The process also demonstrates reduction in chemical oxygen demand load by 80%, total solids load by 85%, and chromium load by 80% as compared to the conventional process, thereby leading toward zero discharge. The input-output audit shows that the biocatalytic three-step tanning process employs a very low amount of chemicals, thereby reducing the discharge by 90% as compared to the conventional multistep processing. Furthermore, it is also demonstrated that the process is technoeconomically viable.

Guiding gate-etch process development using 3D surface reaction modeling for 7nm and beyond

NASA Astrophysics Data System (ADS)

Dunn, Derren; Sporre, John R.; Deshpande, Vaibhav; Oulmane, Mohamed; Gull, Ronald; Ventzek, Peter; Ranjan, Alok

2017-03-01

Increasingly, advanced process nodes such as 7nm (N7) are fundamentally 3D and require stringent control of critical dimensions over high aspect ratio features. Process integration in these nodes requires a deep understanding of complex physical mechanisms to control critical dimensions from lithography through final etch. Polysilicon gate etch processes are critical steps in several device architectures for advanced nodes that rely on self-aligned patterning approaches to gate definition. These processes are required to meet several key metrics: (a) vertical etch profiles over high aspect ratios; (b) clean gate sidewalls free of etch process residue; (c) minimal erosion of liner oxide films protecting key architectural elements such as fins; and (e) residue free corners at gate interfaces with critical device elements. In this study, we explore how hybrid modeling approaches can be used to model a multi-step finFET polysilicon gate etch process. Initial parts of the patterning process through hardmask assembly are modeled using process emulation. Important aspects of gate definition are then modeled using a particle Monte Carlo (PMC) feature scale model that incorporates surface chemical reactions.1 When necessary, species and energy flux inputs to the PMC model are derived from simulations of the etch chamber. The modeled polysilicon gate etch process consists of several steps including a hard mask breakthrough step (BT), main feature etch steps (ME), and over-etch steps (OE) that control gate profiles at the gate fin interface. An additional constraint on this etch flow is that fin spacer oxides are left intact after final profile tuning steps. A natural optimization required from these processes is to maximize vertical gate profiles while minimizing erosion of fin spacer films.2

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.

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.

Influence of Natural Convection and Thermal Radiation Multi-Component Transport in MOCVD Reactors

NASA Technical Reports Server (NTRS)

Lowry, S.; Krishnan, A.; Clark, I.

1999-01-01

The influence of Grashof and Reynolds number in Metal Organic Chemical Vapor (MOCVD) reactors is being investigated under a combined empirical/numerical study. As part of that research, the deposition of Indium Phosphide in an MOCVD reactor is modeled using the computational code CFD-ACE. The model includes the effects of convection, conduction, and radiation as well as multi-component diffusion and multi-step surface/gas phase chemistry. The results of the prediction are compared with experimental data for a commercial reactor and analyzed with respect to the model accuracy.

Comparison between stochastic and machine learning methods for hydrological multi-step ahead forecasting: All forecasts are wrong!

NASA Astrophysics Data System (ADS)

Papacharalampous, Georgia; Tyralis, Hristos; Koutsoyiannis, Demetris

2017-04-01

Machine learning (ML) is considered to be a promising approach to hydrological processes forecasting. We conduct a comparison between several stochastic and ML point estimation methods by performing large-scale computational experiments based on simulations. The purpose is to provide generalized results, while the respective comparisons in the literature are usually based on case studies. The stochastic methods used include simple methods, models from the frequently used families of Autoregressive Moving Average (ARMA), Autoregressive Fractionally Integrated Moving Average (ARFIMA) and Exponential Smoothing models. The ML methods used are Random Forests (RF), Support Vector Machines (SVM) and Neural Networks (NN). The comparison refers to the multi-step ahead forecasting properties of the methods. A total of 20 methods are used, among which 9 are the ML methods. 12 simulation experiments are performed, while each of them uses 2 000 simulated time series of 310 observations. The time series are simulated using stochastic processes from the families of ARMA and ARFIMA models. Each time series is split into a fitting (first 300 observations) and a testing set (last 10 observations). The comparative assessment of the methods is based on 18 metrics, that quantify the methods' performance according to several criteria related to the accurate forecasting of the testing set, the capturing of its variation and the correlation between the testing and forecasted values. The most important outcome of this study is that there is not a uniformly better or worse method. However, there are methods that are regularly better or worse than others with respect to specific metrics. It appears that, although a general ranking of the methods is not possible, their classification based on their similar or contrasting performance in the various metrics is possible to some extent. Another important conclusion is that more sophisticated methods do not necessarily provide better forecasts compared to simpler methods. It is pointed out that the ML methods do not differ dramatically from the stochastic methods, while it is interesting that the NN, RF and SVM algorithms used in this study offer potentially very good performance in terms of accuracy. It should be noted that, although this study focuses on hydrological processes, the results are of general scientific interest. Another important point in this study is the use of several methods and metrics. Using fewer methods and fewer metrics would have led to a very different overall picture, particularly if those fewer metrics corresponded to fewer criteria. For this reason, we consider that the proposed methodology is appropriate for the evaluation of forecasting methods.

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

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.

Seismic imaging of deep crustal melt sills beneath Costa Rica suggests a method for the formation of the Archean continental crust

NASA Astrophysics Data System (ADS)

Harmon, Nicholas; Rychert, Catherine A.

2015-11-01

Continental crust formed billions of years ago but cannot be explained by a simple evolution of primary mantle magmas. A multi-step process is required that likely includes re-melting of wet metamorphosed basalt at high pressures. Such a process could occur at depth in oceanic crust that has been thickened by a large magmatic event. In Central America, variations in geologically inferred, pre-existing oceanic crustal thickness beneath the arc provides an excellent opportunity to study its effect on magma storage, re-melting of meta-basalts, and the potential for creating continental crust. We use surface waves derived from ambient noise tomography to image 6% radially anisotropic structures in the thickened oceanic plateau crust of Costa Rica that likely represent deep crustal melt sills. In Nicaragua, where the arc is forming on thinner oceanic crust, we do not image these deep crustal melt sills. The presence of these deep sills correlates with more felsic arc outputs from the Costa Rican Arc suggesting pre-existing thickened crust accelerates processing of primary basalts to continental compositions. In the Archean, reprocessing thickened oceanic crust by subsequent hydrated hotspot volcanism or subduction zone volcanism may have similarly enhanced formation of early continental crust. This mechanism may have been particularly important if subduction did not initiate until 3 Ga.

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

Filled Co (sub X) Ni (sub 4-x) Sb (sub 12-y) Sn (sub Y) Skutterudites: Processing and Thermoelectric Properties

NASA Technical Reports Server (NTRS)

Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

2015-01-01

Skutterudites have proven to be a useful thermoelectric system as a result of their enhanced figure of merit (ZT1), cheap material cost, favorable mechanical properties, and good thermal stability. The majority of skutterudite interest in recent years has been focused on binary skutterudites like CoSb3 or CoAs3. Binary skutterudites are often double and triple filled, with a range of elements from the lanthanide series, in order to reduce the lattice component of thermal conductivity. Ternary and quaternary skutterudites, such as Co4Ge6Se6 or Ni4Sb8Sn4, provide additional paths to tune the electronic structure. The thermal conductivity can further be improved in these complex skutterudites by the introduction of fillers. The Co (sub X) Ni (sub 4-x) Sb (sub 12-y) Sn (sub Y) system has been investigated as both a p- and n-type thermoelectric material, and is stable up to 200 degrees Centigrade. Yb, Ce, and Dy fillers have been introduced into the skutterudite to study the influence of both the type and the quantity of fillers on processing conditions and thermoelectric properties. The system was processed through a multi-step technique that includes solidification, mechano-chemical alloying, and hot pressing which will be discussed along with thermoelectric transport properties.

Automated production at the curie level of no-carrier-added 6-[(18)F]fluoro-L-dopa and 2-[(18)F]fluoro-L-tyrosine on a FASTlab synthesizer.

PubMed

Lemaire, C; Libert, L; Franci, X; Genon, J-L; Kuci, S; Giacomelli, F; Luxen, A

2015-06-15

An efficient, fully automated, enantioselective multi-step synthesis of no-carrier-added (nca) 6-[(18)F]fluoro-L-dopa ([(18)F]FDOPA) and 2-[(18)F]fluoro-L-tyrosine ([(18)F]FTYR) on a GE FASTlab synthesizer in conjunction with an additional high- performance liquid chromatography (HPLC) purification has been developed. A PTC (phase-transfer catalyst) strategy was used to synthesize these two important radiopharmaceuticals. According to recent chemistry improvements, automation of the whole process was implemented in a commercially available GE FASTlab module, with slight hardware modification using single use cassettes and stand-alone HPLC. [(18)F]FDOPA and [(18)F]FTYR were produced in 36.3 ± 3.0% (n = 8) and 50.5 ± 2.7% (n = 10) FASTlab radiochemical yield (decay corrected). The automated radiosynthesis on the FASTlab module requires about 52 min. Total synthesis time including HPLC purification and formulation was about 62 min. Enantiomeric excesses for these two aromatic amino acids were always >95%, and the specific activity of was >740 GBq/µmol. This automated synthesis provides high amount of [(18)F]FDOPA and [(18)F]FTYR (>37 GBq end of synthesis (EOS)). The process, fully adaptable for reliable production across multiple PET sites, could be readily implemented into a clinical good manufacturing process (GMP) environment. Copyright © 2015 John Wiley & Sons, Ltd.

Polysaccharide of Black cumin (Nigella sativa) modulates molecular signaling cascade of gastric ulcer pathogenesis.

PubMed

Manjegowda, Srikanta Belagihalli; Rajagopal, Harsha Mysore; Dharmesh, Shylaja Mallaiah

2017-08-01

Gastric ulcer is a multi-step disease and healing requires a complex process including repair and re-architecture of gastric mucosa with the involvement of molecular events. Current study was designed to understand the gastric ulcer healing mechanism of rhamnogalacturonan-I type pectic polysaccharide of black cumin (BCPP) utilizing acetic acid induced gastric ulcers in rats. BCPP fed groups at 200mg/kg b.w. for 10days showed up to 85% healing of gastric ulcers with modulation of key molecular events involved in ulcer healing process such as increase in gastric mucin content, cyclooxygenase-2 (Cox-2) and prostaglandin E 2 (PGE 2 ). The increase in extracellular signal-regulated kinase-2 (ERK-2) indicated that, BCPP could induce PGE-2 synthesis by increasing ERK-2 mediated COX-2 activity. Increase in matrix metalloproteinase-2 (MMP-2) and decrease in MMP-9 levels in BCPP treated groups indicated differential regulation of MMP-2 and 9, an essential event required for gastric mucosal re-modulation. BCPP containing bound phenolics (26mg/g) might have also played a role in increasing speed and quality of ulcer healing by inhibiting H + , K + -ATPase and decreasing free radical mediated oxidation and cellular damages. Overall, studies showed that the polysaccharide can mediate ulcer healing by modulating signaling pathways involved in either ulcer aggravation or healing process. Copyright © 2017. Published by Elsevier B.V.

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.

Plasmids as stochastic model systems

NASA Astrophysics Data System (ADS)

Paulsson, Johan

2003-05-01

Plasmids are self-replicating gene clusters present in on average 2-100 copies per bacterial cell. To reduce random fluctuations and thereby avoid extinction, they ubiquitously autoregulate their own synthesis using negative feedback loops. Here I use van Kampen's Ω-expansion for a two-dimensional model of negative feedback including plasmids and ther replication inhibitors. This analytically summarizes the standard perspective on replication control -- including the effects of sensitivity amplification, exponential time-delays and noisy signaling. I further review the two most common molecular sensitivity mechanisms: multistep control and cooperativity. Finally, I discuss more controversial sensitivity schemes, such as noise-enhanced sensitivity, the exploitation of small-number combinatorics and double-layered feedback loops to suppress noise in disordered environments.

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.

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.

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.

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.

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.

The Ocean Observatories Initiative: Data pre-Processing: Diagnostic Tools to Prepare Data for QA/QC Processing.

NASA Astrophysics Data System (ADS)

Belabbassi, L.; Garzio, L. M.; Smith, M. J.; Knuth, F.; Vardaro, M.; Kerfoot, J.

2016-02-01

The Ocean Observatories Initiative (OOI), funded by the National Science Foundation, provides users with access to long-term datasets from a variety of deployed oceanographic sensors. The Pioneer Array in the Atlantic Ocean off the Coast of New England hosts 10 moorings and 6 gliders. Each mooring is outfitted with 6 to 19 different instruments telemetering more than 1000 data streams. These data are available to science users to collaborate on common scientific goals such as water quality monitoring and scale variability measures of continental shelf processes and coastal open ocean exchanges. To serve this purpose, the acquired datasets undergo an iterative multi-step quality assurance and quality control procedure automated to work with all types of data. Data processing involves several stages, including a fundamental pre-processing step when the data are prepared for processing. This takes a considerable amount of processing time and is often not given enough thought in development initiatives. The volume and complexity of OOI data necessitates the development of a systematic diagnostic tool to enable the management of a comprehensive data information system for the OOI arrays. We present two examples to demonstrate the current OOI pre-processing diagnostic tool. First, Data Filtering is used to identify incomplete, incorrect, or irrelevant parts of the data and then replaces, modifies or deletes the coarse data. This provides data consistency with similar datasets in the system. Second, Data Normalization occurs when the database is organized in fields and tables to minimize redundancy and dependency. At the end of this step, the data are stored in one place to reduce the risk of data inconsistency and promote easy and efficient mapping to the database.

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.

Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators

PubMed Central

Aggarwal, Kanu Priya; Narula, Shifa; Kakkar, Monica

2013-01-01

Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation. PMID:24151593

The Rockefeller University Navigation Program: A Structured Multidisciplinary Protocol Development and Educational Program to Advance Translational Research

PubMed Central

Kost, Rhonda G.; Dowd, Kathleen A.; Hurley, Arlene M.; Rainer, Tyler‐Lauren; Coller, Barry S.

2014-01-01

Abstract The development of translational clinical research protocols is complex. To assist investigators, we developed a structured supportive guidance process (Navigation) to expedite protocol development to the standards of good clinical practice (GCP), focusing on research ethics and integrity. Navigation consists of experienced research coordinators leading investigators through a concerted multistep protocol development process from concept initiation to submission of the final protocol. To assess the effectiveness of Navigation, we collect data on the experience of investigators, the intensity of support required for protocol development, IRB review outcomes, and protocol start and completion dates. One hundred forty‐four protocols underwent Navigation and achieved IRB approval since the program began in 2007, including 37 led by trainee investigators, 26 led by MDs, 9 by MD/PhDs, 57 by PhDs, and 12 by investigators with other credentials (e.g., RN, MPH). In every year, more than 50% of Navigated protocols were approved by the IRB within 30 days. For trainees who had more than one protocol navigated, the intensity of Navigation support required decreased over time. Navigation can increase access to translational studies for basic scientists, facilitate GCP training for investigators, and accelerate development and approval of protocols of high ethical and scientific quality. PMID:24405608

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

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

GLI1, a master regulator of the hallmark of pancreatic cancer.

PubMed

Kasai, Kenji

2016-12-01

Hedgehog signaling is highly conserved across species and governs proper embryonic development. Germline gene mutations that reduce this signaling activity cause a variety of developmental abnormalities such as holoprosencephaly, while those that enhance Hedgehog signaling activity induce a tumor-predisposition condition Nevoid basal cell carcinoma syndrome. Furthermore, dysregulated activation of Hedgehog signaling has been recognized in various sporadic malignancies, including pancreatic adenocarcinoma. Pancreatic adenocarcinoma develops through a multistep carcinogenesis starting with oncogenic mutation of the KRAS gene. During this process, precancerous or cancer cells secrete Hedgehog ligand proteins to promote characteristic desmoplastic stroma around the cells, which in turn activates the expression of the downstream transcription factor GLI1 inside the cells. The quantitative and spatiotemporal dysregulation of GLI1 subsequently leads to the expression of transcriptional target genes of GLI1 that govern the hallmark of malignant properties. Here, after a brief introductory outline, a perspective is offered of Hedgehog signaling with a special focus on the role of GLI1 in pancreatic carcinogenesis. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Tumor Cell Invasion Can Be Blocked by Modulators of Collagen Fibril Alignment That Control Assembly of the Extracellular Matrix.

PubMed

Grossman, Moran; Ben-Chetrit, Nir; Zhuravlev, Alina; Afik, Ran; Bassat, Elad; Solomonov, Inna; Yarden, Yosef; Sagi, Irit

2016-07-15

Abnormal architectures of collagen fibers in the extracellular matrix (ECM) are hallmarks of many invasive diseases, including cancer. Targeting specific stages of collagen assembly in vivo presents a great challenge due to the involvement of various crosslinking enzymes in the multistep, hierarchical process of ECM build-up. Using advanced microscopic tools, we monitored stages of fibrillary collagen assembly in a native fibroblast-derived 3D matrix system and identified anti-lysyl oxidase-like 2 (LOXL2) antibodies that alter the natural alignment and width of endogenic fibrillary collagens without affecting ECM composition. The disrupted collagen morphologies interfered with the adhesion and invasion properties of human breast cancer cells. Treatment of mice bearing breast cancer xenografts with the inhibitory antibodies resulted in disruption of the tumorigenic collagen superstructure and in reduction of primary tumor growth. Our approach could serve as a general methodology to identify novel therapeutics targeting fibrillary protein organization to treat ECM-associated pathologies. Cancer Res; 76(14); 4249-58. ©2016 AACR. ©2016 American Association for Cancer Research.

Perception of competence in middle school physical education: instrument development and validation.

PubMed

Scrabis-Fletcher, Kristin; Silverman, Stephen

2010-03-01

Perception of Competence (POC) has been studied extensively in physical activity (PA) research with similar instruments adapted for physical education (PE) research. Such instruments do not account for the unique PE learning environment. Therefore, an instrument was developed and the scores validated to measure POC in middle school PE. A multiphase design was used consisting of an intensive theoretical review, elicitation study, prepilot study, pilot study, content validation study, and final validation study (N=1281). Data analysis included a multistep iterative process to identify the best model fit. A three-factor model for POC was tested and resulted in root mean square error of approximation = .09, root mean square residual = .07, goodness offit index = .90, and adjusted goodness offit index = .86 values in the acceptable range (Hu & Bentler, 1999). A two-factor model was also tested and resulted in a good fit (two-factor fit indexes values = .05, .03, .98, .97, respectively). The results of this study suggest that an instrument using a three- or two-factor model provides reliable and valid scores ofPOC measurement in middle school PE.

Rational therapeutic choice for older patients with lymphoma.

PubMed

Bron, Dominique; Soubeyran, Pierre

2017-09-01

The choice for an optimal treatment in older lymphoma patients is a real challenge for hemato-oncologists. They have to treat a potentially curative lymphoma, and concomitantly protect their patients from unacceptable toxicities. Some recommendations are provided for the major subtypes of lymphomas including the antitumoral treatment and primarily the optimal supportive care. All the recent literature data converge to say that the approach of an older patient with a malignant hemopathy is a multistep procedure. This process comprises the appraisal of life expectancy of the patient with or without the disease, the prognostic factors of the tumor, the functional, physiological and cognitive functions evaluation, the socio-economical environment and the patient's expectancy in terms of quality of life. Major progresses have been achieved in the management of diffuse large B cell lymphoma and mantle cell lymphoma in patients up to 80 and above 80 years old. With all these information in hands, the hematologist will decide if the treatment's objective is the standard treatment with optimal supportive care (fit patients), tailor-made adapted chemotherapy (unfit patients) or preservation of quality of life (frail patients).

Genome-Wide Identification and Expression of Xenopus F-Box Family of Proteins.

PubMed

Saritas-Yildirim, Banu; Pliner, Hannah A; Ochoa, Angelica; Silva, Elena M

2015-01-01

Protein degradation via the multistep ubiquitin/26S proteasome pathway is a rapid way to alter the protein profile and drive cell processes and developmental changes. Many key regulators of embryonic development are targeted for degradation by E3 ubiquitin ligases. The most studied family of E3 ubiquitin ligases is the SCF ubiquitin ligases, which use F-box adaptor proteins to recognize and recruit target proteins. Here, we used a bioinformatics screen and phylogenetic analysis to identify and annotate the family of F-box proteins in the Xenopus tropicalis genome. To shed light on the function of the F-box proteins, we analyzed expression of F-box genes during early stages of Xenopus development. Many F-box genes are broadly expressed with expression domains localized to diverse tissues including brain, spinal cord, eye, neural crest derivatives, somites, kidneys, and heart. All together, our genome-wide identification and expression profiling of the Xenopus F-box family of proteins provide a foundation for future research aimed to identify the precise role of F-box dependent E3 ubiquitin ligases and their targets in the regulatory circuits of development.

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

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.

Molecular Cloning Designer Simulator (MCDS): All-in-one molecular cloning and genetic engineering design, simulation and management software for complex synthetic biology and metabolic engineering projects.

PubMed

Shi, Zhenyu; Vickers, Claudia E

2016-12-01

Molecular Cloning Designer Simulator (MCDS) is a powerful new all-in-one cloning and genetic engineering design, simulation and management software platform developed for complex synthetic biology and metabolic engineering projects. In addition to standard functions, it has a number of features that are either unique, or are not found in combination in any one software package: (1) it has a novel interactive flow-chart user interface for complex multi-step processes, allowing an integrated overview of the whole project; (2) it can perform a user-defined workflow of cloning steps in a single execution of the software; (3) it can handle multiple types of genetic recombineering, a technique that is rapidly replacing classical cloning for many applications; (4) it includes experimental information to conveniently guide wet lab work; and (5) it can store results and comments to allow the tracking and management of the whole project in one platform. MCDS is freely available from https://mcds.codeplex.com.

[Online continuing medical education based on national disease management guidelines. The e-learning platform leitlinien-wissen.de].

PubMed

Vollmar, H C; Schürer-Maly, C-C; Lelgemann, M; Koneczny, N; Koch, M; Butzlaff, M

2006-05-01

Effective translation of relevant knowledge into clinical practice is essential for modern health care systems. National Disease Management Guidelines (NDMG) are considered relevant instruments to support this transfer. To implement NDMG Internet-based continuing medical education (CME), modules and online case-based learning objects were designed and published. To ensure high quality the contents are based on NDMG and subjected to multi-step review processes. Presentation on the web was realized through a modified content management system. To obtain a CME certificate, completing an online questionnaire using a four-point Likert scale was mandatory. Between June 2003 and April 2005, 3,105 physicians were registered and used the platform: 95% of the physicians expressed positive feedback in the evaluation questionnaire, and 35% actually used the corresponding NDMG in practice. This prompted the development of interactive medical case-based learning objects as a second learning pathway. An Internet platform for CME including case-based learning objects can be a helpful tool to assure the provision of scientific knowledge for patient care.

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.

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.

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.

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.

PredPPCrys: Accurate Prediction of Sequence Cloning, Protein Production, Purification and Crystallization Propensity from Protein Sequences Using Multi-Step Heterogeneous Feature Fusion and Selection

PubMed Central

Wang, Huilin; Wang, Mingjun; Tan, Hao; Li, Yuan; Zhang, Ziding; Song, Jiangning

2014-01-01

X-ray crystallography is the primary approach to solve the three-dimensional structure of a protein. However, a major bottleneck of this method is the failure of multi-step experimental procedures to yield diffraction-quality crystals, including sequence cloning, protein material production, purification, crystallization and ultimately, structural determination. Accordingly, prediction of the propensity of a protein to successfully undergo these experimental procedures based on the protein sequence may help narrow down laborious experimental efforts and facilitate target selection. A number of bioinformatics methods based on protein sequence information have been developed for this purpose. However, our knowledge on the important determinants of propensity for a protein sequence to produce high diffraction-quality crystals remains largely incomplete. In practice, most of the existing methods display poorer performance when evaluated on larger and updated datasets. To address this problem, we constructed an up-to-date dataset as the benchmark, and subsequently developed a new approach termed ‘PredPPCrys’ using the support vector machine (SVM). Using a comprehensive set of multifaceted sequence-derived features in combination with a novel multi-step feature selection strategy, we identified and characterized the relative importance and contribution of each feature type to the prediction performance of five individual experimental steps required for successful crystallization. The resulting optimal candidate features were used as inputs to build the first-level SVM predictor (PredPPCrys I). Next, prediction outputs of PredPPCrys I were used as the input to build second-level SVM classifiers (PredPPCrys II), which led to significantly enhanced prediction performance. Benchmarking experiments indicated that our PredPPCrys method outperforms most existing procedures on both up-to-date and previous datasets. In addition, the predicted crystallization targets of currently non-crystallizable proteins were provided as compendium data, which are anticipated to facilitate target selection and design for the worldwide structural genomics consortium. PredPPCrys is freely available at http://www.structbioinfor.org/PredPPCrys. PMID:25148528

TCC: an R package for comparing tag count data with robust normalization strategies

PubMed Central

2013-01-01

Background Differential expression analysis based on “next-generation” sequencing technologies is a fundamental means of studying RNA expression. We recently developed a multi-step normalization method (called TbT) for two-group RNA-seq data with replicates and demonstrated that the statistical methods available in four R packages (edgeR, DESeq, baySeq, and NBPSeq) together with TbT can produce a well-ranked gene list in which true differentially expressed genes (DEGs) are top-ranked and non-DEGs are bottom ranked. However, the advantages of the current TbT method come at the cost of a huge computation time. Moreover, the R packages did not have normalization methods based on such a multi-step strategy. Results TCC (an acronym for Tag Count Comparison) is an R package that provides a series of functions for differential expression analysis of tag count data. The package incorporates multi-step normalization methods, whose strategy is to remove potential DEGs before performing the data normalization. The normalization function based on this DEG elimination strategy (DEGES) includes (i) the original TbT method based on DEGES for two-group data with or without replicates, (ii) much faster methods for two-group data with or without replicates, and (iii) methods for multi-group comparison. TCC provides a simple unified interface to perform such analyses with combinations of functions provided by edgeR, DESeq, and baySeq. Additionally, a function for generating simulation data under various conditions and alternative DEGES procedures consisting of functions in the existing packages are provided. Bioinformatics scientists can use TCC to evaluate their methods, and biologists familiar with other R packages can easily learn what is done in TCC. Conclusion DEGES in TCC is essential for accurate normalization of tag count data, especially when up- and down-regulated DEGs in one of the samples are extremely biased in their number. TCC is useful for analyzing tag count data in various scenarios ranging from unbiased to extremely biased differential expression. TCC is available at http://www.iu.a.u-tokyo.ac.jp/~kadota/TCC/ and will appear in Bioconductor (http://bioconductor.org/) from ver. 2.13. PMID:23837715

Information processing during NREM sleep and sleep quality in insomnia.

PubMed

Ceklic, Tijana; Bastien, Célyne H

2015-12-01

Insomnia sufferers (INS) are cortically hyperaroused during sleep, which seems to translate into altered information processing during nighttime. While information processing, as measured by event-related potentials (ERPs), during wake appears to be associated with sleep quality of the preceding night, the existence of such an association during nighttime has never been investigated. This study aims to investigate nighttime information processing among good sleepers (GS) and INS while considering concomitant sleep quality. Following a multistep clinical evaluation, INS and GS participants underwent 4 consecutive nights of PSG recordings in the sleep laboratory. Thirty nine GS (mean age 34.56±9.02) and twenty nine INS (mean age 43.03±9.12) were included in the study. ERPs (N1, P2, N350) were recorded all night on Night 4 (oddball paradigm) during NREM sleep. Regardless of sleep quality, INS presented a larger N350 amplitude during SWS (p=0.042) while GS showed a larger N350 amplitude during late-night stage 2 sleep (p=0.004). Regardless of diagnosis, those who slept objectively well showed a smaller N350 amplitude (p=0.020) while those who slept subjectively well showed a smaller P2 (p<0.001) and N350 amplitude (p=0.006). Also, those who reported an objectively bad night as good showed smaller P2 (p< 0.001) and N350 (p=0.010) amplitudes. Information processing seems to be associated with concomitant subjective and objective sleep quality for both GS and INS. However, INS show an alteration in information processing during sleep, especially for inhibition processes, regardless of their sleep quality. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Factors affecting the development of somatic cell nuclear transfer embryos in Cattle.

PubMed

Akagi, Satoshi; Matsukawa, Kazutsugu; Takahashi, Seiya

2014-01-01

Nuclear transfer is a complex multistep procedure that includes oocyte maturation, cell cycle synchronization of donor cells, enucleation, cell fusion, oocyte activation and embryo culture. Therefore, many factors are believed to contribute to the success of embryo development following nuclear transfer. Numerous attempts to improve cloning efficiency have been conducted since the birth of the first sheep by somatic cell nuclear transfer. However, the efficiency of somatic cell cloning has remained low, and applications have been limited. In this review, we discuss some of the factors that affect the developmental ability of somatic cell nuclear transfer embryos in cattle.

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.

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

First-Principles Modeling of Hydrogen Storage in Metal Hydride Systems

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

J. Karl Johnson

The objective of this project is to complement experimental efforts of MHoCE partners by using state-of-the-art theory and modeling to study the structure, thermodynamics, and kinetics of hydrogen storage materials. Specific goals include prediction of the heats of formation and other thermodynamic properties of alloys from first principles methods, identification of new alloys that can be tested experimentally, calculation of surface and energetic properties of nanoparticles, and calculation of kinetics involved with hydrogenation and dehydrogenation processes. Discovery of new metal hydrides with enhanced properties compared with existing materials is a critical need for the Metal Hydride Center of Excellence. Newmore » materials discovery can be aided by the use of first principles (ab initio) computational modeling in two ways: (1) The properties, including mechanisms, of existing materials can be better elucidated through a combined modeling/experimental approach. (2) The thermodynamic properties of novel materials that have not been made can, in many cases, be quickly screened with ab initio methods. We have used state-of-the-art computational techniques to explore millions of possible reaction conditions consisting of different element spaces, compositions, and temperatures. We have identified potentially promising single- and multi-step reactions that can be explored experimentally.« less

HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion

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

Cavrois, Marielle; Neidleman, Jason; Yonemoto, Wes

2004-10-15

We recently described a sensitive and specific assay that detects the fusion of HIV-1 virions to a broad range of target cells, including primary CD4 cells. This assay involves the use of virions containing {beta}-lactamase-Vpr (BlaM-Vpr) and the loading of target cells with CCF2, a fluorogenic substrate of {beta}-lactamase. Since Vpr strongly associates with the viral core, uncoating of the viral particle might be required for effective cleavage of CCF2 by BlaM-Vpr. Here, we show that BlaM-Vpr within mature viral cores effectively cleaves CCF2, indicating that this assay measures virion fusion independently of uncoating. We also show that wildtype andmore » Nef-deficient HIV-1 virions fuse with equivalent efficiency to HeLa-CD4 cells, SupT1 T cells, and primary CD4 T cells. Since Nef enhances cytoplasmic delivery of viral cores and increases viral infectivity, these findings indicate that Nef enhances an early post-fusion event in the multistep process of viral entry. Possible sites of Nef action include enlargement of the fusion pore, enhanced uncoating of viral particles, and more efficient passage of viral cores through the dense cortical actin network located immediately beneath the plasma membrane.« less

Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis

PubMed Central

Jiang, Han-Yu; Chen, Jie; Xia, Chun-Chao; Cao, Li-Kun; Duan, Ting; Song, Bin

2018-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major public health problem worldwide. Hepatocarcinogenesis is a complex multistep process at molecular, cellular, and histologic levels with key alterations that can be revealed by noninvasive imaging modalities. Therefore, imaging techniques play pivotal roles in the detection, characterization, staging, surveillance, and prognosis evaluation of HCC. Currently, ultrasound is the first-line imaging modality for screening and surveillance purposes. While based on conclusive enhancement patterns comprising arterial phase hyperenhancement and portal venous and/or delayed phase wash-out, contrast enhanced dynamic computed tomography and magnetic resonance imaging (MRI) are the diagnostic tools for HCC without requirements for histopathologic confirmation. Functional MRI techniques, including diffusion-weighted imaging, MRI with hepatobiliary contrast agents, perfusion imaging, and magnetic resonance elastography, show promise in providing further important information regarding tumor biological behaviors. In addition, evaluation of tumor imaging characteristics, including nodule size, margin, number, vascular invasion, and growth patterns, allows preoperative prediction of tumor microvascular invasion and patient prognosis. Therefore, the aim of this article is to review the current state-of-the-art and recent advances in the comprehensive noninvasive imaging evaluation of HCC. We also provide the basic key concepts of HCC development and an overview of the current practice guidelines. PMID:29904242

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).

Effect of genotyped cows in the reference population on the genomic evaluation of Holstein cattle.

PubMed

Uemoto, Y; Osawa, T; Saburi, J

2017-03-01

This study evaluated the dependence of reliability and prediction bias on the prediction method, the contribution of including animals (bulls or cows), and the genetic relatedness, when including genotyped cows in the progeny-tested bull reference population. We performed genomic evaluation using a Japanese Holstein population, and assessed the accuracy of genomic enhanced breeding value (GEBV) for three production traits and 13 linear conformation traits. A total of 4564 animals for production traits and 4172 animals for conformation traits were genotyped using Illumina BovineSNP50 array. Single- and multi-step methods were compared for predicting GEBV in genotyped bull-only and genotyped bull-cow reference populations. No large differences in realized reliability and regression coefficient were found between the two reference populations; however, a slight difference was found between the two methods for production traits. The accuracy of GEBV determined by single-step method increased slightly when genotyped cows were included in the bull reference population, but decreased slightly by multi-step method. A validation study was used to evaluate the accuracy of GEBV when 800 additional genotyped bulls (POPbull) or cows (POPcow) were included in the base reference population composed of 2000 genotyped bulls. The realized reliabilities of POPbull were higher than those of POPcow for all traits. For the gain of realized reliability over the base reference population, the average ratios of POPbull gain to POPcow gain for production traits and conformation traits were 2.6 and 7.2, respectively, and the ratios depended on heritabilities of the traits. For regression coefficient, no large differences were found between the results for POPbull and POPcow. Another validation study was performed to investigate the effect of genetic relatedness between cows and bulls in the reference and test populations. The effect of genetic relationship among bulls in the reference population was also assessed. The results showed that it is important to account for relatedness among bulls in the reference population. Our studies indicate that the prediction method, the contribution ratio of including animals, and genetic relatedness could affect the prediction accuracy in genomic evaluation of Holstein cattle, when including genotyped cows in the reference population.

Hyperbranched polyglycerol-grafted titanium oxide nanoparticles: synthesis, derivatization, characterization, size separation, and toxicology

NASA Astrophysics Data System (ADS)

Qin, Hongmei; Maruyama, Kyouhei; Amano, Tsukuru; Murakami, Takashi; Komatsu, Naoki

2016-10-01

We have been developing surface functionalization of various nanoparticles including nanodiamond and iron oxide nanoparticles in view of biomedical applications. In this context, TiO2 nanoparticles (TiO2 NP) are functionalized with polyglycerol (PG) to provide water-dispersible TiO2-PG, which is further derivatized through multi-step organic transformations. The resulting TiO2-PG and its derivatives are fully characterized by various analyses including solution-phase 1H and 13C NMR. TiO2-PG was size-tuned with centrifugation by changing the acceleration and duration. At last, no cytotoxicity of TiO2 NP, TiO2-PG, and TiO2-PG functionalized with RGD peptide was observed under dark conditions.

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.

Big Data Geo-Analytical Tool Development for Spatial Analysis Uncertainty Visualization and Quantification Needs

NASA Astrophysics Data System (ADS)

Rose, K.; Bauer, J. R.; Baker, D. V.

2015-12-01

As big data computing capabilities are increasingly paired with spatial analytical tools and approaches, there is a need to ensure uncertainty associated with the datasets used in these analyses is adequately incorporated and portrayed in results. Often the products of spatial analyses, big data and otherwise, are developed using discontinuous, sparse, and often point-driven data to represent continuous phenomena. Results from these analyses are generally presented without clear explanations of the uncertainty associated with the interpolated values. The Variable Grid Method (VGM) offers users with a flexible approach designed for application to a variety of analyses where users there is a need to study, evaluate, and analyze spatial trends and patterns while maintaining connection to and communicating the uncertainty in the underlying spatial datasets. The VGM outputs a simultaneous visualization representative of the spatial data analyses and quantification of underlying uncertainties, which can be calculated using data related to sample density, sample variance, interpolation error, uncertainty calculated from multiple simulations. In this presentation we will show how we are utilizing Hadoop to store and perform spatial analysis 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. The presentation includes examples of the approach being applied to a range of subsurface, geospatial studies (e.g. induced seismicity risk).

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.

Decreasing the load? Is a Multidisciplinary Multistep Medication Review in older people an effective intervention to reduce a patient's Drug Burden Index? Protocol of a randomised controlled trial.

PubMed

van der Meer, Helene G; Wouters, Hans; van Hulten, Rolf; Pras, Niesko; Taxis, Katja

2015-12-23

Older people often use medications with anticholinergic or sedative side effects which increase the risk of falling and worsen cognitive impairment. The Drug Burden Index (DBI) is a measure of the burden of anticholinergic and sedative medications. Medication reviews are typically done by a pharmacist in collaboration with a general practitioner to optimise the medication use and reduce these adverse drug events. We will evaluate whether a Multidisciplinary Multistep Medication Review (3MR) is an effective intervention to reduce a patient's DBI. A randomised controlled trial including 160 patients from 15 community pharmacies will be conducted. Per pharmacy, 1 pharmacist will perform a structured 3MR in close collaboration with the general practitioner, including the objective to reduce the DBI. Primary outcome--the difference in proportion of patients having a decrease in DBI ≥ 0.5 in the intervention and control groups at follow-up. Secondary outcomes--anticholinergic and sedative side effects, falls, cognitive function, activities of daily living, quality of life, hospital admission, and mortality. The burden of patients will be kept at a minimum. The 3MR can be considered as usual care by the pharmacist and general practitioner. Medical specialists will be consulted, if necessary. The intervention is specifically aimed at older community-dwelling patients in an attempt to optimise prescribing, in particular, to reduce medication with anticholinergic and sedative properties. Study results will be published in peer-reviewed journals and will be distributed through information channels targeting professionals. NCT02317666; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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.

Environmental Signals and Regulatory Pathways That Influence Exopolysaccharide Production in Rhizobia

PubMed Central

Janczarek, Monika

2011-01-01

Rhizobia are Gram-negative bacteria that can exist either as free-living bacteria or as nitrogen-fixing symbionts inside root nodules of leguminous plants. The composition of the rhizobial outer surface, containing a variety of polysaccharides, plays a significant role in the adaptation of these bacteria in both habitats. Among rhizobial polymers, exopolysaccharide (EPS) is indispensable for the invasion of a great majority of host plants which form indeterminate-type nodules. Various functions are ascribed to this heteropolymer, including protection against environmental stress and host defense, attachment to abiotic and biotic surfaces, and in signaling. The synthesis of EPS in rhizobia is a multi-step process regulated by several proteins at both transcriptional and post-transcriptional levels. Also, some environmental factors (carbon source, nitrogen and phosphate starvation, flavonoids) and stress conditions (osmolarity, ionic strength) affect EPS production. This paper discusses the recent data concerning the function of the genes required for EPS synthesis and the regulation of this process by several environmental signals. Up till now, the synthesis of rhizobial EPS has been best studied in two species, Sinorhizobium meliloti and Rhizobium leguminosarum. The latest data indicate that EPS synthesis in rhizobia undergoes very complex hierarchical regulation, in which proteins engaged in quorum sensing and the regulation of motility genes also participate. This finding enables a better understanding of the complex processes occurring in the rhizosphere which are crucial for successful colonization and infection of host plant roots. PMID:22174640

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.

Development of an interprofessional program for cardiovascular prevention in primary care: A participatory research approach

PubMed Central

Goudreau, Johanne; Hudon, Éveline; Lussier, Marie-Thérèse; Bareil, Céline; Duhamel, Fabie; Lévesque, Lise; Turcotte, Alain; Lalonde, Gilles

2014-01-01

Background: The chronic care model provides a framework for improving the management of chronic diseases. Participatory research could be useful in developing a chronic care model–based program of interventions, but no one has as yet offered a description of precisely how to apply the approach. Objectives: An innovative, structured, multi-step participatory process was applied to select and develop (1) chronic care model–based interventions program to improve cardiovascular disease prevention that can be adapted to a particular regional context and (2) a set of indicators to monitor its implementation. Methods: Primary care clinicians (n = 16), administrative staff (n = 2), patients and family members (n = 4), decision makers (n = 5), researchers, and a research coordinator (n = 7) took part in the process. Additional primary care actors (n = 26) validated the program. Results: The program targets multimorbid patients at high or moderate risk of cardiovascular disease with uncontrolled hypertension, dyslipidemia or diabetes. It comprises interprofessional follow-up coordinated by case-management nurses, in which motivated patients are referred in a timely fashion to appropriate clinical and community resources. The program is supported by clinical tools and includes training in motivational interviewing. A set of 89 process and clinical indicators were defined. Conclusion: Through a participatory process, a contextualized interventions program to optimize cardiovascular disease prevention and a set of quality indicators to monitor its implementation were developed. Similar approach might be used to develop other health programs in primary care if program developers are open to building on community strengths and priorities. PMID:26770705

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

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.

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.

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.

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.

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

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

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

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.

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.

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.

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.

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

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.

Factors Affecting the Development of Somatic Cell Nuclear Transfer Embryos in Cattle

PubMed Central

AKAGI, Satoshi; MATSUKAWA, Kazutsugu; TAKAHASHI, Seiya

2014-01-01

Nuclear transfer is a complex multistep procedure that includes oocyte maturation, cell cycle synchronization of donor cells, enucleation, cell fusion, oocyte activation and embryo culture. Therefore, many factors are believed to contribute to the success of embryo development following nuclear transfer. Numerous attempts to improve cloning efficiency have been conducted since the birth of the first sheep by somatic cell nuclear transfer. However, the efficiency of somatic cell cloning has remained low, and applications have been limited. In this review, we discuss some of the factors that affect the developmental ability of somatic cell nuclear transfer embryos in cattle. PMID:25341701

Therapeutic Nanodevices

NASA Astrophysics Data System (ADS)

Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Therapeutic Nanodevices

NASA Astrophysics Data System (ADS)

Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

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.

Error analysis on squareness of multi-sensor integrated CMM for the multistep registration method

NASA Astrophysics Data System (ADS)

Zhao, Yan; Wang, Yiwen; Ye, Xiuling; Wang, Zhong; Fu, Luhua

2018-01-01

The multistep registration(MSR) method in [1] is to register two different classes of sensors deployed on z-arm of CMM(coordinate measuring machine): a video camera and a tactile probe sensor. In general, it is difficult to obtain a very precise registration result with a single common standard, instead, this method is achieved by measuring two different standards with a constant distance between them two which are fixed on a steel plate. Although many factors have been considered such as the measuring ability of sensors, the uncertainty of the machine and the number of data pairs, there is no exact analysis on the squareness between the x-axis and the y-axis on the xy plane. For this sake, error analysis on the squareness of multi-sensor integrated CMM for the multistep registration method will be made to examine the validation of the MSR method. Synthetic experiments on the squareness on the xy plane for the simplified MSR with an inclination rotation are simulated, which will lead to a regular result. Experiments have been carried out with the multi-standard device designed also in [1], meanwhile, inspections with the help of a laser interferometer on the xy plane have been carried out. The final results are conformed to the simulations, and the squareness errors of the MSR method are also similar to the results of interferometer. In other word, the MSR can also adopted/utilized to verify the squareness of a CMM.

Quantification of soil water retention parameters using multi-section TDR-waveform analysis

NASA Astrophysics Data System (ADS)

Baviskar, S. M.; Heimovaara, T. J.

2017-06-01

Soil water retention parameters are important for describing flow in variably saturated soils. TDR is one of the standard methods used for determining water content in soil samples. In this study, we present an approach to estimate water retention parameters of a sample which is initially saturated and subjected to an incremental decrease in boundary head causing it to drain in a multi-step fashion. TDR waveforms are measured along the height of the sample at assumed different hydrostatic conditions at daily interval. The cumulative discharge outflow drained from the sample is also recorded. The saturated water content is obtained using volumetric analysis after the final step involved in multi-step drainage. The equation obtained by coupling the unsaturated parametric function and the apparent dielectric permittivity is fitted to a TDR wave propagation forward model. The unsaturated parametric function is used to spatially interpolate the water contents along TDR probe. The cumulative discharge outflow data is fitted with cumulative discharge estimated using the unsaturated parametric function. The weight of water inside the sample estimated at the first and final boundary head in multi-step drainage is fitted with the corresponding weights calculated using unsaturated parametric function. A Bayesian optimization scheme is used to obtain optimized water retention parameters for these different objective functions. This approach can be used for samples with long heights and is especially suitable for characterizing sands with a uniform particle size distribution at low capillary heads.

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.

Complex Degradation Processes Lead to Non-Exponential Decay Patterns and Age-Dependent Decay Rates of Messenger RNA

PubMed Central

Deneke, Carlus; Lipowsky, Reinhard; Valleriani, Angelo

2013-01-01

Experimental studies on mRNA stability have established several, qualitatively distinct decay patterns for the amount of mRNA within the living cell. Furthermore, a variety of different and complex biochemical pathways for mRNA degradation have been identified. The central aim of this paper is to bring together both the experimental evidence about the decay patterns and the biochemical knowledge about the multi-step nature of mRNA degradation in a coherent mathematical theory. We first introduce a mathematical relationship between the mRNA decay pattern and the lifetime distribution of individual mRNA molecules. This relationship reveals that the mRNA decay patterns at steady state expression level must obey a general convexity condition, which applies to any degradation mechanism. Next, we develop a theory, formulated as a Markov chain model, that recapitulates some aspects of the multi-step nature of mRNA degradation. We apply our theory to experimental data for yeast and explicitly derive the lifetime distribution of the corresponding mRNAs. Thereby, we show how to extract single-molecule properties of an mRNA, such as the age-dependent decay rate and the residual lifetime. Finally, we analyze the decay patterns of the whole translatome of yeast cells and show that yeast mRNAs can be grouped into three broad classes that exhibit three distinct decay patterns. This paper provides both a method to accurately analyze non-exponential mRNA decay patterns and a tool to validate different models of degradation using decay data. PMID:23408982

Immortalization of normal human fibroblasts by treatment with 4-nitroquinoline 1-oxide.

PubMed

Bai, L; Mihara, K; Kondo, Y; Honma, M; Namba, M

1993-02-01

Normal human fibroblasts (the OUMS-24 strain), derived from a 6-week-old human embryo, were transformed (into the OUMS-24F line) and immortalized by repeated treatments (59 times) with 4-nitroquinoline 1-oxide (4NQO). Treatment began during primary culture and ended at the 51st population doubling level (PDL). At the 57th PDL (146 days after the last treatment), morphologically altered, epithelial-type cells appeared, began to grow and became immortal (now past the 100th PDL). However, the control fibroblasts, which were not treated with 4NQO, senesced at the 62nd PDL. The finding that extensive, repeated treatments with 4NQO are required for the immortalization of normal human cells, indicates that multiple mutational events are involved in the immortalization of human cells in general. In other words, immortalization itself seems to be a multi-step process. Karyotypic analysis showed that many cells were hypodiploid before immortalization, but that afterwards chromosomes were distributed broadly in the diploid to tetraploid regions. The immortalized cells showed amplification and enhanced expression of c-myc. Two-dimensional electrophoretic analysis showed that the number of disappearing cellular proteins was greater than the number of the newly appearing ones after the cells became immortalized. Since the immortalized cells showed neither anchorage-independent growth nor tumorigenicity, they are useful for studying factors that can contribute to multi-step carcinogenesis in human cells. In addition, genetically matched normal (OUMS-24) and immortalized (OUMS-24F) cells will be useful for analyzing the genes related to cellular mortality and immortalization.

Assessing Face Validity of a Food Behavior Checklist for Limited-resource Filipinos

PubMed Central

Buchthal, Opal Vanessa; Tauyan, Socorro

2015-01-01

Abstract Diet-related chronic health conditions are prevalent in the Filipino American community; however, there is a lack of rigorously validated nutrition education evaluation tools in Tagalog for use in this population. This study aimed to develop and evaluate the face validity of a Tagalog-language food behavior checklist (FBC). A multi-step method was used, involving translation of questionnaire text from English to Tagalog by a team of professionals, creation of accompanying color photographs, cognitive testing with the target population, final review by the team of professionals, and assessment of readability. Subjects for cognitive testing were men (n=6) and women (n=14) 18 years or older in Hawai‘i who received or were eligible to receive Supplemental Nutrition Assistance Program (SNAP) benefits, self-identified as Filipino, and preferred Tagalog rather than English. Participants were recruited from churches, the Filipino Center, and other community sites. Cognitive interviews revealed several issues with text and photographs, such as preferences for specific terms, and images that did not adequately illustrate the text. Image changes were made to reflect items most commonly consumed. The team of professionals agreed with participant suggestions. Assessment of readability revealed a reading level appropriate for a low-literacy population of grade 5.9. The multi-step process, which allowed members of the target audience to reveal the appropriateness of the questionnaire, yielded a Tagalog-language FBC found to have adequate face validity. After further evaluation of validity and reliability, this tool may be used to evaluate behavior change resulting from the United States Department of Agriculture's (USDA) nutrition education programs. PMID:26535163

Multistep bioassay to predict recolonization potential of emerging parasitoids after a pesticide treatment.

PubMed

Desneux, Nicolas; Ramirez-Romero, Ricardo; Kaiser, Laure

2006-10-01

Neurotoxic pyrethroid insecticides are widely used for crop protection, and lethal and sublethal perturbations can be expected in beneficial insects. Under laboratory conditions, the lethal and sublethal effects of deltamethrin on the aphid parasitoid Diaeretiella rapae M'Intosh (Hymenoptera: Braconidae) were studied at the mummy stage and in emerging adults. Following a multistep bioassay, analyses were aimed at evaluating the effects of deltamethrin at various crucial steps in the recolonization process following a deltamethrin treatment: Parasitoid pupal development (emergence from the mummies), adult survival, and host-searching capacity. A four-armed olfactometer was used to investigate the effect of deltamethrin on host-searching behavior (a range of concentrations causing 0.4-79.4% mortality was tested), and a Potter tower was used to test the deltamethrin effect with a realistic application method (four concentrations were tested: 0.5, 5.0, 6.25, and 50 g active ingredient [a.i.]/ha). Deltamethrin reduced the percentage of emergence from mummies, but only when exposed to the 50 g a.i./ha concentration. However, for all concentrations tested, the insecticide induced a decrease in longevity after emergence from sprayed mummies and significant adult mortality when parasitoids walked on fresh residues on leaves. Indices were defined and predicted a high mortality and, thus, reduction of recolonization capacities. However, deltamethrin had no effect on orientation behavior toward aphid-infested plants for adults that survived a residual exposure to the insecticide. The impact of deltamethrin on recolonization via pupal emergence and interest in the methodology used are discussed.

A Multistep Maturity Model for the Implementation of Electronic and Computable Diagnostic Clinical Prediction Rules (eCPRs).

PubMed

Corrigan, Derek; McDonnell, Ronan; Zarabzadeh, Atieh; Fahey, Tom

2015-01-01

The use of Clinical Prediction Rules (CPRs) has been advocated as one way of implementing actionable evidence-based rules in clinical practice. The current highly manual nature of deriving CPRs makes them difficult to use and maintain. Addressing the known limitations of CPRs requires implementing more flexible and dynamic models of CPR development. We describe the application of Information and Communication Technology (ICT) to provide a platform for the derivation and dissemination of CPRs derived through analysis and continual learning from electronic patient data. We propose a multistep maturity model for constructing electronic and computable CPRs (eCPRs). The model has six levels - from the lowest level of CPR maturity (literaturebased CPRs) to a fully electronic and computable service-oriented model of CPRs that are sensitive to specific demographic patient populations. We describe examples of implementations of the core model components - focusing on CPR representation, interoperability, electronic dissemination, CPR learning, and user interface requirements. The traditional focus on derivation and narrow validation of CPRs has severely limited their wider acceptance. The evolution and maturity model described here outlines a progression toward eCPRs consistent with the vision of a learning health system (LHS) - using central repositories of CPR knowledge, accessible open standards, and generalizable models to avoid repetition of previous work. This is useful for developing more ambitious strategies to address limitations of the traditional CPR development life cycle. The model described here is a starting point for promoting discussion about what a more dynamic CPR development process should look like.

The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods.

PubMed

Xiang, Zheng; Sun, Hao; Cai, Xiaojun; Chen, Dahui

2016-04-01

Transmission of biological information is a biochemical process of multistep cascade from genes/proteins to metabolites. However, because most metabolites reflect the terminal information of the biochemical process, it is difficult to describe the transmission process of disease information in terms of the metabolomics strategy. In this paper, by incorporating network and metabolomics methods, an integrated approach was proposed to systematically investigate and explain the molecular mechanism of renal interstitial fibrosis. Through analysis of the network, the cascade transmission process of disease information starting from genes/proteins to metabolites was putatively identified and uncovered. The results indicated that renal fibrosis was involved in metabolic pathways of glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, riboflavin metabolism, tyrosine metabolism, and sphingolipid metabolism. These pathways involve kidney disease genes such as TGF-β1 and P2RX7. Our results showed that combining metabolomics and network analysis can provide new strategies and ideas for the interpretation of pathogenesis of disease with full consideration of "gene-protein-metabolite."

In situ UV curable 3D printing of multi-material tri-legged soft bot with spider mimicked multi-step forward dynamic gait

NASA Astrophysics Data System (ADS)

Zeb Gul, Jahan; Yang, Bong-Su; Yang, Young Jin; Chang, Dong Eui; Choi, Kyung Hyun

2016-11-01

Soft bots have the expedient ability of adopting intricate postures and fitting in complex shapes compared to mechanical robots. This paper presents a unique in situ UV curing three-dimensional (3D) printed multi-material tri-legged soft bot with spider mimicked multi-step dynamic forward gait using commercial bio metal filament (BMF) as an actuator. The printed soft bot can produce controllable forward motion in response to external signals. The fundamental properties of BMF, including output force, contractions at different frequencies, initial loading rate, and displacement-rate are verified. The tri-pedal soft bot CAD model is designed inspired by spider’s legged structure and its locomotion is assessed by simulating strain and displacement using finite element analysis. A customized rotational multi-head 3D printing system assisted with multiple wavelength’s curing lasers is used for in situ fabrication of tri-pedal soft-bot using two flexible materials (epoxy and polyurethane) in three layered steps. The size of tri-pedal soft-bot is 80 mm in diameter and each pedal’s width and depth is 5 mm × 5 mm respectively. The maximum forward speed achieved is 2.7 mm s-1 @ 5 Hz with input voltage of 3 V and 250 mA on a smooth surface. The fabricated tri-pedal soft bot proved its power efficiency and controllable locomotion at three input signal frequencies (1, 2, 5 Hz).

Controlling charge transport mechanisms in molecular junctions: Distilling thermally induced hopping from coherent-resonant conduction.

PubMed

Kim, Hyehwang; Segal, Dvira

2017-04-28

The electrical conductance of molecular junctions may depend strongly on the temperature and weakly on molecular length, under two distinct mechanisms: phase-coherent resonant conduction, with charges proceeding via delocalized molecular orbitals, and incoherent thermally assisted multi-step hopping. While in the case of coherent conduction, the temperature dependence arises from the broadening of the Fermi distribution in the metal electrodes, in the latter case it corresponds to electron-vibration interaction effects on the junction. With the objective to distill the thermally activated hopping component, thus exposing intrinsic electron-vibration interaction phenomena on the junction, we suggest the design of molecular junctions with "spacers," extended anchoring groups that act to filter out phase-coherent resonant electrons. Specifically, we study the electrical conductance of fixed-gap and variable-gap junctions that include a tunneling block, with spacers at the boundaries. Using numerical simulations and analytical considerations, we demonstrate that in our design, resonant conduction is suppressed. As a result, the electrical conductance is dominated by two (rather than three) mechanisms: superexchange (deep tunneling) and multi-step thermally induced hopping. We further exemplify our analysis on DNA junctions with an A:T block serving as a tunneling barrier. Here, we show that the electrical conductance is insensitive to the number of G:C base-pairs at the boundaries. This indicates that the tunneling-to-hopping crossover revealed in such sequences truly corresponds to the properties of the A:T barrier.

Use of scatterometry for resist process control

NASA Astrophysics Data System (ADS)

Bishop, Kenneth P.; Milner, Lisa-Michelle; Naqvi, S. Sohail H.; McNeil, John R.; Draper, B. L.

1992-06-01

The formation of resist lines having submicron critical dimensions (CDs) is a complex multistep process, requiring precise control of each processing step. Optimization of parameters for each processing step may be accomplished through theoretical modeling techniques and/or the use of send-ahead wafers followed by scanning electron microscope measurements. Once the optimum parameters for any process having been selected, (e.g., time duration and temperature for post-exposure bake process), no in-situ CD measurements are made. In this paper we describe the use of scatterometry to provide this essential metrology capability. It involves focusing a laser beam on a periodic grating and predicting the shape of the grating lines from a measurement of the scattered power in the diffraction orders. The inverse prediction of lineshape from a measurement of the scatter power is based on a vector diffraction analysis used in conjunction with photolithography simulation tools to provide an accurate scatter model for latent image gratings. This diffraction technique has previously been applied to looking at latent image grating formation, as exposure is taking place. We have broadened the scope of the application and consider the problem of determination of optimal focus.

Effects of protein and phosphate buffer concentrations on thermal denaturation of lysozyme analyzed by isoconversional method

PubMed Central

Cao, X.M.; Tian, Y.; Wang, Z.Y.; Liu, Y.W.; Wang, C.X.

2016-01-01

ABSTRACT 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. PMID:27459596

Speeding Up Sigmatropic Shifts-To Halve or to Hold.

PubMed

Tantillo, Dean J

2016-04-19

Catalysis is common. Rational catalyst design, however, is at the frontier of chemical science. Although the histories of physical organic and synthetic organic chemistry boast key chapters involving [3s,3s] sigmatropic shifts, catalysis of these reactions is much less common than catalysis of ostensibly more complex processes. The comparative dearth of catalysts for sigmatropic shifts is perhaps a result of the perception that transition state structures for these reactions, like their reactants, are nonpolar and therefore not amenable to selective stabilization and its associated barrier lowering. However, as demonstrated in this Account, transition state structures for [3s,3s] sigmatropic shifts can in fact have charge distributions that differ significantly from those of reactants, even for hydrocarbon substrates, allowing for barriers to be decreased and rates increased. In some cases, differences in charge distribution result from the inclusion of heteroatoms at specific positions in reactants, but in other cases differences are actually induced by catalysts. Perhaps surprisingly, strategies for complexation of transition state structures that remain nonpolar are also possible. In general, the strategies for catalysis employed can be characterized as involving either mechanistic intervention, where a catalyst induces a change from the concerted mechanism expected for a [3s,3s] sigmatropic shift to a multistep process (cutting the transformation into halves or smaller pieces) whose overall barrier is decreased relative to the concerted process, or transition state complexation, where a catalyst simply binds (holds) more tightly to the transition state structure for a [3s,3s] sigmatropic shift than to the reactant, leading to a lower barrier in the presence of the catalyst. Both of these strategies can be considered to be biomimetic in that enzymes frequently induce multistep processes and utilize selective transition state stabilization for the steps involved. In addition, transition state complexation was the principle around which catalytic antibodies were originally designed. The field of catalysis of sigmatropic shifts is now ready for rational design. The studies described here all provide evidence for the origins of rate acceleration, derived in large part from the results of quantum chemical calculations, that can now be applied to the design of new catalysts for [3s,3s] and other sigmatropic shifts.

Step-Up Synthesis of Periodic Mesoporous Organosilicas with a Tyrosine Framework and Performance in Horseradish Peroxidase Immobilization.

PubMed

Wang, Jianqiang; Zhang, Wenqi; Gu, Changqing; Zhang, Wenpei; Zhou, Man; Wang, Zhiwei; Guo, Cheng; Sun, Linbing

2017-12-14

New amino-acid-bridged periodic mesoporous organosilicas (PMOs) were constructed by hydrolysis and condensation reactions under acid conditions in the presence of a template. The tyrosine bissilylated organic precursor (TBOS) was first prepared through a multistep reaction by using tyrosine (a natural amino acid) as the starting material. PMOs with the tyrosine framework (Tyr-PMOs) were constructed by simultaneously using TBOS and tetraethoxysilane as complex silicon sources in the condensation process. All the Tyr-PMOs materials were characterized by XRD, FTIR spectroscopy, N 2 adsorption-desorption, TEM, SEM, and solid-state 29 Si NMR spectroscopy to confirm the structure. The horseradish peroxidase (HRP) enzyme was first immobilized on these new Tyr-PMOs materials. Optimal conditions for enzyme adsorption included a temperature of 40 °C, a time of 8 h, and a pH value of 7. Furthermore, the novel Tyr-PMOs materials could store HRP for approximately 40 days and maintained the enzymatic activity, and the Tyr-PMOs-10 % HRP with the best immobilization effect could be reused at least eight times. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

"I only watch for the commercials": Messages about weight, eating and race in Super Bowl advertisements.

PubMed

Lydecker, Janet A; Izzo, Antonio; Spielberger, Gail; Grilo, Carlos M

2017-11-01

Health experts and communication experts assert that the media influence individuals' health. Yet, incongruously, the public, policy-makers and the media themselves appear reticent to accept that the media could have extensive negative influence on health. The current study examined all ads that aired from Super Bowl XLVI through Super Bowl XLIX (N = 241) using a detailed, multistep coding process. Ads had similar racial/ethnic diversity in the full sample and food/beverage ads. A minority (14.5%) of advertisements contained actors with overweight/obesity, who were more likely to be White and less likely to be Hispanic compared with race/ethnicity in all ads. Humour and tone were similarly present whether or not the ads included actors with overweight/obesity. Findings are striking given the high prevalence of overweight/obesity in the USA, particularly among Black and Hispanic populations, and the comparatively low representation of actors with overweight/obesity in Super Bowl advertisements. Surprising weight findings may signal a change in how the media portray body-size norms (away from exclusively thin), although representations remain disproportionate from actual body-size distributions in the USA. © 2017 John Wiley & Sons Ltd.

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.