Multi-chain Markov chain Monte Carlo methods for computationally expensive models

NASA Astrophysics Data System (ADS)

Huang, M.; Ray, J.; Ren, H.; Hou, Z.; Bao, J.

2017-12-01

Markov chain Monte Carlo (MCMC) methods are used to infer model parameters from observational data. The parameters are inferred as probability densities, thus capturing estimation error due to sparsity of the data, and the shortcomings of the model. Multiple communicating chains executing the MCMC method have the potential to explore the parameter space better, and conceivably accelerate the convergence to the final distribution. We present results from tests conducted with the multi-chain method to show how the acceleration occurs i.e., for loose convergence tolerances, the multiple chains do not make much of a difference. The ensemble of chains also seems to have the ability to accelerate the convergence of a few chains that might start from suboptimal starting points. Finally, we show the performance of the chains in the estimation of O(10) parameters using computationally expensive forward models such as the Community Land Model, where the sampling burden is distributed over multiple chains.

Multinuclear metal-binding ability of a carotene

PubMed Central

Horiuchi, Shinnosuke; Tachibana, Yuki; Yamashita, Mitsuki; Yamamoto, Koji; Masai, Kohei; Takase, Kohei; Matsutani, Teruo; Kawamata, Shiori; Kurashige, Yuki; Yanai, Takeshi; Murahashi, Tetsuro

2015-01-01

Carotenes are naturally abundant unsaturated hydrocarbon pigments, and their fascinating physical and chemical properties have been studied intensively not only for better understanding of the roles in biological processes but also for the use in artificial chemical systems. However, their metal-binding ability has been virtually unexplored. Here we report that β-carotene has the ability to assemble and align ten metal atoms to afford decanuclear homo- and heterometal chain complexes. The metallo–carotenoid framework shows reversible metalation–demetalation reactivity with multiple metals, which allows us to control the size of metal chains as well as the heterobimetallic composition and arrangement of the carotene-supported metal chains. PMID:25857402

Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies.

PubMed

Feichtinger, René G; Oláhová, Monika; Kishita, Yoshihito; Garone, Caterina; Kremer, Laura S; Yagi, Mikako; Uchiumi, Takeshi; Jourdain, Alexis A; Thompson, Kyle; D'Souza, Aaron R; Kopajtich, Robert; Alston, Charlotte L; Koch, Johannes; Sperl, Wolfgang; Mastantuono, Elisa; Strom, Tim M; Wortmann, Saskia B; Meitinger, Thomas; Pierre, Germaine; Chinnery, Patrick F; Chrzanowska-Lightowlers, Zofia M; Lightowlers, Robert N; DiMauro, Salvatore; Calvo, Sarah E; Mootha, Vamsi K; Moggio, Maurizio; Sciacco, Monica; Comi, Giacomo P; Ronchi, Dario; Murayama, Kei; Ohtake, Akira; Rebelo-Guiomar, Pedro; Kohda, Masakazu; Kang, Dongchon; Mayr, Johannes A; Taylor, Robert W; Okazaki, Yasushi; Minczuk, Michal; Prokisch, Holger

2017-10-05

Complement component 1 Q subcomponent-binding protein (C1QBP; also known as p32) is a multi-compartmental protein whose precise function remains unknown. It is an evolutionary conserved multifunctional protein localized primarily in the mitochondrial matrix and has roles in inflammation and infection processes, mitochondrial ribosome biogenesis, and regulation of apoptosis and nuclear transcription. It has an N-terminal mitochondrial targeting peptide that is proteolytically processed after import into the mitochondrial matrix, where it forms a homotrimeric complex organized in a doughnut-shaped structure. Although C1QBP has been reported to exert pleiotropic effects on many cellular processes, we report here four individuals from unrelated families where biallelic mutations in C1QBP cause a defect in mitochondrial energy metabolism. Infants presented with cardiomyopathy accompanied by multisystemic involvement (liver, kidney, and brain), and children and adults presented with myopathy and progressive external ophthalmoplegia. Multiple mitochondrial respiratory-chain defects, associated with the accumulation of multiple deletions of mitochondrial DNA in the later-onset myopathic cases, were identified in all affected individuals. Steady-state C1QBP levels were decreased in all individuals' samples, leading to combined respiratory-chain enzyme deficiency of complexes I, III, and IV. C1qbp -/- mouse embryonic fibroblasts (MEFs) resembled the human disease phenotype by showing multiple defects in oxidative phosphorylation (OXPHOS). Complementation with wild-type, but not mutagenized, C1qbp restored OXPHOS protein levels and mitochondrial enzyme activities in C1qbp -/- MEFs. C1QBP deficiency represents an important mitochondrial disorder associated with a clinical spectrum ranging from infantile lactic acidosis to childhood (cardio)myopathy and late-onset progressive external ophthalmoplegia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of vehicular size on chain-reaction crash

NASA Astrophysics Data System (ADS)

Nagatani, Takashi

2015-11-01

We present the dynamic model of the chain-reaction crash to take account of the vehicular size. Drivers brake according to taillights of the forward vehicle. We investigate the effect of the vehicular size on the chain-reaction crash (multiple-vehicle collision) in the traffic flow controlled by taillights. In the multiple-vehicle collision, the first crash induces more collisions. We investigate how the first collision induces the chain-reaction crash numerically. We derive, analytically, the transition points and the region maps for the chain-reaction crash in the traffic flow of vehicles with finite sizes. We clarify the effect of the vehicular size on the multiple-vehicle collision.

Controlling Synfire Chain by Inhibitory Synaptic Input

NASA Astrophysics Data System (ADS)

Shinozaki, Takashi; Câteau, Hideyuki; Urakubo, Hidetoshi; Okada, Masato

2007-04-01

The propagation of highly synchronous firings across neuronal networks, called the synfire chain, has been actively studied both theoretically and experimentally. The temporal accuracy and remarkable stability of the propagation have been repeatedly examined in previous studies. However, for such a mode of signal transduction to play a major role in processing information in the brain, the propagation should also be controlled dynamically and flexibly. Here, we show that inhibitory but not excitatory input can bidirectionally modulate the propagation, i.e., enhance or suppress the synchronous firings depending on the timing of the input. Our simulations based on the Hodgkin-Huxley neuron model demonstrate this bidirectional modulation and suggest that it should be achieved with any biologically inspired modeling. Our finding may help describe a concrete scenario of how multiple synfire chains lying in a neuronal network are appropriately controlled to perform significant information processing.

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

NASA Astrophysics Data System (ADS)

Ayadi, Omar; Felfel, Houssem; Masmoudi, Faouzi

2017-07-01

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

Inventory decision in a closed-loop supply chain with inspection, sorting, and waste disposal

NASA Astrophysics Data System (ADS)

Dwicahyani, A. R.; Jauhari, W. A.; Kurdhi, N. A.

2016-02-01

The study of returned item inventory management in a closed-loop supply chain system has become an important issue in recent years. So far, investigations about inventory decision making in a closed-loop supply chain system have been confined to traditional forward and reverse oriented material flow supply chain. In this study, we propose an integrated inventory model consisting a supplier, a manufacturer, and a retailer where the manufacturer inspects all of the returned items collected from the customers and classifies them as recoverable or waste. Returned items that recovered through the remanufacturing process and the newly manufactured products are then used to meet the demand of the retailer. However, some recovered items which are not comparable to the ones in quality, classified as refurbished items, are sold to a secondary market at a reduced price. This study also suggests that the flow of returned items is controlled by a decision variable, namely an acceptance quality level of recoverable item in the system. We apply multiple remanufacturing cycle and multiple production cycle policy to the proposed model and give the corresponding iterative procedure to determine the optimal solutions. Further, numerical examples are presented for illustrative purpose.

How did the platypus get its sex chromosome chain? A comparison of meiotic multiples and sex chromosomes in plants and animals.

PubMed

Gruetzner, Frank; Ashley, Terry; Rowell, David M; Marshall Graves, Jennifer A

2006-04-01

The duck-billed platypus is an extraordinary mammal. Its chromosome complement is no less extraordinary, for it includes a system in which ten sex chromosomes form an extensive meiotic chain in males. Such meiotic multiples are unprecedented in vertebrates but occur sporadically in plant and invertebrate species. In this paper, we review the evolution and formation of meiotic multiples in plants and invertebrates to try to gain insights into the origin of the platypus meiotic multiple. We describe the meiotic hurdles that translocated mammalian chromosomes face, which make longer chains disadvantageous in mammals, and we discuss how sex chromosomes and dosage compensation might have affected the evolution of sex-linked meiotic multiples. We conclude that the evolutionary conservation of the chain in monotremes, the structural properties of the translocated chromosomes and the highly accurate segregation at meiosis make the platypus system remarkably different from meiotic multiples in other species. We discuss alternative evolutionary models, which fall broadly into two categories: either the chain is the result of a sequence of translocation events from an ancestral pair of sex chromosomes (Model I) or the entire chain came into being at once by hybridization of two populations with different chromosomal rearrangements sharing monobrachial homology (Model II).

Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster.

PubMed

Landgren, Ola; Zeig-Owens, Rachel; Giricz, Orsolya; Goldfarb, David; Murata, Kaznouri; Thoren, Katie; Ramanathan, Lakshmi; Hultcrantz, Malin; Dogan, Ahmet; Nwankwo, George; Steidl, Ulrich; Pradhan, Kith; Hall, Charles B; Cohen, Hillel W; Jaber, Nadia; Schwartz, Theresa; Crowley, Laura; Crane, Michael; Irby, Shani; Webber, Mayris P; Verma, Amit; Prezant, David J

2018-06-01

The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood. To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS. Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781). WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002. Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS. Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93). Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.

The roles of information technology in global chain supply: a multiple case study of multinational companies of China

NASA Astrophysics Data System (ADS)

He, Mao; Duan, Wanchun

2007-12-01

Nowadays many Chinese companies have being becoming more and more international. Therefore, these Chinese companies have to face global supply chains rather than the former domestic ones. The use of information technology (IT) is considered a prerequisite for the effective control of today's complex global supply chains. Based on empirical data from 10 multinational companies of China, this paper presents a classification of the ways in which companies use IT in SCM, and examines the drivers for these different utilization types. According to the findings of this research, the purposes of using of IT in SCM can be divided into 1) transaction processing, 2) supply chain planning and collaboration, and 3) order tracking and delivery coordination. The findings further suggest that the drivers between these three uses of IT in SCM differ.

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2010 CFR

2010-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2011 CFR

2011-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2014 CFR

2014-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2012 CFR

2012-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

47 CFR 73.3555 - Multiple ownership.

Code of Federal Regulations, 2013 CFR

2013-10-01

... vertical ownership chain and application of the relevant attribution benchmark to the resulting product, except that wherever the ownership percentage for any link in the chain exceeds 50%, it shall not be... multiplication of the ownership percentages for each link in the vertical ownership chain and application of the...

Price competition and equilibrium analysis in multiple hybrid channel supply chain

NASA Astrophysics Data System (ADS)

Kuang, Guihua; Wang, Aihu; Sha, Jin

2017-06-01

The amazing boom of Internet and logistics industry prompts more and more enterprises to sell commodity through multiple channels. Such market conditions make the participants of multiple hybrid channel supply chain compete each other in traditional and direct channel at the same time. This paper builds a two-echelon supply chain model with a single manufacturer and a single retailer who both can choose different channel or channel combination for their own sales, then, discusses the price competition and calculates the equilibrium price under different sales channel selection combinations. Our analysis shows that no matter the manufacturer and retailer choose same or different channel price to compete, the equilibrium price does not necessarily exist the equilibrium price in the multiple hybrid channel supply chain and wholesale price change is not always able to coordinate supply chain completely. We also present the sufficient and necessary conditions for the existence of equilibrium price and coordination wholesale price.

Influence of Temporal Context on Value in the Multiple-Chains and Successive-Encounters Procedures

ERIC Educational Resources Information Center

O'Daly, Matthew; Angulo, Samuel; Gipson, Cassandra; Fantino, Edmund

2006-01-01

This set of studies explored the influence of temporal context across multiple-chain and multiple-successive-encounters procedures. Following training with different temporal contexts, the value of stimuli sharing similar reinforcement schedules was assessed by presenting these stimuli in concurrent probes. The results for the multiple-chain…

Chain-reaction crash on a highway in high visibility

NASA Astrophysics Data System (ADS)

Nagatani, Takashi

2016-05-01

We study the chain-reaction crash (multiple-vehicle collision) in high-visibility condition on a highway. In the traffic situation, drivers control their vehicles by both gear-changing and braking. Drivers change the gears according to the headway and brake according to taillights of the forward vehicle. We investigate whether or not the first collision induces the chain-reaction crash numerically. It is shown that dynamic transitions occur from no collisions, through a single collision, to multiple collisions with decreasing the headway. Also, we find that the dynamic transition occurs from the finite chain reaction to the infinite chain reaction when the headway is less than the critical value. We compare the multiple-vehicle collisions in high-visibility with that in low-visibility. We derive the transition points and the region maps for the chain-reaction crash in high visibility.

Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

PubMed

Matute-Blanch, Clara; Villar, Luisa M; Álvarez-Cermeño, José C; Rejdak, Konrad; Evdoshenko, Evgeniy; Makshakov, Gleb; Nazarov, Vladimir; Lapin, Sergey; Midaglia, Luciana; Vidal-Jordana, Angela; Drulovic, Jelena; García-Merino, Antonio; Sánchez-López, Antonio J; Havrdova, Eva; Saiz, Albert; Llufriu, Sara; Alvarez-Lafuente, Roberto; Schroeder, Ina; Zettl, Uwe K; Galimberti, Daniela; Ramió-Torrentà, Lluís; Robles, René; Quintana, Ester; Hegen, Harald; Deisenhammer, Florian; Río, Jordi; Tintoré, Mar; Sánchez, Alex; Montalban, Xavier; Comabella, Manuel

2018-04-01

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

Metrology requirements for the serial production of ELT primary mirror segments

NASA Astrophysics Data System (ADS)

Rees, Paul C. T.; Gray, Caroline

2015-08-01

The manufacture of the next generation of large astronomical telescopes, the extremely large telescopes (ELT), requires the rapid manufacture of greater than 500 1.44m hexagonal segments for the primary mirror of each telescope. Both leading projects, the Thirty Meter Telescope (TMT) and the European Extremely Large Telescope (E-ELT), have set highly demanding technical requirements for each fabricated segment. These technical requirements, when combined with the anticipated construction schedule for each telescope, suggest that more than one optical fabricator will be involved in the delivery of the primary mirror segments in order to meet the project schedule. For one supplier, the technical specification is challenging and requires highly consistent control of metrology in close coordination with the polishing technologies used in order to optimize production rates. For production using multiple suppliers, however the supply chain is structured, consistent control of metrology along the supply chain will be required. This requires a broader pattern of independent verification than is the case of a single supplier. This paper outlines the metrology requirements for a single supplier throughout all stages of the fabrication process. We identify and outline those areas where metrology accuracy and duration have a significant impact on production efficiency. We use the challenging ESO E-ELT technical specification as an example of our treatment, including actual process data. We further develop this model for the case of a supply chain consisting of multiple suppliers. Here, we emphasize the need to control metrology throughout the supply chain in order to optimize net production efficiency.

Cluster analysis for determining distribution center location

NASA Astrophysics Data System (ADS)

Lestari Widaningrum, Dyah; Andika, Aditya; Murphiyanto, Richard Dimas Julian

2017-12-01

Determination of distribution facilities is highly important to survive in the high level of competition in today’s business world. Companies can operate multiple distribution centers to mitigate supply chain risk. Thus, new problems arise, namely how many and where the facilities should be provided. This study examines a fast-food restaurant brand, which located in the Greater Jakarta. This brand is included in the category of top 5 fast food restaurant chain based on retail sales. There were three stages in this study, compiling spatial data, cluster analysis, and network analysis. Cluster analysis results are used to consider the location of the additional distribution center. Network analysis results show a more efficient process referring to a shorter distance to the distribution process.

Understanding and reducing the risk of supply chain disruptions.

PubMed

Clark, Graham

2012-01-01

Natural disasters can wreck havoc on business operations. When civil unrest swept the UK in August 2011, the effect on business was stark, losing the retail sector £300m in unexpected costs and lost revenues. On the other side of the world, the natural disaster that hit Japan in early 2011 is estimated to have run up costs in the region of £189bn in repairs. Beyond this, the earthquake and its aftermath shattered supply chains, with technology companies expecting delays of up to six months before business could resume fully. It is impossible to predict incidents like these, but businesses can help mitigate disruption in the supply chain by undertaking business continuity management (BCM). A flexible supply chain is essential when it comes to BCM - whether it means being able to cope with altering transport routes at short notice, or finding or replacing a supplier at the last minute. Understanding the supply chain is critical when responding to major impacts that affect supply chains in multiple points - like IT system failures and country-wide fuel strikes. Businesses should carry out detailed business impact assessments and risk assessments right across the end-to-end supply chain and not just at key single points of failure. It is an intensive process that needs dedicated resources and ownership at the highest level. Recognising this, DHL has designed a 10-step process, which it has implemented across its global supply chain business. This paper provides an overview of what a supply chain really looks like, what can cause disruptions and how far up/down the supply chain companies need to go with their BCM planning.

A Markov Chain-based quantitative study of angular distribution of photons through turbid slabs via isotropic light scattering

NASA Astrophysics Data System (ADS)

Li, Xuesong; Northrop, William F.

2016-04-01

This paper describes a quantitative approach to approximate multiple scattering through an isotropic turbid slab based on Markov Chain theorem. There is an increasing need to utilize multiple scattering for optical diagnostic purposes; however, existing methods are either inaccurate or computationally expensive. Here, we develop a novel Markov Chain approximation approach to solve multiple scattering angular distribution (AD) that can accurately calculate AD while significantly reducing computational cost compared to Monte Carlo simulation. We expect this work to stimulate ongoing multiple scattering research and deterministic reconstruction algorithm development with AD measurements.

The Ground-Based Transmission Spectrum of HD 189733b as Generated Through Multiple Broadband Filter Observations

NASA Astrophysics Data System (ADS)

Kasper, David; Cole, Jackson L.; Gardner, Cristilyn N.; Garver, Bethany; Jarka, Kyla L.; Kar, Aman; McGough, Aylin M.; PeQueen, David J.; Rivera, Daniel Ivan; Jang-Condell, Hannah; Kobulnicky, Henry A.; Dale, Daniel A.

2018-06-01

We present new multi-broadband transit photometry of HD 189733b observed with the Wyoming Infrared Observatory. With an ensemble of Sloan filter observations across multiple transits we have created an ultra-low resolution transmission spectrum to discern the nature of the exoplanet atmosphere. This data set exemplifies the capabilities of the 2.3 m observatory. The analysis was performed with a Markov-Chain Monte-Carlo method assisted by a Gaussian-processes regression model. These observations were taken as part of the University of Wyoming's 2017 Research Experience for Undergraduates (REU) and represent one of multiple hot Jupiter exoplanet targets for which we have transit event observations in multiple broadband filters.

Honest Importance Sampling with Multiple Markov Chains

PubMed Central

Tan, Aixin; Doss, Hani; Hobert, James P.

2017-01-01

Importance sampling is a classical Monte Carlo technique in which a random sample from one probability density, π1, is used to estimate an expectation with respect to another, π. The importance sampling estimator is strongly consistent and, as long as two simple moment conditions are satisfied, it obeys a central limit theorem (CLT). Moreover, there is a simple consistent estimator for the asymptotic variance in the CLT, which makes for routine computation of standard errors. Importance sampling can also be used in the Markov chain Monte Carlo (MCMC) context. Indeed, if the random sample from π1 is replaced by a Harris ergodic Markov chain with invariant density π1, then the resulting estimator remains strongly consistent. There is a price to be paid however, as the computation of standard errors becomes more complicated. First, the two simple moment conditions that guarantee a CLT in the iid case are not enough in the MCMC context. Second, even when a CLT does hold, the asymptotic variance has a complex form and is difficult to estimate consistently. In this paper, we explain how to use regenerative simulation to overcome these problems. Actually, we consider a more general set up, where we assume that Markov chain samples from several probability densities, π1, …, πk, are available. We construct multiple-chain importance sampling estimators for which we obtain a CLT based on regeneration. We show that if the Markov chains converge to their respective target distributions at a geometric rate, then under moment conditions similar to those required in the iid case, the MCMC-based importance sampling estimator obeys a CLT. Furthermore, because the CLT is based on a regenerative process, there is a simple consistent estimator of the asymptotic variance. We illustrate the method with two applications in Bayesian sensitivity analysis. The first concerns one-way random effects models under different priors. The second involves Bayesian variable selection in linear regression, and for this application, importance sampling based on multiple chains enables an empirical Bayes approach to variable selection. PMID:28701855

Honest Importance Sampling with Multiple Markov Chains.

PubMed

Tan, Aixin; Doss, Hani; Hobert, James P

2015-01-01

Importance sampling is a classical Monte Carlo technique in which a random sample from one probability density, π 1 , is used to estimate an expectation with respect to another, π . The importance sampling estimator is strongly consistent and, as long as two simple moment conditions are satisfied, it obeys a central limit theorem (CLT). Moreover, there is a simple consistent estimator for the asymptotic variance in the CLT, which makes for routine computation of standard errors. Importance sampling can also be used in the Markov chain Monte Carlo (MCMC) context. Indeed, if the random sample from π 1 is replaced by a Harris ergodic Markov chain with invariant density π 1 , then the resulting estimator remains strongly consistent. There is a price to be paid however, as the computation of standard errors becomes more complicated. First, the two simple moment conditions that guarantee a CLT in the iid case are not enough in the MCMC context. Second, even when a CLT does hold, the asymptotic variance has a complex form and is difficult to estimate consistently. In this paper, we explain how to use regenerative simulation to overcome these problems. Actually, we consider a more general set up, where we assume that Markov chain samples from several probability densities, π 1 , …, π k , are available. We construct multiple-chain importance sampling estimators for which we obtain a CLT based on regeneration. We show that if the Markov chains converge to their respective target distributions at a geometric rate, then under moment conditions similar to those required in the iid case, the MCMC-based importance sampling estimator obeys a CLT. Furthermore, because the CLT is based on a regenerative process, there is a simple consistent estimator of the asymptotic variance. We illustrate the method with two applications in Bayesian sensitivity analysis. The first concerns one-way random effects models under different priors. The second involves Bayesian variable selection in linear regression, and for this application, importance sampling based on multiple chains enables an empirical Bayes approach to variable selection.

Beyond the Bend: Exploring the Conformational Landscape of Decyl, Undecyl, and Dodecylbenzene

NASA Astrophysics Data System (ADS)

Hewett, Daniel M.; Zwier, Timothy S.

2017-06-01

Alkylbenzenes are important components in the combustion process: they make up 20-30% of petroleum fuels and are intermediates on the pathway to soot formation. Understanding their conformational preferences is a vital step in understanding the processes by which fuels begin their journey from small, simple hydrocarbons into the large, graphitic masses of soot. Previous work done in our group, in collaboration with the Sibert group, found that the smallest alkylbenzene which folds its chain back over the ring is octylbenzene. The population of the lone folded structure in octylbenzene is low; however, theory predicts a rapid stabilization of the folded conformations relative to more extended structures as the chain length is increased, suggesting a likely shift in population towards folded structures. This talk will focus on our exploration of this possibility by discussing the UV excitation and single conformation IR spectra of decyl, undecyl, and dodecylbenzene, where increasing chain length allows for multiple stable folded configurations.

Using SCOR as a Supply Chain Management Framework for Government Agency Contract Requirements

NASA Technical Reports Server (NTRS)

Paxton, Joseph; Tucker, Brian

2010-01-01

This paper will present a model that uses the Supply-Chain Operations Reference (SCOR) model as a foundation for a framework to illustrate the information needed throughout a product lifecycle to support a healthy supply chain management function and the subsequent contract requirements to enable it. It will also show where in the supply chain the information must be extracted. The ongoing case study used to exemplify the model is NASA's (National Aeronautics and Space Administration) Ares I program for human spaceflight. Effective supply chain management and contract requirements are ongoing opportunities for continuous improvement within government agencies, specifically development of systems for human spaceflight operations. Multiple reports from the Government Accountability Office (GAO) reinforce this importance. The SCOR model is a framework for describing a supply chain with process building blocks and business activities. It provides a set of metrics for measuring supply chain performance and best practices for continuously improving. This paper expands the application of the SCOR to also provide the framework for defining information needed from different levels of the supply chain and at different phases of the lifecycle. These needs can be incorporated into contracts to enable more effective supply chain management. Depending on the phase of the lifecycle, effective supply chain management will require involvement from different levels of the organization and different levels of the supply chain.

Pituitary adenylate cyclase-activating polypeptide is a potent inhibitor of the growth of light chain-secreting human multiple myeloma cells.

PubMed

Li, Min; Cortez, Shirley; Nakamachi, Tomoya; Batuman, Vecihi; Arimura, Akira

2006-09-01

Multiple myeloma represents a malignant proliferation of plasma cells in the bone marrow, which often overproduces immunoglobulin light chains. We have shown previously that pituitary adenylate cyclase-activating polypeptide (PACAP) markedly suppresses the release of proinflammatory cytokines from light chain-stimulated human renal proximal tubule epithelial cells and prevents the resulting tubule cell injury. In this study, we have shown that PACAP suppresses the proliferation of human kappa and lambda light chain-secreting multiple myeloma-derived cells. The addition of PACAP suppressed light chain-producing myeloma cell-stimulated interleukin 6 (IL-6) secretion by the bone marrow stromal cells (BMSCs). A specific antagonist to either the human PACAP-specific receptor or the vasoactive intestinal peptide receptor attenuated the suppressive effect of PACAP on IL-6 production in the adhesion of human multiple myeloma cells to BMSCs. The secretion of IL-6 by BMSCs was completely inhibited by 10(-9) mol/L PACAP, which also attenuated the phosphorylation of both p42/44 and p38 mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappaB (NF-kappaB) activation in response to the adhesion of multiple myeloma cells to BMSCs, whereas the inhibition of p42/44 MAPK signaling attenuated PACAP action. The signaling cascades involved in the inhibitory effect of PACAP on IL-6-mediated paracrine stimulation of light chain-secreting myeloma cell growth was mediated through the suppression of p38 MAPK as well as modulation of activation of transcription factor NF-kappaB. These findings suggest that PACAP may be a new antitumor agent that directly suppresses light chain-secreting myeloma cell growth and indirectly affects tumor cell growth by modifying the bone marrow milieu of the multiple myeloma.

Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

PubMed

Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

2017-03-16

We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

Design and modeling of sustainable bioethanol supply chain by minimizing the total ecological footprint in life cycle perspective.

PubMed

Ren, Jingzheng; Manzardo, Alessandro; Toniolo, Sara; Scipioni, Antonio; Tan, Shiyu; Dong, Lichun; Gao, Suzhao

2013-10-01

The purpose of this paper is to develop a model for designing the most sustainable bioethanol supply chain. Taking into consideration of the possibility of multiple-feedstock, multiple transportation modes, multiple alternative technologies, multiple transport patterns and multiple waste disposal manners in bioethanol systems, this study developed a model for designing the most sustainable bioethanol supply chain by minimizing the total ecological footprint under some prerequisite constraints including satisfying the goal of the stakeholders', the limitation of resources and energy, the capacity of warehouses, the market demand and some technological constraints. And an illustrative case of multiple-feedstock bioethanol system has been studied by the proposed method, and a global best solution by which the total ecological footprint is the minimal has been obtained. Copyright © 2013 Elsevier Ltd. All rights reserved.

Linear ubiquitin chains: enzymes, mechanisms and biology

PubMed Central

2017-01-01

Ubiquitination is a versatile post-translational modification that regulates a multitude of cellular processes. Its versatility is based on the ability of ubiquitin to form multiple types of polyubiquitin chains, which are recognized by specific ubiquitin receptors to induce the required cellular response. Linear ubiquitin chains are linked through Met 1 and have been established as important players of inflammatory signalling and apoptotic cell death. These chains are generated by a ubiquitin E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) that is thus far the only E3 ligase capable of forming linear ubiquitin chains. The complex consists of three subunits, HOIP, HOIL-1L and SHARPIN, each of which have specific roles in the observed biological functions of LUBAC. Furthermore, LUBAC has been found to be associated with OTULIN and CYLD, deubiquitinases that disassemble linear chains and counterbalance the E3 ligase activity of LUBAC. Gene mutations in HOIP, HOIL-1L and OTULIN are found in human patients who suffer from autoimmune diseases, and HOIL-1L mutations are also found in myopathy patients. In this paper, we discuss the mechanisms of linear ubiquitin chain generation and disassembly by their respective enzymes and review our current understanding of their biological functions and association with human diseases. PMID:28446710

Linear ubiquitin chains: enzymes, mechanisms and biology.

PubMed

Rittinger, Katrin; Ikeda, Fumiyo

2017-04-01

Ubiquitination is a versatile post-translational modification that regulates a multitude of cellular processes. Its versatility is based on the ability of ubiquitin to form multiple types of polyubiquitin chains, which are recognized by specific ubiquitin receptors to induce the required cellular response. Linear ubiquitin chains are linked through Met 1 and have been established as important players of inflammatory signalling and apoptotic cell death. These chains are generated by a ubiquitin E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) that is thus far the only E3 ligase capable of forming linear ubiquitin chains. The complex consists of three subunits, HOIP, HOIL-1L and SHARPIN, each of which have specific roles in the observed biological functions of LUBAC. Furthermore, LUBAC has been found to be associated with OTULIN and CYLD, deubiquitinases that disassemble linear chains and counterbalance the E3 ligase activity of LUBAC. Gene mutations in HOIP, HOIL-1L and OTULIN are found in human patients who suffer from autoimmune diseases, and HOIL-1L mutations are also found in myopathy patients. In this paper, we discuss the mechanisms of linear ubiquitin chain generation and disassembly by their respective enzymes and review our current understanding of their biological functions and association with human diseases. © 2017 The Authors.

Modelling Evolutionary Algorithms with Stochastic Differential Equations.

PubMed

Heredia, Jorge Pérez

2017-11-20

There has been renewed interest in modelling the behaviour of evolutionary algorithms (EAs) by more traditional mathematical objects, such as ordinary differential equations or Markov chains. The advantage is that the analysis becomes greatly facilitated due to the existence of well established methods. However, this typically comes at the cost of disregarding information about the process. Here, we introduce the use of stochastic differential equations (SDEs) for the study of EAs. SDEs can produce simple analytical results for the dynamics of stochastic processes, unlike Markov chains which can produce rigorous but unwieldy expressions about the dynamics. On the other hand, unlike ordinary differential equations (ODEs), they do not discard information about the stochasticity of the process. We show that these are especially suitable for the analysis of fixed budget scenarios and present analogues of the additive and multiplicative drift theorems from runtime analysis. In addition, we derive a new more general multiplicative drift theorem that also covers non-elitist EAs. This theorem simultaneously allows for positive and negative results, providing information on the algorithm's progress even when the problem cannot be optimised efficiently. Finally, we provide results for some well-known heuristics namely Random Walk (RW), Random Local Search (RLS), the (1+1) EA, the Metropolis Algorithm (MA), and the Strong Selection Weak Mutation (SSWM) algorithm.

Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis.

PubMed

Barro, Christian; Benkert, Pascal; Disanto, Giulio; Tsagkas, Charidimos; Amann, Michael; Naegelin, Yvonne; Leppert, David; Gobbi, Claudio; Granziera, Cristina; Yaldizli, Özgür; Michalak, Zuzanna; Wuerfel, Jens; Kappos, Ludwig; Parmar, Katrin; Kuhle, Jens

2018-05-30

Neuro-axonal injury is a key factor in the development of permanent disability in multiple sclerosis. Neurofilament light chain in peripheral blood has recently emerged as a biofluid marker reflecting neuro-axonal damage in this disease. We aimed at comparing serum neurofilament light chain levels in multiple sclerosis and healthy controls, to determine their association with measures of disease activity and their ability to predict future clinical worsening as well as brain and spinal cord volume loss. Neurofilament light chain was measured by single molecule array assay in 2183 serum samples collected as part of an ongoing cohort study from 259 patients with multiple sclerosis (189 relapsing and 70 progressive) and 259 healthy control subjects. Clinical assessment, serum sampling and MRI were done annually; median follow-up time was 6.5 years. Brain volumes were quantified by structural image evaluation using normalization of atrophy, and structural image evaluation using normalization of atrophy, cross-sectional, cervical spinal cord volumes using spinal cord image analyser (cordial). Results were analysed using ordinary linear regression models and generalized estimating equation modelling. Serum neurofilament light chain was higher in patients with a clinically isolated syndrome or relapsing remitting multiple sclerosis as well as in patients with secondary or primary progressive multiple sclerosis than in healthy controls (age adjusted P < 0.001 for both). Serum neurofilament light chain above the 90th percentile of healthy controls values was an independent predictor of Expanded Disability Status Scale worsening in the subsequent year (P < 0.001). The probability of Expanded Disability Status Scale worsening gradually increased by higher serum neurofilament light chain percentile category. Contrast enhancing and new/enlarging lesions were independently associated with increased serum neurofilament light chain (17.8% and 4.9% increase per lesion respectively; P < 0.001). The higher the serum neurofilament light chain percentile level, the more pronounced was future brain and cervical spinal volume loss: serum neurofilament light chain above the 97.5th percentile was associated with an additional average loss in brain volume of 1.5% (P < 0.001) and spinal cord volume of 2.5% over 5 years (P = 0.009). Serum neurofilament light chain correlated with concurrent and future clinical and MRI measures of disease activity and severity. High serum neurofilament light chain levels were associated with both brain and spinal cord volume loss. Neurofilament light chain levels are a real-time, easy to measure marker of neuro-axonal injury that is conceptually more comprehensive than brain MRI.

Age- and Activity-Related Differences in the Abundance of Myosin Essential and Regulatory Light Chains in Human Muscle

PubMed Central

Cobley, James N.; Ab. Malik, Zulezwan; Morton, James P.; Close, Graeme L.; Edwards, Ben J.; Burniston, Jatin G.

2016-01-01

Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry) are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM). We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping. PMID:28248225

A spatially explicit whole-system model of the lignocellulosic bioethanol supply chain: an assessment of decentralised processing potential

PubMed Central

Dunnett, Alex J; Adjiman, Claire S; Shah, Nilay

2008-01-01

Background Lignocellulosic bioethanol technologies exhibit significant capacity for performance improvement across the supply chain through the development of high-yielding energy crops, integrated pretreatment, hydrolysis and fermentation technologies and the application of dedicated ethanol pipelines. The impact of such developments on cost-optimal plant location, scale and process composition within multiple plant infrastructures is poorly understood. A combined production and logistics model has been developed to investigate cost-optimal system configurations for a range of technological, system scale, biomass supply and ethanol demand distribution scenarios specific to European agricultural land and population densities. Results Ethanol production costs for current technologies decrease significantly from $0.71 to $0.58 per litre with increasing economies of scale, up to a maximum single-plant capacity of 550 × 106 l year-1. The development of high-yielding energy crops and consolidated bio-processing realises significant cost reductions, with production costs ranging from $0.33 to $0.36 per litre. Increased feedstock yields result in systems of eight fully integrated plants operating within a 500 × 500 km2 region, each producing between 1.24 and 2.38 × 109 l year-1 of pure ethanol. A limited potential for distributed processing and centralised purification systems is identified, requiring developments in modular, ambient pretreatment and fermentation technologies and the pipeline transport of pure ethanol. Conclusion The conceptual and mathematical modelling framework developed provides a valuable tool for the assessment and optimisation of the lignocellulosic bioethanol supply chain. In particular, it can provide insight into the optimal configuration of multiple plant systems. This information is invaluable in ensuring (near-)cost-optimal strategic development within the sector at the regional and national scale. The framework is flexible and can thus accommodate a range of processing tasks, logistical modes, by-product markets and impacting policy constraints. Significant scope for application to real-world case studies through dynamic extensions of the formulation has been identified. PMID:18662392

Kinetics and mechanism for the sonochemical degradation of a nonionic surfactant.

PubMed

Singla, Ritu; Grieser, Franz; Ashokkumar, Muthupandian

2009-03-26

The sonolytic degradation of the nonionic surfactant, octaethylene glycol monododecyl ether (C(12)E(8)), has been studied at various initial concentrations below and above its critical micelle concentration (CMC). It has been observed that the degradation rate increases with an increase in the initial concentration of the surfactant until the CMC is reached. Above the CMC an almost constant degradation rate is observed, suggesting that the surfactant in its monomer form is involved in the degradation process. The degradation process of C(12)E(8) involves two distinct primary processes occurring at the bubble/solution interface: (a) hydroxylation/oxidation of the surfactant and (b) pyrolytic fragmentation of the surfactant. The oxidative cleavage of ethylene oxide units provides evidence for OH radical attack. Hydroxylation of the ethoxy chain gives rise to various short-chain carboxyalkyl-polyethylene glycol intermediates. The polyethylene glycol chain formed, due to the scission of the C(12)E(8) molecule, undergoes rapid hydroxylation/oxidation to yield simple compounds that have the potential to undergo further degradation. The detection of multiple intermediates indicates that several processes affect the complete degradation pathways of the surfactant molecule. TOC analysis, however, indicates that the sonolytic mineralization of the surfactant is difficult to achieve at reasonable rates due to the relatively low surface activity of the degradation products formed during sonolysis.

Chain-reaction crash in traffic flow controlled by taillights

NASA Astrophysics Data System (ADS)

Nagatani, Takashi

2015-02-01

We study the chain-reaction crash (multiple-vehicle collision) in low-visibility condition on a road. In the traffic situation, drivers brake according to taillights of the forward vehicle. The first crash may induce more collisions. We investigate whether or not the first collision induces the chain-reaction crash, numerically and analytically. The dynamic transitions occur from no collisions through a single collision, double collisions and triple collisions, to multiple collisions with decreasing the headway. Also, we find that the dynamic transition occurs from the finite chain reaction to the infinite chain reaction when the headway is less than the critical value. We derive, analytically, the transition points and the region maps for the chain-reaction crash in traffic flow controlled by taillights.

Characterization of myosin light chain in shrimp hemocytic phagocytosis.

PubMed

Han, Fang; Wang, Zhiyong; Wang, Xiaoqing

2010-11-01

Myosin light chain, a well-known cytoskeleton gene, regulates multiple processes that are involved in material transport, muscle shrink and cell division. However, its function in phagocytosis against invading pathogens in crustacean remains unknown. In this investigation, a myosin light chain gene was obtained from Marsupenaeus japonicus shrimp. The full-length cDNA of this gene was of 766 bp and an open reading frame (ORF) of 462 bp encoding a polypeptide of 153 amino acids. The myosin light chain protein was expressed in Escherichia coli and purified. Subsequently the specific antibody was raised using the purified GST fusion protein. As revealed by immuno-electron microscopy, the myosin light chain protein was only expressed in the dark bands of muscle. In the present study, the myosin light chain gene was up-regulated in the WSSV-resistant shrimp as revealed by real-time PCR and western blot. And the phagocytic percentage and phagocytic index using FITC-labeled Vibrio parahemolyticus were remarkably increased in the WSSV-resistant shrimp, suggesting that the myosin light chain protein was essential in hemocytic phagocytosis. On the other hand, RNAi assays indicated that the phagocytic percentage and phagocytic index were significantly decreased when the myosin light chain gene was silenced by sequence-specific siRNA. These findings suggested that myosin light chain protein was involved in the regulation of hemocytic phagocytosis of shrimp. Copyright 2010 Elsevier Ltd. All rights reserved.

Self-assembly and photoluminescence evolution of hydrophilic and hydrophobic quantum dots in sol–gel processes

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

Yang, Ping, E-mail: mse_yangp@ujn.edu.cn; Matras-Postolek, Katarzyna; Song, Xueling

2015-10-15

Graphical abstract: Highly luminescent quantum dots (QDs) with tunable photoluminescence (PL) wavelength were assembled into various morphologies including chain, hollow spheres, fibers, and ring structures through sol–gel processes. The PL properties during assembly as investigated. - Highlights: • Highly luminescent quantum dots (QDs) were synthesized from several ligands. • The evolution of PL in self-assembly via sol–gel processes was investigated. • CdTe QDs were assembled into a chain by controlling hydrolysis and condensation reactions. • Hollow spheres, fibers, and ring structures were created via CdSe/ZnS QDs in sol–gel processes. - Abstract: Highly luminescent quantum dots (QDs) with tunable photoluminescence (PL)more » wavelength were synthesized from several ligands to investigate the PL evolution in QD self-assembly via sol–gel processes. After ligand exchange, CdTe QDs were assembled into a chain by controlling the hydrolysis and condensation reaction of 3-mercaptopropyl-trimethoxysilane. The chain was then coated with a SiO{sub 2} shell from tetraethyl orthosilicate (TEOS). Hollow spheres, fibers, and ring structures were created from CdSe/ZnS QDs via various sol–gel processes. CdTe QDs revealed red-shifted and narrowed PL spectrum after assembly compared with their initial one. In contrast, the red-shift of PL spectra of CdSe/ZnS QDs is small. By optimizing experimental conditions, SiO{sub 2} spheres with multiple CdSe/ZnS QDs were fabricated using TEOS and MPS. The QDs in these SiO{sub 2} spheres retained their initial PL properties. This result is useful for application because of their high stability and high PL efficiency of 33%.« less

Cultivating a disease management partnership: a value-chain model.

PubMed

Murray, Carolyn F; Monroe, Wendy; Stalder, Sharon A

2003-01-01

Disease management (DM) is one of the health care industry's more innovative value-chain models, whereby multiple relationships are created to bring complex and time-sensitive services to market. The very nature of comprehensive, seamless DM provided through an outsourced arrangement necessitates a level of cooperation, trust, and synergy that may be lacking from more traditional vendor-customer relationships. This discussion highlights the experience of one health plan and its vendor partner and their approach to the development and delivery of an outsourced heart failure (HF) DM program. The program design and rollout are discussed within principles adapted from the theoretical framework of a value-chain model. Within the value-chain model, added value is created by the convergence and synergistic integration of the partners' discrete strengths. Although each partner brings unique attributes to the relationship, those attributes are significantly enhanced by the value-chain model, thus allowing each party to bring the added value of the relationship to their respective customers. This partnership increases innovation, leverages critical capabilities, and improves market responsiveness. Implementing a comprehensive, outsourced DM program is no small task. DM programs incorporate a broad array of services affecting nearly every department in a health plan's organization. When true seamless integration between multiple organizations with multiple stakeholders is the objective, implementation and ongoing operations can become even more complex. To effectively address the complexities presented by an HF DM program, the parties in this case moved beyond a typical purchaser-vendor relationship to one that is more closely akin to a strategic partnership. This discussion highlights the development of this partnership from the perspective of both organizations, as revealed through contracting and implementation activities. It is intended to provide insight into the program development and rollout processes that one health plan and its partner have adopted to advance a DM model that integrates appropriately within the local environment. This discussion also highlights how an organizational culture can shift from an emphasis on cost, growth, and control to an emphasis on quality, innovation, and service within a value-chain model.

3D Printing: Downstream Production Transforming the Supply Chain

DTIC Science & Technology

2017-01-01

generative designs , and tailorable material properties will transform the way both military and civilian products are manufactured —from simple objects... design . Traditional and established subtractive manufacturing (SM) creates objects by removing material (e.g., through drilling or lathing) from solid... manufacturers to build products with highly complex geometry in a single process rather than by combining multiple components manufactured by

Markov Chains For Testing Redundant Software

NASA Technical Reports Server (NTRS)

White, Allan L.; Sjogren, Jon A.

1990-01-01

Preliminary design developed for validation experiment that addresses problems unique to assuring extremely high quality of multiple-version programs in process-control software. Approach takes into account inertia of controlled system in sense it takes more than one failure of control program to cause controlled system to fail. Verification procedure consists of two steps: experimentation (numerical simulation) and computation, with Markov model for each step.

Hypophosphatemic osteomalacia: an unusual clinical presentation of multiple myeloma.

PubMed

Reyskens, M; Sleurs, K; Verresen, L; Janssen, M; van den Bergh, J; van den Berg, J; Geusens, P

2015-07-01

An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery.

Life cycle cost optimization of biofuel supply chains under uncertainties based on interval linear programming.

PubMed

Ren, Jingzheng; Dong, Liang; Sun, Lu; Goodsite, Michael Evan; Tan, Shiyu; Dong, Lichun

2015-01-01

The aim of this work was to develop a model for optimizing the life cycle cost of biofuel supply chain under uncertainties. Multiple agriculture zones, multiple transportation modes for the transport of grain and biofuel, multiple biofuel plants, and multiple market centers were considered in this model, and the price of the resources, the yield of grain and the market demands were regarded as interval numbers instead of constants. An interval linear programming was developed, and a method for solving interval linear programming was presented. An illustrative case was studied by the proposed model, and the results showed that the proposed model is feasible for designing biofuel supply chain under uncertainties. Copyright © 2015 Elsevier Ltd. All rights reserved.

Distribution of model uncertainty across multiple data streams

NASA Astrophysics Data System (ADS)

Wutzler, Thomas

2014-05-01

When confronting biogeochemical models with a diversity of observational data streams, we are faced with the problem of weighing the data streams. Without weighing or multiple blocked cost functions, model uncertainty is allocated to the sparse data streams and possible bias in processes that are strongly constraint is exported to processes that are constrained by sparse data streams only. In this study we propose an approach that aims at making model uncertainty a factor of observations uncertainty, that is constant over all data streams. Further we propose an implementation based on Monte-Carlo Markov chain sampling combined with simulated annealing that is able to determine this variance factor. The method is exemplified both with very simple models, artificial data and with an inversion of the DALEC ecosystem carbon model against multiple observations of Howland forest. We argue that the presented approach is able to help and maybe resolve the problem of bias export to sparse data streams.

Platypus chain reaction: directional and ordered meiotic pairing of the multiple sex chromosome chain in Ornithorhynchus anatinus.

PubMed

Daish, Tasman; Casey, Aaron; Grützner, Frank

2009-01-01

Monotremes are phylogenetically and phenotypically unique animals with an unusually complex sex chromosome system that is composed of ten chromosomes in platypus and nine in echidna. These chromosomes are alternately linked (X1Y1, X2Y2, ...) at meiosis via pseudoautosomal regions and segregate to form spermatozoa containing either X or Y chromosomes. The physical and epigenetic mechanisms involved in pairing and assembly of the complex sex chromosome chain in early meiotic prophase I are completely unknown. We have analysed the pairing dynamics of specific sex chromosome pseudoautosomal regions in platypus spermatocytes during prophase of meiosis I. Our data show a highly coordinated pairing process that begins at the terminal Y5 chromosome and completes with the union of sex chromosomes X1Y1. The consistency of this ordered assembly of the chain is remarkable and raises questions about the mechanisms and factors that regulate the differential pairing of sex chromosomes and how this relates to potential meiotic silencing mechanisms and alternate segregation.

Correlation between morphology, electron band structure, and resistivity of Pb atomic chains on the Si(5 5 3)-Au surface

NASA Astrophysics Data System (ADS)

Jałochowski, M.; Kwapiński, T.; Łukasik, P.; Nita, P.; Kopciuszyński, M.

2016-07-01

Structural and electron transport properties of multiple Pb atomic chains fabricated on the Si(5 5 3)-Au surface are investigated using scanning tunneling spectroscopy, reflection high electron energy diffraction, angular resolved photoemission electron spectroscopy and in situ electrical resistance. The study shows that Pb atomic chains growth modulates the electron band structure of pristine Si(5 5 3)-Au surface and hence changes its sheet resistivity. Strong correlation between chains morphology, electron band structure and electron transport properties is found. To explain experimental findings a theoretical tight-binding model of multiple atomic chains interacting on effective substrate is proposed.

Investigation on bisphenol A levels in human milk and dairy supply chain: A review.

PubMed

Mercogliano, Raffaelina; Santonicola, Serena

2018-04-01

Bisphenol A (BPA), widely used as additive in food packaging, is an environmental and food contaminant that shows a weak estrogenic activity in general population and toxicity in the infant population. A temporary tolerable daily intake (t-TDI) of 4 μg/kg bw/day and a migration limit of 0.6 mg/kg in food from plastic materials, intended to come in contact with food, were fixed. Dietary milk is important in the human diet. The review investigated the contamination levels in human milk and along the dairy supply chain. Despite the reported levels are generally below the fixed limits, breast milk is considered a continuous low-level exposure to endocrine-active compounds for infants. In addition, BPA residues are detected in milk and dairy products posing a risk to human health. BPA enters into milk chain via multiple pathways at various points during milk production (e.g., PVC tubing used during the milking process, transfer from bulk milk to storage tanks, during milk processing). To prevent or mitigate this hazard, a specific TDI for infants is recommended and evaluation of risk factors at each phase of the dairy supply chain, in the quality systems, is recommended. Copyright © 2018 Elsevier Ltd. All rights reserved.

Serum-free light-chain analysis in diagnosis and management of multiple myeloma and related conditions.

PubMed

Milani, Paolo; Palladini, Giovanni; Merlini, Giampaolo

2016-01-01

The introduction of the serum-free light-chain (S-FLC) assay has been a breakthrough in the diagnosis and management of plasma cell dyscrasias, particularly monoclonal light-chain diseases. The first method, proposed in 2001, quantifies serum-free light-chains using polyclonal antibodies. More recently, assays based on monoclonal antibodies have entered into clinical practice. S-FLC measurement plays a central role in the screening for multiple myeloma and related conditions, in association with electrophoretic techniques. Analysis of S-FLC is essential in assessing the risk of progression of precursor diseases to overt plasma cell dyscrasias. It is also useful for risk stratification in solitary plasmacytoma and AL amyloidosis. The S-FLC measurement is part of the new diagnostic criteria for multiple myeloma, and provides a marker to follow changes in clonal substructure over time. Finally, the evaluation of S-FLC is fundamental for assessing the response to treatment in monoclonal light chain diseases.

Partitioning problems in parallel, pipelined and distributed computing

NASA Technical Reports Server (NTRS)

Bokhari, S.

1985-01-01

The problem of optimally assigning the modules of a parallel program over the processors of a multiple computer system is addressed. A Sum-Bottleneck path algorithm is developed that permits the efficient solution of many variants of this problem under some constraints on the structure of the partitions. In particular, the following problems are solved optimally for a single-host, multiple satellite system: partitioning multiple chain structured parallel programs, multiple arbitrarily structured serial programs and single tree structured parallel programs. In addition, the problems of partitioning chain structured parallel programs across chain connected systems and across shared memory (or shared bus) systems are also solved under certain constraints. All solutions for parallel programs are equally applicable to pipelined programs. These results extend prior research in this area by explicitly taking concurrency into account and permit the efficient utilization of multiple computer architectures for a wide range of problems of practical interest.

Hierarchical Robot Control System and Method for Controlling Select Degrees of Freedom of an Object Using Multiple Manipulators

NASA Technical Reports Server (NTRS)

Platt, Robert (Inventor); Wampler, II, Charles W. (Inventor); Abdallah, Muhammad E. (Inventor)

2013-01-01

A robotic system includes a robot having manipulators for grasping an object using one of a plurality of grasp types during a primary task, and a controller. The controller controls the manipulators during the primary task using a multiple-task control hierarchy, and automatically parameterizes the internal forces of the system for each grasp type in response to an input signal. The primary task is defined at an object-level of control, e.g., using a closed-chain transformation, such that only select degrees of freedom are commanded for the object. A control system for the robotic system has a host machine and algorithm for controlling the manipulators using the above hierarchy. A method for controlling the system includes receiving and processing the input signal using the host machine, including defining the primary task at the object-level of control, e.g., using a closed-chain definition, and parameterizing the internal forces for each of grasp type.

Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification.

PubMed

Allen, Richard J; Musante, Cynthia J

2017-01-01

Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing 'transfer function'. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole.

Modeling fructose-load-induced hepatic de-novo lipogenesis by model simplification

PubMed Central

Allen, Richard J; Musante, Cynthia J

2017-01-01

Hepatic de-novo lipogenesis is a metabolic process implemented in the pathogenesis of type 2 diabetes. Clinically, the rate of this process can be ascertained by use of labeled acetate and stimulation by fructose administration. A systems pharmacology model of this process is desirable because it facilitates the description, analysis, and prediction of this experiment. Due to the multiple enzymes involved in de-novo lipogenesis, and the limited data, it is desirable to use single functional expressions to encapsulate the flux between multiple enzymes. To accomplish this we developed a novel simplification technique which uses the available information about the properties of the individual enzymes to bound the parameters of a single governing ‘transfer function’. This method should be applicable to any model with linear chains of enzymes that are well stimulated. We validated this approach with computational simulations and analytical justification in a limiting case. Using this technique we generated a simple model of hepatic de-novo lipogenesis in these experimental conditions that matched prior data. This model can be used to assess pharmacological intervention at specific points on this pathway. We have demonstrated this with prospective simulation of acetyl-CoA carboxylase inhibition. This simplification technique suggests how the constituent properties of an enzymatic chain of reactions gives rise to the sensitivity (to substrate) of the pathway as a whole. PMID:28469410

A Construct for Describing Software Development Risks

DTIC Science & Technology

1994-07-01

consequences during any risk identification process. It is more important and expedient to capture the conditions since the basic statement of conse ...chain of causal events. The contrast between the exploration of conditions rather than conse - quences in risk identification is similar to that of...extent that a general con - dition has a multiplicity of individual characteristics. In the CTC representation, these distinct risks can share common

Learning to Integrate: Supply Chains Reconceptualised

ERIC Educational Resources Information Center

Sense, Andrew J.; Clements, Michael D. J.

2007-01-01

This paper introduces and explains a conception of supply chains from a situated learning perspective. This non-conventional supply chain perspective invites the reader to consider supply chain scenarios as "situated learning opportunities involving multiple communities of practice" interacting and participating together. It is argued that by…

Clinicopathologic characteristics of light chain proximal tubulopathy with light chain inclusions involving multiple renal cell types
.

PubMed

Li, Xiaomei; Xu, Feng; Liang, Dandan; Liang, Shaoshan; Zhu, Xiaodong; Zhang, Mingchao; Huang, Xianghua; Liu, Zhihong; Zeng, Caihong

2018-02-01

Light chain proximal tubulopathy (LCPT) associated with plasma cell dyscrasias is a rare abnormality, especially cases involving multiple cell types. The aim of this study is to explore the characteristics and outcomes of these diseases. We comprehensively evaluated the clinical-pathological data, treatment, and outcomes of 6 LCPT patients with involvement of multiple cell types. In 3 cases, we found that the inclusions largely existed in tubular cells, while in 2 cases they coexisted in podocytes and tubular cells, and in 1 case they coexisted in histiocytes and tubular cells. The stain features and appearances of inclusions were specific and varied. Five patients displayed κ-light chains with crystal formation, while 1 patient displayed a λ subtype with increased lysosomes instead of crystals. Six patients presented with proteinuria, 4 with renal insufficiency, and 4 with complete or partial Fanconi syndrome. Our findings indicate that tubular cells are the most common location of cytoplasmic inclusions. Cases with κ-light chain storage are more common than λ, and the formation of crystals may be associated with the subtype of light chains. Immunoelectron microscopy could be used to increase sensitivity for the detection and location of monoclonal light chains. Therefore, these patients have some common clinical features with varied pathologic characteristics and prognoses but the same subtype of light chains.
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Effect of perception irregularity on chain-reaction crash in low visibility

NASA Astrophysics Data System (ADS)

Nagatani, Takashi

2015-06-01

We present the dynamic model of the chain-reaction crash to take into account the irregularity of the perception-reaction time. When a driver brakes according to taillights of the forward vehicle, the perception-reaction time varies from driver to driver. We study the effect of the perception irregularity on the chain-reaction crash (multiple-vehicle collision) in low-visibility condition. The first crash may induce more collisions. We investigate how the first collision induces the chain-reaction crash numerically. We derive, analytically, the transition points and the region maps for the chain-reaction crash in traffic flow of vehicles with irregular perception times. We clarify the effect of the perception irregularity on the multiple-vehicle collision.

An Alignment Model for Collaborative Value Networks

NASA Astrophysics Data System (ADS)

Bremer, Carlos; Azevedo, Rodrigo Cambiaghi; Klen, Alexandra Pereira

This paper presents parts of the work carried out in several global organizations through the development of strategic projects with high tactical and operational complexity. By investing in long-term relationships, strongly operating in the transformation of the competitive model and focusing on the value chain management, the main aim of these projects was the alignment of multiple value chains. The projects were led by the Axia Transformation Methodology as well as by its Management Model and following the principles of Project Management. As a concrete result of the efforts made in the last years in the Brazilian market this work also introduces the Alignment Model which supports the transformation process that the companies undergo.

Photonic simulation of entanglement growth and engineering after a spin chain quench.

PubMed

Pitsios, Ioannis; Banchi, Leonardo; Rab, Adil S; Bentivegna, Marco; Caprara, Debora; Crespi, Andrea; Spagnolo, Nicolò; Bose, Sougato; Mataloni, Paolo; Osellame, Roberto; Sciarrino, Fabio

2017-11-17

The time evolution of quantum many-body systems is one of the most important processes for benchmarking quantum simulators. The most curious feature of such dynamics is the growth of quantum entanglement to an amount proportional to the system size (volume law) even when interactions are local. This phenomenon has great ramifications for fundamental aspects, while its optimisation clearly has an impact on technology (e.g., for on-chip quantum networking). Here we use an integrated photonic chip with a circuit-based approach to simulate the dynamics of a spin chain and maximise the entanglement generation. The resulting entanglement is certified by constructing a second chip, which measures the entanglement between multiple distant pairs of simulated spins, as well as the block entanglement entropy. This is the first photonic simulation and optimisation of the extensive growth of entanglement in a spin chain, and opens up the use of photonic circuits for optimising quantum devices.

The scent of mixtures: rules of odour processing in ants

PubMed Central

Perez, Margot; Giurfa, Martin; d'Ettorre, Patrizia

2015-01-01

Natural odours are complex blends of numerous components. Understanding how animals perceive odour mixtures is central to multiple disciplines. Here we focused on carpenter ants, which rely on odours in various behavioural contexts. We studied overshadowing, a phenomenon that occurs when animals having learnt a binary mixture respond less to one component than to the other, and less than when this component was learnt alone. Ants were trained individually with alcohols and aldehydes varying in carbon-chain length, either as single odours or binary mixtures. They were then tested with the mixture and the components. Overshadowing resulted from the interaction between chain length and functional group: alcohols overshadowed aldehydes, and longer chain lengths overshadowed shorter ones; yet, combinations of these factors could cancel each other and suppress overshadowing. Our results show how ants treat binary olfactory mixtures and set the basis for predictive analyses of odour perception in insects. PMID:25726692

Plasticization effect of triacetin on structure and properties of starch ester film.

PubMed

Zhu, Jie; Li, Xiaoxi; Huang, Chen; Chen, Ling; Li, Lin

2013-05-15

The aim of this work was to evaluate the plasticizing effect of triacetin on the structure and properties of starch ester film and further establish the structure-property relationships. The presence of triacetin resulted in multiple structure changes of the film. The mobility of macromolecular chain was increased to form scattered crystallite during the film formation process. The amorphous region was enlarged to contain more triacetin squeezed from crystalline region. The plasticization of triacetin and restriction of crystallite oppositely influenced the mobility of macromolecular chains in different regions. The thermal stability of triacetin changed along with its fluctuant interaction with macromolecules. Comparatively, the enhanced ether bond and the restriction from crystalline regions on the mobility of the amorphous chain consequently improved the thermal stability of the film matrix. The interaction between triacetin and starch ester was essential to film forming but unexpectedly lowered the triacetin stability. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multisensor data fusion across time and space

NASA Astrophysics Data System (ADS)

Villeneuve, Pierre V.; Beaven, Scott G.; Reed, Robert A.

2014-06-01

Field measurement campaigns typically deploy numerous sensors having different sampling characteristics for spatial, temporal, and spectral domains. Data analysis and exploitation is made more difficult and time consuming as the sample data grids between sensors do not align. This report summarizes our recent effort to demonstrate feasibility of a processing chain capable of "fusing" image data from multiple independent and asynchronous sensors into a form amenable to analysis and exploitation using commercially-available tools. Two important technical issues were addressed in this work: 1) Image spatial registration onto a common pixel grid, 2) Image temporal interpolation onto a common time base. The first step leverages existing image matching and registration algorithms. The second step relies upon a new and innovative use of optical flow algorithms to perform accurate temporal upsampling of slower frame rate imagery. Optical flow field vectors were first derived from high-frame rate, high-resolution imagery, and then finally used as a basis for temporal upsampling of the slower frame rate sensor's imagery. Optical flow field values are computed using a multi-scale image pyramid, thus allowing for more extreme object motion. This involves preprocessing imagery to varying resolution scales and initializing new vector flow estimates using that from the previous coarser-resolution image. Overall performance of this processing chain is demonstrated using sample data involving complex too motion observed by multiple sensors mounted to the same base. Multiple sensors were included, including a high-speed visible camera, up to a coarser resolution LWIR camera.

Analysis of Food Contaminants, Residues, and Chemical Constituents of Concern

NASA Astrophysics Data System (ADS)

Ismail, Baraem; Reuhs, Bradley L.; Nielsen, S. Suzanne

The food chain that starts with farmers and ends with consumers can be complex, involving multiple stages of production and distribution (planting, harvesting, breeding, transporting, storing, importing, processing, packaging, distributing to retail markets, and shelf storing) (Fig. 18.1). Various practices can be employed at each stage in the food chain, which may include pesticide treatment, agricultural bioengineering, veterinary drug administration, environmental and storage conditions, processing applications, economic gain practices, use of food additives, choice of packaging material, etc. Each of these practices can play a major role in food quality and safety, due to the possibility of contamination with or introduction (intentionally and nonintentionally) of hazardous substances or constituents. Legislation and regulation to ensure food quality and safety are in place and continue to develop to protect the stakeholders, namely farmers, consumers, and industry. [Refer to reference (1) for information on regulations of food contaminants and residues.

A Chemical Engineer's Perspective on Health and Disease

PubMed Central

Androulakis, Ioannis P.

2014-01-01

Chemical process systems engineering considers complex supply chains which are coupled networks of dynamically interacting systems. The quest to optimize the supply chain while meeting robustness and flexibility constraints in the face of ever changing environments necessitated the development of theoretical and computational tools for the analysis, synthesis and design of such complex engineered architectures. However, it was realized early on that optimality is a complex characteristic required to achieve proper balance between multiple, often competing, objectives. As we begin to unravel life's intricate complexities, we realize that that living systems share similar structural and dynamic characteristics; hence much can be learned about biological complexity from engineered systems. In this article, we draw analogies between concepts in process systems engineering and conceptual models of health and disease; establish connections between these concepts and physiologic modeling; and describe how these mirror onto the physiological counterparts of engineered systems. PMID:25506103

Label-Free Fluorescent DNA Dendrimers for microRNA Detection Based On Nonlinear Hybridization Chain Reaction-Mediated Multiple G-Quadruplex with Low Background Signal.

PubMed

Xue, Qingwang; Liu, Chunxue; Li, Xia; Dai, Li; Wang, Huaisheng

2018-04-18

Various fluorescent sensing systems for miRNA detection have been developed, but they mostly contain enzymatic amplification reactions and label procedures. The strict reaction conditions of tool enzymes and the high cost of labeling limit their potential applications, especially in complex biological matrices. Here, we have addressed the difficult problems and report a strategy for label-free fluorescent DNA dendrimers based on enzyme-free nonlinear hybridization chain reaction (HCR)-mediated multiple G-quadruplex for simple, sensitive, and selective detection of miRNAs with low-background signal. In the strategy, a split G-quadruplex (3:1) sequence is ingeniously designed at both ends of two double-stranded DNAs, which is exploited as building blocks for nonlinear HCR assembly, thereby acquiring a low background signal. A hairpin switch probe (HSP) was employed as recognition and transduction element. Upon sensing the target miRNA, the nonlinear HCR assembly of two blocks (blocks-A and blocks-B) was initiated with the help of two single-stranded DNA assistants, resulting in chain-branching growth of DNA dendrimers with multiple G-quadruplex incorporation. With the zinc(II)-protoporphyrin IX (ZnPPIX) selectively intercalated into the multiple G-quadruplexes, fluorescent DNA dendrimers were obtained, leading to an exponential fluorescence intensity increase. Benefiting from excellent performances of nonlinear HCR and low background signal, this strategy possesses the characteristics of a simplified reaction operation process, as well as high sensitivity. Moreover, the proposed fluorescent sensing strategy also shows preferable selectivity, and can be implemented without modified DNA blocks. Importantly, the strategy has also been tested for miRNA quantification with high confidence in breast cancer cells. Thus, this proposed strategy for label-free fluorescent DNA dendrimers based on a nonlinear HCR-mediated multiple G-quadruplex will be turned into an alternative approach for simple, sensitive, and selective miRNA quantification.

Quantum communication beyond the localization length in disordered spin chains.

PubMed

Allcock, Jonathan; Linden, Noah

2009-03-20

We study the effects of localization on quantum state transfer in spin chains. We show how to use quantum error correction and multiple parallel spin chains to send a qubit with high fidelity over arbitrary distances, in particular, distances much greater than the localization length of the chain.

Effective application of multiple locus variable number of tandem repeats analysis to tracing Staphylococcus aureus in food-processing environment.

PubMed

Rešková, Z; Koreňová, J; Kuchta, T

2014-04-01

A total of 256 isolates of Staphylococcus aureus were isolated from 98 samples (34 swabs and 64 food samples) obtained from small or medium meat- and cheese-processing plants in Slovakia. The strains were genotypically characterized by multiple locus variable number of tandem repeats analysis (MLVA), involving multiplex polymerase chain reaction (PCR) with subsequent separation of the amplified DNA fragments by an automated flow-through gel electrophoresis. With the panel of isolates, MLVA produced 31 profile types, which was a sufficient discrimination to facilitate the description of spatial and temporal aspects of contamination. Further data on MLVA discrimination were obtained by typing a subpanel of strains by multiple locus sequence typing (MLST). MLVA coupled to automated electrophoresis proved to be an effective, comparatively fast and inexpensive method for tracing S. aureus contamination of food-processing factories. Subspecies genotyping of microbial contaminants in food-processing factories may facilitate identification of spatial and temporal aspects of the contamination. This may help to properly manage the process hygiene. With S. aureus, multiple locus variable number of tandem repeats analysis (MLVA) proved to be an effective method for the purpose, being sufficiently discriminative, yet comparatively fast and inexpensive. The application of automated flow-through gel electrophoresis to separation of DNA fragments produced by multiplex PCR helped to improve the accuracy and speed of the method. © 2013 The Society for Applied Microbiology.

Multiplicity in public health supply systems: a learning agenda.

PubMed

Bornbusch, Alan; Bates, James

2013-08-01

Supply chain integration-merging products for health programs into a single supply chain-tends to be the dominant model in health sector reform. However, multiplicity in a supply system may be justified as a risk management strategy that can better ensure product availability, advance specific health program objectives, and increase efficiency.

Further Evaluations of Functional Communication Training and Chained Schedules of Reinforcement to Treat Multiple Functions of Challenging Behavior

ERIC Educational Resources Information Center

Falcomata, Terry S.; Muething, Colin S.; Gainey, Summer; Hoffman, Katherine; Fragale, Christina

2013-01-01

We evaluated functional communication training (FCT) combined with a chained schedule of reinforcement procedure for the treatment of challenging behavior exhibited by two individuals diagnosed with Asperger syndrome and autism. Following functional analyses that suggested that challenging behavior served multiple functions for both participants,…

Immunoglobulin light chains, glycosaminoglycans and amyloid.

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

Stevens, F. J.; Kisilevsky, R.; Biosciences Division

2000-03-01

Immunoglobulin light chains are the precursor proteins for fibrils that are formed during primary amyloidosis and in amyloidosis associated with multiple myeloma. As found for the approximately 20 currently described forms of focal, localized, or systemic amyloidoses, light chain-related fibrils extracted from physiological deposits are invariably associated with glycosaminoglycans, predominantly heparan sulfate. Other amyloid-related proteins are either structurally normal, such as g2-microglobulin and islet amyloid polypeptide, fragments of normal proteins such as serum amyloid A protein or the precursor protein of the g peptide involved in Alzheimer's disease, or are inherited forms of single amino acid variants of a normalmore » protein such as found in the familial forms of amyloid associated with transthyretin. In contrast, the primary structures of light chains involved in fibril formation exhibit extensive mutational diversity rendering some proteins highly amyloidogenic and others non-pathological. The interactions between light chains and glycosaminoglycans are also affected by amino acid variation and may influence the clinical course of disease by enhancing fibril stability and contributing to resistance to protease degradation. Relatively little is currently known about the mechanisms by which glycosaminoglycans interact with light chains and light-chain fibrils. It is probable that future studies of this uniquely diverse family of proteins will continue o shed light on the processes of amyloidosis, and contribute as well to a greater understanding of the normal physiological roles of glycosaminoglycans.« less

Building Quantitative Hydrologic Storylines from Process-based Models for Managing Water Resources in the U.S. Under Climate-changed Futures

NASA Astrophysics Data System (ADS)

Arnold, J.; Gutmann, E. D.; Clark, M. P.; Nijssen, B.; Vano, J. A.; Addor, N.; Wood, A.; Newman, A. J.; Mizukami, N.; Brekke, L. D.; Rasmussen, R.; Mendoza, P. A.

2016-12-01

Climate change narratives for water-resource applications must represent the change signals contextualized by hydroclimatic process variability and uncertainty at multiple scales. Building narratives of plausible change includes assessing uncertainties across GCM structure, internal climate variability, climate downscaling methods, and hydrologic models. Work with this linked modeling chain has dealt mostly with GCM sampling directed separately to either model fidelity (does the model correctly reproduce the physical processes in the world?) or sensitivity (of different model responses to CO2 forcings) or diversity (of model type, structure, and complexity). This leaves unaddressed any interactions among those measures and with other components in the modeling chain used to identify water-resource vulnerabilities to specific climate threats. However, time-sensitive, real-world vulnerability studies typically cannot accommodate a full uncertainty ensemble across the whole modeling chain, so a gap has opened between current scientific knowledge and most routine applications for climate-changed hydrology. To close that gap, the US Army Corps of Engineers, the Bureau of Reclamation, and the National Center for Atmospheric Research are working on techniques to subsample uncertainties objectively across modeling chain components and to integrate results into quantitative hydrologic storylines of climate-changed futures. Importantly, these quantitative storylines are not drawn from a small sample of models or components. Rather, they stem from the more comprehensive characterization of the full uncertainty space for each component. Equally important from the perspective of water-resource practitioners, these quantitative hydrologic storylines are anchored in actual design and operations decisions potentially affected by climate change. This talk will describe part of our work characterizing variability and uncertainty across modeling chain components and their interactions using newly developed observational data, models and model outputs, and post-processing tools for making the resulting quantitative storylines most useful in practical hydrology applications.

Forecasting jobs in the supply chain for investments in residential energy efficiency retrofits in Florida

NASA Astrophysics Data System (ADS)

Fobair, Richard C., II

This research presents a model for forecasting the numbers of jobs created in the energy efficiency retrofit (EER) supply chain resulting from an investment in upgrading residential buildings in Florida. This investigation examined material supply chains stretching from mining to project installation for three product types: insulation, windows/doors, and heating, ventilating, and air conditioning (HVAC) systems. Outputs from the model are provided for the project, sales, manufacturing, and mining level. The model utilizes reverse-estimation to forecast the numbers of jobs that result from an investment. Reverse-estimation is a process that deconstructs a total investment into its constituent parts. In this research, an investment is deconstructed into profit, overhead, and hard costs for each level of the supply chain and over multiple iterations of inter-industry exchanges. The model processes an investment amount, the type of work and method of contracting into a prediction of the number of jobs created. The deconstruction process utilizes data from the U.S. Economic Census. At each supply chain level, the cost of labor is reconfigured into full-time equivalent (FTE) jobs (i.e. equivalent to 40 hours per week for 52 weeks) utilizing loaded labor rates and a typical employee mix. The model is sensitive to adjustable variables, such as percentage of work performed per type of product, allocation of worker time per skill level, annual hours for FTE calculations, wage rate, and benefits. This research provides several new insights into job creation. First, it provides definitions that can be used for future research on jobs in supply chains related to energy efficiency. Second, it provides a methodology for future investigators to calculate jobs in a supply chain resulting from an investment in energy efficiency upgrades to a building. The methodology used in this research is unique because it examines gross employment at the sub-industry level for specific commodities. Most research on employment examines the net employment change (job creation less job destruction) at levels for regions, industries, and the aggregate economy. Third, it provides a forecast of the numbers of jobs for an investment in energy efficiency over the entire supply chain for the selected industries and the job factors for major levels of the supply chain.

Removal efficiency of multiple poly- and perfluoroalkyl substances (PFASs) in drinking water using granular activated carbon (GAC) and anion exchange (AE) column tests.

PubMed

McCleaf, Philip; Englund, Sophie; Östlund, Anna; Lindegren, Klara; Wiberg, Karin; Ahrens, Lutz

2017-09-01

Poly- and perfluoroalkyl substances (PFASs) have been detected in drinking water at relatively high concentrations throughout the world which has led to implementation of regulatory guidelines for specific PFASs in drinking water in several European countries and in the U.S. The Swedish National Food Agency has determined that the drinking water of over one third of the country's municipal consumers is at risk or already affected by PFAS contamination. The present study investigated the effects of perfluorocarbon chain length, functional group and isomer structure (branched or linear) on removal of multiple PFASs using granular activated carbon (GAC, Filtrasorb ® 400) and anion exchange (AE, Purolite ® A600) column experiments. The removal of 14 different PFASs, i.e. the C 3 C 11 , C 14 perfluoroalkyl carboxylic acids (PFCAs) (PFBA, PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTeDA), perfluorooctane sulfonamide (FOSA), and the C 4 , C 6 , C 8 perfluoroalkyl sulfonic acids (PFSAs) (PFBS, PFHxS, PFOS), was monitored for a 217 day period. The results indicate the selective nature of PFAS removal as the absorbents are loaded with PFASs and dissolved organic carbon (DOC). A clear relationship between perfluorocarbon chain length and removal efficiency of PFASs using GAC and AE was found while PFASs with sulfonate functional groups displayed greater removal efficiency than those with carboxylate groups. Similarly, time to column breakthrough increased with increasing perfluorocarbon chain length and was greater for the PFSAs than the PFCAs for both GAC and AE. Shorter carbon chained PFASs such as PFBA, PFPeA, PFHxA showed desorption behavior and long-chained PFASs showed increased removal towards the end of the experiment indicating agglomeration or micelle development. Linear isomers of PFOS, PFHxS, and perfluorooctane sulfonamide (FOSA) had greater column removal efficiencies using GAC (and also for AE at greater bed volume throughput) than the branched and this difference increased at greater bed volume throughputs. The GAC and AE columns showed a poor correlation between DOC and PFAS removal efficiency. The results indicate that designers and operators of AE and GAC treatment processes must take into consideration the selective nature of PFAS removal and associated desorption of short-chain PFCAs during co-removal of multiple PFASs. Copyright © 2017 Elsevier Ltd. All rights reserved.

HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains.

PubMed

Shibata, Yuri; Tokunaga, Fuminori; Goto, Eiji; Komatsu, Ginga; Gohda, Jin; Saeki, Yasushi; Tanaka, Keiji; Takahashi, Hirotaka; Sawasaki, Tatsuya; Inoue, Satoshi; Oshiumi, Hiroyuki; Seya, Tsukasa; Nakano, Hiroyasu; Tanaka, Yuetsu; Iwai, Kazuhiro; Inoue, Jun-Ichiro

2017-01-01

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation.

HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains

PubMed Central

Tokunaga, Fuminori; Goto, Eiji; Komatsu, Ginga; Saeki, Yasushi; Tanaka, Keiji; Takahashi, Hirotaka; Sawasaki, Tatsuya; Inoue, Satoshi; Oshiumi, Hiroyuki; Seya, Tsukasa; Nakano, Hiroyasu; Tanaka, Yuetsu; Iwai, Kazuhiro

2017-01-01

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is crucial for the development of adult T-cell leukemia (ATL), a highly malignant CD4+ T cell neoplasm. Among the multiple aberrant Tax-induced effects on cellular processes, persistent activation of transcription factor NF-κB, which is activated only transiently upon physiological stimulation, is essential for leukemogenesis. We and others have shown that Tax induces activation of the IκB kinase (IKK) complex, which is a critical step in NF-κB activation, by generating Lys63-linked polyubiquitin chains. However, the molecular mechanism underlying Tax-induced IKK activation is controversial and not fully understood. Here, we demonstrate that Tax recruits linear (Met1-linked) ubiquitin chain assembly complex (LUBAC) to the IKK complex and that Tax fails to induce IKK activation in cells that lack LUBAC activity. Mass spectrometric analyses revealed that both Lys63-linked and Met1-linked polyubiquitin chains are associated with the IKK complex. Furthermore, treatment of the IKK-associated polyubiquitin chains with Met1-linked-chain-specific deubiquitinase (OTULIN) resulted in the reduction of high molecular weight polyubiquitin chains and the generation of short Lys63-linked ubiquitin chains, indicating that Tax can induce the generation of Lys63- and Met1-linked hybrid polyubiquitin chains. We also demonstrate that Tax induces formation of the active macromolecular IKK complex and that the blocking of Tax-induced polyubiquitin chain synthesis inhibited formation of the macromolecular complex. Taken together, these results lead us to propose a novel model in which the hybrid-chain-dependent oligomerization of the IKK complex triggered by Tax leads to trans-autophosphorylation-mediated IKK activation. PMID:28103322

An Improved Interacting Multiple Model Filtering Algorithm Based on the Cubature Kalman Filter for Maneuvering Target Tracking.

PubMed

Zhu, Wei; Wang, Wei; Yuan, Gannan

2016-06-01

In order to improve the tracking accuracy, model estimation accuracy and quick response of multiple model maneuvering target tracking, the interacting multiple models five degree cubature Kalman filter (IMM5CKF) is proposed in this paper. In the proposed algorithm, the interacting multiple models (IMM) algorithm processes all the models through a Markov Chain to simultaneously enhance the model tracking accuracy of target tracking. Then a five degree cubature Kalman filter (5CKF) evaluates the surface integral by a higher but deterministic odd ordered spherical cubature rule to improve the tracking accuracy and the model switch sensitivity of the IMM algorithm. Finally, the simulation results demonstrate that the proposed algorithm exhibits quick and smooth switching when disposing different maneuver models, and it also performs better than the interacting multiple models cubature Kalman filter (IMMCKF), interacting multiple models unscented Kalman filter (IMMUKF), 5CKF and the optimal mode transition matrix IMM (OMTM-IMM).

Risk assessment in the upstream crude oil supply chain: Leveraging analytic hierarchy process

NASA Astrophysics Data System (ADS)

Briggs, Charles Awoala

For an organization to be successful, an effective strategy is required, and if implemented appropriately the strategy will result in a sustainable competitive advantage. The importance of decision making in the oil industry is reflected in the magnitude and nature of the industry. Specific features of the oil industry supply chain, such as its longer chain, the complexity of its transportation system, its complex production and storage processes, etc., pose challenges to its effective management. Hence, understanding the risks, the risk sources, and their potential impacts on the oil industry's operations will be helpful in proposing a risk management model for the upstream oil supply chain. The risk-based model in this research uses a three-level analytic hierarchy process (AHP), a multiple-attribute decision-making technique, to underline the importance of risk analysis and risk management in the upstream crude oil supply chain. Level 1 represents the overall goal of risk management; Level 2 is comprised of the various risk factors; and Level 3 represents the alternative criteria of the decision maker as indicated on the hierarchical structure of the crude oil supply chain. Several risk management experts from different oil companies around the world were surveyed, and six major types of supply chain risks were identified: (1) exploration and production, (2) environmental and regulatory compliance, (3) transportation, (4) availability of oil, (5) geopolitical, and (6) reputational. Also identified are the preferred methods of managing risks which include; (1) accept and control the risks, (2) avoid the risk by stopping the activity, or (3) transfer or share the risks to other companies or insurers. The results from the survey indicate that the most important risk to manage is transportation risk with a priority of .263, followed by exploration/production with priority of .198, with an overall inconsistency of .03. With respect to major objectives the most preferred risk management policy option based on the result of the composite score is accept and control risk with a priority of .446, followed by transfer or share risk with a priority of .303. The least likely option is to terminate or forgo activity with a priority of .251.

Maximally reliable Markov chains under energy constraints.

PubMed

Escola, Sean; Eisele, Michael; Miller, Kenneth; Paninski, Liam

2009-07-01

Signal-to-noise ratios in physical systems can be significantly degraded if the outputs of the systems are highly variable. Biological processes for which highly stereotyped signal generations are necessary features appear to have reduced their signal variabilities by employing multiple processing steps. To better understand why this multistep cascade structure might be desirable, we prove that the reliability of a signal generated by a multistate system with no memory (i.e., a Markov chain) is maximal if and only if the system topology is such that the process steps irreversibly through each state, with transition rates chosen such that an equal fraction of the total signal is generated in each state. Furthermore, our result indicates that by increasing the number of states, it is possible to arbitrarily increase the reliability of the system. In a physical system, however, an energy cost is associated with maintaining irreversible transitions, and this cost increases with the number of such transitions (i.e., the number of states). Thus, an infinite-length chain, which would be perfectly reliable, is infeasible. To model the effects of energy demands on the maximally reliable solution, we numerically optimize the topology under two distinct energy functions that penalize either irreversible transitions or incommunicability between states, respectively. In both cases, the solutions are essentially irreversible linear chains, but with upper bounds on the number of states set by the amount of available energy. We therefore conclude that a physical system for which signal reliability is important should employ a linear architecture, with the number of states (and thus the reliability) determined by the intrinsic energy constraints of the system.

Autologous Stem Cell Transplant Followed By Maintenance Therapy in Treating Elderly Patients With Multiple Myeloma

ClinicalTrials.gov

2018-02-27

Extramedullary Plasmacytoma; Isolated Plasmacytoma of Bone; Light Chain Deposition Disease; Primary Systemic Amyloidosis; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Protein structure modeling for CASP10 by multiple layers of global optimization.

PubMed

Joo, Keehyoung; Lee, Juyong; Sim, Sangjin; Lee, Sun Young; Lee, Kiho; Heo, Seungryong; Lee, In-Ho; Lee, Sung Jong; Lee, Jooyoung

2014-02-01

In the template-based modeling (TBM) category of CASP10 experiment, we introduced a new protocol called protein modeling system (PMS) to generate accurate protein structures in terms of side-chains as well as backbone trace. In the new protocol, a global optimization algorithm, called conformational space annealing (CSA), is applied to the three layers of TBM procedure: multiple sequence-structure alignment, 3D chain building, and side-chain re-modeling. For 3D chain building, we developed a new energy function which includes new distance restraint terms of Lorentzian type (derived from multiple templates), and new energy terms that combine (physical) energy terms such as dynamic fragment assembly (DFA) energy, DFIRE statistical potential energy, hydrogen bonding term, etc. These physical energy terms are expected to guide the structure modeling especially for loop regions where no template structures are available. In addition, we developed a new quality assessment method based on random forest machine learning algorithm to screen templates, multiple alignments, and final models. For TBM targets of CASP10, we find that, due to the combination of three stages of CSA global optimizations and quality assessment, the modeling accuracy of PMS improves at each additional stage of the protocol. It is especially noteworthy that the side-chains of the final PMS models are far more accurate than the models in the intermediate steps. Copyright © 2013 Wiley Periodicals, Inc.

Circulating polymerase chain reaction chips utilizing multiple-membrane activation

NASA Astrophysics Data System (ADS)

Wang, Chih-Hao; Chen, Yi-Yu; Liao, Chia-Sheng; Hsieh, Tsung-Min; Luo, Ching-Hsing; Wu, Jiunn-Jong; Lee, Huei-Huang; Lee, Gwo-Bin

2007-02-01

This paper reports a new micromachined, circulating, polymerase chain reaction (PCR) chip for nucleic acid amplification. The PCR chip is comprised of a microthermal control module and a polydimethylsiloxane (PDMS)-based microfluidic control module. The microthermal control modules are formed with three individual heating and temperature-sensing sections, each modulating a specific set temperature for denaturation, annealing and extension processes, respectively. Micro-pneumatic valves and multiple-membrane activations are used to form the microfluidic control module to transport sample fluids through three reaction regions. Compared with other PCR chips, the new chip is more compact in size, requires less time for heating and cooling processes, and has the capability to randomly adjust time ratios and cycle numbers depending on the PCR process. Experimental results showed that detection genes for two pathogens, Streptococcus pyogenes (S. pyogenes, 777 bps) and Streptococcus pneumoniae (S. pneumoniae, 273 bps), can be successfully amplified using the new circulating PCR chip. The minimum number of thermal cycles to amplify the DNA-based S. pyogenes for slab gel electrophoresis is 20 cycles with an initial concentration of 42.5 pg µl-1. Experimental data also revealed that a high reproducibility up to 98% could be achieved if the initial template concentration of the S. pyogenes was higher than 4 pg µl-1. The preliminary results of the current paper were presented at the 19th IEEE International Conference on Micro Electro Mechanical Systems (IEEE MEMS 2006), Istanbul, Turkey, 22-26 January, 2006.

Assessment of parameter uncertainty in hydrological model using a Markov-Chain-Monte-Carlo-based multilevel-factorial-analysis method

NASA Astrophysics Data System (ADS)

Zhang, Junlong; Li, Yongping; Huang, Guohe; Chen, Xi; Bao, Anming

2016-07-01

Without a realistic assessment of parameter uncertainty, decision makers may encounter difficulties in accurately describing hydrologic processes and assessing relationships between model parameters and watershed characteristics. In this study, a Markov-Chain-Monte-Carlo-based multilevel-factorial-analysis (MCMC-MFA) method is developed, which can not only generate samples of parameters from a well constructed Markov chain and assess parameter uncertainties with straightforward Bayesian inference, but also investigate the individual and interactive effects of multiple parameters on model output through measuring the specific variations of hydrological responses. A case study is conducted for addressing parameter uncertainties in the Kaidu watershed of northwest China. Effects of multiple parameters and their interactions are quantitatively investigated using the MCMC-MFA with a three-level factorial experiment (totally 81 runs). A variance-based sensitivity analysis method is used to validate the results of parameters' effects. Results disclose that (i) soil conservation service runoff curve number for moisture condition II (CN2) and fraction of snow volume corresponding to 50% snow cover (SNO50COV) are the most significant factors to hydrological responses, implying that infiltration-excess overland flow and snow water equivalent represent important water input to the hydrological system of the Kaidu watershed; (ii) saturate hydraulic conductivity (SOL_K) and soil evaporation compensation factor (ESCO) have obvious effects on hydrological responses; this implies that the processes of percolation and evaporation would impact hydrological process in this watershed; (iii) the interactions of ESCO and SNO50COV as well as CN2 and SNO50COV have an obvious effect, implying that snow cover can impact the generation of runoff on land surface and the extraction of soil evaporative demand in lower soil layers. These findings can help enhance the hydrological model's capability for simulating/predicting water resources.

Modeling relief demands in an emergency supply chain system under large-scale disasters based on a queuing network.

PubMed

He, Xinhua; Hu, Wenfa

2014-01-01

This paper presents a multiple-rescue model for an emergency supply chain system under uncertainties in large-scale affected area of disasters. The proposed methodology takes into consideration that the rescue demands caused by a large-scale disaster are scattered in several locations; the servers are arranged in multiple echelons (resource depots, distribution centers, and rescue center sites) located in different places but are coordinated within one emergency supply chain system; depending on the types of rescue demands, one or more distinct servers dispatch emergency resources in different vehicle routes, and emergency rescue services queue in multiple rescue-demand locations. This emergency system is modeled as a minimal queuing response time model of location and allocation. A solution to this complex mathematical problem is developed based on genetic algorithm. Finally, a case study of an emergency supply chain system operating in Shanghai is discussed. The results demonstrate the robustness and applicability of the proposed model.

Modeling Relief Demands in an Emergency Supply Chain System under Large-Scale Disasters Based on a Queuing Network

PubMed Central

He, Xinhua

2014-01-01

This paper presents a multiple-rescue model for an emergency supply chain system under uncertainties in large-scale affected area of disasters. The proposed methodology takes into consideration that the rescue demands caused by a large-scale disaster are scattered in several locations; the servers are arranged in multiple echelons (resource depots, distribution centers, and rescue center sites) located in different places but are coordinated within one emergency supply chain system; depending on the types of rescue demands, one or more distinct servers dispatch emergency resources in different vehicle routes, and emergency rescue services queue in multiple rescue-demand locations. This emergency system is modeled as a minimal queuing response time model of location and allocation. A solution to this complex mathematical problem is developed based on genetic algorithm. Finally, a case study of an emergency supply chain system operating in Shanghai is discussed. The results demonstrate the robustness and applicability of the proposed model. PMID:24688367

Light, nutrients, and food-chain length constrain planktonic energy transfer efficiency across multiple trophic levels

PubMed Central

Dickman, Elizabeth M.; Newell, Jennifer M.; González, María J.; Vanni, Michael J.

2008-01-01

The efficiency of energy transfer through food chains [food chain efficiency (FCE)] is an important ecosystem function. It has been hypothesized that FCE across multiple trophic levels is constrained by the efficiency at which herbivores use plant energy, which depends on plant nutritional quality. Furthermore, the number of trophic levels may also constrain FCE, because herbivores are less efficient in using plant production when they are constrained by carnivores. These hypotheses have not been tested experimentally in food chains with 3 or more trophic levels. In a field experiment manipulating light, nutrients, and food-chain length, we show that FCE is constrained by algal food quality and food-chain length. FCE across 3 trophic levels (phytoplankton to carnivorous fish) was highest under low light and high nutrients, where algal quality was best as indicated by taxonomic composition and nutrient stoichiometry. In 3-level systems, FCE was constrained by the efficiency at which both herbivores and carnivores converted food into production; a strong nutrient effect on carnivore efficiency suggests a carryover effect of algal quality across 3 trophic levels. Energy transfer efficiency from algae to herbivores was also higher in 2-level systems (without carnivores) than in 3-level systems. Our results support the hypothesis that FCE is strongly constrained by light, nutrients, and food-chain length and suggest that carryover effects across multiple trophic levels are important. Because many environmental perturbations affect light, nutrients, and food-chain length, and many ecological services are mediated by FCE, it will be important to apply these findings to various ecosystem types. PMID:19011082

[A wrong move in an amateur football player reveals a light chain myeloma].

PubMed

Peyneau, Marine; Nassiri, Shiva; Myara, Anne; Ohana, Salomon; Laplanche, Sophie

2016-01-01

Light chain multiple myeloma is a hematologic malignancy characterized by an excess of tumor plasma cells in the bone marrow and a monoclonal light chain in blood. It is generally diagnosed in patients aged 60-75 years old. Hypercalcemia, anemia, kidney failure, and bone pains are the main clinical and biological signs. Here is an atypical case report about a 30 year-old man who was diagnosed a light chain multiple myeloma. This patient had been suffering from back pain for 5 months. Osteolytic lesions were discovered on X-rays prescribed by the family practitioner. Admitted to the Emergency department, all blood tests showed results within the normal range. The serum protein electrophoresis was also normal. Only the urine analysis showed proteinuria. The urine immunofixation electrophoresis showed a massive κ light chain. The bone marrow aspiration cell count confirmed the myeloma diagnosis with an infiltration of dystrophic plasma cells. The patient was transferred to the hematology ward of Necker Hospital for treatment of light chain myeloma.

Quantum spin chains with multiple dynamics

NASA Astrophysics Data System (ADS)

Chen, Xiao; Fradkin, Eduardo; Witczak-Krempa, William

2017-11-01

Many-body systems with multiple emergent time scales arise in various contexts, including classical critical systems, correlated quantum materials, and ultracold atoms. We investigate such nontrivial quantum dynamics in a different setting: a spin-1 bilinear-biquadratic chain. It has a solvable entangled ground state, but a gapless excitation spectrum that is poorly understood. By using large-scale density matrix renormalization group simulations, we find that the lowest excitations have a dynamical exponent z that varies from 2 to 3.2 as we vary a coupling in the Hamiltonian. We find an additional gapless mode with a continuously varying exponent 2 ≤z <2.7 , which establishes the presence of multiple dynamics. In order to explain these striking properties, we construct a continuum wave function for the ground state, which correctly describes the correlations and entanglement properties. We also give a continuum parent Hamiltonian, but show that additional ingredients are needed to capture the excitations of the chain. By using an exact mapping to the nonequilibrium dynamics of a classical spin chain, we find that the large dynamical exponent is due to subdiffusive spin motion. Finally, we discuss the connections to other spin chains and to a family of quantum critical models in two dimensions.

Copy number variations of six and seven α-globin genes in a family with intermedia and major thalassemia phenotypes.

PubMed

Farashi, Samaneh; Vakili, Shadi; Faramarzi Garous, Negin; Ashki, Mehri; Imanian, Hashem; Azarkeivan, Azita; Najmabadi, Hossein

2015-10-01

Copy number variations in α-globin genes are results of unequal crossover between homologous segments in the α-globin gene cluster that misalign during the meiosis phase of the gametogenesis process. Reduction or augmentation of α-globin genes leads to imbalance of α/β chains in hemoglobin tetramer and consequently attenuate or worsen the β-thal clinical symptoms, respectively. Multiplications in α-globin genes have been found in some populations, justifying unexpected severe phenotype of β-thal carriers. Unexpected severe phenotype in the family members may result from coexistence of extra α-globin genes, which is an important factor in the causation of thalassemia intermedia and major in heterozygous β-thalassemia. We described different multiplications in α-globin locus in an Iranian family with one, two or three extra α-globin genes (ααα/αα, αααα/αα and αααα/ααα). The excess α-globin gene/genes cause increment in β/α chain imbalance and leads to worsening pathophysiology and clinical severity of β-thalassemia carriers.

Structural basis of oligosaccharide processing by glycosaminoglycan sulfotransferases.

PubMed

Gesteira, Tarsis F; Coulson-Thomas, Vivien J

2018-06-06

Heparan sulfate (HS) is a sulfated polysaccharide that plays a key role in morphogenesis, physiology and pathogenesis. The biosynthesis of HS takes place in the Golgi apparatus by a group of enzymes that polymerize, epimerize and sulfate the sugar chain. This biosynthetic process introduces varying degrees of sulfate substitution, which are tightly regulated and directly dictate binding specificity to different cytokines, morphogens and growth factors. Here we report the use of molecular dynamics simulations to investigate the dynamics of substrate recognition of two glycosaminoglycan (GAG) sulfotransferases, N-deacetylase-N-sulfotransferase and 2-O-sulfotransferase to the HS chain during the biosynthetic process. We performed multiple simulations of the binding of the sulfotransferase domains to both the HS oligosaccharide substrate and sulfate donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPs). Analysis of extended simulations provide detailed and useful insights into the atomic interactions that are at work during oligosaccharide processing. The Fast Information Matching method was used to detect the enzyme global dynamics and to predict the pairwise contact of residues responsible for GAG-enzyme binding and unbinding. The correlation between HS displacement and the location of the modified GAG chain were calculated, indicating a possible route for HS and heparin during sulfotransferase processing. Our data also show sulfotransferases contain a conserved interspaced positively charged amino acid residues that form a patch which controls the protein-GAG binding equilibrium. Together, our findings provide further understanding on the fine-tuned complex mechanism of GAG biosynthesis. Our findings can also be extrapolated to other systems for calculating rates of protein-GAG binding.

MC3: Multi-core Markov-chain Monte Carlo code

NASA Astrophysics Data System (ADS)

Cubillos, Patricio; Harrington, Joseph; Lust, Nate; Foster, AJ; Stemm, Madison; Loredo, Tom; Stevenson, Kevin; Campo, Chris; Hardin, Matt; Hardy, Ryan

2016-10-01

MC3 (Multi-core Markov-chain Monte Carlo) is a Bayesian statistics tool that can be executed from the shell prompt or interactively through the Python interpreter with single- or multiple-CPU parallel computing. It offers Markov-chain Monte Carlo (MCMC) posterior-distribution sampling for several algorithms, Levenberg-Marquardt least-squares optimization, and uniform non-informative, Jeffreys non-informative, or Gaussian-informative priors. MC3 can share the same value among multiple parameters and fix the value of parameters to constant values, and offers Gelman-Rubin convergence testing and correlated-noise estimation with time-averaging or wavelet-based likelihood estimation methods.

Renal complications in multiple myeloma and related disorders: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

PubMed

Faiman, Beth M; Mangan, Patricia; Spong, Jacy; Tariman, Joseph D

2011-08-01

Kidney dysfunction is a common clinical feature of symptomatic multiple myeloma. Some degree of renal insufficiency or renal failure is present at diagnosis or will occur during the course of the disease and, if not reversed, will adversely affect overall survival and quality of life. Chronic insults to the kidneys from other illnesses, treatment, or multiple myeloma itself can further damage renal function and increase the risk for additional complications, such as anemia. Patients with multiple myeloma who have light chain (Bence Jones protein) proteinuria may experience renal failure or progress to end-stage renal disease (ESRD) and require dialysis because of light chain cast nephropathy. Kidney failure in patients with presumed multiple myeloma also may result from amyloidosis, light chain deposition disease, or acute tubular necrosis caused by nephrotoxic agents; therefore, identification of patients at risk for kidney damage is essential. The International Myeloma Foundation's Nurse Leadership Board has developed practice recommendations for screening renal function, identifying positive and negative contributing risk and environmental factors, selecting appropriate therapies and supportive care measures to decrease progression to ESRD, and enacting dialysis to reduce and manage renal complications in patients with multiple myeloma.

Shifting orders among suppliers considering risk, price and transportation cost

NASA Astrophysics Data System (ADS)

Revitasari, C.; Pujawan, I. N.

2018-04-01

Supplier order allocation is an important supply chain decision for an enterprise. It is related to the supplier’s function as a raw material provider and other supporting materials that will be used in production process. Most of works on order allocation has been based on costs and other supply chain performance, but very limited of them taking risks into consideration. In this paper we address the problem of order allocation of a single commodity sourced from multiple suppliers considering supply risks in addition to the attempt of minimizing transportation costs. The supply chain risk was investigated and a procedure was proposed in the risk mitigation phase as a form of risk profile. The objective including risk profile in order allocation is to maximize the product flow from a risky supplier to a relatively less risky supplier. The proposed procedure is applied to a sugar company. The result suggests that order allocations should be maximized to suppliers that have a relatively low risk and minimized to suppliers that have a relatively larger risks.

The rate dependent response of a bistable chain at finite temperature

NASA Astrophysics Data System (ADS)

Benichou, Itamar; Zhang, Yaojun; Dudko, Olga K.; Givli, Sefi

2016-10-01

We study the rate dependent response of a bistable chain subjected to thermal fluctuations. The study is motivated by the fact that the behavior of this model system is prototypical to a wide range of nonlinear processes in materials physics, biology and chemistry. To account for the stochastic nature of the system response, we formulate a set of governing equations for the evolution of the probability density of meta-stable configurations. Based on this approach, we calculate the behavior for a wide range of parametric values, such as rate, temperature, overall stiffness, and number of elements in the chain. Our results suggest that fundamental characteristics of the response, such as average transition stress and hysteresis, can be captured by a simple law which folds the influence of all these factors into a single non-dimensional quantity. We also show that the applicability of analytical results previously obtained for single-well systems can be extended to systems having multiple wells by proper definition of rate and of the transition stress.

Folding thermodynamics of pseudoknotted chain conformations

PubMed Central

Kopeikin, Zoia; Chen, Shi-Jie

2008-01-01

We develop a statistical mechanical framework for the folding thermodynamics of pseudoknotted structures. As applications of the theory, we investigate the folding stability and the free energy landscapes for both the thermal and the mechanical unfolding of pseudoknotted chains. For the mechanical unfolding process, we predict the force-extension curves, from which we can obtain the information about structural transitions in the unfolding process. In general, a pseudoknotted structure unfolds through multiple structural transitions. The interplay between the helix stems and the loops plays an important role in the folding stability of pseudoknots. For instance, variations in loop sizes can lead to the destabilization of some intermediate states and change the (equilibrium) folding pathways (e.g., two helix stems unfold either cooperatively or sequentially). In both thermal and mechanical unfolding, depending on the nucleotide sequence, misfolded intermediate states can emerge in the folding process. In addition, thermal and mechanical unfoldings often have different (equilibrium) pathways. For example, for certain sequences, the misfolded intermediates, which generally have longer tails, can fold, unfold, and refold again in the pulling process, which means that these intermediates can switch between two different average end-end extensions. PMID:16674261

Summary of the Effort to Use Active-induced Time Correlation Techniques to Measure the Enrichment of HEU

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

McConchie, Seth M.; Crye, Jason Michael; Pena, Kirsten

2015-09-30

This document summarizes the effort to use active-induced time correlation techniques to measure the enrichment of bulk quantities of enriched uranium. In summary, these techniques use an external source to initiate fission chains, and the time distribution of the detected fission chain neutrons is sensitive to the fissile material enrichment. The number of neutrons emitted from a chain is driven by the multiplication of the item, and the enrichment is closely coupled to the multiplication of the item. As the enrichment increases (decreases), the multiplication increases (decreases) if the geometry is held constant. The time distribution of fission chain neutronsmore » is a complex function of the enrichment and material configuration. The enrichment contributes to the probability of a subsequent fission in a chain via the likelihood of fissioning on an even-numbered isotope versus an odd-numbered isotope. The material configuration contributes to the same probability via solid angle effects for neutrons inducing subsequent fissions and the presence of any moderating material. To simplify the ability to accurately measure the enrichment, an associated particle imaging (API) D-T neutron generator and an array of plastic scintillators are used to simultaneously image the item and detect the fission chain neutrons. The image is used to significantly limit the space of enrichment and material configuration and enable the enrichment to be determined unambiguously.« less

The actin multigene family and livestock speciation using the polymerase chain reaction.

PubMed

Fairbrother, K S; Hopwood, A J; Lockley, A K; Bardsley, R G

1998-01-01

Actins constitute a family of highly-conserved multifunctional intracellular proteins, best known as myofibrillar components in striated muscle fibres. Most vertebrate genomes contain numerous actin genes with high sequence homology in protein coding regions but considerable variability in intron number and sizes. This genetic diversity can be utilised for livestock speciation purposes. The high sequence conservation has enabled a single pair of oligonucleotides to be used to prime the polymerase chain reaction (PCR) with DNA extracted from all animals so far studied. Multiple amplification products were obtained which on gel electrophoresis constituted characteristic species-specific 'fingerprints'. The patterns were reproducible, did not vary between individuals of the same breed or between different breeds within a species, and could be generated even from heat-processed muscle held at 120 degrees C for one hour. Given the capacity of PCR to amplify relatively short sequences in highly-degraded DNA, this approach may be suitable for authentication of processed meat products.

Affinity-reversed-phase liquid chromatography assay to quantitate recombinant antibodies and antibody fragments in fermentation broth.

PubMed

Battersby, J E; Snedecor, B; Chen, C; Champion, K M; Riddle, L; Vanderlaan, M

2001-08-24

An automated dual-column liquid chromatography assay comprised of affinity and reversed-phase separations that quantifies the majority of antibody-related protein species found in crude cell extracts of recombinant origin is described. Although potentially applicable to any antibody preparation, we here use samples of anti-CD18 (Fab'2LZ) and a full-length antibody, anti-tissue factor (anti-TF), from various stages throughout a biopharmaceutical production process to describe the assay details. The targeted proteins were captured on an affinity column containing an anti-light-chain (kappa) Fab antibody (AME5) immobilized on controlled pore glass. The affinity column was placed in-line with a reversed-phase column and the captured components were transferred by elution with dilute acid and subsequently resolved by eluting the reversed-phase column with a shallow acetonitrile gradient. Characterization of the resolved components showed that most antibody fragment preparations contained a light-chain fragment, free light chain, light-chain dimer and multiple forms of Fab'. Analysis of full-length antibody preparations also resolved these fragments as well as a completely assembled form. Co-eluting with the full-length antibody were high-molecular-mass variants that were missing one or both light chains. Resolved components were quantified by comparison with peak areas of similarly treated standards. By comparing the two-dimensional polyacrylamide gel electrophoresis patterns of an Escherichia coli blank run, a production run and the material affinity captured (AME5) from a production run, it was determined that the AME5 antibody captured isoforms of light chain, light chain covalently attached to heavy chain, and truncated light chain isoforms. These forms comprise the bulk of the soluble product-related fragments found in E. coli cell extracts of recombinantly produced antibody fragments.

Tactical resource allocation and elective patient admission planning in care processes.

PubMed

Hulshof, Peter J H; Boucherie, Richard J; Hans, Erwin W; Hurink, Johann L

2013-06-01

Tactical planning of resources in hospitals concerns elective patient admission planning and the intermediate term allocation of resource capacities. Its main objectives are to achieve equitable access for patients, to meet production targets/to serve the strategically agreed number of patients, and to use resources efficiently. This paper proposes a method to develop a tactical resource allocation and elective patient admission plan. These tactical plans allocate available resources to various care processes and determine the selection of patients to be served that are at a particular stage of their care process. Our method is developed in a Mixed Integer Linear Programming (MILP) framework and copes with multiple resources, multiple time periods and multiple patient groups with various uncertain treatment paths through the hospital, thereby integrating decision making for a chain of hospital resources. Computational results indicate that our method leads to a more equitable distribution of resources and provides control of patient access times, the number of patients served and the fraction of allocated resource capacity. Our approach is generic, as the base MILP and the solution approach allow for including various extensions to both the objective criteria and the constraints. Consequently, the proposed method is applicable in various settings of tactical hospital management.

Employer-Led Organizations and Skill Supply Chains: Linking Worker Advancement with the Skill Needs of Employers. Issue Brief.

ERIC Educational Resources Information Center

Mills, Jack; Prince, Heath

Skill supply chains apply a chain strategy to human resources to make the labor market more efficient. They link the multiple skill levels in a given labor market within a network of recruitment pathways for employers and advancement pathways for workers. Skill supply chains are based on employers' actual skill needs and on the principle that…

Free energy calculations of short peptide chains using Adaptively Biased Molecular Dynamics

NASA Astrophysics Data System (ADS)

Karpusenka, Vadzim; Babin, Volodymyr; Roland, Christopher; Sagui, Celeste

2008-10-01

We performed a computational study of monomer peptides composed of methionine, alanine, leucine, glutamate, lysine (all amino acids with a helix-forming propensities); and proline, glycine tyrosine, serine, arginine (which all have poor helix-forming propensities). The free energy landscapes as a function of the handedness and radius of gyration have been calculated using the recently introduced Adaptively Biased Molecular Dynamics (ABMD) method, combined with replica exchange, multiple walkers, and post-processing Umbrella Correction (UC). Minima that correspond to some of the left- and right-handed 310-, α- and π-helixes were identified by secondary structure assignment methods (DSSP, Stride). The resulting free energy surface (FES) and the subsequent steered molecular dynamics (SMD) simulation results are in agreement with the empirical evidence of preferred secondary structures for the peptide chains considered.

Mixed-order phase transition of the contact process near multiple junctions.

PubMed

Juhász, Róbert; Iglói, Ferenc

2017-02-01

We have studied the phase transition of the contact process near a multiple junction of M semi-infinite chains by Monte Carlo simulations. As opposed to the continuous transitions of the translationally invariant (M=2) and semi-infinite (M=1) system, the local order parameter is found to be discontinuous for M>2. Furthermore, the temporal correlation length diverges algebraically as the critical point is approached, but with different exponents on the two sides of the transition. In the active phase, the estimate is compatible with the bulk value, while in the inactive phase it exceeds the bulk value and increases with M. The unusual local critical behavior is explained by a scaling theory with an irrelevant variable, which becomes dangerous in the inactive phase. Quenched spatial disorder is found to make the transition continuous in agreement with earlier renormalization group results.

Transmission electron microscopy study of crystal growth, solid solution, and defect formation: Hollandite and synthetic tremolite

NASA Astrophysics Data System (ADS)

Bozhilov, Krassimir Nikolov

Transmission electron microscopy was applied to study the crystal growth, origin of microstructures, and composition of hollandite and synthetic tremolite. The nonequilibrium shape of hollandite crystals, with reentrant angles between prismatic faces, is interpreted to be due to a multistage growth process and the development of lamellar defects that affect the growth rates of the F-faces. The process of crystal growth can be divided into three phases: (1) development of a core of intergrown romanechite and hollandite structures, (2) topotactic transformation of romanechite to hollandite and development of a lamellar microstructure, and (3) extensive overgrowth of hollandite with a high density of chain multiplicity faults, which alters the shapes of the crystals. The products from time-series of hydrothermal tremolite synthesis experiments from an oxide mixture and by recrystallization from diopside, enstatite, quartz, and water have been characterized. The crystallization starts with rapid, metastable formation of pyroxene and Mg-enriched amphibole. Chain multiplicity faults are low in density. The observed Mg enrichment is due primarily to solid solution involving the magnesio-cummingtonite component, which reaches up to 24 mol% in the initial, metastable growth stage. In products from the final stages of the experiments, the magnesio-cummingtonite component in tremolite varies between 7 and 13 mol%. Formation of monoclinic primitive tremolite is also observed. Experimental recrystallization of pyroxenes to amphibole takes place by a complex, multistage mechanism. The product amphibole crystals have low chain-multiplicity fault densities, which in general are not strongly correlated with variations in the Ca/Mg ratio. The yield of tremolitic amphibole is limited by the sluggishness of diopside hydration and dissolution and the formation of persistent, metastable solid solutions rich in the magnesio-cummingtonite component. Distance Least Squares refinements and lattice energy calculations for magnesio-cummingtonite/tremolite solid solutions reproduce the reduction of symmetry that occurs with reduction of the M4 cation size, as observed in natural amphiboles. Tremolitic amphibole with more than 20% magnesio-cummingtonite component in solid solution favors a primitive monoclinic structure. The intermediate compositions show significant structural distortions, which supports other observations suggesting that such intermediate compositions are unstable.

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

Yang, Sangmo; Paranthaman, Mariappan Parans; Noh, Tae Won

The voltage spectroscopies in scanning probe microscopy (SPM) techniques are widely used to investigate the electrochemical processes in nanoscale volumes, which are important for current key applications, such as batteries, fuel cells, catalysts, and memristors. The spectroscopic measurements are commonly performed on a grid of multiple points to yield spatially resolved maps of reversible and irreversible electrochemical functionalities. Hence, the spacing between measurement points is an important parameter to be considered, especially for irreversible electrochemical processes. Here, we report nonlocal electrochemical dynamics in chains of Ag particles fabricated by the SPM tip on a silver ion solid electrolyte. When themore » grid spacing is small compared with the size of the formed Ag particles, anomalous chains of unequally sized particles with double periodicity evolve. This behavior is ascribed to a proximity effect during the tip-induced electrochemical process, specifically, size-dependent silver particle growth following the contact between the particles. In addition, fractal shape evolution of the formed Ag structures indicates that the growth-limiting process changes from Ag +/Ag redox reaction to Ag +-ion diffusion with the increase in the applied voltage and pulse duration. Our study shows that characteristic shapes of the electrochemical products are good indicators for determining the underlying growth-limiting process, and emergence of complex phenomena during spectroscopic mapping of electrochemical functionalities.« less

Probabilistic Round Trip Contamination Analysis of a Mars Sample Acquisition and Handling Process Using Markovian Decompositions

NASA Technical Reports Server (NTRS)

Hudson, Nicolas; Lin, Ying; Barengoltz, Jack

2010-01-01

A method for evaluating the probability of a Viable Earth Microorganism (VEM) contaminating a sample during the sample acquisition and handling (SAH) process of a potential future Mars Sample Return mission is developed. A scenario where multiple core samples would be acquired using a rotary percussive coring tool, deployed from an arm on a MER class rover is analyzed. The analysis is conducted in a structured way by decomposing sample acquisition and handling process into a series of discrete time steps, and breaking the physical system into a set of relevant components. At each discrete time step, two key functions are defined: The probability of a VEM being released from each component, and the transport matrix, which represents the probability of VEM transport from one component to another. By defining the expected the number of VEMs on each component at the start of the sampling process, these decompositions allow the expected number of VEMs on each component at each sampling step to be represented as a Markov chain. This formalism provides a rigorous mathematical framework in which to analyze the probability of a VEM entering the sample chain, as well as making the analysis tractable by breaking the process down into small analyzable steps.

Markov chains and semi-Markov models in time-to-event analysis.

PubMed

Abner, Erin L; Charnigo, Richard J; Kryscio, Richard J

2013-10-25

A variety of statistical methods are available to investigators for analysis of time-to-event data, often referred to as survival analysis. Kaplan-Meier estimation and Cox proportional hazards regression are commonly employed tools but are not appropriate for all studies, particularly in the presence of competing risks and when multiple or recurrent outcomes are of interest. Markov chain models can accommodate censored data, competing risks (informative censoring), multiple outcomes, recurrent outcomes, frailty, and non-constant survival probabilities. Markov chain models, though often overlooked by investigators in time-to-event analysis, have long been used in clinical studies and have widespread application in other fields.

Markov chains and semi-Markov models in time-to-event analysis

PubMed Central

Abner, Erin L.; Charnigo, Richard J.; Kryscio, Richard J.

2014-01-01

A variety of statistical methods are available to investigators for analysis of time-to-event data, often referred to as survival analysis. Kaplan-Meier estimation and Cox proportional hazards regression are commonly employed tools but are not appropriate for all studies, particularly in the presence of competing risks and when multiple or recurrent outcomes are of interest. Markov chain models can accommodate censored data, competing risks (informative censoring), multiple outcomes, recurrent outcomes, frailty, and non-constant survival probabilities. Markov chain models, though often overlooked by investigators in time-to-event analysis, have long been used in clinical studies and have widespread application in other fields. PMID:24818062

Tripartite motif ligases catalyze polyubiquitin chain formation through a cooperative allosteric mechanism.

PubMed

Streich, Frederick C; Ronchi, Virginia P; Connick, J Patrick; Haas, Arthur L

2013-03-22

Ligation of polyubiquitin chains to proteins is a fundamental post-translational modification, often resulting in targeted degradation of conjugated proteins. Attachment of polyubiquitin chains requires the activities of an E1 activating enzyme, an E2 carrier protein, and an E3 ligase. The mechanism by which polyubiquitin chains are formed remains largely speculative, especially for RING-based ligases. The tripartite motif (TRIM) superfamily of ligases functions in many cellular processes including innate immunity, cellular localization, development and differentiation, signaling, and cancer progression. The present results show that TRIM ligases catalyze polyubiquitin chain formation in the absence of substrate, the rates of which can be used as a functional readout of enzyme function. Initial rate studies under biochemically defined conditions show that TRIM32 and TRIM25 are specific for the Ubc5 family of E2-conjugating proteins and, along with TRIM5α, exhibit cooperative kinetics with respect to Ubc5 concentration, with submicromolar [S]0.5 and Hill coefficients of 3-5, suggesting they possess multiple binding sites for their cognate E2-ubiquitin thioester. Mutation studies reveal a second, non-canonical binding site encompassing the C-terminal Ubc5α-helix. Polyubiquitin chain formation requires TRIM subunit oligomerization through the conserved coiled-coil domain, but can be partially replaced by fusing the catalytic domain to GST to promote dimerization. Other results suggest that TRIM32 assembles polyubiquitin chains as a Ubc5-linked thioester intermediate. These results represent the first detailed mechanistic study of TRIM ligase activity and provide a functional context for oligomerization observed in the superfamily.

An Interval Type-2 Fuzzy Multiple Echelon Supply Chain Model

NASA Astrophysics Data System (ADS)

Miller, Simon; John, Robert

Planning resources for a supply chain is a major factor determining its success or failure. In this paper we build on previous work introducing an Interval Type-2 Fuzzy Logic model of a multiple echelon supply chain. It is believed that the additional degree of uncertainty provided by Interval Type-2 Fuzzy Logic will allow for better representation of the uncertainty and vagueness present in resource planning models. First, the subject of Supply Chain Management is introduced, then some background is given on related work using Type-1 Fuzzy Logic. A description of the Interval Type-2 Fuzzy model is given, and a test scenario detailed. A Genetic Algorithm uses the model to search for a near-optimal plan for the scenario. A discussion of the results follows, along with conclusions and details of intended further work.

Influence of temporal context on value in the multiple-chains and successive-encounters procedures.

PubMed

O'Daly, Matthew; Angulo, Samuel; Gipson, Cassandra; Fantino, Edmund

2006-05-01

This set of studies explored the influence of temporal context across multiple-chain and multiple-successive-encounters procedures. Following training with different temporal contexts, the value of stimuli sharing similar reinforcement schedules was assessed by presenting these stimuli in concurrent probes. The results for the multiple-chain schedule indicate that temporal context does impact the value of a conditioned reinforcer consistent with delay-reduction theory, such that a stimulus signaling a greater reduction in delay until reinforcement has greater value. Further, nonreinforced stimuli that are concurrently presented with the preferred terminal link also have greater value, consistent with value transfer. The effects of context on value for conditions with the multiple-successive-encounters procedure, however, appear to depend on whether the search schedule or alternate handling schedule was manipulated, as well as on whether the tested stimuli were the rich or lean schedules in their components. Overall, the results help delineate the conditions under which temporal context affects conditioned-reinforcement value (acting as a learning variable) and the conditions under which it does not (acting as a performance variable), an issue of relevance to theories of choice.

Efficient dynamic simulation for multiple chain robotic mechanisms

NASA Technical Reports Server (NTRS)

Lilly, Kathryn W.; Orin, David E.

1989-01-01

An efficient O(mN) algorithm for dynamic simulation of simple closed-chain robotic mechanisms is presented, where m is the number of chains, and N is the number of degrees of freedom for each chain. It is based on computation of the operational space inertia matrix (6 x 6) for each chain as seen by the body, load, or object. Also, computation of the chain dynamics, when opened at one end, is required, and the most efficient algorithm is used for this purpose. Parallel implementation of the dynamics for each chain results in an O(N) + O(log sub 2 m+1) algorithm.

r.avaflow v1, an advanced open-source computational framework for the propagation and interaction of two-phase mass flows

NASA Astrophysics Data System (ADS)

Mergili, Martin; Fischer, Jan-Thomas; Krenn, Julia; Pudasaini, Shiva P.

2017-02-01

r.avaflow represents an innovative open-source computational tool for routing rapid mass flows, avalanches, or process chains from a defined release area down an arbitrary topography to a deposition area. In contrast to most existing computational tools, r.avaflow (i) employs a two-phase, interacting solid and fluid mixture model (Pudasaini, 2012); (ii) is suitable for modelling more or less complex process chains and interactions; (iii) explicitly considers both entrainment and stopping with deposition, i.e. the change of the basal topography; (iv) allows for the definition of multiple release masses, and/or hydrographs; and (v) serves with built-in functionalities for validation, parameter optimization, and sensitivity analysis. r.avaflow is freely available as a raster module of the GRASS GIS software, employing the programming languages Python and C along with the statistical software R. We exemplify the functionalities of r.avaflow by means of two sets of computational experiments: (1) generic process chains consisting in bulk mass and hydrograph release into a reservoir with entrainment of the dam and impact downstream; (2) the prehistoric Acheron rock avalanche, New Zealand. The simulation results are generally plausible for (1) and, after the optimization of two key parameters, reasonably in line with the corresponding observations for (2). However, we identify some potential to enhance the analytic and numerical concepts. Further, thorough parameter studies will be necessary in order to make r.avaflow fit for reliable forward simulations of possible future mass flow events.

Quantum phase transition in dimerised spin-1/2 chains

NASA Astrophysics Data System (ADS)

Das, Aparajita; Bhadra, Sreeparna; Saha, Sonali

2015-11-01

Quantum phase transition in dimerised antiferromagnetic Heisenberg spin chain has been studied. A staircase structure in the variation of concurrence within strongly coupled pairs with that of external magnetic field has been observed indicating multiple critical (or critical like) points. Emergence of entanglement due to external magnetic field or magnetic entanglement is observed for weakly coupled spin pairs too in the same dimer chain. Though closed dimerised isotropic XXX Heisenberg chains with different dimer strengths were mainly explored, analogous studies on open chains as well as closed anisotropic (XX interaction) chains with tilted external magnetic field have also been studied.

Linking earth science informatics resources into uninterrupted digital value chains

NASA Astrophysics Data System (ADS)

Woodcock, Robert; Angreani, Rini; Cox, Simon; Fraser, Ryan; Golodoniuc, Pavel; Klump, Jens; Rankine, Terry; Robertson, Jess; Vote, Josh

2015-04-01

The CSIRO Mineral Resources Flagship was established to tackle medium- to long-term challenges facing the Australian mineral industry across the value chain from exploration and mining through mineral processing within the framework of an economically, environmentally and socially sustainable minerals industry. This broad portfolio demands collaboration and data exchange with a broad range of participants and data providers across government, research and industry. It is an ideal environment to link geoscience informatics platforms to application across the resource extraction industry and to unlock the value of data integration between traditionally discrete parts of the minerals digital value chain. Despite the potential benefits, data integration remains an elusive goal within research and industry. Many projects use only a subset of available data types in an integrated manner, often maintaining the traditional discipline-based data 'silos'. Integrating data across the entire minerals digital value chain is an expensive proposition involving multiple disciplines and, significantly, multiple data sources both internal and external to any single organisation. Differing vocabularies and data formats, along with access regimes to appropriate analysis software and equipment all hamper the sharing and exchange of information. AuScope has addressed the challenge of data exchange across organisations nationally, and established a national geosciences information infrastructure using open standards-based web services. Federated across a wide variety of organisations, the resulting infrastructure contains a wide variety of live and updated data types. The community data standards and infrastructure platforms that underpin AuScope provide important new datasets and multi-agency links independent of software and hardware differences. AuScope has thus created an infrastructure, a platform of technologies and the opportunity for new ways of working with and integrating disparate data at much lower cost. An early example of this approach is the value generated by combining geological and metallurgical data sets as part of the rapidly growing field of geometallurgy. This not only provides a far better understanding of the impact of geological variability on ore processing but also leads to new thinking on the types and characteristics of data sets collected at various stages of the exploration and mining process. The Minerals Resources Flagship is linking its research activities to the AuScope infrastructure, exploiting the technology internally to create a platform for integrated research across the minerals value chain and improved interaction with industry. Referred to as the 'Early Access Virtual Lab', the system will be fully interoperable with AuScope and international infrastructures using open standards like GeosciML. Secured access is provided to allow confidential collaboration with industry when required. This presentation will discuss how the CSIRO Mineral Resources Flagship is building on the AuScope infrastructure to transform the way that data and data products are identified, shared, integrated, and reused, to unlock the benefits of true integration of research efforts across the minerals digital value chain.

Biased immunoglobulin light chain gene usage in the shark1

PubMed Central

Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

2015-01-01

This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

Biased Immunoglobulin Light Chain Gene Usage in the Shark.

PubMed

Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

2015-10-15

This study of a large family of κ L chain clusters in nurse shark completes the characterization of its classical Ig gene content (two H chain isotypes, μ and ω, and four L chain isotypes, κ, λ, σ, and σ-2). The shark κ clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over an ~500-bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ~39 κ clusters are prerearranged in the germline (germline joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, nonproductive, and sterile transcripts of the κ clusters compared with the other three L chain isotypes. κ cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and nonproductive rearrangements. These results show that the individual activation of the spatially distant κ clusters is nonrandom. Although both split and germline-joined κ genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. Copyright © 2015 by The American Association of Immunologists, Inc.

TRIM5α requires Ube2W to anchor Lys63-linked ubiquitin chains and restrict reverse transcription

PubMed Central

Fletcher, Adam J; Christensen, Devin E; Nelson, Chad; Tan, Choon Ping; Schaller, Torsten; Lehner, Paul J; Sundquist, Wesley I; Towers, Greg J

2015-01-01

TRIM5α is an antiviral, cytoplasmic, E3 ubiquitin (Ub) ligase that assembles on incoming retroviral capsids and induces their premature dissociation. It inhibits reverse transcription of the viral genome and can also synthesize unanchored polyubiquitin (polyUb) chains to stimulate innate immune responses. Here, we show that TRIM5α employs the E2 Ub-conjugating enzyme Ube2W to anchor the Lys63-linked polyUb chains in a process of TRIM5α auto-ubiquitination. Chain anchoring is initiated, in cells and in vitro, through Ube2W-catalyzed monoubiquitination of TRIM5α. This modification serves as a substrate for the elongation of anchored Lys63-linked polyUb chains, catalyzed by the heterodimeric E2 enzyme Ube2N/Ube2V2. Ube2W targets multiple TRIM5α internal lysines with Ub especially lysines 45 and 50, rather than modifying the N-terminal amino group, which is instead αN-acetylated in cells. E2 depletion or Ub mutation inhibits TRIM5α ubiquitination in cells and restores restricted viral reverse transcription, but not infection. Our data indicate that the stepwise formation of anchored Lys63-linked polyUb is a critical early step in the TRIM5α restriction mechanism and identify the E2 Ub-conjugating cofactors involved. PMID:26101372

Immunoglobulin A multiple myeloma with cutaneous involvement in a dog.

PubMed

Mayer, Monique N; Kerr, Moira E; Grier, Candace K; Macdonald, Valerie S

2008-07-01

An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of cutaneous involvement, was treated with chemotherapy and radiation therapy. The diagnostic criteria for canine multiple myeloma, limitations of diagnostic testing for light chain proteinuria in dogs, and the role of radiation therapy in multiple myeloma patients is discussed.

Immunoglobulin A multiple myeloma with cutaneous involvement in a dog

PubMed Central

Mayer, Monique N.; Kerr, Moira E.; Grier, Candace K.; MacDonald, Valerie S.

2008-01-01

An 8-year-old rottweiler, diagnosed with multiple myeloma and multiple sites of cutaneous involvement, was treated with chemotherapy and radiation therapy. The diagnostic criteria for canine multiple myeloma, limitations of diagnostic testing for light chain proteinuria in dogs, and the role of radiation therapy in multiple myeloma patients is discussed. PMID:18827847

Nanoparticle shape evolution and proximity effects during tip-induced electrochemical processes

DOE PAGES

Yang, Sangmo; Paranthaman, Mariappan Parans; Noh, Tae Won; ...

2016-01-08

The voltage spectroscopies in scanning probe microscopy (SPM) techniques are widely used to investigate the electrochemical processes in nanoscale volumes, which are important for current key applications, such as batteries, fuel cells, catalysts, and memristors. The spectroscopic measurements are commonly performed on a grid of multiple points to yield spatially resolved maps of reversible and irreversible electrochemical functionalities. Hence, the spacing between measurement points is an important parameter to be considered, especially for irreversible electrochemical processes. Here, we report nonlocal electrochemical dynamics in chains of Ag particles fabricated by the SPM tip on a silver ion solid electrolyte. When themore » grid spacing is small compared with the size of the formed Ag particles, anomalous chains of unequally sized particles with double periodicity evolve. This behavior is ascribed to a proximity effect during the tip-induced electrochemical process, specifically, size-dependent silver particle growth following the contact between the particles. In addition, fractal shape evolution of the formed Ag structures indicates that the growth-limiting process changes from Ag +/Ag redox reaction to Ag +-ion diffusion with the increase in the applied voltage and pulse duration. Our study shows that characteristic shapes of the electrochemical products are good indicators for determining the underlying growth-limiting process, and emergence of complex phenomena during spectroscopic mapping of electrochemical functionalities.« less

Multiple Scattering in Random Mechanical Systems and Diffusion Approximation

NASA Astrophysics Data System (ADS)

Feres, Renato; Ng, Jasmine; Zhang, Hong-Kun

2013-10-01

This paper is concerned with stochastic processes that model multiple (or iterated) scattering in classical mechanical systems of billiard type, defined below. From a given (deterministic) system of billiard type, a random process with transition probabilities operator P is introduced by assuming that some of the dynamical variables are random with prescribed probability distributions. Of particular interest are systems with weak scattering, which are associated to parametric families of operators P h , depending on a geometric or mechanical parameter h, that approaches the identity as h goes to 0. It is shown that ( P h - I)/ h converges for small h to a second order elliptic differential operator on compactly supported functions and that the Markov chain process associated to P h converges to a diffusion with infinitesimal generator . Both P h and are self-adjoint (densely) defined on the space of square-integrable functions over the (lower) half-space in , where η is a stationary measure. This measure's density is either (post-collision) Maxwell-Boltzmann distribution or Knudsen cosine law, and the random processes with infinitesimal generator respectively correspond to what we call MB diffusion and (generalized) Legendre diffusion. Concrete examples of simple mechanical systems are given and illustrated by numerically simulating the random processes.

Applications of DART-MS for food quality and safety assurance in food supply chain.

PubMed

Guo, Tianyang; Yong, Wei; Jin, Yong; Zhang, Liya; Liu, Jiahui; Wang, Sai; Chen, Qilong; Dong, Yiyang; Su, Haijia; Tan, Tianwei

2017-03-01

Direct analysis in real time (DART) represents a new generation of ion source which is used for rapid ionization of small molecules under ambient conditions. The combination of DART and various mass spectrometers allows analyzing multiple food samples with simple or no sample treatment, or in conjunction with prevailing protocolized sample preparation methods. Abundant applications by DART-MS have been reviewed in this paper. The DART-MS strategy applied to food supply chain (FSC), including production, processing, and storage and transportation, provides a comprehensive solution to various food components, contaminants, authenticity, and traceability. Additionally, typical applications available in food analysis by other ambient ionization mass spectrometers were summarized, and fundamentals mainly including mechanisms, devices, and parameters were discussed as well. © 2015 Wiley Periodicals, Inc. Mass Spec Rev. 36:161-187, 2017. © 2015 Wiley Periodicals, Inc.

Isolation with Migration Models for More Than Two Populations

PubMed Central

Hey, Jody

2010-01-01

A method for studying the divergence of multiple closely related populations is described and assessed. The approach of Hey and Nielsen (2007, Integration within the Felsenstein equation for improved Markov chain Monte Carlo methods in population genetics. Proc Natl Acad Sci USA. 104:2785–2790) for fitting an isolation-with-migration model was extended to the case of multiple populations with a known phylogeny. Analysis of simulated data sets reveals the kinds of history that are accessible with a multipopulation analysis. Necessarily, processes associated with older time periods in a phylogeny are more difficult to estimate; and histories with high levels of gene flow are particularly difficult with more than two populations. However, for histories with modest levels of gene flow, or for very large data sets, it is possible to study large complex divergence problems that involve multiple closely related populations or species. PMID:19955477

Isolation with migration models for more than two populations.

PubMed

Hey, Jody

2010-04-01

A method for studying the divergence of multiple closely related populations is described and assessed. The approach of Hey and Nielsen (2007, Integration within the Felsenstein equation for improved Markov chain Monte Carlo methods in population genetics. Proc Natl Acad Sci USA. 104:2785-2790) for fitting an isolation-with-migration model was extended to the case of multiple populations with a known phylogeny. Analysis of simulated data sets reveals the kinds of history that are accessible with a multipopulation analysis. Necessarily, processes associated with older time periods in a phylogeny are more difficult to estimate; and histories with high levels of gene flow are particularly difficult with more than two populations. However, for histories with modest levels of gene flow, or for very large data sets, it is possible to study large complex divergence problems that involve multiple closely related populations or species.

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

PubMed

Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

2018-01-01

Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration. In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.

Review of the patient positioning reproducibility in head-and-neck radiotherapy using Statistical Process Control.

PubMed

Moore, Sarah J; Herst, Patries M; Louwe, Robert J W

2018-05-01

A remarkable improvement in patient positioning was observed after the implementation of various process changes aiming to increase the consistency of patient positioning throughout the radiotherapy treatment chain. However, no tool was available to describe these changes over time in a standardised way. This study reports on the feasibility of Statistical Process Control (SPC) to highlight changes in patient positioning accuracy and facilitate correlation of these changes with the underlying process changes. Metrics were designed to quantify the systematic and random patient deformation as input for the SPC charts. These metrics were based on data obtained from multiple local ROI matches for 191 patients who were treated for head-and-neck cancer during the period 2011-2016. SPC highlighted a significant improvement in patient positioning that coincided with multiple intentional process changes. The observed improvements could be described as a combination of a reduction in outliers and a systematic improvement in the patient positioning accuracy of all patients. SPC is able to track changes in the reproducibility of patient positioning in head-and-neck radiation oncology, and distinguish between systematic and random process changes. Identification of process changes underlying these trends requires additional statistical analysis and seems only possible when the changes do not overlap in time. Copyright © 2018 Elsevier B.V. All rights reserved.

Value of Conditioned Reinforcers as a Function of Temporal Context

ERIC Educational Resources Information Center

O'Daly, Matthew; Meyer, Steven; Fantino, Edmund

2005-01-01

In two experiments, pigeons were trained on a multiple-chain schedule, in which the initial link for one chain was a variable-interval (VI) 100s schedule and for the other chain a VI 10s schedule. The terminal links were both fixed-time 30s schedules signaled by differently colored stimuli. Following training, the pigeons had their preference for…

Improved modeling of side-chain--base interactions and plasticity in protein--DNA interface design.

PubMed

Thyme, Summer B; Baker, David; Bradley, Philip

2012-06-08

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed "motifs") was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein-DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. Published by Elsevier Ltd.

Manufacturing and Security Challenges in 3D Printing

NASA Astrophysics Data System (ADS)

Zeltmann, Steven Eric; Gupta, Nikhil; Tsoutsos, Nektarios Georgios; Maniatakos, Michail; Rajendran, Jeyavijayan; Karri, Ramesh

2016-07-01

As the manufacturing time, quality, and cost associated with additive manufacturing (AM) continue to improve, more and more businesses and consumers are adopting this technology. Some of the key benefits of AM include customizing products, localizing production and reducing logistics. Due to these and numerous other benefits, AM is enabling a globally distributed manufacturing process and supply chain spanning multiple parties, and hence raises concerns about the reliability of the manufactured product. In this work, we first present a brief overview of the potential risks that exist in the cyber-physical environment of additive manufacturing. We then evaluate the risks posed by two different classes of modifications to the AM process which are representative of the challenges that are unique to AM. The risks posed are examined through mechanical testing of objects with altered printing orientation and fine internal defects. Finite element analysis and ultrasonic inspection are also used to demonstrate the potential for decreased performance and for evading detection. The results highlight several scenarios, intentional or unintentional, that can affect the product quality and pose security challenges for the additive manufacturing supply chain.

The position 68(E11) side chain in myoglobin regulates ligand capture, bond formation with heme iron, and internal movement into the xenon cavities.

PubMed

Dantsker, David; Roche, Camille; Samuni, Uri; Blouin, George; Olson, John S; Friedman, Joel M

2005-11-18

After photodissociation, ligand rebinding to myoglobin exhibits complex kinetic patterns associated with multiple first-order geminate recombination processes occurring within the protein and a simpler bimolecular phase representing second-order ligand rebinding from the solvent. A smooth transition from cryogenic-like to solution phase properties can be obtained by using a combination of sol-gel encapsulation, addition of glycerol as a bathing medium, and temperature tuning (-15 --> 65 degrees C). This approach was applied to a series of double mutants, myoglobin CO (H64L/V68X, where X = Ala, Val, Leu, Asn, and Phe), which were designed to examine the contributions of the position 68(E11) side chain to the appearance and disappearance of internal rebinding phases in the absence of steric and polar interactions with the distal histidine. Based on the effects of viscosity, temperature, and the stereochemistry of the E11 side chain, the three major phases, B --> A, C --> A, and D --> A, can be assigned, respectively, to ligand rebinding from the following: (i) the distal heme pocket, (ii) the xenon cavities prior to large amplitude side chain conformational relaxation, and (iii) the xenon cavities after significant conformational relaxation of the position 68(E11) side chain. The relative amplitudes of the B --> A and C --> A phases depend markedly on the size and shape of the E11 side chain, which regulates sterically both ligand return to the heme iron atom and ligand migration to the xenon cavities. The internal xenon cavities provide a transient docking site that allows side chain relaxations and the entry of water into the vacated distal pocket, which in turn slows ligand recombination markedly.

Simulation study of the initial crystallization processes of poly(3-hexylthiophene) in solution: ordering dynamics of main chains and side chains.

PubMed

Takizawa, Yuumi; Shimomura, Takeshi; Miura, Toshiaki

2013-05-23

We study the initial nucleation dynamics of poly(3-hexylthiophene) (P3HT) in solution, focusing on the relationship between the ordering process of main chains and that of side chains. We carried out Langevin dynamics simulation and found that the initial nucleation processes consist of three steps: the ordering of ring orientation, the ordering of main-chain vectors, and the ordering of side chains. At the start, the normal vectors of thiophene rings aligned in a very short time, followed by alignment of main-chain end-to-end vectors. The flexible side-chain ordering took almost 5 times longer than the rigid-main-chain ordering. The simulation results indicated that the ordering of side chains was induced after the formation of the regular stack structure of main chains. This slow ordering dynamics of flexible side chains is one of the factors that cause anisotropic nuclei growth, which would be closely related to the formation of nanofiber structures without external flow field. Our simulation results revealed how the combined structure of the planar and rigid-main-chain backbones and the sparse flexible side chains lead to specific ordering behaviors that are not observed in ordinary linear polymer crystallization processes.

An automated processing chains for surface temperature monitoring on Earth's most active volcanoes by optical data from multiple satellites

NASA Astrophysics Data System (ADS)

Silvestri, Malvina; Musacchio, Massimo; Fabrizia Buongiorno, Maria

2017-04-01

The Geohazards Exploitation Platform, or GEP is one of six Thematic Exploitation Platforms developed by ESA to serve data user communities. As a new element of the ground segment delivering satellite results to users, these cloud-based platforms provide an online environment to access information, processing tools, computing resources for community collaboration. The aim is to enable the easy extraction of valuable knowledge from vast quantities of satellite-sensed data now being produced by Europe's Copernicus programme and other Earth observation satellites. In this context, the estimation of surface temperature on active volcanoes around the world is considered. E2E processing chains have been developed for different satellite data (ASTER, Landsat8 and Sentinel 3 missions) using thermal infrared (TIR) channels by applying specific algorithms. These chains have been implemented on the GEP platform enabling the use of EO missions and the generation of added value product such as surface temperature map, from not skilled users. This solution will enhance the use of satellite data and improve the dissemination of the results saving valuable time (no manual browsing, downloading or processing is needed) and producing time series data that can be speedily extracted from a single co-registered pixel, to highlight gradual trends within a narrow area. Moreover, thanks to the high-resolution optical imagery of Sentinel 2 (MSI), the detection of lava maps during an eruption can be automatically obtained. The proposed lava detection method is based on a contextual algorithm applied to Sentinel-2 NIR (band 8 - 0.8 micron) and SWIR (band 12 - 2.25 micron) data. Examples derived by last eruptions on active volcanoes are showed.

Processing-Dependent and Clonal Contamination Patterns of Listeria monocytogenes in the Cured Ham Food Chain Revealed by Genetic Analysis

PubMed Central

Morganti, Marina; Scaltriti, Erika; Cozzolino, Paolo; Bolzoni, Luca; Casadei, Gabriele; Pierantoni, Marco; Foni, Emanuela

2015-01-01

The quantitative and qualitative patterns of environmental contamination by Listeria monocytogenes were investigated in the production chain of dry-cured Parma ham. Standard arrays of surfaces were sampled in processing facilities during a single visit per plant in the three compartments of the food chain, i.e., ham production (19 plants) and postproduction, which was divided into deboning (43 plants) and slicing (25 plants) steps. The numbers of sampled surfaces were 384 in ham production, with 25 positive for L. monocytogenes, and 1,084 in postproduction, with 83 positives. Statistical analysis of the prevalence of contaminated surfaces showed that in ham production, contamination was higher at the beginning of processing and declined significantly toward the end, while in postproduction, prevalence rose toward the end of processing. Prevalence was higher in the deboning facilities than in slicing facilities and was dependent on the type of surface (floor/drainage > clothing > equipment). The qualitative pattern of contamination was investigated through an analysis of the survey isolates and a set of isolates derived from routine monitoring, including longitudinal isolations. Pulsed-field gel electrophoresis (PFGE) and whole-genome single-nucleotide polymorphism (SNP) analysis revealed a remarkable clonality of L. monocytogenes within plants, with the detection of 16 plant-specific clones out of 17 establishments with multiple isolates. Repeated detections of clonal isolates >6 months apart were also observed. Six was the maximum number of between-isolate differences in core SNPs observed within these clones. Based on the same six-SNP threshold, three clusters of clonal isolates, shared by six establishments, were also identified. The spread of L. monocytogenes within and between plants, as indicated by its clonal behavior, is a matter of concern for the hygienic management of establishments. PMID:26590278

How to polymerize ethylene in a highly controlled fashion?

PubMed

Kempe, Rhett

2007-01-01

Very fast, reversible, polyethylene (PE) chain transfer or complex-catalysed "Aufbaureaktion" describes a "living" chain-growing process on a main-group metal or zinc atom; this process is catalysed by an organo-transition-metal or lanthanide complex. PE chains are transferred very fast between the two metal sites and chain growth takes place through ethylene insertion into the transition-metal- or lanthanide-carbon bond-coordinative chain-transfer polymerisation (CCTP). The transferred chains "rest" at the main-group or zinc centre, at which chain-termination processes like beta-H transfer/elimination are of low significance. Such protocols can be used to synthesise very narrowly distributed PE materials (M(w)/M(n)<1.1 up to a molecular weight of about 4000 g mol(-1)) with differently functionalised end groups. Higher molecular-weight polymers can be obtained with a slightly increased M(w)/M(n), since diffusion control and precipitation of the polymers influences the chain-transfer process. Recently, a few transition-metal- or lanthanide-based catalyst systems that catalyse such a highly reversible chain-growing process have been described. They are summarised and compared within this contribution.

Scaling up antiretroviral therapy in Uganda: using supply chain management to appraise health systems strengthening.

PubMed

Windisch, Ricarda; Waiswa, Peter; Neuhann, Florian; Scheibe, Florian; de Savigny, Don

2011-08-01

Strengthened national health systems are necessary for effective and sustained expansion of antiretroviral therapy (ART). ART and its supply chain management in Uganda are largely based on parallel and externally supported efforts. The question arises whether systems are being strengthened to sustain access to ART. This study applies systems thinking to assess supply chain management, the role of external support and whether investments create the needed synergies to strengthen health systems. This study uses the WHO health systems framework and examines the issues of governance, financing, information, human resources and service delivery in relation to supply chain management of medicines and the technologies. It looks at links and causal chains between supply chain management for ART and the national supply system for essential drugs. It combines data from the literature and key informant interviews with observations at health service delivery level in a study district. Current drug supply chain management in Uganda is characterized by parallel processes and information systems that result in poor quality and inefficiencies. Less than expected health system performance, stock outs and other shortages affect ART and primary care in general. Poor performance of supply chain management is amplified by weak conditions at all levels of the health system, including the areas of financing, governance, human resources and information. Governance issues include the lack to follow up initial policy intentions and a focus on narrow, short-term approaches. The opportunity and need to use ART investments for an essential supply chain management and strengthened health system has not been exploited. By applying a systems perspective this work indicates the seriousness of missing system prerequisites. The findings suggest that root causes and capacities across the system have to be addressed synergistically to enable systems that can match and accommodate investments in disease-specific interventions. The multiplicity and complexity of existing challenges require a long-term and systems perspective essentially in contrast to the current short term and program-specific nature of external assistance.

Positive contraction mappings for classical and quantum Schrödinger systems

NASA Astrophysics Data System (ADS)

Georgiou, Tryphon T.; Pavon, Michele

2015-03-01

The classical Schrödinger bridge seeks the most likely probability law for a diffusion process, in path space, that matches marginals at two end points in time; the likelihood is quantified by the relative entropy between the sought law and a prior. Jamison proved that the new law is obtained through a multiplicative functional transformation of the prior. This transformation is characterised by an automorphism on the space of endpoints probability measures, which has been studied by Fortet, Beurling, and others. A similar question can be raised for processes evolving in a discrete time and space as well as for processes defined over non-commutative probability spaces. The present paper builds on earlier work by Pavon and Ticozzi and begins by establishing solutions to Schrödinger systems for Markov chains. Our approach is based on the Hilbert metric and shows that the solution to the Schrödinger bridge is provided by the fixed point of a contractive map. We approach, in a similar manner, the steering of a quantum system across a quantum channel. We are able to establish existence of quantum transitions that are multiplicative functional transformations of a given Kraus map for the cases where the marginals are either uniform or pure states. As in the Markov chain case, and for uniform density matrices, the solution of the quantum bridge can be constructed from the fixed point of a certain contractive map. For arbitrary marginal densities, extensive numerical simulations indicate that iteration of a similar map leads to fixed points from which we can construct a quantum bridge. For this general case, however, a proof of convergence remains elusive.

Adapting Poisson-Boltzmann to the self-consistent mean field theory: Application to protein side-chain modeling

NASA Astrophysics Data System (ADS)

Koehl, Patrice; Orland, Henri; Delarue, Marc

2011-08-01

We present an extension of the self-consistent mean field theory for protein side-chain modeling in which solvation effects are included based on the Poisson-Boltzmann (PB) theory. In this approach, the protein is represented with multiple copies of its side chains. Each copy is assigned a weight that is refined iteratively based on the mean field energy generated by the rest of the protein, until self-consistency is reached. At each cycle, the variational free energy of the multi-copy system is computed; this free energy includes the internal energy of the protein that accounts for vdW and electrostatics interactions and a solvation free energy term that is computed using the PB equation. The method converges in only a few cycles and takes only minutes of central processing unit time on a commodity personal computer. The predicted conformation of each residue is then set to be its copy with the highest weight after convergence. We have tested this method on a database of hundred highly refined NMR structures to circumvent the problems of crystal packing inherent to x-ray structures. The use of the PB-derived solvation free energy significantly improves prediction accuracy for surface side chains. For example, the prediction accuracies for χ1 for surface cysteine, serine, and threonine residues improve from 68%, 35%, and 43% to 80%, 53%, and 57%, respectively. A comparison with other side-chain prediction algorithms demonstrates that our approach is consistently better in predicting the conformations of exposed side chains.

Large-scale chromatin remodeling at the immunoglobulin heavy chain locus: a paradigm for multigene regulation.

PubMed

Bolland, Daniel J; Wood, Andrew L; Corcoran, Anne E

2009-01-01

V(D)J recombination in lymphocytes is the cutting and pasting together of antigen receptor genes in cis to generate the enormous variety of coding sequences required to produce diverse antigen receptor proteins. It is the key role of the adaptive immune response, which must potentially combat millions of different foreign antigens. Most antigen receptor loci have evolved to be extremely large and contain multiple individual V, D and J genes. The immunoglobulin heavy chain (Igh) and immunoglobulin kappa light chain (Igk) loci are the largest multigene loci in the mammalian genome and V(D)J recombination is one of the most complicated genetic processes in the nucleus. The challenge for the appropriate lymphocyte is one of macro-management-to make all of the antigen receptor genes in a particular locus available for recombination at the appropriate developmental time-point. Conversely, these large loci must be kept closed in lymphocytes in which they do not normally recombine, to guard against genomic instability generated by the DNA double strand breaks inherent to the V(D)J recombination process. To manage all of these demanding criteria, V(D)J recombination is regulated at numerous levels. It is restricted to lymphocytes since the Rag genes which control the DNA double-strand break step of recombination are only expressed in these cells. Within the lymphocyte lineage, immunoglobulin recombination is restricted to B-lymphocytes and TCR recombination to T-lymphocytes by regulation of locus accessibility, which occurs at multiple levels. Accessibility of recombination signal sequences (RSSs) flanking individual V, D and J genes at the nucleosomal level is the key micro-management mechanism, which is discussed in greater detail in other chapters. This chapter will explore how the antigen receptor loci are regulated as a whole, focussing on the Igh locus as a paradigm for the mechanisms involved. Numerous recent studies have begun to unravel the complex and complementary processes involved in this large-scale locus organisation. We will examine the structure of the Igh locus and the large-scale and higher-order chromatin remodelling processes associated with V(D)J recombination, at the level of the locus itself, its conformational changes and its dynamic localisation within the nucleus.

Fourier Method for Calculating Fission Chain Neutron Multiplicity Distributions

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

Chambers, David H.; Chandrasekaran, Hema; Walston, Sean E.

Here, a new way of utilizing the fast Fourier transform is developed to compute the probability distribution for a fission chain to create n neutrons. We then extend this technique to compute the probability distributions for detecting n neutrons. Lastly, our technique can be used for fission chains initiated by either a single neutron inducing a fission or by the spontaneous fission of another isotope.

Fourier Method for Calculating Fission Chain Neutron Multiplicity Distributions

DOE PAGES

Chambers, David H.; Chandrasekaran, Hema; Walston, Sean E.

2017-03-27

Here, a new way of utilizing the fast Fourier transform is developed to compute the probability distribution for a fission chain to create n neutrons. We then extend this technique to compute the probability distributions for detecting n neutrons. Lastly, our technique can be used for fission chains initiated by either a single neutron inducing a fission or by the spontaneous fission of another isotope.

A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes

PubMed Central

Miyoshi, Eiji; Eguchi, Hidetoshi; Nagano, Hiroaki; Matsunami, Katsuyoshi; Nagaoka, Satoshi; Yamada, Daisaku; Asaoka, Tadafumi; Noda, Takehiro; Wada, Hiroshi; Kawamoto, Koichi; Goto, Kunihito; Taniyama, Kiyomi; Mori, Masaki; Doki, Yuichiro

2017-01-01

Objectives Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy. Methods Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo. Results Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events. Conclusions Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer. PMID:29077749

A practical approach to pancreatic cancer immunotherapy using resected tumor lysate vaccines processed to express α-gal epitopes.

PubMed

Furukawa, Kenta; Tanemura, Masahiro; Miyoshi, Eiji; Eguchi, Hidetoshi; Nagano, Hiroaki; Matsunami, Katsuyoshi; Nagaoka, Satoshi; Yamada, Daisaku; Asaoka, Tadafumi; Noda, Takehiro; Wada, Hiroshi; Kawamoto, Koichi; Goto, Kunihito; Taniyama, Kiyomi; Mori, Masaki; Doki, Yuichiro

2017-01-01

Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy. Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo. Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events. Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer.

The use of multiple imputation for the accurate measurements of individual feed intake by electronic feeders.

PubMed

Jiao, S; Tiezzi, F; Huang, Y; Gray, K A; Maltecca, C

2016-02-01

Obtaining accurate individual feed intake records is the key first step in achieving genetic progress toward more efficient nutrient utilization in pigs. Feed intake records collected by electronic feeding systems contain errors (erroneous and abnormal values exceeding certain cutoff criteria), which are due to feeder malfunction or animal-feeder interaction. In this study, we examined the use of a novel data-editing strategy involving multiple imputation to minimize the impact of errors and missing values on the quality of feed intake data collected by an electronic feeding system. Accuracy of feed intake data adjustment obtained from the conventional linear mixed model (LMM) approach was compared with 2 alternative implementations of multiple imputation by chained equation, denoted as MI (multiple imputation) and MICE (multiple imputation by chained equation). The 3 methods were compared under 3 scenarios, where 5, 10, and 20% feed intake error rates were simulated. Each of the scenarios was replicated 5 times. Accuracy of the alternative error adjustment was measured as the correlation between the true daily feed intake (DFI; daily feed intake in the testing period) or true ADFI (the mean DFI across testing period) and the adjusted DFI or adjusted ADFI. In the editing process, error cutoff criteria are used to define if a feed intake visit contains errors. To investigate the possibility that the error cutoff criteria may affect any of the 3 methods, the simulation was repeated with 2 alternative error cutoff values. Multiple imputation methods outperformed the LMM approach in all scenarios with mean accuracies of 96.7, 93.5, and 90.2% obtained with MI and 96.8, 94.4, and 90.1% obtained with MICE compared with 91.0, 82.6, and 68.7% using LMM for DFI. Similar results were obtained for ADFI. Furthermore, multiple imputation methods consistently performed better than LMM regardless of the cutoff criteria applied to define errors. In conclusion, multiple imputation is proposed as a more accurate and flexible method for error adjustments in feed intake data collected by electronic feeders.

Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease.

PubMed

Priyamvada, P S; Morkhandikar, S; Srinivas, B H; Parameswaran, S

2015-01-01

Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig) light chains. In heavy chain amyloidosis (AH), deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL), the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda) AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

Event-Driven Messaging for Offline Data Quality Monitoring at ATLAS

NASA Astrophysics Data System (ADS)

Onyisi, Peter

2015-12-01

During LHC Run 1, the information flow through the offline data quality monitoring in ATLAS relied heavily on chains of processes polling each other's outputs for handshaking purposes. This resulted in a fragile architecture with many possible points of failure and an inability to monitor the overall state of the distributed system. We report on the status of a project undertaken during the LHC shutdown to replace the ad hoc synchronization methods with a uniform message queue system. This enables the use of standard protocols to connect processes on multiple hosts; reliable transmission of messages between possibly unreliable programs; easy monitoring of the information flow; and the removal of inefficient polling-based communication.

Planetary Crater Detection and Registration Using Marked Point Processes, Multiple Birth and Death Algorithms, and Region-Based Analysis

NASA Technical Reports Server (NTRS)

Solarna, David; Moser, Gabriele; Le Moigne-Stewart, Jacqueline; Serpico, Sebastiano B.

2017-01-01

Because of the large variety of sensors and spacecraft collecting data, planetary science needs to integrate various multi-sensor and multi-temporal images. These multiple data represent a precious asset, as they allow the study of targets spectral responses and of changes in the surface structure; because of their variety, they also require accurate and robust registration. A new crater detection algorithm, used to extract features that will be integrated in an image registration framework, is presented. A marked point process-based method has been developed to model the spatial distribution of elliptical objects (i.e. the craters) and a birth-death Markov chain Monte Carlo method, coupled with a region-based scheme aiming at computational efficiency, is used to find the optimal configuration fitting the image. The extracted features are exploited, together with a newly defined fitness function based on a modified Hausdorff distance, by an image registration algorithm whose architecture has been designed to minimize the computational time.

Detecting abandoned objects using interacting multiple models

NASA Astrophysics Data System (ADS)

Becker, Stefan; Münch, David; Kieritz, Hilke; Hübner, Wolfgang; Arens, Michael

2015-10-01

In recent years, the wide use of video surveillance systems has caused an enormous increase in the amount of data that has to be stored, monitored, and processed. As a consequence, it is crucial to support human operators with automated surveillance applications. Towards this end an intelligent video analysis module for real-time alerting in case of abandoned objects in public spaces is proposed. The overall processing pipeline consists of two major parts. First, person motion is modeled using an Interacting Multiple Model (IMM) filter. The IMM filter estimates the state of a person according to a finite-state, discrete-time Markov chain. Second, the location of persons that stay at a fixed position defines a region of interest, in which a nonparametric background model with dynamic per-pixel state variables identifies abandoned objects. In case of a detected abandoned object, an alarm event is triggered. The effectiveness of the proposed system is evaluated on the PETS 2006 dataset and the i-Lids dataset, both reflecting prototypical surveillance scenarios.

Image sensor with high dynamic range linear output

NASA Technical Reports Server (NTRS)

Yadid-Pecht, Orly (Inventor); Fossum, Eric R. (Inventor)

2007-01-01

Designs and operational methods to increase the dynamic range of image sensors and APS devices in particular by achieving more than one integration times for each pixel thereof. An APS system with more than one column-parallel signal chains for readout are described for maintaining a high frame rate in readout. Each active pixel is sampled for multiple times during a single frame readout, thus resulting in multiple integration times. The operation methods can also be used to obtain multiple integration times for each pixel with an APS design having a single column-parallel signal chain for readout. Furthermore, analog-to-digital conversion of high speed and high resolution can be implemented.

Towards Non-Equilibrium Dynamics with Trapped Ions

NASA Astrophysics Data System (ADS)

Silbert, Ariel; Jubin, Sierra; Doret, Charlie

2016-05-01

Atomic systems are superbly suited to the study of non-equilibrium dynamics. These systems' exquisite isolation from environmental perturbations leads to long relaxation times that enable exploration of far-from-equilibrium phenomena. One example of particular relevance to experiments in trapped ion quantum information processing, metrology, and precision spectroscopy is the approach to thermal equilibrium of sympathetically cooled linear ion chains. Suitable manipulation of experimental parameters permits exploration of the quantum-to-classical crossover between ballistic transport and diffusive, Fourier's Law conduction, a topic of interest not only to the trapped ion community but also for the development of microelectronic devices and other nanoscale structures. We present progress towards trapping chains of multiple co-trapped calcium isotopes geared towards measuring thermal equilibration and discuss plans for future experiments in non-equilibrium statistical mechanics. This work is supported by Cottrell College Science Award from the Research Corporation for Science Advancement and by Williams College.

First principles studies of electron tunneling in proteins

PubMed Central

Hayashi, Tomoyuki; Stuchebrukhov, Alexei A.

2014-01-01

A first principles study of electronic tunneling along the chain of seven Fe/S clusters in respiratory complex I, a key enzyme in the respiratory electron transport chain, is described. The broken-symmetry states of the Fe/S metal clusters calculated at both DFT and semi-empirical ZINDO levels were utilized to examine both the extremely weak electronic couplings between Fe/S clusters and the tunneling pathways, which provide a detailed atomistic-level description of the charge transfer process in the protein. One-electron tunneling approximation was found to hold within a reasonable accuracy, with only a moderate induced polarization of the core electrons. The method is demonstrated to be able to calculate accurately the coupling matrix elements as small as 10−4 cm−1. A distinct signature of the wave properties of electrons is observed as quantum interferences of multiple tunneling pathways. PMID:25383312

Substrate specificity of the ubiquitin and Ubl proteases

PubMed Central

Ronau, Judith A; Beckmann, John F; Hochstrasser, Mark

2016-01-01

Conjugation and deconjugation of ubiquitin and ubiquitin-like proteins (Ubls) to cellular proteins are highly regulated processes integral to cellular homeostasis. Most often, the C-termini of these small polypeptides are attached to lysine side chains of target proteins by an amide (isopeptide) linkage. Deubiquitinating enzymes (DUBs) and Ubl-specific proteases (ULPs) comprise a diverse group of proteases that recognize and remove ubiquitin and Ubls from their substrates. How DUBs and ULPs distinguish among different modifiers, or different polymeric forms of these modifiers, remains poorly understood. The specificity of ubiquitin/Ubl-deconjugating enzymes for particular substrates depends on multiple factors, ranging from the topography of specific substrate features, as in different polyubiquitin chain types, to structural elements unique to each enzyme. Here we summarize recent structural and biochemical studies that provide insights into mechanisms of substrate specificity among various DUBs and ULPs. We also discuss the unexpected specificities of non-eukaryotic proteases in these families. PMID:27012468

A parallel optimization method for product configuration and supplier selection based on interval

NASA Astrophysics Data System (ADS)

Zheng, Jian; Zhang, Meng; Li, Guoxi

2017-06-01

In the process of design and manufacturing, product configuration is an important way of product development, and supplier selection is an essential component of supply chain management. To reduce the risk of procurement and maximize the profits of enterprises, this study proposes to combine the product configuration and supplier selection, and express the multiple uncertainties as interval numbers. An integrated optimization model of interval product configuration and supplier selection was established, and NSGA-II was put forward to locate the Pareto-optimal solutions to the interval multiobjective optimization model.

The optimal manufacturing batch size with rework under time-varying demand process for a finite time horizon

NASA Astrophysics Data System (ADS)

Musa, Sarah; Supadi, Siti Suzlin; Omar, Mohd

2014-07-01

Rework is one of the solutions to some of the main issues in reverse logistic and green supply chain as it reduces production cost and environmental problem. Many researchers focus on developing rework model, but to the knowledge of the author, none of them has developed a model for time-varying demand rate. In this paper, we extend previous works and develop multiple batch production system for time-varying demand rate with rework. In this model, the rework is done within the same production cycle.

Multiple functions of caprylic acid-induced impurity precipitation for process intensification in monoclonal antibody purification.

PubMed

Trapp, Anja; Faude, Alexander; Hörold, Natalie; Schubert, Sven; Faust, Sabine; Grob, Thilo; Schmidt, Stefan

2018-05-02

New emerging technologies delivering benefits in terms of process robustness and economy are an inevitable prerequisite for monoclonal antibody purification processes intensification. Caprylic acid was proven as an effective precipitating agent enabling efficient precipitaton of product- and process-related impurities while leaving the antibody in solution. This purification step at mild acidic pH was therefore introduced in generic antibody platform approaches after Protein A capture and evaluated for its impact regarding process robustness and antibody stability. Comparison of 13 different monoclonal antibodies showed significant differences in antibody recovery between 65-95% during caprylic acid-induced impurity precipitation. Among six compared physicochemical properties, isoelectric point of the antibody domains was figured out to correlate with yield. Antibodies with mild acidic pI of the light chain were significantly susceptible to caprylic acid-induced precipitation resulting in lower yields. Virus clearance studies revealed that caprylic acid provided complete virus inactivation of an enveloped virus. Multiple process relevant factors such as pH range, caprylic acid concentration and antibody stability were investigated in this study to enable an intensified purification process including caprylic acid precipitation for HCP removal of up to 2 log 10 reduction values at mAb yields >90% while also contributing to the virus safety of the process. Copyright © 2018 Elsevier B.V. All rights reserved.

Time-correlated neutron analysis of a multiplying HEU source

NASA Astrophysics Data System (ADS)

Miller, E. C.; Kalter, J. M.; Lavelle, C. M.; Watson, S. M.; Kinlaw, M. T.; Chichester, D. L.; Noonan, W. A.

2015-06-01

The ability to quickly identify and characterize special nuclear material remains a national security challenge. In counter-proliferation applications, identifying the neutron multiplication of a sample can be a good indication of the level of threat. Currently neutron multiplicity measurements are performed with moderated 3He proportional counters. These systems rely on the detection of thermalized neutrons, a process which obscures both energy and time information from the source. Fast neutron detectors, such as liquid scintillators, have the ability to detect events on nanosecond time scales, providing more information on the temporal structure of the arriving signal, and provide an alternative method for extracting information from the source. To explore this possibility, a series of measurements were performed on the Idaho National Laboratory's MARVEL assembly, a configurable HEU source. The source assembly was measured in a variety of different HEU configurations and with different reflectors, covering a range of neutron multiplications from 2 to 8. The data was collected with liquid scintillator detectors and digitized for offline analysis. A gap based approach for identifying the bursts of detected neutrons associated with the same fission chain was used. Using this approach, we are able to study various statistical properties of individual fission chains. One of these properties is the distribution of neutron arrival times within a given burst. We have observed two interesting empirical trends. First, this distribution exhibits a weak, but definite, dependence on source multiplication. Second, there are distinctive differences in the distribution depending on the presence and type of reflector. Both of these phenomena might prove to be useful when assessing an unknown source. The physical origins of these phenomena can be illuminated with help of MCNPX-PoliMi simulations.

Collision of Identical Solitary Waves in Hertzian Chains

NASA Astrophysics Data System (ADS)

Sen, Surajit; Manciu, Marian; Hurd, Alan J.

2000-03-01

We consider a chain of elastic beads, which repel upon contact according to the non-linear Hertz potential. We further assume that the chain is under zero loading, i.e., the grains have zero initial overlap. We show via careful numerical solution of the equations of motion that an impulse propagates as a solitary wave and that the collision of identical solitary waves propagating in opposite directions along the chain spawns a hierarchy of multiple weak solitary waves [1]. [1] M. Manciu, S. Sen and A.J. Hurd, Phys Lett A (submitted).

Interphase and particle dispersion correlations in polymer nanocomposites

NASA Astrophysics Data System (ADS)

Senses, Erkan

Particle dispersion in polymer matrices is a major parameter governing the mechanical performance of polymer nanocomposites. Controlling particle dispersion and understanding aging of composites under large shear and temperature variations determine the processing conditions and lifetime of composites which are very important for diverse applications in biomedicine, highly reinforced materials and more importantly for the polymer composites with adaptive mechanical responses. This thesis investigates the role of interphase layers between particles and polymer matrices in two bulk systems where particle dispersion is altered upon deformation in repulsive composites, and good-dispersion of particles is retained after multiple oscillatory shearing and aging cycles in attractive composites. We demonstrate that chain desorption and re-adsorption processes in attractive composites under shear can effectively enhance the bulk microscopic mechanical properties, and long chains of adsorbed layers lead to a denser entangled interphase layer. We further designed experiments where particles are physically adsorbed with bimodal lengths of homopolymer chains to underpin the entanglement effect in interphases. Bimodal adsorbed chains are shown to improve the interfacial strength and used to modulate the elastic properties of composites without changing the particle loading, dispersion state or polymer conformation. Finally, the role of dynamic asymmetry (different mobilities in polymer blends) and chemical heterogeneity in the interphase layer are explored in systems of poly(methyl methacrylate) adsorbed silica nanoparticles dispersed in poly(ethylene oxide) matrix. Such nanocomposites are shown to exhibit unique thermal-stiffening behavior at temperatures above glass transitions of both polymers. These interesting findings suggest that the mobility of the surface-bound polymer is essential for reinforcement in polymer nanocomposites, contrary to existing glassy layer theories for polymers on attractive particle surfaces. The shown thermally-induced stiffening behavior is reversible and makes this interfacial mechanism highly attractive in developing new active, remotely controllable engineered materials from non-responsive components.

Metal cation dependence of interactions with amino acids: bond dissociation energies of Rb(+) and Cs(+) to the acidic amino acids and their amide derivatives.

PubMed

Armentrout, P B; Yang, Bo; Rodgers, M T

2014-04-24

Metal cation-amino acid interactions are key components controlling the secondary structure and biological function of proteins, enzymes, and macromolecular complexes comprising these species. Determination of pairwise interactions of alkali metal cations with amino acids provides a thermodynamic vocabulary that begins to quantify these fundamental processes. In the present work, we expand a systematic study of such interactions by examining rubidium and cesium cations binding with the acidic amino acids (AA), aspartic acid (Asp) and glutamic acid (Glu), and their amide derivatives, asparagine (Asn) and glutamine (Gln). These eight complexes are formed using electrospray ionization and their bond dissociation energies (BDEs) are determined experimentally using threshold collision-induced dissociation with xenon in a guided ion beam tandem mass spectrometer. Analyses of the energy-dependent cross sections include consideration of unimolecular decay rates, internal energy of the reactant ions, and multiple ion-neutral collisions. Quantum chemical calculations are conducted at the B3LYP, MP2(full), and M06 levels of theory using def2-TZVPPD basis sets, with results showing reasonable agreement with experiment. At 0 and 298 K, most levels of theory predict that the ground-state conformers for M(+)(Asp) and M(+)(Asn) involve tridentate binding of the metal cation to the backbone carbonyl, amino, and side-chain carbonyl groups, although tridentate binding to the carboxylic acid group and side-chain carbonyl is competitive for M(+)(Asn). For the two longer side-chain amino acids, Glu and Gln, multiple structures are competitive. A comparison of these results to those for the smaller alkali cations, Na(+) and K(+), provides insight into the trends in binding energies associated with the molecular polarizability and dipole moment of the side chain. For all four metal cations, the BDEs are inversely correlated with the size of the metal cation and follow the order Asp < Glu < Asn < Gln.

Rotational Dynamics of Solutes with Multiple Single Bond Axes Studied by Infrared Pump-Probe Spectroscopy.

PubMed

Okuda, Masaki; Ohta, Kaoru; Tominaga, Keisuke

2018-02-01

To investigate the relationship between the structural degrees of freedom around a vibrational probe and the rotational relaxation process of a solute in solution, we studied the anisotropy decays of three different N 3 -derivatized amino acids in primary alcohol solutions. By performing polarization-controlled IR pump-probe measurements, we reveal that the anisotropy decays of the vibrational probe molecules in 1-alcohol solutions possess two decay components, at subpicosecond and picosecond time scales. On the basis of results showing that the fast relaxation component is insensitive to the vibrational probe molecule, we suggest that the anisotropy decay of the N 3 group on a subpicosecond time scale results from a local, small-amplitude fluctuation of the flexible vibrational probe, which does not depend on the details of its molecular structure. However, the slow relaxation component depends on the solute: with longer alkyl chains attached to the N 3 group, the anisotropy decay of the slow component is faster. Consequently, we conclude that the slow relaxation component corresponds to the reorientational motion of the N 3 group correlated with other intramolecular rotational motions (e.g., rotational motions of the neighboring alkyl chain). Our experimental results provide important insight into understanding the rotational dynamics of solutes with multiple single bond axes in solution.

IMAAAGINE: a webserver for searching hypothetical 3D amino acid side chain arrangements in the Protein Data Bank

PubMed Central

Nadzirin, Nurul; Willett, Peter; Artymiuk, Peter J.; Firdaus-Raih, Mohd

2013-01-01

We describe a server that allows the interrogation of the Protein Data Bank for hypothetical 3D side chain patterns that are not limited to known patterns from existing 3D structures. A minimal side chain description allows a variety of side chain orientations to exist within the pattern, and generic side chain types such as acid, base and hydroxyl-containing can be additionally deployed in the search query. Moreover, only a subset of distances between the side chains need be specified. We illustrate these capabilities in case studies involving arginine stacks, serine-acid group arrangements and multiple catalytic triad-like configurations. The IMAAAGINE server can be accessed at http://mfrlab.org/grafss/imaaagine/. PMID:23716645

Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.

PubMed

Taylor, Robert W; Pyle, Angela; Griffin, Helen; Blakely, Emma L; Duff, Jennifer; He, Langping; Smertenko, Tania; Alston, Charlotte L; Neeve, Vivienne C; Best, Andrew; Yarham, John W; Kirschner, Janbernd; Schara, Ulrike; Talim, Beril; Topaloglu, Haluk; Baric, Ivo; Holinski-Feder, Elke; Abicht, Angela; Czermin, Birgit; Kleinle, Stephanie; Morris, Andrew A M; Vassallo, Grace; Gorman, Grainne S; Ramesh, Venkateswaran; Turnbull, Douglass M; Santibanez-Koref, Mauro; McFarland, Robert; Horvath, Rita; Chinnery, Patrick F

2014-07-02

Mitochondrial disorders have emerged as a common cause of inherited disease, but their diagnosis remains challenging. Multiple respiratory chain complex defects are particularly difficult to diagnose at the molecular level because of the massive number of nuclear genes potentially involved in intramitochondrial protein synthesis, with many not yet linked to human disease. To determine the molecular basis of multiple respiratory chain complex deficiencies. We studied 53 patients referred to 2 national centers in the United Kingdom and Germany between 2005 and 2012. All had biochemical evidence of multiple respiratory chain complex defects but no primary pathogenic mitochondrial DNA mutation. Whole-exome sequencing was performed using 62-Mb exome enrichment, followed by variant prioritization using bioinformatic prediction tools, variant validation by Sanger sequencing, and segregation of the variant with the disease phenotype in the family. Presumptive causal variants were identified in 28 patients (53%; 95% CI, 39%-67%) and possible causal variants were identified in 4 (8%; 95% CI, 2%-18%). Together these accounted for 32 patients (60% 95% CI, 46%-74%) and involved 18 different genes. These included recurrent mutations in RMND1, AARS2, and MTO1, each on a haplotype background consistent with a shared founder allele, and potential novel mutations in 4 possible mitochondrial disease genes (VARS2, GARS, FLAD1, and PTCD1). Distinguishing clinical features included deafness and renal involvement associated with RMND1 and cardiomyopathy with AARS2 and MTO1. However, atypical clinical features were present in some patients, including normal liver function and Leigh syndrome (subacute necrotizing encephalomyelopathy) seen in association with TRMU mutations and no cardiomyopathy with founder SCO2 mutations. It was not possible to confidently identify the underlying genetic basis in 21 patients (40%; 95% CI, 26%-54%). Exome sequencing enhances the ability to identify potential nuclear gene mutations in patients with biochemically defined defects affecting multiple mitochondrial respiratory chain complexes. Additional study is required in independent patient populations to determine the utility of this approach in comparison with traditional diagnostic methods.

Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting.

PubMed

Zeman, David; Kušnierová, Pavlína; Švagera, Zdeněk; Všianský, František; Byrtusová, Monika; Hradílek, Pavel; Kurková, Barbora; Zapletalová, Olga; Bartoš, Vladimír

2016-01-01

We aimed to compare various methods for free light chain (fLC) quantitation in cerebrospinal fluid (CSF) and serum and to determine whether quantitative CSF measurements could reliably predict intrathecal fLC synthesis. In addition, we wished to determine the relationship between free kappa and free lambda light chain concentrations in CSF and serum in various disease groups. We analysed 166 paired CSF and serum samples by at least one of the following methods: turbidimetry (Freelite™, SPAPLUS), nephelometry (N Latex FLC™, BN ProSpec), and two different (commercially available and in-house developed) sandwich ELISAs. The results were compared with oligoclonal fLC detected by affinity-mediated immunoblotting after isoelectric focusing. Although the correlations between quantitative methods were good, both proportional and systematic differences were discerned. However, no major differences were observed in the prediction of positive oligoclonal fLC test. Surprisingly, CSF free kappa/free lambda light chain ratios were lower than those in serum in about 75% of samples with negative oligoclonal fLC test. In about a half of patients with multiple sclerosis and clinically isolated syndrome, profoundly increased free kappa/free lambda light chain ratios were found in the CSF. Our results show that using appropriate method-specific cut-offs, different methods of CSF fLC quantitation can be used for the prediction of intrathecal fLC synthesis. The reason for unexpectedly low free kappa/free lambda light chain ratios in normal CSFs remains to be elucidated. Whereas CSF free kappa light chain concentration is increased in most patients with multiple sclerosis and clinically isolated syndrome, CSF free lambda light chain values show large interindividual variability in these patients and should be investigated further for possible immunopathological and prognostic significance.

Parallel Markov chain Monte Carlo - bridging the gap to high-performance Bayesian computation in animal breeding and genetics.

PubMed

Wu, Xiao-Lin; Sun, Chuanyu; Beissinger, Timothy M; Rosa, Guilherme Jm; Weigel, Kent A; Gatti, Natalia de Leon; Gianola, Daniel

2012-09-25

Most Bayesian models for the analysis of complex traits are not analytically tractable and inferences are based on computationally intensive techniques. This is true of Bayesian models for genome-enabled selection, which uses whole-genome molecular data to predict the genetic merit of candidate animals for breeding purposes. In this regard, parallel computing can overcome the bottlenecks that can arise from series computing. Hence, a major goal of the present study is to bridge the gap to high-performance Bayesian computation in the context of animal breeding and genetics. Parallel Monte Carlo Markov chain algorithms and strategies are described in the context of animal breeding and genetics. Parallel Monte Carlo algorithms are introduced as a starting point including their applications to computing single-parameter and certain multiple-parameter models. Then, two basic approaches for parallel Markov chain Monte Carlo are described: one aims at parallelization within a single chain; the other is based on running multiple chains, yet some variants are discussed as well. Features and strategies of the parallel Markov chain Monte Carlo are illustrated using real data, including a large beef cattle dataset with 50K SNP genotypes. Parallel Markov chain Monte Carlo algorithms are useful for computing complex Bayesian models, which does not only lead to a dramatic speedup in computing but can also be used to optimize model parameters in complex Bayesian models. Hence, we anticipate that use of parallel Markov chain Monte Carlo will have a profound impact on revolutionizing the computational tools for genomic selection programs.

Parallel Markov chain Monte Carlo - bridging the gap to high-performance Bayesian computation in animal breeding and genetics

PubMed Central

2012-01-01

Background Most Bayesian models for the analysis of complex traits are not analytically tractable and inferences are based on computationally intensive techniques. This is true of Bayesian models for genome-enabled selection, which uses whole-genome molecular data to predict the genetic merit of candidate animals for breeding purposes. In this regard, parallel computing can overcome the bottlenecks that can arise from series computing. Hence, a major goal of the present study is to bridge the gap to high-performance Bayesian computation in the context of animal breeding and genetics. Results Parallel Monte Carlo Markov chain algorithms and strategies are described in the context of animal breeding and genetics. Parallel Monte Carlo algorithms are introduced as a starting point including their applications to computing single-parameter and certain multiple-parameter models. Then, two basic approaches for parallel Markov chain Monte Carlo are described: one aims at parallelization within a single chain; the other is based on running multiple chains, yet some variants are discussed as well. Features and strategies of the parallel Markov chain Monte Carlo are illustrated using real data, including a large beef cattle dataset with 50K SNP genotypes. Conclusions Parallel Markov chain Monte Carlo algorithms are useful for computing complex Bayesian models, which does not only lead to a dramatic speedup in computing but can also be used to optimize model parameters in complex Bayesian models. Hence, we anticipate that use of parallel Markov chain Monte Carlo will have a profound impact on revolutionizing the computational tools for genomic selection programs. PMID:23009363

A high throughput mutagenic analysis of yeast sumo structure and function

PubMed Central

Newman, Heather A.; Lu, Jian; Carson, Caryn; Boeke, Jef D.

2017-01-01

Sumoylation regulates a wide range of essential cellular functions through diverse mechanisms that remain to be fully understood. Using S. cerevisiae, a model organism with a single essential SUMO gene (SMT3), we developed a library of >250 mutant strains with single or multiple amino acid substitutions of surface or core residues in the Smt3 protein. By screening this library using plate-based assays, we have generated a comprehensive structure-function based map of Smt3, revealing essential amino acid residues and residues critical for function under a variety of genotoxic and proteotoxic stress conditions. Functionally important residues mapped to surfaces affecting Smt3 precursor processing and deconjugation from protein substrates, covalent conjugation to protein substrates, and non-covalent interactions with E3 ligases and downstream effector proteins containing SUMO-interacting motifs. Lysine residues potentially involved in formation of polymeric chains were also investigated, revealing critical roles for polymeric chains, but redundancy in specific chain linkages. Collectively, our findings provide important insights into the molecular basis of signaling through sumoylation. Moreover, the library of Smt3 mutants represents a valuable resource for further exploring the functions of sumoylation in cellular stress response and other SUMO-dependent pathways. PMID:28166236

In situ characterization of N-carboxy anhydride polymerization in nanoporous anodic alumina.

PubMed

Lau, K H Aaron; Duran, Hatice; Knoll, Wolfgang

2009-03-12

Poly(gamma-benzyl-L-glutamate) (PBLG) has been a popular model polypeptide for a range of physicochemical studies, and its modifiable ester side chains make it an attractive platform for various potential applications. Thin films of Poly(gamma-benzyl-L-glutamate) PBLG were surface grafted within nanoporous anodic alumina (AAO) by surface-initiated polymerization of the N-carboxy anhydride of benzyl-L-glutamate (BLG-NCA). The grafting process was characterized by optical waveguide spectroscopy (OWS), infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). OWS was able to track the PBLG layer thickness increase in situ, and ex situ FT-IR gave complementary information on the PBLG chain's secondary structure. Transitions in the PBLG growth rate could be correlated with transitions in the polypeptide secondary structure. The emergence of a three-dimensional, anisotropic PBLG morphology within the cylindrical pores of the AAO membrane was also identified as the grafted PBLG average layer thickness increased. Comparison of the PBLG/AAO results with those on a planar silicon dioxide surface indicated that both the conformational transitions and the PBLG nanostructure development could be attributed to the confining geometry within the pores of the nanoporous AAO matrix. The use of a nanoporous AAO matrix, combined with the surface grafting of a thin film of PBLG chains with multiple modifiable side chains, could potentially offer a nanoporous platform with a very high density of functional sites.

Chitosan multiple addition enhances laccase production from Trametes versicolor.

PubMed

Adekunle, Abiodun Emmanuel; Wang, Feng; Hu, Jianhua; Ma, Anzhou; Guo, Chen; Zhuang, Guoqiang; Liu, Chun-Zhao

2015-10-01

Chitosan multiple addition strategy was developed to improve laccase production from Trametes versicolor cultures. The optimized multiple addition strategy was carried out by two-time addition of 0.1 g L(-1) chitosan to a 2-day-old culture media, with 24-h interval between the treatments. Under these conditions, laccase activity of 644.9 U l(-1) was achieved on the seventh day and laccase production was improved by 93.5 % higher than the control. Chitosan treatment increased reactive oxygen species generation and extracellular protein concentration in the treated mycelia. In contrast, the inducer inhibited the mycelia growth. The result of the quantitative reverse transcription polymerase chain reaction showed that the copy number of the laccase gene transcript increased by 16.7-fold in the treated mycelia relative to the control. This study provides insight into some of the intrinsic metabolic processes involved in the upregulation of laccase production in the presence of chitosan inducer in fungal culture.

Polymerase chain reaction amplification as a diagnostic tool in culture-negative multiple-valve endocarditis.

PubMed

Madershahian, Navid; Strauch, Justus T; Breuer, Martin; Bruhin, Raimund; Straube, Eberhard; Wahlers, Thorsten

2005-03-01

We report a case of culture-negative infectious endocarditis in a 17-year-old boy in which the etiologic diagnosis could only be provided by polymerase chain reaction amplification and sequencing of the bacterial 16S rRNA gene from valve tissue.

Dark Solitons in FPU Lattice Chain

NASA Astrophysics Data System (ADS)

Wang, Deng-Long; Yang, Ru-Shu; Yang, You-Tian

2007-11-01

Based on multiple scales method, we study the nonlinear properties of a new Fermi-Pasta-Ulam lattice model analytically. It is found that the lattice chain exhibits a novel nonlinear elementary excitation, i.e. a dark soliton. Moreover, the modulation depth of dark soliton is increasing as the anharmonic parameter increases.

Molecular Modeling and Imaging of Initial Stages of Cellulose Fibril Assembly: Evidence for a Disordered Intermediate Stage

PubMed Central

Haigler, Candace H.; Grimson, Mark J.; Gervais, Julien; Le Moigne, Nicolas; Höfte, Herman; Monasse, Bernard; Navard, Patrick

2014-01-01

The remarkable mechanical strength of cellulose reflects the arrangement of multiple β-1,4-linked glucan chains in a para-crystalline fibril. During plant cellulose biosynthesis, a multimeric cellulose synthesis complex (CSC) moves within the plane of the plasma membrane as many glucan chains are synthesized from the same end and in close proximity. Many questions remain about the mechanism of cellulose fibril assembly, for example must multiple catalytic subunits within one CSC polymerize cellulose at the same rate? How does the cellulose fibril bend to align horizontally with the cell wall? Here we used mathematical modeling to investigate the interactions between glucan chains immediately after extrusion on the plasma membrane surface. Molecular dynamics simulations on groups of six glucans, each originating from a position approximating its extrusion site, revealed initial formation of an uncrystallized aggregate of chains from which a protofibril arose spontaneously through a ratchet mechanism involving hydrogen bonds and van der Waals interactions between glucose monomers. Consistent with the predictions from the model, freeze-fracture transmission electron microscopy using improved methods revealed a hemispherical accumulation of material at points of origination of apparent cellulose fibrils on the external surface of the plasma membrane where rosette-type CSCs were also observed. Together the data support the possibility that a zone of uncrystallized chains on the plasma membrane surface buffers the predicted variable rates of cellulose polymerization from multiple catalytic subunits within the CSC and acts as a flexible hinge allowing the horizontal alignment of the crystalline cellulose fibrils relative to the cell wall. PMID:24722535

Multiple scales and phases in discrete chains with application to folded proteins

NASA Astrophysics Data System (ADS)

Sinelnikova, A.; Niemi, A. J.; Nilsson, Johan; Ulybyshev, M.

2018-05-01

Chiral heteropolymers such as large globular proteins can simultaneously support multiple length scales. The interplay between the different scales brings about conformational diversity, determines the phase properties of the polymer chain, and governs the structure of the energy landscape. Most importantly, multiple scales produce complex dynamics that enable proteins to sustain live matter. However, at the moment there is incomplete understanding of how to identify and distinguish the various scales that determine the structure and dynamics of a complex protein. Here we address this impending problem. We develop a methodology with the potential to systematically identify different length scales, in the general case of a linear polymer chain. For this we introduce and analyze the properties of an order parameter that can both reveal the presence of different length scales and can also probe the phase structure. We first develop our concepts in the case of chiral homopolymers. We introduce a variant of Kadanoff's block-spin transformation to coarse grain piecewise linear chains, such as the C α backbone of a protein. We derive analytically, and then verify numerically, a number of properties that the order parameter can display, in the case of a chiral polymer chain. In particular, we propose that in the case of a chiral heteropolymer the order parameter can reveal traits of several different phases, contingent on the length scale at which it is scrutinized. We confirm that this is the case with crystallographic protein structures in the Protein Data Bank. Thus our results suggest relations between the scales, the phases, and the complexity of folding pathways.

The Origin of Widespread Long-lived Volcanism Across the Galapagos Volcanic Province

NASA Astrophysics Data System (ADS)

O'Connor, J. M.; Stoffers, P.; Wijbrans, J. R.; Worthington, T. J.

2005-12-01

40Ar/39Ar ages for rocks dredged (SO144 PAGANINI expedition) and drilled (DSDP) from the Galapagos Volcanic Province (Cocos, Carnegie, Coiba and Malpelo aseismic ridges and associated seamounts) show evidence of 1) increasing age with distance from the Galapagos Archipelago, 2) long-lived episodic volcanism at many locations, and 3) broad overlapping regions of coeval volcanism. The widespread nature of synchronous volcanism across the Galapagos Volcanic Province (GVP) suggests a correspondingly large Galapagos hotspot melting anomaly (O'Connor et al., 2004). Development of the GVP via Cocos and Nazca plate migration and divergence over this broad melting anomaly would explain continued multiple phases of volcanism over millions of years following the initial onset of hotspot volcanism. The question arising from these observations is whether long-lived GVP episodic volcanism is equivalent to `rejuvenescent' or a `post-erosional' phase of volcanism that occurs hundreds of thousands or million years after the main shield-building phase documented on many mid-plate seamount chains, most notably along the Hawaiian-Emperor Seamount Chain? Thus, investigating the process responsible for long-lived episodic GVP volcanism provides the opportunity to evaluate this little understood process of rejuvenation in a physical setting very different to the Hawaiian-Emperor Chain (i.e. on/near spreading axis versus mid-plate). We consider here timing and geochemical information to test the various geodynamic models proposed to explain the origin of GVP hotspot volcanism, especially the possibility of rejuvenated phases that erupt long after initial shield-building.

Laser Doppler Vibrometry measurements of human cadaveric tympanic membrane vibration

PubMed Central

2013-01-01

Objective To determine the feasibility of measuring tympanic membrane (TM) vibrations at multiple locations on the TM to differentiate normal eardrums from those with associated ossicular pathologies. Design Cadaveric human temporal bone study. Setting Basic science laboratory. Methods A mastoidectomy and facial recess approach was performed on four cadaveric temporal bones to obtain access to the ossicles without disrupting the TM. Ossicles were palpated to ensure normal mobility and an intact ossicular chain. Laser Doppler Vibrometry (LDV) measurements were then taken on all four TMs. LDV measurements were repeated on each TM following stapes footplate fixation, incudo-stapedial joint dislocation, and malleus head fixation. Main outcome measures LDV measurements of TM vibration at the umbo, the lateral process of the malleus, and in each of the four quadrants of the TM. Results The best signal-to-noise ratios were found between 2 and 4 kHz, at the umbo, the anterior superior quadrant, the anterior inferior quadrant, and the posterior inferior quadrant. Since our goal was to assess the ossicular chain, we selected the TM locations closest to the ossicular chain (the umbo and lateral process of the malleus) for further analysis. Differences could be seen between normals and the simulated ossicular pathologies, but values were not statistically significant. Conclusions LDV measurements are technically challenging and require optimization to obtain consistent measurements. This study demonstrates the potential of LDV to differentiate ossicular pathologies behind an intact tympanic membrane. Future studies will further characterize the clinical role of this diagnostic modality. PMID:23663748

Human disease mortality kinetics are explored through a chain model embodying principles of extreme value theory and competing risks.

PubMed

Juckett, D A; Rosenberg, B

1992-04-21

The distributions for human disease-specific mortality exhibit two striking characteristics: survivorship curves that intersect near the longevity limit; and, the clustering of best-fitting Weibull shape parameter values into groups centered on integers. Correspondingly, we have hypothesized that the distribution intersections result from either competitive processes or population partitioning and the integral clustering in the shape parameter results from the occurrence of a small number of rare, rate-limiting events in disease progression. In this report we initiate a theoretical examination of these questions by exploring serial chain model dynamics and parameteric competing risks theory. The links in our chain models are composed of more than one bond, where the number of bonds in a link are denoted the link size and are the number of events necessary to break the link and, hence, the chain. We explored chains with all links of the same size or with segments of the chain composed of different size links (competition). Simulations showed that chain breakage dynamics depended on the weakest-link principle and followed kinetics of extreme-values which were very similar to human mortality kinetics. In particular, failure distributions for simple chains were Weibull-type extreme-value distributions with shape parameter values that were identifiable with the integral link size in the limit of infinite chain length. Furthermore, for chains composed of several segments of differing link size, the survival distributions for the various segments converged at a point in the S(t) tails indistinguishable from human data. This was also predicted by parameteric competing risks theory using Weibull underlying distributions. In both the competitive chain simulations and the parametric competing risks theory, however, the shape values for the intersecting distributions deviated from the integer values typical of human data. We conclude that rare events can be the source of integral shapes in human mortality, that convergence is a salient feature of multiple endpoints, but that pure competition may not be the best explanation for the exact type of convergence observable in human mortality. Finally, while the chain models were not motivated by any specific biological structures, interesting biological correlates to them may be useful in gerontological research.

Acquired Fanconi syndrome with proximal tubular cytoplasmic fibrillary inclusions of λ light chain restriction.

PubMed

Yao, Ying; Wang, Su-Xia; Zhang, You-Kang; Wang, Yan; Liu, Li; Liu, Gang

2014-01-01

Light chain proximal tubulopathy is a rarely reported entity associated with plasma cell dyscrasia that classically manifests as acquired Fanconi syndrome and is characterized by the presence of κ-restricted crystals in the proximal tubular cytoplasm. We herein present a case of multiple myeloma with Fanconi syndrome and acute kidney injury due to light chain proximal tubulopathy with light chain cast nephropathy. Prominent phagolysosomes and numerous irregularly shaped inclusions with a fibrillary matrix in the cytoplasm of the proximal tubules were identified on electron microscopy. A monotypic light chain of the λ type was detected in the distal tubular casts, proximal tubular cytoplasmic lysosomes and fibrillary inclusions on immunofluorescence and immune electron microscopy. This case underscores the importance of conducting careful ultrastructural investigations and immunocytologic examinations of light chains for detecting and diagnosing light chain proximal tubulopathy.

Living Supramolecular Polymerization of a Perylene Bisimide Dye into Fluorescent J-Aggregates.

PubMed

Wagner, Wolfgang; Wehner, Marius; Stepanenko, Vladimir; Ogi, Soichiro; Würthner, Frank

2017-12-11

The self-assembly of a new perylene bisimide (PBI) organogelator with 1,7-dimethoxy substituents in the bay position affords non-fluorescent H-aggregates at high cooling rates and fluorescent J-aggregates at low cooling rates. Under properly adjusted conditions, the kinetically trapped "off-pathway" H-aggregates are transformed into the thermodynamically favored J-aggregates, a process that can be accelerated by the addition of J-aggregate seeds. Spectroscopic studies revealed a subtle interplay of π-π interactions and intra- and intermolecular hydrogen bonding for monomeric, H-, and J-aggregated PBIs. Multiple polymerization cycles initiated from the seed termini demonstrate the living character of this chain-growth supramolecular polymerization process. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiple Redox Modes in the Reversible Lithiation of High-Capacity, Peierls-Distorted Vanadium Sulfide

DOE PAGES

Britto, Sylvia; Leskes, Michal; Hua, Xiao; ...

2015-06-08

Vanadium sulfide VS 4 in the patronite mineral structure, is a linear chain compound comprising vanadium atoms coordinated by disulfide anions [S 2] 2–. 51V NMR shows that the material, despite having V formally in the d 1 configuration, is diamagnetic, suggesting potential dimerization through metal-metal bonding associated with a Peierls distortion of the linear chains. This is supported by density functional calculations, and is also consistent with the observed alternation in V-V distances of 2.8 Å and 3.2 Å along the chains. Partial lithiation results in reduction of the disulfide ions to sulfide S 2–, including via an internalmore » redox process whereby an electron from V 4+ is transferred to [S 2] 2– resulting in oxidation of V 4+ to V 5+ and reduction of the [S 2] 2– to S 2- to form Li 3VS 4 containing tetrahedral [VS 4] 3– anions. On further lithiation this is followed by reduction of the V 5+ in Li 3VS 4 to form Li 3+xVS 4 (x=0.5-1), a mixed valent V 4+/V 5+ compound. Eventually reduction to Li 2S plus elemental V occurs. Despite the complex redox processes involving both the cation and the anion occurring in this material, the system is found to be partially reversible between 0 and 3 V. In conclusion, the unusual redox processes in this system are elucidated using a suite of short range characterization tools including 51V Nuclear Magnetic Resonance spectroscopy (NMR), S Kedge X-ray Absorption Near Edge Spectroscopy (XANES) and Pair Distribution Function (PDF) Analysis of X-ray data.« less

On a Result for Finite Markov Chains

ERIC Educational Resources Information Center

Kulathinal, Sangita; Ghosh, Lagnojita

2006-01-01

In an undergraduate course on stochastic processes, Markov chains are discussed in great detail. Textbooks on stochastic processes provide interesting properties of finite Markov chains. This note discusses one such property regarding the number of steps in which a state is reachable or accessible from another state in a finite Markov chain with M…

Treatment of Acute Renal Failure Secondary to Multiple Myeloma with Chemotherapy and Extended High Cut-Off Hemodialysis

PubMed Central

Hutchison, Colin A.; Bradwell, Arthur R.; Cook, Mark; Basnayake, Kolitha; Basu, Supratik; Harding, Stephen; Hattersley, John; Evans, Neil D.; Chappel, Mike J.; Sampson, Paul; Foggensteiner, Lukas; Adu, Dwomoa; Cockwell, Paul

2009-01-01

Background and objectives: Extended hemodialysis using a high cut-off dialyzer (HCO-HD) removes large quantities of free light chains in patients with multiple myeloma. However, the clinical utility of this method is uncertain. This study assessed the combination of chemotherapy and HCO-HD on serum free light chain concentrations and renal recovery in patients with myeloma kidney (cast nephropathy) and dialysis-dependent acute renal failure. Design, setting, participants, & measurements: An open-label study of the relationship between free light chain levels and clinical outcomes in 19 patients treated with standard chemotherapy regimens and HCO-HD. Results: There were sustained early reductions in serum free light chain concentrations (median 85% [range 50 to 97]) in 13 patients. These 13 patients became dialysis independent at a median of 27 d (range 13 to 120). Six patients had chemotherapy interrupted because of early infections and did not achieve sustained early free light chain reductions; one of these patients recovered renal function (at 105 d) the remaining 5 patients did not recover renal function. Patients who recovered renal function had a significantly improved survival (P < 0.012). Conclusion: In dialysis-dependent acute renal failure secondary to myeloma kidney, patients who received uninterrupted chemotherapy and extended HCO-HD had sustained reductions in serum free light chain concentrations and recovered independent renal function. PMID:19339414

Examples of design and achievement of vision systems for mobile robotics applications

NASA Astrophysics Data System (ADS)

Bonnin, Patrick J.; Cabaret, Laurent; Raulet, Ludovic; Hugel, Vincent; Blazevic, Pierre; M'Sirdi, Nacer K.; Coiffet, Philippe

2000-10-01

Our goal is to design and to achieve a multiple purpose vision system for various robotics applications : wheeled robots (like cars for autonomous driving), legged robots (six, four (SONY's AIBO) legged robots, and humanoid), flying robots (to inspect bridges for example) in various conditions : indoor or outdoor. Considering that the constraints depend on the application, we propose an edge segmentation implemented either in software, or in hardware using CPLDs (ASICs or FPGAs could be used too). After discussing the criteria of our choice, we propose a chain of image processing operators constituting an edge segmentation. Although this chain is quite simple and very fast to perform, results appear satisfactory. We proposed a software implementation of it. Its temporal optimization is based on : its implementation under the pixel data flow programming model, the gathering of local processing when it is possible, the simplification of computations, and the use of fast access data structures. Then, we describe a first dedicated hardware implementation of the first part, which requires 9CPLS in this low cost version. It is technically possible, but more expensive, to implement these algorithms using only a signle FPGA.

Analysing grouping of nucleotides in DNA sequences using lumped processes constructed from Markov chains.

PubMed

Guédon, Yann; d'Aubenton-Carafa, Yves; Thermes, Claude

2006-03-01

The most commonly used models for analysing local dependencies in DNA sequences are (high-order) Markov chains. Incorporating knowledge relative to the possible grouping of the nucleotides enables to define dedicated sub-classes of Markov chains. The problem of formulating lumpability hypotheses for a Markov chain is therefore addressed. In the classical approach to lumpability, this problem can be formulated as the determination of an appropriate state space (smaller than the original state space) such that the lumped chain defined on this state space retains the Markov property. We propose a different perspective on lumpability where the state space is fixed and the partitioning of this state space is represented by a one-to-many probabilistic function within a two-level stochastic process. Three nested classes of lumped processes can be defined in this way as sub-classes of first-order Markov chains. These lumped processes enable parsimonious reparameterizations of Markov chains that help to reveal relevant partitions of the state space. Characterizations of the lumped processes on the original transition probability matrix are derived. Different model selection methods relying either on hypothesis testing or on penalized log-likelihood criteria are presented as well as extensions to lumped processes constructed from high-order Markov chains. The relevance of the proposed approach to lumpability is illustrated by the analysis of DNA sequences. In particular, the use of lumped processes enables to highlight differences between intronic sequences and gene untranslated region sequences.

Mathematical supply-chain modelling: Product analysis of cost and time

NASA Astrophysics Data System (ADS)

Easters, D. J.

2014-03-01

Establishing a mathematical supply-chain model is a proposition that has received attention due to its inherent benefits of evolving global supply-chain efficiencies. This paper discusses the prevailing relationships found within apparel supply-chain environments, and contemplates the complex issues indicated for constituting a mathematical model. Principal results identified within the data suggest, that the multifarious nature of global supply-chain activities require a degree of simplification in order to fully dilate the necessary factors which affect, each sub-section of the chain. Subsequently, the research findings allowed the division of supply-chain components into sub-sections, which amassed a coherent method of product development activity. Concurrently, the supply-chain model was found to allow systematic mathematical formulae analysis, of cost and time, within the multiple contexts of each subsection encountered. The paper indicates the supply-chain model structure, the mathematics, and considers how product analysis of cost and time can improve the comprehension of product lifecycle management.

Automated JPSS VIIRS GEO code change testing by using Chain Run Scripts

NASA Astrophysics Data System (ADS)

Chen, W.; Wang, W.; Zhao, Q.; Das, B.; Mikles, V. J.; Sprietzer, K.; Tsidulko, M.; Zhao, Y.; Dharmawardane, V.; Wolf, W.

2015-12-01

The Joint Polar Satellite System (JPSS) is the next generation polar-orbiting operational environmental satellite system. The first satellite in the JPSS series of satellites, J-1, is scheduled to launch in early 2017. J1 will carry similar versions of the instruments that are on board of Suomi National Polar-Orbiting Partnership (S-NPP) satellite which was launched on October 28, 2011. The center for Satellite Applications and Research Algorithm Integration Team (STAR AIT) uses the Algorithm Development Library (ADL) to run S-NPP and pre-J1 algorithms in a development and test mode. The ADL is an offline test system developed by Raytheon to mimic the operational system while enabling a development environment for plug and play algorithms. The Perl Chain Run Scripts have been developed by STAR AIT to automate the staging and processing of multiple JPSS Sensor Data Record (SDR) and Environmental Data Record (EDR) products. JPSS J1 VIIRS Day Night Band (DNB) has anomalous non-linear response at high scan angles based on prelaunch testing. The flight project has proposed multiple mitigation options through onboard aggregation, and the Option 21 has been suggested by the VIIRS SDR team as the baseline aggregation mode. VIIRS GEOlocation (GEO) code analysis results show that J1 DNB GEO product cannot be generated correctly without the software update. The modified code will support both Op21, Op21/26 and is backward compatible with SNPP. J1 GEO code change version 0 delivery package is under development for the current change request. In this presentation, we will discuss how to use the Chain Run Script to verify the code change and Lookup Tables (LUTs) update in ADL Block2.

Graph transformation method for calculating waiting times in Markov chains.

PubMed

Trygubenko, Semen A; Wales, David J

2006-06-21

We describe an exact approach for calculating transition probabilities and waiting times in finite-state discrete-time Markov processes. All the states and the rules for transitions between them must be known in advance. We can then calculate averages over a given ensemble of paths for both additive and multiplicative properties in a nonstochastic and noniterative fashion. In particular, we can calculate the mean first-passage time between arbitrary groups of stationary points for discrete path sampling databases, and hence extract phenomenological rate constants. We present a number of examples to demonstrate the efficiency and robustness of this approach.

Scaling up antiretroviral therapy in Uganda: using supply chain management to appraise health systems strengthening

PubMed Central

2011-01-01

Background Strengthened national health systems are necessary for effective and sustained expansion of antiretroviral therapy (ART). ART and its supply chain management in Uganda are largely based on parallel and externally supported efforts. The question arises whether systems are being strengthened to sustain access to ART. This study applies systems thinking to assess supply chain management, the role of external support and whether investments create the needed synergies to strengthen health systems. Methods This study uses the WHO health systems framework and examines the issues of governance, financing, information, human resources and service delivery in relation to supply chain management of medicines and the technologies. It looks at links and causal chains between supply chain management for ART and the national supply system for essential drugs. It combines data from the literature and key informant interviews with observations at health service delivery level in a study district. Results Current drug supply chain management in Uganda is characterized by parallel processes and information systems that result in poor quality and inefficiencies. Less than expected health system performance, stock outs and other shortages affect ART and primary care in general. Poor performance of supply chain management is amplified by weak conditions at all levels of the health system, including the areas of financing, governance, human resources and information. Governance issues include the lack to follow up initial policy intentions and a focus on narrow, short-term approaches. Conclusion The opportunity and need to use ART investments for an essential supply chain management and strengthened health system has not been exploited. By applying a systems perspective this work indicates the seriousness of missing system prerequisites. The findings suggest that root causes and capacities across the system have to be addressed synergistically to enable systems that can match and accommodate investments in disease-specific interventions. The multiplicity and complexity of existing challenges require a long-term and systems perspective essentially in contrast to the current short term and program-specific nature of external assistance. PMID:21806826

IgA-kappa type multiple myeloma affecting proximal and distal renal tubules.

PubMed

Minemura, K; Ichikawa, K; Itoh, N; Suzuki, N; Hara, M; Shigematsu, S; Kobayashi, H; Hiramatsu, K; Hashizume, K

2001-09-01

A 45-year-old male was admitted because of chest pain, lumbago, and bilateral ankle pain. Examination disclosed hypophosphatemic osteomalacia, acquired Fanconi syndrome, and abnormalities in distal nephron such as distal renal tubular acidosis and renal diabetes insipidus. Further exploration revealed IgA kappa multiple myeloma excreting urinary Bence Jones protein (kappa-light chain). Renal biopsy revealed thick basement membranes and elec-tron-dense crystals in proximal tubular epithelial cells. Immunofluorescent studies revealed deposition of kappa-light chain in renal tubular epithelial cells that caused the renal tubular damage. Although the osteomalacia was relieved by medical treatment, the urinary Bence Jones protein and the renal tubular defects were not improved by the chemotherapy for the myeloma. The patient died of exacerbation of multiple myeloma at 50 years of age.

Choice between Single and Multiple Reinforcers in Concurrent-Chains Schedules

ERIC Educational Resources Information Center

Mazur, James E.

2006-01-01

Pigeons responded on concurrent-chains schedules with equal variable-interval schedules as initial links. One terminal link delivered a single reinforcer after a fixed delay, and the other terminal link delivered either three or five reinforcers, each preceded by a fixed delay. Some conditions included a postreinforcer delay after the single…

Using the Polymerase Chain Reaction in an Undergraduate Laboratory to Produce "DNA Fingerprints."

ERIC Educational Resources Information Center

Phelps, Tara L.; And Others

1996-01-01

Presents a laboratory exercise that demonstrates the sensitivity of the Polymerase Chain Reaction as well as its potential application to forensic analysis during a criminal investigation. Can also be used to introduce, review, and integrate population and molecular genetics topics such as genotypes, multiple alleles, allelic and genotypic…

The Behavior Chain Interruption Strategy: A Review of Research and Discussion of Future Directions.

ERIC Educational Resources Information Center

Carter, Mark; Grunsell, Julie

2001-01-01

A review of 10 studies that utilize the behavior chain interruption strategy (BCIS) to teach communication skills to individuals with severe disabilities found that BCIS has been successfully applied to individuals across a wide range of ages and levels of disability, including learners with multiple disabilities. Generalization concerns are…

The Hypothesis that the Genetic Code Originated in Coupled Synthesis of Proteins and the Evolutionary Predecessors of Nucleic Acids in Primitive Cells

PubMed Central

Francis, Brian R.

2015-01-01

Although analysis of the genetic code has allowed explanations for its evolution to be proposed, little evidence exists in biochemistry and molecular biology to offer an explanation for the origin of the genetic code. In particular, two features of biology make the origin of the genetic code difficult to understand. First, nucleic acids are highly complicated polymers requiring numerous enzymes for biosynthesis. Secondly, proteins have a simple backbone with a set of 20 different amino acid side chains synthesized by a highly complicated ribosomal process in which mRNA sequences are read in triplets. Apparently, both nucleic acid and protein syntheses have extensive evolutionary histories. Supporting these processes is a complex metabolism and at the hub of metabolism are the carboxylic acid cycles. This paper advances the hypothesis that the earliest predecessor of the nucleic acids was a β-linked polyester made from malic acid, a highly conserved metabolite in the carboxylic acid cycles. In the β-linked polyester, the side chains are carboxylic acid groups capable of forming interstrand double hydrogen bonds. Evolution of the nucleic acids involved changes to the backbone and side chain of poly(β-d-malic acid). Conversion of the side chain carboxylic acid into a carboxamide or a longer side chain bearing a carboxamide group, allowed information polymers to form amide pairs between polyester chains. Aminoacylation of the hydroxyl groups of malic acid and its derivatives with simple amino acids such as glycine and alanine allowed coupling of polyester synthesis and protein synthesis. Use of polypeptides containing glycine and l-alanine for activation of two different monomers with either glycine or l-alanine allowed simple coded autocatalytic synthesis of polyesters and polypeptides and established the first genetic code. A primitive cell capable of supporting electron transport, thioester synthesis, reduction reactions, and synthesis of polyesters and polypeptides is proposed. The cell consists of an iron-sulfide particle enclosed by tholin, a heterogeneous organic material that is produced by Miller-Urey type experiments that simulate conditions on the early Earth. As the synthesis of nucleic acids evolved from β-linked polyesters, the singlet coding system for replication evolved into a four nucleotide/four amino acid process (AMP = aspartic acid, GMP = glycine, UMP = valine, CMP = alanine) and then into the triplet ribosomal process that permitted multiple copies of protein to be synthesized independent of replication. This hypothesis reconciles the “genetics first” and “metabolism first” approaches to the origin of life and explains why there are four bases in the genetic alphabet. PMID:25679748

U.S. Wind Energy Manufacturing and Supply Chain: A Competitiveness Analysis

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

Fullenkamp, Patrick H; Holody, Diane S

The goal of the project was to develop a greater understanding of the key factors determining wind energy component manufacturing costs and pricing on a global basis in order to enhance the competitiveness of U.S. manufacturers, and to reduce installed systems cost. Multiple stakeholders including DOE, turbine OEMs, and large component manufactures will all benefit by better understanding the factors determining domestic competitiveness in the emerging offshore and next generation land-based wind industries. Major objectives of this project were to: 1. Carry out global cost and process comparisons for 5MW jacket foundations, blades, towers, and permanent magnet generators; 2. Assessmore » U.S. manufacturers’ competitiveness and potential for cost reduction; 3. Facilitate informed decision-making on investments in U.S. manufacturing; 4. Develop an industry scorecard representing the readiness of the U.S. manufacturers’ to produce components for the next generations of wind turbines, nominally 3MW land-based and 5MW offshore; 5. Disseminate results through the GLWN Wind Supply Chain GIS Map, a free website that is the most comprehensive public database of U.S. wind energy suppliers; 6. Identify areas and develop recommendations to DOE on potential R&D areas to target for increasing domestic manufacturing competitiveness, per DOE’s Clean Energy Manufacturing Initiative (CEMI). Lists of Deliverables 1. Cost Breakdown Competitive Analyses of four product categories: tower, jacket foundation, blade, and permanent magnet (PM) generator. The cost breakdown for each component includes a complete Bill of Materials with net weights; general process steps for labor; and burden adjusted by each manufacturer for their process categories of SGA (sales general and administrative), engineering, logistics cost to a common U.S. port, and profit. 2. Value Stream Map Competitiveness Analysis: A tool that illustrates both information and material flow from the point of getting a customer order at the manufacturing plant; to the orders being forwarded by the manufacturing plant to the material suppliers; to the material being received at the manufacturing plant and processed through the system; to the final product being shipped to the Customer. 3. Competitiveness Scorecard: GLWN developed a Wind Industry Supply Chain Scorecard that reflects U.S. component manufacturers’ readiness to supply the next generation wind turbines, 3MW and 5MW, for land-based and offshore applications. 4. Wind Supply Chain Database & Map: Expand the current GLWN GIS Wind Supply Chain Map to include offshore elements. This is an on-line, free access, wind supply chain map that provides a platform for identifying active and emerging suppliers for the land-based and offshore wind industry, including turbine component manufacturers and wind farm construction service suppliers.« less

Multiple dynamic regimes in colloid-polymer dispersions: New insight using X-ray photon correlation spectroscopy

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

Srivastava, Sunita; Kishore, Suhasini; Narayanan, Suresh

We present an X-ray photon correlation spectros- copy (XPCS) study of dynamic transitions in an anisotropic colloid-polymer dispersion with multiple arrested states. The results provide insight into the mechanism for formation of repulsive glasses, attractive glasses, and networked gels of col- loids with weakly adsorbing polymer chains. In the presence of adsorbing polymer chains, we observe three distinct regimes: a state with slow dynamics consisting of finite particles and clusters, for which interparticle interactions are predominantly repulsive; a second dynamic regime occurring above the satu- ration concentration of added polymer, in which small clusters of nanoparticles form via a short-rangemore » depletion attraction; and a third regime above the overlap concentration in which dynamics of clusters are independent of polymer chain length. The observed complex dynamic state diagram is primarily gov- erned by the structural reorganization of a nanoparticle cluster and polymer chains at the nanoparticle-polymer surface and in the concentrated medium, which in turn controls the dynamics of the dispersion« less

Short-chain consensus alpha-neurotoxin: a synthetic 60-mer peptide with generic traits and enhanced immunogenic properties.

PubMed

de la Rosa, Guillermo; Corrales-García, Ligia L; Rodriguez-Ruiz, Ximena; López-Vera, Estuardo; Corzo, Gerardo

2018-07-01

The three-fingered toxin family and more precisely short-chain α-neurotoxins (also known as Type I α-neurotoxins) are crucial in defining the elapid envenomation process, but paradoxically, they are barely neutralized by current elapid snake antivenoms. This work has been focused on the primary structural identity among Type I neurotoxins in order to create a consensus short-chain α-neurotoxin with conserved characteristics. A multiple sequence alignment considering the twelve most toxic short-chain α-neurotoxins reported from the venoms of the elapid genera Acanthophis, Oxyuranus, Walterinnesia, Naja, Dendroaspis and Micrurus led us to propose a short-chain consensus α-neurotoxin, here named ScNtx. The synthetic ScNtx gene was de novo constructed and cloned into the expression vector pQE30 containing a 6His-Tag and an FXa proteolytic cleavage region. Escherichia coli Origami cells transfected with the pQE30/ScNtx vector expressed the recombinant consensus neurotoxin in a soluble form with a yield of 1.5 mg/L of culture medium. The 60-amino acid residue ScNtx contains canonical structural motifs similar to α-neurotoxins from African elapids and its LD 50 of 3.8 µg/mice is similar to the most toxic short-chain α-neurotoxins reported from elapid venoms. Furthermore, ScNtx was also able to antagonize muscular, but not neuronal, nicotinic acetylcholine receptors (nAChR). Rabbits immunized with ScNtx were able to immune-recognize short-chain α-neurotoxins within whole elapid venoms. Type I neurotoxins are difficult to isolate and purify from natural sources; therefore, the heterologous expression of molecules such ScNtx, bearing crucial motifs and key amino acids, is a step forward to create common immunogens for developing cost-effective antivenoms with a wider spectrum of efficacy, quality and strong therapeutic value.

Successful treatment of nephrotic syndrome induced by lambda light chain deposition disease using lenalidomide: A case report and review of the literature
.

PubMed

Mima, Akira; Nagahara, Dai; Tansho, Kosuke

2018-06-01

Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease (MIDD) that is characterized by the deposition of monoclonal light chains in multiple organs, including the kidney. It is a rare disorder caused by an underlying monoclonal plasma cell dyscrasia. LCDD with renal involvement causes proteinuria, which sometimes can lead to nephrotic syndrome. The monoclonal light chains are mostly in the κ form. Treatment of LCDD is the same as that for multiple myeloma (MM); however, some conventional anticancer drugs show substantial toxicity and therefore cannot be administered to older patients or those with renal impairment. An 80-year-old woman was referred to our department with severe nephrotic syndrome (13.6 g/gCr) and anemia. A renal biopsy showed mesangial proliferation and mesangial matrix expansion, and immunohistochemistry showed positive staining for λ chains along the glomerular basement membrane, but was negative for κ chains or amyloid deposition. A bone marrow biopsy revealed 64% plasma cells. Immunoglobulin G (IgG)-λ type M protein was detected, and the levels of free λ chain was significantly increased. We concluded that her nephrotic syndrome was caused by LCDD, which resulted from IgG-λ MM. The induction of a BCD (bortezomib, cyclophosphamide, and dexamethasone) treatment regimen did not lead to a hematological response or decrease in proteinuria. The administration of combination therapy of lenalidomide and prednisolone led to the successful reduction of proteinuria and hematuria. We presented a very rare case report describing the successful treatment of LCDD (λ chain)-induced nephrotic syndrome with lenalidomide.
.

High-efficiency integrated piezoelectric energy harvesting systems

NASA Astrophysics Data System (ADS)

Hande, Abhiman; Shah, Pradeep

2010-04-01

This paper describes hierarchically architectured development of an energy harvesting (EH) system that consists of micro and/or macro-scale harvesters matched to multiple components of remote wireless sensor and communication nodes. The micro-scale harvesters consist of thin-film MEMS piezoelectric cantilever arrays and power generation modules in IC-like form to allow efficient EH from vibrations. The design uses new high conversion efficiency thin-film processes combined with novel cantilever structures tuned to multiple resonant frequencies as broadband arrays. The macro-scale harvesters are used to power the collector nodes that have higher power specifications. These bulk harvesters can be integrated with efficient adaptive power management circuits that match transducer impedance and maximize power harvested from multiple scavenging sources with very low intrinsic power consumption. Texas MicroPower, Inc. is developing process based on a composition that has the highest reported energy density as compared to other commercially available bulk PZT-based sensor/actuator ceramic materials and extending it to thin-film materials and miniature conversion transducer structures. The multiform factor harvesters can be deployed for several military and commercial applications such as underground unattended sensors, sensors in oil rigs, structural health monitoring, supply chain management, and battlefield applications such as sensors on soldier apparel, equipment, and wearable electronics.

Untangling interactions: do temperature and habitat fragmentation gradients simultaneously impact biotic relationships?

PubMed Central

Lakeman-Fraser, Poppy; Ewers, Robert M.

2014-01-01

Gaining insight into the impact of anthropogenic change on ecosystems requires investigation into interdependencies between multiple drivers of ecological change and multiple biotic responses. Global environmental change drivers can act simultaneously to impact the abundance and diversity of biota, but few studies have also measured the impact across trophic levels. We firstly investigated whether climate (using temperature differences across a latitudinal gradient as a surrogate) interacts with habitat fragmentation (measured according to fragment area and distance to habitat edges) to impact a New Zealand tri-trophic food chain (plant, herbivore and natural enemy). Secondly, we examined how these interactions might differentially impact both the density and biotic processes of species at each of the three trophic levels. We found evidence to suggest that these drivers act non-additively across trophic levels. The nature of these interactions however varied: location synergistically interacted with fragmentation measures to exacerbate the detrimental effects on consumer density; and antagonistically interacted to ameliorate the impact on plant density and on the interactions between trophic levels (herbivory and parasitoid attack rate). Our findings indicate that the ecological consequences of multiple global change drivers are strongly interactive and vary according to the trophic level studied and whether density or ecological processes are investigated. PMID:24898374

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

Sun, Amy Cha-Tien; Downes, Paula Sue; Heinen, Russell

Analysis of chemical supply chains is an inherently complex task, given the dependence of these supply chains on multiple infrastructure systems (e.g., the petroleum sector, transportation, etc.). This effort requires data and information at various levels of resolution, ranging from network-level distribution systems to individual chemical reactions. Sandia National Laboratories (Sandia) has integrated its existing simulation and infrastructure analysis capabilities with chemical data models to analyze the chemical supply chains of several nationally critical chemical commodities. This paper describes how Sandia models the ethylene supply chain; that is, the supply chain for the most widely used raw material for plasticsmore » production including a description of the types of data and modeling capabilities that are required to represent the ethylene supply chain. The paper concludes with a description of Sandia's use the model to project how the supply chain would be affected by and adapt to a disruptive scenario hurricane.« less

Cross-contact chain

NASA Technical Reports Server (NTRS)

Lieneweg, Udo (Inventor)

1988-01-01

A system is provided for use with wafers that include multiple integrated circuits that include two conductive layers in contact at multiple interfaces. Contact chains are formed beside the integrated circuits, each contact chain formed of the same two layers as the circuits, in the form of conductive segments alternating between the upper and lower layers and with the ends of the segments connected in series through interfaces. A current source passes a current through the series-connected segments, by way of a pair of current tabs connected to opposite ends of the series of segments. While the current flows, voltage measurements are taken between each of a plurality of pairs of voltage tabs, the two tabs of each pair connected to opposite ends of an interface that lies along the series-connected segments. A plot of interface conductances on a normal probability chart, enables prediction of the yield of good integrated circuits from the wafer.

Cross-contact chain

NASA Technical Reports Server (NTRS)

Lieneweg, U. (Inventor)

1986-01-01

A system is provided for use with wafers that include multiple integrated circuits that include two conductive layers in contact at multiple interfaces. Contact chains are formed beside the integrated circuits, each contact chain formed of the same two layers as the circuits, in the form of conductive segments alternating between the upper and lower layers and with the ends of the segments connected in series through interfaces. A current source passes a current through the series-connected segments, by way of a pair of current tabs connected to opposite ends of the series of segments. While the current flows, voltage measurements are taken between each of a plurality of pairs of voltage tabs, the two tabs of each pair connected to opposite ends of an interface that lies along the series-connected segments. A plot of interface conductances on normal probability chart enables prediction of the yield of good integrated circuits from the wafer.

E-commerce for healthcare supply procurement.

PubMed

Arbietman, D; Lirov, E; Lirov, R; Lirov, Y

2001-01-01

The total investment of the more than fifty e-commerce startups that entered healthcare supply chain management in the past three years has surpassed $500 million. However, none of these early entrants has delivered on the initial promise of restructuring the entire supply chain, replacing the traditional intermediaries, or at least achieving substantial revenue. This article offers a new business-to-business (B2B) e-commerce solution classification paradigm and uses it to analyze the functional requirements for an effective and, efficient healthcare supply chain marketplace. The analysis exposes several fundamental B2B market complexities that prevent the early entrants from creating a solid customer base and reaching desired liquidity goals. It also identifies several technological solutions to the problems mentioned. These new technologies create a comprehensive and symmetric order-matching engine that is capable of aggregating buy orders, requesting quotes from multiple vendors simultaneously, and negotiating along multiple criteria.

Exact goodness-of-fit tests for Markov chains.

PubMed

Besag, J; Mondal, D

2013-06-01

Goodness-of-fit tests are useful in assessing whether a statistical model is consistent with available data. However, the usual χ² asymptotics often fail, either because of the paucity of the data or because a nonstandard test statistic is of interest. In this article, we describe exact goodness-of-fit tests for first- and higher order Markov chains, with particular attention given to time-reversible ones. The tests are obtained by conditioning on the sufficient statistics for the transition probabilities and are implemented by simple Monte Carlo sampling or by Markov chain Monte Carlo. They apply both to single and to multiple sequences and allow a free choice of test statistic. Three examples are given. The first concerns multiple sequences of dry and wet January days for the years 1948-1983 at Snoqualmie Falls, Washington State, and suggests that standard analysis may be misleading. The second one is for a four-state DNA sequence and lends support to the original conclusion that a second-order Markov chain provides an adequate fit to the data. The last one is six-state atomistic data arising in molecular conformational dynamics simulation of solvated alanine dipeptide and points to strong evidence against a first-order reversible Markov chain at 6 picosecond time steps. © 2013, The International Biometric Society.

Slide Set: Reproducible image analysis and batch processing with ImageJ.

PubMed

Nanes, Benjamin A

2015-11-01

Most imaging studies in the biological sciences rely on analyses that are relatively simple. However, manual repetition of analysis tasks across multiple regions in many images can complicate even the simplest analysis, making record keeping difficult, increasing the potential for error, and limiting reproducibility. While fully automated solutions are necessary for very large data sets, they are sometimes impractical for the small- and medium-sized data sets common in biology. Here we present the Slide Set plugin for ImageJ, which provides a framework for reproducible image analysis and batch processing. Slide Set organizes data into tables, associating image files with regions of interest and other relevant information. Analysis commands are automatically repeated over each image in the data set, and multiple commands can be chained together for more complex analysis tasks. All analysis parameters are saved, ensuring transparency and reproducibility. Slide Set includes a variety of built-in analysis commands and can be easily extended to automate other ImageJ plugins, reducing the manual repetition of image analysis without the set-up effort or programming expertise required for a fully automated solution.

Biosensors for Sustainable Food Engineering: Challenges and Perspectives.

PubMed

Neethirajan, Suresh; Ragavan, Vasanth; Weng, Xuan; Chand, Rohit

2018-03-12

Current food production faces tremendous challenges from growing human population, maintaining clean resources and food qualities, and protecting climate and environment. Food sustainability is mostly a cooperative effort resulting in technology development supported by both governments and enterprises. Multiple attempts have been promoted in tackling challenges and enhancing drivers in food production. Biosensors and biosensing technologies with their applications, are being widely applied to tackling top challenges in food production and its sustainability. Consequently, a growing demand in biosensing technologies exists in food sustainability. Microfluidics represents a technological system integrating multiple technologies. Nanomaterials, with its technology in biosensing, is thought to be the most promising tool in dealing with health, energy, and environmental issues closely related to world populations. The demand of point of care (POC) technologies in this area focus on rapid, simple, accurate, portable, and low-cost analytical instruments. This review provides current viewpoints from the literature on biosensing in food production, food processing, safety and security, food packaging and supply chain, food waste processing, food quality assurance, and food engineering. The current understanding of progress, solution, and future challenges, as well as the commercialization of biosensors are summarized.

Characterize kinematic rupture history of large earthquakes with Multiple Haskell sources

NASA Astrophysics Data System (ADS)

Jia, Z.; Zhan, Z.

2017-12-01

Earthquakes are often regarded as continuous rupture along a single fault, but the occurrence of complex large events involving multiple faults and dynamic triggering challenges this view. Such rupture complexities cause difficulties in existing finite fault inversion algorithms, because they rely on specific parameterizations and regularizations to obtain physically meaningful solutions. Furthermore, it is difficult to assess reliability and uncertainty of obtained rupture models. Here we develop a Multi-Haskell Source (MHS) method to estimate rupture process of large earthquakes as a series of sub-events of varying location, timing and directivity. Each sub-event is characterized by a Haskell rupture model with uniform dislocation and constant unilateral rupture velocity. This flexible yet simple source parameterization allows us to constrain first-order rupture complexity of large earthquakes robustly. Additionally, relatively few parameters in the inverse problem yields improved uncertainty analysis based on Markov chain Monte Carlo sampling in a Bayesian framework. Synthetic tests and application of MHS method on real earthquakes show that our method can capture major features of large earthquake rupture process, and provide information for more detailed rupture history analysis.

Chain Assembly and Disassembly Processes Differently Affect the Conformational Space of Ubiquitin Chains.

PubMed

Kniss, Andreas; Schuetz, Denise; Kazemi, Sina; Pluska, Lukas; Spindler, Philipp E; Rogov, Vladimir V; Husnjak, Koraljka; Dikic, Ivan; Güntert, Peter; Sommer, Thomas; Prisner, Thomas F; Dötsch, Volker

2018-02-06

Ubiquitination is the most versatile posttranslational modification. The information is encoded by linkage type as well as chain length, which are translated by ubiquitin binding domains into specific signaling events. Chain topology determines the conformational space of a ubiquitin chain and adds an additional regulatory layer to this ubiquitin code. In particular, processes that modify chain length will be affected by chain conformations as they require access to the elongation or cleavage sites. We investigated conformational distributions in the context of chain elongation and disassembly using pulsed electron-electron double resonance spectroscopy in combination with molecular modeling. Analysis of the conformational space of diubiquitin revealed conformational selection or remodeling as mechanisms for chain recognition during elongation or hydrolysis, respectively. Chain elongation to tetraubiquitin increases the sampled conformational space, suggesting that a high intrinsic flexibility of K48-linked chains may contribute to efficient proteasomal degradation. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Overexpression of four fatty acid synthase genes elevated the efficiency of long-chain polyunsaturated fatty acids biosynthesis in mammalian cells].

PubMed

Zhu, Guiming; Saleh, Abdulmomen Ali Mohammed; Bahwal, Said Ahmed; Wang, Kunfu; Wang, Mingfu; Wang, Didi; Ge, Tangdong; Sun, Jie

2014-09-01

Three long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (ARA, 20:4n-6), are the most biologically active polyunsaturated fatty acids in the body. They are important in developing and maintaining the brain function, and in preventing and treating many diseases such as cardiovascular disease, inflammation and cancer. Although mammals can biosynthesize these long-chain polyunsaturated fatty acids, the efficiency is very low and dietary intake is needed to meet the requirement. In this study, a multiple-genes expression vector carrying mammalian A6/A5 fatty acid desaturases and multiple-genes expression vector carrying mammalian Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases coding genes was used to transfect HEK293T cells, then the overexpression of the target genes was detected. GC-MS analysis shows that the biosynthesis efficiency and level of DHA, EPA and ARA were significantly increased in cells transfected with the multiple-genes expression vector. Particularly, DHA level in these cells was 2.5 times higher than in the control cells. This study indicates mammal possess a certain mechanism for suppression of high level of biosynthesis of long chain polyunsaturated fatty acids, and the overexpression of Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases broke this suppression mechanism so that the level of DHA, EPA and ARA was significantly increased. This study also provides a basis for potential applications of this gene construct in transgenic animal to produce high level of these long-chain polyunsaturated fatty acid.

A framework for the computer-aided planning and optimisation of manufacturing processes for components with functional graded properties

NASA Astrophysics Data System (ADS)

Biermann, D.; Gausemeier, J.; Heim, H.-P.; Hess, S.; Petersen, M.; Ries, A.; Wagner, T.

2014-05-01

In this contribution a framework for the computer-aided planning and optimisation of functional graded components is presented. The framework is divided into three modules - the "Component Description", the "Expert System" for the synthetisation of several process chains and the "Modelling and Process Chain Optimisation". The Component Description module enhances a standard computer-aided design (CAD) model by a voxel-based representation of the graded properties. The Expert System synthesises process steps stored in the knowledge base to generate several alternative process chains. Each process chain is capable of producing components according to the enhanced CAD model and usually consists of a sequence of heating-, cooling-, and forming processes. The dependencies between the component and the applied manufacturing processes as well as between the processes themselves need to be considered. The Expert System utilises an ontology for that purpose. The ontology represents all dependencies in a structured way and connects the information of the knowledge base via relations. The third module performs the evaluation of the generated process chains. To accomplish this, the parameters of each process are optimised with respect to the component specification, whereby the result of the best parameterisation is used as representative value. Finally, the process chain which is capable of manufacturing a functionally graded component in an optimal way regarding to the property distributions of the component description is presented by means of a dedicated specification technique.

Processing-Dependent and Clonal Contamination Patterns of Listeria monocytogenes in the Cured Ham Food Chain Revealed by Genetic Analysis.

PubMed

Morganti, Marina; Scaltriti, Erika; Cozzolino, Paolo; Bolzoni, Luca; Casadei, Gabriele; Pierantoni, Marco; Foni, Emanuela; Pongolini, Stefano

2016-02-01

The quantitative and qualitative patterns of environmental contamination by Listeria monocytogenes were investigated in the production chain of dry-cured Parma ham. Standard arrays of surfaces were sampled in processing facilities during a single visit per plant in the three compartments of the food chain, i.e., ham production (19 plants) and postproduction, which was divided into deboning (43 plants) and slicing (25 plants) steps. The numbers of sampled surfaces were 384 in ham production, with 25 positive for L. monocytogenes, and 1,084 in postproduction, with 83 positives. Statistical analysis of the prevalence of contaminated surfaces showed that in ham production, contamination was higher at the beginning of processing and declined significantly toward the end, while in postproduction, prevalence rose toward the end of processing. Prevalence was higher in the deboning facilities than in slicing facilities and was dependent on the type of surface (floor/drainage > clothing > equipment). The qualitative pattern of contamination was investigated through an analysis of the survey isolates and a set of isolates derived from routine monitoring, including longitudinal isolations. Pulsed-field gel electrophoresis (PFGE) and whole-genome single-nucleotide polymorphism (SNP) analysis revealed a remarkable clonality of L. monocytogenes within plants, with the detection of 16 plant-specific clones out of 17 establishments with multiple isolates. Repeated detections of clonal isolates >6 months apart were also observed. Six was the maximum number of between-isolate differences in core SNPs observed within these clones. Based on the same six-SNP threshold, three clusters of clonal isolates, shared by six establishments, were also identified. The spread of L. monocytogenes within and between plants, as indicated by its clonal behavior, is a matter of concern for the hygienic management of establishments. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Growing up Radical: Investigation of Benzyl-Like Radicals with Increasing Chain Lengths

NASA Astrophysics Data System (ADS)

Korn, Joseph A.; Jawad, Khadija M.; Hewett, Daniel M.; Zwier, Timothy S.

2015-06-01

Combustion processes involve complex chemistry including pathways leading to polyaromatic hydrocarbons (PAHs) from small molecule precursors. Resonance stabilized radicals (RSRs) likely play an important role in the pathways to PAHs due to their unusual stability. Benzyl radical is a prototypical RSR that is stabilized by conjugation with the phenyl ring. Earlier work on α-methyl benzyl radical showed perturbations to the spectroscopy due to a hindered methyl rotor. If the alkyl chain is lengthened then multiple conformations become possible. This talk will discuss the jet-cooled spectroscopy of α-ethyl benzyl radical and α-propyl benzyl radical produced from the discharge of 1-phenyl propanol and 1-phenyl butanol respectively. Electronic spectra were obtained via resonant two-photon ionization, and IR spectra were obtained by resonant ion-dip infrared spectroscopy. Kidwell, N. M.; Reilly, N. J.; Nebgen, B.; Mehta-Hurt, D. N.; Hoehn, R. D.; Kokkin, D. L.; McCarthy, M. C.; Slipchenko, L. V.; Zwier, T. S. The Journal of Physical Chemistry A 2013, 117, 13465.

The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism

PubMed Central

den Besten, Gijs; van Eunen, Karen; Groen, Albert K.; Venema, Koen; Reijngoud, Dirk-Jan; Bakker, Barbara M.

2013-01-01

Short-chain fatty acids (SCFAs), the end products of fermentation of dietary fibers by the anaerobic intestinal microbiota, have been shown to exert multiple beneficial effects on mammalian energy metabolism. The mechanisms underlying these effects are the subject of intensive research and encompass the complex interplay between diet, gut microbiota, and host energy metabolism. This review summarizes the role of SCFAs in host energy metabolism, starting from the production by the gut microbiota to the uptake by the host and ending with the effects on host metabolism. There are interesting leads on the underlying molecular mechanisms, but there are also many apparently contradictory results. A coherent understanding of the multilevel network in which SCFAs exert their effects is hampered by the lack of quantitative data on actual fluxes of SCFAs and metabolic processes regulated by SCFAs. In this review we address questions that, when answered, will bring us a great step forward in elucidating the role of SCFAs in mammalian energy metabolism. PMID:23821742

Designing Hysteresis with Dipolar Chains

NASA Astrophysics Data System (ADS)

Concha, Andrés; Aguayo, David; Mellado, Paula

2018-04-01

Materials that have hysteretic response to an external field are essential in modern information storage and processing technologies. A myriad of magnetization curves of several natural and artificial materials have previously been measured and each has found a particular mechanism that accounts for it. However, a phenomenological model that captures all the hysteresis loops and at the same time provides a simple way to design the magnetic response of a material while remaining minimal is missing. Here, we propose and experimentally demonstrate an elementary method to engineer hysteresis loops in metamaterials built out of dipolar chains. We show that by tuning the interactions of the system and its geometry we can shape the hysteresis loop which allows for the design of the softness of a magnetic material at will. Additionally, this mechanism allows for the control of the number of loops aimed to realize multiple-valued logic technologies. Our findings pave the way for the rational design of hysteretical responses in a variety of physical systems such as dipolar cold atoms, ferroelectrics, or artificial magnetic lattices, among others.

Designing Hysteresis with Dipolar Chains.

PubMed

Concha, Andrés; Aguayo, David; Mellado, Paula

2018-04-13

Materials that have hysteretic response to an external field are essential in modern information storage and processing technologies. A myriad of magnetization curves of several natural and artificial materials have previously been measured and each has found a particular mechanism that accounts for it. However, a phenomenological model that captures all the hysteresis loops and at the same time provides a simple way to design the magnetic response of a material while remaining minimal is missing. Here, we propose and experimentally demonstrate an elementary method to engineer hysteresis loops in metamaterials built out of dipolar chains. We show that by tuning the interactions of the system and its geometry we can shape the hysteresis loop which allows for the design of the softness of a magnetic material at will. Additionally, this mechanism allows for the control of the number of loops aimed to realize multiple-valued logic technologies. Our findings pave the way for the rational design of hysteretical responses in a variety of physical systems such as dipolar cold atoms, ferroelectrics, or artificial magnetic lattices, among others.

Integrated Immunomodulatory Mechanisms through which Long-Chain n-3 Polyunsaturated Fatty Acids Attenuate Obese Adipose Tissue Dysfunction

PubMed Central

Liddle, Danyelle M.; Wellings, Hannah R.; Power, Krista A.; Robinson, Lindsay E.; Monk, Jennifer M.

2017-01-01

Obesity is a global health concern with rising prevalence that increases the risk of developing other chronic diseases. A causal link connecting overnutrition, the development of obesity and obesity-associated co-morbidities is visceral adipose tissue (AT) dysfunction, characterized by changes in the cellularity of various immune cell populations, altered production of inflammatory adipokines that sustain a chronic state of low-grade inflammation and, ultimately, dysregulated AT metabolic function. Therefore, dietary intervention strategies aimed to halt the progression of obese AT dysfunction through any of the aforementioned processes represent an important active area of research. In this connection, fish oil-derived dietary long-chain n-3 polyunsaturated fatty acids (PUFA) in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to attenuate obese AT dysfunction through multiple mechanisms, ultimately affecting AT immune cellularity and function, adipokine production, and metabolic signaling pathways, all of which will be discussed herein. PMID:29186929

Hot working behavior of selective laser melted and laser metal deposited Inconel 718

NASA Astrophysics Data System (ADS)

Bambach, Markus; Sizova, Irina

2018-05-01

The production of Nickel-based high-temperature components is of great importance for the transport and energy sector. Forging of high-temperature alloys often requires expensive dies, multiple forming steps and leads to forged parts with tolerances that require machining to create the final shape and a large amount of scrap. Additive manufacturing offers the possibility to print the desired shapes directly as net-shape components, requiring only little additional effort in machining. Especially for high-temperature alloys carrying a large amount of energy per unit mass, additive manufacturing could be more energy-efficient than forging if the energy contained in the machining scrap exceeds the energy needed for powder production and laser processing. However, the microstructure and performance of 3d-printed parts will not reach the level of forged material unless further expensive processes such as hot-isostatic pressing are used. Using the design freedom and possibilities to locally engineer material, additive manufacturing could be combined with forging operations to novel process chains, offering the possibility to reduce the number of forging steps and to create near-net shape forgings with desired local properties. Some innovative process chains combining additive manufacturing and forging have been patented recently, but almost no scientific knowledge on the workability of 3D printed preforms exists. The present study investigates the flow stress and microstructure evolution during hot working of pre-forms produced by laser powder deposition and selective laser melting (Figure 1) and puts forward a model for the flow stress.

The ITSG-Grace2014 Gravity Field Model

NASA Astrophysics Data System (ADS)

Kvas, Andreas; Mayer-Gürr, Torsten; Zehenter, Norbert; Klinger, Beate

2015-04-01

The ITSG-Grace2014 GRACE-only gravity field model consists of a high resolution unconstrained static model (up to degree 200) with trend and annual signal, monthly unconstrained solutions with different spatial resolutions as well as daily snapshots derived by using a Kalman smoother. Apart from the estimated spherical harmonic coefficients, full variance-covariance matrices for the monthly solutions and the static gravity field component are provided. Compared to the previous release, multiple improvements in the processing chain are implemented: updated background models, better ionospheric modeling for GPS observations, an improved satellite attitude by combination of star camera and angular accelerations, estimation of K-band antenna center variations within the gravity field recovery process as well as error covariance function determination. Furthermore, daily gravity field variations have been modeled in the adjustment process to reduce errors caused by temporal leakage. This combined estimation of daily gravity variations field variations together with the static gravity field component represents a computational challenge due to the significantly increased parameter count. The modeling of daily variations up to a spherical harmonic degree of 40 for the whole GRACE observation period results in a system of linear equations with over 6 million unknown gravity field parameters. A least squares adjustment of this size is not solvable in a sensible time frame, therefore measures to reduce the problem size have to be taken. The ITSG-Grace2014 release is presented and selected parts of the processing chain and their effect on the estimated gravity field solutions are discussed.

Knowledge management system for risk mitigation in supply chain uncertainty: case from automotive battery supply chain

NASA Astrophysics Data System (ADS)

Marie, I. A.; Sugiarto, D.; Surjasa, D.; Witonohadi, A.

2018-01-01

Automotive battery supply chain include battery manufacturer, sulphuric acid suppliers, polypropylene suppliers, lead suppliers, transportation service providers, warehouses, retailers and even customers. Due to the increasingly dynamic condition of the environment, supply chain actors were required to improve their ability to overcome various uncertainty issues in the environment. This paper aims to describe the process of designing a knowledge management system for risk mitigation in supply chain uncertainty. The design methodology began with the identification of the knowledge needed to solve the problems associated with uncertainty and analysis of system requirements. The design of the knowledge management system was described in the form of a data flow diagram. The results of the study indicated that key knowledge area that needs to be managed were the knowledge to maintain the stability of process in sulphuric acid process and knowledge to overcome the wastes in battery manufacturing process. The system was expected to be a media acquisition, dissemination and storage of knowledge associated with the uncertainty in the battery supply chain and increase the supply chain performance.

Analysis of reduced monoclonal antibodies using size exclusion chromatography coupled with mass spectrometry

NASA Astrophysics Data System (ADS)

Liu, Hongcheng; Gaza-Bulseco, Georgeen; Chumsae, Chris

2009-12-01

Size-exclusion chromatography (SEC) has been widely used to detect antibody aggregates, monomer, and fragments. SEC coupled to mass spectrometry has been reported to measure the molecular weights of antibody; antibody conjugates, and antibody light chain and heavy chain. In this study, separation of antibody light chain and heavy chain by SEC and direct coupling to a mass spectrometer was further studied. It was determined that employing mobile phases containing acetonitrile, trifluoroacetic acid, and formic acid allowed the separation of antibody light chain and heavy chain after reduction by SEC. In addition, this mobile phase allowed the coupling of SEC to a mass spectrometer to obtain a direct molecular weight measurement. The application of the SEC-MS method was demonstrated by the separation of the light chain and the heavy chain of multiple recombinant monoclonal antibodies. In addition, separation of a thioether linked light chain and heavy chain from the free light chain and the free heavy chain of a recombinant monoclonal antibody after reduction was also achieved. This optimized method provided a separation of antibody light chain and heavy chain based on size and allowed a direct measurement of molecular weights by mass spectrometry. In addition, this method may help to identify peaks eluting from SEC column directly.

Surface Treatment on Physical Properties and Biocompatibility of Orthodontic Power Chains

PubMed Central

Cheng, H. C.; Chen, M. S.; Peng, B. Y.; Lin, W. T.; Wang, Y. H.

2017-01-01

The conventional orthodontic power chain, often composed of polymer materials, has drawbacks such as a reduction of elasticity owing to water absorption as well as surface discoloration and staining resulting from food or beverages consumed by the patient. The goal of this study was to develop a surface treatment (nanoimprinting) for orthodontic power chains and to alleviate their shortcomings. A concave template (anodic alumina) was manufactured by anodization process using pure aluminum substrate by employing the nanoimprinting process. Convex nanopillars were fabricated on the surface of orthodontic power chains, resulting in surface treatment. Distinct parameters of the nanoimprinting process (e.g., imprinting temperature, imprinting pressure, imprinting time, and demolding temperature) were used to fabricate nanopillars on the surface of orthodontic power chains. The results of this study showed that the contact angle of the power chains became larger after surface treatment. In addition, the power chains changed from hydrophilic to hydrophobic. The power chain before surface treatment without water absorption had a water absorption rate of approximately 4%, whereas a modified chain had a water absorption rate of approximately 2%–4%. Furthermore, the color adhesion of the orthodontic power chains after surface modification was less than that before surface modification. PMID:28540299

An analytical derivation of MC-SCF vibrational wave functions for the quantum dynamical simulation of multiple proton transfer reactions: Initial application to protonated water chains

NASA Astrophysics Data System (ADS)

Drukker, Karen; Hammes-Schiffer, Sharon

1997-07-01

This paper presents an analytical derivation of a multiconfigurational self-consistent-field (MC-SCF) solution of the time-independent Schrödinger equation for nuclear motion (i.e. vibrational modes). This variational MC-SCF method is designed for the mixed quantum/classical molecular dynamics simulation of multiple proton transfer reactions, where the transferring protons are treated quantum mechanically while the remaining degrees of freedom are treated classically. This paper presents a proof that the Hellmann-Feynman forces on the classical degrees of freedom are identical to the exact forces (i.e. the Pulay corrections vanish) when this MC-SCF method is used with an appropriate choice of basis functions. This new MC-SCF method is applied to multiple proton transfer in a protonated chain of three hydrogen-bonded water molecules. The ground state and the first three excited state energies and the ground state forces agree well with full configuration interaction calculations. Sample trajectories are obtained using adiabatic molecular dynamics methods, and nonadiabatic effects are found to be insignificant for these sample trajectories. The accuracy of the excited states will enable this MC-SCF method to be used in conjunction with nonadiabatic molecular dynamics methods. This application differs from previous work in that it is a real-time quantum dynamical nonequilibrium simulation of multiple proton transfer in a chain of water molecules.

CERES AuTomAted job Loading SYSTem (CATALYST): An automated workflow manager for satellite data production

NASA Astrophysics Data System (ADS)

Gleason, J. L.; Hillyer, T. N.; Wilkins, J.

2012-12-01

The CERES Science Team integrates data from 5 CERES instruments onboard the Terra, Aqua and NPP missions. The processing chain fuses CERES observations with data from 19 other unique sources. The addition of CERES Flight Model 5 (FM5) onboard NPP, coupled with ground processing system upgrades further emphasizes the need for an automated job-submission utility to manage multiple processing streams concurrently. The operator-driven, legacy-processing approach relied on manually staging data from magnetic tape to limited spinning disk attached to a shared memory architecture system. The migration of CERES production code to a distributed, cluster computing environment with approximately one petabyte of spinning disk containing all precursor input data products facilitates the development of a CERES-specific, automated workflow manager. In the cluster environment, I/O is the primary system resource in contention across jobs. Therefore, system load can be maximized with a throttling workload manager. This poster discusses a Java and Perl implementation of an automated job management tool tailored for CERES processing.

Dynamical modelling of coordinated multiple robot systems

NASA Technical Reports Server (NTRS)

Hayati, Samad

1987-01-01

The state of the art in the modeling of the dynamics of coordinated multiple robot manipulators is summarized and various problems related to this subject are discussed. It is recognized that dynamics modeling is a component used in the design of controllers for multiple cooperating robots. As such, the discussion addresses some problems related to the control of multiple robots. The techniques used to date in the modeling of closed kinematic chains are summarized. Various efforts made to date for the control of coordinated multiple manipulators is summarized.

Complex dynamics in the Leslie-Gower type of the food chain system with multiple delays

NASA Astrophysics Data System (ADS)

Guo, Lei; Song, Zi-Gen; Xu, Jian

2014-08-01

In this paper, we present a Leslie-Gower type of food chain system composed of three species, which are resource, consumer, and predator, respectively. The digestion time delays corresponding to consumer-eat-resource and predator-eat-consumer are introduced for more realistic consideration. It is called the resource digestion delay (RDD) and consumer digestion delay (CDD) for simplicity. Analyzing the corresponding characteristic equation, the stabilities of the boundary and interior equilibrium points are studied. The food chain system exhibits the species coexistence for the small values of digestion delays. Large RDD/CDD may destabilize the species coexistence and induce the system dynamic into recurrent bloom or system collapse. Further, the present of multiple delays can control species population into the stable coexistence. To investigate the effect of time delays on the recurrent bloom of species population, the Hopf bifurcation and periodic solution are investigated in detail in terms of the central manifold reduction and normal form method. Finally, numerical simulations are performed to display some complex dynamics, which include multiple periodic solution and chaos motion for the different values of system parameters. The system dynamic behavior evolves into the chaos motion by employing the period-doubling bifurcation.

On intra-supply chain system with an improved distribution plan, multiple sales locations and quality assurance.

PubMed

Chiu, Singa Wang; Huang, Chao-Chih; Chiang, Kuo-Wei; Wu, Mei-Fang

2015-01-01

Transnational companies, operating in extremely competitive global markets, always seek to lower different operating costs, such as inventory holding costs in their intra- supply chain system. This paper incorporates a cost reducing product distribution policy into an intra-supply chain system with multiple sales locations and quality assurance studied by [Chiu et al., Expert Syst Appl, 40:2669-2676, (2013)]. Under the proposed cost reducing distribution policy, an added initial delivery of end items is distributed to multiple sales locations to meet their demand during the production unit's uptime and rework time. After rework when the remaining production lot goes through quality assurance, n fixed quantity installments of finished items are then transported to sales locations at a fixed time interval. Mathematical modeling and optimization techniques are used to derive closed-form optimal operating policies for the proposed system. Furthermore, the study demonstrates significant savings in stock holding costs for both the production unit and sales locations. Alternative of outsourcing product delivery task to an external distributor is analyzed to assist managerial decision making in potential outsourcing issues in order to facilitate further reduction in operating costs.

Gross-Motor Skill Acquisition by Preschool Dance Students under Self-Instruction Procedures

ERIC Educational Resources Information Center

Vintere, Parsla; Hemmes, Nancy S.; Brown, Bruce L.; Poulson, Claire L.

2004-01-01

The effects of two training procedures -- (a) modeling and praise and (b) self-instruction, modeling, and praise -- on complex gross-motor chain acquisition for preschool dance class students were evaluated. Six girls participated in the study. A multiple baseline design across six gross-motor chains with a secondary group comparison for treatment…

Multiple spatially localized dynamical states in friction-excited oscillator chains

NASA Astrophysics Data System (ADS)

Papangelo, A.; Hoffmann, N.; Grolet, A.; Stender, M.; Ciavarella, M.

2018-03-01

Friction-induced vibrations are known to affect many engineering applications. Here, we study a chain of friction-excited oscillators with nearest neighbor elastic coupling. The excitation is provided by a moving belt which moves at a certain velocity vd while friction is modelled with an exponentially decaying friction law. It is shown that in a certain range of driving velocities, multiple stable spatially localized solutions exist whose dynamical behavior (i.e. regular or irregular) depends on the number of oscillators involved in the vibration. The classical non-repeatability of friction-induced vibration problems can be interpreted in light of those multiple stable dynamical states. These states are found within a "snaking-like" bifurcation pattern. Contrary to the classical Anderson localization phenomenon, here the underlying linear system is perfectly homogeneous and localization is solely triggered by the friction nonlinearity.

Rare Presentation of Primary Extramedullary Plasmacytoma as Lip Lesion.

PubMed

Him, Mali; Meier, Maggie; Mehta, Vikas

2017-01-01

Malignant plasma cell proliferation can be presented as part of disseminated disease of multiple myeloma, as solitary plasmacytoma of bone, or in soft tissue as extramedullary plasmacytoma. Extramedullary plasmacytomas represented approximately 3% of all plasma cell proliferation. Approximately 80% of extramedullary plasmacytomas occur in the head and neck region while the other 4% occur in the skin and to a lesser extent in the lip. In this paper, we report a rare case of primary cutaneous plasmacytoma involving the lip in a 65-year-old male. The patient presented with a nonhealing lower lip sore for the past 3 years. Upon further workup, there was no evidence of multiple myeloma or light chain disease. The patient was treated with radiation therapy and his last follow-up revealed no evidence of multiple myeloma or light chain disease.

Rare Presentation of Primary Extramedullary Plasmacytoma as Lip Lesion

PubMed Central

Meier, Maggie; Mehta, Vikas

2017-01-01

Malignant plasma cell proliferation can be presented as part of disseminated disease of multiple myeloma, as solitary plasmacytoma of bone, or in soft tissue as extramedullary plasmacytoma. Extramedullary plasmacytomas represented approximately 3% of all plasma cell proliferation. Approximately 80% of extramedullary plasmacytomas occur in the head and neck region while the other 4% occur in the skin and to a lesser extent in the lip. In this paper, we report a rare case of primary cutaneous plasmacytoma involving the lip in a 65-year-old male. The patient presented with a nonhealing lower lip sore for the past 3 years. Upon further workup, there was no evidence of multiple myeloma or light chain disease. The patient was treated with radiation therapy and his last follow-up revealed no evidence of multiple myeloma or light chain disease. PMID:28409043

Competence-Based Approach in Value Chain Processes

NASA Astrophysics Data System (ADS)

Azevedo, Rodrigo Cambiaghi; D'Amours, Sophie; Rönnqvist, Mikael

There is a gap between competence theory and value chain processes frameworks. While individually considered as core elements in contemporary management thinking, the integration of the two concepts is still lacking. We claim that this integration would allow for the development of more robust business models by structuring value chain activities around aspects such as capabilities and skills, as well as individual and organizational knowledge. In this context, the objective of this article is to reduce this gap and consequently open a field for further improvements of value chain processes frameworks.

Multiplexed resequencing analysis to identify rare variants in pooled DNA with barcode indexing using next-generation sequencer.

PubMed

Mitsui, Jun; Fukuda, Yoko; Azuma, Kyo; Tozaki, Hirokazu; Ishiura, Hiroyuki; Takahashi, Yuji; Goto, Jun; Tsuji, Shoji

2010-07-01

We have recently found that multiple rare variants of the glucocerebrosidase gene (GBA) confer a robust risk for Parkinson disease, supporting the 'common disease-multiple rare variants' hypothesis. To develop an efficient method of identifying rare variants in a large number of samples, we applied multiplexed resequencing using a next-generation sequencer to identification of rare variants of GBA. Sixteen sets of pooled DNAs from six pooled DNA samples were prepared. Each set of pooled DNAs was subjected to polymerase chain reaction to amplify the target gene (GBA) covering 6.5 kb, pooled into one tube with barcode indexing, and then subjected to extensive sequence analysis using the SOLiD System. Individual samples were also subjected to direct nucleotide sequence analysis. With the optimization of data processing, we were able to extract all the variants from 96 samples with acceptable rates of false-positive single-nucleotide variants.

Multivariate longitudinal data analysis with mixed effects hidden Markov models.

PubMed

Raffa, Jesse D; Dubin, Joel A

2015-09-01

Multiple longitudinal responses are often collected as a means to capture relevant features of the true outcome of interest, which is often hidden and not directly measurable. We outline an approach which models these multivariate longitudinal responses as generated from a hidden disease process. We propose a class of models which uses a hidden Markov model with separate but correlated random effects between multiple longitudinal responses. This approach was motivated by a smoking cessation clinical trial, where a bivariate longitudinal response involving both a continuous and a binomial response was collected for each participant to monitor smoking behavior. A Bayesian method using Markov chain Monte Carlo is used. Comparison of separate univariate response models to the bivariate response models was undertaken. Our methods are demonstrated on the smoking cessation clinical trial dataset, and properties of our approach are examined through extensive simulation studies. © 2015, The International Biometric Society.

On buffer overflow duration in a finite-capacity queueing system with multiple vacation policy

NASA Astrophysics Data System (ADS)

Kempa, Wojciech M.

2017-12-01

A finite-buffer queueing system with Poisson arrivals and generally distributed processing times, operating under multiple vacation policy, is considered. Each time when the system becomes empty, the service station takes successive independent and identically distributed vacation periods, until, at the completion epoch of one of them, at least one job waiting for service is detected in the buffer. Applying analytical approach based on the idea of embedded Markov chain, integral equations and linear algebra, the compact-form representation for the cumulative distribution function (CDF for short) of the first buffer overflow duration is found. Hence, the formula for the CDF of next such periods is obtained. Moreover, probability distributions of the number of job losses in successive buffer overflow periods are found. The considered queueing system can be efficienly applied in modelling energy saving mechanisms in wireless network communication.

Novel strategies to construct complex synthetic vectors to produce DNA molecular weight standards.

PubMed

Chen, Zhe; Wu, Jianbing; Li, Xiaojuan; Ye, Chunjiang; Wenxing, He

2009-05-01

DNA molecular weight standards (DNA markers, nucleic acid ladders) are commonly used in molecular biology laboratories as references to estimate the size of various DNA samples in electrophoresis process. One method of DNA marker production is digestion of synthetic vectors harboring multiple DNA fragments of known sizes by restriction enzymes. In this article, we described three novel strategies-sequential DNA fragment ligation, screening of ligation products by polymerase chain reaction (PCR) with end primers, and "small fragment accumulation"-for constructing complex synthetic vectors and minimizing the mass differences between DNA fragments produced from restrictive digestion of synthetic vectors. The strategy could be applied to construct various complex synthetic vectors to produce any type of low-range DNA markers, usually available commercially. In addition, the strategy is useful for single-step ligation of multiple DNA fragments for construction of complex synthetic vectors and other applications in molecular biology field.

AN OPTIMAL MAINTENANCE MANAGEMENT MODEL FOR AIRPORT CONCRETE PAVEMENT

NASA Astrophysics Data System (ADS)

Shimomura, Taizo; Fujimori, Yuji; Kaito, Kiyoyuki; Obama, Kengo; Kobayashi, Kiyoshi

In this paper, an optimal management model is formulated for the performance-based rehabilitation/maintenance contract for airport concrete pavement, whereby two types of life cycle cost risks, i.e., ground consolidation risk and concrete depreciation risk, are explicitly considered. The non-homogenous Markov chain model is formulated to represent the deterioration processes of concrete pavement which are conditional upon the ground consolidation processes. The optimal non-homogenous Markov decision model with multiple types of risk is presented to design the optimal rehabilitation/maintenance plans. And the methodology to revise the optimal rehabilitation/maintenance plans based upon the monitoring data by the Bayesian up-to-dating rules. The validity of the methodology presented in this paper is examined based upon the case studies carried out for the H airport.

Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting

PubMed Central

Kušnierová, Pavlína; Švagera, Zdeněk; Všianský, František; Byrtusová, Monika; Hradílek, Pavel; Kurková, Barbora; Zapletalová, Olga; Bartoš, Vladimír

2016-01-01

Objectives We aimed to compare various methods for free light chain (fLC) quantitation in cerebrospinal fluid (CSF) and serum and to determine whether quantitative CSF measurements could reliably predict intrathecal fLC synthesis. In addition, we wished to determine the relationship between free kappa and free lambda light chain concentrations in CSF and serum in various disease groups. Methods We analysed 166 paired CSF and serum samples by at least one of the following methods: turbidimetry (Freelite™, SPAPLUS), nephelometry (N Latex FLC™, BN ProSpec), and two different (commercially available and in-house developed) sandwich ELISAs. The results were compared with oligoclonal fLC detected by affinity-mediated immunoblotting after isoelectric focusing. Results Although the correlations between quantitative methods were good, both proportional and systematic differences were discerned. However, no major differences were observed in the prediction of positive oligoclonal fLC test. Surprisingly, CSF free kappa/free lambda light chain ratios were lower than those in serum in about 75% of samples with negative oligoclonal fLC test. In about a half of patients with multiple sclerosis and clinically isolated syndrome, profoundly increased free kappa/free lambda light chain ratios were found in the CSF. Conclusions Our results show that using appropriate method-specific cut-offs, different methods of CSF fLC quantitation can be used for the prediction of intrathecal fLC synthesis. The reason for unexpectedly low free kappa/free lambda light chain ratios in normal CSFs remains to be elucidated. Whereas CSF free kappa light chain concentration is increased in most patients with multiple sclerosis and clinically isolated syndrome, CSF free lambda light chain values show large interindividual variability in these patients and should be investigated further for possible immunopathological and prognostic significance. PMID:27846293

Molecular design of boronic acid-functionalized squarylium cyanine dyes for multiple discriminant analysis of sialic acid in biological samples: selectivity toward monosaccharides controlled by different alkyl side chain lengths.

PubMed

Ouchi, Kazuki; Colyer, Christa L; Sebaiy, Mahmoud; Zhou, Jin; Maeda, Takeshi; Nakazumi, Hiroyuki; Shibukawa, Masami; Saito, Shingo

2015-02-03

We designed a new series of boronic acid-functionalized squarylium cyanine dyes (SQ-BA) with different lengths of alkyl chain residues, suitable for multiple discriminant analysis (MDA) of sialic acid (Neu5Ac) in biological samples. The SQ-BA dyes form aggregates based on hydrophobic interactions, which result in quenched fluorescence in aqueous solutions. When the boronic acid binds with saccharides, the fluorescence intensity increases as a result of dissociation to the emissive monomeric complex. We inferred that different dye aggregate structures (H-aggregates and J-aggregates) were induced depending on the alkyl chain length, so that monosaccharides would be recognized in different ways (especially, multipoint interaction with J-aggregates). A distinctive emission enhancement of SQ-BA dyes with shorter-alkyl-chains in the presence of Neu5Ac was observed (2.4-fold fluorescence enhancement; with formation constant 10(1.7) M(-1)), with no such enhancement for SQ-BA dyes with longer-alkyl-chain. In addition, various enhancement factors for other monosaccharides were observed depending on the alkyl chain length. Detailed thermodynamic and NMR studies of the SQ-BA complexes revealed the unique recognition mechanism: the dye aggregate with a shorter-alkyl-chain causes the slipped parallel structure and forms a stable 2:1 complex with Neu5Ac, as distinct from longer-alkyl-chain dyes, which form a 1:1 monomeric complex. MDA using the four SQ-BA dyes was performed for human urine samples, resulting in the successful discrimination between normal and abnormal Neu5Ac levels characteristic of disease. Thus, we successfully controlled various responses to similar monosaccharides with a novel approach that chemically modified not the boronic acid moiety itself but the length of the alkyl chain residue attached to the dye in order to generate specificity.

Time-based analysis of the apheresis platelet supply chain in England.

PubMed

Wilding, R; Cotton, S; Dobbin, J; Chapman, J; Yates, N

2011-10-01

During 2009/2010 loss of platelets within NHS Blood and Transplant (NHSBT) due to time expiry was 9.3%. Hospitals remain reluctant to hold stocks of platelets due to the poor shelf life at issue. The purpose of this study was to identify areas for time compression in the apheresis platelet supply chain to extend the shelf life available for hospitals and reduce wastage in NHSBT. This was done within the context of NHSBT reconfiguring their supply chain and moving towards a consolidated and centralised approach. Time based process mapping was applied to identify value and non-value adding time in two manufacturing models. A large amount of the non-value adding time in the apheresis platelet supply chain is due to transportation and waiting for the next process in the manufacturing process to take place. Time based process mapping provides an effective 'lens' for supply chain professionals to identify opportunities for improvement in the platelet supply chain. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

Creating Shared Mental Models: The Support of Visual Language

NASA Astrophysics Data System (ADS)

Landman, Renske B.; van den Broek, Egon L.; Gieskes, José F. B.

Cooperative design involves multiple stakeholders that often hold different ideas of the problem, the ways to solve it, and to its solutions (i.e., mental models; MM). These differences can result in miscommunication, misunderstanding, slower decision making processes, and less chance on cooperative decisions. In order to facilitate the creation of a shared mental model (sMM), visual languages (VL) are often used. However, little scientific foundation is behind this choice. To determine whether or not this gut feeling is justified, a research was conducted in which various stakeholders had to cooperatively redesign a process chain, with and without VL. To determine whether or not a sMM was created, scores on agreement in individual MM, communication, and cooperation were analyzed. The results confirmed the assumption that VL can indeed play an important role in the creation of sMM and, hence, can aid the processes of cooperative design and engineering.

IT vendor selection model by using structural equation model & analytical hierarchy process

NASA Astrophysics Data System (ADS)

Maitra, Sarit; Dominic, P. D. D.

2012-11-01

Selecting and evaluating the right vendors is imperative for an organization's global marketplace competitiveness. Improper selection and evaluation of potential vendors can dwarf an organization's supply chain performance. Numerous studies have demonstrated that firms consider multiple criteria when selecting key vendors. This research intends to develop a new hybrid model for vendor selection process with better decision making. The new proposed model provides a suitable tool for assisting decision makers and managers to make the right decisions and select the most suitable vendor. This paper proposes a Hybrid model based on Structural Equation Model (SEM) and Analytical Hierarchy Process (AHP) for long-term strategic vendor selection problems. The five steps framework of the model has been designed after the thorough literature study. The proposed hybrid model will be applied using a real life case study to assess its effectiveness. In addition, What-if analysis technique will be used for model validation purpose.

Neurofilament light polypeptide gene N98S mutation in mice leads to neurofilament network abnormalities and a Charcot-Marie-Tooth Type 2E phenotype.

PubMed

Adebola, Adijat A; Di Castri, Theo; He, Chui-Zhen; Salvatierra, Laura A; Zhao, Jian; Brown, Kristy; Lin, Chyuan-Sheng; Worman, Howard J; Liem, Ronald K H

2015-04-15

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited neurological disorder with a prevalence of 1 in 2500 people worldwide. Patients suffer from degeneration of the peripheral nerves that control sensory information of the foot/leg and hand/arm. Multiple mutations in the neurofilament light polypeptide gene, NEFL, cause CMT2E. Previous studies in transfected cells showed that expression of disease-associated neurofilament light chain variants results in abnormal intermediate filament networks associated with defects in axonal transport. We have now generated knock-in mice with two different point mutations in Nefl: P8R that has been reported in multiple families with variable age of onset and N98S that has been described as an early-onset, sporadic mutation in multiple individuals. Nefl(P8R/+) and Nefl(P8R/P8R) mice were indistinguishable from Nefl(+/+) in terms of behavioral phenotype. In contrast, Nefl(N98S/+) mice had a noticeable tremor, and most animals showed a hindlimb clasping phenotype. Immunohistochemical analysis revealed multiple inclusions in the cell bodies and proximal axons of spinal cord neurons, disorganized processes in the cerebellum and abnormal processes in the cerebral cortex and pons. Abnormal processes were observed as early as post-natal day 7. Electron microscopic analysis of sciatic nerves showed a reduction in the number of neurofilaments, an increase in the number of microtubules and a decrease in the axonal diameters. The Nefl(N98S/+) mice provide an excellent model to study the pathogenesis of CMT2E and should prove useful for testing potential therapies. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A systems-based approach for integrated design of materials, products and design process chains

NASA Astrophysics Data System (ADS)

Panchal, Jitesh H.; Choi, Hae-Jin; Allen, Janet K.; McDowell, David L.; Mistree, Farrokh

2007-12-01

The concurrent design of materials and products provides designers with flexibility to achieve design objectives that were not previously accessible. However, the improved flexibility comes at a cost of increased complexity of the design process chains and the materials simulation models used for executing the design chains. Efforts to reduce the complexity generally result in increased uncertainty. We contend that a systems based approach is essential for managing both the complexity and the uncertainty in design process chains and simulation models in concurrent material and product design. Our approach is based on simplifying the design process chains systematically such that the resulting uncertainty does not significantly affect the overall system performance. Similarly, instead of striving for accurate models for multiscale systems (that are inherently complex), we rely on making design decisions that are robust to uncertainties in the models. Accordingly, we pursue hierarchical modeling in the context of design of multiscale systems. In this paper our focus is on design process chains. We present a systems based approach, premised on the assumption that complex systems can be designed efficiently by managing the complexity of design process chains. The approach relies on (a) the use of reusable interaction patterns to model design process chains, and (b) consideration of design process decisions using value-of-information based metrics. The approach is illustrated using a Multifunctional Energetic Structural Material (MESM) design example. Energetic materials store considerable energy which can be released through shock-induced detonation; conventionally, they are not engineered for strength properties. The design objectives for the MESM in this paper include both sufficient strength and energy release characteristics. The design is carried out by using models at different length and time scales that simulate different aspects of the system. Finally, by applying the method to the MESM design problem, we show that the integrated design of materials and products can be carried out more efficiently by explicitly accounting for design process decisions with the hierarchy of models.

Improved Modeling of Side-Chain–Base Interactions and Plasticity in Protein–DNA Interface Design

PubMed Central

Thyme, Summer B.; Baker, David; Bradley, Philip

2012-01-01

Combinatorial sequence optimization for protein design requires libraries of discrete side-chain conformations. The discreteness of these libraries is problematic, particularly for long, polar side chains, since favorable interactions can be missed. Previously, an approach to loop remodeling where protein backbone movement is directed by side-chain rotamers predicted to form interactions previously observed in native complexes (termed “motifs”) was described. Here, we show how such motif libraries can be incorporated into combinatorial sequence optimization protocols and improve native complex recapitulation. Guided by the motif rotamer searches, we made improvements to the underlying energy function, increasing recapitulation of native interactions. To further test the methods, we carried out a comprehensive experimental scan of amino acid preferences in the I-AniI protein–DNA interface and found that many positions tolerated multiple amino acids. This sequence plasticity is not observed in the computational results because of the fixed-backbone approximation of the model. We improved modeling of this diversity by introducing DNA flexibility and reducing the convergence of the simulated annealing algorithm that drives the design process. In addition to serving as a benchmark, this extensive experimental data set provides insight into the types of interactions essential to maintain the function of this potential gene therapy reagent. PMID:22426128

Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage-induced poly-ADP-ribosylation and by nucleolar transcription.

PubMed

Bütepage, Mareike; Preisinger, Christian; von Kriegsheim, Alexander; Scheufen, Anja; Lausberg, Eva; Li, Jinyu; Kappes, Ferdinand; Feederle, Regina; Ernst, Sabrina; Eckei, Laura; Krieg, Sarah; Müller-Newen, Gerhard; Rossetti, Giulia; Feijs, Karla L H; Verheugd, Patricia; Lüscher, Bernhard

2018-04-30

Macrodomains are conserved protein folds associated with ADP-ribose binding and turnover. ADP-ribosylation is a posttranslational modification catalyzed primarily by ARTD (aka PARP) enzymes in cells. ARTDs transfer either single or multiple ADP-ribose units to substrates, resulting in mono- or poly-ADP-ribosylation. TARG1/C6orf130 is a macrodomain protein that hydrolyzes mono-ADP-ribosylation and interacts with poly-ADP-ribose chains. Interactome analyses revealed that TARG1 binds strongly to ribosomes and proteins associated with rRNA processing and ribosomal assembly factors. TARG1 localized to transcriptionally active nucleoli, which occurred independently of ADP-ribose binding. TARG1 shuttled continuously between nucleoli and nucleoplasm. In response to DNA damage, which activates ARTD1/2 (PARP1/2) and promotes synthesis of poly-ADP-ribose chains, TARG1 re-localized to the nucleoplasm. This was dependent on the ability of TARG1 to bind to poly-ADP-ribose. These findings are consistent with the observed ability of TARG1 to competitively interact with RNA and PAR chains. We propose a nucleolar role of TARG1 in ribosome assembly or quality control that is stalled when TARG1 is re-located to sites of DNA damage.

HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains.

PubMed

Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C L; Tanaka, Yuetsu; Xia, Zongping

2016-04-01

The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation.

HTLV-1 Tax Functions as a Ubiquitin E3 Ligase for Direct IKK Activation via Synthesis of Mixed-Linkage Polyubiquitin Chains

PubMed Central

Wang, Chong; Long, Wenying; Peng, Chao; Hu, Lin; Zhang, Qiong; Wu, Ailing; Zhang, Xiaoqing; Duan, Xiaotao; Wong, Catherine C. L.; Tanaka, Yuetsu; Xia, Zongping

2016-01-01

The HTLV-1 oncoprotein Tax plays a key role in CD4+ T cell transformation by promoting cell proliferation and survival, mainly through permanent activation of the NK-κB pathway and induction of many NF-κB target genes. Elucidating the underlying molecular mechanism is therefore critical in understanding HTLV-1-mediated transformation. Current studies have suggested multiple but controversial mechanisms regarding Tax-induced IKK activation mainly due to blending of primary Tax-induced IKK activation events and secondary IKK activation events induced by cytokines secreted by the primary Tax-induced IKK-NF-κB activation events. We reconstituted Tax-stimulated IKK activation in a cell-free system to dissect the essential cellular components for primary IKK activation by Tax and studied the underlying biochemical mechanism. We found that Tax is a putative E3 ubiquitin ligase, which, together with UbcH2, UhcH5c, or UbcH7, catalyzes the assembly of free mixed-linkage polyubiquitin chains. These free mixed-linkage polyubiquitin chains are then responsible for direct IKK activation by binding to the NEMO subunit of IKK. Our studies revealed the biochemical function of Tax in the process of IKK activation, which utilizes the minimal cellular ubiquitination components for NF-κB activation. PMID:27082114

3. This machine in building #7 plated the hooks used ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. This machine in building #7 plated the hooks used on the cross chains in tire chains, by the 'pean' or mechanical process. This process was replaced when coated wire was introduced. - American Chain & Cable Company, East Princess Street (400 Block), York, York County, PA

The integrable quantum group invariant A2n-1(2) and Dn+1(2) open spin chains

NASA Astrophysics Data System (ADS)

Nepomechie, Rafael I.; Pimenta, Rodrigo A.; Retore, Ana L.

2017-11-01

A family of A2n(2) integrable open spin chains with Uq (Cn) symmetry was recently identified in arxiv:arXiv:1702.01482. We identify here in a similar way a family of A2n-1(2) integrable open spin chains with Uq (Dn) symmetry, and two families of Dn+1(2) integrable open spin chains with Uq (Bn) symmetry. We discuss the consequences of these symmetries for the degeneracies and multiplicities of the spectrum. We propose Bethe ansatz solutions for two of these models, whose completeness we check numerically for small values of n and chain length N. We find formulas for the Dynkin labels in terms of the numbers of Bethe roots of each type, which are useful for determining the corresponding degeneracies. In an appendix, we briefly consider Dn+1(2) chains with other integrable boundary conditions, which do not have quantum group symmetry.

Don't break the chain: importance of supply chain management in the operating room setting.

PubMed

Bilyk, Candis

2008-09-01

Management of supplies within the operating room (OR) has considerable implications for decreasing healthcare costs while maintaining high-quality patient care. This area of healthcare therefore requires more monitoring by end-users including OR management, physicians, and nursing staff. This article is based on understanding supply chain management in the OR setting. Information provided throughout the article can be applied to small or large health care centers. It defines supply chain management and contains a brief overview of supply chain processes. It reviews the benefits of following these processes. The article also includes recommendations for improving the supply chain in the OR.

Stepwise Elastic Behavior in a Model Elastomer

NASA Astrophysics Data System (ADS)

Bhawe, Dhananjay M.; Cohen, Claude; Escobedo, Fernando A.

2004-12-01

MonteCarlo simulations of an entanglement-free cross-linked polymer network of semiflexible chains reveal a peculiar stepwise elastic response. For increasing stress, step jumps in strain are observed that do not correlate with changes in the number of aligned chains. We show that this unusual behavior stems from the ability of the system to form multiple ordered chain domains that exclude the cross-linking species. This novel elastomer shows a toughening behavior similar to that observed in biological structural materials, such as muscle proteins and abalone shell adhesive.

Metrics for Labeled Markov Systems

NASA Technical Reports Server (NTRS)

Desharnais, Josee; Jagadeesan, Radha; Gupta, Vineet; Panangaden, Prakash

1999-01-01

Partial Labeled Markov Chains are simultaneously generalizations of process algebra and of traditional Markov chains. They provide a foundation for interacting discrete probabilistic systems, the interaction being synchronization on labels as in process algebra. Existing notions of process equivalence are too sensitive to the exact probabilities of various transitions. This paper addresses contextual reasoning principles for reasoning about more robust notions of "approximate" equivalence between concurrent interacting probabilistic systems. The present results indicate that:We develop a family of metrics between partial labeled Markov chains to formalize the notion of distance between processes. We show that processes at distance zero are bisimilar. We describe a decision procedure to compute the distance between two processes. We show that reasoning about approximate equivalence can be done compositionally by showing that process combinators do not increase distance. We introduce an asymptotic metric to capture asymptotic properties of Markov chains; and show that parallel composition does not increase asymptotic distance.

Influences of the manufacturing process chain design on the near surface condition and the resulting fatigue behaviour of quenched and tempered SAE 4140

NASA Astrophysics Data System (ADS)

Klein, M.; Eifler, D.

2010-07-01

To analyse interactions between single steps of process chains, variations in material properties, especially the microstructure and the resulting mechanical properties, specimens with tension screw geometry were manufactured with five process chains. The different process chains as well as their parameters influence the near surface condition and consequently the fatigue behaviour in a characteristic manner. The cyclic deformation behaviour of these specimens can be benchmarked equivalently with conventional strain measurements as well as with high-precision temperature and electrical resistance measurements. The development of temperature-values provides substantial information on cyclic load dependent changes in the microstructure.

A Strategy Combining Higher Energy C-Trap Dissociation with Neutral Loss- and Product Ion-Based MSn Acquisition for Global Profiling and Structure Annotation of Fatty Acids Conjugates

NASA Astrophysics Data System (ADS)

Bi, Qi-rui; Hou, Jin-jun; Yang, Min; Shen, Yao; Qi, Peng; Feng, Rui-hong; Dai, Zhuo; Yan, Bing-peng; Wang, Jian-wei; Shi, Xiao-jian; Wu, Wan-ying; Guo, De-an

2017-03-01

Fatty acids conjugates (FACs) are ubiquitous but found in trace amounts in the natural world. They are composed of multiple unknown substructures and side chains. Thus, FACs are difficult to be analyzed by traditional mass spectrometric methods. In this study, an integrated strategy was developed to global profiling and targeted structure annotation of FACs in complex matrix by LTQ Orbitrap. Dicarboxylic acid conjugated bufotoxins (DACBs) in Venenum bufonis (VB) were used as model compounds. The new strategy (abbreviated as HPNA) combined higher-energy C-trap dissociation (HCD) with product ion- (PI), neutral loss- (NL) based MSn (n ≥ 3) acquisition in both positive-ion mode and negative-ion mode. Several advantages are presented. First, various side chains were found under HCD in negative-ion mode, which included both known and unknown side chains. Second, DACBs with multiple side chains were simultaneously detected in one run. Compared with traditional quadrupole-based mass method, it greatly increased analysis throughput. Third, the fragment ions of side chain and steroids substructure could be obtained by PI- and NL-based MSn acquisition, respectively, which greatly increased the accuracy of the structure annotation of DACBs. In all, 78 DACBs have been discovered, of which 68 were new compounds; 25 types of substructure formulas and seven dicarboxylic acid side chains were found, especially five new side chains, including two saturated dicarboxylic acids [(azelaic acid (C9) and sebacic acid (C10)] and three unsaturated dicarboxylic acids (u-C8, u-C9, and u-C10). All these results greatly enriched the structures of DACBs in VB.

Architectural Principles for Orchestration of Cross-Organizational Service Delivery: Case Studies from the Netherlands

NASA Astrophysics Data System (ADS)

van Veenstra, Anne Fleur; Janssen, Marijn

One of the main challenges for e-government is to create coherent services for citizens and businesses. Realizing Integrated Service Delivery (ISD) requires government agencies to collaborate across their organizational boundaries. The coordination of processes across multiple organizations to realize ISD is called orchestration. One way of achieving orchestration is to formalize processes using architecture. In this chapter we identify architectural principles for orchestration by looking at three case studies of cross-organizational service delivery chain formation in the Netherlands. In total, six generic principles were formulated and subsequently validated in two workshops with experts. These principles are: (i) build an intelligent front office, (ii) give processes a clear starting point and end, (iii) build a central workflow application keeping track of the process, (iv) differentiate between simple and complex processes, (v) ensure that the decision-making responsibility and the overview of the process are not performed by the same process role, and (vi) create a central point where risk profiles are maintained. Further research should focus on how organizations can adapt these principles to their own situation.

Serial Learning Process: Test of Chaining, Position, and Dual-Process Hypotheses

ERIC Educational Resources Information Center

Giurintano, S. L.

1973-01-01

The chaining, position, and dual-process hypotheses of serial learning (SL) as well as serial recall, reordering, and relearning of paired-associate learning were examined to establish learning patterns. Results provide evidence for dual-process hypothesis. (DS)

Implementation of Network Leader Sponsored Supply Chain Management Systems: A Case Study of Supplier IT Business Value

ERIC Educational Resources Information Center

Miller, Mark S.

2010-01-01

This qualitative multiple-case study was conducted to explore and understand how the implementation of required relationship-specific supply chain management system (SCMS) dictated by the network leader within a supplier network affects a supplier organization. The study, on a very broad sense, attempted to research the current validity of how the…

Independence of Terminal-Link Entry Rate and Immediacy in Concurrent Chains

ERIC Educational Resources Information Center

Berg, Mark E.; Grace, Randolph C.

2004-01-01

In Phase 1, 4 pigeons were trained on a three-component multiple concurrent-chains procedure in which components differed only in terms of relative terminal-link entry rate. The terminal links were variable-interval schedules and were varied across four conditions to produce immediacy ratios of 4:1, 1:4, 2:1, and 1:2. Relative terminal-link entry…

Follow-up of IgD-κ multiple myeloma by monitoring free light chains and total heavy chain IgD: A case report

PubMed Central

De Santis, Elena; Masi, Serena; Cordone, Iole; Pisani, Francesco; Zuppi, Cecilia; Mattei, Fabrizio; Conti, Laura; Cigliana, Giovanni

2016-01-01

Immunoglobulin (Ig)D-κ multiple myeloma (MM) is a rare neoplastic disease characterized by an aggressive and rapidly progressing course, which constitutes only a very small proportion of all MM cases. In the present report, the clinical case of a 51-year-old Caucasian woman diagnosed with IgD-κ MM is described. The patient underwent different chemotherapeutic treatments subsequently to a single autologous stem cell transplantation. Despite the inherent difficulty of monitoring IgD levels and performing serum immunofixation electrophoresis, the clinical outcome of the patient was almost uniquely monitored by measuring the levels of κ and λ free light chains (FLCs) and total heavy chain IgD. The data suggest the non-invasive potential and usefulness of FLCs evaluation for early detection of stringent complete remission, follow-up and early detection of disease relapse. In addition, this diagnostic procedure has successfully been employed for the therapeutic monitoring of the present patient, and may represent a very helpful, non-invasive tool for the follow-up of IgD myeloma patients without the requirement of serial bone marrow aspirate. PMID:27588135

Microcontroller-based binary integrator for millimeter-wave radar experiments.

PubMed

Eskelinen, Pekka; Ruoskanen, Jukka; Peltonen, Jouni

2010-05-01

An easily on-site reconfigurable multiple binary integrator for millimeter radar experiments has been constructed of static random access memories, an eight bit microcontroller, and high speed video operational amplifiers. The design uses a raw comparator path and two adjustable m-out-of-n chains in a wired-OR configuration. Standard high speed memories allow the use of pulse widths below 100 ns. For eight pulse repetition intervals it gives a maximum improvement of 6.6 dB for stationary low-level target echoes. The doubled configuration enhances the capability against fluctuating targets. Because of the raw comparator path, also single return pulses of relatively high amplitude are processed.

Developmental Defects of Caenorhabditis elegans Lacking Branched-chain α-Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency.

PubMed

Jia, Fan; Cui, Mingxue; Than, Minh T; Han, Min

2016-02-05

Branched-chain α-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue-specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterizing Chain Processes in Visible Light Photoredox Catalysis

PubMed Central

Cismesia, Megan A.

2015-01-01

The recognition that Ru(bpy)32+ andsimilar visible light absorbing transition metal complexes can be photocatalysts for a variety of synthetically useful organic reactions has resulted in a recent resurgence of interest in photoredox catalysis. However, many of the critical mechanistic aspects of this class of reactions remain poorly understood. In particular, the degree to which visible light photoredox reactions involve radical chain processes has been a point of some disagreement that has not been subjected to systematic analysis. We have now performed quantum yield measurements to demonstrate that threerepresentative, mechanistically distinct photoredox processes involve product-forming chain reactions. Moreover, we show that the combination of quantum yield and luminescence quenching experiments provides a rapid method to estimate the length of these chains. Together, these measurements constitute a robust, operationally facile strategy for characterizing chain processes in a wide range of visible light photoredox reactions. PMID:26668708

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

ERIC Educational Resources Information Center

Rao, Shaila; Kane, Martha T.

2009-01-01

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

Recalculation of the Critical Size and Multiplication Constant of a Homogeneous UO{sub 2}-D{sub 2}O Mixtures

DOE R&D Accomplishments Database

Wigner, E. P.; Weinberg, A. M.; Stephenson, J.

1944-02-11

The multiplication constant and optimal concentration of a slurry pile is recalculated on the basis of Mitchell's experiments on resonance absorption. The smallest chain reacting unit contains 45 to 55 m{sup 3}of d{sub 2}O. (auth).

Recalculation of the Critical Size and Multiplication Constant of a Homogeneous UO{sub 2} - D{sub 2}O Mixtures

DOE R&D Accomplishments Database

Wigner, E. P.; Weinberg, A. M.; Stephenson, J.

1944-02-11

The multiplication constant and optimal concentration of a slurry pile is recalculated on the basis of Mitchell`s experiments on resonance absorption. The smallest chain reacting unit contains 45 to 55 m{sup 3}of D{sub 2}O. (auth)

Interaction of Cellulose Chains with Ionic Liquids and Water via MD simulations

NASA Astrophysics Data System (ADS)

Ismail, Ahmed; Rabideau, Brooks

2012-02-01

One promising route for combustible fuel sources which are both renewable and have a low environmental impact is the conversion of waste biomass into tailor-made fuels. An important aspect of this process is the low-energy separation of cellulose from the biomass. Ionic liquids (ILs) have proven to be very good in dissolving cellulose with the added benefit of being essentially non-volatile making them ideal for ``green'' processing. IL research, however, remains relatively new, with many parts of this dissolution process remaining uncertain. We examine the behavior of cellulose with the ionic liquids [BMIM]Cl, [EMIM]Ac and [DMIM]DMP as well as water via MD simulation. All three ionic liquids have been observed to dissolve cellulose quite well yet have differently sized anions. We explore these differences and the impacts they have on their interactions with cellulose. First we examine the dynamics of a single cellulose strand in these ionic liquids. We determine the radius of gyration and the hydrogen bonds that are formed between the anions and cellulose. Next, we probe the dissolution mechanism of multiple, bound cellulose strands examining of multiple, bound cellulose strands examining interactions at the IL/cellulose interface and the breakup of inter-cellulose hydrogen bonds.

How main-chains of proteins explore the free-energy landscape in native states.

PubMed

Senet, Patrick; Maisuradze, Gia G; Foulie, Colette; Delarue, Patrice; Scheraga, Harold A

2008-12-16

Understanding how a single native protein diffuses on its free-energy landscape is essential to understand protein kinetics and function. The dynamics of a protein is complex, with multiple relaxation times reflecting a hierarchical free-energy landscape. Using all-atom molecular dynamics simulations of an alpha/beta protein (crambin) and a beta-sheet polypeptide (BS2) in their "native" states, we demonstrate that the mean-square displacement of dihedral angles, defined by 4 successive C(alpha) atoms, increases as a power law of time, t(alpha), with an exponent alpha between 0.08 and 0.39 (alpha = 1 corresponds to Brownian diffusion), at 300 K. Residues with low exponents are located mainly in well-defined secondary elements and adopt 1 conformational substate. Residues with high exponents are found in loops/turns and chain ends and exist in multiple conformational substates, i.e., they move on multiple-minima free-energy profiles.

How main-chains of proteins explore the free-energy landscape in native states

PubMed Central

Senet, Patrick; Maisuradze, Gia G.; Foulie, Colette; Delarue, Patrice; Scheraga, Harold A.

2008-01-01

Understanding how a single native protein diffuses on its free-energy landscape is essential to understand protein kinetics and function. The dynamics of a protein is complex, with multiple relaxation times reflecting a hierarchical free-energy landscape. Using all-atom molecular dynamics simulations of an α/β protein (crambin) and a β-sheet polypeptide (BS2) in their “native” states, we demonstrate that the mean-square displacement of dihedral angles, defined by 4 successive Cα atoms, increases as a power law of time, tα, with an exponent α between 0.08 and 0.39 (α = 1 corresponds to Brownian diffusion), at 300 K. Residues with low exponents are located mainly in well-defined secondary elements and adopt 1 conformational substate. Residues with high exponents are found in loops/turns and chain ends and exist in multiple conformational substates, i.e., they move on multiple-minima free-energy profiles. PMID:19073932

Comparative Community Proteomics Demonstrates the Unexpected Importance of Actinobacterial Glycoside Hydrolase Family 12 Protein for Crystalline Cellulose Hydrolysis

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

Hiras, Jennifer; Wu, Yu -Wei; Deng, Kai

Glycoside hydrolases (GHs) are key enzymes in the depolymerization of plant-derived cellulose, a process central to the global carbon cycle and the conversion of plant biomass to fuels and chemicals. A limited number of GH families hydrolyze crystalline cellulose, often by a processive mechanism along the cellulose chain. During cultivation of thermophilic cellulolytic microbial communities, substantial differences were observed in the crystalline cellulose saccharification activities of supernatants recovered from divergent lineages. Comparative community proteomics identified a set of cellulases from a population closely related to actinobacterium Thermobispora bispora that were highly abundant in the most active consortium. Among the cellulasesmore » from T. bispora, the abundance of a GH family 12 (GH12) protein correlated most closely with the changes in crystalline cellulose hydrolysis activity. This result was surprising since GH12 proteins have been predominantly characterized as enzymes active on soluble polysaccharide substrates. Heterologous expression and biochemical characterization of the suite of T. bispora hydrolytic cellulases confirmed that the GH12 protein possessed the highest activity on multiple crystalline cellulose substrates and demonstrated that it hydrolyzes cellulose chains by a predominantly random mechanism. This work suggests that the role of GH12 proteins in crystalline cellulose hydrolysis by cellulolytic microbes should be reconsidered.« less

Comparative Community Proteomics Demonstrates the Unexpected Importance of Actinobacterial Glycoside Hydrolase Family 12 Protein for Crystalline Cellulose Hydrolysis

DOE PAGES

Hiras, Jennifer; Wu, Yu -Wei; Deng, Kai; ...

2016-08-23

Glycoside hydrolases (GHs) are key enzymes in the depolymerization of plant-derived cellulose, a process central to the global carbon cycle and the conversion of plant biomass to fuels and chemicals. A limited number of GH families hydrolyze crystalline cellulose, often by a processive mechanism along the cellulose chain. During cultivation of thermophilic cellulolytic microbial communities, substantial differences were observed in the crystalline cellulose saccharification activities of supernatants recovered from divergent lineages. Comparative community proteomics identified a set of cellulases from a population closely related to actinobacterium Thermobispora bispora that were highly abundant in the most active consortium. Among the cellulasesmore » from T. bispora, the abundance of a GH family 12 (GH12) protein correlated most closely with the changes in crystalline cellulose hydrolysis activity. This result was surprising since GH12 proteins have been predominantly characterized as enzymes active on soluble polysaccharide substrates. Heterologous expression and biochemical characterization of the suite of T. bispora hydrolytic cellulases confirmed that the GH12 protein possessed the highest activity on multiple crystalline cellulose substrates and demonstrated that it hydrolyzes cellulose chains by a predominantly random mechanism. This work suggests that the role of GH12 proteins in crystalline cellulose hydrolysis by cellulolytic microbes should be reconsidered.« less

On the polymer physics origins of protein folding thermodynamics.

PubMed

Taylor, Mark P; Paul, Wolfgang; Binder, Kurt

2016-11-07

A remarkable feature of the spontaneous folding of many small proteins is the striking similarity in the thermodynamics of the folding process. This process is characterized by simple two-state thermodynamics with large and compensating changes in entropy and enthalpy and a funnel-like free energy landscape with a free-energy barrier that varies linearly with temperature. One might attribute the commonality of this two-state folding behavior to features particular to these proteins (e.g., chain length, hydrophobic/hydrophilic balance, attributes of the native state) or one might suspect that this similarity in behavior has a more general polymer-physics origin. Here we show that this behavior is also typical for flexible homopolymer chains with sufficiently short range interactions. Two-state behavior arises from the presence of a low entropy ground (folded) state separated from a set of high entropy disordered (unfolded) states by a free energy barrier. This homopolymer model exhibits a funneled free energy landscape that reveals a complex underlying dynamics involving competition between folding and non-folding pathways. Despite the presence of multiple pathways, this simple physics model gives the robust result of two-state thermodynamics for both the cases of folding from a basin of expanded coil states and from a basin of compact globule states.

On the polymer physics origins of protein folding thermodynamics

NASA Astrophysics Data System (ADS)

Taylor, Mark P.; Paul, Wolfgang; Binder, Kurt

2016-11-01

A remarkable feature of the spontaneous folding of many small proteins is the striking similarity in the thermodynamics of the folding process. This process is characterized by simple two-state thermodynamics with large and compensating changes in entropy and enthalpy and a funnel-like free energy landscape with a free-energy barrier that varies linearly with temperature. One might attribute the commonality of this two-state folding behavior to features particular to these proteins (e.g., chain length, hydrophobic/hydrophilic balance, attributes of the native state) or one might suspect that this similarity in behavior has a more general polymer-physics origin. Here we show that this behavior is also typical for flexible homopolymer chains with sufficiently short range interactions. Two-state behavior arises from the presence of a low entropy ground (folded) state separated from a set of high entropy disordered (unfolded) states by a free energy barrier. This homopolymer model exhibits a funneled free energy landscape that reveals a complex underlying dynamics involving competition between folding and non-folding pathways. Despite the presence of multiple pathways, this simple physics model gives the robust result of two-state thermodynamics for both the cases of folding from a basin of expanded coil states and from a basin of compact globule states.

Evaluation of virus reduction efficiency in wastewater treatment unit processes as a credit value in the multiple-barrier system for wastewater reclamation and reuse.

PubMed

Ito, Toshihiro; Kato, Tsuyoshi; Hasegawa, Makoto; Katayama, Hiroyuki; Ishii, Satoshi; Okabe, Satoshi; Sano, Daisuke

2016-12-01

The virus reduction efficiency of each unit process is commonly determined based on the ratio of virus concentration in influent to that in effluent of a unit, but the virus concentration in wastewater has often fallen below the analytical quantification limit, which does not allow us to calculate the concentration ratio at each sampling event. In this study, left-censored datasets of norovirus (genogroup I and II), and adenovirus were used to calculate the virus reduction efficiency in unit processes of secondary biological treatment and chlorine disinfection. Virus concentration in influent, effluent from the secondary treatment, and chlorine-disinfected effluent of four municipal wastewater treatment plants were analyzed by a quantitative polymerase chain reaction (PCR) approach, and the probabilistic distributions of log reduction (LR) were estimated by a Bayesian estimation algorithm. The mean values of LR in the secondary treatment units ranged from 0.9 and 2.2, whereas those in the free chlorine disinfection units were from -0.1 and 0.5. The LR value in the secondary treatment was virus type and unit process dependent, which raised the importance for accumulating the data of virus LR values applicable to the multiple-barrier system, which is a global concept of microbial risk management in wastewater reclamation and reuse.

Towards rapid prototyped convective microfluidic DNA amplification platform

NASA Astrophysics Data System (ADS)

Ajit, Smrithi; Praveen, Hemanth Mithun; Puneeth, S. B.; Dave, Abhishek; Sesham, Bharat; Mohan, K. N.; Goel, Sanket

2017-02-01

Today, Polymerase Chain Reaction (PCR) based DNA amplification plays an indispensable role in the field of biomedical research. Its inherent ability to exponentially amplify sample DNA has proven useful for the identification of virulent pathogens like those causing Multiple Drug-Resistant Tuberculosis (MDR-TB). The intervention of Microfluidics technology has revolutionized the concept of PCR from being a laborious and time consuming process into one that is faster, easily portable and capable of being multifunctional. The Microfluidics based PCR outweighs its traditional counterpart in terms of flexibility of varying reaction rate, operation simplicity, need of a fraction of volume and capability of being integrated with other functional elements. The scope of the present work involves the development of a real-time continuous flow microfluidic device, fabricated by 3D printing-governed rapid prototyping method, eventually leading to an automated and robust platform to process multiple DNA samples for detection of MDRTB-associated mutations. The thermal gradient characteristic to the PCR process is produced using peltier units appropriate to the microfluidic environment fully monitored and controlled by a low cost controller driven by a Data Acquisition System. The process efficiency achieved in the microfluidic environment in terms of output per cycle is expected to be on par with the traditional PCR and capable of earning the additional advantages of being faster and minimizing the handling.

Multiple papillomas in a diamond python, Morelia spilota spilota.

PubMed

Gull, Jessica M; Lange, Christian E; Favrot, Claude; Dorrestein, Gerry M; Hatt, Jean-Michel

2012-12-01

A 4-yr-old male diamond python (Morelia spilota spilota) was evaluated for multiple black papillated exophytic skin proliferations and signs of pneumonia. The histopathologic structure of the skin biopsy specimens led to the diagnosis of a benign papilloma-like neoplasia. In this case, papillomavirus DNA could be amplified from a biopsy sample with a broad range polymerase chain reaction. Nested pan-herpes polymerase chain reaction was negative, and herpesvirus inclusion bodies were not found. Because of the histologically benign nature of the papilloma, the skin proliferations were left untreated. Ten mo after the first presentation, the skin lesions had regressed almost completely; 34 mo later, only scars from the biopsies were left.

Multiple mobility edges in a 1D Aubry chain with Hubbard interaction in presence of electric field: Controlled electron transport

NASA Astrophysics Data System (ADS)

Saha, Srilekha; Maiti, Santanu K.; Karmakar, S. N.

2016-09-01

Electronic behavior of a 1D Aubry chain with Hubbard interaction is critically analyzed in presence of electric field. Multiple energy bands are generated as a result of Hubbard correlation and Aubry potential, and, within these bands localized states are developed under the application of electric field. Within a tight-binding framework we compute electronic transmission probability and average density of states using Green's function approach where the interaction parameter is treated under Hartree-Fock mean field scheme. From our analysis we find that selective transmission can be obtained by tuning injecting electron energy, and thus, the present model can be utilized as a controlled switching device.

Repeats of base oligomers as the primordial coding sequences of the primeval earth and their vestiges in modern genes.

PubMed

Ohno, S

1984-01-01

Three outstanding properties uniquely qualify repeats of base oligomers as the primordial coding sequences of all polypeptide chains. First, when compared with randomly generated base sequences in general, they are more likely to have long open reading frames. Second, periodical polypeptide chains specified by such repeats are more likely to assume either alpha-helical or beta-sheet secondary structures than are polypeptide chains of random sequence. Third, provided that the number of bases in the oligomeric unit is not a multiple of 3, these internally repetitious coding sequences are impervious to randomly sustained base substitutions, deletions, and insertions. This is because the recurring periodicity of their polypeptide chains is given by three consecutive copies of the oligomeric unit translated in three different reading frames. Accordingly, when one reading frame is open, the other two are automatically open as well, all three being capable of coding for polypeptide chains of identical periodicity. Under this circumstance, a frame shift due to the deletion or insertion of a number of bases that is not a multiple of 3 fails to alter the down-stream amino acid sequence, and even a base change causing premature chain-termination can silence only one of the three potential coding units. Newly arisen coding sequences in modern organisms are oligomeric repeats, and most of the older genes retain various vestiges of their original internal repetitions. Some of the genes (e.g., oncogenes) have even inherited the property of being impervious to randomly sustained base changes.

NMR (Nuclear Magnetic Resonance) and macromolecular migration in a melt or in concentrated solutions

NASA Technical Reports Server (NTRS)

Addad, J. P. C.

1983-01-01

The purpose of this paper is to analyze the migration process of long polymer molecules in a melt or in concentrated solutions as it may be observed from the dynamics of the transverse magnetization of nuclear spins linked to these chains. The low frequency viscoelastic relaxation of polymer systems is known to be mainly controlled by the mechanism of dissociation of topological constraints excited on chains and which are called entanglements. This mechanism exhibits a strong dependence upon the chain molecular weight. These topological constraints also govern the diffusion process of polymer chains. So, the accurate description of the diffusion motion of a chain may be a convenient way to characterize disentanglement processes necessarily involved in any model proposed to explain viscoelastic effects.

A binary plasmid system for shuffling combinatorial antibody libraries.

PubMed

Collet, T A; Roben, P; O'Kennedy, R; Barbas, C F; Burton, D R; Lerner, R A

1992-11-01

We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind antigen varied from 43% to 100% and depended strongly on the heavy-chain sequence. Such productive crosses resulted in a set of Fab fragments of similar apparent binding constants, which seemed to differ mainly in the amount of active Fab fragment produced in the bacterial cell. The dominance of the heavy chain in the antibody-antigen interaction was further explored in a set of directed crosses, in which heavy and light chains derived from antigen-specific clones were crossed with nonrelated heavy and light chains. In these crosses, an Fab fragment retained antigen binding only if it contained a heavy chain from an antigen-specific clone. In no case did the light chain confer detectable affinity when paired with indifferent heavy chains. The surprising promiscuity of heavy chains has ramifications for the evaluation of the diversity of combinatorial libraries made against protein antigens and should allow the combination of one such promiscuous heavy chain with an engineered light chain to form an Fab fragment carrying synthetic cofactors to assist in antibody catalysis.

A binary plasmid system for shuffling combinatorial antibody libraries.

PubMed Central

Collet, T A; Roben, P; O'Kennedy, R; Barbas, C F; Burton, D R; Lerner, R A

1992-01-01

We have used a binary system of replicon-compatible plasmids to test the potential for promiscuous recombination of heavy and light chains within sets of human Fab fragments isolated from combinatorial antibody libraries. Antibody molecules showed a surprising amount of promiscuity in that a particular heavy chain could recombine with multiple light chains with retention of binding to a protein antigen. The degree to which a given heavy chain productively paired with any light chain to bind antigen varied from 43% to 100% and depended strongly on the heavy-chain sequence. Such productive crosses resulted in a set of Fab fragments of similar apparent binding constants, which seemed to differ mainly in the amount of active Fab fragment produced in the bacterial cell. The dominance of the heavy chain in the antibody-antigen interaction was further explored in a set of directed crosses, in which heavy and light chains derived from antigen-specific clones were crossed with nonrelated heavy and light chains. In these crosses, an Fab fragment retained antigen binding only if it contained a heavy chain from an antigen-specific clone. In no case did the light chain confer detectable affinity when paired with indifferent heavy chains. The surprising promiscuity of heavy chains has ramifications for the evaluation of the diversity of combinatorial libraries made against protein antigens and should allow the combination of one such promiscuous heavy chain with an engineered light chain to form an Fab fragment carrying synthetic cofactors to assist in antibody catalysis. Images PMID:1438192

A Meta-Analysis and Systematic Review of the Literature to Evaluate Potential Threats to Internal Validity in Probe Procedures for Chained Tasks

ERIC Educational Resources Information Center

Alexander, Jennifer L.; Smith, Katie A.; Mataras, Theologia; Shepley, Sally B.; Ayres, Kevin M.

2015-01-01

The two most frequently used methods for assessing performance on chained tasks are single opportunity probes (SOPs) and multiple opportunity probes (MOPs). Of the two, SOPs may be easier and less time-consuming but can suppress actual performance. In comparison, MOPs can provide more information but present the risk of participants acquiring…

Strategic Mobility 21: Smart and Secure E Corridor Stakeholder Evaluation - Savannah

DTIC Science & Technology

2009-12-07

validated to meet Customs-Trade Partnership Against Terrorism ( CTPAT ) level 3 Customs standards and combined with multiple overlain foreign trade zones... CTPAT level 3 benefits of technology validated supply chains insulating shippers against random inspections as the core elements of smart secure...their carrier partners, Customs-Trade Partnership Against Terrorism ( CTPAT ) level 3 technologically verified supply chain security for all shippers

Rapid Acquisition of Preference in Concurrent Chains when Alternatives Differ on Multiple Dimensions of Reinforcement

ERIC Educational Resources Information Center

Kyonka, Elizabeth G. E.; Grace, Randolph C.

2008-01-01

Pigeons responded in a concurrent-chains procedure in which terminal-link reinforcer variables were changed unpredictably across sessions. In Experiment 1, the terminal-link schedules were fixed-interval (FI) 8 s and FI 16 s, and the reinforcer magnitudes were 2 s and 4 s. In Experiment 2 the probability of reinforcement (100% or 50%) was varied…

Thermochemical emission and transformation of chlorinated paraffins in inert and oxidizing atmospheres.

PubMed

Xin, Shanzhi; Gao, Wei; Wang, Yawei; Jiang, Guibin

2017-10-01

Chlorinated paraffins (CPs) generally function as flame retardants and plasticizers in various materials. They are most likely to be processed by thermal processes during the entire life cycle. However, data on the formation and emission of CPs during thermal processes are still not fully understood. In this study, we simulated industrial thermal processes to investigate the emission of medium-chain chlorinated paraffins (MCCPs) and short-chain chlorinated paraffins (SCCPs) using commercial CP52 as the feedstock. We found that CP52 decomposed very easily at 210-320 °C. The decomposition of CPs generated large quantities of MCCPs and SCCPs. These remained in the residue at low temperature (∼200 °C) and were gradually released into the gas phase at higher temperatures. MCCPs and SCCPs were not detected in either the residue or the gas phase when the temperature exceeded 400 °C. However, considerable concentrations of aromatic and chlorinated aromatic hydrocarbons (Cl-PAHs) were identified in the gas phase, and they were formed as the amount of SCCPs and MCCPs decreased. Cl-PAHs were dominated by low-chlorinated chlorobenzenes, polychlorinated biphenyls, and polychlorinated naphthalenes. Oxygen promoted the release and decomposition of SCCPs in the gas phase. The results of the present study revealed the release of MCCPs and SCCPs and their synergistic emission with Cl-PAHs when CPs were subjected to heat. This work may also provide data for developing multiple techniques to control the emission of CPs and Cl-PAHs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crustal structure of Central Sicily

NASA Astrophysics Data System (ADS)

Giustiniani, Michela; Tinivella, Umberta; Nicolich, Rinaldo

2018-01-01

We processed crustal seismic profile SIRIPRO, acquired across Central Sicily. To improve the seismic image we utilized the wave equation datuming technique, a process of upward or downward continuation of the wave-field between two arbitrarily shaped surfaces. Wave equation datuming was applied to move shots and receivers to a given datum plane, removing time shifts related to topography and to near-surface velocity variations. The datuming procedure largely contributed to attenuate ground roll, enhance higher frequencies, increase resolution and improve the signal/noise ratio. Processed data allow recognizing geometries of crust structures differentiating seismic facies and offering a direct image of ongoing tectonic setting within variable lithologies characterizing the crust of Central Sicily. Migrated sections underline distinctive features of Hyblean Plateau foreland and above all a crustal thinning towards the Caltanissetta trough, to the contact with a likely deep Permo-Triassic rifted basin or rather a zone of a continent to oceanic transition. Inhomogeneity and fragmentation of Sicily crust, with a distinct separation of Central Sicily basin from western and eastern blocks, appear to have guided the tectonic transport inside the Caltanissetta crustal scale syncline and the accumulation of allochthonous terrains with south and north-verging thrusts. Major tectonic stack operated on the construction of a wide anticline of the Maghrebian chain in northern Sicily. Sequential south-verging imbrications of deep elements forming the anticline core denote a crust wedge indenting foreland structures. Deformation processes involved multiple detachment planes down to decoupling levels located near crust/mantle transition, supporting a presence of high-density lenses beneath the chain, interrelated to a southwards push of Tyrrhenian mantle and asthenosphere.

Quantification of short chain amines in aqueous matrices using liquid chromatography electrospray ionization tandem mass spectrometry.

PubMed

Viidanoja, Jyrki

2017-01-13

A new liquid chromatography-electrospray ionization-tandem Mass Spectrometry (LC-ESI-MS/MS) method was developed for the determination of more than 20 C 1 -C 6 alkyl and alkanolamines in aqueous matrices. The method employs Hydrophilic Interaction Liquid Chromatography Multiple Reaction Monitoring (HILIC-MRM) with a ZIC-pHILIC column and four stable isotope labeled amines as internal standards for signal normalization and quantification of the amines. The method was validated using a refinery process water sample that was obtained from a cooling cycle of crude oil distillation. The averaged within run precision, between run precision and accuracy were generally within 2-10%, 1-9% and 80-120%, respectively, depending on the analyte and concentration level. Selected aqueous process samples were analyzed with the method. Copyright © 2016 Elsevier B.V. All rights reserved.

Identifying medication error chains from critical incident reports: a new analytic approach.

PubMed

Huckels-Baumgart, Saskia; Manser, Tanja

2014-10-01

Research into the distribution of medication errors usually focuses on isolated stages within the medication use process. Our study aimed to provide a novel process-oriented approach to medication incident analysis focusing on medication error chains. Our study was conducted across a 900-bed teaching hospital in Switzerland. All reported 1,591 medication errors 2009-2012 were categorized using the Medication Error Index NCC MERP and the WHO Classification for Patient Safety Methodology. In order to identify medication error chains, each reported medication incident was allocated to the relevant stage of the hospital medication use process. Only 25.8% of the reported medication errors were detected before they propagated through the medication use process. The majority of medication errors (74.2%) formed an error chain encompassing two or more stages. The most frequent error chain comprised preparation up to and including medication administration (45.2%). "Non-consideration of documentation/prescribing" during the drug preparation was the most frequent contributor for "wrong dose" during the administration of medication. Medication error chains provide important insights for detecting and stopping medication errors before they reach the patient. Existing and new safety barriers need to be extended to interrupt error chains and to improve patient safety. © 2014, The American College of Clinical Pharmacology.

Stochastic thermodynamics for Ising chain and symmetric exclusion process.

PubMed

Toral, R; Van den Broeck, C; Escaff, D; Lindenberg, Katja

2017-03-01

We verify the finite-time fluctuation theorem for a linear Ising chain in contact with heat reservoirs at its ends. Analytic results are derived for a chain consisting of two spins. The system can be mapped onto a model for particle transport, namely, the symmetric exclusion process in contact with thermal and particle reservoirs. We modify the symmetric exclusion process to represent a thermal engine and reproduce universal features of the efficiency at maximum power.

Multiplication and Presence of Shielding Material from Time-Correlated Pulse-Height Measurements of Subcritical Plutonium Assemblies

DOE PAGES

Monterial, Mateusz; Marleau, Peter; Paff, Marc; ...

2017-01-20

Here, we present the results from the first measurements of the Time-Correlated Pulse-Height (TCPH) distributions from 4.5 kg sphere of α-phase weapons-grade plutonium metal in five configurations: bare, reflected by 1.27 cm and 2.54 cm of tungsten, and 2.54 cm and 7.62 cm of polyethylene. A new method for characterizing source multiplication and shielding configuration is also demonstrated. The method relies on solving for the underlying fission chain timing distribution that drives the spreading of the measured TCPH distribution. We found that a gamma distribution fits the fission chain timing distribution well and that the fit parameters correlate with bothmore » multiplication (rate parameter) and shielding material types (shape parameter). The source-to-detector distance was another free parameter that we were able to optimize, and proved to be the most well constrained parameter. MCNPX-PoliMi simulations were used to complement the measurements and help illustrate trends in these parameters and their relation to multiplication and the amount and type of material coupled to the subcritical assembly.« less

Multiplication and Presence of Shielding Material from Time-Correlated Pulse-Height Measurements of Subcritical Plutonium Assemblies

NASA Astrophysics Data System (ADS)

Monterial, Mateusz; Marleau, Peter; Paff, Marc; Clarke, Shaun; Pozzi, Sara

2017-04-01

We present the results from the first measurements of the Time-Correlated Pulse-Height (TCPH) distributions from 4.5 kg sphere of α-phase weapons-grade plutonium metal in five configurations: bare, reflected by 1.27 cm and 2.54 cm of tungsten, and 2.54 cm and 7.62 cm of polyethylene. A new method for characterizing source multiplication and shielding configuration is also demonstrated. The method relies on solving for the underlying fission chain timing distribution that drives the spreading of the measured TCPH distribution. We found that a gamma distribution fits the fission chain timing distribution well and that the fit parameters correlate with both multiplication (rate parameter) and shielding material types (shape parameter). The source-to-detector distance was another free parameter that we were able to optimize, and proved to be the most well constrained parameter. MCNPX-PoliMi simulations were used to complement the measurements and help illustrate trends in these parameters and their relation to multiplication and the amount and type of material coupled to the subcritical assembly.

Continuity in health care: lessons from supply chain management.

PubMed

Meijboom, Bert R; Bakx, Saskia J W G C; Westert, Gert P

2010-01-01

In health care, multidisciplinary collaboration is both indispensable and complicated. We discuss organizational problems that occur in situations where multiple health care providers are required to cooperate for patients with complex needs. Four problem categories, labelled as communication, patient safety, waiting times and integration are distinguished. Then we develop a supply chain perspective on these problems in the sense of discussing remedies according to supply chain management (SCM) literature. This perspective implies a business focus on inter-organizational conditions and requirements necessary for delivering health care and cure across organizational borders. We conclude by presenting some strategic and policy recommendations.

Selective etching of InGaAs/GaAs(100) multilayers of quantum-dot chains

NASA Astrophysics Data System (ADS)

Wang, Zh. M.; Zhang, L.; Holmes, K.; Salamo, G. J.

2005-04-01

We report selective chemical etching as a promising procedure to study the buried quantum dots in multiple InGaAs/GaAs layers. The dot layer-by-dot layer etching is demonstrated using a mixed solution of NH4OH:H2O2:H2O. Regular plan-view atomic force microscopy reveals that all of the exposed InGaAs layers have a chain-like lateral ordering despite the potential of significant In-Ga intermixing during capping. The vertical self-correlation of quantum dots in the chains is observed.

Interpretation Difficulties of Serum Immunofixation Test in Immunoglobulin D Multiple Myeloma with Hidden Lambda Light Chains.

PubMed

Biaz, A; Uwingabiye, J; Rachid, A; Dami, A; Bouhsain, S; Ouzzif, Z; Idrissi, S El Machtani

2018-06-01

We report a case of immunoglobulin (Ig) D myeloma with hidden lambda light chains in a patient whose immunofixation test was very difficult to interpret: the IgD reacts with the anti-δ heavy chain antiserum but does not react with anti-lambda antiserum. The band in the D heavy chain lane is unmatched in light chain lanes and the band in lambda light chain lane migrates higher. To distinguish between heavy chain disease and immunoglobulin with "hidden" light chains, the sample was exposed to a very high concentration of anti-lambda and anti-kappa antisera for 48 hours. The serum immunofixation test of the sample treated with anti-lambda showed a decrease in the intensity of the band corresponding to D heavy chain lane as well as the modification of its mobility confirming the presence of IgD with the hidden lambda light chains. The IgD myeloma with hidden light chains remains a rare entity, hence the interest of sensitizing health professionals to be vigilant and ensure a good diagnosis. The proposed technique is useful, simple, reliable, and less laborious than those previous reported in the literature. Medical laboratories using Sebia-Hydrasys® system should be aware of the described phenomenon in order to avoid identifying an IgD myeloma as a delta heavy chain disease.

Rapid processing of PET list-mode data for efficient uncertainty estimation and data analysis

NASA Astrophysics Data System (ADS)

Markiewicz, P. J.; Thielemans, K.; Schott, J. M.; Atkinson, D.; Arridge, S. R.; Hutton, B. F.; Ourselin, S.

2016-07-01

In this technical note we propose a rapid and scalable software solution for the processing of PET list-mode data, which allows the efficient integration of list mode data processing into the workflow of image reconstruction and analysis. All processing is performed on the graphics processing unit (GPU), making use of streamed and concurrent kernel execution together with data transfers between disk and CPU memory as well as CPU and GPU memory. This approach leads to fast generation of multiple bootstrap realisations, and when combined with fast image reconstruction and analysis, it enables assessment of uncertainties of any image statistic and of any component of the image generation process (e.g. random correction, image processing) within reasonable time frames (e.g. within five minutes per realisation). This is of particular value when handling complex chains of image generation and processing. The software outputs the following: (1) estimate of expected random event data for noise reduction; (2) dynamic prompt and random sinograms of span-1 and span-11 and (3) variance estimates based on multiple bootstrap realisations of (1) and (2) assuming reasonable count levels for acceptable accuracy. In addition, the software produces statistics and visualisations for immediate quality control and crude motion detection, such as: (1) count rate curves; (2) centre of mass plots of the radiodistribution for motion detection; (3) video of dynamic projection views for fast visual list-mode skimming and inspection; (4) full normalisation factor sinograms. To demonstrate the software, we present an example of the above processing for fast uncertainty estimation of regional SUVR (standard uptake value ratio) calculation for a single PET scan of 18F-florbetapir using the Siemens Biograph mMR scanner.

A novel in situ trigger combination method

DOE PAGES

Buzatu, Adrian; Warburton, Andreas; Krumnack, Nils; ...

2013-01-30

Searches for rare physics processes using particle detectors in high-luminosity colliding hadronic beam environments require the use of multi-level trigger systems to reject colossal background rates in real time. In analyses like the search for the Higgs boson, there is a need to maximize the signal acceptance by combining multiple different trigger chains when forming the offline data sample. In such statistically limited searches, datasets are often amassed over periods of several years, during which the trigger characteristics evolve and system performance can vary significantly. Reliable production cross-section measurements and upper limits must take into account a detailed understanding ofmore » the effective trigger inefficiency for every selected candidate event. We present as an example the complex situation of three trigger chains, based on missing energy and jet energy, that were combined in the context of the search for the Higgs (H) boson produced in association with a $W$ boson at the Collider Detector at Fermilab (CDF). We briefly review the existing techniques for combining triggers, namely the inclusion, division, and exclusion methods. We introduce and describe a novel fourth in situ method whereby, for each candidate event, only the trigger chain with the highest a priori probability of selecting the event is considered. We compare the inclusion and novel in situ methods for signal event yields in the CDF $WH$ search. This new combination method, by virtue of its scalability to large numbers of differing trigger chains and insensitivity to correlations between triggers, will benefit future long-running collider experiments, including those currently operating on the Large Hadron Collider.« less

A novel in situ trigger combination method

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

Buzatu, Adrian; Warburton, Andreas; Krumnack, Nils

Searches for rare physics processes using particle detectors in high-luminosity colliding hadronic beam environments require the use of multi-level trigger systems to reject colossal background rates in real time. In analyses like the search for the Higgs boson, there is a need to maximize the signal acceptance by combining multiple different trigger chains when forming the offline data sample. In such statistically limited searches, datasets are often amassed over periods of several years, during which the trigger characteristics evolve and system performance can vary significantly. Reliable production cross-section measurements and upper limits must take into account a detailed understanding ofmore » the effective trigger inefficiency for every selected candidate event. We present as an example the complex situation of three trigger chains, based on missing energy and jet energy, that were combined in the context of the search for the Higgs (H) boson produced in association with a $W$ boson at the Collider Detector at Fermilab (CDF). We briefly review the existing techniques for combining triggers, namely the inclusion, division, and exclusion methods. We introduce and describe a novel fourth in situ method whereby, for each candidate event, only the trigger chain with the highest a priori probability of selecting the event is considered. We compare the inclusion and novel in situ methods for signal event yields in the CDF $WH$ search. This new combination method, by virtue of its scalability to large numbers of differing trigger chains and insensitivity to correlations between triggers, will benefit future long-running collider experiments, including those currently operating on the Large Hadron Collider.« less

Biosensors for Sustainable Food Engineering: Challenges and Perspectives

PubMed Central

Ragavan, Vasanth; Weng, Xuan; Chand, Rohit

2018-01-01

Current food production faces tremendous challenges from growing human population, maintaining clean resources and food qualities, and protecting climate and environment. Food sustainability is mostly a cooperative effort resulting in technology development supported by both governments and enterprises. Multiple attempts have been promoted in tackling challenges and enhancing drivers in food production. Biosensors and biosensing technologies with their applications, are being widely applied to tackling top challenges in food production and its sustainability. Consequently, a growing demand in biosensing technologies exists in food sustainability. Microfluidics represents a technological system integrating multiple technologies. Nanomaterials, with its technology in biosensing, is thought to be the most promising tool in dealing with health, energy, and environmental issues closely related to world populations. The demand of point of care (POC) technologies in this area focus on rapid, simple, accurate, portable, and low-cost analytical instruments. This review provides current viewpoints from the literature on biosensing in food production, food processing, safety and security, food packaging and supply chain, food waste processing, food quality assurance, and food engineering. The current understanding of progress, solution, and future challenges, as well as the commercialization of biosensors are summarized. PMID:29534552

Re-awakening Magmatic Systems: The Mechanics of an Open-system Event

NASA Astrophysics Data System (ADS)

Bergantz, George; Burgisser, Alain; Schleicher, Jillian

2016-04-01

The re-awakening of magmatic systems requires new magma input, which often induces mixing with a resident magma existing as a crystal-rich mush. This is expressed by complex phenocryst populations, many of which preserve evidence of multiple episodes of recycling. The unlocking and mobilization of these resident mushes conditions the progress of re-awakening, however their processes are poorly understood. Crystal-rich but mobile systems, dominated by their granular mechanics, are not satisfactorily explained from either fluid or solid-like models. We will present a generalizing framework for describing the mechanics of crystal-rich mushes based on the notion of force chains. Force chains arise from crystal-crystal contacts and describe the highly non-uniform way that stress is transmitted in a crystal-rich mush. Using CFD-DEM simulations that resolve crystal-scale mechanics, we will show how the populations of crystal mush force chains and their spatial fabric change during an open-system event. We will show how the various forms of dissipation, such as: fluid drag, particle-fluid drag, particle normal and shear lubrication, and contact friction, jointly contribute to the processes of magma mush unlocking, mobilization and fabric formation. We will also describe non-intuitive constitutive behavior such as non-local and non-affine deformation as well as complex, rheological transitions from continuous to discontinuous shear thickening as a function of the dimensionless shear rate. One implication of this is that many of the commonly-invoked postulates about magma behavior such as lock-up at a critical crystallinity and suspension rheology, are better understood from a micro-physical (crystal-scale) perspective as a combination of far-field geometrical controls, local frictional thickening and shear jamming, each with distinct time scales. This kind of crystal-based unifying framework can simultaneously recover diverse processes such as strain-localization, shear-induced dilatency, and help to identify the volumes of resident magma re-mobilized during magma system re-awakening.

Prediction of Microstructure in High-Strength Ductile Forging Parts

NASA Astrophysics Data System (ADS)

Urban, M.; Keul, C.; Back, A.; Bleck, W.; Hirt, G.

2010-06-01

Governmental, environmental and economic demands call for lighter, stiffer and at the same time cheaper products in the vehicle industry. Especially safety relevant parts have to be stiff and at the same time ductile. The strategy of this project was to improve the mechanical properties of forging steel alloys by employing a high-strength and ductile bainitic microstructure in the parts while maintaining cost effective process chains to reach these goals for high stressed forged parts. Therefore, a new steel alloy combined with an optimized process chain has been developed. To optimize the process chain with a minimum of expensive experiments, a numerical approach was developed to predict the microstructure of the steel alloy after the process chain based on FEM simulations of the forging and cooling combined with deformation-time-temperature-transformation-diagrams.

The multiple imputation method: a case study involving secondary data analysis.

PubMed

Walani, Salimah R; Cleland, Charles M

2015-05-01

To illustrate with the example of a secondary data analysis study the use of the multiple imputation method to replace missing data. Most large public datasets have missing data, which need to be handled by researchers conducting secondary data analysis studies. Multiple imputation is a technique widely used to replace missing values while preserving the sample size and sampling variability of the data. The 2004 National Sample Survey of Registered Nurses. The authors created a model to impute missing values using the chained equation method. They used imputation diagnostics procedures and conducted regression analysis of imputed data to determine the differences between the log hourly wages of internationally educated and US-educated registered nurses. The authors used multiple imputation procedures to replace missing values in a large dataset with 29,059 observations. Five multiple imputed datasets were created. Imputation diagnostics using time series and density plots showed that imputation was successful. The authors also present an example of the use of multiple imputed datasets to conduct regression analysis to answer a substantive research question. Multiple imputation is a powerful technique for imputing missing values in large datasets while preserving the sample size and variance of the data. Even though the chained equation method involves complex statistical computations, recent innovations in software and computation have made it possible for researchers to conduct this technique on large datasets. The authors recommend nurse researchers use multiple imputation methods for handling missing data to improve the statistical power and external validity of their studies.

Theory of Neutron Chain Reactions: Extracts from Volume I, Diffusion and Slowing Down of Neutrons: Chapter I. Elementary Theory of Neutron Diffusion. Chapter II. Second Order Diffusion Theory. Chapter III. Slowing Down of Neutrons

DOE R&D Accomplishments Database

Weinberg, Alvin M.; Noderer, L. C.

1951-05-15

The large scale release of nuclear energy in a uranium fission chain reaction involves two essentially distinct physical phenomena. On the one hand there are the individual nuclear processes such as fission, neutron capture, and neutron scattering. These are essentially quantum mechanical in character, and their theory is non-classical. On the other hand, there is the process of diffusion -- in particular, diffusion of neutrons, which is of fundamental importance in a nuclear chain reaction. This process is classical; insofar as the theory of the nuclear chain reaction depends on the theory of neutron diffusion, the mathematical study of chain reactions is an application of classical, not quantum mechanical, techniques.

Teaching Supply Chain Management Complexities: A SCOR Model Based Classroom Simulation

ERIC Educational Resources Information Center

Webb, G. Scott; Thomas, Stephanie P.; Liao-Troth, Sara

2014-01-01

The SCOR (Supply Chain Operations Reference) Model Supply Chain Classroom Simulation is an in-class experiential learning activity that helps students develop a holistic understanding of the processes and challenges of supply chain management. The simulation has broader learning objectives than other supply chain related activities such as the…

Processes controlling the retreat of the Isles Dernieres, a Louisiana barrier-island chain

USGS Publications Warehouse

Dingler, John R.; Reiss, Thomas E.

1991-01-01

The Isles Dernieres is a low-lying, transgressive barrier-island chain situated about 150 km west of the modern Mississippi delta. Much of the Isles Dernieres consists of highly dissected salt-marsh muds that lie at or slightly above sea level and are covered by a veneer of sand along the shoreline facing the Gulf of Mexico. Maximum berm elevations are generally less than 1.5 m above mean sea level. Since the mid-1800s, the initial island has been fragmented into four islands, and the beach face has retreated landward at a rate of more than 10 m/yr. The dominant processes controlling degradation of the chain are cold fronts that pass through the area several times each year and occasional hurricanes. Beach surveys over a 2-year period on the Isles Dernieres document irreversible beach-face retreat in conjunction with multiple cold fronts and one major hurricane (Gilbert). Although both the hurricane and the cold fronts caused the island to erode, the erosional patterns of the two storm types differed from each other. During the two years, over 60 cold fronts collectively caused about 37 m of beach-face retreat, whereas Gilbert itself produced more than 40 m of retreat. A major difference between the two storm types was in the percentage of washover sand produced by each. Commonly, the cold fronts did not create enough of a storm surge to overtop the berm, so most of the material removed from the beach face must have moved offshore or alongshore. Gilbert, in contrast, inundated the study site, and essentially all the sand removed from the beach face moved to the backshore.

Comparative Confocal and Histopathological Study of Corneal Changes in Multiple Myeloma.

PubMed

Micali, Antonio; Roszkowska, Anna M; Postorino, Elisa I; Rania, Laura; Aragona, Emanuela; Wylegala, Edward; Nowinska, Anna; Ieni, Antonio; Calimeri, Sebastiano; Pisani, Antonina; Aragona, Pasquale; Puzzolo, Domenico

2017-01-01

Corneal opacities rarely occur in multiple myeloma (MM). Our study correlates the findings of in vivo confocal microscopy (IVCM), a useful diagnostic tool, with histopathological features of corneal opacities appearing in a patient with MM. Case report. A 53-year-old man developed corneal opacities in both eyes, more pronounced in the left eye. After IVCM examination, he underwent penetrating keratoplasty in the left eye, and the button was processed for light and electron microscopy and immunohistochemistry. The diagnosis of MM was made, as confirmed by the elevation of IgGk light chains. IVCM demonstrated hyperreflective areas at the epithelial level, hyperreflective keratocytes of dendritic and lamellar morphology in whole stroma, and hyperreflective endothelial cells. Histopathological examination disclosed many vacuoles in the epithelial cell cytoplasm and a homogenous granular material in the Bowman layer. In stroma, keratocytes of different shape and size, with vesicles laden with an abnormal material, were evident. In Descemet membrane, the posterior nonbanded zone had a honeycomb appearance because of the presence of many roundish spaces among wide-spaced collagen fibers. Endothelial cells demonstrated vesicles filled with a material of uneven electron density. Immunohistochemical analysis showed strong positivity for IgGk light chains in keratocytes and among stromal lamellae. This is the first study describing a correspondence between IVCM features and histopathological alterations observed in corneal opacities in MM. The results of this study improve the current understanding of the pictures obtained by IVCM studies.

Supply chain dynamics in healthcare services.

PubMed

Samuel, Cherian; Gonapa, Kasiviswanadh; Chaudhary, P K; Mishra, Ananya

2010-01-01

The purpose of this paper is to analyse health service supply chain systems. A great deal of literature is available on supply chain management in finished goods inventory situations; however, little research exists on managing service capacity when finished goods inventories are absent. System dynamics models for a typical service-oriented supply chain such as healthcare processes are developed, wherein three service stages are presented sequentially. Just like supply chains with finished goods inventory, healthcare service supply chains also show dynamic behaviour. Comparing options, service reduction, and capacity adjustment delays showed that reducing capacity adjustment and service delays gives better results. The study is confined to health service-oriented supply chains. Further work includes extending the study to service-oriented supply chains with parallel processing, i.e. having more than one stage to perform a similar operation and also to study the behaviour in service-oriented supply chains that have re-entrant orders and applications. Specific case studies can also be developed to reveal factors relevant to particular service-oriented supply chains. The paper explains the bullwhip effect in healthcare service-oriented supply chains. Reducing stages and capacity adjustment are strategic options for service-oriented supply chains. The paper throws light on policy options for managing healthcare service-oriented supply chain dynamics.

Simulation modelling of central order processing system under resource sharing strategy in demand-driven garment supply chains

NASA Astrophysics Data System (ADS)

Ma, K.; Thomassey, S.; Zeng, X.

2017-10-01

In this paper we proposed a central order processing system under resource sharing strategy for demand-driven garment supply chains to increase supply chain performances. We examined this system by using simulation technology. Simulation results showed that significant improvement in various performance indicators was obtained in new collaborative model with proposed system.

System and method for inventorying multiple remote objects

DOEpatents

Carrender, Curtis L.; Gilbert, Ronald W.

2007-10-23

A system and method of inventorying multiple objects utilizing a multi-level or a chained radio frequency identification system. The system includes a master tag and a plurality of upper level tags and lower level tags associated with respective objects. The upper and lower level tags communicate with each other and the master tag so that reading of the master tag reveals the presence and absence of upper and lower level tags. In the chained RF system, the upper and lower level tags communicate locally with each other in a manner so that more remote tags that are out of range of some of the upper and lower level tags have their information relayed through adjacent tags to the master tag and thence to a controller.

System and method for inventorying multiple remote objects

DOEpatents

Carrender, Curtis L [Morgan Hill, CA; Gilbert, Ronald W [Morgan Hill, CA

2009-12-29

A system and method of inventorying multiple objects utilizing a multi-level or a chained radio frequency identification system. The system includes a master tag and a plurality of upper level tags and lower level tags associated with respective objects. The upper and lower level tags communicate with each other and the master tag so that reading of the master tag reveals the presence and absence of upper and lower level tags. In the chained RF system, the upper and lower level tags communicate locally with each other in a manner so that more remote tags that are out of range of some of the upper and lower level tags have their information relayed through adjacent tags to the master tag and thence to a controller.

Inhibitors of Fatty Acid Synthase for Prostate Cancer

DTIC Science & Technology

2012-05-01

structure, Figure 3) is highly susceptible to nucelophi lic attack. In addition, well- established Diels - Alder chemistry will b e used to crea te...including each of the precurso rs leading to the compounds. Based on multiple criteria including ability to inhibit recombinant enzyme , ability to...The specificity or hydrophobic channel binds the growing fatty acid chain and guides substrate specificity of the enzyme . The short-chain pock et

Evaluation of Manual Spelling, Observational and Incidental Learning Using Computer-Based Instruction with a Tablet PC, Large Screen Projection, and a Forward Chaining Procedure

ERIC Educational Resources Information Center

Purrazzella, Kimberly; Mechling, Linda C.

2013-01-01

The study employed a multiple probe design to investigate the effects of computer-based instruction (CBI) and a forward chaining procedure to teach manual spelling of words to three young adults with moderate intellectual disability in a small group arrangement. The computer-based program included a tablet PC whereby students wrote words directly…

Applying commodity chain analysis to changing modes of alcohol supply in a developing country.

PubMed

Jernigan, D H

2000-12-01

Development sociology has used global commodity chains as one way of analyzing the dynamics of power and profit-taking in globalized production networks made up of multiple firms and occurring in multiple national settings. A substantial portion of the alcohol supply in developing countries is now produced through such production networks. Particularly in the beer and spirits trade, a small number of transnational firms control networks of local producers, importers, advertisers and distributors. These networks serve to embed transnational or transnationally backed brands in the local culture, using the tools of market research, product design and marketing to influence local drinking practices. Case materials from Malaysia's beer industry help to illustrate how the transnational firms dominate in those links of the commodity chain in which monopoly or oligopoly control is most likely to be found: the design/recipe and marketing/advertising nodes. Their control of the commodity chains and extraction of monopoly or oligopoly profits from them places substantial resources and influence over drinking settings and practices in foreign hands. The impact of this influence on state efficacy and autonomy in setting alcohol policy is an important subject for future research on the creation and implementation of effective alcohol policies in developing societies.

Multicompartmental Microcapsules with Orthogonal Programmable Two-Way Sequencing of Hydrophobic and Hydrophilic Cargo Release.

PubMed

Xu, Weinan; Ledin, Petr A; Iatridi, Zacharoula; Tsitsilianis, Constantinos; Tsukruk, Vladimir V

2016-04-11

Multicompartmental responsive microstructures with the capability for the pre-programmed sequential release of multiple target molecules of opposite solubility (hydrophobic and hydrophilic) in a controlled manner have been fabricated. Star block copolymers with dual-responsive blocks (temperature for poly(N-isopropylacrylamide) chains and pH for poly(acrylic acid) and poly(2-vinylpyridine) arms) and unimolecular micellar structures serve as nanocarriers for hydrophobic molecules in the microcapsule shell. The interior of the microcapsule can be loaded with water-soluble hydrophilic macromolecules. For these dual-loaded microcapsules, a programmable and sequential release of hydrophobic and hydrophilic molecules from the shell and core, respectively, can be triggered independently by temperature and pH variations. These stimuli affect the hydrophobicity and chain conformation of the star block copolymers to initiate out-of-shell release (elevated temperature), or change the overall star conformation and interlayer interactions to trigger increased permeability of the shell and out-of-core release (pH). Reversing stimulus order completely alters the release process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

BIOPEP database and other programs for processing bioactive peptide sequences.

PubMed

Minkiewicz, Piotr; Dziuba, Jerzy; Iwaniak, Anna; Dziuba, Marta; Darewicz, Małgorzata

2008-01-01

This review presents the potential for application of computational tools in peptide science based on a sample BIOPEP database and program as well as other programs and databases available via the World Wide Web. The BIOPEP application contains a database of biologically active peptide sequences and a program enabling construction of profiles of the potential biological activity of protein fragments, calculation of quantitative descriptors as measures of the value of proteins as potential precursors of bioactive peptides, and prediction of bonds susceptible to hydrolysis by endopeptidases in a protein chain. Other bioactive and allergenic peptide sequence databases are also presented. Programs enabling the construction of binary and multiple alignments between peptide sequences, the construction of sequence motifs attributed to a given type of bioactivity, searching for potential precursors of bioactive peptides, and the prediction of sites susceptible to proteolytic cleavage in protein chains are available via the Internet as are other approaches concerning secondary structure prediction and calculation of physicochemical features based on amino acid sequence. Programs for prediction of allergenic and toxic properties have also been developed. This review explores the possibilities of cooperation between various programs.

Effects of protein engineering and rational mutagenesis on crystal lattice of single chain antibody fragments

PubMed Central

Kalyoncu, Sibel; Hyun, Jeongmin; Pai, Jennifer C.; Johnson, Jennifer L.; Entzminger, Kevin; Jain, Avni; Heaner, David P.; Morales, Ivan A.; Truskett, Thomas M.; Maynard, Jennifer A.; Lieberman, Raquel L.

2014-01-01

Protein crystallization is dependent upon, and sensitive to, the intermolecular contacts that assist in ordering proteins into a three dimensional lattice. Here we used protein engineering and mutagenesis to affect the crystallization of single chain antibody fragments (scFvs) that recognize the EE epitope (EYMPME) with high affinity. These hypercrystallizable scFvs are under development to assist difficult proteins, such as membrane proteins, in forming crystals, by acting as crystallization chaperones. Guided by analyses of intermolecular crystal lattice contacts, two second-generation anti-EE scFvs were produced, which bind to proteins with installed EE tags. Surprisingly, although non-complementarity determining region (CDR) lattice residues from the parent scFv framework remained unchanged through the processes of protein engineering and rational design, crystal lattices of the derivative scFvs differ. Comparison of energy calculations and the experimentally-determined lattice interactions for this basis set provides insight into the complexity of the forces driving crystal lattice choice and demonstrates the availability of multiple well-ordered surface features in our scFvs capable of forming versatile crystal contacts. PMID:24615866

Preference, resistance to change, and the cumulative decision model.

PubMed

Grace, Randolph C

2018-01-01

According to behavioral momentum theory (Nevin & Grace, 2000a), preference in concurrent chains and resistance to change in multiple schedules are independent measures of a common construct representing reinforcement history. Here I review the original studies on preference and resistance to change in which reinforcement variables were manipulated parametrically, conducted by Nevin, Grace and colleagues between 1997 and 2002, as well as more recent research. The cumulative decision model proposed by Grace and colleagues for concurrent chains is shown to provide a good account of both preference and resistance to change, and is able to predict the increased sensitivity to reinforcer rate and magnitude observed with constant-duration components. Residuals from fits of the cumulative decision model to preference and resistance to change data were positively correlated, supporting the prediction of behavioral momentum theory. Although some questions remain, the learning process assumed by the cumulative decision model, in which outcomes are compared against a criterion that represents the average outcome value in the current context, may provide a plausible model for the acquisition of differential resistance to change. © 2018 Society for the Experimental Analysis of Behavior.

NMR Characterization of Self-Association Domains Promoted by Interactions with LC8 Hub Protein

PubMed Central

Barbar, Elisar; Nyarko, Afua

2014-01-01

Most proteins in interaction networks have a small number of partners, while a few, called hubs, participate in a large number of interactions and play a central role in cell homeostasis. One highly conserved hub is a protein called LC8 that was originally identified as an essential component of the multi-subunit complex dynein but later shown to be also critical in multiple protein complexes in diverse systems. What is intriguing about this hub protein is that it does not passively bind its various partners but emerging evidence suggests that LC8 acts as a dimerization engine that promotes self-association and/or higher order organization of its primarily disordered monomeric partners. This structural organization process does not require ATP but is triggered by long-range allosteric regulation initiated by LC8 binding a pair of disordered chains forming a bivalent or polybivalent scaffold. This review focuses on the role of LC8 in promoting self-association of two of its binding partners, a dynein intermediate chain and a non dynein protein called Swallow. PMID:24757501

Light Chain Cast Nephropathy: Practical Considerations in the Management of Myeloma Kidney-What We Know and What the Future May Hold.

PubMed

Manohar, Sandhya; Nasr, Samih H; Leung, Nelson

2018-05-03

To update and evaluate the current knowledge on pathogenesis and management of light chain cast nephropathy. Light chain cast nephropathy (LCCN) is the leading cause of acute renal failure in patients with multiple myeloma and is currently recognized as a myeloma defining event. The immunoglobulin free light chain plays an integral role in the pathogenesis of LCCN. The level of free light chain (FLC) in the blood and urine is directly associated with the risk of developing LCCN. Recovery of renal function is related to the speed and degree of the serum FLC reduction. Recently, two randomized trials using high cutoff dialyzer for the removal of serum FLC produced different results in terms of renal recovery. FLC plays a key role in the development and resolution of LCCN. Future therapies will aim to rapidly reduce its concentration or interrupt its interaction with Tamm-Horsfall protein.

Evolutionary inference via the Poisson Indel Process.

PubMed

Bouchard-Côté, Alexandre; Jordan, Michael I

2013-01-22

We address the problem of the joint statistical inference of phylogenetic trees and multiple sequence alignments from unaligned molecular sequences. This problem is generally formulated in terms of string-valued evolutionary processes along the branches of a phylogenetic tree. The classic evolutionary process, the TKF91 model [Thorne JL, Kishino H, Felsenstein J (1991) J Mol Evol 33(2):114-124] is a continuous-time Markov chain model composed of insertion, deletion, and substitution events. Unfortunately, this model gives rise to an intractable computational problem: The computation of the marginal likelihood under the TKF91 model is exponential in the number of taxa. In this work, we present a stochastic process, the Poisson Indel Process (PIP), in which the complexity of this computation is reduced to linear. The Poisson Indel Process is closely related to the TKF91 model, differing only in its treatment of insertions, but it has a global characterization as a Poisson process on the phylogeny. Standard results for Poisson processes allow key computations to be decoupled, which yields the favorable computational profile of inference under the PIP model. We present illustrative experiments in which Bayesian inference under the PIP model is compared with separate inference of phylogenies and alignments.

Evolutionary inference via the Poisson Indel Process

PubMed Central

Bouchard-Côté, Alexandre; Jordan, Michael I.

2013-01-01

We address the problem of the joint statistical inference of phylogenetic trees and multiple sequence alignments from unaligned molecular sequences. This problem is generally formulated in terms of string-valued evolutionary processes along the branches of a phylogenetic tree. The classic evolutionary process, the TKF91 model [Thorne JL, Kishino H, Felsenstein J (1991) J Mol Evol 33(2):114–124] is a continuous-time Markov chain model composed of insertion, deletion, and substitution events. Unfortunately, this model gives rise to an intractable computational problem: The computation of the marginal likelihood under the TKF91 model is exponential in the number of taxa. In this work, we present a stochastic process, the Poisson Indel Process (PIP), in which the complexity of this computation is reduced to linear. The Poisson Indel Process is closely related to the TKF91 model, differing only in its treatment of insertions, but it has a global characterization as a Poisson process on the phylogeny. Standard results for Poisson processes allow key computations to be decoupled, which yields the favorable computational profile of inference under the PIP model. We present illustrative experiments in which Bayesian inference under the PIP model is compared with separate inference of phylogenies and alignments. PMID:23275296

Differential recruitment efficacy of patient-derived amyloidogenic and myeloma light chain proteins by synthetic fibrils-A metric for predicting amyloid propensity.

PubMed

Martin, Emily B; Williams, Angela; Wooliver, Craig; Heidel, R Eric; Adams, Sarah; Dunlap, John; Ramirez-Alvarado, Marina; Blancas-Mejia, Luis M; Lands, Ronald H; Kennel, Stephen J; Wall, Jonathan S

2017-01-01

Monoclonal free light chain (LC) proteins are present in the circulation of patients with immunoproliferative disorders such as light chain (AL) amyloidosis and multiple myeloma (MM). Light chain-associated amyloid is a complex pathology composed of proteinaceous fibrils and extracellular matrix proteins found in all patients with AL and in ~10-30% of patients who presented with MM. Amyloid deposits systemically in multiple organs and tissues leading to dysfunction and ultimately death. The overall survival of patients with amyloidosis is worse than for those with early stage MM. We have developed a sensitive binding assay quantifying the recruitment of full length, patient-derived LC proteins by synthetic amyloid fibrils, as a method for studying their amyloidogenic potential. In a survey of eight urinary LC, both AL and MM-associated proteins were recruited by synthetic amyloid fibrils; however, AL-associated LC bound significantly more efficiently (p < 0.05) than did MM LCs. The LC proteins used in this study were isolated from urine and presumed to represent a surrogate of serum free light chains. The binding of LC to synthetic fibrils in this assay accurately differentiated LC with amyloidogenic propensity from MM LC that were not associated with clinical amyloid disease. Notably, the LC from a MM patient who subsequently developed amyloid behaved as an AL-associated protein in the assay, indicating the possibility for identifying MM patients at risk for developing amyloidosis based on the light chain recruitment efficacy. With this information, at risk patients can be monitored more closely for the development of amyloidosis, allowing timely administration of novel, amyloid-directed immunotherapies-this approach may improve the prognosis for these patients.

The Development of a Strategic Prioritisation Method for Green Supply Chain Initiatives.

PubMed

Masoumik, S Maryam; Abdul-Rashid, Salwa Hanim; Olugu, Ezutah Udoncy

2015-01-01

To maintain a competitive position, companies are increasingly required to integrate their proactive environmental strategies into their business strategies. The shift from reactive and compliance-based to proactive and strategic environmental management has driven companies to consider the strategic factors while identifying the areas in which they should focus their green initiatives. In previous studies little attention was given to providing the managers with a basis from which they could strategically prioritise these green initiatives across their companies' supply chains. Considering this lacuna in the literature, we present a decision-making method for prioritising green supply chain initiatives aligned with the preferred green strategies alternatives for the manufacturing companies. To develop this method, the study considered a position between determinism and the voluntarism orientation of environmental management involving both external pressures and internal competitive drivers and key resources as decision factors. This decision-making method was developed using the analytic network process (ANP) technique. The elements of the decision model were derived from the literature. The causal relationships among the multiple decision variables were validated based on the results of structural equation modelling (SEM) using a dataset collected from a survey of the ISO 14001-certified manufacturers in Malaysia. A portion of the relative weights required for computation in ANP was also calculated using the SEM results. A case study is presented to demonstrate the applicability of the method.

The Development of a Strategic Prioritisation Method for Green Supply Chain Initiatives

PubMed Central

Masoumik, S. Maryam; Abdul-Rashid, Salwa Hanim; Olugu, Ezutah Udoncy

2015-01-01

To maintain a competitive position, companies are increasingly required to integrate their proactive environmental strategies into their business strategies. The shift from reactive and compliance-based to proactive and strategic environmental management has driven companies to consider the strategic factors while identifying the areas in which they should focus their green initiatives. In previous studies little attention was given to providing the managers with a basis from which they could strategically prioritise these green initiatives across their companies’ supply chains. Considering this lacuna in the literature, we present a decision-making method for prioritising green supply chain initiatives aligned with the preferred green strategies alternatives for the manufacturing companies. To develop this method, the study considered a position between determinism and the voluntarism orientation of environmental management involving both external pressures and internal competitive drivers and key resources as decision factors. This decision-making method was developed using the analytic network process (ANP) technique. The elements of the decision model were derived from the literature. The causal relationships among the multiple decision variables were validated based on the results of structural equation modelling (SEM) using a dataset collected from a survey of the ISO 14001-certified manufacturers in Malaysia. A portion of the relative weights required for computation in ANP was also calculated using the SEM results. A case study is presented to demonstrate the applicability of the method. PMID:26618353

Optimization of a Multi-Product Intra-Supply Chain System with Failure in Rework.

PubMed

Chiu, Singa Wang; Chen, Shin-Wei; Chang, Chih-Kai; Chiu, Yuan-Shyi Peter

2016-01-01

Globalization has created tremendous opportunities, but also made business environment highly competitive and turbulent. To gain competitive advantage, management of present-day transnational firms always seeks options to trim down various transaction and coordination costs, especially in the area of controllable intra-supply chain system. This study investigates a multi-product intra-supply chain system with failure in rework. To achieve maximum machine utilization, multiple products are fabricated in succession on a single machine. During the process, production of some defective items is inevitable. Reworking of nonconforming items is used to reduce the quality cost in production and achieving the goal of lower overall production cost. Because reworks are sometimes unsuccessful, failures in rework are also considered in this study. Finished goods for each product are transported to the sales offices when the entire production lot is quality assured after rework. A multi-delivery policy is used, wherein fixed quantity n installments of the finished lot are transported at fixed intervals during delivery time. The objective is to jointly determine the common production cycle time and the number of deliveries needed to minimize the long-term expected production-inventory-delivery costs for the problem. With the help of a mathematical model along with optimization technique, the optimal production-shipment policy is obtained. We have used a numerical example to demonstrate applicability of the result of our research.

Optimization of a Multi–Product Intra-Supply Chain System with Failure in Rework

PubMed Central

2016-01-01

Globalization has created tremendous opportunities, but also made business environment highly competitive and turbulent. To gain competitive advantage, management of present-day transnational firms always seeks options to trim down various transaction and coordination costs, especially in the area of controllable intra-supply chain system. This study investigates a multi–product intra-supply chain system with failure in rework. To achieve maximum machine utilization, multiple products are fabricated in succession on a single machine. During the process, production of some defective items is inevitable. Reworking of nonconforming items is used to reduce the quality cost in production and achieving the goal of lower overall production cost. Because reworks are sometimes unsuccessful, failures in rework are also considered in this study. Finished goods for each product are transported to the sales offices when the entire production lot is quality assured after rework. A multi-delivery policy is used, wherein fixed quantity n installments of the finished lot are transported at fixed intervals during delivery time. The objective is to jointly determine the common production cycle time and the number of deliveries needed to minimize the long–term expected production–inventory–delivery costs for the problem. With the help of a mathematical model along with optimization technique, the optimal production–shipment policy is obtained. We have used a numerical example to demonstrate applicability of the result of our research. PMID:27918588

ONR Far East Scientific Information Bulletin

DTIC Science & Technology

1990-09-01

In bone, grafting onto a polymer chain, inter- continuous processes, such as reactive extru- chain reactions, formation of interpenetrat- sion and...reaction kinetics, rheology, and side- and end-chain grafting , homopolymer transport phenomena occurring during REX. chain coupling, polymer...the Grafting reactions yield block or graft coupling species becomes a part of the chain, copolymers. Polyethylene, polypropylene, or by

Taking stock: protocol for evaluating a family planning supply chain intervention in Senegal.

PubMed

Cavallaro, Francesca L; Duclos, Diane; Baggaley, Rebecca F; Penn-Kekana, Loveday; Goodman, Catherine; Vahanian, Alice; Santos, Andreia C; Bradley, John; Paintain, Lucy; Gallien, Jérémie; Gasparrini, Antonio; Hasselback, Leah; Lynch, Caroline A

2016-04-21

In Senegal, only 12% of women of reproductive age in union (WRAU) were using contraceptives and another 29% had an unmet need for contraceptives in 2010-11. One potential barrier to accessing contraceptives is the lack of stock availability in health facilities where women seek them. Multiple supply chain interventions have been piloted in low- and middle-income countries with the aim of improving contraceptive availability in health facilities. However, there is limited evidence on the effect of these interventions on contraceptive availability in facilities, and in turn on family planning use in the population. This evaluation protocol pertains to a supply chain intervention using performance-based contracting for contraceptive distribution that was introduced throughout Senegal between 2012 and 2015. This multi-disciplinary research project will include quantitative, qualitative and economic evaluations. Trained researchers in the different disciplines will implement the studies separately but alongside each other, sharing findings throughout the project to inform each other's data collection. A non-randomised study with stepped-wedge design will be used to estimate the effect of the intervention on contraceptive stock availability in health facilities, and on the modern contraceptive prevalence rate among women in Senegal, compared to the current pull-based distribution model used for other commodities. Secondary data from annual Service Provision Assessments and Demographic and Health Surveys will be used for this study. Data on stock availability and monthly family planning consultations over a 4-year period will be collected from 200 health facilities in five regions to perform time series analyses. A process evaluation will be conducted to understand the extent to which the intervention was implemented as originally designed, the acceptability of third-party logisticians within the health system and potential unintended consequences. These will be assessed using monthly indicator data from the implementer and multiple ethnographic methods, including in-depth interviews with key informants and stakeholders at all levels of the distribution system, observations of third-party logisticians and clinic diaries. An economic evaluation will estimate the cost of the intervention, as well as its cost-effectiveness compared to the current supply chain model. Given the very limited evidence base, there is an important need for a comprehensive standardised approach to evaluating supply chain management, and distribution specifically. This evaluation will help address this evidence gap by providing rigorous evidence on whether private performance-based contracting for distribution of contraceptives can contribute to improving access to family planning in low- and middle-income countries.

Effects of the internal friction and the solvent quality on the dynamics of a polymer chain closure.

PubMed

Yu, Wancheng; Luo, Kaifu

2015-03-28

Using 3D Langevin dynamics simulations, we investigate the effects of the internal friction and the solvent quality on the dynamics of a polymer chain closure. We show that the chain closure in good solvents is a purely diffusive process. By extrapolation to zero solvent viscosity, we find that the internal friction of a chain plays a non-ignorable role in the dynamics of the chain closure. When the solvent quality changes from good to poor, the mean closure time τc decreases by about 1 order of magnitude for the chain length 20 ≤ N ≤ 100. Furthermore, τc has a minimum as a function of the solvent quality. With increasing the chain length N, the minimum of τc occurs at a better solvent. Finally, the single exponential distributions of the closure time in poor solvents suggest that the negative excluded volume of segments does not alter the nearly Poisson statistical characteristics of the process of the chain closure.

Land transportation model for supply chain manufacturing industries

NASA Astrophysics Data System (ADS)

Kurniawan, Fajar

2017-12-01

Supply chain is a system that integrates production, inventory, distribution and information processes for increasing productivity and minimize costs. Transportation is an important part of the supply chain system, especially for supporting the material distribution process, work in process products and final products. In fact, Jakarta as the distribution center of manufacturing industries for the industrial area. Transportation system has a large influences on the implementation of supply chain process efficiency. The main problem faced in Jakarta is traffic jam that will affect on the time of distribution. Based on the system dynamic model, there are several scenarios that can provide solutions to minimize timing of distribution that will effect on the cost such as the construction of ports approaching industrial areas other than Tanjung Priok, widening road facilities, development of railways system, and the development of distribution center.

Simple model of inhibition of chain-branching combustion processes

NASA Astrophysics Data System (ADS)

Babushok, Valeri I.; Gubernov, Vladimir V.; Minaev, Sergei S.; Miroshnichenko, Taisia P.

2017-11-01

A simple kinetic model has been suggested to describe the inhibition and extinction of flame propagation in reaction systems with chain-branching reactions typical for hydrocarbon systems. The model is based on the generalised model of the combustion process with chain-branching reaction combined with the one-stage reaction describing the thermal mode of flame propagation with the addition of inhibition reaction steps. Inhibitor addition suppresses the radical overshoot in flame and leads to the change of reaction mode from the chain-branching reaction to a thermal mode of flame propagation. With the increase of inhibitor the transition of chain-branching mode of reaction to the reaction with straight-chains (non-branching chain reaction) is observed. The inhibition part of the model includes a block of three reactions to describe the influence of the inhibitor. The heat losses are incorporated into the model via Newton cooling. The flame extinction is the result of the decreased heat release of inhibited reaction processes and the suppression of radical overshoot with the further decrease of the reaction rate due to the temperature decrease and mixture dilution. A comparison of the results of modelling laminar premixed methane/air flames inhibited by potassium bicarbonate (gas phase model, detailed kinetic model) with the results obtained using the suggested simple model is presented. The calculations with the detailed kinetic model demonstrate the following modes of combustion process: (1) flame propagation with chain-branching reaction (with radical overshoot, inhibitor addition decreases the radical overshoot down to the equilibrium level); (2) saturation of chemical influence of inhibitor, and (3) transition to thermal mode of flame propagation (non-branching chain mode of reaction). The suggested simple kinetic model qualitatively reproduces the modes of flame propagation with the addition of the inhibitor observed using detailed kinetic models.

APOE ε4 and the associations of seafood and long-chain omega-3 fatty acids with cognitive decline

PubMed Central

Wang, Yamin; Barnes, Lisa L.; Tangney, Christine; Bennett, David A.; Morris, Martha Clare

2016-01-01

Objective: To examine the association between consumption of seafood and long-chain n-3 fatty acids with change in 5 cognitive domains over an average of 4.9 years. Methods: From an ongoing longitudinal, community-based epidemiologic study of aging and dementia (the Rush Memory and Aging Project), we included 915 participants (age 81.4 ± 7.2 years, 25% men) who had completed at least one follow-up cognitive assessment and dietary data. Diet was assessed by semiquantitative food frequency questionnaire. Scores for global cognitive function and 5 cognitive domains (episodic, semantic, and working memory, perceptual speed, and visuospatial ability) were assessed using 19 cognitive tests. Mixed models adjusted for multiple risk factors of cognitive change were used to assess the associations. Results: Consumption of seafood was associated with slower decline in semantic memory (β = 0.024; p = 0.03) and perceptual speed (β = 0.020; p = 0.05) in separate models adjusted for age, sex, education, participation in cognitive activities, physical activity, alcohol consumption, smoking, and total energy intake. In secondary analyses, APOE ε4 carriers demonstrated slower rates of decline in global cognition and in multiple cognitive domains with weekly seafood consumption and with moderate to high long-chain n-3 fatty acid intake from food. These associations were not present in APOE ε4 noncarriers. Higher intake levels of α-linolenic acid were associated with slower global cognitive decline, but also only in APOE ε4 carriers. Conclusions: These results suggest protective relations of one meal per week of seafood and long-chain n-3 fatty acids against decline in multiple cognitive domains. The role of APOE ε4 in this association needs further study. PMID:27164694

Influence of semisynthetic modification of the scaffold of a contact domain of HbS on polymerization: role of flexible surface topology in polymerization inhibition.

PubMed

Sonati, Srinivasulu; Bhutoria, Savita; Prabhakaran, Muthuchidambaran; Acharya, Seetharama A

2018-02-01

A new variant of HbS, HbS-Einstein with a deletion of segment α 23-26 in the B-helix, has been assembled by semisynthetic approach. B-helix of the α chain of cis αβ-dimer of HbS plays dominant role in the quinary interactions of deoxy HbS dimer. This B-helix is the primary scaffold that provides the orientation for the side chains of contact residues of this intermolecular contact domain. The design of HbS-Einstein has been undertaken to map the influence of perturbation of molecular surface topology and the flexibility of surface residues in the polymerization. The internal deletion exerts a strong inhibitory influence on Val-6 (β)-dependent polymerization, comparable to single contact site mutations and not for complete neutralization of Val-6(β)-dependent polymerization. The scaffold modification in cis-dimer is inhibitory, and is without any effect when present on the trans dimer. The flexibility changes in the surface topology in the region of scaffold modification apparently counteracts the intrinsic polymerization potential of the molecule. The inhibition is close to that of Le Lamentin mutation [His-20 (α) → Gln] wherein a mutation engineered without much change in flexibility of the contact domain. Interestingly, the chimeric HbS with swine-human chimeric α chain with multiple non-conservative mutations completely inhibits the Val-6(β)-dependent polymerization. The deformabilities of surface topology of chimeric HbS are comparable to HbS in spite of the multiple contact site mutations in the α-chain. We conclude that the design of antisickling Hbs for gene therapy of sickle cell disease should involve multiple mutations of intermolecular contact sites.

The controlled relay of multiple protons required at the active site of nitrogenase.

PubMed

Dance, Ian

2012-07-07

The enzyme nitrogenase, when reducing natural and unnatural substrates, requires large numbers of protons per chemical catalytic cycle. The active face of the catalytic site (the FeMo-cofactor, FeMo-co) is situated in a protein domain which is largely hydrophobic and anhydrous, and incapable of serial provision of multiple protons. Through detailed analysis of the high quality protein crystal structures available the characteristics of a chain of water molecules leading from the protein surface to a key sulfur atom (S3B) of FeMo-co are described. The first half of the water chain from the surface inwards is branched, slightly variable, and able to accommodate exogenous small molecules: this is dubbed the proton bay. The second half, from the proton bay to S3B, is comprised of a single chain of eight hydrogen bonded water molecules. This section is strictly conserved, and is intimately involved in hydrogen bonds with homocitrate, an essential component that chelates Mo. This is the proton wire, and a detailed Grotthuss mechanism for serial translocation of protons through this proton wire to S3B is proposed. This controlled serial proton relay from the protein surface to S3B is an essential component of the intramolecular hydrogenation paradigm for the complete chemical mechanisms of nitrogenase. Each proton reaching S3B, instigated by electron transfer to FeMo-co, becomes a hydrogen atom that migrates to other components of the active face of FeMo-co and to bound substrates and intermediates, allowing subsequent multiple proton transfers along the proton wire. Experiments to test the proposed mechanism of proton supply are suggested. The water chain in nitrogenase is comparable with the purported proton pumping pathway of cytochrome c oxidase.

The value marketing chain in health care.

PubMed

MacStravic, S

1999-01-01

In health care, Michael Porter's value chain can be reconceptualized as a "Value Marketing Chain," in which value is reinforced during each step of the customer recruitment and retention process. "Value" is a concept that must jointly be defined by buyer and seller as they interact every step of the way during the process. This requires the establishment of end-to-end mechanisms for soliciting feedback from customers.

Modelling inter-supply chain competition with resource limitation and demand disruption

NASA Astrophysics Data System (ADS)

Chen, Zhaobo; Teng, Chunxian; Zhang, Ding; Sun, Jiayi

2016-05-01

This paper proposes a comprehensive model for studying supply chain versus supply chain competition with resource limitation and demand disruption. We assume that there are supply chains with heterogeneous supply network structures that compete at multiple demand markets. Each supply chain is comprised of internal and external firms. The internal firms are coordinated in production and distribution and share some common but limited resources within the supply chain, whereas the external firms are independent and do not share the internal resources. The supply chain managers strive to develop optimal strategies in terms of production level and resource allocation in maximising their profit while facing competition at the end market. The Cournot-Nash equilibrium of this inter-supply chain competition is formulated as a variational inequality problem. We further study the case when there is demand disruption in the plan-execution phase. In such a case, the managers need to revise their planned strategy in order to maximise their profit with the new demand under disruption and minimise the cost of change. We present a bi-criteria decision-making model for supply chain managers and develop the optimal conditions in equilibrium, which again can be formulated by another variational inequality problem. Numerical examples are presented for illustrative purpose.

Coordinating a Supply Chain with Price and Advertisement Dependent Stochastic Demand

PubMed Central

Li, Liying; Wang, Yong; Yan, Xiaoming

2013-01-01

This paper investigates pricing and ordering as well as advertising coordination issues in a single-manufacturer single-retailer supply chain, where the manufacturer sells a newsvendor-type product through the retailer who faces a stochastic demand depending on both retail price and advertising expenditure. Under the assumption that the market demand has a multiplicative functional form, the Stackelberg and cooperative game models are developed, and the closed form solution to each model is provided as well. Comparisons and insights are presented. We show that a properly designed revenue-cost-sharing contract can achieve supply chain coordination and lead to a Pareto improving win-win situation for channel members. We also discuss the allocation of the extra joint profit according to individual supply chain members' risk preferences and negotiating powers. PMID:24453832

Coordinating a supply chain with price and advertisement dependent stochastic demand.

PubMed

Li, Liying; Wang, Yong; Yan, Xiaoming

2013-01-01

This paper investigates pricing and ordering as well as advertising coordination issues in a single-manufacturer single-retailer supply chain, where the manufacturer sells a newsvendor-type product through the retailer who faces a stochastic demand depending on both retail price and advertising expenditure. Under the assumption that the market demand has a multiplicative functional form, the Stackelberg and cooperative game models are developed, and the closed form solution to each model is provided as well. Comparisons and insights are presented. We show that a properly designed revenue-cost-sharing contract can achieve supply chain coordination and lead to a Pareto improving win-win situation for channel members. We also discuss the allocation of the extra joint profit according to individual supply chain members' risk preferences and negotiating powers.

Linear and nonlinear dynamic analysis of redundant load path bearingless rotor systems

NASA Technical Reports Server (NTRS)

Murthy, V. R.

1985-01-01

The bearingless rotorcraft offers reduced weight, less complexity and superior flying qualities. Almost all the current industrial structural dynamic programs of conventional rotors which consist of single load path rotor blades employ the transfer matrix method to determine natural vibration characteristics because this method is ideally suited for one dimensional chain like structures. This method is extended to multiple load path rotor blades without resorting to an equivalent single load path approximation. Unlike the conventional blades, it isk necessary to introduce the axial-degree-of-freedom into the solution process to account for the differential axial displacements in the different load paths. With the present extension, the current rotor dynamic programs can be modified with relative ease to account for the multiple load paths without resorting to the equivalent single load path modeling. The results obtained by the transfer matrix method are validated by comparing with the finite element solutions. A differential stiffness matrix due to blade rotation is derived to facilitate the finite element solutions.

The South Georgia and the South Sandwich Islands MPA: protecting a biodiverse oceanic island chain situated in the flow of the antarctic circumpolar current.

PubMed

Trathan, Philip N; Collins, Martin A; Grant, Susie M; Belchier, Mark; Barnes, David K A; Brown, Judith; Staniland, Iain J

2014-01-01

South Georgia and the South Sandwich Islands (SGSSI) are surrounded by oceans that are species-rich, have high levels of biodiversity, important endemism and which also support large aggregations of charismatic upper trophic level species. Spatial management around these islands is complex, particularly in the context of commercial fisheries that exploit some of these living resources. Furthermore, management is especially complicated as local productivity relies fundamentally upon biological production transported from outside the area. The MPA uses practical management boundaries, allowing access for the current legal fisheries for Patagonian toothfish, mackerel icefish and Antarctic krill. Management measures developed as part of the planning process designated the whole SGSSI Maritime Zone as an IUCN Category VI reserve, within which a number of IUCN Category I reserves were identified. Multiple-use zones and temporal closures were also designated. A key multiple-use principle was to identify whether the ecological impacts of a particular fishery threatened either the pelagic or benthic domain.

Organization of polymer chains onto long, single-wall carbon nano-tubes: effect of tube diameter and cooling method.

PubMed

Kumar, Sunil; Pattanayek, Sudip K; Pereira, Gerald G

2014-01-14

We use molecular dynamics simulations to investigate the arrangement of polymer chains when absorbed onto a long, single-wall carbon nano-tube (SWCNT). We study the conformation and organization of the polymer chains on the SWCNT and their dependence on the tube's diameter and the rate of cooling. We use two types of cooling processes: direct quenching and gradual cooling. The radial density distribution function and bond orientational order parameter are used to characterize the polymer chain structure near the surface. In the direct cooling process, the beads of the polymer chain organize in lamella-like patterns on the surface of the SWCNT with the long axis of the lamella parallel to the axis of the SWCNT. In a stepwise, gradual cooling process, the polymer beads form a helical pattern on the surface of a relatively thick SWCNT, but form a lamella-like pattern on the surface of a very thin SWCNT. We develop a theoretical (free energy) model to explain this difference in pattern structures for the gradual cooling process and also provide a qualitative explanation for the pattern that forms from the direct cooling process.

Performance of a portable chain flail delimber/debarker processing northern hardwoods.

Treesearch

Michael A. Thompson; John A. Sturos

1991-01-01

Evaluates the performance of a Peterson Pacific 4800 chain flail delimber/debarker processing pole-size hardwoods in northern Michigan. Describes the productivity, cost, and delimbing/debarking quality achieved by the flail.

Supply chain planning classification

NASA Astrophysics Data System (ADS)

Hvolby, Hans-Henrik; Trienekens, Jacques; Bonde, Hans

2001-10-01

Industry experience a need to shift in focus from internal production planning towards planning in the supply network. In this respect customer oriented thinking becomes almost a common good amongst companies in the supply network. An increase in the use of information technology is needed to enable companies to better tune their production planning with customers and suppliers. Information technology opportunities and supply chain planning systems facilitate companies to monitor and control their supplier network. In spite if these developments, most links in today's supply chains make individual plans, because the real demand information is not available throughout the chain. The current systems and processes of the supply chains are not designed to meet the requirements now placed upon them. For long term relationships with suppliers and customers, an integrated decision-making process is needed in order to obtain a satisfactory result for all parties. Especially when customized production and short lead-time is in focus. An effective value chain makes inventory available and visible among the value chain members, minimizes response time and optimizes total inventory value held throughout the chain. In this paper a supply chain planning classification grid is presented based current manufacturing classifications and supply chain planning initiatives.

Design of ligand-targeted nanoparticles for enhanced cancer targeting

NASA Astrophysics Data System (ADS)

Stefanick, Jared F.

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

Countermine Warfare Analysis

DTIC Science & Technology

1981-06-01

which were Matilda and Valentine tanks fitted with heavy chain flails. As a front-mounted drum rotated, the chains were thrust forward to strike the...Detector, truck-mounted (UAZ-69 or UAZ-469 trucks) mine detector. The mine detection device is fitted to the truck brakes to stop it automati- cally...employed by the Soviets. The plows are controlled separately from inside the tank, and rollers are made up-of multiple discs of various I configurations. A

Negotiation-based Order Lot-Sizing Approach for Two-tier Supply Chain

NASA Astrophysics Data System (ADS)

Chao, Yuan; Lin, Hao Wen; Chen, Xili; Murata, Tomohiro

This paper focuses on a negotiation based collaborative planning process for the determination of order lot-size over multi-period planning, and confined to a two-tier supply chain scenario. The aim is to study how negotiation based planning processes would be used to refine locally preferred ordering patterns, which would consequently affect the overall performance of the supply chain in terms of costs and service level. Minimal information exchanges in the form of mathematical models are suggested to represent the local preferences and used to support the negotiation processes.

Improved zeolite regeneration processes for preparing saturated branched-chain fatty acids

USDA-ARS?s Scientific Manuscript database

Ferrierite zeolite solid is an excellent catalyst for the skeletal isomerization of unsaturated linear-chain fatty acids (i.e., oleic acid) to unsaturated branched-chain fatty acids (i.e., iso-oleic acid) follow by hydrogenation to give saturated branched-chain fatty acids (i.e., isostearic acid). ...

The long underestimated carbonyl function of carbohydrates – an organocatalyzed shot into carbohydrate chemistry.

PubMed

Mahrwald, R

2015-09-21

The aggressive and strong development of organocatalysis provides several protocols for the convenient utilization of the carbonyl function of unprotected carbohydrates in C-C-bond formation processes. These amine-catalyzed mechanisms enable multiple cascade-protocols for the synthesis of a wide range of carbohydrate-derived compound classes. Several, only slightly different protocols, have been developed for the application of 1,3-dicarbonyl compounds in the stereoselective chain-elongation of unprotected carbohydrates and the synthesis of highly functionalized C-glycosides of defined configuration. In addition, C-glycosides can also be accessed by amine-catalyzed reactions with methyl ketones. By a one-pot cascade reaction of isocyanides with unprotected aldoses and amino acids access to defined configured glycopeptide mimetics is achieved. Depending on the reaction conditions different origins to control the installation of configuration during the bond-formation process were observed.

From cognition to the system: developing a multilevel taxonomy of patient safety in general practice.

PubMed

Kostopoulou, O

The paper describes the process of developing a taxonomy of patient safety in general practice. The methodologies employed included fieldwork, task analysis and confidential reporting of patient-safety events in five West Midlands practices. Reported events were traced back to their root causes and contributing factors. The resulting taxonomy is based on a theoretical model of human cognition, includes multiple levels of classification to reflect the chain of causation and considers affective and physiological influences on performance. Events are classified at three levels. At level one, the information-processing model of cognition is used to classify errors. At level two, immediate causes are identified, internal and external to the individual. At level three, more remote causal factors are classified as either 'work organization' or 'technical' with subcategories. The properties of the taxonomy (validity, reliability, comprehensiveness) as well as its usability and acceptability remain to be tested with potential users.

Evaluating the efficacy of amino acids as CO2 capturing agents: a first principles investigation.

PubMed

Hussain, M Althaf; Soujanya, Yarasi; Sastry, G Narahari

2011-10-01

Comprehension of the basic concepts for the design of systems for CO2 adsorption is imperative for increasing interest in technology for CO2 capture from the effluents. The efficacy of 20 naturally occurring amino acids (AAs) is demonstrated as the most potent CO2 capturing agents in the process of chemical absorption and physisorption through a systematic computational study using highly parametrized M05-2X/6-311+G(d,p) method. The ability of AAs to bind CO2 both in the noncovalent and covalent fashion and presence of multiple adsorption sites with varying magnitude of binding strengths in all 20 AAs makes them as most promising materials in the process of physisorption. The binding energies (BEs) estimating the strength of noncovalent interaction of AAs and CO2 are calculated and results are interpreted in terms of the nature and strength of the various types of cooperative interactions which are present. The study underlines the possibility to engineer the porous solid materials with extended networks by judiciously employing AA chains as linkers which can substantially augment their efficacy. Results show that a significant increase in the CO2···AA affinity is achieved in the case of AAs with polar neutral side chains. Furthermore, the study proposes AAs as effective alternatives to alkanolamines in chemical dissolution of CO2.

N-body simulations of terrestrial planet formation under the influence of a hot Jupiter

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

Ogihara, Masahiro; Kobayashi, Hiroshi; Inutsuka, Shu-ichiro, E-mail: omasahiro@oca.eu, E-mail: ogihara@nagoya-u.jp

We investigate the formation of multiple-planet systems in the presence of a hot Jupiter (HJ) using extended N-body simulations that are performed simultaneously with semianalytic calculations. Our primary aims are to describe the planet formation process starting from planetesimals using high-resolution simulations, and to examine the dependences of the architecture of planetary systems on input parameters (e.g., disk mass, disk viscosity). We observe that protoplanets that arise from oligarchic growth and undergo type I migration stop migrating when they join a chain of resonant planets outside the orbit of an HJ. The formation of a resonant chain is almost independentmore » of our model parameters, and is thus a robust process. At the end of our simulations, several terrestrial planets remain at around 0.1 AU. The formed planets are not equal mass; the largest planet constitutes more than 50% of the total mass in the close-in region, which is also less dependent on parameters. In the previous work of this paper, we have found a new physical mechanism of induced migration of the HJ, which is called a crowding-out. If the HJ opens up a wide gap in the disk (e.g., owing to low disk viscosity), crowding-out becomes less efficient and the HJ remains. We also discuss angular momentum transfer between the planets and disk.« less

End-to-end System Performance Simulation: A Data-Centric Approach

NASA Astrophysics Data System (ADS)

Guillaume, Arnaud; Laffitte de Petit, Jean-Luc; Auberger, Xavier

2013-08-01

In the early times of space industry, the feasibility of Earth observation missions was directly driven by what could be achieved by the satellite. It was clear to everyone that the ground segment would be able to deal with the small amount of data sent by the payload. Over the years, the amounts of data processed by the spacecrafts have been increasing drastically, leading to put more and more constraints on the ground segment performances - and in particular on timeliness. Nowadays, many space systems require high data throughputs and short response times, with information coming from multiple sources and involving complex algorithms. It has become necessary to perform thorough end-to-end analyses of the full system in order to optimise its cost and efficiency, but even sometimes to assess the feasibility of the mission. This paper presents a novel framework developed by Astrium Satellites in order to meet these needs of timeliness evaluation and optimisation. This framework, named ETOS (for “End-to-end Timeliness Optimisation of Space systems”), provides a modelling process with associated tools, models and GUIs. These are integrated thanks to a common data model and suitable adapters, with the aim of building suitable space systems simulators of the full end-to-end chain. A big challenge of such environment is to integrate heterogeneous tools (each one being well-adapted to part of the chain) into a relevant timeliness simulation.

Analysis of Business Process at PT XYZ by Using SCOR Thread Diagram

NASA Astrophysics Data System (ADS)

Sembiring, M. T.; Rambe, H. C.

2017-03-01

Supply Chain Operations Reference (SCOR) is a standard supply chain performance evaluation model which is proposed by Supply Chain Council (SCC). SCOR makes companies can analyse and evaluate their supply chain performance. SCOR has Thread Diagram which describes business process simply and systematically to help the analysis of company’s business process. This research takes place in PT XYZ that is involved in Crude Palm Oil (CPO) industry. PT XYZ used to be the market leader of CPO industry but nowadays they have a trouble to compete with new competitors. The purpose of this study is to provide the input for PT XYZ business process improvement to enhance the competitiveness of the company with the others. The result obtained shows that there are two performance metrics that are not reached. The analysis of business process shows the lack of control role of PT XYZ to supplier and customer side which is going to be the suggestion of improvement.

Sustainable use of phosphorus: a finite resource.

PubMed

Scholz, Roland W; Ulrich, Andrea E; Eilittä, Marjatta; Roy, Amit

2013-09-01

Phosphorus is an essential element of life and of the modern agricultural system. Today, science, policy, agro-industry and other stakeholder groups are increasingly concerned about the sustainable use of this resource, given the dissipative nature of phosphorus and difficulties in assessing, evaluating, and coping with phosphorus pollution in aquatic and terrestrial systems. We argue that predictions about a forthcoming peak, followed by a quick reduction (i.e., physical phosphate rock scarcity) are unreasoned and stress that access to phosphorus (economic scarcity) is already, and may increasingly become critical, in particular for smallholders farmers in different parts of the world. The paper elaborates on the design, development, goals and cutting-edge contributions of a global transdisciplinary process (i.e. mutual learning between science and society including multiple stakeholders) on the understanding of potential contributions and risks related to the current mode of using phosphorus on multiple scales (Global TraPs). While taking a global and comprehensive view on the whole phosphorus-supply chain, Global TraPs organizes and integrates multiple transdisciplinary case studies to better answer questions which inform sustainable future phosphorus use. Its major goals are to contribute to four issues central to sustainable resource management: i) long-term management of biogeochemical cycles, in particular the challenge of closing the phosphorus cycle, ii) achieving food security, iii) avoiding environmental pollution and iv) sustainability learning on a global level by transdisciplinary processes. Copyright © 2013 Elsevier B.V. All rights reserved.

Quantification of Fatty Acid Oxidation Products Using On-line High Performance Liquid Chromatography Tandem Mass Spectrometry

PubMed Central

Levison, Bruce S.; Zhang, Renliang; Wang, Zeneng; Fu, Xiaoming; DiDonato, Joseph A.; Hazen, Stanley L.

2013-01-01

Oxidized fatty acids formed via lipid peroxidation are implicated in pathological processes such as inflammation and atherosclerosis. A number of methods may be used to detect specific oxidized fatty acids containing a single or multiple combinations of epoxide, hydroxyl, ketone and hydroperoxide moieties on varying carbon chain lengths from C8 up to C30. Some of these methods are nonspecific and their use in biological systems is fraught with difficulty. Measures of specific-oxidized fatty acid derivatives help in identifying oxidation pathways in pathological processes. We used liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) as efficient, selective and sensitive methods for identifying and analyzing multiple specific fatty acid peroxidation products in human plasma and other biological matrices. We then distilled the essential components of a number of these analyses to provide an efficient protocol by which fatty acid oxidation products and their parent compounds can be determined. In this protocol, addition of synthetic internal standard to the sample, followed by base hydrolysis at elevated temperature, and liquid-liquid phase sample extraction with lighter than water solvents facilitates isolation of the oxidized fatty acid species. These species can be identified and accurately quantified using stable isotope dilution and multiple reaction monitoring. Use of a coupled multiplexed gradient HPLC system on the front end enables high-throughput chromatography and more efficient use of mass spectrometer time. PMID:23499838

Cavity-Enhanced Raman Spectroscopy for Food Chain Management

PubMed Central

Sandfort, Vincenz; Goldschmidt, Jens; Wöllenstein, Jürgen

2018-01-01

Comprehensive food chain management requires the monitoring of many parameters including temperature, humidity, and multiple gases. The latter is highly challenging because no low-cost technology for the simultaneous chemical analysis of multiple gaseous components currently exists. This contribution proposes the use of cavity enhanced Raman spectroscopy to enable online monitoring of all relevant components using a single laser source. A laboratory scale setup is presented and characterized in detail. Power enhancement of the pump light is achieved in an optical resonator with a Finesse exceeding 2500. A simulation for the light scattering behavior shows the influence of polarization on the spatial distribution of the Raman scattered light. The setup is also used to measure three relevant showcase gases to demonstrate the feasibility of the approach, including carbon dioxide, oxygen and ethene. PMID:29495501

Shortest multiple disconnected path for the analysis of entanglements in two- and three-dimensional polymeric systems

NASA Astrophysics Data System (ADS)

Kröger, Martin

2005-06-01

We present an algorithm which returns a shortest path and related number of entanglements for a given configuration of a polymeric system in 2 or 3 dimensions. Rubinstein and Helfand, and later Everaers et al. introduced a concept to extract primitive paths for dense polymeric melts made of linear chains (a multiple disconnected multibead 'path'), where each primitive path is defined as a path connecting the (space-fixed) ends of a polymer under the constraint of non-interpenetration (excluded volume) between primitive paths of different chains, such that the multiple disconnected path fulfills a minimization criterion. The present algorithm uses geometrical operations and provides a—model independent—efficient approximate solution to this challenging problem. Primitive paths are treated as 'infinitely' thin (we further allow for finite thickness to model excluded volume), and tensionless lines rather than multibead chains, excluded volume is taken into account without a force law. The present implementation allows to construct a shortest multiple disconnected path (SP) for 2D systems (polymeric chain within spherical obstacles) and an optimal SP for 3D systems (collection of polymeric chains). The number of entanglements is then simply obtained from the SP as either the number of interior kinks, or from the average length of a line segment. Further, information about structure and potentially also the dynamics of entanglements is immediately available from the SP. We apply the method to study the 'concentration' dependence of the degree of entanglement in phantom chain systems. Program summaryTitle of program:Z Catalogue number:ADVG Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADVG Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: Silicon Graphics (Irix), Sun (Solaris), PC (Linux) Operating systems or monitors under which the program has been tested: UNIX, Linux Program language used: USANSI Fortran 77 and Fortran 90 Memory required to execute with typical data: 1 MByte No. of lines in distributed program, including test data, etc.: 10 660 No. of bytes in distributed program, including test data, etc.: 119 551 Distribution formet:tar.gz Nature of physical problem: The problem is to obtain primitive paths substantiating a shortest multiple disconnected path (SP) for a given polymer configuration (chains of particles, with or without additional single particles as obstacles for the 2D case). Primitive paths are here defined as in [M. Rubinstein, E. Helfand, J. Chem. Phys. 82 (1985) 2477; R. Everaers, S.K. Sukumaran, G.S. Grest, C. Svaneborg, A. Sivasubramanian, K. Kremer, Science 303 (2004) 823] as the shortest line (path) respecting 'topological' constraints (from neighboring polymers or point obstacles) between ends of polymers. There is a unique solution for the 2D case. For the 3D case it is unique if we construct a primitive path of a single chain embedded within fixed line obstacles [J.S.B. Mitchell, Geometric shortest paths and network optimization, in: J.-R. Sack, J. Urrutia (Eds.), Handbook of Computational Geometry, Elsevier, Amsterdam, 2000, pp. 633-701]. For a large 3D configuration made of several chains, short is meant to be the Euclidean shortest multiple disconnected path (SP) where primitive paths are constructed for all chains simultaneously. While the latter problem, in general, does not possess a unique solution, the algorithm must return a locally optimal solution, robust against minor displacements of the disconnected path and chain re-labeling. The problem is solved if the number of kinks (or entanglements Z), explicitly deduced from the SP, is quite insensitive to the exact conformation of the SP which allows to estimate Z with a small error. Efficient method of solution: Primitive paths are constructed from the given polymer configuration (a non-shortest multiple disconnected path, including obstacles, if present) by first replacing each polymer contour by a line with a number of 'kinks' (beads, nodes) and 'segments' (edges). To obtain primitive paths, defined to be uncrossable by any other objects (neighboring primitive paths, line or point obstacles), the algorithm minimizes the length of all primitive paths consecutively, until a final minimum Euclidean length of the SP is reached. Fast geometric operations rather than dynamical methods are used to minimize the contour lengths of the primitive paths. Neighbor lists are used to keep track of potentially intersecting segments of other chains. Periodic boundary conditions are employed. A finite small line thickness is used in order to make sure that entanglements are not 'lost' due to finite precision of representation of numbers. Restrictions on the complexity of the problem: For a single chain embedded within fixed line or point obstacles, the algorithm returns the exact SP. For more complex problems, the algorithm returns a locally optimal SP. Except for exotic, probably rare, configurations it turns out that different locally optimal SPs possess quite an identical number of nodes. In general, the problem constructing the SP is known to be NP-hard [J.S.B. Mitchell, Geometric shortest paths and network optimization, in: J.-R. Sack, J. Urrutia (Eds.), Handbook of Computational Geometry, Elsevier, Amsterdam, 2000, pp. 633-701], and we offer a solution which should suffice to analyze physical problems, and gives an estimate about the precision and uniqueness of the result (from a standard deviation by varying the parameter: cyclicswitch). The program is NOT restricted to handle systems for which segment lengths of the SP exceed half the box size. Typical running time: Typical running times are approximately two orders of magnitude shorter compared with the ones needed for a corresponding molecular dynamics approach, and scale mostly linearly with system size. We provide a benchmark table.

ASSERT FY16 Analysis of Feedstock Companion Markets

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

Lamers, Patrick; Hansen, Jason; Jacobson, Jacob J.

2016-09-01

Meeting Co-Optima biofuel production targets will require large quantities of mobilized biomass feedstock. Mobilization is of key importance as there is an abundance of biomass resources, yet little is available for purchase, let alone at desired quantity and quality levels needed for a continuous operation, e.g., a biorefinery. Therefore Co-Optima research includes outlining a path towards feedstock production at scale by understanding routes to mobilizing large quantities of biomass feedstock. Continuing along the vertically-integrated path that pioneer cellulosic biorefineries have taken will constrain the bioenergy industry to high biomass yield areas, limiting its ability to reach biofuel production at scale.more » To advance the cellulosic biofuels industry, a separation between feedstock supply and conversion is necessary. Thus, in contrast to the vertically integrated supply chain, two industries are required: a feedstock industry and a conversion industry. The split is beneficial for growers and feedstock processers as they are able to sell into multiple markets. That is, depots that produce value-add feedstock intermediates that are fully fungible in both the biofuels refining and other, so-called companion markets. As the biofuel industry is currently too small to leverage significant investment in up-stream infrastructure build-up, it requires an established (companion) market to secure demand, which de-risks potential investments and makes a build-up of processing and other logistics infrastructure more likely. A common concern to this theory however is that more demand by other markets could present a disadvantage for biofuels production as resource competition may increase prices leading to reduced availability of low-cost feedstock for biorefineries. To analyze the dynamics across multiple markets vying for the same resources, particularly the potential effects on resource price and distribution, the Companion Market Model (CMM) has been developed in this task by experts in feedstock supply chain analysis, market economics, and System Dynamics from the Idaho National Laboratory and MindsEye Computing.« less

Template based protein structure modeling by global optimization in CASP11.

PubMed

Joo, Keehyoung; Joung, InSuk; Lee, Sun Young; Kim, Jong Yun; Cheng, Qianyi; Manavalan, Balachandran; Joung, Jong Young; Heo, Seungryong; Lee, Juyong; Nam, Mikyung; Lee, In-Ho; Lee, Sung Jong; Lee, Jooyoung

2016-09-01

For the template-based modeling (TBM) of CASP11 targets, we have developed three new protein modeling protocols (nns for server prediction and LEE and LEER for human prediction) by improving upon our previous CASP protocols (CASP7 through CASP10). We applied the powerful global optimization method of conformational space annealing to three stages of optimization, including multiple sequence-structure alignment, three-dimensional (3D) chain building, and side-chain remodeling. For more successful fold recognition, a new alignment method called CRFalign was developed. It can incorporate sensitive positional and environmental dependence in alignment scores as well as strong nonlinear correlations among various features. Modifications and adjustments were made to the form of the energy function and weight parameters pertaining to the chain building procedure. For the side-chain remodeling step, residue-type dependence was introduced to the cutoff value that determines the entry of a rotamer to the side-chain modeling library. The improved performance of the nns server method is attributed to successful fold recognition achieved by combining several methods including CRFalign and to the current modeling formulation that can incorporate native-like structural aspects present in multiple templates. The LEE protocol is identical to the nns one except that CASP11-released server models are used as templates. The success of LEE in utilizing CASP11 server models indicates that proper template screening and template clustering assisted by appropriate cluster ranking promises a new direction to enhance protein 3D modeling. Proteins 2016; 84(Suppl 1):221-232. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Potential Cost-Effective Opportunities for Methane Emission Abatement

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

Warner, Ethan; Steinberg, Daniel; Hodson, Elke

2015-08-01

The energy sector was responsible for approximately 84% of carbon dioxide equivalent (CO 2e) greenhouse gas (GHG) emissions in the U.S. in 2012 (EPA 2014a). Methane is the second most important GHG, contributing 9% of total U.S. CO 2e emissions. A large portion of those methane emissions result from energy production and use; the natural gas, coal, and oil industries produce approximately 39% of anthropogenic methane emissions in the U.S. As a result, fossil-fuel systems have been consistently identified as high priority sectors to contribute to U.S. GHG reduction goals (White House 2015). Only two studies have recently attempted tomore » quantify the abatement potential and cost associated with the breadth of opportunities to reduce GHG emissions within natural gas, oil, and coal supply chains in the United States, namely the U.S. Environmental Protection Agency (EPA) (2013a) and ICF (2014). EPA, in its 2013 analysis, estimated the marginal cost of abatement for non-CO 2 GHG emissions from the natural gas, oil, and coal supply chains for multiple regions globally, including the United States. Building on this work, ICF International (ICF) (2014) provided an update and re-analysis of the potential opportunities in U.S. natural gas and oil systems. In this report we synthesize these previously published estimates as well as incorporate additional data provided by ICF to provide a comprehensive national analysis of methane abatement opportunities and their associated costs across the natural gas, oil, and coal supply chains. Results are presented as a suite of marginal abatement cost curves (MACCs), which depict the total potential and cost of reducing emissions through different abatement measures. We report results by sector (natural gas, oil, and coal) and by supply chain segment - production, gathering and boosting, processing, transmission and storage, or distribution - to facilitate identification of which sectors and supply chain segments provide the greatest opportunities for low cost abatement.« less

Tertiary structure of human {Lambda}6 light chains.

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

Pokkuluri, P. R.; Solomon, A.; Weiss, D. T.

1999-01-01

AL amyloidosis is a disease process characterized by the pathologic deposition of monoclonal light chains in tissue. To date, only limited information has been obtained on the molecular features that render such light chains amyloidogenic. Although protein products of the major human V kappa and V lambda gene families have been identified in AL deposits, one particular subgroup--lambda 6--has been found to be preferentially associated with this disease. Notably, the variable region of lambda 6 proteins (V lambda 6) has distinctive primary structural features including the presence in the third framework region (FR3) of two additional amino acid residues thatmore » distinguish members of this subgroup from other types of light chains. However, the structural consequences of these alterations have not been elucidated. To determine if lambda 6 proteins possess unique tertiary structural features, as compared to light chains of other V lambda subgroups, we have obtained x-ray diffraction data on crystals prepared from two recombinant V lambda 6 molecules. These components, isolated from a bacterial expression system, were generated from lambda 6-related cDNAs cloned from bone marrow-derived plasma cells from a patient (Wil) who had documented AL amyloidosis and another (Jto) with multiple myeloma and tubular cast nephropathy, but no evident fibrillar deposits. The x-ray crystallographic analyses revealed that the two-residue insertion located between positions 68 and 69 (not between 66 and 67 as previously surmised) extended an existing loop region that effectively increased the surface area adjacent to the first complementarity determining region (CDR1). Further, an unusual interaction between the Arg 25 and Phe 2 residues commonly found in lambda 6 molecules was noted. However, the structures of V lambda 6 Wil and Jto also differed from each other, as evidenced by the presence in the latter of certain ionic and hydrophobic interactions that we posit increased protein stability and thus prevented amyloid formation.« less

Chain Reaction Polymerization.

ERIC Educational Resources Information Center

McGrath, James E.

1981-01-01

The salient features and importance of chain-reaction polymerization are discussed, including such topics as the thermodynamics of polymerization, free-radical polymerization kinetics, radical polymerization processes, copolymers, and free-radical chain, anionic, cationic, coordination, and ring-opening polymerizations. (JN)

Length-scale and strain rate-dependent mechanism of defect formation and fracture in carbon nanotubes under tensile loading

NASA Astrophysics Data System (ADS)

Javvaji, Brahmanandam; Raha, S.; Mahapatra, D. Roy

2017-02-01

Electromagnetic and thermo-mechanical forces play a major role in nanotube-based materials and devices. Under high-energy electron transport or high current densities, carbon nanotubes fail via sequential fracture. The failure sequence is governed by certain length scale and flow of current. We report a unified phenomenological model derived from molecular dynamic simulation data, which successfully captures the important physics of the complex failure process. Length-scale and strain rate-dependent defect nucleation, growth, and fracture in single-walled carbon nanotubes with diameters in the range of 0.47 to 2.03 nm and length which is about 6.17 to 26.45 nm are simulated. Nanotubes with long length and small diameter show brittle fracture, while those with short length and large diameter show transition from ductile to brittle fracture. In short nanotubes with small diameters, we observe several structural transitions like Stone-Wales defect initiation, its propagation to larger void nucleation, formation of multiple chains of atoms, conversion to monatomic chain of atoms, and finally complete fracture of the carbon nanotube. Hybridization state of carbon-carbon bonds near the end cap evolves, leading to the formation of monatomic chain in short nanotubes with small diameter. Transition from ductile to brittle fracture is also observed when strain rate exceeds a critical value. A generalized analytical model of failure is established, which correlates the defect energy during the formation of atomic chain with aspect ratio of the nanotube and strain rate. Variation in the mechanical properties such as elastic modulus, tensile strength, and fracture strain with the size and strain rate shows important implications in mitigating force fields and ways to enhance the life of electronic devices and nanomaterial conversion via fracture in manufacturing.

Molecular mechanisms of conformational specificity: A study of Hox in vivo target DNA binding specificities and the structure of a Ure2p mutation that affects fibril formation rates

NASA Astrophysics Data System (ADS)

Bauer, William Joseph, Jr.

The fate of an individual cell, or even an entire organism, is often determined by minute, yet very specific differences in the conformation of a single protein species. Very often, proteins take on alternate folds or even side chain conformations to deal with different situations present within the cell. These differences can be as large as a whole domain or as subtle as the alteration of a single amino acid side chain. Yet, even these seemingly minor side chain conformational differences can determine the development of a cell type during differentiation or even dictate whether a cell will live or die. Two examples of situations where minor conformational differences within a specific protein could lead to major differences in the life cycle of a cell are described herein. The first example describes the variations seen in DNA conformations which can lead to slightly different Hox protein binding conformations responsible for recognizing biologically relevant regulatory sites. These specific differences occur in the minor groove of the bound DNA and are limited to the conformation of only two side chains. The conformation of the bound DNA, however, is not solely determined by the sequence of the DNA, as multiple sequences can result in the same DNA conformation. The second example takes place in the context of a yeast prion protein which contains a mutation that decreases the frequency at which fibrils form. While the specific interactions leading to this physiological change were not directly detected, it can be ascertained from the crystal structure that the structural changes are subtle and most likely involve another binding partner. In both cases, these conformational changes are very slight but have a profound effect on the downstream processes.

Supply Chain: Wake Up; It is Critical to Military Success

DTIC Science & Technology

2015-04-13

In 1998, Steve Jobs hired Tim Cook to improve the supply chain. Cook determined that Apple’s supply chain was overly complex and began a process...Blanchard concurs stating that, “a one supply chain fits all strategy [is a recipe for disaster].”29 They both believe that companies increase their

Illustrating Business Marketing Concepts through the Value Chain Game

ERIC Educational Resources Information Center

Liao-Troth, Sara; Thomas, Stephanie P.; Webb, G. Scott

2015-01-01

The Value Chain Game is an activity that helps students to develop a holistic understanding of the processes and challenges in managing the value chain so that customer needs are met. Competing value chains work to produce and sell two products. Seasonal demand, quality defects, transportation delays, and audits offer complexities that represent…

On Farm and Packhouse: Employment at the Bottom of a Global Value Chain

ERIC Educational Resources Information Center

Dolan, Catherine S.

2004-01-01

The fresh vegetables commodity chain linking Kenyan producers with United Kingdom (UK) consumers employs significant numbers of workers in production and processing. This chain is dominated by UK retailers that determine the production imperatives of Kenyan firms upstream in the chain and, indirectly the employment strategies they adopt. This…

Chain stiffness, salt valency, and concentration influences on titration curves of polyelectrolytes: Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Carnal, Fabrice; Stoll, Serge

2011-01-01

Monte Carlo simulations have been used to study two different models of a weak linear polyelectrolyte surrounded by explicit counterions and salt particles: (i) a rigid rod and (ii) a flexible chain. We focused on the influence of the pH, chain stiffness, salt concentration, and valency on the polyelectrolyte titration process and conformational properties. It is shown that chain acid-base properties and conformational properties are strongly modified when multivalent salt concentration variation ranges below the charge equivalence. Increasing chain stiffness allows to minimize intramolecular electrostatic monomer interactions hence improving the deprotonation process. The presence of di and trivalent salt cations clearly promotes the chain degree of ionization but has only a limited effect at very low salt concentration ranges. Moreover, folded structures of fully charged chains are only observed when multivalent salt at a concentration equal or above charge equivalence is considered. Long-range electrostatic potential is found to influence the distribution of charges along and around the polyelectrolyte backbones hence resulting in a higher degree of ionization and a lower attraction of counterions and salt particles at the chain extremities.

Chain stiffness, salt valency, and concentration influences on titration curves of polyelectrolytes: Monte Carlo simulations.

PubMed

Carnal, Fabrice; Stoll, Serge

2011-01-28

Monte Carlo simulations have been used to study two different models of a weak linear polyelectrolyte surrounded by explicit counterions and salt particles: (i) a rigid rod and (ii) a flexible chain. We focused on the influence of the pH, chain stiffness, salt concentration, and valency on the polyelectrolyte titration process and conformational properties. It is shown that chain acid-base properties and conformational properties are strongly modified when multivalent salt concentration variation ranges below the charge equivalence. Increasing chain stiffness allows to minimize intramolecular electrostatic monomer interactions hence improving the deprotonation process. The presence of di and trivalent salt cations clearly promotes the chain degree of ionization but has only a limited effect at very low salt concentration ranges. Moreover, folded structures of fully charged chains are only observed when multivalent salt at a concentration equal or above charge equivalence is considered. Long-range electrostatic potential is found to influence the distribution of charges along and around the polyelectrolyte backbones hence resulting in a higher degree of ionization and a lower attraction of counterions and salt particles at the chain extremities.

Automatic target recognition apparatus and method

DOEpatents

Baumgart, Chris W.; Ciarcia, Christopher A.

2000-01-01

An automatic target recognition apparatus (10) is provided, having a video camera/digitizer (12) for producing a digitized image signal (20) representing an image containing therein objects which objects are to be recognized if they meet predefined criteria. The digitized image signal (20) is processed within a video analysis subroutine (22) residing in a computer (14) in a plurality of parallel analysis chains such that the objects are presumed to be lighter in shading than the background in the image in three of the chains and further such that the objects are presumed to be darker than the background in the other three chains. In two of the chains the objects are defined by surface texture analysis using texture filter operations. In another two of the chains the objects are defined by background subtraction operations. In yet another two of the chains the objects are defined by edge enhancement processes. In each of the analysis chains a calculation operation independently determines an error factor relating to the probability that the objects are of the type which should be recognized, and a probability calculation operation combines the results of the analysis chains.

Flexibility evaluation of multiechelon supply chains.

PubMed

Almeida, João Flávio de Freitas; Conceição, Samuel Vieira; Pinto, Luiz Ricardo; de Camargo, Ricardo Saraiva; Júnior, Gilberto de Miranda

2018-01-01

Multiechelon supply chains are complex logistics systems that require flexibility and coordination at a tactical level to cope with environmental uncertainties in an efficient and effective manner. To cope with these challenges, mathematical programming models are developed to evaluate supply chain flexibility. However, under uncertainty, supply chain models become complex and the scope of flexibility analysis is generally reduced. This paper presents a unified approach that can evaluate the flexibility of a four-echelon supply chain via a robust stochastic programming model. The model simultaneously considers the plans of multiple business divisions such as marketing, logistics, manufacturing, and procurement, whose goals are often conflicting. A numerical example with deterministic parameters is presented to introduce the analysis, and then, the model stochastic parameters are considered to evaluate flexibility. The results of the analysis on supply, manufacturing, and distribution flexibility are presented. Tradeoff analysis of demand variability and service levels is also carried out. The proposed approach facilitates the adoption of different management styles, thus improving supply chain resilience. The model can be extended to contexts pertaining to supply chain disruptions; for example, the model can be used to explore operation strategies when subtle events disrupt supply, manufacturing, or distribution.

The Kinetic Chain Revisited: New Concepts on Throwing Mechanics and Injury.

PubMed

Chu, Samuel K; Jayabalan, Prakash; Kibler, W Ben; Press, Joel

2016-03-01

The overhead throwing motion is a complex activity that is achieved through activation of the kinetic chain. The kinetic chain refers to the linkage of multiple segments of the body that allows for transfer of forces and motion. The lower extremities and core provide a base of support, generating energy that is transferred eventually through the throwing arm and hand, resulting in release of the ball. The kinetic chain requires optimal anatomy, physiology, and mechanics and is involved in all 6 phases of overhead throwing: windup, stride, arm cocking, acceleration, deceleration, and follow-through. Breaks or deficits in the kinetic chain can lead to injury or decreased performance. Through an understanding of the mechanics and pathomechanics seen in each phase of throwing, the clinician can better evaluate and screen for potential kinetic chain deficits in the overhead throwing athlete. The purpose of this article is to review the biomechanics of the overhead throwing motion, the role of the kinetic chain in throwing, and the clinical evaluation and management of abnormal throwing mechanics and related injuries. Copyright © 2016 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

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

Peterson, Steven K

The U.S. Department of Energy (DOE) has a significant programmatic interest in the safe and secure routing and transportation of Spent Nuclear Fuel (SNF) and High Level Waste (HLW) in the United States, including shipments entering the country from locations outside U.S borders. In any shipment of SNF/HLW, there are multiple chains; a jurisdictional chain as the material moves between jurisdictions (state, federal, tribal, administrative), a physical supply chain (which mode), as well as a custody chain (which stakeholder is in charge/possession) of the materials being transported. Given these interconnected networks, there lies vulnerabilities, whether in lack of communication betweenmore » interested stakeholders or physical vulnerabilities such as interdiction. By identifying key links and nodes as well as administrative weaknesses, decisions can be made to harden the physical network and improve communication between stakeholders. This paper examines the parallel chains of oversight and custody as well as the chain of stakeholder interests for the shipments of SNF/HLW and the potential impacts on systemic resiliency. Using the Crystal River shutdown location as well as a hypothetical international shipment brought into the United States, this paper illustrates the parallel chains and maps them out visually.« less

Flexibility evaluation of multiechelon supply chains

PubMed Central

Conceição, Samuel Vieira; Pinto, Luiz Ricardo; de Camargo, Ricardo Saraiva; Júnior, Gilberto de Miranda

2018-01-01

Multiechelon supply chains are complex logistics systems that require flexibility and coordination at a tactical level to cope with environmental uncertainties in an efficient and effective manner. To cope with these challenges, mathematical programming models are developed to evaluate supply chain flexibility. However, under uncertainty, supply chain models become complex and the scope of flexibility analysis is generally reduced. This paper presents a unified approach that can evaluate the flexibility of a four-echelon supply chain via a robust stochastic programming model. The model simultaneously considers the plans of multiple business divisions such as marketing, logistics, manufacturing, and procurement, whose goals are often conflicting. A numerical example with deterministic parameters is presented to introduce the analysis, and then, the model stochastic parameters are considered to evaluate flexibility. The results of the analysis on supply, manufacturing, and distribution flexibility are presented. Tradeoff analysis of demand variability and service levels is also carried out. The proposed approach facilitates the adoption of different management styles, thus improving supply chain resilience. The model can be extended to contexts pertaining to supply chain disruptions; for example, the model can be used to explore operation strategies when subtle events disrupt supply, manufacturing, or distribution. PMID:29584755

Scattering of waves by impurities in precompressed granular chains.

PubMed

Martínez, Alejandro J; Yasuda, Hiromi; Kim, Eunho; Kevrekidis, P G; Porter, Mason A; Yang, Jinkyu

2016-05-01

We study scattering of waves by impurities in strongly precompressed granular chains. We explore the linear scattering of plane waves and identify a closed-form expression for the reflection and transmission coefficients for the scattering of the waves from both a single impurity and a double impurity. For single-impurity chains, we show that, within the transmission band of the host granular chain, high-frequency waves are strongly attenuated (such that the transmission coefficient vanishes as the wavenumber k→±π), whereas low-frequency waves are well-transmitted through the impurity. For double-impurity chains, we identify a resonance-enabling full transmission at a particular frequency-in a manner that is analogous to the Ramsauer-Townsend (RT) resonance from quantum physics. We also demonstrate that one can tune the frequency of the RT resonance to any value in the pass band of the host chain. We corroborate our theoretical predictions both numerically and experimentally, and we directly observe almost complete transmission for frequencies close to the RT resonance frequency. Finally, we show how this RT resonance can lead to the existence of reflectionless modes in granular chains (including disordered ones) with multiple double impurities.

Effects of Alkylthio and Alkoxy Side Chains in Polymer Donor Materials for Organic Solar Cells.

PubMed

Cui, Chaohua; Wong, Wai-Yeung

2016-02-01

Side chains play a considerable role not only in improving the solubility of polymers for solution-processed device fabrication, but also in affecting the molecular packing, electron affinity and thus the device performance. In particular, electron-donating side chains show unique properties when employed to tune the electronic character of conjugated polymers in many cases. Therefore, rational electron-donating side chain engineering can improve the photovoltaic properties of the resulting polymer donors to some extent. Here, a survey of some representative examples which use electron-donating alkylthio and alkoxy side chains in conjugated organic polymers for polymer solar cell applications will be presented. It is envisioned that an analysis of the effect of such electron-donating side chains in polymer donors would contribute to a better understanding of this kind of side chain behavior in solution-processed conjugated organic polymers for polymer solar cells. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A best on-line algorithm for single machine scheduling the equal length jobs with the special chain precedence and delivery time

NASA Astrophysics Data System (ADS)

Gu, Cunchang; Mu, Yundong

2013-03-01

In this paper, we consider a single machine on-line scheduling problem with the special chains precedence and delivery time. All jobs arrive over time. The chains chainsi arrive at time ri , it is known that the processing and delivery time of each job on the chain satisfy one special condition CD a forehand: if the job J(i)j is the predecessor of the job J(i)k on the chain chaini, then they satisfy p(i)j = p(i)k = p >= qj >= qk , i = 1,2, ---,n , where pj and qj denote the processing time and the delivery time of the job Jj respectively. Obviously, if the arrival jobs have no chains precedence, it shows that the length of the corresponding chain is 1. The objective is to minimize the time by which all jobs have been delivered. We provide an on-line algorithm with a competitive ratio of √2 , and the result is the best possible.

Ownership, financing, and management strategies of the ten largest for-profit nursing home chains in the United States.

PubMed

Harrington, Charlene; Hauser, Clarilee; Olney, Brian; Rosenau, Pauline Vaillancourt

2011-01-01

This study examined the ownership, financing, and management strategies of the 10 largest for-profit nursing home chains in the United States, including the four largest chains purchased by private equity corporations. Descriptive data were collected from Internet searches, company reports, and other sources for the decade 1998-2008. Since 1998, the largest chains have made many changes in their ownership and structure, and some have converted from publicly traded companies to private ownership. This study shows the increasing complexity of corporate nursing home ownership and the lack of public information about ownership and financial status. The chains have used strategies to maximize shareholder and investor value that include increasing Medicare revenues, occupancy rates, and company diversification, establishing multiple layers of corporate ownership, developing real estate investment trusts, and creating limited liability companies. These strategies enhance shareholder and investor profits, reduce corporate taxes, and reduce liability risk. There is a need for greater transparency in ownership and financial reporting and for more government oversight of the largest for-profit chains, including those owned by private equity companies.

Polystyrene/Hyperbranched Polyester Blends and Reactive Polystyrene/Hyperbranched Polyester Blends

DTIC Science & Technology

1999-01-01

interfacial tension between the PE and polystyrene phases. This was brought about by the chemical interaction between the acidic anhydride groups in the...multiple 2,2 dimethylol propionic acid (C5H10O4) chain extenders or repeat units. 11 Core HO \\ HO’ /■ J OH V *OH Pentaerythritol Chain Extender...O 2,2 - Dimethylol propionic acid Figure 11. HBP Building Blocks. These materials were supplied in small quantities with little technical data. The

Dynamic effective connectivity in cortically embedded systems of recurrently coupled synfire chains.

PubMed

Trengove, Chris; Diesmann, Markus; van Leeuwen, Cees

2016-02-01

As a candidate mechanism of neural representation, large numbers of synfire chains can efficiently be embedded in a balanced recurrent cortical network model. Here we study a model in which multiple synfire chains of variable strength are randomly coupled together to form a recurrent system. The system can be implemented both as a large-scale network of integrate-and-fire neurons and as a reduced model. The latter has binary-state pools as basic units but is otherwise isomorphic to the large-scale model, and provides an efficient tool for studying its behavior. Both the large-scale system and its reduced counterpart are able to sustain ongoing endogenous activity in the form of synfire waves, the proliferation of which is regulated by negative feedback caused by collateral noise. Within this equilibrium, diverse repertoires of ongoing activity are observed, including meta-stability and multiple steady states. These states arise in concert with an effective connectivity structure (ECS). The ECS admits a family of effective connectivity graphs (ECGs), parametrized by the mean global activity level. Of these graphs, the strongly connected components and their associated out-components account to a large extent for the observed steady states of the system. These results imply a notion of dynamic effective connectivity as governing neural computation with synfire chains, and related forms of cortical circuitry with complex topologies.

Bayesian inversion of seismic and electromagnetic data for marine gas reservoir characterization using multi-chain Markov chain Monte Carlo sampling

NASA Astrophysics Data System (ADS)

Ren, Huiying; Ray, Jaideep; Hou, Zhangshuan; Huang, Maoyi; Bao, Jie; Swiler, Laura

2017-12-01

In this study we developed an efficient Bayesian inversion framework for interpreting marine seismic Amplitude Versus Angle and Controlled-Source Electromagnetic data for marine reservoir characterization. The framework uses a multi-chain Markov-chain Monte Carlo sampler, which is a hybrid of DiffeRential Evolution Adaptive Metropolis and Adaptive Metropolis samplers. The inversion framework is tested by estimating reservoir-fluid saturations and porosity based on marine seismic and Controlled-Source Electromagnetic data. The multi-chain Markov-chain Monte Carlo is scalable in terms of the number of chains, and is useful for computationally demanding Bayesian model calibration in scientific and engineering problems. As a demonstration, the approach is used to efficiently and accurately estimate the porosity and saturations in a representative layered synthetic reservoir. The results indicate that the seismic Amplitude Versus Angle and Controlled-Source Electromagnetic joint inversion provides better estimation of reservoir saturations than the seismic Amplitude Versus Angle only inversion, especially for the parameters in deep layers. The performance of the inversion approach for various levels of noise in observational data was evaluated - reasonable estimates can be obtained with noise levels up to 25%. Sampling efficiency due to the use of multiple chains was also checked and was found to have almost linear scalability.

A decision model for cost effective design of biomass based green energy supply chains.

PubMed

Yılmaz Balaman, Şebnem; Selim, Hasan

2015-09-01

The core driver of this study is to deal with the design of anaerobic digestion based biomass to energy supply chains in a cost effective manner. In this concern, a decision model is developed. The model is based on fuzzy multi objective decision making in order to simultaneously optimize multiple economic objectives and tackle the inherent uncertainties in the parameters and decision makers' aspiration levels for the goals. The viability of the decision model is explored with computational experiments on a real-world biomass to energy supply chain and further analyses are performed to observe the effects of different conditions. To this aim, scenario analyses are conducted to investigate the effects of energy crop utilization and operational costs on supply chain structure and performance measures. Copyright © 2015 Elsevier Ltd. All rights reserved.

Biogenesis of iron-sulfur clusters in mammalian cells: new insights and relevance to human disease

PubMed Central

Rouault, Tracey A.

2012-01-01

Iron-sulfur (Fe-S) clusters are ubiquitous cofactors composed of iron and inorganic sulfur. They are required for the function of proteins involved in a wide range of activities, including electron transport in respiratory chain complexes, regulatory sensing, photosynthesis and DNA repair. The proteins involved in the biogenesis of Fe-S clusters are evolutionarily conserved from bacteria to humans, and many insights into the process of Fe-S cluster biogenesis have come from studies of model organisms, including bacteria, fungi and plants. It is now clear that several rare and seemingly dissimilar human diseases are attributable to defects in the basic process of Fe-S cluster biogenesis. Although these diseases –which include Friedreich’s ataxia (FRDA), ISCU myopathy, a rare form of sideroblastic anemia, an encephalomyopathy caused by dysfunction of respiratory chain complex I and multiple mitochondrial dysfunctions syndrome – affect different tissues, a feature common to many of them is that mitochondrial iron overload develops as a secondary consequence of a defect in Fe-S cluster biogenesis. This Commentary outlines the basic steps of Fe-S cluster biogenesis as they have been defined in model organisms. In addition, it draws attention to refinements of the process that might be specific to the subcellular compartmentalization of Fe-S cluster biogenesis proteins in some eukaryotes, including mammals. Finally, it outlines several important unresolved questions in the field that, once addressed, should offer important clues into how mitochondrial iron homeostasis is regulated, and how dysfunction in Fe-S cluster biogenesis can contribute to disease. PMID:22382365

An exploration in mineral supply chain mapping using tantalum as an example

USGS Publications Warehouse

Soto-Viruet, Yadira; Menzie, W. David; Papp, John F.; Yager, Thomas R.

2013-01-01

This report uses the supply chain of tantalum (Ta) to investigate the complexity of mineral and metal supply chains in general and show how they can be mapped. A supply chain is made up of all the manufacturers, suppliers, information networks, and so forth, that provide the materials and parts that go into making up a final product. The mineral portion of the supply chain begins with mineral material in the ground (the ore deposit); extends through a series of processes that include mining, beneficiation, processing (smelting and refining), semimanufacture, and manufacture; and continues through transformation of the mineral ore into concentrates, refined mineral commodities, intermediate forms (such as metals and alloys), component parts, and, finally, complex products. This study analyses the supply chain of tantalum beginning with minerals in the ground to many of the final goods that contain tantalum.

Viscoplastic fracture transition of a biopolymer gel.

PubMed

Frieberg, Bradley R; Garatsa, Ray-Shimry; Jones, Ronald L; Bachert, John O; Crawshaw, Benjamin; Liu, X Michael; Chan, Edwin P

2018-06-13

Physical gels are swollen polymer networks consisting of transient crosslink junctions associated with hydrogen or ionic bonds. Unlike covalently crosslinked gels, these physical crosslinks are reversible thus enabling these materials to display highly tunable and dynamic mechanical properties. In this work, we study the polymer composition effects on the fracture behavior of a gelatin gel, which is a thermoreversible biopolymer gel consisting of denatured collagen chains bridging physical network junctions formed from triple helices. Below the critical volume fraction for chain entanglement, which we confirm via neutron scattering measurements, we find that the fracture behavior is consistent with a viscoplastic type process characterized by hydrodynamic friction of individual polymer chains through the polymer mesh to show that the enhancement in fracture scales inversely with the squared of the mesh size of the gelatin gel network. Above this critical volume fraction, the fracture process can be described by the Lake-Thomas theory that considers fracture as a chain scission process due to chain entanglements.

Kidney transplant chains amplify benefit of nondirected donors.

PubMed

Melcher, Marc L; Veale, Jeffrey L; Javaid, Basit; Leeser, David B; Davis, Connie L; Hil, Garet; Milner, John E

2013-02-01

Despite the potential for altruistic nondirected donors (NDDs) to trigger multiple transplants through nonsimultaneous transplant chains, concerns exist that these chains siphon NDDs from the deceased donor wait list and that donors within chains might not donate after their partner receives a transplant. To determine the number of transplantations NDDs trigger through chains. Retrospective review of large, multicenter living donor-recipient database. Fifty-seven US transplant centers contributing donor-recipient pairs to the database. The NDDs initiating chain transplantation. Number of transplants per NDD. Seventy-seven NDDs enabled 373 transplantations during 46 months starting February 2008. Mean chain length initiated by NDDs was 4.8 transplants (median, 3; range, 1-30). The 40 blood type O NDDs triggered a mean chain length of 6.0 (median, 4; range, 2-30). During the interval, 66 of 77 chains were closed to the wait list, 4 of 77 were ongoing, and 7 of 77 were broken because bridge donors became unavailable. No chains were broken in the last 15 months, and every recipient whose incompatible donor donated received a kidney. One hundred thirty-three blood type O recipients were transplanted. This large series demonstrates that NDDs trigger almost 5 transplants on average, more if the NDD is blood type O. There were more blood type O recipients than blood type O NDDs participating. The benefits of transplanting 373 patients and enabling others without living donors to advance outweigh the risk of broken chains that is decreasing with experience. Even 66 patients on the wait list without living donors underwent transplantation with living-donor grafts at the end of these chains.

Breaking of the Bancroft rule for multiple emulsions stabilized by a single stimulable polymer.

PubMed

Besnard, L; Protat, M; Malloggi, F; Daillant, J; Cousin, F; Pantoustier, N; Guenoun, P; Perrin, P

2014-09-28

We investigated emulsions of water and toluene stabilized by (co)polymers consisting of styrene (S) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) monomer units with different compositions and structures such as a PDMAEMA homopolymer, a P(S-co-DMAEMA) random copolymer and various PS-b-PDMAEMA and PS-b-(S-co-DMAEMA) block copolymers. The model system is used to study the fundamental conditions under which the different kinds of polymer-stabilized emulsions (direct oil in water, inverse water in oil and multiple emulsions) are stabilized or destabilized by pH change (at constant temperature). Polymer properties like chain conformation at the toluene-water interface as probed by SANS and neutron reflectivity at the liquid-liquid interface, the oil-water partitioning of the polymer chains (Bancroft's rule of thumb) as determined by UV spectroscopy and interfacial tensions measured by the rising and spinning drop techniques are determined. Overall, results evidence that the curvature sign, as defined by positive and negative values as the chain segments occupy preferentially the water and toluene sides of the interface respectively, reliably predicts the emulsion kind. In contrast, the Bancroft rule failed at foreseeing the emulsion type. In the region of near zero curvature the crossover from direct to inverse emulsions occurs through the formation of either unstable coexisting direct and inverse emulsions (i) or multiple emulsions (ii). The high compact adsorption of the chains at the interface as shown by low interfacial tension values does not allow to discriminate between both cases. However, the toluene-water partitioning of the polymeric emulsifier is still a key factor driving the formation of (i) or (ii) emulsions. Interestingly, the stabilization of the multiple emulsions can be tuned to a large extent as the toluene-water polymer partitioning can be adjusted using quite a large number of physico-chemical parameters linked to polymer architecture like diblock length ratio or polymer total molar mass, for example. Moreover, we show that monitoring the oil-water partitioning aspect of the emulsion system can also be used to lower the interfacial tension at low pH to values slightly higher than 0.01 mN m(-1), irrespective of the curvature sign.

Research on manufacturing service behavior modeling based on block chain theory

NASA Astrophysics Data System (ADS)

Zhao, Gang; Zhang, Guangli; Liu, Ming; Yu, Shuqin; Liu, Yali; Zhang, Xu

2018-04-01

According to the attribute characteristics of processing craft, the manufacturing service behavior is divided into service attribute, basic attribute, process attribute, resource attribute. The attribute information model of manufacturing service is established. The manufacturing service behavior information is successfully divided into public and private domain. Additionally, the block chain technology is introduced, and the information model of manufacturing service based on block chain principle is established, which solves the problem of sharing and secreting information of processing behavior, and ensures that data is not tampered with. Based on the key pairing verification relationship, the selective publishing mechanism for manufacturing information is established, achieving the traceability of product data, guarantying the quality of processing quality.

Impaired neurosteroid synthesis in multiple sclerosis

PubMed Central

Noorbakhsh, Farshid; Ellestad, Kristofor K.; Maingat, Ferdinand; Warren, Kenneth G.; Han, May H.; Steinman, Lawrence; Baker, Glen B.

2011-01-01

High-throughput technologies have led to advances in the recognition of disease pathways and their underlying mechanisms. To investigate the impact of micro-RNAs on the disease process in multiple sclerosis, a prototypic inflammatory neurological disorder, we examined cerebral white matter from patients with or without the disease by micro-RNA profiling, together with confirmatory reverse transcription–polymerase chain reaction analysis, immunoblotting and gas chromatography-mass spectrometry. These observations were verified using the in vivo multiple sclerosis model, experimental autoimmune encephalomyelitis. Brains of patients with or without multiple sclerosis demonstrated differential expression of multiple micro-RNAs, but expression of three neurosteroid synthesis enzyme-specific micro-RNAs (miR-338, miR-155 and miR-491) showed a bias towards induction in patients with multiple sclerosis (P < 0.05). Analysis of the neurosteroidogenic pathways targeted by micro-RNAs revealed suppression of enzyme transcript and protein levels in the white matter of patients with multiple sclerosis (P < 0.05). This was confirmed by firefly/Renilla luciferase micro-RNA target knockdown experiments (P < 0.05) and detection of specific micro-RNAs by in situ hybridization in the brains of patients with or without multiple sclerosis. Levels of important neurosteroids, including allopregnanolone, were suppressed in the white matter of patients with multiple sclerosis (P < 0.05). Induction of the murine micro-RNAs, miR-338 and miR-155, accompanied by diminished expression of neurosteroidogenic enzymes and allopregnanolone, was also observed in the brains of mice with experimental autoimmune encephalomyelitis (P < 0.05). Allopregnanolone treatment of the experimental autoimmune encephalomyelitis mouse model limited the associated neuropathology, including neuroinflammation, myelin and axonal injury and reduced neurobehavioral deficits (P < 0.05). These multi-platform studies point to impaired neurosteroidogenesis in both multiple sclerosis and experimental autoimmune encephalomyelitis. The findings also indicate that allopregnanolone and perhaps other neurosteroid-like compounds might represent potential biomarkers or therapies for multiple sclerosis. PMID:21908875

Translation and assembly of HLA-DR antigens in Xenopus oocytes injected with mRNA from a human B-cell line.

PubMed Central

Long, E O; Gross, N; Wake, C T; Mach, J P; Carrel, S; Accolla, R; Mach, B

1982-01-01

HLA-DR antigens are polymorphic cell surface glycoproteins, expressed primarily in B lymphocytes and macrophages, which are thought to play an important role in the immune response. Two polypeptide chains, alpha and beta, are associated at the cell surface, and a third chain associates with alpha and beta intracellularly. RNA isolated from the human B-cell line Raji was injected in Xenopus laevis oocytes. Immunoprecipitates of translation products with several monoclonal antibodies revealed the presence of HLA-DR antigens similar to those synthesized in Raji cells. One monoclonal antibody was able to bind the beta chain after dissociation of the three polypeptide chains with detergent. The presence of all three chains was confirmed by two-dimensional gel electrophoresis. The glycosylation pattern of the three chains was identical to that observed in vivo, as evidenced in studies using tunicamycin, an inhibitor of N-linked glycosylation. The presence of alpha chains assembled with beta chains in equimolar ratio was further demonstrated by amino-terminal sequencing. An RNA fraction enriched for the three mRNAs, encoding alpha, beta, and intracellular chains, was isolated. This translation-assembly system and the availability of monoclonal antibodies make it possible to assay for mRNA encoding specific molecules among the multiple human Ia-like antigens. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:6821356

Tight focusing properties of the azimuthal discrete phase modulated radially polarized LG11* beam

NASA Astrophysics Data System (ADS)

Zhao, Jiang; Li, Bo; Zhao, Heng; Hu, Yi; Wang, Wenjin; Wang, Youqing

2013-06-01

An novel method for generating an annual periodic optical chain by tight focusing the rotational symmetric π/0 phase plate modulated first order radially polarized Laguerre Gaussian (LG11*) beam with a high-NA lens is proposed. The optical chain is composed of either bright spots or dark spots. Vector diffraction numerical calculation method is employed to analyze the tight focus properties. The analyses indicate that the properties of the optical chains are closely related to the number of phase plate sectors, beam width of radially polarized LG11* beam and the numerical aperture of focusing lens. Furthermore, the average Full Width at Half Maximum (FWHM) of hollow dark spots or bright spots in optical chain is breaking the diffraction limit. These kinds of annular optical chains are expected to be applied in trapping or arranging multiple bar-like micro particles whose refractive index are either higher or lower than that of the ambient.

Thermodynamic description of cellulose chain collapse using coarse grain modeling

NASA Astrophysics Data System (ADS)

Das, Ritankar; Chu, Jhih-Wei

2012-11-01

Biomass contains abundant amounts of cellulose as crystalline microfibrils. A limiting step to using cellulose as an alternative energy source, however, is the hydrolysis of the biomass and subsequent transformation into fuels. Cellulose is insoluble in most solvents including organic solvents and water, but it is soluble in some ionic liquids like BMIM-Cl. This project aims to find alternative solvents that are less expensive and are more environmentally benign than the ionic liquids. All-atom molecular dynamics simulations were performed on dissociated glucan chains separated by multiple (4-5) solvation shells, in the presence of several novel solvents and solvent mixtures. The solubility of the chains in each solvent was indicated by contacts calculations after the equilibration of the molecular dynamics. It was discovered that pyridine and imidazole acted as the best solvents because their aromatic electronic structure was able to effectively disrupt the inter-sheet interactions among the glucan chains in the axial direction, and because perturbation of the solvent interactions in the presence of glucan chains was minimal.

Generation of intervention strategy for a genetic regulatory network represented by a family of Markov Chains.

PubMed

Berlow, Noah; Pal, Ranadip

2011-01-01

Genetic Regulatory Networks (GRNs) are frequently modeled as Markov Chains providing the transition probabilities of moving from one state of the network to another. The inverse problem of inference of the Markov Chain from noisy and limited experimental data is an ill posed problem and often generates multiple model possibilities instead of a unique one. In this article, we address the issue of intervention in a genetic regulatory network represented by a family of Markov Chains. The purpose of intervention is to alter the steady state probability distribution of the GRN as the steady states are considered to be representative of the phenotypes. We consider robust stationary control policies with best expected behavior. The extreme computational complexity involved in search of robust stationary control policies is mitigated by using a sequential approach to control policy generation and utilizing computationally efficient techniques for updating the stationary probability distribution of a Markov chain following a rank one perturbation.

Locations of Racism in Education: A Speech Act Analysis of a Policy Chain

ERIC Educational Resources Information Center

Arneback, Emma; Quennerstedt, Ann

2016-01-01

This article explores how racism is located in an educational policy chain and identifies how its interpretation changes throughout the chain. A basic assumption is that the policy formation process can be seen as a chain in which international, national and local policies are "links"--separate entities yet joined. With Sweden as the…

ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

PubMed Central

Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

2016-01-01

In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

A Simulation Model Articulation of the REA Ontology

NASA Astrophysics Data System (ADS)

Laurier, Wim; Poels, Geert

This paper demonstrates how the REA enterprise ontology can be used to construct simulation models for business processes, value chains and collaboration spaces in supply chains. These models support various high-level and operational management simulation applications, e.g. the analysis of enterprise sustainability and day-to-day planning. First, the basic constructs of the REA ontology and the ExSpect modelling language for simulation are introduced. Second, collaboration space, value chain and business process models and their conceptual dependencies are shown, using the ExSpect language. Third, an exhibit demonstrates the use of value chain models in predicting the financial performance of an enterprise.

Fission Chain Restart Theory

DOE PAGES

Kim, K. S.; Nakae, L. F.; Prasad, M. K.; ...

2017-07-31

We present that fast nanosecond timescale neutron and gamma-ray counting can be performed with a (liquid) scintillator array. Fission chains in metal evolve over a timescale of tens of nanoseconds. If the metal is surrounded by moderator, neutrons leaking from the metal can thermalize and diffuse in the moderator. With finite probability, the diffusing neutrons can return to the metal and restart the fast fission chain. The timescale for this restart process is microseconds. A theory describing time evolving fission chains for metal surrounded by moderator, including this restart process, is presented. Finally, this theory is sufficiently simple for itmore » to be implemented for real-time analysis.« less

Interrelated Dimensional Chains in Predicting Accuracy of Turbine Wheel Assembly Parameters

NASA Astrophysics Data System (ADS)

Yanyukina, M. V.; Bolotov, M. A.; Ruzanov, N. V.

2018-03-01

The working capacity of any device primarily depends on the assembly accuracy which, in its turn, is determined by the quality of each part manufactured, i.e., the degree of conformity between final geometrical parameters and the set ones. However, the assembly accuracy depends not only on a qualitative manufacturing process but also on the assembly process correctness. In this connection, there were preliminary calculations of assembly stages in terms of conformity to real geometrical parameters with their permissible values. This task is performed by means of the calculation of dimensional chains. The calculation of interrelated dimensional chains in the aircraft industry requires particular attention. The article considers the issues of dimensional chain calculation modelling by the example of the turbine wheel assembly process. The authors described the solution algorithm in terms of mathematical statistics implemented in Matlab. The paper demonstrated the results of a dimensional chain calculation for a turbine wheel in relation to the draw of turbine blades to the shroud ring diameter. Besides, the article provides the information on the influence of a geometrical parameter tolerance for the dimensional chain link elements on a closing one.

Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris.

PubMed

Sreenivas, Suma; Krishnaiah, Sateesh M; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N

2015-01-01

Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials.

HIBCH mutations can cause Leigh-like disease with combined deficiency of multiple mitochondrial respiratory chain enzymes and pyruvate dehydrogenase.

PubMed

Ferdinandusse, Sacha; Waterham, Hans R; Heales, Simon J R; Brown, Garry K; Hargreaves, Iain P; Taanman, Jan-Willem; Gunny, Roxana; Abulhoul, Lara; Wanders, Ronald J A; Clayton, Peter T; Leonard, James V; Rahman, Shamima

2013-12-04

Deficiency of 3-hydroxy-isobutyryl-CoA hydrolase (HIBCH) caused by HIBCH mutations is a rare cerebral organic aciduria caused by disturbance of valine catabolism. Multiple mitochondrial respiratory chain (RC) enzyme deficiencies can arise from a number of mechanisms, including defective maintenance or expression of mitochondrial DNA. Impaired biosynthesis of iron-sulphur clusters and lipoic acid can lead to pyruvate dehydrogenase complex (PDHc) deficiency in addition to multiple RC deficiencies, known as the multiple mitochondrial dysfunctions syndrome. Two brothers born to distantly related Pakistani parents presenting in early infancy with a progressive neurodegenerative disorder, associated with basal ganglia changes on brain magnetic resonance imaging, were investigated for suspected Leigh-like mitochondrial disease. The index case had deficiencies of multiple RC enzymes and PDHc in skeletal muscle and fibroblasts respectively, but these were normal in his younger brother. The observation of persistently elevated hydroxy-C4-carnitine levels in the younger brother led to suspicion of HIBCH deficiency, which was investigated by biochemical assay in cultured skin fibroblasts and molecular genetic analysis. Specific spectrophotometric enzyme assay revealed HIBCH activity to be below detectable limits in cultured skin fibroblasts from both brothers. Direct Sanger sequence analysis demonstrated a novel homozygous pathogenic missense mutation c.950G

Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains.

PubMed

Kim, Yunjung; Feng, Sheng; Zeng, Zhao-Bang

2008-05-01

A map of the background levels of disequilibrium between nearby markers can be useful for association mapping studies. In order to assess the background levels of linkage disequilibrium (LD), multilocus LD measures are more advantageous than pairwise LD measures because the combined analysis of pairwise LD measures is not adequate to detect simultaneous allele associations among multiple markers. Various multilocus LD measures based on haplotypes have been proposed. However, most of these measures provide a single index of association among multiple markers and does not reveal the complex patterns and different levels of LD structure. In this paper, we employ non-homogeneous, multiple order Markov Chain models as a statistical framework to measure and partition the LD among multiple markers into components due to different orders of marker associations. Using a sliding window of multiple markers on phased haplotype data, we compute corresponding likelihoods for different Markov Chain (MC) orders in each window. The log-likelihood difference between the lowest MC order model (MC0) and the highest MC order model in each window is used as a measure of the total LD or the overall deviation from the gametic equilibrium for the window. Then, we partition the total LD into lower order disequilibria and estimate the effects from two-, three-, and higher order disequilibria. The relationship between different orders of LD and the log-likelihood difference involving two different orders of MC models are explored. By applying our method to the phased haplotype data in the ENCODE regions of the HapMap project, we are able to identify high/low multilocus LD regions. Our results reveal that the most LD in the HapMap data is attributed to the LD between adjacent pairs of markers across the whole region. LD between adjacent pairs of markers appears to be more significant in high multilocus LD regions than in low multilocus LD regions. We also find that as the multilocus total LD increases, the effects of high-order LD tends to get weaker due to the lack of observed multilocus haplotypes. The overall estimates of first, second, third, and fourth order LD across the ENCODE regions are 64, 23, 9, and 3%.

(Block) Chain Reaction: A Blockchain Revolution Sweeps into Health Care, Offering the Possibility for a Much-Needed Data Solution.

PubMed

Mertz, Leslie

2018-01-01

Electronic health records may have digitized patient data, but getting that data from one clinician to another remains a huge challenge, especially since patients often have multiple doctors ordering tests, prescribing drugs, and providing treatment. Many experts now believe that blockchain technology might be just the thing to get a patient's pertinent medical information from where it is stored to where it is needed, as well as to allow patients to easily view their own medical histories. In addition, blockchain technology might also be able to help with other aspects of health care, such as improving the insurance claim or other administrative processes within healthcare networks and making health-related population data available to biomedical researchers.

An object-based approach for detecting small brain lesions: application to Virchow-Robin spaces.

PubMed

Descombes, Xavier; Kruggel, Frithjof; Wollny, Gert; Gertz, Hermann Josef

2004-02-01

This paper is concerned with the detection of multiple small brain lesions from magnetic resonance imaging (MRI) data. A model based on the marked point process framework is designed to detect Virchow-Robin spaces (VRSs). These tubular shaped spaces are due to retraction of the brain parenchyma from its supplying arteries. VRS are described by simple geometrical objects that are introduced as small tubular structures. Their radiometric properties are embedded in a data term. A prior model includes interactions describing the clustering property of VRS. A Reversible Jump Markov Chain Monte Carlo algorithm (RJMCMC) optimizes the proposed model, obtained by multiplying the prior and the data model. Example results are shown on T1-weighted MRI datasets of elderly subjects.

Preparation of a DNA matrix via an electrochemically directed copolymerization of pyrrole and oligonucleotides bearing a pyrrole group.

PubMed Central

Livache, T; Roget, A; Dejean, E; Barthet, C; Bidan, G; Téoule, R

1994-01-01

A new methodology for the preparation of addressed DNA matrices is described. The process includes an electrochemically directed copolymerization of pyrrole and oligonucleotides bearing on their 5' end a pyrrole moiety introduced by phosphoramidite chemistry. The electro-controlled synthesis of the copolymer (poly-pyrrole) gives, in one step, a solid conducting film deposited on the surface of an electrode. The resulting polymer consists of pyrrole chains bearing covalently linked oligonucleotide. The polymer growth is limited to the electrode surface, so that it is possible to prepare a DNA matrix on a multiple electrode device by successive copolymerizations. A support bearing four oligonucleotides was used to detect three ras mutations on a synthetic DNA fragment. PMID:8065902

Future Supply Chains Enabled by Continuous Processing-Opportunities Challenges May 20-21 2014 Continuous Manufacturing Symposium.

PubMed

Srai, Jagjit Singh; Badman, Clive; Krumme, Markus; Futran, Mauricio; Johnston, Craig

2015-03-01

This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily "continuous processing"-based supply chain. The current predominantly "large batch" and centralized manufacturing system designed for the "blockbuster" drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more "flow-through" operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Electron transport chain-dependent and -independent mechanisms of mitochondrial H2O2 emission during long-chain fatty acid oxidation.

PubMed

Seifert, Erin L; Estey, Carmen; Xuan, Jian Y; Harper, Mary-Ellen

2010-02-19

Oxidative stress in skeletal muscle is a hallmark of various pathophysiologic states that also feature increased reliance on long-chain fatty acid (LCFA) substrate, such as insulin resistance and exercise. However, little is known about the mechanistic basis of the LCFA-induced reactive oxygen species (ROS) burden in intact mitochondria, and elucidation of this mechanistic basis was the goal of this study. Specific aims were to determine the extent to which LCFA catabolism is associated with ROS production and to gain mechanistic insights into the associated ROS production. Because intermediates and by-products of LCFA catabolism may interfere with antioxidant mechanisms, we predicted that ROS formation during LCFA catabolism reflects a complex process involving multiple sites of ROS production as well as modified mitochondrial function. Thus, we utilized several complementary approaches to probe the underlying mechanism(s). Using skeletal muscle mitochondria, our findings indicate that even a low supply of LCFA is associated with ROS formation in excess of that generated by NADH-linked substrates. Moreover, ROS production was evident across the physiologic range of membrane potential and was relatively insensitive to membrane potential changes. Determinations of topology and membrane potential as well as use of inhibitors revealed complex III and the electron transfer flavoprotein (ETF) and ETF-oxidoreductase, as likely sites of ROS production. Finally, ROS production was sensitive to matrix levels of LCFA catabolic intermediates, indicating that mitochondrial export of LCFA catabolic intermediates can play a role in determining ROS levels.

Kinetic characterization of the critical step in HIV-1 protease maturation.

PubMed

Sadiq, S Kashif; Noé, Frank; De Fabritiis, Gianni

2012-12-11

HIV maturation requires multiple cleavage of long polyprotein chains into functional proteins that include the viral protease itself. Initial cleavage by the protease dimer occurs from within these precursors, and yet only a single protease monomer is embedded in each polyprotein chain. Self-activation has been proposed to start from a partially dimerized protease formed from monomers of different chains binding its own N termini by self-association to the active site, but a complete structural understanding of this critical step in HIV maturation is missing. Here, we captured the critical self-association of immature HIV-1 protease to its extended amino-terminal recognition motif using large-scale molecular dynamics simulations, thus confirming the postulated intramolecular mechanism in atomic detail. We show that self-association to a catalytically viable state requires structural cooperativity of the flexible β-hairpin "flap" regions of the enzyme and that the major transition pathway is first via self-association in the semiopen/open enzyme states, followed by enzyme conformational transition into a catalytically viable closed state. Furthermore, partial N-terminal threading can play a role in self-association, whereas wide opening of the flaps in concert with self-association is not observed. We estimate the association rate constant (k(on)) to be on the order of ∼1 × 10(4) s(-1), suggesting that N-terminal self-association is not the rate-limiting step in the process. The shown mechanism also provides an interesting example of molecular conformational transitions along the association pathway.

Efficient hierarchical trans-dimensional Bayesian inversion of magnetotelluric data

NASA Astrophysics Data System (ADS)

Xiang, Enming; Guo, Rongwen; Dosso, Stan E.; Liu, Jianxin; Dong, Hao; Ren, Zhengyong

2018-06-01

This paper develops an efficient hierarchical trans-dimensional (trans-D) Bayesian algorithm to invert magnetotelluric (MT) data for subsurface geoelectrical structure, with unknown geophysical model parameterization (the number of conductivity-layer interfaces) and data-error models parameterized by an auto-regressive (AR) process to account for potential error correlations. The reversible-jump Markov-chain Monte Carlo algorithm, which adds/removes interfaces and AR parameters in birth/death steps, is applied to sample the trans-D posterior probability density for model parameterization, model parameters, error variance and AR parameters, accounting for the uncertainties of model dimension and data-error statistics in the uncertainty estimates of the conductivity profile. To provide efficient sampling over the multiple subspaces of different dimensions, advanced proposal schemes are applied. Parameter perturbations are carried out in principal-component space, defined by eigen-decomposition of the unit-lag model covariance matrix, to minimize the effect of inter-parameter correlations and provide effective perturbation directions and length scales. Parameters of new layers in birth steps are proposed from the prior, instead of focused distributions centred at existing values, to improve birth acceptance rates. Parallel tempering, based on a series of parallel interacting Markov chains with successively relaxed likelihoods, is applied to improve chain mixing over model dimensions. The trans-D inversion is applied in a simulation study to examine the resolution of model structure according to the data information content. The inversion is also applied to a measured MT data set from south-central Australia.

Role for phospholipid acyl chains and cholesterol in pulmonary infections and inflammation

PubMed Central

Shaikh, Saame Raza; Fessler, Michael B.

2016-01-01

Bacterial and viral respiratory tract infections result in millions of deaths worldwide and are currently the leading cause of death from infection. Acute inflammation is an essential element of host defense against infection, but can be damaging to the host when left unchecked. Effective host defense requires multiple lipid mediators, which collectively have proinflammatory and/or proresolving effects on the lung. During pulmonary infections, phospholipid acyl chains and cholesterol can be chemically and enzymatically oxidized, as well as truncated and modified, producing complex mixtures of bioactive lipids. We review recent evidence that phospholipids and cholesterol and their derivatives regulate pulmonary innate and adaptive immunity during infection. We first highlight data that oxidized phospholipids generated in the lung during infection stimulate pattern recognition receptors, such as TLRs and scavenger receptors, thereby amplifying the pulmonary inflammatory response. Next, we discuss evidence that oxidation of endogenous pools of cholesterol during pulmonary infections produces oxysterols that also modify the function of both innate and adaptive immune cells. Last, we conclude with data that n-3 polyunsaturated fatty acids, both in the form of phospholipid acyl chains and through enzymatic processing into endogenous proresolving lipid mediators, aid in the resolution of lung inflammation through distinct mechanisms. Unraveling the complex mechanisms of induction and function of distinct classes of bioactive lipids, both native and modified, may hold promise for developing new therapeutic strategies for improving pulmonary outcomes in response to infection. PMID:27286794

Preparation of 13C/15N-labeled oligomers using the polymerase chain reaction

DOEpatents

Chen, Xian; Gupta, Goutam; Bradbury, E. Morton

2001-01-01

Preparation of .sup.13 C/.sup.15 N-labeled DNA oligomers using the polymerase chain reaction (PCR). A PCR based method for uniform (.sup.13 C/.sup.15 N)-labeling of DNA duplexes is described. Multiple copies of a blunt-ended duplex are cloned into a plasmid, each copy containing the sequence of interest and restriction Hinc II sequences at both the 5' and 3' ends. PCR using bi-directional primers and uniformly .sup.13 C/.sup.15 N-labeled dNTP precursors generates labeled DNA duplexes containing multiple copies of the sequence of interest. Twenty-four cycles of PCR, followed by restriction and purification, gave the uniformly .sup.13 C/.sup.15 N-labeled duplex sequence with a 30% yield. Such labeled duplexes find significant applications in multinuclear magnetic resonance spectroscopy.

IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

PubMed

Djidjik, R; Lounici, Y; Chergeulaïne, K; Berkouk, Y; Mouhoub, S; Chaib, S; Belhani, M; Ghaffor, M

2015-09-01

IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum β2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A modified chain binomial model to analyse the ongoing measles epidemic in Greece, July 2017 to February 2018

PubMed Central

Lytras, Theodore; Georgakopoulou, Theano; Tsiodras, Sotirios

2018-01-01

Greece is currently experiencing a large measles outbreak, in the context of multiple similar outbreaks across Europe. We devised and applied a modified chain-binomial epidemic model, requiring very simple data, to estimate the transmission parameters of this outbreak. Model results indicate sustained measles transmission among the Greek Roma population, necessitating a targeted mass vaccination campaign to halt further spread of the epidemic. Our model may be useful for other countries facing similar measles outbreaks. PMID:29717695

A modified chain binomial model to analyse the ongoing measles epidemic in Greece, July 2017 to February 2018.

PubMed

Lytras, Theodore; Georgakopoulou, Theano; Tsiodras, Sotirios

2018-04-01

Greece is currently experiencing a large measles outbreak, in the context of multiple similar outbreaks across Europe. We devised and applied a modified chain-binomial epidemic model, requiring very simple data, to estimate the transmission parameters of this outbreak. Model results indicate sustained measles transmission among the Greek Roma population, necessitating a targeted mass vaccination campaign to halt further spread of the epidemic. Our model may be useful for other countries facing similar measles outbreaks.

Creating world-class supply chains.

PubMed

Katzorke, M; Lee, W B

2000-08-01

This article will share knowledge in two areas: The elements of world-class supply chains and the linking processes from customers' customers to suppliers' suppliers and the management approaches needed to engage the people and the organization in an effective implementation process to achieve world-class status.

Multi-scale process and supply chain modelling: from lignocellulosic feedstock to process and products

PubMed Central

Hosseini, Seyed Ali; Shah, Nilay

2011-01-01

There is a large body of literature regarding the choice and optimization of different processes for converting feedstock to bioethanol and bio-commodities; moreover, there has been some reasonable technological development in bioconversion methods over the past decade. However, the eventual cost and other important metrics relating to sustainability of biofuel production will be determined not only by the performance of the conversion process, but also by the performance of the entire supply chain from feedstock production to consumption. Moreover, in order to ensure world-class biorefinery performance, both the network and the individual components must be designed appropriately, and allocation of resources over the resulting infrastructure must effectively be performed. The goal of this work is to describe the key challenges in bioenergy supply chain modelling and then to develop a framework and methodology to show how multi-scale modelling can pave the way to answer holistic supply chain questions, such as the prospects for second generation bioenergy crops. PMID:22482032

Future supply chains enabled by continuous processing--opportunities and challenges. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Srai, Jagjit Singh; Badman, Clive; Krumme, Markus; Futran, Mauricio; Johnston, Craig

2015-03-01

This paper examines the opportunities and challenges facing the pharmaceutical industry in moving to a primarily "continuous processing"-based supply chain. The current predominantly "large batch" and centralized manufacturing system designed for the "blockbuster" drug has driven a slow-paced, inventory heavy operating model that is increasingly regarded as inflexible and unsustainable. Indeed, new markets and the rapidly evolving technology landscape will drive more product variety, shorter product life-cycles, and smaller drug volumes, which will exacerbate an already unsustainable economic model. Future supply chains will be required to enhance affordability and availability for patients and healthcare providers alike despite the increased product complexity. In this more challenging supply scenario, we examine the potential for a more pull driven, near real-time demand-based supply chain, utilizing continuous processing where appropriate as a key element of a more "flow-through" operating model. In this discussion paper on future supply chain models underpinned by developments in the continuous manufacture of pharmaceuticals, we have set out; The significant opportunities to moving to a supply chain flow-through operating model, with substantial opportunities in inventory reduction, lead-time to patient, and radically different product assurance/stability regimes. Scenarios for decentralized production models producing a greater variety of products with enhanced volume flexibility. Production, supply, and value chain footprints that are radically different from today's monolithic and centralized batch manufacturing operations. Clinical trial and drug product development cost savings that support more rapid scale-up and market entry models with early involvement of SC designers within New Product Development. The major supply chain and industrial transformational challenges that need to be addressed. The paper recognizes that although current batch operational performance in pharma is far from optimal and not necessarily an appropriate end-state benchmark for batch technology, the adoption of continuous supply chain operating models underpinned by continuous production processing, as full or hybrid solutions in selected product supply chains, can support industry transformations to deliver right-first-time quality at substantially lower inventory profiles. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Reducing the potential for processing contaminant formation in cereal products.

PubMed

Curtis, Tanya Y; Postles, Jennifer; Halford, Nigel G

2014-05-01

Processing contaminants may be defined as substances that are produced in a food when it is cooked or processed, are not present or are present at much lower concentrations in the raw, unprocessed food, and are undesirable either because they have an adverse effect on product quality or because they are potentially harmful. The presence of very low levels of processing contaminants in common foods is becoming an increasingly important issue for the food industry, as developments in analytical techniques and equipment bring foods under closer and closer scrutiny. This review considers the formation of lipid oxidation products, hydrogenation of polyunsaturated fatty acids to prevent lipid oxidation and the associated risk of trans fatty acid formation. The formation of acrylamide in the Maillard reaction is described, as well as the genetic and agronomic approaches being taken to reduce the acrylamide-forming potential of cereal grain. The multiple routes for the formation of furan and associated chemicals, including hydroxymethylfurfuryl, are also described. The evolving regulatory and public perception situations for these processing contaminants and their implications for the cereal supply chain are discussed, emphasising the need for cereal breeders to engage with the contaminants issue.

Oligosaccharide processing at individual glycosylation sites on MOPC 104E immunoglobulin M. Differences in alpha 1,2-linked mannose processing.

PubMed

Brown, P H; Hickman, S

1986-02-25

Processing of the asparagine-linked oligosaccharides at the known glycosylation sites on the mu-chain of IgM secreted by MOPC 104E murine plasmacytoma cells was investigated. Oligosaccharides present on intracellular mu-chain precursors were of the high mannose type, remaining susceptible to endo-beta-N-acetylglucosaminidase H. However, only 26% of the radioactivity was released from [3H]mannose-labeled secreted IgM glycopeptides, consistent with the presence of high mannose-type and complex-type oligosaccharides on the mature mu-chain. [3H]Mannose-labeled cyanogen bromide glycopeptides derived from mu-chains of secreted IgM were isolated and analyzed to identify the glycopeptide containing the high mannose-type oligosaccharide from those containing complex-type structures. [3H]Mannose-labeled intracellular mu-chain cyanogen bromide glycopeptides corresponding to those from secreted IgM were isolated also, and the time courses of oligosaccharide processing at the individual glycosylation sites were determined. The major oligosaccharides on all intracellular mu-chain glycopeptides after 20 min of pulse labeling with [3H]mannose were identified as Man8GlcNAc2, Man9GlcNAc2, and Glc1Man9GlcNAc2. Processing of the oligosaccharide destined to become the high mannose-type structure on the mature protein was rapid. After 30 min of chase incubation the predominant structures of this oligosaccharide were Man5GlcNAc2 and Man6GlcNAc2 which were also identified on the high mannose-type oligosaccharide of the secreted mu-chain. In contrast, processing of oligosaccharides destined to become complex type was considerably slower. Even after 180 min of chase incubation, Man7GlcNAc2 and Man8GlcNAc2 were the predominant structures at some of these glycosylation sites. The isomeric structures of Man8GlcNAc2 obtained from all of the glycosylation sites were identical. Thus, the different rates of processing were not the result of a different sequence of alpha 1,2-mannose removal.

Distributed trace using central performance counter memory

DOEpatents

Satterfield, David L; Sexton, James C

2013-10-22

A plurality of processing cores, are central storage unit having at least memory connected in a daisy chain manner, forming a daisy chain ring layout on an integrated chip. At least one of the plurality of processing cores places trace data on the daisy chain connection for transmitting the trace data to the central storage unit, and the central storage unit detects the trace data and stores the trace data in the memory co-located in with the central storage unit.

Distributed trace using central performance counter memory

DOEpatents

Satterfield, David L.; Sexton, James C.

2013-01-22

A plurality of processing cores, are central storage unit having at least memory connected in a daisy chain manner, forming a daisy chain ring layout on an integrated chip. At least one of the plurality of processing cores places trace data on the daisy chain connection for transmitting the trace data to the central storage unit, and the central storage unit detects the trace data and stores the trace data in the memory co-located in with the central storage unit.

Historical Semantic Chaining and Efficient Communication: The Case of Container Names

ERIC Educational Resources Information Center

Xu, Yang; Regier, Terry; Malt, Barbara C.

2016-01-01

Semantic categories in the world's languages often reflect a historical process of "chaining": A name for one referent is extended to a conceptually related referent, and from there on to other referents, producing a chain of exemplars that all bear the same name. The beginning and end points of such a chain might in principle be rather…

How human IgGs against myelin basic protein (MBP) recognize oligopeptides and MBP.

PubMed

Belov, Sergey; Buneva, Valentina N; Nevinsky, Georgy A

2017-10-01

Myelin basic protein (MBP) is a major protein of myelin-proteolipid shell of axons, and it plays an important role in pathogenesis of multiple sclerosis. In the literature, there are no data on how antibodies recognize different protein antigens including MBP. A stepwise increase in ligand complexity was used to estimate the relative contributions of virtually every amino acid residue (AA) of a specific 12-mer LSRFSWGAEGQK oligopeptide corresponding to immunodominant sequence of MBP to the light chains and to intact anti-MBP IgGs from sera of patients with multiple sclerosis. It was shown that the minimal ligands of the light chains of IgGs are many different free AAs (K d  = 0.51-0.016 M), and each free AA interacts with the specific subsite of the light chain intended for recognition of this AA in specific LSRFSW oligopeptide. A gradual transition from Leu to LSRFSWGAEGQK leads to an increase in the affinity from 10 -1 to 2.3 × 10 -4  M because of additive interactions of the light chain with 6 AAs of this oligopeptide and then the affinity reaches plateau. The contributions of 6 various AAs to the affinity of the oligopeptide are different (K d , M): 0.71 (S), 0.44 (R), 0.14 (F), 0.17 (S), and 0.62 (W). Affinity of nonspecific oligopeptides to the light chains of IgGs is significantly lower. Intact MBP interacts with both light and heavy chains of IgGs demonstrating 192-fold higher affinity than the specific oligopeptide. It is a first quantitative analysis of the mechanism of proteins recognition by antibodies. The thermodynamic model was constructed to describe the interactions of IgGs with MBP. The data obtained can be very useful for understanding how antibodies against many different proteins can recognize these proteins. Copyright © 2017 John Wiley & Sons, Ltd.

Performance analysis of Supply Chain Management with Supply Chain Operation reference model

NASA Astrophysics Data System (ADS)

Hasibuan, Abdurrozzaq; Arfah, Mahrani; Parinduri, Luthfi; Hernawati, Tri; Suliawati; Harahap, Bonar; Rahmah Sibuea, Siti; Krianto Sulaiman, Oris; purwadi, Adi

2018-04-01

This research was conducted at PT. Shamrock Manufacturing Corpora, the company is required to think creatively to implement competition strategy by producing goods/services that are more qualified, cheaper. Therefore, it is necessary to measure the performance of Supply Chain Management in order to improve the competitiveness. Therefore, the company is required to optimize its production output to meet the export quality standard. This research begins with the creation of initial dimensions based on Supply Chain Management process, ie Plan, Source, Make, Delivery, and Return with hierarchy based on Supply Chain Reference Operation that is Reliability, Responsiveness, Agility, Cost, and Asset. Key Performance Indicator identification becomes a benchmark in performance measurement whereas Snorm De Boer normalization serves to equalize Key Performance Indicator value. Analiytical Hierarchy Process is done to assist in determining priority criteria. Measurement of Supply Chain Management performance at PT. Shamrock Manufacturing Corpora produces SC. Responsiveness (0.649) has higher weight (priority) than other alternatives. The result of performance analysis using Supply Chain Reference Operation model of Supply Chain Management performance at PT. Shamrock Manufacturing Corpora looks good because its monitoring system between 50-100 is good.

Multiple Myeloma Presenting as Massive Amyloid Deposition in a Parathyroid Gland Associated with Amyloid Goiter: A Medullary Thyroid Carcinoma Mimic on Intra-operative Frozen Section.

PubMed

Hill, Kirk; Diaz, Jason; Hagemann, Ian S; Chernock, Rebecca D

2018-06-01

Clinical examples of amyloid deposition in parathyroid glands are exceedingly rare and usually present as an incidental finding in a patient with amyloid goiter. Here, we present the first histologically documented case of parathyroid amyloid deposition that presented as a mass. The patient did not have hyperparathyroidism. The parathyroid gland was submitted for intra-operative frozen section and concern for medullary thyroid carcinoma was raised. An important histologic clue arguing against medullary thyroid carcinoma was the evenly dispersed nature of the amyloid. Histologic perinuclear clearing and parathyroid hormone immunohistochemistry confirmed parathyroid origin on permanent sections. The patient was also found to have associated amyloid goiter. Mass spectrometry of the amyloid showed it to be composed of kappa light chains. On further work-up, the patient was diagnosed with multiple myeloma. Awareness of parathyroid amyloid deposition is important as it is a histologic mimic of medullary thyroid carcinoma, especially on frozen section. Amyloid typing with evaluation for multiple myeloma in any patient with kappa or lambda light chain restriction is also important.

Understanding transferable supply chain lessons and practices to a "high-tech" industry using guidelines from a primary sector industry: a case study in the food industry supply chain.

PubMed

Coronado Mondragon, Adrian E; Coronado Mondragon, Christian E; Coronado, Etienne S

2015-01-01

Flexibility and innovation at creating shapes, adapting processes, and modifying materials characterize composites materials, a "high-tech" industry. However, the absence of standard manufacturing processes and the selection of materials with defined properties hinder the configuration of the composites materials supply chain. An interesting alternative for a "high-tech" industry such as composite materials would be to review supply chain lessons and practices in "low-tech" industries such as food. The main motivation of this study is to identify lessons and practices that comprise innovations in the supply chain of a firm in a perceived "low-tech" industry that can be used to provide guidelines in the design of the supply chain of a "high-tech" industry, in this case composite materials. This work uses the case study/site visit with analogy methodology to collect data from a Spanish leading producer of fresh fruit juice which is sold in major European markets and makes use of a cold chain. The study highlights supply base management and visibility/traceability as two elements of the supply chain in a "low-tech" industry that can provide guidelines that can be used in the configuration of the supply chain of the composite materials industry.

Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome

PubMed Central

Saeki, Yasushi; Kudo, Tai; Sone, Takayuki; Kikuchi, Yoshiko; Yokosawa, Hideyoshi; Toh-e, Akio; Tanaka, Keiji

2009-01-01

Recruitment of substrates to the 26S proteasome usually requires covalent attachment of the Lys48-linked polyubiquitin chain. In contrast, modifications with the Lys63-linked polyubiquitin chain and/or monomeric ubiquitin are generally thought to function in proteasome-independent cellular processes. Nevertheless, the ubiquitin chain-type specificity for the proteasomal targeting is still poorly understood, especially in vivo. Using mass spectrometry, we found that Rsp5, a ubiquitin-ligase in budding yeast, catalyzes the formation of Lys63-linked ubiquitin chains in vitro. Interestingly, the 26S proteasome degraded well the Lys63-linked ubiquitinated substrate in vitro. To examine whether Lys63-linked ubiquitination serves in degradation in vivo, we investigated the ubiquitination of Mga2-p120, a substrate of Rsp5. The polyubiquitinated p120 contained relatively high levels of Lys63-linkages, and the Lys63-linked chains were sufficient for the proteasome-binding and subsequent p120-processing. In addition, Lys63-linked chains as well as Lys48-linked chains were detected in the 26S proteasome-bound polyubiquitinated proteins. These results raise the possibility that Lys63-linked ubiquitin chain also serves as a targeting signal for the 26S proteaseome in vivo. PMID:19153599

Development of a group contribution method for estimating free energy of peptides in a dodecane-water system via molecular dynamic simulations.

PubMed

Mora Osorio, Camilo Andrés; González Barrios, Andrés Fernando

2016-12-07

Calculation of the Gibbs free energy changes of biological molecules at the oil-water interface is commonly performed with Molecular Dynamics simulations (MD). It is a process that could be performed repeatedly in order to find some molecules of high stability in this medium. Here, an alternative method of calculation has been proposed: a group contribution method (GCM) for peptides based on MD of the twenty classic amino acids to obtain free energy change during the insertion of any peptide chain in water-dodecane interfaces. Multiple MD of the twenty classic amino acids located at the interface of rectangular simulation boxes with a dodecane-water medium were performed. A GCM to calculate the free energy of entire peptides is then proposed. The method uses the summation of the Gibbs free energy of each amino acid adjusted in function of its presence or absence in the chain as well as its hydrophobic characteristics. Validation of the equation was performed with twenty-one peptides all simulated using MD in dodecane-water rectangular boxes in previous work, obtaining an average relative error of 16%.

Activation of the Slx5–Slx8 Ubiquitin Ligase by Poly-small Ubiquitin-like Modifier Conjugates*S⃞

PubMed Central

Mullen, Janet R.; Brill, Steven J.

2008-01-01

Protein sumoylation is a regulated process that is important for the health of human and yeast cells. In budding yeast, a subset of sumoylated proteins is targeted for ubiquitination by a conserved heterodimeric ubiquitin (Ub) ligase, Slx5–Slx8, which is needed to suppress the accumulation of high molecular weight small ubiquitin-like modifier (SUMO) conjugates. Structure-function analysis indicates that the Slx5–Slx8 complex contains multiple SUMO-binding domains that are collectively required for in vivo function. To determine the specificity of Slx5–Slx8, we assayed its Ub ligase activity using sumoylated Siz2 as an in vitro substrate. In contrast to unsumoylated or multisumoylated Siz2, substrates containing poly-SUMO conjugates were efficiently ubiquitinated by Slx5–Slx8. Although Siz2 itself was ubiquitinated, the bulk of the Ub was conjugated to SUMO residues. Slx5–Slx8 primarily mono-ubiquitinated the N-terminal SUMO moiety of the chain. These data indicate that the Slx5–Slx8 Ub ligase is stimulated by poly-SUMO conjugates and that it can ubiquitinate a poly-SUMO chain. PMID:18499666

A programmable five qubit quantum computer using trapped atomic ions

NASA Astrophysics Data System (ADS)

Debnath, Shantanu

2017-04-01

In order to harness the power of quantum information processing, several candidate systems have been investigated, and tailored to demonstrate only specific computations. In my thesis work, we construct a general-purpose multi-qubit device using a linear chain of trapped ion qubits, which in principle can be programmed to run any quantum algorithm. To achieve such flexibility, we develop a pulse shaping technique to realize a set of fully connected two-qubit rotations that entangle arbitrary pairs of qubits using multiple motional modes of the chain. Following a computation architecture, such highly expressive two-qubit gates along with arbitrary single-qubit rotations can be used to compile modular universal logic gates that are effected by targeted optical fields and hence can be reconfigured according to any algorithm circuit programmed in the software. As a demonstration, we run the Deutsch-Jozsa and Bernstein-Vazirani algorithm, and a fully coherent quantum Fourier transform, that we use to solve the `period finding' and `quantum phase estimation' problem. Combining these results with recent demonstrations of quantum fault-tolerance, Grover's search algorithm, and simulation of boson hopping establishes the versatility of such a computation module that can potentially be connected to other modules for future large-scale computations.

A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction

PubMed Central

Mellert, Hestia S.; Alexander, Kristin E.; Jackson, Leisa P.; Pestano, Gary A.

2018-01-01

We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. Robust detection of cRNA recovered from blood represents a solution to a critical unmet need in clinical diagnostics. The test begins with the collection of whole blood into blood collection tubes containing preservatives that stabilize cRNA. Cell-free, exosomal, and platelet-associated RNA is isolated from plasma in this test system. The cRNA is reverse transcribed to complementary DNA (cDNA) and amplified using digital polymerase chain reaction (dPCR). Samples are evaluated for both the target biomarker as well as a control gene. Test validation included limit of detection, accuracy, and robustness studies with analytic samples. The method developed as a result of these studies reproducibly detect multiple fusion variants for ROS1 (C-Ros proto-oncogene 1; 8 variants) and RET (rearranged during transfection proto-oncogene; 8 variants). The sample processing workflow has been optimized so that test results can consistently be generated within 72 hours of sample receipt. PMID:29683453

Preparation and properties of a calcium(II)-based molecular chain decorated with manganese(II) butterfly-like complexes.

PubMed

Benniston, A C; Melnic, S; Turta, C; Arauzo, A B; Bartolomé, J; Bartolomé, E; Harrington, R W; Probert, M R

2014-09-21

The room temperature reaction of [Mn2O2(bipy)4](ClO4)3 (bipy = 2,2'-bipyridine) with Ca(CHCl2COO)2 in methanol produced a yellow crystalline material. The X-ray determined structure comprises of a multiple calcium(II) carboxylate bridged chain-like structure which is decorated with [Mn(bipy)2(OH2)](2+) subunits. The redox behaviour for the complex in H2O and MeCN is reported. In the latter solvent the oxidation of the manganese ions appears to be facilitated by the presence of the calcium ions. Magnetic susceptibility and low temperature magnetization measurements show that the Mn moment is isotropic, with g = 1.99(1) and S = 5/2, confirming it is in the 2+ oxidation state. A very weak antiferromagnetic interaction is also detected. Frequency-dependent ac measurements evidence slow magnetic relaxation of the Mn(bipy)2 units. Two relaxation mechanisms are identified: a very slow direct process and a faster one caused by the Resonant Phonon Trapping mechanism. This is the first example of field-induced single ion magnet (SIM) behavior in a mononuclear Mn(II) complex.

Random walk hierarchy measure: What is more hierarchical, a chain, a tree or a star?

PubMed Central

Czégel, Dániel; Palla, Gergely

2015-01-01

Signs of hierarchy are prevalent in a wide range of systems in nature and society. One of the key problems is quantifying the importance of hierarchical organisation in the structure of the network representing the interactions or connections between the fundamental units of the studied system. Although a number of notable methods are already available, their vast majority is treating all directed acyclic graphs as already maximally hierarchical. Here we propose a hierarchy measure based on random walks on the network. The novelty of our approach is that directed trees corresponding to multi level pyramidal structures obtain higher hierarchy scores compared to directed chains and directed stars. Furthermore, in the thermodynamic limit the hierarchy measure of regular trees is converging to a well defined limit depending only on the branching number. When applied to real networks, our method is computationally very effective, as the result can be evaluated with arbitrary precision by subsequent multiplications of the transition matrix describing the random walk process. In addition, the tests on real world networks provided very intuitive results, e.g., the trophic levels obtained from our approach on a food web were highly consistent with former results from ecology. PMID:26657012

Random walk hierarchy measure: What is more hierarchical, a chain, a tree or a star?

NASA Astrophysics Data System (ADS)

Czégel, Dániel; Palla, Gergely

2015-12-01

Signs of hierarchy are prevalent in a wide range of systems in nature and society. One of the key problems is quantifying the importance of hierarchical organisation in the structure of the network representing the interactions or connections between the fundamental units of the studied system. Although a number of notable methods are already available, their vast majority is treating all directed acyclic graphs as already maximally hierarchical. Here we propose a hierarchy measure based on random walks on the network. The novelty of our approach is that directed trees corresponding to multi level pyramidal structures obtain higher hierarchy scores compared to directed chains and directed stars. Furthermore, in the thermodynamic limit the hierarchy measure of regular trees is converging to a well defined limit depending only on the branching number. When applied to real networks, our method is computationally very effective, as the result can be evaluated with arbitrary precision by subsequent multiplications of the transition matrix describing the random walk process. In addition, the tests on real world networks provided very intuitive results, e.g., the trophic levels obtained from our approach on a food web were highly consistent with former results from ecology.

A fully synthetic human Fab antibody library based on fixed VH/VL framework pairings with favorable biophysical properties

PubMed Central

Tiller, Thomas; Schuster, Ingrid; Deppe, Dorothée; Siegers, Katja; Strohner, Ralf; Herrmann, Tanja; Berenguer, Marion; Poujol, Dominique; Stehle, Jennifer; Stark, Yvonne; Heßling, Martin; Daubert, Daniela; Felderer, Karin; Kaden, Stefan; Kölln, Johanna; Enzelberger, Markus; Urlinger, Stefanie

2013-01-01

This report describes the design, generation and testing of Ylanthia, a fully synthetic human Fab antibody library with 1.3E+11 clones. Ylanthia comprises 36 fixed immunoglobulin (Ig) variable heavy (VH)/variable light (VL) chain pairs, which cover a broad range of canonical complementarity-determining region (CDR) structures. The variable Ig heavy and Ig light (VH/VL) chain pairs were selected for biophysical characteristics favorable to manufacturing and development. The selection process included multiple parameters, e.g., assessment of protein expression yield, thermal stability and aggregation propensity in fragment antigen binding (Fab) and IgG1 formats, and relative Fab display rate on phage. The framework regions are fixed and the diversified CDRs were designed based on a systematic analysis of a large set of rearranged human antibody sequences. Care was taken to minimize the occurrence of potential posttranslational modification sites within the CDRs. Phage selection was performed against various antigens and unique antibodies with excellent biophysical properties were isolated. Our results confirm that quality can be built into an antibody library by prudent selection of unmodified, fully human VH/VL pairs as scaffolds. PMID:23571156

Random walk hierarchy measure: What is more hierarchical, a chain, a tree or a star?

PubMed

Czégel, Dániel; Palla, Gergely

2015-12-10

Signs of hierarchy are prevalent in a wide range of systems in nature and society. One of the key problems is quantifying the importance of hierarchical organisation in the structure of the network representing the interactions or connections between the fundamental units of the studied system. Although a number of notable methods are already available, their vast majority is treating all directed acyclic graphs as already maximally hierarchical. Here we propose a hierarchy measure based on random walks on the network. The novelty of our approach is that directed trees corresponding to multi level pyramidal structures obtain higher hierarchy scores compared to directed chains and directed stars. Furthermore, in the thermodynamic limit the hierarchy measure of regular trees is converging to a well defined limit depending only on the branching number. When applied to real networks, our method is computationally very effective, as the result can be evaluated with arbitrary precision by subsequent multiplications of the transition matrix describing the random walk process. In addition, the tests on real world networks provided very intuitive results, e.g., the trophic levels obtained from our approach on a food web were highly consistent with former results from ecology.

Human Lipooligosaccharide IGG That Prevents Endemic Meningococcal Disease Recognizes an Internal Lacto-N-neotetraose Structure*

PubMed Central

Cheng, Hui; Yang, Zhijie; Estabrook, Michele M.; John, Constance M.; Jarvis, Gary A.; McLaughlin, Stephanie; Griffiss, J. McLeod

2011-01-01

Antibodies that initiate complement-mediated killing of Neisseria meningitidis as they enter the bloodstream from the oropharynx protect against disseminated disease. Human IgGs that bind the neisserial L7 lipooligosaccharide (LOS) are bactericidal for L3,7 and L2,4 meningococci in the presence of human complement. These strains share a lacto-N-neotetraose (nLc4) LOS α chain. We used a set of mutants that have successive saccharide deletions from the nLc4 α chain to characterize further the binding and bactericidal activity of nLc4 LOS IgG. We found that the nLc4 α chain conforms at least four different antigens. We separately purified IgG that required the nLc4 (non-reducing) terminal galactose (Gal) for binding and IgG that bound the truncated nLc3 α chain that lacks this Gal residue. IgG that bound the internal nLc3 α chain killed both L3,7 and L2,4 strains, whereas IgG that required the nLc4 terminal Gal residue for binding killed L2,4 stains but not L3,7 strains. These results show that the diversity of LOS antibodies in human serum is as much a function of the conformation of multiple antigens by a single glycoform as of the production of multiple glycoforms. Differences in sensitivity to killing by human nLc4 LOS IgG may account for the fact that fully two-thirds of endemic group B meningococcal disease in infants and children is caused by L3,7 strains, but only 20% is caused by L2,4 stains. PMID:22027827

Dynamics Sampling in Transition Pathway Space.

PubMed

Zhou, Hongyu; Tao, Peng

2018-01-09

The minimum energy pathway contains important information describing the transition between two states on a potential energy surface (PES). Chain-of-states methods were developed to efficiently calculate minimum energy pathways connecting two stable states. In the chain-of-states framework, a series of structures are generated and optimized to represent the minimum energy pathway connecting two states. However, multiple pathways may exist connecting two existing states and should be identified to obtain a full view of the transitions. Therefore, we developed an enhanced sampling method, named as the direct pathway dynamics sampling (DPDS) method, to facilitate exploration of a PES for multiple pathways connecting two stable states as well as addition minima and their associated transition pathways. In the DPDS method, molecular dynamics simulations are carried out on the targeting PES within a chain-of-states framework to directly sample the transition pathway space. The simulations of DPDS could be regulated by two parameters controlling distance among states along the pathway and smoothness of the pathway. One advantage of the chain-of-states framework is that no specific reaction coordinates are necessary to generate the reaction pathway, because such information is implicitly represented by the structures along the pathway. The chain-of-states setup in a DPDS method greatly enhances the sufficient sampling in high-energy space between two end states, such as transition states. By removing the constraint on the end states of the pathway, DPDS will also sample pathways connecting minima on a PES in addition to the end points of the starting pathway. This feature makes DPDS an ideal method to directly explore transition pathway space. Three examples demonstrate the efficiency of DPDS methods in sampling the high-energy area important for reactions on the PES.

Origin of diverse time scales in the protein hydration layer solvation dynamics: A simulation study

NASA Astrophysics Data System (ADS)

Mondal, Sayantan; Mukherjee, Saumyak; Bagchi, Biman

2017-10-01

In order to inquire the microscopic origin of observed multiple time scales in solvation dynamics, we carry out several computer experiments. We perform atomistic molecular dynamics simulations on three protein-water systems, namely, lysozyme, myoglobin, and sweet protein monellin. In these experiments, we mutate the charges of the neighbouring amino acid side chains of certain natural probes (tryptophan) and also freeze the side chain motions. In order to distinguish between different contributions, we decompose the total solvation energy response in terms of various components present in the system. This allows us to capture the interplay among different self- and cross-energy correlation terms. Freezing the protein motions removes the slowest component that results from side chain fluctuations, but a part of slowness remains. This leads to the conclusion that the slow component approximately in the 20-80 ps range arises from slow water molecules present in the hydration layer. While the more than 100 ps component has multiple origins, namely, adjacent charges in amino acid side chains, hydrogen bonded water molecules and a dynamically coupled motion between side chain and water. In addition, the charges enforce a structural ordering of nearby water molecules and helps to form a local long-lived hydrogen bonded network. Further separation of the spatial and temporal responses in solvation dynamics reveals different roles of hydration and bulk water. We find that the hydration layer water molecules are largely responsible for the slow component, whereas the initial ultrafast decay arises predominantly (approximately 80%) due to the bulk. This agrees with earlier theoretical observations. We also attempt to rationalise our results with the help of a molecular hydrodynamic theory that was developed using classical time dependent density functional theory in a semi-quantitative manner.

Mechanical response of transient telechelic networks with many-part stickers

NASA Astrophysics Data System (ADS)

Sing, Michelle K.; Ramírez, Jorge; Olsen, Bradley D.

2017-11-01

A central question in soft matter is understanding how several individual, weak bonds act together to produce collective interactions. Here, gel-forming telechelic polymers with multiple stickers at each chain end are studied through Brownian dynamics simulations to understand how collective interaction of the bonds affects mechanical response of the gels. These polymers are modeled as finitely extensible dumbbells using an explicit tau-leap algorithm and the binding energy of these associations was kept constant regardless of the number of stickers. The addition of multiple bonds to the associating ends of telechelic polymers increases or decreases the network relaxation time depending on the relative kinetics of association but increases both shear stress and extensional viscosity. The relationship between the rate of association and the Rouse time of dangling chains results in two different regimes for the equilibrium stress relaxation of associating physical networks. In case I, a dissociated dangling chain is able to fully relax before re-associating to the network, resulting in two characteristic relaxation times and a non-monotonic terminal relaxation time with increasing number of bonds per polymer endgroup. In case II, the dissociated dangling chain is only able to relax a fraction of the way before it re-attaches to the network, and increasing the number of bonds per endgroup monotonically increases the terminal relaxation time. In flow, increasing the number of stickers increases the steady-state shear and extensional viscosities even though the overall bond kinetics and equilibrium constant remain unchanged. Increased dissipation in the simulations is primarily due to higher average chain extension with increasing bond number. These results indicate that toughness and dissipation in physically associating networks can both be increased by breaking single, strong bonds into smaller components.

Triadic instruction of chained food preparation responses: acquisition and observational learning.

PubMed Central

Griffen, A K; Wolery, M; Schuster, J W

1992-01-01

This research examined whether constant time delay would be effective in teaching students with moderate mental retardation in triads to perform chained tasks and whether observational learning would occur. Three chained snack preparation tasks were identified, and each student was directly taught one task. The other 2 students observed the instruction. The instructed student told the observers to watch and to turn pages of a pictorial recipe book. The teacher provided frequent praise to the instructed student based on performance and to the observers for watching the instruction and turning pages. A multiple probe design across students and tasks was used to evaluate the instruction. The results indicated that each student learned the skill he or she was taught directly, and the observers learned nearly all of the steps of the chains they observed. The implications for classroom instruction and future research in observational learning are discussed. PMID:1533856

State-transfer simulation in integrated waveguide circuits

NASA Astrophysics Data System (ADS)

Latmiral, L.; Di Franco, C.; Mennea, P. L.; Kim, M. S.

2015-08-01

Spin-chain models have been widely studied in terms of quantum information processes, for instance for the faithful transmission of quantum states. Here, we investigate the limitations of mapping this process to an equivalent one through a bosonic chain. In particular, we keep in mind experimental implementations, which the progress in integrated waveguide circuits could make possible in the very near future. We consider the feasibility of exploiting the higher dimensionality of the Hilbert space of the chain elements for the transmission of a larger amount of information, and the effects of unwanted excitations during the process. Finally, we exploit the information-flux method to provide bounds to the transfer fidelity.

Tunneling and Origin of Large Access Resistance in Layered-Crystal Organic Transistors

NASA Astrophysics Data System (ADS)

Hamai, Takamasa; Arai, Shunto; Minemawari, Hiromi; Inoue, Satoru; Kumai, Reiji; Hasegawa, Tatsuo

2017-11-01

Layered crystallinity of organic semiconductors is crucial to obtaining high-performance organic thin-film transistors (OTFTs), as it allows both smooth-channel-gate-insulator interface formation and efficient two-dimensional carrier transport along the interface. However, the role of vertical transport across the crystalline molecular layers in device operations has not been a crucial subject so far. Here, we show that the interlayer carrier transport causes unusual nonlinear current-voltage characteristics and enormous access resistance in extremely high-quality single-crystal OTFTs based on 2-decyl-7-phenyl[1]-benzothieno[3 ,2 -b ][1]benzothiophene (Ph -BTBT -C10 ) that involve inherent multiple semiconducting π -conjugated layers interposed, respectively, by electrically inert alkyl-chain layers. The output characteristics present layer-number (n )-dependent nonlinearity that becomes more evident at larger n (1 ≤n ≤15 ), demonstrating tunneling across multiple alkyl-chain layers. The n -dependent device mobility and four-probe measurements reveal that the alkyl-chain layers generate a large access resistance that suppresses the device mobility from the intrinsic value of about 20 cm2 V-1 s-1 . Our findings clarify the reason why device characteristics are distributed in single-crystal OTFTs.

Distributed Finite-Time Cooperative Control of Multiple High-Order Nonholonomic Mobile Robots.

PubMed

Du, Haibo; Wen, Guanghui; Cheng, Yingying; He, Yigang; Jia, Ruting

2017-12-01

The consensus problem of multiple nonholonomic mobile robots in the form of high-order chained structure is considered in this paper. Based on the model features and the finite-time control technique, a finite-time cooperative controller is explicitly constructed which guarantees that the states consensus is achieved in a finite time. As an application of the proposed results, finite-time formation control of multiple wheeled mobile robots is studied and a finite-time formation control algorithm is proposed. To show effectiveness of the proposed approach, a simulation example is given.

Implementing Lean Six Sigma to achieve inventory control in supply chain management

NASA Astrophysics Data System (ADS)

Hong, Chen

2017-11-01

The inventory cost has important impact on the production cost. In order to get the maximum circulation of funds of enterprise with minimum inventory cost, the inventory control with Lean Six Sigma is presented in supply chain management. The inventory includes both the raw material and the semi-finished parts in manufacturing process. Though the inventory is often studied, the inventory control in manufacturing process is seldom mentioned. This paper reports the inventory control from the perspective of manufacturing process by using statistical techniques including DMAIC, Control Chart, and Statistical Process Control. The process stability is evaluated and the process capability is verified with Lean Six Sigma philosophy. The demonstration in power meter production shows the inventory is decreased from 25% to 0.4%, which indicates the inventory control can be achieved with Lean Six Sigma philosophy and the inventory cost in production can be saved for future sustainable development in supply chain management.

The Case for Architecture by Committee

ERIC Educational Resources Information Center

Building Design and Construction, 1972

1972-01-01

Multiple-architect designs and a preservative of chain-store identities accomplish visual variety for a one-of-a-kind campus at Evergreen State College in Olympia, Washington, and an enclosed shopping mall in Los Cerritos, California. (Author)

Dynamic Models and Coordination Analysis of Reverse Supply Chain with Remanufacturing

NASA Astrophysics Data System (ADS)

Yan, Nina

In this paper, we establish a reverse chain system with one manufacturer and one retailer under demand uncertainties. Distinguishing between the recycling process of the retailer and the remanufacturing process of the manufacturer, we formulate a two-stage dynamic model for reverse supply chain based on remanufacturing. Using buyback contract as coordination mechanism and applying dynamic programming the optimal decision problems for each stage are analyzed. It concluded that the reverse supply chain system could be coordinated under the given condition. Finally, we carry out numerical calculations to analyze the expected profits for the manufacturer and the retailer under different recovery rates and recovery prices and the outcomes validate the theoretical analyses.

Endoglycosidase and glycoamidase release of N-linked oligosaccharides.

PubMed

Freeze, H H

2001-05-01

Carbohydrate chain modifications are often used to monitor glycoprotein movement through the secretory pathway. This is because stepwise sugar-chain processing is unidirectional and generally corresponds to the forward or anterograde movement of proteins. This unit offers a group of techniques that will help analyze the general structure of carbohydrate chains on a protein and, therefore, oligosaccharide processing mileposts. The sugar chains themselves are not analyzed, but their presence and structure are inferred from gel mobility differences after one or more enzymatic digestions. This approach is most often used in combination with [35S]Met pulse-chase metabolic labeling protocols, but they can be applied to any suitably labeled protein (e.g., biotinylated or 125I-labeled).

Bayesian inversion of seismic and electromagnetic data for marine gas reservoir characterization using multi-chain Markov chain Monte Carlo sampling

DOE PAGES

Ren, Huiying; Ray, Jaideep; Hou, Zhangshuan; ...

2017-10-17

In this paper we developed an efficient Bayesian inversion framework for interpreting marine seismic Amplitude Versus Angle and Controlled-Source Electromagnetic data for marine reservoir characterization. The framework uses a multi-chain Markov-chain Monte Carlo sampler, which is a hybrid of DiffeRential Evolution Adaptive Metropolis and Adaptive Metropolis samplers. The inversion framework is tested by estimating reservoir-fluid saturations and porosity based on marine seismic and Controlled-Source Electromagnetic data. The multi-chain Markov-chain Monte Carlo is scalable in terms of the number of chains, and is useful for computationally demanding Bayesian model calibration in scientific and engineering problems. As a demonstration, the approach ismore » used to efficiently and accurately estimate the porosity and saturations in a representative layered synthetic reservoir. The results indicate that the seismic Amplitude Versus Angle and Controlled-Source Electromagnetic joint inversion provides better estimation of reservoir saturations than the seismic Amplitude Versus Angle only inversion, especially for the parameters in deep layers. The performance of the inversion approach for various levels of noise in observational data was evaluated — reasonable estimates can be obtained with noise levels up to 25%. Sampling efficiency due to the use of multiple chains was also checked and was found to have almost linear scalability.« less

Bayesian inversion of seismic and electromagnetic data for marine gas reservoir characterization using multi-chain Markov chain Monte Carlo sampling

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

Ren, Huiying; Ray, Jaideep; Hou, Zhangshuan

In this paper we developed an efficient Bayesian inversion framework for interpreting marine seismic Amplitude Versus Angle and Controlled-Source Electromagnetic data for marine reservoir characterization. The framework uses a multi-chain Markov-chain Monte Carlo sampler, which is a hybrid of DiffeRential Evolution Adaptive Metropolis and Adaptive Metropolis samplers. The inversion framework is tested by estimating reservoir-fluid saturations and porosity based on marine seismic and Controlled-Source Electromagnetic data. The multi-chain Markov-chain Monte Carlo is scalable in terms of the number of chains, and is useful for computationally demanding Bayesian model calibration in scientific and engineering problems. As a demonstration, the approach ismore » used to efficiently and accurately estimate the porosity and saturations in a representative layered synthetic reservoir. The results indicate that the seismic Amplitude Versus Angle and Controlled-Source Electromagnetic joint inversion provides better estimation of reservoir saturations than the seismic Amplitude Versus Angle only inversion, especially for the parameters in deep layers. The performance of the inversion approach for various levels of noise in observational data was evaluated — reasonable estimates can be obtained with noise levels up to 25%. Sampling efficiency due to the use of multiple chains was also checked and was found to have almost linear scalability.« less

Bayesian inversion of seismic and electromagnetic data for marine gas reservoir characterization using multi-chain Markov chain Monte Carlo sampling

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

Ren, Huiying; Ray, Jaideep; Hou, Zhangshuan

In this study we developed an efficient Bayesian inversion framework for interpreting marine seismic amplitude versus angle (AVA) and controlled source electromagnetic (CSEM) data for marine reservoir characterization. The framework uses a multi-chain Markov-chain Monte Carlo (MCMC) sampler, which is a hybrid of DiffeRential Evolution Adaptive Metropolis (DREAM) and Adaptive Metropolis (AM) samplers. The inversion framework is tested by estimating reservoir-fluid saturations and porosity based on marine seismic and CSEM data. The multi-chain MCMC is scalable in terms of the number of chains, and is useful for computationally demanding Bayesian model calibration in scientific and engineering problems. As a demonstration,more » the approach is used to efficiently and accurately estimate the porosity and saturations in a representative layered synthetic reservoir. The results indicate that the seismic AVA and CSEM joint inversion provides better estimation of reservoir saturations than the seismic AVA-only inversion, especially for the parameters in deep layers. The performance of the inversion approach for various levels of noise in observational data was evaluated – reasonable estimates can be obtained with noise levels up to 25%. Sampling efficiency due to the use of multiple chains was also checked and was found to have almost linear scalability.« less

Resistant starch derived from processed legumes: in vitro and in vivo fermentation characteristics.

PubMed

Mahadevamma, S; Shamala, T R; Tharanathan, R N

2004-08-01

The effect of processing of legumes on resistant starch formation, its rate of fermentation and the production of short chain fatty acids under in vitro and in vivo systems was assessed. The content of resistant starch in pressure-cooked Bengal gram, black gram and red gram was 3.59%, 1.58% and 3.34%, respectively. Fermentation in vitro of resistant starch derived from processed red gram showed higher amount of short chain fatty acids (2.38 mmol), especially butyric acid (2.22 mmol). Under in vivo conditions (in albino rats) all processed legumes showed a higher faecal bulking, and more short chain fatty acids, with a significant increase in the anaerobic bacterial counts. Compared with a processed legume diet, the caecum of animals fed a raw diet showed a preponderance of propionic acid.

Syntactic analysis in sentence comprehension: effects of dependency types and grammatical constraints.

PubMed

De Vincenzi, M

1996-01-01

This paper presents three experiments on the parsing of Italian wh-questions that manipulate the wh-type (who vs. which-N) and the wh extraction site (main clause, dependent clause with or without complementizer). The aim of these manipulations is to see whether the parser is sensitive to the type of dependencies being processed and whether the processing effects can be explained by a unique processing principle, the minimal chain principle (MCP; De Vincenzi, 1991). The results show that the parser, following the MCP, prefers structures with fewer and less complex chains. In particular: (1) There is a processing advantage for the wh-subject extractions, the structures with less complex chains; (2) there is a processing dissociation between the who and which questions; (3) the parser respects the principle that governs the well-formedness of the empty categories (ECP).

A Bayesian Approach to a Multiple-Group Latent Class-Profile Analysis: The Timing of Drinking Onset and Subsequent Drinking Behaviors among U.S. Adolescents

ERIC Educational Resources Information Center

Chung, Hwan; Anthony, James C.

2013-01-01

This article presents a multiple-group latent class-profile analysis (LCPA) by taking a Bayesian approach in which a Markov chain Monte Carlo simulation is employed to achieve more robust estimates for latent growth patterns. This article describes and addresses a label-switching problem that involves the LCPA likelihood function, which has…

75 FR 22412 - Food and Drug Administration/Xavier University Global Outsourcing Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

... relationships and supply chain control, as well as expectations from global regulators. Pharmaceutical companies...; Quality Agreement Development throughout the product and process lifecycle; Supply Chain Transparency and Pedigree; How to Audit the Supply Chain; Rx-360 and International Pharmaceutical Excipients Council...

On the Supply Chain Management Supported by E-Commerce Service Platform for Agreement based Circulation of Fruits and Vegetables

NASA Astrophysics Data System (ADS)

Bao, Liwei; Huang, Yuchi; Ma, Zengjun; Zhang, Jie; Lv, Qingchu

According to analysis of the supply chain process of agricultural products, the IT application requirements of the market entities participating in the agreement based circulation of fruits and vegetables have been discussed. The strategy of supply chain management basing on E-commerce service platform for fruits and vegetables has been proposed in this paper. The architecture and function composing of the service platform have been designed and implemented. The platform is constructed on a set of application service modules User can choose some of the application service modules and define them according to the business process. The application service modules chosen and defined by user are integrated as an application service package and applied as management information system of business process. With the E-commerce service platform, the supply chain management for agreement based circulation of agricultural products of vegetables and fruits can be implemented.

Multiple productive immunoglobulin heavy chain gene rearrangements in chronic lymphocytic leukemia are mostly derived from independent clones

PubMed Central

Plevova, Karla; Francova, Hana Skuhrova; Burckova, Katerina; Brychtova, Yvona; Doubek, Michael; Pavlova, Sarka; Malcikova, Jitka; Mayer, Jiri; Tichy, Boris; Pospisilova, Sarka

2014-01-01

In chronic lymphocytic leukemia, usually a monoclonal disease, multiple productive immunoglobulin heavy chain gene rearrangements are identified sporadically. Prognostication of such cases based on immunoglobulin heavy variable gene mutational status can be problematic, especially if the different rearrangements have discordant mutational status. To gain insight into the possible biological mechanisms underlying the origin of the multiple rearrangements, we performed a comprehensive immunogenetic and immunophenotypic characterization of 31 cases with the multiple rearrangements identified in a cohort of 1147 patients with chronic lymphocytic leukemia. For the majority of cases (25/31), we provide evidence of the co-existence of at least two B lymphocyte clones with a chronic lymphocytic leukemia phenotype. We also identified clonal drifts in serial samples, likely driven by selection forces. More specifically, higher immunoglobulin variable gene identity to germline and longer complementarity determining region 3 were preferred in persistent or newly appearing clones, a phenomenon more pronounced in patients with stereotyped B-cell receptors. Finally, we report that other factors, such as TP53 gene defects and therapy administration, influence clonal selection. Our findings are relevant to clonal evolution in the context of antigen stimulation and transition of monoclonal B-cell lymphocytosis to chronic lymphocytic leukemia. PMID:24038023

Orientation of chain molecules in ionotropic gels: a Brownian dynamics model

NASA Astrophysics Data System (ADS)

Woelki, Stefan; Kohler, Hans-Helmut

2003-09-01

As is known from birefringence measurements, polysaccharide molecules of ionotropic gels are preferentially orientated normal to the direction of gel growth. In this paper the orientation effect is investigated by means of an off-lattice Brownian dynamics model simulating the gel formation process. The model describes the integration of a single coarse grained phantom chain into the growing gel. The equations of motion of the chain are derived. The computer simulations show that, during the process of integration, the chain is contracting normal to the direction of gel growth. A scaling relation is obtained for the degree of contraction as a function of the length parameters of the chain, the velocity of the gel formation front and the rate constant of the crosslinking reaction. It is shown that the scaling relation, if applied to the example of ionotropic copper alginate gel, leads to reasonable predictions of the time course of the degree of contraction of the alginate chains.

Phosphorylated ubiquitin chain is the genuine Parkin receptor

PubMed Central

Okatsu, Kei; Koyano, Fumika; Kimura, Mayumi; Kosako, Hidetaka; Saeki, Yasushi

2015-01-01

PINK1 selectively recruits Parkin to depolarized mitochondria for quarantine and removal of damaged mitochondria via ubiquitylation. Dysfunction of this process predisposes development of familial recessive Parkinson’s disease. Although various models for the recruitment process have been proposed, none of them adequately explain the accumulated data, and thus the molecular basis for PINK1 recruitment of Parkin remains to be fully elucidated. In this study, we show that a linear ubiquitin chain of phosphomimetic tetra-ubiquitin(S65D) recruits Parkin to energized mitochondria in the absence of PINK1, whereas a wild-type tetra-ubiquitin chain does not. Under more physiologically relevant conditions, a lysosomal phosphorylated polyubiquitin chain recruited phosphomimetic Parkin to the lysosome. A cellular ubiquitin replacement system confirmed that ubiquitin phosphorylation is indeed essential for Parkin translocation. Furthermore, physical interactions between phosphomimetic Parkin and phosphorylated polyubiquitin chain were detected by immunoprecipitation from cells and in vitro reconstitution using recombinant proteins. We thus propose that the phosphorylated ubiquitin chain functions as the genuine Parkin receptor for recruitment to depolarized mitochondria. PMID:25847540

Analysing the external supply chain risk driver competitiveness: a risk mitigation framework and business continuity plan.

PubMed

Blos, Mauricio F; Wee, Hui-Ming; Yang, Joshua

2010-11-01

Innovation challenges for handling supply chain risks have become one of the most important drivers in business competitiveness and differentiation. This study analyses competitiveness at the external supply chain level as a driver of risks and provides a framework for mitigating these risks. The mitigation framework, also called the supply chain continuity framework, provides insight into six stages of the business continuity planning (BCP) process life cycle (risk mitigation management, business impact analysis, supply continuity strategy development, supply continuity plan development, supply continuity plan testing and supply continuity plan maintenance), together with the operational constructs: customer service, inventory management, flexibility, time to market, ordering cycle time and quality. The purpose of the BCP process life cycle and operational constructs working together is to emphasise the way in which a supply chain can deal with disruption risks and, consequently, bring competitive advantage. Future research will consider the new risk scenarios and analyse the consequences to promote the improvement of supply chain resilience.

Chain-Length-Dependent Exciton Dynamics in Linear Oligothiophenes Probed Using Ensemble and Single-Molecule Spectroscopy.

PubMed

Kim, Tae-Woo; Kim, Woojae; Park, Kyu Hyung; Kim, Pyosang; Cho, Jae-Won; Shimizu, Hideyuki; Iyoda, Masahiko; Kim, Dongho

2016-02-04

Exciton dynamics in π-conjugated molecular systems is highly susceptible to conformational disorder. Using time-resolved and single-molecule spectroscopic techniques, the effect of chain length on the exciton dynamics in a series of linear oligothiophenes, for which the conformational disorder increased with increasing chain length, was investigated. As a result, extraordinary features of the exciton dynamics in longer-chain oligothiophene were revealed. Ultrafast fluorescence depolarization processes were observed due to exciton self-trapping in longer and bent chains. Increase in exciton delocalization during dynamic planarization processes was also observed in the linear oligothiophenes via time-resolved fluorescence spectra but was restricted in L-10T because of its considerable conformational disorder. Exciton delocalization was also unexpectedly observed in a bent chain using single-molecule fluorescence spectroscopy. Such delocalization modulates the fluorescence spectral shape by attenuating the 0-0 peak intensity. Collectively, these results provide significant insights into the exciton dynamics in conjugated polymers.

Unlocking Chain Exchange in Highly Amphiphilic Block Polymer Micellar Systems: Influence of Agitation.

PubMed

Murphy, Ryan P; Kelley, Elizabeth G; Rogers, Simon A; Sullivan, Millicent O; Epps, Thomas H

2014-11-18

Chain exchange between block polymer micelles in highly selective solvents, such as water, is well-known to be arrested under quiescent conditions, yet this work demonstrates that simple agitation methods can induce rapid chain exchange in these solvents. Aqueous solutions containing either pure poly(butadiene- b -ethylene oxide) or pure poly(butadiene- b -ethylene oxide- d 4 ) micelles were combined and then subjected to agitation by vortex mixing, concentric cylinder Couette flow, or nitrogen gas sparging. Subsequently, the extent of chain exchange between micelles was quantified using small angle neutron scattering. Rapid vortex mixing induced chain exchange within minutes, as evidenced by a monotonic decrease in scattered intensity, whereas Couette flow and sparging did not lead to measurable chain exchange over the examined time scale of hours. The linear kinetics with respect to agitation time suggested a surface-limited exchange process at the air-water interface. These findings demonstrate the strong influence of processing conditions on block polymer solution assemblies.

Incompressible inelasticity as an essential ingredient for the validity of the kinematic decomposition F =FeFi

NASA Astrophysics Data System (ADS)

Reina, Celia; Conti, Sergio

2017-10-01

The multiplicative decomposition of the total deformation F =FeFi between an elastic (Fe) and an inelastic component (Fi) is standard in the modeling of many irreversible processes such as plasticity, growth, thermoelasticity, viscoelasticty or phase transformations. The heuristic argument for such kinematic assumption is based on the chain rule for the compatible scenario (CurlFi = 0) where the individual deformation tensors are gradients of deformation mappings, i.e. F = D φ = D (φe ∘φi) = (Dφe) ∘φi (Dφi) =FeFi . Yet, the conditions for its validity in the general incompatible case (CurlFi ≠ 0) has so far remained uncertain. We show in this paper that detFi = 1 and CurlFi bounded are necessary and sufficient conditions for the validity of F =FeFi for a wide range of inelastic processes. In particular, in the context of crystal plasticity, we demonstrate via rigorous homogenization from discrete dislocations to the continuum level in two dimensions, that the volume preserving property of the mechanistics of dislocation glide, combined with a finite dislocation density, is sufficient to deliver F =FeFp at the continuum scale. We then generalize this result to general two-dimensional inelastic processes that may be described at a lower dimensional scale via a multiplicative decomposition while exhibiting a finite density of incompatibilities. The necessity of the conditions detFi = 1 and CurlFi bounded for such systems is demonstrated via suitable counterexamples.

Multidimensional competences of supply chain managers: an empirical study

NASA Astrophysics Data System (ADS)

Shou, Yongyi; Wang, Weijiao

2017-01-01

Supply chain manager competences have attracted increasing attention from both practitioners and scholars in recent years. This paper conducted an explorative study to understand the dimensionality of supply chain manager competences. Online job advertisements for supply chain managers were collected as secondary data, since these advertisements reflect employers' real job requirements. We adopted the multidimensional scaling (MDS) technique to process and analyse the data. Five dimensions of supply chain manager competences are identified: generic skills, functional skills, supply chain management (SCM) qualifications and leadership, SCM expertise, and industry-specific and senior management skills. Statistic tests indicate that supply chain manager competence saliences vary in different industries and regions.

Lightweight Hyperspectral Mapping System and a Novel Photogrammetric Processing Chain for UAV-based Sensing

NASA Astrophysics Data System (ADS)

Suomalainen, Juha; Franke, Jappe; Anders, Niels; Iqbal, Shahzad; Wenting, Philip; Becker, Rolf; Kooistra, Lammert

2014-05-01

We have developed a lightweight Hyperspectral Mapping System (HYMSY) and a novel processing chain for UAV based mapping. The HYMSY consists of a custom pushbroom spectrometer (range 450-950nm, FWHM 9nm, ~20 lines/s, 328 pixels/line), a consumer camera (collecting 16MPix raw image every 2 seconds), a GPS-Inertia Navigation System (GPS-INS), and synchronization and data storage units. The weight of the system at take-off is 2.0kg allowing us to mount it on a relatively small octocopter. The novel processing chain exploits photogrammetry in the georectification process of the hyperspectral data. At first stage the photos are processed in a photogrammetric software producing a high-resolution RGB orthomosaic, a Digital Surface Model (DSM), and photogrammetric UAV/camera position and attitude at the moment of each photo. These photogrammetric camera positions are then used to enhance the internal accuracy of GPS-INS data. These enhanced GPS-INS data are then used to project the hyperspectral data over the photogrammetric DSM, producing a georectified end product. The presented photogrammetric processing chain allows fully automated georectification of hyperspectral data using a compact GPS-INS unit while still producingin UAV use higher georeferencing accuracy than would be possible using the traditional processing method. During 2013, we have operated HYMSY on 150+ octocopter flights at 60+ sites or days. On typical flight we have produced for a 2-10ha area: a RGB orthoimagemosaic at 1-5cm resolution, a DSM in 5-10cm resolution, and hyperspectral datacube at 10-50cm resolution. The targets have mostly consisted of vegetated targets including potatoes, wheat, sugar beets, onions, tulips, coral reefs, and heathlands,. In this poster we present the Hyperspectral Mapping System and the photogrammetric processing chain with some of our first mapping results.

An equal force theory for network models of soft materials with arbitrary molecular weight distribution

NASA Astrophysics Data System (ADS)

Verron, E.; Gros, A.

2017-09-01

Most network models for soft materials, e.g. elastomers and gels, are dedicated to idealized materials: all chains admit the same number of Kuhn segments. Nevertheless, such standard models are not appropriate for materials involving multiple networks, and some specific constitutive equations devoted to these materials have been derived in the last few years. In nearly all cases, idealized networks of different chain lengths are assembled following an equal strain assumption; only few papers adopt an equal stress assumption, although some authors argue that such hypothesis would reflect the equilibrium of the different networks in contact. In this work, a full-network model with an arbitrary chain length distribution is derived by considering that chains of different lengths satisfy the equal force assumption in each direction of the unit sphere. The derivation is restricted to non-Gaussian freely jointed chains and to affine deformation of the sphere. Firstly, after a proper definition of the undeformed configuration of the network, we demonstrate that the equal force assumption leads to the equality of a normalized stretch in chains of different lengths. Secondly, we establish that the network with chain length distribution behaves as an idealized full-network of which both chain length and density of are provided by the chain length distribution. This approach is finally illustrated with two examples: the derivation of a new expression for the Young modulus of bimodal interpenetrated polymer networks, and the prediction of the change in fluorescence during deformation of mechanochemically responsive elastomers.

Function of fusion regulatory proteins (FRPs) in immune cells and virus-infected cells.

PubMed

Tsurudome, M; Ito, Y

2000-01-01

Two molecules that regulate cell fusion have been identified and designated fusion regulatory protein-1 (FRP-1) and FRP-2. FRP-1 is a complex composed of a glycosylated heavy chain and a nonglycosylated light chain that are disulfide linked. FRP-1 heavy chain is identical to 4F2/CD98 heavy chain, whereas FRP-2 is identical to integrin alpha3 subunit. The FRP-1 heavy chain is a multifunctional molecule: that is, fusion regulator, amino acid transporter, integrin regulator, comitogenic factor, Na+-Ca2+ exchanger, oncogenic protein, and so on. Several aspects of the structure and function of the FRP-1 system are reviewed: fusion regulatory molecular mechanisms, cross-talk between the FRP-1 and integrin, the FRP-1 system as amino acid transporter, and FRP-1-mediated T-cell activation. The FRP-1 system is involved in virus-mediated cell fusion and multinucleated giant cell formation of blood monocytes. Monoclonal antibodies against human FRP-1 heavy chain induce polykaryocytes that have properties as osteoclasts. Multiple steps participate in molecular mechanisms regulating cell fusion. The FRP-1 heavy chain supports amino acid transport activity and the FRP-1 light chains have recently been cloned as amino acid transporters that require association with the heavy chain to exhibit their activity. Novel pathways for monocyte-dependent regulation of T-cell activation have recently been found that are mediated by the FRP-1 system. In conclusion, the FRP-1 molecules are essential factors for basic cellular functions.

Multisite Phosphorylation Modulates the T Cell Receptor ζ-Chain Potency but not the Switchlike Response.

PubMed

Mukhopadhyay, Himadri; de Wet, Ben; Clemens, Lara; Maini, Philip K; Allard, Jun; van der Merwe, P Anton; Dushek, Omer

2016-04-26

Multisite phosphorylation is ubiquitous in cellular signaling and is thought to provide signaling proteins with additional regulatory mechanisms. Indeed, mathematical models have revealed a large number of mechanisms by which multisite phosphorylation can produce switchlike responses. The T cell antigen receptor (TCR) is a multisubunit receptor on the surface of T cells that is a prototypical multisite substrate as it contains 20 sites that are distributed on 10 conserved immunoreceptor tyrosine-based activation motifs (ITAMs). The TCR ζ-chain is a homodimer subunit that contains six ITAMs (12 sites) and exhibits a number of properties that are predicted to be sufficient for a switchlike response. We have used cellular reconstitution to systematically study multisite phosphorylation of the TCR ζ-chain. We find that multisite phosphorylation proceeds by a nonsequential random mechanism, and find no evidence that multiple ITAMs modulate a switchlike response but do find that they alter receptor potency and maximum phosphorylation. Modulation of receptor potency can be explained by a reduction in molecular entropy of the disordered ζ-chain upon phosphorylation. We further find that the tyrosine kinase ZAP-70 increases receptor potency but does not modulate the switchlike response. In contrast to other multisite proteins, where phosphorylations act in strong concert to modulate protein function, we suggest that the multiple ITAMs on the TCR function mainly to amplify subsequent signaling. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Developing a model for agile supply: an empirical study from Iranian pharmaceutical supply chain.

PubMed

Rajabzadeh Ghatari, Ali; Mehralian, Gholamhossein; Zarenezhad, Forouzandeh; Rasekh, Hamid Reza

2013-01-01

Agility is the fundamental characteristic of a supply chain needed for survival in turbulent markets, where environmental forces create additional uncertainty resulting in higher risk in the supply chain management. In addition, agility helps providing the right product, at the right time to the consumer. The main goal of this research is therefore to promote supplier selection in pharmaceutical industry according to the formative basic factors. Moreover, this paper can configure its supply network to achieve the agile supply chain. The present article analyzes the supply part of supply chain based on SCOR model, used to assess agile supply chains by highlighting their specific characteristics and applicability in providing the active pharmaceutical ingredient (API). This methodology provides an analytical modeling; the model enables potential suppliers to be assessed against the multiple criteria using both quantitative and qualitative measures. In addition, for making priority of critical factors, TOPSIS algorithm has been used as a common technique of MADM model. Finally, several factors such as delivery speed, planning and reorder segmentation, trust development and material quantity adjustment are identified and prioritized as critical factors for being agile in supply of API.

Developing a Model for Agile Supply: an Empirical Study from Iranian Pharmaceutical Supply Chain

PubMed Central

Rajabzadeh Ghatari, Ali; Mehralian, Gholamhossein; Zarenezhad, Forouzandeh; Rasekh, Hamid Reza

2013-01-01

Agility is the fundamental characteristic of a supply chain needed for survival in turbulent markets, where environmental forces create additional uncertainty resulting in higher risk in the supply chain management. In addition, agility helps providing the right product, at the right time to the consumer. The main goal of this research is therefore to promote supplier selection in pharmaceutical industry according to the formative basic factors. Moreover, this paper can configure its supply network to achieve the agile supply chain. The present article analyzes the supply part of supply chain based on SCOR model, used to assess agile supply chains by highlighting their specific characteristics and applicability in providing the active pharmaceutical ingredient (API). This methodology provides an analytical modeling; the model enables potential suppliers to be assessed against the multiple criteria using both quantitative and qualitative measures. In addition, for making priority of critical factors, TOPSIS algorithm has been used as a common technique of MADM model. Finally, several factors such as delivery speed, planning and reorder segmentation, trust development and material quantity adjustment are identified and prioritized as critical factors for being agile in supply of API. PMID:24250689

Neural mechanisms and models underlying joint action.

PubMed

Chersi, Fabian

2011-06-01

Humans, in particular, and to a lesser extent also other species of animals, possess the impressive capability of smoothly coordinating their actions with those of others. The great amount of work done in recent years in neuroscience has provided new insights into the processes involved in joint action, intention understanding, and task sharing. In particular, the discovery of mirror neurons, which fire both when animals execute actions and when they observe the same actions done by other individuals, has shed light on the intimate relationship between perception and action elucidating the direct contribution of motor knowledge to action understanding. Up to date, however, a detailed description of the neural processes involved in these phenomena is still mostly lacking. Building upon data from single neuron recordings in monkeys observing the actions of a demonstrator and then executing the same or a complementary action, this paper describes the functioning of a biologically constraint neural network model of the motor and mirror systems during joint action. In this model, motor sequences are encoded as independent neuronal chains that represent concatenations of elementary motor acts leading to a specific goal. Action execution and recognition are achieved through the propagation of activity within specific chains. Due to the dual property of mirror neurons, the same architecture is capable of smoothly integrating and switching between observed and self-generated action sequences, thus allowing to evaluate multiple hypotheses simultaneously, understand actions done by others, and to respond in an appropriate way.

Knotting probability of a shaken ball-chain.

PubMed

Hickford, J; Jones, R; du Pont, S Courrech; Eggers, J

2006-11-01

We study the formation of knots on a macroscopic ball chain, which is shaken on a horizontal plate at 12 times the acceleration of gravity. We find that above a certain critical length, the knotting probability is independent of chain length, while the time to shake out a knot increases rapidly with chain length. The probability of finding a knot after a certain time is the result of the balance of these two processes. In particular, the knotting probability tends to a constant for long chains.

PS3 CELL Development for Scientific Computation and Research

NASA Astrophysics Data System (ADS)

Christiansen, M.; Sevre, E.; Wang, S. M.; Yuen, D. A.; Liu, S.; Lyness, M. D.; Broten, M.

2007-12-01

The Cell processor is one of the most powerful processors on the market, and researchers in the earth sciences may find its parallel architecture to be very useful. A cell processor, with 7 cores, can easily be obtained for experimentation by purchasing a PlayStation 3 (PS3) and installing linux and the IBM SDK. Each core of the PS3 is capable of 25 GFLOPS giving a potential limit of 150 GFLOPS when using all 6 SPUs (synergistic processing units) by using vectorized algorithms. We have used the Cell's computational power to create a program which takes simulated tsunami datasets, parses them, and returns a colorized height field image using ray casting techniques. As expected, the time required to create an image is inversely proportional to the number of SPUs used. We believe that this trend will continue when multiple PS3s are chained using OpenMP functionality and are in the process of researching this. By using the Cell to visualize tsunami data, we have found that its greatest feature is its power. This fact entwines well with the needs of the scientific community where the limiting factor is time. Any algorithm, such as the heat equation, that can be subdivided into multiple parts can take advantage of the PS3 Cell's ability to split the computations across the 6 SPUs reducing required run time by one sixth. Further vectorization of the code can allow for 4 simultanious floating point operations by using the SIMD (single instruction multiple data) capabilities of the SPU increasing efficiency 24 times.

Mitochondrial respiratory chain complexes as sources and targets of thiol-based redox-regulation.

PubMed

Dröse, Stefan; Brandt, Ulrich; Wittig, Ilka

2014-08-01

The respiratory chain of the inner mitochondrial membrane is a unique assembly of protein complexes that transfers the electrons of reducing equivalents extracted from foodstuff to molecular oxygen to generate a proton-motive force as the primary energy source for cellular ATP-synthesis. Recent evidence indicates that redox reactions are also involved in regulating mitochondrial function via redox-modification of specific cysteine-thiol groups in subunits of respiratory chain complexes. Vice versa the generation of reactive oxygen species (ROS) by respiratory chain complexes may have an impact on the mitochondrial redox balance through reversible and irreversible thiol-modification of specific target proteins involved in redox signaling, but also pathophysiological processes. Recent evidence indicates that thiol-based redox regulation of the respiratory chain activity and especially S-nitrosylation of complex I could be a strategy to prevent elevated ROS production, oxidative damage and tissue necrosis during ischemia-reperfusion injury. This review focuses on the thiol-based redox processes involving the respiratory chain as a source as well as a target, including a general overview on mitochondria as highly compartmentalized redox organelles and on methods to investigate the redox state of mitochondrial proteins. This article is part of a Special Issue entitled: Thiol-Based Redox Processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Hierarchical group testing for multiple infections.

PubMed

Hou, Peijie; Tebbs, Joshua M; Bilder, Christopher R; McMahan, Christopher S

2017-06-01

Group testing, where individuals are tested initially in pools, is widely used to screen a large number of individuals for rare diseases. Triggered by the recent development of assays that detect multiple infections at once, screening programs now involve testing individuals in pools for multiple infections simultaneously. Tebbs, McMahan, and Bilder (2013, Biometrics) recently evaluated the performance of a two-stage hierarchical algorithm used to screen for chlamydia and gonorrhea as part of the Infertility Prevention Project in the United States. In this article, we generalize this work to accommodate a larger number of stages. To derive the operating characteristics of higher-stage hierarchical algorithms with more than one infection, we view the pool decoding process as a time-inhomogeneous, finite-state Markov chain. Taking this conceptualization enables us to derive closed-form expressions for the expected number of tests and classification accuracy rates in terms of transition probability matrices. When applied to chlamydia and gonorrhea testing data from four states (Region X of the United States Department of Health and Human Services), higher-stage hierarchical algorithms provide, on average, an estimated 11% reduction in the number of tests when compared to two-stage algorithms. For applications with rarer infections, we show theoretically that this percentage reduction can be much larger. © 2016, The International Biometric Society.

Hierarchical group testing for multiple infections

PubMed Central

Hou, Peijie; Tebbs, Joshua M.; Bilder, Christopher R.; McMahan, Christopher S.

2016-01-01

Summary Group testing, where individuals are tested initially in pools, is widely used to screen a large number of individuals for rare diseases. Triggered by the recent development of assays that detect multiple infections at once, screening programs now involve testing individuals in pools for multiple infections simultaneously. Tebbs, McMahan, and Bilder (2013, Biometrics) recently evaluated the performance of a two-stage hierarchical algorithm used to screen for chlamydia and gonorrhea as part of the Infertility Prevention Project in the United States. In this article, we generalize this work to accommodate a larger number of stages. To derive the operating characteristics of higher-stage hierarchical algorithms with more than one infection, we view the pool decoding process as a time-inhomogeneous, finite-state Markov chain. Taking this conceptualization enables us to derive closed-form expressions for the expected number of tests and classification accuracy rates in terms of transition probability matrices. When applied to chlamydia and gonorrhea testing data from four states (Region X of the United States Department of Health and Human Services), higher-stage hierarchical algorithms provide, on average, an estimated 11 percent reduction in the number of tests when compared to two-stage algorithms. For applications with rarer infections, we show theoretically that this percentage reduction can be much larger. PMID:27657666

Markov chains at the interface of combinatorics, computing, and statistical physics

NASA Astrophysics Data System (ADS)

Streib, Amanda Pascoe

The fields of statistical physics, discrete probability, combinatorics, and theoretical computer science have converged around efforts to understand random structures and algorithms. Recent activity in the interface of these fields has enabled tremendous breakthroughs in each domain and has supplied a new set of techniques for researchers approaching related problems. This thesis makes progress on several problems in this interface whose solutions all build on insights from multiple disciplinary perspectives. First, we consider a dynamic growth process arising in the context of DNA-based self-assembly. The assembly process can be modeled as a simple Markov chain. We prove that the chain is rapidly mixing for large enough bias in regions of Zd. The proof uses a geometric distance function and a variant of path coupling in order to handle distances that can be exponentially large. We also provide the first results in the case of fluctuating bias, where the bias can vary depending on the location of the tile, which arises in the nanotechnology application. Moreover, we use intuition from statistical physics to construct a choice of the biases for which the Markov chain Mmon requires exponential time to converge. Second, we consider a related problem regarding the convergence rate of biased permutations that arises in the context of self-organizing lists. The Markov chain Mnn in this case is a nearest-neighbor chain that allows adjacent transpositions, and the rate of these exchanges is governed by various input parameters. It was conjectured that the chain is always rapidly mixing when the inversion probabilities are positively biased, i.e., we put nearest neighbor pair x < y in order with bias 1/2 ≤ pxy ≤ 1 and out of order with bias 1 - pxy. The Markov chain Mmon was known to have connections to a simplified version of this biased card-shuffling. We provide new connections between Mnn and Mmon by using simple combinatorial bijections, and we prove that Mnn is always rapidly mixing for two general classes of positively biased { pxy}. More significantly, we also prove that the general conjecture is false by exhibiting values for the pxy, with 1/2 ≤ pxy ≤ 1 for all x < y, but for which the transposition chain will require exponential time to converge. Finally, we consider a model of colloids, which are binary mixtures of molecules with one type of molecule suspended in another. It is believed that at low density typical configurations will be well-mixed throughout, while at high density they will separate into clusters. This clustering has proved elusive to verify, since all local sampling algorithms are known to be inefficient at high density, and in fact a new nonlocal algorithm was recently shown to require exponential time in some cases. We characterize the high and low density phases for a general family of discrete interfering binary mixtures by showing that they exhibit a "clustering property" at high density and not at low density. The clustering property states that there will be a region that has very high area, very small perimeter, and high density of one type of molecule. Special cases of interfering binary mixtures include the Ising model at fixed magnetization and independent sets.

Altered microRNA regulation of short chain fatty acid receptors in the hypertensive kidney is normalized with hydrogen sulfide supplementation.

PubMed

Weber, Gregory J; Foster, Jaleyea; Pushpakumar, Sathnur B; Sen, Utpal

2018-06-15

Hypertension affects nearly one third of the adult US population and is a significant risk factor for chronic kidney disease (CKD). An expanding body of recent studies indicates that gut microbiome has crucial roles in regulating physiological processes through, among other mechanisms, one mode of short chain fatty acids (SCFA) and their target receptors. In addition, these SCFA receptors are potential targets of regulation by host miRNAs, however, the mechanisms through which this occurs is not clearly defined. Hydrogen sulfide (H 2 S) is an important gasotransmitter involved in multiple physiological processes and is known to alleviate adverse effects of hypertension such as reducing inflammation in the kidney. To determine the role of host microRNAs in regulating short chain fatty acid receptors in the kidney as well as the gut, C57BL/6J wild-type mice were treated with or without Ang-II and H 2 S donor GYY4137 (GYY) for 4 weeks to assess whether GYY would normalize adverse effects observed in hypertensive mice and whether this was in part due to altered gut microbiome composition. We observed several changes of SCFA receptors, including Olfr78, Gpr41/43 and predicted microRNA regulators in the kidney among the different treatments. Increased expression of inflammatory markers Il6 and Rorc2, along with Tgfβ, were found in the hypertensive kidney. The glomerular filtration rate (GFR) was improved in mice treated with Ang-II + GYY compared with Ang-II only, indicating improved kidney function. The Erysipelotrichia class of bacteria, linked with high fat diets, was enriched in hypertensive animals but reduced with GYY supplementation. These data point towards a role for miRNA regulation of SCFA receptors in hypertensive kidney and are normalized by H 2 S supplementation. Copyright © 2018 Elsevier Ltd. All rights reserved.

The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for TIF-1γ sumoylation and poly-SUMO chain elongation.

PubMed

Sohn, Sook-Young; Hearing, Patrick

2016-06-14

The adenovirus (Ad) early region 4 (E4)-ORF3 protein regulates diverse cellular processes to optimize the host environment for the establishment of Ad replication. E4-ORF3 self-assembles into multimers to form a nuclear scaffold in infected cells and creates distinct binding interfaces for different cellular target proteins. Previous studies have shown that the Ad5 E4-ORF3 protein induces sumoylation of multiple cellular proteins and subsequent proteasomal degradation of some of them, but the detailed mechanism of E4-ORF3 function remained unknown. Here, we investigate the role of E4-ORF3 in the sumoylation process by using transcription intermediary factor (TIF)-1γ as a substrate. Remarkably, we discovered that purified E4-ORF3 protein stimulates TIF-1γ sumoylation in vitro, demonstrating that E4-ORF3 acts as a small ubiquitin-like modifier (SUMO) E3 ligase. Furthermore, E4-ORF3 significantly increases poly-SUMO3 chain formation in vitro in the absence of substrate, showing that E4-ORF3 has SUMO E4 elongase activity. An E4-ORF3 mutant, which is defective in protein multimerization, exhibited severely decreased activity, demonstrating that E4-ORF3 self-assembly is required for these activities. Using a SUMO3 mutant, K11R, we found that E4-ORF3 facilitates the initial acceptor SUMO3 conjugation to TIF-1γ as well as poly-SUMO chain elongation. The E4-ORF3 protein displays no SUMO-targeted ubiquitin ligase activity in our assay system. These studies reveal the mechanism by which E4-ORF3 targets specific cellular proteins for sumoylation and proteasomal degradation and provide significant insight into how a small viral protein can play a role as a SUMO E3 ligase and E4-like SUMO elongase to impact a variety of cellular responses.

Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features.

PubMed

Beaty, M W; Toro, J; Sorbara, L; Stern, J B; Pittaluga, S; Raffeld, M; Wilson, W H; Jaffe, E S

2001-09-01

Lymphomatoid granulomatosis (LYG) is a rare angiocentric and angiodestructive Epstein-Barr virus-associated B-cell lymphoproliferative disorder (EBV-BLPD), varying widely from an indolent process to an aggressive large cell lymphoma. The skin is the extrapulmonary organ most commonly involved in LYG. We studied 32 skin lesions from 20 patients with known pulmonary LYG, using immunohistochemistry, in situ hybridization for EBV, and polymerase chain reaction for the presence of antigen receptor gene rearrangements (IgH and TCR) to better define both the clinicopathologic spectrum and pathogenesis of the cutaneous lesions. We describe two distinct patterns of cutaneous involvement. Multiple erythematous dermal papules and/or subcutaneous nodules, with or without ulceration, were present in 17 patients (85%). These lesions demonstrate a marked angiocentric lymphohistiocytic infiltrate, composed predominantly of CD4-positive T-cells, with a high propensity for involving the subcutaneous tissues, and exhibiting angiodestruction, necrosis, and cytologic atypia. EBV-positive B-cells were detected in the nodules from five patients; clonal immunoglobulin heavy chain gene (IgH) rearrangements were detected by polymerase chain reaction in two patients. Multiple indurated, erythematous to white plaques were present in three patients (15%). The plaque lesions were negative for EBV and clonal IgH gene rearrangements in all cases studied. The clinical course of overall disease was variable, ranging from spontaneous regression without treatment (1 of 13; 7%), resolution with chemo/immunomodulatory therapy (8 of 13; 62%), and progression (4 of 13; 31%). The clinical and histopathologic features of cutaneous LYG are extremely diverse. However, the majority (85%) of the cutaneous lesions mirrors to some extent LYG in the lung, although EBV+ cells are less frequently identified. This subset of cases shows the histopathologic triad of angiodestruction with associated necrosis, panniculitis, and in some cases atypical lymphoid cells. The commonality of the histologic features in this group suggests a common pathophysiologic basis, possibly mediated by cytokines and chemokines induced by EBV. A small percentage of the lesions (15%) presented as indurated and atrophic plaques, and EBV was not identified in the small number of cases studied. The relationship of the plaque-like lesions to LYG remains uncertain. Whereas some cases of LYG regress spontaneously, most require therapy.

Kinetics of a Collagen-Like Polypeptide Fragmentation after Mid-IR Free-Electron Laser Ablation

PubMed Central

Zavalin, Andrey; Hachey, David L.; Sundaramoorthy, Munirathinam; Banerjee, Surajit; Morgan, Steven; Feldman, Leonard; Tolk, Norman; Piston, David W.

2008-01-01

Tissue ablation with mid-infrared irradiation tuned to collagen vibrational modes results in minimal collateral damage. The hypothesis for this effect includes selective scission of protein molecules and excitation of surrounding water molecules, with the scission process currently favored. In this article, we describe the postablation infrared spectral decay kinetics in a model collagen-like peptide (Pro-Pro-Gly)10. We find that the decay is exponential with different decay times for other, simpler dipeptides. Furthermore, we find that collagen-like polypeptides, such as (Pro-Pro-Gly)10, show multiple decay times, indicating multiple scission locations and cross-linking to form longer chain molecules. In combination with data from high-resolution mass spectrometry, we interpret these products to result from the generation of reactive intermediates, such as free radicals, cyanate ions, and isocyanic acid, which can form cross-links and protein adducts. Our results lead to a more complete explanation of the reduced collateral damage resulting from infrared laser irradiation through a mechanism involving cross-linking in which collagen-like molecules form a network of cross-linked fibers. PMID:18441025

A Multi-organisational Approach to Service Delivery

NASA Astrophysics Data System (ADS)

Purchase, Valerie; Mills, John; Parry, Glenn

Who is involved in delivering a service? There has been growing recognition in a wide variety of contexts that service is increasingly being delivered by multi-rather than single-organisational entities. Such recognition is evident not only in our experience but in a number of areas of literature including strategy development, core competence analysis, operations and supply chain management, and is reflected in and further facilitated by ICT developments. Customers have always been involved in some degree in the process of value delivery and such involvement is increasing to include complex co-creation of value. Such interactions are challenging when they involve individual customers, however, this becomes ever more challenging when the 'customer' is another organisation or when there are multiple 'customers'. Within this chapter we will consider some of the key drivers for a multi-organisational approach to service delivery; examine the ways in which the parties involved in service co-creation have expanded to include multiple service providers and customers; and finally, identify some of the challenges created by a multi-organisational approach to service delivery.

Modeling species occurrence dynamics with multiple states and imperfect detection

USGS Publications Warehouse

MacKenzie, D.I.; Nichols, J.D.; Seamans, M.E.; Gutierrez, R.J.

2009-01-01

Recent extensions of occupancy modeling have focused not only on the distribution of species over space, but also on additional state variables (e.g., reproducing or not, with or without disease organisms, relative abundance categories) that provide extra information about occupied sites. These biologist-driven extensions are characterized by ambiguity in both species presence and correct state classification, caused by imperfect detection. We first show the relationships between independently published approaches to the modeling of multistate occupancy. We then extend the pattern-based modeling to the case of sampling over multiple seasons or years in order to estimate state transition probabilities associated with system dynamics. The methodology and its potential for addressing relevant ecological questions are demonstrated using both maximum likelihood (occupancy and successful reproduction dynamics of California Spotted Owl) and Markov chain Monte Carlo estimation approaches (changes in relative abundance of green frogs in Maryland). Just as multistate capture-recapture modeling has revolutionized the study of individual marked animals, we believe that multistate occupancy modeling will dramatically increase our ability to address interesting questions about ecological processes underlying population-level dynamics. ?? 2009 by the Ecological Society of America.

Dynamic models for problems of species occurrence with multiple states

USGS Publications Warehouse

MacKenzie, D.I.; Nichols, J.D.; Seamans, M.E.; Gutierrez, R.J.

2009-01-01

Recent extensions of occupancy modeling have focused not only on the distribution of species over space, but also on additional state variables (e.g., reproducing or not, with or without disease organisms, relative abundance categories) that provide extra information about occupied sites. These biologist-driven extensions are characterized by ambiguity in both species presence and correct state classification, caused by imperfect detection. We first show the relationships between independently published approaches to the modeling of multistate occupancy. We then extend the pattern-based modeling to the case of sampling over multiple seasons or years in order to estimate state transition probabilities associated with system dynamics. The methodology and its potential for addressing relevant ecological questions are demonstrated using both maximum likelihood (occupancy and successful reproduction dynamics of California Spotted Owl) and Markov chain Monte Carlo estimation approaches (changes in relative abundance of green frogs in Maryland). Just as multistate capture?recapture modeling has revolutionized the study of individual marked animals, we believe that multistate occupancy modeling will dramatically increase our ability to address interesting questions about ecological processes underlying population-level dynamics.

A heuristic approach using multiple criteria for environmentally benign 3PLs selection

NASA Astrophysics Data System (ADS)

Kongar, Elif

2005-11-01

Maintaining competitiveness in an environment where price and quality differences between competing products are disappearing depends on the company's ability to reduce costs and supply time. Timely responses to rapidly changing market conditions require an efficient Supply Chain Management (SCM). Outsourcing logistics to third-party logistics service providers (3PLs) is one commonly used way of increasing the efficiency of logistics operations, while creating a more "core competency focused" business environment. However, this alone may not be sufficient. Due to recent environmental regulations and growing public awareness regarding environmental issues, 3PLs need to be not only efficient but also environmentally benign to maintain companies' competitiveness. Even though an efficient and environmentally benign combination of 3PLs can theoretically be obtained using exhaustive search algorithms, heuristics approaches to the selection process may be superior in terms of the computational complexity. In this paper, a hybrid approach that combines a multiple criteria Genetic Algorithm (GA) with Linear Physical Weighting Algorithm (LPPW) to be used in efficient and environmentally benign 3PLs is proposed. A numerical example is also provided to illustrate the method and the analyses.