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Sample records for oligonucleotide design challenge

  1. Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy

    Goyenvalle Aurélie

    2011-02-01

    Full Text Available Abstract Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.

  2. Design of oligonucleotides for microarrays and perspectives for design of multi-transcriptome arrays

    Nielsen, Henrik Bjørn; Wernersson, Rasmus; Knudsen, Steen

    2003-01-01

    with an overview of these parameters. We present here a flexible tool named OligoWiz for designing oligonucleotides for multiple purposes. OligoWiz presents a set of parameter scores in a graphical interface to facilitate an overview for the user. Additional custom parameter scores can easily be added......Optimal design of oligonucleotides for microarrays involves tedious and laborious work evaluating potential oligonucleotides relative to a series of parameters. The currently available tools for this purpose are limited in their flexibility and do not present the oligonucleotide designer...... to the program to extend the default parameters: homology, DeltaTm, low-complexity, position and GATC-only. Furthermore we present an analysis of the limitations in designing oligonucleotide sets that can detect transcripts from multiple organisms. OligoWiz is available at www.cbs.dtu.dk/services/OligoWiz/....

  3. Virtual Bridge Design Challenge

    Mitts, Charles R.

    2013-01-01

    This design/problem-solving activity challenges students to design a replacement bridge for one that has been designated as either structurally deficient or functionally obsolete. The Aycock MS Technology/STEM Magnet Program Virtual Bridge Design Challenge is an authentic introduction to the engineering design process. It is a socially relevant…

  4. Merlin: Computer-Aided Oligonucleotide Design for Large Scale Genome Engineering with MAGE.

    Quintin, Michael; Ma, Natalie J; Ahmed, Samir; Bhatia, Swapnil; Lewis, Aaron; Isaacs, Farren J; Densmore, Douglas

    2016-06-17

    Genome engineering technologies now enable precise manipulation of organism genotype, but can be limited in scalability by their design requirements. Here we describe Merlin ( http://merlincad.org ), an open-source web-based tool to assist biologists in designing experiments using multiplex automated genome engineering (MAGE). Merlin provides methods to generate pools of single-stranded DNA oligonucleotides (oligos) for MAGE experiments by performing free energy calculation and BLAST scoring on a sliding window spanning the targeted site. These oligos are designed not only to improve recombination efficiency, but also to minimize off-target interactions. The application further assists experiment planning by reporting predicted allelic replacement rates after multiple MAGE cycles, and enables rapid result validation by generating primer sequences for multiplexed allele-specific colony PCR. Here we describe the Merlin oligo and primer design procedures and validate their functionality compared to OptMAGE by eliminating seven AvrII restriction sites from the Escherichia coli genome.

  5. Mismatch oligonucleotides in human and yeast: guidelines for probe design on tiling microarrays

    Jee Justin

    2008-12-01

    Full Text Available Abstract Background Mismatched oligonucleotides are widely used on microarrays to differentiate specific from nonspecific hybridization. While many experiments rely on such oligos, the hybridization behavior of various degrees of mismatch (MM structure has not been extensively studied. Here, we present the results of two large-scale microarray experiments on S. cerevisiae and H. sapiens genomic DNA, to explore MM oligonucleotide behavior with real sample mixtures under tiling-array conditions. Results We examined all possible nucleotide substitutions at the central position of 36-nucleotide probes, and found that nonspecific binding by MM oligos depends upon the individual nucleotide substitutions they incorporate: C→A, C→G and T→A (yielding purine-purine mispairs are most disruptive, whereas A→X were least disruptive. We also quantify a marked GC skew effect: substitutions raising probe GC content exhibit higher intensity (and vice versa. This skew is small in highly-expressed regions (± 0.5% of total intensity range and large (± 2% or more elsewhere. Multiple mismatches per oligo are largely additive in effect: each MM added in a distributed fashion causes an additional 21% intensity drop relative to PM, three-fold more disruptive than adding adjacent mispairs (7% drop per MM. Conclusion We investigate several parameters for oligonucleotide design, including the effects of each central nucleotide substitution on array signal intensity and of multiple MM per oligo. To avoid GC skew, individual substitutions should not alter probe GC content. RNA sample mixture complexity may increase the amount of nonspecific hybridization, magnify GC skew and boost the intensity of MM oligos at all levels.

  6. A comparison of alternative 60-mer probe designs in an in-situ synthesized oligonucleotide microarray

    Fairbanks Benjamin D

    2006-04-01

    Full Text Available Abstract Background DNA microarrays have proven powerful for functional genomics studies. Several technologies exist for the generation of whole-genome arrays. It is well documented that 25mer probes directed against different regions of the same gene produce variable signal intensity values. However, the extent to which this is true for probes of greater length (60mers is not well characterized. Moreover, this information has not previously been reported for whole-genome arrays designed against bacteria, whose genomes may differ substantially in characteristics directly affecting microarray performance. Results We report here an analysis of alternative 60mer probe designs for an in-situ synthesized oligonucleotide array for the GC rich, β-proteobacterium Burkholderia cenocepacia. Probes were designed using the ArrayOligoSel3.5 software package and whole-genome microarrays synthesized by Agilent, Inc. using their in-situ, ink-jet technology platform. We first validated the quality of the microarrays as demonstrated by an average signal to noise ratio of >1000. Next, we determined that the variance of replicate probes (1178 total probes examined of identical sequence was 3.8% whereas the variance of alternative probes (558 total alternative probes examined designs was 9.5%. We determined that depending upon the definition, about 2.4% of replicate and 7.8% of alternative probes produced outlier conclusions. Finally, we determined none of the probe design subscores (GC content, internal repeat, binding energy and self annealment produced by ArrayOligoSel3.5 were predictive or probes that produced outlier signals. Conclusion Our analysis demonstrated that the use of multiple probes per target sequence is not essential for in-situ synthesized 60mer oligonucleotide arrays designed against bacteria. Although probes producing outlier signals were identified, the use of ratios results in less than 10% of such outlier conclusions. We also determined that

  7. Rooftop Garden Design Challenge

    Roman, Harry T.

    2010-01-01

    A small commercial building in a nearby industrial park has decided to install a rooftop garden for its employees to enjoy. The garden will be about 100 feet long and 75 feet wide. This article presents a design challenge for technology and engineering students wherein they will assist in the initial conceptual design of the rooftop garden. The…

  8. Template-Independent Enzymatic Oligonucleotide Synthesis (TiEOS): Its History, Prospects, and Challenges.

    Jensen, Michael A; Davis, Ronald W

    2018-03-27

    There is a growing demand for sustainable methods in research and development, where instead of hazardous chemicals, an aqueous medium is chosen to perform biological reactions. In this Perspective, we examine the history and current methodology of using enzymes to generate artificial single-stranded DNA. By using traditional solid-phase phosphoramidite chemistry as a metric, we also explore criteria for the method of template-independent enzymatic oligonucleotide synthesis (TiEOS). As its key component, we delve into the biology of one of the most enigmatic enzymes, terminal deoxynucleotidyl transferase (TdT). As TdT is found to exponentially increase antigen receptor diversity in the vertebrate immune system by adding nucleotides in a template-free manner, researchers have exploited this function as an alternative to the phosphoramidite synthesis method. Though TdT is currently the preferred enzyme for TiEOS, its random nucleotide incorporation presents a barrier in synthesis automation. Taking a closer look at the TiEOS cycle, particularly the coupling step, we find it is comprised of additions > n+1 and deletions. By tapping into the physical and biochemical properties of TdT, we strive to further elucidate its mercurial behavior and offer ways to better optimize TiEOS for production-grade oligonucleotide synthesis.

  9. Safeguards by Design Challenge

    Alwin, Jennifer Louise [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2016-09-13

    The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA’s limited budget. Dose to workers should always be as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).

  10. Safeguards by Design Challenge

    Alwin, Jennifer Louise

    2016-01-01

    The International Atomic Energy Agency (IAEA) defines Safeguards as a system of inspection and verification of the peaceful uses of nuclear materials as part of the Nuclear Nonproliferation Treaty. IAEA oversees safeguards worldwide. Safeguards by Design (SBD) involves incorporation of safeguards technologies, techniques, and instrumentation during the design phase of a facility, rather that after the fact. Design challenge goals are the following: Design a system of safeguards technologies, techniques, and instrumentation for inspection and verification of the peaceful uses of nuclear materials. Cost should be minimized to work with the IAEA's limited budget. Dose to workers should always be as low are reasonably achievable (ALARA). Time is of the essence in operating facilities and flow of material should not be interrupted significantly. Proprietary process information in facilities may need to be protected, thus the amount of information obtained by inspectors should be the minimum required to achieve the measurement goal. Then three different design challenges are detailed: Plutonium Waste Item Measurement System, Marine-based Modular Reactor, and Floating Nuclear Power Plant (FNPP).

  11. Experimental design, modeling and optimization of polyplex formation between DNA oligonucleotides and branched polyethylenimine.

    Clima, Lilia; Ursu, Elena L; Cojocaru, Corneliu; Rotaru, Alexandru; Barboiu, Mihail; Pinteala, Mariana

    2015-09-28

    The complexes formed by DNA and polycations have received great attention owing to their potential application in gene therapy. In this study, the binding efficiency between double-stranded oligonucleotides (dsDNA) and branched polyethylenimine (B-PEI) has been quantified by processing of the images captured from the gel electrophoresis assays. The central composite experimental design has been employed to investigate the effects of controllable factors on the binding efficiency. On the basis of experimental data and the response surface methodology, a multivariate regression model has been constructed and statistically validated. The model has enabled us to predict the binding efficiency depending on experimental factors, such as concentrations of dsDNA and B-PEI as well as the initial pH of solution. The optimization of the binding process has been performed using simplex and gradient methods. The optimal conditions determined for polyplex formation have yielded a maximal binding efficiency close to 100%. In order to reveal the mechanism of complex formation at the atomic-scale, a molecular dynamic simulation has been carried out. According to the computation results, B-PEI amine hydrogen atoms have interacted with oxygen atoms from dsDNA phosphate groups. These interactions have led to the formation of hydrogen bonds between macromolecules, stabilizing the polyplex structure.

  12. Design, validation and annotation of transcriptome-wide oligonucleotide probes for the oligochaete annelid Eisenia fetida.

    Ping Gong

    Full Text Available High density oligonucleotide probe arrays have increasingly become an important tool in genomics studies. In organisms with incomplete genome sequence, one strategy for oligo probe design is to reduce the number of unique probes that target every non-redundant transcript through bioinformatic analysis and experimental testing. Here we adopted this strategy in making oligo probes for the earthworm Eisenia fetida, a species for which we have sequenced transcriptome-scale expressed sequence tags (ESTs. Our objectives were to identify unique transcripts as targets, to select an optimal and non-redundant oligo probe for each of these target ESTs, and to annotate the selected target sequences. We developed a streamlined and easy-to-follow approach to the design, validation and annotation of species-specific array probes. Four 244K-formatted oligo arrays were designed using eArray and were hybridized to a pooled E. fetida cRNA sample. We identified 63,541 probes with unsaturated signal intensities consistently above the background level. Target transcripts of these probes were annotated using several sequence alignment algorithms. Significant hits were obtained for 37,439 (59% probed targets. We validated and made publicly available 63.5K oligo probes so the earthworm research community can use them to pursue ecological, toxicological, and other functional genomics questions. Our approach is efficient, cost-effective and robust because it (1 does not require a major genomics core facility; (2 allows new probes to be easily added and old probes modified or eliminated when new sequence information becomes available, (3 is not bioinformatics-intensive upfront but does provide opportunities for more in-depth annotation of biological functions for target genes; and (4 if desired, EST orthologs to the UniGene clusters of a reference genome can be identified and selected in order to improve the target gene specificity of designed probes. This approach is

  13. Design and analysis of effects of triplet repeat oligonucleotides in cell models for myotonic dystrophy

    Gonzalez-Barriga, A.; Mulders, S.A.M.; Giessen, J. van der; Hooijer, J.D.; Bijl, S.; Kessel, I.D.G. van; Beers, J. van; Deutekom, J.C. van; Fransen, J.A.M.; Wieringa, B.; Wansink, D.G.

    2013-01-01

    Myotonic dystrophy type 1 (DM1) is caused by DM protein kinase (DMPK) transcripts containing an expanded (CUG)n repeat. Antisense oligonucleotide (AON)-mediated suppression of these mutant RNAs is considered a promising therapeutic strategy for this severe disorder. Earlier, we identified a

  14. MODEST: a web-based design tool for oligonucleotide-mediated genome engineering and recombineering

    Bonde, Mads; Klausen, Michael Schantz; Anderson, Mads Valdemar

    2014-01-01

    Recombineering and multiplex automated genome engineering (MAGE) offer the possibility to rapidly modify multiple genomic or plasmid sites at high efficiencies. This enables efficient creation of genetic variants including both single mutants with specifically targeted modifications as well......, which confers the corresponding genetic change, is performed manually. To address these challenges, we have developed the MAGE Oligo Design Tool (MODEST). This web-based tool allows designing of MAGE oligos for (i) tuning translation rates by modifying the ribosomal binding site, (ii) generating...

  15. Challenges in Designing Mechatronic Systems

    Torry-Smith, Jonas; Qamar, Ahsan; Achiche, Sofiane

    2013-01-01

    Development of mechatronic products is traditionally carried out by several design experts from different design domains. Performing development of mechatronic products is thus greatly challenging. In order to tackle this, the critical challenges in mechatronics have to be well understood and well...... supported through applicable methods and tools. This paper aims at identifying the major challenges, by conducting a systematic and thorough survey of the most relevant research work in mechatronic design. Solutions proposed in literature are assessed and illustrated through a case study in order...... to investigate if the challenges can be handled appropriately by the methods, tools, and mindsets suggested by the mechatronic community. Using a real world mechatronics case, the paper identifies the areas where further research is required, by showing a clear connection between the actual problems faced during...

  16. Challenges of Aircraft Design Integration

    2003-03-01

    predicted by the conceptual stick model and the full FEM of the Challenger wing without winglets . Advanced aerodynamic wing design methods To design wings...Piperni, E. Laurendeau Advanced Aerodynamics Bombardier Aerospace 400 CMte Vertu Road Dorval, Quebec, Canada, H4S 1Y9 Fassi.Kafyeke @notes.canadair.ca Tel...514) 855-7186 Abstract The design of a modern airplane brings together many disciplines: structures, aerodynamics , controls, systems, propulsion

  17. A newly designed 45 to 60 mer oligonucleotide Agilent platform microarray for global gene expression studies of Synechocystis PCC6803: example salt stress experiment

    Aguirre von Wobeser, E.; Huisman, J.; Ibelings, B.; Matthijs, H.C.P.; Matthijs, H.C.P.

    2005-01-01

    A newly designed 45 to 60 mer oligonucleotide Agilent platform microarray for global gene expression studies of Synechocystis PCC6803: example salt stress experiment Eneas Aguirre-von-Wobeser 1, Jef Huisman1, Bas Ibelings2 and Hans C.P. Matthijs1 1 Universiteit van Amsterdam, Amsterdam, The

  18. High-density rhesus macaque oligonucleotide microarray design using early-stage rhesus genome sequence information and human genome annotations

    Magness Charles L

    2007-01-01

    Full Text Available Abstract Background Until recently, few genomic reagents specific for non-human primate research have been available. To address this need, we have constructed a macaque-specific high-density oligonucleotide microarray by using highly fragmented low-pass sequence contigs from the rhesus genome project together with the detailed sequence and exon structure of the human genome. Using this method, we designed oligonucleotide probes to over 17,000 distinct rhesus/human gene orthologs and increased by four-fold the number of available genes relative to our first-generation expressed sequence tag (EST-derived array. Results We constructed a database containing 248,000 exon sequences from 23,000 human RefSeq genes and compared each human exon with its best matching sequence in the January 2005 version of the rhesus genome project list of 486,000 DNA contigs. Best matching rhesus exon sequences for each of the 23,000 human genes were then concatenated in the proper order and orientation to produce a rhesus "virtual transcriptome." Microarray probes were designed, one per gene, to the region closest to the 3' untranslated region (UTR of each rhesus virtual transcript. Each probe was compared to a composite rhesus/human transcript database to test for cross-hybridization potential yielding a final probe set representing 18,296 rhesus/human gene orthologs, including transcript variants, and over 17,000 distinct genes. We hybridized mRNA from rhesus brain and spleen to both the EST- and genome-derived microarrays. Besides four-fold greater gene coverage, the genome-derived array also showed greater mean signal intensities for genes present on both arrays. Genome-derived probes showed 99.4% identity when compared to 4,767 rhesus GenBank sequence tag site (STS sequences indicating that early stage low-pass versions of complex genomes are of sufficient quality to yield valuable functional genomic information when combined with finished genome information from

  19. New challenges for data design

    2015-01-01

    The present work provides a platform for leading data designers whose vision and creativity help us to anticipate major changes occurring in the data design field, and pre-empt the future. Each of them strives to provide new answers to the question, “What challenges await data design?” To avoid falling into too narrow a mind-set, each works hard to elucidate the breadth of data design today and to demonstrate its widespread application across a variety of business sectors. With end users in mind, designer-contributors bring to light the myriad of purposes for which the field was originally intended, forging the bond even further between data design and the aims and intentions of those who contribute to it. The first seven parts of the book outline the scope of data design, and presents a line-up of “viewpoints” that highlight this discipline’s main topics, and offers an in-depth look into practices boasting both foresight and imagination. The eighth and final part features a series of interviews wit...

  20. G4-DNA formation in the HRAS promoter and rational design of decoy oligonucleotides for cancer therapy.

    Alexandro Membrino

    Full Text Available HRAS is a proto-oncogene involved in the tumorigenesis of urinary bladder cancer. In the HRAS promoter we identified two G-rich elements, hras-1 and hras-2, that fold, respectively, into an antiparallel and a parallel quadruplex (qhras-1, qhras-2. When we introduced in sequence hras-1 or hras-2 two point mutations that block quadruplex formation, transcription increased 5-fold, but when we stabilized the G-quadruplexes by guanidinium phthalocyanines, transcription decreased to 20% of control. By ChIP we found that sequence hras-1 is bound only by MAZ, while hras-2 is bound by MAZ and Sp1: two transcription factors recognizing guanine boxes. We also discovered by EMSA that recombinant MAZ-GST binds to both HRAS quadruplexes, while Sp1-GST only binds to qhras-1. The over-expression of MAZ and Sp1 synergistically activates HRAS transcription, while silencing each gene by RNAi results in a strong down-regulation of transcription. All these data indicate that the HRAS G-quadruplexes behave as transcription repressors. Finally, we designed decoy oligonucleotides mimicking the HRAS quadruplexes, bearing (R-1-O-[4-(1-Pyrenylethynyl phenylmethyl] glycerol and LNA modifications to increase their stability and nuclease resistance (G4-decoys. The G4-decoys repressed HRAS transcription and caused a strong antiproliferative effect, mediated by apoptosis, in T24 bladder cancer cells where HRAS is mutated.

  1. Power-Efficient Design Challenges

    Pangrle, Barry

    significant gains can be realized and why power-efficiency requirements will continue to challenge designers into the future. Despite new process technologies, the future will continue to rely on innovative design approaches.

  2. Fluorescence detection of natural RNA using rationally designed "clickable" oligonucleotide probes

    Okholm, Anders; Kjems, Jørgen; Astakhova, Kira

    2014-01-01

    Herein a reliable approach to the design of effective fluorescent probes for RNA detection is described. The fluorescence signalling of hybridization by internally positioned polyaromatic hydrocarbons and rhodamine dyes was achieved with a low fluorescence background signal, high fluorescence qua...... quantum yields at ambient and elevated temperature, high selectivity and signal specificity of the probes when binding to miR-7 and circRNA targets....

  3. A CpG oligonucleotide can protect mice from a low aerosol challenge dose of Burkholderia mallei.

    Waag, David M; McCluskie, Michael J; Zhang, Ningli; Krieg, Arthur M

    2006-03-01

    Treatment with an oligodeoxynucleotide (ODN) containing CPG motifs (CpG ODN 7909) was found to protect BALB/c mice from lung infection or death after aerosol challenge with Burkholderia mallei. Protection was associated with enhanced levels of gamma interferon (IFN-gamma)-inducible protein 10, interleukin-12 (IL-12), IFN-gamma, and IL-6. Preexposure therapy with CpG ODNs may protect victims of a biological attack from glanders.

  4. The Speeding Car Design Challenge

    Roman, Harry T.

    2009-01-01

    All too often, one reads about high-speed police chases in pursuit of stolen cars that result in death and injury to people and innocent bystanders. Isn't there another way to accomplish the apprehension of the thieves that does not put people at such great risk? This article presents a classroom challenge to use technology to remotely shutdown…

  5. Designing the robot inclusive space challenge

    Rajesh Elara Mohan

    2015-11-01

    Full Text Available A novel robotic challenge, namely the robot inclusive spaces (RIS challenge, is proposed in this paper, which is a cross disciplinary and design focused initiative. It aims to foster the roboticists, architects, and designers towards realizing robot friendly social spaces. Contrary to conventional robotics competitions focusing on designing robots and its component technologies, robot inclusive spaces challenge adopts an interdisciplinary “design for robots” strategy to overcome the traditional research problem in real world deployments of social robots. In order to realize the RIS, various architectural elements must be adapted including: design principles for inclusive spaces, lighting schemes, furniture choices and arrangement, wall and floor surfaces, pathways among others. This paper introduces the format and design principles of RIS challenge, presents a first run of the challenge, and gives the corresponding analysis.

  6. Challenges in Nordic Design Research

    Andreasen, Mogens Myrup

    1996-01-01

    Design research has not won a convincing reputation in industry. Nordic research being scattered and small in number of researchers should find its special strengths and focus on creating results, which are based on our peculiar conditions and background.......Design research has not won a convincing reputation in industry. Nordic research being scattered and small in number of researchers should find its special strengths and focus on creating results, which are based on our peculiar conditions and background....

  7. Challenges in physical chip design

    Otten, R.H.J.M.; Stravers, P.

    2000-01-01

    On behalf of the ICCAD-2000 Executive and Technical Program Committees, I would like to welcome you tothe International Conference on Computer-Aided Design, which will take place between November 5-9 at theSan Jose DoubleTree Hotel. The technical program for ICCAD-2000 was assembled by a program

  8. Challenges to Designing Game-Based Business

    Henriksen, Thomas Duus

    2014-01-01

    The four categories labelled game-design, didactic design, organisational design and business design each constitute a set of challenges, each requiring a particular set of competencies. The key conclusion of the paper is that even though the learning game design constitutes the core of establish......The four categories labelled game-design, didactic design, organisational design and business design each constitute a set of challenges, each requiring a particular set of competencies. The key conclusion of the paper is that even though the learning game design constitutes the core...... of establishing game based business (GBB), the subsequent stages of development call for other kinds of competencies in order to become a viable GBB....

  9. Mechatronic Design - Still a Considerable Challenge

    Torry-Smith, Jonas; Qamar, Ahsan; Achiche, Sofiane

    2011-01-01

    Development of mechatronic products is traditionally carried out by several design experts from different design domains. Performing development of mechatronic products is thus greatly challenging. In order to tackle this, the critical challenges in mechatronics have to be well understood and well...... supported through applicable methods and tools. This paper aims at identifying the major challenges, by conducting a survey of the most relevant research work in mechatronic design. Solutions proposed in literature are assessed and illustrated through a case study in order to investigate, if the challenges...... can be handled appropriately by the methods, tools, and mindsets suggested by the mechatronic community. Using a real world mechatronics case, the paper identifies the areas where further research is required, by showing a clear connection between the actual problems faced during the design task...

  10. Challenges in biomimetic design and innovation

    Lenau, Torben Anker; Barfoed, Michael; Shu, Li

    Biomimetic design copies desired principles found in nature and implement them into artificial applications. Applications could be products we use in our daily life but it can also be used to inspire material innovation. However there are significant challenges in performing biomimetic design. One....... This is a key issue in design and innovation work where problem identification and systematic search for suitable solution principle are major activities. One way to deal with this challenge is to use a biology search method. The use of such a method is illustrated with a case story describing the design...... including the terminology and knowledge organisation. It is often easy to recognise the splendour of a biological solution, but it can be much more difficult to understand the underlying mechanisms. Another challenge in biomimetic design is the search and identification of relevant solutions in nature...

  11. Development of bis-locked nucleic acid (bisLNA) oligonucleotides for efficient invasion of supercoiled duplex DNA

    Moreno, Pedro M D; Geny, Sylvain; Pabon, Y Vladimir

    2013-01-01

    In spite of the many developments in synthetic oligonucleotide (ON) chemistry and design, invasion into double-stranded DNA (DSI) under physiological salt and pH conditions remains a challenge. In this work, we provide a new ON tool based on locked nucleic acids (LNAs), designed for strand invasi...

  12. Incorporating Engineering Design Challenges into STEM Courses

    Householder, Daniel L., Ed.; Hailey, Christine E., Ed.

    2012-01-01

    Successful strategies for incorporating engineering design challenges into science, technology, engineering, and mathematics (STEM) courses in American high schools are presented in this paper. The developers have taken the position that engineering design experiences should be an important component of the high school education of all American…

  13. Incorporating Engineering Design Challenges into STEM Courses

    Householder, Daniel L.; Hailey, Christine E.

    2012-01-01

    Successful strategies for incorporating engineering design challenges into science, technology, engineering, and mathematics (STEM) courses in American high schools are presented in this paper. The developers have taken the position that engineering design experiences should be an important component of the high school education of all American youth. In most instances, these experiences in engineering design are infused into instruction programs in standards-based courses in science, technol...

  14. Challenges and progress in turbomachinery design systems

    Van den Braembussche, R A

    2013-01-01

    This paper first describes the requirements that a modern design system should meet, followed by a comparison between design systems based on inverse design or optimization techniques. The second part of the paper presents the way these challenges are realized in an optimization method combining an Evolutionary theory and a Metamodel. Extensions to multi-disciplinary, multi-point and multi-objective optimization are illustrated by examples

  15. Detection of Aeromonas hydrophila DNA oligonucleotide sequence using a biosensor design based on Ceria nanoparticles decorated reduced graphene oxide and Fast Fourier transform square wave voltammetry

    Jafari, Safiye [Center of Excellence in Electrochemistry, University of Tehran, Tehran (Iran, Islamic Republic of); Faridbod, Farnoush, E-mail: faridbodf@khayam.ut.ac.ir [Center of Excellence in Electrochemistry, University of Tehran, Tehran (Iran, Islamic Republic of); Biosensor Research Center, Endocrinology & Metabolism Molecular and Cellular Research Institute, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Norouzi, Parviz [Center of Excellence in Electrochemistry, University of Tehran, Tehran (Iran, Islamic Republic of); Biosensor Research Center, Endocrinology & Metabolism Molecular and Cellular Research Institute, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Dezfuli, Amin Shiralizadeh [Center of Excellence in Electrochemistry, University of Tehran, Tehran (Iran, Islamic Republic of); Ajloo, Davood [School of Chemistry, Damghan University, Damghan (Iran, Islamic Republic of); Mohammadipanah, Fatemeh [Department of Microbial Biotechnology, School of Biology and Center of Excellence in Phylogeny of Living Organisms, College of Science, University of Tehran, 14155-6455 Tehran (Iran, Islamic Republic of); Ganjali, Mohammad Reza [Center of Excellence in Electrochemistry, University of Tehran, Tehran (Iran, Islamic Republic of); Biosensor Research Center, Endocrinology & Metabolism Molecular and Cellular Research Institute, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2015-10-01

    A new strategy was introduced for ssDNA immobilization on a modified glassy carbon electrode. The electrode surface was modified using polyaniline and chemically reduced graphene oxide decorated cerium oxide nanoparticles (CeO{sub 2}NPs-RGO). A single-stranded DNA (ssDNA) probe was immobilized on the modified electrode surface. Fast Fourier transform square wave voltammetry (FFT-SWV) was applied as detection technique and [Ru(bpy){sub 3}]{sup 2+/3+} redox signal was used as electrochemical marker. The hybridization of ssDNA with its complementary target caused a dramatic decrease in [Ru(bpy){sub 3}]{sup 2+/3+} FFT-SW signal. The proposed electrochemical biosensor was able to detect Aeromonas hydrophila DNA oligonucleotide sequence encoding aerolysin protein. Under optimal conditions, the biosensor showed excellent selectivity toward complementary sequence in comparison with noncomplementary and two-base mismatch sequences. The dynamic linear range of this electrochemical DNA biosensor for detecting 20-mer oligonucleotide sequence of A. hydrophila was from 1 × 10{sup −15} to 1 × 10{sup −8} mol L{sup −1}. The proposed biosensor was successfully applied for the detection of DNA extracted from A. hydrophila in fish pond water up to 0.01 μg mL{sup −1} with RSD of 5%. Besides, molecular docking was applied to consider the [Ru(bpy){sub 3}]{sup 2+/3+} interaction with ssDNA before and after hybridization. - Highlights: • New DNA biosensor is designed for sub-femtomolar detection of Aeromonas hydrophila DNA sequence. • Reduced graphene oxide decorated Ceria nanoparticles was used as a new immobilization platform. • Biosensor was successfully used to detect A. hydrophila DNA sequence in fish pond water.

  16. Detection of Aeromonas hydrophila DNA oligonucleotide sequence using a biosensor design based on Ceria nanoparticles decorated reduced graphene oxide and Fast Fourier transform square wave voltammetry

    Jafari, Safiye; Faridbod, Farnoush; Norouzi, Parviz; Dezfuli, Amin Shiralizadeh; Ajloo, Davood; Mohammadipanah, Fatemeh; Ganjali, Mohammad Reza

    2015-01-01

    A new strategy was introduced for ssDNA immobilization on a modified glassy carbon electrode. The electrode surface was modified using polyaniline and chemically reduced graphene oxide decorated cerium oxide nanoparticles (CeO_2NPs-RGO). A single-stranded DNA (ssDNA) probe was immobilized on the modified electrode surface. Fast Fourier transform square wave voltammetry (FFT-SWV) was applied as detection technique and [Ru(bpy)_3]"2"+"/"3"+ redox signal was used as electrochemical marker. The hybridization of ssDNA with its complementary target caused a dramatic decrease in [Ru(bpy)_3]"2"+"/"3"+ FFT-SW signal. The proposed electrochemical biosensor was able to detect Aeromonas hydrophila DNA oligonucleotide sequence encoding aerolysin protein. Under optimal conditions, the biosensor showed excellent selectivity toward complementary sequence in comparison with noncomplementary and two-base mismatch sequences. The dynamic linear range of this electrochemical DNA biosensor for detecting 20-mer oligonucleotide sequence of A. hydrophila was from 1 × 10"−"1"5 to 1 × 10"−"8 mol L"−"1. The proposed biosensor was successfully applied for the detection of DNA extracted from A. hydrophila in fish pond water up to 0.01 μg mL"−"1 with RSD of 5%. Besides, molecular docking was applied to consider the [Ru(bpy)_3]"2"+"/"3"+ interaction with ssDNA before and after hybridization. - Highlights: • New DNA biosensor is designed for sub-femtomolar detection of Aeromonas hydrophila DNA sequence. • Reduced graphene oxide decorated Ceria nanoparticles was used as a new immobilization platform. • Biosensor was successfully used to detect A. hydrophila DNA sequence in fish pond water.

  17. Challenges to Deploy Service Design in Organizations

    Akasaka, Fumiya; Ohno, Takehiko; Jensen, Mika Yasuoka

    2016-01-01

    More and more companies are applying service design approaches to develop services and products. Not every project, however, has achieved its goals. In many cases, difficulties arise from organizational issues such as organization structure and evaluation system. In this research, we held workshops...... where success and failure factors of service design projects in organization are presented. By analysing the results, we construct a model that explains the “difficulties of deploying the service design approach in organization.” On the basis of the model, this paper discusses the challenges...... to the deployment of the service design approach in organizations....

  18. Template-Directed Ligation of Peptides to Oligonucleotides

    Bruick, Richard K.; Dawson, Philip E.; Kent, Stephen BH; Usman, Nassim; Joyce, Gerald F.

    1996-01-01

    Synthetic oligonucleotides and peptides have enjoyed a wide range of applications in both biology and chemistry. As a consequence, oligonucleotide-peptide conjugates have received considerable attention, most notably in the development of antisense constructs with improved pharmacological properties. In addition, oligonucleotide-peptide conjugates have been used as molecular tags, in the assembly of supramolecular arrays and in the construction of encoded combinatorial libraries. To make these chimeric molecules more accessible for a broad range of investigations, we sought to develop a facile method for joining fully deprotected oligonucleotides and peptides through a stable amide bond linkage. Furthermore, we wished to make this ligation reaction addressable, enabling one to direct the ligation of specific oligonucleotide and peptide components.To confer specificity and accelerate the rate of the reaction, the ligation process was designed to be dependent on the presence of a complementary oligonucleotide template.

  19. Challenges in IC design for hearing aids

    Jørgensen, Ivan Harald Holger

    2012-01-01

    Designing modern hearing aids is a formidable challenge. The size of hearing aids is constantly decreasing, making them virtually invisible today. Still, as in all other modern electronics, more and more features are added to these devices driven by the development in modern IC technology....... The demands for performance and features at very low supply voltage and power consumption constantly prove a challenge to the physical design of hearing aids and not at least the design of the ICs for these. As a result of this all large hearing aid manufacturers use fully customized ASICs in their products...... to produce a competitive advantage. This presentation will give a brief insight into the hearing aid market and industry, a brief view of the historic development of hearing aids and an introduction to how a modern hearing is constructed showing the amplifier as the key component in the modern hearing aid...

  20. Spaceflight Flow Cytometry: Design Challenges and Applications

    Pappas, Dimitri; Kao, Shih-Hsin; Jeevarajan, Antony S.

    2004-01-01

    Future space exploration missions will require analytical technology capable of providing both autonomous medical care to the crew and investigative capabilities to researchers. While several promising candidate technologies exist for further development, flow cytometry is an attractive technology as it offers both crew health and a wide array of biochemistry and immunology assays. While flow cytometry has been widely used for cellular analysis in both clinical and research settings, the requirements for proper operation in spaceflight impose constraints on any instrument designs. The challenges of designing a spaceflight-ready flow cytometer are discussed, as well as some preliminary results using a prototype system.

  1. Achievements and Challenges in Computational Protein Design.

    Samish, Ilan

    2017-01-01

    Computational protein design (CPD), a yet evolving field, includes computer-aided engineering for partial or full de novo designs of proteins of interest. Designs are defined by a requested structure, function, or working environment. This chapter describes the birth and maturation of the field by presenting 101 CPD examples in a chronological order emphasizing achievements and pending challenges. Integrating these aspects presents the plethora of CPD approaches with the hope of providing a "CPD 101". These reflect on the broader structural bioinformatics and computational biophysics field and include: (1) integration of knowledge-based and energy-based methods, (2) hierarchical designated approach towards local, regional, and global motifs and the integration of high- and low-resolution design schemes that fit each such region, (3) systematic differential approaches towards different protein regions, (4) identification of key hot-spot residues and the relative effect of remote regions, (5) assessment of shape-complementarity, electrostatics and solvation effects, (6) integration of thermal plasticity and functional dynamics, (7) negative design, (8) systematic integration of experimental approaches, (9) objective cross-assessment of methods, and (10) successful ranking of potential designs. Future challenges also include dissemination of CPD software to the general use of life-sciences researchers and the emphasis of success within an in vivo milieu. CPD increases our understanding of protein structure and function and the relationships between the two along with the application of such know-how for the benefit of mankind. Applied aspects range from biological drugs, via healthier and tastier food products to nanotechnology and environmentally friendly enzymes replacing toxic chemicals utilized in the industry.

  2. Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis

    Christoph Niemietz

    2015-09-01

    Full Text Available The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR, expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP. Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO and small interfering RNA (siRNA designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease.

  3. Deep water challenges for drilling rig design

    Roth, M [Transocean Sedco Forex, Houston, TX (United States)

    2001-07-01

    Drilling rigs designed for deep water must meet specific design considerations for harsh environments. The early lessons for rig design came from experiences in the North Sea. Rig efficiency and safety considerations must include structural integrity, isolated/redundant ballast controls, triple redundant DP systems, enclosed heated work spaces, and automated equipment such as bridge cranes, pipe handling gear, offline capabilities, subsea tree handling, and computerized drill floors. All components must be designed to harmonize man and machine. Some challenges which are unique to Eastern Canada include frequent storms and fog, cold temperature, icebergs, rig ice, and difficult logistics. This power point presentation described station keeping and mooring issues in terms of dynamic positioning issues. The environmental influence on riser management during forced disconnects was also described. Design issues for connected deep water risers must insure elastic stability, and control deflected shape. The design must also keep stresses within acceptable limits. Codes and standards for stress limits, flex joints and tension were also presented. tabs., figs.

  4. Challenges of Collaborative Product Styling in Design Teams

    Ovesen, Nis

    2016-01-01

    Apart from a long list of advantages, design students face certain challenges when working collectively in groups on form, styling and aesthetics. An investigation about these challenges has been carried out and a number of challenges have been identified. The most apparent challenges relate to d...... to different aesthetic preferences, lack of tools and methods, and difficulties in establishing form related requirements. The challenges are presented and design quality, as well as some solution strategies, is discussed....

  5. Design, Results and Plans for Power Beaming Competitive Challenge

    Shelef, Ben

    2008-01-01

    In our context, Power Beaming refers to the extraction of useable electrical power from a directed electromagnetic beam. In order to promote interest in this technology, the Spaceward Foundation proposed and is managing a technology prize challenge based on a Space Elevator design scenario. The challenge has a prize purse of $2M, provided by NASA's Centennial Challenges office. This paper covers the considerations that went into the design of the challenge, a brief chronology of past results, and plans for the future

  6. Fully automated parallel oligonucleotide synthesizer

    Lebl, M.; Burger, Ch.; Ellman, B.; Heiner, D.; Ibrahim, G.; Jones, A.; Nibbe, M.; Thompson, J.; Mudra, Petr; Pokorný, Vít; Poncar, Pavel; Ženíšek, Karel

    2001-01-01

    Roč. 66, č. 8 (2001), s. 1299-1314 ISSN 0010-0765 Institutional research plan: CEZ:AV0Z4055905 Keywords : automated oligonucleotide synthesizer Subject RIV: CC - Organic Chemistry Impact factor: 0.778, year: 2001

  7. Transferring design knowledge : challenges and opportunities

    Hu, J.; Chen, W.; Bartneck, C.; Rauterberg, G.W.M.; Zhang, X.; Zhong, S.; Pan, Z.; et al., xx

    2010-01-01

    Design becomes more and more the art of bringing together expertise and experts from different domains in creating future products. Synthetical knowledge and hands-on kills in design, especially in industrial design, is often implicit, hardly captured and modeled for remote education. The need of

  8. Making Recycled Paper: An Engineering Design Challenge

    Song, Ting; Becker, Kurt

    2013-01-01

    Science, technology, engineering, and mathematics (STEM) educators are facing the challenge of attracting more students. The disparity between the need for engineers and the enrollment of engineering students is growing (Genalo, Bruning, & Adams, 2000), and career aspirations of high school students are inconsistent with the employment…

  9. Designing a Smaller Power Inverter: the Google Littlebox Challenge - Text

    Version | Energy Systems Integration Facility | NREL Designing a Smaller Power Inverter: the Google Littlebox Challenge - Text Version er Power Inverter: the Google Littlebox Challenge - Text Version Below is the text version for the Designing a Smaller Power Inverter: the Google Littlebox

  10. Teaching Strategies to Promote Concept Learning by Design Challenges

    Van Breukelen, Dave; Van Meel, Adrianus; De Vries, Marc

    2017-01-01

    Background: This study is the second study of a design-based research, organised around four studies, that aims to improve student learning, teaching skills and teacher training concerning the design-based learning approach called Learning by Design (LBD). Purpose: LBD uses the context of design challenges to learn, among other things, science.…

  11. The Crab Boat Engineering Design Challenge

    Love, Tyler S.; Ryan, Larry

    2017-01-01

    Crab cakes and football, that's what Maryland does!" (Abrams, Levy, Panay, & Dobkin, 2005). Although the Old Line State is notorious for harvesting delectable blue crabs, the movie "Wedding Crashers" failed to highlight something else Maryland does well: engineering design competitions. This article discusses how a multistate…

  12. The materials challenge for LFR core design

    Grasso, Giacomo; Agostini, Pietro

    2013-01-01

    LFR share the main issues of all Fast Reactors, while presenting specific issues due to the use of lead as coolant. A number of constraints impairs the design of a LFR core, possibly resulting in a viability domain not exploitable for producing electricity in an efficient (hence economic) way. In particular, the most restrictive issues to be faced pend on the cladding. The selection of proper cladding materials provides the solution for the issues impairing the resistance of the cladding against stresses and irradiation effects. On the other hand, the protection of the cladding requires surface protections like oxide scales (passivation) or adherent layers (coating). Oxide scales seem not sufficient for a stable and effective protection of the base material. The application of adherent layers seems the only promising solution for protecting the cladding against corrosion. For the short term (i.e.: ALFRED), advanced 15/15Ti with coating is the reference solution for the cladding, allowing a core design complying with all the design constraints and goals. The candidate coatings are already being tested under irradiation to proceed towards qualification. In parallel, new base materials and/or coatings are presently under investigation. For the long term (i.e.: ELFR), the availability of such advanced materials/coatings might allow the extension of the viability domain towards higher and broader ranges (temperature, dpa, etc.), extending the fields of applications of LFRs and resulting in higher performances

  13. Surface design methodology – challenge the steel

    Bergman, M; Rosen, B-G; Eriksson, L; Anderberg, C

    2014-01-01

    The way a product or material is experienced by its user could be different depending on the scenario. It is also well known that different materials and surfaces are used for different purposes. When optimizing materials and surface roughness for a certain something with the intention to improve a product, it is important to obtain not only the physical requirements, but also the user experience and expectations. Laws and requirements of the materials and the surface function, but also the conservative way of thinking about materials and colours characterize the design of medical equipment. The purpose of this paper is to link the technical- and customer requirements of current materials and surface textures in medical environments. By focusing on parts of the theory of Kansei Engineering, improvements of the companys' products are possible. The idea is to find correlations between desired experience or ''feeling'' for a product, -customer requirements, functional requirements, and product geometrical properties -design parameters, to be implemented on new improved products. To be able to find new materials with the same (or better) technical requirements but a higher level of user stimulation, the current material (stainless steel) and its surface (brushed textures) was used as a reference. The usage of focus groups of experts at the manufacturer lead to a selection of twelve possible new materials for investigation in the project. In collaboration with the topical company for this project, three new materials that fulfil the requirements -easy to clean and anti-bacterial came to be in focus for further investigation in regard to a new design of a washer-disinfector for medical equipment using the Kansei based Clean ability approach CAA

  14. Surface design methodology - challenge the steel

    Bergman, M.; Rosen, B.-G.; Eriksson, L.; Anderberg, C.

    2014-03-01

    The way a product or material is experienced by its user could be different depending on the scenario. It is also well known that different materials and surfaces are used for different purposes. When optimizing materials and surface roughness for a certain something with the intention to improve a product, it is important to obtain not only the physical requirements, but also the user experience and expectations. Laws and requirements of the materials and the surface function, but also the conservative way of thinking about materials and colours characterize the design of medical equipment. The purpose of this paper is to link the technical- and customer requirements of current materials and surface textures in medical environments. By focusing on parts of the theory of Kansei Engineering, improvements of the companys' products are possible. The idea is to find correlations between desired experience or "feeling" for a product, -customer requirements, functional requirements, and product geometrical properties -design parameters, to be implemented on new improved products. To be able to find new materials with the same (or better) technical requirements but a higher level of user stimulation, the current material (stainless steel) and its surface (brushed textures) was used as a reference. The usage of focus groups of experts at the manufacturer lead to a selection of twelve possible new materials for investigation in the project. In collaboration with the topical company for this project, three new materials that fulfil the requirements -easy to clean and anti-bacterial came to be in focus for further investigation in regard to a new design of a washer-disinfector for medical equipment using the Kansei based Clean ability approach CAA.

  15. Man-machine dialogue design and challenges

    Landragin, Frederic

    2013-01-01

    This book summarizes the main problems posed by the design of a man-machine dialogue system and offers ideas on how to continue along the path towards efficient, realistic and fluid communication between humans and machines. A culmination of ten years of research, it is based on the author's development, investigation and experimentation covering a multitude of fields, including artificial intelligence, automated language processing, man-machine interfaces and notably multimodal or multimedia interfaces. Contents Part 1. Historical and Methodological Landmarks 1. An Assessment of the Evolution

  16. Energy efficiency: the challenges of policy design

    Varone, F. [Catholic University of Louvain (Belgium); Aebischer, B. [Swiss Federal Institute of Technolog, Zurich (Switzerland)

    2001-06-01

    This article is about the choice of policy instruments to promote electricity-efficient household appliances and office equipment. We analyse the design process of the energy-efficiency policies implemented by Canada, Denmark, the United States, Sweden and Switzerland from 1973 to 1996. The results of this comparative study suggest that a policy instrument is adopted (1) if the degree of coercion involved is compatible with the party ideology of the ruling majority, (2) if a specialized administrative institution already exists, which helps to minimize the costs of implementation, (3) if other political or administrative jurisdictions have already applied it with success and if the transfer of their experiences is desirable or necessary, or (4) if the groups which are targeted are not opposed to it, and (5) its adoption also depends on the structure of the market and the speed of technological developments affecting household appliances and office equipment. In conclusion, we recommend taking account of these considerations in designing new energy-efficiency policies at both national and international levels. (author)

  17. Folding Topology of a Short Coiled-Coil Peptide Structure Templated by an Oligonucleotide Triplex

    Lou, Chenguang; Christensen, Niels Johan; Martos Maldonado, Manuel Cristo

    2017-01-01

    by oligonucleotide duplex and triplex formation. POC synthesis was achieved by copper-free alkyne-azide cycloaddition between three oligonucleotides and a 23-mer peptide, which by itself exhibited multiple oligomeric states in solution. The oligonucleotide domain was designed to furnish a stable parallel triplex......, small-angle X-ray scattering (SAXS), and molecular modeling. Stabilizing cooperativity was observed between the trimeric peptide and the oligonucleotide triplex domains, and the overall molecular size (ca. 12nm) in solution was revealed to be independent of concentration. The topological folding...

  18. Peptide-LNA oligonucleotide conjugates

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

  19. Versatile functionalization of nanoelectrodes by oligonucleotides via pyrrole electrochemistry.

    Descamps, Emeline; Nguyen, Khoa; Bouchain-Gautier, Christelle; Filoramo, Arianna; Goux-Capes, Laurence; Goffman, Marcello; Bourgoin, Jean-Philippe; Mailley, Pascal; Livache, Thierry

    2010-11-15

    Surface modification at the nanometer scale is a challenge for the future of molecular electronics. In particular, the precise anchoring and electrical addressing of biological scaffolds such as complex DNA nanonetworks is of importance for generating bio-directed assemblies of nano-objects for nanocircuit purposes. Herein, we consider the individual modification of nanoelectrodes with different oligonucleotide sequences by an electrochemically driven co-polymerization process of pyrrole and modified oligonucleotide sequences bearing pyrrole monomers. We demonstrate that this one-step technique presents the advantages of simplicity, localization of surface modification, mechanical, biological and chemical stability of the coatings, and high lateral resolution.

  20. Biomimetics as a design methodology – possibilities and challenges

    Lenau, Torben Anker

    2009-01-01

    Biomimetics – or bionik as it is called in parts of Europe – offer a number of promising opportunities and challenges for the designer. The paper investigates how biomimetics as a design methodology is used in engineering design by looking at examples of biological searches and highlight...

  1. USU AFOSR University Engineering Design Challenge Proposal

    2015-01-02

    ASCENDING AGGIES (National Champions) Row 1 L‐R: Daniel Aguirre, Trevor Park, Mark Ortega, Bobby Johnson, James  Robbins , and Alyssa Wahlin  Row 2... Judging Panel is given in Appendix A.   ACCOMPLISHMENTS YEAR 2 (AY 2012‐2013) – PORTABLE BRIDGE SYSTEMS  Two seven person teams (See team photos... Judges   April 20, 2012                                                          Pages 9‐19      12/28/2014 1 AFOSR/AFRL Design Competition April 20

  2. Electronic Structures of LNA Phosphorothioate Oligonucleotides

    Bohr, Henrik G.; Shim, Irene; Stein, Cy

    2017-01-01

    Important oligonucleotides in anti-sense research have been investigated in silico and experimentally. This involves quantum mechanical (QM) calculations and chromatography experiments on locked nucleic acid (LNA) phosphorothioate (PS) oligonucleotides. iso-potential electrostatic surfaces...

  3. Powering the Future: A Wind Turbine Design Challenge

    Pries, Caitlin Hicks; Hughes, Julie

    2011-01-01

    Nothing brings out the best in eighth-grade physical science students quite like an engineering challenge. The wind turbine design challenge described in this article has proved to be a favorite among students with its focus on teamwork and creativity and its (almost) sneaky reinforcement of numerous physics concepts. For this activity, pairs of…

  4. On stethoscope design: a challenge for biomedical circuit designers.

    Hahn, A W

    2001-01-01

    Most clinicians learned the art and science of auscultation using an acoustic stethoscope. While many models of electronic stethoscopes have been marketed over the years, none of them seem to do a very good job of emulating the most common forms of acoustic stethoscopes available. This paper is an appeal to biomedical circuit designers to learn more about the acoustics of commonly used stethoscopes and to develop an appropriate group of circuits which would emulate them much like music synthesizers can emulate almost any musical instrument. The implications are for creative designers to move toward a rational and acceptable design for both personal physician use and for telemedicine.

  5. Storage/transport cask design and challenges

    Houston, J.V.; Viebrock, J.M.

    1989-01-01

    The concept of spent-fuel casks that could be used for both storage and for transport has been around for some years, but was only seriously evaluated when utilities started becoming concerned about adequate fuel storage. In the early 1980s, the U.S. Department of Energy proposed to solve the problem with their away-from-reactor storage facility concept. This was superceded by passage of the Nuclear Waste Policy Act of 1982, which directed the development of one or more waste repositories, the first of which was to be in operation by 1998. Delays in this program now indicate an opening data of 2003 or later. This, together with the lack of significant progress on a monitored retrievable storage facility, leaves the utility companies to solve their storage problems individually. One alternative is to use dual-purpose casks. The use of such a cask should eliminate the need to move the cask and fuel back into the spent-fuel pool for transfer to a transport cask. However, a dual-purpose cask must be licensed for use under both 10CFR71 and 10CFR72 of the U.S. Code of Federal Regulations. The purpose of this paper is to examine the differences between the requirements of 10CFR71 and 10CFR72, to note the changes over the past several years in the NRC's interpretation of 10CFR71 requirements, and to review the design modifications that the Nuclear Assurance Corporation (NAC) believes are required to make a licensed storage cask acceptable for transport under 10CFR71

  6. The challenge of integrating evidence-based design.

    Martin, Caren S

    2009-01-01

    This paper discusses the integration of evidence-based design (EBD) into the design process as an innovation, illuminates the significance and progress of the diffusion of this innovation, and identifies EBD advocates and the consequences of meeting the EBD challenge. A free tool for engaging in EBD is explored. Healthcare designers are leading the EBD charge, because their clients depend on it. But not all designers engage in EBD, because it may be beyond the resources of a firm or outside its culture. However, as with other meaningful design innovations, designers who do not practice EBD could fall by the wayside. EBD is a product of the diffusion of the innovation of evidence-based medicine. The academy (i.e., the collective of institutions of higher education), design organizations, design communities, and the media all contribute to the diffusion of EBD. However, the quantity, quality, and understandability of evidence continue to challenge its broad adoption. InformeDesign®, a free, Internet-based tool, presents information to designers in a concise, understandable way. Firms must invest in EBD incrementally as a value-added component of design to meet current and future challenges. It is important for designers to realize that engaging in EBD is not a rejection of creativity, but a means by which to elevate their design solutions. ©2009 VENDOME GROUP, LLC

  7. Thermodynamics of Oligonucleotide Duplex Melting

    Schreiber-Gosche, Sherrie; Edwards, Robert A.

    2009-01-01

    Melting temperatures of oligonucleotides are useful for a number of molecular biology applications, such as the polymerase chain reaction (PCR). Although melting temperatures are often calculated with simplistic empirical equations, application of thermodynamics provides more accurate melting temperatures and an opportunity for students to apply…

  8. Combining gene expression data from different generations of oligonucleotide arrays

    Kong Sek

    2004-10-01

    Full Text Available Abstract Background One of the important challenges in microarray analysis is to take full advantage of previously accumulated data, both from one's own laboratory and from public repositories. Through a comparative analysis on a variety of datasets, a more comprehensive view of the underlying mechanism or structure can be obtained. However, as we discover in this work, continual changes in genomic sequence annotations and probe design criteria make it difficult to compare gene expression data even from different generations of the same microarray platform. Results We first describe the extent of discordance between the results derived from two generations of Affymetrix oligonucleotide arrays, as revealed in cluster analysis and in identification of differentially expressed genes. We then propose a method for increasing comparability. The dataset we use consists of a set of 14 human muscle biopsy samples from patients with inflammatory myopathies that were hybridized on both HG-U95Av2 and HG-U133A human arrays. We find that the use of the probe set matching table for comparative analysis provided by Affymetrix produces better results than matching by UniGene or LocusLink identifiers but still remains inadequate. Rescaling of expression values for each gene across samples and data filtering by expression values enhance comparability but only for few specific analyses. As a generic method for improving comparability, we select a subset of probes with overlapping sequence segments in the two array types and recalculate expression values based only on the selected probes. We show that this filtering of probes significantly improves the comparability while retaining a sufficient number of probe sets for further analysis. Conclusions Compatibility between high-density oligonucleotide arrays is significantly affected by probe-level sequence information. With a careful filtering of the probes based on their sequence overlaps, data from different

  9. The Challenges of Designing Digital Services for Multiple Mobile Platforms

    Ghazawneh, Ahmad

    2016-01-01

    on a multiple case study of three mobile application development firms from Sweden, Denmark and Norway, we synthesize the digital service design taxonomy to understand the challenges faced by third-party developers. Our study identifies a set of challenges in four different levels: user level, platform level...... to tap into and join the digital ecosystem. However, while there is an emerging literature on designing digital services, little empirical evidence exists about challenges faced by third-party developers while designing digital services, and in particular for multiple mobile platforms. Drawing......The value of digital services is increasingly recognized by owners of digital platforms. These services have central role in building and sustaining the business of the digital platform. In order to sustain the design of digital services, owners of digital platforms encourage third-party developers...

  10. Structural Design Challenges in Design Certification Applications for New Reactors

    Miranda, M.; Braverman, J.; Wei, X.; Hofmayer, C.; Xu, J.

    2011-07-17

    The licensing framework established by the U.S. Nuclear Regulatory Commission under Title 10 of the Code of Federal Regulations (10 CFR) Part 52, “Licenses, Certifications, and Approvals for Nuclear Power Plants,” provides requirements for standard design certifications (DCs) and combined license (COL) applications. The intent of this process is the early reso- lution of safety issues at the DC application stage. Subsequent COL applications may incorporate a DC by reference. Thus, the COL review will not reconsider safety issues resolved during the DC process. However, a COL application that incorporates a DC by reference must demonstrate that relevant site-specific de- sign parameters are confined within the bounds postulated by the DC, and any departures from the DC need to be justified. This paper provides an overview of structural design chal- lenges encountered in recent DC applications under the 10 CFR Part 52 process, in which the authors have participated as part of the safety review effort.

  11. Mechanical design features and challenges for the ITER ICRH antenna

    Borthwick, A. [UKAEA/Euratom Fusion Association, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom)], E-mail: andy.borthwick@yahoo.co.uk; Agarici, G. [Fusion for Energy, Barcelona (Spain); Davis, A. [UKAEA/Euratom Fusion Association, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Dumortier, P.; Durodie, F. [LPP-ERM-KMS, Association EURATOM-Belgian State, Brussels (Belgium); Fanthome, J.; Hamlyn-Harris, C.; Hancock, A.D.; Lockley, D. [UKAEA/Euratom Fusion Association, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Mitteau, R. [Euratom-CEA Association, DSM/IRFM, CEA-Cadarache, 13108 St Paul lez Durance (France); Nightingale, M. [UKAEA/Euratom Fusion Association, Culham Science Centre, Abingdon, Oxon OX14 3DB (United Kingdom); Sartori, R. [Fusion for Energy, Barcelona (Spain); Vulliez, K. [Euratom-CEA Association, DSM/IRFM, CEA-Cadarache, 13108 St Paul lez Durance (France)

    2009-06-15

    The ITER Ion Cyclotron Resonant Heating (ICRH) antenna provides plasma heating at a power of 20 MW. Operation in the ITER environment imposes significant thermal power handling capability, structural integrity, shielding and operations requirements. The design will require a step change over any predecessor in terms of power, scale and complexity. This paper reports the main mechanical design features that address the challenges and often conflicting requirements during the conceptual design phase.

  12. Rapid and accurate synthesis of TALE genes from synthetic oligonucleotides.

    Wang, Fenghua; Zhang, Hefei; Gao, Jingxia; Chen, Fengjiao; Chen, Sijie; Zhang, Cuizhen; Peng, Gang

    2016-01-01

    Custom synthesis of transcription activator-like effector (TALE) genes has relied upon plasmid libraries of pre-fabricated TALE-repeat monomers or oligomers. Here we describe a novel synthesis method that directly incorporates annealed synthetic oligonucleotides into the TALE-repeat units. Our approach utilizes iterative sets of oligonucleotides and a translational frame check strategy to ensure the high efficiency and accuracy of TALE-gene synthesis. TALE arrays of more than 20 repeats can be constructed, and the majority of the synthesized constructs have perfect sequences. In addition, this novel oligonucleotide-based method can readily accommodate design changes to the TALE repeats. We demonstrated an increased gene targeting efficiency against a genomic site containing a potentially methylated cytosine by incorporating non-conventional repeat variable di-residue (RVD) sequences.

  13. Addressing the challenges of patient-centred design

    Karen LaBat

    2009-11-01

    Full Text Available Patient-centred design is a relatively new term, but a longstanding concept in clinical practice. This discussion looks at patient-centred design and explores the relationships of patient-centred design to universal design, user-centred design and the newer human-centred design. It also explores why interdisciplinary approaches are needed for patient-centred design and how interdisciplinary collaboration works to address the challenges of patient centred design. Successful patient-centred solutions can grow from collaborations which include shared visions, understanding of both the nature and degree of variation in the patient,materials, and the designed solution, clear regular communication among all parties with careful definition of terms, and respect for the inherent cultures of all disciplines involved.

  14. Recommendations of the Oligonucleotide Safety Working Group's Formulated Oligonucleotide Subcommittee for the Safety Assessment of Formulated Oligonucleotide-Based Therapeutics.

    Marlowe, Jennifer L; Akopian, Violetta; Karmali, Priya; Kornbrust, Douglas; Lockridge, Jennifer; Semple, Sean

    2017-08-01

    The use of lipid formulations has greatly improved the ability to effectively deliver oligonucleotides and has been instrumental in the rapid expansion of therapeutic development programs using oligonucleotide drugs. However, the development of such complex multicomponent therapeutics requires the implementation of unique, scientifically sound approaches to the nonclinical development of these drugs, based upon a hybrid of knowledge and experiences drawn from small molecule, protein, and oligonucleotide therapeutic drug development. The relative paucity of directly applicable regulatory guidance documents for oligonucleotide therapeutics in general has resulted in the generation of multiple white papers from oligonucleotide drug development experts and members of the Oligonucleotide Safety Working Group (OSWG). The members of the Formulated Oligonucleotide Subcommittee of the OSWG have utilized their collective experience working with a variety of formulations and their associated oligonucleotide payloads, as well as their insights into regulatory considerations and expectations, to generate a series of consensus recommendations for the pharmacokinetic characterization and nonclinical safety assessment of this unique class of therapeutics. It should be noted that the focus of Subcommittee discussions was on lipid nanoparticle and other types of particulate formulations of therapeutic oligonucleotides and not on conjugates or other types of modifications of oligonucleotide structure intended to facilitate delivery.

  15. Possibilities and Challenges designing low-carbon-energy technologies

    Bjarklev, Araceli

    Though there is broad consensus that one of the solutions to the current environmental challenge will be based on the use of low-carbon technologies, and even though there is a big potential to turn to a more sustainable design and innovation, there are several elements that need to be taken...... as a study object and discusses the question: What are the main possibilities and challenges when designing low-carbon illumination technologies? To answer this question, we use a systemic approach including environmental, economic, energy and political issues using relevant concepts from the Ecological...

  16. High-End Computing Challenges in Aerospace Design and Engineering

    Bailey, F. Ronald

    2004-01-01

    High-End Computing (HEC) has had significant impact on aerospace design and engineering and is poised to make even more in the future. In this paper we describe four aerospace design and engineering challenges: Digital Flight, Launch Simulation, Rocket Fuel System and Digital Astronaut. The paper discusses modeling capabilities needed for each challenge and presents projections of future near and far-term HEC computing requirements. NASA's HEC Project Columbia is described and programming strategies presented that are necessary to achieve high real performance.

  17. Challenges in designing interactive systems for emergency response

    Kristensen, Margit; Kyng, Morten; Nielsen, Esben Toftdahl

    2007-01-01

    and visions as ways to bridge between fieldwork and literature studies on the one hand and the emerging computer based prototypes on the other. Our case concerns design of innovative interactive systems for support in emergency response, including patient identification and monitoring as well as construction......This paper presents research on participatory design of interactive systems for emergency response. We present the work by going through the design method with a focus on the new elements that we developed for the participatory design toolkit, in particular we emphasize the use of challenges...

  18. Barriers and Challenges in the Integrated Design Process Approcach

    Knudstrup, Mary-Ann

    2006-01-01

    ABSTRACT: In the future, it will be a huge challenge to make sustainable building design by using a more holistic and innovative approach in order to be able to decrease or reduce the use of energy for heating and cooling in new building projects. This is seen in the perspective of the Kyoto agre....... It also describes the barriers and the challenges that must be overcome when trying to cross the borders between the two fields of engineering and architecture to design sustainable architecture....... agreement for reducing the global heating. This paper will briefly present the method of the Integrated Design Process, IDP [1]. It describes the background and means for developing a new method for designing integrated architecture in an interdisciplinary approach between architecture and engineering...

  19. Exploring Challenging Group Dynamics in Participatory Design with Children

    Van Mechelen, Maarten; Gielen, Matthieu; Vanden Abeele, Vero; Laenen, Ann; Zaman, Bieke

    2014-01-01

    This paper presents a structured way to evaluate challenging group or 'codesign dynamics' in participatory design processes with children. In the form of a critical reflection on a project in which 103 children were involved as design partners, we describe the most prevalent codesign dynamics. For example, some groups rush too quickly towards consensus to safeguard group cohesiveness instead of examining other choice alternatives (i.e., groupthink). Besides 'groupthink' we describe five more ...

  20. SAFETY BASIS DESIGN DEVELOPMENT CHALLENGES IMECE2007-42747

    RYAN GW

    2007-01-01

    'Designing in Safety' is a desired part of the development of any new potentially hazardous system, process, or facility. It is a required part of nuclear safety activities as specified in the U.S. Department of Energy (DOE) Order 420.B, Facility Safety. This order addresses the design of nuclear related facilities developed under federal regulation IOCFR830, Nuclear Safety Management. IOCFR830 requires that safety basis documentation be provided to identify how nuclear safety is being adequately addressed as a condition for system operation (e.g., the safety basis). To support the development of the safety basis, a safety analysis is performed. Although the concept of developing a design that addresses 'Safety is simple, the execution can be complex and challenging. This paper addresses those complexities and challenges for the design activity of a system to treat sludge, a corrosion product of spent nuclear fuel, at DOE's Hanford Site in Washington State. The system being developed is referred to as the Sludge Treatment Project (STP). This paper describes the portion of the safety analysis that addresses the selection of design basis events using the experience gained from the STP and the development of design requirements for safety features associated with those events. Specifically, the paper describes the safety design process and the application of the process for two types of potential design basis accidents associated with the operation of the system, (1) flashing spray leaks and (2) splash and splatter leaks. Also presented are the technical challenges that are being addressed to develop effective safety features to deal with these design basis accidents

  1. SAFETY BASIS DESIGN DEVELOPMENT CHALLENGES IMECE2007-42747

    RYAN GW

    2007-09-24

    'Designing in Safety' is a desired part of the development of any new potentially hazardous system, process, or facility. It is a required part of nuclear safety activities as specified in the U.S. Department of Energy (DOE) Order 420.B, Facility Safety. This order addresses the design of nuclear related facilities developed under federal regulation IOCFR830, Nuclear Safety Management. IOCFR830 requires that safety basis documentation be provided to identify how nuclear safety is being adequately addressed as a condition for system operation (e.g., the safety basis). To support the development of the safety basis, a safety analysis is performed. Although the concept of developing a design that addresses 'Safety is simple, the execution can be complex and challenging. This paper addresses those complexities and challenges for the design activity of a system to treat sludge, a corrosion product of spent nuclear fuel, at DOE's Hanford Site in Washington State. The system being developed is referred to as the Sludge Treatment Project (STP). This paper describes the portion of the safety analysis that addresses the selection of design basis events using the experience gained from the STP and the development of design requirements for safety features associated with those events. Specifically, the paper describes the safety design process and the application of the process for two types of potential design basis accidents associated with the operation of the system, (1) flashing spray leaks and (2) splash and splatter leaks. Also presented are the technical challenges that are being addressed to develop effective safety features to deal with these design basis accidents.

  2. Challenges of designing fusion reactors for remote maintainability

    Mason, L.S.

    1981-01-01

    One of the major problems faced by the fusion community is the development of the high level of reliability required to assure that fusion will be a viable commercial power source. Much of the responsibility for solving this problem falls directly on the designer in developing concepts that have a high level of maintainability. The problems are both near-term, in developing maintainability for next generation engineering oriented reactors; and long range, in developing full maintainability for the more commercial concepts with their required high level of on-line time. The near-time challenge will include development of unqiue design concepts to perform inspection, maintenance, replacement, and testing under the stringent conditions imposed by the next generation engineering oriented machines. The long range challenge will focus on basic design concepts that will enable the full mainatability required by commerical fusion

  3. The Medicinal Chemistry of Therapeutic Oligonucleotides.

    Wan, W Brad; Seth, Punit P

    2016-11-10

    Oligonucleotide-based therapeutics have made rapid progress in the clinic for treatment of a variety of disease indications. Unmodified oligonucleotides are polyanionic macromolecules with poor drug-like properties. Over the past two decades, medicinal chemists have identified a number of chemical modification and conjugation strategies which can improve the nuclease stability, RNA-binding affinity, and pharmacokinetic properties of oligonucleotides for therapeutic applications. In this perspective, we present a summary of the most commonly used nucleobase, sugar and backbone modification, and conjugation strategies used in oligonucleotide medicinal chemistry.

  4. Stereospecificity of oligonucleotide interactions revisited: no evidence for heterochiral hybridization and ribozyme/DNAzyme activity.

    Kai Hoehlig

    Full Text Available A major challenge for the application of RNA- or DNA-oligonucleotides in biotechnology and molecular medicine is their susceptibility to abundant nucleases. One intriguing possibility to tackle this problem is the use of mirror-image (l-oligonucleotides. For aptamers, this concept has successfully been applied to even develop therapeutic agents, so-called Spiegelmers. However, for technologies depending on RNA/RNA or RNA/DNA hybridization, like antisense or RNA interference, it has not been possible to use mirror-image oligonucleotides because Watson-Crick base pairing of complementary strands is (thought to be stereospecific. Many scientists consider this a general principle if not a dogma. A recent publication proposing heterochiral Watson-Crick base pairing and sequence-specific hydrolysis of natural RNA by mirror-image ribozymes or DNAzymes (and vice versa prompted us to systematically revisit the stereospecificity of oligonucleotides hybridization and catalytic activity. Using hyperchromicity measurements we demonstrate that hybridization only occurs among homochiral anti-parallel complementary oligonucleotide strands. As expected, achiral PNA hybridizes to RNA and DNA irrespective of their chirality. In functional assays we could not confirm an alleged heterochiral hydrolytic activity of ribozymes or DNAzymes. Our results confirm a strict stereospecificity of oligonucleotide hybridization and clearly argue against the possibility to use mirror-image oligonucleotides for gene silencing or antisense applications.

  5. A Kinetic Model Explains Why Shorter and Less Affine Enzyme-recruiting Oligonucleotides Can Be More Potent

    Lykke Pedersen

    2014-01-01

    Full Text Available Antisense oligonucleotides complementary to RNA targets promise generality and ease of drug design. The first systemically administered antisense drug was recently approved for treatment and others are in clinical development. Chemical modifications that increase the hybridization affinity of oligonucleotides are reasoned to confer higher potency, i.e., modified oligonucleotides can be dosed at lower concentrations to achieve the same effect. Surprisingly, shorter and less affine oligonucleotides sometimes display increased potency. To explain this apparent contradiction, increased uptake or decreased propensity to form structures have been suggested as possible mechanisms. Here, we provide an alternative explanation that invokes only the kinetics behind oligonucleotide-mediated cleavage of RNA targets. A model based on the law of mass action predicts, and experiments support, the existence of an optimal binding affinity. Exaggerated affinity, and not length per se, is detrimental to potency. This finding clarifies how to optimally apply high-affinity modifications in the discovery of potent antisense oligonucleotide drugs.

  6. Research of design challenges and new technologies for floating LNG

    Dong-Hyun Lee

    2014-06-01

    Full Text Available With the rate of worldwide LNG demand expected to grow faster than that of gas demand, most major oil companies are currently investing their resources to develop floating LNG-FLNG (i.e. LNG FSRU and LNG FPSO. The global Floating LNG (FLNG market trend will be reviewed based on demand and supply chain relationships. Typical technical issues associated with FLNG design are categorized in terms of global performance evaluation. Although many proven technologies developed through LNG carrier and oil FPSO projects are available for FLNG design, we are still faced with several technical challenges to clear for successful FLNG projects. In this study, some of the challenges encountered during development of the floating LNG facility (i.e. LNG FPSO and FSRU will be reviewed together with their investigated solution. At the same time, research of new LNG-related technologies such as combined containment system will be presented.

  7. Design and manufacturing challenges of optogenetic neural interfaces: a review

    Goncalves, S. B.; Ribeiro, J. F.; Silva, A. F.; Costa, R. M.; Correia, J. H.

    2017-08-01

    Optogenetics is a relatively new technology to achieve cell-type specific neuromodulation with millisecond-scale temporal precision. Optogenetic tools are being developed to address neuroscience challenges, and to improve the knowledge about brain networks, with the ultimate aim of catalyzing new treatments for brain disorders and diseases. To reach this ambitious goal the implementation of mature and reliable engineered tools is required. The success of optogenetics relies on optical tools that can deliver light into the neural tissue. Objective/Approach: Here, the design and manufacturing approaches available to the scientific community are reviewed, and current challenges to accomplish appropriate scalable, multimodal and wireless optical devices are discussed. Significance: Overall, this review aims at presenting a helpful guidance to the engineering and design of optical microsystems for optogenetic applications.

  8. Design challenges for large Arctic crude oil tanker

    Iyerusalimskiy, A.; Noble, P.

    2008-01-01

    The Vasily Dinkov vessel was delivered by Samsung Heavy Industries shipyard to Russian ship-owner Sovcomflot. It is the largest icebreaking tanker ever built. The vessel was designed and constructed to transport crude oil from the Varandey offshore terminal in the southeastern Barents Sea to a transshipment location near Murmansk, Russia. The vessel is under long-term charter for Naryanmarneftegas, a joint venture of Lukoil and ConocoPhillips. The new ship was constructed strictly to the requirements, specification, and concept design provided by the charterer. The Varandey oil transportation concept and the vessel operational profile resulted in some conflicting requirements, compromising technical solutions, and assumptions yet to be proven in operation. This paper described the design challenges and selected approach to solve the solution to the tanker key design elements. These included the ice transit and other Arctic environmental challenges; open water performance issues; and icebreaking hull structure design challenges associated with modern shipbuilding technology standards and cost efficiency. The principle characteristics of the Vasily Dinkov were first presented and the Varandey crude oil transportation system was also described. Several features have made the Vasily Dinkov the most advanced icebreaking tanker to date, such as the icebreaking concept which has expanded the capability of both traditional icebreaking ships fitted with the icebreaker bow and double acting ships intended to operate astern only in the ice; the largest azimuthal twin screw propulsion plant for the Arctic with highest ice torque capacity ever specified for cargo vessel; and the first customized, automated, asymmetric steering control system designed to improve open water maneuverability and steering stability of podded vessels. It was concluded that the transportation system, the overall vessel concept and many of the vessel features require validation based on operational

  9. Electronic health records challenges in design and implementation

    Sittig, Dean F

    2013-01-01

    This book provides an overview of the challenges in electronic health records (EHR) design and implementation along with an introduction to the best practices that have been identified over the past several years. The book examines concerns surrounding EHR use and proposes eight examples of proper EHR use. It discusses the complex strategic planning that accompanies the systemic organizational changes associated with EHR programs and highlights key lessons learned regarding health information-including technology errors and risk management concerns.

  10. Nanomedical device and systems design challenges, possibilities, visions

    2014-01-01

    Nanomedical Device and Systems Design: Challenges, Possibilities, Visions serves as a preliminary guide toward the inspiration of specific investigative pathways that may lead to meaningful discourse and significant advances in nanomedicine/nanotechnology. This volume considers the potential of future innovations that will involve nanomedical devices and systems. It endeavors to explore remarkable possibilities spanning medical diagnostics, therapeutics, and other advancements that may be enabled within this discipline. In particular, this book investigates just how nanomedical diagnostic and

  11. Challenges and opportunities in integration of design and control

    Huusom, Jakob Kjøbsted

    2015-01-01

    Process synthesis and design of plant operation are related topics but current industrial practice solves these problems sequentially. The implication of this sequential strategy may result in design of processing systems which are very hard to control. This paper presents a discussion on drivers...... for an integrated approach and outlines the challenges in formulation of such a multi-objective synthesis problem. This discussion is viewed in relation to some of the changing trends in the industry. Significant results have been published which in different ways seek to handle the integrated problem. Further...

  12. Challenges of designing fusion reactors for remote maintainability

    Masson, L.S.

    1981-01-01

    One of the major problems faced by the fusion community is the development of the high level of reliability required to assure that fusion will be a viable commercial power source. Much of the responsibility for solving this problem falls directly on the designer in developing concepts that have a high level of maintainability for the next generation engineering oriented reactors; and long range, in developing full maintainability for the more complicated commercial concepts with their required high level of on-line time. The near-term challenge will include development of unique design concepts to perform inspection, maintenance, replacement, and testing under the stringent conditions imposed by the next generation engineering oriented machines. The long range challenge will focus on basic design concepts that will enable the full maintainability required by commercial fusion. In addition to the purely technical challenges, the fusion community is also faced with the problem of developing programmatic means to assure that reactor maintenance issues are given proper and timely emphasis as the nuclear phase of fusion is approached

  13. Renewing Theories, Methods and Design Practices: Challenges for Architectural Education

    Andri Yatmo Yandi

    2018-01-01

    Full Text Available Architectural education should promote the advancement of knowledge that is necessary as the basis for the development of excellent design practice. Architectural education needs to respond appropriately to the current issues in the society. To find its way into the society in an appropriate way, architecture needs to be liquid. The ability to address the liquidity of architecture requires educational approach that promotes the ability to work with a range of design methods and approaches. There are several principles that become the basis for developing architectural education that could strengthen its position within the society: to promote knowledge-based design practice, to embrace variety of design methods and approaches; to keep a balance between design knowledge and design skills; while at the same time to aim for mastery and excellence in design. These principles should be the basis for defining and developing the curriculum and the process of design learning architectural education. Then the main challenge is on our willingness to be liquid in developing architectural education, which needs continuous renewal and update to respond to the changing context of knowledge, technology and society.

  14. Big Data in Designing Clinical Trials: Opportunities and Challenges.

    Mayo, Charles S; Matuszak, Martha M; Schipper, Matthew J; Jolly, Shruti; Hayman, James A; Ten Haken, Randall K

    2017-01-01

    Emergence of big data analytics resource systems (BDARSs) as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs) have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

  15. Big Data in Designing Clinical Trials: Opportunities and Challenges

    Charles S. Mayo

    2017-08-01

    Full Text Available Emergence of big data analytics resource systems (BDARSs as a part of routine practice in Radiation Oncology is on the horizon. Gradually, individual researchers, vendors, and professional societies are leading initiatives to create and demonstrate use of automated systems. What are the implications for design of clinical trials, as these systems emerge? Gold standard, randomized controlled trials (RCTs have high internal validity for the patients and settings fitting constraints of the trial, but also have limitations including: reproducibility, generalizability to routine practice, infrequent external validation, selection bias, characterization of confounding factors, ethics, and use for rare events. BDARS present opportunities to augment and extend RCTs. Preliminary modeling using single- and muti-institutional BDARS may lead to better design and less cost. Standardizations in data elements, clinical processes, and nomenclatures used to decrease variability and increase veracity needed for automation and multi-institutional data pooling in BDARS also support ability to add clinical validation phases to clinical trial design and increase participation. However, volume and variety in BDARS present other technical, policy, and conceptual challenges including applicable statistical concepts, cloud-based technologies. In this summary, we will examine both the opportunities and the challenges for use of big data in design of clinical trials.

  16. Oligonucleotide-based biosensors for in vitro diagnostics and environmental hazard detection.

    Jung, Il Young; Lee, Eun Hee; Suh, Ah Young; Lee, Seung Jin; Lee, Hyukjin

    2016-04-01

    Oligonucleotide-based biosensors have drawn much attention because of their broad applications in in vitro diagnostics and environmental hazard detection. They are particularly of interest to many researchers because of their high specificity as well as excellent sensitivity. Recently, oligonucleotide-based biosensors have been used to achieve not only genetic detection of targets but also the detection of small molecules, peptides, and proteins. This has further broadened the applications of these sensors in the medical and health care industry. In this review, we highlight various examples of oligonucleotide-based biosensors for the detection of diseases, drugs, and environmentally hazardous chemicals. Each example is provided with detailed schematics of the detection mechanism in addition to the supporting experimental results. Furthermore, future perspectives and new challenges in oligonucleotide-based biosensors are discussed.

  17. Challenges in design of zirconium alloy reactor components

    Kakodkar, Anil; Sinha, R.K.

    1992-01-01

    Zirconium alloy components used in core-internal assemblies of heavy water reactors have to be designed under constraints imposed by need to have minimum mass, limitations of fabrication, welding and joining techniques with this material, and unique mechanisms for degradation of the operating performance of these components. These constraints manifest as challenges for design and development when the size, shape and dimensions of the components and assemblies are unconventional or untried, or when one is aiming for maximization of service life of these components under severe operating conditions. A number of such challenges were successfully met during the development of core-internal components and assemblies of Dhruva reactor. Some of the then untried ideas which were developed and successfully implemented include use of electron beam welding, cold forming of hemispherical ends of reentrant cans, and a large variety of rolled joints of innovative designs. This experience provided the foundation for taking up and successfully completing several tasks relating to coolant channels, liquid poison channels and sparger channels for PHWRs and test sections for the in-pile loops of Dhruva reactor. For life prediction and safety assessment of coolant channels of PHWRs some analytical tools, notably, a computer code for prediction of creep limited life of coolant channels has been developed. Some of the future challenges include the development of easily replaceable coolant channels and also large diameter coolant channels for Advanced Heavy Water Reactor, and development of solutions to overcome deterioration of service life of coolant channels due to hydriding. (author). 5 refs., 13 figs., 1 tab

  18. Challenges Facing 3-D Audio Display Design for Multimedia

    Begault, Durand R.; Null, Cynthia H. (Technical Monitor)

    1998-01-01

    The challenges facing successful multimedia presentation depend largely on the expectations of the designer and end user for a given application. Perceptual limitations in distance, elevation and azimuth sound source simulation differ significantly between headphone and cross-talk cancellation loudspeaker listening and therefore must be considered. Simulation of an environmental context is desirable but the quality depends on processing resources and lack of interaction with the host acoustical environment. While techniques such as data reduction of head-related transfer functions have been used widely to improve simulation fidelity, another approach involves determining thresholds for environmental acoustic events. Psychoacoustic studies relevant to this approach are reviewed in consideration of multimedia applications

  19. Designing multiple ligands - medicinal chemistry strategies and challenges.

    Morphy, Richard; Rankovic, Zoran

    2009-01-01

    It has been widely recognised over the recent years that parallel modulation of multiple biological targets can be beneficial for treatment of diseases with complex etiologies such as cancer asthma, and psychiatric disease. In this article, current strategies for the generation of ligands with a specific multi-target profile (designed multiple ligands or DMLs) are described and a number of illustrative example are given. Designing multiple ligands is frequently a challenging endeavour for medicinal chemists, with the need to appropriately balance affinity for 2 or more targets whilst obtaining physicochemical and pharmacokinetic properties that are consistent with the administration of an oral drug. Given that the properties of DMLs are influenced to a large extent by the proteomic superfamily to which the targets belong and the lead generation strategy that is pursued, an early assessment of the feasibility of any given DML project is essential.

  20. Data sharing policy design for consortia: challenges for sustainability.

    Kaye, Jane; Hawkins, Naomi

    2014-01-01

    The field of human genomics has led advances in the sharing of data with a view to facilitating translation of research into innovations for human health. This change in scientific practice has been implemented through new policy developed by many principal investigators, project managers and funders, which has ultimately led to new forms of practice and innovative governance models for data sharing. Here, we examine the development of the governance of data sharing in genomics, and explore some of the key challenges associated with the design and implementation of these policies. We examine how the incremental nature of policy design, the perennial problem of consent, the gridlock caused by multiple and overlapping access systems, the administrative burden and the problems with incentives and acknowledgment all have an impact on the potential for data sharing to be maximized. We conclude by proposing ways in which the scientific community can address these problems, to improve the sustainability of data sharing into the future.

  1. Managing the cigeo design: a challenge and an opportunity

    Muscetti, R.

    2015-01-01

    INGEROP is working since years on the French Deep Geological Repository's design for Andra, carrying out since 2012 the preliminary design, the global project management and the technical integration for the engineering of the Cigeo project (in a 50-50 consortium with the French company TECHNIP). The article presents some particular organizational aspects that turned out to be more challenging than foreseen in the course of our activities. Starting from the presentation of real examples, some lessons learned are derived as well as practices of interest in solving analogue issues in similar projects, with focus on its application to the management of engineering phase of geological repositories and other 'megaprojects' in different countries. (author)

  2. Solar Probe Plus: Mission design challenges and trades

    Guo, Yanping

    2010-11-01

    NASA plans to launch the first mission to the Sun, named Solar Probe Plus, as early as 2015, after a comprehensive feasibility study that significantly changed the original Solar Probe mission concept. The original Solar Probe mission concept, based on a Jupiter gravity assist trajectory, was no longer feasible under the new guidelines given to the mission. A complete redesign of the mission was required, which called for developing alternative trajectories that excluded a flyby of Jupiter. Without the very powerful gravity assist from Jupiter it was extremely difficult to get to the Sun, so designing a trajectory to reach the Sun that is technically feasible under the new mission guidelines became a key enabler to this highly challenging mission. Mission design requirements and challenges unique to this mission are reviewed and discussed, including various mission scenarios and six different trajectory designs utilizing various planetary gravity assists that were considered. The V 5GA trajectory design using five Venus gravity assists achieves a perihelion of 11.8 solar radii ( RS) in 3.3 years without any deep space maneuver (DSM). The V 7GA trajectory design reaches a perihelion of 9.5 RS using seven Venus gravity assists in 6.39 years without any DSM. With nine Venus gravity assists, the V 9GA trajectory design shows a solar orbit at inclination as high as 37.9° from the ecliptic plane can be achieved with the time of flight of 5.8 years. Using combined Earth and Venus gravity assists, as close as 9 RS from the Sun can be achieved in less than 10 years of flight time at moderate launch C3. Ultimately the V 7GA trajectory was chosen as the new baseline mission trajectory. Its design allowing for science investigation right after launch and continuing for nearly 7 years is unprecedented for interplanetary missions. The redesigned Solar Probe Plus mission is not only feasible under the new guidelines but also significantly outperforms the original mission concept

  3. STRONG LENS TIME DELAY CHALLENGE. I. EXPERIMENTAL DESIGN

    Dobler, Gregory [Kavli Institute for Theoretical Physics, University of California Santa Barbara, Santa Barbara, CA 93106 (United States); Fassnacht, Christopher D.; Rumbaugh, Nicholas [Department of Physics, University of California, 1 Shields Avenue, Davis, CA 95616 (United States); Treu, Tommaso; Liao, Kai [Department of Physics, University of California, Santa Barbara, CA 93106 (United States); Marshall, Phil [Kavli Institute for Particle Astrophysics and Cosmology, P.O. Box 20450, MS29, Stanford, CA 94309 (United States); Hojjati, Alireza [Department of Physics and Astronomy, University of British Columbia, 6224 Agricultural Road, Vancouver, B.C. V6T 1Z1 (Canada); Linder, Eric, E-mail: tt@astro.ucla.edu [Lawrence Berkeley National Laboratory and University of California, Berkeley, CA 94720 (United States)

    2015-02-01

    The time delays between point-like images in gravitational lens systems can be used to measure cosmological parameters. The number of lenses with measured time delays is growing rapidly; the upcoming Large Synoptic Survey Telescope (LSST) will monitor ∼10{sup 3} strongly lensed quasars. In an effort to assess the present capabilities of the community, to accurately measure the time delays, and to provide input to dedicated monitoring campaigns and future LSST cosmology feasibility studies, we have invited the community to take part in a ''Time Delay Challenge'' (TDC). The challenge is organized as a set of ''ladders'', each containing a group of simulated data sets to be analyzed blindly by participating teams. Each rung on a ladder consists of a set of realistic mock observed lensed quasar light curves, with the rungs' data sets increasing in complexity and realism. The initial challenge described here has two ladders, TDC0 and TDC1. TDC0 has a small number of data sets, and is designed to be used as a practice set by the participating teams. The (non-mandatory) deadline for completion of TDC0 was the TDC1 launch date, 2013 December 1. The TDC1 deadline was 2014 July 1. Here we give an overview of the challenge, we introduce a set of metrics that will be used to quantify the goodness of fit, efficiency, precision, and accuracy of the algorithms, and we present the results of TDC0. Thirteen teams participated in TDC0 using 47 different methods. Seven of those teams qualified for TDC1, which is described in the companion paper.

  4. EPR design features to mitigate severe accident challenges

    Mazurkiewicz, S.M.; Fischer, M.; Bittermann, D.

    2005-01-01

    The EPR, an evolutionary pressurized water reactor (PWR), is a 4300-4500 MWth that incorporates proven technology within an optimized configuration to enhance safety. EPR was originally developed through a joint effort between Framatome ANP and Siemens by incorporating the best technological features from the French and German nuclear reactor fleets into a cost-competitive product. Commercial EPR units are currently being built in Finland at the Olkiluoto site, and planned for France at the Flamanville site. In recent months, Framatome ANP announced their intention to market the EPR units to China in response to a request for vendor bids as well as their intent to pursue design certification in the United States under 10CFR52. The EPR safety philosophy is based on a deterministic consideration of defense-in-depth complemented by probabilistic analyses. Not only is the EPR designed to prevent and mitigate design basis accidents (DBAs), it employs an extra level of safety associated with severe accident response. Therefore, as a design objective, features are included to ensure that radiological consequences are limited such that the need for stringent counter measures, such as evacuation and relocation of the nearby population, can be reasonably excluded. This paper discusses some of the innovative features of the EPR to address severe accident challenges. (author)

  5. Oligonucleotide-based pharmaceuticals: Non-clinical and clinical safety signals and non-clinical testing strategies.

    Mustonen, Enni-Kaisa; Palomäki, Tiina; Pasanen, Markku

    2017-11-01

    Antisense oligonucleotides, short interfering RNAs (siRNAs) and aptamers are oligonucleotide-based pharmaceuticals with a promising role in targeted therapies. Currently, five oligonucleotide-based pharmaceuticals have achieved marketing authorization in Europe or USA and many more are undergoing clinical testing. However, several safety concerns have been raised in non-clinical and clinical studies. Oligonucleotides share properties with both chemical and biological pharmaceuticals and therefore they pose challenges also from the regulatory point of view. We have analyzed the safety data of oligonucleotides and evaluated the applicability of current non-clinical toxicological guidelines for assessing the safety of oligonucleotide-based pharmaceuticals. Oligonucleotide-based pharmaceuticals display a similar toxicological profile, exerting adverse effects on liver and kidney, evoking hematological alterations, as well as causing immunostimulation and prolonging the coagulation time. It is possible to extrapolate some of these effects from non-clinical studies to humans. However, evaluation strategies for genotoxicity testing of "non-natural" oligonucleotides should be revised. Additionally, the selective use of surrogates and prediction of clinical endpoints for non-clinically observed immunostimulation is complicated by its multiple potential manifestations, demanding improvements in the testing strategies. Utilizing more relevant and mechanistic-based approaches and taking better account of species differences, could possibly improve the prediction of relevant immunological/proinflammatory effects in humans. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. THERAPEUTIC ANTISENSE OLIGONUCLEOTIDES AGAINST CANCER: HURDLING TO THE CLINIC

    Pedro Miguel Duarte Moreno

    2014-10-01

    Full Text Available Under clinical development since the early 90’s and with two successfully approved drugs (Fomivirsen and Mipomersen, oligonucleotide-based therapeutics have not yet delivered a clinical drug to the market in the cancer field. Whilst many pre-clinical data has been generated, a lack of understanding still exists on how to efficiently tackle all the different challenges presented for cancer targeting in a clinical setting. Namely, effective drug vectorization, careful choice of target gene or synergistic multi-gene targeting are surely decisive, while caution must be exerted to avoid potential toxic, often misleading off-target-effects. Here a brief overview will be given on the nucleic acid chemistry advances that established oligonucleotide technologies as a promising therapeutic alternative and ongoing cancer related clinical trials. Special attention will be given towards a perspective on the hurdles encountered specifically in the cancer field by this class of therapeutic oligonucleotides and a view on possible avenues for success is presented, with particular focus on the contribution from nanotechnology to the field.

  7. Oligonucleotide aptamers against tyrosine kinase receptors: Prospect for anticancer applications.

    Camorani, Simona; Crescenzi, Elvira; Fedele, Monica; Cerchia, Laura

    2018-04-01

    Transmembrane receptor tyrosine kinases (RTKs) play crucial roles in cancer cell proliferation, survival, migration and differentiation. Area of intense research is searching for effective anticancer therapies targeting these receptors and, to date, several monoclonal antibodies and small-molecule tyrosine kinase inhibitors have entered the clinic. However, some of these drugs show limited efficacy and give rise to acquired resistance. Emerging highly selective compounds for anticancer therapy are oligonucleotide aptamers that interact with their targets by recognizing a specific three-dimensional structure. Because of their nucleic acid nature, the rational design of advanced strategies to manipulate aptamers for both diagnostic and therapeutic applications is greatly simplified over antibodies. In this manuscript, we will provide a comprehensive overview of oligonucleotide aptamers as next generation strategies to efficiently target RTKs in human cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Challenges and learning outcomes of educational design research for PhD students

    Bronkhorst, L.H.; de Kleijn, R.A.M.

    2016-01-01

    Educational design research (EDR) is described as a complex research approach. The challenges resulting from this complexity are typically described as procedural, whereas EDR might also be challenging for different reasons, specifically for early career researchers. Yet challenging experiences may

  9. Nuclear challenges and progress in designing stellarator fusion power plants

    El-Guebaly, L.A.; Wilson, P.; Henderson, D.; Sawan, M.; Sviatoslavsky, G.; Tautges, T.; Slaybaugh, R.; Kiedrowski, B.; Ibrahim, A.

    2008-01-01

    Over the past 5-6 decades, stellarator power plants have been studied in the US, Europe, and Japan as an alternate to the mainline magnetic fusion tokamaks, offering steady-state operation and eliminating the risk of plasma disruptions. The earlier 1980s studies suggested large-scale stellarator power plants with an average major radius exceeding 20 m. The most recent development of the compact stellarator concept delivered ARIES-CS - a compact stellarator with 7.75 m average major radius, approaching that of tokamaks. For stellarators, the most important engineering parameter that determines the machine size and cost is the minimum distance between the plasma boundary and mid-coil. Accommodating the breeding blanket and necessary shield within this distance to protect the ARIES-CS superconducting magnet represents a challenging task. Selecting the ARIES-CS nuclear and engineering parameters to produce an economic optimum, modeling the complex geometry for 3D nuclear analysis to confirm the key parameters, and minimizing the radwaste stream received considerable attention during the design process. These engineering design elements combined with advanced physics helped enable the compact stellarator to be a viable concept. This paper provides a brief historical overview of the progress in designing stellarator power plants and a perspective on the successful integration of the nuclear activity into the final ARIES-CS configuration

  10. Design Challenges for a Wide-Aperture Insertion Quadrupole Magnet

    Russenschuck, S; Perez, J C; Ramos, D; Fessia, P; Karppinen, M; Kirby, G; Sahner, T; Schwerg, N

    2011-01-01

    The design and development of a superconducting (Nb-Ti) quadrupole with 120 mm aperture, for an upgrade of the LHC insertion region, faces challenges arising from the LHC beam optics requirements and the heat-deposition. The first triggered extensive studies of coil alternatives with four and six coil-blocks in view of field quality and operation margins. The latter requires more porous insulation schemes for both the cables and the ground-plane. This in turn necessitates extensive heatpropagation and quench-velocity studies, as well as more efficient quench heaters. The engineering design of the magnet includes innovative features such as self-locking collars, which will enable the collaring to be performed with the coils on a horizontal assembly bench, a spring-loaded and collapsible assembly mandrel, tuning-shims for field quality, porous collaring-shoes, and coil end-spacer design based on differential geometry methods. The project also initiated code extensions in the quench-simulation and CAD/CAM module...

  11. Design and Development of the Blackbird: Challenges and Lessons Learned

    Merlin, Peter W.

    2009-01-01

    The Lockheed Blackbirds hold a unique place in the development of aeronautics. In their day, the A-12, YF-12, M-21, D-21, and SR-71 variants outperformed all other jet airplanes in terms of altitude and speed. Now retired, they remain the only production aircraft capable of sustained Mach 3 cruise and operational altitudes above 80,000 feet. In this paper the author describes the design evolution of the Blackbird from Lockheed's early Archangel studies for the Central Intelligence Agency through Senior Crown, production of the Air Force's SR-71. He describes the construction and materials challenges faced by Lockheed, the Blackbird's performance characteristics and capabilities, and the National Aeronautics and Space Administration's role in using the aircraft as a flying laboratory to collect data on materials, structures, loads, heating, aerodynamics, and performance for high-speed aircraft.

  12. Classifications, applications, and design challenges of drones: A review

    Hassanalian, M.; Abdelkefi, A.

    2017-05-01

    Nowadays, there is a growing need for flying drones with diverse capabilities for both civilian and military applications. There is also a significant interest in the development of novel drones which can autonomously fly in different environments and locations and can perform various missions. In the past decade, the broad spectrum of applications of these drones has received most attention which led to the invention of various types of drones with different sizes and weights. In this review paper, we identify a novel classification of flying drones that ranges from unmanned air vehicles to smart dusts at both ends of this spectrum, with their new defined applications. Design and fabrication challenges of micro drones, existing methods for increasing their endurance, and various navigation and control approaches are discussed in details. Limitations of the existing drones, proposed solutions for the next generation of drones, and recommendations are also presented and discussed.

  13. MISSION PROFILE AND DESIGN CHALLENGES FOR MARS LANDING EXPLORATION

    J. Dong

    2017-07-01

    Full Text Available An orbiter and a descent module will be delivered to Mars in the Chinese first Mars exploration mission. The descent module is composed of a landing platform and a rover. The module will be released into the atmosphere by the orbiter and make a controlled landing on Martian surface. After landing, the rover will egress from the platform to start its science mission. The rover payloads mainly include the subsurface radar, terrain camera, multispectral camera, magnetometer, anemometer to achieve the scientific investigation of the terrain, soil characteristics, material composition, magnetic field, atmosphere, etc. The landing process is divided into three phases (entry phase, parachute descent phase and powered descent phase, which are full of risks. There exit lots of indefinite parameters and design constrain to affect the selection of the landing sites and phase switch (mortaring the parachute, separating the heat shield and cutting off the parachute. A number of new technologies (disk-gap-band parachute, guidance and navigation, etc. need to be developed. Mars and Earth have gravity and atmosphere conditions that are significantly different from one another. Meaningful environmental conditions cannot be recreated terrestrially on earth. A full-scale flight validation on earth is difficult. Therefore the end-to-end simulation and some critical subsystem test must be considered instead. The challenges above and the corresponding design solutions are introduced in this paper, which can provide reference for the Mars exploration mission.

  14. Reporting Qualitative Research: Standards, Challenges, and Implications for Health Design.

    Peditto, Kathryn

    2018-04-01

    This Methods column describes the existing reporting standards for qualitative research, their application to health design research, and the challenges to implementation. Intended for both researchers and practitioners, this article provides multiple perspectives on both reporting and evaluating high-quality qualitative research. Two popular reporting standards exist for reporting qualitative research-the Consolidated Criteria for Reporting Qualitative Research (COREQ) and the Standards for Reporting Qualitative Research (SRQR). Though compiled using similar procedures, they differ in their criteria and the methods to which they apply. Creating and applying reporting criteria is inherently difficult due to the undefined and fluctuating nature of qualitative research when compared to quantitative studies. Qualitative research is expansive and occasionally controversial, spanning many different methods of inquiry and epistemological approaches. A "one-size-fits-all" standard for reporting qualitative research can be restrictive, but COREQ and SRQR both serve as valuable tools for developing responsible qualitative research proposals, effectively communicating research decisions, and evaluating submissions. Ultimately, tailoring a set of standards specific to health design research and its frequently used methods would ensure quality research and aid reviewers in their evaluations.

  15. Competency-based education: programme design and challenges to implementation.

    Gruppen, Larry D; Burkhardt, John C; Fitzgerald, James T; Funnell, Martha; Haftel, Hilary M; Lypson, Monica L; Mullan, Patricia B; Santen, Sally A; Sheets, Kent J; Stalburg, Caren M; Vasquez, John A

    2016-05-01

    Competency-based education (CBE) has been widely cited as an educational framework for medical students and residents, and provides a framework for designing educational programmes that reflect four critical features: a focus on outcomes, an emphasis on abilities, a reduction of emphasis on time-based training, and promotion of learner centredness. Each of these features has implications and potential challenges for implementing CBE. As an experiment in CBE programme design and implementation, the University of Michigan Master of Health Professions Education (UM-MHPE) degree programme was examined for lessons to be learned when putting CBE into practice. The UM-MHPE identifies 12 educational competencies and 20 educational entrustable professional activities (EPAs) that serve as the vehicle for both learning and assessment. The programme also defines distinct roles of faculty members as assessors, mentors and subject-matter experts focused on highly individualised learning plans adapted to each learner. Early experience with implementing the UM-MHPE indicates that EPAs and competencies can provide a viable alternative to traditional courses and a vehicle for rigorous assessment. A high level of individualisation is feasible but carries with it significant costs and makes intentional community building essential. Most significantly, abandoning a time-based framework is a difficult innovation to implement in a university structure that is predicated on time-based education. © 2016 John Wiley & Sons Ltd.

  16. Challenges and opportunities in designing clinical trials for neuromyelitis optica

    Barron, Gerard; Behne, Jacinta M.; Bennett, Jeffery L.; Chin, Peter S.; Cree, Bruce A.C.; de Seze, Jerome; Flor, Armando; Fujihara, Kazuo; Greenberg, Benjamin; Higashi, Sayumi; Holt, William; Khan, Omar; Knappertz, Volker; Levy, Michael; Melia, Angela T.; Palace, Jacqueline; Smith, Terry J.; Sormani, Maria Pia; Van Herle, Katja; VanMeter, Susan; Villoslada, Pablo; Walton, Marc K.; Wasiewski, Warren; Wingerchuk, Dean M.; Yeaman, Michael R.

    2015-01-01

    Current management of neuromyelitis optica (NMO) is noncurative and only partially effective. Immunosuppressive or immunomodulatory agents are the mainstays of maintenance treatment. Safer, better-tolerated, and proven effective treatments are needed. The perceived rarity of NMO has impeded clinical trials for this disease. However, a diagnostic biomarker and recognition of a wider spectrum of NMO presentations has expanded the patient population from which study candidates might be recruited. Emerging insights into the pathogenesis of NMO have provided rationale for exploring new therapeutic targets. Academic, pharmaceutical, and regulatory communities are increasingly interested in meeting the unmet needs of patients with NMO. Clinical trials powered to yield unambiguous outcomes and designed to facilitate rapid evaluation of an expanding pipeline of experimental agents are needed. NMO-related disability occurs incrementally as a result of attacks; thus, limiting attack frequency and severity are critical treatment goals. Yet, the severity of NMO and perception that currently available agents are effective pose challenges to study design. We propose strategies for NMO clinical trials to evaluate agents targeting recovery from acute attacks and prevention of relapses, the 2 primary goals of NMO treatment. Aligning the interests of all stakeholders is an essential step to this end. PMID:25841026

  17. Multidisciplinary design optimization of large wind turbines—Technical, economic, and design challenges

    Ashuri, Turaj; Zaaijer, Michiel B.; Martins, Joaquim R.R.A.; Zhang, Jie

    2016-01-01

    Highlights: • 5, 10 and 20 MW wind turbines are developed using multidisciplinary design optimization. • Technical feasibility and economy of large wind turbines are investigated. • Critical upscaling trends of existing wind turbines are presented up to 20 MW. • Design challenges of large wind turbines are identified, and design solutions proposed. • With no design innovation, upscaling of existing turbines will increase the costs. - Abstract: Wind energy has experienced a continuous cost reduction in the last decades. A popular cost reduction technique is to increase the rated power of the wind turbine by making it larger. However, it is not clear whether further upscaling of the existing wind turbines beyond the 5–7 MW range is technically feasible and economically attractive. To address this question, this study uses 5, 10, and 20 MW wind turbines that are developed using multidisciplinary design optimization as upscaling data points. These wind turbines are upwind, 3-bladed, pitch-regulated, variable-speed machines with a tubular tower. Based on the design data and properties of these wind turbines, scaling trends such as loading, mass, and cost are developed. These trends are used to study the technical and economical aspects of upscaling and its impact on the design and cost. The results of this research show the technical feasibility of the existing wind turbines up to 20 MW, but the design of such an upscaled machine is cost prohibitive. Mass increase of the rotor is identified as a main design challenge to overcome. The results of this research support the development of alternative lightweight materials and design concepts such as a two-bladed downwind design for upscaling to remain a cost effective solution for future wind turbines.

  18. G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents.

    Musumeci, Domenica; Riccardi, Claudia; Montesarchio, Daniela

    2015-09-22

    Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding processes to external stimuli, high structural compactness and chemo-enzymatic and thermodynamic stability. A number of G-quadruplex-forming oligonucleotides having relevant in vitro anti-HIV activity have been discovered in the last two decades through either SELEX or rational design approaches. Improved aptamers have been obtained by chemical modifications of natural oligonucleotides, as terminal conjugations with large hydrophobic groups, replacement of phosphodiester linkages with phosphorothioate bonds or other surrogates, insertion of base-modified monomers, etc. In turn, detailed structural studies have elucidated the peculiar architectures adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. An overview of the state-of-the-art knowledge of the relevance of putative G-quadruplex forming sequences within the viral genome and of the most studied G-quadruplex-forming aptamers, selectively targeting HIV proteins, is here presented.

  19. Hole hopping rates in single strand oligonucleotides

    Borrelli, Raffaele [Dipartimento di Scienze Agrarie, Forestali e Alimentari, Università di Torino, Largo Paolo Braccini 2, I-10095 Grugliasco, TO (Italy); Capobianco, Amedeo [Dipartimento di Chimica e Biologia, Università di Salerno, Via Giovanni Paolo II, I-84084 Fisciano, SA (Italy); Peluso, Andrea, E-mail: apeluso@unisa.it [Dipartimento di Chimica e Biologia, Università di Salerno, Via Giovanni Paolo II, I-84084 Fisciano, SA (Italy)

    2014-08-31

    Highlights: • DNA hole transfer rates have been computed. • Delocalized adenine domains significantly affect hole transfer rates in DNA. • Franck–Condon weighted density of state from DFT normal modes. • DNA application in molecular electronics. - Abstract: The rates of hole transfer between guanine and adenine in single strand DNA have been evaluated by using Fermi’s golden rule and Kubo’s generating function approach for the Franck–Condon weighted density of states. The whole sets of the normal modes and vibrational frequencies of the two nucleobases, obtained at DFT/B3LYP level of calculation, have been considered in computations. The results show that in single strand the pyramidalization/planarization mode of the amino groups of both nucleobases plays the major role. At room temperature, the Franck–Condon density of states extends over a wide range of hole site energy difference, 0–1 eV, giving some hints about the design of oligonucleotides of potential technological interest.

  20. The treatment of severe child aggression (TOSCA study: Design challenges

    Farmer Cristan A

    2011-11-01

    Full Text Available Abstract Background Polypharmacy (the concurrent use of more than one psychoactive drug and other combination interventions are increasingly common for treatment of severe psychiatric problems only partly responsive to monotherapy. This practice and research on it raise scientific, clinical, and ethical issues such as additive side effects, interactions, threshold for adding second drug, appropriate target measures, and (for studies timing of randomization. One challenging area for treatment is severe child aggression. Commonly-used medications, often in combination, include psychostimulants, antipsychotics, mood stabilizers, and alpha-2 agonists, which vary considerably in terms of perceived safety and efficacy. Results In designing our NIMH-funded trial of polypharmacy, we focused attention on the added benefit of a second drug (risperidone to the effect of the first (stimulant. We selected these two drugs because their associated adverse events might neutralize each other (e.g., sleep delay and appetite decrease from stimulant versus sedation and appetite increase from antipsychotic. Moreover, there was considerable evidence of efficacy for each drug individually for the management of ADHD and child aggression. The study sample comprised children (ages 6-12 years with both diagnosed ADHD and disruptive behavior disorder (oppositional-defiant or conduct disorder accompanied by severe physical aggression. In a staged sequence, the medication with the least problematic adverse effects (stimulant was openly titrated in 3 weeks to optimal effect. Participants whose behavioral symptoms were not normalized received additional double-blind medication, either risperidone or placebo, by random assignment. Thus children whose behavioral symptoms were normalized with stimulant medication were not exposed to an antipsychotic. All families participated in an empirically-supported parent training program for disruptive behavior, so that the actual

  1. Nuclear challenges and progress in designing stellarator power plants

    El-Guebaly, L.

    2007-01-01

    As an alternate to the mainline magnetic fusion tokamaks, the stellarator concept offers a steady state operation without external driven current, eliminating the risk of plasma irruptions. Over the past 2-3 decades, stellarator power plants have been studied in the U.S., Japan, and Europe to enhance the physics and engineering aspects and optimize the design parameters that are subject to numerous constraints. The earlier 1980's studies delivered large stellarators with an average major radius exceeding 20 m. The most recent development of the compact stellarator concept has led to the construction of the National Compact Stellarator Experiment (NCSX) in the U.S. and the 3 years power plant study of ARIES-CS, a compact stellarator with 7.75 m average major radius, approaching that of tokamaks. The ARIES-CS first wall configuration deviates from the standard practice of uniform toroidal shape in order to achieve compactness. Modeling such a complex geometry for 3-D nuclear analysis was a challenging engineering task. A novel approach based on coupling the CAD model with the MCNP Monte Carlo code was developed to model, for the first time ever, the complex stellarator geometry for nuclear assessments. The most important parameter that determines the stellarator size and cost is the minimum distance between the plasma boundary and mid-coil. Accommodating the breeding blanket and necessary shield to protect the superconducting magnet represented another challenging task. An innovative approach utilizing a non-uniform blanket combined with a highly efficient WC shield for this highly constrained area reduced the radial standoff (and machine size and cost) by 25- 30%, which is significant. As stellarators generate more radwaste than tokamaks, managing ARIES-CS active materials during operation and after plant decommissioning was essential for the environmental attractiveness of the machine. The geological disposal option could be replaced with more attractive scenarios

  2. Designing and Developing Game-Like Learning Experience in Virtual Worlds: Challenges and Design Decisions of Novice Instructional Designers

    Yilmaz, Turkan Karakus; Cagiltay, Kursat

    2016-01-01

    Many virtual worlds have been adopted for implementation within educational settings because they are potentially useful for building effective learning environments. Since the flexibility of virtual worlds challenges to obtain effective and efficient educational outcomes, the design of such platforms need more attention. In the present study, the…

  3. Degradation product characterization of therapeutic oligonucleotides using liquid chromatography mass spectrometry.

    Elzahar, N M; Magdy, N; El-Kosasy, Amira M; Bartlett, Michael G

    2018-05-01

    Synthetic antisense phosphorothioate oligonucleotides (PS) have undergone rapid development as novel therapeutic agents. The increasing significance of this class of drugs requires significant investment in the development of quality control methods. The determination of the many degradation pathways of such complex molecules presents a significant challenge. However, an understanding of the potential impurities that may arise is necessary to continue to advance these powerful new therapeutics. In this study, four different antisense oligonucleotides representing several generations of oligonucleotide therapeutic agents were evaluated under various stress conditions (pH, thermal, and oxidative stress) using ion-pairing reversed-phase liquid chromatography tandem mass spectrometry (IP-RPLC-MS/MS) to provide in-depth characterization and identification of the degradation products. The oligonucleotide samples were stressed under different pH values at 45 and 90 °C. The main degradation products were observed to be losses of nucleotide moieties from the 3'- and 5'-terminus, depurination, formation of terminal phosphorothioates, and production of ribose, ribophosphorothioates (Rp), and phosphoribophosphorothioates (pRp). Moreover, the effects of different concentrations of hydrogen peroxide were studied resulting in primarily extensive desulfurization and subsequent oxidation of the phosphorothioate linkage to produce the corresponding phosphodiester. The reaction kinetics for the degradation of the oligonucleotides under the different stress conditions were studied and were found to follow pseudo-first-order kinetics. Differences in rates exist even for oligonucleotides of similar length but consisting of different sequences. Graphical abstract Identification of degradation products across several generations of oligonucleotide therapeutics using LC-MS.

  4. Presidential Green Chemistry Challenge: 2014 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2014 award winner, The Solberg Company, replaced fluorinated surfactants in its firefighting foam concentrates with a blend of non-fluorinated surfactants and sugars.

  5. Presidential Green Chemistry Challenge: 2005 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2005 award winner, Archer Daniels Midland, developed Archer RC, a nonvolatile, biobased, reactive coalescent that replaces volatile organic coalescents in architectural latex paints.

  6. Presidential Green Chemistry Challenge: 2010 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2010 award winner, Clarke, developed Natular, a plaster matrix that encapsulates the pesticide spinosad, slowly releasing it into water and effectively controlling mosquito larvae.

  7. Design, challenge, and promise of stimuli-responsive nanoantibiotics

    Edson, Julius A.; Kwon, Young Jik

    2016-10-01

    Over the past few years, there have been calls for novel antimicrobials to combat the rise of drug-resistant bacteria. While some promising new discoveries have met this call, it is not nearly enough. The major problem is that although these new promising antimicrobials serve as a short-term solution, they lack the potential to provide a long-term solution. The conventional method of creating new antibiotics relies heavily on the discovery of an antimicrobial compound from another microbe. This paradigm of development is flawed due to the fact that microbes can easily transfer a resistant mechanism if faced with an environmental pressure. Furthermore, there has been some evidence to indicate that the environment of the microbe can provide a hint as to their virulence. Because of this, the use of materials with antimicrobial properties has been garnering interest. Nanoantibiotics, (nAbts), provide a new way to circumvent the current paradigm of antimicrobial discovery and presents a novel mechanism of attack not found in microbes yet; which may lead to a longer-term solution against drug-resistance formation. This allows for environment-specific activation and efficacy of the nAbts but may also open up and create new design methods for various applications. These nAbts provide promise, but there is still ample work to be done in their development. This review looks at possible ways of improving and optimizing nAbts by making them stimuli-responsive, then consider the challenges ahead, and industrial applications.[Figure not available: see fulltext.

  8. Enzymatic Production of Monoclonal Stoichiometric Single-Stranded DNA Oligonucleotides

    Ducani, Cosimo; Kaul, Corinna; Moche, Martin; Shih, William M.; Högberg, Björn

    2013-01-01

    Single-stranded oligonucleotides are important as research tools as probes for diagnostics and gene therapy. Today, production of oligonucleotides is done via solid-phase synthesis. However, the capabilities of current polymer chemistry are limited in comparison to what can be produced in biological systems. The errors in synthetic DNA increases with oligonucleotide length, and sequence diversity can often be a problem. Here, we present the Monoclonal Stoichiometric (MOSIC) method for enzymatic DNA oligonucleotide production. Using this method, we amplify oligonucleotides from clonal templates followed by digestion of a cutter-hairpin, resulting in pools of monoclonal oligonucleotides with precisely controlled relative stoichiometric ratios. We present data where MOSIC oligonucleotides, 14–378 nt long, were prepared either by in vitro rolling-circle amplification, or by amplification in Escherichia coli in the form of phagemid DNA. The formation of a DNA crystal and folding of DNA nanostructures confirmed the scalability, purity and stoichiometry of the produced oligonucleotides. PMID:23727986

  9. Enzymatic production of 'monoclonal stoichiometric' single-stranded DNA oligonucleotides.

    Ducani, Cosimo; Kaul, Corinna; Moche, Martin; Shih, William M; Högberg, Björn

    2013-07-01

    Single-stranded oligonucleotides are important as research tools, as diagnostic probes, in gene therapy and in DNA nanotechnology. Oligonucleotides are typically produced via solid-phase synthesis, using polymer chemistries that are limited relative to what biological systems produce. The number of errors in synthetic DNA increases with oligonucleotide length, and the resulting diversity of sequences can be a problem. Here we present the 'monoclonal stoichiometric' (MOSIC) method for enzyme-mediated production of DNA oligonucleotides. We amplified oligonucleotides from clonal templates derived from single bacterial colonies and then digested cutter hairpins in the products, which released pools of oligonucleotides with precisely controlled relative stoichiometric ratios. We prepared 14-378-nucleotide MOSIC oligonucleotides either by in vitro rolling-circle amplification or by amplification of phagemid DNA in Escherichia coli. Analyses of the formation of a DNA crystal and folding of DNA nanostructures confirmed the scalability, purity and stoichiometry of the produced oligonucleotides.

  10. Teaching strategies to promote concept learning by design challenges

    Van Breukelen, Dave; Van Meel, Adrianus; De Vries, Marc

    2017-07-01

    Background: This study is the second study of a design-based research, organised around four studies, that aims to improve student learning, teaching skills and teacher training concerning the design-based learning approach called Learning by Design (LBD).

  11. Radio-marking and in vivo imagery of oligonucleotides

    Kuehnast, Bertrand

    2000-01-01

    This research thesis is part of activities aimed at the development of new molecules like oligonucleotides. Its first objective was the development and validation of a marking method with fluorine-18 of oligonucleotides for their in-vivo pharmacological assessment with positron emission tomography (PET). Further investigations addressed the use of iodine-125 for oligonucleotide marking purpose. This radio-marking, and in vivo and ex vivo imagery techniques are described, and their potential is highlighted for the pharmacological assessment of different oligonucleotides

  12. Development, characterization and experimental validation of a cultivated sunflower (Helianthus annuus L.) gene expression oligonucleotide microarray.

    Fernandez, Paula; Soria, Marcelo; Blesa, David; DiRienzo, Julio; Moschen, Sebastian; Rivarola, Maximo; Clavijo, Bernardo Jose; Gonzalez, Sergio; Peluffo, Lucila; Príncipi, Dario; Dosio, Guillermo; Aguirrezabal, Luis; García-García, Francisco; Conesa, Ana; Hopp, Esteban; Dopazo, Joaquín; Heinz, Ruth Amelia; Paniego, Norma

    2012-01-01

    Oligonucleotide-based microarrays with accurate gene coverage represent a key strategy for transcriptional studies in orphan species such as sunflower, H. annuus L., which lacks full genome sequences. The goal of this study was the development and functional annotation of a comprehensive sunflower unigene collection and the design and validation of a custom sunflower oligonucleotide-based microarray. A large scale EST (>130,000 ESTs) curation, assembly and sequence annotation was performed using Blast2GO (www.blast2go.de). The EST assembly comprises 41,013 putative transcripts (12,924 contigs and 28,089 singletons). The resulting Sunflower Unigen Resource (SUR version 1.0) was used to design an oligonucleotide-based Agilent microarray for cultivated sunflower. This microarray includes a total of 42,326 features: 1,417 Agilent controls, 74 control probes for sunflower replicated 10 times (740 controls) and 40,169 different non-control probes. Microarray performance was validated using a model experiment examining the induction of senescence by water deficit. Pre-processing and differential expression analysis of Agilent microarrays was performed using the Bioconductor limma package. The analyses based on p-values calculated by eBayes (psunflower unigene collection, and a custom, validated sunflower oligonucleotide-based microarray using Agilent technology. Both the curated unigene collection and the validated oligonucleotide microarray provide key resources for sunflower genome analysis, transcriptional studies, and molecular breeding for crop improvement.

  13. Presidential Green Chemistry Challenge: 2003 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2003 award winner, Shaw Industries, developed EcoWorx carpet tiles with a backing that uses less toxic materials. The carpet tile fiber and backing are readily separated for recycling.

  14. Presidential Green Chemistry Challenge: 2011 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2011 award winner, Sherwin-Williams, developed water-based acrylic alkyd paints with VOCs that can be made from recycled soda bottle (PET), acrylics, and soybean oil.

  15. Presidential Green Chemistry Challenge: 2006 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2006 award winner, S.C. Johnson & Son, developed Greenlist, a rating system for environmental and health effects of ingredients. SC Johnson uses it to reformulate many of its products.

  16. Presidential Green Chemistry Challenge: 2008 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2008 award winner, Dow AgroSciences, used an artificial neural network to discover spinetoram, an improved spinosad biopesticide to replace organophosphates for key pests of fruit trees.

  17. Presidential Green Chemistry Challenge: 2013 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2013 award winner, Cargill, Inc., developed a vegetable-oil-based transformer fluid that is much less flammable, provides superior performance, is less toxic, and has a substantially lower carbon footprint.

  18. Presidential Green Chemistry Challenge: 1997 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 1997 award winner, Albright & Wilson Americas, discovered that tetrakis(hydroxymethyl)phosphonium sulfate, THPS, is an effective, safer biocide for use in industrial water systems.

  19. Presidential Green Chemistry Challenge: 1999 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 1999 award winner, Dow AgroSciences, developed spinosad, a highly selective, low-toxicity, nonpersistant insecticide made by a soil microorganism. It controls many chewing insect pests.

  20. Presidential Green Chemistry Challenge: 2002 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 2002 award winner, Chemical Specialties, developed an alkaline copper quaternary wood preservative to replace chromated copper arsenate preservative phased out due to risk to children.

  1. Presidential Green Chemistry Challenge: 1996 Designing Greener Chemicals Award

    Presidential Green Chemistry Challenge 1996 award winner, Rohm and Haas, developed Sea-Nine, a marine antifoulant to control plants and animals on ship hulls. Sea-Nine replaces persistent, toxic organotin antifoulants.

  2. Electronic Structures of LNA Phosphorothioate Oligonucleotides

    Henrik G. Bohr

    2017-09-01

    Full Text Available Important oligonucleotides in anti-sense research have been investigated in silico and experimentally. This involves quantum mechanical (QM calculations and chromatography experiments on locked nucleic acid (LNA phosphorothioate (PS oligonucleotides. iso-potential electrostatic surfaces are essential in this study and have been calculated from the wave functions derived from the QM calculations that provide binding information and other properties of these molecules. The QM calculations give details of the electronic structures in terms of e.g., energy and bonding, which make them distinguish or differentiate between the individual PS diastereoisomers determined by the position of sulfur atoms. Rules are derived from the electronic calculations of these molecules and include the effects of the phosphorothioate chirality and formation of electrostatic potential surfaces. Physical and electrochemical descriptors of the PS oligonucleotides are compared to the experiments in which chiral states on these molecules can be distinguished. The calculations demonstrate that electronic structure, electrostatic potential, and topology are highly sensitive to single PS configuration changes and can give a lead to understanding the activity of the molecules. Keywords: LNA phosphorothioate, DNA/LNA oligonucleotide, diastereoisomers, Hartree-Fock calculations, iso-potential surface, anion chromatograms

  3. Associating Oligonucleotides with Positively Charged Liposomes

    Jurkiewicz, P.; Okruszek, A.; Hof, Martin; Langner, M.

    2003-01-01

    Roč. 8, č. 1 (2003), s. 77-84 ISSN 1425-8153 R&D Projects: GA MŠk LN00A032 Institutional research plan: CEZ:AV0Z4040901 Keywords : oligonucleotides * fluorescence correlation spectroscopy * DOTAP Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.455, year: 2003

  4. Triplex-forming ability of modified oligonucleotides

    Højland, Torben; Babu, Bolle Ravindra; Bryld, Torsten

    2007-01-01

    We present our studies on the ability of several different nucleotide analogs as triplex-forming oligonucleotides. The modifications tested include 4'-C-hydroxymethyl, LNA, 2'-amino-LNA and N2'-functionalized 2'-amino-LNA. Triplexes containing monomers of N2'-glycyl-functionalized 2'-amino-LNA ar...

  5. iPad Learning Ecosystem: Developing Challenge-Based Learning Using Design Thinking

    Marin, Catalina; Hargis, Jace; Cavanaugh, Cathy

    2013-01-01

    In order to maximize college English language students' learning, product development, 21st Century skills and engagement with real world meaningful challenges, a course was designed to integrate Challenge Based Learning (CBL) and iPad mobile learning technology. This article describes the course design, which was grounded in design thinking, and…

  6. Binding of Dumbbell Oligonucleotides to MoMuLV Reverse Transcriptase: Inhibitory Properties of RNase H Activity

    Ajay Kumar

    2010-01-01

    Full Text Available Dumbbell oligonucleotides with loops of various chemistry were synthesized. Incubation of dumbbell oligonucleotides containing phosphorothioate bonds or trimethylene phosphate linkages in loops with S1 nuclease did not result in significant cleavage under conditions which led to the degradation of dumbbell oligonucleotide containing phophodiester bonds in the loops. The binding of reverse transcriptase of Moloney Murine Leukemia Virus (MoMuLV was evaluated with all the five oligonucleotides. The protein binds to all the dumbbell oligonucleotides with similar affinity. The dissociation constants evaluated using PAGE band mobility shift assays were of the order of 10-7. The inhibitory properties of the retroviral RNase H activity was evaluated using 3H –UTP-labeled RNA:RNA-DNA hybrid. It was found that the best dumbbell oligonucleotide, inhibitor contained phosphorothioate residues in both the loops. Our value studies demonstrated that this particularly designed oligonucleotide displays an IC50 of 18 nM in its inhibition on the reverse transcriptase RNase H activity, a magnitude lower than that of first nucleotide reverse transcriptase of HIV-1, tenofovir, introduced by Gilead Science in the market.

  7. High School Engineering and Technology Education Integration through Design Challenges

    Mentzer, Nathan

    2011-01-01

    This study contextualized the use of the engineering design process by providing descriptions of how each element in a design process was integrated in an eleventh grade industry and engineering systems course. The guiding research question for this inquiry was: How do students engage in the engineering design process in a course where technology…

  8. The Experience City and challenges for Architects and Urban Designers

    Marling, Gitte

    2008-01-01

    The article discusse the challenges of the experience economy from a Nordic welfare perspective. It argues that the challenges of the experience economy must be combined with the ambition that our cities are not reduced to entertainment engines. The urban life in the Nordic "welfare cities" must...... emphasise experiences that challenge, that urge reflection and that contain elements of learning just as the Nordic welfare city must strive for a socially and culturally inclusive urban life which includes offers for many different lifestyles and cultures in its diversity.     Consequently......, it is not simply a matter of creating a framework for entertainment and "Fun" or of creating architectural icon buildings that can bring fame to the city. The question is whether or not the experience economy can provide for a more versatile urban development in which architectural innovation goes hand in hand...

  9. Analysis and design of VEK for extreme events - a challenge

    Woelfel, H.P.; Technische Univ. Darmstadt

    2006-01-01

    For analysis and design of the VEK building - especially for design against earthquake and airplane crash - a 3D-integral-model had been developed, being able of yielding any global response quantities - displacements, accelerations, sectional forces, response spectra, global reinforcement - for any load actions from one mathematical model. Especially for airplane crash a so called dynamic design results in reinforcement quantities at every time step and so leads to a realistic and economic design. The advantages of the integral-model had been transferred to the design of the processing installation where the structural analysis of steel structures, vessels and piping had been dealt with in one integral mathematical model. (orig.)

  10. Fish Farm Challenge Provides STEM Design Experiences for Youth

    Horton , Robert L.; House, Patty L.

    2015-01-01

    In 2014, Monsanto Corporation partnered with National 4-H Council to help inspire and develop professional skills among young agriculturalists. The Ohio State University created Fish Farm Challenge, which engaged more than 8,000 youth across eight states. Youth were taught about worldwide food insecurity and the importance of aquaculture. They…

  11. Modernisation of Graphic Design: The Possibilities and Challenges of Digitalisation

    Stephen T.F. Poon

    2015-06-01

    Full Text Available As inventions go, the contrivance of design as a dynamic, fluid, operational vehicle of human technology has always been subject to arguments and debates. The digitalisation of graphic design is a comparatively new field of research, a progressive process that evolves with technological developments. Undoubtedly, the evolution of design practices has transformed the entire design process in ways not deemed possible in the past. The advantages of digitalisation are particularly tangible in the range of possibilities generated by computer-based design tools. The main argument for the increase in “design capital” has been the accessibility of modern art tools to both design practitioners and the wider society, through mass digital culture absorption and the emerging technologies of production and reproduction. In presenting the fundamentals of digitalisation in design practices, this paper retraces the key cornerstones in the evolution of graphic design as an aesthetic medium from the 19th - to 21st -century, while pointing out the expanding, reflexive relationships between design and our environment. The researcher’s aim is to connect the socio-historical developmental frames of social progress and the practical uses of digitalisation in art and design today. The innovations in computermediated design work today grew from experimental platforms in the 20th -century, inasmuch as technological diffusion in the 21st -century Information Age derived from the widespread global embrace of the World Wide Web, multimedia and graphical computing systems. As a result of this development of the technological ‘canvas’, the production of design, aesthetic and cultural objects has shifted from the traditional artist-craftsman-specialist paradigm to reflect a more encompassing, diverse scope of ideas fostered by the exposure to different facets of creative capital and inspirations.

  12. Streptavidin-coated gold nanoparticles: critical role of oligonucleotides on stability and fractal aggregation

    Roberta D'Agata

    2017-01-01

    Full Text Available Gold nanoparticles (AuNPs exhibit unique properties that can be modulated through a tailored surface functionalization, enabling their targeted use in biochemical sensing and medical diagnostics. In particular, streptavidin-modified AuNPs are increasingly used for biosensing purposes. We report here a study of AuNPs surface-functionalized with streptavidin-biotinylated oligonucleotide, focussing on the role played by the oligonucleotide probes in the stabilization/destabilization of the functionalized nanoparticle dispersion. The behaviour of the modified AuNP dispersion as a consequence of the competitive displacement of the biotinylated oligonucleotide has been investigated and the critical role of displaced oligonucletides in triggering the quasi one-dimensional aggregation of nanoparticles is demonstrated for the first time. The thorough understanding of the fundamental properties of bioconjugated AuNPs is of great importance for the design of highly sensitive and reliable functionalized AuNP-based assays.

  13. Identifying members of the domain Archaea with rRNA-targeted oligonucleotide probes.

    Burggraf, S; Mayer, T; Amann, R; Schadhauser, S; Woese, C R; Stetter, K O

    1994-09-01

    Two 16S rRNA-targeted oligonucleotide probes were designed for the archaeal kingdoms Euryachaeota and Crenarchaeota. Probe specificities were evaluated by nonradioactive dot blot hybridization against selected reference organisms. The successful application of fluorescent-probe derivatives for whole-cell hybridization required organism-specific optimizations of fixation and hybridization conditions to assure probe penetration and morphological integrity of the cells. The probes allowed preliminary grouping of three new hyperthermophilic isolates. Together with other group-specific rRNA-targeted oligonucleotide probes, these probes will facilitate rapid in situ monitoring of the populations present in hydrothermal systems and support cultivation attempts.

  14. Integrating Engineering Design Challenges into Secondary STEM Education

    Carr, Ronald L.; Strobel, Johannes

    2011-01-01

    Engineering is being currently taught in the full spectrum of the P-12 system, with an emphasis on design-oriented teaching (Brophy, Klein, Portsmore, & Rogers, 2008). Due to only a small amount of research on the learning of engineering design in elementary and middle school settings, the community of practice lacks the necessary knowledge of the…

  15. Teacher Challenges to Implement Engineering Design in Secondary Technology Education

    Kelley, Todd R.; Wicklein, Robert C.

    2009-01-01

    This descriptive study examined the current status of technology education teacher practices with respect to engineering design. This article is the third article in a three-part series presenting the results of this study. The first article in the series titled "Examination of Engineering Design Curriculum Content" highlighted the research…

  16. Some challenges with statistical inference in adaptive designs.

    Hung, H M James; Wang, Sue-Jane; Yang, Peiling

    2014-01-01

    Adaptive designs have generated a great deal of attention to clinical trial communities. The literature contains many statistical methods to deal with added statistical uncertainties concerning the adaptations. Increasingly encountered in regulatory applications are adaptive statistical information designs that allow modification of sample size or related statistical information and adaptive selection designs that allow selection of doses or patient populations during the course of a clinical trial. For adaptive statistical information designs, a few statistical testing methods are mathematically equivalent, as a number of articles have stipulated, but arguably there are large differences in their practical ramifications. We pinpoint some undesirable features of these methods in this work. For adaptive selection designs, the selection based on biomarker data for testing the correlated clinical endpoints may increase statistical uncertainty in terms of type I error probability, and most importantly the increased statistical uncertainty may be impossible to assess.

  17. Design and analysis challenges for advanced nuclear fuel

    Klepfer, H.; Abdollahian, D.; Dias, A.; Durston, C.; Eisenhart, L.; Engel, R.; Gilmore, P.; Rank, P.; Kjaer-Pedersen, N.; Sorensen, J.; Yang, R.; Agee, L.

    2004-01-01

    Significant changes have been incorporated in the light water reactor (LWR) fuel designs now being offered, and advanced fuel designs are currently being developed for the existing and the next generation of reactor designs. These advanced fuel design configurations are intended to offer utilities major economic gains, including: (1) improved fuel characteristics through optimized hydrogen to uranium ratio within the core; (2) increased capacity factor by allowing longer operating cycles, which is implemented by increasing the fuel enrichment and the amount and distribution of burnable poison, gadolinia, boron, or erbium within the fuel assembly to achieve higher discharge burnup; and (3) increased plant power output, if it can be accommodated by the balance of plant, by increasing the power density of the fuel assembly. The authors report here work being done to identify emerging technical issues in support of utility industry evaluations of advanced fuel designs. (author)

  18. Challenges in Design of an Orientation free Micro Direct Methanol Fuel Cell (µDMFC)

    Omidvarnia, Farzaneh; Hansen, Hans Nørgaard; Hales, Jan Harry

    2014-01-01

    the challenges in design and manufacturing of a micro direct methanol fuel cell (μDMFC) as the power generator in hearing aid devices is investigated. Among the different challenges in design for μDMFC, the CO2 bubble management and orientation independency of the cell are addressed by proposing a spring loaded...

  19. NASA Engineering Design Challenges: Environmental Control and Life Support Systems. Water Filtration Challenge. EG-2008-09-134-MSFC

    Schneider, Twila, Ed.

    2010-01-01

    This educator guide is organized into seven chapters: (1) Overview; (2) The Design Challenge; (3) Connections to National Curriculum Standards; (4) Preparing to Teach; (5) Classroom Sessions; (6) Opportunities for Extension; and (7) Teacher Resources. Chapter 1 provides information about Environmental Control and Life Support Systems used on NASA…

  20. Innovating urinary catheter design: An introduction to the engineering challenge.

    Murphy, Cathy

    2018-05-01

    Every day, people around the world rely on intermittent and indwelling urinary catheters to manage bladder dysfunction, but the potential or actual harm caused by these devices is well-recognised. Current catheter designs can cause urinary tract infection and septicaemia, bladder and urethral trauma and indwelling devices frequently become blocked. Furthermore, the devices can severely disrupt users' lives, limiting their daily activities and can be costly to manage for healthcare providers. Despite this, little significant design innovation has taken place in the last 80 years. In this article current catheter designs and their limitations are reviewed, common catheter-associated problems are outlined and areas of design ripe for improvement proposed. The potential to relieve the individual and economic burden of catheter use is high.

  1. Design challenges facing urban development in Dar es Salaam City ...

    The paper shows that in order for the resources to be deployed sustainable ... of environmentally friendly building materials, designs must take into account local ... housing construction in low-income informal settlements which in most urban ...

  2. Splice-correcting oligonucleotides restore BTK function in X-linked agammaglobulinemia model

    Bestas, Burcu; Moreno, Pedro M D; Blomberg, K Emelie M

    2014-01-01

    , splice-correcting oligonucleotides (SCOs) targeting mutated BTK transcripts for treating XLA. Both the SCO structural design and chemical properties were optimized using 2'-O-methyl, locked nucleic acid, or phosphorodiamidate morpholino backbones. In order to have access to an animal model of XLA, we...

  3. Reactor physics challenges in GEN-IV reactor design

    Driscoll, Michael K.; Hejzlar, Pavel

    2005-01-01

    An overview of the reactor physics aspects of GENeration Four (GEN-IV) advanced reactors is presented, emphasizing how their special requirements for enhanced sustainability, safety and economics motivates consideration of features not thoroughly analyzed in the past. The resulting concept-specific requirements for better data and methods are surveyed, and some approaches and initiatives are suggested to meet the challenges faced by the international reactor physics community. No unresolvable impediments to successful development of any of the six major types of proposed reactors are identified, given appropriate and timely devotion of resources

  4. Reactor physics challenges in GEN-IV reactor design

    Driscoll, Michael K.; Hejzlar, Pavel [Massachusetts Institute of Technology, MA (United States)

    2005-02-15

    An overview of the reactor physics aspects of GENeration Four (GEN-IV) advanced reactors is presented, emphasizing how their special requirements for enhanced sustainability, safety and economics motivates consideration of features not thoroughly analyzed in the past. The resulting concept-specific requirements for better data and methods are surveyed, and some approaches and initiatives are suggested to meet the challenges faced by the international reactor physics community. No unresolvable impediments to successful development of any of the six major types of proposed reactors are identified, given appropriate and timely devotion of resources.

  5. Sampling and energy evaluation challenges in ligand binding protein design.

    Dou, Jiayi; Doyle, Lindsey; Jr Greisen, Per; Schena, Alberto; Park, Hahnbeom; Johnsson, Kai; Stoddard, Barry L; Baker, David

    2017-12-01

    The steroid hormone 17α-hydroxylprogesterone (17-OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17-OHP containing an extended, nonpolar, shape-complementary binding pocket for the four-ring core of the compound, and hydrogen bonding residues at the base of the pocket to interact with carbonyl and hydroxyl groups at the more polar end of the ligand. Eight of 16 designed proteins experimentally tested bind 17-OHP with micromolar affinity. A co-crystal structure of one of the designs revealed that 17-OHP is rotated 180° around a pseudo-two-fold axis in the compound and displays multiple binding modes within the pocket, while still interacting with all of the designed residues in the engineered site. Subsequent rounds of mutagenesis and binding selection improved the ligand affinity to nanomolar range, while appearing to constrain the ligand to a single bound conformation that maintains the same "flipped" orientation relative to the original design. We trace the discrepancy in the design calculations to two sources: first, a failure to model subtle backbone changes which alter the distribution of sidechain rotameric states and second, an underestimation of the energetic cost of desolvating the carbonyl and hydroxyl groups of the ligand. The difference between design model and crystal structure thus arises from both sampling limitations and energy function inaccuracies that are exacerbated by the near two-fold symmetry of the molecule. © 2017 The Authors Protein Science published by Wiley Periodicals, Inc. on behalf of The Protein Society.

  6. Linear accelerator for production of tritium: Physics design challenges

    Wangler, T.P.; Lawrence, G.P.; Bhatia, T.S.; Billen, J.H.; Chan, K.C.D.; Garnett, R.W.; Guy, F.W.; Liska, D.; Nath, S.; Neuschaefer, G.; Shubaly, M.

    1990-01-01

    In the summer of 1989, a collaboration between Los Alamos National Laboratory and Brookhaven National Laboratory conducted a study to establish a reference design of a facility for accelerator production of tritium (APT). The APT concept is that of a neutron-spallation source, which is based on the use of high-energy protons to bombard lead nuclei, resulting in the production of large quantities of neutrons. Neutrons from the lead are captured by lithium to produce tritium. This paper describes the design of a 1.6-GeV, 250-mA proton cw linear accelerator for APT.

  7. Remote maintenance challenges presented in the ITER engineering design

    Burgess, T.W.; Herndon, J.N.; Schrock, S.L.; Lousteau, D.C.

    1995-01-01

    Leading fusion energy research institutions are currently engaged in the Engineering Design Activity for the International Thermonuclear Experimental Reactor (ITER). A tokamak reactor design is evolving which emphasizes high system performance in a minimum overall reactor and building size. The resulting high component density dictates careful attention to ITER remote maintenance considerations in the development of the configuration. The complexity and scale of ITER remote maintenance tasks are well beyond the scope of today's experience and technology. This paper discusses the remote maintenance philosophy, describes the basic configuration as it relates to maintenance, and describes the basic procedures and equipment required. Key enabling technology research and development needs are also addressed

  8. Quality Control through Design and Process: Gambrel Roof Truss Challenge

    Ward, Dell; Jones, James

    2011-01-01

    Customers determine whether a product fulfills their needs or satisfies them. "Quality control", then, is the process of finding out what the customer wants, along with designing, producing, delivering, and servicing the product--and ultimately satisfying the customer's expectations. For many years, people considered a product to be of good…

  9. Challenges of Designing the Next Generation of America's Schools.

    Duke, Daniel L.

    1998-01-01

    The Thomas Jefferson Center for Educational Design at the University of Virginia, with associates representing architecture, business, education, engineering, sociology, and technology, wants to redesign both schools and schooling. The goal is to raise standards without destroying hope, promote responsibility without sacrificing safety, expand…

  10. Concept learning by direct current design challenges in secondary education

    Van Breukelen, D.H.J.; De Vries, M.J.; Schure, F.A.

    2016-01-01

    This paper presents a mixed methods study in which 77 students and 3 teachers took part, that investigated the practice of Learning by Design (LBD). The study is part of a series of studies, funded by the Netherlands Organisation for Scientific Research, that aims to improve student learning,

  11. Concept learning by direct current design challenges in secondary education

    MEd Dave van Breukelen; Prof. Dr. Marc de Vries; MEd Frank Schure

    2016-01-01

    This paper presents a mixed methods study in which 77 students and 3 teachers took part, that investigated the practice of Learning by Design (LBD). The study is part of a series of studies, funded by the Netherlands Organisation for Scientific Research (NWO), that aims to improve student learning,

  12. Concept learning by direct current design challenges in secondary education

    van Breukelen, D.H.J.; de Vries, M.J.; Schure, Frank A.

    2016-01-01

    This paper presents a mixed methods study in which 77 students and 3 teachers took part, that investigated the practice of Learning by Design (LBD). The study is part of a series of studies, funded by the Netherlands Organisation for Scientific Research, that aims to improve student learning,

  13. design and operations challenges of a single toggle jaw crusher

    HOD

    [13] showed that the difference between Wall and Bond energies for hard rocks are .... advantages of retaining the structural design of the crusher and decreasing the ..... of aw crusher supporting structure fatigue failure”,. Stro niški Vestnik ...

  14. Activity theory as a challenge to systems design

    Bødker, Susanne

    1991-01-01

    This paper suggests an improvement of the theoretical foundation of information systems research of the 1990s. This foundation is found in human activity theory. The paper deals with how human activity theory can help systems design change, theoretically and practically. Applying activity theory...

  15. Two Paper Airplane Design Challenges: Customizing for Different Learning Objectives

    Meyer, Daniel Z.; Meyer, Allison Antink

    2012-01-01

    The incorporation of scientific inquiry into college classrooms has steadily risen as faculty work to move away from exclusively didactic methods. One type of inquiry structure, the design task, produces a product rather than simply a conclusion. This offers students a context to apply their understanding of content in a tangible way that has…

  16. Challenge Students to Design an Energy-Efficient Home

    Griffith, Jack

    2008-01-01

    This article presents an activity that gives students a practical understanding of how much energy the average home consumes and wastes, and shows how the construction technologies used in home design affect overall energy usage. In this activity, students will outline the cost of a home's electrical system, give a breakdown of how much power the…

  17. Participatory Design and the Challenges of Large-Scale Systems

    Simonsen, Jesper; Hertzum, Morten

    2008-01-01

    With its 10th biannual anniversary conference, Participatory Design (PD) is leaving its teens and must now be considered ready to join the adult world. In this article we encourage the PD community to think big: PD should engage in large-scale information-systems development and opt for a PD...

  18. Spatially Defined Oligonucleotide Arrays. Technical Report for Phase II; FINAL

    None

    2000-01-01

    The goal of the Human Genome Project is to sequence all 3 billion base pairs of the human genome. Progress in this has been rapid; GenBank(reg s ign) finished 1994 with 286 million bases of sequence and grew by 2470 in the first quarter of 1995. The challenge to the scientific community is to understand the biological relevance of this genetic information. In most cases the sequence being generated for any single region of the genome represents the genotype of a single individual. A complete understanding of the function of specific genes and other regions of the genome and their role in human disease and development will only become apparent when the sequence of many more individuals is known. Access to genetic information is ultimately limited by the ability to screen DNA sequence. Although the pioneering sequencing methods of Sanger et al. (15) and Maxam and Gilbert (11) have become standard in virtually all molecular biology laboratories, the basic protocols remain largely unchanged. The throughput of this sequencing technology is now becoming the rate-limiting step in both large-scale sequencing projects such as the Human Genome Project and the subsequent efforts to understand genetic diversity. This has inspired the development of advanced DNA sequencing technologies (9), Incremental improvements to Sanger sequencing have been made in DNA labeling and detection. High-speed electrophoresis methods using ultrathin gels or capillary arrays are now being more widely employed. However, these methods are throughput-limited by their sequential nature and the speed and resolution of separations. This limitation will become more pronounced as the need to rapidly screen newly discovered genes for biologically relevant polymorphisms increases. An alternative to gel-based sequencing is to use high-density oligonucleotide probe arrays. Oligonucleotide probe arrays display specific oligonucleotide probes at precise locations in a high density, information-rich format (5

  19. Materials challenges supporting new sodium fast reactor designs

    Gelineau, O.; Goff, S. Dubiez-le; Dubuisson, Ph.; Dalle, F.; Blat, M.

    2009-01-01

    Sodium Fast Reactor is considered in France as the most mature technology of the different Generation IV systems. In the short-term the designing work is focused on the identification of the potential tracks to improve competitiveness, safety, efficiency and to reduce cost. In that frame the materials have a key role to play. This paper is focused on the new materials envisaged and on the Research and Development program launched in France by Areva NP, CEA and EDF in order to sustain the innovative design options: ferritic steels as candidates for exchangers, steam generators and possibly sodium circuits, optimization of materials and fabrication processes to improve safety and risk management, extension of material databases to take into account the 60 years life duration including irradiation and ageing effect. (author)

  20. The challenges facing ethnographic design research: A proposed methodological solution

    Cash, Philip; Hicks, Ben; Culley, Steve

    2009-01-01

    Central to improving and maintaining high levels of performance in emerging ethnographic design research is a fundamental requirement to address some of the problems associated with the subject. In particular seven core issues are identified and include the complexity of test development......, variability of methods, resource intensiveness, subjectivity, comparability, common metrics and industrial acceptance. To address these problems this paper describes a structured methodological approach in which three main areas are proposed, the modularisation of the research process, the standardisation...... of the dataset and the stratification of the research context. The paper then examines the fundamental requirements of this scheme and how these relate to a Design Observatory approach. Following this, the proposed solution is related back to the initial problem set and potential issues are discussed. Finally...

  1. Designing Effective Serious Games: Opportunities and Challenges for Research

    Francesco Bellotti

    2010-11-01

    Full Text Available Serious Games represent an acknowledged potential for instruction, because they are able to strongly motivate learners. They can also provide immersive environments where advanced users can practice knowledge and skills, also exploiting multimodal interaction. They can combine the effectiveness of computer processing and data storage, with high levels of attractiveness. Our work has investigated the state of the art research on SGs, starting from the cognitive aspects, that are necessary in order to root technological development and applications in sound theoretical foundations. The paper discusses some key aspects about SG design and exploitation: choice of components-off-the-shelf or from-scratch design, tools and methodologies for development or adaptation, intelligent tutoring, virtual coaches and affective learning, living worlds, game mechanics, Human-Computer Interaction. While several SGs have been developed, still the literature stresses a lack of significant, extensive user tests. Further research is necessary to investigate in greater detail the real effectiveness of the various types of SGs. The paper proposes several research questions - that range from requirements elicitation to design and from deployment to use and evaluation - to be answered in order to avoid technology pushing and drive technological research according to the requirements of the end-users and stakeholders. We believe that deepening the analysis about these issues is key to strengthen the foundations of SG research, for which we identify four major directions: definition of metrics and learning progress evaluation tools; methodologies and tools for designing games from various topics and for various users; computing and communication architectures; technologies that can enhance the overall system performance.

  2. Spent Fuel Transportation Package Performance Study - Experimental Design Challenges

    Snyder, A. M.; Murphy, A. J.; Sprung, J. L.; Ammerman, D. J.; Lopez, C.

    2003-01-01

    Numerous studies of spent nuclear fuel transportation accident risks have been performed since the late seventies that considered shipping container design and performance. Based in part on these studies, NRC has concluded that the level of protection provided by spent nuclear fuel transportation package designs under accident conditions is adequate. [1] Furthermore, actual spent nuclear fuel transport experience showcase a safety record that is exceptional and unparalleled when compared to other hazardous materials transportation shipments. There has never been a known or suspected release of the radioactive contents from an NRC-certified spent nuclear fuel cask as a result of a transportation accident. In 1999 the United States Nuclear Regulatory Commission (NRC) initiated a study, the Package Performance Study, to demonstrate the performance of spent fuel and spent fuel packages during severe transportation accidents. NRC is not studying or testing its current regulations, a s the rigorous regulatory accident conditions specified in 10 CFR Part 71 are adequate to ensure safe packaging and use. As part of this study, NRC currently plans on using detailed modeling followed by experimental testing to increase public confidence in the safety of spent nuclear fuel shipments. One of the aspects of this confirmatory research study is the commitment to solicit and consider public comment during the scoping phase and experimental design planning phase of this research

  3. Sustainable hydrogen - A challenge for materials science and equipment design

    Duta, Anca; Enesca, Alexandru Ioan; Perniu, Dana

    2006-01-01

    Full text: Hydrogen is the ideal fuel, considering its fully non-polluting by-products. Still, in discussions on 'sustainable hydrogen', there must be considered all the steps implied in hydrogen production, storage and use and the overall energy balance represents the real starting point of evaluating the sustainability. So far, hydrogen production is related to rather energy-consuming processes; extended research is devoted to develop high efficiency processes, but the industrial hydrogen production makes use of either large electrical or thermal energy amounts. Hydrogen production via water photolysis represents, consequently a viable alternative although many steps have to be elaborated to reached the industrial scale of these processes. Hydrogen storing represents another problem that affects its application; a safe storage way, in metal hydrides, is still under intensive research all over the world. The group of the Centre of Product Design for Sustainable Development is engaged in research for developing a laboratory photolyser, able to produce hydrogen and to offer an efficient storage alternative. The photolyser is a photo-electrochemical cell, and the efficiency of the photolysis process depends on several factors: - the photo-electrodes: thin films of wide band gap semiconductors with tailored properties; - the aqueous environment, with effect on the electrode materials properties and stability; - the external bias; - the cell design. The paper focuses mainly on the photo-electrode materials that were tested. The influence of the composition, crystalline and defect structure, of the morphology and of the interfaces on the photolysis process are reviewed. The effect of the pH in the aqueous media is discussed along with the stability of the materials and the reversibility of the adsorption/desorption processes. The design criteria that must be fulfilled in developing the photolyser are also discussed. (authors)

  4. Remarkable Computing - the Challenge of Designing for the Home

    Petersen, Marianne Graves

    2004-01-01

    The vision of ubiquitous computing is floating into the domain of the household, despite arguments that lessons from design of workplace artefacts cannot be blindly transferred into the domain of the household. This paper discusses why the ideal of unremarkable or ubiquitous computing is too narrow...... with respect to the household. It points out how understanding technology use, is a matter of looking into the process of use and on how the specific context of the home, in several ways, call for technology to be remarkable rather than unremarkable....

  5. From products to services : reflections on the challenges in designing for services

    Bhomer, ten M.; De Lille, C. S. H.; Tomico, O.; Kleinsmann, M.S.

    2013-01-01

    In this paper we will point to implications for designers who support organizations in the transition process from products to services based business models. These implications are based on four important challenges when designing for services: the designerly mindset, collaboration, empathy with

  6. Underwater lidar system: design challenges and application in pollution detection

    Gupta, Pradip; Sankolli, Swati; Chakraborty, A.

    2016-05-01

    The present remote sensing techniques have imposed limitations in the applications of LIDAR Technology. The fundamental sampling inadequacy of the remote sensing data obtained from satellites is that they cannot resolve in the third spatial dimension, the vertical. This limits our possibilities of measuring any vertical variability in the water column. Also the interaction between the physical and biological process in the oceans and their effects at subsequent depths cannot be modeled with present techniques. The idea behind this paper is to introduce underwater LIDAR measurement system by using a LIDAR mounted on an Autonomous Underwater Vehicle (AUV). The paper introduces working principles and design parameters for the LIDAR mounted AUV (AUV-LIDAR). Among several applications the papers discusses the possible use and advantages of AUV-LIDAR in water pollution detection through profiling of Dissolved Organic Matter (DOM) in water bodies.

  7. Challenging aspects of contemporary cochlear implant electrode array design.

    Mistrík, Pavel; Jolly, Claude; Sieber, Daniel; Hochmair, Ingeborg

    2017-12-01

    A design comparison of current perimodiolar and lateral wall electrode arrays of the cochlear implant (CI) is provided. The focus is on functional features such as acoustic frequency coverage and tonotopic mapping, battery consumption and dynamic range. A traumacity of their insertion is also evaluated. Review of up-to-date literature. Perimodiolar electrode arrays are positioned in the basal turn of the cochlea near the modiolus. They are designed to initiate the action potential in the proximity to the neural soma located in spiral ganglion. On the other hand, lateral wall electrode arrays can be inserted deeper inside the cochlea, as they are located along the lateral wall and such insertion trajectory is less traumatic. This class of arrays targets primarily surviving neural peripheral processes. Due to their larger insertion depth, lateral wall arrays can deliver lower acoustic frequencies in manner better corresponding to cochlear tonotopicity. In fact, spiral ganglion sections containing auditory nerve fibres tuned to low acoustic frequencies are located deeper than 1 and half turn inside the cochlea. For this reason, a significant frequency mismatch might be occurring for apical electrodes in perimodiolar arrays, detrimental to speech perception. Tonal languages such as Mandarin might be therefore better treated with lateral wall arrays. On the other hand, closer proximity to target tissue results in lower psychophysical threshold levels for perimodiolar arrays. However, the maximal comfort level is also lower, paradoxically resulting in narrower dynamic range than that of lateral wall arrays. Battery consumption is comparable for both types of arrays. Lateral wall arrays are less likely to cause trauma to cochlear structures. As the current trend in cochlear implantation is the maximal protection of residual acoustic hearing, the lateral wall arrays seem more suitable for hearing preservation CI surgeries. Future development could focus on combining the

  8. Challenges and perspectives in Service Design curricula. The case of the Service Systems Design Master of Aalborg University in Copenhagen

    Götzen, Amalia De; Morelli, Nicola; Grani, Francesco

    2014-01-01

    In this paper the new Master program on Service Systems Design at Aalborg University in Copenhagen will be presented, focusing on the challenges of building such a curriculum and on its peculiar approach to Service Design through the Problem Based Learning methodology. All the semesters will be d...

  9. A comparative analysis of measles virus RNA by oligonucleotide fingerprinting

    Stephenson, J.R.; Meulen, V. ter

    1982-01-01

    Isolates from two cases of acute measles, one case of acute measles encephalitis and three patients with subacute sclerosing panencephalitis were compared. This comparison was based upon the electrophoretic analysis of T 1 oligonucleotides from single-stranded, full-length RNA isolated from cytoplasmic nucleocapsids. Although all viruses have oligonucleotides in common, each isolate generated a unique pattern of oligonucleotides. However, no group of oligonucleotides was observed which would allow differentiation between viruses isolated from acute infections and those isolated from CNS diseases; indicating that probably all measles viruses differ in their nucleotide sequence, regardless of origin. (Author)

  10. CERN Linac4 - The Space Charge Challenge Design and Commission

    Hein, Lutz Matthias; Holzer, Bernhard

    In the first phase of the upgrade program of the CERN accelerator complex the proton injector Linac2 will be replaced by a new, normal-conducting $H^-$ ion Linac, Linac4, allowing a significant increase of the proton flux intensity along the downstream accelerator complex. In the design of Linac4 three beam transport sections are implemented to match the beam between the different accelerator elements and to model the longitudinal pulse structure. These three beam transport sections, which are the most critical locations in terms of beam quality preservation, are in the focus of this thesis. During the work of this thesis the low energy beam transport (LEBT), which is required to match the source beam to the radiofrequency quadrupole (RFQ), has been commissioned and its beam dynamics re-constructed. The measurement campaign used to re-construct the LEBT beam dynamics was performed with the aim to prepare the RFQ commissioning and to maximise the LEBT performance. Downstream of the Linac4 accelerator the beam...

  11. Four categories of design challenges to building game-based business

    Henriksen, Thomas Duus; Harpelund, Christian

    2014-01-01

    Building a business on the basis of designing and selling learning games is seldom a straightforward task. Often, such a project involves a diversity of competencies for handling a wide variety of challenges. On the basis of a longitudinal study of the game ChangeSetter, this chapter proposes...... a four-category approach to understanding such challenges. The four categories include 1) the learning game design, 2) didactic design on how the game is to be used, 3) organisational design for establishing both supply and demand, and finally 4) business design, which concerns the establishment...... of a business model that ensures continual rather than incidental income. While the four categories can be used for understanding the various challenges and what competencies they prompt for, the key argument of the chapter is to start with the business design as it is likely to cause extensive iterations...

  12. Challenges and Limitations of Applying an Emotion-driven Design Approach on Elderly Users

    Andersen, Casper L.; Gudmundsson, Hjalte P.; Achiche, Sofiane

    2011-01-01

    a competitive advantage for companies. In this paper, challenges of applying an emotion-driven design approach applied on elderly people, in order to identify their user needs towards walking frames, are discussed. The discussion will be based on the experiences and results obtained from the case study...... related to the participants’ age and cognitive abilities. The challenges encountered are discussed and guidelines on what should be taken into account to facilitate an emotion-driven design approach for elderly people are proposed....

  13. Chemical Ligation Reactions of Oligonucleotides for Biological and Medicinal Applications.

    Abe, Hiroshi; Kimura, Yasuaki

    2018-01-01

    Chemical ligation of oligonucleotides (ONs) is the key reaction for various ON-based technologies. We have tried to solve the problems of RNA interference (RNAi) technology by applying ON chemical ligation to RNAi. We designed a new RNAi system, called intracellular buildup RNAi (IBR-RNAi), where the RNA fragments are built up into active small-interference RNA (siRNA) in cells through a chemical ligation reaction. Using the phosphorothioate and iodoacetyl groups as reactive functional groups for the ligation, we achieved RNAi effects without inducing immune responses. Additionally, we developed a new chemical ligation for IBR-RNAi, which affords a more native-like structure in the ligated product. The new ligation method should be useful not only for IBR-RNAi but also for the chemical synthesis of biofunctional ONs.

  14. DETECTING LOW-LEVEL SYNTHESIS IMPURITIES IN MODIFIED PHOSPHOROTHIOATE OLIGONUCLEOTIDES USING LIQUID CHROMATOGRAPHY – HIGH RESOLUTION MASS SPECTROMETRY

    Nikcevic, Irena; Wyrzykiewicz, Tadeusz K.; Limbach, Patrick A.

    2010-01-01

    Summary An LC-MS method based on the use of high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTIRCMS) for profiling oligonucleotides synthesis impurities is described. Oligonucleotide phosphorothioatediesters (phosphorothioate oligonucleotides), in which one of the non-bridging oxygen atoms at each phosphorus center is replaced by a sulfur atom, are now one of the most popular oligonucleotide modifications due to their ease of chemical synthesis and advantageous pharmacokinetic properties. Despite significant progress in the solid-phase oligomerization chemistry used in the manufacturing of these oligonucleotides, multiple classes of low-level impurities always accompany synthetic oligonucleotides. Liquid chromatography-mass spectrometry has emerged as a powerful technique for the identification of these synthesis impurities. However, impurity profiling, where the entire complement of low-level synthetic impurities is identified in a single analysis, is more challenging. Here we present an LC-MS method based the use of high resolution-mass spectrometry, specifically Fourier transform ion cyclotron resonance mass spectrometry (FTIRCMS or FTMS). The optimal LC-FTMS conditions, including the stationary phase and mobile phases for the separation and identification of phosphorothioate oligonucleotides, were found. The characteristics of FTMS enable charge state determination from single m/z values of low-level impurities. Charge state information then enables more accurate modeling of the detected isotopic distribution for identification of the chemical composition of the detected impurity. Using this approach, a number of phosphorothioate impurities can be detected by LC-FTMS including failure sequences carrying 3′-terminal phosphate monoester and 3′-terminal phosphorothioate monoester, incomplete backbone sulfurization and desulfurization products, high molecular weight impurities, and chloral, isobutyryl, and N3 (2-cyanoethyl) adducts

  15. The illusion of specific capture: surface and solution studies of suboptimal oligonucleotide hybridization

    2013-01-01

    Background Hybridization based assays and capture systems depend on the specificity of hybridization between a probe and its intended target. A common guideline in the construction of DNA microarrays, for instance, is that avoiding complementary stretches of more than 15 nucleic acids in a 50 or 60-mer probe will eliminate sequence specific cross-hybridization reactions. Here we present a study of the behavior of partially matched oligonucleotide pairs with complementary stretches starting well below this threshold complementarity length – in silico, in solution, and at the microarray surface. The modeled behavior of pairs of oligonucleotide probes and their targets suggests that even a complementary stretch of sequence 12 nt in length would give rise to specific cross-hybridization. We designed a set of binding partners to a 50-mer oligonucleotide containing complementary stretches from 6 nt to 21 nt in length. Results Solution melting experiments demonstrate that stable partial duplexes can form when only 12 bp of complementary sequence are present; surface hybridization experiments confirm that a signal close in magnitude to full-strength signal can be obtained from hybridization of a 12 bp duplex within a 50mer oligonucleotide. Conclusions Microarray and other molecular capture strategies that rely on a 15 nt lower complementarity bound for eliminating specific cross-hybridization may not be sufficiently conservative. PMID:23445545

  16. Development, characterization and experimental validation of a cultivated sunflower (Helianthus annuus L. gene expression oligonucleotide microarray.

    Paula Fernandez

    Full Text Available Oligonucleotide-based microarrays with accurate gene coverage represent a key strategy for transcriptional studies in orphan species such as sunflower, H. annuus L., which lacks full genome sequences. The goal of this study was the development and functional annotation of a comprehensive sunflower unigene collection and the design and validation of a custom sunflower oligonucleotide-based microarray. A large scale EST (>130,000 ESTs curation, assembly and sequence annotation was performed using Blast2GO (www.blast2go.de. The EST assembly comprises 41,013 putative transcripts (12,924 contigs and 28,089 singletons. The resulting Sunflower Unigen Resource (SUR version 1.0 was used to design an oligonucleotide-based Agilent microarray for cultivated sunflower. This microarray includes a total of 42,326 features: 1,417 Agilent controls, 74 control probes for sunflower replicated 10 times (740 controls and 40,169 different non-control probes. Microarray performance was validated using a model experiment examining the induction of senescence by water deficit. Pre-processing and differential expression analysis of Agilent microarrays was performed using the Bioconductor limma package. The analyses based on p-values calculated by eBayes (p<0.01 allowed the detection of 558 differentially expressed genes between water stress and control conditions; from these, ten genes were further validated by qPCR. Over-represented ontologies were identified using FatiScan in the Babelomics suite. This work generated a curated and trustable sunflower unigene collection, and a custom, validated sunflower oligonucleotide-based microarray using Agilent technology. Both the curated unigene collection and the validated oligonucleotide microarray provide key resources for sunflower genome analysis, transcriptional studies, and molecular breeding for crop improvement.

  17. IKEA hackers : The lampan - opportunities for 'new' designers bring challenges for 'old' designers

    Saakes, D.P.

    2011-01-01

    At the beginning of the 20th century, when standardization successfully separated design from manufacturing, a new profession emerged: the industrial designer. Industrial designers cater to mass production by making trade-offs between engineering, human factors, design constraints and marketing.

  18. Characterising Extrinsic Challenges Linked to the Design and Implementation of Inquiry-Based Practical Work

    Akuma, Fru Vitalis; Callaghan, Ronel

    2017-11-01

    Inquiry-based science education has been incorporated in science curricula internationally. In this regard, however, many teachers encounter challenges. The challenges have been characterised into those linked to the personal characteristics of these teachers (intrinsic challenges) and others associated with contextual factors (extrinsic challenges). However, this level of characterisation is inadequate in terms of appreciating the complexity of the challenges, tracking of their development, and discovering knowledge within specific categories. Against this background, the purpose of the research presented here was to characterise extrinsic challenges linked to the design and implementation of inquiry-based practical work. In order to do so, we used a conceptual framework of teaching challenges based on Bronfenbrenner's ecological theory of human development. The data gathered using a multi-method case study of practical work in two South African high schools, was analysed by combining the data-driven inductive approach and the deductive a priori template of codes approach in thematic analysis. On this basis, the extrinsic challenges linked to the design and implementation of inquiry-based practical work that participants are confronted with, were found to consist of macrosystem challenges (such as a restrictive curriculum) and microsystem challenges. At the latter level, the challenges are material-related (e.g., lack of science education equipment and materials) or non-material-related (such as time constraints and the lack of access to interactive computer simulations). We have discussed the theory-, practice- and research-based implications of these results in relation to the design and implementation of inquiry-based practical work in South Africa and internationally.

  19. Teaching chemical product design to engineering students: course contents and challenges

    Skov, Anne Ladegaard; Kiil, Søren

    Chemical product design is not taught in the same way as traditional engineering courses like unit operations or transport phenomena. This paper gives an overview of the challenges that we, as teachers, have faced when teaching chemical product design to engineering students. Specific course...

  20. Design Innovations and Implementation Challenges - A Case of Smart Textiles in Future Hospital Interiors

    Mogensen, Jeppe; Jørgensen, Poul-Erik; Poulsen, Søren Bolvig

    2014-01-01

    Concerned with the overall challenges of implementing design innovations, this paper relates to the specific case of applying smart textiles in future hospital interiors. The methodological approach is inspired by design thinking and implementation processes, and through the scope of a developed ...

  1. Use of a design challenge to develop postural support devices for intermediate wheelchair users

    Brenda N. Onguti

    2017-09-01

    Full Text Available The provision of an appropriate wheelchair, one that provides proper fit and postural support, promotes wheelchair users’ physical health and quality of life. Many wheelchair users have postural difficulties, requiring supplemental postural support devices for added trunk support. However, in many low- and middle-income settings, postural support devices are inaccessible, inappropriate or unaffordable. This article describes the use of the design challenge model, informed by a design thinking approach, to catalyse the development of an affordable, simple and robust postural support device for low- and middle-income countries. The article also illustrates how not-for-profit organisations can utilise design thinking and, in particular, the design challenge model to successfully support the development of innovative solutions to product or process challenges.

  2. TIA-1 RRM23 binding and recognition of target oligonucleotides.

    Waris, Saboora; García-Mauriño, Sofía M; Sivakumaran, Andrew; Beckham, Simone A; Loughlin, Fionna E; Gorospe, Myriam; Díaz-Moreno, Irene; Wilce, Matthew C J; Wilce, Jacqueline A

    2017-05-05

    TIA-1 (T-cell restricted intracellular antigen-1) is an RNA-binding protein involved in splicing and translational repression. It mainly interacts with RNA via its second and third RNA recognition motifs (RRMs), with specificity for U-rich sequences directed by RRM2. It has recently been shown that RRM3 also contributes to binding, with preferential binding for C-rich sequences. Here we designed UC-rich and CU-rich 10-nt sequences for engagement of both RRM2 and RRM3 and demonstrated that the TIA-1 RRM23 construct preferentially binds the UC-rich RNA ligand (5΄-UUUUUACUCC-3΄). Interestingly, this binding depends on the presence of Lys274 that is C-terminal to RRM3 and binding to equivalent DNA sequences occurs with similar affinity. Small-angle X-ray scattering was used to demonstrate that, upon complex formation with target RNA or DNA, TIA-1 RRM23 adopts a compact structure, showing that both RRMs engage with the target 10-nt sequences to form the complex. We also report the crystal structure of TIA-1 RRM2 in complex with DNA to 2.3 Å resolution providing the first atomic resolution structure of any TIA protein RRM in complex with oligonucleotide. Together our data support a specific mode of TIA-1 RRM23 interaction with target oligonucleotides consistent with the role of TIA-1 in binding RNA to regulate gene expression. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Dissecting the hybridization of oligonucleotides to structured complementary sequences.

    Peracchi, Alessio

    2016-06-01

    When oligonucleotides hybridize to long target molecules, the process is slowed by the secondary structure in the targets. The phenomenon has been analyzed in several previous studies, but many details remain poorly understood. I used a spectrofluorometric strategy, focusing on the formation/breaking of individual base pairs, to study the kinetics of association between a DNA hairpin and >20 complementary oligonucleotides ('antisenses'). Hybridization rates differed by over three orders of magnitude. Association was toehold-mediated, both for antisenses binding to the target's ends and for those designed to interact with the loop. Binding of these latter, besides being consistently slower, was affected to variable, non-uniform extents by the asymmetric loop structure. Divalent metal ions accelerated hybridization, more pronouncedly when nucleation occurred at the loop. Incorporation of locked nucleic acid (LNA) residues in the antisenses substantially improved the kinetics only when LNAs participated to the earliest hybridization steps. The effects of individual LNAs placed along the antisense indicated that the reaction transition state occurred after invading at least the first base pair of the stem. The experimental approach helps dissect hybridization reactions involving structured nucleic acids. Toehold-dependent, nucleation-invasion models appear fully appropriate for describing such reactions. Estimating the stability of nucleation complexes formed at internal toeholds is the major hurdle for the quantitative prediction of hybridization rates. While analyzing the mechanisms of a fundamental biochemical process (hybridization), this work also provides suggestions for the improvement of technologies that rely on such process. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Peptide-oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic

    Lou, Chenguang; Martos-Maldonado, Manuel C.; Madsen, Charlotte Stahl

    2016-01-01

    Peptide-based structures can be designed to yield artificial proteins with specific folding patterns and functions. Template-based assembly of peptide units is one design option, but the use of two orthogonal self-assembly principles, oligonucleotide triple helix and a coiled coil protein domain ...

  5. Delft Aerospace Design Projects 2015 : Challenging New Designs in Aeronautics, Astronautics and Wind Energy

    Melkert, J.A.

    2015-01-01

    This book presents an overview of the results of the Fall Design Synthesis Exercise 2014 and the Spring Design Synthesis Exercise of 2015, based on summaries of each of the projects. The Design Synthesis Exercise Coordination Committee, responsible for the organisation and execution of the exercise,

  6. Phage annealing proteins promote oligonucleotide-directed mutagenesis in Escherichia coli and mouse ES cells

    Muyrers Joep PP

    2003-01-01

    Full Text Available Abstract Background The phage protein pairs, RecE/RecT from Rac or Redα/Redβ from λ, initiate efficient double strand break repair (DSBR in Escherichia coli that has proven very useful for DNA engineering. These phage pairs initiate DSBR either by annealing or by another mechanism that is not defined. Results Here we report that these proteins also mediate single strand oligonucleotide repair (ssOR at high efficiencies. The ssOR activity, unlike DSBR, does not require a phage exonuclease (RecE or Redα but only requires a phage annealing protein (RecT or Redβ. Notably, the P22 phage annealing protein Erf, which does not mediate the same DSBR reactions, also delivers ssOR activity. By altering aspects of the oligonucleotides, we document length and design parameters that affect ssOR efficiency to show a simple relationship to homologies either side of the repair site. Notably, ssOR shows strand bias. Oligonucleotides that can prime lagging strand replication deliver more ssOR than their leading complements. This suggests a model in which the annealing proteins hybridize the oligonucleotides to single stranded regions near the replication fork. We also show that ssOR is a highly efficient way to engineer BACs and can be detected in a eukaryotic cell upon expression of a phage annealing protein. Conclusion Phage annealing proteins can initiate the recombination of single stranded oligonucleotides into endogenous targets in Escherichia coli at very high efficiencies. This expands the repertoire of useful DNA engineering strategies, shows promise for applications in eukaryotic cells, and has implications for the unanswered questions regarding DSBR mediated by RecE/RecT and Redα/Redβ.

  7. Some Challenges in the Design of Human-Automation Interaction for Safety-Critical Systems

    Feary, Michael S.; Roth, Emilie

    2014-01-01

    Increasing amounts of automation are being introduced to safety-critical domains. While the introduction of automation has led to an overall increase in reliability and improved safety, it has also introduced a class of failure modes, and new challenges in risk assessment for the new systems, particularly in the assessment of rare events resulting from complex inter-related factors. Designing successful human-automation systems is challenging, and the challenges go beyond good interface development (e.g., Roth, Malin, & Schreckenghost 1997; Christoffersen & Woods, 2002). Human-automation design is particularly challenging when the underlying automation technology generates behavior that is difficult for the user to anticipate or understand. These challenges have been recognized in several safety-critical domains, and have resulted in increased efforts to develop training, procedures, regulations and guidance material (CAST, 2008, IAEA, 2001, FAA, 2013, ICAO, 2012). This paper points to the continuing need for new methods to describe and characterize the operational environment within which new automation concepts are being presented. We will describe challenges to the successful development and evaluation of human-automation systems in safety-critical domains, and describe some approaches that could be used to address these challenges. We will draw from experience with the aviation, spaceflight and nuclear power domains.

  8. Regulation of Gene Expression with Double-Stranded Phosphorothioate Oligonucleotides

    Bielinska, Anna; Shivdasani, Ramesh A.; Zhang, Liquan; Nabel, Gary J.

    1990-11-01

    Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappaB consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappaB. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappaB-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects.

  9. Identifying members of the domain Archaea with rRNA-targeted oligonucleotide probes.

    Burggraf, S; Mayer, T; Amann, R; Schadhauser, S; Woese, C R; Stetter, K O

    1994-01-01

    Two 16S rRNA-targeted oligonucleotide probes were designed for the archaeal kingdoms Euryachaeota and Crenarchaeota. Probe specificities were evaluated by nonradioactive dot blot hybridization against selected reference organisms. The successful application of fluorescent-probe derivatives for whole-cell hybridization required organism-specific optimizations of fixation and hybridization conditions to assure probe penetration and morphological integrity of the cells. The probes allowed prelim...

  10. Rectifier Design Challenges for RF Wireless Power Transfer and Energy Harvesting Systems

    A. Collado

    2017-06-01

    Full Text Available The design of wireless power transfer (WPT and energy harvesting (EH solutions poses different challenges towards achieving maximum RF-DC conversion efficiency in these systems. This paper covers several selected challenges when developing WPT and electromagnetic EH solutions, such as the design of multiband and broadband rectifiers, the minimization of the effect that load and input power variations may have on the system performance and finally the most optimum power combining mechanisms that can be used when dealing with multi-element rectifiers.

  11. LTE and the evolution to 4G wireless design and measurement challenges

    Rumney, Moray

    2013-01-01

    A practical guide to LTE design, test and measurement, this new edition has been updated to include the latest developments This book presents the latest details on LTE from a practical and technical perspective. Written by Agilent's measurement experts, it offers a valuable insight into LTE technology and its design and test challenges. Chapters cover the upper layer signaling and system architecture evolution (SAE). Basic concepts such as MIMO and SC-FDMA, the new uplink modulation scheme, are introduced and explained, and the authors look into the challenges of verifying the

  12. NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A-T phosphoramidite building blocks.

    Schmidtgall, Boris; Höbartner, Claudia; Ducho, Christian

    2015-01-01

    Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T-T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X-T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A-T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues.

  13. What values in design? The challenge of incorporating moral values into design.

    Manders-Huits, Noëmi

    2011-06-01

    Recently, there is increased attention to the integration of moral values into the conception, design, and development of emerging IT. The most reviewed approach for this purpose in ethics and technology so far is Value-Sensitive Design (VSD). This article considers VSD as the prime candidate for implementing normative considerations into design. Its methodology is considered from a conceptual, analytical, normative perspective. The focus here is on the suitability of VSD for integrating moral values into the design of technologies in a way that joins in with an analytical perspective on ethics of technology. Despite its promising character, it turns out that VSD falls short in several respects: (1) VSD does not have a clear methodology for identifying stakeholders, (2) the integration of empirical methods with conceptual research within the methodology of VSD is obscure, (3) VSD runs the risk of committing the naturalistic fallacy when using empirical knowledge for implementing values in design, (4) the concept of values, as well as their realization, is left undetermined and (5) VSD lacks a complimentary or explicit ethical theory for dealing with value trade-offs. For the normative evaluation of a technology, I claim that an explicit and justified ethical starting point or principle is required. Moreover, explicit attention should be given to the value aims and assumptions of a particular design. The criteria of adequacy for such an approach or methodology follow from the evaluation of VSD as the prime candidate for implementing moral values in design.

  14. Modern methods for the synthesis of peptide-oligonucleotide conjugates

    Zubin, Evgenii M; Oretskaya, Tat'yana S; Romanova, Elena A

    2002-01-01

    The published data on the methods of chemical solution and solid-phase synthesis of peptide-oligonucleotide conjugates are reviewed. The known methods are systematised and their advantages and disadvantages are considered. The approaches to the solution synthesis of peptide-oligonucleotide conjugates are systematised according to the type of chemical bonds between the fragments, whereas those to the solid-phase synthesis are classified according to the procedure used for the preparation of conjugates, viz., stepwise elongation of oligonucleotide and peptide chains on the same polymeric support or solid-phase condensation of two presynthesised fragments. The bibliography includes 141 references.

  15. Optical Characterization of Oligonucleotide DNA Influenced by Magnetic Fields

    Seyedeh Maryam Banihashemian

    2013-09-01

    Full Text Available UV-VIS spectroscopic analysis of oligonucleotide DNA exposed to different magnetic fields was performed in order to investigate the relationship between DNA extinction coefficients and optical parameters according to magnetic-field strength. The results with the oligonucleotides adenine-thymine 100 mer (AT-100 DNA and cytosine-guanine 100 mer (CG-100 DNA indicate that the magnetic field influences DNA molar extinction coefficients and refractive indexes. The imaginary parts of the refractive index and molar extinction coefficients of the AT-100 and CG-100 DNA decreased after exposure to a magnetic field of 750 mT due to cleavage of the DNA oligonucleotides into smaller segments.

  16. Positioning Industrial Design Education within Higher Education: How to face increasingly challenging market forces?

    André Liem

    2014-05-01

    Full Text Available This paper discusses how Industrial Design Education should be adapted to pressing future challenges of higher education with respect to promoting high quality mentorship and scholarship, as well as being more economically self-sufficient through stronger collaborative engagements with industry. The four (4 following trends will be presented on how prospective design programs are to be developed: (1 Mass-education and rationalisation, (2 Links between education and research, (3 Globalisation and internationalisation, and (4 Collaboration with industry and research commercialisation.Given the challenges of market forces within academia, a consensus within the design education community should be established in order to expose students more to “active learning” and to vice-versa commute from generic to specialist and from abstract to concrete modes of working. Comprehensive and collaborative studio projects should be implemented as platforms, where social, interdisciplinary and inquiry-based learning can be developed in line with selected design themes, processes and methods.

  17. The MedlinePlus public user interface: studies of design challenges and opportunities

    Marill, Jennifer L.; Miller, Naomi; Kitendaugh, Paula

    2006-01-01

    Question: What are the challenges involved in designing, modifying, and improving a major health information portal that serves over sixty million page views a month? Setting: MedlinePlus, the National Library of Medicine's (NLM's) consumer health Website, is examined. Method: Challenges are presented as six “studies,” which describe selected design issues and how NLM staff resolved them. Main Result: Improving MedlinePlus is an iterative process. Changes in the public user interface are ongoing, reflecting Web design trends, usability testing recommendations, user survey results, new technical requirements, and the need to grow the site in an orderly way. Conclusion: Testing and analysis should accompany Website design modifications. New technologies may enhance a site but also introduce problems. Further modifications to MedlinePlus will be informed by the experiences described here. PMID:16404467

  18. New Challenges for Design Participation in the Era of Ubiquitous Computing

    Brereton, Margot; Buur, Jacob

    2008-01-01

    Since the event of participatory design in the work democracy projects of the 1970’s and 1980’s in Scandinavia, computing technology and people’s engagement with it have undergone fundamental changes. Although participatory design continues to be a precondition for designing computing that aligns...... with human practices, the motivations to engage in participatory design have changed, and the new era requires formats that are different from the original ones. Through the analysis of three case studies this paper seeks to explain why participatory design must be brought to bear on the field of ubiquitous...... computing, and how this challenges the original participatory design thinking. In particular we will argue that more casual, exploratory formats of engagement with people are required, and rather than planning the all-encompassing systems development project, participatory design needs to move towards...

  19. Present day design challenges exemplified by the Clinch River Breeder Reactor Plant

    Dickson, P.W. Jr.; Anderson, C.A. Jr.

    1976-01-01

    The present day design challenges faced by the Clinch River Breeder Reactor Plant engineer result from two causes. The first cause is aspiration to achieve a design that will operate at conditions which are desirable for future LMFBRs in order for them to achieve low power costs and good breeding. The second cause is the licensing impact. Although licensing the CRBRP won't eliminate future licensing effort, many licensing questions will have been resolved and precedents set for the future LMFBR industry

  20. A REVIEW OF OIL PALM BIOCOMPOSITES FOR FURNITURE DESIGN AND APPLICATIONS: POTENTIAL AND CHALLENGES

    Siti Suhaily,; Mohammad Jawaid,; H. P. S. Abdul Khalil,; A. Rahman Mohamed; , F. Ibrahim

    2012-01-01

    This review considers the potential and challenges of using agro-based oil palm biomasses, including the trunk, frond, empty fruit bunch, and palm press fiber biocomposites, for furniture applications. Currently, design and quality rather than price are becoming the primary concern for consumers when buying new furniture. Within this context, this paper focuses on the design of innovative, sustainable furniture from agro-based biocomposites to meet the needs of future population growth and te...

  1. Development of Multiexon Skipping Antisense Oligonucleotide Therapy for Duchenne Muscular Dystrophy

    Yokota, Toshifumi; Wood, Matthew J. A.

    2013-01-01

    Duchenne muscular dystrophy (DMD) is an incurable, X-linked progressive muscle degenerative disorder that results from the absence of dystrophin protein and leads to premature death in affected individuals due to respiratory and/or cardiac failure typically by age of 30. Very recently the exciting prospect of an effective oligonucleotide therapy has emerged which restores dystrophin protein expression to affected tissues in DMD patients with highly promising data from a series of clinical trials. This therapeutic approach is highly mutation specific and thus is personalised. Therefore DMD has emerged as a model genetic disorder for understanding and overcoming of the challenges of developing personalised genetic medicines. One of the greatest weaknesses of the current oligonucleotide approach is that it is a mutation-specific therapy. To address this limitation, we have recently demonstrated that exons 45–55 skipping therapy has the potential to treat clusters of mutations that cause DMD, which could significantly reduce the number of compounds that would need to be developed in order to successfully treat all DMD patients. Here we discuss and review the latest preclinical work in this area as well as a variety of accompanying issues, including efficacy and potential toxicity of antisense oligonucleotides, prior to human clinical trials. PMID:23984357

  2. NASA Green Flight Challenge: Conceptual Design Approaches and Technologies to Enable 200 Passenger Miles per Gallon

    Wells, Douglas P.

    2011-01-01

    The Green Flight Challenge is one of the National Aeronautics and Space Administration s Centennial Challenges designed to push technology and make passenger aircraft more efficient. Airliners currently average around 50 passenger-miles per gallon and this competition will push teams to greater than 200 passenger-miles per gallon. The aircraft must also fly at least 100 miles per hour for 200 miles. The total prize money for this competition is $1.65 Million. The Green Flight Challenge will be run by the Comparative Aircraft Flight Efficiency (CAFE) Foundation September 25 October 1, 2011 at Charles M. Schulz Sonoma County Airport in California. Thirteen custom aircraft were developed with electric, bio-diesel, and other bio-fuel engines. The aircraft are using various technologies to improve aerodynamic, propulsion, and structural efficiency. This paper will explore the feasibility of the rule set, competitor vehicles, design approaches, and technologies used.

  3. Positioning Learning Design: Learner Experience and the challenges of transforming teaching practice

    Johnson, Mark; Griffiths, Dai; Hanslot, Zubair

    2010-01-01

    Johnson, M., Griffiths, D., & Hanslot, Z. (2010). Positioning Learning Design: Learner Experience and the challenges of transforming teaching practice. In D. Griffiths, & R. Koper (Eds.), Rethinking Learning and Employment at a Time of Economic Uncertainty. Proceedings of the 6th TENCompetence Open

  4. Exploring Group Life Design with Teachers in the Context of Poverty Related Psychosocial Challenges

    Setlhare, Rubina; Wood, Lesley; Meyer, Lukas

    2017-01-01

    Working in challenging contexts can impact negatively on a teacher's sense of purpose and efficacy. This article explores the potential of group Life Design (LD), a narrative constructivist career counselling process, for supporting ten South African school teachers working at an under-resourced school with understanding their career aspirations…

  5. Challenges of building and sustaining living labs for designing services and products

    Subasi, Özge; Werner, Katharina; Fitzpatrick, Geraldine

    2016-01-01

    In this paper, we show examples from one of the living labs from the Give&Take project and discuss the observed challenges of establishing and sustaining living labs in a participatory design context. The observations we present are around the mismatch between research language and everyday...

  6. Hybrid Societies: Challenges and Perspectives in the Design of Collective Behavior in Self-organizing Systems

    Heiko eHamann

    2016-04-01

    Full Text Available Hybrid societies are self-organizing, collective systems composed of different components, for example, natural and artificial parts (bio-hybrid or human beings interacting with and through technical systems (socio-technical. Many different disciplines investigate methods and systems closely related to the design of hybrid societies. A~stronger collaboration between these disciplines could allow for re-use of methods and create significant synergies. We identify three main areas of challenges in the design of self-organizing hybrid societies. First, we identify the formalization challenge. There is an urgent need for a generic model that allows a description and comparison of collective hybrid societies. Second, we identify the system design challenge. Starting from the formal specification of the system, we need to develop an integrated design process. Third, we identify the challenge of interdisciplinarity. Current research on self-organizing hybrid societies stretches over many different fields and hence requires the re-use and synthesis of methods at intersections between disciplines. We then conclude by presenting our perspective for future approaches with high potential in this area.

  7. Design challenges for long-term interaction with a robot in a science classroom

    Davison, Daniel Patrick; Charisi, Vasiliki; Wijnen, Frances Martine; Papenmeier, Andrea; van der Meij, Jan; Reidsma, Dennis; Evers, Vanessa

    This paper aims to present the main challenges that emerged during the process of the research design of a longitudinal study on child-robot interaction for science education and to discuss relevant suggestions in the context. The theoretical rationale is based on aspects of the theory of social

  8. Small-Scale Design Experiments as Working Space for Larger Mobile Communication Challenges

    Lowe, Sarah; Stuedahl, Dagny

    2014-01-01

    In this paper, a design experiment using Instagram as a cultural probe is submitted as a method for analyzing the challenges that arise when considering the implementation of social media within a distributed communication space. It outlines how small, iterative investigations can reveal deeper research questions relevant to the education of…

  9. Challenge

    Schwitters, R.F.

    1996-01-01

    The design of new and upgrades of existing high energy particle accelerators is reviewed in light of the current knowledge of the standard model determined from existing and past machines and funding factors. Current financing of science will delay determining unknowns, such as CP violation, proton decay, neutrino properties, and dark matter. Three options are given: (1) obtain more funding, (2) downsize scientific personnel as are private enterprises or (3) develop new technology which will reduce the high cost of building current designs of high energy accelerators. (AIP) copyright 1996 American Institute of Physics

  10. Sequence-dependent theory of oligonucleotide hybridization kinetics

    Marimuthu, Karthikeyan; Chakrabarti, Raj

    2014-01-01

    A theoretical approach to the prediction of the sequence and temperature-dependent rate constants for oligonucleotide hybridization reactions has been developed based on the theory of relaxation kinetics. One-sided and two-sided melting reaction mechanisms for oligonucleotide hybridization reactions have been considered, analyzed, modified, and compared to select a physically consistent as well as robust model for prediction of the relaxation times of DNA hybridization reactions that agrees with the experimental evidence. The temperature- and sequence-dependent parameters of the proposed model have been estimated using available experimental data. The relaxation time model that we developed has been combined with the nearest neighbor model of hybridization thermodynamics to estimate the temperature- and sequence-dependent rate constants of an oligonucleotide hybridization reaction. The model-predicted rate constants are compared to experimentally determined rate constants for the same oligonucleotide hybridization reactions. Finally, we consider a few important applications of kinetically controlled DNA hybridization reactions

  11. Oligonucleotide-based theranostic nanoparticles in cancer therapy

    Shahbazi, Reza; Ozpolat, Bulent; Ulubayram, Kezban

    2016-01-01

    Theranostic approaches, combining the functionality of both therapy and imaging, have shown potential in cancer nanomedicine. Oligonucleotides such as small interfering RNA and microRNA, which are powerful therapeutic agents, have been effectively employed in theranostic systems against various cancers. Nanoparticles are used to deliver oligonucleotides into tumors by passive or active targeting while protecting the oligonucleotides from nucleases in the extracellular environment. The use of quantum dots, iron oxide nanoparticles and gold nanoparticles and tagging with contrast agents, like fluorescent dyes, optical or magnetic agents and various radioisotopes, has facilitated early detection of tumors and evaluation of therapeutic efficacy. In this article, we review the advantages of theranostic applications in cancer therapy and imaging, with special attention to oligonucleotide-based therapeutics. PMID:27102380

  12. Challenges and Opportunities for Establishing Design as a Research Discipline in Civil and Environmental Engineering

    Thompson, Mary Kathryn

    2013-01-01

    faculty, research and education communities, conferences, and journals. However, design remains an emerging sub-discipline in civil and environmental engineering – practiced, valued, and taught but not subject to rigorous academic research. This paper presents some of the challenges associated...... with the establishment of design as a research discipline within civil and environmental engineering, some of the benefits and opportunities that will come from that establishment, and some evidence for the fact that this process has already begun.......There are a number of fields including architecture, industrial design, and urban planning and design, where design is the discipline upon which all research and teaching activities are based. In other fields such as aerospace and mechanical engineering, design is a sub-discipline with its own...

  13. Device and Circuit Design Challenges in the Digital Subthreshold Region for Ultralow-Power Applications

    Ramesh Vaddi

    2009-01-01

    Full Text Available In recent years, subthreshold operation has gained a lot of attention due to ultra low-power consumption in applications requiring low to medium performance. It has also been shown that by optimizing the device structure, power consumption of digital subthreshold logic can be further minimized while improving its performance. Therefore, subthreshold circuit design is very promising for future ultra low-energy sensor applications as well as high-performance parallel processing. This paper deals with various device and circuit design challenges associated with the state of the art in optimal digital subthreshold circuit design and reviews device design methodologies and circuit topologies for optimal digital subthreshold operation. This paper identifies the suitable candidates for subthreshold operation at device and circuit levels for optimal subthreshold circuit design and provides an effective roadmap for digital designers interested to work with ultra low-power applications.

  14. Advances in Antisense Oligonucleotide Development for Target Identification, Validation, and as Novel Therapeutics

    Moizza Mansoor

    2008-01-01

    Full Text Available Antisense oligonucleotides (As-ODNs are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt, 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases.

  15. Silver and Cyanine Staining of Oligonucleotides in Polyacrylamide Gel.

    Tang, Weizhong; Zhou, Huafu; Li, Wei

    2015-01-01

    To explore why some oligonucleotides in denaturing polyacrylamide gel could not be silver-stained, 134 different oligonucleotides were analyzed using denaturing polyacrylamide gel electrophoresis stained with silver and asymmetric cyanine. As a result, we found that the sensitivity of oligos (dA), (dC), (dG) and (dT) to silver staining could be ranged as (dA) > (dG) > (dC) > (dT) from high to low. It was unexpected that oligo (dT) was hard to be silver-stained. Moreover, the silver staining of an oligonucleotide containing base T could be partially or completely inhibited by base T. The inhibition of silver staining by base T was a competitive inhibition which could be affected by the amounts of the argyrophil nucleobase and base T, the cis-distance between the argyrophil nucleobase and base T, and the gel concentration. The changes of the intensity of an oligonucleotide band caused by the changes of DNA base composition were diverse and interesting. The intensity of some oligonucleotide bands would significantly change when the changes of DNA base composition accumulated to a certain extent (usually ≥ 4 nt). The sensitivity of cyanine staining of ≤ 11-nt long oligonucleotides could be enhanced about 250-fold by fixing the gels with methanol fixing solution.

  16. Design and Fabrication Challenges for Millimeter-Scale Three-Dimensional Phononic Crystals

    Frieder Lucklum

    2017-11-01

    Full Text Available While phononic crystals can be theoretically modeled with a variety of analytical and numerical methods, the practical realization and comprehensive characterization of complex designs is often challenging. This is especially important for the nearly limitless possibilities of periodic, three-dimensional structures. In this contribution, we take a look at these design and fabrication challenges of different 3D phononic elements based on recent research using additive manufacturing. Different fabrication technologies introduce specific limitations in terms of, e.g., material choices, minimum feature size, aspect ratios, or support requirements that have to be taken into account during design and theoretical modeling. We discuss advantages and disadvantages of additive technologies suitable for millimeter and sub-millimeter feature sizes. Furthermore, we present comprehensive experimental characterization of finite, simple cubic lattices in terms of wave polarization and propagation direction to demonstrate the substantial differences between complete phononic band gap and application oriented directional band gaps of selected propagation modes.

  17. A one-step reaction for the rapid identification of Lactobacillus mindensis, Lactobacillus panis, Lactobacillus paralimentarius, Lactobacillus pontis and Lactobacillus frumenti using oligonucleotide primers designed from the 16S-23S rRNA intergenic sequences.

    Ferchichi, M; Valcheva, R; Prévost, H; Onno, B; Dousset, X

    2008-06-01

    Species-specific primers targeting the 16S-23S ribosomal DNA (rDNA) intergenic spacer region (ISR) were designed to rapidly discriminate between Lactobacillus mindensis, Lactobacillus panis, Lactobacillus paralimentarius, Lactobacillus pontis and Lactobacillus frumenti species recently isolated from French sourdough. The 16S-23S ISRs were amplified using primers 16S/p2 and 23S/p7, which anneal to positions 1388-1406 of the 16S rRNA gene and to positions 207-189 of the 23S rRNA gene respectively, Escherichia coli numbering (GenBank accession number V00331). Clone libraries of the resulting amplicons were constructed using a pCR2.1 TA cloning kit and sequenced. Species-specific primers were designed based on the sequences obtained and were used to amplify the 16S-23S ISR in the Lactobacillus species considered. For all of them, two PCR amplicons, designated as small ISR (S-ISR) and large ISR (L-ISR), were obtained. The L-ISR is composed of the corresponding S-ISR, interrupted by a sequence containing tRNA(Ile) and tRNA(Ala) genes. Based on these sequences, species-specific primers were designed and proved to identify accurately the species considered among 30 reference Lactobacillus species tested. Designed species-specific primers enable a rapid and accurate identification of L. mindensis, L. paralimentarius, L. panis, L. pontis and L. frumenti species among other lactobacilli. The proposed method provides a powerful and convenient means of rapidly identifying some sourdough lactobacilli, which could be of help in large starter culture surveys.

  18. Two approaches to meeting the economic challenge for advanced BWR designs

    Arnold, H.; Rao, A.S.; Sawyer, C.D.

    1996-01-01

    In developing next generation nuclear power plants many economic challenges must be addressed before they become economically attractive to utilities. The economic challenges vary from country to country but have several common characteristics. First and foremost, a plant has to have the lowest construction (costs) to even be considered for design and construction. Additionally, the plant design has to a have a reasonable chance of being licensed by the regulatory authorities in order to minimize the financial risk to the constructing utility. With the long lead times involved in the design and development of advanced plants nowadays, the overall development costs have also become a key factor in the evolution of advanced plants. This paper presents the design overview and approach to addressing the aforementioned economic challenges for two Advanced Boiling Water Reactor (ABWR) designs. The first plant is the ABWR and the second is the European Simplified Boiling Water. The ABWR relies on proven technology and components and an extensive infrastructure that has been built up over the last 20 year. Because it has proven and standard safety systems, which have been licensed in two countries, it has very limited uncertainly regarding licensing. Finally, it relies on the economies of scale and design flexibility to improve the overall economics of power generation. The ESBWR on the other hand has taken an innovative approach to reduce systems and components to simplify the overall plant to improve plant economics. The overall plant design is indeed simpler, but improved economics required reliance on some economies of scale also. This design embodied in the ESBWR, also has minimized the overall development cost by utilizing features and components from the ABWR and Simplified Boiling Water Reactor technology programs. (authors)

  19. ACCELERATOR PHYSICS CHALLENGES IN THE DESIGN OF MULTI-BEND-ACHROMAT-BASED STORAGE RINGS

    Borland, M.; Hettel, R.; Leemann, S. C.; Robin, D. S.

    2017-06-01

    With the recent success in commissioning of MAX IV, the multi-bend achromat (MBA) lattice has begun to deliver on its promise to usher in a new generation of higher-brightness synchrotron light sources. In this paper, we begin by reviewing the challenges, recent success, and lessons learned of the MAX-IV project. Drawing on these lessons, we then describe the physics challenges in even more ambitious rings and how these can be met. In addition, we touch on engineering issues and choices that are tightly linked with the physics design.

  20. Pharmacokinetics on a microscale: visualizing Cy5-labeled oligonucleotide release from poly(n-butylcyanoacrylate nanocapsules in cells

    Tomcin S

    2014-11-01

    Full Text Available Stephanie Tomcin,1 Grit Baier,1 Katharina Landfester,1 Volker Mailänder1,21Max Planck Institute for Polymer Research, 2University Medical Center of the Johannes Gutenberg University, III Medical Clinic, Mainz, GermanyAbstract: For successful design of a nanoparticulate drug delivery system, the fate of the carrier and cargo need to be followed. In this work, we fluorescently labeled poly(n-butylcyanoacrylate (PBCA nanocapsules as a shell and separately an oligonucleotide (20 mer as a payload. The nanocapsules were formed by interfacial anionic polymerization on aqueous droplets generated by an inverse miniemulsion process. After uptake, the PBCA capsules were shown to be round-shaped, endosomal structures and the payload was successfully released. Cy5-labeled oligonucleotides accumulated at the mitochondrial membrane due to a combination of the high mitochondrial membrane potential and the specific molecular structure of Cy5. The specificity of this accumulation at the mitochondria was shown as the uncoupler dinitrophenol rapidly diminished the accumulation of the Cy5-labeled oligonucleotide. Importantly, a fluorescence resonance energy transfer investigation showed that the dye-labeled cargo (Cy3/Cy5-labeled oligonucleotides reached its target site without degradation during escape from an endosomal compartment to the cytoplasm. The time course of accumulation of fluorescent signals at the mitochondria was determined by evaluating the colocalization of Cy5-labeled oligonucleotides and mitochondrial markers for up to 48 hours. As oligonucleotides are an ideal model system for small interfering RNA PBCA nanocapsules demonstrate to be a versatile delivery platform for small interfering RNA to treat a variety of diseases.Keywords: drug delivery, mitochondria, miniemulsion, colocalization

  1. Two approaches to meeting the economic challenge for advanced BWR designs

    Rao, A.S.; Sawyer, C.D.

    1997-01-01

    This paper presents the design overview and approach to addressing the aforementioned economic challenges for two Advanced BWR designs. The first plant is the ABWR and the second is the ESBWR. The ABWR relies on proven technology and components and an extensive infrastructure that has been built up over the last 20 years. Because it has proven and standards safety systems it has very limited uncertainty regarding licensing. Finally, it relies on the economies of scale and overall design flexibility to improve the overall economics of power generation. The ESBWR on the other hand has taken an innovative approach to reduce systems and components to simplify the overall plant to improve plant economics. The overall plant design is indeed simpler, but improved economics required reliance on some economies of scale also. This design embodied in the ESBWR, also has minimized the overall development cost by utilizing features and components from the ABWR and SBWR technology programs

  2. Structural and mechanical design challenges of space shuttle solid rocket boosters separation and recovery subsystems

    Woodis, W. R.; Runkle, R. E.

    1985-01-01

    The design of the space shuttle solid rocket booster (SRB) subsystems for reuse posed some unique and challenging design considerations. The separation of the SRBs from the cluster (orbiter and external tank) at 150,000 ft when the orbiter engines are running at full thrust meant the two SRBs had to have positive separation forces pushing them away. At the same instant, the large attachments that had reacted launch loads of 7.5 million pounds thrust had to be servered. These design considerations dictated the design requirements for the pyrotechnics and separation rocket motors. The recovery and reuse of the two SRBs meant they had to be safely lowered to the ocean, remain afloat, and be owed back to shore. In general, both the pyrotechnic and recovery subsystems have met or exceeded design requirements. In twelve vehicles, there has only been one instance where the pyrotechnic system has failed to function properly.

  3. Membrane-based oligonucleotide array developed from multiple markers for the detection of many Phytophthora species.

    Chen, Wen; Djama, Zeinab Robleh; Coffey, Michael D; Martin, Frank N; Bilodeau, Guillaume J; Radmer, Lorien; Denton, Geoff; Lévesque, C André

    2013-01-01

    Most Phytophthora spp. are destructive plant pathogens; therefore, effective monitoring and accurate early detection are important means of preventing potential epidemics and outbreaks of diseases. In the current study, a membrane-based oligonucleotide array was developed that can detect Phytophthora spp. reliably using three DNA regions; namely, the internal transcribed spacer (ITS), the 5' end of cytochrome c oxidase 1 gene (cox1), and the intergenic region between cytochrome c oxidase 2 gene (cox2) and cox1 (cox2-1 spacer). Each sequence data set contained ≈250 sequences representing 98 described and 15 undescribed species of Phytophthora. The array was validated with 143 pure cultures and 35 field samples. Together, nonrejected oligonucleotides from all three markers have the ability to reliably detect 82 described and 8 undescribed Phytophthora spp., including several quarantine or regulated pathogens such as Phytophthora ramorum. Our results showed that a DNA array containing signature oligonucleotides designed from multiple genomic regions provided robustness and redundancy for the detection and differentiation of closely related taxon groups. This array has the potential to be used as a routine diagnostic tool for Phytophthora spp. from complex environmental samples without the need for extensive growth of cultures.

  4. Ultrasensitive Detection of Ebola Virus Oligonucleotide Based on Upconversion Nanoprobe/Nanoporous Membrane System.

    Tsang, Ming-Kiu; Ye, WeiWei; Wang, Guojing; Li, Jingming; Yang, Mo; Hao, Jianhua

    2016-01-26

    Ebola outbreaks are currently of great concern, and therefore, development of effective diagnosis methods is urgently needed. The key for lethal virus detection is high sensitivity, since early-stage detection of virus may increase the probability of survival. Here, we propose a luminescence scheme of assay consisting of BaGdF5:Yb/Er upconversion nanoparticles (UCNPs) conjugated with oligonucleotide probe and gold nanoparticles (AuNPs) linked with target Ebola virus oligonucleotide. As a proof of concept, a homogeneous assay was fabricated and tested, yielding a detection limit at picomolar level. The luminescence resonance energy transfer is ascribed to the spectral overlapping of upconversion luminescence and the absorption characteristics of AuNPs. Moreover, we anchored the UCNPs and AuNPs on a nanoporous alumina (NAAO) membrane to form a heterogeneous assay. Importantly, the detection limit was greatly improved, exhibiting a remarkable value at the femtomolar level. The enhancement is attributed to the increased light-matter interaction throughout the nanopore walls of the NAAO membrane. The specificity test suggested that the nanoprobes were specific to Ebola virus oligonucleotides. The strategy combining UCNPs, AuNPs, and NAAO membrane provides new insight into low-cost, rapid, and ultrasensitive detection of different diseases. Furthermore, we explored the feasibility of clinical application by using inactivated Ebola virus samples. The detection results showed great potential of our heterogeneous design for practical application.

  5. Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

    Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

    2014-01-01

    Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

  6. Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

    Tamar Canello

    Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

  7. Effect of oligonucleotide primers in determining viral variability within hosts

    Moya Andrés

    2004-12-01

    Full Text Available Abstract Background Genetic variability in viral populations is usually estimated by means of polymerase chain reaction (PCR based methods in which the relative abundance of each amplicon is assumed to be proportional to the frequency of the corresponding template in the initial sample. Although bias in template-to-product ratios has been described before, its relevance in describing viral genetic variability at the intrapatient level has not been fully assessed yet. Results To investigate the role of oligonucleotide design in estimating viral variability within hosts, genetic diversity in hepatitis C virus (HCV populations from eight infected patients was characterised by two parallel PCR amplifications performed with two slightly different sets of primers, followed by cloning and sequencing (mean = 89 cloned sequences per patient. Population genetics analyses of viral populations recovered by pairs of amplifications revealed that in seven patients statistically significant differences were detected between populations sampled with different set of primers. Conclusions Genetic variability analyses demonstrates that PCR selection due to the choice of primers, differing in their degeneracy degree at some nucleotide positions, can eclipse totally or partially viral variants, hence yielding significant different estimates of viral variability within a single patient and therefore eventually producing quite different qualitative and quantitative descriptions of viral populations within each host.

  8. Effect of oligonucleotide primers in determining viral variability within hosts.

    Bracho, Maria Alma; García-Robles, Inmaculada; Jiménez, Nuria; Torres-Puente, Manuela; Moya, Andrés; González-Candelas, Fernando

    2004-12-09

    Genetic variability in viral populations is usually estimated by means of polymerase chain reaction (PCR) based methods in which the relative abundance of each amplicon is assumed to be proportional to the frequency of the corresponding template in the initial sample. Although bias in template-to-product ratios has been described before, its relevance in describing viral genetic variability at the intrapatient level has not been fully assessed yet. To investigate the role of oligonucleotide design in estimating viral variability within hosts, genetic diversity in hepatitis C virus (HCV) populations from eight infected patients was characterised by two parallel PCR amplifications performed with two slightly different sets of primers, followed by cloning and sequencing (mean = 89 cloned sequences per patient). Population genetics analyses of viral populations recovered by pairs of amplifications revealed that in seven patients statistically significant differences were detected between populations sampled with different set of primers. Genetic variability analyses demonstrates that PCR selection due to the choice of primers, differing in their degeneracy degree at some nucleotide positions, can eclipse totally or partially viral variants, hence yielding significant different estimates of viral variability within a single patient and therefore eventually producing quite different qualitative and quantitative descriptions of viral populations within each host.

  9. Respirable antisense oligonucleotides: a new drug class for respiratory disease

    Tanaka Makoto

    2000-12-01

    Full Text Available Abstract Respirable antisense oligonucleotides (RASONs, which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery.

  10. Recent advances in antisense oligonucleotide therapy in genetic neuromuscular diseases

    Ashok Verma

    2018-01-01

    Full Text Available Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Mutant genes may reduce expression of wild-type proteins, and strategies to activate expression of the wild-type proteins might provide therapeutic benefits. Also, a toxic mutant protein may cause cell death, and strategies that reduce mutant gene expression may provide therapeutic benefit. Synthetic antisense oligonucleotide (ASO can recognize cellular RNA and control gene expression. In recent years, advances in ASO chemistry, creation of designer ASO molecules to enhance their safety and target delivery, and scientific controlled clinical trials to ascertain their therapeutic safety and efficacy have led to an era of plausible application of ASO technology to treat currently incurable neuromuscular diseases. Over the past 1 year, for the first time, the United States Food and Drug Administration has approved two ASO therapies in genetic neuromuscular diseases. This overview summarizes the recent advances in ASO technology, evolution and use of synthetic ASOs as a therapeutic platform, and the mechanism of ASO action by exon-skipping in Duchenne muscular dystrophy and exon-inclusion in spinal muscular atrophy, with comments on their advantages and limitations.

  11. Defibrotide: An Oligonucleotide for Sinusoidal Obstruction Syndrome.

    Aziz, May T; Kakadiya, Payal P; Kush, Samantha M; Weigel, Kylie; Lowe, Denise K

    2018-02-01

    To review the efficacy and safety of defibrotide as well as its pharmacology, mechanism of action, pharmacokinetics (PK), drug-drug interactions, dosing, cost considerations, and place in therapy. A PubMed search was performed through August 2017 using the terms defibrotide, oligonucleotide, hepatic veno-occlusive disease (VOD), sinusoidal obstruction syndrome (SOS), and hematopoietic cell transplantation (HCT). Other data sources were from references of identified studies, review articles, and conference abstracts plus manufacturer product labeling and website, the Food and Drug Administration website, and clinicaltrials.gov. English-language trials that examined defibrotide's pharmacodynamics, mechanism, PK, efficacy, safety, dosing, and cost-effectiveness were included. Trials have confirmed the safety and efficacy of defibrotide for treatment of VOD/SOS in adult and pediatric HCT patients, with complete response rates and day +100 overall survival rates ranging from 25.5% to 76% and 35% to 64%, respectively. The British Committee for Standards in Haematology/British Society for Blood and Marrow Transplantation Guidelines recommend defibrotide prophylaxis in pediatric and adult HCT patients with risk factors for VOD/SOS; however, its prophylactic use in the United States is controversial. Although there are efficacy data to support this strategy, cost-effectiveness data have not shown it to be cost-effective. Defibrotide has manageable toxicities, with low rates of grade 3 to 4 adverse effects. Defibrotide is the first medication approved in the United States for the treatment of adults and children with hepatic VOD/SOS, with renal or pulmonary dysfunction following HCT. Data evaluating defibrotide for VOD/SOS prevention are conflicting and have not shown cost-effectiveness.

  12. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  13. Challenges and design solutions of the liquid hydrogen circuit at the European Spallation Source

    Gallimore, S.; Nilsson, P.; Sabbagh, P.; Takibayev, A.; Weisend II, J. G. [European Spallation Source ESS AB, SE-22100 Lund (Sweden); Beßler, Y. [Forschungzentrum Jülich, Jülich (Germany); Klaus, M. [Technische Universität Dresden, Dresden (Germany)

    2014-01-29

    The European Spallation Source (ESS), Lund, Sweden will be a 5MW long-pulse neutron spallation research facility and will enable new opportunities for researchers in the fields of life sciences, energy, environmental technology, cultural heritage and fundamental physics. Neutrons are produced by accelerating a high-energy proton beam into a rotating helium-cooled tungsten target. These neutrons pass through moderators to reduce their energy to an appropriate range (< 5 meV for cold neutrons); two of which will use liquid hydrogen at 17 K as the moderating and cooling medium. There are several technical challenges to overcome in the design of a robust system that will operate under such conditions, not least the 20 kW of deposited heat. These challenges and the associated design solutions will be detailed in this paper.

  14. Design Challenges Encountered in a Propulsion-Controlled Aircraft Flight Test Program

    Maine, Trindel; Burken, John; Burcham, Frank; Schaefer, Peter

    1994-01-01

    The NASA Dryden Flight Research Center conducted flight tests of a propulsion-controlled aircraft system on an F-15 airplane. This system was designed to explore the feasibility of providing safe emergency landing capability using only the engines to provide flight control in the event of a catastrophic loss of conventional flight controls. Control laws were designed to control the flightpath and bank angle using only commands to the throttles. Although the program was highly successful, this paper highlights some of the challenges associated with using engine thrust as a control effector. These challenges include slow engine response time, poorly modeled nonlinear engine dynamics, unmodeled inlet-airframe interactions, and difficulties with ground effect and gust rejection. Flight and simulation data illustrate these difficulties.

  15. Integration of scholastic curriculum in computergames – impossible or a design challenge?

    Larsen, Lasse Juel

    The present paper argues that integration of scholastic knowledge in computer games is a design challenge and one that will only work if you preserve the computer game as a game. This is important cause if you don’t adhere to or understand the dynamics of computer games you run the risk of destro......The present paper argues that integration of scholastic knowledge in computer games is a design challenge and one that will only work if you preserve the computer game as a game. This is important cause if you don’t adhere to or understand the dynamics of computer games you run the risk...... of destroying your own goal. In order to integrate the scholastic curriculum in computer games for a learning purpose it is and can not be stressed enough important to preserve the action-outcome circle inside the game world. Stated in simpler terms this means that users of learning games must see...

  16. Review of Design Aspects and Challenges of Efficient and Quiet Amphibious Aircraft

    D, Rhea P. Liem Ph.

    2018-04-01

    Apart from the commercial and military aviation sectors, the general aviation (GA) sector is expected to experience a rapid growth, especially in Asia. The increasing economic activities in the region would demand for more efficient and convenient transportation, which would open door to more GA services. This development would require sufficient infrastructure supports, including airports. However, insufficient land area has often imposed limitations in airport development. As such, some areas (e.g., remote islands) are not easily accessible by air. One implication is that travels can only be done via land or water, which might prolong the travel time. This applies to business travels, with the significant increase in business and economic activities, which in turns demands for more efficient and faster mobility. In other cases, this involves some rural areas where the infrastructures are not very well-developed, and where the geographical terrains are too challenging to build a pad for vertical takeoff and landing (VTOL) air vehicles. Under such circumstances, it would be imperative to enable air travels to carry critical logistics such as medical supplies, food, and even sick patients. In this regard, we propose to develop a low-payload, low-altitude amphibious aircraft, which can takeoff and land on both water and land. Aircraft design process is a complex procedure and multidisciplinary in nature, and for amphibious aircraft design we need to consider the two takeoff and landing modes, which imposes further challenges to the design. In this paper we present two preliminary design projects, for two-seater and ten-seater aircraft. To design an efficient and quiet amphibious aircraft, we conduct some experiments on noise shielding mechanisms to reduce the propeller noise. The challenges and resulting designs are briefly discussed in this paper. Amphibious aircraft development will be very relevant to Indonesia, which is the world’s largest archipelago with

  17. The space shuttle ascent vehicle aerodynamic challenges configuration design and data base development

    Dill, C. C.; Young, J. C.; Roberts, B. B.; Craig, M. K.; Hamilton, J. T.; Boyle, W. W.

    1985-01-01

    The phase B Space Shuttle systems definition studies resulted in a generic configuration consisting of a delta wing orbiter, and two solid rocket boosters (SRB) attached to an external fuel tank (ET). The initial challenge facing the aerodynamic community was aerodynamically optimizing, within limits, this configuration. As the Shuttle program developed and the sensitivities of the vehicle to aerodynamics were better understood the requirements of the aerodynamic data base grew. Adequately characterizing the vehicle to support the various design studies exploded the size of the data base to proportions that created a data modeling/management challenge for the aerodynamicist. The ascent aerodynamic data base originated primarily from wind tunnel test results. The complexity of the configuration rendered conventional analytic methods of little use. Initial wind tunnel tests provided results which included undesirable effects from model support tructure, inadequate element proximity, and inadequate plume simulation. The challenge to improve the quality of test results by determining the extent of these undesirable effects and subsequently develop testing techniques to eliminate them was imposed on the aerodynamic community. The challenges to the ascent aerodynamics community documented are unique due to the aerodynamic complexity of the Shuttle launch. Never before was such a complex vehicle aerodynamically characterized. The challenges were met with innovative engineering analyses/methodology development and wind tunnel testing techniques.

  18. Designing capacity-building in e-learning expertise: Challenges and strategies

    Aczel, J. C.; Peake, S. R.; Hardy, P.

    2008-01-01

    This research study looks at how organizations in developing countries perceive the challenge of building capacity in e-learning expertise. Data was collected on six such organizations, and a range of perceived rationales and constraints were identified. The paper hypothesizes a four-part framework to define the e-learning capacity gaps that these circumstances appear to represent: the 'instructional design capacity gap', the 'production capacity gap', the 'tutorial capacity gap' and the 'com...

  19. 77 FR 31161 - Designation of Officers of the Millennium Challenge Corporation To Act as Chief Executive Officer...

    2012-05-25

    ... of May 21, 2012 Designation of Officers of the Millennium Challenge Corporation To Act as Chief Executive Officer of the Millennium Challenge Corporation Memorandum for the Chief Executive Officer of the... following officers of the Millennium Challenge Corporation (MCC), in the order listed, shall act as and...

  20. Turning challenges into design principles: Telemonitoring systems for patients with multiple chronic conditions.

    Sultan, Mehwish; Kuluski, Kerry; McIsaac, Warren J; Cafazzo, Joseph A; Seto, Emily

    2018-01-01

    People with multiple chronic conditions often struggle with managing their health. The purpose of this research was to identify specific challenges of patients with multiple chronic conditions and to use the findings to form design principles for a telemonitoring system tailored for these patients. Semi-structured interviews with 15 patients with multiple chronic conditions and 10 clinicians were conducted to gain an understanding of their needs and preferences for a smartphone-based telemonitoring system. The interviews were analyzed using a conventional content analysis technique, resulting in six themes. Design principles developed from the themes included that the system must be modular to accommodate various combinations of conditions, reinforce a routine, consolidate record keeping, as well as provide actionable feedback to the patients. Designing an application for multiple chronic conditions is complex due to variability in patient conditions, and therefore, design principles developed in this study can help with future innovations aimed to help manage this population.

  1. HDPE (High Density Polyethylene) pipeline and riser design in Guanabara Bay: challenges and solutions

    Bomfimsilva, Carlos; Jorge, Joao Paulo Carrijo; Schmid, Dominique; Gomes, Rodrigo Klim [INTECSEA, Sao Paulo, SP (Brazil); Lima, Alexander Piraja [GDK, Salvador, BA (Brazil)

    2009-12-19

    Worldwide shipments of plastic pipes are forecasted to increase 5.2% per year since 2008, being commonly used for water supply and sewage disposal. The HDPE (High Density Polyethylene) pipes have been applied recently to deliver potable water and fire fighting water for the main pier of the LNG system in Guanabara Bay, Rio de Janeiro. The system contains three sizes of pipe outside diameter, 110 mm and 160 mm for water supply, and 500 mm for the fire fighting system. The main design challenges of the pipeline system included providing on-bottom stability, a suitable installation procedure and a proper riser design. The on-bottom stability calculations, which are quite different from the conventional steel pipelines, were developed by designing concrete blocks to be assembled on the pipeline in a required spacing to assure long term stability, knowing that plastic pipes are buoyant even in flooded conditions. The installation procedure was developed considering the lay down methodology based on surface towing technique. The riser was designed to be installed together with additional steel support structure to allow the entire underwater system to have the same plastic pipe specification up to the surface. This paper presents the main challenges that were faced during the design of the HDPE pipelines for the LNG system in Guanabara Bay, addressing the solutions and recommendations adopted for the plastic underwater pipeline system.

  2. Technology Transfer Challenges: A Case Study of User-Centered Design in NASA's Systems Engineering Culture

    Quick, Jason

    2009-01-01

    The Upper Stage (US) section of the National Aeronautics and Space Administration's (NASA) Ares I rocket will require internal access platforms for maintenance tasks performed by humans inside the vehicle. Tasks will occur during expensive critical path operations at Kennedy Space Center (KSC) including vehicle stacking and launch preparation activities. Platforms must be translated through a small human access hatch, installed in an enclosed worksite environment, support the weight of ground operators and be removed before flight - and their design must minimize additional vehicle mass at attachment points. This paper describes the application of a user-centered conceptual design process and the unique challenges encountered within NASA's systems engineering culture focused on requirements and "heritage hardware". The NASA design team at Marshall Space Flight Center (MSFC) initiated the user-centered design process by studying heritage internal access kits and proposing new design concepts during brainstorming sessions. Simultaneously, they partnered with the Technology Transfer/Innovative Partnerships Program to research inflatable structures and dynamic scaffolding solutions that could enable ground operator access. While this creative, technology-oriented exploration was encouraged by upper management, some design stakeholders consistently opposed ideas utilizing novel, untested equipment. Subsequent collaboration with an engineering consulting firm improved the technical credibility of several options, however, there was continued resistance from team members focused on meeting system requirements with pre-certified hardware. After a six-month idea-generating phase, an intensive six-week effort produced viable design concepts that justified additional vehicle mass while optimizing the human factors of platform installation and use. Although these selected final concepts closely resemble heritage internal access platforms, challenges from the application of the

  3. Assessing Cognitive Function in Bipolar Disorder: Challenges and Recommendations for Clinical Trial Design

    Burdick, Katherine E.; Ketter, Terence A.; Goldberg, Joseph F.; Calabrese, Joseph R.

    2015-01-01

    OBJECTIVE Neurocognitive impairment in schizophrenia has been recognized for more than a century. In contrast, only recently have significant neurocognitive deficits been recognized in bipolar disorder. Converging data suggest the importance of cognitive problems in relation to quality of life in bipolar disorder, highlighting the need for treatment and prevention efforts targeting cognition in bipolar patients. Future treatment trials targeting cognitive deficits will be met with methodological challenges due to the inherent complexity and heterogeneity of the disorder, including significant diagnostic comorbidities, the episodic nature of the illness, frequent use of polypharmacy, cognitive heterogeneity, and a lack of consensus regarding measurement of cognition and outcome in bipolar patients. Guidelines for use in designing future trials are needed. PARTICIPANTS The members of the consensus panel (each of the bylined authors) were selected based upon their expertise in bipolar disorder. Dr. Burdick is a neuropsychologist who has studied cognition in this illness for 15 years; Drs. Ketter, Calabrese, and Goldberg each bring considerable expertise in the treatment of bipolar disorder both within and outside of controlled clinical trials. This consensus statement was derived from work together at scientific meetings (e.g. symposium presention at the 2014 Annual meeting of the American Society of Clinical Psychopharmacology, among others) and ongoing discussions by conference call. With the exception of the public presentations on this topic, these meetings were closed to outside participants. EVIDENCE A literature review was undertaken by the authors to identify illness-specific challenges relevant to the design and conduct of treatment trials targeting neurocognition in bipolar disorder. Expert opinion from each of the authors guided the consensus recommendations. CONSENSUS PROCESS Consensus recommendations, reached by unanimous opinion of the authors, are

  4. Smart Industry Research in the Field of HRM : Resetting Job Design as an Example of Upcoming Challenges

    Habraken, Milou Maria Petronella; Bondarouk, Tatiana; Bondarouk, Tanya; Ruel, Huub; Parry, Emma

    2017-01-01

    Purpose – This chapter aims to encourage and guide Smart Industry HRM-related research by addressing upcoming challenges developed using a Job Design lens. Methodology/approach – The challenges are constructed based on a developed overview of the existing body of work related to Job Design and a

  5. Opportunities and Challenges for Drug Development: Public-Private Partnerships, Adaptive Designs and Big Data.

    Yildirim, Oktay; Gottwald, Matthias; Schüler, Peter; Michel, Martin C

    2016-01-01

    Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public-private partnerships, adaptive designs and big data. Public-private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical, and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development.

  6. Opportunities and challenges for drug development: public-private partnerships, adaptive designs and big data

    Oktay Yildirim

    2016-12-01

    Full Text Available Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research & Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e. public-private partnerships, adaptive designs and big data. Public-private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development.

  7. Opportunities and Challenges for Drug Development: Public–Private Partnerships, Adaptive Designs and Big Data

    Yildirim, Oktay; Gottwald, Matthias; Schüler, Peter; Michel, Martin C.

    2016-01-01

    Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public–private partnerships, adaptive designs and big data. Public–private partnerships come in many different forms with regard to scope, duration and type and number of participants. They range from project-specific collaborations to strategic alliances to large multi-party consortia. Each of them offers specific opportunities and faces distinct challenges. Among types of collaboration, investigator-initiated studies are becoming increasingly popular but have legal, ethical, and financial implications. Adaptive trial designs are also increasingly discussed. However, adaptive should not be used as euphemism for the repurposing of a failed trial; rather it requires carefully planning and specification before a trial starts. Adaptive licensing can be a counter-part of adaptive trial design. The use of Big Data is another opportunity to leverage existing information into knowledge useable for drug discovery and development. Respecting limitations of informed consent and privacy is a key challenge in the use of Big Data. Speakers and participants at the symposium were convinced that appropriate use of the above new options may indeed help to increase the efficiency of future drug development. PMID:27999543

  8. Device reliability challenges for modern semiconductor circuit design – a review

    C. Schlünder

    2009-05-01

    Full Text Available Product development based on highly integrated semiconductor circuits faces various challenges. To ensure the function of circuits the electrical parameters of every device must be in a specific window. This window is restricted by competing mechanisms like process variations and device degradation (Fig. 1. Degradation mechanisms like Negative Bias Temperature Instability (NBTI or Hot Carrier Injection (HCI lead to parameter drifts during operation adding on top of the process variations.

    The safety margin between real lifetime of MOSFETs and product lifetime requirements decreases at advanced technologies. The assignment of tasks to ensure the product lifetime has to be changed for the future. Up to now technology development has the main responsibility to adjust the technology processes to achieve the required lifetime. In future, reliability can no longer be the task of technology development only. Device degradation becomes a collective challenge for semiconductor technologist, reliability experts and circuit designers. Reliability issues have to be considered in design as well to achieve reliable and competitive products. For this work, designers require support by smart software tools with built-in reliability know how. Design for reliability will be one of the key requirements for modern product designs.

    An overview will be given of the physical device damage mechanisms, the operation conditions within circuits leading to stress and the impact of the corresponding device parameter degradation on the function of the circuit. Based on this understanding various approaches for Design for Reliability (DfR will be described. The function of aging simulators will be explained and the flow of circuit-simulation will be described. Furthermore, the difference between full custom and semi custom design and therefore, the different required approaches will be discussed.

  9. Building Information Modelling: Challenges and Barriers in Implement of BIM for Interior Design Industry in Malaysia

    Hamid, A. B. Abd; Taib, M. Z. Mohd; Razak, A. H. N. Abdul; Embi, M. R.

    2018-04-01

    Building Information Modelling (BIM) is an innovative approach that has developed crossways the global in architecture, engineering and construction (AEC) industry. The construction industry of Malaysia has undergone a rapid development and dynamic technology adoption in advance and methods between the players industry and stakeholders. Consequently, limited technologies and devices have not been successful as it should have been. This study will be emphasizing scenarios of challenges and barriers in adopting BIM in interior design industry in Malaysia. The study was emphasizing the challenges and barriers in BIM usage from the designer’s perspective. The data are collected through the questionnaires as to identifying the barriers, knowledge, readiness and awareness and distributed to interior design firms were selected randomly. The finding of this research is to examine the barriers and causes of variables BIM usage for interior design industry in Malaysia. The outcome of this study is to identify the constraint of adoption BIM in interior design industry compare to others players in same industry.

  10. Interaction design challenges and solutions for ALMA operations monitoring and control

    Pietriga, Emmanuel; Cubaud, Pierre; Schwarz, Joseph; Primet, Romain; Schilling, Marcus; Barkats, Denis; Barrios, Emilio; Vila Vilaro, Baltasar

    2012-09-01

    The ALMA radio-telescope, currently under construction in northern Chile, is a very advanced instrument that presents numerous challenges. From a software perspective, one critical issue is the design of graphical user interfaces for operations monitoring and control that scale to the complexity of the system and to the massive amounts of data users are faced with. Early experience operating the telescope with only a few antennas has shown that conventional user interface technologies are not adequate in this context. They consume too much screen real-estate, require many unnecessary interactions to access relevant information, and fail to provide operators and astronomers with a clear mental map of the instrument. They increase extraneous cognitive load, impeding tasks that call for quick diagnosis and action. To address this challenge, the ALMA software division adopted a user-centered design approach. For the last two years, astronomers, operators, software engineers and human-computer interaction researchers have been involved in participatory design workshops, with the aim of designing better user interfaces based on state-of-the-art visualization techniques. This paper describes the process that led to the development of those interface components and to a proposal for the science and operations console setup: brainstorming sessions, rapid prototyping, joint implementation work involving software engineers and human-computer interaction researchers, feedback collection from a broader range of users, further iterations and testing.

  11. Component design challenges for the ground-based SP-100 nuclear assembly test

    Markley, R.A.; Disney, R.K.; Brown, G.B.

    1989-01-01

    The SP-100 ground engineering system (GES) program involves a ground test of the nuclear subsystems to demonstrate their design. The GES nuclear assembly test (NAT) will be performed in a simulated space environment within a vessel maintained at ultrahigh vacuum. The NAT employs a radiation shielding system that is comprised of both prototypical and nonprototypical shield subsystems to attenuate the reactor radiation leakage and also nonprototypical heat transport subsystems to remove the heat generated by the reactor. The reactor is cooled by liquid lithium, which will operate at temperatures prototypical of the flight system. In designing the components for these systems, a number of design challenges were encountered in meeting the operational requirements of the simulated space environment (and where necessary, prototypical requirements) while also accommodating the restrictions of a ground-based test facility with its limited available space. This paper presents a discussion of the design challenges associated with the radiation shield subsystem components and key components of the heat transport systems

  12. Overview of the main challenges for the engineering design of the test facilities system of IFMIF

    Molla, J.; Nakamura, K.

    2009-01-01

    High intense radiation fields were demanded to IFMIF to address the lack of information on effects in materials due to radiation fields with fusion reactor features. Such intense radiation fields will also produce a number of unwanted effects in exposed materials and components. The main difficulties to achieve a reliable engineering design of the Test Facilities System during the Engineering Validation and the Engineering Design phase of IFMIF now under development are reviewed in this paper. The most challenging activities will be the design of the high flux test module, the creep fatigue test module, the test cell and the remote handling system. The intense radiation fields in the irradiation area and the high availability required for IFMIF (70%) are the main reasons for these difficulties.

  13. Entrepreneurship and response strategies to challenges in engineering and design education

    Jørgensen, Ulrik; Pineda, Andres Felipe Valderrama

    2012-01-01

    Entrepreneurship is one of the contemporary expectations to engineers and their training at engineering schools. But what is entrepreneurship? We propose three different conceptualizations of entrepreneurship in engineering and design programs. They are: (1) the technology-driven promotion response...... centered in technological development; (2) the business selection response strategy centered in business skills (which should be additional to the technical skills); and (3) the design intervention response strategy focused on a network approach to technology, business and society. These conceptualizations...... are response strategies from engineering communities, professors and institutions to perceived challenges. We argue that all engineering educators deal in one way or another with the three response strategies when approaching issues of curricular design, academicreform and the international accreditation...

  14. Mechatronic futures challenges and solutions for mechatronic systems and their designers

    Bradley, David

    2016-01-01

    Offering a comprehensive overview of the challenges, risks and options facing the future of mechatronics, this book provides insights into how these issues are currently assessed and managed. Building on the previously published book ‘Mechatronics in Action,’ it identifies and discusses the key issues likely to impact on future mechatronic systems. It supports mechatronics practitioners in identifying key areas in design, modeling and technology and places these in the wider context of concepts such as cyber-physical systems and the Internet of Things. For educators it considers the potential effects of developments in these areas on mechatronic course design, and ways of integrating these. Written by experts in the field, it explores topics including systems integration, design, modeling, privacy, ethics and future application domains. Highlighting novel innovation directions, it is intended for academics, engineers and students working in the field of mechatronics, particularly those developing new conc...

  15. Co-design and implementation research: challenges and solutions for ethics committees.

    Goodyear-Smith, Felicity; Jackson, Claire; Greenhalgh, Trisha

    2015-11-16

    Implementation science research, especially when using participatory and co-design approaches, raises unique challenges for research ethics committees. Such challenges may be poorly addressed by approval and governance mechanisms that were developed for more traditional research approaches such as randomised controlled trials. Implementation science commonly involves the partnership of researchers and stakeholders, attempting to understand and encourage uptake of completed or piloted research. A co-creation approach involves collaboration between researchers and end users from the onset, in question framing, research design and delivery, and influencing strategy, with implementation and broader dissemination strategies part of its design from gestation. A defining feature of co-creation is its emergent and adaptive nature, making detailed pre-specification of interventions and outcome measures impossible. This methodology sits oddly with ethics committee protocols that require precise pre-definition of interventions, mode of delivery, outcome measurements, and the role of study participants. But the strict (and, some would say, inflexible) requirements of ethics committees were developed for a purpose - to protect participants from harm and help ensure the rigour and transparency of studies. We propose some guiding principles to help square this circle. First, ethics committees should acknowledge and celebrate the diversity of research approaches, both formally (through training) and informally (by promoting debate and discussion); without active support, their members may not understand or value participatory designs. Second, ground rules should be established for co-design applications (e.g. how to judge when 'consultation' or 'engagement' becomes research) and communicated to committee members and stakeholders. Third, the benefits of power-sharing should be recognised and credit given to measures likely to support this important goal, especially in research with

  16. Oligonucleotide Therapy for Obstructive and Restrictive Respiratory Diseases

    Wupeng Liao

    2017-01-01

    Full Text Available Inhaled oligonucleotide is an emerging therapeutic modality for various common respiratory diseases, including obstructive airway diseases like asthma and chronic obstructive pulmonary disease (COPD and restrictive airway diseases like idiopathic pulmonary fibrosis (IPF. The advantage of direct accessibility for oligonucleotide molecules to the lung target sites, bypassing systemic administration, makes this therapeutic approach promising with minimized potential systemic side effects. Asthma, COPD, and IPF are common chronic respiratory diseases, characterized by persistent airway inflammation and dysregulated tissue repair and remodeling, although each individual disease has its unique etiology. Corticosteroids have been widely prescribed for the treatment of asthma, COPD, and IPF. However, the effectiveness of corticosteroids as an anti-inflammatory drug is limited by steroid resistance in severe asthma, the majority of COPD cases, and pulmonary fibrosis. There is an urgent medical need to develop target-specific drugs for the treatment of these respiratory conditions. Oligonucleotide therapies, including antisense oligonucleotide (ASO, small interfering RNA (siRNA, and microRNA (miRNA are now being evaluated both pre-clinically and clinically as potential therapeutics. The mechanisms of action of ASO and siRNA are highly target mRNA specific, ultimately leading to target protein knockdown. miRNA has both biomarker and therapeutic values, and its knockdown by a miRNA antagonist (antagomir has a broader but potentially more non-specific biological outcome. This review will compile the current findings of oligonucleotide therapeutic targets, verified in various respiratory disease models and in clinical trials, and evaluate different chemical modification approaches to improve the stability and potency of oligonucleotides for the treatment of respiratory diseases.

  17. Design challenges for electronic medication administration record systems in residential aged care facilities: a formative evaluation.

    Tariq, A; Lehnbom, E; Oliver, K; Georgiou, A; Rowe, C; Osmond, T; Westbrook, J

    2014-01-01

    Electronic medication administration record (eMAR) systems are promoted as a potential intervention to enhance medication safety in residential aged care facilities (RACFs). The purpose of this study was to conduct an in-practice evaluation of an eMAR being piloted in one Australian RACF before its roll out, and to provide recommendations for system improvements. A multidisciplinary team conducted direct observations of workflow (n=34 hours) in the RACF site and the community pharmacy. Semi-structured interviews (n=5) with RACF staff and the community pharmacist were conducted to investigate their views of the eMAR system. Data were analysed using a grounded theory approach to identify challenges associated with the design of the eMAR system. The current eMAR system does not offer an end-to-end solution for medication management. Many steps, including prescribing by doctors and communication with the community pharmacist, are still performed manually using paper charts and fax machines. Five major challenges associated with the design of eMAR system were identified: limited interactivity; inadequate flexibility; problems related to information layout and semantics; the lack of relevant decision support; and system maintenance issues. We suggest recommendations to improve the design of the eMAR system and to optimize existing workflows. Immediate value can be achieved by improving the system interactivity, reducing inconsistencies in data entry design and offering dedicated organisational support to minimise connectivity issues. Longer-term benefits can be achieved by adding decision support features and establishing system interoperability requirements with stakeholder groups (e.g. community pharmacies) prior to system roll out. In-practice evaluations of technologies like eMAR system have great value in identifying design weaknesses which inhibit optimal system use.

  18. Addressing Challenges to the Design & Test of Operational Lighting Environments for the International Space Station

    Clark, Toni A.

    2014-01-01

    In our day to day lives, the availability of light, with which to see our environment, is often taken for granted. The designers of land based lighting systems use sunlight and artificial light as their toolset. The availability of power, quantity of light sources, and variety of design options are often unlimited. The accessibility of most land based lighting systems makes it easy for the architect and engineer to verify and validate their design ideas. Failures with an implementation, while sometimes costly, can easily be addressed by renovation. Consider now, an architectural facility orbiting in space, 260 miles above the surface of the earth. This human rated architectural facility, the International Space Station (ISS) must maintain operations every day, including life support and appropriate human comforts without fail. The facility must also handle logistics of regular shipments of cargo, including new passengers. The ISS requires accommodations necessary for human control of machine systems. Additionally, the ISS is a research facility and supports investigations performed inside and outside its livable volume. Finally, the facility must support remote operations and observations by ground controllers. All of these architectural needs require a functional, safe, and even an aesthetic lighting environment. At Johnson Space Center, our Habitability and Human Factors team assists our diverse customers with their lighting environment challenges, via physical test and computer based analysis. Because of the complexity of ISS operational environment, our team has learned and developed processes that help ISS operate safely. Because of the dynamic exterior lighting environment, uses computational modeling to predict the lighting environment. The ISS' orbit exposes it to a sunrise every 90 minutes, causing work surfaces to quickly change from direct sunlight to earthshine to total darkness. Proper planning of vehicle approaches, robotics operations, and crewed

  19. Challenges for eco-design of emerging technologies: The case of electronic textiles

    Köhler, Andreas R.

    2013-01-01

    Highlights: • Recent innovations of electronic textiles and their end-of-life impacts are reviewed. • The properties of e-textiles are examined against Design for Recycling (DfR) principles. • Eco-design strategies for sustainable product development are discussed. • Compatibility standards for e-textiles are proposed as a waste prevention strategy. • Labelling of e-textiles is suggested as a measure to facilitate recycling. - Abstract: The combination of textile and electronic technologies results in new challenges for sustainable product design. Electronic textiles (e-textiles) feature a seamless integration of textiles with electronics and other high-tech materials. Such products may, if they become mass consumer applications, result in a new kind of waste that could be difficult to recycle. The ongoing innovation process of e-textiles holds opportunities to prevent future end-of-life impacts. Implementing eco-design in the technological development process can help to minimise future waste. However, the existing Design for Recycling (DfR) principles for textiles or electronics do not match with the properties of the combined products. This article examines possibilities to advance eco-design of a converging technology. DfR strategies for e-textiles are discussed from the background of contemporary innovation trends. Three waste preventative eco-design approaches for e-textiles are discussed: 1 harnessing the inherent advantages of smart materials for sustainable design; 2 establishing open compatibility standards; 3 labelling the e-textiles to facilitate their recycling. It is argued that life-cycle thinking needs to be implemented concurrent to the technological development process

  20. A facile one-step fluorescence method for the quantitation of low-content single base deamination impurity in synthetic oligonucleotides.

    Su, Xiaoye; Liang, Ruiting; Stolee, Jessica A

    2018-06-05

    Oligonucleotides are being researched and developed as potential drug candidates for the treatment of a broad spectrum of diseases. The characterization of antisense oligonucleotide (ASO) impurities caused by base mutations (e.g. deamination) which are closely related to the target ASO is a significant analytical challenge. Herein, we describe a novel one-step method, utilizing a strategy that combines fluorescence-ON detection with competitive hybridization, to achieve single base mutation quantitation in extensively modified synthetic ASOs. Given that this method is highly specific and sensitive (LoQ = 4 nM), we envision that it will find utility for screening other impurities as well as sequencing modified oligonucleotides. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. A novel multifunctional oligonucleotide microarray for Toxoplasma gondii

    Chen Feng

    2010-10-01

    Full Text Available Abstract Background Microarrays are invaluable tools for genome interrogation, SNP detection, and expression analysis, among other applications. Such broad capabilities would be of value to many pathogen research communities, although the development and use of genome-scale microarrays is often a costly undertaking. Therefore, effective methods for reducing unnecessary probes while maintaining or expanding functionality would be relevant to many investigators. Results Taking advantage of available genome sequences and annotation for Toxoplasma gondii (a pathogenic parasite responsible for illness in immunocompromised individuals and Plasmodium falciparum (a related parasite responsible for severe human malaria, we designed a single oligonucleotide microarray capable of supporting a wide range of applications at relatively low cost, including genome-wide expression profiling for Toxoplasma, and single-nucleotide polymorphism (SNP-based genotyping of both T. gondii and P. falciparum. Expression profiling of the three clonotypic lineages dominating T. gondii populations in North America and Europe provides a first comprehensive view of the parasite transcriptome, revealing that ~49% of all annotated genes are expressed in parasite tachyzoites (the acutely lytic stage responsible for pathogenesis and 26% of genes are differentially expressed among strains. A novel design utilizing few probes provided high confidence genotyping, used here to resolve recombination points in the clonal progeny of sexual crosses. Recent sequencing of additional T. gondii isolates identifies >620 K new SNPs, including ~11 K that intersect with expression profiling probes, yielding additional markers for genotyping studies, and further validating the utility of a combined expression profiling/genotyping array design. Additional applications facilitating SNP and transcript discovery, alternative statistical methods for quantifying gene expression, etc. are also pursued at

  2. Opportunities and challenges for innovation in the design of low-carbon energy technologies

    Bjarklev, Araceli; Kjær, Tyge; Andersen, Jan

    2012-01-01

    into account to be able to achieve efficient reductions of energy and CO2 emissions and at the same time design a product attractive for the consumer, in terms of price, level of service and aesthetical demands, to ensure its strategic implementation. This paper takes the Danish office lighting sector......-psychological aspects such as consumers’ demands (aesthetic disposition, habits and different light tastes and needs). This is done by integrating relevant elements from eco-innovation and Service –Product System frameworks. Our empirical material is based on iterative interviews with relevant actors and experts within......Though there is broad consensus that one of the solutions to the current environmental challenge will be based on the use of low-carbon technologies, and even though there is a big potential to turn to a more sustainable design and innovation, there are several elements that need to be taken...

  3. Design to Process Capabilities: challenges for the use of Process Capability Databases (PCDBs) in development

    Eifler, Tobias; Göhler, Simon Moritz; Howard, Thomas J.

    2014-01-01

    capabilities may lead to low yields and a cost/time overrun, conservatively underestimated capabilities affect quality through the reduced design space, or through increased play, rattle/noise, size or weight. A possibility to overcome the subjective assessment of variation in development projects is a Process...... and Maiti (2012), Breyfogle (2003)]. At the same time, information on the achievable manufacturing accuracy or the supplier’s performance is usually inaccurate and largely qualitative in early development stages. Design decisions as well as the choice of manufacturing processes, therefore, often rely...... Capability Data Base (PCDB) offering valuable insight into the actual or expected performance of production processes (Tata and Thornton, 1999). But although the potential benefits as well as initial challenges for the use of PCDBs have been addressed in earlier research, e. g. by Delaney and Phelan (2008...

  4. Challenges and Approaches to Statistical Design and Inference in High Dimensional Investigations

    Garrett, Karen A.; Allison, David B.

    2015-01-01

    Summary Advances in modern technologies have facilitated high-dimensional experiments (HDEs) that generate tremendous amounts of genomic, proteomic, and other “omic” data. HDEs involving whole-genome sequences and polymorphisms, expression levels of genes, protein abundance measurements, and combinations thereof have become a vanguard for new analytic approaches to the analysis of HDE data. Such situations demand creative approaches to the processes of statistical inference, estimation, prediction, classification, and study design. The novel and challenging biological questions asked from HDE data have resulted in many specialized analytic techniques being developed. This chapter discusses some of the unique statistical challenges facing investigators studying high-dimensional biology, and describes some approaches being developed by statistical scientists. We have included some focus on the increasing interest in questions involving testing multiple propositions simultaneously, appropriate inferential indicators for the types of questions biologists are interested in, and the need for replication of results across independent studies, investigators, and settings. A key consideration inherent throughout is the challenge in providing methods that a statistician judges to be sound and a biologist finds informative. PMID:19588106

  5. Challenges and approaches to statistical design and inference in high-dimensional investigations.

    Gadbury, Gary L; Garrett, Karen A; Allison, David B

    2009-01-01

    Advances in modern technologies have facilitated high-dimensional experiments (HDEs) that generate tremendous amounts of genomic, proteomic, and other "omic" data. HDEs involving whole-genome sequences and polymorphisms, expression levels of genes, protein abundance measurements, and combinations thereof have become a vanguard for new analytic approaches to the analysis of HDE data. Such situations demand creative approaches to the processes of statistical inference, estimation, prediction, classification, and study design. The novel and challenging biological questions asked from HDE data have resulted in many specialized analytic techniques being developed. This chapter discusses some of the unique statistical challenges facing investigators studying high-dimensional biology and describes some approaches being developed by statistical scientists. We have included some focus on the increasing interest in questions involving testing multiple propositions simultaneously, appropriate inferential indicators for the types of questions biologists are interested in, and the need for replication of results across independent studies, investigators, and settings. A key consideration inherent throughout is the challenge in providing methods that a statistician judges to be sound and a biologist finds informative.

  6. Challenges in the design of a Home Telemanagement trial for patients with ulcerative colitis.

    Cross, Raymond K; Finkelstein, Joseph

    2009-12-01

    Nonadherence, inadequate monitoring, and side-effects result in suboptimal outcomes in ulcerative colitis (UC). We hypothesize that telemanagement for UC will improve symptoms, quality of life, adherence, and decrease costs. This article describes the challenges encountered in the design of the home telemanagement in patients with UC trial. In a randomized trial to assess the effectiveness of telemanagement for UC compared to best available care, 100 patients will be enrolled. Subjects in the intervention arm will complete self-testing with telemanagement weekly; best available care subjects will receive scheduled follow up, educational fact sheets, and written action plans. Telemanagement consists of a home-unit, decision support server, and web-based clinician portal. The home-unit includes a scale and laptop. Subjects will respond to questions about symptoms, side-effects, adherence, and knowledge weekly; subjects will receive action plans after self-testing. Outcome variables to be assessed every 4 months include: disease activity, using the Seo index; quality of life, using the Inflammatory Bowel Disease Questionnaire; adherence, using pharmacy refill data and the Morisky Medication Adherence Scale; utilization of healthcare resources, using urgent care visits and hospitalizations. We encountered several challenges during design and implementation of our trial. First, we selected a randomized controlled trial design. We could have selected a quasiexperimental design to decrease the sample size needed and costs. Second, identification of a control group was challenging. Telemanagement patients received self-care plans and an educational curriculum. Since controls would not receive these interventions, we thought our results would be biased in favor of telemanagement. In addition, we wanted to evaluate the mode of delivery of these components of care. Therefore, we included written action plans and educational materials for patients in the control group ('best

  7. The front end electronics of the NA62 Gigatracker: challenges, design and experimental measurements

    Noy, M.; Aglieri Rinella, G.; Ceccucci, A.; Dellacasa, G.; Fiorini, M.; Garbolino, S.; Jarron, P.; Kaplon, J.; Kluge, A.; Marchetto, F.; Martin, E.; Mazza, G.; Martoiu, S.; Morel, M.; Perktold, L.; Rivetti, A.; Tiuraniemi, S.

    2011-06-01

    The beam spectrometer of the NA62 experiment consists of 3 Gigatracker (GTK) stations. Each station comprises a pixel detector of 16 cm active area made of an assembly of 10 readout ASICs bump bonded to a 200 μm thick pixel silicon sensor, comprising 18000 pixels of 300 μm×300 μm. The main challenge of the NA62 pixel GTK station is the combination of an extremely high kaon/pion beam rate, where the intensity in the center of the beam reaches up to 1.5 Mhit s mm together with an extreme time resolution of 100 ps. To date, it is the first silicon tracking system with this time resolution. To face this challenge, the pixel analogue front end has been designed with a peaking time of 4 ns, with a planar silicon sensor operating up to 300 V over depletion. Moreover, the radiation level is severe, 2×10 1 MeV n cm per year of operation. Easy replacement of the GTK stations is foreseen as a design requirement. The amount of material of a single station should also be less than 0.5% X to minimize the background, which imposes strong constraints on the mechanics and the cooling system. We report upon the design and architecture of the 2 prototype demonstrator chips both designed in 130 nm CMOS technology, one with a constant fraction discriminator and the time stamp digitisation in each pixel (In-Pixel), and the other with a time-over-threshold discriminator and the processing of the time stamp located in the End of Column (EoC) region at the chip periphery. Some preliminary results are presented.

  8. Creating wheelchair-controlled video games: challenges and opportunities when involving young people with mobility impairments and game design experts

    Gerling, Kathrin; Linehan, Conor; Kirman, Ben; Kalyn, Michael; Evans, Adam; Hicks, Kieran

    2016-01-01

    Although participatory design (PD) is currently the most acceptable and respectful process we have for designing technology, recent discussions suggest that there may be two barriers to the successful application of PD to the design of digital games: First, the involvement of audiences with special needs can introduce new practical and ethical challenges to the design process. Second, the use of non-experts in game design roles has been criticised in that participants lack skills necessary to...

  9. Factor XI Antisense Oligonucleotide for Prevention of Venous Thrombosis

    Büller, Harry R.; Bethune, Claudette; Bhanot, Sanjay; Gailani, David; Monia, Brett P.; Raskob, Gary E.; Segers, Annelise; Verhamme, Peter; Weitz, Jeffrey I.; Weitz, Jeffrey; Prins, Martin; Beenen, Ludo; Otten, Hans-Martin; Roos, Yvo; Slagboom, Ton; Vandenbriele, Christophe; Vanassche, Thomas; Dani, Vidhi; Schulz, Dan; Shapiro, Cara; Kwoh, Katherine; Jung, Bill; Gawinek-Samelczak, Agata; Kaemmer, Christina; Angelov, S.; Stavrev, V.; Kinov, P.; Dessouki, E.; Abuzgaya, F.; Baurovskis, A.; Peredistijs, A.; Petronis, S.; Danilyak, V.; Driagin, V.; Kuropatkin, G.; Parfeev, S.; Safronov, A.; Ankin, M.; Korzh, M.; Olinichenko, G.; Polivoda, A.; Shevchenko, V.; Sulyma, V.

    2015-01-01

    Background Experimental data indicate that reducing factor XI levels attenuates thrombosis without causing bleeding, but the role of factor XI in the prevention of postoperative venous thrombosis in humans is unknown. FXI-ASO (ISIS 416858) is a second-generation antisense oligonucleotide that

  10. Tandem Oligonucleotide Probe Annealing and Elongation To Discriminate Viral Sequence

    Taskova, Maria; Uhd, Jesper; Miotke, Laura

    2017-01-01

    opportunities in transcriptome analysis, virology, and other fields. Herein, we report for the first time a "click" chemistry approach to oligonucleotide probe elongation as a novel approach to specifically detect a viral sequence. We hybridized a library of short, terminally labeled probes to Ebola virus RNA...

  11. Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles

    Cogoi, S; Jakobsen, U; Pedersen, E B

    2016-01-01

    KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription fa...

  12. Effects of Atelocollagen Formulation Containing Oligonucleotide on Endothelial Permeability

    Koji Hanai

    2012-01-01

    Full Text Available Atelocollagen is a major animal protein that is used as a highly biocompatible biomaterial. To date, atelocollagen has been used as an effective drug delivery technology to sustain the release of antitumor proteins and to enhance the antitumor activity of oligonucleotides in in vivo models. However, the biological effects of this technology are not fully understood. In the present study, we investigated the effects of atelocollagen on endothelial paracellular barrier function. An atelocollagen formulation containing oligonucleotides specifically increased the permeability of two types of endothelial cells, and the change was dependent on the molecular size, structure of the oligonucleotides used and the concentrations of the oligonucleotide and atelocollagen in the formulation. An immunohistochemical examination revealed that the formulation had effects on the cellular skeleton and intercellular structure although it did not affect the expression of adherens junction or tight junction proteins. These changes were induced through p38 MAP kinase signaling. It is important to elucidate the biological functions of atelocollagen in order to be able to exploit its drug delivery properties.

  13. Identification of clinically relevant viridans streptococci by an oligonucleotide array.

    Chen, Chao Chien; Teng, Lee Jene; Kaiung, Seng; Chang, Tsung Chain

    2005-04-01

    Viridans streptococci (VS) are common etiologic agents of subacute infective endocarditis and are capable of causing a variety of pyogenic infections. Many species of VS are difficult to differentiate by phenotypic traits. An oligonucleotide array based on 16S-23S rRNA gene intergenic spacer (ITS) sequences was developed to identify 11 clinically relevant VS. These 11 species were Streptococcus anginosus, S. constellatus, S. gordonii, S. intermedius, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. salivarius, S. sanguinis, and S. uberis. The method consisted of PCR amplification of the ITS regions by using a pair of universal primers, followed by hybridization of the digoxigenin-labeled PCR products to a panel of species-specific oligonucleotides immobilized on a nylon membrane. After 120 strains of the 11 species of VG and 91 strains of other bacteria were tested, the sensitivity and specificity of the oligonucleotide array were found to be 100% (120 of 120 strains) and 95.6% (87 of 91 strains), respectively. S. pneumoniae cross-hybridized to the probes used for the identification of S. mitis, and simple biochemical tests such as optochin susceptibility or bile solubility should be used to differentiate S. pneumoniae from S. mitis. In conclusion, identification of species of VS by use of the present oligonucleotide array is accurate and could be used as an alternative reliable method for species identification of strains of VS.

  14. Analysis of oligonucleotide array experiments with repeated measures using mixed models

    Getchell Thomas V

    2004-12-01

    Full Text Available Abstract Background Two or more factor mixed factorial experiments are becoming increasingly common in microarray data analysis. In this case study, the two factors are presence (Patients with Alzheimer's disease or absence (Control of the disease, and brain regions including olfactory bulb (OB or cerebellum (CER. In the design considered in this manuscript, OB and CER are repeated measurements from the same subject and, hence, are correlated. It is critical to identify sources of variability in the analysis of oligonucleotide array experiments with repeated measures and correlations among data points have to be considered. In addition, multiple testing problems are more complicated in experiments with multi-level treatments or treatment combinations. Results In this study we adopted a linear mixed model to analyze oligonucleotide array experiments with repeated measures. We first construct a generalized F test to select differentially expressed genes. The Benjamini and Hochberg (BH procedure of controlling false discovery rate (FDR at 5% was applied to the P values of the generalized F test. For those genes with significant generalized F test, we then categorize them based on whether the interaction terms were significant or not at the α-level (αnew = 0.0033 determined by the FDR procedure. Since simple effects may be examined for the genes with significant interaction effect, we adopt the protected Fisher's least significant difference test (LSD procedure at the level of αnew to control the family-wise error rate (FWER for each gene examined. Conclusions A linear mixed model is appropriate for analysis of oligonucleotide array experiments with repeated measures. We constructed a generalized F test to select differentially expressed genes, and then applied a specific sequence of tests to identify factorial effects. This sequence of tests applied was designed to control for gene based FWER.

  15. Challenges and models in supporting logistics system design for dedicated-biomass-based bioenergy industry.

    Zhu, Xiaoyan; Li, Xueping; Yao, Qingzhu; Chen, Yuerong

    2011-01-01

    This paper analyzed the uniqueness and challenges in designing the logistics system for dedicated biomass-to-bioenergy industry, which differs from the other industries, due to the unique features of dedicated biomass (e.g., switchgrass) including its low bulk density, restrictions on harvesting season and frequency, content variation with time and circumambient conditions, weather effects, scattered distribution over a wide geographical area, and so on. To design it, this paper proposed a mixed integer linear programming model. It covered from planting and harvesting switchgrass to delivering to a biorefinery and included the residue handling, concentrating on integrating strategic decisions on the supply chain design and tactical decisions on the annual operation schedules. The present numerical examples verified the model and demonstrated its use in practice. This paper showed that the operations of the logistics system were significantly different for harvesting and non-harvesting seasons, and that under the well-designed biomass logistics system, the mass production with a steady and sufficient supply of biomass can increase the unit profit of bioenergy. The analytical model and practical methodology proposed in this paper will help realize the commercial production in biomass-to-bioenergy industry. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

    Mullen, Douglas Gurnett

    Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules

  17. Efficient oligonucleotide probe selection for pan-genomic tiling arrays

    Zhang Wei

    2009-09-01

    Full Text Available Abstract Background Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. Results This paper presents a new probe selection algorithm (PanArray that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pan-genome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. Conclusion PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on

  18. Design of fixed and mobile PET/CT facilities: the similarities and the challenges

    Peet, Debbie J.; Pryor, M.

    2008-01-01

    Design of PET/CT facilities present particular challenges for Radiation Protection. The high energy gamma ray emitted from the radionuclides used, the prolonged uptake period with patients within the facility and the relatively high dose rates from those patients result in some shielding being required and a careful consideration of the layout within each unit. This paper will present the approach used for the design of a fixed facility and will present staff dose data demonstrating that the design has resulted in low staff doses. The approach used to design mobile facilities will then be described, and a consideration of the doses received on this type of unit will also be given. The fixed facility was installed into a wooden clad building and was extremely small. The building was shared with other non radiation workers. Walls were constructed from dense concrete blocks and the layout arranged to prevent a direct line of site between the patient and workers at any point apart from the scan room where a lead glass window was used. For the mobile facility lead was used as the shielding material. The basic approach was to maximise the distance between operators and resting patients. Because of weight restrictions and limitation on the dose rate at the scanner defined by the scanner manufacturer, a higher dose constraint had to be adopted for staff on the unit. Additional complications include the mobility of the unit which can be parked adjacent to buildings with a variety of construction materials. Results of whole body monitoring for staff in the fixed facility over 5 years will be presented with the results from the mobile units over the last year. These will demonstrate the difficulties in keeping doses as low as reasonably achievable in the mobile scenario and the importance of designing the facility with staff dose in mind from the outset. (author)

  19. Reliable Assessment and Quantification of the Fluorescence-Labeled Antisense Oligonucleotides In Vivo

    Maria Chiara Munisso

    2014-01-01

    Full Text Available The availability of fluorescent dyes and the advances in the optical systems for in vivo imaging have stimulated an increasing interest in developing new methodologies to study and quantify the biodistribution of labeled agents. However, despite these great achievements, we are facing significant challenges in determining if the observed fluorescence does correspond to the quantity of the dye in the tissues. In fact, although the far-red and near-infrared lights can propagate through several centimetres of tissue, they diffuse within a few millimetres as consequence of the elastic scattering of photons. In addition, when dye-labeled oligonucleotides form stable complex with cationic carriers, a large change in the fluorescence intensity of the dye is observed. Therefore, the measured fluorescence intensity is altered by the tissue heterogeneity and by the fluctuation of dye intensity. Hence, in this study a quantification strategy for fluorescence-labeled oligonucleotides was developed to solve these disadvantageous effects. Our results proved that upon efficient homogenization and dilution with chaotropic agents, such as guanidinium thiocyanate, it is possible to achieve a complete fluorescence intensity recovery. Furthermore, we demonstrated that this method has the advantage of good sensitivity and reproducibility, as well as easy handling of the tissue samples.

  20. Recent Advances of MEMS Resonators for Lorentz Force Based Magnetic Field Sensors: Design, Applications and Challenges

    Agustín Leobardo Herrera-May

    2016-08-01

    Full Text Available Microelectromechanical systems (MEMS resonators have allowed the development of magnetic field sensors with potential applications such as biomedicine, automotive industry, navigation systems, space satellites, telecommunications and non-destructive testing. We present a review of recent magnetic field sensors based on MEMS resonators, which operate with Lorentz force. These sensors have a compact structure, wide measurement range, low energy consumption, high sensitivity and suitable performance. The design methodology, simulation tools, damping sources, sensing techniques and future applications of magnetic field sensors are discussed. The design process is fundamental in achieving correct selection of the operation principle, sensing technique, materials, fabrication process and readout systems of the sensors. In addition, the description of the main sensing systems and challenges of the MEMS sensors are discussed. To develop the best devices, researches of their mechanical reliability, vacuum packaging, design optimization and temperature compensation circuits are needed. Future applications will require multifunctional sensors for monitoring several physical parameters (e.g., magnetic field, acceleration, angular ratio, humidity, temperature and gases.

  1. Software Design Challenges in Time Series Prediction Systems Using Parallel Implementation of Artificial Neural Networks

    Narayanan Manikandan

    2016-01-01

    Full Text Available Software development life cycle has been characterized by destructive disconnects between activities like planning, analysis, design, and programming. Particularly software developed with prediction based results is always a big challenge for designers. Time series data forecasting like currency exchange, stock prices, and weather report are some of the areas where an extensive research is going on for the last three decades. In the initial days, the problems with financial analysis and prediction were solved by statistical models and methods. For the last two decades, a large number of Artificial Neural Networks based learning models have been proposed to solve the problems of financial data and get accurate results in prediction of the future trends and prices. This paper addressed some architectural design related issues for performance improvement through vectorising the strengths of multivariate econometric time series models and Artificial Neural Networks. It provides an adaptive approach for predicting exchange rates and it can be called hybrid methodology for predicting exchange rates. This framework is tested for finding the accuracy and performance of parallel algorithms used.

  2. A REVIEW OF OIL PALM BIOCOMPOSITES FOR FURNITURE DESIGN AND APPLICATIONS: POTENTIAL AND CHALLENGES

    Siti Suhaily,

    2012-07-01

    Full Text Available This review considers the potential and challenges of using agro-based oil palm biomasses, including the trunk, frond, empty fruit bunch, and palm press fiber biocomposites, for furniture applications. Currently, design and quality rather than price are becoming the primary concern for consumers when buying new furniture. Within this context, this paper focuses on the design of innovative, sustainable furniture from agro-based biocomposites to meet the needs of future population growth and technology. This research also discusses the need for biocomposite materials that do not depend on the growth of populations, but on the growth and development of the economy. This study focuses on globally available agro-based biocomposites, especially those from oil palm biomass: plywood, medium density fiberboard (MDF, wood plastic composite (WPC, laminated veneer lumber (LVL, oriented strand board (OSB, hardboards, and particleboard. Additional positive aspects of biocomposites are their environmentally friendly character, high quality, competitive design, and capacity to improve the value proposition of high-end products. These attributes increase the demand for agro-based biocomposite furniture on the international market.

  3. Meeting the physics design challenges of modern LWRs being inducted into the Indian nuclear power programme

    Jagannathan, V.; Pal, Usha; Karthikeyan, R.; Raj, Devesh; Srivastava, Argala; Khan, Suhail Ahmad

    2007-01-01

    Indian nuclear power programme started with the two Boiling Water Reactors (BWR) of 210 MWe capacity at Tarapur. Two VVER-1000 MWe reactors which are Pressurized Water Reactors (PWR) of Russian design are being constructed at Kudankulam, Tamilnadu and are expected to be commissioned by end 2008. There may be also a possibility of inducting some western PWRs in future. These reactors belong to the category of light water reactors (LWR). The LWRs are compact and have complex physical characteristics distinctly different from those of the Pressurized Heavy Water Reactors (PHWR) which, currently form the mainstay of our indigenous nuclear power programme. The physics design and analysis capability for the modern LWRs (BWR, PWR and VVER) has been developed at Light Water Reactors Physics Section, BARC. This paper presents the current state of art in this key technology area to meet the physics design and operation challenges when LWRs would be inducted in a major way into the Indian nuclear power programme and commence operating in the coming decades. (author)

  4. Development and production of an oligonucleotide MuscleChip: use for validation of ambiguous ESTs

    Lanfranchi Gerolamo

    2002-10-01

    Full Text Available Abstract Background We describe the development, validation, and use of a highly redundant 120,000 oligonucleotide microarray (MuscleChip containing 4,601 probe sets representing 1,150 known genes expressed in muscle and 2,075 EST clusters from a non-normalized subtracted muscle EST sequencing project (28,074 EST sequences. This set included 369 novel EST clusters showing no match to previously characterized proteins in any database. Each probe set was designed to contain 20–32 25 mer oligonucleotides (10–16 paired perfect match and mismatch probe pairs per gene, with each probe evaluated for hybridization kinetics (Tm and similarity to other sequences. The 120,000 oligonucleotides were synthesized by photolithography and light-activated chemistry on each microarray. Results Hybridization of human muscle cRNAs to this MuscleChip (33 samples showed a correlation of 0.6 between the number of ESTs sequenced in each cluster and hybridization intensity. Out of 369 novel EST clusters not showing any similarity to previously characterized proteins, we focused on 250 EST clusters that were represented by robust probe sets on the MuscleChip fulfilling all stringent rules. 102 (41% were found to be consistently "present" by analysis of hybridization to human muscle RNA, of which 40 ESTs (39% could be genome anchored to potential transcription units in the human genome sequence. 19 ESTs of the 40 ESTs were furthermore computer-predicted as exons by one or more than three gene identification algorithms. Conclusion Our analysis found 40 transcriptionally validated, genome-anchored novel EST clusters to be expressed in human muscle. As most of these ESTs were low copy clusters (duplex and triplex in the original 28,000 EST project, the identification of these as significantly expressed is a robust validation of the transcript units that permits subsequent focus on the novel proteins encoded by these genes.

  5. Ultrasensitive electrochemical biosensor based on the oligonucleotide self-assembled monolayer-mediated immunosensing interface

    Liu, Dengyou; Luo, Qimei [Science College of Hunan Agricultural University, Changsha 410128 (China); Deng, Fawen [The Fourth Hospital of Chansha, Changsha 410006 (China); Li, Zhen [Science College of Hunan Agricultural University, Changsha 410128 (China); Li, Benxiang, E-mail: 172170960@qq.com [Science College of Hunan Agricultural University, Changsha 410128 (China); Shen, Zhifa, E-mail: shenzhifa@wmu.edu.cn [Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035 (China)

    2017-06-08

    Highly sensitive and selective quantitation of a variety of proteins over a wide concentration range is highly desirable for increased accuracy of biomarker detection or for multidisease diagnostics. In the present contribution, using human immunoglobulin G (HIgG) as the model target protein, an electrochemical ultrasensitive immunosensing platform was developed based on the oligonucleotide self-assembled monolayer-mediated (OSAM) sensing interface. For this immunosensor, the “signal-on” signaling mechanism and enzymatic signal amplification effect were integrated into one sensing architecture. Moreover, the thiolated flexible single-stranded DNAs immobilized onto gold electrode surface not only performs the wobbling motion to facilitate the electron transfer between the electrode surface and biosensing layer but also fundamentally prohibiting the direct interaction of proteins with gold substrate. Thus, the electrochemical signal could be efficiently enhanced and the unspecific adsorption or cross-reaction might be eliminated. As a result, utilizing the newly-proposed immunosensor, the HIgG can be detected down to 0.5 ng/mL, and the high detection specificity is offered. The successful design of OSAM and the highly desirable detection capability of new immunosensor are expected to provide a perspective for fabricating new robust immunosensing platform and for promising potential of oligonucleotide probe in biological research and biomedical diagnosis. - Highlights: • An electrochemical ultrasensitive immunosensing platform was developed based on the oligonucleotide self-assembled monolayer (OASM). • OASM severs as a flexible monolayer to promote electron transfer and prohibits the direct interaction of proteins with gold substrate. • The electrochemical signal is efficiently enhanced and the unspecific adsorption or cross-reaction is eliminated. • Target protein can be detected down to 0.5 ng/mL, and the high detection specificity can be obtained.

  6. Simplified Paper Format for Detecting HIV Drug Resistance in Clinical Specimens by Oligonucleotide Ligation

    Panpradist, Nuttada; Beck, Ingrid A.; Chung, Michael H.; Kiarie, James N.; Frenkel, Lisa M.; Lutz, Barry R.

    2016-01-01

    Human immunodeficiency virus (HIV) is a chronic infection that can be managed by antiretroviral treatment (ART). However, periods of suboptimal viral suppression during lifelong ART can select for HIV drug resistant (DR) variants. Transmission of drug resistant virus can lessen or abrogate ART efficacy. Therefore, testing of individuals for drug resistance prior to initiation of treatment is recommended to ensure effective ART. Sensitive and inexpensive HIV genotyping methods are needed in low-resource settings where most HIV infections occur. The oligonucleotide ligation assay (OLA) is a sensitive point mutation assay for detection of drug resistance mutations in HIV pol. The current OLA involves four main steps from sample to analysis: (1) lysis and/or nucleic acid extraction, (2) amplification of HIV RNA or DNA, (3) ligation of oligonucleotide probes designed to detect single nucleotide mutations that confer HIV drug resistance, and (4) analysis via oligonucleotide surface capture, denaturation, and detection (CDD). The relative complexity of these steps has limited its adoption in resource-limited laboratories. Here we describe a simplification of the 2.5-hour plate-format CDD to a 45-minute paper-format CDD that eliminates the need for a plate reader. Analysis of mutations at four HIV-1 DR codons (K103N, Y181C, M184V, and G190A) in 26 blood specimens showed a strong correlation of the ratios of mutant signal to total signal between the paper CDD and the plate CDD. The assay described makes the OLA easier to perform in low resource laboratories. PMID:26751207

  7. Security challenges in designing I and C systems for nuclear power plant

    Behera, Rajendra Prasad; Jayanthi, T.; Madhusoodanan, K.; Satya Murty, S.A.V.

    2016-01-01

    Geographically distributed instrumentation and control (I and C) systems in any nuclear power plant (NPP) facilitate the operator with remote access to real-time data and issue supervisory command to remote control devices deployed in the field. The increased connectivity to plant communication network has exposed I and C systems to security vulnerabilities both in terms of physical and logical access. For example, denial-of service and fault induction attack can disrupt the operation of I and C systems by delaying or blocking the flow of data through plant communication network. The design process of I and C system is quite challenging since an engineer has to consider both safety and security features implemented in hardware and software components of the system. This paper analyzes attack taxonomy based on available data and presents Security Tree Analysis (STA) technique towards building safe and secures I and C systems for Nuclear Power Plant. (author)

  8. The offshoring challenge strategic design and innovation for tomorrow’s organization

    Bals, Lydia; Jensen, Peter; Larsen, Marcus

    2013-01-01

    The continuous search for efficiency gains and the goal of attaining a sustainable competitive advantage have steadily increased the volume of goods and services procured globally from third party vendors. In this context, named as “the next wave of globalization”, the offshoring phenomenon has stimulated research and political debates. With the rise of services offshoring, international value chain disaggregation for services has reached a formerly unknown scale. Also, it is increasingly complex transactions, requiring a higher degree of qualification, which are becoming subject to offshoring as well. The Offshoring Challenge: Strategic Design and Innovation for Tomorrow’s Organization features selected chapters by an international research community on the topic of offshoring. All potential business models from offshore outsourcing to third party providers are covered, from cooperative arrangements to internal organizational set-ups including captive offshore centers. Contributions have significant in...

  9. Antisense Oligonucleotides Internally Labeled with Peptides Show Improved Target Recognition and Stability to Enzymatic Degradation

    Taskova, Maria; Madsen, Charlotte S.; Jensen, Knud J.

    2017-01-01

    Specific target binding and stability in diverse biological media is of crucial importance for applications of synthetic oligonucleotides as diagnostic and therapeutic tools. So far, these issues have been addressed by chemical modification of oligonucleotides and by conjugation with a peptide, m...... and makes internally labeled POCs an exciting object of study, i.e., showing high target specificity and simultaneous stability in biological media.......Specific target binding and stability in diverse biological media is of crucial importance for applications of synthetic oligonucleotides as diagnostic and therapeutic tools. So far, these issues have been addressed by chemical modification of oligonucleotides and by conjugation with a peptide......, most often at the terminal position of the oligonucleotide. Herein, we for the first time systematically investigate the influence of internally attached short peptides on the properties of antisense oligonucleotides. We report the synthesis and internal double labeling of 21-mer oligonucleotides...

  10. Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

    Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

    2016-03-01

    Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (Prooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer.

  11. Applied & Computational MathematicsChallenges for the Design and Control of Dynamic Energy Systems

    Brown, D L; Burns, J A; Collis, S; Grosh, J; Jacobson, C A; Johansen, H; Mezic, I; Narayanan, S; Wetter, M

    2011-03-10

    The Energy Independence and Security Act of 2007 (EISA) was passed with the goal 'to move the United States toward greater energy independence and security.' Energy security and independence cannot be achieved unless the United States addresses the issue of energy consumption in the building sector and significantly reduces energy consumption in buildings. Commercial and residential buildings account for approximately 40% of the U.S. energy consumption and emit 50% of CO{sub 2} emissions in the U.S. which is more than twice the total energy consumption of the entire U.S. automobile and light truck fleet. A 50%-80% improvement in building energy efficiency in both new construction and in retrofitting existing buildings could significantly reduce U.S. energy consumption and mitigate climate change. Reaching these aggressive building efficiency goals will not happen without significant Federal investments in areas of computational and mathematical sciences. Applied and computational mathematics are required to enable the development of algorithms and tools to design, control and optimize energy efficient buildings. The challenge has been issued by the U.S. Secretary of Energy, Dr. Steven Chu (emphasis added): 'We need to do more transformational research at DOE including computer design tools for commercial and residential buildings that enable reductions in energy consumption of up to 80 percent with investments that will pay for themselves in less than 10 years.' On July 8-9, 2010 a team of technical experts from industry, government and academia were assembled in Arlington, Virginia to identify the challenges associated with developing and deploying newcomputational methodologies and tools thatwill address building energy efficiency. These experts concluded that investments in fundamental applied and computational mathematics will be required to build enabling technology that can be used to realize the target of 80% reductions in energy

  12. Designing an Assistive Learning Aid for Writing Acquisition: A Challenge for Children with Dyslexia.

    Latif, Seemab; Tariq, Rabbia; Tariq, Shehla; Latif, Rabia

    2015-01-01

    In Pakistan, the biggest challenge is to provide high quality education to the individuals with learning disabilities. Besides the well known affordance issue, there is a lack of awareness regarding the term dyslexia and remedial teaching training that causes the identification as well as remediation of the dyslexic individuals at early stages in Pakistan. The research was focused to exploit the benefits of using the modern mobile technology features in providing a learning platform for young dyslexic writers. Based on potential usability requirements of young dyslexic writers stated by remedial teachers of dyslexics, an android based application is designed and implemented using the usability engineering process model to encourage the learning process and help dyslexic children improve their fundamental handwriting skill. In addition, a handwriting learning algorithm based on concepts of machine learning is designed and implemented to decide the learning content, evaluate the learning performance, display the performance results and record the learning growth to show the strengths and weaknesses of a dyslexic child. The research was also aimed to assess the usability of the learner-centered application by the targeted population by conducting a user acceptance test to evaluate their learning experience and benefits of the developed application to dyslexic users. The results of the evaluation provided by the participants revealed that application has potential benefits to foster the learning process and help children with dyslexia by improving their foundational writing skills.

  13. Columbia Estuary Ecosystem Restoration Program: Restoration Design Challenges for Topographic Mounds, Channel Outlets, and Reed Canarygrass

    Diefenderfer, Heida L. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Borde, Amy B. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Sinks, Ian A. [Columbia Land Trust, Vancouver, WA (United States); Cullinan, Valerie I. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Zimmerman, Shon A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-08-31

    The purpose of this study was to provide science-based information to practitioners and managers of restoration projects in the Columbia Estuary Ecosystem Restoration Program (CEERP) regarding aspects of restoration techniques that currently pose known challenges and uncertainties. The CEERP is a program of the Bonneville Power Administration (BPA) and the U.S. Army Corps of Engineers (Corps), Portland District, in collaboration with the National Marine Fisheries Service and five estuary sponsors implementing restoration. The estuary sponsors are Columbia Land Trust, Columbia River Estuary Study Taskforce, Cowlitz Tribe, Lower Columbia Estuary Partnership, and Washington Department of Fish and Wildlife. The scope of the research conducted during federal fiscal year 2015 included three aspects of hydrologic reconnection that were selected based on available scientific information and feedback from restoration practitioners during project reviews: the design of mounds (also called hummocks, peninsulas, or berms); the control of reed canarygrass (Phalaris arundinaceae); and aspects of channel network design related to habitat connectivity for juvenile salmonids.

  14. Challenging issues in the design and manufacturing of the European sectors of the ITER vacuum vessel

    Dans, Andres; Jucker, P.; Bayon, A.; Arbogast, J.-F.; Caixas, J.; Fernández, J.; Micó, G.; Pacheco, J.; Trentea, A.; Stamos, V.

    2014-01-01

    Highlights: • ITER Vacuum Vessel was described with its features and particularities. • Engineering and CAD design of Sector 5 is finish; the work of sectors 3 and 4 is ongoing. • Fabrication Mock Ups almost finished with an important know-how acquired. • Procurement of raw material (plates and forgings) started. • Qualification of welding, NDT and forming close to be finished. - Abstract: Fusion for Energy (F4E), the European Domestic Agency for the ITER project, has to supply seven sectors as part of the European contribution to the project. F4E signed the Procurement Agreement with ITER Organization (IO) in 2009. After a call for tender in 2010, the contract for the manufacturing of seven sectors was placed in October 2010 to a consortium of three Italian companies, Ansaldo, Mangiarotti and Walter Tosto (AMW). The first sector in the manufacturing route is Sector 5 (later will come 4, 3, 2, 9, 8, 7). This paper will cover: the status of the engineering activities, design, procurement and preparation to begin the manufacturing in 2013. Also will be presented the statutory and regulatory requirements of the French Nuclear Safety regulator and the status of the relevant R and D mock-ups to demonstrate manufacturing feasibility control of distortions (using predictions with analysis and algorithms to change in real time the manufacturing route in order to correct such distortions, inspectability and metrology). Another important aspect at this stage of the manufacturing is qualification of activities like welding, Non-destructive Examination and Hot Forming. This paper describes the status of the activities currently in process in order to meet with the challenging design, schedule and high quality requirements of the project

  15. Challenging issues in the design and manufacturing of the European sectors of the ITER vacuum vessel

    Dans, Andres, E-mail: andresdans@gmail.com; Jucker, P.; Bayon, A.; Arbogast, J.-F.; Caixas, J.; Fernández, J.; Micó, G.; Pacheco, J.; Trentea, A.; Stamos, V.

    2014-10-15

    Highlights: • ITER Vacuum Vessel was described with its features and particularities. • Engineering and CAD design of Sector 5 is finish; the work of sectors 3 and 4 is ongoing. • Fabrication Mock Ups almost finished with an important know-how acquired. • Procurement of raw material (plates and forgings) started. • Qualification of welding, NDT and forming close to be finished. - Abstract: Fusion for Energy (F4E), the European Domestic Agency for the ITER project, has to supply seven sectors as part of the European contribution to the project. F4E signed the Procurement Agreement with ITER Organization (IO) in 2009. After a call for tender in 2010, the contract for the manufacturing of seven sectors was placed in October 2010 to a consortium of three Italian companies, Ansaldo, Mangiarotti and Walter Tosto (AMW). The first sector in the manufacturing route is Sector 5 (later will come 4, 3, 2, 9, 8, 7). This paper will cover: the status of the engineering activities, design, procurement and preparation to begin the manufacturing in 2013. Also will be presented the statutory and regulatory requirements of the French Nuclear Safety regulator and the status of the relevant R and D mock-ups to demonstrate manufacturing feasibility control of distortions (using predictions with analysis and algorithms to change in real time the manufacturing route in order to correct such distortions, inspectability and metrology). Another important aspect at this stage of the manufacturing is qualification of activities like welding, Non-destructive Examination and Hot Forming. This paper describes the status of the activities currently in process in order to meet with the challenging design, schedule and high quality requirements of the project.

  16. Thermoplastic polymers surfaces for Dip-Pen Nanolithography of oligonucleotides

    Suriano, Raffaella; Biella, Serena; Cesura, Federico; Levi, Marinella; Turri, Stefano

    2013-01-01

    Different thermoplastic polymers were spin-coated to prepare smooth surfaces for the direct deposition of end-group modified oligonucleotides by Dip-Pen Nanolithography. A study of the diffusion process was done in order to investigate the dependence of calibration coefficient and quality of deposited features on environmental parameters (temperature, relative humidity) and ink's molecular weight and functionality. The optimization of the process parameters led to the realization of high quality and density nanoarrays on plastics.

  17. Thermoplastic polymers surfaces for Dip-Pen Nanolithography of oligonucleotides

    Suriano, Raffaella [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Biella, Serena, E-mail: serena.biella@polimi.it [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy); Cesura, Federico; Levi, Marinella; Turri, Stefano [Dipartimento di Chimica, Materiali e Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milano (Italy)

    2013-05-15

    Different thermoplastic polymers were spin-coated to prepare smooth surfaces for the direct deposition of end-group modified oligonucleotides by Dip-Pen Nanolithography. A study of the diffusion process was done in order to investigate the dependence of calibration coefficient and quality of deposited features on environmental parameters (temperature, relative humidity) and ink's molecular weight and functionality. The optimization of the process parameters led to the realization of high quality and density nanoarrays on plastics.

  18. Peroxide-mediated desulfurization of phosphorothioate oligonucleotides and its prevention.

    Krotz, Achim H; Mehta, Rahul C; Hardee, Gregory E

    2005-02-01

    Desulfurization at the internucleotide phosphorothioate linkage of antisense oligonucleotides (ASOs) in dermatological formulations has been investigated using strong ion exchange chromatography and mass spectroscopy. The formation of phosphate diester linkages appeared to arise from a reaction between the phosphorothioate oligonucleotide and a potent oxidizing agent. Screening of excipients used in the formulation indicated that the cause of desulfurization was related to the presence of polyethylene glycol-derived nonionic surfactants MYRJ 52 or BRIJ 58. Autoxidation of the polyethylene glycol chain is suggested as the probable origin for the observed incompatibility. The ability of various antioxidants to prevent oxidative degradation of ASO-1 in simple test systems and in oil-in-water emulsions is described. It is found that in test systems both lipophilic and hydrophilic antioxidants are effective. However, in cream formulation (oil-in-water emulsions) of ASO-1 the addition of hydrophilic antioxidants L-cysteine or DL-alpha-lipoic acid has been shown to be superior in protecting the oligonucleotide from desulfurization upon storage. Copyright 2004 Wiley-Liss, Inc.

  19. Constructed Wetlands for Treatment of Combined Sewer Overflow in the US: A Review of Design Challenges and Application Status

    Wendong Tao

    2014-11-01

    Full Text Available As combined sewer systems and centralized wastewater treatment facilities age, many communities in the world are challenged by management of combined sewer overflow (CSO. Constructed wetlands are considered to be one of the green infrastructure solutions to CSOs in the US. Despite the wide application of constructed wetlands to different types of wastewaters, the stochastic and intermittent nature of CSO presents challenges for design and performance assessment of constructed wetlands. This paper reviews the application status of CSO constructed wetlands in the US, assesses the benefits of CSO constructed wetlands, identifies challenges to designing CSO constructed wetlands, and proposes design considerations. This review finds that constructed wetlands are effective in CSO treatment and relatively less expensive to build than comparable grey infrastructure. Constructed wetlands not only remove pollutants, but also mitigate the event-associated flow regime. The design challenges include incorporating considerations of green infrastructure into permit requirements, determining design capacity for highly variable flows, requiring pretreatment, and needing adaptive design and intensive monitoring. Simultaneous monitoring of flow rate and water quality at both the inflow and outflow of CSO constructed wetlands is required for performance assessment and needed to support design, but is rarely available.

  20. Capacity Market Design: Motivation and Challenges in Alberta’s Electricity Market

    David Brown

    2018-03-01

    Full Text Available Alberta’s electricity market is currently undergoing a period of substantial transition. The province should proceed with caution as it switches from an energy-only electricity market to a capacity market by 2021. Many other jurisdictions have already made the changeover and Alberta can learn from their experiences in order to avoid common mistakes and pitfalls that can arise with the deployment of a capacity market.There were growing concerns that the existing electricity market structure would not attract sufficient investment from conventional generation (e.g., natural gas due to the increased penetration of zero marginal cost renewable generation. As a result, the Alberta government has chosen to transition to a capacity market. For consumers, a capacity market aims to ensure there is sufficient investment in new generation capacity to “keep the lights on” and reduce price swings in the wholesale market. The capacity market will also help the province meet its goals for attracting investors and transitioning away from its dependence on coal-fired electricity generation.However, a switchover is not as simple as it sounds. In an energy-only market, firms are paid solely based on the provision of electricity in hourly wholesale markets. In capacity markets, electricity-generating firms are also paid for providing generation capacity, reflecting the potential to provide electricity at some point in the future. While capacity markets can help ensure there is a reliable supply of electricity, there are several challenges in the implementation of capacity markets. This paper discusses the motivation for the adoption of capacity markets, highlights challenges regulators face when implementing this market design in the context of Alberta, and summarizes the key trade-offs associated with energy-only versus capacity market designs.Relative to an energy-only market, a capacity market is more complex and requires that regulators specify numerous

  1. A pilot study of transcription unit analysis in rice using oligonucleotide tiling-path microarray

    Stolc, Viktor; Li, Lei; Wang, Xiangfeng

    2005-01-01

    As the international efforts to sequence the rice genome are completed, an immediate challenge and opportunity is to comprehensively and accurately define all transcription units in the rice genome. Here we describe a strategy of using high-density oligonucleotide tiling-path microarrays to map...... transcription of the japonica rice genome. In a pilot experiment to test this approach, one array representing the reverse strand of the last 11.2 Mb sequence of chromosome 10 was analyzed in detail based on a mathematical model developed in this study. Analysis of the array data detected 77% of the reference...... gene models in a mixture of four RNA populations. Moreover, significant transcriptional activities were found in many of the previously annotated intergenic regions. These preliminary results demonstrate the utility of genome tiling microarrays in evaluating annotated rice gene models...

  2. Cy3 and Cy5 dyes attached to oligonucleotide terminus stabilize DNA duplexes: predictive thermodynamic model.

    Moreira, Bernardo G; You, Yong; Owczarzy, Richard

    2015-03-01

    Cyanine dyes are important chemical modifications of oligonucleotides exhibiting intensive and stable fluorescence at visible light wavelengths. When Cy3 or Cy5 dye is attached to 5' end of a DNA duplex, the dye stacks on the terminal base pair and stabilizes the duplex. Using optical melting experiments, we have determined thermodynamic parameters that can predict the effects of the dyes on duplex stability quantitatively (ΔG°, Tm). Both Cy dyes enhance duplex formation by 1.2 kcal/mol on average, however, this Gibbs energy contribution is sequence-dependent. If the Cy5 is attached to a pyrimidine nucleotide of pyrimidine-purine base pair, the stabilization is larger compared to the attachment to a purine nucleotide. This is likely due to increased stacking interactions of the dye to the purine of the complementary strand. Dangling (unpaired) nucleotides at duplex terminus are also known to enhance duplex stability. Stabilization originated from the Cy dyes is significantly larger than the stabilization due to the presence of dangling nucleotides. If both the dangling base and Cy3 are present, their thermodynamic contributions are approximately additive. New thermodynamic parameters improve predictions of duplex folding, which will help design oligonucleotide sequences for biophysical, biological, engineering, and nanotechnology applications. Copyright © 2015. Published by Elsevier B.V.

  3. Antiproliferation effects of an androgen receptor triple-helix forming oligonucleotide on prostate cancer cells

    Zhang Yong; Chen Weizhen; Xie Yao; Gao Jinhui

    2005-01-01

    Objective: To provide experimental basis for antigene radiation therapy through exploring the effects of antigene strategy on androgen receptor (AR) expression and proliferation of prostate cancer cells. Methods: The triple-helix forming oligonucleotide (TFO) targeting 2447-2461nt of AR cDNA was designed and transfected LNCaP prostate cancer cells with liposome. 24-72 h after transfection, the cellular proliferation was detected by 3 H-thymidine (TdR) incorporation test, the expression of AR gene was examined by reverse transcription-polymerase chain reaction (RT-PCR) and expression of AR protein was performed by radioligand binding assay. The results of TFO were compared with antisense oligonucleotide (ASON). Results: At all time points, the AR expression levels in TFO group were markedly lower than that of ASON group (P<0.05). The inhibitory rate of TFO for cellular proliferation was significantly higher than that of ASON (P<0.05). Conclusion: The TFO was a potent inhibitor for AR expression and cell proliferation of LNCaP cells , and could be used in antigene radiotherapy. (authors)

  4. Short Oligonucleotides Aligned in Stretched Humid Matrix: Secondary DNA Structure in Poly(vinyl alcohol) Environment

    Hanczyc, Piotr

    2012-04-24

    We report that short, synthetic, double- as well as single-stranded DNA can be aligned in stretched humid poly(vinyl alcohol) (PVA) matrix, and the secondary structure (nucleobase orientation) can be characterized with linear dichroism (LD) spectroscopy. Oligonucleotides of lengths varying between 10 (3.4 nm) and 60 bases (20.4 nm) were investigated with respect to structural properties in the gel-like polymer environment. The DNA conformation as a function of relative humidity reveals a strong dependence of helical structure of DNA on PVA hydration level, results of relevance for nanotechnical studies of DNA-based supramolecular systems. Also, the PVA gel could provide possibilities to test models for nucleic acid interactions and distribution in cell contexts, including structural stability of genetic material in the cell and PVA-packaging for gene delivery. A method by which duplex oligonucleotides, with sequences designed to provide specific binding sites, become amenable to polarized-light spectroscopy opens up new possibilities for studying structure in DNA complexes with small adduct molecules as well as proteins. © 2012 American Chemical Society.

  5. Efficacy and Safety Profile of Tricyclo-DNA Antisense Oligonucleotides in Duchenne Muscular Dystrophy Mouse Model

    Karima Relizani

    2017-09-01

    Full Text Available Antisense oligonucleotides (AONs hold promise for therapeutic splice-switching correction in many genetic diseases. However, despite advances in AON chemistry and design, systemic use of AONs is limited due to poor tissue uptake and sufficient therapeutic efficacy is still difficult to achieve. A novel class of AONs made of tricyclo-DNA (tcDNA is considered very promising for the treatment of Duchenne muscular dystrophy (DMD, a neuromuscular disease typically caused by frameshifting deletions or nonsense mutations in the gene-encoding dystrophin and characterized by progressive muscle weakness, cardiomyopathy, and respiratory failure in addition to cognitive impairment. Herein, we report the efficacy and toxicology profile of a 13-mer tcDNA in mdx mice. We show that systemic delivery of 13-mer tcDNA allows restoration of dystrophin in skeletal muscles and to a lower extent in the brain, leading to muscle function improvement and correction of behavioral features linked to the emotional/cognitive deficiency. More importantly, tcDNA treatment was generally limited to minimal glomerular changes and few cell necroses in proximal tubules, with only slight variation in serum and urinary kidney toxicity biomarker levels. These results demonstrate an encouraging safety profile for tcDNA, albeit typical of phosphorothiate AONs, and confirm its therapeutic potential for the systemic treatment of DMD patients. Keywords: antisense oligonucleotides, Duchenne muscular dystrophy, preclinical, splice switching, tcDNA-AONs

  6. Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

    Katebi, Samira; Esmaeili, Abolghasem; Ghaedi, Kamran

    2016-01-01

    Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. - Highlights: • Core/shell type Iron oxide nanoparticles were used as a novel and efficient method. • This method increases exogenous DNA uptake by rooster spermatozoa. • Static magnetic field decreased DNA uptake by rooster spermatozoa.

  7. Static magnetic field reduced exogenous oligonucleotide uptake by spermatozoa using magnetic nanoparticle gene delivery system

    Katebi, Samira; Esmaeili, Abolghasem, E-mail: aesmaeili@sci.ui.ac.ir; Ghaedi, Kamran

    2016-03-15

    Spermatozoa could introduce exogenous oligonucleotides of interest to the oocyte. The most important reason of low efficiency of sperm mediated gene transfer (SMGT) is low uptake of exogenous DNA by spermatozoa. The aim of this study was to evaluate the effects of static magnetic field on exogenous oligonucleotide uptake of spermatozoa using magnetofection method. Magnetic nanoparticles (MNPs) associated with the labeled oligonucleotides were used to increase the efficiency of exogenous oligonucleotide uptake by rooster spermatozoa. We used high-field/high-gradient magnet (NdFeB) to enhance and accelerate exogenous DNA sedimentation at the spermatozoa surface. Flow cytometry analysis was performed to measure viability and percentage of exogenous oligonucleotide uptake by sperm. Flow cytometry analysis showed a significant increase in exogenous oligonucleotide uptake by rooster spermatozoa (P<0.001) when spermatozoa were incubated in exogenous oligonucleotide solution and MNPs. However, by applying static magnetic field during magnetofection method, a significant decrease in exogenous oligonucleotide uptake was observed (P<0.05). Findings of this study showed that MNPs were effective to increase exogenous oligonucleotide uptake by rooster spermatozoa; however unlike others studies, static magnetic field, was not only ineffective to enhance exogenous oligonucleotide uptake by rooster spermatozoa but also led to reduction in efficiency of magnetic nanoparticles in gene transfer. - Highlights: • Core/shell type Iron oxide nanoparticles were used as a novel and efficient method. • This method increases exogenous DNA uptake by rooster spermatozoa. • Static magnetic field decreased DNA uptake by rooster spermatozoa.

  8. Challenges and considerations for the design and production of a purpose-optimized body-worn wrist-watch computer

    Narayanaswami, Chandra; Raghunath, Mandayam T.

    2004-09-01

    We outline a collection of technological challenges in the design of wearable computers with a focus on one of the most desirable form-factors, the wrist watch. We describe our experience with building three generations of wrist watch computers. We built these research prototypes as platforms to investigate the fundamental limitations of wearable computing. Results of our investigations are presented in the form of challenges that have been overcome and those that still remain.

  9. Energy Transition: Missed Opportunities and Emerging Challenges for Landscape Planning and Designing

    Renée M. de Waal

    2014-07-01

    Full Text Available Making the shift from fossil fuels to renewable energy seems inevitable. Because energy transition poses new challenges and opportunities to the discipline of landscape architecture, the questions addressed in this paper are: (1 what landscape architects can learn from successful energy transitions in Güssing, Jühnde and Samsø; and (2 to what extent landscape architecture (or other spatial disciplines contributed to energy transition in the aforementioned cases. An exploratory, comparative case study was conducted to identify differences and similarities among the cases, to answer the research questions, and to formulate recommendations for further research and practice. The comparison indicated that the realized renewable energy systems are context-dependent and, therefore, specifically designed to meet the respective energy demand, making use of the available potentials for renewable energy generation and efficiency. Further success factors seemed to be the presence of (local frontrunners and a certain degree of citizen participation. The relatively smooth implementation of renewable energy technologies in Jühnde and on Samsø may indicate the importance of careful and (partly institutionalized consideration of landscape impact, siting and design. Comparing the cases against the literature demonstrated that landscape architects were not as involved as they, theoretically, could have been. However, particularly when the aim is sustainable development, rather than “merely” renewable energy provision, the integrative concept of “sustainable energy landscapes” can be the arena where landscape architecture and other disciplines meet to pursue global sustainability goals, while empowering local communities and safeguarding landscape quality.

  10. Design of experiments and data analysis challenges in calibration for forensics applications

    Anderson-Cook, Christine M.; Burr, Thomas L.; Hamada, Michael S.; Ruggiero, Christy E.; Thomas, Edward V.

    2015-01-01

    Forensic science aims to infer characteristics of source terms using measured observables. Our focus is on statistical design of experiments and data analysis challenges arising in nuclear forensics. More specifically, we focus on inferring aspects of experimental conditions (of a process to produce product Pu oxide powder), such as temperature, nitric acid concentration, and Pu concentration, using measured features of the product Pu oxide powder. The measured features, Y, include trace chemical concentrations and particle morphology such as particle size and shape of the produced Pu oxide power particles. Making inferences about the nature of inputs X that were used to create nuclear materials having particular characteristics, Y, is an inverse problem. Therefore, statistical analysis can be used to identify the best set (or sets) of Xs for a new set of observed responses Y. One can fit a model (or models) such as Y = f(X) + error, for each of the responses, based on a calibration experiment and ''invert'' to solve for the best set of Xs for a new set of Ys. This perspectives paper uses archived experimental data to consider aspects of data collection and experiment design for the calibration data to maximize the quality of the predicted Ys in the forward models; that is, we assume that well-estimated forward models are effective in the inverse problem. In addition, we consider how to identify a best solution for the inferred X, and evaluate the quality of the result and its robustness to a variety of initial assumptions, and different correlation structures between the responses. In addition, we also briefly review recent advances in metrology issues related to characterizing particle morphology measurements used in the response vector, Y

  11. Engineering challenges encountered in the design of the ELMO BUMPY TORUS proof-of-principle fusion device

    Dillow, C.F.; Imster, H.F.

    1982-01-01

    This paper first provides a summary of the history and current status of the Elmo Bumpy Torus (EBT) fusion concept. A brief description of the EBT-P is then provided in which the many unique features of this fusion device are highlighted. This description will provide the technical background for the following discussions of some of the more challenging mechanical engineering problems encountered to date in the evolution of the EBT-P design. The problems discussed are: optimization of the device primary structure design, optimization of the superconducting magnet x-ray shield design, design of the liquid helium supply and distribution system, and selection of high vacuum seals and pumps and their protection from the high power microwave environment. The common challenge in each of these design issues was to assure adequate performance at minimum cost

  12. Understanding the selection of core head design features to match precisely challenging well applications

    Zambrana, Roberto; Sousa, J. Tadeu V. de; Antunes, Ricardo [Halliburton Servicos Ltda., Rio de Janeiro, RJ (Brazil)

    2008-07-01

    Reliable rock mechanical information is very important for optimum reservoir development. This information can help specialists to accurately estimate reserves, reservoir compaction, sand production, stress field orientation, etc. In all cases, the solutions to problems involving rock mechanics lead to significant cost savings. Consequently, it is important that the decisions be based on the most accurate information possible. For the describing rock mechanics, cores represent the major source of data and therefore should be of good quality. However, there are several well conditions that cause coring and core recovery to be difficult, for example: unconsolidated formations; laminated and fractured rocks; critical mud losses, etc. The problem becomes even worse in high-inclination wells with long horizontal sections. In such situations, the optimum selections of core heads become critical. This paper will discuss the most important design features that enable core heads to be matched precisely to various challenging applications. Cases histories will be used to illustrate the superior performance of selected core heads. They include coring in horizontal wells and in harsh well conditions with critical mud losses. (author)

  13. An exploration of neuromorphic systems and related design issues/challenges in dark silicon era

    Chandaliya, Mudit; Chaturvedi, Nitin; Gurunarayanan, S.

    2018-03-01

    The current microprocessors has shown a remarkable performance and memory capacity improvement since its innovation. However, due to power and thermal limitations, only a fraction of cores can operate at full frequency at any instant of time irrespective of the advantages of new technology generation. This phenomenon of under-utilization of microprocessor is called as dark silicon which leads to distraction in innovative computing. To overcome the limitation of utilization wall, IBM technologies explored and invented neurosynaptic system chips. It has opened a wide scope of research in the field of innovative computing, technology, material sciences, machine learning etc. In this paper, we first reviewed the diverse stages of research that have been influential in the innovation of neurosynaptic architectures. These, architectures focuses on the development of brain-like framework which is efficient enough to execute a broad set of computations in real time while maintaining ultra-low power consumption as well as area considerations in mind. We also reveal the inadvertent challenges and the opportunities of designing neuromorphic systems as presented by the existing technologies in the dark silicon era, which constitute the utmost area of research in future.

  14. Fundamental and Technical Challenges for a Compatible Design Scheme of Oxyfuel Combustion Technology

    Chuguang Zheng

    2015-03-01

    Full Text Available Oxyfuel combustion with carbon capture and sequestration (CCS is a carbon-reduction technology for use in large-scale coal-fired power plants. Significant progress has been achieved in the research and development of this technology during its scaling up from 0.4 MWth to 3 MWth and 35 MWth by the combined efforts of universities and industries in China. A prefeasibility study on a 200 MWe large-scale demonstration has progressed well, and is ready for implementation. The overall research development and demonstration (RD&D roadmap for oxyfuel combustion in China has become a critical component of the global RD&D roadmap for oxyfuel combustion. An air combustion/oxyfuel combustion compatible design philosophy was developed during the RD&D process. In this paper, we briefly address fundamental research and technology innovation efforts regarding several technical challenges, including combustion stability, heat transfer, system operation, mineral impurities, and corrosion. To further reduce the cost of carbon capture, in addition to the large-scale deployment of oxyfuel technology, increasing interest is anticipated in the novel and next-generation oxyfuel combustion technologies that are briefly introduced here, including a new oxygen-production concept and flameless oxyfuel combustion.

  15. Risks and challenges associated with the design and construction of a nuclear power plant

    Liebana Martinez, B.; Armas Garcia, A.; Martinez Gozalo, I.

    2011-01-01

    The construction of a nuclear power plant project, considering the period prior to the operation of the plant, requires a very strict risk control to ensure compliance with a series of challenges. The present paper identifying the most important challenges facing the construct ability and license requirements of the process, identifying the interfaces and proposing a methodology of construction to meet the challenge of a construction process in 5 years.

  16. Oligonucleotide assisted light-emitting Alq3 microrods: energy transfer effect with fluorescent dyes.

    Cui, Chunzhi; Park, Dong Hyuk; Kim, Jeongyong; Joo, Jinsoo; Ahn, Dong June

    2013-06-14

    Oligonucleotide assisted tri(8-hydroxyquinoline) aluminium (Alq3) microrods were prepared for the first time. When hybridized with oligonucleotide labeled by Cy3 fluorescent dye, a significant photoluminescence variation of the Alq3 microrods was observed due to Förster resonance energy transfer, unlike when Cy5-oligonucleotide was used. Versatile nucleotide manipulation would open up wider applications of Alq3-based materials, based on this fundamental observation.

  17. Opportunity by Design: New High School Models for Student Success. Carnegie Challenge

    Hamilton, Leah; Mackinnon, Anne

    2013-01-01

    The goal of Carnegie "Challenge" papers is to lift up ideas and issues in a way that elevates them to the nation's agenda. This paper is a "Challenge" paper, and serves as a call to realize the full power of the Common Core by redesigning and reshaping schools to support teachers and maximize key resources, rather than…

  18. The Consumer Behavior Challenge: Designing an Assignment to Motivate Student Reflection and Self-Growth

    Gravois, Renée; Lopez, Tará Burnthorne; Budden, Michael C.

    2017-01-01

    The tension caused by change pushes students to reflect on their new situation, examine preconceived ideas, and synthesize new with existing knowledge. In the Consumer Behavior Challenge, students are challenged to step outside of their comfort zone by changing a behavior or trying something new for a period of time. Through guided reflection…

  19. Status of Foreground and Instrument Challenges for 21cm EoR experiments - Design Strategies for SKA and HERA

    Thyagarajan, Nithyanandan

    2018-05-01

    Direct detection of the Epoch of Reionization (EoR) via redshifted 21 cm line of H i will reveal the nature of the first stars and galaxies as well as revolutionize our understanding of a poorly explored evolutionary phase of the Universe. Projects such as the MWA, LOFAR, and PAPER commenced in the last decade with the promise of high significance statistical detection of the EoR, but have so far only weakly constrained models owing to unforeseen challenges from bright foreground sources and instrument systematics. It is essential for next generation instruments like the HERA and SKA to have these challenges addressed. I present an analysis of these challenges - wide-field measurements, antenna beam chromaticity, reflections in the instrument, and antenna position errors - along with performance specifications and design solutions that will be critical to designing successful next-generation instruments in enabling the first detection and also in placing meaningful constraints on reionization models.

  20. Challenges Inherent in the Design and Implementation of After-School Intervention Programs for Middle Grade Underachieving Readers

    Velten, Justin; Mokhtari, Kouider

    2016-01-01

    In this brief report, we share three challenges we encountered when designing and implementing an after school intervention program for an ethnically diverse group of middle grade underachieving readers. We also offer practical solutions to help guide middle school teams in anticipating and addressing potential problems when putting in place…

  1. Using an Iterative Mixed-Methods Research Design to Investigate Schools Facing Exceptionally Challenging Circumstances within Trinidad and Tobago

    De Lisle, Jerome; Seunarinesingh, Krishna; Mohammed, Rhoda; Lee-Piggott, Rinnelle

    2017-01-01

    In this study, methodology and theory were linked to explicate the nature of education practice within schools facing exceptionally challenging circumstances (SFECC) in Trinidad and Tobago. The research design was an iterative quan>QUAL-quan>qual multi-method research programme, consisting of 3 independent projects linked together by overall…

  2. Virtual communities, research groups and projects on IMS Learning Design. State of the art, key factors and forthcoming challenges

    Burgos, Daniel; Koper, Rob

    2005-01-01

    Burgos, D., Koper, R. (2005) Virtual communities, research groups and projects on IMS Learning Design. State of the art, key factors and forthcoming challenges. In E-Journal of Educational Research, Assessment and Evaluation, vol. 11, issue 2 [www.uv.es/RELIEVE]. Available at

  3. Chemically modified oligonucleotides with efficient RNase H response

    Vester, Birte; Boel, Anne Marie; Lobedanz, Sune

    2008-01-01

    Ten different chemically modified nucleosides were incorporated into short DNA strands (chimeric oligonucleotides ON3-ON12 and ON15-ON24) and then tested for their capacity to mediate RNAse H cleavage of the complementary RNA strand. The modifications were placed at two central positions directly...... in the RNase H cleaving region. The RNA strand of duplexes with ON3, ON5 and ON12 were cleaved more efficiently than the RNA strand of the DNA:RNA control duplex. There seems to be no correlation between the thermal stability between the duplexes and RNase H cleavage....

  4. Characterization of peptide-oligonucleotide heteroconjugates by mass spectrometry.

    Jensen, O N; Kulkarni, S; Aldrich, J V; Barofsky, D F

    1996-01-01

    Two peptide-oligothymidylic acids, prepared by joining an 11 residue synthetic peptide containing one internal carboxyl group (Asp side chain) to amino-linker-5'pdT6 and amino-linker-5'pdT10 oligonucleotides, were analyzed by matrix-assisted laser desorption/ionization (MALDI) on a linear time-of-flight mass spectrometer and by electrospray ionization (ESI) on a triple-quadrupole system. These synthetic compounds model peptide-nucleic acid heteroconjugates encountered in antisense research an...

  5. PCR amplification on microarrays of gel immobilized oligonucleotides

    Strizhkov, Boris; Tillib, Sergei; Mikhailovich, Vladimir; Mirzabekov, Andrei

    2003-11-04

    The invention relates two general methods for performing PCR amplification, combined with the detection and analysis of the PCR products on a microchip. In the first method, the amplification occurs both outside and within a plurality of gel pads on a microchip, with at least one oligonucleotide primer immobilized in a gel pad. In the second method, PCR amplification also takes place within gel pads on a microchip, but the pads are surrounded by a hydrophobic liquid such as that which separates the individual gel pads into environments which resemble micro-miniaturized test tubes.

  6. Synthesis and Structural Characterization of 2'-Fluoro-α-L-RNA-Modified Oligonucleotides

    Bundgaard Jensen, Troels; Pasternak, Anna; Stahl Madsen, Andreas

    2011-01-01

    with the smallest destabilization towards RNA. Thermodynamic data show that the duplex formation with 2'-fluoro-α-L-RNA nucleotides is enthalpically disfavored but entropically favored. 2'-Fluoro-α-L-RNA nucleotides exhibit very good base pairing specificity following Watson-Crick rules. The 2'-fluoro......-α-L-RNA monomer was designed as a monocyclic mimic of the bicyclic α-L-LNA, and molecular modeling showed that this indeed is the case as the 2'-fluoro monomer adopts a C3'-endo/C2'-exo sugar pucker. Molecular modeling of modified duplexes show that the 2'-fluoro-α-L-RNA nucleotides partake in Watson-Crick base......We describe the synthesis and binding properties of oligonucleotides that contain one or more 2'-fluoro-α-L-RNA thymine monomer(s). Incorporation of 2'-fluoro-α-L-RNA thymine into oligodeoxynucleotides decreased thermal binding stability slightly upon hybridization with complementary DNA and RNA...

  7. An algorithm and program for finding sequence specific oligo-nucleotide probes for species identification

    Tautz Diethard

    2002-03-01

    Full Text Available Abstract Background The identification of species or species groups with specific oligo-nucleotides as molecular signatures is becoming increasingly popular for bacterial samples. However, it shows also great promise for other small organisms that are taxonomically difficult to tract. Results We have devised here an algorithm that aims to find the optimal probes for any given set of sequences. The program requires only a crude alignment of these sequences as input and is optimized for performance to deal also with very large datasets. The algorithm is designed such that the position of mismatches in the probes influences the selection and makes provision of single nucleotide outloops. Program implementations are available for Linux and Windows.

  8. Educational Modelling Language and Learning Design: new challenges for instructional re-usability and personalized learning

    Hummel, Hans; Manderveld, Jocelyn; Tattersall, Colin; Koper, Rob

    2003-01-01

    Published: Hummel, H. G. K., Manderveld, J. M., Tattersall, C.,& Koper, E. J. R. (2004). Educational Modelling Language: new challenges for instructional re-usability and personalized learning. International Journal of Learning Technology, 1, 1, 110-111.

  9. Presidential Green Chemistry Challenge: 2016 Designing Greener Chemicals and Specific Environmental Benefit: Climate Change Awards

    Presidential Green Chemistry Challenge 2016 award winner, Newlight Technologies, developed a net carbon negative plastic made from methane-based GHG. It is cheaper than petroleum-based plastic; used to make cell phone cases, furniture, and other products.

  10. The Spectrometer/Telescope for Imaging X-rays on Solar Orbiter: Flight design, challenges and trade-offs

    Krucker, S.; Bednarzik, M.; Grimm, O.; Hurford, G.J.; Limousin, O.; Meuris, A.; Orleański, P.; Seweryn, K.; Skup, K.R.

    2016-01-01

    STIX is the X-ray spectral imaging instrument on-board the Solar Orbiter space mission of the European Space Agency, and together with nine other instruments will address questions of the interaction between the Sun and the heliosphere. STIX will study the properties of thermal and accelerated electrons near the Sun through their Bremsstrahlung X-ray emission, addressing in particular the emission from flaring regions on the Sun. The design phase of STIX has been concluded. This paper reports the final flight design of the instrument, focusing on design challenges that were faced recently and how they were addressed.

  11. Design and challenges for a tsunami early warning system in the Marmara Sea

    Necmioğlu, Öcal

    2016-01-01

    Since 1900, around 90,000 people have lost their lives in 76 earthquakes in Turkey, with a total affected population of around 7 million and direct losses of around 25 billion USD. Based on a time-dependent model that includes coseismic and post-seismic effects of the 1999 Kocaeli earthquake with moment magnitude Mw = 7.4, Parsons (J Geophys Res. 109, 2004) concluded that the probability of an earthquake with Mw > 7 in the Sea of Marmara near Istanbul is 35 to 70 % in the next 30 years. According to a 2011 study, an earthquake with Mw = 7.25 on the Main Marmara Fault is expected to heavily damage or destroy 2 to 4 % of around 1,000,000 buildings in Istanbul with a population around 13 million, with 9 to 15 % of the buildings receiving medium damage and 20 to 34 % of the buildings damaged lightly (Erdik, Science 341:72, 2013). In the absence of adequate post-earthquake assembly areas especially in the heavily urbanized Istanbul, it is evident that after a major earthquake, especially in the coastal parts of the city, citizens would be storming to landfill assembly and recreational areas. Besides earthquakes, around 30 tsunamis have been reported by Altınok et al. (Natural Hazards Earth System Science 11:273-293, 2011) in the Marmara Sea. Among those, catastrophic earthquakes such as 1509, 1766, and 1894 resulted in considerable tsunamis and some damage. The latest tsunami observed in Marmara was due to a triggered submarine landslide of the 1999 Mw = 7.4 Kocaeli earthquake which led to reported run-up heights of 1-3 m in most places (Tinti et al., Marine Geology 225:311-330, 2006). In this study, I propose a design for a tsunami warning system specific for the Marmara region that is strongly coupled with the earthquake early warning system (due to the short arrival times of tsunami) and stakeholders of the tsunami mitigation activities, such as local and regional components of disaster and emergency management and civil protection units, to ensure that the citizens

  12. Oligonucleotide Aptamers: New Tools for Targeted Cancer Therapy

    Hongguang Sun

    2014-01-01

    Full Text Available Aptamers are a class of small nucleic acid ligands that are composed of RNA or single-stranded DNA oligonucleotides and have high specificity and affinity for their targets. Similar to antibodies, aptamers interact with their targets by recognizing a specific three-dimensional structure and are thus termed “chemical antibodies.” In contrast to protein antibodies, aptamers offer unique chemical and biological characteristics based on their oligonucleotide properties. Hence, they are more suitable for the development of novel clinical applications. Aptamer technology has been widely investigated in various biomedical fields for biomarker discovery, in vitro diagnosis, in vivo imaging, and targeted therapy. This review will discuss the potential applications of aptamer technology as a new tool for targeted cancer therapy with emphasis on the development of aptamers that are able to specifically target cell surface biomarkers. Additionally, we will describe several approaches for the use of aptamers in targeted therapeutics, including aptamer-drug conjugation, aptamer-nanoparticle conjugation, aptamer-mediated targeted gene therapy, aptamer-mediated immunotherapy, and aptamer-mediated biotherapy.

  13. The use of oligonucleotide probes for meningococcal serotype characterization

    SACCHI Claudio Tavares

    1998-01-01

    Full Text Available In the present study we examine the potential use of oligonucleotide probes to characterize Neisseria meningitidis serotypes without the use of monoclonal antibodies (MAbs. Antigenic diversity on PorB protein forms the bases of serotyping method. However, the current panel of MAbs underestimated, by at least 50% the PorB variability, presumably because reagents for several PorB variable regions (VRs are lacking, or because a number of VR variants are not recognized by serotype-defining MAbs12. We analyzed the use of oligonucleotide probes to characterize serotype 10 and serotype 19 of N. meningitidis. The porB gene sequence for the prototype strain of serotype 10 was determined, aligned with 7 other porB sequences from different serotypes, and analysis of individual VRs were performed. The results of DNA probes 21U (VR1-A and 615U (VR3-B used against 72 N. meningitidis strains confirm that VR1 type A and VR3 type B encode epitopes for serotype-defined MAbs 19 and 10, respectively. The use of probes for characterizing serotypes possible can type 100% of the PorB VR diversity. It is a simple and rapid method specially useful for analysis of large number of samples.

  14. Differentiation of the seven major lyssavirus species by oligonucleotide microarray.

    Xi, Jin; Guo, Huancheng; Feng, Ye; Xu, Yunbin; Shao, Mingfu; Su, Nan; Wan, Jiayu; Li, Jiping; Tu, Changchun

    2012-03-01

    An oligonucleotide microarray, LyssaChip, has been developed and verified as a highly specific diagnostic tool for differentiation of the 7 major lyssavirus species. As with conventional typing microarray methods, the LyssaChip relies on sequence differences in the 371-nucleotide region coding for the nucleoprotein. This region was amplified using nested reverse transcription-PCR primers that bind to the 7 major lyssaviruses. The LyssaChip includes 57 pairs of species typing and corresponding control oligonucleotide probes (oligoprobes) immobilized on glass slides, and it can analyze 12 samples on a single slide within 8 h. Analysis of 111 clinical brain specimens (65 from animals with suspected rabies submitted to the laboratory and 46 of butchered dog brain tissues collected from restaurants) showed that the chip method was 100% sensitive and highly consistent with the "gold standard," a fluorescent antibody test (FAT). The chip method could detect rabies virus in highly decayed brain tissues, whereas the FAT did not, and therefore the chip test may be more applicable to highly decayed brain tissues than the FAT. LyssaChip may provide a convenient and inexpensive alternative for diagnosis and differentiation of rabies and rabies-related diseases.

  15. Benefits and challenges of using the cohort multiple randomised controlled trial design for testing an intervention for depression.

    Viksveen, Petter; Relton, Clare; Nicholl, Jon

    2017-07-06

    Trials which test the effectiveness of interventions compared with the status quo frequently encounter challenges. The cohort multiple randomised controlled trial (cmRCT) design is an innovative approach to the design and conduct of pragmatic trials which seeks to address some of these challenges. In this article, we report our experiences with the first completed randomised controlled trial (RCT) using the cmRCT design. This trial-the Depression in South Yorkshire (DEPSY) trial-involved comparison of treatment as usual (TAU) with TAU plus the offer of an intervention for people with self-reported long-term moderate to severe depression. In the trial, we used an existing large population-based cohort: the Yorkshire Health Study. We discuss our experiences with recruitment, attrition, crossover, data analysis, generalisability of results, and cost. The main challenges in using the cmRCT design were the high crossover to the control group and the lower questionnaire response rate among patients who refused the offer of treatment. However, the design did help facilitate efficient and complete recruitment of the trial population as well as analysable data that were generalisable to the population of interest. Attrition rates were also smaller than those reported in other depression trials. This first completed full trial using the cmRCT design testing an intervention for self-reported depression was associated with a number of important benefits. Further research is required to compare the acceptability and cost effectiveness of standard pragmatic RCT design with the cmRCT design. ISRCTN registry: ISRCTN02484593 . Registered on 7 Jan 2013.

  16. 2015 Summer Design Challenge: Team A&E (2241) Additively Manufactured Discriminator.

    Miller, Sarah E. [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States); Moore, Brandon James [Sandia National Laboratories (SNL-NM), Albuquerque, NM (United States)

    2016-11-01

    Current discriminator designs are based on historical designs and traditional manufacturing methods. The goal of this project was to form non-traditional groups to create novel discriminator designs by taking advantage of additive manufacturing. These designs would expand current discriminator designs and provide insight on the applicability of additive manufacturing for future projects. Our design stretched the current abilities of additive manufacturing and noted desired improvements for the future. Through collaboration with NSC, we noted several additional technologies which work well with additive manufacturing such as topology optimization and CT scanning and determined how these technologies could be improved to better combine with additive manufacturing.

  17. Academic Performance as a Predictor of Student Growth in Achievement and Mental Motivation During an Engineering Design Challenge in Engineering and Technology Education

    Mentzer, Nathan

    2008-01-01

    The purpose of this correlational research study was to determine if students’ academic success was correlated with: (a) the student change in achievement during an engineering design challenge; and (b) student change in mental motivation toward solving problems and critical thinking during an engineering design challenge. Multiple experimental studies have shown engineering design challenges increase student achievement and attitude toward learning, but conflicting evidence surrounded the im...

  18. Synthesis of 3'-, or 5'-, or internal methacrylamido-modified oligonucleotides

    Golova, Julia B.; Chernov, Boris K.

    2010-04-27

    New modifiers were synthesized for incorporation of a methacrylic function in 3'-, 5'- and internal positions of oligonucleotides during solid phase synthesis. A modifier was used for synthesis of 5'-methacrylated oligonucleotides for preparation of microarrays by a co-polymerization method.

  19. Nucleobase-modified antisense oligonucleotides containing 5-(phenyltriazol)-2′-deoxyuridine nucleotides induce exon-skipping

    Le, Bao T.; Hornum, Mick; Sharma, Pawan K.

    2017-01-01

    Chemically-modified antisense oligonucleotide-mediated exon-skipping has been validated as a therapeutic strategy for tackling several disease pathologies, particularly duchenne muscular dystrophy. To date, only sugar-modified and internucleotide linkage-modified oligonucleotide chemistries have...

  20. [Oligonucleotide derivatives in the nucleic acid hybridization analysis. I. Covalent immobilization of oligonucleotide probes onto the nylon].

    Dmitrienko, E V; Pyshnaia, I A; Pyshnyĭ, D V

    2010-01-01

    The features of UV-induced immobilization of oligonucleotides on a nylon membranes and the effectiveness of enzymatic labeling of immobilized probes at heterophase detection of nucleic acids are studied. Short terminal oligothymidilate (up to 10 nt) sequences are suggested to attach to the probe via a flexible ethylene glycol based linker. The presence of such fragment enhances the intensity of immobilization and reduces UV-dependent degradation of the targeted (sequence-specific) part of the probe by reducing the dose needed for the immobilization of DNA. The optimum dose of UV-irradiation is determined to be ~0.4 J/cm(2) at the wavelength 254 nm. This dose provides high level of hybridization signal for immobilized probes with various nucleotide composition of the sequence specific moiety. The amide groups of the polyamide are shown to play the key role in the photoinduced immobilization of nucleic acids, whereas the primary amino groups in the structure of PA is not the center responsible for the covalent binding of DNA by UV-irradiation, as previously believed. Various additives in the soaking solution during the membrane of UV-dependent immobilization of probes are shown to influence its effectiveness. The use of alternative to UV-irradiation system of radical generation are shown to provide the immobilization of oligonucleotides onto the nylon membrane.

  1. Thermal Protection for Mars Sample Return Earth Entry Vehicle: A Grand Challenge for Design Methodology and Reliability Verification

    Venkatapathy, Ethiraj; Gage, Peter; Wright, Michael J.

    2017-01-01

    Mars Sample Return is our Grand Challenge for the coming decade. TPS (Thermal Protection System) nominal performance is not the key challenge. The main difficulty for designers is the need to verify unprecedented reliability for the entry system: current guidelines for prevention of backward contamination require that the probability of spores larger than 1 micron diameter escaping into the Earth environment be lower than 1 million for the entire system, and the allocation to TPS would be more stringent than that. For reference, the reliability allocation for Orion TPS is closer to 11000, and the demonstrated reliability for previous human Earth return systems was closer to 1100. Improving reliability by more than 3 orders of magnitude is a grand challenge indeed. The TPS community must embrace the possibility of new architectures that are focused on reliability above thermal performance and mass efficiency. MSR (Mars Sample Return) EEV (Earth Entry Vehicle) will be hit with MMOD (Micrometeoroid and Orbital Debris) prior to reentry. A chute-less aero-shell design which allows for self-righting shape was baselined in prior MSR studies, with the assumption that a passive system will maximize EEV robustness. Hence the aero-shell along with the TPS has to take ground impact and not break apart. System verification will require testing to establish ablative performance and thermal failure but also testing of damage from MMOD, and structural performance at ground impact. Mission requirements will demand analysis, testing and verification that are focused on establishing reliability of the design. In this proposed talk, we will focus on the grand challenge of MSR EEV TPS and the need for innovative approaches to address challenges in modeling, testing, manufacturing and verification.

  2. Human-Centred Design Projects and Co-Design in/outside the Turkish Classroom: Responses and Challenges

    Emmanouil, Marina

    2015-01-01

    Perhaps more than any other professional group in modern history, designers have felt compelled to undertake the responsibility of addressing and engaging with societal problems in their practice. Initially, this liability involved concerns of form and production methods during the industrial revolution era, and developed into existential, ethical…

  3. Teaching Social Media Journalism: Challenges and Opportunities for Future Curriculum Design

    Bor, Stephanie E.

    2014-01-01

    In response to the growing demand for digitally competent employees in the news media industry, journalism schools are cautiously integrating social media reporting into their curriculum. This study explores techniques for teaching news reporting on social media platforms focusing on challenges and opportunities for learning engagement that…

  4. Identity-Centered Conflicts, Authority, and Dogmatism: Challenges for the Design of Social Studies Curriculum

    Brandhorst, Allan R.

    2004-01-01

    One of the greatest challenges to a peace education curriculum is preparing young people to deal with conflicts over issues central to identity. These kinds of conflict can threaten beliefs derived from authority and, accordingly, may be characterized by cognitive rigidity. Various factors central to constructive conflict resolution are…

  5. Designing Capacity-Building in E-Learning Expertise: Challenges and Strategies

    Aczel, J. C.; Peake, S. R.; Hardy, P.

    2008-01-01

    This research study looks at how organizations in developing countries perceive the challenge of building capacity in e-learning expertise. Data was collected on six such organizations, and a range of perceived rationales and constraints were identified. The paper hypothesizes a four-part framework to define the e-learning capacity gaps that these…

  6. Capturing Collaborative Challenges: Designing Complexity-Sensitive Theories of Change for Cross-Sector Partnerships

    R.J.M. van Tulder (Rob); Keen, N. (Nienke)

    2018-01-01

    textabstractSystems change requires complex interventions. Cross-sector partnerships (CSPs) face the daunting task of addressing complex societal problems by aligning different backgrounds, values, ideas and resources. A major challenge for CSPs is how to link the type of partnership to the

  7. Mechanism of inhibition of HIV-1 integrase by G-tetrad-forming oligonucleotides in Vitro.

    Jing, N; Marchand, C; Liu, J; Mitra, R; Hogan, M E; Pommier, Y

    2000-07-14

    The G-tetrad-forming oligonucleotides and have been identified as potent inhibitors of human immunodeficiency virus type 1 integrase (HIV-1 IN) activity (Rando, R. F., Ojwang, J., Elbaggari, A., Reyes, G. R., Tinder, R., McGrath, M. S., and Hogan, M. E. (1995) J. Biol. Chem. 270, 1754-1760; Mazumder, A., Neamati, N., Ojwang, J. O., Sunder, S., Rando, R. F., and Pommier, Y. (1996) Biochemistry 35, 13762-13771; Jing, N., and Hogan, M. E. (1998) J. Biol. Chem. 273, 34992-34999). To understand the inhibition of HIV-1 IN activity by the G-quartet inhibitors, we have designed the oligonucleotides and, composed of three and four G-quartets with stem lengths of 19 and 24 A, respectively. The fact that increasing the G-quartet stem length from 15 to 24 A kept inhibition of HIV-1 IN activity unchanged suggests that the binding interaction occurs between a GTGT loop domain of the G-quartet inhibitors and a catalytic site of HIV-1 IN, referred to as a face-to-face interaction. Docking the NMR structure of (Jing and Hogan (1998)) into the x-ray structure of the core domain of HIV-1 IN, HIV-1 IN-(51-209) (Maignan, S., Guilloteau, J.-P. , Qing, Z.-L., Clement-Mella, C., and Mikol, V. (1998) J. Mol. Biol. 282, 359-368), was performed using the GRAMM program. The statistical distributions of hydrogen bonding between HIV-1 IN and were obtained from the analyses of 1000 random docking structures. The docking results show a high probability of interaction between the GTGT loop residues of the G-quartet inhibitors and the catalytic site of HIV-1 IN, in agreement with the experimental observation.

  8. Public Health Insurance in Vietnam towards Universal Coverage: Identifying the challenges, issues, and problems in its design and organizational practices

    Midori Matsushima; Hiroyuki Yamada

    2013-01-01

    Vietnam is attempting to achieve universal health insurance coverage by 2014. Despite great progress, the country faces some challenges, issues and problems. This paper reviewed official documents, existing reports, and related literature to address: (1) grand design for achieving universal health coverage, (2) current insurance coverage, (3) health insurance premium and subsidies by the government, (4) benefit package and payment rule, and (5) organizational practices. From the review, it be...

  9. From print to web to e-paper: the challenge of designing the e-newspaper

    C. Ihlström; M.Å. kesson; S. Nodqvist

    2004-01-01

    This paper presents future scenarios of use and design of the e-newspaper, i.e. the newspaper on epaper. These scenarios are based on experiences from prototyping e-newspaper interfaces and from a survey with newspaper designers and management. The findings show e.g. that the design from the printed edition and the functionality of the online newspaper were considered preferable attributes for the e-newspaper, and that mobility, interactivity, adjustment for special target groups and personal...

  10. Challenges in thermal design of industrial single-phase power inverter

    Ninković Predrag

    2016-01-01

    Full Text Available This paper presents the influence of thermal aspects in design process of an industrial single-phase inverter, choice of its topology and components. Stringent design inputs like very high overload level, demand for natural cooling and very wide input voltage range have made conventional circuit topology inappropriate therefore asking for alternative solution. Different power losses calculations in semiconductors are performed and compared, outlining the guidelines how to choose the final topology. Some recommendations in power magnetic components design are given. Based on the final project, a 20kVA single-phase inverter for thermal power plant supervisory and control system is designed and commissioned.

  11. Challenges of implementation and implementation research: Learning from an intervention study designed to improve tumor registry reporting

    Ann Scheck McAlearney

    2016-08-01

    Full Text Available Objectives: Implementation of interventions designed to improve the quality of medical care often proceeds differently from what is planned. Improving existing conceptual models to better understand the sources of these differences can help future projects avoid these pitfalls and achieve desired effectiveness. To inform an adaptation of an existing theoretical model, we examined unanticipated changes that occurred in an intervention designed to improve reporting of adjuvant therapies for breast cancer patients at a large, urban academic medical center. Methods: Guided by the complex innovation implementation conceptual framework, our study team observed and evaluated the implementation of an intervention designed to improve reporting to a tumor registry. Findings were assessed against the conceptual framework to identify boundary conditions and modifications that could improve implementation effectiveness. Results: The intervention successfully increased identification of the managing medical oncologist and treatment reporting. During implementation, however, unexpected external challenges including hospital acquisitions of community practices and practices’ responses to government incentives to purchase electronic medical record systems led to unanticipated changes and associated threats to implementation. We present a revised conceptual model that incorporates the sources of these unanticipated challenges. Conclusion: This report of our experience highlights the importance of monitoring implementation over time and accounting for changes that affect both implementation and measurement of intervention impact. In this article, we use our study to examine the challenges of implementation research in health care, and our experience can help future implementation efforts.

  12. Two conceptual designs of helical fusion reactor FFHR-d1A based on ITER technologies and challenging ideas

    Sagara, A.; Miyazawa, J.; Tamura, H.; Tanaka, T.; Goto, T.; Yanagi, N.; Sakamoto, R.; Masuzaki, S.; Ohtani, H.; The FFHR Design Group

    2017-08-01

    The Fusion Engineering Research Project (FERP) at the National Institute for Fusion Science (NIFS) is conducting conceptual design activities for the LHD-type helical fusion reactor FFHR-d1A. This paper newly defines two design options, ‘basic’ and ‘challenging.’ Conservative technologies, including those that will be demonstrated in ITER, are chosen in the basic option in which two helical coils are made of continuously wound cable-in-conduit superconductors of Nb3Sn strands, the divertor is composed of water-cooled tungsten monoblocks, and the blanket is composed of water-cooled ceramic breeders. In contrast, new ideas that would possibly be beneficial for making the reactor design more attractive are boldly included in the challenging option in which the helical coils are wound by connecting high-temperature REBCO superconductors using mechanical joints, the divertor is composed of a shower of molten tin jets, and the blanket is composed of molten salt FLiNaBe including Ti powers to increase hydrogen solubility. The main targets of the challenging option are early construction and easy maintenance of a large and three-dimensionally complicated helical structure, high thermal efficiency, and, in particular, realistic feasibility of the helical reactor.

  13. Design Research with a Focus on Learning Processes: An Overview on Achievements and Challenges

    Prediger, Susanne; Gravemeijer, Koeno; Confrey, Jere

    2015-01-01

    Design research continues to gain prominence as a significant methodology in the mathematics education research community. This overview summarizes the origins and the current state of design research practices focusing on methodological requirements and processes of theorizing. While recognizing the rich variations in the foci and scale of design…

  14. Explicit teaching and scaffolding to enhance concept learning by design challenges

    MEd Maurice Smeets; MEd Dave van Breukelen; Prof. Dr. Marc de Vries

    2016-01-01

    This paper presents a mixed methods study in which 21 first-year student teachers took part that investigated learning outcomes of a modified learning by design task. The study is part of a series of studies that aims to improve student learning, teaching skills and teacher training. Design-based

  15. Challenges of extreme load hexapod design and modularization for large ground-based telescopes

    Gloess, Rainer; Lula, Brian

    2010-07-01

    The hexapod is a parallel kinematic manipulator that is the minimum arrangement for independent control of six degrees of freedom. Advancing needs for hexapod performance, capacity and configurations have driven development of highly capable new actuator designs. This paper describes new compact hexapod design proposals for high load capacity, and corresponding hexapod actuator only mechanisms suitable for integration as structural motion elements in next-generation telescope designs. These actuators provide up to 90 000N load capability while preserving sub-micrometer positional capability and in-position stability. The design is optimized for low power dissipation and incorporates novel encoders direct manufactured with the nut flange to achieve more than 100000 increments per revolution. In the hexapod design we choose cardan joints for the actuator that have axis offsets to provide optimized stiffness. The additional computational requirements for offset axes are readily solved by advanced kinematic algorithms and modern hardware. The paper also describes the hexapod controller concept with individual actuator designs, which allows the integration of hexapod actuators into the main telescope structure to reduce mass and provide the telescope designer more design freedom in the incorporation of these types of motion systems. An adaptive software package was developed including collision control feature for real-time safety during hexapod movements.

  16. Oligonucleotides with 1,4-dioxane-based nucleotide monomers

    Madsen, Andreas S; Wengel, Jesper

    2012-01-01

    An epimeric mixture of H-phosphonates 5R and 5S has been synthesized in three steps from known secouridine 1. Separation of the epimers has been accomplished by RP-HPLC, allowing full characterization and incorporation of monomers X and Y into 9-mer oligonucleotides using H-phosphonates building...... blocks 5R and 5S, respectively. A single incorporation of either monomer X or monomer Y in the central position of a DNA 9-mer results in decreased thermal affinity toward both DNA and RNA complements (ΔT(m) = -3.5 °C/-3.5 °C for monomer X and ΔT(m) = -11.0 °C/-6.5 °C for monomer Y). CD measurements do...

  17. The Spectral Properties and Photostability of DNA, RNA and Oligonucleotides

    Kudrya, V.Yu.; Yashchuk, V.M.

    2012-01-01

    The present work discusses the results of comparative investigations of the optical absorption, luminescence, and photostability of the biomacromolecules (DNA, RNA), as well as synthetic poly- and oligonucleotides. The separate nucleotides in DNA and RNA are examined as almost independent absorbing centers. It is confirmed that the main triplet excitons traps responsible for the DNA phosphorescence emission are AT-complexes in DNA. In contrast to DNA, the main triplet excitons traps in RNA are adenosine bases. These bases are the most photostable against UV-irradiation as compared with all other nucleotides in both DNA and RNA. The fact of the photostability of adenosine bases and the AT-complex provides the existence of the DNA/RNA self-protection mechanisms against a damage caused by UV-irradiation. It is found the deoxyribonucleotides are more photostable than the corresponding ribonucleotides. So, the results presented here show that DNA is more photostable than RNA.

  18. Electrical manipulation of oligonucleotides grafted to charged surfaces.

    Rant, Ulrich; Arinaga, Kenji; Fujita, Shozo; Yokoyama, Naoki; Abstreiter, Gerhard; Tornow, Marc

    2006-09-21

    The electrical manipulation of short DNA molecules on surfaces offers novel functionalities with fascinating possibilities in the field of bio-interfaces. Here we present systematic investigations of the electrical interactions which govern the structure of oligonucleotides on charged gold surfaces. Successively, we address influences of the applied field strength, the role of DC electrode potentials, in particular for polycrystalline surfaces, as well as screening effects of the surrounding electrolyte solution. Data obtained for single and double stranded DNA exhibit differences which can be attributed to the dissimilar flexibility of the different molecular conformations. A comparison of the experimental results with a basic model shows how the alignment of the molecules adjusts according to a balance between electrically induced ordering and stochastic thermal motions. The presented conclusions are expected to be of general relevance for the behaviour of polyelectrolytes exposed to localized electric fields at interfaces.

  19. A challenge for higher education: Wearable technology for fashion design departments

    Elif Buğra Kuzu Demir

    2016-04-01

    Full Text Available As the technology is integrated into different disciplines, we witness how powerful it can be. Rather than standing in isolation, technology changes the nature of the field it arrives in. Wearable technologies in fashion design education is a good example for this. Wearable technology defined as lightweight, easy portable and wearable smart devices that have sensors and computing capabilities. The structure of wearable technologies has brought a new trend to fashion design area. Fashion design, as known to be a very dynamic application area, has already accepted the issue and started using the most powerful examples of wearable technologies already. However, although the stages are using wearable technologies, the schools that graduate fashion designers of the future are far beyond the capacity of the stages. It is therefore; this paper brings suggestions for the integration of technology into fashion design departments in Turkey and while doing this it tries to be country specific.

  20. Direct microcontact printing of oligonucleotides for biochip applications

    Trévisiol E

    2005-07-01

    Full Text Available Abstract Background A critical step in the fabrication of biochips is the controlled placement of probes molecules on solid surfaces. This is currently performed by sequential deposition of probes on a target surface with split or solid pins. In this article, we present a cost-effective procedure namely microcontact printing using stamps, for a parallel deposition of probes applicable for manufacturing biochips. Results Contrary to a previous work, we showed that the stamps tailored with an elastomeric poly(dimethylsiloxane material did not require any surface modification to be able to adsorb oligonucleotides or PCR products. The adsorbed DNA molecules are subsequently printed efficiently on a target surface with high sub-micron resolution. Secondly, we showed that successive stamping is characterized by an exponential decay of the amount of transferred DNA molecules to the surface up the 4th print, then followed by a second regime of transfer that was dependent on the contact time and which resulted in reduced quality of the features. Thus, while consecutive stamping was possible, this procedure turned out to be less reproducible and more time consuming than simply re-inking the stamps between each print. Thirdly, we showed that the hybridization signals on arrays made by microcontact printing were 5 to 10-times higher than those made by conventional spotting methods. Finally, we demonstrated the validity of this microcontact printing method in manufacturing oligonucleotides arrays for mutations recognition in a yeast gene. Conclusion The microcontact printing can be considered as a new potential technology platform to pattern DNA microarrays that may have significant advantages over the conventional spotting technologies as it is easy to implement, it uses low cost material to make the stamp, and the arrays made by this technology are 10-times more sensitive in term of hybridization signals than those manufactured by conventional spotting

  1. An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases

    Fiszer Agnieszka

    2012-03-01

    Full Text Available Abstract Background RNA interference (RNAi and antisense strategies provide experimental therapeutic agents for numerous diseases, including polyglutamine (polyQ disorders caused by CAG repeat expansion. We compared the potential of different oligonucleotide-based strategies for silencing the genes responsible for several polyQ diseases, including Huntington's disease and two spinocerebellar ataxias, type 1 and type 3. The strategies included nonallele-selective gene silencing, gene replacement, allele-selective SNP targeting and CAG repeat targeting. Results Using the patient-derived cell culture models of polyQ diseases, we tested various siRNAs, and antisense reagents and assessed their silencing efficiency and allele selectivity. We showed considerable allele discrimination by several SNP targeting siRNAs based on a weak G-G or G-U pairing with normal allele and strong G-C pairing with mutant allele at the site of RISC-induced cleavage. Among the CAG repeat targeting reagents the strongest allele discrimination is achieved by miRNA-like functioning reagents that bind to their targets and inhibit their translation without substantial target cleavage. Also, morpholino analog performs well in mutant and normal allele discrimination but its efficient delivery to cells at low effective concentration still remains a challenge. Conclusions Using three cellular models of polyQ diseases and the same experimental setup we directly compared the performance of different oligonucleotide-based treatment strategies that are currently under development. Based on the results obtained by us and others we discussed the advantages and drawbacks of these strategies considering them from several different perspectives. The strategy aimed at nonallele-selective inhibiting of causative gene expression by targeting specific sequence of the implicated gene is the easiest to implement but relevant benefits are still uncertain. The gene replacement strategy that

  2. Lessons learned in induced fit docking and metadynamics in the Drug Design Data Resource Grand Challenge 2

    Baumgartner, Matthew P.; Evans, David A.

    2018-01-01

    Two of the major ongoing challenges in computational drug discovery are predicting the binding pose and affinity of a compound to a protein. The Drug Design Data Resource Grand Challenge 2 was developed to address these problems and to drive development of new methods. The challenge provided the 2D structures of compounds for which the organizers help blinded data in the form of 35 X-ray crystal structures and 102 binding affinity measurements and challenged participants to predict the binding pose and affinity of the compounds. We tested a number of pose prediction methods as part of the challenge; we found that docking methods that incorporate protein flexibility (Induced Fit Docking) outperformed methods that treated the protein as rigid. We also found that using binding pose metadynamics, a molecular dynamics based method, to score docked poses provided the best predictions of our methods with an average RMSD of 2.01 Å. We tested both structure-based (e.g. docking) and ligand-based methods (e.g. QSAR) in the affinity prediction portion of the competition. We found that our structure-based methods based on docking with Smina (Spearman ρ = 0.614), performed slightly better than our ligand-based methods (ρ = 0.543), and had equivalent performance with the other top methods in the competition. Despite the overall good performance of our methods in comparison to other participants in the challenge, there exists significant room for improvement especially in cases such as these where protein flexibility plays such a large role.

  3. Challenging encapsulation in the design of high-risk control systems

    Dvorak, D.

    2002-01-01

    An apporpriate architectural approach is to acknowledge the underlying physics and to elevate the concepts of state and models to first-class design elements that are not encapsulated within subsystem objects.

  4. Establishing Design Storm Values from Climate Models in Coastal Regions: Challenges and Opportunities

    Dynamic interactions of atmospheric and hydrological processes result in large spatiotemporal changes of precipitation and wind speed in coastal storm events under both current and future climates. This variability can impact the design and sustainability of water infrastructure ...

  5. Designing flexibility into the U.S. transportation system : adapting to the challenges of climate change

    2009-01-01

    Fundamental to the application of engineering design standards is an understanding of how environmental factors and conditions will affect both the behavior of the overall structure itself as well as of the individual material components of the desig...

  6. On challenges and opportunities of designing integrated IT platforms for supporting knowledge works in organizations

    Laha, Arijit

    2009-01-01

    Designing and implementing comprehensive IT-based support environments for KM in organizations is fraught with many problems. Solving them requires intimate knowledge about the information usage in knowledge works and the scopes of technology intervention. In this paper, the Task-oriented Organizational Knowledge Management or TOKM, a design theory for building integrated IT platforms for supporting organizational KM, is proposed. TOKM brings together two apparently mutually exclusive practic...

  7. Polymerase-endonuclease amplification reaction (PEAR for large-scale enzymatic production of antisense oligonucleotides.

    Xiaolong Wang

    Full Text Available Antisense oligonucleotides targeting microRNAs or their mRNA targets prove to be powerful tools for molecular biology research and may eventually emerge as new therapeutic agents. Synthetic oligonucleotides are often contaminated with highly homologous failure sequences. Synthesis of a certain oligonucleotide is difficult to scale up because it requires expensive equipment, hazardous chemicals and a tedious purification process. Here we report a novel thermocyclic reaction, polymerase-endonuclease amplification reaction (PEAR, for the amplification of oligonucleotides. A target oligonucleotide and a tandem repeated antisense probe are subjected to repeated cycles of denaturing, annealing, elongation and cleaving, in which thermostable DNA polymerase elongation and strand slipping generate duplex tandem repeats, and thermostable endonuclease (PspGI cleavage releases monomeric duplex oligonucleotides. Each round of PEAR achieves over 100-fold amplification. The product can be used in one more round of PEAR directly, and the process can be further repeated. In addition to avoiding dangerous materials and improved product purity, this reaction is easy to scale up and amenable to full automation. PEAR has the potential to be a useful tool for large-scale production of antisense oligonucleotide drugs.

  8. Optimal design of microalgae-based biorefinery: Economics, opportunities and challenges

    Rizwan, Muhammad; Lee, Jay H.; Gani, Rafiqul

    2015-01-01

    Microalgae have great potential as a feedstock for the production of a wide range of end-products under the broad concept of biorefinery. In an earlier work, we proposed a superstructure based optimization model to find the optimal processing pathway for the production of biodiesel from microalgal...... biomass, and identified several challenges with the focus being on utilizing lipids extracted microalgal biomass for economic and environmentally friendly production of useful energy products. In this paper, we expand the previous optimization framework by considering the processing of microalgae residue...

  9. R&D Challenges for SFR Design and Safety Analysis – Opportunities for International Cooperations

    Devictor, Nicolas

    2013-01-01

    Examples of R&D challenges related to safety have been presented. For any domain, R&D activities includes modelling, codes development and their V&V process, with the support of experimental programs. The success in the R&D will help the safety case and the acceptability of SFR. Some of these activities are relevant for international cooperation especially benchmarks and sharing of experimental facilities. This last point could take benefit of recent catalogues experimental facilities (already operational or in project), for example from the TAREF Task Force of OECD/NEA and the European project ADRIANA

  10. mathFISH, a Web Tool That Uses Thermodynamics-Based Mathematical Models for In Silico Evaluation of Oligonucleotide Probes for Fluorescence In Situ Hybridization▿ †

    Yilmaz, L. Safak; Parnerkar, Shreyas; Noguera, Daniel R.

    2010-01-01

    Mathematical models of RNA-targeted fluorescence in situ hybridization (FISH) for perfectly matched and mismatched probe/target pairs are organized and automated in web-based mathFISH (http://mathfish.cee.wisc.edu). Offering the users up-to-date knowledge of hybridization thermodynamics within a theoretical framework, mathFISH is expected to maximize the probability of success during oligonucleotide probe design.

  11. mathFISH, a web tool that uses thermodynamics-based mathematical models for in silico evaluation of oligonucleotide probes for fluorescence in situ hybridization.

    Yilmaz, L Safak; Parnerkar, Shreyas; Noguera, Daniel R

    2011-02-01

    Mathematical models of RNA-targeted fluorescence in situ hybridization (FISH) for perfectly matched and mismatched probe/target pairs are organized and automated in web-based mathFISH (http://mathfish.cee.wisc.edu). Offering the users up-to-date knowledge of hybridization thermodynamics within a theoretical framework, mathFISH is expected to maximize the probability of success during oligonucleotide probe design.

  12. Introduction on Using the FastPCR Software and the Related Java Web Tools for PCR and Oligonucleotide Assembly and Analysis.

    Kalendar, Ruslan; Tselykh, Timofey V; Khassenov, Bekbolat; Ramanculov, Erlan M

    2017-01-01

    This chapter introduces the FastPCR software as an integrated tool environment for PCR primer and probe design, which predicts properties of oligonucleotides based on experimental studies of the PCR efficiency. The software provides comprehensive facilities for designing primers for most PCR applications and their combinations. These include the standard PCR as well as the multiplex, long-distance, inverse, real-time, group-specific, unique, overlap extension PCR for multi-fragments assembling cloning and loop-mediated isothermal amplification (LAMP). It also contains a built-in program to design oligonucleotide sets both for long sequence assembly by ligase chain reaction and for design of amplicons that tile across a region(s) of interest. The software calculates the melting temperature for the standard and degenerate oligonucleotides including locked nucleic acid (LNA) and other modifications. It also provides analyses for a set of primers with the prediction of oligonucleotide properties, dimer and G/C-quadruplex detection, linguistic complexity as well as a primer dilution and resuspension calculator. The program consists of various bioinformatical tools for analysis of sequences with the GC or AT skew, CG% and GA% content, and the purine-pyrimidine skew. It also analyzes the linguistic sequence complexity and performs generation of random DNA sequence as well as restriction endonucleases analysis. The program allows to find or create restriction enzyme recognition sites for coding sequences and supports the clustering of sequences. It performs efficient and complete detection of various repeat types with visual display. The FastPCR software allows the sequence file batch processing that is essential for automation. The program is available for download at http://primerdigital.com/fastpcr.html , and its online version is located at http://primerdigital.com/tools/pcr.html .

  13. Quantification of Different Eubacterium spp. in Human Fecal Samples with Species-Specific 16S rRNA-Targeted Oligonucleotide Probes

    Schwiertz, Andreas; Le Blay, Gwenaelle; Blaut, Michael

    2000-01-01

    Species-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)-labeled oligonucleotide probes were designed and validated to quantify different Eubacterium species in human fecal samples. Probes were directed at Eubacterium barkeri, E. biforme, E. contortum, E. cylindroides (two probes), E. dolichum, E. hadrum, E. lentum, E. limosum, E. moniliforme, and E. ventriosum. The specificity of the probes was tested with the type strains and a range of common intestinal bacteria. With one exception, none...

  14. Lap time simulation and design optimisation of a brushed DC electric motorcycle for the Isle of Man TT Zero Challenge

    Dal Bianco, N.; Lot, R.; Matthys, K.

    2018-01-01

    This works regards the design of an electric motorcycle for the annual Isle of Man TT Zero Challenge. Optimal control theory was used to perform lap time simulation and design optimisation. A bespoked model was developed, featuring 3D road topology, vehicle dynamics and electric power train, composed of a lithium battery pack, brushed DC motors and motor controller. The model runs simulations over the entire ? or ? of the Snaefell Mountain Course. The work is validated using experimental data from the BX chassis of the Brunel Racing team, which ran during the 2009 to 2015 TT Zero races. Optimal control is used to improve drive train and power train configurations. Findings demonstrate computational efficiency, good lap time prediction and design optimisation potential, achieving a 2 minutes reduction of the reference lap time through changes in final drive gear ratio, battery pack size and motor configuration.

  15. Design and Evaluation of Reform Plan for Local Academic Nursing Challenges Using Action Research.

    Asadizaker, Marziyeh; Abedsaeedi, Zhila; Abedi, Heidarali; Saki, Azadeh

    2016-12-01

    This study identifies challenges to the first nurse training program for undergraduate nursing students at a nursing and midwifery school in Iran using a collaborative approach in order to improve the program. Action research was used as a research strategy with qualitative content analysis and quantitative evaluation. The participants were 148 individuals from nursing academic and clinical settings, including administrators, faculty members, students, and staff nurses. We obtained approval from the research deputy and ethics committee of Shahid Beheshti University of Medical Sciences in Tehran, Iran for this study. Lack of coherence in the educational program and implementation of the program, inadequate communication between management inside and outside the organization, insufficient understanding of situations by students, and improper control of inhibitors and use of facilitators in teaching and in practice were among the major challenges in the first training process in the context of this study. After classification of problems, the educational decision-making authorities of the school developed an operational program with stakeholder cooperation to plan initial reforms, implementation of reforms, reflection about the actions, and evaluation. Comparison of student satisfaction with the collaborative learning process versus the traditional method showed that except for the atmosphere in the clinical learning environment (p>.05), the mean differences for all dimensions were statistically significant. The results confirm the overall success of the revised partnership program, but stressed the need for further modification of some details for its implementation in future rounds. Copyright © 2016. Published by Elsevier B.V.

  16. Opportunities and Challenges in the Design and Analysis of Biomass Supply Chains

    Lautala, Pasi T.; Hilliard, Michael R.; Webb, Erin; Busch, Ingrid; Richard Hess, J.; Roni, Mohammad S.; Hilbert, Jorge; Handler, Robert M.; Bittencourt, Roger; Valente, Amir; Laitinen, Tuuli

    2015-12-01

    The biomass supply chain is one of the most critical elements of large-scale bioenergy production and in many cases a key barrier for procuring initial funding for new developments on specific energy crops. Most productions rely on complex transforming chains linked to feed and food markets. The term `supply chain' covers various aspects from cultivation and harvesting of the biomass, to treatment, transportation, and storage. After energy conversion, the product must be delivered to final consumption, whether it is in the form of electricity, heat, or more tangible products, such as pellets and biofuels. Effective supply chains are of utmost importance for bioenergy production, as biomass tends to possess challenging seasonal production cycles and low mass, energy and bulk densities. Additionally, the demand for final products is often also dispersed, further complicating the supply chain. The goal of this paper is to introduce key components of biomass supply chains, examples of related modeling applications, and if/how they address aspects related to environmental metrics and management. The paper will introduce a concept of integrated supply systems for sustainable biomass trade and the factors influencing the bioenergy supply chain landscape, including models that can be used to investigate the factors. The paper will also cover various aspects of transportation logistics, ranging from alternative modal and multi-modal alternatives to introduction of support tools for transportation analysis. Finally gaps and challenges in supply chain research are identified and used to outline research recommendations for the future direction in this area of study.

  17. Opportunities and Challenges in the Design and Analysis of Biomass Supply Chains.

    Lautala, Pasi T; Hilliard, Michael R; Webb, Erin; Busch, Ingrid; Richard Hess, J; Roni, Mohammad S; Hilbert, Jorge; Handler, Robert M; Bittencourt, Roger; Valente, Amir; Laitinen, Tuuli

    2015-12-01

    The biomass supply chain is one of the most critical elements of large-scale bioenergy production and in many cases a key barrier for procuring initial funding for new developments on specific energy crops. Most productions rely on complex transforming chains linked to feed and food markets. The term 'supply chain' covers various aspects from cultivation and harvesting of the biomass, to treatment, transportation, and storage. After energy conversion, the product must be delivered to final consumption, whether it is in the form of electricity, heat, or more tangible products, such as pellets and biofuels. Effective supply chains are of utmost importance for bioenergy production, as biomass tends to possess challenging seasonal production cycles and low mass, energy and bulk densities. Additionally, the demand for final products is often also dispersed, further complicating the supply chain. The goal of this paper is to introduce key components of biomass supply chains, examples of related modeling applications, and if/how they address aspects related to environmental metrics and management. The paper will introduce a concept of integrated supply systems for sustainable biomass trade and the factors influencing the bioenergy supply chain landscape, including models that can be used to investigate the factors. The paper will also cover various aspects of transportation logistics, ranging from alternative modal and multi-modal alternatives to introduction of support tools for transportation analysis. Finally gaps and challenges in supply chain research are identified and used to outline research recommendations for the future direction in this area of study.

  18. Synthetic Method for Oligonucleotide Block by Using Alkyl-Chain-Soluble Support.

    Matsuno, Yuki; Shoji, Takao; Kim, Shokaku; Chiba, Kazuhiro

    2016-02-19

    A straightforward method for the synthesis of oligonucleotide blocks using a Cbz-type alkyl-chain-soluble support (Z-ACSS) attached to the 3'-OH group of 3'-terminal nucleosides was developed. The Z-ACSS allowed for the preparation of fully protected deoxyribo- and ribo-oligonucleotides without chromatographic purification and released dimer- to tetramer-size oligonucleotide blocks via hydrogenation using a Pd/C catalyst without significant loss or migration of protective groups such as 5'-end 4,4'-dimethoxtrityl, 2-cyanoethyl on internucleotide bonds, or 2'-TBS.

  19. Solid-phase synthesis of 2{sup '}-O-methoxyethyl oligonucleotides using dimeric phosphoramidate blocks

    Yu, Gi Weon; Kang, Yong Han [Dept. of Applied Chemistry, Hanyang University, Ansan (Korea, Republic of)

    2016-11-15

    This research focused on the method of using dimeric phosphoramidite blocks to synthesize oligonucleotides for development as oligonucleotide drugs. A 16-mer oligonucleotide with the randomly selected sequence of C*C*T*C*G*C *T*C*T*C*G*C*C* C*G*C was synthesized using CC, GC, and TC dimers, a combination of monomers and dimers, or only monomers as building blocks. Using dimer blocks in this synthetic method provided a significant decrease in critical impurities that had similar properties to the main product, which was confirmed by LC-MS and HPLC analysis.

  20. Dielectric properties of DNA oligonucleotides on the surface of silicon nanostructures

    Bagraev, N. T., E-mail: bagraev@mail.ioffe.ru [St. Petersburg Polytechnic University (Russian Federation); Chernev, A. L. [Russian Academy of Sciences, St. Petersburg Academic University—Nanotechnology Research and Education Center (Russian Federation); Klyachkin, L. E. [St. Petersburg Polytechnic University (Russian Federation); Malyarenko, A. M. [Russian Academy of Sciences, Ioffe Physical–Technical Institute (Russian Federation); Emel’yanov, A. K.; Dubina, M. V. [Russian Academy of Sciences, St. Petersburg Academic University—Nanotechnology Research and Education Center (Russian Federation)

    2016-10-15

    Planar silicon nanostructures that are formed as a very narrow silicon quantum well confined by δ barriers heavily doped with boron are used to study the dielectric properties of DNA oligonucleotides deposited onto the surface of the nanostructures. The capacitance characteristics of the silicon nanostructures with oligonucleotides deposited onto their surface are determined by recording the local tunneling current–voltage characteristics by means of scanning tunneling microscopy. The results show the possibility of identifying the local dielectric properties of DNA oligonucleotide segments consisting of repeating G–C pairs. These properties apparently give grounds to correlate the segments with polymer molecules exhibiting the properties of multiferroics.

  1. From Playground to Salon: Challenges in Designing a System for Online Public Debate

    Løvlie, Anders Sundnes

    2017-01-01

    This article brings together two separate strands of media research: Online comments and media design. Online comments have long been a topic of much concern, both among scholars and the public at large, fearing negative effects from phenomena such as echo chambers, filter bubbles and hate speech......" model to a "salon" model. Building on Löwgren and Reimer's work on collaborative media, I suggest some of the broadcaster's struggles point to a lack of adequate methods for balancing interaction design concerns with the concerns of mass communication and journalism....

  2. Rational design of new materials using recombinant structural proteins: Current state and future challenges.

    Sutherland, Tara D; Huson, Mickey G; Rapson, Trevor D

    2018-01-01

    Sequence-definable polymers are seen as a prerequisite for design of future materials, with many polymer scientists regarding such polymers as the holy grail of polymer science. Recombinant proteins are sequence-defined polymers. Proteins are dictated by DNA templates and therefore the sequence of amino acids in a protein is defined, and molecular biology provides tools that allow redesign of the DNA as required. Despite this advantage, proteins are underrepresented in materials science. In this publication we investigate the advantages and limitations of using proteins as templates for rational design of new materials. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  3. Social innovation through disruptive interactions based on new media as a design strategy for empowering socially challenged communities

    Messeter, Jörn

    media can counteract negative influences in the community, e.g. drug abuse and gangsterism. Interviews with staff and participants reveal that social media use differ from what is reported in earlier research, in particular regarding how people connect, and relations between online and offline......This article explores potential roles of social media in community upliftment and empowement, based on a study of a non-profit NGO in a socially challenged suburb of Cape Town, South Africa. In particular, it focuses on the relation between online and offline behaviour, and how the use of social...... activities. These differences may arguably inform design for disruptive interaction to address negative influences, such as drugs and gangsterism, in socially challenged communities....

  4. The Challenge of Designing Blended Courses: From Structured Design to Creative Faculty Support! | Les beaux défis du design de cours hybrides : du design structuré à l’accompagnement créatif !

    Catherine Carré

    2015-11-01

    Full Text Available This case study deals with the implementation of an e-learning program in a business school in Canada. Cabot Business School decided to offer the program in a blended format so as to increase the flexibility of the program for clientele enrolled in the undergraduate certificate program. A pilot was initiated in 2009 starting with four hybrid courses. Now, three years later, 35 courses are being offered in blended mode by lecturers and a handful of professors who, for the most part, had no previous experience teaching online. Given the rapid development of this program, this case deals with how the instructional designer, without the benefit of any additional resources, managed to juggle both the development of the certificate program as well as parallel projects. The issues encountered deal with the extent to which the instructional designer can support faculty who are converting their courses from in-class to online, one of the main design challenges encountered by faculty. This case describes training strategies and implemented solutions provided by the instructional designer as well as the results obtained, faculty perceptions, and food for thought on the possible evolution of the role of the instructional designer.

  5. Main flexible pavement and mix design methods in Europe and challenges for the development of an European method

    Paulo Pereira

    2017-08-01

    Full Text Available Pavement and mix design represent one of the key components within the life cycle of a road infrastructure, with links to political, economic, technical, societal and environmental issues. Recent researches related to the characteristics of materials and associated behavior models both for materials and pavement, made it appropriate to consider updating current pavement design methods, and especially in the USA this has already been in process while in Europe uses of the methods developed in the early 1970s. Thus, this paper firstly presents a brief historical overview of pavement design methods, highlighting early limitations of old empirical methods. Afterwards, French, UK and Shell methods currently in use in Europe will be presented, underlining their main components in terms of methodology, traffic, climatic conditions and subgrade. The asphalt mix design and modeling in Europe are presented with their inclusion in the pavement design methods. Finally, the main challenges for the development of a European pavement design method are presented as well as the recent research developments that can be used for that method.

  6. Engineering Design Challenges in High School STEM Courses: A Compilation of Invited Position Papers

    Householder, Daniel L., Ed.

    2011-01-01

    Since its initial funding by the National Science Foundation in 2004, the National Center for Engineering and Technology Education (NCETE) has worked to understand the infusion of engineering design experiences into the high school setting. Over the years, an increasing number of educators and professional groups have participated in the expanding…

  7. Review of the application of ergonomics design of trackless mining equipment (TME) - lessons and challenges

    James, JP

    2007-06-01

    Full Text Available the design of trackless mining equipment (TME) is poor, with improvised seating, poor cabin layouts and sub-standard display instrumentation. This paper will present the key findings of two studies assessing ergonomics risk factors associated with automated...

  8. Challenges associated with the design of underground grinding plant at McArthur River project

    Jamrozek, J.S.

    2000-01-01

    McArthur River is an unique high grade uranium underground mine. Ore grinding and thickening are part of the underground operation. The grinding circuit is designed to operate in conditions different from conventional plant environments. Design of the grinding plant was a collective effort of a multi-disciplinary engineering team closely cooperating with project operating personnel. The equipment had to be selected to reflect widely varying ore properties. A user-friendly plant layout provides access to equipment inspections, services, and the delivery of necessary components. The size of the grinding chamber was limited in order to keep the rock stress levels within allowable values. All underground equipment brought to the construction site was restricted in size and weight. Plant construction faced limited storage space underground, tight erection sequencing, and schedule. Plant ventilation is a critical design feature. It efficiently removes radioactive dust from work areas, eliminates stagnant air pockets, and separates clean air from contaminated air areas. Radiation shielding on the equipment is designed to correspond with operational and maintenance functions. Plant operation is remotely controlled and requires little attendance. Video cameras are used on critical equipment and in controlled access areas. An extensive program of preventive and predictive maintenance allows highly reliable plant operation. (author)

  9. Textiles as Tangible Working Materials in Participatory Design Processes: Potentials and Challenges

    Heimdal, Elisabeth Jacobsen; Rosenqvist, Tanja Schultz

    2010-01-01

    Participatory design (PD) methods are currently of little use in the textile industry, even though the need for multiple stakeholder involvement in the industry is growing. In this paper, we argue that PD represents a potential for innovation in the textile industry, due to PD’s collaborative nat...

  10. Engineering Design and Manufacturing Challenges for a Wide-Aperture, Superconducting Quadrupole Magnet

    Kirby, G A; Bielert, E; Fessia, P; Karppinen, M; Lepoittevin, B; Lorin, C; Luzieux, S; Perez, J C; Russenschuck, S; Sahner, T; Smekens, D; Segreti, M; Durante, M

    2012-01-01

    The design and construction of a wide-aperture, superconducting quadrupole magnet for the LHC insertion region is part of a study towards a luminosity upgrade of the LHC at CERN. The engineering design of components and tooling, the procurement, and the construction work presented in this paper includes innovative features such as more porous cable insulation, a new collar structure allowing horizontal assembly with a hydraulic collaring press, tuning shims for the adjustment of field quality, a fishbone like structure for the ground-plane insulation, and an improved quench-heater design. Rapid prototyping of coil-end spacers and trial-coil winding led to improved shapes, thus avoiding the need to impregnate the ends with epoxy resin, which would block the circulation of helium. The magnet construction follows established procedures for the curing and assembly of the coils, in order to match the workflow established in CERN’s ”large magnet facility.” This requirement led to the design and procurement of...

  11. Challenging the Curriculum: Exploring the Discipline Boundaries in Art, Design and Media

    Wareing, Shan

    2011-01-01

    This review of the 5th International Conference held by the University of the Arts London's Centre for Learning and Teaching in Art and Design, 12 and 13 April 2010 at the Novotel, Tiergarten, Berlin, briefly summarizes the contributions of three keynote speakers, and considers some of the issues they raised. (Contains 1 note.)

  12. Asian American and Pacific Islander Serving Institutions: The Motivations and Challenges behind Seeking a Federal Designation

    Park, Julie J.; Chang, Mitchell J.

    2010-01-01

    This article examines the development of legislation to create a Minority Serving Institution federal designation for Asian American and Pacific Islander (AAPI) serving institutions. Specifically, the article draws from interviews with nineteen policy makers, congressional staffers, and community advocates in order to address their motivations for…

  13. Analysis of Nordic educational projects designed to meet challenges in society

    Liveng, Anne; Manninen, Jyri; Àrnason, Hróbjartur

    , process or structure identified in the successful projects: 1.Networking: Planning, implementation and development of the programme is based on networking of various - and even unexpected - organizations and players/participants. 2.Process evaluation: Continuous project development, documentation...... and analysis of results is inte-grated in the project, using Process Evaluation or Action Research 3.Flexibility: Programme offers flexible access and participation, individualized content or individualized study methods (ICT) 4.Focus on needs: A programme focuses on authentic regional, sectorial or individual...... learning providers, trade unions and other agencies supporting human development to create learning inter-ventions to address specific crisis, challenges or changes. In view of recent crises experienced by the Nordic countries The Education and Training Service Centre in Ice-land (www.frae.is) proposed...

  14. Evolving from Planning and Scheduling to Real-Time Operations Support: Design Challenges

    Marquez, Jessica J.; Ludowise, Melissa; McCurdy, Michael; Li, Jack

    2010-01-01

    Versions of Scheduling and Planning Interface for Exploration (SPIFe) have supported a variety of mission operations across NASA. This software tool has evolved and matured over several years, assisting planners who develop intricate schedules. While initially conceived for surface Mars missions, SPIFe has been deployed in other domains, where people rather than robotic explorers, execute plans. As a result, a diverse set of end-users has compelled growth in a new direction: supporting real-time operations. This paper describes the new needs and challenges that accompany this development. Among the key features that have been built for SPIFe are current time indicators integrated into the interface and timeline, as well as other plan attributes that enable execution of scheduled activities. Field tests include mission support for the Lunar CRater Observation and Sensing Satellite (LCROSS), NASA Extreme Environment Mission Operations (NEEMO) and Desert Research and Technology Studies (DRATS) campaigns.

  15. Challenges in design of Kitaev materials: Magnetic interactions from competing energy scales

    Winter, Stephen M.; Li, Ying; Jeschke, Harald O.; Valentí, Roser

    2016-06-01

    In this study, we reanalyze the magnetic interactions in the Kitaev spin-liquid candidate materials Na2IrO3,α -RuCl3 , and α -Li2IrO3 using nonperturbative exact diagonalization methods. These methods are more appropriate given the relatively itinerant nature of the systems suggested in previous works. We treat all interactions up to third neighbors on equal footing. The computed terms reveal significant long-range coupling, bond anisotropy, and/or off-diagonal couplings which we argue naturally explain the observed ordered phases in these systems. Given these observations, the potential for realizing the spin-liquid state in real materials is analyzed, and synthetic challenges are defined and explained.

  16. JSFR: Japan's challenge towards the competitive SFR design concept with innovative technologies

    Mihara, T.; Kotake, S.

    2006-01-01

    JSFR is a sodium-cooled, MOX(or metal) fuelled, advanced loop type fast reactor design concept conducting by Japan Atomic Energy Agency(JAEA) through the Feasibility Study on commercialized Fast Reactor(FR) Cycle Systems with participation of all parties concerned in Japan since 1999. The economic competitiveness is one of the crucial points and has been emphasized in the design study of JSFR. One of the ways for less construction cost is the compact NSSS design by introducing the following innovative technologies; Shortening the piping length, simplified configuration with the inverse L-shaped-pipes and a two-loop system even for a l,500MWe power plant, by adopting high chromium steel with lower thermal expansion and higher strength, Upgrading of the structural design standards at elevated temperature for sodium-cooled FR system, and Development of an integrated intermediate heat exchanger (IHX) with a mechanical pump. The other way is introducing passive decay heat removal system with natural circulation. The elimination of active components such as pony motors and blowers leads to reduction of the capacity of the BOP system such as electricity supply system, emergency DGs, HVAC system and component cooling water system. In order to attain lower power generation cost, not only less construction cost but also less operational cost including fuel cycle cost is crucial. Therefore higher burn-up of the averaged core, more than 150GWd/t, has been applied by introducing ODS steel cladding material. As a result, it is confirmed that the JSFR design concept is well suited to the development target equivalent to l,000USD/kWe (as NOAK, overnight cost), while ensuring safety. The most of the cost reduction comes from the innovative technologies. The R and D plan of these technologies was summarized as a roadmap and the R and D efforts are on going for establishing a technical scheme of FR cycle systems by around 2015

  17. A regenerated electrochemical biosensor for label-free detection of glucose and urea based on conformational switch of i-motif oligonucleotide probe

    Gao, Zhong Feng; Chen, Dong Mei [Key Laboratory of Eco-environments in Three Gorges Reservoir Region (Ministry of Education), School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Lei, Jing Lei [School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044 (China); Luo, Hong Qun, E-mail: luohq@swu.edu.cn [Key Laboratory of Eco-environments in Three Gorges Reservoir Region (Ministry of Education), School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Li, Nian Bing, E-mail: linb@swu.edu.cn [Key Laboratory of Eco-environments in Three Gorges Reservoir Region (Ministry of Education), School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)

    2015-10-15

    Improving the reproducibility of electrochemical signal remains a great challenge over the past decades. In this work, i-motif oligonucleotide probe-based electrochemical DNA (E-DNA) sensor is introduced for the first time as a regenerated sensing platform, which enhances the reproducibility of electrochemical signal, for label-free detection of glucose and urea. The addition of glucose or urea is able to activate glucose oxidase-catalyzed or urease-catalyzed reaction, inducing or destroying the formation of i-motif oligonucleotide probe. The conformational switch of oligonucleotide probe can be recorded by electrochemical impedance spectroscopy. Thus, the difference of electron transfer resistance is utilized for the quantitative determination of glucose and urea. We further demonstrate that the E-DNA sensor exhibits high selectivity, excellent stability, and remarkable regenerated ability. The human serum analysis indicates that this simple and regenerated strategy holds promising potential in future biosensing applications. - Highlights: • Conformational switch of i-motif is used for the detection of glucose and urea. • The sensor can be regenerated. • The proposed method is successfully applied in real sample assay. • Our method is label-free and inexpensive.

  18. Microsystems for enhanced control of cell behavior fundamentals, design and manufacturing strategies, applications and challenges

    2016-01-01

    This handbook focuses on the entire development process of biomedical microsystems that promote special interactions with cells. Fundamentals of cell biology and mechanobiology are described as necessary preparatory input for design tasks. Advanced design, simulation, and micro/nanomanufacturing resources, whose combined use enables the development of biomedical microsystems capable of interacting at a cellular level, are covered in depth. A detailed series of chapters is then devoted to applications based on microsystems that offer enhanced cellular control, including microfluidic devices for diagnosis and therapy, cell-based sensors and actuators (smart biodevices), microstructured prostheses for improvement of biocompatibility, microstructured and microtextured cell culture matrices for promotion of cell growth and differentiation, electrophoretic microsystems for study of cell mechanics, microstructured and microtextured biodevices for study of cell adhesion and dynamics, and biomimetic microsystems (incl...

  19. Probing a Proactive Home: Challenges in Researching and Designing Everyday Smart Environments

    Frans Mäyrä

    2006-01-01

    Full Text Available Based on the results of a 3-year interdisciplinary study, this article presents an approach in which proactive information technology was introduced into homes, and discusses the derived design principles from a human-centered perspective. The application of proactive computing in homes will face particularly sensitive conditions, as familiar and reliable household elements remain strongly preferred. Since there is considerable resistance towards the increase of information technology in homes, both the calm system behaviors and the degree of variety in aesthetic designs will play major roles in the acceptance of proactive technology. If proactive technology will be an embedded part of a home’s structures and furniture, it needs to blend with the normal, cozy standards of a real living environment and aim to enhance the homeyness or the key social and aesthetic qualities of homes.

  20. Towards a Lean Product Service Systems (PSS) Design: State of the Art, Opportunities and Challenges

    Sassanelli, Claudio; Pezzotta, Giuditta; Rossi, Monica; Terzi, Sergio; Cavalieri, Sergio

    2015-01-01

    As for conventional products, the profit generation and the market success of Product Service Systems (PSS) critically depend on the decisions taken during the initial lifecycle stages, when PSSs are conceptualized, designed, developed and engineered. Successful cases show the adoption of lean techniques in the early stages of products development, impelling the authors to assess the application of the same approaches also to PSS development. For this reasons the paper aims to report the stat...

  1. Technical Reference Suite Addressing Challenges of Providing Assurance for Fault Management Architectural Design

    Fitz, Rhonda; Whitman, Gerek

    2016-01-01

    Research into complexities of software systems Fault Management (FM) and how architectural design decisions affect safety, preservation of assets, and maintenance of desired system functionality has coalesced into a technical reference (TR) suite that advances the provision of safety and mission assurance. The NASA Independent Verification and Validation (IV&V) Program, with Software Assurance Research Program support, extracted FM architectures across the IV&V portfolio to evaluate robustness, assess visibility for validation and test, and define software assurance methods applied to the architectures and designs. This investigation spanned IV&V projects with seven different primary developers, a wide range of sizes and complexities, and encompassed Deep Space Robotic, Human Spaceflight, and Earth Orbiter mission FM architectures. The initiative continues with an expansion of the TR suite to include Launch Vehicles, adding the benefit of investigating differences intrinsic to model-based FM architectures and insight into complexities of FM within an Agile software development environment, in order to improve awareness of how nontraditional processes affect FM architectural design and system health management. The identification of particular FM architectures, visibility, and associated IV&V techniques provides a TR suite that enables greater assurance that critical software systems will adequately protect against faults and respond to adverse conditions. Additionally, the role FM has with regard to strengthened security requirements, with potential to advance overall asset protection of flight software systems, is being addressed with the development of an adverse conditions database encompassing flight software vulnerabilities. Capitalizing on the established framework, this TR suite provides assurance capability for a variety of FM architectures and varied development approaches. Research results are being disseminated across NASA, other agencies, and the

  2. Business Challenges and Design: Theory and Practice in the Furniture Industry in the Republic of Croatia

    Radović, Romina

    2013-01-01

    Background: A systematic and continuous product policy management is important for a company's competitiveness and the question is to what extent and in what way companies engaged in the furniture manufacturing sector actually apply them. Objectives: The objective of this paper is to explore to what extent the design profession is involved in the product policy and teams which define market properties of products in the furniture industry. Methods: In order to achieve the objectives of this p...

  3. Interregional Knowledge Management Workshop on Life Cycle Management of Design Basis Information. Issues, Challenges, Approaches

    Šula, Radek

    2013-01-01

    Introduction and objectives: • It is evident that the design basis area is from the point of view of knowledge sharing extremely complicated. • Time is changing and puts on us ever greater demands. • We have to analyze the near and remote surroundings and have to simplified the problem of knowledge sharing in that area. • I believe that it is graspable task for knowledge management and I will try to outline some possible context and approaches

  4. Meeting the challenges with the Douglas Aircraft Company Aeroelastic Design Optimization Program (ADOP)

    Rommel, Bruce A.

    1989-01-01

    An overview of the Aeroelastic Design Optimization Program (ADOP) at the Douglas Aircraft Company is given. A pilot test program involving the animation of mode shapes with solid rendering as well as wire frame displays, a complete aircraft model of a high-altitude hypersonic aircraft to test ADOP procedures, a flap model, and an aero-mesh modeler for doublet lattice aerodynamics are discussed.

  5. Internationalisation of the BNFL fuel and waste treatment plant designs the challenges and benefits

    Hall, M.; Lomax, J. D.

    1995-01-01

    Since the late 1970's BNFL has considerably expanded its range of fuel cycle plants, involving an investment of over US$7.5bn (55bn Won). This has included significant development of its Sellafield site with a wide variety of plants and processes to deal with spent fuel and development of its fuel fabrication facilities at the Spring fields Site. In contrast to reactors, fuel plants are constructed infrequently and it is therefore crucial to 'get it right first time'. The achievement of high levels of safety has been an important factor in the development of these facilities. BNFL has applied safety criteria which are as stringent as any other international safety criteria in terms of the extent to which radiation doses to plant workers and people off-site are minimised from both routine operations and possible fault conditions. Because the plant designs are established and supported by robust safety cases they are capable of being licensed overseas. The benefits of this are lower financial risk and shorter project timescales, due to avoiding the high design and safety case development costs (typically of the order of 20% of project cost) which are incurred in the production of a 'first of a kind' design. This paper briefly discusses the role of safety cases in the UK licensing process and the principle safety standards which are applied to BNFL plants and shows how they achieve high levels of safety by comparing them with equivalent IAEA and US based standards. It illustrates how the plants meet or exceed these safety standards by using specific data from existing safety cases supported by operational data where applicable. It discusses some of the important features of the UK approach to safety and licensing and emphasises the need to examine safety provisions on a case by case basis rather than adopting a prescriptive approach to implementing design provisions if cost effectiveness is to be achieved

  6. THE CHALLENGE OF THE PERFORMANCE CONCEPT WITHIN THE SUSTAINABILITY AND COMPUTATIONAL DESIGN FIELD

    Marcio Nisenbaum

    2017-11-01

    Full Text Available This paper discusses the notion of performance and its appropriation within the research fields related to sustainability and computational design, focusing on the design processes of the architectural and urban fields. Recently, terms such as “performance oriented design” or “performance driven architecture”, especially when related to sustainability, have been used by many authors and professionals as an attempt to engender project guidelines based on simulation processes and systematic use of digital tools. In this context, the notion of performance has basically been understood as the way in which an action is fulfilled, agreeing to contemporary discourses of efficiency and optimization – in this circumstance it is considered that a building or urban area “performs” if it fulfills certain objective sustainability evaluation criteria, reduced to mathematical parameters. This paper intends to broaden this understanding by exploring new theoretical interpretations, referring to etymological investigation, historical research, and literature review, based on authors from different areas and on the case study of the solar houses academic competition, Solar Decathlon. This initial analysis is expected to contribute to the emergence of new forms of interpretation of the performance concept, relativizing the notion of the “body” that “performs” in different manners, thus enhancing its appropriation and use within the fields of sustainability and computational design.

  7. The Politics of Reflexive Governance: Challenges for Designing Adaptive Management and Transition Management

    Jan-Peter Voß

    2011-06-01

    Full Text Available New concepts of governance take account of ambivalence, uncertainty, and distributed power in societal change. They aim for reflexivity regarding the limits of prognostic knowledge and actual control of complex processes of change. Adaptive management and transition management are two examples that evolved from the analysis of social-ecological and sociotechnical systems, respectively. Both feature strategies of collective experimentation and learning. In this paper, we ask how these two designs of reflexive governance consider politics. Based on a framework of different dimensions and levels of politics, we show that they are mainly concerned with problem solving by a focal process, but conflict and asymmetric power relations, as well as the embedding of processes within broader political contexts, are neglected. We suggest two routes for integrating politics into the design of reflexive governance: (1 recognize the politics of learning for sustainable development and develop safeguards against domination and capture by powerful actors, and (2 systematically consider the embedding of governance designs in political contexts and their ongoing dynamics for political fit.

  8. Biogas Production from Sugarcane Waste: Assessment on Kinetic Challenges for Process Designing

    Janke, Leandro; Leite, Athaydes; Nikolausz, Marcell; Schmidt, Thomas; Liebetrau, Jan; Nelles, Michael; Stinner, Walter

    2015-01-01

    Biogas production from sugarcane waste has large potential for energy generation, however, to enable the optimization of the anaerobic digestion (AD) process each substrate characteristic should be carefully evaluated. In this study, the kinetic challenges for biogas production from different types of sugarcane waste were assessed. Samples of vinasse, filter cake, bagasse, and straw were analyzed in terms of total and volatile solids, chemical oxygen demand, macronutrients, trace elements, and nutritional value. Biochemical methane potential assays were performed to evaluate the energy potential of the substrates according to different types of sugarcane plants. Methane yields varied considerably (5–181 Nm3·tonFM−1), mainly due to the different substrate characteristics and sugar and/or ethanol production processes. Therefore, for the optimization of AD on a large-scale, continuous stirred-tank reactor with long hydraulic retention times (>35 days) should be used for biogas production from bagasse and straw, coupled with pre-treatment process to enhance the degradation of the fibrous carbohydrates. Biomass immobilization systems are recommended in case vinasse is used as substrate, due to its low solid content, while filter cake could complement the biogas production from vinasse during the sugarcane offseason, providing a higher utilization of the biogas system during the entire year. PMID:26404248

  9. Biosensor-based microRNA detection: techniques, design, performance, and challenges.

    Johnson, Blake N; Mutharasan, Raj

    2014-04-07

    The current state of biosensor-based techniques for amplification-free microRNA (miRNA) detection is critically reviewed. Comparison with non-sensor and amplification-based molecular techniques (MTs), such as polymerase-based methods, is made in terms of transduction mechanism, associated protocol, and sensitivity. Challenges associated with miRNA hybridization thermodynamics which affect assay selectivity and amplification bias are briefly discussed. Electrochemical, electromechanical, and optical classes of miRNA biosensors are reviewed in terms of transduction mechanism, limit of detection (LOD), time-to-results (TTR), multiplexing potential, and measurement robustness. Current trends suggest that biosensor-based techniques (BTs) for miRNA assay will complement MTs due to the advantages of amplification-free detection, LOD being femtomolar (fM)-attomolar (aM), short TTR, multiplexing capability, and minimal sample preparation requirement. Areas of future importance in miRNA BT development are presented which include focus on achieving high measurement confidence and multiplexing capabilities.

  10. Evaluation of fluorine-18-labeled alkylating agents as potential synthons for the labeling of oligonucleotides

    de Vries, EFJ; Vroegh, J; Elsinga, PH; Vaalburg, W

    Six fluorine-18-labeled alkylating agents were selected as potentially suitable synthons for the labeling of antisense oligonucleotides. The selected synthons were evaluated in a model reaction with the monomer adenosine 5'-O-thiomonophosphate. Of these synthons,

  11. Novel approaches to study low-energy electron-induced damage to DNA oligonucleotides

    Rackwitz, Jenny; Bald, Ilko; Ranković, Miloš Lj; Milosavljević, Aleksandar R

    2015-01-01

    The novel approach of DNA origami structures as templates for precise quantification of various well- defined oligonucleotides provides the opportunity to determine the sensitivity of complex DNA sequences towards low-energy electrons. (paper)

  12. Functionalization of PVC membrane with ss oligonucleotides for a potentiometric biosensor.

    Shishkanova, T V; Volf, R; Krondak, M; Král, V

    2007-05-15

    A novel application of a single stranded (ss) oligonucleotide as an active component of polymeric membrane in an ion-selective electrode (ISE) is described. The original oligonucleotides, oligo(dA)(15), modified by cholesterol, triphenylmethyl and hexadecyl derivatives, were immobilized into poly(vinyl chloride) (PVC) membrane using extraction protocol. In parallel, the adsorption protocol was used to immobilize unmodified oligo(dA)(15) on the PVC membrane based on tridodecylmethyammonium chloride (TDDMA(+)Cl(-)). Immobilization of ss oligonucleotide probe through spacer was more effective for the potentiometric detection of the hybridization between complementary oligonucleotides. It was found that cholesterol-oligo(dA)(15) modified membranes were sensitive toward complementary oligo(dT)(15) in the concentration range 2-80 nM at pH 7. An explanation for the detection mechanism is proposed.

  13. Thermal Stability of Modified i-Motif Oligonucleotides with Naphthalimide Intercalating Nucleic Acids

    El-Sayed, Ahmed Ali; Pedersen, Erik B.; Khaireldin, Nahid Y.

    2016-01-01

    In continuation of our investigation of characteristics and thermodynamic properties of the i-motif 5′-d[(CCCTAA)3CCCT)] upon insertion of intercalating nucleotides into the cytosine-rich oligonucleotide, this article evaluates the stabilities of i-motif oligonucleotides upon insertion of naphtha......In continuation of our investigation of characteristics and thermodynamic properties of the i-motif 5′-d[(CCCTAA)3CCCT)] upon insertion of intercalating nucleotides into the cytosine-rich oligonucleotide, this article evaluates the stabilities of i-motif oligonucleotides upon insertion...... of naphthalimide (1H-benzo[de]isoquinoline-1,3(2H)-dione) as the intercalating nucleic acid. The stabilities of i-motif structures with inserted naphthalimide intercalating nucleotides were studied using UV melting temperatures (Tm) and circular dichroism spectra at different pH values and conditions (crowding...

  14. Rapid Induction of Protective Immunity Against Biothreat Agents Using CPG-Based Oligonucleotides

    Klinman, Dennis

    2003-01-01

    This research project examines the ability of synthetic oligonucleotides (ODN) containing immunostimulatory "CpG motifs' to trigger the innate immune system, thereby improving the host's ability to survive infection by biowarfare agents...

  15. Efficient assessment of modified nucleoside stability under conditions of automated oligonucleotide synthesis: characterization of the oxidation and oxidative desulfurization of 2-thiouridine.

    Sochacka, E

    2001-01-01

    In order to efficiently assess the chemical stability of modified nucleosides to the reagents and conditions of automated oligonucleotide synthesis, we designed, developed and tested a scheme in which the modified nucleoside, directly attached to a solid support, is exposed to the cyclic chemistry of the instrument. Stability of 2-thiouridine against different oxidizers was investigated. Tertbutyl hydroperoxide (1 M) in anhydrous acetonitrile was a more effective oxidizer for the incorporation of 2-thiouridine into oligonucleotide chains than the same oxidizer in methylene chloride. Carbon tetrachloride/water in the presence of a basic catalyst was superior in maintaining the thiocarbonyl function, but its utility for RNA synthesis has yet to be fully tested, whereas 2-phenylsulfonyloxaziridine was a very efficient reagent for oxidative desulfurization of 2-thiouridine.

  16. Design considerations and challenges for mechanical stretch bioreactors in tissue engineering.

    Lei, Ying; Ferdous, Zannatul

    2016-05-01

    With the increase in average life expectancy and growing aging population, lack of functional grafts for replacement surgeries has become a severe problem. Engineered tissues are a promising alternative to this problem because they can mimic the physiological function of the native tissues and be cultured on demand. Cyclic stretch is important for developing many engineered tissues such as hearts, heart valves, muscles, and bones. Thus a variety of stretch bioreactors and corresponding scaffolds have been designed and tested to study the underlying mechanism of tissue formation and to optimize the mechanical conditions applied to the engineered tissues. In this review, we look at various designs of stretch bioreactors and common scaffolds and offer insights for future improvements in tissue engineering applications. First, we summarize the requirements and common configuration of stretch bioreactors. Next, we present the features of different actuating and motion transforming systems and their applications. Since most bioreactors must measure detailed distributions of loads and deformations on engineered tissues, techniques with high accuracy, precision, and frequency have been developed. We also cover the key points in designing culture chambers, nutrition exchanging systems, and regimens used for specific tissues. Since scaffolds are essential for providing biophysical microenvironments for residing cells, we discuss materials and technologies used in fabricating scaffolds to mimic anisotropic native tissues, including decellularized tissues, hydrogels, biocompatible polymers, electrospinning, and 3D bioprinting techniques. Finally, we present the potential future directions for improving stretch bioreactors and scaffolds. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:543-553, 2016. © 2016 American Institute of Chemical Engineers.

  17. Inter-regional Knowledge Management Workshop on Life-cycle Management of Design Basis Information – Issues, Challenges, Approaches. Presentations

    2013-01-01

    This Workshop had a strategic focus on identifying and clarifying long-term issues and objectives related to our collective responsibilities to ensure that both existing nuclear facilities and future new build projects properly address life-cycle management of plant design basis knowledge (i.e. from design to decommissioning). The workshop attempted to bring together key stakeholders and build a better collective understanding, recognizing that very different perspectives exist and there are a wide range of national contexts and approaches. The various issues and challenges related to this topic and facing the nuclear energy sector both today and in the long-term were discussed in a senior management context and at strategic level

  18. Research and Development Projects with ICT and students as learning designers in Primary Schools: A methodological challenge

    Levinsen, Karin Ellen Tweddell; Sørensen, Birgitte Holm; Tosca, Susana

    of how: • ICT supports students learning, • ICT release time for more teaching, and • teachers digital literacy impact on the role of ICT in the educational practice. Further the call required collaboration between universities and university colleges in order to disseminate knowledge and new practices......In this paper we present some methodological challenges that emerged during the process of shaping the research design for the comprehensive and complex research project Children as learning designers in a digital school. The project is the realization of our proposal to a research call from...... the Danish Ministry of Education named Development projects and pilot school experiments (Udviklingsprojekter med demonstrationsskoleforsøg vedr. it i folkeskolen – see Undervisningsministeriet 2013) in the spring 2013. The call was based on a governmental decision to allocate 500 million DKR to increase...

  19. Utilizing food effects to overcome challenges in delivery of lipophilic bioactives: structural design of medical and functional foods.

    McClements, David Julian

    2013-12-01

    The oral bioavailability of many lipophilic bioactives, such as pharmaceuticals and nutraceuticals, is relatively low due to their poor solubility, permeability and/or chemical stability within the human gastrointestinal tract (GIT). The oral bioavailability of lipophilic bioactives can be improved by designing food matrices that control their release, solubilization, transport and absorption within the GIT. This article discusses the challenges associated with delivering lipophilic bioactive components, the impact of food composition and structure on oral bioavailability and the design of functional and medical foods for improving the oral bioavailability of lipophilic bioactives. Food-based delivery systems can be used to improve the oral bioavailability of lipophilic bioactives. There are a number of potential advantages to delivering lipophilic bioactives using functional or medical foods: greater compliance than conventional delivery forms; increased bioavailability and efficacy; and reduced variability in biological effects. However, food matrices are structurally complex multicomponent materials and research is still needed to identify optimum structures and compositions for particular bioactives.

  20. Advances and Challenges in the Implementation of DiD in Siting, Design, and Construction of Nuclear Installations in Vietnam

    Nguyen, H.A., E-mail: nhanh@varans.vn [Vietnam Agency for Radiation and Nuclear Safety, Hanoi (Viet Nam)

    2014-10-15

    Vietnam is embarking on a development of a nuclear power program. The main focus is now on the initial 1000 MWe x 2 units of the nuclear power plant in Ninh Thuan province. Now, the nuclear projects of Vietnam are in the phase of siting approval and investment projects approval. The design assessment will be performed in 2013-2014; the construction and installation will be performed from now until the operating licensing is obtained in 2020-2021. With state of development of a nuclear power program in Vietnam, this paper only focuses on advances and challenges in the implementation of Defence in Depth (DID) in siting, design, and construction of nuclear installations in Vietnam. (author)

  1. C.N. Cofrentes power up-rate up to 110 %. A challenge for cycle 14 core design

    Gomez Bernal, M.I.; Lopez Carbonell, M.T.; Garcia Delgado, L.

    2001-01-01

    C.N.Cofrentes is a GE design BWR reactor with 624 bundles in the core, a rated power of 2894 MWt and it is currently operating Cycle 13 at 104.2 % power. Commercial operation started in 1984 with 12-month cycles at rated power. Both cycle length and thermal power have been increased since then. Power has been up-rated in two steps, first at 102 % in Cycle 4 and later in Cycle 11 at 104.2%. Cycle length has been extended from the original 12-month to the currently 18-month cycles. Next cycle, Cycle 14, will be an 18-month cycle operating at 110 % power. This goal is a challenge for the in-house nuclear design team. Start up for Cycle 14 is planned for the first quarter of 2002. (author)

  2. Structural Determinants of Photoreactivity of Triplex Forming Oligonucleotides Conjugated to Psoralens

    Krishnan, Rajagopal; Oh, Dennis H.

    2010-01-01

    Triplex-forming oligonucleotides (TFOs) with both DNA and 2′-O-methyl RNA backbones can direct psoralen photoadducts to specific DNA sequences. However, the functional consequences of these differing structures on psoralen photoreactivity are unknown. We designed TFO sequences with DNA and 2′-O-methyl RNA backbones conjugated to psoralen by 2-carbon linkers and examined their ability to bind and target damage to model DNA duplexes corresponding to sequences within the human HPRT gene. While TFO binding affinity was not dramatically affected by the type of backbone, psoralen photoreactivity was completely abrogated by the 2′-O-methyl RNA backbone. Photoreactivity was restored when the psoralen was conjugated to the RNA TFO via a 6-carbon linker. In contrast to the B-form DNA of triplexes formed by DNA TFOs, the CD spectra of triplexes formed with 2′-O-methyl RNA TFOs exhibited features of A-form DNA. These results indicate that 2′-O-methyl RNA TFOs induce a partial B-to-A transition in their target DNA sequences which may impair the photoreactivity of a conjugated psoralen and suggest that optimal design of TFOs to target DNA damage may require a balance between binding ability and drug reactivity. PMID:20725628

  3. Tritium containment and blanket design challenges for a 1 GWe mirror fusion central power station

    Galloway, T.R.

    1976-06-01

    Tritium containment and removal problems associated with the blanket and power-systems for a mirror fusion reactor are identified and conceptual process designs are devised to reduce emissions to the environment below 1 Ci/day. The blanket concept development proceeds by starting with this emission goal of 1 Ci/day and working inward to the blanket. At each decision point, worker safety, operational labor costs, and capital cost tradeoffs are contrasted. The conceptual design uses air for the reactor hall with a continuous catalytic oxidizer-molecular sieve adsorber cleanup system to maintain a 40 μCi/m 3 tritium level (5 μCi/m 3 HTO) against 180 Ci/day leakage from reactor components, energy recovery systems, and process piping. This blanket contains submodules with Li 2 Be 2 O 3 --Be for tritium breeding and submodules with Be for mostly energy production. Tritium production in both is handled by separately containing this breeding material and scavenging this container with lithium vapor-doped helium gas stream

  4. The TAHMO sensor design challenge: unlocking and empowering local African talent

    Hut, R.; Van De Giesen, N.

    2013-12-01

    The TAHMO initiative aims to develop and install 20.000 weather stations in sub Saharan Africa. The success of this endeavor greatly depends on using local knowledge, as well as support from local communities. A sensor design competition was held in which participants were asked to design a novel weather sensor. Promotion of the competition was focused on Africa and mainly African student teams responded. The best 15 out of 34 submission were send a 'maker package' containing the tools and materials to physically make their sensors. Winners of the maker packages were asked to upload a video of the process of building their sensors. Using these videos, 9 teams were invited to a final one-week workshop in which all teams worked together to connect all their sensors and automatically upload measurement readings to the internet. This goal was achieved on the last day of the workshop. http://www.youtube.com/watch?v=EOTPMp-13Bs The main results of this competition, the lessons learned and the road ahead for TAHMO will be presented.

  5. [Oligonucleotide derivatives in the nucleic acid hybridization analysis. III. Synthesis and investigation of properties of oligonucleotides, bearing bifunctional non-nucleotide insert].

    Kupriushkin, M S; Pyshnyĭ, D V

    2012-01-01

    Non-nucleotide phosporamidites were synthetized, having branched backbone with different position of functional groups. Obtained phosphoramidite monomers contain intercalator moiety--6-chloro-2-methoxyacridine, and additional hydroxyl residue protected with dimethoxytrityl group or with tert-butyldimethylsilyl group for post-synthetic modification. Synthesized oligothymidilates contain one or more modified units in different positions of sequence. Melting temperature and thermodynamic parameters of formation of complementary duplexes formed by modified oligonucleotides was defined (change in enthalpy and entropy). The introduction of intercalating residue causes a significant stabilization of DNA duplexes. It is shown that the efficiency of the fluorescence of acridine residue in the oligonucleotide conjugate significantly changes upon hybridization with DNA.

  6. Active debris removal GNC challenges over design and required ground validation

    Colmenarejo, Pablo; Avilés, Marcos; di Sotto, Emanuele

    2015-06-01

    Because of the exponential growth of space debris, the access to space in the medium-term future is considered as being seriously compromised, particularly within LEO polar Sun-synchronous orbits and within geostationary orbits. The active debris removal (ADR) application poses new and challenging requirements on: first, the new required Guidance, Navigation and Control (GNC) technologies and, second, how to validate these new technologies before being applied in real missions. There is no doubt about the strong safety and collision risk aspects affecting the real operational ADR missions. But it shall be considered that even ADR demonstration missions will be affected by significant risk of collision during the demonstration, and that the ADR GNC systems/technologies to be used shall be well mature before using/demonstrating them in space. Specific and dedicated on-ground validation approaches, techniques and facilities are mandatory. The different ADR techniques can be roughly catalogued in three main groups (rigid capture, non-rigid capture and contactless). All of them have a strong impact on the GNC system of the active vehicle during the capture/proximity phase and, particularly, during the active vehicle/debris combo control phase after capture and during the de-orbiting phase. The main operational phases on an ADR scenario are: (1) ground controlled phase (ADR vehicle and debris are far), (2) fine orbit synchronization phase (ADR vehicle to reach debris ±V-bar), (3) short range phase (along track distance reduction till 10-100 s of metres), (4) terminal approach/capture phase and (5) de-orbiting. While phases 1-3 are somehow conventional and already addressed in detail during past/on-going studies related to rendezvous and/or formation flying, phases 4-5 are very specific and not mature in terms of GNC needed technologies and HW equipment. GMV is currently performing different internal activities and ESA studies/developments related to ADR mission, GNC and

  7. Oligonucleotide Length-Dependent Formation of Virus-Like Particles.

    Maassen, Stan J; de Ruiter, Mark V; Lindhoud, Saskia; Cornelissen, Jeroen J L M

    2018-05-23

    Understanding the assembly pathway of viruses can contribute to creating monodisperse virus-based materials. In this study, the cowpea chlorotic mottle virus (CCMV) is used to determine the interactions between the capsid proteins of viruses and their cargo. The assembly of the capsid proteins in the presence of different lengths of short, single-stranded (ss) DNA is studied at neutral pH, at which the protein-protein interactions are weak. Chromatography, electrophoresis, microscopy, and light scattering data show that the assembly efficiency and speed of the particles increase with increasing length of oligonucleotides. The minimal length required for assembly under the conditions used herein is 14 nucleotides. Assembly of particles containing such short strands of ssDNA can take almost a month. This slow assembly process enabled the study of intermediate states, which confirmed a low cooperative assembly for CCMV and allowed for further expansion of current assembly theories. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Selective Covalent Conjugation of Phosphorothioate DNA Oligonucleotides with Streptavidin

    Christof M. Niemeyer

    2011-08-01

    Full Text Available Protein-DNA conjugates have found numerous applications in the field of diagnostics and nanobiotechnology, however, their intrinsic susceptibility to DNA degradation by nucleases represents a major obstacle for many applications. We here report the selective covalent conjugation of the protein streptavidin (STV with phosphorothioate oligonucleotides (psDNA containing a terminal alkylthiolgroup as the chemically addressable linking unit, using a heterobifunctional NHS-/maleimide crosslinker. The psDNA-STV conjugates were synthesized in about 10% isolated yields. We demonstrate that the terminal alkylthiol group selectively reacts with the maleimide while the backbone sulfur atoms are not engaged in chemical conjugation. The novel psDNA-STV conjugates retain their binding capabilities for both biotinylated macromolecules and the complementary nucleic acid. Moreover, the psDNA-STV conjugate retained its binding capacity for complementary oligomers even after a nuclease digestion step, which effectively degrades deoxyribonucleotide oligomers and thus the binding capability of regular DNA-STV conjugates. The psDNA-STV therefore hold particular promise for applications e.g. in proteome research and novel biosensing devices, where interfering endogenous nucleic acids need to be removed from analytes by nuclease digestion.

  9. Characterization of adjacent breast tumors using oligonucleotide microarrays

    Unger, Meredith A; Rishi, Mazhar; Clemmer, Virginia B; Hartman, Jennifer L; Keiper, Elizabeth A; Greshock, Joel D; Chodosh, Lewis A; Liebman, Michael N; Weber, Barbara L

    2001-01-01

    Current methodology often cannot distinguish second primary breast cancers from multifocal disease, a potentially important distinction for clinical management. In the present study we evaluated the use of oligonucleotide-based microarray analysis in determining the clonality of tumors by comparing gene expression profiles. Total RNA was extracted from two tumors with no apparent physical connection that were located in the right breast of an 87-year-old woman diagnosed with invasive ductal carcinoma (IDC). The RNA was hybridized to the Affymetrix Human Genome U95A Gene Chip ® (12,500 known human genes) and analyzed using the Gene Chip Analysis Suite ® 3.3 (Affymetrix, Inc, Santa Clara, CA, USA) and JMPIN ® 3.2.6 (SAS Institute, Inc, Cary, NC, USA). Gene expression profiles of tumors from five additional patients were compared in order to evaluate the heterogeneity in gene expression between tumors with similar clinical characteristics. The adjacent breast tumors had a pairwise correlation coefficient of 0.987, and were essentially indistinguishable by microarray analysis. Analysis of gene expression profiles from different individuals, however, generated a pairwise correlation coefficient of 0.710. Transcriptional profiling may be a useful diagnostic tool for determining tumor clonality and heterogeneity, and may ultimately impact on therapeutic decision making

  10. Correction of Spatial Bias in Oligonucleotide Array Data

    Philippe Serhal

    2013-01-01

    Full Text Available Background. Oligonucleotide microarrays allow for high-throughput gene expression profiling assays. The technology relies on the fundamental assumption that observed hybridization signal intensities (HSIs for each intended target, on average, correlate with their target’s true concentration in the sample. However, systematic, nonbiological variation from several sources undermines this hypothesis. Background hybridization signal has been previously identified as one such important source, one manifestation of which appears in the form of spatial autocorrelation. Results. We propose an algorithm, pyn, for the elimination of spatial autocorrelation in HSIs, exploiting the duality of desirable mutual information shared by probes in a common probe set and undesirable mutual information shared by spatially proximate probes. We show that this correction procedure reduces spatial autocorrelation in HSIs; increases HSI reproducibility across replicate arrays; increases differentially expressed gene detection power; and performs better than previously published methods. Conclusions. The proposed algorithm increases both precision and accuracy, while requiring virtually no changes to users’ current analysis pipelines: the correction consists merely of a transformation of raw HSIs (e.g., CEL files for Affymetrix arrays. A free, open-source implementation is provided as an R package, compatible with standard Bioconductor tools. The approach may also be tailored to other platform types and other sources of bias.

  11. Correction of Spatial Bias in Oligonucleotide Array Data

    Lemieux, Sébastien

    2013-01-01

    Background. Oligonucleotide microarrays allow for high-throughput gene expression profiling assays. The technology relies on the fundamental assumption that observed hybridization signal intensities (HSIs) for each intended target, on average, correlate with their target's true concentration in the sample. However, systematic, nonbiological variation from several sources undermines this hypothesis. Background hybridization signal has been previously identified as one such important source, one manifestation of which appears in the form of spatial autocorrelation. Results. We propose an algorithm, pyn, for the elimination of spatial autocorrelation in HSIs, exploiting the duality of desirable mutual information shared by probes in a common probe set and undesirable mutual information shared by spatially proximate probes. We show that this correction procedure reduces spatial autocorrelation in HSIs; increases HSI reproducibility across replicate arrays; increases differentially expressed gene detection power; and performs better than previously published methods. Conclusions. The proposed algorithm increases both precision and accuracy, while requiring virtually no changes to users' current analysis pipelines: the correction consists merely of a transformation of raw HSIs (e.g., CEL files for Affymetrix arrays). A free, open-source implementation is provided as an R package, compatible with standard Bioconductor tools. The approach may also be tailored to other platform types and other sources of bias. PMID:23573083

  12. Advancements of antisense oligonucleotides in treatment of breast cancer

    YANGShuan-Ping; SONGSan-Tai; 等

    2003-01-01

    Breast cancer is one kind of multi-gene related malignancy.Overexpression of some oncogenes such as HER-2(c-erbB-2,Neu),bcl-2/bcl-xL,protein kinase A(PKA),and transferrin receptor gene(TfR gene),etc significantly affect the prognosis of breast cancer.It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer.Antisense interference.one of useful tools for inhibiting the overexpression of specific oncogenes,was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides(ON)could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases;some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts.Furthermore,the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects,which was probably the best utilization of antisense ON in the treatment of breast cancer.

  13. Methods for the preparation of protein-oligonucleotide-lipid constructs.

    Takasaki, Jennifer; Raney, Sameersingh G; Chikh, Ghania; Sekirov, Laura; Brodsky, Irina; Tam, Ying; Ansell, Steven M

    2006-01-01

    A mixture of ionizable cationic lipids, steric barrier lipids, and colipids is used to encapsulate oligonucleotide DNA in lipidic particles called SALP. This material is under development as an adjuvant for vaccines. Previously we have shown that coupling the antigen directly to the surface of SALP can lead to enhanced immunological responses in vivo. Two different methods for preparing ovalbumin-SALP were assessed in this work. Originally the conjugates were prepared by treating SALP containing a maleimide-derivatized lipid with thiolated ovalbumin, a method we refer to as active coupling. This reaction was found to be difficult to control and generally resulted in low coupling efficiencies. The issues relating to this approach were characterized. We have recently developed alternative techniques based on first coupling ovalbumin to a micelle and then incubating the resultant product with SALP, methods we refer to as passive coupling. We have shown that this method allows accurate control of the levels of protein associated SALP and does not suffer from surface saturation effects seen with the active coupling method that places maximum limits on the amount of protein that can be coupled to the SALP surface. The products from the passive coupling protocol are shown to have activity comparable to those derived from the active coupling protocol in investigations of in vivo immune responses.

  14. The use of oligonucleotide aptamers in cancer therapy

    Adrian Odrzywolski

    2016-05-01

    Full Text Available Aptamers are a new class of molecules which originated in the 1990s. They are usually RNA or DNA oligonucleotides, the length of which ranges between 20 and 80 nt. They are produced using the SELEX method that allows one to obtain aptamers that bind to virtually any molecule of interest, providing a high specificity. Aptamers are an alternative to antibodies because on the one hand, their sensitivity is at a similar or sometimes even higher level, while on the other hand they do not show immunogenicity, and may be synthesized in vitro. To date, a broad range of different applications of aptamers has been described: as components of biosensors, or use in various laboratory techniques, such as microarrays or chromatography. One of the most important is the use of aptamers in medicine, especially in the fight against cancer. They can be used both for diagnosis and for the eradication of cancers – particularly through the delivery of drugs. Currently, most transport-related research is devoted to the delivery of chemotherapeutic drugs, such as doxorubicin. This was used in research on liver cancer cells, prostate, and acute lymphoblastic leukemia blast cells. Another possibility is to use aptamers to deliver siRNAs. In this way inhibition of the quality control process of the mRNA in tumor cells is possible. An aptamer complex with the drug allows for direct delivery of the active substance in a particular cell type, substantially eliminating the non-specific effect of the drug.

  15. Syntheses of prodrug-type phosphotriester oligonucleotides responsive to intracellular reducing environment for improvement of cell membrane permeability and nuclease resistance.

    Hayashi, Junsuke; Samezawa, Yusuke; Ochi, Yosuke; Wada, Shun-Ichi; Urata, Hidehito

    2017-07-15

    We synthesized prodrug-type phosphotriester (PTE) oligonucleotides containing the six-membered cyclic disulfide moiety by using phosphoramidite chemistry. Prodrug-type oligonucleotides named "Reducing-Environment-Dependent Uncatalyzed Chemical Transforming (REDUCT) PTE oligonucleotides" were converted into natural oligonucleotides under cytosol-mimetic reductive condition. Furthermore, the REDUCT PTE oligonucleotides were robust to nuclease digestion and exhibited good cell membrane permeability. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. In vitro transcription in the presence of DNA oligonucleotides can generate strong anomalous initiation sites.

    Chow, C W; Clark, M P; Rinaldo, J E; Chalkley, R

    1996-03-01

    In the present study, we have explored an unexpected observation in transcription initiation that is mediated by single-stranded oligonucleotides. Initially, our goal was to understand the function of different upstream regulatory elements/initiation sites in the rat xanthine dehydrogenase/oxidase (XDH/XO) promoter. We performed in vitro transcription with HeLa nuclear extracts in the presence of different double-stranded oligonucleotides against upstream elements as competitors. A new and unusual transcription initiation site was detected by primer extension. This new initiation site maps to the downstream region of the corresponding competitor. Subsequent analyses have indicated that the induction of a new transcription initiation site is anomalous which is due to the presence of a small amount of single-stranded oligonucleotide in the competitor. We found that this anomalous initiation site is insensitive to the orientation of the promoter and requires only a small amount of single-stranded oligonucleotide (< 2-fold molar excess relative to template). We surmise that a complementary interaction between the single-stranded oligonucleotide and transiently denatured promoter template may be responsible for this sequence-specific transcription initiation artifact. To study the regulation of transcription initiation by in vitro transcription approaches, we propose that one should probe the effect of removing transacting factors by adding an excess of a cognate oligonucleotide which does not bear exact sequence identity to the template.

  17. Systematic validation and atomic force microscopy of non-covalent short oligonucleotide barcode microarrays.

    Michael A Cook

    Full Text Available BACKGROUND: Molecular barcode arrays provide a powerful means to analyze cellular phenotypes in parallel through detection of short (20-60 base unique sequence tags, or "barcodes", associated with each strain or clone in a collection. However, costs of current methods for microarray construction, whether by in situ oligonucleotide synthesis or ex situ coupling of modified oligonucleotides to the slide surface are often prohibitive to large-scale analyses. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that unmodified 20mer oligonucleotide probes printed on conventional surfaces show comparable hybridization signals to covalently linked 5'-amino-modified probes. As a test case, we undertook systematic cell size analysis of the budding yeast Saccharomyces cerevisiae genome-wide deletion collection by size separation of the deletion pool followed by determination of strain abundance in size fractions by barcode arrays. We demonstrate that the properties of a 13K unique feature spotted 20 mer oligonucleotide barcode microarray compare favorably with an analogous covalently-linked oligonucleotide array. Further, cell size profiles obtained with the size selection/barcode array approach recapitulate previous cell size measurements of individual deletion strains. Finally, through atomic force microscopy (AFM, we characterize the mechanism of hybridization to unmodified barcode probes on the slide surface. CONCLUSIONS/SIGNIFICANCE: These studies push the lower limit of probe size in genome-scale unmodified oligonucleotide microarray construction and demonstrate a versatile, cost-effective and reliable method for molecular barcode analysis.

  18. Challenges in designing for horizontal learning in the Danish VET system

    Riis, Marianne; Bergstedt, Palle; Jørgensen, Claus Bo

    2016-01-01

    on a sociocultural framework with cultural-historical activity theory (CHAT) guiding the initial phases. In this short paper, we present preliminary findings based on six ethnographic interviews with vocational teachers, and we zoom in on the teachers' experiences with central elements of their bounded systems. We......As part of an on-going research project (2015-2017) at The National Centre for Vocational Pedagogy, Metropolitan University College, we are studying why and how vocational teachers understand and design for boundary crossing through the use of ICT-based artefacts. The research project is based...... found that these teachers use ICT as mediating tool within a single system, but rarely as boundary object in and between systems....

  19. Design features which mitigate severe accident challenges in the GE ABWR and SBWR

    Buchholz, Carol E.

    2004-01-01

    A reduction of the requirements for the emergency planning zone (EPZ) is a goal of advanced light water reactors. The technical basis for reducing the EPZ requirements is based on a very low frequency of a severe accident and high confidence that the offsite dose would be low even if a severe accident was to occur. Design features have been included in both the ABWR and SBWR to ensure that both of these goals are achieved. Probabilistic Risk Assessments (PRAs) have been performed for both plants. The PRAs indicate a core damage frequency on the order of IE-7 for both plants. The PRAs also show that the containments will not fail even if a severe accident should occur. The potential offsite is extremely low. (author)

  20. Limited take-up of health coverage tax credits: a challenge to future tax credit design.

    Dorn, Stan; Varon, Janet; Pervez, Fouad

    2005-10-01

    The Trade Act of 2002 created federal tax credits to subsidize health coverage for certain early retirees and workers displaced by international trade. Though small, this program offers the opportunity to learn how to design future tax credits for larger groups of uninsured. During September 2004, the most recent month for which there are data about all forms of Trade Act credits, roughly 22 percent of eligible individuals received credits. The authors find that health insurance tax credits are more likely to reach their target populations if such credits: 1) limit premium costs for the low-income uninsured and do not require full premium payments while applications are pending; 2) provide access to coverage that beneficiaries value, including care for preexisting conditions; 3) are combined with outreach that uses easily understandable, multilingual materials and proactive enrollment efforts; and 4) feature a simple application process involving one form filed with one agency.

  1. Biopiracy after the Nagoya Protocol: Problem Structure, Regime Design and Implementation Challenges

    Florian Rabitz

    2015-08-01

    Full Text Available This article assesses the effectiveness of the 2010 Nagoya Protocol to the Convention on Biological Diversity (CBD for addressing "biopiracy" of genetic resources; that is, their biotechnological utilization in violation of either the provider country legislation or mutually agreed contractual obligations. Biopiracy is defined as a problem resulting from a distributive conflict between provider and user countries, the practical difficulties of monitoring the utilization of genetic resources in a transnational context, and the pervasive scientific uncertainty about the nature and extent of the problem. The Nagoya Protocol predominantly focuses on compliance management while lacking the necessary enforcement provisions for deterring non-compliance through effective monitoring and sanctions. Using the example of recent European Union implementing legislation, this article underscores how parties may use the Protocol's legal ambiguities to soften its regulatory impact on domestic industry. As a result, in light of both problem structure and regime design, the Protocol only offers modest improvements over the status quo ante.

  2. Design challenges of a tunable laser interrogator for geo-stationary communication satellites

    Ibrahim, Selwan K.; Honniball, Arthur; McCue, Raymond; Todd, Michael; O'Dowd, John A.; Sheils, David; Voudouris, Liberis; Farnan, Martin; Hurni, Andreas; Putzer, Philipp; Lemke, Norbert; Roner, Markus

    2017-09-01

    Recently optical sensing solutions based on fiber Bragg grating (FBG) technology have been proposed for temperature monitoring in telecommunication satellite platforms with an operational life time beyond 15 years in geo-stationary orbit. Developing radiation hardened optical interrogators designed to be used with FBG sensors inscribed in radiation tolerant fibers offer the capabilities of multiplexing multiple sensors on the same fiber and reducing the overall weight by removing the copper wiring harnesses associated with electrical sensors. Here we propose the use of a tunable laser based optical interrogator that uses a semiconductor MG-Y type laser that has no moving parts and sweeps across the C-band wavelength range providing optical power to FBG sensors and optical wavelength references such as athermal Etalons and Gas Cells to guarantee stable operation of the interrogator over its targeted life time in radiation exposed environments. The MG-Y laser was calibrated so it remains in a stable operation mode which ensures that no mode hops occur due to aging of the laser, and/or thermal or radiation effects. The key optical components including tunable laser, references and FBGs were tested for radiation tolerances by emulating the conditions on a geo-stationary satellite including a Total Ionizing Dose (TID) radiation level of up to 100 krad for interrogator components and 25 Mrad for FBGs. Different tunable laser control, and signal processing algorithms have been designed and developed to fit within specific available radiation hardened FPGAs to guarantee operation of a single interrogator module providing at least 1 sample per second measurement capability across engineering model system developed in the frame of an ESA-ARTES program and is planned to be deployed as a flight demonstrator on-board the German Heinrich Hertz geo-stationary satellite.

  3. Scaling laws for free piston Stirling engine design: Benefits and challenges of miniaturization

    Formosa, Fabien; Fréchette, Luc G.

    2013-01-01

    This work explores the scaling effects for FPSE (free piston Stirling engines), which are known for their simple architecture and potentially high thermodynamic performances. Scaling laws are given and their potential for miniaturization is highlighted. A simple model which allows the design of the geometrical parameters of the heat exchangers, the regenerator and the masses of the pistons is proposed. It is based on the definition of six characteristic dimensionless groups. They are derived from the physics underlying the behavior of the free piston Stirling machine and their relevancy is backed up by comparisons between documented Stirling engines from the literature. Keeping constant values for each group throughout the scaling range theoretically ensures constant performance. The main losses of Stirling engine (heat conduction loss, reheat loss in the regenerator, pressure drop and gas-spring hysteresis) can be expressed as a function of the geometrical and operating parameters. Additionally, the consequences of leakage due to the manufacturing precision of pistons architectures are underlined. From the proposed scaling laws, potential power and efficiency of Stirling cycle engines at a millimeter scale can be anticipated. It appears that the power density increases with miniaturization. It is also shown that the dynamic masses related to the engine size are increased when scaling down and that the gap leakage presents the highest detrimental effects on the efficiency. These results call for dedicated architectures for micro-engines. - Highlights: • Similitude strategy is applied to Stirling engines and allows preliminary design. • New scaling laws are derived. • The power density can be increased with miniaturization. • The gap between the piston and casing is highly detrimental to the performances. • High engine operating pressure is required when miniaturizing

  4. Synthesis, hybridization characteristics, and fluorescence properties of oligonucleotides modified with nucleobase-functionalized locked nucleic acid adenosine and cytidine monomers.

    Kaura, Mamta; Kumar, Pawan; Hrdlicka, Patrick J

    2014-07-03

    Conformationally restricted nucleotides such as locked nucleic acid (LNA) are very popular as affinity-, specificity-, and stability-enhancing modifications in oligonucleotide chemistry to produce probes for nucleic acid targeting applications in molecular biology, biotechnology, and medicinal chemistry. Considerable efforts have been devoted in recent years to optimize the biophysical properties of LNA through additional modification of the sugar skeleton. We recently introduced C5-functionalization of LNA uridines as an alternative and synthetically more straightforward approach to improve the biophysical properties of LNA. In the present work, we set out to test the generality of this concept by studying the characteristics of oligonucleotides modified with four different C5-functionalized LNA cytidine and C8-functionalized LNA adenosine monomers. The results strongly suggest that C5-functionalization of LNA pyrimidines is indeed a viable approach for improving the binding affinity, target specificity, and/or enzymatic stability of LNA-modified ONs, whereas C8-functionalization of LNA adenosines is detrimental to binding affinity and specificity. These insights will impact the future design of conformationally restricted nucleotides for nucleic acid targeting applications.

  5. Workplace restructurings in intervention studies – a challenge for design, analysis and interpretation

    Olsen, Ole; Albertsen, Karen; Nielsen, Martin Lindhardt; Poulsen, Kjeld Børge; Gron, Sisse Malene Frydendal; Brunnberg, Hans Lennart

    2008-01-01

    Background Interventions in occupational health often target worksites rather than individuals. The objective of this paper is to describe the (lack of) stability in units of analysis in occupational health and safety intervention projects directed toward worksites. Methods A case study approach is used to describe naturally occurring organizational changes in four, large, Nordic intervention projects that ran 3–5 years, covered 3–52 worksites, cost 0.25 mill–2.2 mill €, and involved 3–7 researchers. Results In all four cases, high rates of closing, merging, moving, downsizing or restructuring was observed, and in all four cases at least one company/worksite experienced two or more re-organizations during the project period. If individual worksites remained, ownership or (for publicly owned) administrative or legal base often shifted. Forthcoming closure led employees and managers to seek employment at other worksites participating in the studies. Key employees involved in the intervention process often changed. Conclusion Major changes were the rule rather than the exception. Frequent fundamental changes at worksites need to be taken into account when planning intervention studies and raises serious questions concerning design, analyses and interpretation of results. The frequent changes may also have deleterious implications for the potential effectiveness of many real life interventions directed toward worksites. We urge researchers and editors to prioritize this subject in order to improve the quality of future intervention research and preventive action. PMID:18554380

  6. Workplace restructurings in intervention studies – a challenge for design, analysis and interpretation

    Poulsen Kjeld

    2008-06-01

    Full Text Available Abstract Background Interventions in occupational health often target worksites rather than individuals. The objective of this paper is to describe the (lack of stability in units of analysis in occupational health and safety intervention projects directed toward worksites. Methods A case study approach is used to describe naturally occurring organizational changes in four, large, Nordic intervention projects that ran 3–5 years, covered 3–52 worksites, cost 0.25 mill–2.2 mill €, and involved 3–7 researchers. Results In all four cases, high rates of closing, merging, moving, downsizing or restructuring was observed, and in all four cases at least one company/worksite experienced two or more re-organizations during the project period. If individual worksites remained, ownership or (for publicly owned administrative or legal base often shifted. Forthcoming closure led employees and managers to seek employment at other worksites participating in the studies. Key employees involved in the intervention process often changed. Conclusion Major changes were the rule rather than the exception. Frequent fundamental changes at worksites need to be taken into account when planning intervention studies and raises serious questions concerning design, analyses and interpretation of results. The frequent changes may also have deleterious implications for the potential effectiveness of many real life interventions directed toward worksites. We urge researchers and editors to prioritize this subject in order to improve the quality of future intervention research and preventive action.

  7. Post graduate clinical placements: evaluating benefits and challenges with a mixed methods cross sectional design.

    Yiend, Jenny; Tracy, Derek K; Sreenan, Brian; Cardi, Valentina; Foulkes, Tina; Koutsantoni, Katerina; Kravariti, Eugenia; Tchanturia, Kate; Willmott, Lucy; Shergill, Sukhi; Reedy, Gabriel

    2016-02-16

    Systematic evaluations of clinical placements are rare, especially when offered alongside academic postgraduate courses. An evidence-based approach is important to allow pedagogically-driven provision, rather than that solely governed by opinion or market demand. Our evaluation assessed a voluntary clinical placement scheme allied to a mental health course. Data were collected over academic years 2010/11- 2013/14, from participating students (n = 20 to 58) and clinician supervisors (n = 10-12), using a mixed-methods cross-sectional design. Quantitative evaluation captured information on uptake, dropout, resource use, attitudes and experience, using standardized (the Placement Evaluation Questionnaire; the Scale To Assess the Therapeutic Relationship - Clinical version and the University of Toronto Placement Supervisor Evaluation) and bespoke questionnaires and audit data. Qualitative evaluation comprised two focus groups (5 clinicians, 5 students), to investigate attitudes, experience, perceived benefits, disadvantages and desired future developments. Data were analysed using framework analysis to identify a priori and emergent themes. High uptake (around 70 placements per annum), low dropout (2-3 students per annum; 5 %) and positive focus group comments suggested placements successfully provided added value and catered sufficiently to student demand. Students' responses confirmed that placements met expectations and the perception of benefit remained after completion with 70 % (n = 14) reporting an overall positive experience, 75 % (n = 15) reporting a pleasant learning experience, 60 % (n = 12) feeling that their clinical skills were enhanced and 85 % (n = 17) believing that it would benefit other students. Placements contributed the equivalent of seven full time unskilled posts per annum to local health care services. While qualitative data revealed perceived 'mutual benefit' for both students and clinicians, this was qualified by

  8. Antitumor effects of radioiodinated antisense oligonucleotide mediated by VIP receptor

    Ou Xiaohong; Tan Tianzhi; Li Yunchun; Kuang Anren

    2004-01-01

    Purpose: we had constructed a targeting delivery system based on intestinal peptide (VIP) for antisense oligonucleotide (ASON) transfer into VIP receptor-positive cells in previous study. The aims of present studies are to observe the antitumor effect of VIP-131I-ASON in HT29 human colon adenocarcinoma xenografts. Methods: A 15-met phosphorothioate ASON, which was complementary to the translation start region of the C-myc oncogene mRNA, was labeled with 131I and the labelled compound was linked to the VIP bound covalently 'to a polylysine chain so as to deliver oligonucleotide into tumor cells. Distribution experiments for evaluating the radiolabeled antisense complexe uptake in tumor tissue were performed in BALB/c nude mice bearing with HT29 tumor xenografts. Nude mice beating HT29 tumor xenografts were adminstered VIP-131I-ASON (3.7,7.4 MBq) or 131I-ASON (3.7 MBq), 131I labeled control sense and nosense DNA (3.7 MBq), or saline. Antitumor effects were assessed using endpoints of tumor growth delay. C-myc-encoded protein expression of tumor was measured by immunocytohistochemical staining. Results: Distribution experiment performed with athymic mice bearing human colon tumor xenografts revealed maximal accumulation of conjugated ASON in the tumor tissue 2 h after administration and significantly higher than that in nude mice injected unconjngated ASON [(5.89±1.03)%ID/g and(1.56±0.31)%ID/g, respectively; t=7.7954 P<0.001]. The radioratio of tumor to muscle was peaked 4h after administration. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing their growth rate 7-fold compare with that in saline-treated mice(tumor growth delay, 25.4±0.89 day). The antitumor effects of unconjugated 131I-ASON were much less profound than VIP-131I-ASON (tumor growth delay, 3.2±1.3 and 25.4±0.89 day, respectively; q=51.4126 P<0.01). Sense, nosense control ON with VIP carder caused no therapeutic effect. There was no progressive weight loss or

  9. Antisense oligonucleotides targeting translation inhibitory elements in 5' UTRs can selectively increase protein levels.

    Liang, Xue-Hai; Sun, Hong; Shen, Wen; Wang, Shiyu; Yao, Joyee; Migawa, Michael T; Bui, Huynh-Hoa; Damle, Sagar S; Riney, Stan; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T

    2017-09-19

    A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs. Levels of human RNASEH1, LDLR, and ACP1 and of mouse ACP1 and ARF1 were increased up to 2.7-fold in different cell types and species upon treatment with chemically modified ASOs targeting 5' UTR inhibitory regions in the mRNAs encoding these proteins. The activities of ASOs in enhancing translation were sequence and position dependent and required helicase activity. The ASOs appear to improve the recruitment of translation initiation factors to the target mRNA. Importantly, ASOs targeting ACP1 mRNA significantly increased the level of ACP1 protein in mice, suggesting that this approach has therapeutic and research potentials. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Nano and Microtechnologies for the Delivery of Oligonucleotides with Gene Silencing Properties

    Giuseppe De Rosa

    2009-07-01

    Full Text Available Oligonucleotides (ONs are synthetic fragments of nucleic acid designed to modulate the expression of target proteins. DNA-based ONs (antisense, antigene, aptamer or decoy and more recently a new class of RNA-based ONs, the small interfering RNAs (siRNAs, have gained great attention for the treatment of different disease states, such as viral infections, inflammation, diabetes, and cancer. However, the development of therapeutic strategies based on ONs is hampered by their low bioavailability, poor intracellular uptake and rapid degradation in biological fluids. The use of a non-viral carrier can be a powerful tool to overcome these drawbacks. Lipid or polymer-based nanotechnologies can improve biological stability and cellular uptake of ONs, with possibility of tissue and/or cellular targeting. The use of polymeric devices can also produce a prolonged release of the ON, thus reducing the need of frequent administrations. This review summarizes advantages and issues related to the main non-viral vectors used for ON delivery.

  11. Spotting and validation of a genome wide oligonucleotide chip with duplicate measurement of each gene

    Thomassen, Mads; Skov, Vibe; Eiriksdottir, Freyja; Tan, Qihua; Jochumsen, Kirsten; Fritzner, Niels; Brusgaard, Klaus; Dahlgaard, Jesper; Kruse, Torben A.

    2006-01-01

    The quality of DNA microarray based gene expression data relies on the reproducibility of several steps in a microarray experiment. We have developed a spotted genome wide microarray chip with oligonucleotides printed in duplicate in order to minimise undesirable biases, thereby optimising detection of true differential expression. The validation study design consisted of an assessment of the microarray chip performance using the MessageAmp and FairPlay labelling kits. Intraclass correlation coefficient (ICC) was used to demonstrate that MessageAmp was significantly more reproducible than FairPlay. Further examinations with MessageAmp revealed the applicability of the system. The linear range of the chips was three orders of magnitude, the precision was high, as 95% of measurements deviated less than 1.24-fold from the expected value, and the coefficient of variation for relative expression was 13.6%. Relative quantitation was more reproducible than absolute quantitation and substantial reduction of variance was attained with duplicate spotting. An analysis of variance (ANOVA) demonstrated no significant day-to-day variation

  12. Specific Increase of Protein Levels by Enhancing Translation Using Antisense Oligonucleotides Targeting Upstream Open Frames.

    Liang, Xue-Hai; Shen, Wen; Crooke, Stanley T

    2017-01-01

    A number of diseases are caused by low levels of key proteins; therefore, increasing the amount of specific proteins in human bodies is of therapeutic interest. Protein expression is downregulated by some structural or sequence elements present in the 5' UTR of mRNAs, such as upstream open reading frames (uORF). Translation initiation from uORF(s) reduces translation from the downstream primary ORF encoding the main protein product in the same mRNA, leading to a less efficient protein expression. Therefore, it is possible to use antisense oligonucleotides (ASOs) to specifically inhibit translation of the uORF by base-pairing with the uAUG region of the mRNA, redirecting translation machinery to initiate from the primary AUG site. Here we review the recent findings that translation of specific mRNAs can be enhanced using ASOs targeting uORF regions. Appropriately designed and optimized ASOs are highly specific, and they act in a sequence- and position-dependent manner, with very minor off-target effects. Protein levels can be increased using this approach in different types of human and mouse cells, and, importantly, also in mice. Since uORFs are present in around half of human mRNAs, the uORF-targeting ASOs may thus have valuable potential as research tools and as therapeutics to increase the levels of proteins for a variety of genes.

  13. Antisense Oligonucleotide-mediated Exon Skipping as a Systemic Therapeutic Approach for Recessive Dystrophic Epidermolysis Bullosa.

    Bremer, Jeroen; Bornert, Olivier; Nyström, Alexander; Gostynski, Antoni; Jonkman, Marcel F; Aartsma-Rus, Annemieke; van den Akker, Peter C; Pasmooij, Anna Mg

    2016-10-18

    The "generalized severe" form of recessive dystrophic epidermolysis bullosa (RDEB-gen sev) is caused by bi-allelic null mutations in COL7A1, encoding type VII collagen. The absence of type VII collagen leads to blistering of the skin and mucous membranes upon the slightest trauma. Because most patients carry exonic point mutations or small insertions/deletions, most exons of COL7A1 are in-frame, and low levels of type VII collagen already drastically improve the disease phenotype, this gene seems a perfect candidate for antisense oligonucleotide (AON)-mediated exon skipping. In this study, we examined the feasibility of AON-mediated exon skipping in vitro in primary cultured keratinocytes and fibroblasts, and systemically in vivo using a human skin-graft mouse model. We show that treatment with AONs designed against exon 105 leads to in-frame exon 105 skipping at the RNA level and restores type VII collagen protein production in vitro. Moreover, we demonstrate that systemic delivery in vivo induces de novo expression of type VII collagen in skin grafts generated from patient cells. Our data demonstrate strong proof-of-concept for AON-mediated exon skipping as a systemic therapeutic strategy for RDEB.

  14. A dystrophic Duchenne mouse model for testing human antisense oligonucleotides.

    Marcel Veltrop

    Full Text Available Duchenne muscular dystrophy (DMD is a severe muscle-wasting disease generally caused by reading frame disrupting mutations in the DMD gene resulting in loss of functional dystrophin protein. The reading frame can be restored by antisense oligonucleotide (AON-mediated exon skipping, allowing production of internally deleted, but partially functional dystrophin proteins as found in the less severe Becker muscular dystrophy. Due to genetic variation between species, mouse models with mutations in the murine genes are of limited use to test and further optimize human specific AONs in vivo. To address this we have generated the del52hDMD/mdx mouse. This model carries both murine and human DMD genes. However, mouse dystrophin expression is abolished due to a stop mutation in exon 23, while the expression of human dystrophin is abolished due to a deletion of exon 52. The del52hDMD/mdx model, like mdx, shows signs of muscle dystrophy on a histological level and phenotypically mild functional impairment. Local administration of human specific vivo morpholinos induces exon skipping and dystrophin restoration in these mice. Depending on the number of mismatches, occasional skipping of the murine Dmd gene, albeit at low levels, could be observed. Unlike previous models, the del52hDMD/mdx model enables the in vivo analysis of human specific AONs targeting exon 51 or exon 53 on RNA and protein level and muscle quality and function. Therefore, it will be a valuable tool for optimizing human specific AONs and genome editing approaches for DMD.

  15. Profiled support vector machines for antisense oligonucleotide efficacy prediction

    Martín-Guerrero José D

    2004-09-01

    Full Text Available Abstract Background This paper presents the use of Support Vector Machines (SVMs for prediction and analysis of antisense oligonucleotide (AO efficacy. The collected database comprises 315 AO molecules including 68 features each, inducing a problem well-suited to SVMs. The task of feature selection is crucial given the presence of noisy or redundant features, and the well-known problem of the curse of dimensionality. We propose a two-stage strategy to develop an optimal model: (1 feature selection using correlation analysis, mutual information, and SVM-based recursive feature elimination (SVM-RFE, and (2 AO prediction using standard and profiled SVM formulations. A profiled SVM gives different weights to different parts of the training data to focus the training on the most important regions. Results In the first stage, the SVM-RFE technique was most efficient and robust in the presence of low number of samples and high input space dimension. This method yielded an optimal subset of 14 representative features, which were all related to energy and sequence motifs. The second stage evaluated the performance of the predictors (overall correlation coefficient between observed and predicted efficacy, r; mean error, ME; and root-mean-square-error, RMSE using 8-fold and minus-one-RNA cross-validation methods. The profiled SVM produced the best results (r = 0.44, ME = 0.022, and RMSE= 0.278 and predicted high (>75% inhibition of gene expression and low efficacy (http://aosvm.cgb.ki.se/. Conclusions The SVM approach is well suited to the AO prediction problem, and yields a prediction accuracy superior to previous methods. The profiled SVM was found to perform better than the standard SVM, suggesting that it could lead to improvements in other prediction problems as well.

  16. Application of heteronuclear couplings to conformational analysis of oligonucleotides

    Zhu, G.; Live, D.; Bax, A.

    1994-01-01

    The value of vicinal coupling constants extracted from NMR spectra in deducing torsion angles for conformational analysis is well recognized. Due to the abundance of protons, their couplings have been mostly widely used. In many instances, couplings between protons and other nuclei may be a valuable complement to proton-proton couplings or, in some instances, may be the only coupling available to characterize the torsion angle about a bond. Recently, heteronuclear couplings have been used to great benefit in studies of isotopically enriched proteins, and this general approach has been extended to peptides at natural abundance. The possibility of using this approach to study oligonucleotides is also attractive but has not as yet been widely exploited. With the development of strategies for labeling such molecules, particularly RNAs, this may become an important component in conformational analysis. For DNA, labeling is less accessible, but sufficient quantities of unlabeled material are readily available for measuring these couplings at natural abundance. We chose several DNA systems to explore the usefulness of heteronuclear couplings in addressing the sugar conformation and the glycosidic torsion angle. Intensities of cross peaks in long-range HMQC experiments can be related to the couplings. Crosspeaks involving H1' and C1' atoms have been emphasized because of the superior shift dispersion at these positions between sugar protons and carbon atoms. Results will be shown for the self-complementary Dickerson duplex dodecamer sequence d(CGCGAATTCGCG) and for d(GGTCGG), which dimerizes to form a G-tetrad structure incorporating both syn and anti base orientations. The couplings provide a clear discrimination between presence of C3'-endo and C2'-endo conformations of the sugars and syn and anti bases arrangements

  17. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease.

    Monteleone, Giovanni; Neurath, Markus F; Ardizzone, Sandro; Di Sabatino, Antonio; Fantini, Massimo C; Castiglione, Fabiana; Scribano, Maria L; Armuzzi, Alessandro; Caprioli, Flavio; Sturniolo, Giacomo C; Rogai, Francesca; Vecchi, Maurizio; Atreya, Raja; Bossa, Fabrizio; Onali, Sara; Fichera, Maria; Corazza, Gino R; Biancone, Livia; Savarino, Vincenzo; Pica, Roberta; Orlando, Ambrogio; Pallone, Francesco

    2015-03-19

    Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease. We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).

  18. Application of heteronuclear couplings to conformational analysis of oligonucleotides

    Zhu, G. [Univ. of Maryland, College Park, MD (United States); Live, D. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Bax, A. [NIDDK National Institutes of Health, Bethesda, MD (United States)

    1994-12-01

    The value of vicinal coupling constants extracted from NMR spectra in deducing torsion angles for conformational analysis is well recognized. Due to the abundance of protons, their couplings have been mostly widely used. In many instances, couplings between protons and other nuclei may be a valuable complement to proton-proton couplings or, in some instances, may be the only coupling available to characterize the torsion angle about a bond. Recently, heteronuclear couplings have been used to great benefit in studies of isotopically enriched proteins, and this general approach has been extended to peptides at natural abundance. The possibility of using this approach to study oligonucleotides is also attractive but has not as yet been widely exploited. With the development of strategies for labeling such molecules, particularly RNAs, this may become an important component in conformational analysis. For DNA, labeling is less accessible, but sufficient quantities of unlabeled material are readily available for measuring these couplings at natural abundance. We chose several DNA systems to explore the usefulness of heteronuclear couplings in addressing the sugar conformation and the glycosidic torsion angle. Intensities of cross peaks in long-range HMQC experiments can be related to the couplings. Crosspeaks involving H1{prime} and C1{prime} atoms have been emphasized because of the superior shift dispersion at these positions between sugar protons and carbon atoms. Results will be shown for the self-complementary Dickerson duplex dodecamer sequence d(CGCGAATTCGCG) and for d(GGTCGG), which dimerizes to form a G-tetrad structure incorporating both syn and anti base orientations. The couplings provide a clear discrimination between presence of C3{prime}-endo and C2{prime}-endo conformations of the sugars and syn and anti bases arrangements.

  19. Design challenges for matrix assisted pulsed laser evaporation and infrared resonant laser evaporation equipment

    Greer, James A.

    2011-11-01

    Since the development of the Matrix Assisted Pulsed Laser Evaporation (MAPLE) process by the Naval Research Laboratory (NRL) in the late 1990s, MAPLE has become an active area of research for the deposition of a variety of polymer, biological, and organic thin films. As is often the case with advancements in thin-film deposition techniques new technology sometimes evolves by making minor or major adjustments to existing deposition process equipment and techniques. This is usually the quickest and least expensive way to try out new ideas and to "push the envelope" in order to obtain new and unique scientific results as quickly as possible. This process of "tweaking" current equipment usually works to some degree, but once the new process is further refined overall designs for a new deposition tool based on the critical attributes of the new process typically help capitalize more fully on the all the salient features of the new and improved process. This certainly has been true for the MAPLE process. In fact the first MAPLE experiments the polymer/solvent matrix was mixed and poured into a copper holder held at LN2 temperature on a laboratory counter top. The holder was then quickly placed onto a LN2 cooled reservoir in a vacuum deposition chamber and placed in a vertical position on a LN2 cooled stage and pumped down as quickly as possible. If the sample was not placed into the chamber quickly enough the frozen matrix would melt and drip into the bottom of the chamber onto the chambers main gate valve making a bit of a mess. However, skilled and motivated scientists usually worked quickly enough to make this process work most of the time. The initial results from these experiments were encouraging and led to several publications which sparked considerable interest in this newly developed technique Clearly this approach provided the vision that MAPLE was a viable deposition process, but the equipment was not optimal for conducting MAPLE experiments on a regular basis

  20. Challenges in designing a very compact 130 MeV Moeller polarimeter for the S-DALINAC

    Bahlo, Thore; Enders, Joachim; Kuerzeder, Thorsten; Pietralla, Norbert; Wissmann, Jan [Institut fuer Kernphysik, TU Darmstadt, Darmstadt (Germany)

    2016-07-01

    The Superconducting Darmstadt Linear Accelerator is capable of accelerating polarized electron beams produced by the S-DALINAC Polarized Injector (SPIN). For electron energies of up to 14 MeV it is possible to measure the absolute polarization of the electrons with two Mott polarimeters that are already mounted in the injector beamline. Until now it is not possible to measure the absolute electron beam polarization after the passage of the main accelerator. Therefore a Moeller polarimeter for energies between 50 MeV and 130 MeV is currently being developed. The rather low incident beam energy, the variability of the incident beam energy, and spatial restrictions necessitate a compact set-up with large acceptance. The very restrictive boundary conditions introduce technical and geometrical challenges. We will present the design of the target chamber, of the separation dipole magnet as well as the beam dump.

  1. Considerations for design and use of container challenge sets for qualification and validation of visible particulate inspection.

    Melchore, James A; Berdovich, Dan

    2012-01-01

    The major compendia require sterile injectable and ophthalmic drugs, to be prepared in a manner that is designed to exclude particulate matter. This requirement is satisfied by testing for subvisual particles in the laboratory and 100% inspection of all containers for the presence of visible particles. Inspection for visible particles is performed in the operations area using one of three methods. Manual inspection is based on human visual acuity, the ability of the inspector to discern between conforming and nonconforming containers, and the ability to remove nonconforming units. Semi-automated inspection is a variation of manual inspection, in which a roller conveyor handles and presents the containers to the human inspector. Fully automated inspection systems perform handling, inspection, and rejection of defective containers. All inspection methods must meet the compendial requirement for sterile drug product to be "essentially free" of visible particulates. Given the random occurrence of particles within the batch, visual detection of a particle in an individual container is probabilistic. The probability of detection for a specific particle is affected by many variables that include product attributes, container size and shape, particle composition and size, and inspection capability. The challenge set is a useful tool to assess the particle detection in a product, and it may also be used to evaluate detection of container/closure defects. While the importance of a well-designed challenge set is not always recognized or understood, it serves as the cornerstone for qualification and/or validation of all inspection methods. This article is intended to provide useful information for the design, composition, and use of container challenge sets for particulate inspection studies. Regulations require drug products intended for injection or ophthalmic use to be sterile and free of particles that could harm the patient. This requirement is meet by 100% inspection of

  2. University Engineering Design Challenge

    2015-01-29

    27.5641   Detached  from  the   cement ,  not  the   acryllic.     50       51     C6: Fabric Test Results UV...summary, we learned that our fish hook pad has a stronger grip on rough surfaces like cinderblock and rock than smooth surfaces like a smooth cement ...unique concepts for travel. After evaluating the fluency , variety, and originality of the candidate set, the team determined to begin eliminating the

  3. Engineering Design Challenge

    Wheeler, Lindsay B.; Whitworth, Brooke A.; Gonczi, Amanda L.

    2014-01-01

    The number of students majoring in science, technology, engineering, and math (STEM) is declining due in part to a lack of student interest (Fairweather 2008; NRC 2012; PCAST 2010). One reason may be the difference between how science is done in school and how it is done in the field (Osborne, Simon, and Collins 2003). An interdisciplinary…

  4. Surface modification of plasmonic nanostructured materials with thiolated oligonucleotides in 10 seconds using selective microwave heating

    Abel, B.; Aslan, K.

    2012-01-01

    This study demonstrates the proof-of-principle of rapid surface modification of plasmonic nanostructured materials with oligonucleotides using low power microwave heating. Due to their interesting optical and electronic properties, silver nanoparticle films (SNFs, 2 nm thick) deposited onto glass slides were used as the model plasmonic nanostructured materials. Rapid surface modification of SNFs with oligonucleotides was carried out using two strategies (1) Strategy 1: for ss-oligonucleotides, surface hybridization and (2) Strategy 2: for ds-oligonucleotides, solution hybridization, where the samples were exposed to 10, 15, 30 and 60 seconds microwave heating. To assess the efficacy of our new rapid surface modification technique, identical experiments carried out without the microwave heating (i.e., conventional method), which requires 24 hours for the completion of the identical steps. It was found that SNFs can be modified with ss- and ds-oligonucleotides in 10 seconds, which typically requires several hours of incubation time for the chemisorption of thiol groups on to the planar metal surface using conventional techniques. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  5. Comparison of gene coverage of mouse oligonucleotide microarray platforms

    Medrano Juan F

    2006-03-01

    Full Text Available Abstract Background The increasing use of DNA microarrays for genetical genomics studies generates a need for platforms with complete coverage of the genome. We have compared the effective gene coverage in the mouse genome of different commercial and noncommercial oligonucleotide microarray platforms by performing an in-house gene annotation of probes. We only used information about probes that is available from vendors and followed a process that any researcher may take to find the gene targeted by a given probe. In order to make consistent comparisons between platforms, probes in each microarray were annotated with an Entrez Gene id and the chromosomal position for each gene was obtained from the UCSC Genome Browser Database. Gene coverage was estimated as the percentage of Entrez Genes with a unique position in the UCSC Genome database that is tested by a given microarray platform. Results A MySQL relational database was created to store the mapping information for 25,416 mouse genes and for the probes in five microarray platforms (gene coverage level in parenthesis: Affymetrix430 2.0 (75.6%, ABI Genome Survey (81.24%, Agilent (79.33%, Codelink (78.09%, Sentrix (90.47%; and four array-ready oligosets: Sigma (47.95%, Operon v.3 (69.89%, Operon v.4 (84.03%, and MEEBO (84.03%. The differences in coverage between platforms were highly conserved across chromosomes. Differences in the number of redundant and unspecific probes were also found among arrays. The database can be queried to compare specific genomic regions using a web interface. The software used to create, update and query the database is freely available as a toolbox named ArrayGene. Conclusion The software developed here allows researchers to create updated custom databases by using public or proprietary information on genes for any organisms. ArrayGene allows easy comparisons of gene coverage between microarray platforms for any region of the genome. The comparison presented here

  6. Detection of genomic deletions in rice using oligonucleotide microarrays

    Bordeos Alicia

    2009-03-01

    Full Text Available Abstract Background The induction of genomic deletions by physical- or chemical- agents is an easy and inexpensive means to generate a genome-saturating collection of mutations. Different mutagens can be selected to ensure a mutant collection with a range of deletion sizes. This would allow identification of mutations in single genes or, alternatively, a deleted group of genes that might collectively govern a trait (e.g., quantitative trait loci, QTL. However, deletion mutants have not been widely used in functional genomics, because the mutated genes are not tagged and therefore, difficult to identify. Here, we present a microarray-based approach to identify deleted genomic regions in rice mutants selected from a large collection generated by gamma ray or fast neutron treatment. Our study focuses not only on the utility of this method for forward genetics, but also its potential as a reverse genetics tool through accumulation of hybridization data for a collection of deletion mutants harboring multiple genetic lesions. Results We demonstrate that hybridization of labeled genomic DNA directly onto the Affymetrix Rice GeneChip® allows rapid localization of deleted regions in rice mutants. Deletions ranged in size from one gene model to ~500 kb and were predicted on all 12 rice chromosomes. The utility of the technique as a tool in forward genetics was demonstrated in combination with an allelic series of mutants to rapidly narrow the genomic region, and eventually identify a candidate gene responsible for a lesion mimic phenotype. Finally, the positions of mutations in 14 mutants were aligned onto the rice pseudomolecules in a user-friendly genome browser to allow for rapid identification of untagged mutations http://irfgc.irri.org/cgi-bin/gbrowse/IR64_deletion_mutants/. Conclusion We demonstrate the utility of oligonucleotide arrays to discover deleted genes in rice. The density and distribution of deletions suggests the feasibility of a

  7. Design and preliminary evaluation of the FINGER rehabilitation robot: controlling challenge and quantifying finger individuation during musical computer game play.

    Taheri, Hossein; Rowe, Justin B; Gardner, David; Chan, Vicki; Gray, Kyle; Bower, Curtis; Reinkensmeyer, David J; Wolbrecht, Eric T

    2014-02-04

    This paper describes the design and preliminary testing of FINGER (Finger Individuating Grasp Exercise Robot), a device for assisting in finger rehabilitation after neurologic injury. We developed FINGER to assist stroke patients in moving their fingers individually in a naturalistic curling motion while playing a game similar to Guitar Hero. The goal was to make FINGER capable of assisting with motions where precise timing is important. FINGER consists of a pair of stacked single degree-of-freedom 8-bar mechanisms, one for the index and one for the middle finger. Each 8-bar mechanism was designed to control the angle and position of the proximal phalanx and the position of the middle phalanx. Target positions for the mechanism optimization were determined from trajectory data collected from 7 healthy subjects using color-based motion capture. The resulting robotic device was built to accommodate multiple finger sizes and finger-to-finger widths. For initial evaluation, we asked individuals with a stroke (n = 16) and without impairment (n = 4) to play a game similar to Guitar Hero while connected to FINGER. Precision design, low friction bearings, and separate high speed linear actuators allowed FINGER to individually actuate the fingers with a high bandwidth of control (-3 dB at approximately 8 Hz). During the tests, we were able to modulate the subject's success rate at the game by automatically adjusting the controller gains of FINGER. We also used FINGER to measure subjects' effort and finger individuation while playing the game. Test results demonstrate the ability of FINGER to motivate subjects with an engaging game environment that challenges individuated control of the fingers, automatically control assistance levels, and quantify finger individuation after stroke.

  8. The challenge of the global management of plant design modifications. example of the new EJ system at Vandellos NPP

    Ortega, Fernando; Valdivia, Carlos; Fernandez Illobre, Luis; Trueba, Pedro

    2010-01-01

    One of the most challenging areas in the operation of nuclear power plants (NPP) is related to the management of plant design modifications. Plant modifications can be made to improve reliability, facilitate operation, improve safety or get better results. In any of these situations, plant modifications imply many different activities that have to be done in a coordinated manner. NUREG-0711 (Human Factors Engineering Program Review Model) shows a global approach to manage most of these activities. Although this approach is mainly focused on the design and construction of new plants, it can also be applied to plant modification management. Successful global management will require performing every activity in a specific order, taking advantage of the output coming from some tasks as input for others and finalizing every task when necessary. This will provide the best results in terms of quality, time required for implementation, safe and reliable operation and maintenance, and cost. Tecnatom is involved in most of the activities related to the operational areas and has applied a global approach to get advantages in terms of quality and cost, which is outlined in this paper. As an example of this approach, the Vandellos NPP experience is shown in this presentation. Vandellos NPP carried out an important design modification that consists of replacing an old essential service water system with a new one. This was a three-year project that implied the construction of new reservoirs, new buildings, the implementation of new equipment, and new panels in the main control room. This paper shows the way in which all of these activities were performed. (authors)

  9. Hydration-dependent dynamics of human telomeric oligonucleotides in the picosecond timescale: A neutron scattering study

    Sebastiani, F.; Comez, L.; Sacchetti, F. [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); CNR, Istituto Officina dei Materiali, Unità di Perugia, c/o Dipartimento di Fisica e Geologia, Università di Perugia, 06123 Perugia (Italy); Longo, M. [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); Elettra—Sincrotrone Trieste, 34149 Basovizza, Trieste (Italy); Orecchini, A.; Petrillo, C.; Paciaroni, A., E-mail: alessandro.paciaroni@fisica.unipg.it [Dipartimento di Fisica e Geologia, Università degli Studi di Perugia, Via A. Pascoli, 06123 Perugia (Italy); De Francesco, A. [CNR-IOM OGG c/o Institut Laue-Langevin, 71 Avenue des Martyrs, CS20156, 38042 Grenoble Cedex 9 (France); Muthmann, M. [Jülich Centre for Neutron Science, Forschungszentrum Jülich GmbH, Outstation at Heinz Maier-Leibnitz Zentrum, Lichtenbergstrasse 1, 85747 Garching (Germany); Teixeira, S. C. M. [EPSAM, Keele University, Staffordshire ST5 5BG (United Kingdom); Institut Laue–Langevin, 71 Avenue des Martyrs, CS20156, 38042 Grenoble Cedex 9 (France)

    2015-07-07

    The dynamics of the human oligonucleotide AG{sub 3}(T{sub 2}AG{sub 3}){sub 3} has been investigated by incoherent neutron scattering in the sub-nanosecond timescale. A hydration-dependent dynamical activation of thermal fluctuations in weakly hydrated samples was found, similar to that of protein powders. The amplitudes of such thermal fluctuations were evaluated in two different exchanged wave-vector ranges, so as to single out the different contributions from intra- and inter-nucleotide dynamics. The activation energy was calculated from the temperature-dependent characteristic times of the corresponding dynamical processes. The trends of both amplitudes and activation energies support a picture where oligonucleotides possess a larger conformational flexibility than long DNA sequences. This additional flexibility, which likely results from a significant relative chain-end contribution to the average chain dynamics, could be related to the strong structural polymorphism of the investigated oligonucleotides.

  10. Reliability and applications of statistical methods based on oligonucleotide frequencies in bacterial and archaeal genomes

    Bohlin, J; Skjerve, E; Ussery, David

    2008-01-01

    with here are mainly used to examine similarities between archaeal and bacterial DNA from different genomes. These methods compare observed genomic frequencies of fixed-sized oligonucleotides with expected values, which can be determined by genomic nucleotide content, smaller oligonucleotide frequencies......, or be based on specific statistical distributions. Advantages with these statistical methods include measurements of phylogenetic relationship with relatively small pieces of DNA sampled from almost anywhere within genomes, detection of foreign/conserved DNA, and homology searches. Our aim was to explore...... the reliability and best suited applications for some popular methods, which include relative oligonucleotide frequencies (ROF), di- to hexanucleotide zero'th order Markov methods (ZOM) and 2.order Markov chain Method (MCM). Tests were performed on distant homology searches with large DNA sequences, detection...

  11. Ultramild protein-mediated click chemistry creates efficient oligonucleotide probes for targeting and detecting nucleic acids

    Nåbo, Lina J.; Madsen, Charlotte S.; Jensen, Knud J.

    2015-01-01

    Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid...... targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides. This was performed under ultramild...... conditions with fluorophore, peptide, and carbohydrate azide derivatives. In thermal denaturation studies, the modified probes showed specific binding to complementary DNA and RNA targets. Finally, we demonstrated the pH sensitivity of the new rhodamine-based fluorescent probes in vitro and rationalize our...

  12. Detection of DNA oligonucleotides with base mutations by terahertz spectroscopy and microstructures.

    Mingjie Tang

    Full Text Available DNA oligonucleotides with a 5-base mutation at the 3'-terminus were investigated by terahertz (THz spectroscopy in a marker-free manner. The four single-stranded oligonucleotides with 17nt have been detected with specificity on a microfluidic chip, and corroborated by spectral measurements with split-ring resonators. The number of hydrogen bonds formed between the oligonucleotide and its surrounding water molecules, deemed a key contribution to the THz absorption of biological solutions, was explored by molecular dynamics simulations to explain the experimental findings. Our work underlies the feasibility of THz spectroscopy combined with microstructures for marker-free detection of DNA, which may form the basis of a prospective diagnostic tool for studying genic mutation.

  13. The Diabetes Telephone Study: Design and challenges of a pragmatic cluster randomized trial to improve diabetic peripheral neuropathy treatment.

    Adams, Alyce S; Bayliss, Elizabeth A; Schmittdiel, Julie A; Altschuler, Andrea; Dyer, Wendy; Neugebauer, Romain; Jaffe, Marc; Young, Joseph D; Kim, Eileen; Grant, Richard W

    2016-06-01

    Challenges to effective pharmacologic management of symptomatic diabetic peripheral neuropathy include the limited effectiveness of available medicines, frequent side effects, and the need for ongoing symptom assessment and treatment titration for maximal effectiveness. We present here the rationale and implementation challenges of the Diabetes Telephone Study, a randomized trial designed to improve medication treatment, titration, and quality of life among patients with symptomatic diabetic peripheral neuropathy. We implemented a pragmatic cluster randomized controlled trial to test the effectiveness of an automated interactive voice response tool designed to provide physicians with real-time patient-reported data about responses to newly prescribed diabetic peripheral neuropathy medicines. A total of 1834 primary care physicians treating patients in the diabetes registry at Kaiser Permanente Northern California were randomized into the intervention or control arm. In September 2014, we began identification and recruitment of patients assigned to physicians in the intervention group who receive three brief interactive calls every 2 months after a medication is prescribed to alleviate diabetic peripheral neuropathy symptoms. These calls provide patients with the opportunity to report on symptoms, side effects, self-titration of medication dose and overall satisfaction with treatment. We plan to compare changes in self-reported quality of life between the intervention group and patients in the control group who receive three non-interactive automated educational phone calls. Successful implementation of this clinical trial required robust stakeholder engagement to help tailor the intervention and to address pragmatic concerns such as provider time constraints. As of 27 October 2015, we had screened 2078 patients, 1447 of whom were eligible for participation. We consented and enrolled 1206 or 83% of those eligible. Among those enrolled, 53% are women and the mean age

  14. Polynucleotides. XXXII. Further studies on the synthesis of oligonucleotides containing 8,2'-S-cycloadenosine.

    Ikehara, M; Tezuka, T

    1975-01-01

    A dinucleoside monophosphate, 8,2'-anhydro-8-mercapto-9-beta-D-arabinofuranosyladenine phosphoryl-(3'-5')-inosine (AspI) was synthesized by the condensation of protected 8-mercapto-adenosine 2',3'-cyclic phosphate and 2',3'-isopropylideneinosine with diphenylphosphorochloridate. 8-Mercaptoadenosine 2',3'-cyclic phosphate was polymerized by using tetraphenyl pyrophosphate as the condensing reagent. As oligonucleotides, thus obtained, contained some uncyclized 8-mercaptoadenosine residues and were cleaved at these sites with 0.3N KOH. As 5'-phosphate was synthesized and polymerized with DCC to give oligonucleotides with chain lengths 2 to 9. PMID:170595

  15. Functional regulation of RNA-induced silencing complex by photoreactive oligonucleotides.

    Matsuyama, Yohei; Yamayoshi, Asako; Kobori, Akio; Murakami, Akira

    2014-02-01

    We developed a novel method for regulation of RISC function by photoreactive oligonucleotides (Ps-Oligo) containing 2'-O-psoralenylmethoxyethyl adenosine (Aps). We observed that inhibitory effects of Ps-Oligos on RISC function were enhanced by UV-irradiation compared with 2'-O-methyl-oligonucleotide without Aps. These results suggest Ps-Oligo inhibited RISC function by cross-linking effect, and we propose that the concept described in this report may be promising and applicable one to regulate the small RNA-mediated post-transcriptional regulation. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  16. Reliability of digital ulcer definitions as proposed by the UK Scleroderma Study Group: A challenge for clinical trial design.

    Hughes, Michael; Tracey, Andrew; Bhushan, Monica; Chakravarty, Kuntal; Denton, Christopher P; Dubey, Shirish; Guiducci, Serena; Muir, Lindsay; Ong, Voon; Parker, Louise; Pauling, John D; Prabu, Athiveeraramapandian; Rogers, Christine; Roberts, Christopher; Herrick, Ariane L

    2018-06-01

    The reliability of clinician grading of systemic sclerosis-related digital ulcers has been reported to be poor to moderate at best, which has important implications for clinical trial design. The aim of this study was to examine the reliability of new proposed UK Scleroderma Study Group digital ulcer definitions among UK clinicians with an interest in systemic sclerosis. Raters graded (through a custom-built interface) 90 images (80 unique and 10 repeat) of a range of digital lesions collected from patients with systemic sclerosis. Lesions were graded on an ordinal scale of severity: 'no ulcer', 'healed ulcer' or 'digital ulcer'. A total of 23 clinicians - 18 rheumatologists, 3 dermatologists, 1 hand surgeon and 1 specialist rheumatology nurse - completed the study. A total of 2070 (1840 unique + 230 repeat) image gradings were obtained. For intra-rater reliability, across all images, the overall weighted kappa coefficient was high (0.71) and was moderate (0.55) when averaged across individual raters. Overall inter-rater reliability was poor (0.15). Although our proposed digital ulcer definitions had high intra-rater reliability, the overall inter-rater reliability was poor. Our study highlights the challenges of digital ulcer assessment by clinicians with an interest in systemic sclerosis and provides a number of useful insights for future clinical trial design. Further research is warranted to improve the reliability of digital ulcer definition/rating as an outcome measure in clinical trials, including examining the role for objective measurement techniques, and the development of digital ulcer patient-reported outcome measures.

  17. Lessons Learned in Evaluating a Multisite, Comprehensive Teen Dating Violence Prevention Strategy: Design and Challenges of the Evaluation of Dating Matters: Strategies to Promote Healthy Teen Relationships.

    Niolon, Phyllis Holditch; Taylor, Bruce G; Latzman, Natasha E; Vivolo-Kantor, Alana M; Valle, Linda Anne; Tharp, Andra T

    2016-03-01

    This paper describes the multisite, longitudinal cluster randomized controlled trial (RCT) design of the evaluation of the Dating Matters: Strategies to Promote Healthy Relationships initiative, and discusses challenges faced in conducting this evaluation. Health departments in 4 communities are partnering with middle schools in high-risk, urban communities to implement 2 models of teen dating violence (TDV) prevention over 4 years. Schools were randomized to receive either the Dating Matters comprehensive strategy or the "standard of care" strategy (an existing, evidence-based TDV prevention curriculum). Our design permits comparison of the relative effectiveness of the comprehensive and standard of care strategies. Multiple cohorts of students from 46 middle schools are surveyed in middle school and high school, and parents and educators from participating schools are also surveyed. Challenges discussed in conducting a multisite RCT include site variability, separation of implementation and evaluation responsibilities, school retention, parent engagement in research activities, and working within the context of high-risk urban schools and communities. We discuss the strengths and weaknesses of our approaches to these challenges in the hopes of informing future research. Despite multiple challenges, the design of the Dating Matters evaluation remains strong. We hope this paper provides researchers who are conducting complex evaluations of behavioral interventions with thoughtful discussion of the challenges we have faced and potential solutions to such challenges.

  18. Synthesis and Biophysical Investigations of Oligonucleotides Containing Galactose-Modified DNA, LNA and 2'-Amino-LNA Monomers

    Ries, Annika; Kumar, Rajesh; Lou, Chenguang

    2016-01-01

    Galactose-modified thymidine, LNA-T and 2'-amino-LNA-T nucleosides were synthesized, converted into the corresponding phosphoramidite derivatives and introduced into short oligonucleotides. Compared to the unmodified control strands, the galactose-modified oligonucleotides in general, and the N2'...

  19. Intergenerational Programs May Be Especially Engaging for Aged Care Residents With Cognitive Impairment: Findings From the Avondale Intergenerational Design Challenge.

    Baker, Jess Rose; Webster, Lindl; Lynn, Nigel; Rogers, Julie; Belcher, Jessica

    2017-06-01

    Intergenerational programs are an authentic way to engage elders in meaningful activity and report benefits to both elders and youth. The Avondale Intergenerational Design Challenge (AVID) randomly assigned small teams of technology students aged 13 to 15 years (total N = 59) to 1 of 24 aged care residents with a range of cognitive impairment. Students met with the resident 4 times over 15 weeks and ultimately crafted a personalized item for them. Students showed no change in self-reported attitudes to elders, empathy, or self-esteem post-AVID or at 3-month follow-up, compared to a 3-month within-subject control period pre-AVID. Compared to usual lifestyle activities, residents showed significant improvements in self-reported positive affect and negative affect after student visits and were observed to be significantly more engaged during visits, especially residents with greater cognitive impairment. The personal and guided nature of intergenerational programs may be especially effective in engaging elders with cognitive impairment in meaningful activity.

  20. Multi-gene detection and identification of mosquito-borne RNA viruses using an oligonucleotide microarray.

    Nathan D Grubaugh

    Full Text Available BACKGROUND: Arthropod-borne viruses are important emerging pathogens world-wide. Viruses transmitted by mosquitoes, such as dengue, yellow fever, and Japanese encephalitis viruses, infect hundreds of millions of people and animals each year. Global surveillance of these viruses in mosquito vectors using molecular based assays is critical for prevention and control of the associated diseases. Here, we report an oligonucleotide DNA microarray design, termed ArboChip5.1, for multi-gene detection and identification of mosquito-borne RNA viruses from the genera Flavivirus (family Flaviviridae, Alphavirus (Togaviridae, Orthobunyavirus (Bunyaviridae, and Phlebovirus (Bunyaviridae. METHODOLOGY/PRINCIPAL FINDINGS: The assay utilizes targeted PCR amplification of three genes from each virus genus for electrochemical detection on a portable, field-tested microarray platform. Fifty-two viruses propagated in cell-culture were used to evaluate the specificity of the PCR primer sets and the ArboChip5.1 microarray capture probes. The microarray detected all of the tested viruses and differentiated between many closely related viruses such as members of the dengue, Japanese encephalitis, and Semliki Forest virus clades. Laboratory infected mosquitoes were used to simulate field samples and to determine the limits of detection. Additionally, we identified dengue virus type 3, Japanese encephalitis virus, Tembusu virus, Culex flavivirus, and a Quang Binh-like virus from mosquitoes collected in Thailand in 2011 and 2012. CONCLUSIONS/SIGNIFICANCE: We demonstrated that the described assay can be utilized in a comprehensive field surveillance program by the broad-range amplification and specific identification of arboviruses from infected mosquitoes. Furthermore, the microarray platform can be deployed in the field and viral RNA extraction to data analysis can occur in as little as 12 h. The information derived from the ArboChip5.1 microarray can help to establish