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Sample records for achieve fast mutation

  1. Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol.

    PubMed

    Cheng, Kian-Kai; Lee, Baek-Seok; Masuda, Takeshi; Ito, Takuro; Ikeda, Kazutaka; Hirayama, Akiyoshi; Deng, Lingli; Dong, Jiyang; Shimizu, Kazuyuki; Soga, Tomoyoshi; Tomita, Masaru; Palsson, Bernhard O; Robert, Martin

    2014-01-01

    Comparative whole-genome sequencing enables the identification of specific mutations during adaptation of bacteria to new environments and allelic replacement can establish their causality. However, the mechanisms of action are hard to decipher and little has been achieved for epistatic mutations, especially at the metabolic level. Here we show that a strain of Escherichia coli carrying mutations in the rpoC and glpK genes, derived from adaptation in glycerol, uses two distinct metabolic strategies to gain growth advantage. A 27-bp deletion in the rpoC gene first increases metabolic efficiency. Then, a point mutation in the glpK gene promotes growth by improving glycerol utilization but results in increased carbon wasting as overflow metabolism. In a strain carrying both mutations, these contrasting carbon/energy saving and wasting mechanisms work together to give an 89% increase in growth rate. This study provides insight into metabolic reprogramming during adaptive laboratory evolution for fast cellular growth.

  2. Fast-channel congenital myasthenic syndrome with a novel acetylcholine receptor mutation at the α-ε subunit interface.

    PubMed

    Webster, Richard; Liu, Wei-Wei; Chaouch, Amina; Lochmüller, Hanns; Beeson, David

    2014-02-01

    Congenital myasthenic syndromes (CMS) result from the failure to achieve muscle depolarisation due to disorders in the structure and/or function of the neuromuscular synapse. Mutations of the nicotinic acetylcholine receptor (nAChR) form a major subset of CMS. We describe a patient who presented with recurrent apnoeic crises in the neonatal period requiring ventilator support. Electromyography revealed compound muscle action potential decrement upon repetitive stimulation. Sequencing of nAChR subunit genes revealed two missense mutations. One previously reported null mutation p.εTyr15His, and a second novel missense mutation, p.εThr38Lys, that is well expressed in mammalian cell culture and thus likely to exert its effect via alteration of ion channel kinetics. Functional analysis revealed abbreviated ion channel bursts characteristic of a fast channel CMS. The mutation p.εThr38Lys occurs at the interface between the α and ε subunits of the nAChR pentamer and leads to instability of the open channel. The effects of this mutation on channel function were investigated in relation to other fast channel mutants at an analogous subunit interface within the nAChR pentamer. Fast channel syndromes are frequently characterised by severe myasthenic weakness with apnoeic crises; knowledge of the underlying mutation and its functional consequences can be vital for appropriate therapy and patient management.

  3. How to Achieve Fast Entrainment? The Timescale to Synchronization

    PubMed Central

    Granada, Adrián E.; Herzel, Hanspeter

    2009-01-01

    Entrainment, where oscillators synchronize to an external signal, is ubiquitous in nature. The transient time leading to entrainment plays a major role in many biological processes. Our goal is to unveil the specific dynamics that leads to fast entrainment. By studying a generic model, we characterize the transient time to entrainment and show how it is governed by two basic properties of an oscillator: the radial relaxation time and the phase velocity distribution around the limit cycle. Those two basic properties are inherent in every oscillator. This concept can be applied to many biological systems to predict the average transient time to entrainment or to infer properties of the underlying oscillator from the observed transients. We found that both a sinusoidal oscillator with fast radial relaxation and a spike-like oscillator with slow radial relaxation give rise to fast entrainment. As an example, we discuss the jet-lag experiments in the mammalian circadian pacemaker. PMID:19774087

  4. Achieving fast and stable failure detection in WDM Networks

    NASA Astrophysics Data System (ADS)

    Gao, Donghui; Zhou, Zhiyu; Zhang, Hanyi

    2005-02-01

    In dynamic networks, the failure detection time takes a major part of the convergence time, which is an important network performance index. To detect a node or link failure in the network, traditional protocols, like Hello protocol in OSPF or RSVP, exchanges keep-alive messages between neighboring nodes to keep track of the link/node state. But by default settings, it can get a minimum detection time in the measure of dozens of seconds, which can not meet the demands of fast network convergence and failure recovery. When configuring the related parameters to reduce the detection time, there will be notable instability problems. In this paper, we analyzed the problem and designed a new failure detection algorithm to reduce the network overhead of detection signaling. Through our experiment we found it is effective to enhance the stability by implicitly acknowledge other signaling messages as keep-alive messages. We conducted our proposal and the previous approaches on the ASON test-bed. The experimental results show that our algorithm gives better performances than previous schemes in about an order magnitude reduction of both false failure alarms and queuing delay to other messages, especially under light traffic load.

  5. Achieving fast timing performance with multiplexed SiPMs.

    PubMed

    Bieniosek, M F; Cates, J W; Levin, C S

    2016-04-07

    Using time of flight (ToF) measurements for positron emission tomography (PET) is an attractive avenue for increasing the signal to noise (SNR) ratio of PET images. However, achieving excellent time resolution required for high SNR gain using silicon photomultipliers (SiPM) requires many resource heavy high bandwidth readout channels. A method of multiplexing many SiPM signals into a single electronic channel would greatly simplify ToF PET systems. However, multiplexing SiPMs degrades time resolution because of added dark counts and signal shaping. In this work the relative contribution of dark counts and signal shaping to timing degradation is simulated and a baseline correction technique to mitigate the effect of multiplexing on the time resolution of analog SiPMs is simulated and experimentally verified. A charge sharing network for multiplexing is proposed and tested. Results show a full width at half maximum (FWHM) coincidence time resolution of [Formula: see text] ps for a single 3 mm  ×  3 mm  ×  20 mm LYSO scintillation crystals coupled to an array of sixteen 3 mm  ×  3 mm SiPMs that are multiplexed to a single timing channel (in addition to 4 position channels). A [Formula: see text] array of 3 mm  ×  3 mm  ×  20 mm LFS crystals showed an average FWHM coincidence time resolution of [Formula: see text] ps using the same timing scheme. All experiments were performed at room temperature with no thermal regulation. These results show that excellent time resolution for ToF can be achieved with a highly multiplexed analog SiPM readout.

  6. ZIKA--How fast does this virus mutate?

    PubMed

    Logan, Ian S

    2016-03-18

    The World Health Organization has declared the present Zika virus epidemic to be a 'Public Health Emergency of International Concern'. The virus appears to have spread from Thailand to French Polynesia in 2013, and has since infected over a million people in the countries of South and Central America. In most cases the infection is mild and transient, but the virus does appear to be strongly neurotropic and the presumptive cause of both birth defects in fetuses and Guillain-Barré syndrome in some adults. In this paper, the techniques and utilities developed in the study of mitochondrial DNA were applied to the Zika virus. As a result, it is possible to show in a simple manner how a phylogenetic tree may be constructed and how the mutation rate of the virus can be measured. The study showed the mutation rate to vary between 12 and 25 bases a year, in a viral genome of 10272 bases. This rapid mutation rate will enable the geographic spread of the epidemic to be monitored easily and may also prove useful in assisting the identification of preventative measures that are working, and those that are not.

  7. ZIKA-How fast does this virus mutate?

    PubMed Central

    LOGAN, Ian S.

    2016-01-01

    The World Health Organization has declared the present Zika virus epidemic to be a ‘Public Health Emergency of International Concern’. The virus appears to have spread from Thailand to French Polynesia in 2013, and has since infected over a million people in the countries of South and Central America. In most cases the infection is mild and transient, but the virus does appear to be strongly neurotropic and the presumptive cause of both birth defects in fetuses and Guillain-Barré syndrome in some adults. In this paper, the techniques and utilities developed in the study of mitochondrial DNA were applied to the Zika virus. As a result, it is possible to show in a simple manner how a phylogenetic tree may be constructed and how the mutation rate of the virus can be measured. The study showed the mutation rate to vary between 12 and 25 bases a year, in a viral genome of 10 272 bases. This rapid mutation rate will enable the geographic spread of the epidemic to be monitored easily and may also prove useful in assisting the identification of preventative measures that are working, and those that are not. PMID:27029869

  8. Fast time-resolved electrostatic force microscopy: Achieving sub-cycle time resolution

    NASA Astrophysics Data System (ADS)

    Karatay, Durmus U.; Harrison, Jeffrey S.; Glaz, Micah S.; Giridharagopal, Rajiv; Ginger, David S.

    2016-05-01

    The ability to measure microsecond- and nanosecond-scale local dynamics below the diffraction limit with widely available atomic force microscopy hardware would enable new scientific studies in fields ranging from biology to semiconductor physics. However, commercially available scanning-probe instruments typically offer the ability to measure dynamics only on time scales of milliseconds to seconds. Here, we describe in detail the implementation of fast time-resolved electrostatic force microscopy using an oscillating cantilever as a means to measure fast local dynamics following a perturbation to a sample. We show how the phase of the oscillating cantilever relative to the perturbation event is critical to achieving reliable sub-cycle time resolution. We explore how noise affects the achievable time resolution and present empirical guidelines for reducing noise and optimizing experimental parameters. Specifically, we show that reducing the noise on the cantilever by using photothermal excitation instead of piezoacoustic excitation further improves time resolution. We demonstrate the discrimination of signal rise times with time constants as fast as 10 ns, and simultaneous data acquisition and analysis for dramatically improved image acquisition times.

  9. Genome-wide analysis of mutations in mutant lineages selected following fast-neutron irradiation mutagenesis of Arabidopsis thaliana

    PubMed Central

    Belfield, Eric J.; Gan, Xiangchao; Mithani, Aziz; Brown, Carly; Jiang, Caifu; Franklin, Keara; Alvey, Elizabeth; Wibowo, Anjar; Jung, Marko; Bailey, Kit; Kalwani, Sharan; Ragoussis, Jiannis; Mott, Richard; Harberd, Nicholas P.

    2012-01-01

    Ionizing radiation has long been known to induce heritable mutagenic change in DNA sequence. However, the genome-wide effect of radiation is not well understood. Here we report the molecular properties and frequency of mutations in phenotypically selected mutant lines isolated following exposure of the genetic model flowering plant Arabidopsis thaliana to fast neutrons (FNs). Previous studies suggested that FNs predominantly induce deletions longer than a kilobase in A. thaliana. However, we found a higher frequency of single base substitution than deletion mutations. While the overall frequency and molecular spectrum of fast-neutron (FN)–induced single base substitutions differed substantially from those of “background” mutations arising spontaneously in laboratory-grown plants, G:C>A:T transitions were favored in both. We found that FN-induced G:C>A:T transitions were concentrated at pyrimidine dinucleotide sites, suggesting that FNs promote the formation of mutational covalent linkages between adjacent pyrimidine residues. In addition, we found that FNs induced more single base than large deletions, and that these single base deletions were possibly caused by replication slippage. Our observations provide an initial picture of the genome-wide molecular profile of mutations induced in A. thaliana by FN irradiation and are particularly informative of the nature and extent of genome-wide mutation in lines selected on the basis of mutant phenotypes from FN-mutagenized A. thaliana populations. PMID:22499668

  10. Life insurance and genetic test results: a mutation carrier's fight to achieve full cover.

    PubMed

    Keogh, Louise A; Otlowski, Margaret F A

    2013-09-02

    Currently, there is debate about life insurance companies' use of genetic information for assessing applicants. In his early 20s, James (pseudonym) was denied full life insurance cover because he revealed that he had discussed genetic testing with a genetic counsellor. He was later tested and found to carry a mutation in the MSH6 gene; after disclosing this, he was denied cover for cancer by two other life insurance companies. Unsatisfied with the insurance companies' risk assessments, and based on his understanding that regular colonoscopy significantly reduced his risk of cancer, James made a complaint to the Australian Human Rights Commission. After informing the third insurance company that he had done so, he was offered full coverage, which suggests that the company did not have actuarial data to justify its decision. This case provides evidence of the high level of initiative and proactivity required for a consumer to achieve a fair result. Few Australians would be in a position to pursue the level of research and advocacy undertaken by James (a professional with scientific training). We call on a collaborative approach between industry, government and researchers to address the issues that James's case raises about genetic testing and life insurance.

  11. A novel somatic mutation achieves partial rescue in a child with Hutchinson-Gilford progeria syndrome

    PubMed Central

    Bar, Daniel Z; Arlt, Martin F; Brazier, Joan F; Norris, Wendy E; Campbell, Susan E; Chines, Peter; Larrieu, Delphine; Jackson, Stephen P; Collins, Francis S; Glover, Thomas W; Gordon, Leslie B

    2017-01-01

    Background Hutchinson-Gilford progeria syndrome (HGPS) is a fatal sporadic autosomal dominant premature ageing disease caused by single base mutations that optimise a cryptic splice site within exon 11 of the LMNA gene. The resultant disease-causing protein, progerin, acts as a dominant negative. Disease severity relies partly on progerin levels. Methods and results We report a novel form of somatic mosaicism, where a child possessed two cell populations with different HGPS disease-producing mutations of the same nucleotide—one producing severe HGPS and one mild HGPS. The proband possessed an intermediate phenotype. The mosaicism was initially discovered when Sanger sequencing showed a c.1968+2T>A mutation in blood DNA and a c.1968+2T>C in DNA from cultured fibroblasts. Deep sequencing of DNA from the proband's blood revealed 4.7% c.1968+2T>C mutation, and 41.3% c.1968+2T>A mutation. Conclusions We hypothesise that the germline mutation was c.1968+2T>A, but a rescue event occurred during early development, where the somatic mutation from A to C at 1968+2 provided a selective advantage. This type of mosaicism where a partial phenotypic rescue event results from a second but milder disease-causing mutation in the same nucleotide has not been previously characterised for any disease. PMID:27920058

  12. Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae

    PubMed Central

    Oud, Bart; Guadalupe-Medina, Victor; Nijkamp, Jurgen F.; de Ridder, Dick; Pronk, Jack T.; van Maris, Antonius J. A.; Daran, Jean-Marc

    2013-01-01

    Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to manipulating cell sedimentation in laboratory and industrial applications of S. cerevisiae. Multicellular, fast-sedimenting lineages obtained from a haploid S. cerevisiae strain in two independent evolution experiments were analyzed by whole genome resequencing. The two evolved cell lines showed different frameshift mutations in a stretch of eight adenosines in ACE2, which encodes a transcriptional regulator involved in cell cycle control and mother-daughter cell separation. Introduction of the two ace2 mutant alleles into the haploid parental strain led to slow-sedimenting cell clusters that consisted of just a few cells, thus representing only a partial reconstruction of the evolved phenotype. In addition to single-nucleotide mutations, a whole-genome duplication event had occurred in both evolved multicellular strains. Construction of a diploid reference strain with two mutant ace2 alleles led to complete reconstruction of the multicellular-fast sedimenting phenotype. This study shows that whole-genome duplication and a frameshift mutation in ACE2 are sufficient to generate a fast-sedimenting, multicellular phenotype in S. cerevisiae. The nature of the ace2 mutations and their occurrence in two independent evolution experiments encompassing fewer than 500 generations of selective growth suggest that switching between unicellular and multicellular phenotypes may be relevant for competitiveness of S. cerevisiae in natural environments. PMID:24145419

  13. Evolution in Fast Forward: a Potential Role for Mutators in Accelerating Staphylococcus aureus Pathoadaptation

    PubMed Central

    Canfield, Gregory S.; Schwingel, Johanna M.; Foley, Matthew H.; Vore, Kelly L.; Boonanantanasarn, Kanitsak; Gill, Ann L.; Sutton, Mark D.

    2013-01-01

    Pathogen evolution and subsequent phenotypic heterogeneity during chronic infection are proposed to enhance Staphylococcus aureus survival during human infection. We tested this theory by genetically and phenotypically characterizing strains with mutations constructed in the mismatch repair (MMR) and oxidized guanine (GO) system, termed mutators, which exhibit increased spontaneous-mutation frequencies. Analysis of these mutators revealed not only strain-dependent increases in the spontaneous-mutation frequency but also shifts in mutational type and hot spots consistent with loss of GO or MMR functions. Although the GO and MMR systems are relied upon in some bacterial species to prevent reactive oxygen species-induced DNA damage, no deficit in hydrogen peroxide sensitivity was found when either of these DNA repair pathways was lost in S. aureus. To gain insight into the contribution of increased mutation supply to S. aureus pathoadaptation, we measured the rate of α-hemolysin and staphyloxanthin inactivation during serial passage. Detection of increased rates of α-hemolysin and staphyloxanthin inactivation in GO and MMR mutants suggests that these strains are capable of modifying virulence phenotypes implicated in mediating infection. Accelerated derivation of altered virulence phenotypes, combined with the absence of increased ROS sensitivity, highlights the potential of mutators to drive pathoadaptation in the host and serve as catalysts for persistent infections. PMID:23204459

  14. The Impact of Fast ForWord on MCT Scores and Student Achievement

    ERIC Educational Resources Information Center

    Van Vinkle, Michael Harvey

    2009-01-01

    Educators today were concerned with how the No Child Left Behind Act of 2001 dealt with the improvement of education throughout the United States. Schools should have put forth a greater effort and reduced the achievement gap between different groups of students based on race, gender, special education status, and if that student was economically…

  15. Improvement of Nannochloropsis oceanica growth performance through chemical mutation and characterization of fast growth physiology by transcriptome profiling

    NASA Astrophysics Data System (ADS)

    Liang, Sijie; Guo, Li; Lin, Genmei; Zhang, Zhongyi; Ding, Haiyan; Wang, Yamei; Yang, Guanpin

    2016-09-01

    Nannochloropsis oceanica promises to be an industrial-level producer of polyunsaturated fatty acids. In this study, the fastest and slowest growing N. oceanica mutants were selected through N-methyl-N'-nitro-N-nitrosoguanidine mutation, and two mutant strains and the wild type (WT) subjected to transcriptome profiling. It was found that the OD680 reads at stationary growth phase of both WT and its mutants were proportional to their cell density, thus indicating their division rate and growth speed during culture. This chemical mutation was effective for improving growth performance, and the fast strain divided faster by upregulating the expression of genes functioning in the cell cycle and downregulating genes involved in synthesis of amino acids, fatty acids, and sugars as well as the construction of ribosome and photosynthetic machinery. However, the relationship among the effected genes responsible for cell cycle, metabolism of fatty and amino acids, and construction of ribosome and photosynthetic machinery remained unclear. Further genetic studies are required for clarifying the genetic/metabolic networks underpinning the growth performance of N. oceanica. These findings demonstrated that this mutation strategy was effective for improving the growth performance of this species and explored a means of microalgal genetic improvement, particularly in species possessing a monoploid nucleus and asexual reproduction.

  16. Achieving Fast Self Healing in Wireless Sensor Networks Using Multi-generation Deployment Schemes

    NASA Astrophysics Data System (ADS)

    Yılmaz, Ömer Zekvan; Levi, Albert; Savaş, Erkay

    The majority of studies on security in resource limited wireless sensor networks (WSN) focus on finding an efficient balance among energy consumption, computational speed and memory usage. Besides these resources, time is a relatively immature aspect that can be considered in system design and performance evaluations. In a recent study by Castelluccia and Spognardi , the time dimension is used to lower the ratio of compromised links, thus, improving resiliency in key distribution in WSNs. This is achieved by making the old and possibly compromised keys useful only for a limited amount of time. In this way, the effect of compromised keys diminish in time, so the WSN selfheals. In this study we further manipulate the time dimension and propose a deployment model that speeds up the resilience improvement process with a tradeoff between connectivity and resiliency. In our method, self healing speeds up by introducing nodes that belong to future generations in the time scale. In this way, the duration that the adversary can make use of compromised keys become smaller.

  17. Inherited pain: sodium channel Nav1.7 A1632T mutation causes erythromelalgia due to a shift of fast inactivation.

    PubMed

    Eberhardt, Mirjam; Nakajima, Julika; Klinger, Alexandra B; Neacsu, Cristian; Hühne, Kathrin; O'Reilly, Andrias O; Kist, Andreas M; Lampe, Anne K; Fischer, Kerstin; Gibson, Jane; Nau, Carla; Winterpacht, Andreas; Lampert, Angelika

    2014-01-24

    Inherited erythromelalgia (IEM) causes debilitating episodic neuropathic pain characterized by burning in the extremities. Inherited "paroxysmal extreme pain disorder" (PEPD) differs in its clinical picture and affects proximal body areas like the rectal, ocular, or jaw regions. Both pain syndromes have been linked to mutations in the voltage-gated sodium channel Nav1.7. Electrophysiological characterization shows that IEM-causing mutations generally enhance activation, whereas mutations leading to PEPD alter fast inactivation. Previously, an A1632E mutation of a patient with overlapping symptoms of IEM and PEPD was reported (Estacion, M., Dib-Hajj, S. D., Benke, P. J., Te Morsche, R. H., Eastman, E. M., Macala, L. J., Drenth, J. P., and Waxman, S. G. (2008) NaV1.7 Gain-of-function mutations as a continuum. A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders. J. Neurosci. 28, 11079-11088), displaying a shift of both activation and fast inactivation. Here, we characterize a new mutation of Nav1.7, A1632T, found in a patient suffering from IEM. Although transfection of A1632T in sensory neurons resulted in hyperexcitability and spontaneous firing of dorsal root ganglia (DRG) neurons, whole-cell patch clamp of transfected HEK cells revealed that Nav1.7 activation was unaltered by the A1632T mutation but that steady-state fast inactivation was shifted to more depolarized potentials. This is a characteristic normally attributed to PEPD-causing mutations. In contrast to the IEM/PEPD crossover mutation A1632E, A1632T failed to slow current decay (i.e. open-state inactivation) and did not increase resurgent currents, which have been suggested to contribute to high-frequency firing in physiological and pathological conditions. Reduced fast inactivation without increased resurgent currents induces symptoms of IEM, not PEPD, in the new Nav1.7 mutation, A1632T. Therefore

  18. Evolution of fast mutating replicators—RNA viruses and the RNA world

    NASA Astrophysics Data System (ADS)

    Manrubia, Susanna C.

    2006-11-01

    In the last two decades, viruses have become the model system to witness evolution in the laboratory. Large population sizes, high mutation rates, and short generation times are the three features that permit to carry out in vitro experiments under controlled conditions. In this contribution we briefly review a number of recent experiments that open new prospectives in our understanding of molecular evolutionary mechanisms, in their dependence with population dynamics and quasispecies organization, and in the interaction between heterogeneous populations and the environment. One of the possible origins of RNA viruses is a hypothetical RNA world, previous to our present DNA world, where information coding and catalytic functions would be simultaneously performed by RNA molecules.

  19. Fast fish face fewer mitochondrial mutations: Patterns of dN/dS across fish mitogenomes.

    PubMed

    Strohm, Jeff H T; Gwiazdowski, Rodger A; Hanner, Robert

    2015-11-01

    Mitochondrial DNA is routinely used to answer a variety of biological questions; and there is growing evidence suggesting that its accumulation of mutations is influenced by life history, effective population size and cellular energy requirements. This study examines the influence of phylogenetic patterns of metabolic activity on the evolution of mitochondrial DNA in fishes, given energy requirements associated with high performance versus sedentary life histories. It was determined that all 13 protein coding genes of the mitogenome experience a relaxation of purifying selection in sedentary fishes. This phenomenon was not detected in nuclear housekeeping genes, suggesting that it can be explained by the energy requirements of these groups, and possibly their effective population sizes. This study also examined the subunit binding sites of two subunits of cytochrome c oxidase (COXI and COXIII), and did not detect any differences in selection between these groups of fishes. These cytochrome c oxidase subunits interact with subunits that are encoded by the nuclear genome and it has been suggested that a unique form of coevolution occurs between these genomes in order to maintain function, and may have implications for speciation. Although this was not a main focus of this study, our preliminary results suggest that substitutions in subunit binding site regions are rare. The results from this study add to the growing literature on the complex relationship between mitochondrial DNA and the evolution of life histories across the tree of life.

  20. Mutation discovery for Mendelian traits in non-laboratory animals: a review of achievements up to 2012.

    PubMed

    Nicholas, Frank W; Hobbs, Matthew

    2014-04-01

    Within two years of the re-discovery of Mendelism, Bateson and Saunders had described six traits in non-laboratory animals (five in chickens and one in cattle) that show single-locus (Mendelian) inheritance. In the ensuing decades, much progress was made in documenting an ever-increasing number of such traits. In 1987 came the first discovery of a causal mutation for a Mendelian trait in non-laboratory animals: a non-sense mutation in the thyroglobulin gene (TG), causing familial goitre in cattle. In the years that followed, the rate of discovery of causal mutations increased, aided mightily by the creation of genome-wide microsatellite maps in the 1990s and even more mightily by genome assemblies and single-nucleotide polymorphism (SNP) chips in the 2000s. With sequencing costs decreasing rapidly, by 2012 causal mutations were being discovered in non-laboratory animals at a rate of more than one per week. By the end of 2012, the total number of Mendelian traits in non-laboratory animals with known causal mutations had reached 499, which was half the number of published single-locus (Mendelian) traits in those species. The distribution of types of mutations documented in non-laboratory animals is fairly similar to that in humans, with almost half being missense or non-sense mutations. The ratio of missense to non-sense mutations in non-laboratory animals to the end of 2012 was 193:78. The fraction of non-sense mutations (78/271 = 0.29) was not very different from the fraction of non-stop codons that are just one base substitution away from a stop codon (21/61 = 0.34).

  1. Investigations on the heat transport capability of a cryogenic oscillating heat pipe and its application in achieving ultra-fast cooling rates for cell vitrification cryopreservation.

    PubMed

    Han, Xu; Ma, Hongbin; Jiao, Anjun; Critser, John K

    2008-06-01

    Theoretically, direct vitrification of cell suspensions with relatively low concentrations ( approximately 1 M) of permeating cryoprotective agents (CPA) is suitable for cryopreservation of almost all cell types and can be accomplished by ultra-fast cooling rates that are on the order of 10(6-7) K/min. However, the methods and devices currently available for cell cryopreservation cannot achieve such high cooling rates. In this study, we constructed a novel cryogenic oscillating heat pipe (COHP) using liquid nitrogen as its working fluid and investigated its heat transport capability to assess its application for achieving ultra-fast cooling rates for cell cryopreservation. The experimental results showed that the apparent heat transfer coefficient of the COHP can reach 2 x 10(5) W/m(2).K, which is two orders of the magnitude higher than traditional heat pipes. Theoretical analyzes showed that the average local heat transfer coefficient in the thin film evaporation region of the COHP can reach 1.2 x 10(6) W/m(2).K, which is approximately 10(3) times higher than that achievable with standard pool-boiling approaches. Based on these results, a novel device design applying the COHP and microfabrication techniques is proposed and its efficiency for cell vitrification is demonstrated through numerical simulation. The estimated average cooling rates achieved through this approach is 10(6-7)K/min, which is much faster than the currently available methods and sufficient for achieving vitrification with relatively low concentrations of CPA.

  2. A fast but accurate excitonic simulation of the electronic circular dichroism of nucleic acids: how can it be achieved?

    PubMed

    Loco, Daniele; Jurinovich, Sandro; Di Bari, Lorenzo; Mennucci, Benedetta

    2016-01-14

    We present and discuss a simple and fast computational approach to the calculation of electronic circular dichroism spectra of nucleic acids. It is based on a exciton model in which the couplings are obtained in terms of the full transition-charge distributions, as resulting from TDDFT methods applied on the individual nucleobases. We validated the method on two systems, a DNA G-quadruplex and a RNA β-hairpin whose solution structures have been accurately determined by means of NMR. We have shown that the different characteristics of composition and structure of the two systems can lead to quite important differences in the dependence of the accuracy of the simulation on the excitonic parameters. The accurate reproduction of the CD spectra together with their interpretation in terms of the excitonic composition suggest that this method may lend itself as a general computational tool to both predict the spectra of hypothetic structures and define clear relationships between structural and ECD properties.

  3. Fast capillary electrophoresis-laser induced fluorescence analysis of ligase chain reaction products: human mitochondrial DNA point mutations causing Leber's hereditary optic neuropathy.

    PubMed

    Muth, J; Williams, P M; Williams, S J; Brown, M D; Wallace, D C; Karger, B L

    1996-12-01

    High speed capillary electrophoresis-laser-induced fluorescence (CE-LIF) has been used to separate and detect point mutations using the ligase chain reaction (LCR). The method utilizes short capillary columns (7.5 cm effective length) and fields of 400 V/cm to analyze DNA-ethidium bromide complexes using an He/Ne laser. The method was first demonstrated with a commercially available kit for LCR based on a lacI gene fragment inserted in a Bluescript II phagemid. LCR-CE-LIF was then applied to detect point mutations in human mitochondrial DNA, resulting in Leber's hereditary optic neuropathy (LHON). Three severe mutations were analyzed in which the original base is substituted by a thymidine base at positions 3460, 11778 and 14459. Appropriate primers were designed with polyT tails for length discrimination of pooled samples. Successful detection of mutated samples was achieved, with appropriate correction for small amounts of nonspecific ligated product. The method is rapid, easy to implement, and automatable.

  4. Achieving cholesterol targets by individualizing starting doses of statin according to baseline low-density lipoprotein cholesterol and coronary artery disease risk category: The CANadians Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (CanACTFAST) study

    PubMed Central

    Ur, Ehud; Langer, Anatoly; Rabkin, Simon W; Calciu, Cristina-Dana; Leiter, Lawrence A

    2010-01-01

    BACKGROUND: Despite an increasing body of evidence on the benefit of lowering elevated levels of low-density lipoprotein cholesterol (LDL-C), there is still considerable concern that patients are not achieving target LDL-C levels. OBJECTIVE: The CANadians Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (CanACTFAST) trial tested whether an algorithm-based statin dosing approach would enable patients to achieve LDL-C and total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio targets quickly. METHODS: Subjects requiring statin therapy, but with an LDL-C level of 5.7 mmol/L or lower, and triglycerides of 6.8 mmol/L or lower at screening participated in the 12-week study, which had two open-label, six-week phases: a treatment period during which patients received 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin based on an algorithm incorporating baseline LDL-C value and cardiovascular risk; and patients who achieved both LDL-C and TC/HDL-C ratio targets at six weeks continued on the same atorvastatin dose. Patients who did not achieve both targets received dose uptitration using a single-step titration regimen. The primary efficacy outcome was the proportion of patients achieving target LDL-C levels after 12 weeks. RESULTS: Of 2016 subjects screened at 88 Canadian sites, 1258 were assigned to a study drug (1101 were statin-free and 157 were statin-treated at baseline). The proportion of subjects who achieved LDL-C targets after 12 weeks of treatment was 86% (95% CI 84% to 88%) for statin-free patients and 54% (95% CI 46% to 61%) for statin-treated patients. Overall, 1003 subjects (80%; 95% CI 78% to 82%) achieved both lipid targets. CONCLUSIONS: Algorithm-based statin dosing enables patients to achieve LDL-C and TC/HDL-C ratio targets quickly, with either no titration or a single titration. PMID:20151053

  5. Next-generation sequencing (NGS) as a fast molecular diagnosis tool for left ventricular noncompaction in an infant with compound mutations in the MYBPC3 gene.

    PubMed

    Schaefer, Elise; Helms, Pauline; Marcellin, Luc; Desprez, Philippe; Billaud, Philippe; Chanavat, Valérie; Rousson, Robert; Millat, Gilles

    2014-03-01

    Left ventricular noncompaction (LVNC) is a clinically heterogeneous disorder characterized by a trabecular meshwork and deep intertrabecular myocardial recesses that communicate with the left ventricular cavity. LVNC is classified as a rare genetic cardiomyopathy. Molecular diagnosis is a challenge for the medical community as the condition shares morphologic features of hypertrophic and dilated cardiomyopathies. Several genetic causes of LVNC have been reported, with variable modes of inheritance, including autosomal dominant and X-linked inheritance, but relatively few responsible genes have been identified. In this report, we describe a case of a severe form of LVNC leading to death at 6 months of life. NGS sequencing using a custom design for hypertrophic cardiomyopathy panel allowed us to identify compound heterozygosity in the MYBPC3 gene (p.Lys505del, p.Pro955fs) in 3 days, confirming NGS sequencing as a fast molecular diagnosis tool. Other studies have reported neonatal presentation of cardiomyopathies associated with compound heterozygous or homozygous MYBPC3 mutations. In this family and in families in which parental truncating MYBPC3 mutations are identified, preimplantation or prenatal genetic screening should be considered as these genotypes leads to neonatal mortality and morbidity.

  6. Differential screening of mutated SOD1 transgenic mice reveals early up-regulation of a fast axonal transport component in spinal cord motor neurons.

    PubMed

    Dupuis, L; de Tapia, M; René, F; Lutz-Bucher, B; Gordon, J W; Mercken, L; Pradier, L; Loeffler, J P

    2000-08-01

    In the present study we analyze the molecular mechanisms underlying motor neuron degeneration in familial amyotrophic lateral sclerosis (FALS). For this, we used a transgenic mouse model expressing the Cu/Zn superoxide dismutase (SOD1) gene with a Gly(86) to Arg (G86R) mutation equivalent to that found in a subset of human FALS. Using an optimized suppression subtractive hybridization method, a cDNA specifically up-regulated during the asymptomatic phase in the lumbar spinal cord of G86R mice was identified by sequence analysis as the KIF3-associated protein (KAP3), a regulator of fast axonal transport. RT-PCR analysis revealed that KAP3 induction was an early event arising long before axonal degeneration. Immunohistochemical studies further revealed that KAP3 protein predominantly accumulates in large motor neurons of the ventral spinal cord. We further demonstrated that KAP3 up-regulation occurs independent of any change in the other components of the kinesin II complex. However, since the ubiquitous KIF1A motor is up-regulated, our results show an early and complex rearrangement of the fast axonal transport machinery in the course of FALS pathology.

  7. Analog electro-optical readout of SiPMs achieves fast timing required for time-of-flight PET/MR

    PubMed Central

    Bieniosek, MF

    2015-01-01

    The design of combined positron emission tomography/magnetic resonance (PET/MR) systems presents a number of challenges to engineers, as it forces the PET system to acquire data in space constrained environment that is sensitive to electro-magnetic interference and contains high static, radio frequency (RF) and gradient fields. In this work we validate fast timing performance of a PET scintillation detector using a potentially very compact, very low power, and MR compatible readout method in which analog silicon photomultipliers (SiPM) signals are transmitted optically away from the MR bore with little or even no additional readout electronics. This analog ‘electro-optial’ method could reduce the entire PET readout in the MR bore to two compact, low power components (SiPMs and lasers). Our experiments show fast timing performance from analog electro-optical readout with and without pre-amplification. With 3mm × 3mm × 20mm lutetium-yttrium oxyorthosilicate (LYSO) crystals and Excelitas SiPMs the best two-sided fwhm coincident timing resolution achieved was 220 +/- 3ps in electrical mode, 230 +/- 2ps in electro-optical with preamp mode, and 253 +/- 2ps in electro-optical without preamp mode. Timing measurements were also performed with Hamamatsu SiPMs and 3mm × 3mm × 5mm crystals. In the future the timing degradation seen can be further reduced with lower laser noise or improvements SiPM rise time or gain. PMID:25905626

  8. Analog electro-optical readout of SiPMs achieves fast timing required for time-of-flight PET/MR.

    PubMed

    Bieniosek, M F; Levin, C S

    2015-05-07

    The design of combined positron emission tomography/magnetic resonance (PET/MR) systems presents a number of challenges to engineers, as it forces the PET system to acquire data in a space constrained environment that is sensitive to electro-magnetic interference and contains high static, radio frequency and gradient fields. In this work we validate fast timing performance of a PET scintillation detector using a potentially very compact, very low power, and MR compatible readout method in which analog silicon photomultipliers (SiPM) signals are transmitted optically away from the MR bore with little or even no additional readout electronics. This analog 'electro-optial' method could reduce the entire PET readout in the MR bore to two compact, low power components (SiPMs and lasers). Our experiments show fast timing performance from analog electro-optical readout with and without pre-amplification. With 3 mm × 3 mm × 20 mm lutetium-yttrium oxyorthosilicate (LYSO) crystals and Excelitas SiPMs the best two-sided fwhm coincident timing resolution achieved was 220 +/- 3 ps in electrical mode, 230 +/- 2 ps in electro-optical with preamp mode, and 253 +/- 2 ps in electro-optical without preamp mode. Timing measurements were also performed with Hamamatsu SiPMs and 3 mm × 3 mm × 5 mm crystals. In the future the timing degradation seen can be further reduced with lower laser noise or improvements SiPM rise time or gain.

  9. Fast super-resolution imaging with ultra-high labeling density achieved by joint tagging super-resolution optical fluctuation imaging.

    PubMed

    Zeng, Zhiping; Chen, Xuanze; Wang, Hening; Huang, Ning; Shan, Chunyan; Zhang, Hao; Teng, Junlin; Xi, Peng

    2015-02-10

    Previous stochastic localization-based super-resolution techniques are largely limited by the labeling density and the fidelity to the morphology of specimen. We report on an optical super-resolution imaging scheme implementing joint tagging using multiple fluorescent blinking dyes associated with super-resolution optical fluctuation imaging (JT-SOFI), achieving ultra-high labeling density super-resolution imaging. To demonstrate the feasibility of JT-SOFI, quantum dots with different emission spectra were jointly labeled to the tubulin in COS7 cells, creating ultra-high density labeling. After analyzing and combining the fluorescence intermittency images emanating from spectrally resolved quantum dots, the microtubule networks are capable of being investigated with high fidelity and remarkably enhanced contrast at sub-diffraction resolution. The spectral separation also significantly decreased the frame number required for SOFI, enabling fast super-resolution microscopy through simultaneous data acquisition. As the joint-tagging scheme can decrease the labeling density in each spectral channel, thereby bring it closer to single-molecule state, we can faithfully reconstruct the continuous microtubule structure with high resolution through collection of only 100 frames per channel. The improved continuity of the microtubule structure is quantitatively validated with image skeletonization, thus demonstrating the advantage of JT-SOFI over other localization-based super-resolution methods.

  10. Migrant Students with Limited English Proficiency: Can Fast ForWord Language? Make a Difference in Their Language Skills and Academic Achievement?

    ERIC Educational Resources Information Center

    Troia, Gary A.

    2004-01-01

    This study evaluated the efficacy of the computer-assisted intervention program known as Fast ForWord Language? in a sample of migrant students in Grades 1 through 6 who were native Spanish speakers. Fast ForWord Language? combines intensive training in multiple receptive English language skills with adaptive acoustic waveform lengthening and…

  11. Competitive allele-specific TaqMan PCR (Cast-PCR) is a sensitive, specific and fast method for BRAF V600 mutation detection in Melanoma patients

    PubMed Central

    Barbano, Raffaela; Pasculli, Barbara; Coco, Michelina; Fontana, Andrea; Copetti, Massimiliano; Rendina, Michelina; Valori, Vanna Maria; Graziano, Paolo; Maiello, Evaristo; Fazio, Vito Michele; Parrella, Paola

    2015-01-01

    BRAF codon 600 mutation testing of melanoma patients is mandatory for the choice of the most appropriate therapy in the clinical setting. Competitive allele specific TaqMan PCR (Cast-PCR) technology allows not only the selective amplification of minor alleles, but it also blocks the amplification of non-mutant allele. We genotyped codon 600 of the BRAF gene in 54 patients’ samples by Cast-PCR and bidirectional direct sequence analysis. All the mutations detected by sequencing were also identified by Cast-PCR. In addition, Cast-PCR assay detected four samples carrying mutations and was able to clearly identify two mutations of uncertain interpretation by Sanger sequencing. The limit of detection of Cast-PCR was evaluated by constructing dilution curves of BRAFV600E and BRAFV600K mutated clinical samples mixed with a not-mutated specimens. Both mutations could be detected until a 1:100 mutated/not mutated ratio. Cloning and sequencing of the clones was used to confirm mutations on representative discrepant cases. Cast PCR performances were not affected by intratumour heterogeneity, and less affected by melanin content. Our results indicate that Cast-PCR is a reliable diagnostic tool for the identification of melanoma patients as eligible to be treated with TKIs and might be implemented in the clinical setting as elective screening method. PMID:26690267

  12. Fast Atomic-Scale Elemental Mapping of Crystalline Materials by STEM Energy-Dispersive X-Ray Spectroscopy Achieved with Thin Specimens.

    PubMed

    Lu, Ping; Yuan, Renliang; Zuo, Jian Min

    2017-02-01

    Elemental mapping at the atomic-scale by scanning transmission electron microscopy (STEM) using energy-dispersive X-ray spectroscopy (EDS) provides a powerful real-space approach to chemical characterization of crystal structures. However, applications of this powerful technique have been limited by inefficient X-ray emission and collection, which require long acquisition times. Recently, using a lattice-vector translation method, we have shown that rapid atomic-scale elemental mapping using STEM-EDS can be achieved. This method provides atomic-scale elemental maps averaged over crystal areas of ~few 10 nm2 with the acquisition time of ~2 s or less. Here we report the details of this method, and, in particular, investigate the experimental conditions necessary for achieving it. It shows, that in addition to usual conditions required for atomic-scale imaging, a thin specimen is essential for the technique to be successful. Phenomenological modeling shows that the localization of X-ray signals to atomic columns is a key reason. The effect of specimen thickness on the signal delocalization is studied by multislice image simulations. The results show that the X-ray localization can be achieved by choosing a thin specimen, and the thickness of less than about 22 nm is preferred for SrTiO3 in [001] projection for 200 keV electrons.

  13. The fast-spectrum transmutation experimental facility FASTEF: Main design achievements (Part 1: Core and primary system) within the FP7-CDT collaborative project of the European Commission

    SciTech Connect

    De Bruyn, D.; Fernandez, R.; Mansani, L.; Woaye-Hune, A.; Sarotto, M.; Bubelis, E.

    2012-07-01

    MYRRHA (Multi-purpose hybrid Research Reactor for High-tech Applications) is the flexible experimental accelerator-driven system (ADS) in development at SCK CEN in replacement of its material testing reactor BR2. SCK CEN in association with 17 European partners from industry, research centres and academia, responded to the FP7 (Seventh Framework Programme) call from the European Commission to establish a Central Design Team (CDT) for the design of a Fast Spectrum Transmutation Experimental Facility (FASTEF) able to demonstrate efficient transmutation and associated technology through a system working in subcritical and/or critical mode. The project has started on April 01, 2009 for a period of three years. In this paper, we present the latest configuration of the reactor core and primary system. The FASTEF facility has evolved quite a lot since the intermediate reporting done at the ICAPP'10 and ICAPP'11 conferences 1 2. If it remains a small-scale facility, the core power amounts now up to 100 MWth in critical mode. In a companion paper 3, we present the concept of the reactor building and the plant layout. (authors)

  14. The use of primary rat hepatocytes to achieve metabolic activation of promutagens in the Chinese hamster ovary/hypoxantine-guanine phosphoribosyl transferase mutational assay

    SciTech Connect

    Bermudez, E.; Couch, D.B.; Tillery, D.

    1982-01-01

    A method is described in which primary rat hepatocytes have been cocultured with chinese hamster ovary (CHO) cells to provide metabolic activation of promutgens in the Chinese hamster ovary/hypoxanthine-guanine phosphoribosyl transferase (CHO/HGPRT) mutational assay. Single cell hepatocyte suspensions were prepared from male Fisher-344 rats using the in situ collagenase perfusion technique. Hepatocytes were allowed to attach for 1.5 hours in tissue culture dishes containing an approximately equal number of CHO cells in log growth. The cocultures were exposed to promutagens for up to 20 hours in serum-free medium. The survival and 6-thioguanine-resistant fraction of treated CHO cells were then determined as in the standard CHO/HGPRT assay. Aflatoxin B/sub 1/ (AFB/sub 1/) 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (B(a)P) were found to produce increases in the mutant fractions of treated CHO cells as a function of concentration. The time required for optimum expression of the mutant phenotype following exposure to DMBA and AFB/sub 1/ was approximately 8 days. Primary cell-mediated mutagenesis may be useful in elucidating methobolic pathways important in the production and detoxification of genotoxic products in vivo.

  15. Novel mass spectrometry mutation screening for contaminant impact analysis. 1998 annual progress report

    SciTech Connect

    Chen, C.H.

    1998-06-01

    'The objective is to develop innovative mass spectrometry technology to achieve fast mutation screening from contaminated area and to reveal the linkage between gene mutation and contaminants. In this program, the author will try innovative approaches to improve mass resolution and detection efficiency for large DNA ions. Allel specific polymerase chain reaction will be coupled with mass spectrometry for rapid DNA mutation detection. The ultimate goal is to lead to the risk analysis of hazardous wastes to be routinely assessed at DNA level at an affordable cost. This report is for the work after 7 months of a 3-year project.'

  16. Impact of diabetes duration on achieved reductions in glycated haemoglobin, fasting plasma glucose and body weight with liraglutide treatment for up to 28 weeks: a meta‐analysis of seven phase III trials

    PubMed Central

    Bailey, T.; Barkholt Christensen, S.; Nauck, M. A.

    2016-01-01

    This meta‐analysis of seven randomized, placebo‐controlled studies (total 3222 patients) evaluated whether type 2 diabetes (T2D) duration affects the changes in blood glucose control and body weight that can be achieved with liraglutide and placebo. With liraglutide 1.2 mg, shorter diabetes duration was associated with a significantly greater, but clinically non‐relevant, difference in glycated haemoglobin (HbA1c) reduction (p < 0.05), i.e. a 0.18% (1.96 mmol/mol) reduction in HbA1c per 10 years shorter diabetes duration. With liraglutide 1.8 mg, shorter diabetes duration was associated with a small but statistically significant trend for greater fasting plasma glucose (FPG) reduction (p < 0.05), i.e. a 0.38 mmol/l reduction in FPG per 10 years shorter diabetes duration. Neither the liraglutide 1.8 mg nor placebo results showed a significant association between HbA1c and diabetes duration and neither the liraglutide 1.2 mg nor placebo results showed a significant association between FPG and diabetes duration. Likewise, neither liraglutide nor placebo showed a significant association between change in weight and diabetes duration. These results suggest diabetes duration has a clinically negligible effect on achievable blood glucose control and weight outcomes with liraglutide and placebo in patients with T2D. PMID:26679282

  17. How Fast Is Fast?

    ERIC Educational Resources Information Center

    Korn, Abe

    1994-01-01

    Presents an activity that enables students to answer for themselves the question of how fast a body must travel before the nonrelativistic expression must be replaced with the correct relativistic expression by deciding on the accuracy required in describing the kinetic energy of a body. (ZWH)

  18. A global study of the unmet need for glycemic control and predictor factors among patients with type 2 diabetes mellitus who have achieved optimal fasting plasma glucose control on basal insulin

    PubMed Central

    Chou, Engels; Colagiuri, Stephen; Gaàl, Zsolt; Lavalle, Fernando; Mkrtumyan, Ashot; Nikonova, Elena; Tentolouris, Nikolaos; Vidal, Josep; Davies, Melanie

    2016-01-01

    Abstract Background This study used data from different sources to identify the extent of the unmet need for postprandial glycemic control in patients with type 2 diabetes mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia Pacific, the United States, and Latin America. Methods Different levels of evidence were used as available for each country/region, with data extracted from seven randomized controlled trials (RCTs), three clinical trial registries (CTRs), and three electronic medical record (EMR) databases. Glycemic status was categorized as “well controlled” (glycated hemoglobin [HbA1c] at target [<7%]), “residual hyperglycemia” (fasting plasma glucose [FPG] but not HbA1c at target [FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country‐specific recommendations]), or “uncontrolled” (both FPG and HbA1c above target). Predictor factors were identified from the RCT data set using logistic regression analysis. Results RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1% of patients with T2DM had well‐controlled glycemia, residual hyperglycemia, and uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8% to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to 21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of residual hyperglycemia identified from RCT data included high baseline HbA1c (all countries/regions except Brazil), high baseline FPG (United Kingdom/Japan), longer duration of diabetes (Brazil), and female sex (Europe/Latin America). Conclusions Irrespective of intrinsic differences between data sources, 24% to 54% of patients with T2DM globally had residual hyperglycemia with HbA1c not at target, despite achieving FPG control, indicating a significant unmet need for postprandial glycemic control. PMID:27606888

  19. Fast Reactors

    NASA Astrophysics Data System (ADS)

    Esposito, S.; Pisanti, O.

    The following sections are included: * Elementary Considerations * The Integral Equation to the Neutron Distribution * The Critical Size for a Fast Reactor * Supercritical Reactors * Problems and Exercises

  20. Integral Fast Reactor concept

    SciTech Connect

    Till, C.E.; Chang, Y.I.

    1986-01-01

    The Integral Fast Reactor (IFR) is an innovative LMR concept, being developed at Argonne National Laboratory, that fully exploits the inherent properties of liquid metal cooling and metallic fuel to achieve breakthroughs in economics and inherent safety. This paper describes key features and potential advantages of the IFR concept, technology development status, fuel cycle economics potential, and future development path.

  1. DiMeX: A Text Mining System for Mutation-Disease Association Extraction.

    PubMed

    Mahmood, A S M Ashique; Wu, Tsung-Jung; Mazumder, Raja; Vijay-Shanker, K

    2016-01-01

    The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases.

  2. DiMeX: A Text Mining System for Mutation-Disease Association Extraction

    PubMed Central

    Mahmood, A. S. M. Ashique; Wu, Tsung-Jung; Mazumder, Raja; Vijay-Shanker, K.

    2016-01-01

    The number of published articles describing associations between mutations and diseases is increasing at a fast pace. There is a pressing need to gather such mutation-disease associations into public knowledge bases, but manual curation slows down the growth of such databases. We have addressed this problem by developing a text-mining system (DiMeX) to extract mutation to disease associations from publication abstracts. DiMeX consists of a series of natural language processing modules that preprocess input text and apply syntactic and semantic patterns to extract mutation-disease associations. DiMeX achieves high precision and recall with F-scores of 0.88, 0.91 and 0.89 when evaluated on three different datasets for mutation-disease associations. DiMeX includes a separate component that extracts mutation mentions in text and associates them with genes. This component has been also evaluated on different datasets and shown to achieve state-of-the-art performance. The results indicate that our system outperforms the existing mutation-disease association tools, addressing the low precision problems suffered by most approaches. DiMeX was applied on a large set of abstracts from Medline to extract mutation-disease associations, as well as other relevant information including patient/cohort size and population data. The results are stored in a database that can be queried and downloaded at http://biotm.cis.udel.edu/dimex/. We conclude that this high-throughput text-mining approach has the potential to significantly assist researchers and curators to enrich mutation databases. PMID:27073839

  3. Neighborhood fast food availability and fast food consumption

    PubMed Central

    Oexle, Nathalie; Barnes, Timothy L; Blake, Christine E; Bell, Bethany A; Liese, Angela D

    2015-01-01

    Recent nutritional and public health research has focused on how the availability of various types of food in a person’s immediate area or neighborhood influences his or her food choices and eating habits. It has been theorized that people living in areas with a wealth of unhealthy fast-food options may show higher levels of fast-food consumption, a factor that often coincides with being overweight or obese. However, measuring food availability in a particular area is difficult to achieve consistently: there may be differences in the strict physical locations of food options as compared to how individuals perceive their personal food availability, and various studies may use either one or both of these measures. The aim of this study was to evaluate the association between weekly fast-food consumption and both a person’s perceived availability of fast-food and an objective measure of fast-food presence—Geographic Information Systems (GIS)—within that person’s neighborhood. A randomly selected population-based sample of eight counties in South Carolina was used to conduct a cross-sectional telephone survey assessing self-report fast-food consumption and perceived availability of fast food. GIS was used to determine the actual number of fast-food outlets within each participant’s neighborhood. Using multinomial logistic regression analyses, we found that neither perceived availability nor GIS-based presence of fast-food was significantly associated with weekly fast-food consumption. Our findings indicate that availability might not be the dominant factor influencing fast-food consumption. We recommend using subjective availability measures and considering individual characteristics that could influence both perceived availability of fast food and its impact on fast-food consumption. If replicated, our findings suggest that interventions aimed at reducing fast-food consumption by limiting neighborhood fast-food availability might not be completely

  4. Neighborhood fast food availability and fast food consumption.

    PubMed

    Oexle, Nathalie; Barnes, Timothy L; Blake, Christine E; Bell, Bethany A; Liese, Angela D

    2015-09-01

    Recent nutritional and public health research has focused on how the availability of various types of food in a person's immediate area or neighborhood influences his or her food choices and eating habits. It has been theorized that people living in areas with a wealth of unhealthy fast-food options may show higher levels of fast-food consumption, a factor that often coincides with being overweight or obese. However, measuring food availability in a particular area is difficult to achieve consistently: there may be differences in the strict physical locations of food options as compared to how individuals perceive their personal food availability, and various studies may use either one or both of these measures. The aim of this study was to evaluate the association between weekly fast-food consumption and both a person's perceived availability of fast-food and an objective measure of fast-food presence - Geographic Information Systems (GIS) - within that person's neighborhood. A randomly selected population-based sample of eight counties in South Carolina was used to conduct a cross-sectional telephone survey assessing self-report fast-food consumption and perceived availability of fast food. GIS was used to determine the actual number of fast-food outlets within each participant's neighborhood. Using multinomial logistic regression analyses, we found that neither perceived availability nor GIS-based presence of fast-food was significantly associated with weekly fast-food consumption. Our findings indicate that availability might not be the dominant factor influencing fast-food consumption. We recommend using subjective availability measures and considering individual characteristics that could influence both perceived availability of fast food and its impact on fast-food consumption. If replicated, our findings suggest that interventions aimed at reducing fast-food consumption by limiting neighborhood fast-food availability might not be completely effective.

  5. Fast CRCs

    DTIC Science & Technology

    2009-10-01

    Detecting Codes: General Theory and Their Application in Feedback Communication Systems. Kluwer Academic, 1995. [8] D.E. Knuth , The Art of Computer ... computation . Index Terms—Fast CRC, low-complexity CRC, checksum, error-detection code, Hamming code, period of polynomial, fast software implementation...simulations, and performance analysis of systems and networks. CRC implementation in software is desirable, because many computers do not have hardware

  6. Fast valve

    DOEpatents

    Van Dyke, W.J.

    1992-04-07

    A fast valve is disclosed that can close on the order of 7 milliseconds. It is closed by the force of a compressed air spring with the moving parts of the valve designed to be of very light weight and the valve gate being of wedge shaped with O-ring sealed faces to provide sealing contact without metal to metal contact. The combination of the O-ring seal and an air cushion create a soft final movement of the valve closure to prevent the fast air acting valve from having a harsh closing. 4 figs.

  7. Fast valve

    DOEpatents

    Van Dyke, William J.

    1992-01-01

    A fast valve is disclosed that can close on the order of 7 milliseconds. It is closed by the force of a compressed air spring with the moving parts of the valve designed to be of very light weight and the valve gate being of wedge shaped with O-ring sealed faces to provide sealing contact without metal to metal contact. The combination of the O-ring seal and an air cushion create a soft final movement of the valve closure to prevent the fast air acting valve from having a harsh closing.

  8. Project FAST.

    ERIC Educational Resources Information Center

    Essexville-Hampton Public Schools, MI.

    Described are components of Project FAST (Functional Analysis Systems Training) a nationally validated project to provide more effective educational and support services to learning disordered children and their regular elementary classroom teachers. The program is seen to be based on a series of modules of delivery systems ranging from mainstream…

  9. Novel Mass Spectrometry Mutation Screening for Contaminant Impact Analysis

    SciTech Connect

    Chen, Winston Chung-Hsuan; Lee, Kai-Lin

    2000-09-30

    present DNA analysis technology. Thus, our approach is to develop novel new DNA technologies which can potentially achieve rapid, reliable and inexpensive DNA analysis for environmental applications. The objective of this program is to develop innovative mass spectrometry technology to achieve fast mutation screening and to reveal the linkage between gene mutation and contaminants. Mass spectrometry has the potential to achieve very fast speed sample analysis.New innovative approaches for improving mass resolution and detection sensitivity were pursued to help to achieve rapid DNA screening. Allele specific polymerase chain reaction (ASPCR) coupled with mass spectrometry for DNA mutation detection was also pursued. This technology was applied to wildlife species such as fish for the genotoxic effect of hazardous waste to be assessed at DNA level.

  10. Myostatin gene mutated mice induced with tale nucleases.

    PubMed

    Zhou, Fangfang; Sun, Ruilin; Chen, Hongyan; Fei, Jian; Lu, Daru

    2015-01-01

    Myostain gene (MSTN) is expressed primarily in skeletal muscle, and negatively regulates skeletal muscle mass; it has been suggested that mice with MSTN inhibition have reduced adiposity and improved insulin sensitivity. Therefore, it is important to establish a fast and effective gene editing method. In this report, we established the myostatin mutated-mouse model by microinjection of Transcription Activator-Like Effector Nucleases (TALENs) mRNA within the mouse fertilized oocytes and achieved high rates of mutagenesis of the mouse MSTN in C57BL/6J. Six of 45 born mice carried target mutations and we appointed one as the parental mating with wild mouse to produce the F1 and backcross to produce the F2 generation. All the mutations of the mice were examined quickly and efficiently by high-resolution melting curve analysis (HRMA) and then verified by direct sequencing. We obtained the homozygous of the F2 generation which transmitted the mutant alleles to the progeny with 100% efficiency. Mutant mice exhibited increases in muscle mass comparable to those observed in wild-type mice. Therefore, combining TALEN-mediated gene targeting with HRMA technology is a superior method of constructing genetically modified mice through microinjection in the mouse fertilized oocytes with high efficiency and short time of selection.

  11. Identification of outcome-related driver mutations in cancer using conditional co-occurrence distributions

    PubMed Central

    Treviño, Victor; Martínez-Ledesma, Emmanuel; Tamez-Peña, José

    2017-01-01

    Previous methods proposed for the detection of cancer driver mutations have been based on the estimation of background mutation rate, impact on protein function, or network influence. In this paper, we instead focus on those factors influencing patient survival. To this end, an approximation of the log-rank test has been systematically applied, even though it assumes a large and similar number of patients in both risk groups, which is violated in cancer genomics. Here, we propose VALORATE, a novel algorithm for the estimation of the null distribution for the log-rank, independent of the number of mutations. VALORATE is based on conditional distributions of the co-occurrences between events and mutations. The results, achieved through simulations, comparisons with other methods, analyses of TCGA and ICGC cancer datasets, and validations, suggest that VALORATE is accurate, fast, and can identify both known and novel gene mutations. Our proposal and results may have important implications in cancer biology, bioinformatics analyses, and ultimately precision medicine. PMID:28240231

  12. Mutation and the environment

    SciTech Connect

    Mendelsohn, M.L. ); Albertini, R.J. )

    1990-01-01

    This book is covered under the following topics: Somatic Mutation: Animal Model; Somatic Mutation: Human; Heritable Mutation: Animal Model; Heritable Mutation: Approaches to Human Induction Rates; Heritable Mutation: Human Risk; Epidemiology: Population Studies on Genotoxicity; and Epidemiology: Workplace Studies of Genotoxicity.

  13. Fasting - the ultimate diet?

    PubMed

    Johnstone, A M

    2007-05-01

    Adult humans often undertake acute fasts for cosmetic, religious or medical reasons. For example, an estimated 14% of US adults have reported using fasting as a means to control body weight and this approach has long been advocated as an intermittent treatment for gross refractory obesity. There are unique historical data sets on extreme forms of food restriction that give insight into the consequences of starvation or semi-starvation in previously healthy, but usually non-obese subjects. These include documented medical reports on victims of hunger strike, famine and prisoners of war. Such data provide a detailed account on how the body adapts to prolonged starvation. It has previously been shown that fasting for the biblical period of 40 days and 40 nights is well within the overall physiological capabilities of a healthy adult. However, the specific effects on the human body and mind are less clearly documented, either in the short term (hours) or in the longer term (days). This review asks the following three questions, pertinent to any weight-loss therapy, (i) how effective is the regime in achieving weight loss, (ii) what impact does it have on psychology? and finally, (iii) does it work long-term?

  14. [Research on discrimination method of tomato via space mutation breeding based on spectroscopy technology].

    PubMed

    Shi, Jia-Hui; Shao, Yong-Ni; He, Yong; Li, Duo; Feng, Pan; Zhu, Jia-Jin

    2009-11-01

    In order to quickly analyze varieties of tomato via space mutation breeding with near infrared spectra, firstly, principal component analysis was used to analyze the clustering of tomato leaf samples, and then abundant spectral data were compressed by wavelet transform and the model was built with radial basis function neural network, which offered a quantitative analysis of tomato varieties discrimination. The model regarded the compressed data as the input of neural network input vectors and the training process speeded up. One hundred and five leaf samples of CK, M1 and M2 were selected randomly to build the training model, and forty five samples formed the prediction set. The discrimination rate of 97.8% was achieved by this method. It offered a new approach to the fast discrimination of varieties of tomato via space mutation breeding.

  15. Graded Achievement, Tested Achievement, and Validity

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2015-01-01

    Twenty-eight studies of grades, over a century, were reviewed using the argument-based approach to validity suggested by Kane as a theoretical framework. The review draws conclusions about the meaning of graded achievement, its relation to tested achievement, and changes in the construct of graded achievement over time. "Graded…

  16. Fast-Acting Valve

    NASA Technical Reports Server (NTRS)

    Wojciechowski, Bogdan V. (Inventor); Pegg, Robert J. (Inventor)

    2003-01-01

    A fast-acting valve includes an annular valve seat that defines an annular valve orifice between the edges of the annular valve seat, an annular valve plug sized to cover the valve orifice when the valve is closed, and a valve-plug holder for moving the annular valve plug on and off the annular valve seat. The use of an annular orifice reduces the characteristic distance between the edges of the valve seat. Rather than this distance being equal to the diameter of the orifice, as it is for a conventional circular orifice, the characteristic distance equals the distance between the inner and outer radii (for a circular annulus). The reduced characteristic distance greatly reduces the gap required between the annular valve plug and the annular valve seat for the valve to be fully open, thereby greatly reducing the required stroke and corresponding speed and acceleration of the annular valve plug. The use of a valve-plug holder that is under independent control to move the annular valve plug between its open and closed positions is important for achieving controllable fast operation of the valve.

  17. Future Assets, Student Talent (FAST)

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Future Assets, Student Talent (FAST) motivates and prepares talented students with disabilities to further their education and achieve High Tech and professional employment. The FAST program is managed by local professionals, business, and industry leaders; it is modeled after High School High Tech project TAKE CHARGE started in Los Angeles in 1983. Through cooperative efforts of Alabama Department of Education, Vocational Rehabilitation, Adult and Children Services, and the President's Committee on Employment of People with Disabilities, north central Alabama was chosen as the second site for a High School High Tech project. In 1986 local business, industry, education, government agencies, and rehabilitation representatives started FAST. The program objectives and goals, results and accomplishments, and survey results are included.

  18. Leader as achiever.

    PubMed

    Dienemann, Jacqueline

    2002-01-01

    This article examines one outcome of leadership: productive achievement. Without achievement one is judged to not truly be a leader. Thus, the ideal leader must be a visionary, a critical thinker, an expert, a communicator, a mentor, and an achiever of organizational goals. This article explores the organizational context that supports achievement, measures of quality nursing care, fiscal accountability, leadership development, rewards and punishments, and the educational content and teaching strategies to prepare graduates to be achievers.

  19. UV Signature Mutations

    PubMed Central

    2014-01-01

    Sequencing complete tumor genomes and exomes has sparked the cancer field's interest in mutation signatures for identifying the tumor's carcinogen. This review and meta-analysis discusses signatures and their proper use. We first distinguish between a mutagen's canonical mutations – deviations from a random distribution of base changes to create a pattern typical of that mutagen – and the subset of signature mutations, which are unique to that mutagen and permit inference backward from mutations to mutagen. To verify UV signature mutations, we assembled literature datasets on cells exposed to UVC, UVB, UVA, or solar simulator light (SSL) and tested canonical UV mutation features as criteria for clustering datasets. A confirmed UV signature was: ≥60% of mutations are C→T at a dipyrimidine site, with ≥5% CC→TT. Other canonical features such as a bias for mutations on the non-transcribed strand or at the 3' pyrimidine had limited application. The most robust classifier combined these features with criteria for the rarity of non-UV canonical mutations. In addition, several signatures proposed for specific UV wavelengths were limited to specific genes or species; non-signature mutations induced by UV may cause melanoma BRAF mutations; and the mutagen for sunlight-related skin neoplasms may vary between continents. PMID:25354245

  20. Fast food (image)

    MedlinePlus

    Fast foods are quick, reasonably priced, and readily available alternatives to home cooking. While convenient and economical for a busy lifestyle, fast foods are typically high in calories, fat, saturated ...

  1. [Afatinib as first-line therapy in mutation-positive EGFR. Results by type of mutation].

    PubMed

    Vidal, Óscar Juan

    2016-04-01

    The discovery of endothelial growth factor receptor (EGFR) mutations has laid the foundations for personalized medicine in non-small cell lung carcinoma (NSCLC). In phase III trials, the first-generation tyrosine kinase inhibitors (TKI), gefitinib and erlotinib, demonstrated greater efficacy compared with chemotherapy in patients with EGFR mutations, achieving progression-free survival of 8-13.5 months. Afatinib, a second-generation irreversible pan-ErbB inhibitor, is the first TKI that has shown a benefit in overall survival (OS) compared with chemotherapy in EGFR mutation-positive NSCLC when used as first-line treatment. Exon 19 deletion (Del19) and the single-point substitution mutation (L858R) in exon 21, called activating mutations due to their ability to confer sensitivity to TKI, represent approximately 90% of the EGFR mutations in NSCLC. Distinct sensitivity to TKI has been observed depending on the type of mutation, with greater progression-free survival in patients with the Del19 mutation. The analysis of OS in the LUX-Lung 3 and LUX-Lung 6 trials showed a statistically significant increase in survival in afatinib-treated patients with the Del 19 mutation, but no significant increase in that of patients with the L858R mutation. Direct comparison of afatinib and gefitinib as first-line therapy (LUX-Lung 7 trial) showed a statistically-significant increase in progression-free survival (hazard ratio: 0.73; 95% confidence interval, 0.57-0.95; p=0.0165) with afatinib. In the analysis by type of mutation, this benefit was observed for both the Del19 and the L858R mutations.

  2. Is fast food addictive?

    PubMed

    Garber, Andrea K; Lustig, Robert H

    2011-09-01

    Studies of food addiction have focused on highly palatable foods. While fast food falls squarely into that category, it has several other attributes that may increase its salience. This review examines whether the nutrients present in fast food, the characteristics of fast food consumers or the presentation and packaging of fast food may encourage substance dependence, as defined by the American Psychiatric Association. The majority of fast food meals are accompanied by a soda, which increases the sugar content 10-fold. Sugar addiction, including tolerance and withdrawal, has been demonstrated in rodents but not humans. Caffeine is a "model" substance of dependence; coffee drinks are driving the recent increase in fast food sales. Limited evidence suggests that the high fat and salt content of fast food may increase addictive potential. Fast food restaurants cluster in poorer neighborhoods and obese adults eat more fast food than those who are normal weight. Obesity is characterized by resistance to insulin, leptin and other hormonal signals that would normally control appetite and limit reward. Neuroimaging studies in obese subjects provide evidence of altered reward and tolerance. Once obese, many individuals meet criteria for psychological dependence. Stress and dieting may sensitize an individual to reward. Finally, fast food advertisements, restaurants and menus all provide environmental cues that may trigger addictive overeating. While the concept of fast food addiction remains to be proven, these findings support the role of fast food as a potentially addictive substance that is most likely to create dependence in vulnerable populations.

  3. Multiplex Chromosomal Exome Sequencing Accelerates Identification of ENU-Induced Mutations in the Mouse.

    PubMed

    Sun, Miao; Mondal, Kajari; Patel, Viren; Horner, Vanessa L; Long, Alyssa B; Cutler, David J; Caspary, Tamara; Zwick, Michael E

    2012-01-01

    Forward genetic screens in Mus musculus have proved powerfully informative by revealing unsuspected mechanisms governing basic biological processes. This approach uses potent chemical mutagens, such as N-ethyl-N-nitrosourea (ENU), to randomly induce mutations in mice, which are then bred and phenotypically screened to identify lines that disrupt a specific biological process of interest. Although identifying a mutation using the rich resources of mouse genetics is straightforward, it is unfortunately neither fast nor cheap. Here we show that detecting newly induced causal variants in a forward genetic screen can be accelerated dramatically using a methodology that combines multiplex chromosome-specific exome capture, next-generation sequencing, rapid mapping, sequence annotation, and variation filtering. The key innovation of our method is multiplex capture and sequence that allows the simultaneous survey of both mutant, parental, and background strains in a single experiment. By comparing variants identified in mutant offspring with those found in dbSNP, the unmutagenized background strains, and parental lines, induced causative mutations can be distinguished immediately from preexisting variation or experimental artifact. Here we demonstrate this approach to find the causative mutations induced in four novel ENU lines identified from a recent ENU screen. In all four cases, after applying our method, we found six or fewer putative mutations (and sometimes only a single one). Determining the causative variant was then easily achieved through standard segregation approaches. We have developed this process into a community resource that will speed up individual labs' ability to identify the genetic lesion in mutant mouse lines; all of our reagents and software tools are open source and available to the broader scientific community.

  4. Enhanced Model for Fast Ignition

    SciTech Connect

    Mason, Rodney J.

    2010-10-12

    Laser Fusion is a prime candidate for alternate energy production, capable of serving a major portion of the nation's energy needs, once fusion fuel can be readily ignited. Fast Ignition may well speed achievement of this goal, by reducing net demands on laser pulse energy and timing precision. However, Fast Ignition has presented a major challenge to modeling. This project has enhanced the computer code ePLAS for the simulation of the many specialized phenomena, which arise with Fast Ignition. The improved code has helped researchers to understand better the consequences of laser absorption, energy transport, and laser target hydrodynamics. ePLAS uses efficient implicit methods to acquire solutions for the electromagnetic fields that govern the accelerations of electrons and ions in targets. In many cases, the code implements fluid modeling for these components. These combined features, "implicitness and fluid modeling," can greatly facilitate calculations, permitting the rapid scoping and evaluation of experiments. ePLAS can be used on PCs, Macs and Linux machines, providing researchers and students with rapid results. This project has improved the treatment of electromagnetics, hydrodynamics, and atomic physics in the code. It has simplified output graphics, and provided new input that avoids the need for source code access by users. The improved code can now aid university, business and national laboratory users in pursuit of an early path to success with Fast Ignition.

  5. Very fast approximate reconstruction of MR images.

    PubMed

    Angelidis, P A

    1998-11-01

    The ultra fast Fourier transform (UFFT) provides the means for a very fast computation of a magnetic resonance (MR) image, because it is implemented using only additions and no multiplications at all. It achieves this by approximating the complex exponential functions involved in the Fourier transform (FT) sum with computationally simpler periodic functions. This approximation introduces erroneous spectrum peaks of small magnitude. We examine the performance of this transform in some typical MRI signals. The results show that this transform can very quickly provide an MR image. It is proposed to be used as a replacement of the classically used FFT whenever a fast general overview of an image is required.

  6. Management of the asymptomatic BRCA mutation carrier

    PubMed Central

    Teller, Paige; Kramer, Rita K

    2010-01-01

    Current management of an asymptomatic BRCA mutation carrier includes early initiation and intensive cancer screening in combination with risk reduction strategies. The primary objectives of these interventions are earlier detection and cancer prevention to increase quality of life and prolonged survival. Existing recommendations are often based on the consensus of experts as there are few, supportive, randomized control trials. Management strategies for unaffected patients with BRCA mutations are continually redefined and customized as more evidence-based knowledge is acquired with regard to current intervention efficacy, mutation-related histology, and new treatment modalities. This review provides an outline of current, supported management principles, and interventions in the care of the asymptomatic BRCA mutation carrier. Topics covered include surveillance modalities and risk reduction achieved through behavioral modification, chemoprevention, and prophylactic surgery. PMID:23776357

  7. Comparing Science Achievement Constructs: Targeted and Achieved

    ERIC Educational Resources Information Center

    Ferrara, Steve; Duncan, Teresa

    2011-01-01

    This article illustrates how test specifications based solely on academic content standards, without attention to other cognitive skills and item response demands, can fall short of their targeted constructs. First, the authors inductively describe the science achievement construct represented by a statewide sixth-grade science proficiency test.…

  8. Integrative Physiology of Fasting.

    PubMed

    Secor, Stephen M; Carey, Hannah V

    2016-03-15

    Extended bouts of fasting are ingrained in the ecology of many organisms, characterizing aspects of reproduction, development, hibernation, estivation, migration, and infrequent feeding habits. The challenge of long fasting episodes is the need to maintain physiological homeostasis while relying solely on endogenous resources. To meet that challenge, animals utilize an integrated repertoire of behavioral, physiological, and biochemical responses that reduce metabolic rates, maintain tissue structure and function, and thus enhance survival. We have synthesized in this review the integrative physiological, morphological, and biochemical responses, and their stages, that characterize natural fasting bouts. Underlying the capacity to survive extended fasts are behaviors and mechanisms that reduce metabolic expenditure and shift the dependency to lipid utilization. Hormonal regulation and immune capacity are altered by fasting; hormones that trigger digestion, elevate metabolism, and support immune performance become depressed, whereas hormones that enhance the utilization of endogenous substrates are elevated. The negative energy budget that accompanies fasting leads to the loss of body mass as fat stores are depleted and tissues undergo atrophy (i.e., loss of mass). Absolute rates of body mass loss scale allometrically among vertebrates. Tissues and organs vary in the degree of atrophy and downregulation of function, depending on the degree to which they are used during the fast. Fasting affects the population dynamics and activities of the gut microbiota, an interplay that impacts the host's fasting biology. Fasting-induced gene expression programs underlie the broad spectrum of integrated physiological mechanisms responsible for an animal's ability to survive long episodes of natural fasting.

  9. Which Achievement Gap?

    ERIC Educational Resources Information Center

    Anderson, Sharon; Medrich, Elliott; Fowler, Donna

    2007-01-01

    From the halls of Congress to the local elementary school, conversations on education reform have tossed around the term "achievement gap" as though people all know precisely what that means. As it's commonly used, "achievement gap" refers to the differences in scores on state or national achievement tests between various…

  10. Phenotypic and genomic analysis of a fast neutron mutant population resource in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mutagenized populations have become indispensable resources for introducing variation and studying gene function in plant genomics research. We utilized fast neutron radiation to induce deletion mutations in the soybean genome and phenotypically screened the resulting population. We exposed approxim...

  11. Determining mutation density using Restriction Enzyme Sequence Comparative Analysis (RESCAN)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The average mutation density of a mutant population is a major consideration when developing resources for the efficient, cost-effective implementation of reverse genetics methods such as Targeting of Induced Local Lesions in Genomes (TILLING). Reliable estimates of mutation density can be achieved ...

  12. Research Program of a Super Fast Reactor

    SciTech Connect

    Oka, Yoshiaki; Ishiwatari, Yuki; Liu, Jie; Terai, Takayuki; Nagasaki, Shinya; Muroya, Yusa; Abe, Hiroaki; Akiba, Masato; Akimoto, Hajime; Okumura, Keisuke; Akasaka, Naoaki; GOTO, Shoji

    2006-07-01

    Research program of a supercritical-pressure light water cooled fast reactor (Super Fast Reactor) is funded by MEXT (Ministry of Education, Culture, Sports, Science and Technology) in December 2005 as one of the research programs of Japanese NERI (Nuclear Energy Research Initiative). It consists of three programs. (1) development of Super Fast Reactor concept; (2) thermal-hydraulic experiments; (3) material developments. The purpose of the concept development is to pursue the advantage of high power density of fast reactor over thermal reactors to achieve economic competitiveness of fast reactor for its deployment without waiting for exhausting uranium resources. Design goal is not breeding, but maximizing reactor power by using plutonium from spent LWR fuel. MOX will be the fuel of the Super Fast Reactor. Thermal-hydraulic experiments will be conducted with HCFC22 (Hydro chlorofluorocarbons) heat transfer loop of Kyushu University and supercritical water loop at JAEA. Heat transfer data including effect of grid spacers will be taken. The critical flow and condensation of supercritical fluid will be studied. The materials research includes the development and testing of austenitic stainless steel cladding from the experience of PNC1520 for LMFBR. Material for thermal insulation will be tested. SCWR (Supercritical-Water Cooled Reactor) of GIF (Generation-4 International Forum) includes both thermal and fast reactors. The research of the Super Fast Reactor will enhance SCWR research and the data base. The research period will be until March 2010. (authors)

  13. Effective Temperature of Mutations

    NASA Astrophysics Data System (ADS)

    Derényi, Imre; Szöllősi, Gergely J.

    2015-02-01

    Biological macromolecules experience two seemingly very different types of noise acting on different time scales: (i) point mutations corresponding to changes in molecular sequence and (ii) thermal fluctuations. Examining the secondary structures of a large number of microRNA precursor sequences and model lattice proteins, we show that the effects of single point mutations are statistically indistinguishable from those of an increase in temperature by a few tens of kelvins. The existence of such an effective mutational temperature establishes a quantitative connection between robustness to genetic (mutational) and environmental (thermal) perturbations.

  14. Bypass of genetic constraints during mutator evolution to antibiotic resistance.

    PubMed

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2015-04-07

    Genetic constraints can block many mutational pathways to optimal genotypes in real fitness landscapes, yet the extent to which this can limit evolution remains to be determined. Interestingly, mutator bacteria elevate only specific types of mutations, and therefore could be very sensitive to genetic constraints. Testing this possibility is not only clinically relevant, but can also inform about the general impact of genetic constraints in adaptation. Here, we evolved 576 populations of two mutator and one wild-type Escherichia coli to doubling concentrations of the antibiotic cefotaxime. All strains carried TEM-1, a β-lactamase enzyme well known by its low availability of mutational pathways. Crucially, one of the mutators does not elevate any of the relevant first-step mutations known to improve cefatoximase activity. Despite this, both mutators displayed a similar ability to evolve more than 1000-fold resistance. Initial adaptation proceeded in parallel through general multi-drug resistance mechanisms. High-level resistance, in contrast, was achieved through divergent paths; with the a priori inferior mutator exploiting alternative mutational pathways in PBP3, the target of the antibiotic. These results have implications for mutator management in clinical infections and, more generally, illustrate that limits to natural selection in real organisms are alleviated by the existence of multiple loci contributing to fitness.

  15. Isochoric implosions for fast ignition

    SciTech Connect

    Clark, D S; Tabak, M

    2006-06-05

    Fast Ignition (FI) exploits the ignition of a dense, uniform fuel assembly by an external energy source to achieve high gain. In conventional ICF implosions, however, the fuel assembles as a dense shell surrounding a low density, high-pressure hotspot. Such configurations are far from optimal for FI. Here, it is shown that a self-similar spherical implosion of the type originally studied by Guderley [Luftfahrtforschung 19, 302 (1942).] may be employed to implode a dense, quasi-uniform fuel assembly with minimal energy wastage in forming a hotspot. A scheme for realizing these specialized implosions in a practical ICF target is also described.

  16. Ultra-fast silicon detectors

    NASA Astrophysics Data System (ADS)

    Sadrozinski, H. F.-W.; Ely, S.; Fadeyev, V.; Galloway, Z.; Ngo, J.; Parker, C.; Petersen, B.; Seiden, A.; Zatserklyaniy, A.; Cartiglia, N.; Marchetto, F.; Bruzzi, M.; Mori, R.; Scaringella, M.; Vinattieri, A.

    2013-12-01

    We propose to develop a fast, thin silicon sensor with gain capable to concurrently measure with high precision the space (∼10 μm) and time (∼10 ps) coordinates of a particle. This will open up new application of silicon detector systems in many fields. Our analysis of detector properties indicates that it is possible to improve the timing characteristics of silicon-based tracking sensors, which already have sufficient position resolution, to achieve four-dimensional high-precision measurements. The basic sensor characteristics and the expected performance are listed, the wide field of applications are mentioned and the required R&D topics are discussed.

  17. Gestational mutations in radiation carcinogenesis

    NASA Astrophysics Data System (ADS)

    Meza, R.; Luebeck, G.; Moolgavkar, S.

    Mutations in critical genes during gestation could increase substantially the risk of cancer. We examine the consequences of such mutations using the Luebeck-Moolgavkar model for colorectal cancer and the Lea-Coulson modification of the Luria-Delbruck model for the accumulation of mutations during gestation. When gestational mutation rates are high, such mutations make a significant contribution to cancer risk even for adult tumors. Furthermore, gestational mutations ocurring at distinct times during emryonic developmemt lead to substantially different numbers of mutated cells at birth, with early mutations leading to a large number (jackpots) of mutated cells at birth and mutation occurring late leading to only a few mutated cells. Thus gestational mutations could confer considerable heterogeneity of the risk of cancer. If the fetus is exposed to an environmental mutagen, such as ionizing radiation, the gestational mutation rate would be expected to increase. We examine the consequences of such exposures during gestation on the subsequent development of cancer.

  18. Fast wave current drive

    SciTech Connect

    Goree, J.; Ono, M.; Colestock, P.; Horton, R.; McNeill, D.; Park, H.

    1985-07-01

    Fast wave current drive is demonstrated in the Princeton ACT-I toroidal device. The fast Alfven wave, in the range of high ion-cyclotron harmonics, produced 40 A of current from 1 kW of rf power coupled into the plasma by fast wave loop antenna. This wave excites a steady current by damping on the energetic tail of the electron distribution function in the same way as lower-hybrid current drive, except that fast wave current drive is appropriate for higher plasma densities.

  19. fast-matmul

    SciTech Connect

    Grey Ballard, Austin Benson

    2014-11-26

    This software provides implementations of fast matrix multiplication algorithms. These algorithms perform fewer floating point operations than the classical cubic algorithm. The software uses code generation to automatically implement the fast algorithms based on high-level descriptions. The code serves two general purposes. The first is to demonstrate that these fast algorithms can out-perform vendor matrix multiplication algorithms for modest problem sizes on a single machine. The second is to rapidly prototype many variations of fast matrix multiplication algorithms to encourage future research in this area. The implementations target sequential and shared memory parallel execution.

  20. Fast and Accurate Accessible Surface Area Prediction Without a Sequence Profile.

    PubMed

    Faraggi, Eshel; Kouza, Maksim; Zhou, Yaoqi; Kloczkowski, Andrzej

    2017-01-01

    A fast accessible surface area (ASA) predictor is presented. In this new approach no residue mutation profiles generated by multiple sequence alignments are used as inputs. Instead, we use only single sequence information and global features such as single-residue and two-residue compositions of the chain. The resulting predictor is both highly more efficient than sequence alignment based predictors and of comparable accuracy to them. Introduction of the global inputs significantly helps achieve this comparable accuracy. The predictor, termed ASAquick, is found to perform similarly well for so-called easy and hard cases indicating generalizability and possible usability for de-novo protein structure prediction. The source code and a Linux executables for ASAquick are available from Research and Information Systems at http://mamiris.com and from the Battelle Center for Mathematical Medicine at http://mathmed.org .

  1. Mutation and premating isolation

    NASA Technical Reports Server (NTRS)

    Woodruff, R. C.; Thompson, J. N. Jr

    2002-01-01

    While premating isolation might be traceable to different genetic mechanisms in different species, evidence supports the idea that as few as one or two genes may often be sufficient to initiate isolation. Thus, new mutation can theoretically play a key role in the process. But it has long been thought that a new isolation mutation would fail, because there would be no other individuals for the isolation-mutation-carrier to mate with. We now realize that premeiotic mutations are very common and will yield a cluster of progeny carrying the same new mutant allele. In this paper, we discuss the evidence for genetically simple premating isolation barriers and the role that clusters of an isolation mutation may play in initiating allopatric, and even sympatric, species divisions.

  2. Mutation and premating isolation.

    PubMed

    Woodruff, R C; Thompson, J N

    2002-11-01

    While premating isolation might be traceable to different genetic mechanisms in different species, evidence supports the idea that as few as one or two genes may often be sufficient to initiate isolation. Thus, new mutation can theoretically play a key role in the process. But it has long been thought that a new isolation mutation would fail, because there would be no other individuals for the isolation-mutation-carrier to mate with. We now realize that premeiotic mutations are very common and will yield a cluster of progeny carrying the same new mutant allele. In this paper, we discuss the evidence for genetically simple premating isolation barriers and the role that clusters of an isolation mutation may play in initiating allopatric, and even sympatric, species divisions.

  3. Biological basis of germline mutation: comparisons of spontaneous germline mutation rates among drosophila, mouse, and human.

    PubMed

    Drost, J B; Lee, W R

    1995-01-01

    Spontaneous mutation rates per generation are similar among the three species considered here--Drosophila, mouse, and human--and are not related to time, as is often assumed. Spontaneous germline mutation rates per generation averaged among loci are less variable among species than they are among loci and tests and between gender. Mutation rates are highly variable over time in diverse lineages. Recent estimates of the number of germ cell divisions per generation are: for humans, 401 (30-year generation) in males and 31 in females; for mice, 62 (9-month generation) in males and 25 in females; and for Drosophila melanogaster, 35.5 (18-day generation) in males and 36.5 (25-day generation) in females. The relationships between germ cell division estimates of the two sexes in the three species closely reflect those between mutation rates in the sexes, although mutation rates per cell division vary among species. Whereas the overall rate per generation is constant among species, this consistency must be achieved by diverse mechanisms. Modifiers of mutation rates, on which selection might act, include germline characteristics that contribute disproportionately to the total mutation rates. The germline mutation rates between the sexes within a species are largely influenced by germ cell divisions per generation. Also, a large portion of the total mutations occur during the interval between the beginning of meiosis and differentiation of the soma from the germline. Significant genetic events contributing to mutations during this time may include meiosis, lack of DNA repair in sperm cells, methylation of CpG dinucleotides in mammalian sperm and early embryo, gonomeric fertilization, and rapid cleavage divisions.

  4. 'No delays achiever'.

    PubMed

    2007-05-01

    The latest version of the NHS Institute for Innovation and Improvement's 'no delays achiever', a web based tool created to help NHS organisations achieve the 18-week target for GP referrals to first treatment, is available at www.nodelaysachiever.nhs.uk.

  5. Vicarious Achievement Orientation.

    ERIC Educational Resources Information Center

    Leavitt, Harold J.; And Others

    This study tests hypotheses about achievement orientation, particularly vicarious achievement. Undergraduate students (N=437) completed multiple-choice questionnaires, indicating likely responses of one person to the success of another. The sex of succeeder and observer, closeness of relationship, and setting (medical school or graduate school of…

  6. Heritability of Creative Achievement

    ERIC Educational Resources Information Center

    Piffer, Davide; Hur, Yoon-Mi

    2014-01-01

    Although creative achievement is a subject of much attention to lay people, the origin of individual differences in creative accomplishments remain poorly understood. This study examined genetic and environmental influences on creative achievement in an adult sample of 338 twins (mean age = 26.3 years; SD = 6.6 years). Twins completed the Creative…

  7. Confronting the Achievement Gap

    ERIC Educational Resources Information Center

    Gardner, David

    2007-01-01

    This article talks about the large achievement gap between children of color and their white peers. The reasons for the achievement gap are varied. First, many urban minorities come from a background of poverty. One of the detrimental effects of growing up in poverty is receiving inadequate nourishment at a time when bodies and brains are rapidly…

  8. Achievement-Based Resourcing.

    ERIC Educational Resources Information Center

    Fletcher, Mike; And Others

    1992-01-01

    This collection of seven articles examines achievement-based resourcing (ABR), the concept that the funding of educational institutions should be linked to their success in promoting student achievement, with a focus on the application of ABR to postsecondary education in the United Kingdom. The articles include: (1) "Introduction" (Mick…

  9. States Address Achievement Gaps.

    ERIC Educational Resources Information Center

    Christie, Kathy

    2002-01-01

    Summarizes 2 state initiatives to address the achievement gap: North Carolina's report by the Advisory Commission on Raising Achievement and Closing Gaps, containing an 11-point strategy, and Kentucky's legislation putting in place 10 specific processes. The North Carolina report is available at www.dpi.state.nc.us.closingthegap; Kentucky's…

  10. Novel strategies for comprehensive mutation screening of the APC gene.

    PubMed

    Wachsmannova, L; Mego, M; Stevurkova, V; Zajac, V; Ciernikova, S

    2017-03-03

    Colorectal cancer is the 4th most common cause of cancer related deaths worldwide and new possibilities in accurate diagnosis and targeted treatment are highly required. Mutations in adenomatous polyposis coli (APC) gene play a pivotal role in adenoma-carcinoma pathway of colorectal tumorigenesis. The quarter century from its´ first cloning, APC became one of the most frequently mutated, known driver genes in colorectal cancer. Intensive routine molecular testing of APC has brought the benefits for patients with family history of polyposis or colorectal cancer. Nevertheless, multiple mutational disease-causing mechanisms make the genetic testing still challenging. This minireview is focused on implementation of novel APC mutation screening diagnostic strategies for polyposis families according to the current findings. A further understanding and improved algorithms may help to increase the mutation detection rate. APC germline mutations achieve close to 100% penetrance, so more comprehensive approach followed by preventive and therapeutic strategies might reflect in decrease in burden of colorectal cancer.

  11. Fast protein folding kinetics

    PubMed Central

    Gelman, Hannah; Gruebele, Martin

    2014-01-01

    Fast folding proteins have been a major focus of computational and experimental study because they are accessible to both techniques: they are small and fast enough to be reasonably simulated with current computational power, but have dynamics slow enough to be observed with specially developed experimental techniques. This coupled study of fast folding proteins has provided insight into the mechanisms which allow some proteins to find their native conformation well less than 1 ms and has uncovered examples of theoretically predicted phenomena such as downhill folding. The study of fast folders also informs our understanding of even “slow” folding processes: fast folders are small, relatively simple protein domains and the principles that govern their folding also govern the folding of more complex systems. This review summarizes the major theoretical and experimental techniques used to study fast folding proteins and provides an overview of the major findings of fast folding research. Finally, we examine the themes that have emerged from studying fast folders and briefly summarize their application to protein folding in general as well as some work that is left to do. PMID:24641816

  12. Fast and effective?

    PubMed

    Trueland, Jennifer

    2013-12-18

    The 5.2 diet involves two days of fasting each week. It is being promoted as the key to sustained weight loss, as well as wider health benefits, despite the lack of evidence on the long-term effects. Nurses need to support patients who wish to try intermittent fasting.

  13. fastKDE

    SciTech Connect

    O'Brien, Travis A.; Kashinath, Karthik

    2015-05-22

    This software implements the fast, self-consistent probability density estimation described by O'Brien et al. (2014, doi: ). It uses a non-uniform fast Fourier transform technique to reduce the computational cost of an objective and self-consistent kernel density estimation method.

  14. Fast optical pyrometry

    NASA Technical Reports Server (NTRS)

    Cezairliyan, Ared

    1988-01-01

    Design and operation of accurate millisecond and microsecond resolution optical pyrometers developed at the National Bureau of Standards during the last two decades are described. Results of tests are presented and estimates of uncertainties in temperature measurements are given. Calibration methods are discussed and examples of applications of fast pyrometry are given. Ongoing research in developing fast multiwavelength and spatial scanning pyrometers are summarized.

  15. Achievability for telerobotic systems

    NASA Astrophysics Data System (ADS)

    Kress, Reid L.; Draper, John V.; Hamel, William R.

    2001-02-01

    Methods are needed to improve the capabilities of autonomous robots to perform tasks that are difficult for contemporary robots, and to identify those tasks that robots cannot perform. Additionally, in the realm of remote handling, methods are needed to assess which tasks and/or subtasks are candidates for automation. We are developing a new approach to understanding the capability of autonomous robotic systems. This approach uses formalized methods for determining the achievability of tasks for robots, that is, the likelihood that an autonomous robot or telerobot can successfully complete a particular task. Any autonomous system may be represented in achievability space by the volume describing that system's capabilities within the 3-axis space delineated by perception, cognition, and action. This volume may be thought of as a probability density with achievability decreasing as the distance from the centroid of the volume increases. Similarly, any task may be represented within achievability space. However, as tasks have more finite requirements for perception, cognition, and action, each may be represented as a point (or, more accurately, as a small sphere) within achievability space. Analysis of achievability can serve to identify, a priori, the survivability of robotic systems and the likelihood of mission success; it can be used to plan a mission or portions of a mission; it can be used to modify a mission plan to accommodate unpredicted occurrences; it can also serve to identify needs for modifications to robotic systems or tasks to improve achievability. .

  16. A Vertical Organic Transistor Architecture for Fast Nonvolatile Memory.

    PubMed

    She, Xiao-Jian; Gustafsson, David; Sirringhaus, Henning

    2017-02-01

    A new device architecture for fast organic transistor memory is developed, based on a vertical organic transistor configuration incorporating high-performance ambipolar conjugated polymers and unipolar small molecules as the transport layers, to achieve reliable and fast programming and erasing of the threshold voltage shift in less than 200 ns.

  17. Culture and Achievement Motivation

    ERIC Educational Resources Information Center

    Maehr, Martin L.

    1974-01-01

    A framework is suggested for the cross-cultural study of motivation that stresses the importance of contextual conditions in eliciting achievement motivation and emphasizes cultural relativity in the definition of the concept. (EH)

  18. Achieving Salary Equity

    ERIC Educational Resources Information Center

    Nevill, Dorothy D.

    1975-01-01

    Three techniques are outlined for use by higher education institutions to achieve salary equity: salary prediction (using various statistical procedures), counterparting (comparing salaries of persons of similar rank), and grievance procedures. (JT)

  19. Radiation-induced mutations and plant breeding

    SciTech Connect

    Naqvi, S.H.M.

    1985-01-01

    Ionizing radiation could cause genetic changes in an organism and could modify gene linkages. The induction of mutation through radiation is random and the probability of getting the desired genetic change is low but can be increased by manipulating different parameters such as dose rate, physical conditions under which the material has been irradiated, etc. Induced mutations have been used as a supplement to conventional plant breeding, particularly for creating genetic variability for specific characters such as improved plant structure, pest and disease resistance, and desired changes in maturity period; more than 200 varieties of crop plants have been developed by this technique. The Pakistan Atomic Energy Commission has used this technique fruitfully to evolve better germplasm in cotton, rice, chickpea, wheat and mungbean; some of the mutants have become popular commercial varieties. This paper describes some uses of radiation induced mutations and the results achieved in Pakistan so far.

  20. Reusable fast opening switch

    DOEpatents

    Van Devender, J.P.; Emin, D.

    1983-12-21

    A reusable fast opening switch for transferring energy, in the form of a high power pulse, from an electromagnetic storage device such as an inductor into a load. The switch is efficient, compact, fast and reusable. The switch comprises a ferromagnetic semiconductor which undergoes a fast transition between conductive and metallic states at a critical temperature and which undergoes the transition without a phase change in its crystal structure. A semiconductor such as europium rich europhous oxide, which undergoes a conductor to insulator transition when it is joule heated from its conductor state, can be used to form the switch.

  1. Reusable fast opening switch

    DOEpatents

    Van Devender, John P.; Emin, David

    1986-01-01

    A reusable fast opening switch for transferring energy, in the form of a high power pulse, from an electromagnetic storage device such as an inductor into a load. The switch is efficient, compact, fast and reusable. The switch comprises a ferromagnetic semiconductor which undergoes a fast transition between conductive and insulating states at a critical temperature and which undergoes the transition without a phase change in its crystal structure. A semiconductor such as europium rich europhous oxide, which undergoes a conductor to insulator transition when it is joule heated from its conductor state, can be used to form the switch.

  2. Fast Breeder Reactor studies

    SciTech Connect

    Till, C.E.; Chang, Y.I.; Kittel, J.H.; Fauske, H.K.; Lineberry, M.J.; Stevenson, M.G.; Amundson, P.I.; Dance, K.D.

    1980-07-01

    This report is a compilation of Fast Breeder Reactor (FBR) resource documents prepared to provide the technical basis for the US contribution to the International Nuclear Fuel Cycle Evaluation. The eight separate parts deal with the alternative fast breeder reactor fuel cycles in terms of energy demand, resource base, technical potential and current status, safety, proliferation resistance, deployment, and nuclear safeguards. An Annex compares the cost of decommissioning light-water and fast breeder reactors. Separate abstracts are included for each of the parts.

  3. FAST Construction Progress

    NASA Astrophysics Data System (ADS)

    Nan, R. D.; Zhang, H. Y.; Zhang, Y.; Yang, L.; Cai, W. J.; Liu, N.; Xie, J. T.; Zhang, S. X.

    2016-11-01

    The Five-hundred-meter Aperture Spherical radio Telescope (FAST) is a Chinese mega-science project to build the largest single dish radio telescope in the world. A unique karst depression in Guizhou province has been selected as the site to build an active reflector radio telescope with a diameter of 500 m and three outstanding aspects, which enables FAST to have a large sky coverage and the ability of observing astronomical targets with a high precision. Chinese Academy of Sciences and Guizhou province are in charge of FAST construction. The first light of the telescope was expected on September 25, 2016.

  4. Six Homeoproteins and a linc-RNA at the Fast MYH Locus Lock Fast Myofiber Terminal Phenotype

    PubMed Central

    Sakakibara, Iori; Santolini, Marc; Ferry, Arnaud; Hakim, Vincent; Maire, Pascal

    2014-01-01

    Abstract Thousands of long intergenic non-coding RNAs (lincRNAs) are encoded by the mammalian genome. However, the function of most of these lincRNAs has not been identified in vivo. Here, we demonstrate a role for a novel lincRNA, linc-MYH, in adult fast-type myofiber specialization. Fast myosin heavy chain (MYH) genes and linc-MYH share a common enhancer, located in the fast MYH gene locus and regulated by Six1 homeoproteins. linc-MYH in nuclei of fast-type myofibers prevents slow-type and enhances fast-type gene expression. Functional fast-sarcomeric unit formation is achieved by the coordinate expression of fast MYHs and linc-MYH, under the control of a common Six-bound enhancer. PMID:24852826

  5. FATRAS - the ATLAS Fast Track Simulation project

    NASA Astrophysics Data System (ADS)

    Mechnich, Jörg; ATLAS Collaboration

    2011-12-01

    The Monte Carlo simulation of the detector response is an integral component of any analysis performed with data from the LHC experiments. As these simulated data sets must be both large and precise, their production is a CPU-intensive task. ATLAS has developed full and fast detector simulation techniques to achieve this goal within the computing limits of the collaboration. At the current early stages of data-taking, it is necessary to reprocess the Monte Carlo event samples continuously, while integrating adaptations to the simulation modules in order to improve the agreement with data taken by means of the detector itself. FATRAS is a fast track simulation engine which produces a Monte Carlo simulation based on modules and the geometry of the standard ATLAS track reconstruction algorithm. It can be combined with a fast parametrized-response simulation of the calorimeters. This approach shows a high level of agreement with the full simulation, while achieving a relative timing gain of two orders of magnitude. FATRAS was designed to provide a fast feedback cycle for tuning the MC simulation with real data: this includes the material distribution inside the detector, the integration of misalignment and current conditions, as well as calibration at the hit level. We present the updated and calibrated version of FATRAS based on the first LHC data. Extensive comparisons of the fast track simulation with the full simulation and data at 900 GeV are shown.

  6. Impact of Fast Ignition on Laser Fusion Energy Development

    NASA Astrophysics Data System (ADS)

    Mirna, Kunioki

    2016-10-01

    Reviewed are the early history of Japanese laser fusion research and the recent achievement of fast ignition research at Institute of Laser Engineering (ILE), Osaka University. After the achievement of high density compression at Osaka University, LLE of University Rochester, and LLNL, the critical issue of Inertial Fusion Energy (IFE) research became the formation of hot spark in a compressed plasma. In this lecture, the history of the fast ignition research will be reviewed and future prospects are presented.

  7. Comparing Mutational Variabilities

    PubMed Central

    Houle, D.; Morikawa, B.; Lynch, M.

    1996-01-01

    We have reviewed the available data on V(M), the amount of genetic variation in phenotypic traits produced each generation by mutation. We use these data to make several qualitative tests of the mutation-selection balance hypothesis for the maintenance of genetic variance (MSB). To compare V(M) values, we use three dimensionless quantities: mutational heritability, V(M)/V(E); the mutational coefficient of variation, CV(M); and the ratio of the standing genetic variance to V(M), V(G)/V(M). Since genetic coefficients of variation for life history traits are larger than those for morphological traits, we predict that under MSB, life history traits should also have larger CV(M). This is confirmed; life history traits have a median CV(M) value more than six times higher than that for morphological traits. V(G)/V(M) approximates the persistence time of mutations under MSB in an infinite population. In order for MSB to hold, V(G)/V(M) must be small, substantially less than 1000, and life history traits should have smaller values than morphological traits. V(G)/V(M) averages about 50 generations for life history traits and 100 generations for morphological traits. These observations are all consistent with the predictions of a mutation-selection balance model. PMID:8807316

  8. FAST joins Breakthrough programme

    NASA Astrophysics Data System (ADS)

    Banks, Michael

    2016-11-01

    The 180m Five-hundred-meter Aperture Spherical radio Telescope (FAST) - the world's largest single-aperture radio receiver - has become part of the Breakthrough Listen programme, which launched in July 2015 to look for intelligent life beyond Earth.

  9. Pneumococcal Disease Fast Facts

    MedlinePlus

    ... Home About Pneumococcal Types of Infection Risk Factors & Transmission Symptoms & Complications Diagnosis & Treatment Prevention Photos Fast Facts Pneumococcal Vaccination For Clinicians Streptococcus pneumoniae Transmission Clinical Features Risk Factors Diagnosis & Management Prevention For ...

  10. Calorie count - Fast food

    MedlinePlus

    ... count - fast food FOOD ITEM SERVING SIZE CALORIES Breakfast Foods Dunkin Donuts Egg White Veggie Wrap 1 ... Cheese Biscuit Sandwich 1 sandwich 510 BK Ultimate Breakfast Platter 1 platter 1190 McDonalds Fruit 'n Yogurt ...

  11. Discovery with FAST

    NASA Astrophysics Data System (ADS)

    Wilkinson, P.

    2016-02-01

    FAST offers "transformational" performance well-suited to finding new phenomena - one of which might be polarised spectral transients. But discoveries will only be made if "the system" provides its users with the necessary opportunities. In addition to designing in as much observational flexibility as possible, FAST should be operated with a philosophy which maximises its "human bandwidth". This band includes the astronomers of tomorrow - many of whom not have yet started school or even been born.

  12. SALT and Spelling Achievement.

    ERIC Educational Resources Information Center

    Nelson, Joan

    A study investigated the effects of suggestopedic accelerative learning and teaching (SALT) on the spelling achievement, attitudes toward school, and memory skills of fourth-grade students. Subjects were 20 male and 28 female students from two self-contained classrooms at Kennedy Elementary School in Rexburg, Idaho. The control classroom and the…

  13. Iowa Women of Achievement.

    ERIC Educational Resources Information Center

    Ohrn, Deborah Gore, Ed.

    1993-01-01

    This issue of the Goldfinch highlights some of Iowa's 20th century women of achievement. These women have devoted their lives to working for human rights, education, equality, and individual rights. They come from the worlds of politics, art, music, education, sports, business, entertainment, and social work. They represent Native Americans,…

  14. Schools Achieving Gender Equity.

    ERIC Educational Resources Information Center

    Revis, Emma

    This guide is designed to assist teachers presenting the Schools Achieving Gender Equity (SAGE) curriculum for vocational education students, which was developed to align gender equity concepts with the Kentucky Education Reform Act (KERA). Included in the guide are lesson plans for classes on the following topics: legal issues of gender equity,…

  15. Achieving Peace through Education.

    ERIC Educational Resources Information Center

    Clarken, Rodney H.

    While it is generally agreed that peace is desirable, there are barriers to achieving a peaceful world. These barriers are classified into three major areas: (1) an erroneous view of human nature; (2) injustice; and (3) fear of world unity. In a discussion of these barriers, it is noted that although the consciousness and conscience of the world…

  16. Explorations in achievement motivation

    NASA Technical Reports Server (NTRS)

    Helmreich, Robert L.

    1982-01-01

    Recent research on the nature of achievement motivation is reviewed. A three-factor model of intrinsic motives is presented and related to various criteria of performance, job satisfaction and leisure activities. The relationships between intrinsic and extrinsic motives are discussed. Needed areas for future research are described.

  17. Increasing Male Academic Achievement

    ERIC Educational Resources Information Center

    Jackson, Barbara Talbert

    2008-01-01

    The No Child Left Behind legislation has brought greater attention to the academic performance of American youth. Its emphasis on student achievement requires a closer analysis of assessment data by school districts. To address the findings, educators must seek strategies to remedy failing results. In a mid-Atlantic district of the Unites States,…

  18. Appraising Reading Achievement.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    To determine quality sequence in pupil progress, evaluation approaches need to be used which guide the teacher to assist learners to attain optimally. Teachers must use a variety of procedures to appraise student achievement in reading, because no one approach is adequate. Appraisal approaches might include: (1) observation and subsequent…

  19. Cognitive Processes and Achievement.

    ERIC Educational Resources Information Center

    Hunt, Dennis; Randhawa, Bikkar S.

    For a group of 165 fourth- and fifth-grade students, four achievement test scores were correlated with success on nine tests designed to measure three cognitive functions: sustained attention, successive processing, and simultaneous processing. This experiment was designed in accordance with Luria's model of the three functional units of the…

  20. Graders' Mathematics Achievement

    ERIC Educational Resources Information Center

    Bond, John B.; Ellis, Arthur K.

    2013-01-01

    The purpose of this experimental study was to investigate the effects of metacognitive reflective assessment instruction on student achievement in mathematics. The study compared the performance of 141 students who practiced reflective assessment strategies with students who did not. A posttest-only control group design was employed, and results…

  1. Achieving All Our Ambitions

    ERIC Educational Resources Information Center

    Hartley, Tricia

    2009-01-01

    National learning and skills policy aims both to build economic prosperity and to achieve social justice. Participation in higher education (HE) has the potential to contribute substantially to both aims. That is why the Campaign for Learning has supported the ambition to increase the proportion of the working-age population with a Level 4…

  2. Improving Educational Achievement.

    ERIC Educational Resources Information Center

    New York University Education Quarterly, 1979

    1979-01-01

    This is a slightly abridged version of the report of the National Academy of Education panel, convened at the request of HEW Secretary Joseph Califano and Assistant Secretary for Education Mary F. Berry, to study recent declines in student achievement and methods of educational improvement. (SJL)

  3. The Achievement Club

    ERIC Educational Resources Information Center

    Rogers, Ibram

    2009-01-01

    When Gabrielle Carpenter became a guidance counselor in Northern Virginia nine years ago, she focused on the academic achievement gap and furiously tried to close it. At first, she was compelled by tremendous professional interest. However, after seeing her son lose his zeal for school, Carpenter joined forces with other parents to form an…

  4. Achievement in Problem Solving

    ERIC Educational Resources Information Center

    Friebele, David

    2010-01-01

    This Action Research Project is meant to investigate the effects of incorporating research-based instructional strategies into instruction and their subsequent effect on student achievement in the area of problem-solving. The two specific strategies utilized are the integration of manipulatives and increased social interaction on a regular basis.…

  5. Essays on Educational Achievement

    ERIC Educational Resources Information Center

    Ampaabeng, Samuel Kofi

    2013-01-01

    This dissertation examines the determinants of student outcomes--achievement, attainment, occupational choices and earnings--in three different contexts. The first two chapters focus on Ghana while the final chapter focuses on the US state of Massachusetts. In the first chapter, I exploit the incidence of famine and malnutrition that resulted to…

  6. Advancing Student Achievement

    ERIC Educational Resources Information Center

    Walberg, Herbert J.

    2010-01-01

    For the last half century, higher spending and many modern reforms have failed to raise the achievement of students in the United States to the levels of other economically advanced countries. A possible explanation, says Herbert Walberg, is that much current education theory is ill informed about scientific psychology, often drawing on fads and…

  7. NCLB: Achievement Robin Hood?

    ERIC Educational Resources Information Center

    Bracey, Gerald W.

    2008-01-01

    In his "Wall Street Journal" op-ed on the 25th of anniversary of "A Nation At Risk", former assistant secretary of education Chester E. Finn Jr. applauded the report for turning U.S. education away from equality and toward achievement. It was not surprising, then, that in mid-2008, Finn arranged a conference to examine the…

  8. [Introduction of mutations in insulin molecule: positive and negative mutations].

    PubMed

    Ksenofontova, O I

    2014-01-01

    Introduction of mutations in an insulin molecule is one of the important approaches to drug development for treatment of diabetes mellitus. Generally, usage of mutations is aimed at activation of insulin and insulin receptor interaction. Such mutations can be considered as positive. Mutations that reduce the binding efficacy are negative. There are neutral mutations as well. This article considers both natural mutations that are typical for various members of the insulin superfamily and artificial ones which are introduced to improve the insulin pharmacological characteristics. Data presented here can be useful in developing new effective insulin analogues for treatment of diabetes mellitus.

  9. Slow and Fast Light in Coupled Microresonators

    NASA Technical Reports Server (NTRS)

    Chang, Hongrok; Smith, David D.; Fuller, Kirk A.; Dimmock, John O.; Gregory, Don A.; Frazier, Donald O.

    2005-01-01

    We predict the propagation of slow and fast light in two co-resonant coupled optical resonators. In coupled resonators, slow light can propagate without attenuation by a cancellation of absorption as a result of mode splitting and destructive interference, whereas transparent fast light propagation can be achieved by the assistance of gain and splitting of the intracavity resonances, which consequently change the dispersion from normal to anomalous. The effective steady-state response of coupled-resonators is derived using the temporal coupled-mode formalism, and the absorptive and dispersive responses are described. Specifically, the occurrence of slow light via coupled-resonator-induced transparency and gain-assisted fast light are discussed.

  10. Fast wave current drive

    NASA Astrophysics Data System (ADS)

    Goree, J.; Ono, M.; Colestock, P.; Horton, R.; McNeill, D.; Park, H.

    1985-07-01

    Experiments on the fast wave in the range of high ion cyclotron harmonics in the ACT-1 device show that current drive is possible with the fast wave just as it is for the lower hybrid wave, except that it is suitable for higher plasma densities. A 140° loop antenna launched the high ion cyclotron harmonic fast wave [ω/Ω=O(10)] into a He+ plasma with ne≂4×1012 cm-3 and B=4.5 kG. Probe and magnetic loop diagnostics and FIR laser scattering confirmed the presence of the fast wave, and the Rogowski loop indicated that the circulating plasma current increased by up to 40A with 1 kW of coupled power, which is comparable to lower hybrid current drive in the same device with the same unidirectional fast electron beam used as the target for the rf. A phased antenna array would be used for FWCD in a tokamak without the E-beam.

  11. Faculty achievement tracking tool.

    PubMed

    Pettus, Sarah; Reifschneider, Ellen; Burruss, Nancy

    2009-03-01

    Faculty development and scholarship is an expectation of nurse educators. Accrediting institutions, such as the Commission on Collegiate Nursing Education, the National League for Nursing Accrediting Commission, and the Higher Learning Commission, all have criteria regarding faculty achievement. A faculty achievement tracking tool (FATT) was developed to facilitate documentation of accreditation criteria attainment. Based on criteria from accrediting organizations, the roles that are addressed include scholarship, service, and practice. Definitions and benchmarks for the faculty as an aggregate are included. Undergoing reviews from different accrediting organizations, the FATT has been used once for accreditation of the undergraduate program and once for accreditation of the graduate program. The FATT is easy to use and has become an excellent adjunct for the preparation for accreditation reports. In addition, the FATT may be used for yearly evaluations, advancement, and merit.

  12. Project ACHIEVE final report

    SciTech Connect

    1997-06-13

    Project ACHIEVE was a math/science academic enhancement program aimed at first year high school Hispanic American students. Four high schools -- two in El Paso, Texas and two in Bakersfield, California -- participated in this Department of Energy-funded program during the spring and summer of 1996. Over 50 students, many of whom felt they were facing a nightmare future, were given the opportunity to work closely with personal computers and software, sophisticated calculators, and computer-based laboratories -- an experience which their regular academic curriculum did not provide. Math and science projects, exercises, and experiments were completed that emphasized independent and creative applications of scientific and mathematical theories to real world problems. The most important outcome was the exposure Project ACHIEVE provided to students concerning the college and technical-field career possibilities available to them.

  13. TP53 mutations predict decitabine-induced complete responses in patients with myelodysplastic syndromes.

    PubMed

    Chang, Chun-Kang; Zhao, You-Shan; Xu, Feng; Guo, Juan; Zhang, Zheng; He, Qi; Wu, Dong; Wu, Ling-Yun; Su, Ji-Ying; Song, Lu-Xi; Xiao, Chao; Li, Xiao

    2017-02-01

    To identify the molecular signatures that predict responses to decitabine (DAC), we examined baseline gene mutations (28 target genes) in 109 myelodysplastic syndrome (MDS) patients at diagnosis. We determined that TP53 mutations predicted complete response (CR), as 10 of 15 patients (66·7%) who possessed TP53 mutations achieved a CR. Univariate and multivariate analyses showed that TP53 mutations are the only molecular signatures predictive of a CR to DAC in MDS. Among the ten patients with TP53 mutations who achieved a CR, nine presented with complex karyotypes due to abnormalities involving chromosome 5 and/or chromosome 7, and eight possessed monosomies. Although TP53 mutations were associated with a higher frequency of CRs, they were not associated with improved survival. Poor outcomes were attributed to early relapses and transformation to acute myeloid leukaemia after CR. Post-DAC therapy patient gene mutation profiles showed that most CR patients exhibited fewer gene mutations after achieving a CR. It seems that suppression of these gene mutations was facilitated by DAC, resulting in a CR. In summary, TP53 mutations might predict decitabine-induced complete responses in patients with MDS. DAC-induced responses may result from partial suppression of malignant clones containing mutated TP53 genes.

  14. ALS2 mutations

    PubMed Central

    Schneider, Susanne A.; Carr, Lucinda; Deuschl, Guenther; Hopfner, Franziska; Stamelou, Maria; Wood, Nicholas W.; Bhatia, Kailash P.

    2014-01-01

    Objective: To determine the genetic etiology in 2 consanguineous families who presented a novel phenotype of autosomal recessive juvenile amyotrophic lateral sclerosis associated with generalized dystonia. Methods: A combination of homozygosity mapping and whole-exome sequencing in the first family and Sanger sequencing of candidate genes in the second family were used. Results: Both families were found to have homozygous loss-of-function mutations in the amyotrophic lateral sclerosis 2 (juvenile) (ALS2) gene. Conclusions: We report generalized dystonia and cerebellar signs in association with ALS2-related disease. We suggest that the ALS2 gene should be screened for mutations in patients who present with a similar phenotype. PMID:24562058

  15. A Fast Hermite Transform.

    PubMed

    Leibon, Gregory; Rockmore, Daniel N; Park, Wooram; Taintor, Robert; Chirikjian, Gregory S

    2008-12-17

    We present algorithms for fast and stable approximation of the Hermite transform of a compactly supported function on the real line, attainable via an application of a fast algebraic algorithm for computing sums associated with a three-term relation. Trade-offs between approximation in bandlimit (in the Hermite sense) and size of the support region are addressed. Numerical experiments are presented that show the feasibility and utility of our approach. Generalizations to any family of orthogonal polynomials are outlined. Applications to various problems in tomographic reconstruction, including the determination of protein structure, are discussed.

  16. Antiproton fast ignition for Inertial Confinement Fusion

    SciTech Connect

    Perkins, L.J.

    1997-10-24

    With 180MJ/{micro}g, antiprotons offer the highest stored energy per unit mass of any known entity. We investigate the use of antiprotons to promote fast ignition in an ICF capsule and seek high gains with only modest compression of the main fuel. Unlike standard fast ignition where the ignition energy is supplied by an energetic, short pulse laser, the energy here is supplied through the ionization energy deposited when antiprotons annihilate at the center of a compressed fuel capsule. In the first of two candidate fast ignition schemes, the antiproton package is delivered by a low energy external ion beam. In the second, ''autocatalytic'' scheme, the antiprotons are pre-emplaced at the center of the capsule prior to compression. In both schemes, we estimate that {approximately}3x10{sup 13} antiprotons are required to initiate fast ignition in a typical ICF capsule and show that incorporation of a thin, heavy metal shell is desirable to enhance energy deposition in the igniter zone. In addition to obviating the need for a second energetic fast laser and vulnerable final optics, this scheme would achieve central without reliance on laser channeling through halo plasma or houlrahm debris. However, in addition to the unknowns involved in the storage and manipulation of antiprotons at low energy, the other large uncertainty for the practicality of such a scheme is the ultimate efficiency of antiproton production in, an external, optimized facility.

  17. Fast Quantum Rabi Model with Trapped Ions

    PubMed Central

    Moya-Cessa, Héctor M.

    2016-01-01

    We show how to produce a fast quantum Rabi model with trapped ions. Its importance resides not only in the acceleration of the phenomena that may be achieved with these systems, from quantum gates to the generation of nonclassical states of the vibrational motion of the ion, but also in reducing unwanted effects such as the decay of coherences that may appear in such systems. PMID:27941846

  18. Fast Quantum Rabi Model with Trapped Ions.

    PubMed

    Moya-Cessa, Héctor M

    2016-12-12

    We show how to produce a fast quantum Rabi model with trapped ions. Its importance resides not only in the acceleration of the phenomena that may be achieved with these systems, from quantum gates to the generation of nonclassical states of the vibrational motion of the ion, but also in reducing unwanted effects such as the decay of coherences that may appear in such systems.

  19. PCR-RFLP to Detect Codon 248 Mutation in Exon 7 of "p53" Tumor Suppressor Gene

    ERIC Educational Resources Information Center

    Ouyang, Liming; Ge, Chongtao; Wu, Haizhen; Li, Suxia; Zhang, Huizhan

    2009-01-01

    Individual genome DNA was extracted fast from oral swab and followed up with PCR specific for codon 248 of "p53" tumor suppressor gene. "Msp"I restriction mapping showed the G-C mutation in codon 248, which closely relates to cancer susceptibility. Students learn the concepts, detection techniques, and research significance of point mutations or…

  20. Fast ForWord.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

    This paper provides an overview of Fast ForWord, a CD-ROM and Internet-based training program for children (pre-K to grade 8) with language and reading problems that helps children rapidly build oral language comprehension and other critical skills necessary for learning to read or becoming a better reader. With the help of computers, speech…

  1. The Integral Fast Reactor

    SciTech Connect

    Till, C.E.; Chang, Y.I. ); Lineberry, M.J. )

    1990-01-01

    Argonne National Laboratory, since 1984, has been developing the Integral Fast Reactor (IFR). This paper will describe the way in which this new reactor concept came about; the technical, public acceptance, and environmental issues that are addressed by the IFR; the technical progress that has been made; and our expectations for this program in the near term. 5 refs., 3 figs.

  2. Prevention of avoidable mutational disease: memorandum from a WHO meeting.

    PubMed

    1986-01-01

    About 1% of children are born with a serious disorder which is the direct result of a mutational event in a parent or a more distant ancestor. These disorders, of which several thousand are known, mainly afflict the blood, bone, brain, ear, eye or muscle and the changes are usually irrevocable by the time of diagnosis. Another 1% of individuals will develop a serious genetic disease some time after birth. In addition to these direct consequences of a mutant event, far higher proportions will suffer from the indirect effects of one or several mutations.In view of their chronic and severe nature most of these disorders impose a burden disproportionate to their frequency, and it is sound public health policy to avoid the birth of babies known to have the established mutations and prevent further cases in the immediate or distant future by minimizing the exposure of people at risk to known mutagens. The advantages in permitting certain mutagenic exposures must be assessed against the later costs.Owing to the natural mutation rate and the vast backlog of previous mutations, the prospects of prevention are limited to preventing an increase, rather than to achieving any substantial decrease. This Memorandum describes progress in the ability to dissect and interpret the mutational process, to identify populations at risk, and to evaluate the consequences of the various types of mutational event and emphasizes that the current approach to prevention of mutational disease must involve improving our ability to study populations that appear to be at increased risk.

  3. Mutations and epimutations in the origin of cancer

    SciTech Connect

    Peltomaeki, Paeivi

    2012-02-15

    Cancer is traditionally viewed as a disease of abnormal cell proliferation controlled by a series of mutations. Mutations typically affect oncogenes or tumor suppressor genes thereby conferring growth advantage. Genomic instability facilitates mutation accumulation. Recent findings demonstrate that activation of oncogenes and inactivation of tumor suppressor genes, as well as genomic instability, can be achieved by epigenetic mechanisms as well. Unlike genetic mutations, epimutations do not change the base sequence of DNA and are potentially reversible. Similar to genetic mutations, epimutations are associated with specific patterns of gene expression that are heritable through cell divisions. Knudson's hypothesis postulates that inactivation of tumor suppressor genes requires two hits, with the first hit occurring either in somatic cells (sporadic cancer) or in the germline (hereditary cancer) and the second one always being somatic. Studies on hereditary and sporadic forms of colorectal carcinoma have made it evident that, apart from genetic mutations, epimutations may serve as either hit or both. Furthermore, recent next-generation sequencing studies show that epigenetic genes, such as those encoding histone modifying enzymes and subunits for chromatin remodeling systems, are themselves frequent targets of somatic mutations in cancer and can act like tumor suppressor genes or oncogenes. This review discusses genetic vs. epigenetic origin of cancer, including cancer susceptibility, in light of recent discoveries. Situations in which mutations and epimutations occur to serve analogous purposes are highlighted.

  4. Achieving closure at Fernald

    SciTech Connect

    Bradburne, John; Patton, Tisha C.

    2001-02-25

    When Fluor Fernald took over the management of the Fernald Environmental Management Project in 1992, the estimated closure date of the site was more than 25 years into the future. Fluor Fernald, in conjunction with DOE-Fernald, introduced the Accelerated Cleanup Plan, which was designed to substantially shorten that schedule and save taxpayers more than $3 billion. The management of Fluor Fernald believes there are three fundamental concerns that must be addressed by any contractor hoping to achieve closure of a site within the DOE complex. They are relationship management, resource management and contract management. Relationship management refers to the interaction between the site and local residents, regulators, union leadership, the workforce at large, the media, and any other interested stakeholder groups. Resource management is of course related to the effective administration of the site knowledge base and the skills of the workforce, the attraction and retention of qualified a nd competent technical personnel, and the best recognition and use of appropriate new technologies. Perhaps most importantly, resource management must also include a plan for survival in a flat-funding environment. Lastly, creative and disciplined contract management will be essential to effecting the closure of any DOE site. Fluor Fernald, together with DOE-Fernald, is breaking new ground in the closure arena, and ''business as usual'' has become a thing of the past. How Fluor Fernald has managed its work at the site over the last eight years, and how it will manage the new site closure contract in the future, will be an integral part of achieving successful closure at Fernald.

  5. Phenotype-optimized sequence ensembles substantially improve prediction of disease-causing mutation in cystic fibrosis.

    PubMed

    Masica, David L; Sosnay, Patrick R; Cutting, Garry R; Karchin, Rachel

    2012-08-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) mutation is associated with a phenotypic spectrum that includes cystic fibrosis (CF). The disease liability of some common CFTR mutations is known, but rare mutations are seen in too few patients to categorize unequivocally, making genetic diagnosis difficult. Computational methods can predict the impact of mutation, but prediction specificity is often below that required for clinical utility. Here, we present a novel supervised learning approach for predicting CF from CFTR missense mutation. The algorithm begins by constructing custom multiple sequence alignments called phenotype-optimized sequence ensembles (POSEs). POSEs are constructed iteratively, by selecting sequences that optimize predictive performance on a training set of CFTR mutations of known clinical significance. Next, we predict CF disease liability from a different set of CFTR mutations (test-set mutations). This approach achieves improved prediction performance relative to popular methods recently assessed using the same test-set mutations. Of clinical significance, our method achieves 94% prediction specificity. Because databases such as HGMD and locus-specific mutation databases are growing rapidly, methods that automatically tailor their predictions for a specific phenotype may be of immediate utility. If the performance achieved here generalizes to other systems, the approach could be an excellent tool to help establish genetic diagnoses.

  6. Fast stochastic algorithm for simulating evolutionary population dynamics

    NASA Astrophysics Data System (ADS)

    Tsimring, Lev; Hasty, Jeff; Mather, William

    2012-02-01

    Evolution and co-evolution of ecological communities are stochastic processes often characterized by vastly different rates of reproduction and mutation and a coexistence of very large and very small sub-populations of co-evolving species. This creates serious difficulties for accurate statistical modeling of evolutionary dynamics. In this talk, we introduce a new exact algorithm for fast fully stochastic simulations of birth/death/mutation processes. It produces a significant speedup compared to the direct stochastic simulation algorithm in a typical case when the total population size is large and the mutation rates are much smaller than birth/death rates. We illustrate the performance of the algorithm on several representative examples: evolution on a smooth fitness landscape, NK model, and stochastic predator-prey system.

  7. Synonymous mutations frequently act as driver mutations in human cancers.

    PubMed

    Supek, Fran; Miñana, Belén; Valcárcel, Juan; Gabaldón, Toni; Lehner, Ben

    2014-03-13

    Synonymous mutations change the sequence of a gene without directly altering the sequence of the encoded protein. Here, we present evidence that these "silent" mutations frequently contribute to human cancer. Selection on synonymous mutations in oncogenes is cancer-type specific, and although the functional consequences of cancer-associated synonymous mutations may be diverse, they recurrently alter exonic motifs that regulate splicing and are associated with changes in oncogene splicing in tumors. The p53 tumor suppressor (TP53) also has recurrent synonymous mutations, but, in contrast to those in oncogenes, these are adjacent to splice sites and inactivate them. We estimate that between one in two and one in five silent mutations in oncogenes have been selected, equating to ~6%- 8% of all selected single-nucleotide changes in these genes. In addition, our analyses suggest that dosage-sensitive oncogenes have selected mutations in their 3' UTRs.

  8. Gastrointestinal stromal tumors with KIT exon 9 mutations: Update on genotype-phenotype correlation and validation of a high-resolution melting assay for mutational testing.

    PubMed

    Künstlinger, Helen; Huss, Sebastian; Merkelbach-Bruse, Sabine; Binot, Elke; Kleine, Michaela Angelika; Loeser, Heike; Mittler, Jens; Hartmann, Wolfgang; Hohenberger, Peter; Reichardt, Peter; Büttner, Reinhard; Wardelmann, Eva; Schildhaus, Hans-Ulrich

    2013-11-01

    KIT exon 9 mutations in gastrointestinal stromal tumors (GISTs) are highly relevant and have direct therapeutic implications. In this context, we established and validated a fast and sensitive high-resolution melting assay. Analyzing 126 primary and 18 metastatic KIT exon 9-mutated cases from our registry, we demonstrate that the mutational spectrum of exon 9 is broader than previously thought and describe 3 novel mutations. Including these cases and the common p.A502_Y503dup mutation, we provide a comprehensive list of all known KIT exon 9 mutations according to the Human Genome Variation Society nomenclature. Two of the newly described mutations were associated with an aggressive phenotype and tumor progression while being treated with 400 mg imatinib, indicating that also GIST with rare exon 9 mutations could be treated with increased imatinib dosage. On the basis of >1500 GISTs from our registry, we have determined the frequency of KIT exon 9 mutations to be 9.2% among all GISTs and 22.5% among small-bowel cases. We describe for the first time that nearly 20% of exon 9-mutated GIST occur in the stomach or rectum. Furthermore, we provide first evidence that exon 9-mutated GISTs metastasize significantly more often to the peritoneum than to the liver. Performing extensive statistical analyses on data from our registry and from the literature, we demonstrate that KIT exon 9 mutations are neither associated with intermediate-risk/high-risk status nor overrepresented among metastatic lesions. Thus, we conclude that exon 9 mutations per se do not have prognostic relevance.

  9. Novel SCN9A mutations underlying extreme pain phenotypes: unexpected electrophysiological and clinical phenotype correlations.

    PubMed

    Emery, Edward C; Habib, Abdella M; Cox, James J; Nicholas, Adeline K; Gribble, Fiona M; Woods, C Geoffrey; Reimann, Frank

    2015-05-20

    The importance of NaV1.7 (encoded by SCN9A) in the regulation of pain sensing is exemplified by the heterogeneity of clinical phenotypes associated with its mutation. Gain-of-function mutations are typically pain-causing and have been associated with inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD). IEM is usually caused by enhanced NaV1.7 channel activation, whereas mutations that alter steady-state fast inactivation often lead to PEPD. In contrast, nonfunctional mutations in SCN9A are known to underlie congenital insensitivity to pain (CIP). Although well documented, the correlation between SCN9A genotypes and clinical phenotypes is still unclear. Here we report three families with novel SCN9A mutations. In a multiaffected dominant family with IEM, we found the heterozygous change L245 V. Electrophysiological characterization showed that this mutation did not affect channel activation but instead resulted in incomplete fast inactivation and a small hyperpolarizing shift in steady-state slow inactivation, characteristics more commonly associated with PEPD. In two compound heterozygous CIP patients, we found mutations that still retained functionality of the channels, with two C-terminal mutations (W1775R and L1831X) exhibiting a depolarizing shift in channel activation. Two mutations (A1236E and L1831X) resulted in a hyperpolarizing shift in steady-state fast inactivation. To our knowledge, these are the first descriptions of mutations with some retained channel function causing CIP. This study emphasizes the complex genotype-phenotype correlations that exist for SCN9A and highlights the C-terminal cytoplasmic region of NaV1.7 as a critical region for channel function, potentially facilitating analgesic drug development studies.

  10. Achievement Goals and Achievement Emotions: A Meta-Analysis

    ERIC Educational Resources Information Center

    Huang, Chiungjung

    2011-01-01

    This meta-analysis synthesized 93 independent samples (N = 30,003) in 77 studies that reported in 78 articles examining correlations between achievement goals and achievement emotions. Achievement goals were meaningfully associated with different achievement emotions. The correlations of mastery and mastery approach goals with positive achievement…

  11. Fast electrochemical actuator

    NASA Astrophysics Data System (ADS)

    Uvarov, I. V.; Postnikov, A. V.; Svetovoy, V. B.

    2016-03-01

    Lack of fast and strong microactuators is a well-recognized problem in MEMS community. Electrochemical actuators can develop high pressure but they are notoriously slow. Water electrolysis produced by short voltage pulses of alternating polarity can overcome the problem of slow gas termination. Here we demonstrate an actuation regime, for which the gas pressure is relaxed just for 10 μs or so. The actuator consists of a microchamber filled with the electrolyte and covered with a flexible membrane. The membrane bends outward when the pressure in the chamber increases. Fast termination of gas and high pressure developed in the chamber are related to a high density of nanobubbles in the chamber. The physical processes happening in the chamber are discussed so as problems that have to be resolved for practical applications of this actuation regime. The actuator can be used as a driving engine for microfluidics.

  12. OXPHOS mutations and neurodegeneration

    PubMed Central

    Koopman, Werner J H; Distelmaier, Felix; Smeitink, Jan AM; Willems, Peter HGM

    2013-01-01

    Mitochondrial oxidative phosphorylation (OXPHOS) sustains organelle function and plays a central role in cellular energy metabolism. The OXPHOS system consists of 5 multisubunit complexes (CI–CV) that are built up of 92 different structural proteins encoded by the nuclear (nDNA) and mitochondrial DNA (mtDNA). Biogenesis of a functional OXPHOS system further requires the assistance of nDNA-encoded OXPHOS assembly factors, of which 35 are currently identified. In humans, mutations in both structural and assembly genes and in genes involved in mtDNA maintenance, replication, transcription, and translation induce ‘primary' OXPHOS disorders that are associated with neurodegenerative diseases including Leigh syndrome (LS), which is probably the most classical OXPHOS disease during early childhood. Here, we present the current insights regarding function, biogenesis, regulation, and supramolecular architecture of the OXPHOS system, as well as its genetic origin. Next, we provide an inventory of OXPHOS structural and assembly genes which, when mutated, induce human neurodegenerative disorders. Finally, we discuss the consequences of mutations in OXPHOS structural and assembly genes at the single cell level and how this information has advanced our understanding of the role of OXPHOS dysfunction in neurodegeneration. PMID:23149385

  13. Mutator and MULE Transposons.

    PubMed

    Lisch, Damon

    2015-04-01

    The Mutator system of transposable elements (TEs) is a highly mutagenic family of transposons in maize. Because they transpose at high rates and target genic regions, these transposons can rapidly generate large numbers of new mutants, which has made the Mutator system a favored tool for both forward and reverse mutagenesis in maize. Low copy number versions of this system have also proved to be excellent models for understanding the regulation and behavior of Class II transposons in plants. Notably, the availability of a naturally occurring locus that can heritably silence autonomous Mutator elements has provided insights into the means by which otherwise active transposons are recognized and silenced. This chapter will provide a review of the biology, regulation, evolution and uses of this remarkable transposon system, with an emphasis on recent developments in our understanding of the ways in which this TE system is recognized and epigenetically silenced as well as recent evidence that Mu-like elements (MULEs) have had a significant impact on the evolution of plant genomes.

  14. "Fast" Capitalism and "Fast" Schools: New Realities and New Truths.

    ERIC Educational Resources Information Center

    Robertson, Susan L.

    This paper locates the phenomenon of self-managing schools within the framework of "fast capitalism" and identifies themes of organization central to fast capitalism, which are argued to also underpin the self-managing schools. "Fast capitalism" refers to the rapidly intensified integration of regionalized productive activities into the global…

  15. PHENIX Fast TOF

    SciTech Connect

    Soha, Aria; Chiu, Mickey; Mannel, Eric; Stoll, Sean; Lynch, Don; Boose, Steve; Northacker, Dave; Alfred, Marcus; Lindesay, James; Chujo, Tatsuya; Inaba, Motoi; Nonaka, Toshihiro; Sato, Wataru; Sakatani, Ikumi; Hirano, Masahiro; Choi, Ihnjea

    2014-01-15

    This is a technical scope of work (TSW) between the Fermi National Accelerator Laboratory (Fermilab) and the experimenters of PHENIX Fast TOF group who have committed to participate in beam tests to be carried out during the FY2014 Fermilab Test Beam Facility program. The goals for this test beam experiment are to verify the timing performance of the two types of time-of-flight detector prototypes.

  16. The Integral Fast Reactor

    SciTech Connect

    Chang, Y.I.

    1988-01-01

    The Integral Fast Reactor (IFR) is an innovative liquid metal reactor concept being developed at Argonne National Laboratory. It seeks to specifically exploit the inherent properties of liquid metal cooling and metallic fuel in a way that leads to substantial improvements in the characteristics of the complete reactor system. This paper describes the key features and potential advantages of the IFR concept, with emphasis on its safety characteristics. 3 refs., 4 figs., 1 tab.

  17. Fast tracking hospital construction.

    PubMed

    Quirk, Andrew

    2013-03-01

    Hospital leaders should consider four factors in determining whether to fast track a hospital construction project: Expectations of project length, quality, and cost. Whether decisions can be made quickly as issues arise. Their own time commitment to the project, as well as that of architects, engineers, construction managers, and others. The extent to which they are willing to share with the design and construction teams how and why decisions are being made.

  18. Lipid metabolism during fasting.

    PubMed

    Jensen, M D; Ekberg, K; Landau, B R

    2001-10-01

    These studies were conducted to understand the relationship between measures of systemic free fatty acid (FFA) reesterification and regional FFA, glycerol, and triglyceride metabolism during fasting. Indirect calorimetry was used to measure fatty acid oxidation in six men after a 60-h fast. Systemic and regional (splanchnic, renal, and leg) FFA ([(3)H]palmitate) and glycerol ([(3)H]glycerol) kinetics, as well as splanchnic triglyceride release, were measured. The rate of systemic FFA reesterification was 366 +/- 93 micromol/min, which was greater (P < 0.05) than splanchnic triglyceride fatty acid output (64 +/- 6 micromol/min), a measure of VLDL triglyceride fatty acid export. The majority of glycerol uptake occurred in the splanchnic and renal beds, although some leg glycerol uptake was detected. Systemic FFA release was approximately double that usually present in overnight postabsorptive men, yet the regional FFA release rates were of the same proportions previously observed in overnight postabsorptive men. In conclusion, FFA reesterification at rest during fasting far exceeds splanchnic triglyceride fatty acid output. This indicates that nonhepatic sites of FFA reesterification are important, and that peripheral reesterification of FFA exceeds the rate of simultaneous intracellular triglyceride fatty acid oxidation.

  19. Fast Track Study

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The NASA Fast Track Study supports the efforts of a Special Study Group (SSG) made up of members of the Advanced Project Management Class number 23 (APM-23) that met at the Wallops Island Management Education Center from April 28 - May 8, 1996. Members of the Class expressed interest to Mr. Vem Weyers in having an input to the NASA Policy Document (NPD) 7120.4, that will replace NASA Management Institute (NMI) 7120.4, and the NASA Program/Project Management Guide. The APM-23 SSG was tasked with assisting in development of NASA policy on managing Fast Track Projects, defined as small projects under $150 million and completed within three years. 'Me approach of the APM-23 SSG was to gather data on successful projects working in a 'Better, Faster, Cheaper' environment, within and outside of NASA and develop the Fast Track Project section of the NASA Program/Project Management Guide. Fourteen interviews and four other data gathering efforts were conducted by the SSG, and 16 were conducted by Strategic Resources, Inc. (SRI), including five interviews at the Jet Propulsion Laboratory (JPL) and one at the Applied Physics Laboratory (APL). The interviews were compiled and analyzed for techniques and approaches commonly used to meet severe cost and schedule constraints.

  20. Septin Mutations in Human Cancers

    PubMed Central

    Angelis, Dimitrios; Spiliotis, Elias T.

    2016-01-01

    Septins are GTP-binding proteins that are evolutionarily and structurally related to the RAS oncogenes. Septin expression levels are altered in many cancers and new advances point to how abnormal septin expression may contribute to the progression of cancer. In contrast to the RAS GTPases, which are frequently mutated and actively promote tumorigenesis, little is known about the occurrence and role of septin mutations in human cancers. Here, we review septin missense mutations that are currently in the Catalog of Somatic Mutations in Cancer (COSMIC) database. The majority of septin mutations occur in tumors of the large intestine, skin, endometrium and stomach. Over 25% of the annotated mutations in SEPT2, SEPT4, and SEPT9 belong to large intestine tumors. From all septins, SEPT9 and SEPT14 exhibit the highest mutation frequencies in skin, stomach and large intestine cancers. While septin mutations occur with frequencies lower than 3%, recurring mutations in several invariant and highly conserved amino acids are found across different septin paralogs and tumor types. Interestingly, a significant number of these mutations occur in the GTP-binding pocket and septin dimerization interfaces. Future studies may determine how these somatic mutations affect septin structure and function, whether they contribute to the progression of specific cancers and if they could serve as tumor-specific biomarkers. PMID:27882315

  1. Estimation of spontaneous mutation rates.

    PubMed

    Natarajan, Loki; Berry, Charles C; Gasche, Christoph

    2003-09-01

    Spontaneous or randomly occurring mutations play a key role in cancer progression. Estimation of the mutation rate of cancer cells can provide useful information about the disease. To ascertain these mutation rates, we need mathematical models that describe the distribution of mutant cells. In this investigation, we develop a discrete time stochastic model for a mutational birth process. We assume that mutations occur concurrently with mitosis so that when a nonmutant parent cell splits into two progeny, one of these daughter cells could carry a mutation. We propose an estimator for the mutation rate and investigate its statistical properties via theory and simulations. A salient feature of this estimator is the ease with which it can be computed. The methods developed herein are applied to a human colorectal cancer cell line and compared to existing continuous time models.

  2. Mucopolysaccharidosis IVA mutations in Chinese patients: 16 novel mutations.

    PubMed

    Wang, Zheng; Zhang, Weimin; Wang, Yun; Meng, Yan; Su, Liang; Shi, Huiping; Huang, Shangzhi

    2010-08-01

    Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a lysosomal storage disease caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS) and transmitted as an autosomal recessive trait. This is the first systematic mutation screen in Chinese MPS IVA patients. Mutation detections in 24 unrelated Chinese MPS IVA patients were performed by PCR and direct sequencing of exons or the mRNA of GALNS. A total of 42 mutant alleles were identified, belonging to 27 different mutations. Out of the 27 mutations, 16 were novel, including 2 splicing mutations (c.567-1G>T and c.634-1G>A), 2 nonsense mutations (p.W325X and p.Q422X) and 12 missense mutations (p.T88I, p.H142R, p.P163H, p.G168L, p.H236D, p.N289S, p.T312A, p.G316V, p.A324E, p.L366P, p.Q422K and p.F452L). p.G340D was found to be a common mutation in the Chinese MPS IVA patients, accounting for 16.7% of the total number of mutant alleles. The results show that the mutations in Chinese MPS IVA patients are also family specific but have a different mutation spectrum as compared to those of other populations.

  3. Calreticulin Mutations in Myeloproliferative Neoplasms

    PubMed Central

    Lavi, Noa

    2014-01-01

    With the discovery of the JAK2V617F mutation in patients with Philadelphia chromosome-negative (Ph−) myeloproliferative neoplasms (MPNs) in 2005, major advances have been made in the diagnosis of MPNs, in understanding of their pathogenesis involving the JAK/STAT pathway, and finally in the development of novel therapies targeting this pathway. Nevertheless, it remains unknown which mutations exist in approximately one-third of patients with non-mutated JAK2 or MPL essential thrombocythemia (ET) and primary myelofibrosis (PMF). At the end of 2013, two studies identified recurrent mutations in the gene encoding calreticulin (CALR) using whole-exome sequencing. These mutations were revealed in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations) and recurrent 5-bp insertions (type 2 mutations) in exon 9 of the CALR gene (the last exon encoding the C-terminal amino acids of the protein calreticulin) were detected and found always to generate frameshift mutations. All detected mutant calreticulin proteins shared a novel amino acid sequence at the C-terminal. Mutations in CALR are acquired early in the clonal history of the disease, and they cause activation of JAK/STAT signaling. The CALR mutations are the second most frequent mutations in Ph− MPN patients after the JAK2V617F mutation, and their detection has significantly improved the diagnostic approach for ET and PMF. The characteristics of the CALR mutations as well as their diagnostic, clinical, and pathogenesis implications are discussed in this review. PMID:25386351

  4. Acquired mutations associated with ibrutinib resistance in Waldenstrom Macroglobulinemia.

    PubMed

    Xu, Lian; Tsakmaklis, Nicholas; Yang, Guang; Chen, Jiaji G; Liu, Xia; Demos, Maria; Kofides, Amanda; Patterson, Christopher J; Meid, Kirsten; Gustine, Joshua; Dubeau, Toni; Palomba, M Lia; Advani, Ranjana; Castillo, Jorge J; Furman, Richard R; Hunter, Zachary R; Treon, Steven P

    2017-02-24

    Ibrutinib produces high response rates and durable remissions in Waldenstrom's Macroglobulinemia (WM) that are impacted by MYD88 and CXCR4(WHIM) mutations. Disease progression can develop on ibrutinib, though the molecular basis remains to be clarified. We sequenced sorted CD19(+) lymphoplasmacytic cells from 6 WM patients who progressed after achieving major responses on ibrutinib using Sanger, TA cloning and sequencing, and highly sensitive and specific AS-PCR assays that we developed for BTK mutations. AS-PCR assays were used to screen patients with and without progressive disease on ibrutinib, and ibrutinib-naïve disease. Targeted next generation sequencing was used to validate AS-PCR findings, assess for other BTK mutations, and other targets in BCR and MYD88 signaling. Among the 6 progressing patients, 3 had BTK(Cys481) variants that included BTK(Cys481Ser(c.1635G>C and c.1634T>A)) and BTK(Cys481Arg(c.1634T>C)) Two of these patients had multiple BTK mutations. Screening of 38 additional patients on ibrutinib without clinical progression identified BTK(Cys481) mutations in 2 (5.1%) individuals, both of whom subsequently progressed. BTK(Cys481) mutations were not detected in baseline samples or in 100 ibrutinib-naive WM patients. Using mutated MYD88 as a tumor marker, BTK(Cys481) mutations were subclonal, with a highly variable clonal distribution. Targeted deep sequencing confirmed AS-PCR findings, and identified an additional BTK(Cys481Tyr(c.1634G>A)) mutation in the two patients with multiple other BTK(Cys481) mutations, as well as CARD11(Leu878Phe(c.2632C>T)) and PLCγ2(Tyr495His(c.1483T>C)) mutations. Four of the five patients with BTK(C481) variants were CXCR4 mutated. BTK(Cys481) mutations are common in WM patients with clinical progression on ibrutinib, and are associated with mutated CXCR4.

  5. Slow and fast light in semiconductors

    NASA Astrophysics Data System (ADS)

    Sedgwick, Forrest Grant

    Slow and fast light are the propagation of optical signals at group velocities below and above the speed of light in a given medium. There has been great interest in the use of nonlinear optics to engineer slow and fast light dispersion for applications in optical communications and radio-frequency or microwave photonics. Early results in this field were primarily confined to dilute atomic systems. While these results were impressive, they had two major barriers to practical application. First, the wavelengths were not compatible with fiber optic telecommunications. More importantly, the bandwidth obtainable in these experiments was inherently low; 100 kHz or less. Within the last five years slow and fast light effects have been observed and engineered in a much wider variety of systems. In this work, we detail our efforts to realize slow and fast light in semiconductor systems. There are three primary advantages of semiconductor systems: fiber-compatible wavelengths, larger bandwidth, and simplification of integration with other optical components. In this work we will explore three different types of physical mechanisms for implementing slow and fast light. The first is electromagnetically induced transparency (EIT). In transporting this process to semiconductors, we initially turn our attention to quantum dots or "artificial atoms". We present simulations of a quantum dot EIT-based device within the context of an optical communications link and we derive results which are generally applicable to a broad class of slow light devices. We then present experimental results realizing EIT in quantum wells by using long-lived electron spin coherence. The second mechanism we will explore is coherent population oscillations (CPO), also known as carrier density pulsations (CDP). We examine for the first time how both slow and fast light may be achieved in a quantum well semiconductor optical amplifier (SOA) while operating in the gain regime. Again, we simulate the device

  6. Three Specialized Innovations for FAST Wideband Receiver

    NASA Astrophysics Data System (ADS)

    Zhang, Xia; Yu, Xinying; Duan, Ran; Hao, Jie; Li, Di

    2015-08-01

    The National Astronomical Observatories of the Chinese Academy of Sciences (NAOC) will soon finish the largest antenna in the world. Known as FAST, the Five-hundred-meter Aperture Spherical Radio Telescope will be the most sensitive single-dish radio telescope in the low frequency radio bands between 70 MHz and 3 GHz.To take advantage of its giant aperture, all relevant cutting-edge technology should be applied to FAST to ensure that it achieves the best possible overall performance. The wideband receiver that is currently under development can not only be directly applied to FAST, but also used for other Chinese radio telescopes, such as the Shanghai 65-meter telescope and the Xinjiang 110-meter telescope, to ensure that these telescopes are among the best in the world. Recently, rapid development related to this wideband receiver has been underway. In this paper, we will introduce three key aspects of the FAST wideband receiver project. First is the use of a high-performance analog-to-digital converter (ADC). With the cooperation of Hao Jie’s team from the Institute of Automation of the Chinese Academy of Sciences(CASIA), we have developed 3-Gsps,12-bit ADCs, which have not been used previously in astronomy, and we expect to realize the 3-GHz bandwidth in a single step by covering the entire bandwidth via interleaving or a complex fast Fourier transform (FFT).Second is the front-end analog signal integrated circuit board. We wish to achieve a series of amplification, attenuation, and mixing filtering operations on a single small board, thereby achieving digital control of the bandpass behavior both flexibly and highly-efficiently. This design will not only greatly reduce the required cost and power but will also make the best use of the digital-system’s flexibility. Third is optimization of the FFT: the existing FFT is not very efficient; therefore, we will optimize the FFT for large-scale operation. For this purpose, we intend to cascade two FFTs. Another

  7. Atypical phenotype in two patients with LAMA2 mutations.

    PubMed

    Marques, Joana; Duarte, Sofia T; Costa, Sónia; Jacinto, Sandra; Oliveira, Jorge; Oliveira, Márcia E; Santos, Rosário; Bronze-da-Rocha, Elsa; Silvestre, Ana Rita; Calado, Eulália; Evangelista, Teresinha

    2014-05-01

    Congenital muscular dystrophy type 1A is caused by mutations in the LAMA2 gene, which encodes the α2-chain of laminin. We report two patients with partial laminin-α2 deficiency and atypical phenotypes, one with almost exclusive central nervous system involvement (cognitive impairment and refractory epilepsy) and the second with marked cardiac dysfunction, rigid spine syndrome and limb-girdle weakness. Patients underwent clinical, histopathological, imaging and genetic studies. Both cases have two heterozygous LAMA2 variants sharing a potentially pathogenic missense mutation c.2461A>C (p.Thr821Pro) located in exon 18. Brain MRI was instrumental for the diagnosis, since muscular examination and motor achievements were normal in the first patient and there was a severe cardiac involvement in the second. The clinical phenotype of the patients is markedly different which could in part be explained by the different combination of mutations types (two missense versus a missense and a truncating mutation).

  8. Livedoid vasculopathy and its association with factor V Leiden mutation.

    PubMed

    Yong, Angeline Anning; Tan, Audrey Wei Hsia; Giam, Yoke Chin; Tang, Mark Boon Yang

    2012-12-01

    Livedoid vasculopathy is a rare chronic relapsing disorder characterised by recurrent painful thrombotic and vasculitic ulcers on the legs. We present the cases of two Indian women with livedoid vasculopathy that were found to be associated with an underlying factor V Leiden heterozygous mutation. There were no other thrombotic manifestations, and livedoid vasculopathy was the sole presenting feature of the factor V Leiden mutation, although this could also be coincidental. Initial treatment with high-dose immunosuppressive therapy was suboptimal, and the addition of pentoxifylline and antiplatelet therapy was crucial in achieving disease control and remission. These cases highlight the possible association with an underlying prothrombotic disorder, such as factor V Leiden mutation, in patients with livedoid vasculopathy. Although this association is relatively uncommon, it is more relevant to Indian patients, as the presence of factor V Leiden mutation is highest in this ethnicity as compared to the local Malay and Chinese populations.

  9. Fast quench reactor method

    DOEpatents

    Detering, Brent A.; Donaldson, Alan D.; Fincke, James R.; Kong, Peter C.; Berry, Ray A.

    1999-01-01

    A fast quench reaction includes a reactor chamber having a high temperature heating means such as a plasma torch at its inlet and a means of rapidly expanding a reactant stream, such as a restrictive convergent-divergent nozzle at its outlet end. Metal halide reactants are injected into the reactor chamber. Reducing gas is added at different stages in the process to form a desired end product and prevent back reactions. The resulting heated gaseous stream is then rapidly cooled by expansion of the gaseous stream.

  10. Simplified fast neutron dosimeter

    DOEpatents

    Sohrabi, Mehdi

    1979-01-01

    Direct fast-neutron-induced recoil and alpha particle tracks in polycarbonate films may be enlarged for direct visual observation and automated counting procedures employing electrochemical etching techniques. Electrochemical etching is, for example, carried out in a 28% KOH solution at room temperature by applying a 2000 V peak-to-peak voltage at 1 kHz frequency. Such recoil particle amplification can be used for the detection of wide neutron dose ranges from 1 mrad. to 1000 rads. or higher, if desired.

  11. Fast neutron dosimetry

    SciTech Connect

    DeLuca, P.M. Jr.; Pearson, D.W.

    1992-01-01

    This progress report concentrates on two major areas of dosimetry research: measurement of fast neutron kerma factors for several elements for monochromatic and white spectrum neutron fields and determination of the response of thermoluminescent phosphors to various ultra-soft X-ray energies and beta-rays. Dr. Zhixin Zhou from the Shanghai Institute of Radiation Medicine, People's Republic of China brought with him special expertise in the fabrication and use of ultra-thin TLD materials. Such materials are not available in the USA. The rather unique properties of these materials were investigated during this grant period.

  12. The fast encryption package

    NASA Technical Reports Server (NTRS)

    Bishop, Matt

    1988-01-01

    The organization of some tools to help improve passwork security at a UNIX-based site is described along with how to install and use them. These tools and their associated library enable a site to force users to pick reasonably safe passwords (safe being site configurable) and to enable site management to try to crack existing passworks. The library contains various versions of a very fast implementation of the Data Encryption Standard and of the one-way encryption functions used to encryp the password.

  13. Fast neutron nuclear reactor

    SciTech Connect

    Cabrillat, M. Th.; Lions, N.

    1985-01-08

    The invention relates to a fast neutron nuclear reactor of the integrated type comprising a cylindrical inner vessel. The inner vessel comprises two concentric ferrules and the connection between the hot collector defined within this vessel and the inlet port of the exchangers is brought about by a hot structure forming a heat baffle and supported by the inner ferrule and by a cold structure surrounding the hot structure, supported by the outer ferrule and sealingly connected to the exchanger. Application to the generation of electric power in nuclear power stations.

  14. FAST NEUTRONIC REACTOR

    DOEpatents

    Snell, A.H.

    1957-12-01

    This patent relates to a reactor and process for carrying out a controlled fast neutron chain reaction. A cubical reactive mass, weighing at least 920 metric tons, of uranium metal containing predominantly U/sup 238/ and having a U/sup 235/ content of at least 7.63% is assembled and the maximum neutron reproduction ratio is limited to not substantially over 1.01 by insertion and removal of a varying amount of boron, the reactive mass being substantially freed of moderator.

  15. Fast quench reactor method

    SciTech Connect

    Detering, B.A.; Donaldson, A.D.; Fincke, J.R.; Kong, P.C.; Berry, R.A.

    1999-08-10

    A fast quench reaction includes a reactor chamber having a high temperature heating means such as a plasma torch at its inlet and a means of rapidly expanding a reactant stream, such as a restrictive convergent-divergent nozzle at its outlet end. Metal halide reactants are injected into the reactor chamber. Reducing gas is added at different stages in the process to form a desired end product and prevent back reactions. The resulting heated gaseous stream is then rapidly cooled by expansion of the gaseous stream. 8 figs.

  16. Fasting and sport: an introduction.

    PubMed

    Maughan, R J

    2010-06-01

    Most humans observe an overnight fast on a daily basis, and the human body copes well with short duration fasting. Periodic fasting is widely practised for cultural, religious or health reasons. Fasting may take many different forms. Prolonged restriction of food and fluid is harmful to health and performance, and it is often automatically assumed that intermittent fasting will lead to decrements in exercise performance. Athletes who choose to fast during training or competitions may therefore be at a disadvantage. The available evidence does not entirely support this view, but there is little or no information on the effects on elite athletes competing in challenging environments. Prolonged periods of training in the fasted state may not allow optimum adaptation of muscles and other tissues. Further research on a wide range of athletes with special nutrition needs is urgently required. In events where performance might be affected, other strategies to eliminate or minimise any effects must be sought.

  17. Lifting Minority Achievement: Complex Answers. The Achievement Gap.

    ERIC Educational Resources Information Center

    Viadero, Debra; Johnston, Robert C.

    2000-01-01

    This fourth in a four-part series on why academic achievement gaps exist describes the Minority Achievement Committee scholars program at Shaker Heights High School in Cleveland, Ohio, a powerful antidote to the achievement gap between minority and white and Asian American students. It explains the need to break down stereotypes about academic…

  18. Achievement Motivation of Women: Effects of Achievement and Affiliation Arousal.

    ERIC Educational Resources Information Center

    Gama, Elizabeth Maria Pinheiro

    1985-01-01

    Assigned 139 Brazilian women to neutral, affiliation arousal, and achievement arousal conditions based on their levels of achievement (Ach) and affiliative (Aff) needs. Results of story analyses revealed that achievement arousal increased scores of high Ach subjects and that high Aff subjects obtained higher scores than low Aff subjects. (BL)

  19. Attitude Towards Physics and Additional Mathematics Achievement Towards Physics Achievement

    ERIC Educational Resources Information Center

    Veloo, Arsaythamby; Nor, Rahimah; Khalid, Rozalina

    2015-01-01

    The purpose of this research is to identify the difference in students' attitude towards Physics and Additional Mathematics achievement based on gender and relationship between attitudinal variables towards Physics and Additional Mathematics achievement with achievement in Physics. This research focused on six variables, which is attitude towards…

  20. The Impact of Reading Achievement on Overall Academic Achievement

    ERIC Educational Resources Information Center

    Churchwell, Dawn Earheart

    2009-01-01

    This study examined the relationship between reading achievement and achievement in other subject areas. The purpose of this study was to determine if there was a correlation between reading scores as measured by the Standardized Test for the Assessment of Reading (STAR) and academic achievement in language arts, math, science, and social studies…

  1. Irradiation behavior of metallic fast reactor fuels

    SciTech Connect

    Pahl, R.G.; Porter, D.L.; Crawford, D.C.; Walters, L.C.

    1991-01-01

    Metallic fuels were the first fuels chosen for liquid metal cooled fast reactors (LMR's). In the late 1960's world-wide interest turned toward ceramic LMR fuels before the full potential of metallic fuel was realized. However, during the 1970's the performance limitations of metallic fuel were resolved in order to achieve a high plant factor at the Argonne National Laboratory's Experimental Breeder Reactor II. The 1980's spawned renewed interest in metallic fuel when the Integral Fast Reactor (IFR) concept emerged at Argonne National Laboratory. A fuel performance demonstration program was put into place to obtain the data needed for the eventual licensing of metallic fuel. This paper will summarize the results of the irradiation program carried out since 1985.

  2. A fast, preconditioned conjugate gradient Toeplitz solver

    NASA Technical Reports Server (NTRS)

    Pan, Victor; Schrieber, Robert

    1989-01-01

    A simple factorization is given of an arbitrary hermitian, positive definite matrix in which the factors are well-conditioned, hermitian, and positive definite. In fact, given knowledge of the extreme eigenvalues of the original matrix A, an optimal improvement can be achieved, making the condition numbers of each of the two factors equal to the square root of the condition number of A. This technique is to applied to the solution of hermitian, positive definite Toeplitz systems. Large linear systems with hermitian, positive definite Toeplitz matrices arise in some signal processing applications. A stable fast algorithm is given for solving these systems that is based on the preconditioned conjugate gradient method. The algorithm exploits Toeplitz structure to reduce the cost of an iteration to O(n log n) by applying the fast Fourier Transform to compute matrix-vector products. Matrix factorization is used as a preconditioner.

  3. Fast atomic transport without vibrational heating

    SciTech Connect

    Torrontegui, E.; Ibanez, S.; Chen Xi; Ruschhaupt, A.; Guery-Odelin, D.; Muga, J. G.

    2011-01-15

    We use the dynamical invariants associated with the Hamiltonian of an atom in a one dimensional moving trap to inverse engineer the trap motion and perform fast atomic transport without final vibrational heating. The atom is driven nonadiabatically through a shortcut to the result of adiabatic, slow trap motion. For harmonic potentials this only requires designing appropriate trap trajectories, whereas perfect transport in anharmonic traps may be achieved by applying an extra field to compensate the forces in the rest frame of the trap. The results can be extended to atom stopping or launching. The limitations due to geometrical constraints, energies, and accelerations involved are analyzed along with the relation to previous approaches based on classical trajectories or ''fast-forward'' and ''bang-bang'' methods, which can be integrated in the invariant-based framework.

  4. MECP2 mutations in males

    PubMed Central

    Villard, Laurent

    2007-01-01

    Rett syndrome (RS; MIM 312750) is a severe neurological disorder affecting exclusively females. Its prevalence is about 1 in 10 000 female births, and it is a prominent cause of profound mental handicap in women. RS is caused by mutations in the X‐linked methyl CpG‐binding protein 2 (MECP2) gene. These mutations were initially thought to be lethal in males. However, MECP2 mutations are now frequently identified in mentally retarded male patients. The frequency of disease‐causing MECP2 mutations in this population is between 1.3% and 1.7%. Surprisingly, MECP2 mutations in males are responsible for a wide spectrum of neurological disorders, ranging from mild mental retardation to severe neonatal encephalopathy. The aim of this review is to describe the nature of the MECP2 mutations identified in male patients to date and their associated phenotypes. PMID:17351020

  5. A fast algorithm for finding point sources in the Fermi data stream: FermiFAST

    NASA Astrophysics Data System (ADS)

    Asvathaman, Asha; Omand, Conor; Barton, Alistair; Heyl, Jeremy S.

    2017-04-01

    We present a new and efficient algorithm for finding point sources in the photon event data stream from the Fermi Gamma-Ray Space Telescope, FermiFAST. The key advantage of FermiFAST is that it constructs a catalogue of potential sources very fast by arranging the photon data in a hierarchical data structure. Using this structure, FermiFAST rapidly finds the photons that could have originated from a potential gamma-ray source. It calculates a likelihood ratio for the contribution of the potential source using the angular distribution of the photons within the region of interest. It can find within a few minutes the most significant half of the Fermi Third Point Source catalogue (3FGL) with nearly 80 per cent purity from the 4 yr of data used to construct the catalogue. If a higher purity sample is desirable, one can achieve a sample that includes the most significant third of the Fermi 3FGL with only 5 per cent of the sources unassociated with Fermi sources. Outside the Galactic plane, all but eight of the 580 FermiFAST detections are associated with 3FGL sources. And of these eight, six yield significant detections of greater than 5σ when a further binned likelihood analysis is performed. This software allows for rapid exploration of the Fermi data, simulation of the source detection to calculate the selection function of various sources and the errors in the obtained parameters of the sources detected.

  6. Fast evaluation of polarizable forces.

    PubMed

    Wang, Wei; Skeel, Robert D

    2005-10-22

    Polarizability is considered to be the single most significant development in the next generation of force fields for biomolecular simulations. However, the self-consistent computation of induced atomic dipoles in a polarizable force field is expensive due to the cost of solving a large dense linear system at each step of a simulation. This article introduces methods that reduce the cost of computing the electrostatic energy and force of a polarizable model from about 7.5 times the cost of computing those of a nonpolarizable model to less than twice the cost. This is probably sufficient for the routine use of polarizable forces in biomolecular simulations. The reduction in computing time is achieved by an efficient implementation of the particle-mesh Ewald method, an accurate and robust predictor based on least-squares fitting, and non-stationary iterative methods whose fast convergence is accelerated by a simple preconditioner. Furthermore, with these methods, the self-consistent approach with a larger timestep is shown to be faster than the extended Lagrangian approach. The use of dipole moments from previous timesteps to calculate an accurate initial guess for iterative methods leads to an energy drift, which can be made acceptably small. The use of a zero initial guess does not lead to perceptible energy drift if a reasonably strict convergence criterion for the iteration is imposed.

  7. Instrumentation, Monitoring and NDE for New Fast Reactors

    SciTech Connect

    Bond, Leonard J.; Doctor, Steven; Bunch, Kyle; Good, Morris; Waltar, Alan E.

    2007-07-01

    The Global Nuclear Energy Partnership (GNEP) will require the development of actinide transmutation, which can most effectively be accomplished in a fast-spectrum reactor. To achieve higher standards of safety and reliability, operate with longer intervals between outages, and achieve high operating capacity factors, new instrumentation and on-line monitoring capabilities will be required-- during both fabrication and operation. This paper reports parts of a knowledge capture and technology state-of-the-art assessment for fast-reactor instrumentation and controls, monitoring and diagnostics. (authors)

  8. Fast SCR Thyratron Driver

    SciTech Connect

    Nguyen, M.N.; /SLAC

    2007-06-18

    As part of an improvement project on the linear accelerator at SLAC, it was necessary to replace the original thyratron trigger generator, which consisted of two chassis, two vacuum tubes, and a small thyratron. All solid-state, fast rise, and high voltage thyratron drivers, therefore, have been developed and built for the 244 klystron modulators. The rack mounted, single chassis driver employs a unique way to control and generate pulses through the use of an asymmetric SCR, a PFN, a fast pulse transformer, and a saturable reactor. The resulting output pulse is 2 kV peak into 50 {Omega} load with pulse duration of 1.5 {mu}s FWHM at 180 Hz. The pulse risetime is less than 40 ns with less than 1 ns jitter. Various techniques are used to protect the SCR from being damaged by high voltage and current transients due to thyratron breakdowns. The end-of-line clipper (EOLC) detection circuit is also integrated into this chassis to interrupt the modulator triggering in the event a high percentage of line reflections occurred.

  9. The effect of one additional driver mutation on tumor progression.

    PubMed

    Reiter, Johannes G; Bozic, Ivana; Allen, Benjamin; Chatterjee, Krishnendu; Nowak, Martin A

    2013-01-01

    Tumor growth is caused by the acquisition of driver mutations, which enhance the net reproductive rate of cells. Driver mutations may increase cell division, reduce cell death, or allow cells to overcome density-limiting effects. We study the dynamics of tumor growth as one additional driver mutation is acquired. Our models are based on two-type branching processes that terminate in either tumor disappearance or tumor detection. In our first model, both cell types grow exponentially, with a faster rate for cells carrying the additional driver. We find that the additional driver mutation does not affect the survival probability of the lesion, but can substantially reduce the time to reach the detectable size if the lesion is slow growing. In our second model, cells lacking the additional driver cannot exceed a fixed carrying capacity, due to density limitations. In this case, the time to detection depends strongly on this carrying capacity. Our model provides a quantitative framework for studying tumor dynamics during different stages of progression. We observe that early, small lesions need additional drivers, while late stage metastases are only marginally affected by them. These results help to explain why additional driver mutations are typically not detected in fast-growing metastases.

  10. Conformational SERS Classification of K-Ras Point Mutations for Cancer Diagnostics.

    PubMed

    Morla-Folch, Judit; Gisbert-Quilis, Patricia; Masetti, Matteo; Garcia-Rico, Eduardo; Alvarez-Puebla, Ramon A; Guerrini, Luca

    2017-02-20

    Point mutations in Ras oncogenes are routinely screened for diagnostics and treatment of tumors (especially in colorectal cancer). Here, we develop an optical approach based on direct SERS coupled with chemometrics for the study of the specific conformations that single-point mutations impose on a relatively large fragment of the K-Ras gene (141 nucleobases). Results obtained offer the unambiguous classification of different mutations providing a potentially useful insight for diagnostics and treatment of cancer in a sensitive, fast, direct and inexpensive manner.

  11. BRAF Mutations in Canine Cancers.

    PubMed

    Mochizuki, Hiroyuki; Kennedy, Katherine; Shapiro, Susan G; Breen, Matthew

    2015-01-01

    Activating mutations of the BRAF gene lead to constitutive activation of the MAPK pathway. Although many human cancers carry the mutated BRAF gene, this mutation has not yet been characterized in canine cancers. As human and canine cancers share molecular abnormalities, we hypothesized that BRAF gene mutations also exist in canine cancers. To test this hypothesis, we sequenced the exon 15 of BRAF, mutation hot spot of the gene, in 667 canine primary tumors and 38 control tissues. Sequencing analysis revealed that a single nucleotide T to A transversion at nucleotide 1349 occurred in 64 primary tumors (9.6%), with particularly high frequency in prostatic carcinoma (20/25, 80%) and urothelial carcinoma (30/45, 67%). This mutation results in the amino acid substitution of glutamic acid for valine at codon 450 (V450E) of canine BRAF, corresponding to the most common BRAF mutation in human cancer, V600E. The evolutional conservation of the BRAF V600E mutation highlights the importance of MAPK pathway activation in neoplasia and may offer opportunity for molecular diagnostics and targeted therapeutics for dogs bearing BRAF-mutated cancers.

  12. Recurrent gene mutations in CLL.

    PubMed

    Martínez-Trillos, Alejandra; Quesada, Víctor; Villamor, Neus; Puente, Xose S; López-Otín, Carlos; Campo, Elías

    2013-01-01

    Next-generation sequencing of whole genomes and exomes in chronic lymphocytic leukemia (CLL) has provided the first comprehensive view of somatic mutations in this disease. Subsequent studies have characterized the oncogenic pathways and clinical implications of a number of these mutations. The global number of somatic mutations per case is lower than those described in solid tumors but is in agreement with previous estimates of less than one mutation per megabase in hematological neoplasms. The number and pattern of somatic mutations differ in tumors with unmutated and mutated IGHV, extending at the genomic level the clinical differences observed in these two CLL subtypes. One of the striking conclusions of these studies has been the marked genetic heterogeneity of the disease, with a relatively large number of genes recurrently mutated at low frequency and only a few genes mutated in up to 10-15 % of the patients. The mutated genes tend to cluster in different pathways that include NOTCH1 signaling, RNA splicing and processing machinery, innate inflammatory response, Wnt signaling, and DNA damage and cell cycle control, among others. These results highlight the molecular heterogeneity of CLL and may provide new biomarkers and potential therapeutic targets for the diagnosis and management of the disease.

  13. Achievements in Stratospheric Ozone Protection

    EPA Pesticide Factsheets

    This report describes achievements in protecting the ozone layer, the benefits of these achievements, and strategies involved (e.g., using alternatives to ozone-depleting substances, phasing out harmful substances, and creating partnerships).

  14. Islamic fasting and multiple sclerosis

    PubMed Central

    2014-01-01

    Background Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. Discussion In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. Summary These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient. PMID:24655543

  15. Fast Food Jobs. National Study of Fast Food Employment.

    ERIC Educational Resources Information Center

    Charner, Ivan; Fraser, Bryna Shore

    A study examined employment in the fast-food industry. The national survey collected data from employees at 279 fast-food restaurants from seven companies. Female employees outnumbered males by two to one. The ages of those fast-food employees in the survey sample ranged from 14 to 71, with fully 70 percent being in the 16- to 20-year-old age…

  16. New Software for the Fast Estimation of Population Recombination Rates (FastEPRR) in the Genomic Era

    PubMed Central

    Gao, Feng; Ming, Chen; Hu, Wangjie; Li, Haipeng

    2016-01-01

    Genetic recombination is a very important evolutionary mechanism that mixes parental haplotypes and produces new raw material for organismal evolution. As a result, information on recombination rates is critical for biological research. In this paper, we introduce a new extremely fast open-source software package (FastEPRR) that uses machine learning to estimate recombination rate ρ (=4Ner) from intraspecific DNA polymorphism data. When ρ>10 and the number of sampled diploid individuals is large enough (≥50), the variance of ρFastEPRR remains slightly smaller than that of ρLDhat. The new estimate ρcomb (calculated by averaging ρFastEPRR and ρLDhat) has the smallest variance of all cases. When estimating ρFastEPRR, the finite-site model was employed to analyze cases with a high rate of recurrent mutations, and an additional method is proposed to consider the effect of variable recombination rates within windows. Simulations encompassing a wide range of parameters demonstrate that different evolutionary factors, such as demography and selection, may not increase the false positive rate of recombination hotspots. Overall, accuracy of FastEPRR is similar to the well-known method, LDhat, but requires far less computation time. Genetic maps for each human population (YRI, CEU, and CHB) extracted from the 1000 Genomes OMNI data set were obtained in less than 3 d using just a single CPU core. The Pearson Pairwise correlation coefficient between the ρFastEPRR and ρLDhat maps is very high, ranging between 0.929 and 0.987 at a 5-Mb scale. Considering that sample sizes for these kinds of data are increasing dramatically with advances in next-generation sequencing technologies, FastEPRR (freely available at http://www.picb.ac.cn/evolgen/) is expected to become a widely used tool for establishing genetic maps and studying recombination hotspots in the population genomic era. PMID:27172192

  17. Determinants of weight loss success with alternate day fasting.

    PubMed

    Varady, Krista A; Hoddy, Kristin K; Kroeger, Cynthia M; Trepanowski, John F; Klempel, Monica C; Barnosky, Adrienne; Bhutani, Surabhi

    2016-01-01

    This study examined what characteristics predict weight loss success with alternate day fasting (ADF). Four 8-week trials of ADF (n=121) were included in the analysis. Subjects aged 50-59 y achieved greater (P=0.01) weight loss than other age groups. Males and females achieved similar weight loss. Caucasian subjects achieved greater (P=0.03) weight loss than other races. Baseline body weight and baseline BMI did not predict degree of weight loss achieved with the diet. These findings may help clinicians to decide which population groups may benefit most from an ADF approach.

  18. Students’ Achievement Goals, Learning-Related Emotions and Academic Achievement

    PubMed Central

    Lüftenegger, Marko; Klug, Julia; Harrer, Katharina; Langer, Marie; Spiel, Christiane; Schober, Barbara

    2016-01-01

    In the present research, the recently proposed 3 × 2 model of achievement goals is tested and associations with achievement emotions and their joint influence on academic achievement are investigated. The study was conducted with 388 students using the 3 × 2 Achievement Goal Questionnaire including the six proposed goal constructs (task-approach, task-avoidance, self-approach, self-avoidance, other-approach, other-avoidance) and the enjoyment and boredom scales from the Achievement Emotion Questionnaire. Exam grades were used as an indicator of academic achievement. Findings from CFAs provided strong support for the proposed structure of the 3 × 2 achievement goal model. Self-based goals, other-based goals and task-approach goals predicted enjoyment. Task-approach goals negatively predicted boredom. Task-approach and other-approach predicted achievement. The indirect effects of achievement goals through emotion variables on achievement were assessed using bias-corrected bootstrapping. No mediation effects were found. Implications for educational practice are discussed. PMID:27199836

  19. Fiber optic thermal/fast neutron and gamma ray scintillation detector

    DOEpatents

    Neal, John S.; Mihalczo, John T.

    2006-11-28

    A detector system that combines a .sup.6Li loaded glass fiber scintillation thermal neutron detector with a fast scintillation detector in a single layered structure. Detection of thermal and fast neutrons and ionizing electromagnetic radiation is achieved in the unified detector structure. The fast scintillator replaces the polyethelene moderator layer adjacent the .sup.6Li loaded glass fiber panel of the neutron detector and acts as the moderator for the glass fibers. Fast neutrons, x-rays and gamma rays are detected in the fast scintillator. Thermal neutrons, x-rays and gamma rays are detected in the glass fiber scintillator.

  20. FAST ACTING CURRENT SWITCH

    DOEpatents

    Batzer, T.H.; Cummings, D.B.; Ryan, J.F.

    1962-05-22

    A high-current, fast-acting switch is designed for utilization as a crowbar switch in a high-current circuit such as used to generate the magnetic confinement field of a plasma-confining and heat device, e.g., Pyrotron. The device particularly comprises a cylindrical housing containing two stationary, cylindrical contacts between which a movable contact is bridged to close the switch. The movable contact is actuated by a differential-pressure, airdriven piston assembly also within the housing. To absorb the acceleration (and the shock imparted to the device by the rapidly driven, movable contact), an adjustable air buffer assembly is provided, integrally connected to the movable contact and piston assembly. Various safety locks and circuit-synchronizing means are also provided to permit proper cooperation of the invention and the high-current circuit in which it is installed. (AEC)

  1. FAST OPENING SWITCH

    DOEpatents

    Bender, M.; Bennett, F.K.; Kuckes, A.F.

    1963-09-17

    A fast-acting electric switch is described for rapidly opening a circuit carrying large amounts of electrical power. A thin, conducting foil bridges a gap in this circuit and means are provided for producing a magnetic field and eddy currents in the foil, whereby the foil is rapidly broken to open the circuit across the gap. Advantageously the foil has a hole forming two narrow portions in the foil and the means producing the magnetic field and eddy currents comprises an annular coil having its annulus coaxial with the hole in the foil and turns adjacent the narrow portions of the foil. An electrical current flows through the coil to produce the magnetic field and eddy currents in the foil. (AEC)

  2. Fast thyratron driver

    SciTech Connect

    Nguyen, M.N.; Cassel, R.L.

    1991-04-01

    A fast solid-state pulse generator used as a thyratron grid driver for kicker pulsers, has been developed and built with power MOSFETs and a transmission line transformer. The MOSFET, pulsed on and off by a pair of P-N channel HEXFETs, switches charged capacitors into the transformer connected in parallel on one end and in series on the other end to step up the voltage. The resulting output pulse parameters are 2 kilovolts peak (into 50 Ohms), 13 nanoseconds risetime (10--90%), 250 nanoseconds duration, and less than 50 picoseconds pulse-to-pulse jitter. Various methods are employed to protect the MOSFETs from thyratron arc back, including the use of TransZorbs and a magnetic diode. 3 refs., 3 figs.

  3. FAST NEUTRON SPECTROMETER

    DOEpatents

    Davis, F.J.; Hurst, G.S.; Reinhardt, P.W.

    1959-08-18

    An improved proton recoil spectrometer for determining the energy spectrum of a fast neutron beam is described. Instead of discriminating against and thereby"throwing away" the many recoil protons other than those traveling parallel to the neutron beam axis as do conventional spectrometers, this device utilizes protons scattered over a very wide solid angle. An ovoidal gas-filled recoil chamber is coated on the inside with a scintillator. The ovoidal shape of the sensitive portion of the wall defining the chamber conforms to the envelope of the range of the proton recoils from the radiator disposed within the chamber. A photomultiplier monitors the output of the scintillator, and a counter counts the pulses caused by protons of energy just sufficient to reach the scintillator.

  4. Fast Radio Bursts

    NASA Astrophysics Data System (ADS)

    Kaspi, Victoria M.

    2017-01-01

    Fast Radio Bursts (FRBs) are a recently discovered phenomenon consisting of short (few ms) bursts of radio waves that have dispersion measures that strongly suggest an extragalactic and possibly cosmological origin. Current best estimates for the rate of FRBs is several thousand per sky per day at radio frequencies near 1.4 GHz. Even with so high a rate, to date, fewer than 20 FRBs have been reported, with one source showing repeated bursts. In this talk I will describe known FRB properties including what is known about the lone repeating source, as well as models for the origin of these mysterious events. I will also describe the CHIME radio telescope, currently under construction in Canada. Thanks to its great sensitivity and unprecedented field-of-view, CHIME promises major progress on FRBs.

  5. Fast Parallel Computation Of Manipulator Inverse Dynamics

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Bejczy, Antal K.

    1991-01-01

    Method for fast parallel computation of inverse dynamics problem, essential for real-time dynamic control and simulation of robot manipulators, undergoing development. Enables exploitation of high degree of parallelism and, achievement of significant computational efficiency, while minimizing various communication and synchronization overheads as well as complexity of required computer architecture. Universal real-time robotic controller and simulator (URRCS) consists of internal host processor and several SIMD processors with ring topology. Architecture modular and expandable: more SIMD processors added to match size of problem. Operate asynchronously and in MIMD fashion.

  6. Exposing synonymous mutations.

    PubMed

    Hunt, Ryan C; Simhadri, Vijaya L; Iandoli, Matthew; Sauna, Zuben E; Kimchi-Sarfaty, Chava

    2014-07-01

    Synonymous codon changes, which do not alter protein sequence, were previously thought to have no functional consequence. Although this concept has been overturned in recent years, there is no unique mechanism by which these changes exert biological effects. A large repertoire of both experimental and bioinformatic methods has been developed to understand the effects of synonymous variants. Results from this body of work have provided global insights into how biological systems exploit the degeneracy of the genetic code to control gene expression, protein folding efficiency, and the coordinated expression of functionally related gene families. Although it is now clear that synonymous variants are important in a variety of contexts, from human disease to the safety and efficacy of therapeutic proteins, there is no clear consensus on the approaches to identify and validate these changes. Here, we review the diverse methods to understand the effects of synonymous mutations.

  7. PTCH mutations: distribution and analyses.

    PubMed

    Lindström, Erika; Shimokawa, Takashi; Toftgård, Rune; Zaphiropoulos, Peter G

    2006-03-01

    Mutations in the PTCH (PTCH1) gene are the underlying cause of nevoid basal cell carcinoma syndrome (NBCCS), and are also found in many different sporadic tumors in which PTCH is thought to act as a tumor suppressor gene. To investigate the distribution pattern of these mutations in tumors and NBCCS, we analyzed 284 mutations and 48 SNPs located in the PTCH gene that were compiled from our PTCH mutation database. We found that the PTCH mutations were mainly clustered into the predicted two large extracellular loops and the large intracellular loop. The SNPs appeared to be clustered around the sterol sensing domain and the second half of the protein. The NBCCS cases and each class of tumor analyzed revealed a different distribution of the mutations in the various PTCH domains. Moreover, the types of mutations were also unique for the different groups. Finally, the PTCH gene harbors mutational hot spot residues and regions, including a slippage-sensitive sequence in the N-terminus.

  8. ENAM Mutations with Incomplete Penetrance

    PubMed Central

    Seymen, F.; Lee, K.-E.; Koruyucu, M.; Gencay, K.; Bayram, M.; Tuna, E.B.; Lee, Z.H.; Kim, J.-W.

    2014-01-01

    Amelogenesis imperfecta (AI) is a genetic disease affecting tooth enamel formation. AI can be an isolated entity or a phenotype of syndromes. To date, more than 10 genes have been associated with various forms of AI. We have identified 2 unrelated Turkish families with hypoplastic AI and performed mutational analysis. Whole-exome sequencing identified 2 novel heterozygous nonsense mutations in the ENAM gene (c.454G>T p.Glu152* in family 1, c.358C>T p.Gln120* in family 2) in the probands. Affected individuals were heterozygous for the mutation in each family. Segregation analysis within each family revealed individuals with incomplete penetrance or extremely mild enamel phenotype, in spite of having the same mutation with the other affected individuals. We believe that these findings will broaden our understanding of the clinical phenotype of AI caused by ENAM mutations. PMID:25143514

  9. Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism

    PubMed Central

    Kim, Hyunbae; Mendez, Roberto; Chen, Xuequn; Fang, Deyu

    2015-01-01

    Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH acetylation in mouse livers in a time-dependent manner, and this event is critical for CREBH transcriptional activity in regulating hepatic lipid homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH acetylation states under fasting conditions. Site-directed mutagenesis and functional analyses revealed that the lysine (K) residue at position 294 (K294) within the bZIP domain of the CREBH protein is the site where fasting-induced acetylation/deacetylation occurs. Introduction of the acetylation-deficient (K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH transcriptional activity, respectively. Importantly, CREBH acetylation at lysine 294 was required for the interaction and synergy between CREBH and peroxisome proliferator-activated receptor α (PPARα) in activating their target genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294 mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals under prolonged fasting. In summary, our study reveals a molecular mechanism by which fasting or glucagon stimulation modulates lipid homeostasis through acetylation of CREBH. PMID:26438600

  10. Lysine Acetylation of CREBH Regulates Fasting-Induced Hepatic Lipid Metabolism.

    PubMed

    Kim, Hyunbae; Mendez, Roberto; Chen, Xuequn; Fang, Deyu; Zhang, Kezhong

    2015-12-01

    Cyclic AMP-responsive element-binding protein 3-like 3, hepatocyte specific (CREBH), is a hepatic transcription factor that functions as a key regulator of energy homeostasis. Here, we defined a regulatory CREBH posttranslational modification process, namely, lysine-specific acetylation, and its functional involvement in fasting-induced hepatic lipid metabolism. Fasting induces CREBH acetylation in mouse livers in a time-dependent manner, and this event is critical for CREBH transcriptional activity in regulating hepatic lipid homeostasis. The histone acetyltransferase PCAF-mediated acetylation and the deacetylase sirtuin-1-mediated deacetylation coexist to maintain CREBH acetylation states under fasting conditions. Site-directed mutagenesis and functional analyses revealed that the lysine (K) residue at position 294 (K294) within the bZIP domain of the CREBH protein is the site where fasting-induced acetylation/deacetylation occurs. Introduction of the acetylation-deficient (K294R) or acetylation-mimicking (K294Q) mutation inhibited or enhanced CREBH transcriptional activity, respectively. Importantly, CREBH acetylation at lysine 294 was required for the interaction and synergy between CREBH and peroxisome proliferator-activated receptor α (PPARα) in activating their target genes upon fasting or glucagon stimulation. Introduction of the CREBH lysine 294 mutation in the liver leads to hepatic steatosis and hyperlipidemia in animals under prolonged fasting. In summary, our study reveals a molecular mechanism by which fasting or glucagon stimulation modulates lipid homeostasis through acetylation of CREBH.

  11. Fast word reading in pure alexia: "fast, yet serial".

    PubMed

    Bormann, Tobias; Wolfer, Sascha; Hachmann, Wibke; Neubauer, Claudia; Konieczny, Lars

    2015-01-01

    Pure alexia is a severe impairment of word reading in which individuals process letters serially with a pronounced length effect. Yet, there is considerable variation in the performance of alexic readers with generally very slow, but also occasionally fast responses, an observation addressed rarely in previous reports. It has been suggested that "fast" responses in pure alexia reflect residual parallel letter processing or that they may even be subserved by an independent reading system. Four experiments assessed fast and slow reading in a participant (DN) with pure alexia. Two behavioral experiments investigated frequency, neighborhood, and length effects in forced fast reading. Two further experiments measured eye movements when DN was forced to read quickly, or could respond faster because words were easier to process. Taken together, there was little support for the proposal that "qualitatively different" mechanisms or reading strategies underlie both types of responses in DN. Instead, fast responses are argued to be generated by the same serial-reading strategy.

  12. A genotypic mutation system measuring mutations in restriction recognition sequences.

    PubMed Central

    Felley-Bosco, E; Pourzand, C; Zijlstra, J; Amstad, P; Cerutti, P

    1991-01-01

    The RFLP/PCR approach (restriction fragment length polymorphism/polymerase chain reaction) to genotypic mutation analysis described here measures mutations in restriction recognition sequences. Wild-type DNA is restricted before the resistant, mutated sequences are amplified by PCR and cloned. We tested the capacity of this experimental design to isolate a few copies of a mutated sequence of the human c-Ha-ras1 gene from a large excess of wild-type DNA. For this purpose we constructed a 272 bp fragment with 2 mutations in the PvuII recognition sequence 1727-1732 and studied the rescue by RFLP/PCR of a few copies of this 'PvuII mutant standard'. Following amplification with Taq-polymerase and cloning into lambda gt10, plaques containing wild-type sequence, PvuII mutant standard or Taq-polymerase induced bp changes were quantitated by hybridization with specific oligonucleotide probes. Our results indicate that 10 PvuII mutant standard copies can be rescued from 10(8) to 10(9) wild-type sequences. Taq polymerase errors originating from unrestricted, residual wild-type DNA were sequence dependent and consisted mostly of transversions originating at G.C bp. In contrast to a doubly mutated 'standard' the capacity to rescue single bp mutations by RFLP/PCR is limited by Taq-polymerase errors. Therefore, we assessed the capacity of our protocol to isolate a G to T transversion mutation at base pair 1698 of the MspI-site 1695-1698 of the c-Ha-ras1 gene from excess wild-type ras1 DNA. We found that 100 copies of the mutated ras1 fragment could be readily rescued from 10(8) copies of wild-type DNA. Images PMID:1676153

  13. Phase measurement of fast light pulse in electromagnetically induced absorption.

    PubMed

    Lee, Yoon-Seok; Lee, Hee Jung; Moon, Han Seb

    2013-09-23

    We report the phase measurement of a fast light pulse in electromagnetically induced absorption (EIA) of the 5S₁/₂ (F = 2)-5P₃/₂ (F' = 3) transition of ⁸⁷Rb atoms. Using a beat-note interferometer method, a stable measurement without phase dithering of the phase of the probe pulse before and after it has passed through the EIA medium was achieved. Comparing the phases of the light pulse in air and that of the fast light pulse though the EIA medium, the phase of the fast light pulse at EIA resonance was not shifted and maintained to be the same as that of the free-space light pulse. The classical fidelity of the fast light pulse according to the advancement of the group velocity by adjusting the atomic density was estimated to be more than 97%.

  14. Fast Approximate Quadratic Programming for Graph Matching

    PubMed Central

    Vogelstein, Joshua T.; Conroy, John M.; Lyzinski, Vince; Podrazik, Louis J.; Kratzer, Steven G.; Harley, Eric T.; Fishkind, Donniell E.; Vogelstein, R. Jacob; Priebe, Carey E.

    2015-01-01

    Quadratic assignment problems arise in a wide variety of domains, spanning operations research, graph theory, computer vision, and neuroscience, to name a few. The graph matching problem is a special case of the quadratic assignment problem, and graph matching is increasingly important as graph-valued data is becoming more prominent. With the aim of efficiently and accurately matching the large graphs common in big data, we present our graph matching algorithm, the Fast Approximate Quadratic assignment algorithm. We empirically demonstrate that our algorithm is faster and achieves a lower objective value on over 80% of the QAPLIB benchmark library, compared with the previous state-of-the-art. Applying our algorithm to our motivating example, matching C. elegans connectomes (brain-graphs), we find that it efficiently achieves performance. PMID:25886624

  15. Fast approximate quadratic programming for graph matching.

    PubMed

    Vogelstein, Joshua T; Conroy, John M; Lyzinski, Vince; Podrazik, Louis J; Kratzer, Steven G; Harley, Eric T; Fishkind, Donniell E; Vogelstein, R Jacob; Priebe, Carey E

    2015-01-01

    Quadratic assignment problems arise in a wide variety of domains, spanning operations research, graph theory, computer vision, and neuroscience, to name a few. The graph matching problem is a special case of the quadratic assignment problem, and graph matching is increasingly important as graph-valued data is becoming more prominent. With the aim of efficiently and accurately matching the large graphs common in big data, we present our graph matching algorithm, the Fast Approximate Quadratic assignment algorithm. We empirically demonstrate that our algorithm is faster and achieves a lower objective value on over 80% of the QAPLIB benchmark library, compared with the previous state-of-the-art. Applying our algorithm to our motivating example, matching C. elegans connectomes (brain-graphs), we find that it efficiently achieves performance.

  16. Fast pitch softball injuries.

    PubMed

    Meyers, M C; Brown, B R; Bloom, J A

    2001-01-01

    The popularity of fast pitch softball in the US and throughout the world is well documented. Along with this popularity, there has been a concomitant increase in the number of injuries. Nearly 52% of cases qualify as major disabling injuries requiring 3 weeks or more of treatment and 2% require surgery. Interestingly, 75% of injuries occur during away games and approximately 31% of traumas occur during nonpositional and conditioning drills. Injuries range from contusions and tendinitis to ligamentous disorders and fractures. Although head and neck traumas account for 4 to 12% of cases, upper extremity traumas account for 23 to 47% of all injuries and up to 19% of cases involve the knee. Approximately 34 to 42% of injuries occur when the athlete collides with another individual or object. Other factors involved include the quality of playing surface, athlete's age and experience level, and the excessive physical demands associated with the sport. Nearly 24% of injuries involve base running and are due to poor judgement, sliding technique, current stationary base design, unorthodox joint and extremity position during ground impact and catching of cleats. The increasing prevalence of overtraining syndrome among athletes has been attributed to an unclear definition of an optimal training zone, poor communication between player and coach, and the limited ability of bone and connective tissue to quickly respond to match the demands of the sport. This has led routinely to arm, shoulder and lumbar instability, chronic nonsteroidal anti-inflammatory drug (NSAID) use and time loss injuries in 45% of pitching staff during a single season. Specific attention to a safer playing environment, coaching and player education, and sport-specific training and conditioning would reduce the risk, rate and severity of fast pitch traumas. Padding of walls, backstops, rails and dugout areas, as well as minimising use of indoor facilities, is suggested to decrease the number of collision

  17. The Mechanics of Human Achievement.

    PubMed

    Duckworth, Angela L; Eichstaedt, Johannes C; Ungar, Lyle H

    2015-07-01

    Countless studies have addressed why some individuals achieve more than others. Nevertheless, the psychology of achievement lacks a unifying conceptual framework for synthesizing these empirical insights. We propose organizing achievement-related traits by two possible mechanisms of action: Traits that determine the rate at which an individual learns a skill are talent variables and can be distinguished conceptually from traits that determine the effort an individual puts forth. This approach takes inspiration from Newtonian mechanics: achievement is akin to distance traveled, effort to time, skill to speed, and talent to acceleration. A novel prediction from this model is that individual differences in effort (but not talent) influence achievement (but not skill) more substantially over longer (rather than shorter) time intervals. Conceptualizing skill as the multiplicative product of talent and effort, and achievement as the multiplicative product of skill and effort, advances similar, but less formal, propositions by several important earlier thinkers.

  18. The Mechanics of Human Achievement

    PubMed Central

    Duckworth, Angela L.; Eichstaedt, Johannes C.; Ungar, Lyle H.

    2015-01-01

    Countless studies have addressed why some individuals achieve more than others. Nevertheless, the psychology of achievement lacks a unifying conceptual framework for synthesizing these empirical insights. We propose organizing achievement-related traits by two possible mechanisms of action: Traits that determine the rate at which an individual learns a skill are talent variables and can be distinguished conceptually from traits that determine the effort an individual puts forth. This approach takes inspiration from Newtonian mechanics: achievement is akin to distance traveled, effort to time, skill to speed, and talent to acceleration. A novel prediction from this model is that individual differences in effort (but not talent) influence achievement (but not skill) more substantially over longer (rather than shorter) time intervals. Conceptualizing skill as the multiplicative product of talent and effort, and achievement as the multiplicative product of skill and effort, advances similar, but less formal, propositions by several important earlier thinkers. PMID:26236393

  19. Status of Fast Ignition Program at LLNL

    NASA Astrophysics Data System (ADS)

    Patel, P. K.; Bellei, C.; Chawla, S.; Chen, C.; Cohen, B.; Divol, L.; Higginson, D.; Kemp, A.; Kemp, G.; Key, M.; Larson, D.; Link, A.; Ma, T.; McLean, H.; Ping, Y.; Sawada, H.; Shay, H.; Strozzi, D.; Tabak, M.; Westover, B.; Wilks, S.

    2011-10-01

    The fast ignition (FI) approach to inertial confinement fusion offers the potential for achieving the high target gains required for Inertial Fusion Energy (IFE). This paper reports progress at LLNL on the development of a point design for an indirect-drive re-entrant-cone FI target. Integrated hohlraum and capsule designs are described that optimize the peak density, ρR and spatial uniformity of the fuel assembly around the cone tip. The interaction of the short-pulse ignitor beam in the cone is simulated with the PSC explicit particle-in-cell (PIC) code, and the subsequent transport of the electrons and core heating calculated with the Zuma hybrid transport code coupled to the Hydra radiation-hydrodynamics code. Progress will be described in the integrated modeling approach to fast ignition target design through the self-consistent treatment of the hohlraum radiation drive, capsule implosion, fast electron generation and transport, and core heating. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  20. FABRICATION AND CHARACTERIZATION OF FAST IGNITION TARGETS

    SciTech Connect

    HILL,D.W; CASTILLO,E; CHEN,K.C; GRANT,S.E; GREENWOOD,A.L; KAAE,J.L; NIKROO,A; PAGUIO,S.P; SHEARER,C; SMITH,JR.,J.N; STEPHENS,R.B; STEINMAN,D.A; WALL,J

    2003-06-01

    OAK-B135 Fast ignition is a novel scheme for achieving laser fusion. A class of these targets involves cone mounted CH shells. The authors have been fabricating such targets with shells with a wide variety of diameters and wall thicknesses for several years at General Atomics. In addition, recently such shells were needed for implosion experiments at Laboratory for Laser Energetics (LLE) that for the first time were required to be gas retentive. Fabrication of these targets requires producing appropriate cones and shells, assembling the targets, and characterization of the assembled targets. The cones are produced using micromachining and plating techniques. The shells are fabricated using the depolymerizable mandrel technique followed by micromachining a hole for the cone. The cone and the shell then need to be assembled properly for gas retention and precisely in order to position the cone tip at the desired position within the shell. Both are critical for the fast ignition experiments. The presence of the cone in the shell creates new challenges in characterization of the assembled targets. Finally, for targets requiring a gas fill, the cone-shell assembly needs to be tested for gas retention and proper strength at the glue joint. This paper presents an overview of the developmental efforts and technical issues addressed during the fabrication of fast ignition targets.

  1. Fabrication and Characterization of Fast Ignition Targets

    SciTech Connect

    Hill, D.W.; Castillo, E.; Chen, K.C.; Grant, S.E.; Greenwood, A.L.; Kaae, J.L.; Nikroo, A.; Paguio, S.P.; Shearer, C.; Smith, J.N. Jr.; Stephens, R.B.; Steinman, D.A.; Wall, J.

    2004-03-15

    Fast ignition is a novel scheme for achieving laser fusion. A class of these targets involves cone mounted CH shells. We have been fabricating such targets with shells with a wide variety of diameters and wall thicknesses for several years at General Atomics. In addition, recently such shells were needed for implosion experiments at Laboratory for Laser Energetics (LLE) that for the first time were required to be gas retentive. Fabrication of these targets requires producing appropriate cones and shells, assembling the targets, and characterization of the assembled targets. The cones are produced using micromachining and plating techniques. The shells are fabricated using the depolymerizable mandrel technique followed by micromachining a hole for the cone. The cone and the shell then need to be assembled properly for gas retention and precisely in order to position the cone tip at the desired position within the shell. Both are critical for the fast ignition experiments. The presence of the cone in the shell creates new challenges in characterization of the assembled targets. Finally, for targets requiring a gas fill, the cone-shell assembly needs to be tested for gas retention and proper strength at the glue joint. This paper presents an overview of the developmental efforts and technical issues addressed during the fabrication of fast ignition targets.

  2. A point mutation and a RNA processing mutation in a carbamyl phosphate synthetase I (CPSI) deficient patient

    SciTech Connect

    Hall, L.; Summer, M.; Sierra-Rivera, E.; Freeman, M.

    1994-09-01

    Deficiency of carbamyl phosphate synthetase I (CPSID) results in a life-threatening disease due to hyperammonemia. A better understanding of the molecular basis of CPSID was achieved by studying the genetic defects in a CPSID patient. CPSI message was analyzed from hepatic tissue through Northern blot analysis, reverse transcription of liver mRNA followed by polymerase chain reaction amplification (RT-PCR), dideoxy fingerprinting, and direct DNA sequencing. Northern blot analysis of the patient revealed a diminished amount of normal sized CPSI message and multiple other bands not detected in controls. Analysis of the amplified coding region revealed a single point mutation leading to an asparagine to lysine substitution at codon 715. The patient`s cDNA was homozygous and genomic DNA heterozygous for the point mutation which was not found in ten unrelated CPSID patients. The point mutation causes a change from a highly-conserved neutral amino acid to a polar basic residue within a nucleotide/bicarbonate binding domain which points to its importance in normal CPSI function. The other allele which was absent in RT-PCR fragements presumably leads to the multi-form poly-A message detected by Northern blot analysis and allows the point mutation to become the dominant expressed allele. These mutations represent the second reported molecular defect in CPSI and the first to involve a mutation in a functional domain and in RNA processing.

  3. Evolutionary Stability of Minimal Mutation Rates in an Evo-epidemiological Model.

    PubMed

    Birch, Michael; Bolker, Benjamin M

    2015-11-01

    We consider the evolution of mutation rate in a seasonally forced, deterministic, compartmental epidemiological model with a transmission-virulence trade-off. We model virulence as a quantitative genetic trait in a haploid population and mutation as continuous diffusion in the trait space. There is a mutation rate threshold above which the pathogen cannot invade a wholly susceptible population. The evolutionarily stable (ESS) mutation rate is the one which drives the lowest average density, over the course of one forcing period, of susceptible individuals at steady state. In contrast with earlier eco-evolutionary models in which higher mutation rates allow for better evolutionary tracking of a dynamic environment, numerical calculations suggest that in our model the minimum average susceptible population, and hence the ESS, is achieved by a pathogen strain with zero mutation. We discuss how this result arises within our model and how the model might be modified to obtain a nonzero optimum.

  4. Boosted Fast Flux Loop Alternative Cooling Assessment

    SciTech Connect

    Glen R. Longhurst; Donna Post Guillen; James R. Parry; Douglas L. Porter; Bruce W. Wallace

    2007-08-01

    The Gas Test Loop (GTL) Project was instituted to develop the means for conducting fast neutron irradiation tests in a domestic radiation facility. It made use of booster fuel to achieve the high neutron flux, a hafnium thermal neutron absorber to attain the high fast-to-thermal flux ratio, a mixed gas temperature control system for maintaining experiment temperatures, and a compressed gas cooling system to remove heat from the experiment capsules and the hafnium thermal neutron absorber. This GTL system was determined to provide a fast (E > 0.1 MeV) flux greater than 1.0E+15 n/cm2-s with a fast-to-thermal flux ratio in the vicinity of 40. However, the estimated system acquisition cost from earlier studies was deemed to be high. That cost was strongly influenced by the compressed gas cooling system for experiment heat removal. Designers were challenged to find a less expensive way to achieve the required cooling. This report documents the results of the investigation leading to an alternatively cooled configuration, referred to now as the Boosted Fast Flux Loop (BFFL). This configuration relies on a composite material comprised of hafnium aluminide (Al3Hf) in an aluminum matrix to transfer heat from the experiment to pressurized water cooling channels while at the same time providing absorption of thermal neutrons. Investigations into the performance this configuration might achieve showed that it should perform at least as well as its gas-cooled predecessor. Physics calculations indicated that the fast neutron flux averaged over the central 40 cm (16 inches) relative to ATR core mid-plane in irradiation spaces would be about 1.04E+15 n/cm2-s. The fast-to-thermal flux ratio would be in excess of 40. Further, the particular configuration of cooling channels was relatively unimportant compared with the total amount of water in the apparatus in determining performance. Thermal analyses conducted on a candidate configuration showed the design of the water coolant and

  5. Fast clinical molecular diagnosis of hyperphenylalaninemia using next-generation sequencing-based on a custom AmpliSeq™ panel and Ion Torrent PGM sequencing.

    PubMed

    Cao, Yan-yan; Qu, Yu-jin; Song, Fang; Zhang, Ting; Bai, Jin-li; Jin, Yu-wei; Wang, Hong

    2014-12-01

    Hyperphenylalaninemia (HPA) can be classified into phenylketonuria (PKU) and tetrahydrobiopterin deficiency (BH4D), according to the defect of enzyme activity, both of which vary substantially in severity, treatment, and prognosis of the disease. To set up a fast and comprehensive assay in order to achieve early etiological diagnosis and differential diagnosis for children with HPA, we designed a custom AmpliSeq™ panel for the sequencing of coding DNA sequence (CDS), flanking introns, 5' untranslated region (UTR) and 3' UTR from five HPA-causing genes (PAH, PTS, QDPR, GCH1, and PCBD1) using the Ion Torrent Personal Genome Machine (PGM) Sequencer. A standard group of 15 samples with previously known DNA sequences and a test group of 37 HPA patients with unknown mutations were used for assay validation and application, respectively. All variations were confirmed by Sanger sequencing. In the standard group, all the known mutations were detected and were consistent with the results of previous Sanger sequencing. In the test group, we identified mutations in 71 of 74 alleles, with a mutation detection rate of 95.9%. We also found a frame shift deletion p.Ile25Metfs*13 in PAH that was previously unreported. In addition, 1 of 37 in the test group was inconsistent with either the molecular diagnosis or clinical diagnosis by traditional differential methods. In conclusion, our comprehensive assay based on a custom AmpliSeq™ panel and Ion Torrent PGM sequencing has wider coverage, higher throughput, is much faster, and more efficient when compared with the traditional molecular detection method for HPA patients, which could meet the medical need for individualized diagnosis and treatment.

  6. Fast dual tomography

    NASA Astrophysics Data System (ADS)

    Carrion, Philip M.

    1990-09-01

    This paper can be considered as a continuation of the work by Carrion and Carneiro (1989), where a generalized approach to linearized inversion of geophysical data was developed. Their method allows one to incorporate virtually any constraints in the inversion and reformulate the problem in the dual space of Langrangian multipliers (see also Carrion, 1989a). The constrained tomography makes traveltime inversion robust: it automatically rejects “bad data” which correspond to solutions beyond the chosen constraints and allows one to start inversion with an arbitrary chosen initial model.In this paper, I will derive basic formulas for constrained tomographic imaging that can be used in such areas of geophysics as global mapping of the earth interior, exploration geophysics, etc. The method is fast: an example that will be shown in the paper took only 6 min. of VAX CPU time. Had the conventional least-squares matrix inversion been used it would have taken more than 10 hours of the CPU time to solve the same problem.

  7. Fast foldable tent domes

    NASA Astrophysics Data System (ADS)

    Jägers, Aswin P. L.; Sliepen, Guus; Bettonvil, Felix C. M.; Hammerschlag, Robert H.

    2008-07-01

    In the near future ELTs (Extreme Large Telescopes) will be built. Preferably these telescopes should operate without obstructions in the near surrounding to reach optimal seeing conditions and avoid large turbulences with wind-gust accelerations around large obstacles. This applies also to future large solar telescopes. At present two foldable dome prototypes have been built on the Canary Islands: the Dutch Open Telescope (DOT, La Palma) and the GREGOR Telescope (Tenerife), having a diameter of 7 and 9 meter, respectively. The domes are usually fully retracted during observations. The research consists of measurements on the two domes. New camera systems are developed and placed inside the domes for precise dome deformation measurements within 0.1 mm over the whole dome size. Simultaneously, a variety of wind-speed and -direction sensors measure the wind field around the dome. In addition, fast sensitive air-pressure sensors placed on the supporting bows measure the wind pressure. The aim is to predict accurately the expected forces and deformations on up-scaled, fully retractable domes to make their construction more economically. The dimensions of 7 and 9 meter are large enough for realistic on-site tests in gusty wind and will give much more information than wind tunnel experiments.

  8. Parallel fast gauss transform

    SciTech Connect

    Sampath, Rahul S; Sundar, Hari; Veerapaneni, Shravan

    2010-01-01

    We present fast adaptive parallel algorithms to compute the sum of N Gaussians at N points. Direct sequential computation of this sum would take O(N{sup 2}) time. The parallel time complexity estimates for our algorithms are O(N/n{sub p}) for uniform point distributions and O( (N/n{sub p}) log (N/n{sub p}) + n{sub p}log n{sub p}) for non-uniform distributions using n{sub p} CPUs. We incorporate a plane-wave representation of the Gaussian kernel which permits 'diagonal translation'. We use parallel octrees and a new scheme for translating the plane-waves to efficiently handle non-uniform distributions. Computing the transform to six-digit accuracy at 120 billion points took approximately 140 seconds using 4096 cores on the Jaguar supercomputer. Our implementation is 'kernel-independent' and can handle other 'Gaussian-type' kernels even when explicit analytic expression for the kernel is not known. These algorithms form a new class of core computational machinery for solving parabolic PDEs on massively parallel architectures.

  9. Fast Feedback in Classroom Practice

    ERIC Educational Resources Information Center

    Emmett, Katrina; Klaassen, Kees; Eijkelhof, Harrie

    2009-01-01

    In this article we describe one application of the fast feedback method (see Berg 2003 "Aust. Sci. Teach. J." 28-34) in secondary mechanics education. Two teachers tried out a particular sequence twice, in consecutive years, once with and once without the use of fast feedback. We found the method to be successful, and the data that we obtained…

  10. Glycemic management during Jain fasts

    PubMed Central

    Julka, Sandeep; Sachan, Alok; Bajaj, Sarita; Sahay, Rakesh; Chawla, Rajeev; Agrawal, Navneet; Saboo, Banshi; Unnikrishnan, A. G.; Baruah, Manash P.; Parmar, Girish; Kalra, Sanjay

    2017-01-01

    This review describes the various fasts observed by adherents of the Jain religion. It attempts to classify them according to their suitability for people with diabetes and suggests appropriate regime and dose modification for those observing these fasts. The review is an endeavor to encourage rational and evidence-based management in this field of diabetology. PMID:28217525

  11. Clusters of mutations from transient hypermutability.

    PubMed

    Drake, John W; Bebenek, Anna; Kissling, Grace E; Peddada, Shyamal

    2005-09-06

    Collections of mutants usually contain more mutants bearing multiple mutations than expected from the mutant frequency and a random distribution of mutations. This excess is seen in a variety of organisms and also after DNA synthesis in vitro. The excess is unlikely to originate in mutator mutants but rather from transient hypermutability resulting from a perturbation of one of the many transactions that maintain genetic fidelity. The multiple mutations are sometimes clustered and sometimes randomly distributed. We model some spectra as populations comprising a majority with a low mutation frequency and a minority with a high mutation frequency. In the case of mutants produced in vitro by a bacteriophage RB69 mutator DNA polymerase, mutants with two mutations are in approximately 10-fold excess and mutants with three mutations are in even greater excess. However, phenotypically undetectable mutations seen only as hitchhikers with detectable mutations are approximately 5-fold more frequent than mutants bearing detectable mutations, indicating that they arose in a subpopulation with a higher mutation frequency. Excess multiple mutations may contribute critically to carcinogenesis and to adaptive mutation, including the adaptations of pathogens as they move from host to host. In the case of the rapidly mutating riboviruses, the viral population appears to be composed of a majority with a mutation frequency substantially lower than the average and a minority with a huge mutational load.

  12. Fast causal multicast

    NASA Technical Reports Server (NTRS)

    Birman, Kenneth P.; Schiper, Andre; Stephenson, Pat

    1990-01-01

    A new protocol is presented that efficiently implements a reliable, causally ordered multicast primitive and is easily extended into a totally ordered one. Intended for use in the ISIS toolkit, it offers a way to bypass the most costly aspects of ISIS while benefiting from virtual synchrony. The facility scales with bounded overhead. Measured speedups of more than an order of magnitude were obtained when the protocol was implemented within ISIS. One conclusion is that systems such as ISIS can achieve performance competitive with the best existing multicast facilities - a finding contradicting the widespread concern that fault-tolerance may be unacceptably costly.

  13. Fast casual multicast

    NASA Technical Reports Server (NTRS)

    Birman, Kenneth; Schiper, Andre; Stephenson, Pat

    1990-01-01

    A new protocol is presented that efficiently implements a reliable, causally ordered multicast primitive and is easily extended into a totally ordered one. Intended for use in the ISIS toolkit, it offers a way to bypass the most costly aspects of ISIS while benefiting from virtual synchrony. The facility scales with bounded overhead. Measured speedups of more than an order of magnitude were obtained when the protocol was implemented within ISIS. One conclusion is that systems such as ISIS can achieve performance competitive with the best existing multicast facilities--a finding contradicting the widespread concern that fault-tolerance may be unacceptably costly.

  14. The FAST (FRC Acceleration Space Thruster) Experiment

    NASA Technical Reports Server (NTRS)

    Martin, Adam; Eskridge, R.; Lee, M.; Richeson, J.; Smith, J.; Thio, Y. C. F.; Slough, J.; Rodgers, Stephen L. (Technical Monitor)

    2001-01-01

    The Field Reverse Configuration (FRC) is a magnetized plasmoid that has been developed for use in magnetic confinement fusion. Several of its properties suggest that it may also be useful as a thruster for in-space propulsion. The FRC is a compact toroid that has only poloidal field, and is characterized by a high plasma beta = (P)/(B (sup 2) /2Mu0), the ratio of plasma pressure to magnetic field pressure, so that it makes efficient use of magnetic field to confine a plasma. In an FRC thruster, plasmoids would be repetitively formed and accelerated to high velocity; velocities of = 250 km/s (Isp = 25,000s) have already been achieved in fusion experiments. The FRC is inductively formed and accelerated, and so is not subject to the problem of electrode erosion. As the plasmoid may be accelerated over an extended length, it can in principle be made very efficient. And the achievable jet powers should be scalable to the MW range. A 10 kW thruster experiment - FAST (FRC Acceleration Space Thruster) has just started at the Marshall Space Flight Center. The design of FAST and the status of construction and operation will be presented.

  15. Mutation breeding by ion implantation

    NASA Astrophysics Data System (ADS)

    Yu, Zengliang; Deng, Jianguo; He, Jianjun; Huo, Yuping; Wu, Yuejin; Wang, Xuedong; Lui, Guifu

    1991-07-01

    Ion implantation as a new mutagenic method has been used in the rice breeding program since 1986, and for mutation breeding of other crops later. It has been shown, in principle and in practice, that this method has many outstanding advantages: lower damage rate; higher mutation rate and wider mutational spectrum. Many new lines of rice with higher yield rate; broader disease resistance; shorter growing period but higher quality have been bred from ion beam induced mutants. Some of these lines have been utilized for the intersubspecies hybridization. Several new lines of cotton, wheat and other crops are now in breeding. Some biophysical effects of ion implantation for crop seeds have been studied.

  16. EDUCATIONAL ACHIEVEMENT AND THE NAVAJO.

    ERIC Educational Resources Information Center

    HAAS, JOHN; MELVILLE, ROBERT

    A STUDY WAS DEVISED TO APPRAISE THE ACADEMIC ACHIEVEMENT OF NAVAJO STUDENTS LIVING IN DORMITORIES AWAY FROM THE INDIAN RESERVATION. THE FOLLOWING SEVEN FACTORS WERE CHOSEN TO BE INVESTIGATED AS BEING DIRECTLY RELATED TO ACHIEVEMENT--(1) INTELLIGENCE, (2) READING ABILITY, (3) ANXIETY, (4) SELF-CONCEPT, (5) MOTIVATION, (6) VERBAL DEVELOPMENT, (7)…

  17. Sociocultural Origins of Achievement Motivation

    ERIC Educational Resources Information Center

    Maehr, Martin L.

    1977-01-01

    Presents a theoretical review of work on sociocultural influences on achievement, focusing on a critical evaluation of the work of David McClellan. Offers an alternative conception of achievement motivation which stresses the role of contextual and situational factors in addition to personality factors. Available from: Transaction Periodicals…

  18. Raising Boys' Achievement in Schools.

    ERIC Educational Resources Information Center

    Bleach, Kevan, Ed.

    This book offers insights into the range of strategies and good practice being used to raise the achievement of boys. Case studies by school-based practitioners suggest ideas and measures to address the issue of achievement by boys. The contributions are: (1) "Why the Likely Lads Lag Behind" (Kevan Bleach); (2) "Helping Boys Do…

  19. Teaching the Low Level Achiever.

    ERIC Educational Resources Information Center

    Salomone, Ronald E., Ed.

    1986-01-01

    Intended for teachers of the English language arts, the articles in this issue offer suggestions and techniques for teaching the low level achiever. Titles and authors of the articles are as follows: (1) "A Point to Ponder" (Rachel Martin); (2) "Tracking: A Self-Fulfilling Prophecy of Failure for the Low Level Achiever" (James Christopher Davis);…

  20. Early Intervention and Student Achievement

    ERIC Educational Resources Information Center

    Hormes, Mridula T.

    2009-01-01

    The United States Department of Education has been rigorous in holding all states accountable with regard to student achievement. The No Child Left Behind Act of 2001 clearly laid out federal mandates for all schools to follow. K-12 leaders of public schools are very aware of the fact that results in terms of student achievement need to improve…

  1. Parental Involvement and Academic Achievement

    ERIC Educational Resources Information Center

    Goodwin, Sarah Christine

    2015-01-01

    This research study examined the correlation between student achievement and parent's perceptions of their involvement in their child's schooling. Parent participants completed the Parent Involvement Project Parent Questionnaire. Results slightly indicated parents of students with higher level of achievement perceived less demand or invitations…

  2. Asperger Syndrome and Academic Achievement.

    ERIC Educational Resources Information Center

    Griswold, Deborah E.; Barnhill, Gena P.; Myles, Brenda Smith; Hagiwara, Taku; Simpson, Richard L.

    2002-01-01

    A study focused on identifying the academic characteristics of 21 children and youth who have Asperger syndrome. Students had an extraordinary range of academic achievement scores, extending from significantly above average to far below grade level. Lowest achievement scores were shown for numerical operations, listening comprehension, and written…

  3. Perils of Standardized Achievement Testing

    ERIC Educational Resources Information Center

    Haladyna, Thomas M.

    2006-01-01

    This article argues that the validity of standardized achievement test-score interpretation and use is problematic; consequently, confidence and trust in such test scores may often be unwarranted. The problem is particularly severe in high-stakes situations. This essay provides a context for understanding standardized achievement testing, then…

  4. Stress Correlates and Academic Achievement.

    ERIC Educational Resources Information Center

    Bentley, Donna Anderson; And Others

    An ongoing concern for educators is the identification of factors that contribute to or are associated with academic achievement; one such group of variables that has received little attention are those involving stress. The relationship between perceived sources of stress and academic achievement was examined to determine if reactions to stress…

  5. School Size and Student Achievement

    ERIC Educational Resources Information Center

    Riggen, Vicki

    2013-01-01

    This study examined whether a relationship between high school size and student achievement exists in Illinois public high schools in reading and math, as measured by the Prairie State Achievement Exam (PSAE), which is administered to all Illinois 11th-grade students. This study also examined whether the factors of socioeconomic status, English…

  6. SCN10A Mutation in a Patient with Erythromelalgia Enhances C-Fiber Activity Dependent Slowing

    PubMed Central

    Neacsu, Cristian; Eberhardt, Esther; Schmidt, Roland; Lunden, Lars Kristian; Ørstavik, Kristin; Kaluza, Luisa; Meents, Jannis; Zhang, Zhiping; Carr, Thomas Hedley; Salter, Hugh; Malinowsky, David; Wollberg, Patrik; Krupp, Johannes; Kleggetveit, Inge Petter; Schmelz, Martin; Jørum, Ellen; Namer, Barbara

    2016-01-01

    Gain-of-function mutations in the tetrodotoxin (TTX) sensitive voltage-gated sodium channel (Nav) Nav1.7 have been identified as a key mechanism underlying chronic pain in inherited erythromelalgia. Mutations in TTX resistant channels, such as Nav1.8 or Nav1.9, were recently connected with inherited chronic pain syndromes. Here, we investigated the effects of the p.M650K mutation in Nav1.8 in a 53 year old patient with erythromelalgia by microneurography and patch-clamp techniques. Recordings of the patient’s peripheral nerve fibers showed increased activity dependent slowing (ADS) in CMi and less spontaneous firing compared to a control group of erythromelalgia patients without Nav mutations. To evaluate the impact of the p.M650K mutation on neuronal firing and channel gating, we performed current and voltage-clamp recordings on transfected sensory neurons (DRGs) and neuroblastoma cells. The p.M650K mutation shifted steady-state fast inactivation of Nav1.8 to more hyperpolarized potentials and did not significantly alter any other tested gating behaviors. The AP half-width was significantly broader and the stimulated action potential firing rate was reduced for M650K transfected DRGs compared to WT. We discuss the potential link between enhanced steady state fast inactivation, broader action potential width and the potential physiological consequences. PMID:27598514

  7. Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma

    PubMed Central

    2011-01-01

    Background The genetics of advanced biliary tract cancers (BTC), which encompass intra- and extra-hepatic cholangiocarcinomas as well as gallbladder carcinomas, are heterogeneous and remain to be fully defined. Methods To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases. Results Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%). KRAS mutations were identified in 3 (13%) intra-hepatic cholangiocarcinomas and 1 (33%) perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma. Conclusions The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors. PMID:21303542

  8. Mutations of c-Cbl in myeloid malignancies

    PubMed Central

    Katzav, Shulamit; Schmitz, M. Lienhard

    2015-01-01

    Next generation sequencing has shown the frequent occurrence of point mutations in the ubiquitin E3 ligase c-Cbl in myeloid malignancies. Mouse models revealed a causal contribution of c-Cbl for the onset of such neoplasms. The point mutations typically cluster in the linker region and RING finger domain and affect both alleles by acquired uniparental disomy. The fast progress in the detection of c-Cbl mutations is contrasted by our scarce knowledge on their functional consequences. The c-Cbl protein displays several enzymatic functions by promoting the attachment of differentially composed ubiquitin chains and of the ubiquitin-like protein NEDD8 to its target proteins. In addition, c-Cbl functions as an adapter protein and undergoes phosphorylation-dependent inducible conformation changes. Studies on the impact of c-Cbl mutations on its functions as a dynamic and versatile adapter protein, its interactomes and on its various enzymatic activities are now important to allow the identification of druggable targets within the c-Cbl signaling network. PMID:26028666

  9. Single molecule targeted sequencing for cancer gene mutation detection

    PubMed Central

    Gao, Yan; Deng, Liwei; Yan, Qin; Gao, Yongqian; Wu, Zengding; Cai, Jinsen; Ji, Daorui; Li, Gailing; Wu, Ping; Jin, Huan; Zhao, Luyang; Liu, Song; Ge, Liangjin; Deem, Michael W.; He, Jiankui

    2016-01-01

    With the rapid decline in cost of sequencing, it is now affordable to examine multiple genes in a single disease-targeted clinical test using next generation sequencing. Current targeted sequencing methods require a separate step of targeted capture enrichment during sample preparation before sequencing. Although there are fast sample preparation methods available in market, the library preparation process is still relatively complicated for physicians to use routinely. Here, we introduced an amplification-free Single Molecule Targeted Sequencing (SMTS) technology, which combined targeted capture and sequencing in one step. We demonstrated that this technology can detect low-frequency mutations using artificially synthesized DNA sample. SMTS has several potential advantages, including simple sample preparation thus no biases and errors are introduced by PCR reaction. SMTS has the potential to be an easy and quick sequencing technology for clinical diagnosis such as cancer gene mutation detection, infectious disease detection, inherited condition screening and noninvasive prenatal diagnosis. PMID:27193446

  10. Hitting cancers' weak spots: vulnerabilities imposed by p53 mutation.

    PubMed

    Gurpinar, Evrim; Vousden, Karen H

    2015-08-01

    The tumor suppressor protein p53 plays a critical role in limiting malignant development and progression. Almost all cancers show loss of p53 function, through either mutation in the p53 gene itself or defects in the mechanisms that activate p53. While reactivation of p53 can effectively limit tumor growth, this is a difficult therapeutic goal to achieve in the many cancers that do not retain wild type p53. An alternative approach focuses on identifying vulnerabilities imposed on cancers by virtue of the loss of or alterations in p53, to identify additional pathways that can be targeted to specifically kill or inhibit the growth of p53 mutated cells. These indirect ways of exploiting mutations in p53 - which occur in more than half of all human cancers - provide numerous exciting therapeutic possibilities.

  11. Fast centrifugal partition chromatography as a preparative-scale separation technique for citrus flavones

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fast centrifugal partition chromatography (FCPC) is a preparative-scale separations methodology based on the principles of counter current chromatography. Separations by FCPC are typically achieved with higher recoveries and with lower solvent use compared to conventional column chromatography. HSCP...

  12. Fast dispersion estimation in coherent optical 16QAM fast OFDM systems.

    PubMed

    Zhao, J; Shams, H

    2013-01-28

    Fast channel estimation is crucial to increase the payload efficiency which is of particular importance for optical packet networks. In this paper, we propose a novel least-square based dispersion estimation method in coherent optical fast OFDM (F-OFDM) systems. Additionally, we experimentally demonstrate for the first time a 37.5 Gb/s 16QAM coherent F-OFDM system with 480 km transmission using the proposed scheme. The results show that this method outperforms the conventional channel estimation methods in minimizing the overhead load. A single training symbol can achieve near-optimum channel estimation without any prior information of the transmission distance. This makes optical F-OFDM a very promising scheme for the future burst-mode applications.

  13. Achievement First: Developing a Teacher Performance Management System That Recognizes Excellence

    ERIC Educational Resources Information Center

    Curtis, Rachel

    2011-01-01

    Teachers are the single most important school-related factor in students' learning, and improving student learning is the single most important goal at Achievement First (AF), a fast-growing public charter school network in the Northeast. To achieve this goal, the AF team has worked to establish a common understanding of effective instructional…

  14. Rare mutations in evolutionary dynamics

    NASA Astrophysics Data System (ADS)

    Amadori, Anna Lisa; Calzolari, Antonella; Natalini, Roberto; Torti, Barbara

    2015-12-01

    In this paper we study the effect of rare mutations, driven by a marked point process, on the evolutionary behavior of a population. We derive a Kolmogorov equation describing the expected values of the different frequencies and prove some rigorous analytical results about their behavior. Finally, in a simple case of two different quasispecies, we are able to prove that the rarity of mutations increases the survival opportunity of the low fitness species.

  15. A new sieving matrix for DNA sequencing, genotyping and mutation detection and high-throughput genotyping with a 96-capillary array system

    SciTech Connect

    Gao, David

    1999-11-08

    Capillary electrophoresis has been widely accepted as a fast separation technique in DNA analysis. In this dissertation, a new sieving matrix is described for DNA analysis, especially DNA sequencing, genetic typing and mutation detection. A high-throughput 96 capillary array electrophoresis system was also demonstrated for simultaneous multiple genotyping. The authors first evaluated the influence of different capillary coatings on the performance of DNA sequencing. A bare capillary was compared with a DB-wax, an FC-coated and a polyvinylpyrrolidone dynamically coated capillary with PEO as sieving matrix. It was found that covalently-coated capillaries had no better performance than bare capillaries while PVP coating provided excellent and reproducible results. The authors also developed a new sieving Matrix for DNA separation based on commercially available poly(vinylpyrrolidone) (PVP). This sieving matrix has a very low viscosity and an excellent self-coating effect. Successful separations were achieved in uncoated capillaries. Sequencing of M13mp18 showed good resolution up to 500 bases in treated PVP solution. Temperature gradient capillary electrophoresis and PVP solution was applied to mutation detection. A heteroduplex sample and a homoduplex reference were injected during a pair of continuous runs. A temperature gradient of 10 C with a ramp of 0.7 C/min was swept throughout the capillary. Detection was accomplished by laser induced fluorescence detection. Mutation detection was performed by comparing the pattern changes between the homoduplex and the heteroduplex samples. High throughput, high detection rate and easy operation were achieved in this system. They further demonstrated fast and reliable genotyping based on CTTv STR system by multiple-capillary array electrophoresis. The PCR products from individuals were mixed with pooled allelic ladder as an absolute standard and coinjected with a 96-vial tray. Simultaneous one-color laser-induced fluorescence

  16. Long Range Fast Tool Servo

    DTIC Science & Technology

    1993-05-31

    AD-A271 614 r, FINAL REPORT w to I OFFICE OF NAVAL RESEARCH [I on * LONG RANGE FAST TOOL SERVO I ONR CONTRACT NO. N00014-92-J-4082-PII Covering the...n I I 1 INTRODUCTION The PEC’s MAC 100 Fast Tool Servo (FTS) System has demonstrated the efficacy of fabricating off-axis parabolic segments on axis...by utilizing a fast tool motion to machine non-rotationally symmetric surfaces [1]. The key to this technique was a servo for the tool motion that had

  17. Genome destabilizing mutator alleles drive specific mutational trajectories in Saccharomyces cerevisiae.

    PubMed

    Stirling, Peter C; Shen, Yaoqing; Corbett, Richard; Jones, Steven J M; Hieter, Philip

    2014-02-01

    In addition to environmental factors and intrinsic variations in base substitution rates, specific genome-destabilizing mutations can shape the mutational trajectory of genomes. How specific alleles influence the nature and position of accumulated mutations in a genomic context is largely unknown. Understanding the impact of genome-destabilizing alleles is particularly relevant to cancer genomes where biased mutational signatures are identifiable. We first created a more complete picture of cellular pathways that impact mutation rate using a primary screen to identify essential Saccharomyces cerevisiae gene mutations that cause mutator phenotypes. Drawing primarily on new alleles identified in this resource, we measure the impact of diverse mutator alleles on mutation patterns directly by whole-genome sequencing of 68 mutation-accumulation strains derived from wild-type and 11 parental mutator genotypes. The accumulated mutations differ across mutator strains, displaying base-substitution biases, allele-specific mutation hotspots, and break-associated mutation clustering. For example, in mutants of POLα and the Cdc13-Stn1-Ten1 complex, we find a distinct subtelomeric bias for mutations that we show is independent of the target sequence. Together our data suggest that specific genome-instability mutations are sufficient to drive discrete mutational signatures, some of which share properties with mutation patterns seen in tumors. Thus, in a population of cells, genome-instability mutations could influence clonal evolution by establishing discrete mutational trajectories for genomes.

  18. Childhood Obesity and Cognitive Achievement.

    PubMed

    Black, Nicole; Johnston, David W; Peeters, Anna

    2015-09-01

    Obese children tend to perform worse academically than normal-weight children. If poor cognitive achievement is truly a consequence of childhood obesity, this relationship has significant policy implications. Therefore, an important question is to what extent can this correlation be explained by other factors that jointly determine obesity and cognitive achievement in childhood? To answer this question, we exploit a rich longitudinal dataset of Australian children, which is linked to national assessments in math and literacy. Using a range of estimators, we find that obesity and body mass index are negatively related to cognitive achievement for boys but not girls. This effect cannot be explained by sociodemographic factors, past cognitive achievement or unobserved time-invariant characteristics and is robust to different measures of adiposity. Given the enormous importance of early human capital development for future well-being and prosperity, this negative effect for boys is concerning and warrants further investigation.

  19. Using Design To Achieve Sustainability

    EPA Science Inventory

    Sustainability is defined as meeting the needs of this generation without compromising the ability of future generations to meet their needs. This is a conditional statement that places the responsibility for achieving sustainability squarely in hands of designers and planners....

  20. Achieving Efficiencies in Army Installations.

    DTIC Science & Technology

    2007-11-02

    34" ’■■"■" 1 USAWC STRATEGY RESEARCH PROJECT Achieving Efficiencies in Army Installations by Richard Fliss Col. Richard M. Meinhart Project...government agency. STRATEGY RESEARCH PROJECT ACHIEVING EFFICIENCIES IN ARMY INSTALLATIONS BY RICHARD FLISS DISTRIBUTION STATEMENT A: Approved...for public release. Distribution is unlimited. DTIC QUALITY INSPECTED & USAWC CLASS OF 1998 U.S. ARMY WAR COLLEGE, CARLISLE BARRACKS, PA 17013-5050

  1. Fast Ignition Experimental and Theoretical Studies

    SciTech Connect

    Akli, Kramer Ugerthen

    2006-01-01

    We are becoming dependent on energy more today than we were a century ago, and with increasing world population and booming economies, sooner or later our energy sources will be exhausted. Moreover, our economy and welfare strongly depends on foreign oil and in the shadow of political uncertainties, there is an urgent need for a reliable, safe, and cheap energy source. Thermonuclear fusion, if achieved, is that source of energy which not only will satisfy our demand for today but also for centuries to come. Today, there are two major approaches to achieve fusion: magnetic confinement fusion (MFE) and inertial confinement fusion (ICF). This dissertation explores the inertial confinement fusion using the fast ignition concept. Unlike the conventional approach where the same laser is used for compression and ignition, in fast ignition separate laser beams are used. This dissertation addresses three very important topics to fast ignition inertial confinement fusion. These are laser-to-electron coupling efficiency, laser-generated electron beam transport, and the associated isochoric heating. First, an integrated fast ignition experiment is carried out with 0.9 kJ of energy in the compression beam and 70 J in the ignition beam. Measurements of absolute Kα yield from the imploded core revealed that about 17% of the laser energy is coupled to the suprathermal electrons. Modeling of the transport of these electrons and the associated isochoric heating, with the previously determined laser-to-electron conversion efficiency, showed a maximum target temperature of 166 eV at the front where the electron flux is higher and the density is lower. The contribution of the potential, induced by charge separation, in opposing the motion of the electrons was moderate. Second, temperature sensitivity of Cu Kα imaging efficiency using a spherical Bragg reflecting crystal is investigated. It was found that due to the shifting and broadening of the K

  2. FastStats: Contraceptive Use

    MedlinePlus

    ... Inflicted Injury Life Stages and Populations Age Groups Adolescent Health Child Health Infant Health Older Persons' Health ... Contraceptive Use Infertility Reproductive Health Notice Regarding FastStats Mobile Application Get Email Updates To receive email updates ...

  3. FastStats: Sinus Conditions

    MedlinePlus

    ... please visit this page: About CDC.gov . FastStats Homepage Diseases and Conditions Anemia or Iron Deficiency Arthritis ... Statistics Tables for U.S. Adults: National Health Interview Survey, 2014, Table A-2 [PDF - 219 KB] Physician ...

  4. Fast Food: Tips for Choosing Healthier Options

    MedlinePlus

    ... make wise meal choices when going to a fast-food restaurant. By Mayo Clinic Staff Does following ... or healthy diet mean you must swear off fast food? Not necessarily. An occasional stop for fast ...

  5. The androgen receptor gene mutations database.

    PubMed

    Patterson, M N; Hughes, I A; Gottlieb, B; Pinsky, L

    1994-09-01

    The androgen receptor gene mutations database is a comprehensive listing of mutations published in journals and meetings proceedings. The majority of mutations are point mutations identified in patients with androgen insensitivity syndrome. Information is included regarding the phenotype, the nature and location of the mutations, as well as the effects of the mutations on the androgen binding activity of the receptor. The current version of the database contains 149 entries, of which 114 are unique mutations. The database is available from EMBL (NetServ@EMBL-Heidelberg.DE) or as a Macintosh Filemaker file (mc33001@musica.mcgill.ca).

  6. Fasting in paediatric ambulatory surgery.

    PubMed

    Klemetti, Seija; Suominen, Tarja

    2008-02-01

    The purpose of this descriptive study was to examine how preoperative fasting and postoperative termination of the fast was experienced in ambulatory surgery by child patients and their mothers. The target group consisted of children (n = 12, age 2-10 years) who had undergone tonsillectomy/adenoidectomy, and their mothers. In the interviews, the mothers were asked to describe the problems connected with their child's preoperative fast and postoperative termination of the fast, as well as the things that went well in the process. Content analysis was carried out inductively. Preoperatively, the children were thirsty and anxious, but understood the fasting situation well. In some cases, there were conflicts between the child and his/her parent if fasting was prolonged. Parents also had doubts about their ability to implement the child's fast. Postoperatively, children had pains in their throats and stomachs, suffered from nausea, and had difficulty taking in nutrition and medication. Parents had worries about their child's home care, such as food intake and administration of pain medication. The possibility of postoperative bleeding and exacerbation of the child's condition was also worrying for the parents. The most evident result of the study was that parents need more information before their child's operation. Preparing the child for the operation by giving him/her nutrition as long as permitted enhances postoperative recovery and improves parents' control over the ambulatory surgical experience. Nurses should take a more active part in children's perioperative fasting and preoperative preparation of children and their parents. In further research, experimental studies should be designed in order to receive more evidence-based information for clinical practice.

  7. Fast Fight Detection

    PubMed Central

    Serrano Gracia, Ismael; Deniz Suarez, Oscar; Bueno Garcia, Gloria; Kim, Tae-Kyun

    2015-01-01

    Action recognition has become a hot topic within computer vision. However, the action recognition community has focused mainly on relatively simple actions like clapping, walking, jogging, etc. The detection of specific events with direct practical use such as fights or in general aggressive behavior has been comparatively less studied. Such capability may be extremely useful in some video surveillance scenarios like prisons, psychiatric centers or even embedded in camera phones. As a consequence, there is growing interest in developing violence detection algorithms. Recent work considered the well-known Bag-of-Words framework for the specific problem of fight detection. Under this framework, spatio-temporal features are extracted from the video sequences and used for classification. Despite encouraging results in which high accuracy rates were achieved, the computational cost of extracting such features is prohibitive for practical applications. This work proposes a novel method to detect violence sequences. Features extracted from motion blobs are used to discriminate fight and non-fight sequences. Although the method is outperformed in accuracy by state of the art, it has a significantly faster computation time thus making it amenable for real-time applications. PMID:25860667

  8. Fast fight detection.

    PubMed

    Serrano Gracia, Ismael; Deniz Suarez, Oscar; Bueno Garcia, Gloria; Kim, Tae-Kyun

    2015-01-01

    Action recognition has become a hot topic within computer vision. However, the action recognition community has focused mainly on relatively simple actions like clapping, walking, jogging, etc. The detection of specific events with direct practical use such as fights or in general aggressive behavior has been comparatively less studied. Such capability may be extremely useful in some video surveillance scenarios like prisons, psychiatric centers or even embedded in camera phones. As a consequence, there is growing interest in developing violence detection algorithms. Recent work considered the well-known Bag-of-Words framework for the specific problem of fight detection. Under this framework, spatio-temporal features are extracted from the video sequences and used for classification. Despite encouraging results in which high accuracy rates were achieved, the computational cost of extracting such features is prohibitive for practical applications. This work proposes a novel method to detect violence sequences. Features extracted from motion blobs are used to discriminate fight and non-fight sequences. Although the method is outperformed in accuracy by state of the art, it has a significantly faster computation time thus making it amenable for real-time applications.

  9. The development of rapid and accurate screening test for RET hotspot somatic and germline mutations in MEN2 syndromes.

    PubMed

    Zupan, Andrej; Glavač, Damjan

    2015-12-01

    Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy with distinctive features separating it from other thyroid cancers. Cancer may be sporadic or occur as a consequence of the hereditary syndrome called multiple endocrine neoplasia type 2 (MEN2) with three distinct phenotypes in MEN2A, MEN2B and FMTC. Each variant of MEN2 results from different RET gene mutations, with a good genotype-phenotype correlation. The goal of the study was to develop a fast and accurate screening method for a reliable detection of hot-spot RET germline and sporadic tumor mutations. From a cohort of 191 patients with MTC and their relatives, 38 tested positive and 31 tested negative for a germline or somatic tumor RET mutation were selected. A positive HRM mutation pattern was detected in all mutation-positive patients and altogether the method was able to clearly differentiate between twenty different genotypes. A novel germline variant p.Ala639Thr was detected in MTC patient, which was determined to be likely benign. Analytical specificity was determined to be 98.6% and a sensitivity threshold was determined to be 30%. The fast and accurate HRM method reduces the turnaround time providing fast and important information, especially when targeted anti-tyrosine kinase therapy on tumor samples is considered. Overall, we developed a high-throughput, accurate and cost-effective approach for the detection of RET germline and sporadic tumor mutations.

  10. Fast-Tracking Colostomy Closures.

    PubMed

    Nanavati, Aditya J; Prabhakar, Subramaniam

    2015-12-01

    There have been very few studies on applying fast-track principles to colostomy closures. We believe that outcome may be significantly improved with multimodal interventions in the peri-operative care of patients undergoing this procedure. A retrospective study was carried out comparing patients who had undergone colostomy closures by the fast-track and traditional care protocols at our centre. We intended to analyse peri-operative period and recovery in colostomy closures to confirm that fast-track surgery principles improved outcomes. Twenty-six patients in the fast-track arm and 24 patients in the traditional care arm had undergone colostomy closures. Both groups were comparable in terms of their baseline parameters. Patients in the fast-track group were ambulatory and accepted oral feeding earlier. There was a significant reduction in the duration of stay (4.73 ± 1.43 days vs. 7.21 ± 1.38 days, p = 0.0000). We did not observe a rise in complications or 30-day re-admissions. Fast-track surgery can safely be applied to colostomy closures. It shows earlier ambulation and reduction in length of hospital stay.

  11. Optimization of 3D Poisson-Nernst-Planck model for fast evaluation of diverse protein channels.

    PubMed

    Dyrka, Witold; Bartuzel, Maciej M; Kotulska, Malgorzata

    2013-10-01

    We show the accuracy and applicability of our fast algorithmic implementation of a three-dimensional Poisson-Nernst-Planck (3D-PNP) flow model for characterizing different protein channels. Due to its high computational efficiency, our model can predict the full current-voltage characteristics of a channel within minutes, based on the experimental 3D structure of the channel or its computational model structure. Compared with other methods, such as Brownian dynamics, which currently needs a few weeks of the computational time, or even much more demanding molecular dynamics modeling, 3D-PNP is the only available method for a function-based evaluation of very numerous tentative structural channel models. Flow model tests of our algorithm and its optimal parametrization are provided for five native channels whose experimental structures are available in the protein data bank (PDB) in an open conductive state, and whose experimental current-voltage characteristics have been published. The channels represent very different geometric and structural properties, which makes it the widest test to date of the accuracy of 3D-PNP on real channels. We test whether the channel conductance, rectification, and charge selectivity obtained from the flow model, could be sufficiently sensitive to single-point mutations, related to unsignificant changes in the channel structure. Our results show that the classical 3D-PNP model, under proper parametrization, is able to achieve a qualitative agreement with experimental data for a majority of the tested characteristics and channels, including channels with narrow and irregular conductivity pores. We propose that although the standard PNP model cannot provide insight into complex physical phenomena due to its intrinsic limitations, its semiquantitative agreement is achievable for rectification and selectivity at a level sufficient for the bioinformatical purpose of selecting the best structural models with a great advantage of a very short

  12. Coexistence of JAK2 and CALR mutations and their clinical implications in patients with essential thrombocythemia

    PubMed Central

    Lee, Jun Hyung; Choi, Yong Jun; Choi, Hyun-Jung; Shin, Jong-Hee; Suh, Soon-Pal; Szardenings, Michael; Kim, Hye-Ran; Shin, Myung-Geun

    2016-01-01

    Janus kinase 2 (JAK2) and calreticulin (CALR) constitute the two most frequent mutations in essential thrombocythemia (ET), and both are reported to be mutually exclusive. Hence, we examined a cohort of 123 myeloproliferative neoplasm (MPN) patients without BCR-ABL1 rearrangement and additional ET patients (n=96) for coexistence of JAK2 and CALR mutations. The frequency of CALR mutations was 20.3% in 123 MPN patients; 31.1% in ET (n=74), 25% in primary myelofibrosis (n=4) and 2.2% in polycythemia vera (n=45). JAK2 and CALR mutations coexisted in 7 (4.2%) of 167 ET patients. Clinical characteristics, progression-free survival (PFS), and elapsed time to achieve partial remission across 4 groups (JAK2+/CALR+, JAK2+/CALR-, JAK2-/CALR+, JAK2-/CALR-) were reviewed. The JAK2+/CALR- group had higher leukocyte counts and hemoglobin levels and more frequent thrombotic events than JAK2-/CALR- group. JAK2 mutations have a greater effect on the disease phenotype and the clinical features of MPN patients rather than do CALR mutation. JAK2+ groups showed a tendency of poor PFS than JAK2- groups regardless of CALR mutation. CALR+ was a predictor of late response to the treatment. Our study also showed that thrombosis was more frequent in ET patients with type 2 CALR mutations than in those with type 1 CALR mutations. PMID:27486987

  13. Coexistence of JAK2 and CALR mutations and their clinical implications in patients with essential thrombocythemia.

    PubMed

    Kang, Min-Gu; Choi, Hyun-Woo; Lee, Jun Hyung; Choi, Yong Jun; Choi, Hyun-Jung; Shin, Jong-Hee; Suh, Soon-Pal; Szardenings, Michael; Kim, Hye-Ran; Shin, Myung-Geun

    2016-08-30

    Janus kinase 2 (JAK2) and calreticulin (CALR) constitute the two most frequent mutations in essential thrombocythemia (ET), and both are reported to be mutually exclusive. Hence, we examined a cohort of 123 myeloproliferative neoplasm (MPN) patients without BCR-ABL1 rearrangement and additional ET patients (n=96) for coexistence of JAK2 and CALR mutations. The frequency of CALR mutations was 20.3% in 123 MPN patients; 31.1% in ET (n=74), 25% in primary myelofibrosis (n=4) and 2.2% in polycythemia vera (n=45). JAK2 and CALR mutations coexisted in 7 (4.2%) of 167 ET patients. Clinical characteristics, progression-free survival (PFS), and elapsed time to achieve partial remission across 4 groups (JAK2+/CALR+, JAK2+/CALR-, JAK2-/CALR+, JAK2-/CALR-) were reviewed. The JAK2+/CALR- group had higher leukocyte counts and hemoglobin levels and more frequent thrombotic events than JAK2-/CALR- group. JAK2 mutations have a greater effect on the disease phenotype and the clinical features of MPN patients rather than do CALR mutation. JAK2+ groups showed a tendency of poor PFS than JAK2- groups regardless of CALR mutation. CALR+ was a predictor of late response to the treatment. Our study also showed that thrombosis was more frequent in ET patients with type 2 CALR mutations than in those with type 1 CALR mutations.

  14. The Five-Hundred Aperture Spherical Radio Telescope (fast) Project

    NASA Astrophysics Data System (ADS)

    Nan, Rendong; Li, Di; Jin, Chengjin; Wang, Qiming; Zhu, Lichun; Zhu, Wenbai; Zhang, Haiyan; Yue, Youling; Qian, Lei

    Five-hundred-meter Aperture Spherical radio Telescope (FAST) is a Chinese mega-science project to build the largest single dish radio telescope in the world. Its innovative engineering concept and design pave a new road to realize a huge single dish in the most effective way. FAST also represents Chinese contribution in the international efforts to build the square kilometer array (SKA). Being the most sensitive single dish radio telescope, FAST will enable astronomers to jump-start many science goals, such as surveying the neutral hydrogen in the Milky Way and other galaxies, detecting faint pulsars, looking for the first shining stars, hearing the possible signals from other civilizations, etc. The idea of sitting a large spherical dish in a karst depression is rooted in Arecibo telescope. FAST is an Arecibo-type antenna with three outstanding aspects: the karst depression used as the site, which is large to host the 500-meter telescope and deep to allow a zenith angle of 40 degrees; the active main reflector correcting for spherical aberration on the ground to achieve a full polarization and a wide band without involving complex feed systems; and the light-weight feed cabin driven by cables and servomechanism plus a parallel robot as a secondary adjustable system to move with high precision. The feasibility studies for FAST have been carried out for 14 years, supported by Chinese and world astronomical communities. Funding for FAST has been approved by the National Development and Reform Commission in July of 2007 with a capital budget ~ 700 million RMB. The project time is 5.5 years from the commencement of work in March of 2011 and the first light is expected to be in 2016. This review intends to introduce the project of FAST with emphasis on the recent progress since 2006. In this paper, the subsystems of FAST are described in modest details followed by discussions of the fundamental science goals and examples of early science projects.

  15. Achieving BLISS: Challenges for Building Fast, Ultra-Sensitive Transition-Edge Sensors

    NASA Technical Reports Server (NTRS)

    Beyer, Andrew D.; Runyan, M. C.; Kenyon, M.; Echternach, P. M .; Chui, T.; Bumble, B.; Bradford, C. M.; Holmes, W. A.; Bock, J. J.

    2012-01-01

    Topics: 1.Motivation and Intro to TESs. 2. BLISS Specifications-tolerance to dark power. 3.Measuring stray (dark) power-Tc (alpha) and G measurements. a) Overview two methods: JTD vs. TES. b) TES arrays: measurement and complications for Pd, Tc, and alpha. 4. Results: Pd compare, NEP, tau, 1/f issues. LIRGs and ULIRGs: Excellent example of distinct optical/UV and IR luminosity. Interaction long known, but huge luminosity is not predicted based on optical studies. (greater than 90% of the energy is emitted at in the far-IR). Large luminosity has both starburst and accretion components.

  16. Driven by Mutations: The Predictive Value of Mutation Subtype in EGFR-Mutated Non-Small Cell Lung Cancer.

    PubMed

    Castellanos, Emily; Feld, Emily; Horn, Leora

    2016-12-23

    EGFR-mutated NSCLC is a genetically heterogeneous disease that includes more than 200 distinct mutations. The implications of mutational subtype for both prognostic and predictive value are being increasingly understood. Although the most common EGFR mutations-exon 19 deletions or L858R mutations-predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), it is now being recognized that outcomes may be improved in patients with exon 19 deletions. Additionally, 10% of patients will have an uncommon EGFR mutation, and response to EGFR TKI therapy is highly variable depending on the mutation. Given the growing recognition of the genetic and clinical variation seen in this disease, the development of comprehensive bioinformatics-driven tools to both analyze response in uncommon mutation subtypes and inform clinical decision making will be increasingly important. Clinical trials of novel EGFR TKIs should prospectively account for the presence of uncommon mutation subtypes in study design.

  17. Heterozygosity increases microsatellite mutation rate

    PubMed Central

    Amos, William

    2016-01-01

    Whole genome sequencing of families of Arabidopsis has recently lent strong support to the heterozygote instability (HI) hypothesis that heterozygosity locally increases mutation rate. However, there is an important theoretical difference between the impact on base substitutions, where mutation rate increases in regions surrounding a heterozygous site, and the impact of HI on sequences such as microsatellites, where mutations are likely to occur at the heterozygous site itself. At microsatellite loci, HI should create a positive feedback loop, with heterozygosity and mutation rate mutually increasing each other. Direct support for HI acting on microsatellites is limited and contradictory. I therefore analysed AC microsatellites in 1163 genome sequences from the 1000 genomes project. I used the presence of rare alleles, which are likely to be very recent in origin, as a surrogate measure of mutation rate. I show that rare alleles are more likely to occur at locus-population combinations with higher heterozygosity even when all populations carry exactly the same number of alleles. PMID:26740567

  18. The external domains of the HIV-1 envelope are a mutational cold spot

    PubMed Central

    Geller, Ron; Domingo-Calap, Pilar; Cuevas, José M.; Rossolillo, Paola; Negroni, Matteo; Sanjuán, Rafael

    2015-01-01

    In RNA viruses, mutations occur fast and have large fitness effects. While this affords remarkable adaptability, it can also endanger viral survival due to the accumulation of deleterious mutations. How RNA viruses reconcile these two opposed facets of mutation is still unknown. Here we show that, in human immunodeficiency virus (HIV-1), spontaneous mutations are not randomly located along the viral genome. We find that the viral mutation rate experiences a threefold reduction in the region encoding the most external domains of the viral envelope, which are strongly targeted by neutralizing antibodies. This contrasts with the hypermutation mechanisms deployed by other, more slowly mutating pathogens such as DNA viruses and bacteria, in response to immune pressure. We show that downregulation of the mutation rate in HIV-1 is exerted by the template RNA through changes in sequence context and secondary structure, which control the activity of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (A3)-mediated cytidine deamination and the fidelity of the viral reverse transcriptase. PMID:26450412

  19. The external domains of the HIV-1 envelope are a mutational cold spot.

    PubMed

    Geller, Ron; Domingo-Calap, Pilar; Cuevas, José M; Rossolillo, Paola; Negroni, Matteo; Sanjuán, Rafael

    2015-10-09

    In RNA viruses, mutations occur fast and have large fitness effects. While this affords remarkable adaptability, it can also endanger viral survival due to the accumulation of deleterious mutations. How RNA viruses reconcile these two opposed facets of mutation is still unknown. Here we show that, in human immunodeficiency virus (HIV-1), spontaneous mutations are not randomly located along the viral genome. We find that the viral mutation rate experiences a threefold reduction in the region encoding the most external domains of the viral envelope, which are strongly targeted by neutralizing antibodies. This contrasts with the hypermutation mechanisms deployed by other, more slowly mutating pathogens such as DNA viruses and bacteria, in response to immune pressure. We show that downregulation of the mutation rate in HIV-1 is exerted by the template RNA through changes in sequence context and secondary structure, which control the activity of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (A3)-mediated cytidine deamination and the fidelity of the viral reverse transcriptase.

  20. Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

    SciTech Connect

    Kukat, Alexandra; Edgar, Daniel; Bratic, Ivana; Maiti, Priyanka; Trifunovic, Aleksandra

    2011-06-10

    Highlights: {yields} Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. {yields} This process is independent of endogenous ROS production. {yields} Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O{sub 2}) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

  1. MODY 2: mutation identification and molecular ancestry in a Brazilian family.

    PubMed

    Mota, Adolfo J; Brüggemann, Simone; Costa, Fabrício F

    2013-01-10

    Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2-5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil.

  2. Accelerating Mutational Load Is Not Due to Synergistic Epistasis or Mutator Alleles in Mutation Accumulation Lines of Yeast.

    PubMed

    Jasmin, Jean-Nicolas; Lenormand, Thomas

    2016-02-01

    Much of our knowledge about the fitness effects of new mutations has been gained from mutation accumulation (MA) experiments. Yet the fitness effect of single mutations is rarely measured in MA experiments. This raises several issues, notably for inferring epistasis for fitness. The acceleration of fitness decline in MA lines has been taken as evidence for synergistic epistasis, but establishing the role of epistasis requires measuring the fitness of genotypes carrying known numbers of mutations. Otherwise, accelerating fitness loss could be explained by increased genetic mutation rates. Here we segregated mutations accumulated over 4800 generations in haploid and diploid MA lines of the yeast Saccharomyces cerevisiae. We found no correspondence between an accelerated fitness decline and synergistic epistasis among deleterious mutations in haploid lines. Pairs of mutations showed no overall epistasis. Furthermore, several lines of evidence indicate that genetic mutation rates did not increase in the MA lines. Crucially, segregant fitness analyses revealed that MA accelerated in both haploid and diploid lines, even though the fitness of diploid lines was nearly constant during the MA experiment. This suggests that the accelerated fitness decline in haploids was caused by cryptic environmental factors that increased mutation rates in all lines during the last third of the lines' transfers. In addition, we provide new estimates of deleterious mutation rates, including lethal mutations, and highlight that nearly all the mutational load we observed was due to one or two mutations having a large effect on fitness.

  3. Childhood vaccination: achievements and challenges.

    PubMed

    Ndumbe, P

    1996-09-01

    As the goal of eradicating smallpox was being met, the World Health Organization created its Expanded Programme on Immunisation (EPI) in 1974 and reached its initial goal of achieving full vaccination of 80% of the world's children by 1990. This effort was aided by the creation of "cold chain" delivery systems and resulted in the annual saving of 3.5 million children in less-developed countries. Current EPI vaccination goals include 1) eradication of poliomyelitis by the year 2000, 2) elimination of neonatal tetanus by the year 1995, 3) control of measles and hepatitis B, and 4) immunization of 90% of the world's children 1 year or younger by the year 2000. Goals of the Children's Vaccine Initiative (formed in 1991) include 1) provision of an adequate supply of affordable, safe, and effective vaccines; 2) production of improved and new vaccines; and 3) simplification of the logistics of vaccine delivery. Future challenges are to sustain high vaccination coverage, reach the unreached, achieve proper storage of vaccines and reduce waste, integrate new vaccines into national programs, and achieve vaccine self-sufficiency. The fact that these challenges will be difficult to achieve is illustrated by the situation in Africa where the high immunization levels achieved in 1990 have dropped dramatically. Those who must act to implement immunization programs are health personnel, families, governments, and development partners. In order to achieve equity in health, every child must be reached, governments must be made accountable for programs, health workers must convince families of the importance of vaccination, delivery systems must be in place to take advantage of the new vaccines being delivered, and a multisectoral approach must be taken to assure sustainability.

  4. Fast evaluation of surface sensitivity on ghost

    NASA Astrophysics Data System (ADS)

    Boehme, Beate

    2015-09-01

    Real optical systems are often suffering from false light caused by ghosts. In particular single reflections are critical in applications like reflected light illumination microscopy or confocal systems. The degradations of performance can be bright spots in the image or contrast, signal to noise or dynamic range reduction. Thus in these systems the suppression of first order reflections is important. State of the art optical design software supports ray trace based ghost image analysis. The automatic generation of reflex light paths is provided, but for systems with a large number of surfaces the analysis of all ghost light paths is time-consuming. Conventional Monte Carlo based non sequential ray trace sums up the reflections of all surfaces simultaneously. To achieve high accuracy a huge number of rays is necessary, what results in long computational time, especially if the distinction of surface influences needs multiple calculations. In this paper a fast method is proposed for the ranking of ghosts. It was developed for single reflections in centered optical systems. For each surface the ghost light path is calculated with paraxial and real ray trace. The ghost diameter and the corresponding illumination NA are calculated. Usually the distance of the reflex focus to the image is used as criterion to access the importance of a ghost. Here we use the power of the ghost ray bundle. It is compared with the signal strength and listed for all surfaces generating a ghost. So in one step a surface contribution of reflex powers as well as an estimation of total flux of reflected light is obtained. Due to the fact, that only a few rays have to be calculated, the method is rather fast. The accuracy can be estimated by comparison of paraxial and marginal ray trace. In the proposed method, some assumptions and approximations are made. They are assessed in respect to some practical examples, and by comparison with full brute force non-sequential ray trace. The usefulness of

  5. Fast molecular shocks. II - Emission from fast dissociative shocks

    NASA Technical Reports Server (NTRS)

    Neufeld, David A.; Dalgarno, A.

    1989-01-01

    The line radiations emitted in the cooling gas behind a fast dissociative shock are studied. The intensities emitted in high rotational transitions of the neutral molecules CO, SiO, HCN, CN, NO, and SO are estimated, as well as in rovibrational transitions of the molecular ions HeH(+) and OH(+) in radio recombination lines of atomic hydrogen and in fine-structure transitions of C, C(+), O, and Si(+). The predictions are compared with the observed intensities of line emission from the Orion-KL region. For Orion-KL the observations do not exclude, but probably do not require, the presence of a fast dissociative shock. Emission from SiO in high-J rotational states and from vibrationally excited OH(+), HeH(+), HeH(+), and SO(+) may be detectable from dissociative shocks under suitable conditions of preshock density and shock velocity; such emission may prove to be a useful diagnostic probe of fast shock activity.

  6. [Diabetic patients in the Yom Kippur fast--who can fast and how to treat the fasting patients].

    PubMed

    Katz, Yisrael; Zangen, David; Leibowitz, Gil; Szalalt, Auryan

    2009-09-01

    Jews all over the world fast on Yom Kippur, a fast lasting 25 hours. For diabetic patients and their physicians the fast is a significant challenge. The Jewish law exempts patients from fasting if the fast endangers the patient's health. In order to know if they can fast safely, many diabetic patients consult their physicians. In this review, the authors summarize the potential risk for fasting in diabetic patients and propose treatment protocols for patients who intend to fast. The principle recommendations are based on data related to fasting diabetic patients during the Ramadan fast, which is shorter than Yom Kippur. Furthermore, practical suggestions are based on a recent Israeli study on type 1 diabetic patients fasting for 25 hours, taking into account the Jewish law. Every diabetic patient who intends to fast should consult his physician for assurance that fasting is safe. The physician should pay special attention to patients on intensive insulin treatment or on sulfonylureas. Some, but not all these patients, should avoid fasting. In case these patients decide to fast, intensive monitoring of blood glucose is required during the fast to prevent severe hypoglycemia.

  7. Gene mutations in Cushing's disease

    PubMed Central

    Xiong, Qi; Ge, Wei

    2016-01-01

    Cushing's disease (CD) is a severe (and potentially fatal) disease caused by adrenocorticotropic hormone (ACTH)-secreting adenomas of the pituitary gland (often termed pituitary adenomas). The majority of ACTH-secreting corticotroph tumors are sporadic and CD rarely appears as a familial disorder, thus, the genetic mechanisms underlying CD are poorly understood. Studies have reported that various mutated genes are associated with CD, such as those in menin 1, aryl hydrocarbon receptor-interacting protein and the nuclear receptor subfamily 3 group C member 1. Recently it was identified that ubiquitin-specific protease 8 mutations contribute to CD, which was significant towards elucidating the genetic mechanisms of CD. The present study reviews the associated gene mutations in CD patients. PMID:27588171

  8. Rapid generation of hypomorphic mutations

    PubMed Central

    Arthur, Laura L.; Chung, Joyce J.; Jankirama, Preetam; Keefer, Kathryn M.; Kolotilin, Igor; Pavlovic-Djuranovic, Slavica; Chalker, Douglas L.; Grbic, Vojislava; Green, Rachel; Menassa, Rima; True, Heather L.; Skeath, James B.; Djuranovic, Sergej

    2017-01-01

    Hypomorphic mutations are a valuable tool for both genetic analysis of gene function and for synthetic biology applications. However, current methods to generate hypomorphic mutations are limited to a specific organism, change gene expression unpredictably, or depend on changes in spatial-temporal expression of the targeted gene. Here we present a simple and predictable method to generate hypomorphic mutations in model organisms by targeting translation elongation. Adding consecutive adenosine nucleotides, so-called polyA tracks, to the gene coding sequence of interest will decrease translation elongation efficiency, and in all tested cell cultures and model organisms, this decreases mRNA stability and protein expression. We show that protein expression is adjustable independent of promoter strength and can be further modulated by changing sequence features of the polyA tracks. These characteristics make this method highly predictable and tractable for generation of programmable allelic series with a range of expression levels. PMID:28106166

  9. Flexible Conversion Ratio Fast Reactor Systems Evaluation

    SciTech Connect

    Neil Todreas; Pavel Hejzlar

    2008-06-30

    Conceptual designs of lead-cooled and liquid salt-cooled fast flexible conversion ratio reactors were developed. Both concepts have cores reated at 2400 MWt placed in a large-pool-type vessel with dual-free level, which also contains four intermediate heat exchanges coupling a primary coolant to a compact and efficient supercritical CO2 Brayton cycle power conversion system. Decay heat is removed passively using an enhanced Reactor Vessel Auxiliary Cooling System and a Passive Secondary Auxiliary Cooling System. The most important findings were that (1) it is feasible to design the lead-cooled and salt-cooled reactor with the flexible conversion ratio (CR) in the range of CR=0 and CR=1 n a manner that achieves inherent reactor shutdown in unprotected accidents, (2) the salt-cooled reactor requires Lithium thermal Expansion Modules to overcme the inherent salt coolant's large positive coolant temperature reactivity coefficient, (3) the preferable salt for fast spectrum high power density cores is NaCl-Kcl-MgCl2 as opposed to fluoride salts due to its better themal-hydraulic and neutronic characteristics, and (4) both reactor, but attain power density 3 times smaller than that of the sodium-cooled reactor.

  10. Fast Image Reconstruction with L2-Regularization

    PubMed Central

    Bilgic, Berkin; Chatnuntawech, Itthi; Fan, Audrey P.; Setsompop, Kawin; Cauley, Stephen F.; Wald, Lawrence L.; Adalsteinsson, Elfar

    2014-01-01

    Purpose We introduce L2-regularized reconstruction algorithms with closed-form solutions that achieve dramatic computational speed-up relative to state of the art L1- and L2-based iterative algorithms while maintaining similar image quality for various applications in MRI reconstruction. Materials and Methods We compare fast L2-based methods to state of the art algorithms employing iterative L1- and L2-regularization in numerical phantom and in vivo data in three applications; 1) Fast Quantitative Susceptibility Mapping (QSD), 2) Lipid artifact suppression in Magnetic Resonance Spectroscopic Imaging (MRSI), and 3) Diffusion Spectrum Imaging (DSI). In all cases, proposed L2-based methods are compared with the state of the art algorithms, and two to three orders of magnitude speed up is demonstrated with similar reconstruction quality. Results The closed-form solution developed for regularized QSM allows processing of a 3D volume under 5 seconds, the proposed lipid suppression algorithm takes under 1 second to reconstruct single-slice MRSI data, while the PCA based DSI algorithm estimates diffusion propagators from undersampled q-space for a single slice under 30 seconds, all running in Matlab using a standard workstation. Conclusion For the applications considered herein, closed-form L2-regularization can be a faster alternative to its iterative counterpart or L1-based iterative algorithms, without compromising image quality. PMID:24395184

  11. Fast analysis of radionuclide decay chain migration

    NASA Astrophysics Data System (ADS)

    Chen, J. S.; Liang, C. P.; Liu, C. W.; Li, L.

    2014-12-01

    A novel tool for rapidly predicting the long-term plume behavior of an arbitrary length radionuclide decay chain is presented in this study. This fast tool is achieved based on generalized analytical solutions in compact format derived for a set of two-dimensional advection-dispersion equations coupled with sequential first-order decay reactions in groundwater system. The performance of the developed tool is evaluated by a numerical model using a Laplace transform finite difference scheme. The results of performance evaluation indicate that the developed model is robust and accurate. The developed model is then used to fast understand the transport behavior of a four-member radionuclide decay chain. Results show that the plume extents and concentration levels of any target radionuclide are very sensitive to longitudinal, transverse dispersion, decay rate constant and retardation factor. The developed model are useful tools for rapidly assessing the ecological and environmental impact of the accidental radionuclide releases such as the Fukushima nuclear disaster where multiple radionuclides leaked through the reactor, subsequently contaminating the local groundwater and ocean seawater in the vicinity of the nuclear plant.

  12. Impacts of the Callipyge Mutation on Ovine Plasma Metabolites and Muscle Fibre Type

    PubMed Central

    Li, Juan; Greenwood, Paul L.; Cockett, Noelle E.; Hadfield, Tracy S.; Vuocolo, Tony; Byrne, Keren; White, Jason D.; Tellam, Ross L.; Schirra, Horst Joachim

    2014-01-01

    The ovine Callipyge mutation causes postnatal muscle hypertrophy localized to the pelvic limbs and torso, as well as body leanness. The mechanism underpinning enhanced muscle mass is unclear, as is the systemic impact of the mutation. Using muscle fibre typing immunohistochemistry, we confirmed muscle specific effects and demonstrated that affected muscles had greater prevalence and hypertrophy of type 2X fast twitch glycolytic fibres and decreased representation of types 1, 2C, 2A and/or 2AX fibres. To investigate potential systemic effects of the mutation, proton NMR spectra of plasma taken from lambs at 8 and 12 weeks of age were measured. Multivariate statistical analysis of plasma metabolite profiles demonstrated effects of development and genotype but not gender. Plasma from Callipyge lambs at 12 weeks of age, but not 8 weeks, was characterized by a metabolic profile consistent with contributions from the affected hypertrophic fast twitch glycolytic muscle fibres. Microarray analysis of the perirenal adipose tissue depot did not reveal a transcriptional effect of the mutation in this tissue. We conclude that there is an indirect systemic effect of the Callipyge mutation in skeletal muscle in the form of changes of blood metabolites, which may contribute to secondary phenotypes such as body leanness. PMID:24937646

  13. ``Fast Track'' nuclear thermal propulsion concept

    NASA Astrophysics Data System (ADS)

    Johnson, Richard A.; Zweig, Herbert R.; Cooper, Martin H.; Wett, Jack

    1993-01-01

    The objective of the Space Exploration Initiative (``America at the Threshold...,'' 1991) is the exploration of Mars by man in the second decade of the 21st century. The NASA ``Fast Track'' approach (NASA-LeRC Presentation, 1992) could accelerate the manned exploration of Mars to 2007. NERVA-derived nuclear propulsion represents a viable near-term technology approach to accomplish the accelerated schedule. Key milestones in the progression to the manned Mars mission are (1) demonstration of TRL-6 for the man-rateable system by 1999, (2) a robotic lunar mission by 2000, (3) the first cargo mission to Mars by 2005, and (4) the piloted Mars mission in 2007. The Rocketdyne-Westinghouse concept for nuclear thermal propulsion to achieve these milestones combines the nuclear reactor technology of the Rover/NERVA programs and the state-of-the-art hardware designs from hydrogen-fueled rocket engine successes like the Space Shuttle Main Engine (SSME).

  14. FOGSAA: Fast Optimal Global Sequence Alignment Algorithm

    NASA Astrophysics Data System (ADS)

    Chakraborty, Angana; Bandyopadhyay, Sanghamitra

    2013-04-01

    In this article we propose a Fast Optimal Global Sequence Alignment Algorithm, FOGSAA, which aligns a pair of nucleotide/protein sequences faster than any optimal global alignment method including the widely used Needleman-Wunsch (NW) algorithm. FOGSAA is applicable for all types of sequences, with any scoring scheme, and with or without affine gap penalty. Compared to NW, FOGSAA achieves a time gain of (70-90)% for highly similar nucleotide sequences (> 80% similarity), and (54-70)% for sequences having (30-80)% similarity. For other sequences, it terminates with an approximate score. For protein sequences, the average time gain is between (25-40)%. Compared to three heuristic global alignment methods, the quality of alignment is improved by about 23%-53%. FOGSAA is, in general, suitable for aligning any two sequences defined over a finite alphabet set, where the quality of the global alignment is of supreme importance.

  15. Fast ensemble representations for abstract visual impressions

    PubMed Central

    Leib, Allison Yamanashi; Kosovicheva, Anna; Whitney, David

    2016-01-01

    Much of the richness of perception is conveyed by implicit, rather than image or feature-level, information. The perception of animacy or lifelikeness of objects, for example, cannot be predicted from image level properties alone. Instead, perceiving lifelikeness seems to be an inferential process and one might expect it to be cognitively demanding and serial rather than fast and automatic. If perceptual mechanisms exist to represent lifelikeness, then observers should be able to perceive this information quickly and reliably, and should be able to perceive the lifelikeness of crowds of objects. Here, we report that observers are highly sensitive to the lifelikeness of random objects and even groups of objects. Observers' percepts of crowd lifelikeness are well predicted by independent observers' lifelikeness judgements of the individual objects comprising that crowd. We demonstrate that visual impressions of abstract dimensions can be achieved with summary statistical representations, which underlie our rich perceptual experience. PMID:27848949

  16. Leader selection for fast consensus in networks

    NASA Astrophysics Data System (ADS)

    Wang, Ying; Yang, Wen; Wang, Lin; Wang, Xiaofan

    2015-12-01

    This paper considers a leader-follower system with the aim to select an optimal leader so as to drive the remaining nodes to reach the desired consensus with the fastest convergence speed. An index called consensus centrality (CC) is proposed to quantify how fast a leader could guide the network to achieve the desired consensus. The experiment results explored the big similarities between the distributions of CC and degree in the network, which suggest that the suboptimal leader selected by the maximum degree can approximately approach the optimal leader in heterogeneous networks. Combining the degree-based k-shell decomposition with consensus centrality, a leader selection algorithm is proposed to reduce the computational complexity in large-scale networks. Finally, the convergence time of an equivalent discrete-time model is given to illustrate the properties of the suboptimal solutions.

  17. Synchrotron masers and fast radio bursts

    NASA Astrophysics Data System (ADS)

    Ghisellini, G.

    2017-02-01

    Fast radio bursts, with a typical duration of 1 ms and 1 Jy flux density at gigahertz frequencies, have brightness temperatures exceeding 1033 K, requiring a coherent emission process. This can be achieved by bunching particles in volumes smaller than the typical wavelength, but this may be challenging. Maser emission is a possibility. Under certain conditions, the synchrotron-stimulated emission process can be more important than true absorption, and a synchrotron maser can be created. This occurs when the emitting electrons have a very narrow distribution of pitch angles and energies. This process overcomes the difficulties of having extremely dense bunches of particles and relaxes the light-crossing time limits, since there is no simple relation between the actual size of the source and the observed variability time-scale.

  18. Fast Photochromic Molecules toward Realization of Photosynergetic Effects.

    PubMed

    Kobayashi, Yoichi; Mutoh, Katsuya; Abe, Jiro

    2016-09-15

    There has been a growing interest toward the development of advanced photofunctional materials whose photoresponses involve multiple photons and molecules because these materials show the photoresponses which cannot be achieved by a one-photon reaction of a single chromophore. These cooperative interactions of multiple photons and molecules are recently termed as the "photosynergetic" effects, and the understanding and utilization of these effects are becoming important research topics. In this Perspective, we overview the recent progress of the fast T-type photochromic molecules involving the stepwise two-photon absorption processes. Although high power pulse lasers were necessary to induce conventional simultaneous and stepwise two-photon absorption processes, the stepwise two-photon absorption process with the fast photochromic compound can be initiated by extremely weak continuous wave (CW) LEDs. The basic concept and future outlook of the fast photochromism involving the stepwise two-photon absorption process will be discussed.

  19. Washington State's Student Achievement Initiative

    ERIC Educational Resources Information Center

    Pettitt, Maureen; Prince, David

    2010-01-01

    This article describes Washington State's Student Achievement Initiative, an accountability system implemented in 2005-06 that measures students' gains in college readiness, college credits earned, and degree or certificate completion. The goal of the initiative is to increase educational attainment by focusing on the critical momentum points…

  20. Meeting a Math Achievement Crisis

    ERIC Educational Resources Information Center

    Jennings, Lenora; Likis, Lori

    2005-01-01

    An urban community spotlighted declining mathematics achievement and took some measures, in which the students' performance increased substantially. The Benjamin Banneker Charter Public School in Cambridge, Massachusetts, engaged the entire community and launched the campaign called "Math Everywhere", which changed Benjamin Banneker's…

  1. Socioeconomic Determinants of Academic Achievement

    ERIC Educational Resources Information Center

    Tomul, Ekber; Savasci, Havva Sebile

    2012-01-01

    This study aims to investigate the relationship between academic achievement and the socioeconomic characteristics of elementary school 7th grade students in Burdur. The population of the study are 7th grade students who had education at elementary schools in Burdur in the 2007-2008 academic year. Two staged sampling was chosen as suitable for the…

  2. Goal Setting to Achieve Results

    ERIC Educational Resources Information Center

    Newman, Rich

    2012-01-01

    Both districts and individual schools have a very clear set of goals and skills for their students to achieve and master. In fact, except in rare cases, districts and schools develop very detailed goals they wish to pursue. In most cases, unfortunately, only the teachers and staff at a particular school or district-level office are aware of the…

  3. School Districts and Student Achievement

    ERIC Educational Resources Information Center

    Chingos, Matthew M.; Whitehurst, Grover J.; Gallaher, Michael R.

    2015-01-01

    School districts are a focus of education reform efforts in the United States, but there is very little existing research about how important they are to student achievement. We fill this gap in the literature using 10 years of student-level, statewide data on fourth- and fifth-grade students in Florida and North Carolina. A variance decomposition…

  4. Student Achievement, 1986-87.

    ERIC Educational Resources Information Center

    Mangino, Evangelina

    This report summarizes results of student achievement in the Austin (Texas) Independent School District (AISD) on the Texas Educational Assessment of Minimum Skills (TEAMS) tests in 1986-87. Major findings indicate the following: (1) 99.4% of AISD seniors to graduate in May 1987 passed the Exit-Level TEAMS tests, with only 17 denied diplomas in…

  5. Sociocultural Variation in Literacy Achievement

    ERIC Educational Resources Information Center

    Verhoeven, Ludo

    2006-01-01

    The purpose of this study was to describe the variations in literacy achievement among native and non-native upper primary school children (grades three to six) in the Netherlands. Various measures of word decoding, reading literacy and writing skill were collected from 1091 native Dutch children, 753 children with a former Dutch colonial…

  6. Game Addiction and Academic Achievement

    ERIC Educational Resources Information Center

    Sahin, Mehmet; Gumus, Yusuf Yasin; Dincel, Sezen

    2016-01-01

    The primary aim of this study was to investigate the correlation between game addiction and academic achievement. The secondary aim was to adapt a self-report instrument to measure game addiction. Three hundred and seventy high school students participated in this study. Data were collected via an online questionnaire that included a brief…

  7. The Widening Income Achievement Gap

    ERIC Educational Resources Information Center

    Reardon, Sean F.

    2013-01-01

    Has the academic achievement gap between high-income and low-income students changed over the last few decades? If so, why? And what can schools do about it? Researcher Sean F. Reardon conducted a comprehensive analysis of research to answer these questions and came up with some striking findings. In this article, he shows that income-related…

  8. Attribution Theory in Science Achievement

    ERIC Educational Resources Information Center

    Craig, Martin

    2013-01-01

    Recent research reveals consistent lags in American students' science achievement scores. Not only are the scores lower in the United States compared to other developed nations, but even within the United States, too many students are well below science proficiency scores for their grade levels. The current research addresses this problem by…

  9. Grouping Students for Increased Achievements.

    ERIC Educational Resources Information Center

    Holloway, John H.

    2001-01-01

    Reviews results of four recent studies exploring the effects of various student-grouping schemes on academic achievement. Grouping plans included multiage classrooms, full-time ability grouping, and within-classroom grouping. Two studies investigated administrator attitudes toward student grouping. Several studies found that grouping plans…

  10. Achievement, Hedonism and the Teacher.

    ERIC Educational Resources Information Center

    Ryan, Kevin

    1991-01-01

    The problem of poor school achievement is in part because students lack work and discipline values. The article suggests moral and ethical teachings inspire students to be better scholars and people; and teacher education must prepare teachers to be moral educators by reintroducing moral education into the curriculum. (SM)

  11. School Desegregation and Black Achievement.

    ERIC Educational Resources Information Center

    Cook, Thomas; And Others

    Seven papers commissioned by the National Institute of Education in order to clarify the state of recent knowledge about the effects of school desegregation on the academic achievement of black students are contained in this report. The papers, which analyze 19 "core" empirical studies on this topic, include: (1) "What Have Black Children Gained…

  12. Institutional Climate and Minority Achievement.

    ERIC Educational Resources Information Center

    Richardson, Richard C.

    This paper discusses ways that institutions can change the higher education system and environment to accommodate more minority students. The first section, "Institutional Climate and Minority Achievement," presents an overview of the problems facing colleges and universities with respect to recruiting and retaining minority students. In the…

  13. Faculty Development: Assessing Learner Achievement.

    ERIC Educational Resources Information Center

    Frey, Barbara A.; Overfield, Karen

    This study addressed the challenges of developing a faculty professional development workshop on assessment, measurement, and evaluation of achievement in adult learners. The setting for the workshop was a system of postsecondary career colleges throughout the United States. The curriculum development model of D. Kirkpatrick (1994) was used as a…

  14. Can Judges Improve Academic Achievement?

    ERIC Educational Resources Information Center

    Greene, Jay P.; Trivitt, Julie R.

    2008-01-01

    Over the last 3 decades student achievement has remained essentially unchanged in the United States, but not for a lack of spending. Over the same period a myriad of education reforms have been suggested and per-pupil spending has more than doubled. Since the 1990s the education reform attempts have frequently included judicial decisions to revise…

  15. Achieving a sustainable service advantage.

    PubMed

    Coyne, K P

    1993-01-01

    Many managers believe that superior service should play little or no role in competitive strategy; they maintain that service innovations are inherently copiable. However, the author states that this view is too narrow. For a company to achieve a lasting service advantage, it must base a new service on a capability gap that competitors cannot or will not copy.

  16. Teacher Dispositions and Student Achievement

    ERIC Educational Resources Information Center

    Vaughn, Kathleen Adams

    2012-01-01

    In an effort to close the achievement gap between students of minority and majority populations and between students in higher and lower economic circumstances, the National Council for the Accreditation of Teacher Education (NCATE) added instruction and evaluation of teacher dispositions to its requirements for credentialing prospective teachers.…

  17. Epistemological Beliefs and Academic Achievement

    ERIC Educational Resources Information Center

    Arslantas, Halis Adnan

    2016-01-01

    This study aimed to identify the relationship between teacher candidates' epistemological beliefs and academic achievement. The participants of the study were 353 teacher candidates studying their fourth year at the Education Faculty. The Epistemological Belief Scale was used which adapted to Turkish through reliability and validity work by…

  18. Fast wave current drive: Experimental status and reactor prospects

    SciTech Connect

    Ehst, D.A.

    1988-03-01

    The fast wave is one of the two possible wave polarizations which propagate according to the basic theory of cold plasmas. It is distinguished from the other (slow wave) branch by having an electric field vector which is mainly orthogonal to the confining magnetic field of the plasma. The plasma and fast wave qualitatively assume different behavior depending on the frequency range of the launched wave. The high frequency fast wave (HFFW), with a frequency (..omega..2..pi.. )approximately) GHz) much higher than the ion cyclotron frequency (..cap omega../sub i/), suffers electron Landau damping and drives current by supplying parallel momentum to superthermal electrons in a fashion similar to lower hybrid (slow wave) current drive. In the simple theory the HFFW should be superior to the slow wave and can propagate to very high density and temperature without impediment. Experiments, however, have not conclusively shown that HFFW current drive can be achieved at densities above the slow wave current drive limit, possibly due to conversion of the launched fast waves into slow waves by density fluctuations. Alternatively, the low frequency fast wave (LFFW), with frequencies ()approxreverse arrowlt) 100 MHz) only a few times the ion cyclotron frequency, is damped by electron Landau damping and, in a hot plasma ()approxreverse arrowgt) 10 keV), by electron transit time magnetic pumping; current drive is achieved by pushing superthermal electrons, and efficiency is prediocted to be slightly better than for lower hybrid current drive. Most significantly, the slow wave does not propagate in high density plasma when ..omega.. )approximately) ..cap omega../sub i/, so parasitic coupling to the slow wave can be avoided, and no density and temperture limitations are foreseen. Experiments with fast wve current drive invariably find current drive efficiency as good as obtained in lower hybrid experiments at comparable, low temperatures. 45 refs., 4 figs., 1 tab

  19. Fast Responding Voltage Regulator and Dynamic VAR Compensator

    SciTech Connect

    Divan, Deepak; Moghe, Rohit; Tholomier, Damien

    2014-12-31

    The objectives of this project were to develop a dynamic VAR compensator (DVC) for voltage regulation through VAR support to demonstrate the ability to achieve greater levels of voltage control on electricity distribution networks, and faster response compared to existing grid technology. The goal of the project was to develop a prototype Fast Dynamic VAR Compensator (Fast DVC) hardware device, and this was achieved. In addition to developing the dynamic VAR compensator device, Varentec in partnership with researchers at North Carolina State University (NCSU) successfully met the objectives to model the potential positive impact of such DVCs on representative power networks. This modeling activity validated the ability of distributed dynamic VAR compensators to provide fast voltage regulation and reactive power control required to respond to grid disturbances under high penetration of fluctuating and intermittent distributed energy resources (DERs) through extensive simulation studies. Specifically the following tasks were set to be accomplished: 1) Development of dynamic VAR compensator to support dynamic voltage variations on the grid through VAR control 2) Extensive testing of the DVC in the lab environment 3) Present the operational DVC device to the DOE at Varentec’s lab 4) Formulation of a detailed specification sheet, unit assembly document, test setup document, unit bring-up plan, and test plan 5) Extensive simulations of the DVC in a system with high PV penetration. Understanding the operation with many DVC on a single distribution system 6) Creation and submittal of quarterly and final reports conveying the design documents, unit performance data, modeling simulation charts and diagrams, and summary explanations of the satisfaction of program goals. This report details the various efforts that led to the development of the Fast DVC as well as the modeling & simulation results. The report begins with the introduction in Section II which outlines the

  20. The heat-transfer method: a versatile low-cost, label-free, fast, and user-friendly readout platform for biosensor applications.

    PubMed

    van Grinsven, Bart; Eersels, Kasper; Peeters, Marloes; Losada-Pérez, Patricia; Vandenryt, Thijs; Cleij, Thomas J; Wagner, Patrick

    2014-08-27

    In recent years, biosensors have become increasingly important in various scientific domains including medicine, biology, and pharmacology, resulting in an increased demand for fast and effective readout techniques. In this Spotlight on Applications, we report on the recently developed heat-transfer method (HTM) and illustrate the use of the technique by zooming in on four established bio(mimetic) sensor applications: (i) mutation analysis in DNA sequences, (ii) cancer cell identification through surface-imprinted polymers, (iii) detection of neurotransmitters with molecularly imprinted polymers, and (iv) phase-transition analysis in lipid vesicle layers. The methodology is based on changes in heat-transfer resistance at a functionalized solid-liquid interface. To this extent, the device applies a temperature gradient over this interface and monitors the temperature underneath and above the functionalized chip in time. The heat-transfer resistance can be obtained by dividing this temperature gradient by the power needed to achieve a programmed temperature. The low-cost, fast, label-free and user-friendly nature of the technology in combination with a high degree of specificity, selectivity, and sensitivity makes HTM a promising sensor technology.

  1. HI Intensity Mapping with FAST

    NASA Astrophysics Data System (ADS)

    Bigot-Sazy, M.-A.; Ma, Y.-Z.; Battye, R. A.; Browne, I. W. A.; Chen, T.; Dickinson, C.; Harper, S.; Maffei, B.; Olivari, L. C.; Wilkinsondagger, P. N.

    2016-02-01

    We discuss the detectability of large-scale HI intensity fluctuations using the FAST telescope. We present forecasts for the accuracy of measuring the Baryonic Acoustic Oscillations and constraining the properties of dark energy. The FAST 19-beam L-band receivers (1.05-1.45 GHz) can provide constraints on the matter power spectrum and dark energy equation of state parameters (w0,wa) that are comparable to the BINGO and CHIME experiments. For one year of integration time we find that the optimal survey area is 6000 deg2. However, observing with larger frequency coverage at higher redshift (0.95-1.35 GHz) improves the projected errorbars on the HI power spectrum by more than 2 σ confidence level. The combined constraints from FAST, CHIME, BINGO and Planck CMB observations can provide reliable, stringent constraints on the dark energy equation of state.

  2. Fast reactors and nuclear nonproliferation

    SciTech Connect

    Avrorin, E.N.; Rachkov, V.I.; Chebeskov, A.N.

    2013-07-01

    Problems are discussed with regard to nuclear fuel cycle resistance in fast reactors to nuclear proliferation risk due to the potential for use in military programs of the knowledge, technologies and materials gained from peaceful nuclear power applications. Advantages are addressed for fast reactors in the creation of a more reliable mode of nonproliferation in the closed nuclear fuel cycle in comparison with the existing fully open and partially closed fuel cycles of thermal reactors. Advantages and shortcomings are also discussed from the point of view of nonproliferation from the start with fast reactors using plutonium of thermal reactor spent fuel and enriched uranium fuel to the gradual transition using their own plutonium as fuel. (authors)

  3. Fast Setting Cement - Literature Survey

    DTIC Science & Technology

    1973-01-01

    materials does produce early set times and high strengths . It is re- ported, also, that the addition of 1.5 percent Ca"l 2 to clinkers contain- Ing more than...produce high strength concrete. They include addition of iron asggregate, physical treatment of clinker , ’ addition of highly reactive SiO2 or Ca0, and...Fast-Fix. The Western Co. has developed materials designated as Fast-Fix with rapid setting and high strength properties. Published data show i .1

  4. [Preoperative fasting guidelines: an update].

    PubMed

    López Muñoz, A C; Busto Aguirreurreta, N; Tomás Braulio, J

    2015-03-01

    Anesthesiology societies have issued various guidelines on preoperative fasting since 1990, not only to decrease the incidence of lung aspiration and anesthetic morbidity, but also to increase patient comfort prior to anesthesia. Some of these societies have been updating their guidelines, as such that, since 2010, we now have 2 evidence-based preoperative fasting guidelines available. In this article, an attempt is made to review these updated guidelines, as well as the current instructions for more controversial patients such as infants, the obese, and a particular type of ophthalmic surgery.

  5. Mutational Effects on the Folding Dynamics of a Minimized Hairpin‡

    PubMed Central

    Scian, Michele; Shu, Irene; Olsen, Katherine A.; Hassam, Khalil; Andersen, Niels H.

    2013-01-01

    The fold stabilities and folding dynamics of a series of mutants of a model hairpin, KTW-NPATGK-WTE (HP7), are reported. The parent system and the corresponding DPATGK loop species display sub-μs folding time constants. The mutational studies revealed that ultrafast folding requires both some pre-structuring of the loop and a favorable interaction between the chain termini at the transition state. In the case of YY-DPETGT-WY, another sub-μs folding species [Davis, C. M.; Xiao, S.; Raleigh, D. P.; Dyer, R. B. (2012) J. Am. Chem. Soc. 134, 14476–14482], a hydrophobic cluster provides the latter. In the case of HP7, the Coulombic interaction between the terminal NH3+ and CO2− units provides this; a C-terminal Glu to amidated Ala mutation results in a 5-fold folding rate retardation. The effects of mutations within the reversing loop indicate the balance between loop flexibility (favoring fast conformational searching) and turn-formation in the unfolded state is a major factor in determining the folding dynamics. The –NAAAKX- loops examined display no detectable turn formation propensity in other hairpin constructs, but do result in stable analogs of HP7. Peptide KTW-NAAAKK-WTE displays the same fold stability as HP7 but both the folding and unfolding time constants are greater by a factor of 20. PMID:23521619

  6. Mutational analysis using oligonucleotide microarrays

    PubMed Central

    Hacia, J.; Collins, F.

    1999-01-01

    The development of inexpensive high throughput methods to identify individual DNA sequence differences is important to the future growth of medical genetics. This has become increasingly apparent as epidemiologists, pathologists, and clinical geneticists focus more attention on the molecular basis of complex multifactorial diseases. Such undertakings will rely upon genetic maps based upon newly discovered, common, single nucleotide polymorphisms. Furthermore, candidate gene approaches used in identifying disease associated genes necessitate screening large sequence blocks for changes tracking with the disease state. Even after such genes are isolated, large scale mutational analyses will often be needed for risk assessment studies to define the likely medical consequences of carrying a mutated gene.
This review concentrates on the use of oligonucleotide arrays for hybridisation based comparative sequence analysis. Technological advances within the past decade have made it possible to apply this technology to many different aspects of medical genetics. These applications range from the detection and scoring of single nucleotide polymorphisms to mutational analysis of large genes. Although we discuss published scientific reports, unpublished work from the private sector12 could also significantly affect the future of this technology.


Keywords: mutational analysis; oligonucleotide microarrays; DNA chips PMID:10528850

  7. Sporadic medulloblastomas contain PTCH mutations.

    PubMed

    Raffel, C; Jenkins, R B; Frederick, L; Hebrink, D; Alderete, B; Fults, D W; James, C D

    1997-03-01

    Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin's syndrome, is an autosomal dominant disorder that predisposes to developmental defects and various forms of cancer. PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome. Another NBCCS-associated cancer is medulloblastoma, a common central nervous system tumor in children. Most medulloblastomas, however, occur without indication of an inherited predisposition. We have examined 24 sporadic medulloblastomas for loss of heterozygosity (LOH) at loci flanking as well as within PTCH. In cases with LOH, single-strand conformational polymorphism and sequencing analysis were performed to determine the status of the remaining PTCH allele. Microsatellite analysis indicated LOH of PTCH in 5 of 24 tumors, and in three of these cases a mutation of the remaining allele was identified. Two of the mutations were duplication insertions, and the third consisted of a single base deletion. It is interesting that all three mutations occur in exon 17 of the PTCH gene. These data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas.

  8. New mutation to Huntington's disease.

    PubMed

    Wolff, G; Deuschl, G; Wienker, T F; Hummel, K; Bender, K; Lücking, C H; Schumacher, M; Hammer, J; Oepen, G

    1989-01-01

    We report a large family with an isolated case of Huntington's disease (HD), which is probably the result of a new mutation. The patient developed clinical signs typical of HD at the age of 36. The clinical course of the patient's disease is documented by several clinical admissions over a period of 14 years at present. The family history is strikingly negative with the parents having been clearly unaffected into their 80s and with 13 older and two younger, living, healthy sibs. Extensive testing of polymorphic markers (blood groups, red cell and serum proteins, HLA antigens) showed no indication of non-paternity, but rather gave strong support to the hypothesis that the proband is a full sib. In addition, DNA typing for several RFLPs known to be closely linked to the HD gene locus indicated that several clearly unaffected sibs share one or the other or both of the patient's haplotypes. This is further evidence in favour of the hypothesis of a new mutation at the HD locus. The posterior probability of a new mutation to HD in the patient exceeds 99%, even if an a priori probability of non-paternity of 10% and a mutation rate of HD of 10(-7) is assumed.

  9. Isocitrate dehydrogenase mutations in gliomas

    PubMed Central

    Waitkus, Matthew S.; Diplas, Bill H.; Yan, Hai

    2016-01-01

    Over the last decade, extraordinary progress has been made in elucidating the underlying genetic causes of gliomas. In 2008, our understanding of glioma genetics was revolutionized when mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) were identified in the vast majority of progressive gliomas and secondary glioblastomas (GBMs). IDH enzymes normally catalyze the decarboxylation of isocitrate to generate α-ketoglutarate (αKG), but recurrent mutations at Arg132 of IDH1 and Arg172 of IDH2 confer a neomorphic enzyme activity that catalyzes reduction of αKG into the putative oncometabolite D-2-hydroxyglutate (D2HG). D2HG inhibits αKG-dependent dioxygenases and is thought to create a cellular state permissive to malignant transformation by altering cellular epigenetics and blocking normal differentiation processes. Herein, we discuss the relevant literature on mechanistic studies of IDH1/2 mutations in gliomas, and we review the potential impact of IDH1/2 mutations on molecular classification and glioma therapy. PMID:26188014

  10. Metacognition, Achievement Goals, Study Strategies and Academic Achievement: Pathways to Achievement

    ERIC Educational Resources Information Center

    Vrugt, Anneke; Oort, Frans J.

    2008-01-01

    The purpose of this research was to develop and test a model of effective self-regulated learning. Based on effort expenditure we discerned effective self-regulators and less effective self-regulators. The model comprised achievement goals (mastery, performance-approach and -avoidance goals), metacognition (metacognitive knowledge, regulation and…

  11. The incongruous achiever in adolescence.

    PubMed

    Kline, S A; Golombek, H

    1974-06-01

    The authors wished to study some of the internal psychological dynamics of achievement in a nonpatient identified high school population. Questionnaires were administered to the Grade 13 students and their parents in a large high school. A number of students whose achievement and educational plans were not congruous with their general background were selected for interview. The findings suggest that a wide variety of ages and developmental stages can be discerned as critical points in the development of a student's attitude toward higher education. These students have many values in common, and their values appear related to a positive or negative identification with parental values. The students themselves show a wide range of personality integration. They relate in a special way to a wide variety of teachers' personalities.

  12. Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis

    PubMed Central

    Pedrero, Marion; Campone, Mario; Soria, Jean-Charles; Massard, Christophe; Lévy, Christelle; Arnedos, Monica; Lacroix-Triki, Magali; Garrabey, Julie; Boursin, Yannick; Deloger, Marc; Commo, Frédéric; Scott, Véronique; Kamal, Maud; Diéras, Véronique; Gonçalves, Anthony; Romieu, Gilles; Vanlemmens, Laurence; Mouret Reynier, Marie-Ange; Théry, Jean-Christophe; Le Du, Fanny; Guiu, Séverine; Dalenc, Florence; Bonnefoi, Hervé; Jimenez, Marta; Le Tourneau, Christophe; André, Fabrice

    2016-01-01

    Background Major advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing. Methods and Findings Whole-exome sequencing was performed on 216 tumor–blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A) were identified as significantly mutated in mBC (false discovery rate [FDR] < 0.1). Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN) were more frequently mutated in mBC as compared to eBC (FDR < 0.01). ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI [9–155], p = 1.2e-12) and also presented with focal amplification (n = 9) for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+) and HER2 negative (HER2−) mBCs (19%). HR+/HER2− mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR) pathway (TSC1 and TSC2) as compared to HR+/HER2− eBC (respectively 6% and 0.7%, p = 0.0004). Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8), NOTCH3 (n = 7), and ALK (n = 7). Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2− metastatic tumors as compared to primary TCGA samples (p < 2e-16). The main limitations of this study include the absence of bone

  13. Beam cooling: Principles and achievements

    SciTech Connect

    Mohl, Dieter; Sessler, Andrew M.

    2003-05-18

    After a discussion of Liouville's theorem, and its implications for beam cooling, a brief description is given of each of the various methods of beam cooling: stochastic, electron, radiation, laser, ionization, etc. For each, we present the type of particle for which it is appropriate, its range of applicability, and the currently achieved degree of cooling. For each method we also discuss the present applications and, also, possible future developments and further applications.

  14. Predicting educational achievement from DNA

    PubMed Central

    Selzam, S; Krapohl, E; von Stumm, S; O'Reilly, P F; Rimfeld, K; Kovas, Y; Dale, P S; Lee, J J; Plomin, R

    2017-01-01

    A genome-wide polygenic score (GPS), derived from a 2013 genome-wide association study (N=127,000), explained 2% of the variance in total years of education (EduYears). In a follow-up study (N=329,000), a new EduYears GPS explains up to 4%. Here, we tested the association between this latest EduYears GPS and educational achievement scores at ages 7, 12 and 16 in an independent sample of 5825 UK individuals. We found that EduYears GPS explained greater amounts of variance in educational achievement over time, up to 9% at age 16, accounting for 15% of the heritable variance. This is the strongest GPS prediction to date for quantitative behavioral traits. Individuals in the highest and lowest GPS septiles differed by a whole school grade at age 16. Furthermore, EduYears GPS was associated with general cognitive ability (~3.5%) and family socioeconomic status (~7%). There was no evidence of an interaction between EduYears GPS and family socioeconomic status on educational achievement or on general cognitive ability. These results are a harbinger of future widespread use of GPS to predict genetic risk and resilience in the social and behavioral sciences. PMID:27431296

  15. The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe.

    PubMed

    Santer, René; Rischewski, Johannes; von Weihe, Michaela; Niederhaus, Marko; Schneppenheim, Sonja; Baerlocher, Kurt; Kohlschütter, Alfried; Muntau, Ania; Posselt, Hans-Georg; Steinmann, Beat; Schneppenheim, Reinhard

    2005-06-01

    We investigated the molecular basis of hereditary fructose intolerance (HFI) in 80 patients from 72 families by means of a PCR-based mutation screening strategy, consisting of heteroduplex analysis, restriction enzyme digest, DNA single strand electrophoresis, and direct sequencing. For a subset of patients mutation screening with DHPLC was established which turned out to be as fast and as sensitive as the more conventional methods. Fifteen different mutations of the aldolase B (ALDOB) gene were identified in HFI patients. As in smaller previous studies, p.A150P (65%), p.A175D (11%) and p.N335K (8%) were the most common mutated alleles, followed by c.360_363delCAAA, p.R60X, p.Y204X, and c.865delC. Eight novel mutations were identified in eight families with HFI: a small indel mutation (c.1044_1049delTTCTGGinsACACT), two small deletions (c.345_372del28; c.841_842delAC), two splice site mutations (c.113-1G>A, c.799+2T>A), one nonsense mutation (c.612T>G (p.Y204X)), and two missense mutations (c.532T>C (p.C178R), c.851T>C (p.L284P)). By mutation screening for the three most common ALDOB mutations by DHPLC in 2,000 randomly selected newborns we detected 21 heterozygotes. Based on these data and after correction for less common and private ALDOB mutations, HFI prevalence in central Europe is estimated to be 1:26,100 (95% confidence interval 1: 12,600-79,000).

  16. Is low-energy-ion bombardment generated X-ray emission a secondary mutational source to ion-beam-induced genetic mutation?

    NASA Astrophysics Data System (ADS)

    Thongkumkoon, P.; Prakrajang, K.; Thopan, P.; Yaopromsiri, C.; Suwannakachorn, D.; Yu, L. D.

    2013-07-01

    Low-energy ion beam biotechnology has achieved tremendous successes in inducing crop mutation and gene transfer. However, mechanisms involved in the related processes are not yet well understood. In ion-beam-induced mutation, ion-bombardment-produced X-ray has been proposed to be one of the secondary mutation sources, but the speculation has not yet been experimentally tested. We carried out this investigation to test whether the low-energy ion-beam-produced X-ray was a source of ion-beam-induced mutation. In the investigation, X-ray emission from 29-keV nitrogen- or argon- ion beam bombarded bacterial Escherichia coli (E. coli) cells held in a metal or plastic sample holder was in situ detected using a highly sensitive X-ray detector. The ion beam bombarded bacterial cells held in different material holders were observed for mutation induction. The results led to a conclusion that secondary X-ray emitted from ion-beam-bombarded biological living materials themselves was not a, or at least a negligible, mutational source, but the ion-beam-induced X-ray emission from the metal that made the sample holder could be a source of mutation.

  17. Ultra-fast boriding of metal surfaces for improved properties

    SciTech Connect

    Timur, Servet; Kartal, Guldem; Eryilmaz, Osman L.; Erdemir, Ali

    2015-02-10

    A method of ultra-fast boriding of a metal surface. The method includes the step of providing a metal component, providing a molten electrolyte having boron components therein, providing an electrochemical boriding system including an induction furnace, operating the induction furnace to establish a high temperature for the molten electrolyte, and boriding the metal surface to achieve a boride layer on the metal surface.

  18. Hybridization Capture-Based Next-Generation Sequencing to Evaluate Coding Sequence and Deep Intronic Mutations in the NF1 Gene

    PubMed Central

    Cunha, Karin Soares; Oliveira, Nathalia Silva; Fausto, Anna Karoline; de Souza, Carolina Cruz; Gros, Audrey; Bandres, Thomas; Idrissi, Yamina; Merlio, Jean-Philippe; de Moura Neto, Rodrigo Soares; Silva, Rosane; Geller, Mauro; Cappellen, David

    2016-01-01

    Neurofibromatosis 1 (NF1) is one of the most common genetic disorders and is caused by mutations in the NF1 gene. NF1 gene mutational analysis presents a considerable challenge because of its large size, existence of highly homologous pseudogenes located throughout the human genome, absence of mutational hotspots, and diversity of mutations types, including deep intronic splicing mutations. We aimed to evaluate the use of hybridization capture-based next-generation sequencing to screen coding and noncoding NF1 regions. Hybridization capture-based next-generation sequencing, with genomic DNA as starting material, was used to sequence the whole NF1 gene (exons and introns) from 11 unrelated individuals and 1 relative, who all had NF1. All of them met the NF1 clinical diagnostic criteria. We showed a mutation detection rate of 91% (10 out of 11). We identified eight recurrent and two novel mutations, which were all confirmed by Sanger methodology. In the Sanger sequencing confirmation, we also included another three relatives with NF1. Splicing alterations accounted for 50% of the mutations. One of them was caused by a deep intronic mutation (c.1260 + 1604A > G). Frameshift truncation and missense mutations corresponded to 30% and 20% of the pathogenic variants, respectively. In conclusion, we show the use of a simple and fast approach to screen, at once, the entire NF1 gene (exons and introns) for different types of pathogenic variations, including the deep intronic splicing mutations. PMID:27999334

  19. Hybridization Capture-Based Next-Generation Sequencing to Evaluate Coding Sequence and Deep Intronic Mutations in the NF1 Gene.

    PubMed

    Cunha, Karin Soares; Oliveira, Nathalia Silva; Fausto, Anna Karoline; de Souza, Carolina Cruz; Gros, Audrey; Bandres, Thomas; Idrissi, Yamina; Merlio, Jean-Philippe; de Moura Neto, Rodrigo Soares; Silva, Rosane; Geller, Mauro; Cappellen, David

    2016-12-17

    Neurofibromatosis 1 (NF1) is one of the most common genetic disorders and is caused by mutations in the NF1 gene. NF1 gene mutational analysis presents a considerable challenge because of its large size, existence of highly homologous pseudogenes located throughout the human genome, absence of mutational hotspots, and diversity of mutations types, including deep intronic splicing mutations. We aimed to evaluate the use of hybridization capture-based next-generation sequencing to screen coding and noncoding NF1 regions. Hybridization capture-based next-generation sequencing, with genomic DNA as starting material, was used to sequence the whole NF1 gene (exons and introns) from 11 unrelated individuals and 1 relative, who all had NF1. All of them met the NF1 clinical diagnostic criteria. We showed a mutation detection rate of 91% (10 out of 11). We identified eight recurrent and two novel mutations, which were all confirmed by Sanger methodology. In the Sanger sequencing confirmation, we also included another three relatives with NF1. Splicing alterations accounted for 50% of the mutations. One of them was caused by a deep intronic mutation (c.1260 + 1604A > G). Frameshift truncation and missense mutations corresponded to 30% and 20% of the pathogenic variants, respectively. In conclusion, we show the use of a simple and fast approach to screen, at once, the entire NF1 gene (exons and introns) for different types of pathogenic variations, including the deep intronic splicing mutations.

  20. Identification of mutations from phenotype-driven ENU mutagenesis in mouse chromosome 7.

    PubMed

    Culiat, Cymbeline T; Klebig, Mitchell L; Liu, Zhaowei; Monroe, Heidi; Stanford, Beverly; Desai, Jayashree; Tandan, Samvit; Hughes, Lori; Kerley, Marilyn K; Carpenter, Donald A; Johnson, Dabney K; Rinchik, Eugene M; Li, Qingbo

    2005-08-01

    We have used the new high-throughput mutation-scanning technique temperature-gradient capillary electrophoresis (TGCE) for the identification of point mutations induced by N-ethyl-N-nitrosourea (ENU) in the mouse genome. TGCE detects the presence of heteroduplex molecules formed between a wild-type gene segment and the corresponding homologous segment containing an induced mutation or a naturally occurring single nucleotide polymorphism (SNP). Partially denatured heteroduplex molecules are resolved from homoduplexes by virtue of their differential mobilities during capillary electrophoresis conducted in a finely controlled temperature gradient. Simultaneous heteroduplex analysis of 96 amplicons ranging from 150 to 600 bp in size is achieved in approximately 45 min without the need for predetermining the melting profile of each fragment. Initially, we exploited known mouse mutations to develop TGCE protocols for analyzing unpurified PCR samples amplified from crude tail-DNA preparations. TGCE was then applied to the rapid identification of three new ENU-induced mutations recovered from regional mutagenesis screens of a segment of mouse Chromosome 7. Enzyme assays and quantitative reverse transcription-PCR (qRT-PCR) methods validated these new mutations. Our data demonstrate that rapid mutation scanning with TGCE, followed by sequence verification only of detected positives, is an efficient approach to the identification of point mutations in the mouse genome.

  1. Fast Paced, Low Cost Projects at MSFC

    NASA Technical Reports Server (NTRS)

    Watson-Morgan, Lisa; Clinton, Raymond

    2012-01-01

    What does an orbiting microsatellite, a robotic lander and a ruggedized camera and telescope have in common? They are all fast paced, low cost projects managed by Marshall Space Flight Center (MSFC) teamed with successful industry partners. MSFC has long been synonymous with human space flight large propulsion programs, engineering acumen and risk intolerance. However, there is a growing portfolio/product line within MSFC that focuses on these smaller, fast paced projects. While launching anything into space is expensive, using a managed risk posture, holding to schedule and keeping costs low by stopping at egood enough f were key elements to their success. Risk is defined as the possibility of loss or failure per Merriam Webster. The National Aeronautics and Space Administration (NASA) defines risk using procedural requirement 8705.4 and establishes eclasses f to discern the acceptable risk per a project. It states a Class D risk has a medium to significant risk of not achieving mission success. MSFC, along with industry partners, has created a niche in Class D efforts. How did the big, cautious MSFC succeed on these projects that embodied the antithesis of its heritage in human space flight? A key factor toward these successful projects was innovative industry partners such as Dynetics Corporation, University of Alabama in Huntsville (UAHuntsville), Johns Hopkins Applied Physics Laboratory (JHU APL), Teledyne Brown Engineering (TBE), Von Braun Center for Science and Innovation (VCSI), SAIC, and Jacobs. Fast Affordable Satellite Technology (FastSat HSV01) is a low earth orbit microsatellite that houses six instruments with the primary scientific objective of earth observation and technology demonstration. The team was comprised of Dynetics, UAHuntsvile, SAIC, Goddard Space Flight Center (GSFC) and VCSI with the United States Air Force Space Test Program as the customer. The team completed design, development, manufacturing, environmental test and integration in

  2. Myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK) is caused by heterozygous KCNC1 mutations.

    PubMed

    Nascimento, Fábio A; Andrade, Danielle M

    2016-09-01

    Progressive myoclonus epilepsy (PME) is a distinct group of seizure disorders characterized by gradual neurological decline with ataxia, myoclonus and recurring seizures. There are several forms of PME, among which the most recently described is MEAK - myoclonus epilepsy and ataxia due to potassium channel mutation. This particular subtype is caused by a recurrent de novo heterozygous mutation (c.959G>A, p.Arg320His) in the KCNC1 gene, which maps to chromosome 11 and encodes for the Kv3.1 protein (a subunit of the Kv3 subfamily of voltage-gated potassium channels). Loss of Kv3 function disrupts the firing properties of fast-spiking neurons, affects neurotransmitter release and induces cell death. Specifically regarding Kv3.1 malfunctioning, the most affected neurons include inhibitory GABAergic interneurons and cerebellar neurons. Impairment of the former cells is believed to contribute to myoclonus and seizures, whereas dysfunction of the latter to ataxia and tremor. Phenotypically, MEAK patients generally have a normal early development. At the age of 6 to 14 years, they present with myoclonus, which tends to progressively worsen with time. Tonic-clonic seizures may or may not be present, and some patients develop mild cognitive impairment following seizure onset. Typical electroencephalographic features comprise generalized epileptiform discharges and, in some cases, photosensitivity. Brain imaging is either normal or shows cerebellar atrophy. The identification of MEAK has both expanded the phenotypic and genotypic spectra of PME and established an emerging role for de novo mutations in PME.

  3. Fast, Massively Parallel Data Processors

    NASA Technical Reports Server (NTRS)

    Heaton, Robert A.; Blevins, Donald W.; Davis, ED

    1994-01-01

    Proposed fast, massively parallel data processor contains 8x16 array of processing elements with efficient interconnection scheme and options for flexible local control. Processing elements communicate with each other on "X" interconnection grid with external memory via high-capacity input/output bus. This approach to conditional operation nearly doubles speed of various arithmetic operations.

  4. Fast excitation variable period wiggler

    SciTech Connect

    van Steenbergen, A.; Gallardo, J.; Romano, T.; Woodle, M.

    1991-01-01

    The design of an easily stackable, variable period length, fast excitation driven wiggler, making use of geometrically alternating substacks of Vanadium Permandur ferromagnetic laminations, interspaced with conductive, non magnetic, laminations which act as eddy current induced field reflectors,'' is discussed and experimental results obtained with short wiggler models are presented.

  5. Fast excitation variable period wiggler

    SciTech Connect

    van Steenbergen, A.; Gallardo, J.; Romano, T.; Woodle, M.

    1991-12-31

    The design of an easily stackable, variable period length, fast excitation driven wiggler, making use of geometrically alternating substacks of Vanadium Permandur ferromagnetic laminations, interspaced with conductive, non magnetic, laminations which act as eddy current induced ``field reflectors,`` is discussed and experimental results obtained with short wiggler models are presented.

  6. Fast Atom Bombardment Mass Spectrometry.

    ERIC Educational Resources Information Center

    Rinehart, Kenneth L., Jr.

    1982-01-01

    Discusses reactions and characteristics of fast atom bombardment (FAB) mass spectroscopy in which samples are ionized in a condensed state by bombardment with xenon or argon atoms, yielding positive/negative secondary ions. Includes applications of FAB to structural problems and considers future developments using the technique. (Author/JN)

  7. Fast-response cloud chamber

    NASA Technical Reports Server (NTRS)

    Fogal, G. L.

    1977-01-01

    Wall structure keeps chambers at constant, uniform temperature, yet allows them to be cooled rapidly if necessary. Wall structure, used in fast-response cloud chamber, has surface heater and coolant shell separated by foam insulation. It is lightweight and requires relatively little power.

  8. Signatures of mutational processes in human cancer

    PubMed Central

    Alexandrov, Ludmil B.; Nik-Zainal, Serena; Wedge, David C.; Aparicio, Samuel A.J.R.; Behjati, Sam; Biankin, Andrew V.; Bignell, Graham R.; Bolli, Niccolo; Borg, Ake; Børresen-Dale, Anne-Lise; Boyault, Sandrine; Burkhardt, Birgit; Butler, Adam P.; Caldas, Carlos; Davies, Helen R.; Desmedt, Christine; Eils, Roland; Eyfjörd, Jórunn Erla; Foekens, John A.; Greaves, Mel; Hosoda, Fumie; Hutter, Barbara; Ilicic, Tomislav; Imbeaud, Sandrine; Imielinsk, Marcin; Jäger, Natalie; Jones, David T.W.; Jones, David; Knappskog, Stian; Kool, Marcel; Lakhani, Sunil R.; López-Otín, Carlos; Martin, Sancha; Munshi, Nikhil C.; Nakamura, Hiromi; Northcott, Paul A.; Pajic, Marina; Papaemmanuil, Elli; Paradiso, Angelo; Pearson, John V.; Puente, Xose S.; Raine, Keiran; Ramakrishna, Manasa; Richardson, Andrea L.; Richter, Julia; Rosenstiel, Philip; Schlesner, Matthias; Schumacher, Ton N.; Span, Paul N.; Teague, Jon W.; Totoki, Yasushi; Tutt, Andrew N.J.; Valdés-Mas, Rafael; van Buuren, Marit M.; van ’t Veer, Laura; Vincent-Salomon, Anne; Waddell, Nicola; Yates, Lucy R.; Zucman-Rossi, Jessica; Futreal, P. Andrew; McDermott, Ultan; Lichter, Peter; Meyerson, Matthew; Grimmond, Sean M.; Siebert, Reiner; Campo, Elías; Shibata, Tatsuhiro; Pfister, Stefan M.; Campbell, Peter J.; Stratton, Michael R.

    2013-01-01

    All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy. PMID:23945592

  9. Radiation-induced mutation at minisatellite loci

    SciTech Connect

    Dubrova, Y.E. |; Nesterov, V.N.; Krouchinsky, N.G.

    1997-10-01

    We are studying the radiation-induced increase of mutation rate in minisatellite loci in mice and humans. Minisatellite mutations were scored by multilocus DNA fingerprint analysis in the progeny of {gamma}-irradiated and non-irradiated mice. The frequency of mutation in offspring of irradiated males was 1.7 higher that in the control group. Germline mutation at human minisatellite loci was studied among children born in heavily polluted areas of the Mogilev district of Belarus after the Chernobyl accident and in a control population. The frequency of mutation assayed both by DNA fingerprinting and by eight single locus probes was found to be two times higher in the exposed families than in the control group. Furthermore, mutation rate was correlated with the parental radiation dose for chronic exposure {sup 137}Cs, consistent with radiation-induction of germline mutation. The potential use of minisatellites in monitoring germline mutation in humans will be discussed.

  10. Presynaptic CaV2.1 calcium channels carrying familial hemiplegic migraine mutation R192Q allow faster recovery from synaptic depression in mouse calyx of Held

    PubMed Central

    Inchauspe, Carlota González; Urbano, Francisco J.; Di Guilmi, Mariano N.; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Forsythe, Ian D.

    2012-01-01

    CaV2.1 Ca2+ channels have a dominant and specific role in initiating fast synaptic transmission at central excitatory synapses, through a close association between release sites and calcium sensors. Familial hemiplegic migraine type 1 (FHM-1) is an autosomal-dominant subtype of migraine with aura, caused by missense mutations in the CACNA1A gene that encodes the α1A pore-forming subunit of CaV2.1 channel. We used knock-in (KI) transgenic mice harboring the FHM-1 mutation R192Q to study the consequences of this mutation in neurotransmission at the giant synapse of the auditory system formed by the presynaptic calyx of Held terminal and the postsynaptic neurons of the medial nucleus of the trapezoid body (MNTB). Although synaptic transmission seems unaffected by low-frequency stimulation in physiological Ca2+ concentration, we observed that with low Ca2+ concentrations (<1 mM) excitatory postsynaptic currents (EPSCs) showed increased amplitudes in R192Q KI mice compared with wild type (WT), meaning significant differences in the nonlinear calcium dependence of nerve-evoked transmitter release. In addition, when EPSCs were evoked by broadened presynaptic action potentials (achieved by inhibition of K+ channels) via Cav2.1-triggered exocytosis, R192Q KI mice exhibited further enhancement of EPSC amplitude and charge compared with WT mice. Repetitive stimulation of afferent axons to the MNTB at different frequencies caused short-term depression of EPSCs that recovered significantly faster in R192Q KI mice than in WT mice. Faster recovery in R192Q KI mice was prevented by the calcium chelator EGTA-AM, pointing to enlarged residual calcium as a key factor in accelerating the replenishment of synaptic vesicles. PMID:22956801

  11. Novel MMP20 and KLK4 Mutations in Amelogenesis Imperfecta.

    PubMed

    Seymen, F; Park, J-C; Lee, K-E; Lee, H-K; Lee, D-S; Koruyucu, M; Gencay, K; Bayram, M; Tuna, E B; Lee, Z H; Kim, Y-J; Kim, J-W

    2015-08-01

    In order to achieve highly mineralized tooth enamel, enamel proteinases serve the important function of removing the remaining organic matrix in the mineralization and maturation of the enamel matrix. Mutations in the kallikrein 4 (KLK4), enamelysin (MMP20), and WDR72 genes have been identified as causing hypomaturation enamel defects in an autosomal-recessive hereditary pattern. In this report, 2 consanguineous families with a hypomaturation-type enamel defect were recruited, and mutational analysis was performed to determine the molecular genetic etiology of the disease. Whole exome sequencing and autozygosity mapping identified novel homozygous mutations in the KLK4 (c.620_621delCT, p.Ser207Trpfs*38) and MMP20 (c.1054G>A, p.Glu352Lys) genes. Further analysis on the effect of the mutations on the translation, secretion, and function of KLK4 and MMP20 revealed that mutant KLK4 was degraded intracellularly and became inactive while mutant MMP20 was expressed at a normal level but secreted only minimally with proteolytic function.

  12. Mutation analysis in Turkish phenylketonuria patients.

    PubMed Central

    Ozgüç, M; Ozalp, I; Coşkun, T; Yilmaz, E; Erdem, H; Ayter, S

    1993-01-01

    Forty-four classical PKU patients have been screened for various mutations. The newly identified IVS 10 splicing mutation was found in 32% of the mutant alleles and comprises 74.5% of the mutations that could be typed: 261arg-gln (6.8%), 158arg-gly (2.3%), 252arg-trp (1.1%), 280glu-lys (-), and 272gly-stop (-) were the other mutations that were screened. Images PMID:8445616

  13. Plastome Mutations and Recombination Events in Barley Chloroplast Mutator Seedlings.

    PubMed

    Landau, Alejandra; Lencina, Franco; Pacheco, María G; Prina, Alberto R

    2016-05-01

    The barley chloroplast mutator (cpm) is an allele of a nuclear gene that when homozygous induces several types of cytoplasmically inherited chlorophyll deficiencies. In this work, a plastome Targeting Induced Local Lesions in Genomes (TILLING) strategy based on mismatch digestion was used on families that carried the cpm genotype through many generations. Extensive scanning of 33 plastome genes and a few intergenic regions was conducted. Numerous polymorphisms were detected on both genic and intergenic regions. The detected polymorphisms can be accounted for by at least 61 independent mutational events. The vast majority of the polymorphisms originated in substitutions and small indels (insertions/deletions) in microsatellites. The rpl23 and the rps16 genes were the most polymorphic. Interestingly, the variation observed in the rpl23 gene consisted of several combinations of 5 different one nucleotide polymorphisms. Besides, 4 large indels that have direct repeats at both ends were also observed, which appear to be originated from recombinational events. The cpm mutation spectrum suggests that the CPM gene product is probably involved in plastome mismatch repair. The numerous subtle molecular changes that were localized in a wide range of plastome sites show the cpm as a valuable source of plastome variability for plant research and/or plant breeding. Moreover, the cpm mutant appears to be an interesting experimental material for investigating the mechanisms responsible for maintaining the stability of plant organelle DNA.

  14. WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.

    PubMed

    Yokote, Koutaro; Chanprasert, Sirisak; Lee, Lin; Eirich, Katharina; Takemoto, Minoru; Watanabe, Aki; Koizumi, Naoko; Lessel, Davor; Mori, Takayasu; Hisama, Fuki M; Ladd, Paula D; Angle, Brad; Baris, Hagit; Cefle, Kivanc; Palanduz, Sukru; Ozturk, Sukru; Chateau, Antoinette; Deguchi, Kentaro; Easwar, T K M; Federico, Antonio; Fox, Amy; Grebe, Theresa A; Hay, Beverly; Nampoothiri, Sheela; Seiter, Karen; Streeten, Elizabeth; Piña-Aguilar, Raul E; Poke, Gemma; Poot, Martin; Posmyk, Renata; Martin, George M; Kubisch, Christian; Schindler, Detlev; Oshima, Junko

    2017-01-01

    Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.

  15. WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects

    PubMed Central

    Yokote, Koutaro; Chanprasert, Sirisak; Lee, Lin; Eirich, Katharina; Takemoto, Minoru; Watanabe, Aki; Koizumi, Naoko; Lessel, Davor; Mori, Takayasu; Hisama, Fuki M.; Ladd, Paula D.; Angle, Brad; Baris, Hagit; Cefle, Kivanc; Palanduz, Sukru; Ozturk, Sukru; Chateau, Antoinette; Deguchi, Kentaro; Easwar, T.K.M; Federico, Antonio; Fox, Amy; Grebe, Theresa A.; Hay, Beverly; Nampoothiri, Sheela; Seiter, Karen; Streeten, Elizabeth; Piña-Aguilar, Raul E.; Poke, Gemma; Poot, Martin; Posmyk, Renata; Martin, George M.; Kubisch, Christian; Schindler, Detlev; Oshima, Junko

    2017-01-01

    Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation. PMID:27667302

  16. Chaos based crossover and mutation for securing DICOM image.

    PubMed

    Ravichandran, Dhivya; Praveenkumar, Padmapriya; Balaguru Rayappan, John Bosco; Amirtharajan, Rengarajan

    2016-05-01

    This paper proposes a novel encryption scheme based on combining multiple chaotic maps to ensure the safe transmission of medical images. The proposed scheme uses three chaotic maps namely logistic, tent and sine maps. To achieve an efficient encryption, the proposed chao-cryptic system employs a bio-inspired crossover and mutation units to confuse and diffuse the Digital Imaging and Communications in Medicine (DICOM) image pixels. The crossover unit extensively permutes the image pixels row-wise and column-wise based on the chaotic key streams generated from the Combined Logistic-Tent (CLT) system. Prior to mutation, the pixels of the crossed over image are decomposed into two images with reduced bit depth. The decomposed images are then mutated by XOR operation with quantized chaotic sequences from Combined Logistic-Sine (CLS) system. In order to validate the sternness of the proposed algorithm, the developed chao-cryptic scheme is subjected to various security analyses such as statistical, differential, key space, key sensitivity, intentional cropping attack and chosen plaintext attack analyses. The experimental results prove the proposed DICOM cryptosystem has achieved a desirable amount of protection for real time medical image security applications.

  17. Updates and achievements in virology.

    PubMed

    Buonaguro, Franco M; Campadelli-Fiume, Gabriella; De Giuli Morghen, Carlo; Palù, Giorgio

    2010-07-01

    The 4th European Congress of Virology, hosted by the Italian Society for Virology, attracted approximately 1300 scientists from 46 countries worldwide. It also represented the first conference of the European Society for Virology, which was established in Campidoglio, Rome, Italy in 2009. The main goal of the meeting was to share research activities and results achieved in European virology units/institutes and to strengthen collaboration with colleagues from both western and developing countries. The worldwide representation of participants is a testament to the strength and attraction of European virology. The 5-day conference brought together the best of current virology; topics covered all three living domains (bacteria, archaea and eucarya), with special sessions on plant and veterinary virology as well as human virology, including two oral presentations on mimiviruses. The conference included five plenary sessions, 31 workshops, one hepatitis C virus roundtable, ten special workshops and three poster sessions, as well as 45 keynote lectures, 191 oral presentations and 845 abstracts. Furthermore, the Gesellschaft fur Virologie Loeffler-Frosch medal award was given to Peter Vogt for his long-standing career and achievements; the Gardner Lecture of the European Society for Clinical Virology was presented by Yoshihiro Kawaoka, and the Pioneer in Virology Lecture of the Italian Society for Virology was presented by Ulrich Koszinowski.

  18. Achieving permanency for LGBTQ youth.

    PubMed

    Jacobs, Jill; Freundlich, Madelyn

    2006-01-01

    This article brings together two significant efforts in the child welfare field: achieving permanence for youth in out-of-home care and meeting the needs of lesbian, gay, bisexual, transgender and questioning (LGBTQ) youth. During the past several years, a national movement has taken place to assure all children and youth have a permanent family connection before leaving the child welfare system; however, LGBTQ youth are not routinely included in the permanency discussions. At the same time, efforts in addressing the needs of LGBTQ youth have increased, but permanency is rarely mentioned as a need. This article offers models of permanence and practices to facilitate permanence with LGBTQ youth and their families. It also offers a youth-driven, individualized process, using youth development principles to achieve relational, physical, and legal permanence. Reunification efforts are discussed, including services, supports, and education required for youth to return to their family of origin. For those who cannot return home, other family resources are explored. The article also discusses cultural issues as they affect permanence for LGBTQ youth, and, finally, addresses the need for ongoing support services to sustain and support permanency.

  19. IDH mutation detection in formalin-fixed paraffin-embedded gliomas using multiplex PCR and single-base extension.

    PubMed

    Perizzolo, Marco; Winkfein, Bob; Hui, Susan; Krulicki, Wally; Chan, Jennifer A; Demetrick, Douglas J

    2012-09-01

    Isocitrate dehydrogenase (IDH) genes are mutated in a significant portion of gliomas, myeloid leukemias and chondroid neoplasms. In gliomas, IDH mutations are prognostic, as those tumors with the mutation are associated with a proneural subclass and have longer survival compared with those without the mutation. We developed a simple, PCR-based SNaPshot® assay (Life Technologies, Carlsbad, CA, USA) to detect IDH1/2 mutations. This protocol combines a single, multiplexed PCR reaction using gene specific primers followed by a single, multiplexed SNaPshot reaction and detection by capillary electrophoresis. In a blinded study of 32 paraffin-embedded glioma specimens previously screened for IDH mutations by a PCR/direct sequencing method, concordance of our IDH SNaPshot test with sequencing was 100%. We performed the assay on an additional 57 specimens submitted for diagnostic IDH mutation evaluation. Data analysis was much faster and easier to perform than analysis of the sequencing data, and results could be obtained in 1 day from DNA extraction to analysis. Furthermore, we could readily identify a mixture of 5% mutant allele vs. 95% wild-type allele in our SNaPshot assay, in comparison to approximately 20% mutant allele in our PCR-sequencing assay. Our assay represents a fast, sensitive, straightforward method of reliably detecting common mutations of IDH genes in glial neoplasms, or other tumors.

  20. Mutations in the human GlyT2 gene define a presynaptic component of human startle disease

    PubMed Central

    Rees, Mark I.; Harvey, Kirsten; Pearce, Brian R.; Chung, Seo-Kyung; Duguid, Ian C.; Thomas, Philip; Beatty, Sarah; Graham, Gail E.; Armstrong, Linlea; Shiang, Rita; Abbott, Kim J.; Zuberi, Sameer M.; Stephenson, John B.P.; Owen, Michael J.; Tijssen, Marina A.J.; van den Maagdenberg, Arn M.J.M.; Smart, Trevor G.; Supplisson, Stéphane; Harvey, Robert J.

    2011-01-01

    Hyperekplexia is a human neurological disorder characterized by an excessive startle response and is typically caused by missense and nonsense mutations in the gene encoding the inhibitory glycine receptor (GlyR) α1 subunit (GLRA1)1-3. Genetic heterogeneity has been confirmed in isolated sporadic cases with mutations in other postsynaptic glycinergic proteins including the GlyR β subunit (GLRB)4, gephyrin (GPHN)5 and RhoGEF collybistin (ARHGEF9)6. However, many sporadic patients diagnosed with hyperekplexia do not carry mutations in these genes2-7. Here we reveal that missense, nonsense and frameshift mutations in the presynaptic glycine transporter 2 (GlyT2) gene (SLC6A5)8 also cause hyperekplexia. Patients harbouring mutations in SLC6A5 presented with hypertonia, an exaggerated startle response to tactile or acoustic stimuli, and life-threatening neonatal apnoea episodes. GlyT2 mutations result in defective subcellular localisation and/or decreased glycine uptake, with selected mutations affecting predicted glycine and Na+ binding sites. Our results demonstrate that SLC6A5 is a major gene for hyperekplexia and define the first neurological disorder linked to mutations in a Na+/Cl−-dependent transporter for a classical fast neurotransmitter. By analogy, we suggest that in other human disorders where defects in postsynaptic receptors have been identified, similar symptoms could result from defects in the cognate presynaptic neurotransmitter transporter. PMID:16751771

  1. Anaerobically Grown Escherichia coli Has an Enhanced Mutation Rate and Distinct Mutational Spectra

    PubMed Central

    Shewaramani, Sonal; Finn, Thomas J.; Kassen, Rees; Rainey, Paul B.

    2017-01-01

    Oxidative stress is a major cause of mutation but little is known about how growth in the absence of oxygen impacts the rate and spectrum of mutations. We employed long-term mutation accumulation experiments to directly measure the rates and spectra of spontaneous mutation events in Escherichia coli populations propagated under aerobic and anaerobic conditions. To detect mutations, whole genome sequencing was coupled with methods of analysis sufficient to identify a broad range of mutational classes, including structural variants (SVs) generated by movement of repetitive elements. The anaerobically grown populations displayed a mutation rate nearly twice that of the aerobic populations, showed distinct asymmetric mutational strand biases, and greater insertion element activity. Consistent with mutation rate and spectra observations, genes for transposition and recombination repair associated with SVs were up-regulated during anaerobic growth. Together, these results define differences in mutational spectra affecting the evolution of facultative anaerobes. PMID:28103245

  2. LFR "Lead-Cooled Fast Reactor"

    SciTech Connect

    Cinotti, L; Fazio, C; Knebel, J; Monti, S; Abderrahim, H A; Smith, C; Suh, K

    2006-05-11

    The main purpose of this paper is to present the current status of development of the Lead-cooled Fast Reactor (LFR) in Generation IV (GEN IV), including the European contribution, to identify needed R&D and to present the corresponding GEN IV International Forum (GIF) R&D plan [1] to support the future development and deployment of lead-cooled fast reactors. The approach of the GIF plan is to consider the research priorities of each member country in proposing an integrated, coordinated R&D program to achieve common objectives, while avoiding duplication of effort. The integrated plan recognizes two principal technology tracks: (1) a small, transportable system of 10-100 MWe size that features a very long refuelling interval, and (2) a larger-sized system rated at about 600 MWe, intended for central station power generation. This paper provides some details of the important European contributions to the development of the LFR. Sixteen European organizations have, in fact, taken the initiative to present to the European Commission the proposal for a Specific Targeted Research and Training Project (STREP) devoted to the development of a European Lead-cooled System, known as the ELSY project; two additional organizations from the US and Korea have joined the project. Consequently, ELSY will constitute the reference system for the large lead-cooled reactor of GEN IV. The ELSY project aims to demonstrate the feasibility of designing a competitive and safe fast power reactor based on simple technical engineered features that achieves all of the GEN IV goals and gives assurance of investment protection. As far as new technology development is concerned, only a limited amount of R&D will be conducted in the initial phase of the ELSY project since the first priority is to define the design guidelines before launching a larger and expensive specific R&D program. In addition, the ELSY project is expected to benefit greatly from ongoing lead and lead-alloy technology

  3. Fast Reactor Fuel Type and Reactor Safety Performance

    SciTech Connect

    R. Wigeland; J. Cahalan

    2009-09-01

    thermophysical properties of the fuel and their compatibility with the reactor coolant, with corresponding differences in the challenges presented to the reactor developers. Accident phenomena are discussed for the sodium-cooled fast reactor based on the mechanistic progression of conditions from accident initiation to accident termination, whether a benign state is achieved or more severe consequences are expected. General principles connecting accident phenomena and fuel properties are developed from the oxide and metal fuel safety analyses, providing guidelines that can be used as part of the evaluation for selection of fuel type for the sodium-cooled fast reactor.

  4. Techniques for Fast Stereoscopic MRI

    PubMed Central

    Guttman, Michael A.; McVeigh, Elliot R.

    2007-01-01

    Stereoscopic MRI can impart 3D perception with only two image acquisitions. This economy over standard multiplanar 3D volume renderings allows faster frame rates, which are needed for real-time imaging applications. Real-time 3D perception may enhance the appreciation of complex anatomical structures, and may improve hand-eye coordination while manipulating a medical device during an image-guided interventional procedure. To this goal, a system is being developed to acquire and display stereoscopic MR images in real-time. A clinically used, fast gradient-recalled echo-train sequence has been modified to produce stereo image pairs. Features have been added for depth cueing, view sharing, and bulk signal suppression. A workstation was attached to a clinical MR scanner for fast data extraction, image reconstruction and stereoscopic image display. PMID:11477636

  5. Fast Moreau envelope computation I

    NASA Astrophysics Data System (ADS)

    Lucet, Yves

    2006-11-01

    The present article summarizes the state of the art algorithms to compute the discrete Moreau envelope, and presents a new linear-time algorithm, named NEP for NonExpansive Proximal mapping. Numerical comparisons between the NEP and two existing algorithms: The Linear-time Legendre Transform (LLT) and the Parabolic Envelope (PE) algorithms are performed. Worst-case time complexity, convergence results, and examples are included. The fast Moreau envelope algorithms first factor the Moreau envelope as several one-dimensional transforms and then reduce the brute force quadratic worst-case time complexity to linear time by using either the equivalence with Fast Legendre Transform algorithms, the computation of a lower envelope of parabolas, or, in the convex case, the non expansiveness of the proximal mapping.

  6. Causes of Extremely Fast CMEs

    NASA Technical Reports Server (NTRS)

    Feynman, Joan; Ruzmaikin, Alexander

    2006-01-01

    We study CMEs observed by LASCO to have plane of the sky velocities exceeding 1500 km/sec. We find that these extremely fast CMEs are typically associated with flares accompanied by erupting prominences. Our results are consistent with a single CME initiation process that consists of three stages. The initial stage is brought about by the emergence of new magnetic flux, which interacts with the pre-existing magnetic configuration and results in a slow rise of the magnetic structure. The second stage is a fast reconnection phase with flaring, filament eruption and a sudden increase of the rise velocity of the magnetic structure (CME). The third stage consists of propagation in the corona. We discuss the sources of these CMEs and the need for improved understanding of the first and third stages.

  7. Why are idioms recognized fast?

    PubMed

    Tabossi, Patrizia; Fanari, Rachele; Wolf, Kinou

    2009-06-01

    It is an established fact that idiomatic expressions are fast to process. However, the explanation of the phenomenon is controversial. Using a semantic judgment paradigm, where people decide whether a string is meaningful or not, the present experiment tested the predictions deriving from the three main theories of idiom recognition-the lexical representation hypothesis, the idiom decomposition hypothesis, and the configuration hypothesis. Participants were faster at judging decomposable idioms, nondecomposable idioms, and clichés than at judging their matched controls. The effect was comparable for all conventional expressions. The results were interpreted as suggesting that, as posited by the configuration hypothesis, the fact that they are known expressions, rather than idiomaticity, explains their fast recognition.

  8. A fast meteor detection algorithm

    NASA Astrophysics Data System (ADS)

    Gural, P.

    2016-01-01

    A low latency meteor detection algorithm for use with fast steering mirrors had been previously developed to track and telescopically follow meteors in real-time (Gural, 2007). It has been rewritten as a generic clustering and tracking software module for meteor detection that meets both the demanding throughput requirements of a Raspberry Pi while also maintaining a high probability of detection. The software interface is generalized to work with various forms of front-end video pre-processing approaches and provides a rich product set of parameterized line detection metrics. Discussion will include the Maximum Temporal Pixel (MTP) compression technique as a fast thresholding option for feeding the detection module, the detection algorithm trade for maximum processing throughput, details on the clustering and tracking methodology, processing products, performance metrics, and a general interface description.

  9. Ellis-van Creveld Syndrome: Mutations Uncovered in Lebanese Families.

    PubMed

    Valencia, Maria; Tabet, Lara; Yazbeck, Nadine; Araj, Alia; Ruiz-Perez, Victor L; Charaffedine, Khalil; Fares, Farah; Badra, Rebecca; Farra, Chantal

    2015-01-01

    Background. Ellis-van Creveld (EvC) syndrome is a rare, autosomal recessive disorder characterized by short stature, short limbs, growth retardation, polydactyly, and ectodermal defects with cardiac anomalies occurring in around 60% of cases. EVC syndrome has been linked to mutations in EVC and EVC2 genes. Case Presentation. We report EvC syndrome in two unrelated Lebanese families both having homozygous mutations in the EVC2 gene, c.2653C>T (p.(Arg885(*))) and c.2012_2015del (p.(Leu671(*))) in exons 15 and 13, respectively, with the latter being reported for the first time. Conclusion. Although EvC has been largely described in the medical literature, clinical features of this syndrome vary. While more research is required to explore other genes involved in EvC, early diagnosis and therapeutic care are important to achieve a better quality of life.

  10. Fast quench reactor and method

    DOEpatents

    Detering, Brent A.; Donaldson, Alan D.; Fincke, James R.; Kong, Peter C.

    2002-09-24

    A fast quench reaction includes a reactor chamber having a high temperature heating means such as a plasma torch at its inlet and a restrictive convergent-divergent nozzle at its outlet end. Reactants are injected into the reactor chamber. The resulting heated gaseous stream is then rapidly cooled by passage through the nozzle. This "freezes" the desired end product(s) in the heated equilibrium reaction stage.

  11. Fast quench reactor and method

    DOEpatents

    Detering, Brent A.; Donaldson, Alan D.; Fincke, James R.; Kong, Peter C.

    1998-01-01

    A fast quench reaction includes a reactor chamber having a high temperature heating means such as a plasma torch at its inlet and a restrictive convergent-divergent nozzle at its outlet end. Reactants are injected into the reactor chamber. The resulting heated gaseous stream is then rapidly cooled by passage through the nozzle. This "freezes" the desired end product(s) in the heated equilibrium reaction stage.

  12. Fast quench reactor and method

    DOEpatents

    Detering, B.A.; Donaldson, A.D.; Fincke, J.R.; Kong, P.C.

    1998-05-12

    A fast quench reactor includes a reactor chamber having a high temperature heating means such as a plasma torch at its inlet and a restrictive convergent-divergent nozzle at its outlet end. Reactants are injected into the reactor chamber. The resulting heated gaseous stream is then rapidly cooled by passage through the nozzle. This ``freezes`` the desired end product(s) in the heated equilibrium reaction stage. 7 figs.

  13. Fast Anomaly Discovery Given Duplicates

    DTIC Science & Technology

    2012-12-01

    skipping the computations for duplicate points in SN(ui) that have ci larger than k, the runtime complexity is enhanced significantly. That is, in...Fast anomaly discovery given duplicates Jay-Yoon Lee, U Kang, Danai Koutra, Christos Faloutsos Dec 2012 CMU-CS-12-146 School of Computer Science...ES) Carnegie Mellon University,School of Computer Science,Pittsburgh,PA,15213 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING

  14. Fast track to 340B.

    PubMed

    Gricius, Robert F; Wong, Douglas

    2016-01-01

    Hospitals that are newly qualified for the 340B Drug Pricing Program may have an opportunity for fast-track approval to participate in the program. Three steps are required to seize this opportunity: Use data analytics to assess current and future percentages of Medicaid utilization and eligibility for federal SSI cash benefits. Determine the feasibility of early cost report filing. Prepare appropriate documentation and undertake the initial enrollment process.

  15. Fast quench reactor and method

    DOEpatents

    Detering, Brent A.; Donaldson, Alan D.; Fincke, James R.; Kong, Peter C.

    2002-01-01

    A fast quench reaction includes a reactor chamber having a high temperature heating means such as a plasma torch at its inlet and a restrictive convergent-divergent nozzle at its outlet end. Reactants are injected into the reactor chamber. The resulting heated gaseous stream is then rapidly cooled by passage through the nozzle. This "freezes" the desired end product(s) in the heated equilibrium reaction stage.

  16. Sputtering of fast meteoroids' surface

    NASA Astrophysics Data System (ADS)

    Popova, O. P.; Strelkov, A. S.; Sidneva, S. N.

    Entering meteoroids are subjected by direct impacts of molecules of the individual constituents of the air, when the body approaching the Earth at heights of about 300-100 km. At meteor velocities about 72 km/s the energy of air molecules is about 800 eV and oxygen atoms have energy about 400 eV. Particles with such energies don't penetrate into deep layers of entering body and are concentrated in narrow surface layer of about hundreds angstroms. Action of air particles on meteoroid leads to both heating of meteoroid and sputtering of meteoroid surface. Sputtering effect was supposed as explanation of this high altitude ionization and luminosity (Brosch et al, 2001), which aren't explained by classical ablation theory. Sputtering results in appearance of fast particles, which also may be exited and/or ionized. Flux of these particles causes formation of ionized meteor trails recording by radars. For bigger bodies fast particles may create luminous area at the altitudes above altitude of intensive evaporation. We demonstrate physical model, which allows us to describe sputtering of meteoroid surface under impacts of incoming air particles. We consider sputtering of meteoroid with composition close to hondritic one at the altitude 150 km. Fast particles are really sputtered from meteoroid surface. They carry out about 10% of incoming flux energy. There are also reflected particles, but the most part of total particle outcome is formed by particles of meteor substance. Presence of fast particles possibly explains a large size of meteors in diffuse stage at high altitudes (above 130 km). The sputtering is neglectable in the case of meteor velocities below 30 km/s. Sputtered and reflected particles have enough high ionization degree (˜ (1-5) 10-2, that is larger than ionization degree of surrounding atmosphere (˜ 10-5div 10-6)).

  17. Rare beneficial mutations can halt Muller's ratchet

    NASA Astrophysics Data System (ADS)

    Balick, Daniel; Goyal, Sidhartha; Jerison, Elizabeth; Neher, Richard; Shraiman, Boris; Desai, Michael

    2012-02-01

    In viral, bacterial, and other asexual populations, the vast majority of non-neutral mutations are deleterious. This motivates the application of models without beneficial mutations. Here we show that the presence of surprisingly few compensatory mutations halts fitness decay in these models. Production of deleterious mutations is balanced by purifying selection, stabilizing the fitness distribution. However, stochastic vanishing of fitness classes can lead to slow fitness decay (i.e. Muller's ratchet). For weakly deleterious mutations, production overwhelms purification, rapidly decreasing population fitness. We show that when beneficial mutations are introduced, a stable steady state emerges in the form of a dynamic mutation-selection balance. We argue this state is generic for all mutation rates and population sizes, and is reached as an end state as genomes become saturated by either beneficial or deleterious mutations. Assuming all mutations have the same magnitude selective effect, we calculate the fraction of beneficial mutations necessary to maintain the dynamic balance. This may explain the unexpected maintenance of asexual genomes, as in mitochondria, in the presence of selection. This will affect in the statistics of genetic diversity in these populations.

  18. Achieving Quality in Occupational Health

    NASA Technical Reports Server (NTRS)

    O'Donnell, Michele (Editor); Hoffler, G. Wyckliffe (Editor)

    1997-01-01

    The conference convened approximately 100 registered participants of invited guest speakers, NASA presenters, and a broad spectrum of the Occupational Health disciplines representing NASA Headquarters and all NASA Field Centers. Centered on the theme, "Achieving Quality in Occupational Health," conferees heard presentations from award winning occupational health program professionals within the Agency and from private industry; updates on ISO 9000 status, quality assurance, and information technologies; workshops on ergonomics and respiratory protection; an overview from the newly commissioned NASA Occupational Health Assessment Team; and a keynote speech on improving women's health. In addition, NASA occupational health specialists presented 24 poster sessions and oral deliveries on various aspects of current practice at their field centers.

  19. Androgen receptor gene mutation, rearrangement, polymorphism

    PubMed Central

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E.

    2013-01-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents. PMID:25045626

  20. Diagnostics for Fast Ignition Science

    SciTech Connect

    MacPhee, A; Akli, K; Beg, F; Chen, C; Chen, H; Clarke, R; Hey, D; Freeman, R; Kemp, A; Key, M; King, J; LePape, S; Link, A; Ma, T; Nakamura, N; Offermann, D; Ovchinnikov, V; Patel, P; Phillips, T; Stephens, R; Town, R; Wei, M; VanWoerkom, L; Mackinnon, A

    2008-05-06

    The concept for Electron Fast Ignition Inertial Confinement Fusion demands sufficient laser energy be transferred from the ignitor pulse to the assembled fuel core via {approx}MeV electrons. We have assembled a suite of diagnostics to characterize such transfer. Recent experiments have simultaneously fielded absolutely calibrated extreme ultraviolet multilayer imagers at 68 and 256eV; spherically bent crystal imagers at 4 and 8keV; multi-keV crystal spectrometers; MeV x-ray bremmstrahlung and electron and proton spectrometers (along the same line of sight); nuclear activation samples and a picosecond optical probe based interferometer. These diagnostics allow careful measurement of energy transport and deposition during and following laser-plasma interactions at extremely high intensities in both planar and conical targets. Augmented with accurate on-shot laser focal spot and pre-pulse characterization, these measurements are yielding new insight into energy coupling and are providing critical data for validating numerical PIC and hybrid PIC simulation codes in an area that is crucial for many applications, particularly fast ignition. Novel aspects of these diagnostics and how they are combined to extract quantitative data on ultra high intensity laser plasma interactions are discussed, together with implications for full-scale fast ignition experiments.

  1. [Fasting and physical endurance capacity].

    PubMed

    Schürch, P M

    1993-03-01

    Fasting, or zero calorie diets are used not only by overweight people as a means of losing weight, but by athletes too. Their use is then explained on philosophical grounds, with the aim of even enhancing sports performance. The purpose of this investigation consisted of quantifying the effects of a 10-day fast on maximum performance capacity and endurance (as measured on a bicycle ergometer) of 12 female students of physical education of normal weight. The measurements included resting and exercise metabolism determinants, as well as weight and lean body mass. The main results show that after the diet period the maximum ergometric performance was lower in absolute terms as well as in relation to weight or lean body mass. Performance capacity for submaximal exercise was also reduced. Fat combustion was enhanced both at rest and during exercise. The reduction of maximum performance and endurance capacity may be explained by an enhanced muscle breakdown, an efficiency drop of muscular work, and an inadequate glycogen content of the acting muscles. Shorter fasting periods of 24-36 hours also lead to a lower performance level for exercise bouts extending from several minutes to 1-3 hours. An enhancement of fat combustion was always conspicuous. One may conclude that optimal physical performance is dependent on full hepatic and muscle glycogen stores. Glycogen concentration in the liver decreases sharply as a matter of fact after merely one day of carbohydrate shortage. Zero calorie or low carbohydrate diets are thus at variance with an optimal physical work capacity.

  2. A repeating fast radio burst

    NASA Astrophysics Data System (ADS)

    Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.

    2016-03-01

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  3. Heterogeneous Transmutation Sodium Fast Reactor

    SciTech Connect

    S. E. Bays

    2007-09-01

    The threshold-fission (fertile) nature of Am-241 is used to destroy this minor actinide by capitalizing upon neutron capture instead of fission within a sodium fast reactor. This neutron-capture and its subsequent decay chain leads to the breeding of even neutron number plutonium isotopes. A slightly moderated target design is proposed for breeding plutonium in an axial blanket located above the active “fast reactor” driver fuel region. A parametric study on the core height and fuel pin diameter-to-pitch ratio is used to explore the reactor and fuel cycle aspects of this design. This study resulted in both non-flattened and flattened core geometries. Both of these designs demonstrated a high capacity for removing americium from the fuel cycle. A reactivity coefficient analysis revealed that this heterogeneous design will have comparable safety aspects to a homogeneous reactor of comparable size. A mass balance analysis revealed that the heterogeneous design may reduce the number of fast reactors needed to close the current once-through light water reactor fuel cycle.

  4. A repeating fast radio burst.

    PubMed

    Spitler, L G; Scholz, P; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-03-10

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  5. Fast superconducting magnetic field switch

    DOEpatents

    Goren, Yehuda; Mahale, Narayan K.

    1996-01-01

    The superconducting magnetic switch or fast kicker magnet is employed with electron stream or a bunch of electrons to rapidly change the direction of flow of the electron stream or bunch of electrons. The apparatus employs a beam tube which is coated with a film of superconducting material. The tube is cooled to a temperature below the superconducting transition temperature and is subjected to a constant magnetic field which is produced by an external dc magnet. The magnetic field produced by the dc magnet is less than the critical field for the superconducting material, thus, creating a Meissner Effect condition. A controllable fast electromagnet is used to provide a magnetic field which supplements that of the dc magnet so that when the fast magnet is energized the combined magnetic field is now greater that the critical field and the superconducting material returns to its normal state allowing the magnetic field to penetrate the tube. This produces an internal field which effects the direction of motion and of the electron stream or electron bunch. The switch can also operate as a switching mechanism for charged particles.

  6. Fast superconducting magnetic field switch

    DOEpatents

    Goren, Y.; Mahale, N.K.

    1996-08-06

    The superconducting magnetic switch or fast kicker magnet is employed with electron stream or a bunch of electrons to rapidly change the direction of flow of the electron stream or bunch of electrons. The apparatus employs a beam tube which is coated with a film of superconducting material. The tube is cooled to a temperature below the superconducting transition temperature and is subjected to a constant magnetic field which is produced by an external dc magnet. The magnetic field produced by the dc magnet is less than the critical field for the superconducting material, thus, creating a Meissner Effect condition. A controllable fast electromagnet is used to provide a magnetic field which supplements that of the dc magnet so that when the fast magnet is energized the combined magnetic field is now greater that the critical field and the superconducting material returns to its normal state allowing the magnetic field to penetrate the tube. This produces an internal field which effects the direction of motion and of the electron stream or electron bunch. The switch can also operate as a switching mechanism for charged particles. 6 figs.

  7. The effects of chronic achievement motivation and achievement primes on the activation of achievement and fun goals.

    PubMed

    Hart, William; Albarracín, Dolores

    2009-12-01

    This research examined the hypothesis that situational achievement cues can elicit achievement or fun goals depending on chronic differences in achievement motivation. In 4 studies, chronic differences in achievement motivation were measured, and achievement-denoting words were used to influence behavior. The effects of these variables were assessed on self-report inventories, task performance, task resumption following an interruption, and the pursuit of means relevant to achieving or having fun. Findings indicated that achievement priming (vs. control priming) activated a goal to achieve and inhibited a goal to have fun in individuals with chronically high-achievement motivation but activated a goal to have fun and inhibited a goal to achieve in individuals with chronically low-achievement motivation.

  8. The Effects of Chronic Achievement Motivation and Achievement Primes on the Activation of Achievement and Fun Goals

    PubMed Central

    Hart, William; Albarracín, Dolores

    2013-01-01

    This research examined the hypothesis that situational achievement cues can elicit achievement or fun goals depending on chronic differences in achievement motivation. In 4 studies, chronic differences in achievement motivation were measured, and achievement-denoting words were used to influence behavior. The effects of these variables were assessed on self-report inventories, task performance, task resumption following an interruption, and the pursuit of means relevant to achieving or having fun. Findings indicated that achievement priming (vs. control priming) activated a goal to achieve and inhibited a goal to have fun in individuals with chronically high-achievement motivation but activated a goal to have fun and inhibited a goal to achieve in individuals with chronically low-achievement motivation. PMID:19968423

  9. Spectrum of mutations in the CFTR gene in cystic fibrosis patients of Spanish ancestry.

    PubMed

    Alonso, M J; Heine-Suñer, D; Calvo, M; Rosell, J; Giménez, J; Ramos, M D; Telleria, J J; Palacio, A; Estivill, X; Casals, T

    2007-03-01

    We analyzed 1,954 Spanish cystic fibrosis (CF) alleles in order to define the molecular spectrum of mutations in the CFTR gene in Spanish CF patients. Commercial panels showed a limited detection power, leading to the identification of only 76% of alleles. Two scanning techniques, denaturing gradient gel electrophoresis (DGGE) and single strand conformation polymorphism/hetroduplex (SSCP/HD), were carried out to detect CFTR sequence changes. In addition, intragenic markers IVS8CA, IVS8-6(T)n and IVS17bTA were also analyzed. Twelve mutations showed frequencies above 1%, p.F508del being the most frequent mutation (51%). We found that eighteen mutations need to be studied to achieve a detection level of 80%. Fifty-one mutations (42%) were observed once. In total, 121 disease-causing mutations were identified, accounting for 96% (1,877 out of 1,954) of CF alleles. Specific geographic distributions for the most common mutations, p.F508del, p.G542X, c.1811 + 1.6kbA > G and c.1609delCA, were confirmed. Furthermore, two other relatively common mutations (p.V232D and c.2789 + 5G > A) showed uneven geographic distributions. This updated information on the spectrum of CF mutations in Spain will be useful for improving genetic testing, as well as to facilitate counselling in people of Spanish ancestry. In addition, this study contributes to defining the molecular spectrum of CF in Europe, and corroborates the high molecular mutation heterogeneity of Mediterranean populations.

  10. Fast wave current drive on DIII-D

    SciTech Connect

    deGrassie, J.S.; Petty, C.C.; Pinsker, R.I.

    1995-07-01

    The physics of electron heating and current drive with the fast magnetosonic wave has been demonstrated on DIII-D, in reasonable agreement with theoretical modeling. A recently completed upgrade to the fast wave capability should allow full noninductive current drive in steady state advanced confinement discharges and provide some current density profile control for the Advanced Tokamak Program. DIII-D now has three four-strap fast wave antennas and three transmitters, each with nominally 2 MW of generator power. Extensive experiments have been conducted with the first system, at 60 MHz, while the two newer systems have come into operation within the past year. The newer systems are configured for 60 to 120 MHz. The measured FWCD efficiency is found to increase linearly with electron temperature as {gamma} = 0.4 {times} 10{sup 18} T{sub eo} (keV) [A/m{sup 2}W], measured up to central electron temperature over 5 keV. A newly developed technique for determining the internal noninductive current density profile gives efficiencies in agreement with this scaling and profiles consistent with theoretical predictions. Full noninductive current drive at 170 kA was achieved in a discharge prepared by rampdown of the Ohmic current. Modulation of microwave reflectometry signals at the fast wave frequency is being used to investigate fast wave propagation and damping. Additionally, rf pick-up probes on the internal boundary of the vessel provide a comparison with ray tracing codes, with dear evidence for a toroidally directed wave with antenna phasing set for current drive. There is some experimental evidence for fast wave absorption by energetic beam ions at high cyclotron harmonic resonances.

  11. New mutation of the Na channel in the severe form of potassium-aggravated myotonia.

    PubMed

    Kubota, Tomoya; Kinoshita, Masanobu; Sasaki, Ryogen; Aoike, Futoshi; Takahashi, Masanori P; Sakoda, Saburo; Hirose, Kazuhiko

    2009-05-01

    Myotonia manifests in several hereditary diseases, including hyperkalemic periodic paralysis (HyperPP), paramyotonia congenita (PMC), and potassium-aggravated myotonia (PAM). These are allelic disorders originating from missense mutations in the gene that codes the skeletal muscle sodium channel, Nav1.4. Moreover, a severe form of PAM has been designated as myotonia permanens. A new mutation of Nav1.4, Q1633E, was identified in a Japanese family presenting with the PAM phenotype. The proband suffered from cyanotic attacks during infancy. The mutated amino acid residue is located on the EF-hand calcium-binding motif in the intracellular C-terminus. A functional analysis of the mutant channel using the voltage-clamp method revealed disruption of fast inactivation, a slower rate of current decay, and a depolarized shift in the voltage dependence of availability. This study has identified a new mutation of PAM with a severe phenotype and emphasizes the importance of the C-terminus for fast inactivation of the sodium channel. Muscle Nerve 39: 666-673, 2009.

  12. Enhanced slow inactivation by V445M: a sodium channel mutation associated with myotonia.

    PubMed Central

    Takahashi, M P; Cannon, S C

    1999-01-01

    Over 20 different missense mutations in the alpha subunit of the adult skeletal muscle Na channel have been identified in families with either myotonia (muscle stiffness) or periodic paralysis, or both. The V445M mutation was recently found in a family with myotonia but no weakness. This mutation in transmembrane segment IS6 is novel because no other disease-associated mutations are in domain I. Na currents were recorded from V445M and wild-type channels transiently expressed in human embryonic kidney cells. In common with other myotonic mutants studied to date, fast gating behavior was altered by V445M in a manner predicted to increase excitability: an impairment of fast inactivation increased the persistent Na current at 10 ms and activation had a hyperpolarized shift (4 mV). In contrast, slow inactivation was enhanced by V445M due to both a slower recovery (10 mV left shift in beta(V)) and an accelerated entry rate (1.6-fold). Our results provide additional evidence that IS6 is crucial for slow inactivation and show that enhanced slow inactivation cannot prevent myotonia, whereas previous studies have shown that disrupted slow inactivation predisposes to episodic paralysis. PMID:9929487

  13. Boosted Fast Flux Loop Final Report

    SciTech Connect

    Boosted Fast Flux Loop Project Staff

    2009-09-01

    that further funding for the project would be suspended. Remaining funds have been used to prepare and irradiate mini-plates of the proposed booster fuel. The current baseline design is for a set of three test positions inside an in-pile tube with a thermal neutron absorber and heat sink made of aluminum mixed with hafnium. Operating the ATR at power levels needed to achieve the required fast flux will result in an estimated increase in ATR fuel consumption between 15 and 20% above present rates and a reduction in the time between fuel replacements. Preliminary safety analyses conducted have indicted safe operation of the ATR with the GTL under normal, abnormal, and postulated accident conditions. More comprehensive analyses are needed.

  14. Fast skeletal muscle troponin activation increases force of mouse fast skeletal muscle and ameliorates weakness due to nebulin-deficiency.

    PubMed

    Lee, Eun-Jeong; De Winter, Josine M; Buck, Danielle; Jasper, Jeffrey R; Malik, Fady I; Labeit, Siegfried; Ottenheijm, Coen A; Granzier, Henk

    2013-01-01

    The effect of the fast skeletal muscle troponin activator, CK-2066260, on calcium-induced force development was studied in skinned fast skeletal muscle fibers from wildtype (WT) and nebulin deficient (NEB KO) mice. Nebulin is a sarcomeric protein that when absent (NEB KO mouse) or present at low levels (nemaline myopathy (NM) patients with NEB mutations) causes muscle weakness. We studied the effect of fast skeletal troponin activation on WT muscle and tested whether it might be a therapeutic mechanism to increase muscle strength in nebulin deficient muscle. We measured tension-pCa relations with and without added CK-2066260. Maximal active tension in NEB KO tibialis cranialis fibers in the absence of CK-2066260 was ∼60% less than in WT fibers, consistent with earlier work. CK-2066260 shifted the tension-calcium relationship leftwards, with the largest relative increase (up to 8-fold) at low to intermediate calcium levels. This was a general effect that was present in both WT and NEB KO fiber bundles. At pCa levels above ∼6.0 (i.e., calcium concentrations <1 µM), CK-2066260 increased tension of NEB KO fibers to beyond that of WT fibers. Crossbridge cycling kinetics were studied by measuring k(tr) (rate constant of force redevelopment following a rapid shortening/restretch). CK-2066260 greatly increased k(tr) at submaximal activation levels in both WT and NEB KO fiber bundles. We also studied the sarcomere length (SL) dependence of the CK-2066260 effect (SL 2.1 µm and 2.6 µm) and found that in the NEB KO fibers, CK-2066260 had a larger effect on calcium sensitivity at the long SL. We conclude that fast skeletal muscle troponin activation increases force at submaximal activation in both wildtype and NEB KO fiber bundles and, importantly, that this troponin activation is a potential therapeutic mechanism for increasing force in NM and other skeletal muscle diseases with loss of muscle strength.

  15. A fast collocation method for a variable-coefficient nonlocal diffusion model

    NASA Astrophysics Data System (ADS)

    Wang, Che; Wang, Hong

    2017-02-01

    We develop a fast collocation scheme for a variable-coefficient nonlocal diffusion model, for which a numerical discretization would yield a dense stiffness matrix. The development of the fast method is achieved by carefully handling the variable coefficients appearing inside the singular integral operator and exploiting the structure of the dense stiffness matrix. The resulting fast method reduces the computational work from O (N3) required by a commonly used direct solver to O (Nlog ⁡ N) per iteration and the memory requirement from O (N2) to O (N). Furthermore, the fast method reduces the computational work of assembling the stiffness matrix from O (N2) to O (N). Numerical results are presented to show the utility of the fast method.

  16. Stationary Liquid Fuel Fast Reactor

    SciTech Connect

    Yang, Won Sik; Grandy, Andrew; Boroski, Andrew; Krajtl, Lubomir; Johnson, Terry

    2015-09-30

    For effective burning of hazardous transuranic (TRU) elements of used nuclear fuel, a transformational advanced reactor concept named SLFFR (Stationary Liquid Fuel Fast Reactor) was proposed based on stationary molten metallic fuel. The fuel enters the reactor vessel in a solid form, and then it is heated to molten temperature in a small melting heater. The fuel is contained within a closed, thick container with penetrating coolant channels, and thus it is not mixed with coolant nor flow through the primary heat transfer circuit. The makeup fuel is semi- continuously added to the system, and thus a very small excess reactivity is required. Gaseous fission products are also removed continuously, and a fraction of the fuel is periodically drawn off from the fuel container to a processing facility where non-gaseous mixed fission products and other impurities are removed and then the cleaned fuel is recycled into the fuel container. A reference core design and a preliminary plant system design of a 1000 MWt TRU- burning SLFFR concept were developed using TRU-Ce-Co fuel, Ta-10W fuel container, and sodium coolant. Conservative design approaches were adopted to stay within the current material performance database. Detailed neutronics and thermal-fluidic analyses were performed to develop a reference core design. Region-dependent 33-group cross sections were generated based on the ENDF/B-VII.0 data using the MC2-3 code. Core and fuel cycle analyses were performed in theta-r-z geometries using the DIF3D and REBUS-3 codes. Reactivity coefficients and kinetics parameters were calculated using the VARI3D perturbation theory code. Thermo-fluidic analyses were performed using the ANSYS FLUENT computational fluid dynamics (CFD) code. Figure 0.1 shows a schematic radial layout of the reference 1000 MWt SLFFR core, and Table 0.1 summarizes the main design parameters of SLFFR-1000 loop plant. The fuel container is a 2.5 cm thick cylinder with an inner radius of 87.5 cm. The fuel

  17. Application of Fast Multipole Methods to the NASA Fast Scattering Code

    NASA Technical Reports Server (NTRS)

    Dunn, Mark H.; Tinetti, Ana F.

    2008-01-01

    The NASA Fast Scattering Code (FSC) is a versatile noise prediction program designed to conduct aeroacoustic noise reduction studies. The equivalent source method is used to solve an exterior Helmholtz boundary value problem with an impedance type boundary condition. The solution process in FSC v2.0 requires direct manipulation of a large, dense system of linear equations, limiting the applicability of the code to small scales and/or moderate excitation frequencies. Recent advances in the use of Fast Multipole Methods (FMM) for solving scattering problems, coupled with sparse linear algebra techniques, suggest that a substantial reduction in computer resource utilization over conventional solution approaches can be obtained. Implementation of the single level FMM (SLFMM) and a variant of the Conjugate Gradient Method (CGM) into the FSC is discussed in this paper. The culmination of this effort, FSC v3.0, was used to generate solutions for three configurations of interest. Benchmarking against previously obtained simulations indicate that a twenty-fold reduction in computational memory and up to a four-fold reduction in computer time have been achieved on a single processor.

  18. Fast neutron imaging device and method

    SciTech Connect

    Popov, Vladimir; Degtiarenko, Pavel; Musatov, Igor V.

    2014-02-11

    A fast neutron imaging apparatus and method of constructing fast neutron radiography images, the apparatus including a neutron source and a detector that provides event-by-event acquisition of position and energy deposition, and optionally timing and pulse shape for each individual neutron event detected by the detector. The method for constructing fast neutron radiography images utilizes the apparatus of the invention.

  19. Fast Foods, Organic Foods, Fad Diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is no standard definition of fast food. Generally, fast food is eaten without cutlery, and fast-food restaurants have no wait staff. Failure to have a standardized definition makes it difficult to compare studies. Foods available outside the home tend to be high in energy and fat compared w...

  20. Joint inference of microsatellite mutation models, population history and genealogies using transdimensional Markov Chain Monte Carlo.

    PubMed

    Wu, Chieh-Hsi; Drummond, Alexei J

    2011-05-01

    We provide a framework for Bayesian coalescent inference from microsatellite data that enables inference of population history parameters averaged over microsatellite mutation models. To achieve this we first implemented a rich family of microsatellite mutation models and related components in the software package BEAST. BEAST is a powerful tool that performs Bayesian MCMC analysis on molecular data to make coalescent and evolutionary inferences. Our implementation permits the application of existing nonparametric methods to microsatellite data. The implemented microsatellite models are based on the replication slippage mechanism and focus on three properties of microsatellite mutation: length dependency of mutation rate, mutational bias toward expansion or contraction, and number of repeat units changed in a single mutation event. We develop a new model that facilitates microsatellite model averaging and Bayesian model selection by transdimensional MCMC. With Bayesian model averaging, the posterior distributions of population history parameters are integrated across a set of microsatellite models and thus account for model uncertainty. Simulated data are used to evaluate our method in terms of accuracy and precision of estimation and also identification of the true mutation model. Finally we apply our method to a red colobus monkey data set as an example.

  1. Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing

    PubMed Central

    Weisschuh, Nicole; Mayer, Anja K.; Strom, Tim M.; Kohl, Susanne; Glöckle, Nicola; Schubach, Max; Andreasson, Sten; Bernd, Antje; Birch, David G.; Hamel, Christian P.; Heckenlively, John R.; Jacobson, Samuel G.; Kamme, Christina; Kellner, Ulrich; Kunstmann, Erdmute; Maffei, Pietro; Reiff, Charlotte M.; Rohrschneider, Klaus; Rosenberg, Thomas; Rudolph, Günther; Vámos, Rita; Varsányi, Balázs; Weleber, Richard G.; Wissinger, Bernd

    2016-01-01

    Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes. PMID:26766544

  2. Epigenomic annotation of noncoding mutations identifies mutated pathways in primary liver cancer

    PubMed Central

    Lowdon, Rebecca F.

    2017-01-01

    Evidence that noncoding mutation can result in cancer driver events is mounting. However, it is more difficult to assign molecular biological consequences to noncoding mutations than to coding mutations, and a typical cancer genome contains many more noncoding mutations than protein-coding mutations. Accordingly, parsing functional noncoding mutation signal from noise remains an important challenge. Here we use an empirical approach to identify putatively functional noncoding somatic single nucleotide variants (SNVs) from liver cancer genomes. Annotation of candidate variants by publicly available epigenome datasets finds that 40.5% of SNVs fall in regulatory elements. When assigned to specific regulatory elements, we find that the distribution of regulatory element mutation mirrors that of nonsynonymous coding mutation, where few regulatory elements are recurrently mutated in a patient population but many are singly mutated. We find potential gain-of-binding site events among candidate SNVs, suggesting a mechanism of action for these variants. When aggregating noncoding somatic mutation in promoters, we find that genes in the ERBB signaling and MAPK signaling pathways are significantly enriched for promoter mutations. Altogether, our results suggest that functional somatic SNVs in cancer are sporadic, but occasionally occur in regulatory elements and may affect phenotype by creating binding sites for transcriptional regulators. Accordingly, we propose that noncoding mutation should be formally accounted for when determining gene- and pathway-mutation burden in cancer. PMID:28333948

  3. Comparison of uncommon EGFR exon 21 L858R compound mutations with single mutation.

    PubMed

    Peng, Liang; Song, Zhigang; Jiao, Shunchang

    2015-01-01

    Non-small-cell lung cancer with epidermal growth factor receptor (EGFR) mutation is sensitive to EGFR tyrosine kinase inhibitors (TKIs). But little is known about the response to EGFR TKIs and the prognostic role of compound mutations. This study compared the uncommon EGFR exon 21 L858R compound mutations with single mutation to characterize EGFR compound mutations and investigated their response to EGFR TKI treatment. We retrospectively screened 799 non-small-cell lung cancer patients from August 1, 2009 to June 1, 2012 by EGFR mutation testing. EGFR mutations were detected in 443 patients, with 22 (4.97%) compound mutations. Subsequently, six patients with EGFR exon 21 L858R compound mutations and 18 paired patients with single L858R mutation were well characterized. Finally, we also analyzed the EGFR TKI treatment response and patients' outcomes of compound or single L858R mutations. There was no differential treatment effect on the disease control rate and objective response rate between the L858R compound mutations and single mutation groups. No significant difference in overall survival or progression-free survival of these two groups was found by log-rank test. In conclusion, we demonstrated that no significant difference was detected in the response to EGFR TKIs and patients' outcomes in the compound and single mutation groups.

  4. In situ fast ellipsometric analysis of repetitive surface phenomena

    NASA Astrophysics Data System (ADS)

    Costa, J.; Campmany, J.; Canillas, A.; Andújar, J. L.; Bertran, E.

    1997-08-01

    We present an ellipsometric technique and ellipsometric analysis of repetitive phenomena, based on the experimental arrangement of conventional phase modulated ellipsometers (PME) conceived to study fast surface phenomena in repetitive processes such as periodic and triggered experiments. Phase modulated ellipsometry is a highly sensitive surface characterization technique that is widely used in the real-time study of several processes such as thin film deposition and etching. However, fast transient phenomena cannot be analyzed with this technique because precision requirements limit the data acquisition rate to about 25 Hz. The presented new ellipsometric method allows the study of fast transient phenomena in repetitive processes with a time resolution that is mainly limited by the data acquisition system. As an example, we apply this new method to the study of surface changes during plasma enhanced chemical vapor deposition of amorphous silicon in a modulated radio frequency discharge of SiH4. This study has revealed the evolution of the optical parameters of the film on the millisecond scale during the plasma on and off periods. The presented ellipsometric method extends the capabilities of PME arrangements and permits the analysis of fast surface phenomena that conventional PME cannot achieve.

  5. Fast reciprocating probe system on the EAST superconducting tokamak.

    PubMed

    Zhang, W; Chang, J F; Wan, B N; Xu, G S; Xiao, C J; Li, B; Xu, C S; Yan, N; Wang, L; Liu, S C; Jiang, M; Liu, P

    2010-11-01

    A new fast reciprocating probe system (FRPS) has been built and installed on the outer midplane of the EAST tokamak to investigate the profiles of the boundary plasma parameters such as electron density and temperature. The system consists of a two-stage motion drive mechanism: slow motion and fast motion. The fast motion is powered by a servo motor, which drives the probe horizontally up to 50 cm to scan the edge region of the EAST tokamak. The maximum velocity achieved is 2 m/s. High velocity and flexible control of the fast motion are the remarkable features of this FRPS. A specially designed connector installed at the front end of the probe shaft makes it easy to install or replace the probe head on FRPS. During the latest experimental campaign in the spring of 2010, a probe head with seven tips, including two tips for a Mach probe, has been used. An example is given for simultaneous profile measurements of the plasma temperature, plasma density, and the plasma flow velocity.

  6. Competency-Based Achievement System

    PubMed Central

    Ross, Shelley; Poth, Cheryl N.; Donoff, Michel; Humphries, Paul; Steiner, Ivan; Schipper, Shirley; Janke, Fred; Nichols, Darren

    2011-01-01

    Abstract Problem addressed Family medicine residency programs require innovative means to assess residents’ competence in “soft” skills (eg, patient-centred care, communication, and professionalism) and to identify residents who are having difficulty early enough in their residency to provide remedial training. Objective of program To develop a method to assess residents’ competence in various skills and to identify residents who are having difficulty. Program description The Competency-Based Achievement System (CBAS) was designed to measure competence using 3 main principles: formative feedback, guided self-assessment, and regular face-to-face meetings. The CBAS is resident driven and provides a framework for meaningful interactions between residents and advisors. Residents use the CBAS to organize and review their feedback, to guide their own assessment of their progress, and to discern their future learning needs. Advisors use the CBAS to monitor, guide, and verify residents’ knowledge of and competence in important skills. Conclusion By focusing on specific skills and behaviour, the CBAS enables residents and advisors to make formative assessments and to communicate their findings. Feedback indicates that the CBAS is a user-friendly and helpful system to assess competence. PMID:21918129

  7. Academic Achievement Among Juvenile Detainees

    PubMed Central

    Grigorenko, Elena L.; Macomber, Donna; Hart, Lesley; Naples, Adam; Chapman, John; Geib, Catherine F.; Chart, Hilary; Tan, Mei; Wolhendler, Baruch; Wagner, Richard

    2016-01-01

    The literature has long pointed to heightened frequencies of learning disabilities (LD) within the population of law offenders; however, a systematic appraisal of these observations, careful estimation of these frequencies, and investigation of their correlates and causes have been lacking. Here we present data collected from all youth (1,337 unique admissions, mean age 14.81, 20.3% females) placed in detention in Connecticut (January 1, 2010–July 1, 2011). All youth completed a computerized educational screener designed to test a range of performance in reading (word and text levels) and mathematics. A subsample (n = 410) received the Wide Range Achievement Test, in addition to the educational screener. Quantitative (scale-based) and qualitative (grade-equivalence-based) indicators were then analyzed for both assessments. Results established the range of LD in this sample from 13% to 40%, averaging 24.9%. This work provides a systematic exploration of the type and severity of word and text reading and mathematics skill deficiencies among juvenile detainees and builds the foundation for subsequent efforts that may link these deficiencies to both more formal, structured, and variable definitions and classifications of LD, and to other types of disabilities (e.g., intellectual disability) and developmental disorders (e.g., ADHD) that need to be conducted in future research. PMID:24064502

  8. Academic Achievement Among Juvenile Detainees.

    PubMed

    Grigorenko, Elena L; Macomber, Donna; Hart, Lesley; Naples, Adam; Chapman, John; Geib, Catherine F; Chart, Hilary; Tan, Mei; Wolhendler, Baruch; Wagner, Richard

    2015-01-01

    The literature has long pointed to heightened frequencies of learning disabilities (LD) within the population of law offenders; however, a systematic appraisal of these observations, careful estimation of these frequencies, and investigation of their correlates and causes have been lacking. Here we present data collected from all youth (1,337 unique admissions, mean age 14.81, 20.3% females) placed in detention in Connecticut (January 1, 2010-July 1, 2011). All youth completed a computerized educational screener designed to test a range of performance in reading (word and text levels) and mathematics. A subsample (n = 410) received the Wide Range Achievement Test, in addition to the educational screener. Quantitative (scale-based) and qualitative (grade-equivalence-based) indicators were then analyzed for both assessments. Results established the range of LD in this sample from 13% to 40%, averaging 24.9%. This work provides a systematic exploration of the type and severity of word and text reading and mathematics skill deficiencies among juvenile detainees and builds the foundation for subsequent efforts that may link these deficiencies to both more formal, structured, and variable definitions and classifications of LD, and to other types of disabilities (e.g., intellectual disability) and developmental disorders (e.g., ADHD) that need to be conducted in future research.

  9. Instrumentation, Monitoring and NDE for New Fast Reactors

    SciTech Connect

    Bond, Leonard J.; Doctor, Steven R.; Bunch, Kyle J.; Good, Morris S.; Waltar, Alan E.

    2007-07-28

    The Global Nuclear Energy Partnership (GNEP) has been proposed as a viable system in which to close the fuel cycle in a manner consistent with markedly expanding the global role of nuclear power while significantly reducing proliferation risks. A key part of this system relies on the development of actinide transmutation, which can only be effectively accomplished in a fast-spectrum reactor. The fundamental physics for fast reactors is well established. However, to achieve higher standards of safety and reliability, operate with longer intervals between outages, and achieve high operating capacity factors, new instrumentation and on-line monitoring capabilities will be required--during both fabrication and operation. Since the Fast Flux Test Facility (FFTF) and Experimental Breeder Reactor – II (EBR-II) reactors were operational in the USA, there have been major advances in instrumentation, not the least being the move to digital systems. Some specific capabilities have been developed outside the USA, but new or at least re-established capabilities will be required. In many cases the only available information is in reports and papers. New and improved sensors and instrumentation will be required. Advanced instrumentation has been developed for high-temperature/high-flux conditions in some cases, but most of the original researchers and manufacturers are retired or no longer in business.

  10. Coronal Seismology -- Achievements and Perspectives

    NASA Astrophysics Data System (ADS)

    Ruderman, Michael

    Coronal seismology is a new and fast developing branch of the solar physics. The main idea of coronal seismology is the same as of any branches of seismology: to determine basic properties of a medium using properties of waves propagating in this medium. The waves and oscillations in the solar corona are routinely observed in the late space missions. In our brief review we concentrate only on one of the most spectacular type of oscillations observed in the solar corona - the transverse oscillations of coronal magnetic loops. These oscillations were first observed by TRACE on 14 July 1998. At present there are a few dozens of similar observations. Shortly after the first observation of the coronal loop transverse oscillations they were interpreted as kink oscillations of magnetic tubes with the ends frozen in the dense photospheric plasma. The frequency of the kink oscillation is proportional to the magnetic field magnitude and inversely proportional to the tube length times the square root of the plasma density. This fact was used to estimate the magnetic field magnitude in the coronal loops. In 2004 the first simultaneous observation of the fundamental mode and first overtone of the coronal loop transverse oscillation was reported. If we model a coronal loop as a homogeneous magnetic tube, then the ratio of the frequencies of the first overtone and the fundamental mode should be equal to 2. However, the ratio of the observed frequencies was smaller than 2. This is related to the density variation along the loop. If we assume that the corona is isothermal and prescribe the loop shape (usually it is assumed that it has the shape of half-circle), then, using the ratio of the two frequencies, we can determine the temperature of the coronal plasma. The first observation of transverse oscillations of the coronal loops showed that they were strongly damped. This phenomenon was confirmed by the subsequent observations. At present, the most reliable candidate for the

  11. Too Many Mutants with Multiple Mutations

    PubMed Central

    Drake, John W.

    2007-01-01

    It has recently become clear that the classical notion of the random nature of mutation does not hold for the distribution of mutations among genes: most collections of mutants contain more isolates with two or more mutations than predicted by the mutant frequency on the assumption of a random distribution of mutations. Excesses of multiples are seen in a wide range of organisms, including riboviruses, DNA viruses, prokaryotes, yeasts, and higher eukaryotic cell lines and tissues. In addition, such excesses are produced by DNA polymerases in vitro. These “multiples” appear to be generated by transient, localized hypermutation rather than by heritable mutator mutations. The components of multiples are sometimes scattered at random and sometimes display an excess of smaller distances between mutations. As yet, almost nothing is known about the mechanisms that generate multiples, but such mutations have the capacity to accelerate those evolutionary pathways that require multiple mutations where the individual mutations are neutral or deleterious. Examples that impinge on human health may include carcinogenesis and the adaptation of microbial pathogens as they move between individual hosts. PMID:17687667

  12. Too many mutants with multiple mutations.

    PubMed

    Drake, John W

    2007-01-01

    It has recently become clear that the classical notion of the random nature of mutation does not hold for the distribution of mutations among genes: most collections of mutants contain more isolates with two or more mutations than predicted by the mutant frequency on the assumption of a random distribution of mutations. Excesses of multiples are seen in a wide range of organisms, including riboviruses, DNA viruses, prokaryotes, yeasts, and higher eukaryotic cell lines and tissues. In addition, such excesses are produced by DNA polymerases in vitro. These "multiples" appear to be generated by transient, localized hypermutation rather than by heritable mutator mutations. The components of multiples are sometimes scattered at random and sometimes display an excess of smaller distances between mutations. As yet, almost nothing is known about the mechanisms that generate multiples, but such mutations have the capacity to accelerate those evolutionary pathways that require multiple mutations where the individual mutations are neutral or deleterious. Examples that impinge on human health may include carcinogenesis and the adaptation of microbial pathogens as they move between individual hosts.

  13. [TP53 mutations and molecular epidemiology].

    PubMed

    Otsuka, Kazunori; Ishioka, Chikashi

    2007-05-01

    Tumor suppressor p53 protein is activated by a variety of cellular stresses through several pathways and transactivates its downstream genes, including regulators of cell cycle, apoptosis and DNA repair. The loss of p53 function by TP53 gene mutations therefore fails to activate these genes and is thought to be a critical cause of carcinogenesis and/or tumor progression. TP53 is one of the most frequently mutated genes in human cancer. TP53 mutations are found in about 50% of human cancers, although the frequency of TP53 mutations differs among tumor types. However, the degree of functional disorder of mutant p53 varies according to the type of TP53 mutation. And the effects of p53 on cancer formation and/or progression are influenced by the degree of p53 dysfunction. So it is important to analyze the effects of TP53 mutations carefully according to the oncogenicity of each mutation from the molecular epidemiological point of view. Here, together with some cautions needed for analyzing and interpreting the significance of TP53 gene mutations, we present some examples of the identified specific mutation spectrum and the correlation between the prognosis and TP53 mutation in some cancers.

  14. Specific Early Number Skills Mediate the Association between Executive Functioning Skills and Mathematics Achievement

    ERIC Educational Resources Information Center

    Fuhs, Mary Wagner; Hornburg, Caroline Byrd; McNeil, Nicole M.

    2016-01-01

    A growing literature reports significant associations between children's executive functioning skills and their mathematics achievement. The purpose of this study was to examine if specific early number skills, such as quantity discrimination, number line estimation, number sets identification, fast counting, and number word comprehension, mediate…

  15. Mutations affecting enzymatic activity in liver arginase

    SciTech Connect

    Vockley, J.G.; Tabor, D.E.; Goodman, B.K.

    1994-09-01

    The hydrolysis of arginine to ornithine and urea is catalyzed by arginase in the last step of the urea cycle. We examined a group of arginase deficient patients by PCR-SSCP analysis to characterize the molecular basis of this disorder. A heterogeneous population of nonsense mutations, microdeletions, and missense mutations has been identified in our cohort. Microdeletions which introduce premature stop codons downstream of the deletion and nonsense mutations result in no arginase activity. These mutations occur randomly along the gene. The majority of missense mutations identified appear to occur in regions of high cross-species homology. To test the effect of these missense mutations on arginase activity, site-directed mutagenesis was used to re-create the patient mutations for in vivo expression studies in a prokaryotic fusion-protein expression system. Of 4 different missense mutations identified in 6 individuals, only one was located outside of a conserved region. The three substitution mutations within the conserved regions had a significant effect on enzymatic activity (0-3.1 nmole/30min, normal is 1300-1400 nmoles/30min, as determined by in vitro arginase assay), while the fourth mutation, a T to S substitution, did not. In addition, site-directed mutagenesis was utilized to create mutations not in residues postulated to play a significant role in the enzymatic function or active site formation in manganese-binding proteins such as arginase. We have determined that the substitution of glycine for a histidine residue, located in a very highly conserved region of exon 3, and the substitution of a histidine and an aspartic acid residue within a similarly conserved region in exon 4, totally abolishes enzymatic activity. Mutations substituting glycine for an additional histidine and aspartic acid residue in exon 4 and two aspartic acid residues in exon 7 have also been created. We are currently in the process of characterizing these mutations.

  16. Independent Mobility Achieved through a Wireless Brain-Machine Interface

    PubMed Central

    Xu, Zhiming; Kyar, Toe K.; Ho, Duncun; Lim, Clement; Chan, Louiza; Chua, Yuanwei; Yao, Lei; Cheong, Jia Hao; Lee, Jung Hyup; Vishal, Kulkarni Vinayak; Guo, Yongxin; Chen, Zhi Ning; Lim, Lay K.; Li, Peng; Liu, Lei; Zou, Xiaodan; Ang, Kai K.; Gao, Yuan; Ng, Wai Hoe; Han, Boon Siew; Chng, Keefe; Guan, Cuntai; Je, Minkyu; Yen, Shih-Cheng

    2016-01-01

    Individuals with tetraplegia lack independent mobility, making them highly dependent on others to move from one place to another. Here, we describe how two macaques were able to use a wireless integrated system to control a robotic platform, over which they were sitting, to achieve independent mobility using the neuronal activity in their motor cortices. The activity of populations of single neurons was recorded using multiple electrode arrays implanted in the arm region of primary motor cortex, and decoded to achieve brain control of the platform. We found that free-running brain control of the platform (which was not equipped with any machine intelligence) was fast and accurate, resembling the performance achieved using joystick control. The decoding algorithms can be trained in the absence of joystick movements, as would be required for use by tetraplegic individuals, demonstrating that the non-human primate model is a good pre-clinical model for developing such a cortically-controlled movement prosthetic. Interestingly, we found that the response properties of some neurons differed greatly depending on the mode of control (joystick or brain control), suggesting different roles for these neurons in encoding movement intention and movement execution. These results demonstrate that independent mobility can be achieved without first training on prescribed motor movements, opening the door for the implementation of this technology in persons with tetraplegia. PMID:27802344

  17. Independent Mobility Achieved through a Wireless Brain-Machine Interface.

    PubMed

    Libedinsky, Camilo; So, Rosa; Xu, Zhiming; Kyar, Toe K; Ho, Duncun; Lim, Clement; Chan, Louiza; Chua, Yuanwei; Yao, Lei; Cheong, Jia Hao; Lee, Jung Hyup; Vishal, Kulkarni Vinayak; Guo, Yongxin; Chen, Zhi Ning; Lim, Lay K; Li, Peng; Liu, Lei; Zou, Xiaodan; Ang, Kai K; Gao, Yuan; Ng, Wai Hoe; Han, Boon Siew; Chng, Keefe; Guan, Cuntai; Je, Minkyu; Yen, Shih-Cheng

    2016-01-01

    Individuals with tetraplegia lack independent mobility, making them highly dependent on others to move from one place to another. Here, we describe how two macaques were able to use a wireless integrated system to control a robotic platform, over which they were sitting, to achieve independent mobility using the neuronal activity in their motor cortices. The activity of populations of single neurons was recorded using multiple electrode arrays implanted in the arm region of primary motor cortex, and decoded to achieve brain control of the platform. We found that free-running brain control of the platform (which was not equipped with any machine intelligence) was fast and accurate, resembling the performance achieved using joystick control. The decoding algorithms can be trained in the absence of joystick movements, as would be required for use by tetraplegic individuals, demonstrating that the non-human primate model is a good pre-clinical model for developing such a cortically-controlled movement prosthetic. Interestingly, we found that the response properties of some neurons differed greatly depending on the mode of control (joystick or brain control), suggesting different roles for these neurons in encoding movement intention and movement execution. These results demonstrate that independent mobility can be achieved without first training on prescribed motor movements, opening the door for the implementation of this technology in persons with tetraplegia.

  18. Comparison of Fast-Food and Non-Fast-Food Children's Menu Items

    ERIC Educational Resources Information Center

    Serrano, Elena L.; Jedda, Virginia B.

    2009-01-01

    Objective: Compare the macronutrient content of children's meals sold by fast-food restaurants (FFR) and non-fast-food restaurants (NFF). Design: All restaurants within the designated city limits were surveyed. Non-fast-food children's meals were purchased, weighed, and analyzed using nutrition software. All fast-food children's meals were…

  19. Sharing Leadership Responsibilities Results in Achievement Gains

    ERIC Educational Resources Information Center

    Armistead, Lew

    2010-01-01

    Collective, not individual, leadership in schools has a greater impact on student achievement; when principals and teachers share leadership responsibilities, student achievement is higher; and schools having high student achievement also display a vision for student achievement and teacher growth. Those are just a few of the insights into school…

  20. Closing the Achievement Gap: Challenges and Opportunities

    ERIC Educational Resources Information Center

    Robards, Shirley N.

    2008-01-01

    Closing the achievement gap between low- and high-achieving public school students is an important goal of public education. This article explores background information and research and discusses examples of best practices to close the achievement gap. Several plans have been proposed as ways to enhance the achievement of under-represented…

  1. Mechanisms for fast flare reconnection

    NASA Technical Reports Server (NTRS)

    Vanhoven, G.; Deeds, D.; Tachi, T.

    1988-01-01

    Normal collisional-resistivity mechanisms of magnetic reconnection have the drawback that they are too slow to explain the fast rise of solar flares. Two methods are examined which are proposed for the speed-up of the magnetic tearing instability: the anomalous enhancement of resistivity by the injection of MHD turbulence and the increase of Coulomb resistivity by radiative cooling. The results are described for nonlinear numerical simulations of these processes which show that the first does not provide the claimed effects, while the second yields impressive rates of reconnection, but low saturated energy outputs.

  2. Fast-acting valve actuator

    DOEpatents

    Cho, Nakwon

    1980-01-01

    A fast-acting valve actuator utilizes a spring driven pneumatically loaded piston to drive a valve gate. Rapid exhaust of pressurized gas from the pneumatically loaded side of the piston facilitates an extremely rapid piston stroke. A flexible selector diaphragm opens and closes an exhaust port in response to pressure differentials created by energizing and de-energizing a solenoid which controls the pneumatic input to the actuator as well as selectively providing a venting action to one side of the selector diaphragm.

  3. Fast pulse nonthermal plasma reactor

    DOEpatents

    Rosocha, Louis A.

    2005-06-14

    A fast pulsed nonthermal plasma reactor includes a discharge cell and a charging assembly electrically connected thereto. The charging assembly provides plural high voltage pulses to the discharge cell. Each pulse has a rise time between one and ten nanoseconds and a duration of three to twenty nanoseconds. The pulses create nonthermal plasma discharge within the discharge cell. Accordingly, the nonthermal plasma discharge can be used to remove pollutants from gases or break the gases into smaller molecules so that they can be more efficiently combusted.

  4. Fast feedback for linear colliders

    SciTech Connect

    Hendrickson, L.; Adolphsen, C.; Allison, S.; Gromme, T.; Grossberg, P.; Himel, T.; Krauter, K.; MacKenzie, R.; Minty, M.; Sass, R.

    1995-05-01

    A fast feedback system provides beam stabilization for the SLC. As the SLC is in some sense a prototype for future linear colliders, this system may be a prototype for future feedbacks. The SLC provides a good base of experience for feedback requirements and capabilities as well as a testing ground for performance characteristics. The feedback system controls a wide variety of machine parameters throughout the SLC and associated experiments, including regulation of beam position, angle, energy, intensity and timing parameters. The design and applications of the system are described, in addition to results of recent performance studies.

  5. Searches for Fast Radio Transients

    NASA Astrophysics Data System (ADS)

    Cordes, J. M.; McLaughlin, M. A.

    2003-10-01

    We discuss optimal detection of fast radio transients from astrophysical objects while taking into account the effects of propagation through intervening ionized media, including dispersion, scattering, and scintillation. Our analysis applies to the giant-pulse phenomenon exhibited by some pulsars, for which we show examples, and to radio pulses from other astrophysical sources, such as prompt radio emission from gamma-ray burst sources and modulated signals from extraterrestrial civilizations. We estimate scintillation parameters for extragalactic sources that take into account scattering both in the host galaxy and in foreground Galactic plasma.

  6. Fast, efficient lossless data compression

    NASA Technical Reports Server (NTRS)

    Ross, Douglas

    1991-01-01

    This paper presents lossless data compression and decompression algorithms which can be easily implemented in software. The algorithms can be partitioned into their fundamental parts which can be implemented at various stages within a data acquisition system. This allows for efficient integration of these functions into systems at the stage where they are most applicable. The algorithms were coded in Forth to run on a Silicon Composers Single Board Computer (SBC) using the Harris RTX2000 Forth processor. The algorithms require very few system resources and operate very fast. The performance of the algorithms with the RTX enables real time data compression and decompression to be implemented for a wide range of applications.

  7. Fast Translation Invariant Multiscale Image Denoising.

    PubMed

    Li, Meng; Ghosal, Subhashis

    2015-12-01

    Translation invariant (TI) cycle spinning is an effective method for removing artifacts from images. However, for a method using O(n) time, the exact TI cycle spinning by averaging all possible circulant shifts requires O(n(2)) time where n is the number of pixels, and therefore is not feasible in practice. Existing literature has investigated efficient algorithms to calculate TI version of some denoising approaches such as Haar wavelet. Multiscale methods, especially those based on likelihood decomposition, such as penalized likelihood estimator and Bayesian methods, have become popular in image processing because of their effectiveness in denoising images. As far as we know, there is no systematic investigation of the TI calculation corresponding to general multiscale approaches. In this paper, we propose a fast TI (FTI) algorithm and a more general k-TI (k-TI) algorithm allowing TI for the last k scales of the image, which are applicable to general d-dimensional images (d = 2, 3, …) with either Gaussian or Poisson noise. The proposed FTI leads to the exact TI estimation but only requires O(n log2 n) time. The proposed k-TI can achieve almost the same performance as the exact TI estimation, but requires even less time. We achieve this by exploiting the regularity present in the multiscale structure, which is justified theoretically. The proposed FTI and k-TI are generic in that they are applicable on any smoothing techniques based on the multiscale structure. We demonstrate the FTI and k-TI algorithms on some recently proposed state-of-the-art methods for both Poisson and Gaussian noised images. Both simulations and real data application confirm the appealing performance of the proposed algorithms. MATLAB toolboxes are online accessible to reproduce the results and be implemented for general multiscale denoising approaches provided by the users.

  8. A fast operator perturbation method for the solution of the special relativistic equation of radiative transfer in spherical symmetry

    NASA Technical Reports Server (NTRS)

    Hauschildt, P. H.

    1992-01-01

    A fast method for the solution of the radiative transfer equation in rapidly moving spherical media, based on an approximate Lambda-operator iteration, is described. The method uses the short characteristic method and a tridiagonal approximate Lambda-operator to achieve fast convergence. The convergence properties and the CPU time requirements of the method are discussed for the test problem of a two-level atom with background continuum absorption and Thomson scattering. Details of the actual implementation for fast vector and parallel computers are given. The method is accurate and fast enough to be incorporated in radiation-hydrodynamic calculations.

  9. Trichohepatoenteric syndrome: founder mutation in asian indians.

    PubMed

    Kotecha, U H; Movva, S; Puri, R D; Verma, I C

    2012-08-01

    Trichohepatoenteric syndrome (THES) is characterized by chronic diarrhea, dysmorphic facies and hair abnormalities. Hepatic involvement varies from no abnormality to cirrhosis and hemochromatosis. Recently, mutations in the tetratricopeptide repeat domain 37 (TTC37) gene were identified to cause THES. The c.2808G>A variation was suggested as a possible founder mutation among the South Asians. We further report 2 unrelated cases of Asian-Indian ethnicity (Gujrati) with THES, wherein targeted mutation analysis revealed the same mutation in homozygous form in both cases. These findings, as well as haplotype analysis, corroborate the founder mutation hypothesis amongst Asian Indo-Pakistani ethnic groups. A restriction enzyme-based method is also described to identify this founder mutation. One of our probands had multiple hepatic hemangiomas, a feature not previously observed in this syndrome.

  10. Mutations in the liver glycogen synthase gene in children with hypoglycemia due to glycogen storage disease type 0.

    PubMed Central

    Orho, M; Bosshard, N U; Buist, N R; Gitzelmann, R; Aynsley-Green, A; Blümel, P; Gannon, M C; Nuttall, F Q; Groop, L C

    1998-01-01

    Glycogen storage disease type 0 (GSD-0) is a rare form of fasting hypoglycemia presenting in infancy or early childhood and accompanied by high blood ketones and low alanine and lactate concentrations. Although feeding relieves symptoms, it often results in postprandial hyperglycemia and hyperlactatemia. The glycogen synthase (GS) activity has been low or immeasurable in liver biopsies, whereas the liver glycogen content has been only moderately decreased. To investigate whether mutations in the liver GS gene (GYS2) on chromosome 12p12.2 were involved in GSD-0, we determined the exon-intron structure of the GYS2 gene and examined nine affected children from five families for linkage of GSD-0 to the GYS2 gene. Mutation screening of the 16 GYS2 exons was done by single-strand conformational polymorphism (SSCP) and direct sequencing. Liver GS deficiency was diagnosed from liver biopsies (GS activity and glycogen content). GS activity in the liver of the affected children was extremely low or nil, resulting in subnormal glycogen content. After suggestive linkage to the GYS2 gene had been established (LOD score = 2.9; P < 0.01), mutation screening revealed several different mutations in these families, including a premature stop codon in exon 5 (Arg246X), a 5'-donor splice site mutation in intron 6 (G+1T--> CT), and missense mutations Asn39Ser, Ala339Pro, His446Asp, Pro479Gln, Ser483Pro, and Met491Arg. Seven of the affected children carried mutations on both alleles. The mutations could not be found in 200 healthy persons. Expression of the mutated enzymes in COS7 cells indicated severely impaired GS activity. In conclusion, the results demonstrate that GSD-0 is caused by different mutations in the GYS2 gene. PMID:9691087

  11. Does dragonfly's abdomen flexion help with fast turning maneuvers?

    NASA Astrophysics Data System (ADS)

    Liu, Geng; Li, Chengyu; Dong, Haibo; Flow Simulation Research Group Team

    2013-11-01

    Dragonflies are able to achieve fast turning maneuvers during take-off flights. Both asymmetric wing flapping and abdomen flexion have been observed during the fast turning. It's widely thought that the asymmetric wing beats are responsible of producing the aerodynamic moment needed for the body rotation. However, the dynamic effect of the abdomen flexion is not clear yet. In this study, an integrated experimental and computational approach is used to study the underlying dynamic effect of dragonfly abdomen flexion. It's found that dragonfly abdomen tended to bend towards the same side as the body reorienting to. Quantitative analysis have shown that during take-off turning maneuver the abdomen flexion can modulate the arm of force by changing the position of the center of mass relative to the thorax. As a result, roll and yaw moments produced by the wing flapping can be enhanced. This work is supported by NSF CBET-1313217. This work is supported by NSF CBET-1313217.

  12. Ultra-Fast Silicon Detectors for 4D tracking

    NASA Astrophysics Data System (ADS)

    Sola, V.; Arcidiacono, R.; Bellora, A.; Cartiglia, N.; Cenna, F.; Cirio, R.; Durando, S.; Ferrero, M.; Galloway, Z.; Gruey, B.; Freeman, P.; Mashayekhi, M.; Mandurrino, M.; Monaco, V.; Mulargia, R.; Obertino, M. M.; Ravera, F.; Sacchi, R.; Sadrozinski, H. F.-W.; Seiden, A.; Spencer, N.; Staiano, A.; Wilder, M.; Woods, N.; Zatserklyaniy, A.

    2017-02-01

    We review the progress toward the development of a novel type of silicon detectors suited for tracking with a picosecond timing resolution, the so called Ultra-Fast Silicon Detectors. The goal is to create a new family of particle detectors merging excellent position and timing resolution with GHz counting capabilities, very low material budget, radiation resistance, fine granularity, low power, insensitivity to magnetic field, and affordability. We aim to achieve concurrent precisions of ~ 10 ps and ~ 10 μm with a 50 μm thick sensor. Ultra-Fast Silicon Detectors are based on the concept of Low-Gain Avalanche Detectors, which are silicon detectors with an internal multiplication mechanism so that they generate a signal which is factor ~ 10 larger than standard silicon detectors.

  13. High Bandwidth Short Stroke Rotary Fast Tool Servo

    SciTech Connect

    Montesanti, R C; Trumper, D L

    2003-08-22

    This paper presents the design and performance of a new rotary fast tool servo (FTS) capable of developing the 40 g's tool tip acceleration required to follow a 5 micron PV sinusoidal surface at 2 kHz with a planned accuracy of 50 nm, and having a full stroke of 50 micron PV at lower frequencies. Tests with de-rated power supplies have demonstrated a closed-loop unity-gain bandwidth of 2 kHz with 20 g's tool acceleration, and we expect to achieve 40 g's with supplies providing {+-} 16 Amp to the Lorentz force actuator. The use of a fast tool servo with a diamond turning machine for producing non-axisymmetric or textured surfaces on a workpiece is well known. Our new rotary FTS was designed to specifically accommodate fabricating prescription textured surfaces on 5 mm diameter spherical target components for High Energy Density Physics experiments on the National Ignition Facility Laser (NIF).

  14. A Fast Technology Infusion Model for Aerospace Organizations

    NASA Technical Reports Server (NTRS)

    Shapiro, Andrew A.; Schone, Harald; Brinza, David E.; Garrett, Henry B.; Feather, Martin S.

    2006-01-01

    A multi-year Fast Technology Infusion initiative proposes a model for aerospace organizations to improve the cost-effectiveness by which they mature new, in-house developed software and hardware technologies for space mission use. The first year task under the umbrella of this initiative will provide the framework to demonstrate and document the fast infusion process. The viability of this approach will be demonstrated on two technologies developed in prior years with internal Jet Propulsion Laboratory (JPL) funding. One hardware technology and one software technology were selected for maturation within one calendar year or less. The overall objective is to achieve cost and time savings in the qualification of technologies. At the end of the recommended three-year effort, we will have demonstrated for six or more in-house developed technologies a clear path to insertion using a documented process that permits adaptation to a broad range of hardware and software projects.

  15. Study on a fast loading high vacuum multilayer insulation (MLI)

    NASA Astrophysics Data System (ADS)

    Shen, Xian; Zhang, Sheng; Wang, Bo; Gan, Zhihu; Ying, Jianming; Zhang, Chunlin

    2014-01-01

    With the continuous development of vacuum technology, the proportion of high vacuum multilayer insulation method in all kinds of insulation methods is growing [1]. For large cryogenic tanks, the multilayer insulation traditional layer by layer winding way is very inconvenient and takes a lot of time. Different layer density of the multilayer insulation material leads to different thermal insulation performance [2]. Because of the influence of man-made factors, the traditional way of winding is difficult to achieve a consistent density. This paper compared the fast loading type insulation and traditional insulation in a different degree of vacuum, it can be seen that the apparent thermal conductivity of these two types is similar. But fast loading multilayer insulation material is more convenient on the installation and it can eliminate the man-made factors. So it has practical value in engineering applications.

  16. Accurate Anisotropic Fast Marching for Diffusion-Based Geodesic Tractography

    PubMed Central

    Jbabdi, S.; Bellec, P.; Toro, R.; Daunizeau, J.; Pélégrini-Issac, M.; Benali, H.

    2008-01-01

    Using geodesics for inferring white matter fibre tracts from diffusion-weighted MR data is an attractive method for at least two reasons: (i) the method optimises a global criterion, and hence is less sensitive to local perturbations such as noise or partial volume effects, and (ii) the method is fast, allowing to infer on a large number of connexions in a reasonable computational time. Here, we propose an improved fast marching algorithm to infer on geodesic paths. Specifically, this procedure is designed to achieve accurate front propagation in an anisotropic elliptic medium, such as DTI data. We evaluate the numerical performance of this approach on simulated datasets, as well as its robustness to local perturbation induced by fiber crossing. On real data, we demonstrate the feasibility of extracting geodesics to connect an extended set of brain regions. PMID:18299703

  17. A Space/Fast-Time Adaptive Monopulse Technique

    NASA Astrophysics Data System (ADS)

    Seliktar, Yaron; Williams, Douglas B.; Holder, E. Jeff

    2006-12-01

    Mainbeam jamming poses a particularly difficult challenge for conventional monopulse radars. In such cases spatially adaptive processing provides some interference suppression when the target and jammer are not exactly coaligned. However, as the target angle approaches that of the jammer, mitigation performance is increasingly hampered and distortions are introduced into the resulting beam pattern. Both of these factors limit the reliability of a spatially adaptive monopulse processor. The presence of coherent multipath in the form of terrain-scattered interference (TSI), although normally considered a nuisance, can be exploited to suppress mainbeam jamming with space/fast-time processing. A method is presented offering space/fast-time monopulse processing with distortionless spatial array patterns that can achieve improved angle estimation over spatially adaptive monopulse. Performance results for the monopulse processor are obtained for mountaintop data containing a jammer and TSI, which demonstrate a dramatic improvement in performance over conventional monopulse and spatially adaptive monopulse.

  18. Fast Multiplexed Readout of Xmon Qubits Part I: Design

    NASA Astrophysics Data System (ADS)

    Sank, Daniel; Jeffrey, E.; Mutus, J. Y.; White, T. C.; Barends, R.; Kelly, J.; Chen, Y.; Roushan, P.; Campbell, B.; Chen, Z.; Chiaro, B.; Dunsworth, A.; Megrant, A.; Neill, C.; O'Malley, P.; Quintana, C.; Vainsencher, A.; Wenner, J.; Cleland, A. N.; Martinis, J. M.

    2014-03-01

    Realization of a surface code quantum computer requires fast scalable qubit readout. Previous systems have shown accurate readout in continuous wave mode. This neglects the transient response time which is crucial for the operation of the surface code and for measurement accuracy in the presence of finite qubit T1. We have designed a readout system, based on an integrated band pass filter, which achieves very fast transient response while maintaining long qubit T1. Our design uses separate readout resonators for each qubit. This allows individual qubit readout with frequency multiplexing while preventing correlated measurement errors. By connecting each resonator to a single filter the device requires zero additional on chip area and no extra control lines. We present design considerations, theory of operation, and physical layout of the device. With high fidelity gates this system forms the final element needed for a surface code cell.

  19. Next-generation sequencing-based method shows increased mutation detection sensitivity in an Indian retinoblastoma cohort

    PubMed Central

    Singh, Jaya; Mishra, Avshesh; Pandian, Arunachalam Jayamuruga; Mallipatna, Ashwin C.; Khetan, Vikas; Sripriya, S.; Kapoor, Suman; Agarwal, Smita; Sankaran, Satish; Katragadda, Shanmukh; Veeramachaneni, Vamsi; Hariharan, Ramesh; Subramanian, Kalyanasundaram

    2016-01-01

    Purpose Retinoblastoma (Rb) is the most common primary intraocular cancer of childhood and one of the major causes of blindness in children. India has the highest number of patients with Rb in the world. Mutations in the RB1 gene are the primary cause of Rb, and heterogeneous mutations are distributed throughout the entire length of the gene. Therefore, genetic testing requires screening of the entire gene, which by conventional sequencing is time consuming and expensive. Methods In this study, we screened the RB1 gene in the DNA isolated from blood or saliva samples of 50 unrelated patients with Rb using the TruSight Cancer panel. Next-generation sequencing (NGS) was done on the Illumina MiSeq platform. Genetic variations were identified using the Strand NGS software and interpreted using the StrandOmics platform. Results We were able to detect germline pathogenic mutations in 66% (33/50) of the cases, 12 of which were novel. We were able to detect all types of mutations, including missense, nonsense, splice site, indel, and structural variants. When we considered bilateral Rb cases only, the mutation detection rate increased to 100% (22/22). In unilateral Rb cases, the mutation detection rate was 30% (6/20). Conclusions Our study suggests that NGS-based approaches increase the sensitivity of mutation detection in the RB1 gene, making it fast and cost-effective compared to the conventional tests performed in a reflex-testing mode. PMID:27582626

  20. High rate of mutation K103N causing resistance to nevirapine in Indian children with acquired immunodeficiency syndrome.

    PubMed

    Sehgal, S; Pasricha, N; Singh, S

    2008-01-01

    In north India the number of paediatric cases with acquired immunodeficiency syndrome (AIDS) is on the rise. Most drug combinations used for treatment of AIDS incorporate nevirapine, resistance to which develops very fast if given singly or because of unplanned interruptions. This paper investigates presence of mutations at codon 103 and codon 215 of the HIV pol gene causing resistance to nevirapine and zidovudine (AZT) respectively in 25 children with AIDS. Mutations T215Y and K103N were detected by a nested cum amplification refractory mutation system polymerase chain reaction (ARMS PCR) and the results were confirmed by direct sequencing in five randomly selected cases. Nineteen patients had received nevirapine containing regimen and six were drug naive. Mutation K103N was observed in 56% (14/25) of the children while mutation T215Y was found in none. Two of the six drug naïve children also showed K103N mutation. Thus, Indian children drug naïve or treated with nevirapine containing regimens show a high rate of mutation conferring resistance to nevirapine which calls for a judicious use of nevirapine both in antenatal and postnatal setting.

  1. Fast flexible electronics with strained silicon nanomembranes

    PubMed Central

    Zhou, Han; Seo, Jung-Hun; Paskiewicz, Deborah M.; Zhu, Ye; Celler, George K.; Voyles, Paul M.; Zhou, Weidong; Lagally, Max G.; Ma, Zhenqiang

    2013-01-01

    Fast flexible electronics operating at radio frequencies (>1 GHz) are more attractive than traditional flexible electronics because of their versatile capabilities, dramatic power savings when operating at reduced speed and broader spectrum of applications. Transferrable single-crystalline Si nanomembranes (SiNMs) are preferred to other materials for flexible electronics owing to their unique advantages. Further improvement of Si-based device speed implies significant technical and economic advantages. While the mobility of bulk Si can be enhanced using strain techniques, implementing these techniques into transferrable single-crystalline SiNMs has been challenging and not demonstrated. The past approach presents severe challenges to achieve effective doping and desired material topology. Here we demonstrate the combination of strained- NM-compatible doping techniques with self-sustained-strain sharing by applying a strain-sharing scheme between Si and SiGe multiple epitaxial layers, to create strained print-transferrable SiNMs. We demonstrate a new speed record of Si-based flexible electronics without using aggressively scaled critical device dimensions. PMID:23416347

  2. How Fast is Famous Face Recognition?

    PubMed Central

    Barragan-Jason, Gladys; Lachat, Fanny; Barbeau, Emmanuel J.

    2012-01-01

    The rapid recognition of familiar faces is crucial for social interactions. However the actual speed with which recognition can be achieved remains largely unknown as most studies have been carried out without any speed constraints. Different paradigms have been used, leading to conflicting results, and although many authors suggest that face recognition is fast, the speed of face recognition has not been directly compared to “fast” visual tasks. In this study, we sought to overcome these limitations. Subjects performed three tasks, a familiarity categorization task (famous faces among unknown faces), a superordinate categorization task (human faces among animal ones), and a gender categorization task. All tasks were performed under speed constraints. The results show that, despite the use of speed constraints, subjects were slow when they had to categorize famous faces: minimum reaction time was 467 ms, which is 180 ms more than during superordinate categorization and 160 ms more than in the gender condition. Our results are compatible with a hierarchy of face processing from the superordinate level to the familiarity level. The processes taking place between detection and recognition need to be investigated in detail. PMID:23162503

  3. Fast box-counting algorithm on GPU.

    PubMed

    Jiménez, J; Ruiz de Miras, J

    2012-12-01

    The box-counting algorithm is one of the most widely used methods for calculating the fractal dimension (FD). The FD has many image analysis applications in the biomedical field, where it has been used extensively to characterize a wide range of medical signals. However, computing the FD for large images, especially in 3D, is a time consuming process. In this paper we present a fast parallel version of the box-counting algorithm, which has been coded in CUDA for execution on the Graphic Processing Unit (GPU). The optimized GPU implementation achieved an average speedup of 28 times (28×) compared to a mono-threaded CPU implementation, and an average speedup of 7 times (7×) compared to a multi-threaded CPU implementation. The performance of our improved box-counting algorithm has been tested with 3D models with different complexity, features and sizes. The validity and accuracy of the algorithm has been confirmed using models with well-known FD values. As a case study, a 3D FD analysis of several brain tissues has been performed using our GPU box-counting algorithm.

  4. Direct fast neutron detection: A status report

    SciTech Connect

    Peurrung, A.J.; Hansen, R.R.; Craig, R.A.; Hensley, W.K.; Hubbard, C.W.; Keller, P.E.; Reeder, P.L.; Sunberg, D.S.

    1997-12-01

    This report describes the status of efforts to develop direct fast-neutron detection via proton recoil within plastic scintillator. Since recording proton recoil events is of little practical use without a means to discriminate effectively against gamma-ray interactions, the present effort is concentrated on demonstrating a method that distinguishes between pulse types. The proposed method exploits the different pulse shapes that are to be expected primarily on the basis of the slower speed of the recoiling fission neutrons. Should this effort ultimately prove successful, the resulting novel technology will have the potential to significantly lower cost and increase capability for a number of critical neutron-detection applications. Considerable progress has been made toward a clear and compelling demonstration of this new technique. An exhaustive theoretical and numerical investigation of the method has been completed. The authors have been able to better understand the laboratory results and estimate the performance that could ultimately be achieved using the proposed technique. They have assessed the performance of a number of different algorithms for discriminating between neutron and gamma ray events. The results of this assessment will be critical when the construction of low-cost, field-portable neutron detectors becomes necessary. Finally, a laboratory effort to realize effective discrimination is well underway and has resulted in partial success.

  5. Fast Sparse Level Sets on Graphics Hardware.

    PubMed

    Jalba, Andrei C; van der Laan, Wladimir J; Roerdink, Jos B T M

    2013-01-01

    The level-set method is one of the most popular techniques for capturing and tracking deformable interfaces. Although level sets have demonstrated great potential in visualization and computer graphics applications, such as surface editing and physically based modeling, their use for interactive simulations has been limited due to the high computational demands involved. In this paper, we address this computational challenge by leveraging the increased computing power of graphics processors, to achieve fast simulations based on level sets. Our efficient, sparse GPU level-set method is substantially faster than other state-of-the-art, parallel approaches on both CPU and GPU hardware. We further investigate its performance through a method for surface reconstruction, based on GPU level sets. Our novel multiresolution method for surface reconstruction from unorganized point clouds compares favorably with recent, existing techniques and other parallel implementations. Finally, we point out that both level-set computations and rendering of level-set surfaces can be performed at interactive rates, even on large volumetric grids. Therefore, many applications based on level sets can benefit from our sparse level-set method.

  6. Feedback controlled hybrid fast ferrite tuners

    SciTech Connect

    Remsen, D.B.; Phelps, D.A.; deGrassie, J.S.; Cary, W.P.; Pinsker, R.I.; Moeller, C.P.; Arnold, W.; Martin, S.; Pivit, E.

    1993-09-01

    A low power ANT-Bosch fast ferrite tuner (FFT) was successfully tested into (1) the lumped circuit equivalent of an antenna strap with dynamic plasma loading, and (2) a plasma loaded antenna strap in DIII-D. When the FFT accessible mismatch range was phase-shifted to encompass the plasma-induced variation in reflection coefficient, the 50 {Omega} source was matched (to within the desired 1.4 : 1 voltage standing wave ratio). The time required to achieve this match (i.e., the response time) was typically a few hundred milliseconds, mostly due to a relatively slow network analyzer-computer system. The response time for the active components of the FFT was 10 to 20 msec, or much faster than the present state-of-the-art for dynamic stub tuners. Future FFT tests are planned, that will utilize the DIII-D computer (capable of submillisecond feedback control), as well as several upgrades to the active control circuit, to produce a FFT feedback control system with a response time approaching 1 msec.

  7. Fast wavelet estimation of weak biosignals.

    PubMed

    Causevic, Elvir; Morley, Robert E; Wickerhauser, M Victor; Jacquin, Arnaud E

    2005-06-01

    Wavelet-based signal processing has become commonplace in the signal processing community over the past decade and wavelet-based software tools and integrated circuits are now commercially available. One of the most important applications of wavelets is in removal of noise from signals, called denoising, accomplished by thresholding wavelet coefficients in order to separate signal from noise. Substantial work in this area was summarized by Donoho and colleagues at Stanford University, who developed a variety of algorithms for conventional denoising. However, conventional denoising fails for signals with low signal-to-noise ratio (SNR). Electrical signals acquired from the human body, called biosignals, commonly have below 0 dB SNR. Synchronous linear averaging of a large number of acquired data frames is universally used to increase the SNR of weak biosignals. A novel wavelet-based estimator is presented for fast estimation of such signals. The new estimation algorithm provides a faster rate of convergence to the underlying signal than linear averaging. The algorithm is implemented for processing of auditory brainstem response (ABR) and of auditory middle latency response (AMLR) signals. Experimental results with both simulated data and human subjects demonstrate that the novel wavelet estimator achieves superior performance to that of linear averaging.

  8. The Mutational Robustness of Influenza A Virus

    PubMed Central

    McCrone, John T.; Lauring, Adam S.

    2016-01-01

    A virus’ mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE. The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution. Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation. In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations. The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock. A mutation was considered lethal only after we failed to rescue virus in three independent transfections. We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells. We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome. Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution. The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16) than in the other 6 segments (0.78 ± 0.24), and their respective beta distributions had slightly different shape parameters. The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses. These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects. PMID:27571422

  9. Activating GNAS mutations in parosteal osteosarcoma.

    PubMed

    Carter, Jodi M; Inwards, Carrie Y; Jin, Long; Evers, Barbara; Wenger, Doris E; Oliveira, Andre M; Fritchie, Karen J

    2014-03-01

    Parosteal osteosarcoma is a surface-based osteosarcoma that often exhibits deceptively bland cytologic features, hindering diagnosis in small biopsies or when correlative radiologic imaging is not readily available. A number of benign and malignant fibro-osseous lesions, including fibrous dysplasia (FD) and low-grade central osteosarcoma, fall within the morphologic differential diagnosis of parosteal osteosarcoma. Somatic mutations in GNAS, encoding the α-subunit of the heterotrimeric G protein complex (Gsα), occur in FD and McCune-Albright syndrome but have not been reported in parosteal osteosarcoma. We evaluated GNAS mutational status in parosteal osteosarcoma and several of its histologic mimics to determine its utility in differentiating these entities. Eleven of 14 (79%) FD cases had GNAS mutations within codon 201 (5 R201C and 6 R201H mutations). GNAS mutations were not detected in any cases of adamantinoma or osteofibrous dysplasia. Direct sequencing of 9 parosteal osteosarcomas, including 3 of low grade and 6 with dedifferentiation, revealed activating GNAS mutations in 5 cases (55%), distributed as 4 R201C-mutated tumors and 1 tumor with an R201H mutation. GNAS codon 227 mutations were not detected in any of the cases. There was no association between GNAS mutational status and patient demographics, histologic dedifferentiation, or clinical outcome. To our knowledge, we report the first series of parosteal osteosarcomas harboring activating GNAS mutations. Our data suggest that GNAS mutational status may have limited utility as an ancillary technique in differentiating benign and malignant fibro-osseous lesions of the bone.

  10. The Mutational Robustness of Influenza A Virus.

    PubMed

    Visher, Elisa; Whitefield, Shawn E; McCrone, John T; Fitzsimmons, William; Lauring, Adam S

    2016-08-01

    A virus' mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE. The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution. Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation. In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations. The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock. A mutation was considered lethal only after we failed to rescue virus in three independent transfections. We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells. We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome. Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution. The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16) than in the other 6 segments (0.78 ± 0.24), and their respective beta distributions had slightly different shape parameters. The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses. These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects.

  11. Mutation detection using Surveyor nuclease.

    PubMed

    Qiu, Peter; Shandilya, Harini; D'Alessio, James M; O'Connor, Kevin; Durocher, Jeffrey; Gerard, Gary F

    2004-04-01

    We have developed a simple and flexible mutation detection technology for the discovery and mapping of both known and unknown mutations. This technology is based on a new mismatch-specific DNA endonuclease from celery, Surveyor nuclease, which is a member of the CEL nuclease family of plant DNA endonucleases. Surveyor nuclease cleaves with high specificity at the 3' side of any mismatch site in both DNA strands, including all base substitutions and insertion/deletions up to at least 12 nucleotides. Surveyor nuclease technology involves four steps: (i) PCR to amplify target DNA from both mutant and wild-type reference DNA; (ii) hybridization to form heteroduplexes between mutant and wild-type reference DNA; (iii) treatment of annealed DNA with Surveyor nuclease to cleave heteroduplexes; and (iv) analysis of digested DNA products using the detection/separation platform of choice. The technology is highly sensitive, detecting rare mutants present at as low as 1 in 32 copies. Unlabeled Surveyor nuclease digestion products can be analyzed using conventional gel electrophoresis or high-performance liquid chromatography (HPLC), while end labeled digestion products are suitable for analysis by automated gel or capillary electrophoresis. The entire protocol can be performed in less than a day and is suitable for automated and high-throughput procedures.

  12. Determination of a mutational spectrum

    DOEpatents

    Thilly, William G.; Keohavong, Phouthone

    1991-01-01

    A method of resolving (physically separating) mutant DNA from nonmutant DNA and a method of defining or establishing a mutational spectrum or profile of alterations present in nucleic acid sequences from a sample to be analyzed, such as a tissue or body fluid. The present method is based on the fact that it is possible, through the use of DGGE, to separate nucleic acid sequences which differ by only a single base change and on the ability to detect the separate mutant molecules. The present invention, in another aspect, relates to a method for determining a mutational spectrum in a DNA sequence of interest present in a population of cells. The method of the present invention is useful as a diagnostic or analytical tool in forensic science in assessing environmental and/or occupational exposures to potentially genetically toxic materials (also referred to as potential mutagens); in biotechnology, particularly in the study of the relationship between the amino acid sequence of enzymes and other biologically-active proteins or protein-containing substances and their respective functions; and in determining the effects of drugs, cosmetics and other chemicals for which toxicity data must be obtained.

  13. SNaPshot Assay for the Detection of the Most Common CFTR Mutations in Infertile Men

    PubMed Central

    Mircevska, Marija; Plaseski, Toso; Filipovski, Vanja; Plaseska-Karanfilska, Dijana

    2014-01-01

    Congenital bilateral absence of vas deferens (CBAVD) is the most common CFTR-related disorder (CFTR-RD) that explains about 1–2% of the male infertility cases. Controversial data have been published regarding the involvement of CFTR mutations in infertile men with non-obstructive azoospermia and oligozoospermia. Here, we describe single base extension (SNaPshot) assay for detection of 11 common CFTR mutations: F508del, G542X, N1303K, 621+1G->T, G551D, R553X, R1162X, W1282X, R117H, 2184insA and 1717-1G->A and IVS8polyT variants. The assay was validated on 50 previously genotyped samples and was used to screen a total of 369 infertile men with different impairment of spermatogenesis and 136 fertile controls. Our results show that double heterozygosity of cystic fibrosis (CF) and CFTR-related disorder (CFTR-RD) mutations are found in a high percentage (22.7%) of infertile men with obstructive azoospermia, but not in other studied groups of infertile men. The SNaPshot assay described here is an inexpensive, fast and robust method for primary screening of the most common CFTR mutations both in patients with classical CF and CFTR-RD. It can contribute to better understanding of the role of CFTR mutations in impaired spermatogenesis, ultimately leading to improved management of infertile men. PMID:25386751

  14. GRIFFIN's Fast-Timing Array

    NASA Astrophysics Data System (ADS)

    Olaizola, Bruno; Griffin Collaboration

    2016-09-01

    The Gamma-Ray Infrastructure For Fundamental Investigations of Nuclei (GRIFFIN) is the new β-decay spectrometer facility at TRIUMF-ISAC. Consists of an array of 16 large-volume HPGe clover detectors with an unparalleled efficiency of 19% at 1.33 MeV. Its strongest advantage is the versatility of the ancillary detectors that can be coupled to the main array to tag on β particles, neutrons or precisely measure conversion electron spectra. An ancillary array of 8 LaBr3(Ce) detectors for γ-rays and a fast plastic scintillator for β-particles has been optimized for fast-timing experiments with GRIFFIN. The 51 mm x 51 mm cylindrical LaBr3(Ce) crystals are coupled to Hamamatsu R2083 photomultipliers. Timing resolutions as good as FWHM 200 ps and time-walks below +/- 30 ps have been obtained for individual crystals using analog electronics. There is also an ongoing project to develop an active BGO shield for the LaBr3(Ce) crystals. The LaBr3(Ce) array commissioning experiment to measure the 145,146Cs decay to 145,146Ba will test its capabilities over a wide range of lifetimes. Preliminary results on the lifetimes of some of the low-laying states will be presented.

  15. RCD+: Fast loop modeling server

    PubMed Central

    López-Blanco, José Ramón; Canosa-Valls, Alejandro Jesús; Li, Yaohang; Chacón, Pablo

    2016-01-01

    Modeling loops is a critical and challenging step in protein modeling and prediction. We have developed a quick online service (http://rcd.chaconlab.org) for ab initio loop modeling combining a coarse-grained conformational search with a full-atom refinement. Our original Random Coordinate Descent (RCD) loop closure algorithm has been greatly improved to enrich the sampling distribution towards near-native conformations. These improvements include a new workflow optimization, MPI-parallelization and fast backbone angle sampling based on neighbor-dependent Ramachandran probability distributions. The server starts by efficiently searching the vast conformational space from only the loop sequence information and the environment atomic coordinates. The generated closed loop models are subsequently ranked using a fast distance-orientation dependent energy filter. Top ranked loops are refined with the Rosetta energy function to obtain accurate all-atom predictions that can be interactively inspected in an user-friendly web interface. Using standard benchmarks, the average root mean squared deviation (RMSD) is 0.8 and 1.4 Å for 8 and 12 residues loops, respectively, in the challenging modeling scenario in where the side chains of the loop environment are fully remodeled. These results are not only very competitive compared to those obtained with public state of the art methods, but also they are obtained ∼10-fold faster. PMID:27151199

  16. Cortical Specializations Underlying Fast Computations.

    PubMed

    Volgushev, Maxim

    2016-04-01

    The time course of behaviorally relevant environmental events sets temporal constraints on neuronal processing. How does the mammalian brain make use of the increasingly complex networks of the neocortex, while making decisions and executing behavioral reactions within a reasonable time? The key parameter determining the speed of computations in neuronal networks is a time interval that neuronal ensembles need to process changes at their input and communicate results of this processing to downstream neurons. Theoretical analysis identified basic requirements for fast processing: use of neuronal populations for encoding, background activity, and fast onset dynamics of action potentials in neurons. Experimental evidence shows that populations of neocortical neurons fulfil these requirements. Indeed, they can change firing rate in response to input perturbations very quickly, within 1 to 3 ms, and encode high-frequency components of the input by phase-locking their spiking to frequencies up to 300 to 1000 Hz. This implies that time unit of computations by cortical ensembles is only few, 1 to 3 ms, which is considerably faster than the membrane time constant of individual neurons. The ability of cortical neuronal ensembles to communicate on a millisecond time scale allows for complex, multiple-step processing and precise coordination of neuronal activity in parallel processing streams, while keeping the speed of behavioral reactions within environmentally set temporal constraints.

  17. Fast generic polar harmonic transforms.

    PubMed

    Hoang, Thai V; Tabbone, Salvatore

    2014-07-01

    Generic polar harmonic transforms have recently been proposed to extract rotation-invariant features from images and their usefulness has been demonstrated in a number of pattern recognition problems. However, direct computation of these transforms from their definition is inefficient and is usually slower than some efficient computation strategies that have been proposed for other methods. This paper presents a number of novel computation strategies to compute these transforms rapidly. The proposed methods are based on the inherent recurrence relations among complex exponential and trigonometric functions used in the definition of the radial and angular kernels of these transforms. The employment of these relations leads to recursive and addition chain-based strategies for fast computation of harmonic function-based kernels. Experimental results show that the proposed method is about 10× faster than direct computation and 5× faster than fast computation of Zernike moments using the q-recursive strategy. Thus, among all existing rotation-invariant feature extraction methods, polar harmonic transforms are the fastest.

  18. Manybeam velocimeter for fast surfaces

    SciTech Connect

    Goosman, D.; Avara, G.; Steinmetz, L.; Lai, C.; Perry, S.

    1996-09-01

    For the past 5 years, we have conceived, built and successfully used a new 10 beam laser velocimeter for monitoring velocity vs time histories of fast moving surfaces, and will have a 20 beam capability soon. We conceived a method to multiplex 5 to 10 beams through a single Fabry-Perot interferometer, without losing any light that our equivalently-performing single beam system could use, and with negligible cross- talk. This saves the cost of 16 interferometers, simplifies operation and takes less space than without multiplexing. We devised special efficient light collecting probes, streak cameras that change sweep speed during the course of the record, and a new double cavity interferometer which is better, cheaper and more flexible than our previous versions. With the 10 recorders, we conceived and employ a method of using both a fast and a slow streak camera on each of 5 beams without reducing the light that is available to either camera separately. Five new galvanometrically-driven triggerable CCD streak cameras will be installed soon.

  19. Identification of CYP4V2 mutation in 36 Chinese families with Bietti crystalline corneoretinal dystrophy.

    PubMed

    Yin, Xiaobei; Yang, Liping; Chen, Ningning; Cui, Hui; Zhao, Lin; Feng, Lina; Li, Aijun; Zhang, Huirong; Ma, Zhizhong; Li, Genlin

    2016-05-01

    Bietti crystalline corneoretinal dystrophy (BCD) is an inherited eye disease that is most common in the Chinese. It is caused by a mutation in the CYP4V2 gene. In this study, 43 Chinese BCD families were recruited; most patients manifested the characteristic phenotype of BCD, with 2 families initially misdiagnosed with retinitis pigmentosa. Five patients in our cohort presented with BCD and choroidal neovascularization (CNV), and 1 patient presented with typical BCD and abnormality in the terminals of both fingers and toes. A total of 17 pathogenic mutations involving 68 alleles were identified from 36 families using targeted exon sequencing and Sanger sequencing; we achieved a diagnostic rate of approximately 84%. Fifteen families were found to carry homozygous mutations, 17 families carried compound heterozygous mutations, and 4 families carried a single heterozygous mutation. Of the mutations identified, four variants c.802-8_810del17bpinsGC, c.802-8_810del17bpinsGT, c.992A > C (p.H331P), and c.1091-2A > G accounted for 71% of the mutations identified in CYP4V2. These mutations were hotspots in Chinese populations for BCD. Five among them were novel and predicted to be disease-causing, including c.65T > A (p.L22H), c.681_4delTGAG (p.S227Rfs*1), c.802-8_810del17bpinsGT, c.965_7delAAG (p.321delE), and c.994G > A (p.D332N). No apparent correlation between genotype and phenotype was identified. Our findings broaden the spectrum of CYP4V2 mutations that cause BCD and the phenotypic spectrum of the disease in Chinese families. These results will be useful for the genetic diagnosis of BCD, genetic consultation, and gene therapy in the future.

  20. Lung adenocarcinoma: Sustained subtyping with immunohistochemistry and EGFR, HER2 and KRAS mutational status.

    PubMed

    Sousa, Vitor; Rodrigues, Carolina; Silva, Maria; Alarcão, Ana Maria; Carvalho, Lina

    2015-01-01

    Pulmonary adenocarcinomas are still in the process of achieving morphological, immunohistochemical and genetic standardization. The ATS/ERS/IASLC proposed classification for lung adenocarcinomas supports the value of the identification of histological patterns, specifically in biopsies. Thirty pulmonary adenocarcinomas were subjected to immunohistochemical study (CK7, CK5, 6, 18, CK20, TTF1, CD56, HER2, EGFR and Ki-67), FISH and PCR followed by sequencing and fragment analysis for EGFR, HER2 and KRAS. Solid pattern showed lower TTF1 and higher Ki-67 expression. TTF1 expression was higher in non-mucinous lepidic and micropapillary patterns when compared to acinar and solid and acinar, solid and mucinous respectively. Higher Ki67 expression was present in lepidic and solid patterns compared to mucinous. EGFR membranous staining had increasing expression from non-mucinous lepidic/BA pattern to solid pattern and micropapillary until acinar pattern. EGFR mutations, mainly in exon 19, were more frequent in females, together with non-smoking status, while KRAS exon 2 mutations were statistically more frequent in males, especially in solid pattern. FISH EGFR copy was correlated gross, with mutations. HER2 copy number was raised in female tumours without mutations, in all cases. Although EGFR and KRAS mutations are generally considered mutually exclusive, in rare cases they can coexist as it happened in one of this series, and was represented in acinar pattern with rates of 42.9% and 17.9%, respectively. EGFR mutations were more frequent in lepidic/BA and acinar patterns. Some cases showed different EGFR mutations. The differences identified between the adenocarcinoma patterns reinforce the need to carefully identify the patterns present, with implications in diagnosis and in pathogenic understanding. EGFR and KRAS mutational status can be determined in biopsies representing bronchial pulmonary carcinomas because when a mutation is present it is generally present in all the

  1. Sequence specificity of streptozotocin-induced mutations.

    PubMed Central

    Mack, S L; Fram, R J; Marinus, M G

    1988-01-01

    The isolation and characterization of streptozotocin (STZ)-induced mutations in the phage P22 mnt repressor gene is described. Cells carrying the plasmid-borne mnt gene were exposed to STZ to give 10-20 percent survival and at least an eleven-fold increase in mutation frequency. DNA sequence analysis showed that 50 of 51 STZ-induced mutations were GC to AT transitions, and one was an AT to GC transition. We have also compared the STZ mutational spectrum to that for N-methyl-N'-nitro-N-nitroso-guanidine (MNNG). There are sites in the mnt gene which are mutated only by STZ; only by MNNG, or by both agents. Sites at which only STZ induced GC to AT transition mutations occur were in sequences that are pyrimidine rich 5' to the mutated site and purine rich 3' to the mutated site. Induction of mutations by both STZ and MNNG should be considered to maximize the number of mutable sites. PMID:2972994

  2. Evolution of Mutation Rate in Asexual Populations

    NASA Astrophysics Data System (ADS)

    Wylie, Scott; Levine, Herbert; Kessler, David

    2007-03-01

    Several evolution experiments with E. coli document the spontaneous emergence and eventual fixation of so called ``mutator'' alleles that increase the genomic mutation rate by the order of 100-fold. Variations in mutation rates are due to polymorphisms in the molecular machinery that copies and checks the genome for errors. These polymorphisms are coded in the genome and thus heritable. Like any heritable trait, elevated mutation rates are subject to natural selection and evolution. However, unlike other traits, mutation rate does not directly affect the rate at which an organism reproduces, i.e. its fitness. Rather, it affects the statistical distribution of the offspring's fitness. This fitness distribution, in turn, leads via ``hitchhiking'' to a change in the frequency of the mutator allele, i.e. evolution of the mutation rate itself. In our work we simulate a birth-death process that approximates simple asexual populations and we measure the fixation probability of rare mutators. We then develop an approximate analytic model of the population dynamics, the results of which agree reasonably well with simulation. In particular, we are able to analytically predict the ``effective fitness'' of mutators and the conditions under which they are expected to emerge.

  3. The population genetics of beneficial mutations

    PubMed Central

    Orr, H. Allen

    2010-01-01

    The population genetic study of advantageous mutations has lagged behind that of deleterious and neutral mutations. But over the past two decades, a number of significant developments, both theoretical and empirical, have occurred. Here, I review two of these developments: the attempt to determine the distribution of fitness effects among beneficial mutations and the attempt to determine their average dominance. Considering both theory and data, I conclude that, while considerable theoretical progress has been made, we still lack sufficient data to draw confident conclusions about the distribution of effects or the dominance of beneficial mutations. PMID:20308094

  4. Methods for detection of ataxia telangiectasia mutations

    DOEpatents

    Gatti, Richard A.

    2005-10-04

    The present invention is directed to a method of screening large, complex, polyexonic eukaryotic genes such as the ATM gene for mutations and polymorphisms by an improved version of single strand conformation polymorphism (SSCP) electrophoresis that allows electrophoresis of two or three amplified segments in a single lane. The present invention also is directed to new mutations and polymorphisms in the ATM gene that are useful in performing more accurate screening of human DNA samples for mutations and in distinguishing mutations from polymorphisms, thereby improving the efficiency of automated screening methods.

  5. Calreticulin Exon 9 Mutations in Myeloproliferative Neoplasms

    PubMed Central

    Kim, Yu-Kyung

    2015-01-01

    Background Calreticulin (CALR) mutations were recently discovered in patients with myeloproliferative neoplasms (MPNs). We studied the frequency and type of CALR mutations and their hematological characteristics. Methods A total of 168 MPN patients (36 polycythemia vera [PV], 114 essential thrombocythemia [ET], and 18 primary myelofibrosis [PMF] cases) were included in the study. CALR mutation was analyzed by the direct sequencing method. Results CALR mutations were detected in 21.9% of ET and 16.7% of PMF patients, which accounted for 58.5% and 33.3% of ET and PMF patients without Janus kinase 2 (JAK2) or myeloproliferative leukemia virus oncogenes (MPL) mutations, respectively. A total of five types of mutation were detected, among which, L367fs*46 (53.6%) and K385fs*47 (35.7%) were found to be the most common. ET patients with CALR mutation had lower leukocyte counts and ages compared with JAK2-mutated ET patients. Conclusion Genotyping for CALR could be a useful diagnostic tool for JAK2-or MPL-negative ET or PMF patients. CALR mutation may be a distinct disease group, with different hematological characteristics than that of JAK2-positive patients. PMID:25553276

  6. DHPLC screening of cystic fibrosis gene mutations.

    PubMed

    Ravnik-Glavac, Metka; Atkinson, Andrew; Glavac, Damjan; Dean, Michael

    2002-04-01

    Denaturing high performance liquid chromatography (DHPLC) using ion-pairing reverse phase chromatography (IPRPC) columns is a technique for the screening of gene mutations. In order to evaluate the potential utility of this assay method in a clinical laboratory setting, we subjected the PCR products of 73 CF patients known to bear CFTR mutations to this analytic technique. We used thermal denaturation profile parameters specified by the MELT program tool, made available by Stanford University. Using this strategy, we determined an initial analytic sensitivity of 90.4% for any of 73 known CFTR mutations. Most of the mutations not detected by DHPLC under these conditions are alpha-substitutions. This information may eventually help to improve the MELT algorithm. Increasing column denaturation temperatures for one or two degrees above those recommended by the MELT program allowed 100% detection of CFTR mutations tested. By comparing DHPLC methodology used in this study with the recently reported study based on Wavemaker 3.4.4 software (Transgenomic, Omaha, NE) [Le Marechal et al., 2001) and with previous SSCP analysis of CFTR mutations [Ravnik-Glavac et al., 1994] we emphasized differences and similarities in order to refine the DHPLC system and discuss the relationship to the alternative approaches. We conclude that the DHPLC method, under optimized conditions, is highly accurate, rapid, and efficient in detecting mutations in the CFTR gene and may find high utility in screening individuals for CFTR mutations. Hum Mutat 19:374-383, 2002. Published 2002 Wiley-Liss, Inc.

  7. Gene mutations in chronic lymphocytic leukemia.

    PubMed

    Amin, Nisar A; Malek, Sami N

    2016-04-01

    The recent discovery of genes mutated in chronic lymphocytic leukemia (CLL) has stimulated new research into the role of these genes in CLL pathogenesis. CLL cases carry approximately 5-20 mutated genes per exome, a lower number than detected in many human tumors. Of the recurrently mutated genes in CLL, all are mutated in 10% or less of patients when assayed in unselected CLL cohorts at diagnosis. Mutations in TP53 are of major clinical relevance, are often associated with del17p and gain in frequency over time. TP53 mutated and associated del17p states substantially lower response rates, remission duration, and survival in CLL. Mutations in NOTCH1 and SF3B1 are recurrent, often associated with progressive CLL that is also IgVH unmutated and ZAP70-positive and are under investigation as targets for novel therapies and as factors influencing CLL outcome. There are an estimated 20-50 additional mutated genes with frequencies of 1%-5% in CLL; more work is needed to identify these and to study their significance. Finally, of the major biological aberration categories influencing CLL as a disease, gene mutations will need to be placed into context with regard to their ultimate role and importance. Such calibrated appreciation necessitates studies incorporating multiple CLL driver aberrations into biological and clinical analyses.

  8. Factors affecting the nature of induced mutations

    SciTech Connect

    Russell, L.B.; Russell, W.L.; Rinchik, E.M.; Hunsicker, P.R.

    1989-01-01

    The recent considerable expansion of specific-locus-mutation data has made possible an examination of the effects of germ-cell stage on both quantity of mutation yield and nature of mutations. For chemicals mutagenic in poststem-cell stages, three patterns have been identified according to the stages in which they elicit maximum response: (1) early spermatozoa and late spermatids; (2) early spermatids; and (3) differentiating spermatogonia. The majority of chemicals tested fall into Pattern 1. Chemicals that are also mutagenic in stem-cell spermatogonia do not preferentially belong to any one of these three categories. For only one chemical (CHL) has an entire set of mutations been analyzed molecularly. However, the results of genetic and molecular analyses of genomic regions surrounding six of the specific-locus markers allow us to conclude that any mutation that causes lethality of homozygotes (in the case of d, prenatal lethality, specifically) must involve one or more loci in addition to the marked one. Such mutations have been classified as large lesions'' (LL), the remainder as other lesions'' (OL). Analysis of the data shows that, regardless of the nature of the chemical (Pattern-1, -2, or -3), (1) LLs constitute a very low proportion of the mutations induced in either stem-cell or differentiating spermatogonia, and (b) LLs constitute a high proportion of mutations induced in postmeiotic stages. Chemicals that are active in both pre- and postmeiotic stages produce LL or OL mutations depending on cell stage.

  9. Drastic reduction of the slow gate of human muscle chloride channel (ClC-1) by mutation C277S

    PubMed Central

    Accardi, Alessio; Ferrera, Loretta; Pusch, Michael

    2001-01-01

    Single channel measurements suggest that the human muscle chloride channel ClC-1 presumably has a double barrelled structure, with a fast single protopore gate and a slow common pore gate similar to that of ClC-0, the chloride channel from Torpedo. The single point mutation C212S has been shown to abolish the slow gating of ClC-0 locking the slow gate in the open state. In order to test the hypothesis that the slow gating process found in ClC-1 corresponds to the well characterised slow gate found in ClC-0 we investigated the gating effects in ClC-1 of the homologous mutation corresponding to C212S, C277S. We found that the mutation C277S strongly reduced the slow component of macroscopic gating relaxations at negative and at positive voltages. Time constants of the fast gating relaxations were not affected by the mutation but the minimal open probability of the fast gate at negative voltages was slightly reduced to 0.08 compared with the WT value of 0.22. Additionally, we characterised the block of WT ClC-1 and mutant C277S by the S(—) enantiomer of CPB (2-(p-chlorophenoxy) butyric acid), and found that the block is practically unaffected by the mutation suggesting that CPB does not interact with the slow gate of ClC-1. We conclude that the slow and fast gating processes of ClC-1, respectively, reflect the slow common pore gate and the single protopore gate of the double-barrelled ClC-1 channel. PMID:11483705

  10. Drastic reduction of the slow gate of human muscle chloride channel (ClC-1) by mutation C277S.

    PubMed

    Accardi, A; Ferrera, L; Pusch, M

    2001-08-01

    1. Single channel measurements suggest that the human muscle chloride channel ClC-1 presumably has a double barrelled structure, with a fast single protopore gate and a slow common pore gate similar to that of ClC-0, the chloride channel from Torpedo. The single point mutation C212S has been shown to abolish the slow gating of ClC-0 locking the slow gate in the open state. In order to test the hypothesis that the slow gating process found in ClC-1 corresponds to the well characterised slow gate found in ClC-0 we investigated the gating effects in ClC-1 of the homologous mutation corresponding to C212S, C277S. 2. We found that the mutation C277S strongly reduced the slow component of macroscopic gating relaxations at negative and at positive voltages. 3. Time constants of the fast gating relaxations were not affected by the mutation but the minimal open probability of the fast gate at negative voltages was slightly reduced to 0.08 compared with the WT value of 0.22. 4. Additionally, we characterised the block of WT ClC-1 and mutant C277S by the S(-) enantiomer of CPB (2-(p-chlorophenoxy) butyric acid), and found that the block is practically unaffected by the mutation suggesting that CPB does not interact with the slow gate of ClC-1. 5. We conclude that the slow and fast gating processes of ClC-1, respectively, reflect the slow common pore gate and the single protopore gate of the double-barrelled ClC-1 channel.

  11. WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations.

    PubMed

    Friedrich, Katrin; Lee, Lin; Leistritz, Dru F; Nürnberg, Gudrun; Saha, Bidisha; Hisama, Fuki M; Eyman, Daniel K; Lessel, Davor; Nürnberg, Peter; Li, Chumei; Garcia-F-Villalta, María J; Kets, Carolien M; Schmidtke, Joerg; Cruz, Vítor Tedim; Van den Akker, Peter C; Boak, Joseph; Peter, Dincy; Compoginis, Goli; Cefle, Kivanc; Ozturk, Sukru; López, Norberto; Wessel, Theda; Poot, Martin; Ippel, P F; Groff-Kellermann, Birgit; Hoehn, Holger; Martin, George M; Kubisch, Christian; Oshima, Junko

    2010-07-01

    Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by null mutations at the WRN locus, which codes for a member of the RecQ family of DNA helicases. Since 1988, the International Registry of Werner syndrome had enrolled 130 molecularly confirmed WS cases from among 110 worldwide pedigrees. We now report 18 new mutations, including two genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and two rare missense mutations. We also review evidence for founder mutations among various ethnic/geographic groups. Founder WRN mutations had been previously reported in Japan and Northern Sardinia. Our Registry now suggests characteristic mutations originated in Morocco, Turkey, The Netherlands and elsewhere.

  12. WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations

    PubMed Central

    Friedrich, Katrin; Lee, Lin; Leistritz, Dru F.; Nürnberg, Gudrun; Saha, Bidisha; Hisama, Fuki M.; Eyman, Daniel K.; Lessel, Davor; Nürnberg, Peter; Li, Chumei; Garcia-F-Villalta, María J.; Kets, Carolien M.; Schmidtke, Joerg; Cruz, Vítor Tedim; Van den Akker, Peter C.; Boak, Joseph; Peter, Dincy; Compoginis, Goli; Cefle, Kivanc; Ozturk, Sukru; López, Norberto; Wessel, Theda; Poot, Martin; Ippel, P. F.; Groff-Kellermann, Birgit; Hoehn, Holger; Martin, George M.; Kubisch, Christian; Oshima, Junko

    2015-01-01

    Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by null mutations at the WRN locus, which codes for a member of the RecQ family of DNA helicases. Since 1988, the International Registry of Werner syndrome had enrolled 130 molecularly confirmed WS cases from among 110 worldwide pedigrees. We now report 18 new mutations, including two genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and two rare missense mutations. We also review evidence for founder mutations among various ethnic/geographic groups. Founder WRN mutations had been previously reported in Japan and Northern Sardinia. Our Registry now suggests characteristic mutations originated in Morocco, Turkey, The Netherlands and elsewhere. PMID:20443122

  13. Ultrarapid mutation detection by multiplex, solid-phase chemical cleavage

    SciTech Connect

    Rowley, G.; Saad, S.; Giannelli, F.; Green, P.M.

    1995-12-10

    The chemical cleavage of mismatches in heteroduplexes formed by probe and test DNA detects and locates any sequence change in long DNA segments ({approximately}1.8 kb), and its efficiency has been well tested in the analysis of both average (e.g., coagulation factor IX) and large, complex genes (e.g., coagulation factor VIII and dystrophin). In the latter application RT/PCR products allow the examination of all essential sequences of the gene in a minimum number of reactions. We use two specific chemical reactants (hydroxylamine and osmium tetroxide) and piperidine cleavage of the above procedure to develop a very fast mutation screening method. This is based on: (1) 5{prime} or internal fluorescent labeling to allow concurrent screening of three to four DNA fragments and (2) solid-phase chemistry to use a microliter format and reduce the time required for the procedure, from amplification of sequence to gel loading inclusive, to one person-working-day. We test the two variations of the method, one entailing 5{prime} labeling of probe DNA and the other uniform labeling of both probe and target DNA, by detecting 114 known hemophilia B (coagulation factor IX) mutations and by analyzing 129 new patients. Uniform labeling of both probe and target DNA prior to formation of the heteroduplexes leads to almost twofold redundancy in the ability to detect mutations. Alternatively, the latter procedure may offer very efficient though less than 100% screening for sequence changes with only hydroxylamine. The full method with two chemical reactions (hydroxylamine and osmium tetroxide) should allow one person to screen with virtually 100% accuracy more than 300 kb of sequence in three ABI 373 gels in 1 day. 26 refs., 7 figs., 1 tab.

  14. High-contrast and fast electrochromic switching enabled by plasmonics

    PubMed Central

    Xu, Ting; Walter, Erich C.; Agrawal, Amit; Bohn, Christopher; Velmurugan, Jeyavel; Zhu, Wenqi; Lezec, Henri J.; Talin, A. Alec

    2016-01-01

    With vibrant colours and simple, room-temperature processing methods, electrochromic polymers have attracted attention as active materials for flexible, low-power-consuming devices. However, slow switching speeds in devices realized to date, as well as the complexity of having to combine several distinct polymers to achieve a full-colour gamut, have limited electrochromic materials to niche applications. Here we achieve fast, high-contrast electrochromic switching by significantly enhancing the interaction of light—propagating as deep-subwavelength-confined surface plasmon polaritons through arrays of metallic nanoslits, with an electrochromic polymer—present as an ultra-thin coating on the slit sidewalls. The switchable configuration retains the short temporal charge-diffusion characteristics of thin electrochromic films, while maintaining the high optical contrast associated with thicker electrochromic coatings. We further demonstrate that by controlling the pitch of the nanoslit arrays, it is possible to achieve a full-colour response with high contrast and fast switching speeds, while relying on just one electrochromic polymer. PMID:26814453

  15. High-contrast and fast electrochromic switching enabled by plasmonics

    SciTech Connect

    Xu, Ting; Walter, Erich C.; Agrawal, Amit; Bohn, Christopher; Velmurugan, Jeyavel; Zhu, Wenqi; Lezec, Henri J.; Talin, A. Alec

    2016-01-27

    With vibrant colours and simple, room-temperature processing methods, electrochromic polymers have attracted attention as active materials for flexible, low-power-consuming devices. However, slow switching speeds in devices realized to date, as well as the complexity of having to combine several distinct polymers to achieve a full-colour gamut, have limited electrochromic materials to niche applications. Here we achieve fast, high-contrast electrochromic switching by significantly enhancing the interaction of light—propagating as deep-subwavelength-confined surface plasmon polaritons through arrays of metallic nanoslits, with an electrochromic polymer—present as an ultra-thin coating on the slit sidewalls. The switchable configuration retains the short temporal charge-diffusion characteristics of thin electrochromic films, while maintaining the high optical contrast associated with thicker electrochromic coatings. In conclusion, we further demonstrate that by controlling the pitch of the nanoslit arrays, it is possible to achieve a full-colour response with high contrast and fast switching speeds, while relying on just one electrochromic polymer.

  16. High-contrast and fast electrochromic switching enabled by plasmonics.

    PubMed

    Xu, Ting; Walter, Erich C; Agrawal, Amit; Bohn, Christopher; Velmurugan, Jeyavel; Zhu, Wenqi; Lezec, Henri J; Talin, A Alec

    2016-01-27

    With vibrant colours and simple, room-temperature processing methods, electrochromic polymers have attracted attention as active materials for flexible, low-power-consuming devices. However, slow switching speeds in devices realized to date, as well as the complexity of having to combine several distinct polymers to achieve a full-colour gamut, have limited electrochromic materials to niche applications. Here we achieve fast, high-contrast electrochromic switching by significantly enhancing the interaction of light--propagating as deep-subwavelength-confined surface plasmon polaritons through arrays of metallic nanoslits, with an electrochromic polymer--present as an ultra-thin coating on the slit sidewalls. The switchable configuration retains the short temporal charge-diffusion characteristics of thin electrochromic films, while maintaining the high optical contrast associated with thicker electrochromic coatings. We further demonstrate that by controlling the pitch of the nanoslit arrays, it is possible to achieve a full-colour response with high contrast and fast switching speeds, while relying on just one electrochromic polymer.

  17. High-contrast and fast electrochromic switching enabled by plasmonics

    NASA Astrophysics Data System (ADS)

    Talin, Albert; Xu, Ting; Walter, Erich; Agrawal, Amit; Bohn, Christopher; Velmurugan, Jeyavel; Zhu, Wenqi; Lezec, Henri

    With vibrant colors and simple, room-temperature processing methods, electrochromic polymers have long attracted attention as active materials for flexible, low-power consuming devices such as smart windows and displays. However, despite their many advantages, slow switching speed and complexity of combining several separate polymers to achieve full-color gamut has limited electrochromic materials to niche applications. Here we exploit the enhanced light-matter interaction associated with the deep-subwavelength mode confinement of surface plasmon polaritons propagating in metallic nanoslit arrays coated with ultra-thin electrochromic polymers to build a novel configuration for achieving high-contrast and fast electrochromic switching. The switchable configuration retains the short temporal charge-diffusion characteristics of thin electrochromic films while maintaining the high optical-contrast associated with thicker electrochromic coatings. We further demonstrate that by controlling the pitch of the nanoslit arrays, it is possible to achieve a full-color response with high-contrast and fast switching-speeds while relying on just one electrochromic polymer.

  18. High-contrast and fast electrochromic switching enabled by plasmonics

    NASA Astrophysics Data System (ADS)

    Xu, Ting; Walter, Erich C.; Agrawal, Amit; Bohn, Christopher; Velmurugan, Jeyavel; Zhu, Wenqi; Lezec, Henri J.; Talin, A. Alec

    2016-01-01

    With vibrant colours and simple, room-temperature processing methods, electrochromic polymers have attracted attention as active materials for flexible, low-power-consuming devices. However, slow switching speeds in devices realized to date, as well as the complexity of having to combine several distinct polymers to achieve a full-colour gamut, have limited electrochromic materials to niche applications. Here we achieve fast, high-contrast electrochromic switching by significantly enhancing the interaction of light--propagating as deep-subwavelength-confined surface plasmon polaritons through arrays of metallic nanoslits, with an electrochromic polymer--present as an ultra-thin coating on the slit sidewalls. The switchable configuration retains the short temporal charge-diffusion characteristics of thin electrochromic films, while maintaining the high optical contrast associated with thicker electrochromic coatings. We further demonstrate that by controlling the pitch of the nanoslit arrays, it is possible to achieve a full-colour response with high contrast and fast switching speeds, while relying on just one electrochromic polymer.

  19. High-contrast and fast electrochromic switching enabled by plasmonics

    DOE PAGES

    Xu, Ting; Walter, Erich C.; Agrawal, Amit; ...

    2016-01-27

    With vibrant colours and simple, room-temperature processing methods, electrochromic polymers have attracted attention as active materials for flexible, low-power-consuming devices. However, slow switching speeds in devices realized to date, as well as the complexity of having to combine several distinct polymers to achieve a full-colour gamut, have limited electrochromic materials to niche applications. Here we achieve fast, high-contrast electrochromic switching by significantly enhancing the interaction of light—propagating as deep-subwavelength-confined surface plasmon polaritons through arrays of metallic nanoslits, with an electrochromic polymer—present as an ultra-thin coating on the slit sidewalls. The switchable configuration retains the short temporal charge-diffusion characteristics of thinmore » electrochromic films, while maintaining the high optical contrast associated with thicker electrochromic coatings. In conclusion, we further demonstrate that by controlling the pitch of the nanoslit arrays, it is possible to achieve a full-colour response with high contrast and fast switching speeds, while relying on just one electrochromic polymer.« less

  20. BRAF mutation testing with a rapid, fully integrated molecular diagnostics system

    PubMed Central

    Huang, Helen J.; Falchook, Gerald S.; Devogelaere, Benoit; Kockx, Mark; Bempt, Isabelle Vanden; Reijans, Martin; Naing, Aung; Fu, Siqing; Piha-Paul, Sarina A.; Hong, David S.; Holley, Veronica R.; Tsimberidou, Apostolia M.; Stepanek, Vanda M.; Patel, Sapna P.; Kopetz, E. Scott; Subbiah, Vivek; Wheler, Jennifer J.; Zinner, Ralph G.; Karp, Daniel D.; Luthra, Rajyalakshmi; Roy-Chowdhuri, Sinchita; Sablon, Erwin; Meric-Bernstam, Funda; Maertens, Geert; Kurzrock, Razelle

    2015-01-01

    Fast and accurate diagnostic systems are needed for further implementation of precision therapy of BRAF-mutant and other cancers. The novel IdyllaTM BRAF Mutation Test has high sensitivity and shorter turnaround times compared to other methods. We used Idylla to detect BRAF V600 mutations in archived formalin-fixed paraffin-embedded (FFPE) tumor samples and compared these results with those obtained using the cobas 4800 BRAF V600 Mutation Test or MiSeq deep sequencing system and with those obtained by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory employing polymerase chain reaction–based sequencing, mass spectrometric detection, or next-generation sequencing. In one set of 60 FFPE tumor samples (15 with BRAF mutations per Idylla), the Idylla and cobas results had an agreement of 97%. Idylla detected BRAF V600 mutations in two additional samples. The Idylla and MiSeq results had 100% concordance. In a separate set of 100 FFPE tumor samples (64 with BRAF mutation per Idylla), the Idylla and CLIA-certified laboratory results demonstrated an agreement of 96% even though the tests were not performed simultaneously and different FFPE blocks had to be used for 9 cases. The IdyllaTM BRAF Mutation Test produced results quickly (sample to results time was about 90 minutes with about 2 minutes of hands on time) and the closed nature of the cartridge eliminates the risk of PCR contamination. In conclusion, our observations demonstrate that the Idylla test is rapid and has high concordance with other routinely used but more complex BRAF mutation–detecting tests. PMID:26330075

  1. Can robots patch-clamp as well as humans? Characterization of a novel sodium channel mutation.

    PubMed

    Estacion, M; Choi, J S; Eastman, E M; Lin, Z; Li, Y; Tyrrell, L; Yang, Y; Dib-Hajj, S D; Waxman, S G

    2010-06-01

    Ion channel missense mutations cause disorders of excitability by changing channel biophysical properties. As an increasing number of new naturally occurring mutations have been identified, and the number of other mutations produced by molecular approaches such as in situ mutagenesis has increased, the need for functional analysis by patch-clamp has become rate limiting. Here we compare a patch-clamp robot using planar-chip technology with human patch-clamp in a functional assessment of a previously undescribed Nav1.7 sodium channel mutation, S211P, which causes erythromelalgia. This robotic patch-clamp device can increase throughput (the number of cells analysed per day) by 3- to 10-fold. Both modes of analysis show that the mutation hyperpolarizes activation voltage dependence (8 mV by manual profiling, 11 mV by robotic profiling), alters steady-state fast inactivation so that it requires an additional Boltzmann function for a second fraction of total current (approximately 20% manual, approximately 40% robotic), and enhances slow inactivation (hyperpolarizing shift--15 mV by human,--13 mV robotic). Manual patch-clamping demonstrated slower deactivation and enhanced (approximately 2-fold) ramp response for the mutant channel while robotic recording did not, possibly due to increased temperature and reduced signal-to-noise ratio on the robotic platform. If robotic profiling is used to screen ion channel mutations, we recommend that each measurement or protocol be validated by initial comparison to manual recording. With this caveat, we suggest that, if results are interpreted cautiously, robotic patch-clamp can be used with supervision and subsequent confirmation from human physiologists to facilitate the initial profiling of a variety of electrophysiological parameters of ion channel mutations.

  2. Variegated RHOA mutations in adult T-cell leukemia/lymphoma

    PubMed Central

    Nagata, Yasunobu; Kontani, Kenji; Enami, Terukazu; Kataoka, Keisuke; Ishii, Ryohei; Totoki, Yasushi; Kataoka, Tatsuki R.; Hirata, Masahiro; Aoki, Kazuhiro; Nakano, Kazumi; Kitanaka, Akira; Sakata-Yanagimoto, Mamiko; Egami, Sachiko; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko; Shiozawa, Yusuke; Yoshizato, Tetsuichi; Suzuki, Hiromichi; Kon, Ayana; Yoshida, Kenichi; Sato, Yusuke; Sato-Otsubo, Aiko; Sanada, Masashi; Munakata, Wataru; Nakamura, Hiromi; Hama, Natsuko; Miyano, Satoru; Nureki, Osamu; Shibata, Tatsuhiro; Haga, Hironori; Shimoda, Kazuya; Katada, Toshiaki; Chiba, Shigeru; Watanabe, Toshiki

    2016-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a distinct form of peripheral T-cell lymphoma with poor prognosis, which is caused by the human T-lymphotropic virus type 1 (HTLV-1). In contrast to the unequivocal importance of HTLV-1 infection in the pathogenesis of ATLL, the role of acquired mutations in HTLV-1 infected T cells has not been fully elucidated, with a handful of genes known to be recurrently mutated. In this study, we identified unique RHOA mutations in ATLL through whole genome sequencing of an index case, followed by deep sequencing of 203 ATLL samples. RHOA mutations showed distinct distribution and function from those found in other cancers. Involving 15% (30/203) of ATLL cases, RHOA mutations were widely distributed across the entire coding sequence but almost invariably located at the guanosine triphosphate (GTP)-binding pocket, with Cys16Arg being most frequently observed. Unexpectedly, depending on mutation types and positions, these RHOA mutants showed different or even opposite functional consequences in terms of GTP/guanosine diphosphate (GDP)-binding kinetics, regulation of actin fibers, and transcriptional activation. The Gly17Val mutant did not bind GTP/GDP and act as a dominant negative molecule, whereas other mutants (Cys16Arg and Ala161Pro) showed fast GTP/GDP cycling with enhanced transcriptional activation. These findings suggest that both loss- and gain-of-RHOA functions could be involved in ATLL leukemogenesis. In summary, our study not only provides a novel insight into the molecular pathogenesis of ATLL but also highlights a unique role of variegation of heterologous RHOA mutations in human cancers. PMID:26574607

  3. Trigger of Fast Reconnection via Collapsing Current Sheets

    NASA Astrophysics Data System (ADS)

    Tenerani, A.; Velli, M.; Rappazzo, A. F.; Pucci, F.

    2015-12-01

    It has been widely believed that reconnection is the underlying mechanism of many explosive processes observed both in astrophysical and laboratory plasmas. However, both the questions of how magnetic reconnection is triggered in high Lundquist (S) and Reynolds (R) number plasmas, and how it can then occur on fast, ideal, time-scales remain open. Indeed, it has been argued that fast reconnection rates could be achieved once kinetic scales are reached, or, alternatively, by the onset of the so-called plasmoid instability within Sweet-Parker current sheets. However, it has been shown recently that a tearing mode instability (the "ideal tearing") can grow on an ideal, i.e., S-independent, timescale once the width a of a current sheet becomes thin enough with respect to its macroscopic length L, a/L ~ S-1/3. This suggests that current sheet thinning down to such a threshold aspect ratio —much larger, for S>>1, than the Sweet-Parker one that scales as a/L ~ S-1/2— might provide the trigger for fast reconnection even within the fluid plasma framework. Here we discuss the transition to fast reconnection by studying with visco-resistive MHD simulations the onset and evolution of the tearing instability within a single collapsing current sheet. We indeed show that the transition to a fast tearing mode instability takes place when an inverse aspect ratio of the order of the threshold a/L ~ S-1/3 is reached, and that the secondary current sheets forming nonlinearly become the source of a succession of recursive tearing instabilities. The latter is reminiscent of the fractal reconnection model of flares, which we modify in the light of the "ideal tearing" scenario.

  4. Development of ultra-fast 2D ion Doppler tomography using image intensified CMOS fast camera

    NASA Astrophysics Data System (ADS)

    Tanabe, Hiroshi; Kuwahata, Akihiro; Yamanaka, Haruki; Inomoto, Michiaki; Ono, Yasushi; TS-group Team

    2015-11-01

    The world fastest novel time-resolved 2D ion Doppler tomography diagnostics has been developed using fast camera with high-speed gated image intensifier (frame rate: 200kfps. phosphor decay time: ~ 1 μ s). Time evolution of line-integrated spectra are diffracted from a f=1m, F/8.3 and g=2400L/mm Czerny-Turner polychromator, whose output is intensified and recorded to a high-speed camera with spectral resolution of ~0.005nm/pixel. The system can accommodate up to 36 (9 ×4) spatial points recorded at 5 μs time resolution, tomographic reconstruction is applied for the line-integrated spectra, time-resolved (5 μs/frame) local 2D ion temperature measurement has been achieved without any assumption of shot repeatability. Ion heating during intermittent reconnection event which tends to happen during high guide field merging tokamak was measured around diffusion region in UTST. The measured 2D profile shows ion heating inside the acceleration channel of reconnection outflow jet, stagnation point and downstream region where reconnected field forms thick closed flux surface as in MAST. Achieved maximum ion temperature increases as a function of Brec2 and shows good fit with MAST experiment, demonstrating promising CS-less startup scenario for spherical tokamak. This work is supported by JSPS KAKENHI Grant Number 15H05750 and 15K20921.

  5. A frequent splicing mutation and novel missense mutations color the updated mutational spectrum of classic galactosemia in Portugal.

    PubMed

    Coelho, Ana I; Ramos, Ruben; Gaspar, Ana; Costa, Cláudia; Oliveira, Anabela; Diogo, Luísa; Garcia, Paula; Paiva, Sandra; Martins, Esmeralda; Teles, Elisa Leão; Rodrigues, Esmeralda; Cardoso, M Teresa; Ferreira, Elena; Sequeira, Sílvia; Leite, Margarida; Silva, Maria João; de Almeida, Isabel Tavares; Vicente, João B; Rivera, Isabel

    2014-01-01

    Classic galactosemia is an autosomal recessive disorder caused by deficient galactose-1-phosphate uridylyltransferase (GALT) activity. Patients develop symptoms in the neonatal period, which can be ameliorated by dietary restriction of galactose. Many patients develop long-term complications, with a broad range of clinical symptoms whose pathophysiology is poorly understood. The high allelic heterogeneity of GALT gene that characterizes this disorder is thought to play a determinant role in biochemical and clinical phenotypes. We aimed to characterize the mutational spectrum of GALT deficiency in Portugal and to assess potential genotype-phenotype correlations. Direct sequencing of the GALT gene and in silico analyses were employed to evaluate the impact of uncharacterized mutations upon GALT functionality. Molecular characterization of 42 galactosemic Portuguese patients revealed a mutational spectrum comprising 14 nucleotide substitutions: ten missense, two nonsense and two putative splicing mutations. Sixteen different genotypic combinations were detected, half of the patients being p.Q188R homozygotes. Notably, the second most frequent variation is a splicing mutation. In silico predictions complemented by a close-up on the mutations in the protein structure suggest that uncharacterized missense mutations have cumulative point effects on protein stability, oligomeric state, or substrate binding. One splicing mutation is predicted to cause an alternative splicing event. This study reinforces the difficulty in establishing a genotype-phenotype correlation in classic galactosemia, a monogenic disease whose complex pathogenesis and clinical features emphasize the need to expand the knowledge on this "cloudy" disorder.

  6. The Relationship among Achievement Motivation Orientations, Achievement Goals, and Academic Achievement and Interest: A Multiple Mediation Analysis

    ERIC Educational Resources Information Center

    Abd-El-Fattah, Sabry M.; Patrick, Rosan R.

    2011-01-01

    The aim of the present study is to examine the relationships among achievement motivation orientations and academic achievement and interest and whether achievement goals mediate these relationships. A sample of 503 students aged 14-16 years from 8 secondary schools in two Australia cities responded to a questionnaire package, comprising measures…

  7. FKRP mutations, including a founder mutation, cause phenotype variability in Chinese patients with dystroglycanopathies.

    PubMed

    Fu, Xiaona; Yang, Haipo; Wei, Cuijie; Jiao, Hui; Wang, Shuo; Yang, Yanling; Han, Chunxi; Wu, Xiru; Xiong, Hui

    2016-12-01

    Mutations in the fukutin-related protein (FKRP) gene have been associated with dystroglycanopathies, which are common in Europe but rare in Asia. Our study aimed to retrospectively analyze and characterize the clinical, myopathological and genetic features of 12 Chinese patients with FKRP mutations. Three patients were diagnosed with congenital muscular dystrophy type 1C (MDC1C) and nine patients were diagnosed with limb girdle muscular dystrophy type 2I (LGMD2I). Three muscle biopsy specimens had dystrophic changes and reduced glycosylated α-dystroglycan staining, and two showed reduced expression of laminin α2. Two known and 13 novel mutations were identified in our single center cohort. Interestingly, the c.545A>G mutation was found in eight of the nine LGMD2I patients as a founder mutation and this founder mutation in Chinese patients differs from the one seen in European patients. Moreover, patients homozygous for the c.545A>G mutation were clinically asymptomatic, a less severe phenotype than in compound heterozygous patients with the c.545A>G mutation. The 13 novel mutations of FKRP significantly expanded the mutation spectrum of MDC1C and LGMD2I, and the different founder mutations indicate the ethnic difference in FKRP mutations.

  8. TERT promoter mutations in thyroid cancer.

    PubMed

    Liu, Rengyun; Xing, Mingzhao

    2016-03-01

    The 2013 discovery of Telomerase reverse transcriptase (TERT) promoter mutations chr5, 1,295,228 C>T (C228T) and 1,295,250 C>T (C250T) in thyroid cancer represents an important event in the thyroid cancer field and much progress has occurred since then. This article provides a comprehensive review of this exciting new thyroid cancer field. The oncogenic role of TERT promoter mutations involves their creation of consensus binding sites for E-twenty-six transcriptional factors. TERT C228T is far more common than TERT C250T and their collective prevalence is, on average, 0, 11.3, 17.1, 43.2 and 40.1% in benign thyroid tumors, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer and anaplastic thyroid cancer, respectively, displaying an association with aggressive types of thyroid cancer. TERT promoter mutations are associated with aggressive thyroid tumor characteristics, tumor recurrence and patient mortality as well as BRAF V600E mutation. Coexisting BRAF V600E and TERT promoter mutations have a robust synergistic impact on the aggressiveness of PTC, including a sharply increased tumor recurrence and patient mortality, while either mutation alone has a modest impact. Thus, TERT with promoter mutations represents a prominent new oncogene in thyroid cancer and the mutations are promising new diagnostic and prognostic genetic markers for thyroid cancer, which, in combination with BRAF V600E mutation or other genetic markers (e.g. RAS mutations), are proving to be clinically useful for the management of thyroid cancer. Future studies will specifically define such clinical utilities, elucidate the biological mechanisms and explore the potential as therapeutic targets of TERT promoter mutations in thyroid cancer.

  9. New real-time-PCR method to identify single point mutations in hepatitis C virus

    PubMed Central

    Chen, Qian; Belmonte, Irene; Buti, Maria; Nieto, Leonardo; Garcia-Cehic, Damir; Gregori, Josep; Perales, Celia; Ordeig, Laura; Llorens, Meritxell; Soria, Maria Eugenia; Esteban, Rafael; Esteban, Juan Ignacio; Rodriguez-Frias, Francisco; Quer, Josep

    2016-01-01

    AIM To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus (HCV). METHODS In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir. Low-cost, highly sensitive techniques enabling routine detection of these single point mutations would be useful to identify patients at a risk of treatment failure. LightCycler methods, based on real-time PCR with sequence-specific probe hybridization, have been implemented in most diagnostic laboratories. However, this technique cannot identify single point mutations in highly variable genetic environments, such as the HCV genome. To circumvent this problem, we developed a new method to homogenize all nucleotides present in a region except the point mutation of interest. RESULTS Using nucleotide-specific probes Q, K, and R substitutions at position 80 were clearly identified at a sensitivity of 10% (mutations present at a frequency of at least 10% were detected). The technique was successfully applied to identify the Q80K substitution in 240 HCV G1 serum samples, with performance comparable to that of direct Sanger sequencing, the current standard procedure for this purpose. The new method was then validated in a Catalonian population of 202 HCV G1-infected individuals. Q80K was detected in 14.6% of G1a patients and 0% of G1b in our setting. CONCLUSION A fast, low-cost diagnostic strategy based on real-time PCR and fluorescence resonance energy transfer probe melting curve analysis has been successfully developed to identify single point mutations in highly variable genomes such as hepatitis C virus. This

  10. Clock-like mutational processes in human somatic cells

    SciTech Connect

    Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; Sale, Julian E.; Campbell, Peter J.; Nik-Zainal, Serena; Stratton, Michael R.

    2015-11-09

    During the course of a lifetime, somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell's genome. Some processes generate mutations throughout life at a constant rate in all individuals, and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated, indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This paper provides the first survey of clock-like mutational processes operating in human somatic cells.

  11. Clock-like mutational processes in human somatic cells

    PubMed Central

    Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.; Sale, Julian E.; Campbell, Peter J.; Nik-Zainal, Serena; Stratton, Michael R.

    2016-01-01

    During the course of a lifetime somatic cells acquire mutations. Different mutational processes may contribute to the mutations accumulated in a cell, with each imprinting a mutational signature on the cell’s genome. Some processes generate mutations throughout life at a constant rate in all individuals and the number of mutations in a cell attributable to these processes will be proportional to the chronological age of the person. Using mutations from 10,250 cancer genomes across 36 cancer types, we investigated clock-like mutational processes that have been operating in normal human cells. Two mutational signatures show clock-like properties. Both exhibit different mutation rates in different tissues. However, their mutation rates are not correlated indicating that the underlying processes are subject to different biological influences. For one signature, the rate of cell division may influence its mutation rate. This study provides the first survey of clock-like mutational processes operative in human somatic cells. PMID:26551669

  12. Simultaneous detection of fourteen Italian cystic fibrosis mutations in seven exons by reverse dot-blot analysis.

    PubMed

    Rady, M; D'Alcamo, E; Seia, M; Iapichino, L; Ferrari, M; Russo, S; Romeo, G; Maggio, A

    1995-10-01

    The increasing number of cystic fibrosis (CF) mutations is a great obstacle to the use of DNA procedures in the detection of gene defects. We describe a fast, cheap and non-radioactive procedure, Reverse dot-blot analysis (RDB), for the simultaneous detection of CF mutations in the Italian population. We used this approach to study seven exons of the CF gene for 14 CF gene defects and were able to characterize 222 of 272 CF chromosomes (80%). The cost of the procedure was $25 per sample analysed.

  13. Evolution of extended-spectrum beta-lactamases by mutation.

    PubMed

    Gniadkowski, M

    2008-01-01

    Antimicrobial resistance genes in pathogenic bacteria belong to the most rapidly evolving DNA sequences, which results in an enormous structural diversity of resistance effectors. Structural modifications of resistance genes by mutation and recombination, together with a multitude of events that stimulate their mobility and expression, allow microorganisms to survive in environments saturated with antimicrobial agents of various types and generations. Genes coding for beta-lactamases in Gram-negative bacteria are a fascinating example of this multifocal and multidirectional evolution, with the extended-spectrum beta-lactamases (ESBLs) being one of the most spectacular 'achievements'. Some of the ESBLs known today are 'ready-to-use' enzymes in their natural producers but these are often of low pathogenic potential, or none at all. The problem appears upon mobilisation of a gene encoding such an ESBL, and its acquisition and sufficient expression by a more virulent organism. Many ESBLs are generated by mutations in genes coding for broad-spectrum enzymes, which have been mobile since at least the 1960s and which have disseminated very widely in populations of pathogenic bacteria. Strong selection pressure exerted by antimicrobial use, especially with newer-generation beta-lactam antibiotics, efficiently promotes these two modes of ESBL emergence and subsequent spread. It also stimulates further evolution of ESBLs by accumulation of other mutations with an astonishing variety of effects on beta-lactamase structure and activity. Remarkably, more than 300 natural ESBL variants have been identified since the mid-1980s but in-vitro studies suggest that ESBL evolution has certainly not come to an end; they may also help in predicting future developments. The aim of this review is to briefly overview the role of various mutations in ESBL evolution.

  14. Fast breeder reactor protection system

    DOEpatents

    van Erp, J.B.

    1973-10-01

    Reactor protection is provided for a liquid-metal-fast breeder reactor core by measuring the coolant outflow temperature from each of the subassemblies of the core. The outputs of the temperature sensors from a subassembly region of the core containing a plurality of subassemblies are combined in a logic circuit which develops a scram alarm if a predetermined number of the sensors indicate an over temperature condition. The coolant outflow from a single subassembly can be mixed with the coolant outflow from adjacent subassemblies prior to the temperature sensing to increase the sensitivity of the protection system to a single subassembly failure. Coherence between the sensors can be required to discriminate against noise signals. (Official Gazette)

  15. Rotor for centrifugal fast analyzers

    DOEpatents

    Lee, N.E.

    1984-01-01

    The invention is an improved photometric analyzer of the rotary cuvette type, the analyzer incorporating a multicuvette rotor of novel design. The rotor (a) is leaktight, (b) permits operation in the 90/sup 0/ and 180/sup 0/ excitation modes, (c) is compatible with extensively used Centrifugal Fast Analyzers, and (d) can be used thousands of times. The rotor includes an assembly comprising a top plate, a bottom plate, and a central plate, the rim of the central plate being formed with circumferentially spaced indentations. A uv-transmitting ring is sealably affixed to the indented rim to define with the indentations an array of cuvettes. The ring serves both as a sealing means and an end window for the cuvettes.

  16. Rotor for centrifugal fast analyzers

    DOEpatents

    Lee, Norman E.

    1985-01-01

    The invention is an improved photometric analyzer of the rotary cuvette type, the analyzer incorporating a multicuvette rotor of novel design. The rotor (a) is leaktight, (b) permits operation in the 90.degree. and 180.degree. excitation modes, (c) is compatible with extensively used Centrifugal Fast Analyzers, and (d) can be used thousands of times. The rotor includes an assembly comprising a top plate, a bottom plate, and a central plate, the rim of the central plate being formed with circumferentially spaced indentations. A UV-transmitting ring is sealably affixed to the indented rim to define with the indentations an array of cuvettes. The ring serves both as a sealing means and an end window for the cuvettes.

  17. Fast Steerable Principal Component Analysis

    PubMed Central

    Zhao, Zhizhen; Shkolnisky, Yoel; Singer, Amit

    2016-01-01

    Cryo-electron microscopy nowadays often requires the analysis of hundreds of thousands of 2-D images as large as a few hundred pixels in each direction. Here, we introduce an algorithm that efficiently and accurately performs principal component analysis (PCA) for a large set of 2-D images, and, for each image, the set of its uniform rotations in the plane and their reflections. For a dataset consisting of n images of size L × L pixels, the computational complexity of our algorithm is O(nL3 + L4), while existing algorithms take O(nL4). The new algorithm computes the expansion coefficients of the images in a Fourier–Bessel basis efficiently using the nonuniform fast Fourier transform. We compare the accuracy and efficiency of the new algorithm with traditional PCA and existing algorithms for steerable PCA. PMID:27570801

  18. Integral fast reactor safety features

    SciTech Connect

    Cahalan, J.E.; Kramer, J.M.; Marchaterre, J.F.; Mueller, C.J.; Pedersen, D.R.; Sevy, R.H.; Wade, D.C.; Wei, T.Y.C.

    1988-01-01

    The Integral Fast Reactor (IFR) is an advanced liquid-metal-cooled reactor concept being developed at Argonne National Laboratory. The two major goals of the IFR development effort are improved economics and enhanced safety. In addition to liquid metal cooling, the principal design features that distinguish the IFR are: (1) a pool-type primary system, (2) an advanced ternary alloy metallic fuel, and (3) an integral fuel cycle with on-site fuel reprocessing and fabrication. This paper focuses on the technical aspects of the improved safety margins available in the IFR concept. This increased level of safety is made possible by (1) the liquid metal (sodium) coolant and pool-type primary system layout, which together facilitate passive decay heat removal, and (2) a sodium-bonded metallic fuel pin design with thermal and neutronic properties that provide passive core responses which control and mitigate the consequences of reactor accidents.

  19. Fast Steerable Principal Component Analysis.

    PubMed

    Zhao, Zhizhen; Shkolnisky, Yoel; Singer, Amit

    2016-03-01

    Cryo-electron microscopy nowadays often requires the analysis of hundreds of thousands of 2-D images as large as a few hundred pixels in each direction. Here, we introduce an algorithm that efficiently and accurately performs principal component analysis (PCA) for a large set of 2-D images, and, for each image, the set of its uniform rotations in the plane and their reflections. For a dataset consisting of n images of size L × L pixels, the computational complexity of our algorithm is O(nL(3) + L(4)), while existing algorithms take O(nL(4)). The new algorithm computes the expansion coefficients of the images in a Fourier-Bessel basis efficiently using the nonuniform fast Fourier transform. We compare the accuracy and efficiency of the new algorithm with traditional PCA and existing algorithms for steerable PCA.

  20. Fast data parallel polygon rendering

    SciTech Connect

    Ortega, F.A.; Hansen, C.D.

    1993-09-01

    This paper describes a parallel method for polygonal rendering on a massively parallel SIMD machine. This method, based on a simple shading model, is targeted for applications which require very fast polygon rendering for extremely large sets of polygons such as is found in many scientific visualization applications. The algorithms described in this paper are incorporated into a library of 3D graphics routines written for the Connection Machine. The routines are implemented on both the CM-200 and the CM-5. This library enables a scientists to display 3D shaded polygons directly from a parallel machine without the need to transmit huge amounts of data to a post-processing rendering system.