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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. PMID:24481126

  2. Fast Diagnostics of BRAF Mutations in Biopsies from Malignant Melanoma.

    PubMed

    Huber, François; Lang, Hans Peter; Glatz, Katharina; Rimoldi, Donata; Meyer, Ernst; Gerber, Christoph

    2016-09-14

    According to the American skin cancer foundation, there are more new cases of skin cancer than the combined incidence of cancers of the breast, prostate, lung, and colon each year, and malignant melanoma represents its deadliest form. About 50% of all cases are characterized by a particular mutation BRAF(V600E) in the BRAF (Rapid Acceleration of Fibrosarcoma gene B) gene. Recently developed highly specific drugs are able to fight BRAF(V600E) mutated tumors but require diagnostic tools for fast and reliable mutation detection to warrant treatment efficiency. We completed a preliminary clinical trial applying cantilever array sensors to demonstrate identification of a BRAF(V600E) single-point mutation using total RNA obtained from biopsies of metastatic melanoma of diverse sources (surgical material either frozen or fixated with formalin and embedded in paraffin). The method is faster than the standard Sanger or pyrosequencing methods and comparably sensitive as next-generation sequencing. Processing time from biopsy to diagnosis is below 1 day and does not require PCR amplification, sequencing, and labels. PMID:27490749

  3. FAST20XX: Achievements On European Suborbital Space Flight

    NASA Astrophysics Data System (ADS)

    Mack, A.; Steelant, J.; Adirim, H.; Lentsch, A.; Marini, M.; Pilz, N.

    2011-05-01

    In Europe, the EC co-funded project FAST20XX aims at exploring the borderline between aviation and space by investigating suborbital vehicles. The main focus is the identification and mastering of critical technologies for such vehicles rather than the vehicle development itself. Besides the objectives and overall layout of the project, the paper addresses also the progress made during the first period of the project. Two vehicle concepts are considered. A first one is a space vehicle launched from an airplane providing a low-energy ballistic flight experience using hybrid propulsion. The second is a vertically starting two-stage rocket space vehicle system concept taken as a basis to identify the conditions and constraints experienced during high- energy suborbital ultra-fast transport. The paper mainly discusses the two actual reference vehicles and the technical aspects of prerequisites for commercial operation including safety, human spaceflight, business cases, environmental and legal issues.

  4. Domain III S4 in closed-state fast inactivation: insights from a periodic paralysis mutation.

    PubMed

    Groome, James R; Jurkat-Rott, Karin; Lehmann-Horn, Frank

    2014-01-01

    Heterologous expression of sodium channel mutations in hypokalemic periodic paralysis reveals 2 variants on channel dysfunction. Charge-reducing mutations of voltage sensing S4 arginine residues alter channel gating as typically studied with expression in mammalian cells. These mutations also produce leak currents through the voltage sensor module, as typically studied with expression in Xenopus oocytes. DIIIS4 mutations at R3 in the skeletal muscle sodium channel produce gating defects and omega current consistent with the phenotype of reduced excitability. Here, we confirm DIIIS4 R3C gating defects in the oocyte expression system for fast inactivation and its recovery. We provide novel data for the effects of the cysteine mutation on voltage sensor movement, to further our understanding of sodium channel defects in hypokalemic periodic paralysis. Gating charge movement and its remobilization are selectively altered by the mutation at hyperpolarized membrane potential, as expected with reduced serum potassium. PMID:25483590

  5. Domain III S4 in closed-state fast inactivation: Insights from a periodic paralysis mutation

    PubMed Central

    Groome, James R; Jurkat-Rott, Karin; Lehmann-Horn, Frank

    2014-01-01

    Heterologous expression of sodium channel mutations in hypokalemic periodic paralysis reveals 2 variants on channel dysfunction. Charge-reducing mutations of voltage sensing S4 arginine residues alter channel gating as typically studied with expression in mammalian cells. These mutations also produce leak currents through the voltage sensor module, as typically studied with expression in Xenopus oocytes. DIIIS4 mutations at R3 in the skeletal muscle sodium channel produce gating defects and omega current consistent with the phenotype of reduced excitability. Here, we confirm DIIIS4 R3C gating defects in the oocyte expression system for fast inactivation and its recovery. We provide novel data for the effects of the cysteine mutation on voltage sensor movement, to further our understanding of sodium channel defects in hypokalemic periodic paralysis. Gating charge movement and its remobilization are selectively altered by the mutation at hyperpolarized membrane potential, as expected with reduced serum potassium. PMID:25483590

  6. Fast, single-molecule localization that achieves theoretically minimum uncertainty.

    PubMed

    Smith, Carlas S; Joseph, Nikolai; Rieger, Bernd; Lidke, Keith A

    2010-05-01

    We describe an iterative algorithm that converges to the maximum likelihood estimate of the position and intensity of a single fluorophore. Our technique efficiently computes and achieves the Cramér-Rao lower bound, an essential tool for parameter estimation. An implementation of the algorithm on graphics processing unit hardware achieved more than 10(5) combined fits and Cramér-Rao lower bound calculations per second, enabling real-time data analysis for super-resolution imaging and other applications. PMID:20364146

  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. 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.

  9. Achieving fast timing performance with multiplexed SiPMs.

    PubMed

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

    2016-04-01

    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. PMID:26987898

  10. Achieving fast timing performance with multiplexed SiPMs

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

    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 232+/- 2 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 4× 4 array of 3 mm  ×  3 mm  ×  20 mm LFS crystals showed an average FWHM coincidence time resolution of 278+/- 7 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.

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

    PubMed

    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. PMID:27250430

  12. 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.

  13. Paroxysmal extreme pain disorder mutations within the D3/S4–S5 linker of Nav1.7 cause moderate destabilization of fast inactivation

    PubMed Central

    Jarecki, Brian W; Sheets, Patrick L; Jackson II, James O; Cummins, Theodore R

    2008-01-01

    Single-point missense mutations in the peripheral neuronal voltage-gated sodium channel Nav1.7 are implicated in the painful inherited neuropathy paroxysmal extreme pain disorder (PEPD). The Nav1.7 PEPD mutations are located in regions of the channel suggested to play important roles in fast inactivation. PEPD mutations in the putative inactivation gate have been reported to significantly impair fast inactivation, resulting in pronounced persistent currents. However, PEPD mutations in the S4–S5 linker of domain 3 (D3/S4–S5) had not been characterized and the roles of specific residues in this linker in channel gating are unclear. We functionally characterized two of the D3/S4–S5 PEPD mutations (V1298F and V1299F) and compared their effects on gating to an adjacent non-PEPD mutation (V1300F) and the I1461T PEPD mutation, located in the putative inactivation gate. The primary effect of the V1298F and V1299F mutations is to shift the voltage dependence of fast inactivation by ∼20 mV in the depolarizing direction. We observed a similar effect with the PEPD mutation I1461T. Interestingly, while all three PEPD mutations increased persistent currents, the relative amplitudes (∼6% of peak) were much smaller than previously reported for the I1461T mutation. In contrast, the main effect of the V1300F mutation was a depolarizing shift in the voltage dependence of activation. These data demonstrate that (1) mutations within D3/S4–S5 affect inactivation of Nav1.7 in a residue-specific manner and (2) disruption of the fast-inactivated state by PEPD mutations can be more moderate than previously indicated, which has important implications for the pathophysiology of PEPD. PMID:18599537

  14. Evolution in fast forward: a potential role for mutators in accelerating Staphylococcus aureus pathoadaptation.

    PubMed

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

    2013-02-01

    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

  15. Fast Ignition: Physics Progress in the US Fusion Energy Program and Prospects for Achieving Ignition.

    SciTech Connect

    Key, M H; Andersen, C; Cowan, T; Fisch, N; Freeman, R; Hatchett, S; Hill, J; King, J; Koch, J; Lasinski, B; Langdon, B; MacKinnon, A; Parks, P; Rosenbluth, M; Ruhl, H; Snavely, R; Stephens, R; Tabak, M; Town, R

    2002-10-16

    Fast ignition (FI) has significant potential advantages for inertial fusion energy and it is therefore being studied as an exploratory concept in the US fusion energy program. FI is based on short pulse isochoric heating of pre-compressed DT by intense beams of laser accelerated MeV electrons or protons. Recent experimental progress in the study of these two heating processes is discussed. The goal is to benchmark new models in order to predict accurately the requirements for full-scale fast ignition. An overview is presented of the design and experimental testing of a cone target implosion concept for fast ignition. Future prospects and conceptual designs for larger scale FI experiments using planned high energy petawatt upgrades of major lasers in the US are outlined. A long-term roadmap for FI is defined.

  16. Fast Growth Increases the Selective Advantage of a Mutation Arising Recurrently during Evolution under Metal Limitation

    PubMed Central

    Chou, Hsin-Hung; Berthet, Julia; Marx, Christopher J.

    2009-01-01

    Understanding the evolution of biological systems requires untangling the molecular mechanisms that connect genetic and environmental variations to their physiological consequences. Metal limitation across many environments, ranging from pathogens in the human body to phytoplankton in the oceans, imposes strong selection for improved metal acquisition systems. In this study, we uncovered the genetic and physiological basis of adaptation to metal limitation using experimental populations of Methylobacterium extorquens AM1 evolved in metal-deficient growth media. We identified a transposition mutation arising recurrently in 30 of 32 independent populations that utilized methanol as a carbon source, but not in any of the 8 that utilized only succinate. These parallel insertion events increased expression of a novel transporter system that enhanced cobalt uptake. Such ability ensured the production of vitamin B12, a cobalt-containing cofactor, to sustain two vitamin B12–dependent enzymatic reactions essential to methanol, but not succinate, metabolism. Interestingly, this mutation provided higher selective advantages under genetic backgrounds or incubation temperatures that permit faster growth, indicating growth-rate–dependent epistatic and genotype-by-environment interactions. Our results link beneficial mutations emerging in a metal-limiting environment to their physiological basis in carbon metabolism, suggest that certain molecular features may promote the emergence of parallel mutations, and indicate that the selective advantages of some mutations depend generically upon changes in growth rate that can stem from either genetic or environmental influences. PMID:19763169

  17. Research Results Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

    NASA Astrophysics Data System (ADS)

    2009-01-01

    Ultra-fast Energy Transfer from Monomer to Dimer within a Trimeric Molecule New Progress in Heterogeneous Catalysis Research Key Progress in Research on Terrestrial Carbon Cycle in China A New Progress in Research on the Mechanism of Bio-Invasion New Findings in Anti-viral infection and Control of Inflammation Major Headway in Avian Origin Research New Progress in Gold-Nanoparticle-Based Biochips Topological Insulator Research Made Important Progress Major Progress in Biodiversity Achieved New Developments of Direct Methods in Protein Crystallography Major Progress in China-UK Collaboration on the Causal Relationship between Volcanic Activity and Biological Distinction News in Brief: NSFC set up "Research Fund for Young Foreign Scholars" How Often Does Human DNA Mutate? Research Progress on Colossal Anisotropic Magneto Resistive Effect

  18. Rapid tenderisation of lamb M. longissimus with very fast chilling depends on rapidly achieving sub-zero temperatures.

    PubMed

    Jacob, Robin; Rosenvold, Katja; North, Michael; Kemp, Robert; Warner, Robyn; Geesink, Geert

    2012-09-01

    A study was undertaken to determine whether variations within the defined temperature-by-time profile for very fast chilling (VFC), might explain variations in tenderness found with VFC. Loins from 32 lambs were subjected to one of five cooling regimes; defined by the average temperature between the meat surface and centre reached at a specific time post mortem. These were: -0.3 °C at 22 h (Control), 2.6 °C at 1.5 h (Fast(supra-zero)), 0.7 °C at 5.5 h (Slow(supra-zero)), -1.6 °C at 1.5 h (Fast(sub-zero)) and -2.3 °C at 5.5 h (Slow(sub-zero)), respectively. Shear force values considered very tender by consumers (less than 50 N, MIRINZ tenderometer) were found 2 days post mortem in Fast(sub-zero) loins only. Both time and temperature at the end of the cooling period contributed to variations in shear force. To achieve low shear force, the loins needed to be cooled to less than 0 °C at 1.5 h post mortem. PMID:22551870

  19. 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…

  20. Dependence of mutation induction on fast-neutron energy in a human epithelial teratocarcinoma cell line (P3).

    PubMed

    Sharma, S; Hill, C K

    1996-03-01

    To date, few studies have evaluated the magnitude of the risks of somatic effects in humans from low-dose or protracted radiation exposure to neutrons using in vitro or in vivo techniques (A. Kronenberg, Radiat. Res. 128, S87-S93, 1991). In earlier study a strong energy dependence was shown for neutron-induced mutations at both the hprt and the tk loci in a rodent fibroblast cell line (Zhu and Hill, Radiat. Res. 139, 300-306, 1994). Using fast neutrons produced by impinging protons on a beryllium target at the UCLA/VA cyclotron, we have been examining the energy dependence of mutation induction at the HPRT locus in a human epithelial cell line derived from solid tumor tissue. In the present study, human epithelial teratocarcinoma cells were exposed to neutron beams produced from protons with 46, 30, 20 and 14 MeV energy. We found that cytotoxicity increased by 50% as the neutron beams produced from 46 MeV to 14 MeV, confirming many earlier reports. But as with the Chinese hamster cells, the mutation frequency at the HPRT locus increased 2.5-4-fold with decreasing neutron energy. Additionally, although there was a strong energy dependence for mutation induction, we noted that the shape of the induction curves was curvilinear for the human cells compared to the linearity of the curves obtained for the Chinese hamster cells and some other non-solid tissue human cell lines. Calculations of the RBE, using gamma rays as the standard reflected these differences. The RBE for mutation at the HPRT locus was dependent not only upon energy but also on dose, giving rise to RBEs that were in some cases distinctly different from those found in the Chinese hamster cell line. In the low-dose region (doses below 75 cGy) the maximum RBE of about 5 resulted from irradiation by the lowest-energy neutron beam (14 MeV protons on beryllium). PMID:8927701

  1. Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection.

    PubMed

    MacLeod, J A; Nemeth, A C; Dicke, W C; Wang, D; Manalili Wheeler, S; Hannis, J C; Collier, G B; Drader, J J

    2016-07-01

    Point of care molecular diagnostics benefits from a portable battery-operated device capable of performing a fast turnaround using reliable inexpensive cartridges. We describe a prototype device for performing a molecular diagnostics test for clinical and biodefense samples in 16 minutes using a prototype capable of an 8 minute PCR reaction, followed by hybridization and detection on an electrochemical microarray based on the i-STAT® system. We used human buccal swabs for hemochromatosis testing including in-device DNA extraction. Additional clinical and biodefense samples included influenza A and bacterial select agents Bacillus anthracis, Yersinia pestis and Francisella tularensis. PMID:27280174

  2. 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.

  3. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia

    PubMed Central

    Thompson, Philip A.; Tam, Constantine S.; O’Brien, Susan M.; Wierda, William G.; Stingo, Francesco; Plunkett, William; Smith, Susan C.; Kantarjian, Hagop M.; Freireich, Emil J.

    2016-01-01

    Accurate identification of patients likely to achieve long-progression-free survival (PFS) after chemoimmunotherapy is essential given the availability of less toxic alternatives, such as ibrutinib. Fludarabine, cyclophosphamide, and rituximab (FCR) achieved a high response rate, but continued relapses were seen in initial reports. We reviewed the original 300 patient phase 2 FCR study to identify long-term disease-free survivors. Minimal residual disease (MRD) was assessed posttreatment by a polymerase chain reaction-based ligase chain reaction assay (sensitivity 0.01%). At the median follow-up of 12.8 years, PFS was 30.9% (median PFS, 6.4 years). The 12.8-year PFS was 53.9% for patients with mutated immunoglobulin heavy chain variable (IGHV) gene (IGHV-M) and 8.7% for patients with unmutated IGHV (IGHV-UM). 50.7% of patients with IGHV-M achieved MRD-negativity posttreatment; of these, PFS was 79.8% at 12.8 years. A plateau was seen on the PFS curve in patients with IGHV-M, with no relapses beyond 10.4 years in 42 patients (total follow-up 105.4 patient-years). On multivariable analysis, IGHV-UM (hazard ratio, 3.37 [2.18-5.21]; P < .001) and del(17p) by conventional karyotyping (hazard ratio, 7.96 [1.02-61.92]; P = .048) were significantly associated with inferior PFS. Fifteen patients with IGHV-M had 4-color MRD flow cytometry (sensitivity 0.01%) performed in peripheral blood, at a median of 12.8 years posttreatment (range, 9.5-14.7). All were MRD-negative. The high rate of very long-term PFS in patients with IGHV-M after FCR argues for the continued use of chemoimmunotherapy in this patient subgroup outside clinical trials; alternative strategies may be preferred in patients with IGHV-UM, to limit long-term toxicity. PMID:26492934

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

    PubMed Central

    Nicholas, Frank W; Hobbs, Matthew

    2014-01-01

    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). PMID:24372556

  5. The large diameter and fast growth of self-organized TiO2 nanotube arrays achieved via electrochemical anodization

    NASA Astrophysics Data System (ADS)

    Yin, H.; Liu, H.; Shen, W. Z.

    2010-01-01

    We have carried out a detailed investigation of the effect of water content on the electrochemical anodization of Ti in electrolytes consisting of ammonium fluoride, water, and ethylene glycol. We have explored the possible growth of ordered TiO2 nanotubes in the electrolyte with water concentrations from 1 to 100 vol% and the applied voltage from 10 to 150 V, where large diameter (~600 nm) and fast growth rate (~100 µm h-1) have been successfully realized for the self-organized TiO2 nanotube arrays. The achievement benefits from the clear understanding of the effects of both the water content and the anodization voltage on the formation of TiO2 nanotube arrays. We have further shown crystalline formation of TiO2 nanotubes by simple thermal annealing. The mechanisms of the effect of the water content on the diameter and growth rate revealed here should establish a basis for further optimization of the TiO2 nanotube geometries.

  6. Holographic polymer networks formed in liquid crystal phase modulators via a He-Ne laser to achieve ultra-fast optical response.

    PubMed

    Chien, Chun-Yu; Hsu, Che-Ju; Chen, Yu-Wen; Tseng, Sheng-Hao; Sheu, Chia-Rong

    2016-04-01

    The holographic polymer network formed in liquid crystal (LC) phase modulators via a He-Ne laser in this study demonstrates ultra-fast optically response and low light scattering. These advantages are mainly caused by the small LC domains and uniform polymer network when processing LC cells via holographic exposure to a He-Ne laser. The use of this method to fabricate LC cells as phase modulators results in a decay time of 49 μs under 2π phase modulation at room temperature. The predicted fast optical response can be achieved when operating devices at high temperatures. PMID:27137042

  7. 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 Central

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

    2010-01-01

    Theoretically, direct vitrification of cell suspensions with relatively low concentrations (~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 106–7 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 × 105 W/m2·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 × 106 W/m2·K, which is approximately 103 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 106–7 K/min, which is much faster than the currently available methods and sufficient for achieving vitrification with relatively low concentrations of CPA. PMID:18430413

  8. The V499G/Y501H Mutation Impairs Fast Motor Kinetics of Prestin and Has Significance for Defining Functional Independence of Individual Prestin Subunits*

    PubMed Central

    Homma, Kazuaki; Duan, Chongwen; Zheng, Jing; Cheatham, Mary Ann; Dallos, Peter

    2013-01-01

    Outer hair cells (OHCs) are a mammalian innovation for mechanically amplifying sound energy to overcome the viscous damping of the cochlear partition. Although the voltage-dependent OHC membrane motor, prestin, has been demonstrated to be essential for mammalian cochlear amplification, the molecular mechanism by which prestin converts electrical energy into mechanical displacement/force remains elusive. Identifying mutations that alter the motor function of prestin provides vital information for unraveling the energy transduction mechanism of prestin. We show that the V499G/Y501H mutation does not deprive prestin of its voltage-induced motor activity, but it does significantly impair the fast motor kinetics and voltage operating range. Furthermore, mutagenesis studies suggest that Val-499 is the primary site responsible for these changes. We also show that V499G/Y501H prestin forms heteromers with wild-type prestin and that the fast motor kinetics of wild-type prestin is not affected by heteromer formation with V499G/Y501H prestin. These results suggest that prestin subunits are individually functional within a given multimer. PMID:23212912

  9. Standing variation and new mutations both contribute to a fast response to selection for flowering time in maize inbreds

    PubMed Central

    2010-01-01

    Background In order to investigate the rate and limits of the response to selection from highly inbred genetic material and evaluate the respective contribution of standing variation and new mutations, we conducted a divergent selection experiment from maize inbred lines in open-field conditions during 7 years. Two maize commercial seed lots considered as inbred lines, F252 and MBS847, constituted two biological replicates of the experiment. In each replicate, we derived an Early and a Late population by selecting and selfing the earliest and the latest individuals, respectively, to produce the next generation. Results All populations, except the Early MBS847, responded to selection despite a short number of generations and a small effective population size. Part of the response can be attributed to standing genetic variation in the initial seed lot. Indeed, we identified one polymorphism initially segregating in the F252 seed lot at a candidate locus for flowering time, which explained 35% of the trait variation within the Late F252 population. However, the model that best explained our data takes into account both residual polymorphism in the initial seed lots and a constant input of heritable genetic variation by new (epi)mutations. Under this model, values of mutational heritability range from 0.013 to 0.025, and stand as an upper bound compare to what is reported in other species. Conclusions Our study reports a long-term divergent selection experiment for a complex trait, flowering time, conducted on maize in open-field conditions. Starting from a highly inbred material, we created within a few generations populations that strikingly differ from the initial seed lot for flowering time while preserving most of the phenotypic characteristics of the initial inbred. Such material is unique for studying the dynamics of the response to selection and its determinants. In addition to the fixation of a standing beneficial mutation associated with a large phenotypic

  10. 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. PMID:24602869

  11. 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. PMID:26646952

  12. Rapid adaptation of phytoplankters to geothermal waters is achieved by single mutations: were extreme environments 'Noah's Arks' for photosynthesizers during the Neoproterozoic 'snowball Earth'?

    PubMed

    Costas, Eduardo; Flores-Moya, Antonio; López-Rodas, Victoria

    2008-01-01

    Geothermal waters often support remarkable communities of microalgae and cyanobacteria apparently living at the extreme limits of their tolerance. Little is known about the mechanisms allowing adaptation of mesophilic phytoplankters to such extreme conditions, but recent studies are challenging many preconceived notions about this. The aim of this study was to analyse mechanisms allowing adaptation of mesophilic microalgae and cyanobacteria to stressful geothermal waters. To distinguish between the pre-selective or post-selective origin of adaptation processes allowing the proliferation of mesophilic phytoplankters in geothermal waters, several Luria-Delbrück fluctuation analysis were performed with the microalga Dictyosphaerium chlorelloides and the cyanobacterium Microcystis aeruginosa, both isolated from nonextreme waters. Geothermal waters from seven places in Italy and five icebound places at Los Andes in Argentina were used as selective agents. Physiological adaptation was achieved in the least toxic waters. In contrast, rapid genetic adaptation was observed in waters ostensibly lethal for the experimental organisms. This adaptation was achieved as consequence of single mutations at one locus. It was hypothesized that a similar mechanism of rapid genetic adaptation could explain the survival of photosynthetic life during the Neoproterozoic 'snowball Earth,' where geothermal refuges such as those studied could have been 'Noah's Arks' for microalgae and cyanobacteria. PMID:18803596

  13. 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

  14. 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

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

    NASA Astrophysics Data System (ADS)

    Bieniosek, M. F.; Levin, C. S.

    2015-05-01

    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 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.

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

    PubMed

    Bieniosek, M F; Levin, C S

    2015-05-01

    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 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. PMID:25905626

  17. 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

  18. 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…

  19. High-performance liquid chromatography under partially denaturing conditions (dHPLC) is a fast and cost-effective method for screening molecular defects: four novel mutations found in X-linked chronic granulomatous disease.

    PubMed

    de Oliveira-Junior, E B; Prando, C; Lopez, J A; Arango, J C; Buzolin, M; Rehder, J; Pedroza, L A; Frazão, J B; Dantas, V M; Roxo-Junior, P; Grumach, A S; Costa-Carvalho, B T; Bustamante, J; Condino-Neto, A

    2012-08-01

    Implementing precise techniques in routine diagnosis of chronic granulomatous disease (CGD), which expedite the screening of molecular defects, may be critical for a quick assumption of patient prognosis. This study compared the efficacy of single-strand conformation polymorphism analysis (SSCP) and high-performance liquid chromatography under partially denaturing conditions (dHPLC) for screening mutations in CGD patients. We selected 10 male CGD patients with a clinical history of severe recurrent infections and abnormal respiratory burst function. gDNA, mRNA and cDNA samples were prepared by standard methods. CYBB exons were amplified by PCR and screened by SSCP or dHPLC. Abnormal DNA fragments were sequenced to reveal the nature of the mutations. The SSCP and dHPLC methods showed DNA abnormalities, respectively, in 55% and 100% of the cases. Sequencing of the abnormal DNA samples confirmed mutations in all cases. Four novel mutations in CYBB were identified which were picked up only by the dHPLC screening (c.904 insC, c.141+5 g>t, c.553 T>C, and c.665 A>T). This work highlights the relevance of dHPLC, a sensitive, fast, reliable and cost-effective method for screening mutations in CGD, which in combination with functional assays assessing the phagocyte respiratory burst will contribute to expedite the definitive diagnosis of X-linked CGD, direct treatment, genetic counselling and to have a clear assumption of the prognosis. This strategy is especially suitable for developing countries. PMID:22540226

  20. A fast and simple approach for the simultaneous detection of hematopoietic chimerism, NPM1, and FLT3-ITD mutations after allogeneic stem cell transplantation.

    PubMed

    Waterhouse, Miguel; Bertz, Hartmut; Finke, Juergen

    2014-02-01

    Hematopoietic chimerism can be used as a tool for patient management after allogeneic hematopoietic stem cell transplantation (HSCT). An increase in the proportion of recipient cells after transplantation is strongly associated with relapse in chronic myeloid leukemia. However, in acute myeloid leukemia (AML) the significance of increasing mixed chimerism (MC) as a predictive marker for relapse is less clear. Several mutations frequently found in AML have been employed for minimal residual disease detection and relapse prediction. Therefore, a combined analysis of hematopoietic chimerism and of the molecular aberrations found in AML could be used to improve MC characterization. We developed a multiplex PCR for use in the simultaneous detection of hematopoietic chimerism and mutations in nucleophosmin (NPM1) and fms-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD). A total of 303 samples from 20 AML patients were analyzed after HSCT. The microsatellite markers used for hematopoietic chimerism detection were D1S80, D7S1517, D4S2366, THO1, and SE33. A total of 149 samples from 18 patients showed MC with a mean detection time of 9.7 months. From the 18 patients with MC, in 6 of the patients, no FLT3-ITD or NPM1 mutation was found at any time point tested, and these patients remained in complete hematological remission. In 12 patients with MC, FLT3-ITD and NPM1 mutations were found, and these patients showed signs of hematological relapse. Our combined analysis of NPM1/FLT3-ITD mutations and hematopoietic chimerism improved the characterization of patients with MC after HSCT. The present approach may be further expanded by combining additional mutations found in AML with hematopoietic chimerism detection. PMID:23907410

  1. 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.

  2. 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)

  3. Detecting Arbitrary DNA Mutations Using Graphene Oxide and Ethidium Bromide.

    PubMed

    Huang, Jiahao; Wang, Zhenyu; Kim, Jang-Kyo; Su, Xuefen; Li, Zhigang

    2015-12-15

    We propose a simple and fast method for detecting arbitrary DNA mutations. Single-stranded DNA probes labeled with fluorescein amidite (FAM-ssDNA), ethidium bromide (EB), and graphene oxide (GO) are employed in the sensing system. The detection is achieved in two steps. In the first step, the sensing system contains FAM-ssDNA probes and EB molecules. It exhibits different fluorescence emissions in the presence of perfectly matched, mismatched, and random DNA sequences. With the addition of GO in the second step, the fluorescence signal for perfectly matched and random DNA does not vary greatly, which, however, experiences a significant change for mismatched DNA targets. The signal ratio before and after the addition of GO can clearly distinguish mutations from normal and random DNA sequences. The detection method works well regardless of the mutation positions and only requires "mix-and-detect" steps, which are completed within 15 min. PMID:26559174

  4. 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

    Seufert, J; Bailey, T; Barkholt Christensen, S; Nauck, M A

    2016-07-01

    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

  5. The role of vitamin B12 in fasting hyperhomocysteinemia and its interaction with the homozygous C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. A case-control study of patients with early-onset thrombotic events.

    PubMed

    D'Angelo, A; Coppola, A; Madonna, P; Fermo, I; Pagano, A; Mazzola, G; Galli, L; Cerbone, A M

    2000-04-01

    Total fasting plasma homocysteine (tHcy), homozygosity for the C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene and for the A2756G mutation of the methionine synthase (MS) gene, vitamin B12 and folate plasma levels were evaluated in 170 consecutive patients (89 M, 81 F; mean age 41 +/- 12 yrs) with documented early-onset thrombosis (89 venous, 69 arterial, 12 both; mean age at first episode 36 +/- 11 yrs), and in 182 age- and sex-matched healthy control subjects. Moderate hyperhomocysteinemia (HHcy, tHcy >19.5 microM in men and >15 microM in women) was detected in 45 patients (26.5%) and in 18 controls (9.9%, Mantel-Haenszel OR and 95% C.I. after stratification for arterial or venous thrombosis: 3.25, 1.78-5.91). The 677TT MTHFR genotype was not significantly more prevalent in patients (27.6%) than in controls (21.4%, RR = 1.42: 0.84-2.41), and markedly contributed to HHcy (Mantel-Haenszel RR after stratification for case/control status: 8.29, 4.61-14.9). The 2756GG MS genotype, observed in 4 patients (2.4%) and 8 controls (4.4%), was not associated to HHcy. tHcy was negatively correlated to folate and vitamin B12 levels, with better correlation found in subjects with the 677TT mutation (r = -0.42 and -0.25) than with the 677CC or CT MTHFR genotype (r = 0).37 and -0.11). However, folate was similar in patients and controls and vitamin B12 was higher in patients (460 +/- 206 vs. 408 +/-185 pg/ml, p = 0.011). In a generalized linear model, 44% of the variation in tHcy levels was explained by folate and vitamin B12 levels, the MTHFR genotype, gender, and by the interaction of the MTHFR genotype with folate (p < or =0.028); the interactions of vitamin B12 with the MTHFR genotype, gender and patient/control status also significantly contributed to the variation in tHcy levels (p < or =0.028). A 4-week administration of 5-methyltetrahydrofolate (15 mg/day) markedly lowered plasma tHcy in 24 patients with MTHFR 677TT genotype, but the response to

  6. KRAS Mutation

    PubMed Central

    Franklin, Wilbur A.; Haney, Jerry; Sugita, Michio; Bemis, Lynne; Jimeno, Antonio; Messersmith, Wells A.

    2010-01-01

    Treatment of colon carcinoma with the anti-epidermal growth factor receptor antibody Cetuximab is reported to be ineffective in KRAS-mutant tumors. Mutation testing techniques have therefore become an urgent concern. We have compared three methods for detecting KRAS mutations in 59 cases of colon carcinoma: 1) high resolution melting, 2) the amplification refractory mutation system using a bifunctional self-probing primer (ARMS/Scorpion, ARMS/S), and 3) direct sequencing. We also evaluated the effects of the methods of sectioning and coring of paraffin blocks to obtain tumor DNA on assay sensitivity and specificity. The most sensitive and specific combination of block sampling and mutational analysis was ARMS/S performed on DNA derived from 1-mm paraffin cores. This combination of tissue sampling and testing method detected KRAS mutations in 46% of colon tumors. Four samples were positive by ARMS/S, but initially negative by direct sequencing. Cloned DNA samples were retested by direct sequencing, and in all four cases KRAS mutations were identified in the DNA. In six cases, high resolution melting abnormalities could not be confirmed as specific mutations either by ARMS/S or direct sequencing. We conclude that coring of the paraffin blocks and testing by ARMS/S is a sensitive, specific, and efficient method for KRAS testing. PMID:20007845

  7. 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. PMID:27073839

  8. 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

  9. Assessment of high resolution melt analysis feasibility for evaluation of beta-globin gene mutations as a reproducible, cost-efficient and fast alternative to the present conventional method

    PubMed Central

    Ramezanzadeh, Mahboubeh; Salehi, Mansour; Salehi, Rasoul

    2016-01-01

    Background: Beta-thalassemia is the most prevalent monogenic disease throughout the world. It was the first genetic disorder nominated for nation-wide prevention programs involving population screening for heterozygotes and prenatal diagnosis (PND) in Iran. Due to the high prevalence of beta-thalassemia, the shift from conventional mutation detection methods to more recently developed techniques based on novel innovative technologies are essential. We aimed to develop a real-time polymerase chain reaction (PCR) based protocol using high resolution melting (HRM) analysis for diagnosis of common beta-thalassemia mutations. Materials and Methods: Forty DNA samples extracted from peripheral blood of suspected beta-thalassemia carriers participated in this study were subjected to amplification refractory mutation system (ARMS). We then used 20 of these samples for HRM optimization. When 100% sensitivity and specificity was obtained with HRM procedure, we applied the technique for mutation detection on another remaining 20 samples as thalassemia cases with unknown mutations (detected mutations with ARMS-PCR kept confidential). Finally, the HRM procedure applied on 2 chorionic villous sample (CVS) biopsied from 12 weeks gestational age pregnant women for routine PND analysis. Results: In the first step of study, Fr 8/9 (+G), IVSI-1 (G > A), IVSI-5 (G > C), IVSI-110 (G > A), and CD44 (−C) mutations were diagnosed in samples under study using ARMS-PCR technique. Finally, the HRM procedure applied on 20 unknown samples and 2 CVS The results of HRM were in complete concordance with ARMS and confirmed by sequencing. Conclusions: The advantages of HRM analysis over conventional methods is high throughput, rapid, accurate, cost-effective, and reproducible. PMID:27169102

  10. Implementation of two high through-put techniques in a novel application: detecting point mutations in large EMS mutated plant populations

    PubMed Central

    Gady, Antoine LF; Hermans, Freddy WK; Van de Wal, Marion HBJ; van Loo, Eibertus N; Visser, Richard GF; Bachem, Christian WB

    2009-01-01

    Background The establishment of mutant populations together with the strategies for targeted mutation detection has been applied successfully to a large number of organisms including many species in the plant kingdom. Considerable efforts have been invested into research on tomato as a model for berry-fruit plants. With the progress of the tomato sequencing project, reverse genetics becomes an obvious and achievable goal. Results Here we describe the treatment of Solanum lycopersicum seeds with 1% EMS and the development of a new mutated tomato population. To increase targeted mutant detection throughput an automated seed DNA extraction has been combined with novel mutation detection platforms for TILLING in plants. We have adapted two techniques used in human genetic diagnostics: Conformation Sensitive Capillary Electrophoresis (CSCE) and High Resolution DNA Melting Analysis (HRM) to mutation screening in DNA pools. Classical TILLING involves critical and time consuming steps such as endonuclease digestion reactions and gel electrophoresis runs. Using CSCE or HRM, the only step required is a simple PCR before either capillary electrophoresis or DNA melting curve analysis. Here we describe the development of a mutant tomato population, the setting up of two polymorphism detection platforms for plants and the results of the first screens as mutation density in the populations and estimation of the false-positives rate when using HRM to screen DNA pools. Conclusion These results demonstrate that CSCE and HRM are fast, affordable and sensitive techniques for mutation detection in DNA pools and therefore allow the rapid identification of new allelic variants in a mutant population. Results from the first screens indicate that the mutagen treatment has been effective with an average mutation detection rate per diploid genome of 1.36 mutation/kb/1000 lines. PMID:19811648

  11. 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.

  12. 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. PMID

  13. 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. PMID:25695746

  14. Estimating mutation rate: how to count mutations?

    PubMed Central

    Fu, Yun-Xin; Huai, Haying

    2003-01-01

    Mutation rate is an essential parameter in genetic research. Counting the number of mutant individuals provides information for a direct estimate of mutation rate. However, mutant individuals in the same family can share the same mutations due to premeiotic mutation events, so that the number of mutant individuals can be significantly larger than the number of mutation events observed. Since mutation rate is more closely related to the number of mutation events, whether one should count only independent mutation events or the number of mutants remains controversial. We show in this article that counting mutant individuals is a correct approach for estimating mutation rate, while counting only mutation events will result in underestimation. We also derived the variance of the mutation-rate estimate, which allows us to examine a number of important issues about the design of such experiments. The general strategy of such an experiment should be to sample as many families as possible and not to sample much more offspring per family than the reciprocal of the pairwise correlation coefficient within each family. To obtain a reasonably accurate estimate of mutation rate, the number of sampled families needs to be in the same or higher order of magnitude as the reciprocal of the mutation rate. PMID:12807798

  15. 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.

  16. 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.

  17. 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…

  18. The Fast-spectrum Transmutation Experimental Facility FASTEF: Main design achievements (part 2: Reactor building design and plant layout) within the FP7-CDT collaborative project of the European Commission

    SciTech Connect

    De Bruyn, D.; Engelen, J.; Ortega, A.; Aguado, M. P.

    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 concept of the reactor building and the plant layout. The FASTEF facility has evolved quite a lot since the intermediate reporting done at the ICAPP'10 and ICAPP'11 conferences 1,2. Many iterations have been performed to take into account the safety requirements. The present configuration enables an easy operation and maintenance of the facility, including the possibility to change large components of the reactor. In a companion paper 3, we present the latest configuration of the reactor core and primary system. (authors)

  19. Mutation and the environment

    SciTech Connect

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

    1990-01-01

    This book is organized under the following headings: Plenary lectures; Brook mutational mechanisms; Adduction and DNA damage; Recombination and gene conversion; Repair: Prokoyote mechanisms and induction; Repair: Lower eukaryote and plant mechanisms; Repair: Higher eukaryote mechanisms and selectivity; Repair: Human genes and mechanisms; Mutation: Spectra and mechanisms; Mutation: Shuttle vectors; Mutation: Transgenic animals; New methods: Polymerase chain reaction.

  20. How resilient is the soybean genome? Insights from fast neutron mutagenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously, we described the development of a fast neutron mutant population resource in soybean and identified mutations of interest through phenotypic screening. Here, we consider the resiliency of the soybean genome by examining genomic rearrangements and mutations that arise from fast neutron ra...

  1. Fast Ignitor coupling physics

    SciTech Connect

    Mason, R.J.; Tabak, M.

    1997-10-01

    The Fast Ignitor is an alternate approach to ICF in which short pulse lasers are used to initiate burn at the surface of the compressed DT fuel. The aim is to avoid the need for careful central focusing of final shocks, and possibly to lower substantially the energy requirements for ignition. Ultimately, both goals may prove crucial to Science Based Stockpile Stewardship (SBSS). This will be the case should either emerging energetic needs, or finding difficulties render the presently planned radiative fusion approach to ignition with the NIF impractical. Ignition is a first step towards the achievement of substantial energy and neutron outputs for such Stewardship.

  2. CF Mutation Panel

    MedlinePlus

    ... page: Was this page helpful? Also known as: Cystic Fibrosis Genotyping; CF DNA Analysis; CF Gene Mutation Panel; CF Molecular Genetic Testing Formal name: Cystic Fibrosis Gene Mutation Panel Related tests: Sweat Test ; Trypsinogen ; ...

  3. Colorectal cancer prognosis: is it all mutation, mutation, mutation?

    PubMed Central

    Hassan, A B; Paraskeva, C

    2005-01-01

    For the 500 000 new cases of colorectal cancer in the world each year, identification of patients with a worse prognosis and those who are more likely to respond to treatment is a challenge. There is an increasing body of evidence correlating genetic mutations with outcome in tumours derived from human colorectal cancer cohorts. K-ras, but not p53 or APC, mutations appear to be associated with poorer overall survival in colorectal cancer patients. PMID:16099785

  4. Fast quasiadiabatic dynamics

    NASA Astrophysics Data System (ADS)

    Martínez-Garaot, S.; Ruschhaupt, A.; Gillet, J.; Busch, Th.; Muga, J. G.

    2015-10-01

    We work out the theory and applications of a fast quasiadiabatic approach to speed up slow adiabatic manipulations of quantum systems by driving a control parameter as near to the adiabatic limit as possible over the entire protocol duration. We find characteristic time scales, such as the minimal time to achieve fidelity 1, and the optimality of the approach within the iterative superadiabatic sequence. Specifically, we show that the population inversion in a two-level system, the splitting and cotunneling of two-interacting bosons, and the stirring of a Tonks-Girardeau gas on a ring to achieve mesoscopic superpositions of many-body rotating and nonrotating states can be significantly speeded up.

  5. Fast ignitor coupling physics

    SciTech Connect

    Mason, R.J.; Tabak, M.

    1997-10-01

    The Fast Ignitor is an alternate approach to ICF in which short pulse lasers are used to initiate burn at the surface of the compressed DT fuel. The aim is to avoid the need for careful central focusing of final shocks, and possibly to lower substantially the energy requirements for ignition. Ultimately, both goals may prove crucial to Science Based Stockpile Stewardship (SBSS). This will be the case should either emerging energetic needs, or funding difficulties render the presently planned radiative fusion approach to ignition with the NIF impractical. Ignition is a first step towards the achievement of substantial energy and neutron outputs for such Stewardship. For success with the Fast Ignitor, the laser energy must be efficiently deposited into megavolt electrons (suprathermal), which must, in turn, couple to the background ions within an alpha particle range. To understand the electron fuel coupling, we have used ANTHEM plasma simulation code to model the transport of hot electrons generated by an intense short pulse laser into plasma targets over a broad range of densities. Our study will spell out the acceleration and transport mechanisms active in the Fast Ignitor environment.

  6. 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? PMID:17444963

  7. 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

  8. 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…

  9. [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. PMID:27426243

  10. UV signature mutations.

    PubMed

    Brash, Douglas E

    2015-01-01

    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 nontranscribed 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; UV's nonsignature mutations may cause melanoma BRAF mutations; and the mutagen for sunlight-related skin neoplasms may vary between continents. PMID:25354245

  11. New AGS fast extraction system

    SciTech Connect

    Weng, W.T.

    1980-09-01

    Both the high energy physics program and ISA injection require an improved fast extraction system from the AGS. The proposed new system consists of a fast kicker at H5 and an ejector magnet at H10. The H5 kicker is capable of producing 1.2 mrad deflection and rising up to 99% strength in 150 nsec with flat top ripple within +- 1%. It is found that the focusing strengths and positions of UQ3-UQ7 have to be modified to achieve an achromatic condition at the end of 8/sup 0/-bend. Also, the conceptual design of the H5 magnet and the pulser system are discussed.

  12. Stationary mutation models.

    PubMed

    Simonsson, Ivar; Mostad, Petter

    2016-07-01

    Probability calculations for relationship inference based on DNA tests are often performed with computer packages such as Familias. When mutations are assumed to be a possibility, one may notice a curious and problematic effect of including untested parents: results tend to change slightly. In this paper, we trace this effect back to fundamental model-formulating issues which can only be resolved by using stationary mutation models. We present several methods for obtaining such stationary mutation matrices from original mutation matrices, and evaluate essential properties of these methods. Our conclusion is that typically, stationary mutation models can be obtained, but for many types of markers, it may be impossible to combine specific biologically reasonable requirements for a mutation matrix with the requirement of stationarity. PMID:27231805

  13. FAST: FAST Analysis of Sequences Toolbox.

    PubMed

    Lawrence, Travis J; Kauffman, Kyle T; Amrine, Katherine C H; Carper, Dana L; Lee, Raymond S; Becich, Peter J; Canales, Claudia J; Ardell, David H

    2015-01-01

    FAST (FAST Analysis of Sequences Toolbox) provides simple, powerful open source command-line tools to filter, transform, annotate and analyze biological sequence data. Modeled after the GNU (GNU's Not Unix) Textutils such as grep, cut, and tr, FAST tools such as fasgrep, fascut, and fastr make it easy to rapidly prototype expressive bioinformatic workflows in a compact and generic command vocabulary. Compact combinatorial encoding of data workflows with FAST commands can simplify the documentation and reproducibility of bioinformatic protocols, supporting better transparency in biological data science. Interface self-consistency and conformity with conventions of GNU, Matlab, Perl, BioPerl, R, and GenBank help make FAST easy and rewarding to learn. FAST automates numerical, taxonomic, and text-based sorting, selection and transformation of sequence records and alignment sites based on content, index ranges, descriptive tags, annotated features, and in-line calculated analytics, including composition and codon usage. Automated content- and feature-based extraction of sites and support for molecular population genetic statistics make FAST useful for molecular evolutionary analysis. FAST is portable, easy to install and secure thanks to the relative maturity of its Perl and BioPerl foundations, with stable releases posted to CPAN. Development as well as a publicly accessible Cookbook and Wiki are available on the FAST GitHub repository at https://github.com/tlawrence3/FAST. The default data exchange format in FAST is Multi-FastA (specifically, a restriction of BioPerl FastA format). Sanger and Illumina 1.8+ FastQ formatted files are also supported. FAST makes it easier for non-programmer biologists to interactively investigate and control biological data at the speed of thought. PMID:26042145

  14. FAST: FAST Analysis of Sequences Toolbox

    PubMed Central

    Lawrence, Travis J.; Kauffman, Kyle T.; Amrine, Katherine C. H.; Carper, Dana L.; Lee, Raymond S.; Becich, Peter J.; Canales, Claudia J.; Ardell, David H.

    2015-01-01

    FAST (FAST Analysis of Sequences Toolbox) provides simple, powerful open source command-line tools to filter, transform, annotate and analyze biological sequence data. Modeled after the GNU (GNU's Not Unix) Textutils such as grep, cut, and tr, FAST tools such as fasgrep, fascut, and fastr make it easy to rapidly prototype expressive bioinformatic workflows in a compact and generic command vocabulary. Compact combinatorial encoding of data workflows with FAST commands can simplify the documentation and reproducibility of bioinformatic protocols, supporting better transparency in biological data science. Interface self-consistency and conformity with conventions of GNU, Matlab, Perl, BioPerl, R, and GenBank help make FAST easy and rewarding to learn. FAST automates numerical, taxonomic, and text-based sorting, selection and transformation of sequence records and alignment sites based on content, index ranges, descriptive tags, annotated features, and in-line calculated analytics, including composition and codon usage. Automated content- and feature-based extraction of sites and support for molecular population genetic statistics make FAST useful for molecular evolutionary analysis. FAST is portable, easy to install and secure thanks to the relative maturity of its Perl and BioPerl foundations, with stable releases posted to CPAN. Development as well as a publicly accessible Cookbook and Wiki are available on the FAST GitHub repository at https://github.com/tlawrence3/FAST. The default data exchange format in FAST is Multi-FastA (specifically, a restriction of BioPerl FastA format). Sanger and Illumina 1.8+ FastQ formatted files are also supported. FAST makes it easier for non-programmer biologists to interactively investigate and control biological data at the speed of thought. PMID:26042145

  15. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:25716795

  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. 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.

  19. 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.

  20. Mutations in Lettuce Improvement.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mutations can make profound impact on the evolution and improvement of a self-pollinated crop such as lettuce. Since it is nontransgenic, mutation breeding is more acceptable to consumers. Combined with genomic advances in new technologies like TILLING, mutagenesis is becoming an even more powerfu...

  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 rates as adaptations.

    PubMed

    Maley, C

    1997-06-01

    In order to better understand life, it is helpful to look beyond the envelop of life as we know it. A simple model of coevolution was implemented with the addition of a gene for the mutation rate of the individual. This allowed the mutation rate itself to evolve in a lineage. The model shows that when the individuals interact in a sort of zero-sum game, the lineages maintain relatively high mutation rates. However, when individuals engage in interactions that have greater consequences for one individual in the interaction than the other, lineages tend to evolve relatively low mutation rates. This model suggests that one possible cause for differential mutation rates across genes may be the coevolutionary pressure of the various forms of interactions with other genes. PMID:9219670

  3. Targeted sequencing using a 47 gene multiple myeloma mutation panel (M3P) in -17p high risk disease

    PubMed Central

    Kortüm, Klaus M.; Langer, Christian; Monge, Jorge; Bruins, Laura; Egan, Jan B.; Zhu, Yuan X.; Shi, Chang Xin; Jedlowski, Patrick; Schmidt, Jessica; Ojha, Juhi; Bullinger, Lars; Liebisch, Peter; Kull, Miriam; Champion, Mia D.; Van Wier, Scott; Ahmann, Gregory; Rasche, Leo; Knop, Stefan; Fonseca, Rafael; Einsele, Hermann; Stewart, A Keith; Braggio, Esteban

    2015-01-01

    Summary We constructed a multiple myeloma (MM)-specific gene panel for targeted sequencing and investigated 72 untreated high-risk (del17p) MM patients. Mutations were identified in 78% of the patients. While the majority of studied genes were mutated at similar frequency to published literature, the prevalence of TP53 mutation was increased (28%) and no mutations were found in FAM46C. This study provides a comprehensive insight into the mutational landscape of del17p high-risk MM. Additionally, our work demonstrates the practical use of a customized sequencing panel, as an easy, cheap and fast approach to characterize the mutational profile of MM. PMID:25302557

  4. Targeted sequencing using a 47 gene multiple myeloma mutation panel (M(3) P) in -17p high risk disease.

    PubMed

    Kortüm, Klaus M; Langer, Christian; Monge, Jorge; Bruins, Laura; Egan, Jan B; Zhu, Yuan X; Shi, Chang Xin; Jedlowski, Patrick; Schmidt, Jessica; Ojha, Juhi; Bullinger, Lars; Liebisch, Peter; Kull, Miriam; Champion, Mia D; Van Wier, Scott; Ahmann, Gregory; Rasche, Leo; Knop, Stefan; Fonseca, Rafael; Einsele, Hermann; Stewart, A Keith; Braggio, Esteban

    2015-02-01

    We constructed a multiple myeloma (MM)-specific gene panel for targeted sequencing and investigated 72 untreated high-risk (del17p) MM patients. Mutations were identified in 78% of the patients. While the majority of studied genes were mutated at similar frequency to published literature, the prevalence of TP53 mutation was increased (28%) and no mutations were found in FAM46C. This study provides a comprehensive insight into the mutational landscape of del17p high-risk MM. Additionally, our work demonstrates the practical use of a customized sequencing panel, as an easy, cheap and fast approach to characterize the mutational profile of MM. PMID:25302557

  5. Responder fast steering mirror

    NASA Astrophysics Data System (ADS)

    Bullard, Andrew; Shawki, Islam

    2013-09-01

    Raytheon Space and Airborne Systems (SAS) has designed, built and tested a 3.3-inch diameter fast steering mirror (FSM) for space application. This 2-axis FSM operates over a large angle (over 10 degree range), has a very high servo bandwidth (over 3.3 Khz closed loop bandwidth), has nanoradian-class noise, and is designed to support microradian class line of sight accuracy. The FSM maintains excellent performance over large temperature ranges (which includes wave front error) and has very high reliability with the help of fully redundant angle sensors and actuator circuits. The FSM is capable of achieving all its design requirements while also being reaction-compensated. The reaction compensation is achieved passively and does not need a separate control loop. The FSM has undergone various environmental testing which include exported forces and torques and thermal vacuum testing that support the FSM design claims. This paper presents the mechanical design and test results of the mechanism which satisfies the rigorous vacuum and space application requirements.

  6. Responder fast steering mirror

    NASA Astrophysics Data System (ADS)

    Bullard, Andrew; Shawki, Islam

    2013-10-01

    Raytheon Space and Airborne Systems (SAS) has designed, built and tested a 3.3-inch diameter fast steering mirror (FSM) for space application. This 2-axis FSM operates over a large angle (over 10 degree range), has a very high servo bandwidth (over 3.3 Khz closed loop bandwidth), has nanoradian-class noise, and is designed to support microradian class line of sight accuracy. The FSM maintains excellent performance over large temperature ranges (which includes wave front error) and has very high reliability with the help of fully redundant angle sensors and actuator circuits. The FSM is capable of achieving all its design requirements while also being reaction-compensated. The reaction compensation is achieved passively and does not need a separate control loop. The FSM has undergone various environmental testing which include exported forces and torques and thermal vacuum testing that support the FSM design claims. This paper presents the mechanical design and test results of the mechanism which satisfies the rigorous vacuum and space application requirements.

  7. Costs and Benefits of High Mutation Rates: Adaptive Evolution of Bacteria in the Mouse Gut

    NASA Astrophysics Data System (ADS)

    Giraud, Antoine; Matic, Ivan; Tenaillon, Olivier; Clara, Antonio; Radman, Miroslav; Fons, Michel; Taddei, François

    2001-03-01

    We have shown that bacterial mutation rates change during the experimental colonization of the mouse gut. A high mutation rate was initially beneficial because it allowed faster adaptation, but this benefit disappeared once adaptation was achieved. Mutator bacteria accumulated mutations that, although neutral in the mouse gut, are often deleterious in secondary environments. Consistently, the competitiveness of mutator bacteria is reduced during transmission to and re-colonization of similar hosts. The short-term advantages and long-term disadvantages of mutator bacteria could account for their frequency in nature.

  8. 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...

  9. Mutations in man

    SciTech Connect

    Obe, G.

    1984-01-01

    This book contains 13 selections that cover some of the following topics: DNA repair, gene or point mutations, aspects of nondisjunction, origin and significance of chromosomal alterations, structure and organization of the human genome, and mutagenic activity of cigarette smoke.

  10. 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.…

  11. 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.

  12. Varieties of Achievement Motivation.

    ERIC Educational Resources Information Center

    Kukla, Andre; Scher, Hal

    1986-01-01

    A recent article by Nicholls on achievement motivation is criticized on three points: (1) definitions of achievement motives are ambiguous; (2) behavioral consequences predicted do not follow from explicit theoretical assumptions; and (3) Nicholls's account of the relation between his theory and other achievement theories is factually incorrect.…

  13. Motivation and School Achievement.

    ERIC Educational Resources Information Center

    Maehr, Martin L.; Archer, Jennifer

    Addressing the question, "What can be done to promote school achievement?", this paper summarizes the literature on motivation relating to classroom achievement and school effectiveness. Particular attention is given to how values, ideology, and various cultural patterns impinge on classroom performance and serve to enhance motivation to achieve.…

  14. Mobility and Reading Achievement.

    ERIC Educational Resources Information Center

    Waters, Theresa Z.

    A study examined the effect of geographic mobility on elementary school students' achievement. Although such mobility, which requires students to make multiple moves among schools, can have a negative impact on academic achievement, the hypothesis for the study was that it was not a determining factor in reading achievement test scores. Subjects…

  15. PASS and Reading Achievement.

    ERIC Educational Resources Information Center

    Kirby, John R.

    Two studies examined the effectiveness of the PASS (Planning, Attention, Simultaneous, and Successive cognitive processes) theory of intelligence in predicting reading achievement scores of normally achieving children and distinguishing children with reading disabilities from normally achieving children. The first study dealt with predicting…

  16. 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

  17. Experiments on the role of deleterious mutations as stepping stones in adaptive evolution.

    PubMed

    Covert, Arthur W; Lenski, Richard E; Wilke, Claus O; Ofria, Charles

    2013-08-20

    Many evolutionary studies assume that deleterious mutations necessarily impede adaptive evolution. However, a later mutation that is conditionally beneficial may interact with a deleterious predecessor before it is eliminated, thereby providing access to adaptations that might otherwise be inaccessible. It is unknown whether such sign-epistatic recoveries are inconsequential events or an important factor in evolution, owing to the difficulty of monitoring the effects and fates of all mutations during experiments with biological organisms. Here, we used digital organisms to compare the extent of adaptive evolution in populations when deleterious mutations were disallowed with control populations in which such mutations were allowed. Significantly higher fitness levels were achieved over the long term in the control populations because some of the deleterious mutations served as stepping stones across otherwise impassable fitness valleys. As a consequence, initially deleterious mutations facilitated the evolution of complex, beneficial functions. We also examined the effects of disallowing neutral mutations, of varying the mutation rate, and of sexual recombination. Populations evolving without neutral mutations were able to leverage deleterious and compensatory mutation pairs to overcome, at least partially, the absence of neutral mutations. Substantially raising or lowering the mutation rate reduced or eliminated the long-term benefit of deleterious mutations, but introducing recombination did not. Our work demonstrates that deleterious mutations can play an important role in adaptive evolution under at least some conditions. PMID:23918358

  18. Acid-fast stain

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003766.htm Acid-fast stain To use the sharing features on this page, please enable JavaScript. The acid-fast stain is a laboratory test that determines ...

  19. 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 fat, ...

  20. Fast food tips (image)

    MedlinePlus

    ... challenge to eat healthy when going to a fast food place. In general, avoiding items that are deep ... challenge to eat healthy when going to a fast food place. In general, avoiding items that are deep ...

  1. 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.

  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. PMID:21999689

  3. 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)

  4. Fast Neutron Mutagenesis of Soybean: A Resource for the Community

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mutagenized populations have become indispensable resources for introducing variation and studying gene function in plant genomics research. To create a soybean population for forward and reverse genetic screens, we chose to use fast neutron irradiation to induce deletion mutations in the soybean ge...

  5. FAST User Guide

    NASA Technical Reports Server (NTRS)

    Walatka, Pamela P.; Clucas, Jean; McCabe, R. Kevin; Plessel, Todd; Potter, R.; Cooper, D. M. (Technical Monitor)

    1994-01-01

    The Flow Analysis Software Toolkit, FAST, is a software environment for visualizing data. FAST is a collection of separate programs (modules) that run simultaneously and allow the user to examine the results of numerical and experimental simulations. The user can load data files, perform calculations on the data, visualize the results of these calculations, construct scenes of 3D graphical objects, and plot, animate and record the scenes. Computational Fluid Dynamics (CFD) visualization is the primary intended use of FAST, but FAST can also assist in the analysis of other types of data. FAST combines the capabilities of such programs as PLOT3D, RIP, SURF, and GAS into one environment with modules that share data. Sharing data between modules eliminates the drudgery of transferring data between programs. All the modules in the FAST environment have a consistent, highly interactive graphical user interface. Most commands are entered by pointing and'clicking. The modular construction of FAST makes it flexible and extensible. The environment can be custom configured and new modules can be developed and added as needed. The following modules have been developed for FAST: VIEWER, FILE IO, CALCULATOR, SURFER, TOPOLOGY, PLOTTER, TITLER, TRACER, ARCGRAPH, GQ, SURFERU, SHOTET, and ISOLEVU. A utility is also included to make the inclusion of user defined modules in the FAST environment easy. The VIEWER module is the central control for the FAST environment. From VIEWER, the user can-change object attributes, interactively position objects in three-dimensional space, define and save scenes, create animations, spawn new FAST modules, add additional view windows, and save and execute command scripts. The FAST User Guide uses text and FAST MAPS (graphical representations of the entire user interface) to guide the user through the use of FAST. Chapters include: Maps, Overview, Tips, Getting Started Tutorial, a separate chapter for each module, file formats, and system

  6. Mutations in lettuce improvement.

    PubMed

    Mou, Beiquan

    2011-01-01

    Lettuce is a major vegetable in western countries. Mutations generated genetic variations and played an important role in the domestication of the crop. Many traits derived from natural and induced mutations, such as dwarfing, early flowering, male sterility, and chlorophyll deficiency, are useful in physiological and genetic studies. Mutants were also used to develop new lettuce products including miniature and herbicide-tolerant cultivars. Mutant analysis was critical in lettuce genomic studies including identification and cloning of disease-resistance genes. Mutagenesis combined with genomic technology may provide powerful tools for the discovery of novel gene alleles. In addition to radiation and chemical mutagens, unconventional approaches such as tissue or protoplast culture, transposable elements, and space flights have been utilized to generate mutants in lettuce. Since mutation breeding is considered nontransgenic, it is more acceptable to consumers and will be explored more in the future for lettuce improvement. PMID:22287955

  7. Mutations in Lettuce Improvement

    PubMed Central

    Mou, Beiquan

    2011-01-01

    Lettuce is a major vegetable in western countries. Mutations generated genetic variations and played an important role in the domestication of the crop. Many traits derived from natural and induced mutations, such as dwarfing, early flowering, male sterility, and chlorophyll deficiency, are useful in physiological and genetic studies. Mutants were also used to develop new lettuce products including miniature and herbicide-tolerant cultivars. Mutant analysis was critical in lettuce genomic studies including identification and cloning of disease-resistance genes. Mutagenesis combined with genomic technology may provide powerful tools for the discovery of novel gene alleles. In addition to radiation and chemical mutagens, unconventional approaches such as tissue or protoplast culture, transposable elements, and space flights have been utilized to generate mutants in lettuce. Since mutation breeding is considered nontransgenic, it is more acceptable to consumers and will be explored more in the future for lettuce improvement. PMID:22287955

  8. 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…

  9. 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…

  10. 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…

  11. Wechsler Individual Achievement Test.

    ERIC Educational Resources Information Center

    Taylor, Ronald L.

    1999-01-01

    This article describes the Wechsler Individual Achievement Test, a comprehensive measure of achievement for individuals in grades K-12. Eight subtests assess mathematics reasoning, spelling, reading comprehension, numerical operations, listening comprehension, oral expression, and written expression. Its administration, standardization,…

  12. Inverting the Achievement Pyramid

    ERIC Educational Resources Information Center

    White-Hood, Marian; Shindel, Melissa

    2006-01-01

    Attempting to invert the pyramid to improve student achievement and increase all students' chances for success is not a new endeavor. For decades, educators have strategized, formed think tanks, and developed school improvement teams to find better ways to improve the achievement of all students. Currently, the No Child Left Behind Act (NCLB) is…

  13. Achievement Test Program.

    ERIC Educational Resources Information Center

    Ohio State Dept. of Education, Columbus. Trade and Industrial Education Service.

    The Ohio Trade and Industrial Education Achievement Test battery is comprised of seven basic achievement tests: Machine Trades, Automotive Mechanics, Basic Electricity, Basic Electronics, Mechanical Drafting, Printing, and Sheet Metal. The tests were developed by subject matter committees and specialists in testing and research. The Ohio Trade and…

  14. General Achievement Trends: Maryland

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  15. General Achievement Trends: Arkansas

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  16. General Achievement Trends: Idaho

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  17. General Achievement Trends: Nebraska

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  18. General Achievement Trends: Colorado

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  19. General Achievement Trends: Iowa

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  20. General Achievement Trends: Hawaii

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  1. General Achievement Trends: Kentucky

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  2. General Achievement Trends: Florida

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  3. General Achievement Trends: Texas

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  4. General Achievement Trends: Oregon

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  5. General Achievement Trends: Virginia

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  6. Honoring Student Achievement

    ERIC Educational Resources Information Center

    Education Digest: Essential Readings Condensed for Quick Review, 2004

    2004-01-01

    Is the concept of "honor roll" obsolete? The honor roll has always been a way for schools to recognize the academic achievement of their students. But does it motivate students? In this article, several elementary school principals share their views about honoring student achievement. Among others, Virginia principal Nancy Moga said that students…

  7. Aiming at Achievement.

    ERIC Educational Resources Information Center

    Martinez, Paul

    The Raising Quality and Achievement Program is a 3-year initiative to support further education (FE) colleges in the United Kingdom in their drive to improve students' achievement and the quality of provision. The program offers the following: (1) quality information and advice; (2) onsite support for individual colleges; (3) help with…

  8. Achieving Perspective Transformation.

    ERIC Educational Resources Information Center

    Nowak, Jens

    Perspective transformation is a consciously achieved state in which the individual's perspective on life is transformed. The new perspective serves as a vantage point for life's actions and interactions, affecting the way life is lived. Three conditions are basic to achieving perspective transformation: (1) "feeling" experience, i.e., getting in…

  9. Achieving Public Schools

    ERIC Educational Resources Information Center

    Abowitz, Kathleen Knight

    2011-01-01

    Public schools are functionally provided through structural arrangements such as government funding, but public schools are achieved in substance, in part, through local governance. In this essay, Kathleen Knight Abowitz explains the bifocal nature of achieving public schools; that is, that schools are both subject to the unitary Public compact of…

  10. General Achievement Trends: Tennessee

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  11. 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…

  12. Spectrum of AGL mutations in Chinese patients with glycogen storage disease type III: identification of 31 novel mutations.

    PubMed

    Lu, Chaoxia; Qiu, Zhengqing; Sun, Miao; Wang, Wei; Wei, Min; Zhang, Xue

    2016-07-01

    Glycogen storage disease type III (GSD III), a rare autosomal recessive disease characterized by hepatomegaly, fasting hypoglycemia, growth retardation, progressive myopathy and cardiomyopathy, is caused by deficiency of the glycogen debranching enzyme (AGL). Direct sequencing of human AGL cDNA and genomic DNA has enabled analysis of the underlying genetic defects responsible for GSD III. To date, the frequent mutations in different areas and populations have been described in Italy, Japan, Faroe Islands and Mediterranean area, whereas little has been performed in Chinese population. Here we report a sequencing-based mutation analysis in 43 Chinese patients with GSD III from 41 families. We identified 51 different mutations, including 15 splice-site (29.4%), 11 small deletions (21.6%), 12 nonsense (23.5%), 7 missense (13.7%), 5 duplication (9.8%) and 1 complex deletion/insertion (2.0%), 31 of which are novel mutations. The most common mutation is c.1735+1G>T (11.5%). The association of AGL missense and small in-frame deletion mutations with normal creatine kinase level was observed. Our study extends the spectrum of AGL mutations and suggests a genotype-phenotype correlation in GSD III. PMID:26984562

  13. Fast ignition without hole boring.

    PubMed

    Hain, S; Mulser, P

    2001-02-01

    A fast-ignitor scheme for inertial confinement fusion is proposed which works without hole boring. It is shown that a thermonuclear burn wave starts from the pellet corona when an adequate amount of energy (typically 10 kJ) is deposited in the critical layer by a petawatt laser ("coronal ignition"). Burn efficiencies as high as predicted for standard central spark ignition are achieved. In addition, the scheme is surprisingly insensitive to large deviations from spherical precompression symmetry. It may open a new prospect for direct drive. PMID:11177998

  14. 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.

  15. [Achievement of therapeutic objectives].

    PubMed

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. PMID:25043543

  16. Combined Complement Gene Mutations in Atypical Hemolytic Uremic Syndrome Influence Clinical Phenotype

    PubMed Central

    Bresin, Elena; Rurali, Erica; Caprioli, Jessica; Sanchez-Corral, Pilar; Fremeaux-Bacchi, Veronique; Rodriguez de Cordoba, Santiago; Pinto, Sheila; Goodship, Timothy H.J.; Alberti, Marta; Ribes, David; Valoti, Elisabetta; Remuzzi, Giuseppe

    2013-01-01

    Several abnormalities in complement genes reportedly contribute to atypical hemolytic uremic syndrome (aHUS), but incomplete penetrance suggests that additional factors are necessary for the disease to manifest. Here, we sought to describe genotype–phenotype correlations among patients with combined mutations, defined as mutations in more than one complement gene. We screened 795 patients with aHUS and identified single mutations in 41% and combined mutations in 3%. Only 8%–10% of patients with mutations in CFH, C3, or CFB had combined mutations, whereas approximately 25% of patients with mutations in MCP or CFI had combined mutations. The concomitant presence of CFH and MCP risk haplotypes significantly increased disease penetrance in combined mutated carriers, with 73% penetrance among carriers with two risk haplotypes compared with 36% penetrance among carriers with zero or one risk haplotype. Among patients with CFH or CFI mutations, the presence of mutations in other genes did not modify prognosis; in contrast, 50% of patients with combined MCP mutation developed end stage renal failure within 3 years from onset compared with 19% of patients with an isolated MCP mutation. Patients with combined mutations achieved remission with plasma treatment similar to patients with single mutations. Kidney transplant outcomes were worse, however, for patients with combined MCP mutation compared with an isolated MCP mutation. In summary, these data suggest that genotyping for the risk haplotypes in CFH and MCP may help predict the risk of developing aHUS in unaffected carriers of mutations. Furthermore, screening patients with aHUS for all known disease-associated genes may inform decisions about kidney transplantation. PMID:23431077

  17. Predicting Achievement and Motivation.

    ERIC Educational Resources Information Center

    Uguroglu, Margaret; Walberg, Herbert J.

    1986-01-01

    Motivation and nine other factors were measured for 970 students in grades five through eight in a study of factors predicting achievement and predicting motivation. Results are discussed. (Author/MT)

  18. Attractiveness and School Achievement

    ERIC Educational Resources Information Center

    Salvia, John; And Others

    1977-01-01

    The purpose of this study was to ascertain the relationship between rated attractiveness and two measures of school performance. Attractive children received significantly higher report cards and, to some degree, higher achievement test scores than their unattractive peers. (Author)

  19. Student Achievement and Motivation

    ERIC Educational Resources Information Center

    Flammer, Gordon H.; Mecham, Robert C.

    1974-01-01

    Compares the lecture and self-paced methods of instruction on the basis of student motivation and achieveme nt, comparing motivating and demotivating factors in each, and their potential for motivation and achievement. (Authors/JR)

  20. Fast food (image)

    MedlinePlus

    ... 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 fat, ...

  1. 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.

  2. 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.

  3. Somatic mutations in disorders with disrupted brain connectivity

    PubMed Central

    Lee, Jeong Ho

    2016-01-01

    Mutations occur during cell division in all somatic lineages. Because neurogenesis persists throughout human life, somatic mutations in the brain arise during development and accumulate with the aging process. The human brain consists of 100 billion neurons that form an extraordinarily intricate network of connections to achieve higher level cognitive functions. Due to this network architecture, perturbed neuronal functions are rarely restricted to a focal area; instead, they are often spread via the neuronal network to affect other connected areas. Although somatic diversity is an evident feature of the brain, the extent to which somatic mutations affect the neuronal structure and function and their contribution to neurological disorders associated with disrupted brain connectivity remain largely unexplored. Notably, recent reports indicate that brain somatic mutations can indeed play a critical role that leads to the structural and functional abnormalities of the brain observed in several neurodevelopmental disorders. Here, I review the extent and significance of brain somatic mutations and provide my perspective regarding these mutations as potential molecular lesions underlying relatively common conditions with disrupted brain connectivity. Moreover, I discuss emerging technical platforms that will facilitate the detection of low-frequency somatic mutations and validate the biological functions of the identified mutations in the context of brain connectivity. PMID:27282107

  4. Somatic mutations in disorders with disrupted brain connectivity.

    PubMed

    Lee, Jeong Ho

    2016-01-01

    Mutations occur during cell division in all somatic lineages. Because neurogenesis persists throughout human life, somatic mutations in the brain arise during development and accumulate with the aging process. The human brain consists of 100 billion neurons that form an extraordinarily intricate network of connections to achieve higher level cognitive functions. Due to this network architecture, perturbed neuronal functions are rarely restricted to a focal area; instead, they are often spread via the neuronal network to affect other connected areas. Although somatic diversity is an evident feature of the brain, the extent to which somatic mutations affect the neuronal structure and function and their contribution to neurological disorders associated with disrupted brain connectivity remain largely unexplored. Notably, recent reports indicate that brain somatic mutations can indeed play a critical role that leads to the structural and functional abnormalities of the brain observed in several neurodevelopmental disorders. Here, I review the extent and significance of brain somatic mutations and provide my perspective regarding these mutations as potential molecular lesions underlying relatively common conditions with disrupted brain connectivity. Moreover, I discuss emerging technical platforms that will facilitate the detection of low-frequency somatic mutations and validate the biological functions of the identified mutations in the context of brain connectivity. PMID:27282107

  5. Fast-tracking in cardiac surgery.

    PubMed

    Aps, C

    Fast-tracking in cardiac surgery evolved as the pressure on bed space in intensive therapy units (ITU) grew and clinical management improved. It relies on achieving a patient condition that allows for earlier extubation and postoperative management in alternative facilities to the ITU. PMID:7582363

  6. High power fast ramping power supplies

    SciTech Connect

    Marneris,I.; Bajon, E.; Bonati, R.; Sandberg, J.; Roser, T.; Tsoupas, N.

    2009-05-04

    Hundred megawatt level fast ramping power converters to drive proton and heavy ion machines are under research and development at accelerator facilities in the world. This is a leading edge technology. There are several topologies to achieve this power level. Their advantages and related issues will be discussed.

  7. [Medical aspects of fasting].

    PubMed

    Gavrankapetanović, F

    1997-01-01

    Fasting (arabic-savm) was proclaimed through islam, and thus it is an obligation for Holly Prophet Muhammad s.a.v.s.-Peace be to Him-in the second year after Hijra (in 624 after Milad-born of Isa a.s.). There is a month of fasting-Ramadan-each lunar (hijra) year. So, it was 1415th fasting this year. Former Prophets have brought obligative messages on fasting to their people; so there are also certain forms of fasting with other religions i.e. with Catholics, Jews, Orthodox. These kinds of fasting above differ from muslim fasting, but they also appear obligative. All revelations have brought fasting as obligative. From medical point of view, fasting has two basical components: psychical and physical. Psychical sphere correlate closely with its fundamental ideological message. Allah dz.s. says in Quran: "... Fasting is obligative for you, as it was obligative to your precedents, as to avoid sins; during very few days (II, II, 183 & 184)." Will strength, control of passions, effort and self-discipline makes a pure faithfull person, who purify its mind and body through fasting. Thinking about The Creator is more intensive, character is more solid; and spirit and will get stronger. We will mention the hadith saying: "Essaihune humus saimun!" That means: "Travellers at the Earth are fasters (of my ummet)." The commentary of this hadith, in the Collection of 1001 hadiths (Bin bir hadis), number 485, says: "There are no travelling dervishs or monks in islam; thus there is no such a kind of relligousity in islam. In stead, it is changed by fasting and constant attending of mosque. That was proclaimed as obligation, although there were few cases of travelling in the name of relligousity, like travelling dervishs and sheichs." In this paper, the author discusses medical aspects of fasting and its positive characteristics in the respect of healthy life style and prevention of many sicks. The author mentions positive influence of fasting to certain system and organs of human

  8. Integrative Physiology of Fasting.

    PubMed

    Secor, Stephen M; Carey, Hannah V

    2016-04-01

    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. PMID:27065168

  9. Towards linked open gene mutations data

    PubMed Central

    2012-01-01

    Background With the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework. In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data. Methods A version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest. Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite. Results We have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application. Conclusions This has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development. The publication of variation information as Linked Data opens new perspectives

  10. Fast-ion Dα measurements of the fast-ion distribution (invited).

    PubMed

    Heidbrink, W W

    2010-10-01

    The fast-ion Dα (FIDA) diagnostic is an application of charge-exchange recombination spectroscopy. Fast ions that neutralize in an injected neutral beam emit Balmer-α light with a large Doppler shift. The spectral shift is exploited to distinguish the FIDA emission from other bright sources of Dα light. Background subtraction is the main technical challenge. A spectroscopic diagnostic typically achieves temporal, energy, and transverse spatial resolution of ∼1 ms, ∼10 keV, and ∼2 cm, respectively. Installations that use narrow-band filters achieve high spatial and temporal resolution at the expense of spectral information. For high temporal resolution, the bandpass-filtered light goes directly to a photomultiplier, allowing detection of ∼50 kHz oscillations in FIDA signal. For two-dimensional spatial profiles, the bandpass-filtered light goes to a charge-coupled device camera; detailed images of fast-ion redistribution at instabilities are obtained. Qualitative and quantitative models relate the measured FIDA signals to the fast-ion distribution function. The first quantitative comparisons between theory and experiment found excellent agreement in beam-heated magnetohydrodynamics (MHD)-quiescent plasmas. FIDA diagnostics are now in operation at magnetic-fusion facilities worldwide. They are used to study fast-ion acceleration by ion cyclotron heating, to detect fast-ion transport by MHD modes and microturbulence, and to study fast-ion driven instabilities. PMID:21033920

  11. 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…

  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. PMID:24345130

  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 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

  15. RFI Mitigation for FAST

    NASA Astrophysics Data System (ADS)

    Zhang, Haiyan; Nan, Rendong; Gan, Hengqian; Yue, Youling; Wu, Mingchang; Zhang, Zhiwei; Jin, Chengjin; Peng, Bo

    2015-08-01

    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. The construction was officially commenced in March 2011. The first light of FAST is expected in 2016. Due to the high sensitivity of FAST, Radio Frequency Interference (RFI) mitigation for the telescope is required to assure the realization of the scientific goals. In order to protect the radio environment of FAST site, the local government has established a radio quiet zone with 30 km radius. Moreover, Electromagnetic Compatibility (EMC) designs and measurements for FAST have also been carried out, and some examples, such as EMC designs for actuator and focus cabin, have been introduced briefly.

  16. 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

  17. Mutation detection by chemical cleavage.

    PubMed

    Cotton, R G

    1999-02-01

    Detection and amplification of mutations in genes in a cheap, 100% effective manner is a major objective in modern molecular genetics. This ideal is some way away and many methods are used each of which have their own particular advantages and disadvantages. Sequencing is often thought of as the 'gold standard' for mutation detection. This perception is distorted due to the fact that this is the ONLY method of mutation identification but this does not mean it is the best for mutation detection. The fact that many scanning methods detect 5-10% of mutant molecules in a wild type environment immediately indicates these methods are advantageous over sequencing. One such method, the Chemical Cleavage method, is able to cut the costs of detecting a mutation on order of magnitude and guarantees mutation detection as evidenced by track record and the fact that each mutation has two chances of being detected. PMID:10084109

  18. Novel SCN9A Mutations Underlying Extreme Pain Phenotypes: Unexpected Electrophysiological and Clinical Phenotype Correlations

    PubMed Central

    Emery, Edward C.; Habib, Abdella M.; Cox, James J.; Nicholas, Adeline K.; Gribble, Fiona M.

    2015-01-01

    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. PMID:25995458

  19. 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

  20. 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.

  1. Achieving health care affordability.

    PubMed

    Payson, Norman C

    2002-10-01

    Not all plans are jumping headlong into the consumer-centric arena. In this article, the CEO of Oxford Health Plans discusses how advanced managed care can achieve what other consumer-centric programs seek to do--provide affordable, quality health care. PMID:12391815

  2. Issues in Achievement Testing.

    ERIC Educational Resources Information Center

    Baker, Eva L.

    This booklet is intended to help school personnel, parents, students, and members of the community understand concepts and research relating to achievement testing in public schools. The paper's sections include: (1) test use with direct effects on students (test of certification, selection, and placement); (2) test use with indirect effects on…

  3. 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…

  4. 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…

  5. Intelligence and Educational Achievement

    ERIC Educational Resources Information Center

    Deary, Ian J.; Strand, Steve; Smith, Pauline; Fernandes, Cres

    2007-01-01

    This 5-year prospective longitudinal study of 70,000+ English children examined the association between psychometric intelligence at age 11 years and educational achievement in national examinations in 25 academic subjects at age 16. The correlation between a latent intelligence trait (Spearman's "g"from CAT2E) and a latent trait of educational…

  6. 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…

  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 potential "Robin Hood…

  8. INTELLIGENCE, PERSONALITY AND ACHIEVEMENT.

    ERIC Educational Resources Information Center

    MUIR, R.C.; AND OTHERS

    A LONGITUDINAL DEVELOPMENTAL STUDY OF A GROUP OF MIDDLE CLASS CHILDREN IS DESCRIBED, WITH EMPHASIS ON A SEGMENT OF THE RESEARCH INVESTIGATING THE RELATIONSHIP OF ACHIEVEMENT, INTELLIGENCE, AND EMOTIONAL DISTURBANCE. THE SUBJECTS WERE 105 CHILDREN AGED FIVE TO 6.3 ATTENDING TWO SCHOOLS IN MONTREAL. EACH CHILD WAS ASSESSED IN THE AREAS OF…

  9. School Students' Science Achievement

    ERIC Educational Resources Information Center

    Shymansky, James; Wang, Tzu-Ling; Annetta, Leonard; Everett, Susan; Yore, Larry D.

    2013-01-01

    This paper is a report of the impact of an externally funded, multiyear systemic reform project on students' science achievement on a modified version of the Third International Mathematics and Science Study (TIMSS) test in 33 small, rural school districts in two Midwest states. The systemic reform effort utilized a cascading leadership strategy…

  10. 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…

  11. 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…

  12. 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,…

  13. Setting and Achieving Objectives.

    ERIC Educational Resources Information Center

    Knoop, Robert

    1986-01-01

    Provides basic guidelines which school officials and school boards may find helpful in negotiating, establishing, and managing objectives. Discusses characteristics of good objectives, specific and directional objectives, multiple objectives, participation in setting objectives, feedback on goal process and achievement, and managing a school…

  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. 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,…

  16. Achievements or Disasters?

    ERIC Educational Resources Information Center

    Goodwin, MacArthur

    2000-01-01

    Focuses on policy issues that have affected arts education in the twentieth century, such as: interest in discipline-based arts education, influence of national arts associations, and national standards and coordinated assessment. States that whether the policy decisions are viewed as achievements or disasters are for future determination. (CMK)

  17. Minority Achievement Report.

    ERIC Educational Resources Information Center

    Prince George's Community Coll., Largo, MD. Office of Institutional Research and Analysis.

    This report summarizes the achievements of Prince George's Community College (PGCC) with regard to minority outcomes. Table 1 summarizes the undergraduate enrollment trends for African Americans as well as total minorities from fall 1994 through fall 1998. Both the headcount number of African American students and the proportion of African…

  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. 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

  20. Calreticulin mutations in myeloproliferative neoplasms.

    PubMed

    Lavi, Noa

    2014-10-01

    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

  1. 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.

  2. 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.

  3. fast-matmul

    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 fastmore » matrix multiplication algorithms to encourage future research in this area. The implementations target sequential and shared memory parallel execution.« less

  4. Fasting and cognitive function.

    PubMed

    Pollitt, E; Lewis, N L; Garza, C; Shulman, R J

    The effects of short-term fasting (skipping breakfast) on the problem-solving performance of 9 to 11 yr old children were studied under the controlled conditions of a metabolic ward. The behavioral test battery included an assessment of IQ, the Matching Familiar Figure Test and Hagen Central Incidental Test. Glucose and insulin levels were measured in blood. All assessments were made under fasting and non-fasting conditions. Skipping breakfast was found to have adverse effects on the children's late morning problem-solving performance. These findings support observations that the timing and nutrient composition of meals have acute and demonstrable effects on behavior. PMID:6764933

  5. 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). PMID:24534542

  6. 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.

  7. Achieving Goal Blood Pressure.

    PubMed

    Laurent, Stéphane

    2015-07-01

    Both monotherapy and combination therapy options are appropriate for antihypertensive therapy according to the 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines. Most patients require more than one agent to achieve blood pressure (BP) control, and adding a second agent is more effective than doubling the dose of existing therapy. The addition of a third agent may be required to achieve adequate BP reductions in some patients. Single-pill fixed-dose combinations (FDCs) allow multiple-drug regimens to be delivered without any negative impact on patient compliance or persistence with therapy. FDCs also have documented beneficial clinical effects and use of FDCs containing two or three agents is recommended by the 2013 ESH/ESC guidelines. PMID:26002423

  8. Detection of hepatitis B virus genotypic resistance mutations by coamplification at lower denaturation temperature-PCR coupled with sanger sequencing.

    PubMed

    Liu, Can; Lin, Jinpiao; Chen, Huijuan; Shang, Hongyan; Jiang, Ling; Chen, Jing; Ye, Yang; Yang, Bin; Ou, Qishui

    2014-08-01

    Mutations in the reverse transcriptase (rt) region of the DNA polymerase gene are the primary cause of hepatitis B virus (HBV) drug resistance. In this study, we established a novel method that couples coamplification at lower denaturation temperature (COLD)-PCR and Sanger sequencing, and we applied it to the detection of known and unknown HBV mutations. Primers were designed based on the common mutations in the HBV rt sequence at positions 180 to 215. The critical denaturation temperature (Tc) was established as a denaturing temperature for both fast and full COLD-PCR procedures. For single mutations, when a melting temperature (Tm)-reducing mutation occurred (e.g., C-G → T-A), the sensitivities of fast and full COLD-PCR for mutant detection were 1% and 2%, respectively; when the mutation caused no change in Tm (e.g., C-G → G-C) or raised Tm (e.g., T-A → C-G), only full COLD-PCR improved the sensitivity for mutant detection (2%). For combination mutations, the sensitivities of both full and fast COLD-PCR were increased to 0.5%. The limits of detection for fast and full COLD-PCR were 50 IU/ml and 100 IU/ml, respectively. In 30 chronic hepatitis B (CHB) cases, no mutations were detected by conventional PCR, whereas 18 mutations were successfully detected by COLD-PCR, including low-prevalence mutations (<10%), as confirmed by ultradeep pyrosequencing. In conclusion, COLD-PCR provides a highly sensitive, simple, inexpensive, and practical tool for significantly improving amplification efficacy and detecting low-level mutations in clinical CHB cases. PMID:24899029

  9. Acid-fast stain

    MedlinePlus

    The acid-fast stain is a laboratory test that determines if a sample of tissue, blood, or other body ... dye. The slide is then washed with an acid solution and a different stain is applied. Bacteria ...

  10. 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.

  11. Mutation prediction by PolyPhen or functional assay, a detailed comparison of CYP27B1 missense mutations.

    PubMed

    Zou, Minjing; Baitei, Essa Y; Alzahrani, Ali S; Parhar, Ranjit S; Al-Mohanna, Futwan A; Meyer, Brian F; Shi, Yufei

    2011-08-01

    Vitamin D-dependent rickets type 1 (VDDR-I) is caused by mutation in CYP27B1. The glycine residue at codon 102 is not conserved between human (G(102)) and rodent (S(102)). G102E mutation results in 80% reduction in its enzymatic activity but PolyPhen predicts benign change. It is not known whether G102S has any damaging effect on 1α-hydroxylase activity. We investigated the effect of CYP27B1 (G102S) on its enzymatic activity and compared mutation prediction accuracy for all known CYP27B1 mutations among three free online protein prediction programs: PolyPhen, PolyPhen-2, and PSIPRED. G102S has no damaging effect on 1α-hydroxylase activity. G102D retained 30% enzymatic activity. All three programs correctly predicted damaging change for G102D. PolyPhen predicted benign change for G102S, whereas PolyPhen-2 and PSIPRED indicated possible damaging effect. Among 24 reported damaging mutations, PSIPRED, PolyPhen-2, and PolyPhen achieved 100%, 91.7% (22/24), and 75% (18/24) accuracy rate, respectively. The residues of incorrectly predicted mutations were not conserved. We conclude that G102D resulted in a significant reduction in 1α-hydroxylase activity, whereas G102S did not. PSIPRED and PolyPhen-2 are superior to PolyPhen in predicting damaging mutations. PMID:21604088

  12. Mutation analysis of the entire PKD1 gene: genetic and diagnostic implications.

    PubMed

    Rossetti, S; Strmecki, L; Gamble, V; Burton, S; Sneddon, V; Peral, B; Roy, S; Bakkaloglu, A; Komel, R; Winearls, C G; Harris, P C

    2001-01-01

    Mutation screening of the major autosomal dominant polycystic kidney disease (ADPKD) locus, PKD1, has proved difficult because of the large transcript and complex reiterated gene region. We have developed methods, employing long polymerase chain reaction (PCR) and specific reverse transcription-PCR, to amplify all of the PKD1 coding area. The gene was screened for mutations in 131 unrelated patients with ADPKD, using the protein-truncation test and direct sequencing. Mutations were identified in 57 families, and, including 24 previously characterized changes from this cohort, a detection rate of 52.3% was achieved in 155 families. Mutations were found in all areas of the gene, from exons 1 to 46, with no clear hotspot identified. There was no significant difference in mutation frequency between the single-copy and duplicated areas, but mutations were more than twice as frequent in the 3' half of the gene, compared with the 5' half. The majority of changes were predicted to truncate the protein through nonsense mutations (32%), insertions or deletions (29.6%), or splicing changes (6.2%), although the figures were biased by the methods employed, and, in sequenced areas, approximately 50% of all mutations were missense or in-frame. Studies elsewhere have suggested that gene conversion may be a significant cause of mutation at PKD1, but only 3 of 69 different mutations matched PKD1-like HG sequence. A relatively high rate of new PKD1 mutation was calculated, 1.8x10-5 mutations per generation, consistent with the many different mutations identified (69 in 81 pedigrees) and suggesting significant selection against mutant alleles. The mutation detection rate, in this study, of >50% is comparable to that achieved for other large multiexon genes and shows the feasibility of genetic diagnosis in this disorder. PMID:11115377

  13. Two new Gaucher disease mutations.

    PubMed

    Beutler, E; Gelbart, T

    1994-02-01

    Recently, a mutation at nucleotide 1193 of the glucocerebrosidase gene was described in a patient with type 1 Gaucher disease. This mutation destroys a TaqI site in a polymerase chain reaction (PCR)-amplified fragment. We used digestion with this enzyme to screen DNA samples from Gaucher disease patients representing 23 previously unidentified alleles and discovered that this site had been destroyed in three samples. However, the mutation that caused this change proved to be a CT substitution at cDNA nucleotide 1192 (Genomic 5408; 359Arg-->End). Fortuitously, another TaqI site was destroyed by a different mutation, a GA mutation at nt 1312 (Genomic 5927; 399AspAsn). Both of these mutations were functionally severe in that they were associated with type 2 (acute neuronopathic) Gaucher disease. PMID:8112750

  14. ENU-induced phenovariance in mice: inferences from 587 mutations

    PubMed Central

    2012-01-01

    Background We present a compendium of N-ethyl-N-nitrosourea (ENU)-induced mouse mutations, identified in our laboratory over a period of 10 years either on the basis of phenotype or whole genome and/or whole exome sequencing, and archived in the Mutagenetix database. Our purpose is threefold: 1) to formally describe many point mutations, including those that were not previously disclosed in peer-reviewed publications; 2) to assess the characteristics of these mutations; and 3) to estimate the likelihood that a missense mutation induced by ENU will create a detectable phenotype. Findings In the context of an ENU mutagenesis program for C57BL/6J mice, a total of 185 phenotypes were tracked to mutations in 129 genes. In addition, 402 incidental mutations were identified and predicted to affect 390 genes. As previously reported, ENU shows strand asymmetry in its induction of mutations, particularly favoring T to A rather than A to T in the sense strand of coding regions and splice junctions. Some amino acid substitutions are far more likely to be damaging than others, and some are far more likely to be observed. Indeed, from among a total of 494 non-synonymous coding mutations, ENU was observed to create only 114 of the 182 possible amino acid substitutions that single base changes can achieve. Based on differences in overt null allele frequencies observed in phenotypic vs. non-phenotypic mutation sets, we infer that ENU-induced missense mutations create detectable phenotype only about 1 in 4.7 times. While the remaining mutations may not be functionally neutral, they are, on average, beneath the limits of detection of the phenotypic assays we applied. Conclusions Collectively, these mutations add to our understanding of the chemical specificity of ENU, the types of amino acid substitutions it creates, and its efficiency in causing phenovariance. Our data support the validity of computational algorithms for the prediction of damage caused by amino acid substitutions

  15. Achieving Magnet status.

    PubMed

    Ellis, Beckie; Gates, Judy

    2005-01-01

    Magnet has become the gold standard for nursing excellence. It is the symbol of effective and safe patient care. It evaluates components that inspire safe care, including employee satisfaction and retention, professional education, and effective interdisciplinary collaboration. In an organization whose mission focuses on excellent patient care, Banner Thunderbird Medical Center found that pursuing Magnet status was clearly the next step. In this article, we will discuss committee selection, education, team building, planning, and the discovery process that define the Magnet journey. The road to obtaining Magnet status has permitted many opportunities to celebrate our achievements. PMID:16056158

  16. BRAF Mutations in Canine Cancers

    PubMed Central

    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. PMID:26053201

  17. Hyperinsulinemic hypoglycemia syndrome associated with mutations in the human insulin receptor gene: report of two cases.

    PubMed

    Kuroda, Yohei; Iwahashi, Hiromi; Mineo, Ikuo; Fukui, Kenji; Fukuhara, Atsunori; Iwamoto, Ryuya; Imagawa, Akihisa; Shimomura, Iichiro

    2015-01-01

    Insulinoma and insulin or insulin receptor (IR) autoantibodies are the main causes of hyperinsulinemic hypoglycemia in adults, but the exact cause in other cases remains obscure. This study is to determine the genetic basis of hyperinsulinemic hypoglycemia in two cases without the above abnormalities. Sequence analysis of IR gene in two patients with adult-onset hyperinsulinemic hypoglycemia and their relatives were performed, and the mutant gene observed in one case was analyzed. Both cases had normal levels of fasting plasma glucose (FPG), fasting hyperinsulinemia, low insulin sensitivity, and hypoglycemia with excessive insulin secretion during oral glucose tolerance test (OGTT). Both reported adult-onset postprandial hypoglycemic symptoms. In one patient, a missense mutation (Arg256Cys) was detected in both alleles of the IR gene, and his parents had the same mutation in only one allele but no hypoglycemia. The other had a novel nonsense mutation (Trp1273X) followed by a mutation (Gln1274Lys) in one allele, and his 9-year old son had the same mutation in one allele, together with hyperinsulinemic hypoglycemia during OGTT. Overexpression experiments of the mutant gene found in Case 1 in mammalian cells showed abnormal processing of the IR protein and demonstrated reduced function of Akt/Erk phosphorylation by insulin in the cells. In two cases of hyperinsulinemic hypoglycemia in adults, we found novel mutations in IR gene considered to be linked to hypoglycemia. We propose a disease entity of adult-onset hyperinsulinemic hypoglycemia syndrome associated with mutations in IR gene. PMID:25753915

  18. Recognizing outstanding achievements

    NASA Astrophysics Data System (ADS)

    Speiss, Fred

    One function of any professional society is to provide an objective, informed means for recognizing outstanding achievements in its field. In AGU's Ocean Sciences section we have a variety of means for carrying out this duty. They include recognition of outstanding student presentations at our meetings, dedication of special sessions, nomination of individuals to be fellows of the Union, invitations to present Sverdrup lectures, and recommendations for Macelwane Medals, the Ocean Sciences Award, and the Ewing Medal.Since the decision to bestow these awards requires initiative and judgement by members of our section in addition to a deserving individual, it seems appropriate to review the selection process for each and to urge you to identify those deserving of recognition.

  19. Driver Mutations in Uveal Melanoma

    PubMed Central

    Decatur, Christina L.; Ong, Erin; Garg, Nisha; Anbunathan, Hima; Bowcock, Anne M.; Field, Matthew G.; Harbour, J. William

    2016-01-01

    IMPORTANCE Frequent mutations have been described in the following 5 genes in uveal melanoma (UM): BAP1, EIF1AX, GNA11, GNAQ, and SF3B1. Understanding the prognostic significance of these mutations could facilitate their use in precision medicine. OBJECTIVE To determine the associations between driver mutations, gene expression profile (GEP) classification, clinicopathologic features, and patient outcomes in UM. DESIGN, SETTING, AND PARTICIPANTS Retrospective study of patients with UM treated by enucleation by a single ocular oncologist between November 1, 1998, and July 31, 2014. MAIN OUTCOMES AND MEASURES Clinicopathologic features, patient outcomes, GEP classification (class 1 or class 2), and mutation status were recorded. RESULTS The study cohort comprised 81 participants. Their mean age was 61.5 years, and 37% (30 of 81) were female. The GEP classification was class 1 in 35 of 81 (43%), class 2 in 42 of 81 (52%), and unknown in 4 of 81 (5%). BAP1 mutations were identified in 29 of 64 (45%), GNAQ mutations in 36 of 81 (44%), GNA11 mutations in 36 of 81 (44%), SF3B1 mutations in 19 of 81 (24%), and EIF1AX mutations in 14 of 81 (17%). Sixteen of the mutations in BAP1 and 6 of the mutations in EIF1AX were previously unreported in UM. GNAQ and GNA11 mutations were mutually exclusive. BAP1, SF3B1, and EIF1AX mutations were almost mutually exclusive with each other. Using multiple regression analysis, BAP1 mutations were associated with class 2 GEP and older patient. EIF1AX mutations were associated with class 1 GEP and the absence of ciliary body involvement. SF3B1 mutations were associated with younger patient age. GNAQ mutations were associated with the absence of ciliary body involvement and greater largest basal diameter. GNA11 mutations were not associated with any of the analyzed features. Using Cox proportional hazards modeling, class 2 GEP was the prognostic factor most strongly associated with metastasis (relative risk, 9.4; 95% CI, 3.1–28.5) and

  20. 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.

  1. FAST2 Code validation

    SciTech Connect

    Wilson, R.E.; Freeman, L.N.; Walker, S.N.

    1995-09-01

    The FAST2 Code which is capable of determining structural loads of a flexible, teetering, horizontal axis wind turbine is described and comparisons of calculated loads with test data at two wind speeds for the ESI-80 are given. The FAST2 Code models a two-bladed HAWT with degrees of freedom for blade flap, teeter, drive train flexibility, yaw, and windwise and crosswind tower motion. The code allows blade dimensions, stiffness, and weights to differ and models tower shadow, wind shear, and turbulence. Additionally, dynamic stall is included as are delta-3 and an underslung rotor. Load comparisons are made with ESI-80 test data in the form of power spectral density, rainflow counting, occurrence histograms and azimuth averaged bin plots. It is concluded that agreement between the FAST2 Code and test results is good.

  2. 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.

  3. FAST MOLECULAR SOLVATION ENERGETICS AND FORCE COMPUTATION.

    PubMed

    Bajaj, Chandrajit; Zhao, Wenqi

    2010-01-20

    The total free energy of a molecule includes the classical molecular mechanical energy (which is understood as the free energy in vacuum) and the solvation energy which is caused by the change of the environment of the molecule (solute) from vacuum to solvent. The solvation energy is important to the study of the inter-molecular interactions. In this paper we develop a fast surface-based generalized Born method to compute the electrostatic solvation energy along with the energy derivatives for the solvation forces. The most time-consuming computation is the evaluation of the surface integrals over an algebraic spline molecular surface (ASMS) and the fast computation is achieved by the use of the nonequispaced fast Fourier transform (NFFT) algorithm. The main results of this paper involve (a) an efficient sampling of quadrature points over the molecular surface by using nonlinear patches, (b) fast linear time estimation of energy and inter-molecular forces, (c) error analysis, and (d) efficient implementation combining fast pairwise summation and the continuum integration using nonlinear patches. PMID:20200598

  4. 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…

  5. Fast Reactor Technology Preservation

    SciTech Connect

    Wootan, David W.; Omberg, Ronald P.

    2008-01-11

    There is renewed worldwide interest in developing and implementing a new generation of advanced fast reactors. International cooperative efforts are underway such as the Global Nuclear Energy Partnership (GNEP). Advanced computer modeling and simulation efforts are a key part of these programs. A recognized and validated set of Benchmark Cases are an essential component of such modeling efforts. Testing documentation developed during the operation of the Fast Flux Test Facility (FFTF) provide the information necessary to develop a very useful set of Benchmark Cases.

  6. Ramifications of four concurrent thrombophilic mutations and one hypofibrinolytic mutation.

    PubMed

    Glueck, Charles J; Goldenberg, Naila; Wang, Ping; Aregawi, Dawit

    2004-10-01

    A kindred was examined in which the 48-year-old white female proband with three deep venous thrombosis-pulmonary emboli events had four thrombophilic and one hypofibrinolytic mutations, and in which her 14-year-old asymptomatic daughter had four thrombophilic mutations. The proband was heterozygous for the G1691A factor V Leiden, G20210A prothrombin, and platelet glycoprotein IIIa PL A1/A2 mutations, had high factor VIII (221%), and was homozygous for the 4G4G plasminogen activator inhibitor-1 gene mutation, with high plasminogen activator inhibitor activity (23.7 U/mL). Her 14-year-old daughter was homozygous for the G1691A factor V Leiden and platelet glycoprotein IIb-IIIa PL A2/A2 mutations, compound heterozygous for the C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) mutations, and heterozygous for the G20210A prothrombin mutation, a combination with an estimated likelihood of 1.6 x 10(-7). In 247 white healthy controls, there was no V Leiden homozygosity and no V Leiden-prothrombin gene compound heterozygosity. Heterozygosity for the V Leiden and prothrombin gene mutations was 3.2% and 4.1%, respectively. Homozygosity for the platelet glycoprotein IIb-IIIa PL A2A2, PAI-1 gene 4G4G, and C677T MTHFR mutations was 3.2%, 22.7%, and 12%, respectively. The proband will receive anticoagulation therapy for life. Beyond aspirin, avoidance of exogenous estrogens, and enoxaparin prophylaxis during pregnancy, it is not known whether the proband's daughter should have lifelong anticoagulation therapy, or only after her first thrombotic event. PMID:15497023

  7. Entrepreneur achievement. Liaoning province.

    PubMed

    Zhao, R

    1994-03-01

    This paper reports the successful entrepreneurial endeavors of members of a 20-person women's group in Liaoning Province, China. Jing Yuhong, a member of the Family Planning Association at Shileizi Village, Dalian City, provided the basis for their achievements by first building an entertainment/study room in her home to encourage married women to learn family planning. Once stocked with books, magazines, pamphlets, and other materials on family planning and agricultural technology, dozens of married women in the neighborhood flocked voluntarily to the room. Yuhong also set out to give these women a way to earn their own income as a means of helping then gain greater equality with their husbands and exert greater control over their personal reproductive and social lives. She gave a section of her farming land to the women's group, loaned approximately US$5200 to group members to help them generate income from small business initiatives, built a livestock shed in her garden for the group to raise marmots, and erected an awning behind her house under which mushrooms could be grown. The investment yielded $12,000 in the first year, allowing each woman to keep more than $520 in dividends. Members then soon began going to fairs in the capital and other places to learn about the outside world, and have successfully ventured out on their own to generate individual incomes. Ten out of twenty women engaged in these income-generating activities asked for and got the one-child certificate. PMID:12287775

  8. Clinical and molecular response to interferon-α therapy in essential thrombocythemia patients with CALR mutations.

    PubMed

    Verger, Emmanuelle; Cassinat, Bruno; Chauveau, Aurélie; Dosquet, Christine; Giraudier, Stephane; Schlageter, Marie-Hélène; Ianotto, Jean-Christophe; Yassin, Mohammed A; Al-Dewik, Nader; Carillo, Serge; Legouffe, Eric; Ugo, Valerie; Chomienne, Christine; Kiladjian, Jean-Jacques

    2015-12-10

    Myeloproliferative neoplasms are clonal disorders characterized by the presence of several gene mutations associated with particular hematologic parameters, clinical evolution, and prognosis. Few therapeutic options are available, among which interferon α (IFNα) presents interesting properties like the ability to induce hematologic responses (HRs) and molecular responses (MRs) in patients with JAK2 mutation. We report on the response to IFNα therapy in a cohort of 31 essential thrombocythemia (ET) patients with CALR mutations (mean follow-up of 11.8 years). HR was achieved in all patients. Median CALR mutant allelic burden (%CALR) significantly decreased from 41% at baseline to 26% after treatment, and 2 patients even achieved complete MR. In contrast, %CALR was not significantly modified in ET patients treated with hydroxyurea or aspirin only. Next-generation sequencing identified additional mutations in 6 patients (affecting TET2, ASXL1, IDH2, and TP53 genes). The presence of additional mutations was associated with poorer MR on CALR mutant clones, with only minor or no MRs in this subset of patients. Analysis of the evolution of the different variant allele frequencies showed that the mutated clones had a differential sensitivity to IFNα in a given patient, but no new mutation emerged during treatment. In all, this study shows that IFNα induces high rates of HRs and MRs in CALR-mutated ET, and that the presence of additional nondriver mutations may influence the MR to therapy. PMID:26486786

  9. 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.

  10. 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.

  11. The Homogeneity of School Achievement.

    ERIC Educational Resources Information Center

    Cahan, Sorel

    Since the measurement of school achievement involves the administration of achievement tests to various grades on various subjects, both grade level and subject matter contribute to within-school achievement variations. To determine whether achievement test scores vary most among different fields within a grade level, or within fields among…

  12. HEPEX - achievements and challenges!

    NASA Astrophysics Data System (ADS)

    Pappenberger, Florian; Ramos, Maria-Helena; Thielen, Jutta; Wood, Andy; Wang, Qj; Duan, Qingyun; Collischonn, Walter; Verkade, Jan; Voisin, Nathalie; Wetterhall, Fredrik; Vuillaume, Jean-Francois Emmanuel; Lucatero Villasenor, Diana; Cloke, Hannah L.; Schaake, John; van Andel, Schalk-Jan

    2014-05-01

    HEPEX is an international initiative bringing together hydrologists, meteorologists, researchers and end-users to develop advanced probabilistic hydrological forecast techniques for improved flood, drought and water management. HEPEX was launched in 2004 as an independent, cooperative international scientific activity. During the first meeting, the overarching goal was defined as: "to develop and test procedures to produce reliable hydrological ensemble forecasts, and to demonstrate their utility in decision making related to the water, environmental and emergency management sectors." The applications of hydrological ensemble predictions span across large spatio-temporal scales, ranging from short-term and localized predictions to global climate change and regional modeling. Within the HEPEX community, information is shared through its blog (www.hepex.org), meetings, testbeds and intercompaison experiments, as well as project reportings. Key questions of HEPEX are: * What adaptations are required for meteorological ensemble systems to be coupled with hydrological ensemble systems? * How should the existing hydrological ensemble prediction systems be modified to account for all sources of uncertainty within a forecast? * What is the best way for the user community to take advantage of ensemble forecasts and to make better decisions based on them? This year HEPEX celebrates its 10th year anniversary and this poster will present a review of the main operational and research achievements and challenges prepared by Hepex contributors on data assimilation, post-processing of hydrologic predictions, forecast verification, communication and use of probabilistic forecasts in decision-making. Additionally, we will present the most recent activities implemented by Hepex and illustrate how everyone can join the community and participate to the development of new approaches in hydrologic ensemble prediction.

  13. Parkinsonism Associated with Glucocerebrosidase Mutation

    PubMed Central

    Sunwoo, Mun-Kyung; Kim, Seung-Min; Lee, Sarah

    2011-01-01

    Background Gaucher's disease is an autosomal recessive, lysosomal storage disease caused by mutations of the β-glucocerebrosidase gene (GBA). There is increasing evidence that GBA mutations are a genetic risk factor for the development of Parkinson's disease (PD). We report herein a family of Koreans exhibiting parkinsonism-associated GBA mutations. Case Report A 44-year-old woman suffering from slowness and paresthesia of the left arm for the previous 1.5years, visited our hospital to manage known invasive ductal carcinoma. During a preoperative evaluation, she was diagnosed with Gaucher's disease and double mutations of S271G and R359X in GBA. Parkinsonian features including low amplitude postural tremors, rigidity, bradykinesia and shuffling gait were observed. Genetic analysis also revealed that her older sister, who had also been diagnosed with PD and had been taking dopaminergic drugs for 8-years, also possessed a heterozygote R359X mutation in GBA. 18F-fluoropropylcarbomethoxyiodophenylnortropane positron-emission tomography in these patients revealed decreased uptake of dopamine transporter in the posterior portion of the bilateral putamen. Conclusions This case study demonstrates Korean familial cases of PD with heterozygote mutation of GBA, further supporting the association between PD and GBA mutation. PMID:21779299

  14. Bladder Cancer and Genetic Mutations.

    PubMed

    Zhang, Xiaoying; Zhang, Yangde

    2015-09-01

    The most common type of urinary bladder cancer is called as transitional cell carcinoma. The major risk factors for bladder cancer are environmental, tobacco smoking, exposure to toxic industrial chemicals and gases, bladder inflammation due to microbial and parasitic infections, as well as some adverse side-effects of medications. The genetic mutations in some chromosomal genes, such as FGFR3, RB1, HRAS, TP53, TSC1, and others, occur which form tumors in the urinary bladder. These genes play an important role in the regulation of cell division which prevents cells from dividing too quickly. The changes in the genes of human chromosome 9 are usually responsible for tumor in bladder cancer, but the genetic mutation of chromosome 22 can also result in bladder cancer. The identification of p53 gene mutation has been studied at NIH, Washington, DC, USA, in urine samples of bladder cancer patients. The invasive bladder cancers were determined for the presence of gene mutations on p53 suppressor gene. The 18 different bladder tumors were evaluated, and 11 (61 %) had genetic mutations of p53 gene. The bladder cancer studies have suggested that 70 % of bladder cancers involve a specific mutation in a particular gene, namely telomerase reverse transcriptase (TERT) gene. The TERT gene is involved in DNA protection, cellular aging processes, and cancer. The Urothelial carcinomas of the bladder have been described in Atlas of genetics and cytogenetics in oncology and hematology. HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder. The TSC1 c. 1907 1908 del (E636fs) mutation in bladder cancer suggests that the location of the mutation is Exon 15 with frequency of TSC1 mutation of 11.7 %. The recent findings of BAP1 mutations have shown that it contributes to BRCA pathway alterations in bladder cancer. The discoveries of more gene mutations and new biomarkers and polymerase chain reaction bioassays for gene mutations in bladder

  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. Glucocerebrosidase mutations in Gaucher disease.

    PubMed Central

    Beutler, E.; Demina, A.; Gelbart, T.

    1994-01-01

    BACKGROUND: Thirty-six mutations that cause Gaucher disease, the most common glycolipid storage disorder, are known. Although both alleles of most patients with the disease contain one of these mutations, in a few patients one or both disease-producing alleles have remained unidentified. Identification of mutations in these patients is useful for genetic counseling. MATERIALS AND METHODS: The DNA from 23 Gaucher disease patients in whom at least one glucocerebrosidase allele did not contain any of the 36 previously described mutations has been examined by single strand conformation polymorphism (SSCP) analysis, followed by sequencing of regions in which abnormalities were detected. RESULTS: Eight previously undescribed mutations were detected. In exon 3, a deletion of a cytosine at cDNA nt 203 was found. In exon 6, three missense mutations were identified: a C-->A transversion at cDNA nt 644 (Ala176-->Asp), a C-->A transversion at cDNA nt 661 that resulted in a (Pro182-->Thr), and a G-->A transition at cDNA nt 721 (Gly202-->Arg). Two missense mutations were found in exon 7: a G-->A transition at cDNA nt 887 (Arg257-->Gln) and a C-->T at cDNA nt 970 (Arg285-->Cys). Two missense mutations were found in exon 9: a T-->G at cDNA nt 1249 (Trp378-->Gly) and a G-->A at cDNA nt 1255 (Asp380-->Asn). In addition to these disease-producing mutations, a silent C-->G transversion at cDNA nt 1431, occurring in a gene that already contained the 1226G mutation, was found in one family. CONCLUSIONS: The mutations described here and previously known can be classified as mild, severe, or lethal, on the basis of their effect on enzyme production and on clinical phenotype, and as polymorphic or sporadic, on the basis of the haplotype in which they are found. Rare mutations such as the new ones described here are sporadic in nature. PMID:8790604

  17. Impact of Baseline BCR-ABL Mutations on Response to Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase

    PubMed Central

    Hughes, Timothy; Saglio, Giuseppe; Branford, Susan; Soverini, Simona; Kim, Dong-Wook; Müller, Martin C.; Martinelli, Giovanni; Cortes, Jorge; Beppu, Lan; Gottardi, Enrico; Kim, Dongho; Erben, Philipp; Shou, Yaping; Haque, Ariful; Gallagher, Neil; Radich, Jerald; Hochhaus, Andreas

    2009-01-01

    Purpose Nilotinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with chronic myeloid leukemia (CML) in chronic phase (CP; CML-CP) and accelerated phase (AP; CML-AP) who are resistant to or intolerant of prior imatinib therapy. In this subanalysis of a phase II study of nilotinib in patients with imatinib-resistant or imatinib-intolerant CML-CP, the occurrence and impact of baseline and newly detectable BCR-ABL mutations were assessed. Patients and Methods Baseline mutation data were assessed in 281 (88%) of 321 patients with CML-CP in the phase II nilotinib registration trial. Results Among imatinib-resistant patients, the frequency of mutations at baseline was 55%. After 12 months of therapy, major cytogenetic response (MCyR) was achieved in 60%, complete cytogenetic response (CCyR) in 40%, and major molecular response (MMR) in 29% of patients without baseline mutations versus 49% (P = .145), 32% (P = .285), and 22% (P = .366), respectively, of patients with mutations. Responses in patients who harbored mutations with high in vitro sensitivity to nilotinib (50% inhibitory concentration [IC50] ≤ 150 nM) or mutations with unknown nilotinib sensitivity were equivalent to those responses for patients without mutations (not significant). Patients with mutations that were less sensitive to nilotinib in vitro (IC50 > 150 nM; Y253H, E255V/K, F359V/C) had less favorable responses, as 13%, 43%, and 9% of patients with each of these mutations, respectively, achieved MCyR; none achieved CCyR. Conclusion For most patients with imatinib resistance and with mutations, nilotinib offers a substantial probability of response. However, mutational status at baseline may influence response. Less sensitive mutations that occurred at three residues defined in this study, as well as the T315I mutation, may be associated with less favorable responses to nilotinib. PMID:19652056

  18. Cellular Defense Enzyme Drives Exceptionally High Rate of Mutation in HIV.

    PubMed

    Robinson, Richard

    2015-09-01

    HIV-1 is already known to have an extremely fast mutation rate, but a new study shows it to be more than two orders of magnitude higher than previously believed, and that this is largely due to host cytidine deaminases. Read the Research Article. PMID:26375682

  19. Sox17 Regulates Liver Lipid Metabolism and Adaptation to Fasting

    PubMed Central

    Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/− mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting. PMID:25141153

  20. Sox17 regulates liver lipid metabolism and adaptation to fasting.

    PubMed

    Rommelaere, Samuel; Millet, Virginie; Vu Manh, Thien-Phong; Gensollen, Thomas; Andreoletti, Pierre; Cherkaoui-Malki, Mustapha; Bourges, Christophe; Escalière, Bertrand; Du, Xin; Xia, Yu; Imbert, Jean; Beutler, Bruce; Kanai, Yoshiakira; Malissen, Bernard; Malissen, Marie; Tailleux, Anne; Staels, Bart; Galland, Franck; Naquet, Philippe

    2014-01-01

    Liver is a major regulator of lipid metabolism and adaptation to fasting, a process involving PPARalpha activation. We recently showed that the Vnn1 gene is a PPARalpha target gene in liver and that release of the Vanin-1 pantetheinase in serum is a biomarker of PPARalpha activation. Here we set up a screen to identify new regulators of adaptation to fasting using the serum Vanin-1 as a marker of PPARalpha activation. Mutagenized mice were screened for low serum Vanin-1 expression. Functional interactions with PPARalpha were investigated by combining transcriptomic, biochemical and metabolic approaches. We characterized a new mutant mouse in which hepatic and serum expression of Vanin-1 is depressed. This mouse carries a mutation in the HMG domain of the Sox17 transcription factor. Mutant mice display a metabolic phenotype featuring lipid abnormalities and inefficient adaptation to fasting. Upon fasting, a fraction of the PPARα-driven transcriptional program is no longer induced and associated with impaired fatty acid oxidation. The transcriptional phenotype is partially observed in heterozygous Sox17+/- mice. In mutant mice, the fasting phenotype but not all transcriptomic signature is rescued by the administration of the PPARalpha agonist fenofibrate. These results identify a novel role for Sox17 in adult liver as a modulator of the metabolic adaptation to fasting. PMID:25141153

  1. 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…

  2. 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…

  3. Predicting Mathematics Achievement: The Influence of Prior Achievement and Attitudes

    ERIC Educational Resources Information Center

    Hemmings, Brian; Grootenboer, Peter; Kay, Russell

    2011-01-01

    Achievement in mathematics is inextricably linked to future career opportunities, and therefore, understanding those factors that influence achievement is important. This study sought to examine the relationships among attitude towards mathematics, ability and mathematical achievement. This examination was also supported by a focus on gender…

  4. "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…

  5. 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.

  6. Identification of previously unreported mutations in CHRNA1, CHRNE and RAPSN genes in three unrelated Italian patients with congenital myasthenic syndromes.

    PubMed

    Brugnoni, Raffaella; Maggi, Lorenzo; Canioni, Eleonora; Moroni, Isabella; Pantaleoni, Chiara; D'Arrigo, Stefano; Riva, Daria; Cornelio, Ferdinando; Bernasconi, Pia; Mantegazza, Renato

    2010-07-01

    Congenital myasthenic syndromes are rare genetic disorders compromising neuromuscular transmission. The defects are mainly mutations in the muscle acetylcholine receptor, or associated proteins rapsyn and Dok-7. We analyzed three unrelated Italian patients with typical clinical features of congenital myasthenic syndrome, who all benefitted from cholinesterase inhibitors. We found five mutations: a previously unreported homozygous alphaG378D mutation in the CHRNA1 gene, a previously unreported heterozygous epsilonY8X mutation associated with a known heterozygous epsilonM292del deletion in the CHRNE gene, and the common heterozygous N88K mutation associated with a previously unreported heterozygous IVS1 + 2T > G splice site mutation in the RAPSN gene. All three patients had two mutant alleles; parents or offspring with a single mutated allele were asymptomatic, thus all mutations exerted their effects recessively. The previously unreported mutations are likely to reduce the number of AChRs at the motor endplate, although the alphaG378D mutation might produce a mild fast channel syndrome. The alphaG378D mutation was recessive, but recessive CHRNA1 mutations have rarely been reported previously, so studies on the effect of this mutation at the cellular level would be of interest. PMID:20157724

  7. Fast fission phenomenon

    NASA Astrophysics Data System (ADS)

    In these lectures we have described two different phenomena occuring in dissipative heavy ion collisions : neutron-proton asymmetry and fast fission. Neutron-proton asymmetry has provided us with an example of a fast collective motion. As a consequence quantum fluctuations can be observed. The observation of quantum or statistical fluctuations is directly connected to the comparison between the phonon energy and the temperature of the intrinsic system. This means that this mode might also provide a good example for the investigation of the transition between quantum and statistical fluctuations which might occur when the bombarding energy is raised above 10 MeV/A. However it is by no means sure that in this energy domain enough excitation energy can be put into the system in order to reach such high temperatures over the all system. The other interest in investigating neutron-proton asymmetry above 10 MeV/A is that the interaction time between the two incident nuclei will decrease. Consequently, if some collective motion should still be observed, it will be one of the last which can be seen. Fast fission corresponds on the contrary to long interaction times. The experimental indications are still rather weak and mainly consist of experimental data which cannot be understood in the framework of standard dissipative models. We have seen that a model which can describe both the entrance and the exit configuration gives this mechanism in a natural way and that the experimental data can, to a good extend, be explained. The nicest thing is probably that our old understanding of dissipative heavy ion collisions is not changed at all except for the problems that can now be understood in terms of fast fission. Nevertheless this area desserve further studies, especially on the experimental side to be sure that the consistent picture which we have on dissipative heavy ion collisions still remain coherent in the future.

  8. 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. PMID:23513759

  9. 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.

  10. 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.

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

    PubMed

    Kist, Andreas M; Sagafos, Dagrun; Rush, Anthony M; 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; Lampert, Angelika; 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

  12. Routine implementation of EGFR mutation testing in clinical practice in Flanders: 'HERMES' project.

    PubMed

    Janssens, A; De Droogh, E; Lefebure, A; Kockx, M; Pauwels, P; Germonpre, P; van Meerbeeck, J P

    2014-04-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the recommended first-line treatment in metastatic EGFR-mutation-positive non-small cell lung cancer (NSCLC) patients. Such a personalized treatment requires fast EGFR mutation testing. This study was performed to determine the turn around time (TAT) for EGFR mutation testing on tumour samples of NSCLC in the clinical care in the region of Antwerp (Belgium). The secondary aim was to determine the frequency of EGFR mutations in this Flemish population. Tumour tissue was prospectively obtained from lung cancer patients in participating hospitals and sent from the local pathology laboratory (lab) to two central laboratories (labs) where EGFR-mutation analysis was performed. Results were returned from the central labs to the clinicians and the local pathology lab. TAT was defined as the interval between the request from the oncologist and the result obtained by the oncologist. One hundred and seven specimens were analysed. The clinician got the result from the local lab in a median time of 10 days (3-37 days) and from the central lab in 9 days (3-29 days). We detected seven mutations (7%) in this study population, all occurring in tumours with an adenocarcinoma histology, four (57%) in men and five (71%) in (ex-)smokers. There were six exon 19 deletions and one L858R mutation. It is possible to implement EGFR-mutation testing with timely reporting of the EGFR-mutation status. EGFR-mutation occurs in 7% of Flemish patients with NSCLC. Patients with advanced non-squamous NSCLC should be tested for EGFR mutation regardless of their gender and smoking history. PMID:24724747

  13. 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.

  14. The fast Hartley transform

    NASA Astrophysics Data System (ADS)

    Mar, Mark H.

    1990-11-01

    The purpose of this paper is to report the results of testing the fast Hartley transform (FHT) and comparing it with the fast Fourier transform (FFT). All the definitions and equations in this paper are quoted and cited from the series of references. The author of this report developed a FORTRAN program which computes the Hartley transform. He tested the program with a generalized electromagnetic pulse waveform and verified the results with the known value. Fourier analysis is an essential tool to obtain frequency domain information from transient time domain signals. The FFT is a popular tool to process many of today's audio and electromagnetic signals. System frequency response, digital filtering of signals, and signal power spectrum are the most practical applications of the FFT. However, the Fourier integral transform of the FFT requires computer resources appropriate for the complex arithmetic operations. On the other hand, the FHT can accomplish the same results faster and requires fewer computer resources. The FHT is twice as fast as the FFT, uses only half the computer resources, and so could be more useful than the FFT in typical applications such as spectral analysis, signal processing, and convolution. This paper presents a FORTRAN computer program for the FHT algorithm along with a brief description and compares the results and performance of the FHT and the FFT algorithms.

  15. Construction of targeted insertion mutations in Francisella tularensis subsp. novicida.

    PubMed

    Liu, Jirong; Zogaj, Xhavit; Barker, Jeffrey R; Klose, Karl E

    2007-10-01

    Francisella tularensis is one of the most deadly bacterial agents, yet most of the genetic determinants of pathogenesis are still unknown. We have developed an efficient targeted mutagenesis strategy in the model organism F. tularensis subsp. novicida by utilizing universal priming of optimized antibiotic resistance cassettes and splicing by overlap extension (SOE). This process enables fast and efficient construction of targeted insertion mutations in F. tularensis subsp. novicida that have characteristics of nonpolar mutations; optimized targeted mutagenesis strategies will promote the study of this mysterious bacterium and facilitate vaccine development against tularemia. Moreover the general strategy of gene disruption by PCR-based antibiotic resistance cassette insertion is broadly applicable to many bacterial species. PMID:18019340

  16. Single molecule targeted sequencing for cancer gene mutation detection.

    PubMed

    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

  17. 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

  18. Genome Destabilizing Mutator Alleles Drive Specific Mutational Trajectories in Saccharomyces cerevisiae

    PubMed Central

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

    2014-01-01

    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. PMID:24336748

  19. Pulsar Observations with Radio Telescope FAST

    NASA Astrophysics Data System (ADS)

    Nan, Ren-Dong; Wang, Qi-Ming; Zhu, Li-Chun; Zhu, Wen-Bai; Jin, Cheng-Jin; Gan, Heng-Qian

    2006-12-01

    FAST, Five hundred meter Aperture Spherical Telescope, is the Chinese effort for the international project SKA, Square Kilometer Array. An innovative engineering concept and design pave a new road to realizing huge single dish in the most effective way. Three outstanding features of the telescope are the unique karst depressions as the sites, the active main reflector which corrects spherical aberration on the ground to achieve full polarization and wide band without involving complex feed system, and the light focus cabin driven by cables and servomechanism plus a parallel robot as secondary adjustable system to carry the most precise parts of the receivers. Besides a general coverage of those critical technologies involved in FAST concept, the progresses in demonstrating model being constructed at the Miyun Radio Observatory of the NAOC is introduced. Being the most sensitive radio telescope, FAST will enable astronomers to jumpstart many of science goals, for example, the natural hydrogen line surveying in distant galaxies, looking for the first generation of shining objects, hearing the possible signal from other civilizations, etc. Among these subjects, the most striking one could be pulsar study. Large scale survey by FAST will not only improve the statistics of the pulsar population, but also may offer us a good fortune to pick up more of the most exotic, even unknown types like a sub-millisecond pulsar or a neutron star -- black hole binary as the telescope is put into operation.

  20. Particle Filtration for Ultra Fast Laser Processing

    NASA Astrophysics Data System (ADS)

    Jakschik, S.; Kesslau, D.

    Ultra fast laser processing is marketed for processes which require small thermal impact to the product. The process has its advantages in processing speed and quality. Recent applications have been in photo-voltaic processing, surface treatment or preparation of electrodes for lithium ion batteries. As soon as the fast laser is utilized for ablation, particles are generated. Driven by product quality, tool conservation and governmental restrictions a well-defined air filter is necessary for laser processes. The layout and design of such a filter system is not strait forward. First of all acquisition plays a major role on the overall quality of the system. In addition the filter itself needs to be well defined in terms of deposition rate and endurance. The latter is determined by the generated particles. We present an investigation of particles as generated by ultra fast laser processing of silicon, inox and ceramics. Our investigation proves thermal impact on generated particles by the ultra-fast laser. The particle spectrum is clearly determined by sub micrometer particles, making nano-filtration a necessary step. Based on this investigation an extraction and filter solution was designed and successfully demonstrated on silicon, inox and ceramic process. A filter quality according to governmental regulation is achieved, based on an extraction which delivers best product quality.

  1. 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

  2. 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

  3. Hispanics in Fast Food Jobs.

    ERIC Educational Resources Information Center

    Charner, Ivan; Fraser, Bryna Shore

    A study examined the employment of Hispanics in the fast-food industry. Data were obtained from a national survey of employees at 279 fast-food restaurants from seven companies in which 194 (4.2 percent) of the 4,660 respondents reported being Hispanic. Compared with the total sample, Hispanic fast-food employees were slightly less likely to be…

  4. [Research Reports on Academic Achievement.

    ERIC Educational Resources Information Center

    Latts, Sander; And Others

    1969-01-01

    Four counselors studied the relation between achievement and choice of major, achievement and motivation, counseling and motivation, and achievement and employment. To see if those with definite majors or career choices in mind did better than those without, 300 students were tested according to the certainty of their choice. No significant…

  5. Cherokee Culture and School Achievement.

    ERIC Educational Resources Information Center

    Brown, Anthony D.

    1980-01-01

    Compares the effect of cooperative and competitive behaviors of Cherokee and Anglo American elementary school students on academic achievement. Suggests changes in teaching techniques and lesson organization that might raise academic achievement while taking into consideration tribal traditions that limit scholastic achievement in an…

  6. Efficient Recovery of Enu-Induced Mutations from the Zebrafish Germline

    PubMed Central

    Solnica-Krezel, L.; Schier, A. F.; Driever, W.

    1994-01-01

    We studied the efficiency with which two chemical mutagens, ethyl methanesulfonate (EMS) and N-ethyl-N-nitrosourea (ENU) can induce mutations at different stages of spermatogenesis in zebrafish (Brachydanio rerio). Both EMS and ENU induced mutations at high rates in post-meiotic germ cells, as indicated by the incidence of F(1) progeny mosaic for the albino mutation. For pre-meiotic germ cells, however, only ENU was found to be an effective mutagen, as indicated by the frequencies of non-mosaic mutant progeny at four different pigmentation loci. Several mutagenic regimens that varied in either the number of treatments or the concentration of ENU were studied to achieve an optimal ratio between the mutagenicity and toxicity. For the two most mutagenic regimens: 4 X 1 hr in 3 mM ENU and 6 X 1 hr in 3 mM ENU, the minimum estimate of frequencies of independent mutations per locus per gamete was 0.9-1.3 X 10(-3). We demonstrate that embryonic lethal mutations induced with ENU were transmitted to offspring and that they could be recovered in an F(2) screen. An average frequency of specific-locus mutations of 1.1 X 10(-3) corresponded to approximately 1.7 embryonic lethal mutations per single mutagenized genome. The high rates of mutations achievable with ENU allow for rapid identification of large numbers of genes involved in a variety of aspects of zebrafish development. PMID:8013916

  7. Differential evolution enhanced with multiobjective sorting-based mutation operators.

    PubMed

    Wang, Jiahai; Liao, Jianjun; Zhou, Ying; Cai, Yiqiao

    2014-12-01

    Differential evolution (DE) is a simple and powerful population-based evolutionary algorithm. The salient feature of DE lies in its mutation mechanism. Generally, the parents in the mutation operator of DE are randomly selected from the population. Hence, all vectors are equally likely to be selected as parents without selective pressure at all. Additionally, the diversity information is always ignored. In order to fully exploit the fitness and diversity information of the population, this paper presents a DE framework with multiobjective sorting-based mutation operator. In the proposed mutation operator, individuals in the current population are firstly sorted according to their fitness and diversity contribution by nondominated sorting. Then parents in the mutation operators are proportionally selected according to their rankings based on fitness and diversity, thus, the promising individuals with better fitness and diversity have more opportunity to be selected as parents. Since fitness and diversity information is simultaneously considered for parent selection, a good balance between exploration and exploitation can be achieved. The proposed operator is applied to original DE algorithms, as well as several advanced DE variants. Experimental results on 48 benchmark functions and 12 real-world application problems show that the proposed operator is an effective approach to enhance the performance of most DE algorithms studied. PMID:24802378

  8. Mutation as a Stress Response and the Regulation of Evolvability

    PubMed Central

    Galhardo, Rodrigo S.; Hastings, P. J.; Rosenberg, Susan M.

    2010-01-01

    Our concept of a stable genome is evolving to one in which genomes are plastic and responsive to environmental changes. Growing evidence shows that a variety of environmental stresses induce genomic instability in bacteria, yeast, and human cancer cells, generating occasional fitter mutants and potentially accelerating adaptive evolution. The emerging molecular mechanisms of stress-induced mutagenesis vary but share telling common components that underscore two common themes. The first is the regulation of mutagenesis in time by cellular stress responses, which promote random mutations specifically when cells are poorly adapted to their environments, i.e., when they are stressed. A second theme is the possible restriction of random mutagenesis in genomic space, achieved via coupling of mutation-generating machinery to local events such as DNA-break repair or transcription. Such localization may minimize accumulation of deleterious mutations in the genomes of rare fitter mutants, and promote local concerted evolution. Although mutagenesis induced by stresses other than direct damage to DNA was previously controversial, evidence for the existence of various stress-induced mutagenesis programs is now overwhelming and widespread. Such mechanisms probably fuel evolution of microbial pathogenesis and antibiotic-resistance, and tumor progression and chemotherapy resistance, all of which occur under stress, driven by mutations. The emerging commonalities in stress-induced-mutation mechanisms provide hope for new therapeutic interventions for all of these processes. PMID:17917874

  9. Efficient algorithms for probing the RNA mutation landscape.

    PubMed

    Waldispühl, Jérôme; Devadas, Srinivas; Berger, Bonnie; Clote, Peter

    2008-01-01

    The diversity and importance of the role played by RNAs in the regulation and development of the cell are now well-known and well-documented. This broad range of functions is achieved through specific structures that have been (presumably) optimized through evolution. State-of-the-art methods, such as McCaskill's algorithm, use a statistical mechanics framework based on the computation of the partition function over the canonical ensemble of all possible secondary structures on a given sequence. Although secondary structure predictions from thermodynamics-based algorithms are not as accurate as methods employing comparative genomics, the former methods are the only available tools to investigate novel RNAs, such as the many RNAs of unknown function recently reported by the ENCODE consortium. In this paper, we generalize the McCaskill partition function algorithm to sum over the grand canonical ensemble of all secondary structures of all mutants of the given sequence. Specifically, our new program, RNAmutants, simultaneously computes for each integer k the minimum free energy structure MFE(k) and the partition function Z(k) over all secondary structures of all k-point mutants, even allowing the user to specify certain positions required not to mutate and certain positions required to base-pair or remain unpaired. This technically important extension allows us to study the resilience of an RNA molecule to pointwise mutations. By computing the mutation profile of a sequence, a novel graphical representation of the mutational tendency of nucleotide positions, we analyze the deleterious nature of mutating specific nucleotide positions or groups of positions. We have successfully applied RNAmutants to investigate deleterious mutations (mutations that radically modify the secondary structure) in the Hepatitis C virus cis-acting replication element and to evaluate the evolutionary pressure applied on different regions of the HIV trans-activation response element. In

  10. Students' Achievement Goals, Learning-Related Emotions and Academic Achievement.

    PubMed

    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

  11. 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

  12. 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)

  13. Fast Pulsing Neutron Generators for Security Application

    SciTech Connect

    Ji, Q.; Regis, M.; Kwan, J. W.

    2009-04-24

    Active neutron interrogation has been demonstrated to be an effective method of detecting shielded fissile material. A fast fall-time/fast pulsing neutron generator is needed primarily for differential die-away technique (DDA) interrogation systems. A compact neutron generator, currently being developed in Lawrence Berkeley National Laboratory, employs an array of 0.6-mm-dia apertures (instead of one 6-mm-dia aperture) such that gating the beamlets can be done with low voltage and a small gap to achieve sub-microsecond ion beam fall time and low background neutrons. Arrays of 16 apertures (4x4) and 100 apertures (10x10) have been designed and fabricated for a beam extraction experiment. The preliminary results showed that, using a gating voltage of 1200 V and a gap distance of 1 mm, the fall time of extracted ion beam pulses is approximately 0.15 mu s at beam energies of 1000 eV.

  14. Fast diffusion of water nanodroplets on graphene

    NASA Astrophysics Data System (ADS)

    Ma, Ming; Tocci, Gabriele; Michaelides, Angelos; Aeppli, Gabriel

    2016-01-01

    Diffusion across surfaces generally involves motion on a vibrating but otherwise stationary substrate. Here, using molecular dynamics, we show that a layered material such as graphene opens up a new mechanism for surface diffusion whereby adsorbates are carried by propagating ripples in a motion similar to surfing. For water nanodroplets, we demonstrate that the mechanism leads to exceedingly fast diffusion that is 2-3 orders of magnitude faster than the self-diffusion of water molecules in liquid water. We also reveal the underlying principles that regulate this new mechanism for diffusion and show how it also applies to adsorbates other than water, thus opening up the prospect of achieving fast and controllable motion of adsorbates across material surfaces more generally.

  15. Fast diffusion of water nanodroplets on graphene.

    PubMed

    Ma, Ming; Tocci, Gabriele; Michaelides, Angelos; Aeppli, Gabriel

    2016-01-01

    Diffusion across surfaces generally involves motion on a vibrating but otherwise stationary substrate. Here, using molecular dynamics, we show that a layered material such as graphene opens up a new mechanism for surface diffusion whereby adsorbates are carried by propagating ripples in a motion similar to surfing. For water nanodroplets, we demonstrate that the mechanism leads to exceedingly fast diffusion that is 2-3 orders of magnitude faster than the self-diffusion of water molecules in liquid water. We also reveal the underlying principles that regulate this new mechanism for diffusion and show how it also applies to adsorbates other than water, thus opening up the prospect of achieving fast and controllable motion of adsorbates across material surfaces more generally. PMID:26480227

  16. 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.

  17. 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.

  18. 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

  19. EGFR Mutation Analysis of Circulating Tumor DNA Using an Improved PNA-LNA PCR Clamp Method

    PubMed Central

    Watanabe, Kana; Fukuhara, Tatsuro; Tsukita, Yoko; Morita, Mami; Suzuki, Aya; Tanaka, Nobuyuki; Terasaki, Hiroshi; Nukiwa, Toshihiro

    2016-01-01

    Introduction. Rebiopsies have become more crucial in non-small cell lung cancer (NSCLC). Instead of invasive biopsies, development of collecting biological data of the tumor from blood samples is expected. We conducted a prospective study to assess the feasibility of detection of epidermal growth factor receptor (EGFR) mutation in plasma samples. Method. NSCLC patients harboring EGFR activating mutations, who were going to receive EGFR-tyrosine kinase inhibitors (TKIs) as first-line treatment, were enrolled in this study. Plasma EGFR activating mutations and the T790M resistance mutation were analyzed by an improved PNA-LNA PCR clamp method, characterized by a 10-fold or more sensitivity compared with the original methods. Result. Six patients with wild-type EGFR and 24 patients with EGFR mutations were enrolled in this study. Pretreatment plasma samples achieved sensitivity of 79%. The 6 patients with wild-type EGFR were all negative for plasma EGFR mutations. At the time of disease progression, plasma T790M mutation was detected in 8 of 16 cases. Absence of T790M before and during TKI treatment and disappearance of activating mutations during TKI treatment were considered as predictors of EGFR-TKIs efficacy. Conclusion. We were able to detect EGFR mutations in plasma samples by using an improved PNA-LNA PCR clamp method. PMID:27478396

  20. Achievement as Resistance: The Development of a Critical Race Achievement Ideology among Black Achievers

    ERIC Educational Resources Information Center

    Carter, Dorinda J.

    2008-01-01

    In this article, Dorinda Carter examines the embodiment of a critical race achievement ideology in high-achieving black students. She conducted a yearlong qualitative investigation of the adaptive behaviors that nine high-achieving black students developed and employed to navigate the process of schooling at an upper-class, predominantly white,…

  1. 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.

  2. 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.

  3. Fast quench reactor method

    SciTech Connect

    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.

  4. Fast quench reactor method

    DOEpatents

    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.

  5. 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.

  6. 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.

  7. 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

  8. Phenotypic and genomic analyses 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. In this study, fast neutron (FN) radiation was used to induce deletion mutations in the soybean (Glycine max (L.) Merrill) genome. Approximately 120,000 soybea...

  9. 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. PMID:16268681

  10. SQSTM1 Mutations and Glaucoma

    PubMed Central

    Scheetz, Todd E.; Roos, Ben R.; Solivan-Timpe, Frances; Miller, Kathy; DeLuca, Adam P.; Stone, Edwin M.; Kwon, Young H.; Alward, Wallace L. M.; Wang, Kai; Fingert, John H.

    2016-01-01

    Glaucoma is the most common cause of irreversible blindness worldwide. One subset of glaucoma, normal tension glaucoma (NTG) occurs in the absence of high intraocular pressure. Mutations in two genes, optineurin (OPTN) and TANK binding kinase 1 (TBK1), cause familial NTG and have known roles in the catabolic cellular process autophagy. TKB1 encodes a kinase that phosphorylates OPTN, an autophagy receptor, which ultimately activates autophagy. The sequestosome (SQSTM1) gene also encodes an autophagy receptor and also is a target of TBK1 phosphorylation. Consequently, we hypothesized that mutations in SQSTM1 may also cause NTG. We tested this hypothesis by searching for glaucoma-causing mutations in a cohort of NTG patients (n = 308) and matched controls (n = 157) using Sanger sequencing. An additional 1098 population control samples were also analyzed using whole exome sequencing. A total of 17 non-synonymous mutations were detected which were not significantly skewed between cases and controls when analyzed separately, or as a group (p > 0.05). These data suggest that SQSTM1 mutations are not a common cause of NTG. PMID:27275741

  11. [Founder mutation in Lynch syndrome].

    PubMed

    Cajal, Andrea R; Piñero, Tamara A; Verzura, Alicia; Santino, Juan Pablo; Solano, Angela R; Kalfayan, Pablo G; Ferro, Alejandra; Vaccaro, Carlos

    2016-01-01

    Lynch syndrome is the most frequent syndrome in hereditary colorectal cancer, a family-specific deleterious mutations in genes encoding DNA reparation proteins: MLH1 (mutL homolog 1), MSH2, MSH6 (mutS homolog 2 y 6, respectively), PMS2 (PMS1 homolog 2, mismatch repair system component) y MUTYH (mutY DNA glycosylase). The c.2252_2253delAA, p.Lys751Serfs*3 mutation in MLH1 gene segregates with a haplotype reported in the northern region of Italy and whose origin was attributed to a founder effect. This mutation co-segregates with typical characteristics of Lynch syndrome, including early age at onset and multiple primary tumors in the same individual, a high frequency of pancreatic cancer, high microsatellite instability and lack of PMS2 expression. This report describes a mutation in an Argentinian patient with endometrioid adenocarcinoma of uterus. Her first-degree relatives had a history of colon cancer diagnosed before 50 years, fulfilling the Amsterdam Criteria I and Lynch syndrome II. The high pathogenicity associated to this mutation makes necessary the study of all members from families with hereditary cancer, allowing pre-symptomatic genetic diagnosis, early assessment and the instauration of preventive treatments. PMID:27295708

  12. Driver mutations of cancer epigenomes.

    PubMed

    Roy, David M; Walsh, Logan A; Chan, Timothy A

    2014-04-01

    Epigenetic alterations are associated with all aspects of cancer, from tumor initiation to cancer progression and metastasis. It is now well understood that both losses and gains of DNA methylation as well as altered chromatin organization contribute significantly to cancer-associated phenotypes. More recently, new sequencing technologies have allowed the identification of driver mutations in epigenetic regulators, providing a mechanistic link between the cancer epigenome and genetic alterations. Oncogenic activating mutations are now known to occur in a number of epigenetic modifiers (i.e. IDH1/2, EZH2, DNMT3A), pinpointing epigenetic pathways that are involved in tumorigenesis. Similarly, investigations into the role of inactivating mutations in chromatin modifiers (i.e. KDM6A, CREBBP/EP300, SMARCB1) implicate many of these genes as tumor suppressors. Intriguingly, a number of neoplasms are defined by a plethora of mutations in epigenetic regulators, including renal, bladder, and adenoid cystic carcinomas. Particularly striking is the discovery of frequent histone H3.3 mutations in pediatric glioma, a particularly aggressive neoplasm that has long remained poorly understood. Cancer epigenetics is a relatively new, promising frontier with much potential for improving cancer outcomes. Already, therapies such as 5-azacytidine and decitabine have proven that targeting epigenetic alterations in cancer can lead to tangible benefits. Understanding how genetic alterations give rise to the cancer epigenome will offer new possibilities for developing better prognostic and therapeutic strategies. PMID:24622842

  13. Fasting, Circadian Rhythms, and Time-Restricted Feeding in Healthy Lifespan.

    PubMed

    Longo, Valter D; Panda, Satchidananda

    2016-06-14

    Most animals alternate periods of feeding with periods of fasting often coinciding with sleep. Upon >24 hr of fasting, humans, rodents, and other mammals enter alternative metabolic phases, which rely less on glucose and more on ketone body-like carbon sources. Both intermittent and periodic fasting result in benefits ranging from the prevention to the enhanced treatment of diseases. Similarly, time-restricted feeding (TRF), in which food consumption is restricted to certain hours of the day, allows the daily fasting period to last >12 hr, thus imparting pleiotropic benefits. Understanding the mechanistic link between nutrients and the fasting benefits is leading to the identification of fasting-mimicking diets (FMDs) that achieve changes similar to those caused by fasting. Given the pleiotropic and sustained benefits of TRF and FMDs, both basic science and translational research are warranted to develop fasting-associated interventions into feasible, effective, and inexpensive treatments with the potential to improve healthspan. PMID:27304506

  14. 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. PMID:26385599

  15. A comparison of methods for EGFR mutation testing in non-small cell lung cancer.

    PubMed

    Young, Elizabeth C; Owens, Martina M; Adebiyi, Idowu; Bedenham, Tina; Butler, Rachel; Callaway, Jonathan; Cranston, Treena; Crosby, Charlene; Cree, Ian A; Dutton, Laura; Faulkes, Catherine; Faulkner, Claire; Howard, Emma; Knight, Julia; Huang, Yuanxue; Lavender, Louise; Lazarou, Lazarus P; Liu, Hongxiang; Mair, Debbie; Milano, Antonio; Sandell, Stacey; Skinner, Alison; Wallace, Andrew; Williams, Maggie; Spivey, Vicky; Goodall, John; Frampton, Jonathan; Ellard, Sian

    2013-12-01

    EGFR mutation testing of tumor samples is routinely performed to predict sensitivity to treatment with tyrosine kinase inhibitors for patients with non-small cell lung cancer. At least 9 different methodologies are employed in UK laboratories, and the aim of this study was to compare the sensitivity of different methods for the detection of EGFR mutations. Participating laboratories were sent coded samples with varying mutation loads (from 0% to 15%) to be tested for the p.Leu858Arg (p.L858R) missense mutation and c.2235_2249del exon 19 deletion. The p.L858R mutation and deletions within exon 19 of the EGFR gene account for ∼90% of mutation-positive cases. The 11 laboratories used their standard testing method(s) and submitted 15 sets of results for the p.L858R samples and 10 for the exon 19 deletion. The p.Leu858Arg (p.L858R) mutation was detected at levels between 1% and 7.5% by Sanger sequencing, pyrosequencing, real-time polymerase chain reaction (PCR), amplification refractory mutation system, and capillary electrophoresis single-strand conformation analysis. The c.2235_2249del mutation was detected at 1% to 5% by fragment size analysis, Sanger sequencing or real-time PCR. A mutation was detected in 24/25 (96%) of the samples tested which contained 5% mutated DNA. The 1% sensitivity claimed for commercial real-time PCR-targeted EGFR tests was achieved and our results show greater sensitivity for the Sanger sequencing and pyrosequencing screening methods compared to the 10% to 20% detection levels cited on clinical diagnostic reports. We conclude that multiple methodologies are suitable for the detection of acquired EGFR mutations. PMID:24193010

  16. 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.

  17. Fast ignitor coupling physics

    SciTech Connect

    Mason, R.J.; Tabak, M.

    1997-10-01

    The Fast Ignitor is an alternate approach to ICF in which short pulse lasers are used to initiate burn at the surface of the compressed DT fuel. The aim is to avoid the need for careful central focussing of final shocks, and possibly to lower substantially the energy requirements for ignition. Ultimately, both goals may prove crucial to Stockpile Stewardship. For success with the Fast Ignitor, the laser energy must be efficiently deposited into megavolt electrons, which must, in turn, couple to the background ions within an alpha particle range. To understand this coupling, we have used ANTHEM plasma simulation code to model the transport of hot electrons generated by an intense ({ge} 3 x 10{sup 18} W/cm{sup 2}) short pulse 1.06 {mu}m laser into plasma targets over a broad range of densities (0.35 to 10{sup 4} x n{sub crit}). Ponderomotive effects are included as a force on the cold background and hot emission electrons of the form, F{sub h,c} = -({omega}{sup 2}{sub Ph,c}/2{omega}{sup 2}){del}I, in which I is the laser intensity and {omega}{sub p}{sup 2} = 4{pi}e{sup 2}n/m{sub 0}{gamma} with m{sub 0} the electron rest mass.

  18. Fast separable nonlocal means

    NASA Astrophysics Data System (ADS)

    Ghosh, Sanjay; Chaudhury, Kunal N.

    2016-03-01

    We propose a simple and fast algorithm called PatchLift for computing distances between patches (contiguous block of samples) extracted from a given one-dimensional signal. PatchLift is based on the observation that the patch distances can be efficiently computed from a matrix that is derived from the one-dimensional signal using lifting; importantly, the number of operations required to compute the patch distances using this approach does not scale with the patch length. We next demonstrate how PatchLift can be used for patch-based denoising of images corrupted with Gaussian noise. In particular, we propose a separable formulation of the classical nonlocal means (NLM) algorithm that can be implemented using PatchLift. We demonstrate that the PatchLift-based implementation of separable NLM is a few orders faster than standard NLM and is competitive with existing fast implementations of NLM. Moreover, its denoising performance is shown to be consistently superior to that of NLM and some of its variants, both in terms of peak signal-to-noise ratio/structural similarity index and visual quality.

  19. Fast statistical alignment.

    PubMed

    Bradley, Robert K; Roberts, Adam; Smoot, Michael; Juvekar, Sudeep; Do, Jaeyoung; Dewey, Colin; Holmes, Ian; Pachter, Lior

    2009-05-01

    We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment--previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches--yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/. PMID:19478997

  20. 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.

  1. 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

  2. Human norovirus hyper-mutation revealed by ultra-deep sequencing.

    PubMed

    Cuevas, José M; Combe, Marine; Torres-Puente, Manoli; Garijo, Raquel; Guix, Susana; Buesa, Javier; Rodríguez-Díaz, Jesús; Sanjuán, Rafael

    2016-07-01

    Human noroviruses (NoVs) are a major cause of gastroenteritis worldwide. It is thought that, similar to other RNA viruses, high mutation rates allow NoVs to evolve fast and to undergo rapid immune escape at the population level. However, the rate and spectrum of spontaneous mutations of human NoVs have not been quantified previously. Here, we analyzed the intra-patient diversity of the NoV capsid by carrying out RT-PCR and ultra-deep sequencing with 100,000-fold coverage of 16 stool samples from symptomatic patients. This revealed the presence of low-frequency sequences carrying large numbers of U-to-C or A-to-G base transitions, suggesting a role for hyper-mutation in NoV diversity. To more directly test for hyper-mutation, we performed transfection assays in which the production of mutations was restricted to a single cell infection cycle. This confirmed the presence of sequences with multiple U-to-C/A-to-G transitions, and suggested that hyper-mutation contributed a large fraction of the total NoV spontaneous mutation rate. The type of changes produced and their sequence context are compatible with ADAR-mediated editing of the viral RNA. PMID:27094861

  3. 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. PMID:23085272

  4. NUBPL mutations in patients with complex I deficiency and a distinct MRI pattern

    PubMed Central

    Kevelam, Sietske H.; Rodenburg, Richard J.; Wolf, Nicole I.; Ferreira, Patrick; Lunsing, Roelineke J.; Nijtmans, Leo G.; Mitchell, Anne; Arroyo, Hugo A.; Rating, Dietz; Vanderver, Adeline; van Berkel, Carola G.M.; Abbink, Truus E.M.; Heutink, Peter

    2013-01-01

    Objective: To identify the mutated gene in a group of patients with an unclassified heritable white matter disorder sharing the same, distinct MRI pattern. Methods: We used MRI pattern recognition analysis to select a group of patients with a similar, characteristic MRI pattern. We performed whole-exome sequencing to identify the mutated gene. We examined patients' fibroblasts for biochemical consequences of the mutant protein. Results: We identified 6 patients from 5 unrelated families with a similar MRI pattern showing predominant abnormalities of the cerebellar cortex, deep cerebral white matter, and corpus callosum. The 4 tested patients had a respiratory chain complex І deficiency. Exome sequencing revealed mutations in NUBPL, encoding an iron-sulfur cluster assembly factor for complex І, in all patients. Upon identification of the mutated gene, we analyzed the MRI of a previously published case with NUBPL mutations and found exactly the same pattern. A strongly decreased amount of NUBPL protein and fully assembled complex I was found in patients' fibroblasts. Analysis of the effect of mutated NUBPL on the assembly of the peripheral arm of complex I indicated that NUBPL is involved in assembly of iron-sulfur clusters early in the complex I assembly pathway. Conclusion: Our data show that NUBPL mutations are associated with a unique, consistent, and recognizable MRI pattern, which facilitates fast diagnosis and obviates the need for other tests, including assessment of mitochondrial complex activities in muscle or fibroblasts. PMID:23553477

  5. 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.

  6. 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

  7. Unmet Promise: Raising Minority Achievement. The Achievement Gap.

    ERIC Educational Resources Information Center

    Johnston, Robert C.; Viadero, Debra

    2000-01-01

    This first in a four-part series on why academic achievement gaps persist discusses how to raise minority achievement. It explains how earlier progress in closing the gap has stalled, while at the same time, the greater diversity of student populations and the rapid growth of the Hispanic population and of other ethnic groups have reshaped the…

  8. To Achieve or Not to Achieve: The Question of Women.

    ERIC Educational Resources Information Center

    Gilmore, Beatrice

    Questionnaire and projective data from 323 women aged 18 to 50 were analyzed in order to study the relationships of need achievement and motive to avoid success to age, sex role ideology, and stage in the family cycle. Family background and educational variables were also considered. Level of need achievement was found to be significantly related…

  9. Mathematics Achievement in High- and Low-Achieving Secondary Schools

    ERIC Educational Resources Information Center

    Mohammadpour, Ebrahim; Shekarchizadeh, Ahmadreza

    2015-01-01

    This paper identifies the amount of variance in mathematics achievement in high- and low-achieving schools that can be explained by school-level factors, while controlling for student-level factors. The data were obtained from 2679 Iranian eighth graders who participated in the 2007 Trends in International Mathematics and Science Study. Of the…

  10. 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

  11. 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…

  12. Affective Processes and Academic Achievement.

    ERIC Educational Resources Information Center

    Feshbach, Norma Deitch; Feshbach, Seymour

    1987-01-01

    Data indicate that for girls, affective dispositional factors (empathy, depressive affectivity, aggression, and self-concept) are intimately linked to cognitive development and academic achievement. (PCB)

  13. Attribution theory in science achievement

    NASA Astrophysics Data System (ADS)

    Craig, Martin

    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 examining potential malleable factors that may predict science achievement in twelfth graders using 2009 data from the National Assessment of Educational Progress (NAEP). Principle component factor analysis was conducted to determine the specific items that contribute to each overall factor. A series of multiple regressions were then analyzed and formed the predictive value of each of these factors for science achievement. All significant factors were ultimately examined together (also using multiple regression) to determine the most powerful predictors of science achievement, identifying factors that predict science achievement, the results of which suggested interventions to strengthen students' science achievement scores and encourage persistence in the sciences at the college level and beyond. Although there is a variety of research highlighting how students in the US are falling behind other developing nations in science and math achievement, as yet, little research has addressed ways of intervening to address this gap. The current research is a starting point, seeking to identify malleable factors that contribute to science achievement. More specifically, this research examined the types of attributions that predict science achievement in twelfth grade students.

  14. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations

    PubMed Central

    Müller, Martin C.; Cortes, Jorge E.; Kim, Dong-Wook; Druker, Brian J.; Erben, Philipp; Pasquini, Ricardo; Branford, Susan; Hughes, Timothy P.; Radich, Jerald P.; Ploughman, Lynn; Mukhopadhyay, Jaydip

    2009-01-01

    Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib resistance or suboptimal response. Sixty-threedifferent BCR-ABL mutations affecting 49 amino acids were detected at baseline, with G250, M351, M244, and F359 most frequently affected. After 2 years of follow-up, dasatinib treatment of imatinib-resistant patients with or without a mutation resulted in notable response rates (complete cytogenetic response: 43% vs 47%) and durable progression-free survival (70% vs 80%). High response rates were achieved with different mutations except T315I, including highly imatinib-resistant mutations in the P-loop region. Impaired responses were observed with some mutations with a dasatinib median inhibitory concentration (IC50) greater than 3nM; among patients with mutations with lower or unknown IC50, efficacy was comparable with those with no mutation. Overall, dasatinib has durable efficacy in patients with or without BCR-ABL mutations. All trials were registered at http://www.clinicaltrials.gov as NCT00123474, NCT00101660, and NCT00103844. PMID:19779040

  15. 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.

  16. 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)

  17. Fast approximate motif statistics.

    PubMed

    Nicodème, P

    2001-01-01

    We present in this article a fast approximate method for computing the statistics of a number of non-self-overlapping matches of motifs in a random text in the nonuniform Bernoulli model. This method is well suited for protein motifs where the probability of self-overlap of motifs is small. For 96% of the PROSITE motifs, the expectations of occurrences of the motifs in a 7-million-amino-acids random database are computed by the approximate method with less than 1% error when compared with the exact method. Processing of the whole PROSITE takes about 30 seconds with the approximate method. We apply this new method to a comparison of the C. elegans and S. cerevisiae proteomes. PMID:11535175

  18. 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.

  19. 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)

  20. Fast Censored Linear Regression

    PubMed Central

    HUANG, YIJIAN

    2013-01-01

    Weighted log-rank estimating function has become a standard estimation method for the censored linear regression model, or the accelerated failure time model. Well established statistically, the estimator defined as a consistent root has, however, rather poor computational properties because the estimating function is neither continuous nor, in general, monotone. We propose a computationally efficient estimator through an asymptotics-guided Newton algorithm, in which censored quantile regression methods are tailored to yield an initial consistent estimate and a consistent derivative estimate of the limiting estimating function. We also develop fast interval estimation with a new proposal for sandwich variance estimation. The proposed estimator is asymptotically equivalent to the consistent root estimator and barely distinguishable in samples of practical size. However, computation time is typically reduced by two to three orders of magnitude for point estimation alone. Illustrations with clinical applications are provided. PMID:24347802

  1. Chemistry of fast electrons

    PubMed Central

    Maximoff, Sergey N.; Head-Gordon, Martin P.

    2009-01-01

    A chemicurrent is a flux of fast (kinetic energy ≳ 0.5−1.3 eV) metal electrons caused by moderately exothermic (1−3 eV) chemical reactions over high work function (4−6 eV) metal surfaces. In this report, the relation between chemicurrent and surface chemistry is elucidated with a combination of top-down phenomenology and bottom-up atomic-scale modeling. Examination of catalytic CO oxidation, an example which exhibits a chemicurrent, reveals 3 constituents of this relation: The localization of some conduction electrons to the surface via a reduction reaction, 0.5 O2 + δe− → Oδ− (Red); the delocalization of some surface electrons into a conduction band in an oxidation reaction, Oδ− + CO → CO2δ− → CO2 + δe− (Ox); and relaxation without charge transfer (Rel). Juxtaposition of Red, Ox, and Rel produces a daunting variety of metal electronic excitations, but only those that originate from CO2 reactive desorption are long-range and fast enough to dominate the chemicurrent. The chemicurrent yield depends on the universality class of the desorption process and the distribution of the desorption thresholds. This analysis implies a power-law relation with exponent 2.66 between the chemicurrent and the heat of adsorption, which is consistent with experimental findings for a range of systems. This picture also applies to other oxidation-reduction reactions over high work function metal surfaces. PMID:19561296

  2. Impacts of the Callipyge mutation on ovine plasma metabolites and muscle fibre type.

    PubMed

    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

  3. 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

  4. General Achievement Trends: South Dakota

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  5. The Process of Science Achievement.

    ERIC Educational Resources Information Center

    Papanastasiou, Constantinos; Papanastasiou, Elena C.

    2002-01-01

    Investigates the science achievement of 8th grade students in Cyprus by using a structural equation model with three exogenous constructs--family's educational background, reinforcements, and school climate, and three endogenous constructs--teaching, student attitudes, and achievement. Proposes a model for the effects of family, school, student…

  6. Examination Regimes and Student Achievement

    ERIC Educational Resources Information Center

    Cosentino de Cohen, Clemencia

    2010-01-01

    Examination regimes at the end of secondary school vary greatly intra- and cross-nationally, and in recent years have undergone important reforms often geared towards increasing student achievement. This research presents a comparative analysis of the relationship between examination regimes and student achievement in the OECD. Using a micro…

  7. 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…

  8. Motivational Factors in School Achievement.

    ERIC Educational Resources Information Center

    Maehr, Martin L.

    A summary is presented of the literature on motivation relating to achievement in the classroom. Special attention is given to how values, ideology, and various cultural patterns may serve to enhance motivation to achieve in the classroom. In considering what determines motivation and personal investment in educational pursuits, the following…

  9. 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…

  10. General Achievement Trends: New Jersey

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  11. General Achievement Trends: North Carolina

    ERIC Educational Resources Information Center

    Center on Education Policy, 2009

    2009-01-01

    This general achievement trends profile includes information that the Center on Education Policy (CEP) and the Human Resources Research Organization (HumRRO) obtained from states from fall 2008 through April 2009. Included herein are: (1) Bullet points summarizing key findings about achievement trends in that state at three performance…

  12. 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…

  13. 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 Better in Their…

  14. 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…

  15. Achievement in Writing Geometry Proofs.

    ERIC Educational Resources Information Center

    Senk, Sharon L.

    In 1981 a nationwide assessment of achievement in writing geometry proofs was conducted by the Cognitive Development and Achievement in Secondary School Geometry project. Over 1,500 students in 11 schools in 5 states participated. This paper describes the sample, instruments, grading procedures, and selected results. Results include: (1) at the…

  16. 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);…

  17. Predicting Achievement in Foreign Language.

    ERIC Educational Resources Information Center

    Hart, Mary Elizabeth

    A review of research is inconclusive concerning the relationship between intelligence and language proficiency. A study of 10th grade students (n=35) examined scores on a high school entrance exam and achievement in foreign language after 1 year of study. Both math and reading showed a significant correlation with foreign language achievement; the…

  18. Superintendent Tenure and Student Achievement

    ERIC Educational Resources Information Center

    Simpson, Jennifer

    2013-01-01

    A correlational research design was used to examine the influence of superintendent tenure on student achievement in rural Appalachian Kentucky school districts. Superintendent tenure was compared to aggregated student achievement scores for 2011 and to changes in students' learning outcomes over the course of the superintendents' tenure. The…

  19. Accumulation of neutral mutations in growing cell colonies with competition

    PubMed Central

    Sorace, Ron; Komarova, Natalia L.

    2012-01-01

    Neutral mutations play an important role in many biological processes including cancer initiation and progression, the generation of drug resistance in bacterial and viral diseases as well as cancers, and the development of organs in multicellular organisms. In this paper we study how neutral mutants are accumulated in nonlinearly-growing colonies of cells subject to growth constraints such as crowding or lack of resources. We investigate different types of growth control which range from “division-controlled” to “death-controlled” growth (and various mixtures of both). In division-controlled growth, the burden of handling overcrowding lies with the process of cell-divisions, the divisions slow down as the carrying capacity is approached. In death-controlled growth, it is death rate that increases to slow down expansion. We show that division-controlled growth minimizes the number of accumulated mutations, and death-controlled growth corresponds to the maximum number of mutants. We check that these results hold in both deterministic and stochastic settings. We further develop a general (deterministic) theory of neutral mutations and achieve an analytical understanding of the mutant accumulation in colonies of a given size in the absence of back-mutations. The long-term dynamics of mutants in the presence of back-mutations is also addressed. In particular, with equal forward-and back-mutation rates, if division-controlled and a death-controlled types are competing for space and nutrients, cells obeying division-controlled growth will dominate the population. PMID:22940236

  20. AID-initiated purposeful mutations in immunoglobulin genes.

    PubMed

    Goodman, Myron F; Scharff, Matthew D; Romesberg, Floyd E

    2007-01-01

    Exposure brings risk to all living organisms. Using a remarkably effective strategy, higher vertebrates mitigate risk by mounting a complex and sophisticated immune response to counter the potentially toxic invasion by a virtually limitless army of chemical and biological antagonists. Mutations are almost always deleterious, but in the case of antibody diversification there are mutations occurring at hugely elevated rates within the variable (V) and switch regions (SR) of the immunoglobulin (Ig) genes that are responsible for binding to and neutralizing foreign antigens throughout the body. These mutations are truly purposeful. This chapter is centered on activation-induced cytidine deaminase (AID). AID is required for initiating somatic hypermutation (SHM) in the V regions and class switch recombination (CSR) in the SR portions of Ig genes. By converting C --> U, while transcription takes place, AID instigates a cascade of mutational events involving error-prone DNA polymerases, base excision and mismatch repair enzymes, and recombination pathways. Together, these processes culminate in highly mutated antibody genes and the B cells expressing antibodies that have achieved optimal antigenic binding undergo positive selection in germinal centers. We will discuss the biological role of AID in this complex process, primarily in terms of its biochemical properties in relation to SHM in vivo. The chapter also discusses recent advances in experimental methods to characterize antibody dynamics as a function of SHM to help elucidate the role that the AID-induced mutations play in tailoring molecular recognition. The emerging experimental techniques help to address long-standing conundrums concerning evolution-imposed constraints on antibody structure and function. PMID:17560274

  1. Spatial kinetics in fast reactors

    NASA Astrophysics Data System (ADS)

    Seleznev, E. F.; Belov, A. A.; Panova, I. S.; Matvienko, I. P.; Zhukov, A. M.

    2013-12-01

    The analysis of the solution to the spatial nonstationary equation of neutron transport is presented by the example of a fast reactor. Experiments in spatial kinetics conducted recently at the complex of critical assemblies (fast physical stand) and computations of their data using the TIMER code (for solving the nonstationary equation in multidimensional diffusion approximation for direct and inverse problems of reactor kinetics) have shown that kinetics of fast reactors substantially differs from kinetics of thermal reactors. The difference is connected with influence of the delayed neutron spectrum on rates of the process in a fast reactor.

  2. 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%. PMID:24104135

  3. FastPM: a new scheme for fast simulations of dark matter and halos

    NASA Astrophysics Data System (ADS)

    Feng, Yu; Chu, Man-Yat; Seljak, Uroš; McDonald, Patrick

    2016-08-01

    We introduce FastPM, a highly-scalable approximated particle mesh N-body solver, which implements the particle mesh (PM) scheme enforcing correct linear displacement (1LPT) evolution via modified kick and drift factors. Employing a 2-dimensional domain decomposing scheme, FastPM scales extremely well with a very large number of CPUs. In contrast to COmoving-LAgrangian (COLA) approach, we do not require to split the force or track separately the 2LPT solution, reducing the code complexity and memory requirements. We compare FastPM with different number of steps (Ns) and force resolution factor (B) against 3 benchmarks: halo mass function from Friends of Friends halo finder, halo and dark matter power spectrum, and cross correlation coefficient (or stochasticity), relative to a high resolution TreePM simulation. We show that the modified time stepping scheme reduces the halo stochasticity when compared to COLA with the same number of steps and force resolution. While increasing Ns and B improves the transfer function and cross correlation coefficient, for many applications FastPM achieves sufficient accuracy at low Ns and B. For example, Ns = 10 and B = 2 simulation provides a substantial saving (a factor of 10) of computing time relative to Ns = 40, B = 3 simulation, yet the halo benchmarks are very similar at z = 0. We find that for abundance matched halos the stochasticity remains low even for Ns = 5. FastPM compares well against less expensive schemes, being only 7 (4) times more expensive than 2LPT initial condition generator for Ns = 10 (Ns = 5). Some of the applications where FastPM can be useful are generating a large number of mocks, producing non-linear statistics where one varies a large number of nuisance or cosmological parameters, or serving as part of an initial conditions solver.

  4. 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

  5. Fast steering mirror for laser communication

    NASA Astrophysics Data System (ADS)

    Langenbach, Harald; Schmid, Manfred

    2005-07-01

    Future multimedia satellites require communication at large bandwidth which can be achieved by means of optical communication links. TESAT Spacecom is currently developing a Laser Communication Terminal (LCT) for such applications under DLR contract. EADS Astrium is developing and building the mechanisms for Pointing, Acquisition and Tracking (PAT) of the laser beam between two Laser Communication Terminals. Based on this development work the development of mechanism H/W to be flown on TerraSar X is currently under way. After a short description of the general arrangement of the Mechanisms inside the LCT, the paper describes the design of the fast steering mirrors (FSM) reflecting the critical requirements and the solutions how to achieve them.

  6. 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. PMID:25886624

  7. Mutation in the Human HPRT1 Gene and the Lesch-Nyhan Syndrome.

    PubMed

    Nguyen, Khue Vu; Nyhan, William L

    2016-08-01

    Lesch-Nyhan syndrome (LNS) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report a novel mutation which led to HGprt-related neurological dysfunction (HND) in two brothers from the same family with a missense mutation in exon 6 of the coding region of the HPRT1 gene: c.437T>C, p.L146S. Molecular diagnosis discloses the genetic heterogeneity of the HPRT1 gene responsible for HGprt deficiency. It allows fast, accurate carrier detection and genetic counseling. PMID:27379977

  8. 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.

  9. Molecular analysis of the APC gene in 71 Israeli families: 17 novel mutations.

    PubMed

    Gavert, Nancy; Yaron, Yuval; Naiman, Tova; Bercovich, Dani; Rozen, Paul; Shomrat, Ruth; Legum, Cyril; Orr-Urtreger, Avi

    2002-06-01

    Familial adenomatous polyposis (FAP) is caused by germline mutations in the APC gene. This study included 71 Israeli families referred for molecular analysis of the APC gene. Analysis was performed by the protein truncation test (PTT) of exon 15, and if negative, by direct sequencing of exon 1 to 14. Mutations were found in 36 (50.7%) probands. Mutation detection rates depended on the pattern of referral, such that among the 40 probands referred from the Service for Hereditary Cancer the mutation detection rate was 70%, whereas among the 31 probands referred by other gastroenterologists detection rate was significantly lower (25.8%). Of the 36 mutations detected, 21 were within exon 15, 13 within exons 1 to 14 and 2 were newly-described splicing mutations in introns 9 and 14. A relatively high proportion of the mutations was detected in exon 9 (6/36), five of them newly described. Altogether, we describe here 17 new mutations. Within the two major ethnic groups in Israel, patients of Ashkenazi and non-Ashkenazi origin, there was no significant differences in the mutation detection rate or the distribution of mutations within the APC gene. No founder mutation was detected in any of these populations. Our data confirm that higher detection rates may be expected in patients referred by clinical services specializing in hereditary colon cancer. These results further underscore the importance of complete analysis of all exons and exon/intron boundaries, in order to achieve maximal detection rate in patients suspected of FAP. PMID:12007223

  10. Summary statistics of neutral mutations in longitudinal DNA samples.

    PubMed

    Liu, Xiaoming; Fu, Yun-Xin

    2008-08-01

    Longitudinal samples of DNA sequences are the DNA sequences sampled from the same population at different time points. For fast evolving organisms, e.g. RNA virus, these kind of samples have increasingly been used to study the evolutionary process in action. Longitudinal samples provide some interesting new summary statistics of genetic variation, such as the frequency of mutation of size i in one sample and size j in another, the average number of mutations accumulated since the common ancestor of two sequences each from a different sample, and number of private, shared and fixed mutations within samples. To make the results more applicable, we used in this study a general two-sample model, which assumes two longitudinal samples were taken from the same measurably evolving population. Inspired by the HIV study, we also studied a two-sample-two-stage model, which is a special case of two-sample model and assumes a treatment after the first sampling instantaneously changes the population size. We derived the formulas for calculating statistical properties, e.g. expectations, variances and covariances, of these new summary statistics under the two models. Potential applications of these results were discussed. PMID:18547598

  11. 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

  12. Mutational effects on the folding dynamics of a minimized hairpin.

    PubMed

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

    2013-04-16

    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 submicrosecond folding time constants. The mutational studies revealed that ultrafast folding requires both some prestructuring of the loop and a favorable interaction between the chain termini in the transition state. In the case of YY-DPETGT-WY, another submicrosecond folding species [Davis, C. M., Xiao, S., Raleigh, D. P., and 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 retardation of the folding rate. 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 analogues 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

  13. 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.

  14. 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

  15. 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…

  16. 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

  17. Mutational Heterogeneity in Melanoma: An Inconvenient Truth.

    PubMed

    Chang, Gregory A; Polsky, David

    2015-12-01

    Identification of oncogenic BRAF mutations in primary and metastatic melanomas supports a linear model of clonal evolution in cancer. Some mutational studies, however, have failed to identify BRAF mutations in metastatic tumors from patients with BRAFmutant primary melanomas. Using a combination of methods, Riveiro-Falkenbach et al. (2015) assert that technical issues, and not clonal heterogeneity, may explain prior discordant mutational results. PMID:26569584

  18. MECHANISMS OF STATIONARY PHASE MUTATION: A Decade of Adaptive Mutation

    PubMed Central

    Foster, P. L.

    2010-01-01

    A decade of research on adaptive mutation has revealed a plethora of mutagenic mechanisms that may be important in evolution. The DNA synthesis associated with recombination could be an important source of spontaneous mutation in cells that are not proliferating. The movement of insertion elements can be responsive to environmental conditions. Insertion elements not only activate and inactivate genes, they also provide sequence homology that allows large-scale genomic rearrangements. Some conjugative plasmids can recombine with their host’s chromosome, and may acquire chromosomal genes that could then spread through the population and even to other species. Finally, a subpopulation of transient hypermutators could be a source of multiple variant alleles, providing a mechanism for rapid evolution under adverse conditions. PMID:10690404

  19. Exon 19 L747P mutation presented as a primary resistance to EGFR-TKI: a case report

    PubMed Central

    Wang, Yu-Ting; Ning, Wei-Wei; Li, Jing

    2016-01-01

    Active mutations of the EGFR gene have been proved to predict the activity of EGFR-TKI. The most common mutations are the exon 19 deletion and exon 21 point mutation, both of which are sensitive to EGFR-TKI. However, rare EGFR mutations or complex mutations still exist, and data of which are scarce and controversial. Their response to EGFR-TKI remains uncertain. We presented a patient diagnosed with stage IV lung adenocarcinoma who was found to have the EGFR mutation in exon 19 (L747P) before any treatment. The disease progressed 2 months after the chemotherapy containing cisplatin and pemetrexed, and erlotinib was administered, but there was no response found. This EGFR-TKI naïve patient failed to achieve the desired effect with the therapy of EGFR-TKI. L747P may be associated with primary resistance to EGFR-TKI in this case. PMID:27499993

  20. 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. PMID:26123250

  1. 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....

  2. 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…

  3. Tracking Down Mutations Cell by Cell.

    PubMed

    Kosik, Kenneth S

    2016-03-16

    Using somatic cell nuclear transfer, Hazen et al. (2016) examined clonally expanded single neurons for mutations and found ∼100 mutations from a variety of classes. Post-mitotic mutations in individual neurons represent an exploratory direction for finding fundamental origins of neurodegeneration. PMID:26985720

  4. Fast Resistive Bolometry

    NASA Astrophysics Data System (ADS)

    Graham, Jeffrey

    2005-10-01

    A bolometer with microsecond scale response time is under construction for the Caltech spheromak experiment to measure radiation from a ˜20 μs duration plasma discharge emitting ˜10^2---10^3 kW/m^2. A gold film several micrometers thick absorbs the radiation, heats up, and the consequent change in resistance can be measured. The film itself is vacuum deposited upon a glass slide. Several geometries for the film are under consideration to optimize the amount of radiation absorbed, the response time and the signal-to-noise ratio. We measure the change in voltage across the film for a known current driven through it; a square pulse (3---30A, ˜20 μs) is used to avoid Joule heating. Results from prototypes tested with a UV flashlamp will be presented. After optimizing the bolometer design, the final vacuum-compatible diagnostic would consist of a plasma-facing bolometer and a reference in a camera obscura. This device could provide a design for fast resistive bolometry.

  5. Fast Fuzzy Arithmetic Operations

    NASA Technical Reports Server (NTRS)

    Hampton, Michael; Kosheleva, Olga

    1997-01-01

    In engineering applications of fuzzy logic, the main goal is not to simulate the way the experts really think, but to come up with a good engineering solution that would (ideally) be better than the expert's control, In such applications, it makes perfect sense to restrict ourselves to simplified approximate expressions for membership functions. If we need to perform arithmetic operations with the resulting fuzzy numbers, then we can use simple and fast algorithms that are known for operations with simple membership functions. In other applications, especially the ones that are related to humanities, simulating experts is one of the main goals. In such applications, we must use membership functions that capture every nuance of the expert's opinion; these functions are therefore complicated, and fuzzy arithmetic operations with the corresponding fuzzy numbers become a computational problem. In this paper, we design a new algorithm for performing such operations. This algorithm is applicable in the case when negative logarithms - log(u(x)) of membership functions u(x) are convex, and reduces computation time from O(n(exp 2))to O(n log(n)) (where n is the number of points x at which we know the membership functions u(x)).

  6. 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.

  7. Mutation analysis in patients with Wilson disease: identification of 4 novel mutations. Mutation in brief no. 250. Online.

    PubMed

    Haas, R; Gutierrez-Rivero, B; Knoche, J; Böker, K; Manns, M P; Schmidt, H H

    1999-01-01

    In order to obtain novel mutations in the recently discovered Wilson disease gene, we screened 5 unrelated German individuals for mutations in the 21 exons and their flanking intronic sequences. We detected 9 mutations affecting the Wilson disease gene. Four of those, designated 802-808delTGTAAGT, 2008-2013delTATATG, Cys985Thr, and Ile1148Thr have not yet been reported. One patient had a homozygous mutation whereas the remaining four subjects were compound heterozygous. Therefore these data confirm, that mutations causing Wilson disease are frequently found in affected subjects and they are very heterogenous. PMID:10447265

  8. 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. PMID:26774059

  9. 60 MHz fast wave current drive experiment for DIII-D

    SciTech Connect

    Mayberry, M.J.; Chiu, S.C.; Porkolab, M.; Chan, V.; Freeman, R.; Harvey, R.; Pinsker, R. )

    1989-07-01

    The DIII-D facility provides an opportunity to test fast wave current drive appoach. Efficient FWCD is achieved by direct electron absorption due to Landa damping and transit time magnetic pumping. To avoid competing damping mechamisms we seek to maximize the single-pass asorption of the fast waves by electrons. (AIP)

  10. 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.

  11. Genetic Analysis of 63 Mutations Affecting Maize Kernel Development Isolated from Mutator Stocks

    PubMed Central

    Scanlon, M. J.; Stinard, P. S.; James, M. G.; Myers, A. M.; Robertson, D. S.

    1994-01-01

    Sixty-three mutations affecting development of the maize kernel were isolated from active Robertson's Mutator (Mu) stocks. At least 14 previously undescribed maize gene loci were defined by mutations in this collection. Genetic mapping located 53 of these defective kernel (dek) mutations to particular chromosome arms, and more precise map determinations were made for 21 of the mutations. Genetic analyses identified 20 instances of allelism between one of the novel mutations and a previously described dek mutation, or between new dek mutations identified in this study; phenotypic variability was observed in three of the allelic series. Viability testing of homozygous mutant kernels identified numerous dek mutations with various pleiotropic effects on seedling and plant development. The mutations described here presumably arose by insertion of a Mu transposon within a dek gene; thus, many of the affected loci are expected to be accessible to molecular cloning via transposon-tagging. PMID:8138165

  12. 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. PMID:27046666

  13. 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

  14. 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. PMID:23389231

  15. Interplay of mutation and disassortativity

    NASA Astrophysics Data System (ADS)

    Dwivedi, Sanjiv K.; Jalan, Sarika

    2015-08-01

    Despite disassortativity being commonly observed in many biological networks, our current understanding of its evolutionary origin is inadequate. Motivated by the occurrence of mutations during an evolutionary time span that results in changes in the behavior of interactions, we demonstrate that if we maximize the stability of the underlying system, the genetic algorithm leads to the evolution of a disassortative structure. The mutation probability governs the degree of saturation of the disassortativity coefficient, and this reveals the origin of the wide range of disassortativity values found in real systems. We analytically verify these results for star networks, and by considering various values for the antisymmetric couplings, we find a regime in which scale-free networks are more stable than the corresponding random networks.

  16. [Pathologic manifestations of hormonal receptor mutations].

    PubMed

    Milgrom, E

    2000-01-01

    Mutations of receptor genes are involved in various aspects of thyroid and gonadal pathology. Activating mutations of TSH and LH receptors are associated with hyperthyroidism and premature puberty. These mutations are dominant and lead to the synthesis of a constitutive receptor, i.e. a receptor active even in the absence of hormone. Inactivating mutations of TSH, gonadotropin and GnRH receptors are recessive. They determine either a hypothyroidism or a hypogonadism. In the case of alterations of gonadotropin receptors the hypogonadism is hypergonadotrophic. It is hypogonadotrophic in the case of mutations of the GnRH receptor. PMID:10989556

  17. Opportunity's Fast Progress Southward

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] [figure removed for brevity, see original site] Opportunity's Traverse from Landing through Sol 413 Opportunity's Fast Progress Southward

    As of the Mars Exploration Rover Opportunity's 413th martian day, or sol, (March 23, 2005), the robot had driven a total of 4.62 kilometers (2.87 miles) since. The red line on this image traces the rover's route. The base image is a mosaic combining images from the Mars Observer Camera on NASA's Mars Global Surveyor orbiter, the Thermal Emission Imaging System on NASA's Mars Odyssey orbiter, and Opportunity's own Descent Image Motion Estimation System.

    The rover has been making rapid progress southward since it finished examining its jettisoned heat shield on sol 357 (Jan. 24, 2005, one year after landing). Scientists are eager for Opportunity to reach an area to the south called the 'Etched Terrain,' which appears mottled in the map's base images and might offer access to different layers of bedrock than what the rover has seen so far. See figure 1.

    As of the Mars Exploration Rover Opportunity's 414th martian day, or sol, (March 24, 2005), the robot had driven a total of 4.81 kilometers (2.99 miles) since landing. In this two-month period, Opportunity drove 2.69 kilometers (1.67 miles). As landmarks along the route, it used craters that the rover team informally named for ships of historic voyages of exploration. See figure 2. Figures 1 and 2 are traverse maps overlaid on a mosaic of images from NASA's Mars Global Surveyor and Mars Odyssey orbiters and from Opportunity's descent camera. The scale bar in figure 1 at lower left is 2 kilometers (1.24 miles) long and the scale bar in figure 2 is 1 kilometer (0.62 mile) long.

  18. The Free Energy Landscape of GABA Binding to a Pentameric Ligand-Gated Ion Channel and Its Disruption by Mutations.

    PubMed

    Comitani, Federico; Limongelli, Vittorio; Molteni, Carla

    2016-07-12

    Pentameric ligand-gated ion channels (pLGICs) of the Cys-loop superfamily are important neuroreceptors that mediate fast synaptic transmission. They are activated by the binding of a neurotransmitter, but the details of this process are still not fully understood. As a prototypical pLGIC, here we choose the insect resistance to dieldrin (RDL) receptor involved in resistance to insecticides and investigate the binding of the neurotransmitter GABA to its extracellular domain at the atomistic level. We achieve this by means of μ-sec funnel-metadynamics simulations, which efficiently enhance the sampling of bound and unbound states by using a funnel-shaped restraining potential to limit the exploration in the solvent. We reveal the sequence of events in the binding process from the capture of GABA from the solvent to its pinning between the charged residues Arg111 and Glu204 in the binding pocket. We characterize the associated free energy landscapes in the wild-type RDL receptor and in two mutant forms, where the key residues Arg111 and Glu204 are mutated to Ala. Experimentally these mutations produce nonfunctional channels, which is reflected in the reduced ligand binding affinities due to the loss of essential interactions. We also analyze the dynamical behavior of the crucial loop C, whose opening allows the access of GABA to the binding site and closure locks the ligand into the protein. The RDL receptor shares structural and functional features with other pLGICs; hence, our work outlines a valuable protocol to study the binding of ligands to pLGICs beyond conventional docking and molecular dynamics techniques. PMID:27228114

  19. Stepwise Exposure of Staphylococcus aureus to Pleuromutilins Is Associated with Stepwise Acquisition of Mutations in rplC and Minimally Affects Susceptibility to Retapamulin▿

    PubMed Central

    Gentry, Daniel R.; Rittenhouse, Stephen F.; McCloskey, Lynn; Holmes, David J.

    2007-01-01

    To assess their effects on susceptibility to retapamulin in Staphylococcus aureus, first-, second-, and third-step mutants with elevated MICs to tiamulin and other investigational pleuromutilin compounds were isolated and characterized through exposure to high drug concentrations. All first- and second-step mutations were in rplC, encoding ribosomal protein L3. Most third-step mutants acquired a third mutation in rplC. While first- and second-step mutations did cause an elevation in tiamulin and retapamulin MICs, a significant decrease in activity was not seen until a third mutation was acquired. All third-step mutants exhibited severe growth defects, and faster-growing variants arose at a high frequency from most isolates. These faster-growing variants were found to be more susceptible to pleuromutilins. In the case of a mutant with three alterations in rplC, the fast-growing variants acquired an additional mutation in rplC. In the case of fast-growing variants of isolates with two mutations in rplC and at least one mutation at an unmapped locus, one of the two rplC mutations reverted to wild type. These data indicate that mutations in rplC that lead to pleuromutilin resistance have a direct, negative effect on fitness. While reduction in activity of retapamulin against S. aureus can be seen through mutations in rplC, it is likely that target-specific resistance to retapamulin will be slow to emerge due to the need for three mutations for a significant effect on activity and the fitness cost of each mutational step. PMID:17404009

  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. Lags in Minority Achievement Defy Traditional Explanations. The Achievement Gap.

    ERIC Educational Resources Information Center

    Viadero, Debra; Johnston, Robert C.

    2000-01-01

    This second in a four-part series on why academic achievement gaps exist notes that standard explanations for why minority students trail behind non-Hispanic whites are not good enough, suggesting that no single explanation for the gap exists, but instead a multitude of factors are influential. Poverty, though not the single most important cause,…

  2. Central Iowa Low Achiever Mathematics Project - Low Achiever Motivational Project.

    ERIC Educational Resources Information Center

    Zimmerman, Joseph T.

    The materials in this booklet are designed especially for the low achieving student in mathematics. Containing some materials from a course in general mathematics, the booklet is intended to be used in conjunction with conventional textbook materials and is designed to serve as a source of new ideas for teachers and to relieve the teacher of much…

  3. Mechanisms of Mutation in Nondividing Cells

    PubMed Central

    Foster, Patricia L.; Rosche, William A.

    2010-01-01

    When populations of cells are subjected to nonlethal selection, mutations arise in the absence of cell division, a phenomenon that has been called “adaptive mutation.” In a strain of Escherichia coli that cannot metabolize lactose (Lac−) but that reverts to lactose utilization (Lac+) when lactose is its sole energy and carbon source, the mutational process consists of two components. (1) A highly efficient, recombination-dependent mechanism giving rise to mutations on the F′ episome that carries the Lac− allele; and (2) a less efficient, unknown mechanism giving rise to mutations elsewhere in the genome. Both selected and nonselected mutations arise in the Lac− population, but nonselected mutations are enriched in Lac+ mutants, suggesting that some Lac+ cells have passed though a transient period of increased mutation. These results have several evolutionary implications. (1) DNA synthesis initiated by recombination could be an important source of spontaneous mutation, particularly in cells that are not undergoing genomic replication. (2) The highly active mutational mechanism on the episome could be important in the horizontal transfer of variant alleles among species that carry and exchange conjugal plasmids. (3) A subpopulation of cells in a state of transient mutation could be a source of multiple variant alleles and could provide a mechanism for rapid adaptive evolution under adverse conditions. PMID:10415479

  4. A fast neighbor joining method.

    PubMed

    Li, J F

    2015-01-01

    With the rapid development of sequencing technologies, an increasing number of sequences are available for evolutionary tree reconstruction. Although neighbor joining is regarded as the most popular and fastest evolutionary tree reconstruction method [its time complexity is O(n(3)), where n is the number of sequences], it is not sufficiently fast to infer evolutionary trees containing more than a few hundred sequences. To increase the speed of neighbor joining, we herein propose FastNJ, a fast implementation of neighbor joining, which was motivated by RNJ and FastJoin, two improved versions of conventional neighbor joining. The main difference between FastNJ and conventional neighbor joining is that, in the former, many pairs of nodes selected by the rule used in RNJ are joined in each iteration. In theory, the time complexity of FastNJ can reach O(n(2)) in the best cases. Experimental results show that FastNJ yields a significant increase in speed compared to RNJ and conventional neighbor joining with a minimal loss of accuracy. PMID:26345805

  5. Fast food: unfriendly and unhealthy.

    PubMed

    Stender, S; Dyerberg, J; Astrup, A

    2007-06-01

    Although nutrition experts might be able to navigate the menus of fast-food restaurant chains, and based on the nutritional information, compose apparently 'healthy' meals, there are still many reasons why frequent fast-food consumption at most chains is unhealthy and contributes to weight gain, obesity, type 2 diabetes and coronary artery disease. Fast food generally has a high-energy density, which, together with large portion sizes, induces over consumption of calories. In addition, we have found it to be a myth that the typical fast-food meal is the same worldwide. Chemical analyses of 74 samples of fast-food menus consisting of French fries and fried chicken (nuggets/hot wings) bought in McDonalds and KFC outlets in 35 countries in 2005-2006 showed that the total fat content of the same menu varies from 41 to 65 g at McDonalds and from 42 to 74 g at KFC. In addition, fast food from major chains in most countries still contains unacceptably high levels of industrially produced trans-fatty acids (IP-TFA). IP-TFA have powerful biological effects and may contribute to increased weight gain, abdominal obesity, type 2 diabetes and coronary artery disease. The food quality and portion size need to be improved before it is safe to eat frequently at most fast-food chains. PMID:17452996

  6. TCF12 is mutated in anaplastic oligodendroglioma.

    PubMed

    Labreche, Karim; Simeonova, Iva; Kamoun, Aurélie; Gleize, Vincent; Chubb, Daniel; Letouzé, Eric; Riazalhosseini, Yasser; Dobbins, Sara E; Elarouci, Nabila; Ducray, Francois; de Reyniès, Aurélien; Zelenika, Diana; Wardell, Christopher P; Frampton, Mathew; Saulnier, Olivier; Pastinen, Tomi; Hallout, Sabrina; Figarella-Branger, Dominique; Dehais, Caroline; Idbaih, Ahmed; Mokhtari, Karima; Delattre, Jean-Yves; Huillard, Emmanuelle; Mark Lathrop, G; Sanson, Marc; Houlston, Richard S

    2015-01-01

    Anaplastic oligodendroglioma (AO) are rare primary brain tumours that are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosomes 1p/19q co-deletion and an IDH mutation. Here we analysed 51 AO by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall, 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. Eighty percent of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frameshift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumour type. Our analysis provides further insights into the unique and shared pathways driving AO. PMID:26068201

  7. TCF12 is mutated in anaplastic oligodendroglioma

    PubMed Central

    Labreche, Karim; Simeonova, Iva; Kamoun, Aurélie; Gleize, Vincent; Chubb, Daniel; Letouzé, Eric; Riazalhosseini, Yasser; Dobbins, Sara E.; Elarouci, Nabila; Ducray, Francois; de Reyniès, Aurélien; Zelenika, Diana; Wardell, Christopher P.; Frampton, Mathew; Saulnier, Olivier; Pastinen, Tomi; Hallout, Sabrina; Figarella-Branger, Dominique; Dehais, Caroline; Idbaih, Ahmed; Mokhtari, Karima; Delattre, Jean-Yves; Huillard, Emmanuelle; Mark Lathrop, G.; Sanson, Marc; Houlston, Richard S.; Adam, Clovis; Andraud, Marie; Aubriot-Lorton, Marie-Hélène; Bauchet, Luc; Beauchesne, Patrick; Blechet, Claire; Campone, Mario; Carpentier, Antoine; Carpentier, Catherine; Carpiuc, Ioana; Chenard, Marie-Pierre; Chiforeanu, Danchristian; Chinot, Olivier; Cohen-Moyal, Elisabeth; Colin, Philippe; Dam-Hieu, Phong; Desenclos, Christine; Desse, Nicolas; Dhermain, Frederic; Diebold, Marie-Danièle; Eimer, Sandrine; Faillot, Thierry; Fesneau, Mélanie; Fontaine, Denys; Gaillard, Stéphane; Gauchotte, Guillaume; Gaultier, Claude; Ghiringhelli, Francois; Godard, Joel; Marcel Gueye, Edouard; Sebastien Guillamo, Jean; Hamdi-Elouadhani, Selma; Honnorat, Jerome; Louis Kemeny, Jean; Khallil, Toufik; Jouvet, Anne; Labrousse, Francois; Langlois, Olivier; Laquerriere, Annie; Lechapt-Zalcman, Emmanuelle; Le Guérinel, Caroline; Levillain, Pierre-Marie; Loiseau, Hugues; Loussouarn, Delphine; Maurage, Claude-Alain; Menei, Philippe; Janette Motsuo Fotso, Marie; Noel, Georges; Parker, Fabrice; Peoc'h, Michel; Polivka, Marc; Quintin-Roué, Isabelle; Ramirez, Carole; Ricard, Damien; Richard, Pomone; Rigau, Valérie; Rousseau, Audrey; Runavot, Gwenaelle; Sevestre, Henri; Christine Tortel, Marie; Uro-Coste, Emmanuelle; Burel-Vandenbos, Fanny; Vauleon, Elodie; Viennet, Gabriel; Villa, Chiara; Wager, Michel

    2015-01-01

    Anaplastic oligodendroglioma (AO) are rare primary brain tumours that are generally incurable, with heterogeneous prognosis and few treatment targets identified. Most oligodendrogliomas have chromosomes 1p/19q co-deletion and an IDH mutation. Here we analysed 51 AO by whole-exome sequencing, identifying previously reported frequent somatic mutations in CIC and FUBP1. We also identified recurrent mutations in TCF12 and in an additional series of 83 AO. Overall, 7.5% of AO are mutated for TCF12, which encodes an oligodendrocyte-related transcription factor. Eighty percent of TCF12 mutations identified were in either the bHLH domain, which is important for TCF12 function as a transcription factor, or were frameshift mutations leading to TCF12 truncated for this domain. We show that these mutations compromise TCF12 transcriptional activity and are associated with a more aggressive tumour type. Our analysis provides further insights into the unique and shared pathways driving AO. PMID:26068201

  8. Digenic mutations in severe congenital neutropenia

    PubMed Central

    Germeshausen, Manuela; Zeidler, Cornelia; Stuhrmann, Manfred; Lanciotti, Marina; Ballmaier, Matthias; Welte, Karl

    2010-01-01

    Severe congenital neutropenia a clinically and genetically heterogeneous disorder. Mutations in different genes have been described as causative for severe neutropenia, e.g. ELANE, HAX1 and G6PC3. Although congenital neutropenia is considered to be a group of monogenic disorders, the phenotypic heterogeneity even within the yet defined genetic subtypes points to additional genetic and/or epigenetic influences on the disease phenotype. We describe congenital neutropenia patients with mutations in two candidate genes each, including 6 novel mutations. Two of them had a heterozygous ELANE mutation combined with a homozygous mutation in G6PC3 or HAX1, respectively. The other 2 patients combined homozygous or compound heterozygous mutations in G6PC3 or HAX1 with a heterozygous mutation in the respective other gene. Our results suggest that digenicity may underlie this disorder of myelopoiesis at least in some congenital neutropenia patients. PMID:20220065

  9. Mutational patterns in oncogenes and tumour suppressors.

    PubMed

    Baeissa, Hanadi M; Benstead-Hume, Graeme; Richardson, Christopher J; Pearl, Frances M G

    2016-06-15

    All cancers depend upon mutations in critical genes, which confer a selective advantage to the tumour cell. Knowledge of these mutations is crucial to understanding the biology of cancer initiation and progression, and to the development of targeted therapeutic strategies. The key to understanding the contribution of a disease-associated mutation to the development and progression of cancer, comes from an understanding of the consequences of that mutation on the function of the affected protein, and the impact on the pathways in which that protein is involved. In this paper we examine the mutation patterns observed in oncogenes and tumour suppressors, and discuss different approaches that have been developed to identify driver mutations within cancers that contribute to the disease progress. We also discuss the MOKCa database where we have developed an automatic pipeline that structurally and functionally annotates all proteins from the human proteome that are mutated in cancer. PMID:27284061

  10. Optimal Control of Gene Mutation in DNA Replication

    PubMed Central

    Yu, Juanyi; Li, Jr-Shin; Tarn, Tzyh-Jong

    2012-01-01

    We propose a molecular-level control system view of the gene mutations in DNA replication from the finite field concept. By treating DNA sequences as state variables, chemical mutagens and radiation as control inputs, one cell cycle as a step increment, and the measurements of the resulting DNA sequence as outputs, we derive system equations for both deterministic and stochastic discrete-time, finite-state systems of different scales. Defining the cost function as a summation of the costs of applying mutagens and the off-trajectory penalty, we solve the deterministic and stochastic optimal control problems by dynamic programming algorithm. In addition, given that the system is completely controllable, we find that the global optimum of both base-to-base and codon-to-codon deterministic mutations can always be achieved within a finite number of steps. PMID:22454557

  11. [Artificial nutrition and preoperative fasting].

    PubMed

    Francq, B; Sohawon, S; Perlot, I; Sekkat, H; Noordally, S O

    2012-01-01

    Preoperative fasting is a currently adopted measure since Mendelson's report pertaining to aspiration pneumonia as a cause of death following general anesthesia. From a metabolic point of view fasting is detrimental because surgery in itself causes a state of hypercatabolism and hyperglycemia as a result of insulinresistance. Preoperative fasting has become almost obsolete in certain elective surgical procedures. In these cases the use of clear liquids is now well established and this paper focuses on the safe use of clear fluids, postoperative insulinresistance, patient comfort and postoperative outcome as well as its effect on the length of stay. PMID:22812052

  12. [Fast food promotes weight gain].

    PubMed

    Stender, Steen; Dyerberg, Jørn; Astrup, Arne V

    2007-05-01

    The total amounts of fat in a fast food menu consisting of French fries and fried Chicken Nuggets from McDonald's and KFC, respectively, bought in 35 different countries vary from 41 to 71 gram. In most countries the menu contained unacceptably high amounts of industrially-produced trans fat which contributes to an increased risk of ischaemic heart disease, weight gain, abdominal fat accumulation and type 2 diabetes. The quality of the ingredients in fast food ought to be better and the size of the portions smaller and less energy-dense so that frequent fast food meals do not increase the risk of obesity and diseases among customers. PMID:17537359

  13. Fast Burst Synchronization for Power Line Communication Systems

    NASA Astrophysics Data System (ADS)

    Bumiller, Gerd; Lampe, Lutz

    2007-12-01

    Fast burst synchronization is an important requirement in asynchronous communication networks, where devices transmit short data packets in an unscheduled fashion. Such a synchronization is typically achieved by means of a preamble sent in front of the data packet. In this paper, we study fast burst synchronization for power line communication (PLC) systems operating below 500 kHz and transmitting data rates of up to about 500 kbps as it is typical in various PLC network applications. In particular, we are concerned with the receiver processing of the preamble signal and the actual design of preambles suitable for fast burst synchronization in such PLC systems. Our approach is comprehensive in that it takes into account the most distinctive characteristics of the power line channel, which are multipath propagation, highly varying path loss, and disturbance by impulse noise, as well as important practical constraints, especially the need for spectral shaping of the preamble signal and fast adjustment of the automatic gain control (AGC). In fact, we regard the explicit incorporation of these various requirements into the preamble design as the main contribution of this work. We devise an optimization criterion and a stochastic algorithm to search for suitable preamble sequences. A comprehensive performance comparison of a designed and two conventional preambles shows that the designed sequence is superior in terms of (a) fast burst synchronization in various transmission environments, (b) fast AGC adjustment, and (c) compliance of its spectrum with the spectral mask applied to the data transmit signal.

  14. Fast ignition experimental and theoretical studies

    NASA Astrophysics Data System (ADS)

    Akli, Kramer Ugerthen

    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 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 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 K-alpha yield from the imploded core revealed that 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. The contribution of the potential, induced by charge separation, in opposing the motion of the electrons was moderate. Second, temperature sensitivity of Cu K-alpha imaging efficiency using a spherical Bragg reflecting crystal is investigated. It was found that due to the shifting and broadening of the K-alpha line, with increasing temperature, both the brightness and the

  15. Fast Ignition Experimental and Theoretical Studies

    SciTech Connect

    Akli, K

    2006-10-20

    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 K{sub {alpha}} 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 K{sub {alpha}} imaging efficiency using a spherical Bragg reflecting crystal is investigated. It was found that due to the shifting and broadening of the K{sub {alpha

  16. Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.

    PubMed

    Clarke, Nigel F; Waddell, Leigh B; Cooper, Sandra T; Perry, Margaret; Smith, Robert L L; Kornberg, Andrew J; Muntoni, Francesco; Lillis, Suzanne; Straub, Volker; Bushby, Kate; Guglieri, Michela; King, Mary D; Farrell, Michael A; Marty, Isabelle; Lunardi, Joel; Monnier, Nicole; North, Kathryn N

    2010-07-01

    The main histological abnormality in congenital fiber type disproportion (CFTD) is hypotrophy of type 1 (slow twitch) fibers compared to type 2 (fast twitch) fibers. To investigate whether mutations in RYR1 are a cause of CFTD we sequenced RYR1 in seven CFTD families in whom the other known causes of CFTD had been excluded. We identified compound heterozygous changes in the RYR1 gene in four families (five patients), consistent with autosomal recessive inheritance. Three out of five patients had ophthalmoplegia, which may be the most specific clinical indication of mutations in RYR1. Type 1 fibers were at least 50% smaller, on average, than type 2 fibers in all biopsies. Recessive mutations in RYR1 are a relatively common cause of CFTD and can be associated with extreme fiber size disproportion. PMID:20583297

  17. An RNA Aptamer Inhibits a Mutation-Induced Inactivating Misfolding of a Serpin.

    PubMed

    Madsen, Jeppe B; Andersen, Lisbeth M; Dupont, Daniel M; Trelle, Morten B; Johansen, Jesper S; Jensen, Jan K; Jørgensen, Thomas J D; Andreasen, Peter A

    2016-06-23

    Most serpins are fast and specific inhibitors of extracellular serine proteases controlling biological processes such as blood coagulation, fibrinolysis, tissue remodeling, and inflammation. The inhibitory activity of serpins is based on a conserved metastable structure and their conversion to a more stable state during reaction with the target protease. However, the metastable state also makes serpins vulnerable to mutations, resulting in disease caused by inactive and misfolded monomeric or polymeric forms ("serpinopathy"). Misfolding can occur either intracellularly (type-I serpinopathies) or extracellularly (type-II serpinopathies). We have isolated a 2'-fluoropyrimidine-modified RNA aptamer, which inhibits a mutation-induced inactivating misfolding of the serpin α1-antichymotrypsin. It is the first agent able to stabilize a type-II mutation of a serpin without interfering with the inhibitory mechanism, thereby presenting a solution for the long-standing challenge of preventing pathogenic misfolding without compromising the inhibitory function. PMID:27265748

  18. Managing diabetes during the Muslim fasting month of Ramadan.

    PubMed

    Velayudhan, M

    2012-06-01

    Target blood sugar levels in diabetes are achieved through manipulation of diet, exercise and medication. A change in any one of these three things can skew blood sugar levels and create complications associated with hyperglycemia or hypoglycemia. Fasting during the month of Ramadan is a religious activity that devout Muslims practice whether they are diabetic or not. Since such fasting involves abstinence from food and water for twelve hours or more during the day from dawn to dusk, it is evident that advice regarding exercise and medication will have to be modified during this period. PMID:23082439

  19. BRAF mutation testing with a rapid, fully integrated molecular diagnostics system.

    PubMed

    Janku, Filip; Claes, Bart; 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

    2015-09-29

    Fast and accurate diagnostic systems are needed for further implementation of precision therapy of BRAF-mutant and other cancers. The novel IdyllaTMBRAF 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 IdyllaTMBRAF 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

  20. Fast Adaptation in Vestibular Hair Cells Requires Myosin-1c Activity

    PubMed Central

    Stauffer, Eric A.; Scarborough, John D.; Hirono, Moritoshi; Miller, Emilie D.; Shah, Kavita; Mercer, John A.; Holt, Jeffrey R.; Gillespie, Peter G.

    2009-01-01

    Summary In sensory hair cells of the inner ear, mechanical amplification of small stimuli requires fast adaptation, the rapid closing of mechanically activated transduction channels. In frog and mouse vestibular hair cells, we found that the rate of fast adaptation depends on both channel opening and stimulus size and that it is modeled well as a release of a mechanical element in series with the transduction apparatus. To determine whether myosin-1c molecules of the adaptation motor are responsible for the release, we introduced the Y61G mutation into the Myo1c locus and generated mice homozygous for this sensitized allele. Measuring transduction and adaptation in the presence of NMB-ADP, an allele-specific inhibitor, we found that the inhibitor not only blocked slow adaptation, as demonstrated previously in transgenic mice, but also inhibited fast adaptation. These results suggest that mechanical activity of myosin-1c is required for fast adaptation in vestibular hair cells. PMID:16102537

  1. Potential-Based Achievement Goals

    ERIC Educational Resources Information Center

    Elliot, Andrew; Murayama, Kou; Kobeisy, Ahmed; Lichtenfeld, Stephanie

    2015-01-01

    Background: Self-based achievement goals use one's own intrapersonal trajectory as a standard of evaluation, and this intrapersonal trajectory may be grounded in one's past (past-based goals) or one's future potential (potential-based goals). Potential-based goals have been overlooked in the literature to date. Aims: The primary aim of the present…

  2. The Racial Academic Achievement Gap

    ERIC Educational Resources Information Center

    Green, Toneka M.

    2008-01-01

    Closing the racial academic achievement gap is a problem that must be solved in order for future society to properly function. Minorities including African-American and Latino students' standardized test scores are much lower than white students. By the end of fourth grade, African American, Latino, and poor students of all races are two years…

  3. The Achievement-Assessment Link

    ERIC Educational Resources Information Center

    Wallace, Virginia; Husid, Whitney

    2011-01-01

    The recent recession, school budget cuts, and predictions of school libraries' demise because of technology advances put pressure on school librarians to prove the utility, relevance, and value of school libraries to student learning. While national studies document that school libraries increase student achievement, school librarians must…

  4. Cooperative Learning and Student Achievement.

    ERIC Educational Resources Information Center

    Slavin, Robert E.

    1988-01-01

    Research evidence shows that cooperative learning strategies are not equally effective, though most positively affect self-esteem, intergroup relations, and the ability to work with others. To produce achievement gains, these methods must include both a group goal and individual accountability. Includes 19 references. (MLH)

  5. Curricular Diversity and Academic Achievement.

    ERIC Educational Resources Information Center

    Wilson, Reginald

    1991-01-01

    Educational achievement should be intellectually and philosophically divorced from cultural affirmation, which is merely a byproduct of the inclusion of diverse voices in the search for truth. A model based on the relationship between the valuation of oneself by others and by oneself is presented to explain differential effects of schooling on…

  6. School Readiness and Later Achievement

    ERIC Educational Resources Information Center

    Duncan, Greg J.; Dowsett, Chantelle J.; Claessens, Amy; Magnuson, Katherine; Huston, Aletha C.; Klebanov, Pamela; Pagani, Linda S.; Feinstein, Leon; Engel, Mimi; Brooks-Gunn, Jeanne; Sexton, Holly; Duckworth, Kathryn; Japel, Crista

    2007-01-01

    Using 6 longitudinal data sets, the authors estimate links between three key elements of school readiness--school-entry academic, attention, and socioemotional skills--and later school reading and math achievement. In an effort to isolate the effects of these school-entry skills, the authors ensured that most of their regression models control for…

  7. Teacher Certification and Student Achievement

    ERIC Educational Resources Information Center

    Moss, Patricia Lewis

    2012-01-01

    The purpose of this mixed-method study was to determine if there is a significant difference between the achievement of students who are taught by traditionally prepared teachers and that of students who are taught by alternatively prepared teachers. The study further addressed the perspectives of both groups of teachers regarding selected…

  8. Achieving Safety through Security Management

    NASA Astrophysics Data System (ADS)

    Ridgway, John

    Whilst the achievement of safety objectives may not be possible purely through the administration of an effective Information Security Management System (ISMS), your job as safety manager will be significantly eased if such a system is in place. This paper seeks to illustrate the point by drawing a comparison between two of the prominent standards within the two disciplines of security and safety management.

  9. 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…

  10. 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…

  11. 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…

  12. Measuring and Recording Student Achievement

    ERIC Educational Resources Information Center

    Universities UK, 2004

    2004-01-01

    The Measuring and Recording Student Achievement Scoping Group was established by Universities UK and the Standing Conference of Principals (SCOP), with the support of the Higher Education Funding Council for England (HEFCE) in October 2003 to review the recommendations from the UK Government White Paper "The Future of Higher Education" relating…

  13. Academic Achievement in Effective Schools

    ERIC Educational Resources Information Center

    Basque, Marc; Bouchamma, Yamina

    2013-01-01

    Purpose: The purpose of this study is to identify predictors of achievement in mathematics in elementary schools in New Brunswick (Canada). Data Collection: Both teachers and school leaders (N = 111) completed a questionnaire on their practices and on school functioning. Findings: Multiple regression analyses revealed that the students'…

  14. Adequacy, Litigation, and Student Achievement

    ERIC Educational Resources Information Center

    Glenn, William

    2008-01-01

    The court system has been an increasingly important forum in the attempts to remedy the persistent achievement gaps in American education. In the past twenty years, school finance adequacy litigation has replaced desegregation as the most widely used legal strategy in these efforts. Despite the widespread use of adequacy litigation, few…

  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. PMID:10123422

  16. 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…

  17. Florida's Fit to Achieve Program.

    ERIC Educational Resources Information Center

    Sander, Allan N.; And Others

    1993-01-01

    Describes Florida's "Fit to Achieve," a cardiovascular fitness education program for elementary students. Children are taught responsibility for their own cardiovascular fitness through proper exercise, personal exercise habits, and regular aerobic exercise. The program stresses collaborative effort between physical educators and classroom…

  18. Believing and Achieving. Issue Brief

    ERIC Educational Resources Information Center

    Jerald, Craig D.

    2007-01-01

    This research brief takes a look at the role of teacher efficacy-how teachers' beliefs in their own abilities affect student achievement. The brief examines the influence of perceived efficacy and building teacher confidence (social persuasion, collegiality, and shared decision making). It concludes by asserting that more positive steps must be…

  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. Achieving Ideological Change within Psychology.

    ERIC Educational Resources Information Center

    Fox, Dennis R.

    Psychologists who are interested in the nature of ideology and the achievement of social change generally focus their primary theoretical and empirical attention on those people outside academia who are trying to change or to prevent change in one political sphere or another. There may be some value in looking at psychology and psychologists as…

  1. Five Standards and Student Achievement.

    ERIC Educational Resources Information Center

    Doherty, R. William; Hilberg, R. Soleste; Pinal, America; Tharp, Roland G.

    2003-01-01

    Two studies examine the influence of the Standards for Effective Pedagogy on student achievement gains. Participants were 15 teachers and 266 students (grades 3 to 5) in a public elementary school serving predominantly low-income Latino English Language Learners (ELLs). Implications for teaching practice and research are discussed. (Author/VWL)

  2. 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…

  3. Mobility and the Achievement Gap.

    ERIC Educational Resources Information Center

    Skandera, Hanna; Sousa, Richard

    2002-01-01

    Research indicates that low achievement scores relate significantly to high school mobility rates. One explanation for this relationship is curricular inconsistency. Some suggest that school choice could contribute to a solution by breaking the link between a child's home address and school address, thus allowing students to remain at one school…

  4. 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…

  5. 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…

  6. 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…

  7. 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 culture as…

  8. 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.

  9. Fast and thermal neutron radiography

    NASA Astrophysics Data System (ADS)

    Cremer, Jay T.; Piestrup, Melvin A.; Wu, Xizeng

    2005-09-01

    There is a need for high brightness neutron sources that are portable, relatively inexpensive, and capable of neutron radiography in short imaging times. Fast and thermal neutron radiography is as an excellent method to penetrate high-density, high-Z objects, thick objects and image its interior contents, especially hydrogen-based materials. In this paper we model the expected imaging performance characteristics and limitations of fast and thermal radiography systems employing a Rose Model based transfer analysis. For fast neutron detection plastic fiber array scintllators or liquid scintillator filled capillary arrays are employed for fast neutron detection, and 6Li doped ZnS(Cu) phosphors are employed for thermal neutron detection. These simulations can provide guidance in the design, construction, and testing of neutron imaging systems. In particular we determined for a range of slab thickness, the range of thicknesses of embedded cracks (air-filled or filled with material such as water) which can be detected and imaged.

  10. Evolution of digital organisms at high mutation rates leads to survival of the flattest

    NASA Astrophysics Data System (ADS)

    Wilke, Claus O.; Wang, Jia Lan; Ofria, Charles; Lenski, Richard E.; Adami, Christoph

    2001-07-01

    Darwinian evolution favours genotypes with high replication rates, a process called `survival of the fittest'. However, knowing the replication rate of each individual genotype may not suffice to predict the eventual survivor, even in an asexual population. According to quasi-species theory, selection favours the cloud of genotypes, interconnected by mutation, whose average replication rate is highest. Here we confirm this prediction using digital organisms that self-replicate, mutate and evolve. Forty pairs of populations were derived from 40 different ancestors in identical selective environments, except that one of each pair experienced a 4-fold higher mutation rate. In 12 cases, the dominant genotype that evolved at the lower mutation rate achieved a replication rate >1.5-fold faster than its counterpart. We allowed each of these disparate pairs to compete across a range of mutation rates. In each case, as mutation rate was increased, the outcome of competition switched to favour the genotype with the lower replication rate. These genotypes, although they occupied lower fitness peaks, were located in flatter regions of the fitness surface and were therefore more robust with respect to mutations.

  11. Transgenic mice with overexpression of mutated human optineurin(E50K) in the retina.

    PubMed

    Meng, Qingfeng; Xiao, Zheng; Yuan, Huiping; Xue, Fei; Zhu, Yuanmao; Zhou, Xinrong; Yang, Binbin; Sun, Jingbo; Meng, Bo; Sun, Xian; Cheng, Fang

    2012-02-01

    In the present work, Site-directed mutagenesis to insert the Glu50Lys amino acid substitution was achieved by PCR using plasmid pBluescript-OPTN. Mutated human OPTN(E50K) gene-driven mouse c-kit promoter was constructed and confirmed by endonuclease digestion and sequence analysis. Transgenic mice were generated via the microinjection method. PCR and DNA dot blot were used to screen the positive transgenic mice. RT-PCR analyzed the RNA level and location of mutated human OPTN(E50K) mRNA expression in transgenic mice. Western blot and immunohistochemistry were used to detect the level and location of mutated human OPTN(E50K) expression in transgenic mice. A transgenic mouse model with overexpression of mutated human OPTN(E50K) in retina was successfully established. The transgene was integrated and transmitted into the chromosome of transgenic mice. Mutated human OPTN(E50K) gene was controlled by c-kit promoter and expressed in the retina in mice. Mutated human OPTN(E50K) in transgenic mice was higher than that of wild type C57BL/6J mice. Our studies had provided a new transgenic model for investigating the molecular properties of mutated human OPTN(E50K). PMID:21681420

  12. 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

  13. Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa

    PubMed Central

    Perez-Carro, Raquel; Corton, Marta; Sánchez-Navarro, Iker; Zurita, Olga; Sanchez-Bolivar, Noelia; Sánchez-Alcudia, Rocío; Lelieveld, Stefan H.; Aller, Elena; Lopez-Martinez, Miguel Angel; López-Molina, Mª Isabel; Fernandez-San Jose, Patricia; Blanco-Kelly, Fiona; Riveiro-Alvarez, Rosa; Gilissen, Christian; Millan, Jose M; Avila-Fernandez, Almudena; Ayuso, Carmen

    2016-01-01

    Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) characterized by photoreceptor degeneration. RP is highly heterogeneous both clinically and genetically, which complicates the identification of causative genes and mutations. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for the detection of mutations in RP. In our study, an in-house gene panel comprising 75 known RP genes was used to analyze a cohort of 47 unrelated Spanish families pre-classified as autosomal recessive or isolated RP. Disease-causing mutations were found in 27 out of 47 cases achieving a mutation detection rate of 57.4%. In total, 33 pathogenic mutations were identified, 20 of which were novel mutations (60.6%). Furthermore, not only single nucleotide variations but also copy-number variations, including three large deletions in the USH2A and EYS genes, were identified. Finally seven out of 27 families, displaying mutations in the ABCA4, RP1, RP2 and USH2A genes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis. PMID:26806561

  14. Predicting the Impact of Missense Mutations on Protein-Protein Binding Affinity.

    PubMed

    Li, Minghui; Petukh, Marharyta; Alexov, Emil; Panchenko, Anna R

    2014-04-01

    The crucial prerequisite for proper biological function is the protein's ability to establish highly selective interactions with macromolecular partners. A missense mutation that alters the protein binding affinity may cause significant perturbations or complete abolishment of the function, potentially leading to diseases. The availability of computational methods to evaluate the impact of mutations on protein-protein binding is critical for a wide range of biomedical applications. Here, we report an efficient computational approach for predicting the effect of single and multiple missense mutations on protein-protein binding affinity. It is based on a well-tested simulation protocol for structure minimization, modified MM-PBSA and statistical scoring energy functions with parameters optimized on experimental sets of several thousands of mutations. Our simulation protocol yields very good agreement between predicted and experimental values with Pearson correlation coefficients of 0.69 and 0.63 and root-mean-square errors of 1.20 and 1.90 kcal mol(-1) for single and multiple mutations, respectively. Compared with other available methods, our approach achieves high speed and prediction accuracy and can be applied to large datasets generated by modern genomics initiatives. In addition, we report a crucial role of water model and the polar solvation energy in estimating the changes in binding affinity. Our analysis also reveals that prediction accuracy and effect of mutations on binding strongly depends on the type of mutation and its location in a protein complex. PMID:24803870

  15. TET2 mutations in secondary acute myeloid leukemias: a French retrospective study

    PubMed Central

    Kosmider, Olivier; Delabesse, Eric; Mas, Véronique Mansat-De; Cornillet-Lefebvre, Pascale; Blanchet, Odile; Delmer, Alain; Recher, Christian; Raynaud, Sophie; Bouscary, Didier; Viguié, Franck; Lacombe, Catherine; Bernard, Olivier A.; Ifrah, Norbert; Dreyfus, François; Fontenay, Michaëla

    2011-01-01

    Ten-eleven translocation 2 (TET2) mutations have been involved in myeloid malignancies. This retrospective study aims at evaluating the frequency and impact of TET2 mutations in 247 secondary acute myeloid leukemia cases referred to as myelodysplasia-related changes (n=201) or therapy-related (n=46) leukemias. Mutation of at least one copy of the TET2 gene was detected in 49 of 247 (19.8%) patients who presented with older age, higher hemoglobin level, higher neutrophil and monocyte counts, and lower platelet count. TET2 mutations were significantly less frequent in therapy-related (8.7%) than myelodysplasia-related changes (22.3%; P=0.035) leukemias and strongly associated with normal karyotype (P<0.001). TET2 mutations did not significantly associate with NPM1, FLT3-ITD or FLT3-D835, WT1, or N- or K-RAS mutations. Complete remission was achieved in 57% of evaluable patients who had received intensive chemotherapy. In this group, TET2 mutations did not influence the complete remission rate or overall survival. PMID:21508122

  16. Fast Access Data Acquisition System

    SciTech Connect

    Dr. Vladimir Katsman

    1998-03-17

    Our goal in this program is to develop Fast Access Data Acquisition System (FADAS) by combining the flexibility of Multilink's GaAs and InP electronics and electro-optics with an extremely high data rate for the efficient handling and transfer of collider experimental data. This novel solution is based on Multilink's and Los Alamos National Laboratory's (LANL) unique components and technologies for extremely fast data transfer, storage, and processing.

  17. Use of mutation spectra analysis software.

    PubMed

    Rogozin, I; Kondrashov, F; Glazko, G

    2001-02-01

    The study and comparison of mutation(al) spectra is an important problem in molecular biology, because these spectra often reflect on important features of mutations and their fixation. Such features include the interaction of DNA with various mutagens, the function of repair/replication enzymes, and properties of target proteins. It is known that mutability varies significantly along nucleotide sequences, such that mutations often concentrate at certain positions, called "hotspots," in a sequence. In this paper, we discuss in detail two approaches for mutation spectra analysis: the comparison of mutation spectra with a HG-PUBL program, (FTP: sunsite.unc.edu/pub/academic/biology/dna-mutations/hyperg) and hotspot prediction with the CLUSTERM program (www.itba.mi.cnr.it/webmutation; ftp.bionet.nsc.ru/pub/biology/dbms/clusterm.zip). Several other approaches for mutational spectra analysis, such as the analysis of a target protein structure, hotspot context revealing, multiple spectra comparisons, as well as a number of mutation databases are briefly described. Mutation spectra in the lacI gene of E. coli and the human p53 gene are used for illustration of various difficulties of such analysis. PMID:11180592

  18. 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

  19. 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. PMID:25860667

  20. 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

  1. 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.

  2. 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. PMID:27011527

  3. Fast Hadamard Spectroscopic Imaging Techniques

    NASA Astrophysics Data System (ADS)

    Goelman, G.

    1994-07-01

    Fast Hadamard spectroscopic imaging (HSI) techniques are presented. These techniques combine transverse and longitudinal encoding to obtain multiple-volume localization. The fast techniques are optimized for nuclei with short T2 and long T1 relaxation times and are therefore suitable for in vivo31P spectroscopy. When volume coils are used in fast HSI techniques, the signal-to-noise ratio per unit time (SNRT) is equal to the SNRT in regular HSI techniques. When surface coils are used, fast HSI techniques give significant improvement of SNRT over conventional HSI. Several fast techniques which are different in total experimental time and pulse demands are presented. When the number of acquisitions in a single repetition time is not higher than two, fast HSI techniques can be used with surface coils and the B1 inhomogeneity does not affect the localization. Surface-coil experiments on phantoms and on human calf muscles in vivo are presented. In addition, it is shown that the localization obtained by the HSI techniques are independent of the repetition times.

  4. Direct Fast-Neutron Detection

    SciTech Connect

    DC Stromswold; AJ Peurrung; RR Hansen; PL Reeder

    2000-01-18

    Direct fast-neutron detection is the detection of fast neutrons before they are moderated to thermal energy. We have investigated two approaches for using proton-recoil in plastic scintillators to detect fast neutrons and distinguish them from gamma-ray interactions. Both approaches use the difference in travel speed between neutrons and gamma rays as the basis for separating the types of events. In the first method, we examined the pulses generated during scattering in a plastic scintillator to see if they provide a means for distinguishing fast-neutron events from gamma-ray events. The slower speed of neutrons compared to gamma rays results in the production of broader pulses when neutrons scatter several times within a plastic scintillator. In contrast, gamma-ray interactions should produce narrow pulses, even if multiple scattering takes place, because the time between successive scattering is small. Experiments using a fast scintillator confirmed the presence of broader pulses from neutrons than from gamma rays. However, the difference in pulse widths between neutrons and gamma rays using the best commercially available scintillators was not sufficiently large to provide a practical means for distinguishing fast neutrons and gamma rays on a pulse-by-pulse basis. A faster scintillator is needed, and that scintillator might become available in the literature. Results of the pulse-width studies were presented in a previous report (peurrung et al. 1998), and they are only summarized here.

  5. Sterol Regulatory Transcription Factor-1: Key Regulator of Fasting Response in the Adipose Tissue inGPigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genetic mechanisms controlling appetite and feeding behaviors are not well understood. In this study, transcriptional profiling was used to identify porcine genes and pathways that respond to a fasting treatment or to a missense mutation (D298N) in the melanocortin-4 receptor (MC4R) gene, which...

  6. 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…

  7. 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

  8. Mutation, Witten index, and quiver invariant

    NASA Astrophysics Data System (ADS)

    Kim, Heeyeon; Lee, Seung-Joo; Yi, Piljin

    2015-07-01

    We explore Seiberg-like dualities, or mutations, for quiver quantum mechanics in the context of wall-crossing. In contrast to higher dimensions, the 1d Seiberg-duality must be performed with much care. With fixed Fayet-Iliopoulos constants, at most two nodes can be mutated, one left and the other right, mapping a chamber of a quiver into a chamber of a mutated quiver. We delineate this complex pattern for triangle quivers and show how the Witten indices are preserved under such finely chosen mutations. On the other hand, the quiver invariants, or wall-crossing-safe part of supersymmetric spectra, mutate more straightforwardly, whereby a quiver is mapped to a quiver. The mutation rule that preserves the quiver invariant is different from the usual one, however, which we explore and confirm numerically.

  9. Fast Poisson, Fast Helmholtz and fast linear elastostatic solvers on rectangular parallelepipeds

    SciTech Connect

    Wiegmann, A.

    1999-06-01

    FFT-based fast Poisson and fast Helmholtz solvers on rectangular parallelepipeds for periodic boundary conditions in one-, two and three space dimensions can also be used to solve Dirichlet and Neumann boundary value problems. For non-zero boundary conditions, this is the special, grid-aligned case of jump corrections used in the Explicit Jump Immersed Interface method. Fast elastostatic solvers for periodic boundary conditions in two and three dimensions can also be based on the FFT. From the periodic solvers we derive fast solvers for the new 'normal' boundary conditions and essential boundary conditions on rectangular parallelepipeds. The periodic case allows a simple proof of existence and uniqueness of the solutions to the discretization of normal boundary conditions. Numerical examples demonstrate the efficiency of the fast elastostatic solvers for non-periodic boundary conditions. More importantly, the fast solvers on rectangular parallelepipeds can be used together with the Immersed Interface Method to solve problems on non-rectangular domains with general boundary conditions. Details of this are reported in the preprint The Explicit Jump Immersed Interface Method for 2D Linear Elastostatics by the author.

  10. Fast imaging applications in the Nuclear Test Program

    SciTech Connect

    Lear, R.

    1983-10-14

    Applications of fast imaging employ both streak cameras and fast framing techniques. Image intensifier tubes are gated to provide fast two-dimensional shutters of 2 to 3 ns duration with shatter ratios of greater than 10/sup 6/ and resolution greater than 10/sup 4/ pixels. Shutters of less than 1 ns have been achieved with experimental tubes. Characterization data demonstrate the importance of tube and pulser design. Streak cameras are used to simultaneously record temporal and intensity information from up to 200 spatial points. Streak cameras are combined with remote readout for downhole uses and are coupled to fiber optic cables for uphole uses. Optical wavelength multiplexing is being studied as a means of compressing additional image data onto optical fibers. Performance data demonstrate trade-offs between image resolution and system sensitivity.

  11. 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. PMID:27571422

  12. 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

  13. History of fast reactor fuel development

    NASA Astrophysics Data System (ADS)

    Kittel, J. H.; Frost, B. R. T.; Mustelier, J. P.; Bagley, K. Q.; Crittenden, G. C.; Van Dievoet, J.

    1993-09-01

    The first fast breeder reactors, constructed in the 1945-1960 time period, used metallic fuels composed of uranium, plutonium, or their alloys. They were chosen because most existing reactor operating experience had been obtained on metallic fuels and because they provided the highest breeding ratios. Difficulties in obtaining adequate dimensional stability in metallic fuel elements under conditions of high fuel burnup led in the 1960s to the virtual worldwide choice of ceramic fuels. Although ceramic fuels provide lower breeding performance, this objective is no longer an important consideration in most national programs. Mixed uranium and plutonium dioxide became the ceramic fuel that has received the widest use. The more advanced ceramic fuels, mixed uranium and plutonium carbides and nitrides, continue under development. More recently, metal fuel elements of improved design have joined ceramic fuels in achieving goal burnups of 15 to 20 percent. Low-swelling fuel cladding alloys have also been continuously developed to deal with the unexpected problem of void formation in stainless steels subjected to fast neutron irradiation, a phenomenon first observed in the 1960s.

  14. Fast planar segmentation of depth images

    NASA Astrophysics Data System (ADS)

    Javan Hemmat, Hani; Pourtaherian, Arash; Bondarev, Egor; de With, Peter H. N.

    2015-03-01

    One of the major challenges for applications dealing with the 3D concept is the real-time execution of the algorithms. Besides this, for the indoor environments, perceiving the geometry of surrounding structures plays a prominent role in terms of application performance. Since indoor structures mainly consist of planar surfaces, fast and accurate detection of such features has a crucial impact on quality and functionality of the 3D applications, e.g. decreasing model size (decimation), enhancing localization, mapping, and semantic reconstruction. The available planar-segmentation algorithms are mostly developed using surface normals and/or curvatures. Therefore, they are computationally expensive and challenging for real-time performance. In this paper, we introduce a fast planar-segmentation method for depth images avoiding surface normal calculations. Firstly, the proposed method searches for 3D edges in a depth image and finds the lines between identified edges. Secondly, it merges all the points on each pair of intersecting lines into a plane. Finally, various enhancements (e.g. filtering) are applied to improve the segmentation quality. The proposed algorithm is capable of handling VGA-resolution depth images at a 6 FPS frame-rate with a single-thread implementation. Furthermore, due to the multi-threaded design of the algorithm, we achieve a factor of 10 speedup by deploying a GPU implementation.

  15. 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.

  16. 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.

  17. 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

  18. Pulsars and Fast Transients with LOFAR

    NASA Astrophysics Data System (ADS)

    Stappers, Ben; Hessels, Jason; Alexov, Anastasia; Anderson, Kenneth; Coenen, Thijs; Hassall, Tom; Karastergiou, Aris; Kondratiev, Vlad; Kramer, Michael; van Leeuwen, Joeri; Mol, Jan David; Noutsos, A.; Romein, John; Weltevrede, Patrick; Fender, Robert; Wijers, Ralph

    2011-08-01

    The LOw Frequency ARray is the first of the next generation of radio telescopes to be completed. It uses large numbers of small receptors and vast computing and data transport capabilities to achieve a high degree of sensitivity over large fields of view. It uses two different types of receptor to enable it to observe over the frequency range 10-260 MHz. Here we report on some of the capabilities of this telescope for pulsar and fast transient research. We also present some results of the commissioning work that we have been carrying out which highlight the exciting potential of this telescope. These include simultaneous imaging and pulsar observations, simultaneous observations spanning 30-8000 MHz, a large number of known pulsars detected in the high band and the detection of PSR B0809+74 down to a frequency of 16 MHz.

  19. Fast Track'' nuclear thermal propulsion concept

    SciTech Connect

    Johnson, R.A.; Zweig, H.R. ); Cooper, M.H.; Wett, J. Jr. )

    1993-01-10

    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).

  20. Copy number variation and mutation

    NASA Astrophysics Data System (ADS)

    Clark, Brian; Weidner, Jacob; Wabick, Kevin

    2009-11-01

    Until very recently, the standard model of DNA included two genes for each trait. This dated model has given way to a model that includes copies of some genes well in excess of the canonical two. Copy number variations in the human genome play critical roles in causing or aggravating a number of syndromes and diseases while providing increased resistance to others. We explore the role of mutation, crossover, inversion, and reproduction in determining copy number variations in a numerical simulation of a population. The numerical model consists of a population of individuals, where each individual is represented by a single strand of DNA with the same number of genes. Each gene is initially assigned to one of two traits. Fitness of the individual is determined by the two most fit genes for trait one, and trait two genetic material is treated as a reservoir of junk DNA. After a sufficient number of generations, during which the genetic distribution is allowed to reach a steady-state, the mean numberof genes per trait and the copy number variation are recorded. Here, we focus on the role of mutation and compare simulation results to theory.

  1. 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.

  2. Determination of a mutational spectrum

    SciTech Connect

    Thilly, W.G.; Keohavong, P.

    1991-09-03

    A method is disclosed of resolving (physically separating) mutant DNA from nonmutant DNA. A method is also described 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. 3 figures.

  3. Stationary solutions for metapopulation Moran models with mutation and selection.

    PubMed

    Constable, George W A; McKane, Alan J

    2015-03-01

    We construct an individual-based metapopulation model of population genetics featuring migration, mutation, selection, and genetic drift. In the case of a single "island," the model reduces to the Moran model. Using the diffusion approximation and time-scale separation arguments, an effective one-variable description of the model is developed. The effective description bears similarities to the well-mixed Moran model with effective parameters that depend on the network structure and island sizes, and it is amenable to analysis. Predictions from the reduced theory match the results from stochastic simulations across a range of parameters. The nature of the fast-variable elimination technique we adopt is further studied by applying it to a linear system, where it provides a precise description of the slow dynamics in the limit of large time-scale separation. PMID:25871148

  4. 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

  5. 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.

  6. 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.

  7. Three Turkish families with different transthyretin mutations.

    PubMed

    Bekircan-Kurt, Can Ebru; Güneş, Nalan; Yılmaz, Arda; Erdem-Özdamar, Sevim; Tan, Ersin

    2015-09-01

    Transthyretin (TTR)-related hereditary amyloidosis, also called familial amyloid polyneuropathy (FAP), is a rare autosomal dominant systemic disorder that presents with progressive axonal sensory, autonomic and/or motor neuropathies. The present report describes three families with three different TTR mutations who were followed from 1995 to 2014. Only one of these families expressed the Val30Met mutation, which is the most common mutation in endemic regions; all members of this family had late disease onset but varied severities and clinical presentations of the disease. The second family expressed the Thr49Ser mutation, which has not been well documented previously. Our limited experience obtained from these patients indicates that this mutation presents with autonomic neuropathy but a greater degree of cardiac involvement, especially fatal heart failure. The third mutation, Glu54Lys, has been identified as a cause of severe familial amyloid polyneuropathy; the family members with this mutation exhibited severe motor and autonomic neuropathy, early vitreous opacity, and fatal heart failure. Three of the patients with the Val30Met mutation were treated with tafamidis for longer than one year and cessation of the polyneuropathy resulted. However, a short trial of tafamidis in two patients with the Glu54Lys mutation, who showed severe systemic and neurological involvement, did not gain any clinical benefits. PMID:26115788

  8. Compensating the Fitness Costs of Synonymous Mutations.

    PubMed

    Knöppel, Anna; Näsvall, Joakim; Andersson, Dan I

    2016-06-01

    Synonymous mutations do not change the sequence of the polypeptide but they may still influence fitness. We investigated in Salmonella enterica how four synonymous mutations in the rpsT gene (encoding ribosomal protein S20) reduce fitness (i.e., growth rate) and the mechanisms by which this cost can be genetically compensated. The reduced growth rates of the synonymous mutants were correlated with reduced levels of the rpsT transcript and S20 protein. In an adaptive evolution experiment, these fitness impairments could be compensated by mutations that either caused up-regulation of S20 through increased gene dosage (due to duplications), increased transcription of the rpsT gene (due to an rpoD mutation or mutations in rpsT), or increased translation from the rpsT transcript (due to rpsT mutations). We suggest that the reduced levels of S20 in the synonymous mutants result in production of a defective subpopulation of 30S subunits lacking S20 that reduce protein synthesis and bacterial growth and that the compensatory mutations restore S20 levels and the number of functional ribosomes. Our results demonstrate how specific synonymous mutations can cause substantial fitness reductions and that many different types of intra- and extragenic compensatory mutations can efficiently restore fitness. Furthermore, this study highlights that also synonymous sites can be under strong selection, which may have implications for the use of dN/dS ratios as signature for selection. PMID:26882986

  9. A Landscape of Driver Mutations in Melanoma

    PubMed Central

    Hodis, Eran; Watson, Ian R.; Kryukov, Gregory V.; Arold, Stefan T.; Imielinski, Marcin; Theurillat, Jean-Philippe; Nickerson, Elizabeth; Auclair, Daniel; Li, Liren; Place, Chelsea; DiCara, Daniel; Ramos, Alex H.; Lawrence, Michael S.; Cibulskis, Kristian; Sivachenko, Andrey; Voet, Douglas; Saksena, Gordon; Stransky, Nicolas; Onofrio, Robert C.; Winckler, Wendy; Ardlie, Kristin; Wagle, Nikhil; Wargo, Jennifer; Chong, Kelly; Morton, Donald L.; Stemke-Hale, Katherine; Chen, Guo; Noble, Michael; Meyerson, Matthew; Ladbury, John E.; Davies, Michael A.; Gershenwald, Jeffrey E.; Wagner, Stephan N.; Hoon, Dave S.B.; Schadendorf, Dirk; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Garraway, Levi A.; Chin, Lynda

    2012-01-01

    SUMMARY Despite recent insights into melanoma genetics, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic ultraviolet (UV) light exposure. We developed a permutation-based framework to address this challenge, employing mutation data from intronic sequences to control for passenger mutational load on a per gene basis. Analysis of large-scale melanoma exome data by this approach discovered six novel melanoma genes (PPP6C, RAC1, SNX31, TACC1, STK19 and ARID2), three of which - RAC1, PPP6C and STK19 - harbored recurrent and potentially targetable mutations. Integration with chromosomal copy number data contextualized the landscape of driver mutations, providing oncogenic insights in BRAF- and NRAS-driven melanoma as well as those without known NRAS/BRAF mutations. The landscape also clarified a mutational basis for RB and p53 pathway deregulation in this malignancy. Finally, the spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis. PMID:22817889

  10. Compensating the Fitness Costs of Synonymous Mutations

    PubMed Central

    Knöppel, Anna; Näsvall, Joakim; Andersson, Dan I.

    2016-01-01

    Synonymous mutations do not change the sequence of the polypeptide but they may still influence fitness. We investigated in Salmonella enterica how four synonymous mutations in the rpsT gene (encoding ribosomal protein S20) reduce fitness (i.e., growth rate) and the mechanisms by which this cost can be genetically compensated. The reduced growth rates of the synonymous mutants were correlated with reduced levels of the rpsT transcript and S20 protein. In an adaptive evolution experiment, these fitness impairments could be compensated by mutations that either caused up-regulation of S20 through increased gene dosage (due to duplications), increased transcription of the rpsT gene (due to an rpoD mutation or mutations in rpsT), or increased translation from the rpsT transcript (due to rpsT mutations). We suggest that the reduced levels of S20 in the synonymous mutants result in production of a defective subpopulation of 30S subunits lacking S20 that reduce protein synthesis and bacterial growth and that the compensatory mutations restore S20 levels and the number of functional ribosomes. Our results demonstrate how specific synonymous mutations can cause substantial fitness reductions and that many different types of intra- and extragenic compensatory mutations can efficiently restore fitness. Furthermore, this study highlights that also synonymous sites can be under strong selection, which may have implications for the use of dN/dS ratios as signature for selection. PMID:26882986

  11. Haplotypes and mutations in Wilson disease

    SciTech Connect

    Thomas, G.R.; Roberts, E.A.; Cox, D.W.

    1995-06-01

    Wilson disease is a disorder of copper transport, resulting in neurological and hepatic damage due to copper toxicity. We have recently identified >20 mutations in the copper-transporting ATPase defective in this disease. Given the difficulties of searching for mutations in a gene spanning >80 kb of genomic DNA, haplotype data are important as a guide to mutation detection. Here we examine the haplotypes associated with specific mutations. We have extended previous studies of DNA haplotypes of dinucleotide-repeat polymorphisms (CA repeats) in the Wilson disease region to include an additional marker, in 58 families. These haplotypes, combining three markers (D13S314, D12S316, and D13S301), are usually specific for each different mutation, even though highly polymorphic CA repeat markers have been used. Haplotypes, as well as their accompanying mutations, differ between populations. In the patients whom we have studied, the haplotype data indicate that as many as 20 mutations may still be unidentified. The use of the haplotypes that we have identified provides an important guide for the identification of known mutations and can facilitate future mutation searches. 15 refs., 1 fig., 2 tabs.

  12. 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. PMID:26971461

  13. 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

  14. 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

  15. Mutation analysis in exons 22 and 24 of SCN4A gene in Iranian patients with non-dystrophic myotonia

    PubMed Central

    Heidari, Mohammad Mehdi; Khatami, Mehri; Nafissi, Shahriar; Hesami-Zokai, Faezeh; Khorrami, Afshin

    2015-01-01

    Background: Non-dystrophic myotonias are a heterogeneous set of skeletal, muscular channelopathies, which have been associated with point mutations within sodium channel α-subunit (SCN4A) gene. Because exons 22 and 24 of SCN4A gene are recognized as hot spots for this disease, the purpose of the study is to identify mutation in exons 22 and 24 of SCN4A gene in Iranian non-dystrophic myotonias patients. Methods: In this study, 28 Iranian patients with non-dystrophic myotonia analyzed for the mutation scanning in exons 22 and 24 of SCN4A gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and sequencing. Results: We found 29073G>C substitution in SCN4A gene in one case and 31506A>G substitution in seven cases. The 29073G>C substitution causes a missense mutation G1306A, located in the conserved cytoplasmic loop connecting repeat III and IV of the SCN4A channel but, 31506A>G substitution do not alter amino acid in SCN4A protein. Conclusion: G1306A residue is located in functionally important protein region. In “hinged-lid model” for Na+ channel inactivation in which glycines1306 act as the hinge of the lid occluding the channel pore. Mutation in this region slowed fast inactivation. Therefore, it might be a pathogenic mutation. The causal relationship of this mutation with the disease is an object for further discussion. PMID:26885337

  16. 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

  17. Mechanism for fast radio bursts

    NASA Astrophysics Data System (ADS)

    Romero, G. E.; del Valle, M. V.; Vieyro, F. L.

    2016-01-01

    Fast radio bursts are mysterious transient sources likely located at cosmological distances. The derived brightness temperatures exceed by many orders of magnitude the self-absorption limit of incoherent synchrotron radiation, implying the operation of a coherent emission process. We propose a radiation mechanism for fast radio bursts where the emission arises from collisionless bremsstrahlung in strong plasma turbulence excited by relativistic electron beams. We discuss possible astrophysical scenarios in which this process might operate. The emitting region is a turbulent plasma hit by a relativistic jet, where Langmuir plasma waves produce a concentration of intense electrostatic soliton-like regions (cavitons). The resulting radiation is coherent and, under some physical conditions, can be polarized and have a power-law distribution in energy. We obtain radio luminosities in agreement with the inferred values for fast radio bursts. The time scale of the radio flare in some cases can be extremely fast, of the order of 1 0-3 s . The mechanism we present here can explain the main features of fast radio bursts and is plausible in different astrophysical sources, such as gamma-ray bursts and some active galactic nuclei.

  18. Superheavy Elements - Achievements and Challenges

    SciTech Connect

    Ackermann, Dieter

    2009-03-04

    The search for superheavy elements (SHE) has yielded exciting results for both the 'cold fusion' approach with reactions employing Pb and Bi targets and the ''hot fusion'' reactions with {sup 48}Ca beams on actinide targets. The most recent activities at GSI were the successful production of a more neutron rich isotope of element 112 in the reaction {sup 48}Ca+{sup 238}U confirming earlier result from FLNR, and the attempt to synthesize an isotope with Z 120 in the reaction {sup 64}Ni+{sup 238}U. Apart from the synthesis of new elements, advanced nuclear structure studies for heavy and super heavy elements promise a detailed insight in the properties of nuclear matter under the extreme conditions of high Z and A. The means are evaporation residue(ER)-{alpha}-{alpha} and -{alpha}-{gamma} coincidence techniques applied after separation of the reaction products from the beam. Recent examples of interesting physics to be discovered in this region of the chart of nuclides are the investigation of K-isomers observed for {sup 252,254}No and indicated for {sup 270}Ds. Fast chemistry and precision mass measurements deliver in addition valuable information on the fundamental properties of the SHE.

  19. 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

  20. Clinical Outcomes and Correlates of TP53 Mutations and Cancer

    PubMed Central

    Robles, Ana I.; Harris, Curtis C.

    2010-01-01

    The initial observation that p53 accumulation might serve as a surrogate biomarker for TP53 mutation has been the cornerstone for vast translational efforts aimed at validating its clinical use for the diagnosis, prognosis, and treatment of cancer. Early on, it was realized that accurate evaluation of p53 status and function could not be achieved through protein-expression analysis only. As our understanding of the p53 pathway has evolved and more sophisticated methods for assessment of p53 functional integrity have become available, the clinical and molecular epidemiological implications of p53 abnormalities in cancers are being revealed. They include diagnostic testing for germline p53 mutations, and the assessment of selected p53 mutations as biomarkers of carcinogen exposure and cancer risk and prognosis. Here, we describe the strengths and limitations of the most frequently used techniques for determination of p53 status in tumors, as well as the most remarkable latest findings relating to its clinical and epidemiological value. PMID:20300207

  1. Role of conservative mutations in protein multi-property adaptation.

    PubMed

    Rodriguez-Larrea, David; Perez-Jimenez, Raul; Sanchez-Romero, Inmaculada; Delgado-Delgado, Asuncion; Fernandez, Julio M; Sanchez-Ruiz, Jose M

    2010-07-15

    Protein physicochemical properties must undergo complex changes during evolution, as a response to modifications in the organism environment, the result of the proteins taking up new roles or because of the need to cope with the evolution of molecular interacting partners. Recent work has emphasized the role of stability and stability-function trade-offs in these protein adaptation processes. In the present study, on the other hand, we report that combinations of a few conservative, high-frequency-of-fixation mutations in the thioredoxin molecule lead to largely independent changes in both stability and the diversity of catalytic mechanisms, as revealed by single-molecule atomic force spectroscopy. Furthermore, the changes found are evolutionarily significant, as they combine typically hyperthermophilic stability enhancements with modulations in function that span the ranges defined by the quite different catalytic patterns of thioredoxins from bacterial and eukaryotic origin. These results suggest that evolutionary protein adaptation may use, in some cases at least, the potential of conservative mutations to originate a multiplicity of evolutionarily allowed mutational paths leading to a variety of protein modulation patterns. In addition the results support the feasibility of using evolutionary information to achieve protein multi-feature optimization, an important biotechnological goal. PMID:20446918

  2. 'Post antibiotic apocalypse': discourses of mutation in narratives of MRSA.

    PubMed

    Brown, Brian; Crawford, Paul

    2009-05-01

    In this paper we will consider the question of mutation as it is manifested in press coverage of MRSA in UK hospitals. This represents a fertile field of discourse which brings into focus issues relating to microbes, people and working practices as well as the concepts of risk and vulnerability. A regular feature of reporting has been the presence of explanations for drug resistance involving repeated random mutations of the microbe to achieve progressively greater resistance and versatility, largely through a Darwinian process which is 'clever' at overcoming human attempts at elimination. More recently a discourse has emerged which foregrounds also the vulnerability of patients who are very young, old or otherwise immunocompromised, or whose own genetic makeup might put them at risk from the microbe. The hospital is decentred as a source of infection, and attention is turned instead to nursing homes and gymnasia as sources of infection in the community. This latter development mitigates the responsibilities of hospitals and statutory healthcare providers and turns the risk back towards the individual as a responsible actor in an ecology of mutation. PMID:19144082

  3. The ATLAS Fast Monte Carlo Production Chain Project

    NASA Astrophysics Data System (ADS)

    Jansky, Roland

    2015-12-01

    During the last years ATLAS has successfully deployed a new integrated simulation framework (ISF) which allows a flexible mixture of full and fast detector simulation techniques within the processing of one event. The thereby achieved possible speed-up in detector simulation of up to a factor 100 makes subsequent digitization and reconstruction the dominant contributions to the Monte Carlo (MC) production CPU cost. The slowest components of both digitization and reconstruction are inside the Inner Detector due to the complex signal modeling needed in the emulation of the detector readout and in reconstruction due to the combinatorial nature of the problem to solve, respectively. Alternative fast approaches have been developed for these components: for the silicon based detectors a simpler geometrical clustering approach has been deployed replacing the charge drift emulation in the standard digitization modules, which achieves a very high accuracy in describing the standard output. For the Inner Detector track reconstruction, a Monte Carlo generator information based trajectory building has been deployed with the aim of bypassing the CPU intensive pattern recognition. Together with the ISF all components have been integrated into a new fast MC production chain, aiming to produce fast MC simulated data with sufficient agreement with fully simulated and reconstructed data at a processing time of seconds per event, compared to several minutes for full simulation.

  4. Fast ion beam chopping system for neutron generators

    NASA Astrophysics Data System (ADS)

    Hahto, S. K.; Hahto, S. T.; Leung, K. N.; Reijonen, J.; Miller, T. G.; Van Staagen, P. K.

    2005-02-01

    Fast deuterium (D+) and tritium (T+) ion beam pulses are needed in some neutron-based imaging systems. A compact, integrated fast ion beam extraction and chopping system has been developed and tested at the Lawrence Berkeley National Laboratory for these applications, and beam pulses with 15ns full width at half maximum have been achieved. Computer simulations together with experimental tests indicate that even faster pulses are achievable by shortening the chopper voltage rise time. This chopper arrangement will be implemented in a coaxial neutron generator, in which a small point-like neutron source is created by multiple 120keV D+ ion beams hitting a titanium target at the center of the source.

  5. Fast ion beam chopping system for neutron generators

    SciTech Connect

    Hahto, S.K.; Hahto, S.T.; Leung, K.N.; Reijonen, J.; Miller, T.G.; Van Staagen, P.K.

    2005-02-01

    Fast deuterium (D{sup +}) and tritium (T{sup +}) ion beam pulses are needed in some neutron-based imaging systems. A compact, integrated fast ion beam extraction and chopping system has been developed and tested at the Lawrence Berkeley National Laboratory for these applications, and beam pulses with 15 ns full width at half maximum have been achieved. Computer simulations together with experimental tests indicate that even faster pulses are achievable by shortening the chopper voltage rise time. This chopper arrangement will be implemented in a coaxial neutron generator, in which a small point-like neutron source is created by multiple 120 keV D{sup +} ion beams hitting a titanium target at the center of the source.

  6. Mutations, mutation rates, and evolution at the hypervariable VNTR loci of Yersinia pestis.

    PubMed

    Vogler, Amy J; Keys, Christine E; Allender, Christopher; Bailey, Ira; Girard, Jessica; Pearson, Talima; Smith, Kimothy L; Wagner, David M; Keim, Paul

    2007-03-01

    VNTRs are able to discriminate among closely related isolates of recently emerged clonal pathogens, including Yersinia pestis the etiologic agent of plague, because of their great diversity. Diversity is driven largely by mutation but little is known about VNTR mutation rates, factors affecting mutation rates, or the mutational mechanisms. The molecular epidemiological utility of VNTRs will be greatly enhanced when this foundational knowledge is available. Here, we measure mutation rates for 43 VNTR loci in Y. pestis using an in vitro generated population encompassing approximately 96,000 generations. We estimate the combined 43-locus rate and individual rates for 14 loci. A comparison of Y. pestis and Escherichia coli O157:H7 VNTR mutation rates and products revealed a similar relationship between diversity and mutation rate in these two species. Likewise, the relationship between repeat copy number and mutation rate is nearly identical between these species, suggesting a generalized relationship that may be applicable to other species. The single- versus multiple-repeat mutation ratios and the insertion versus deletion mutation ratios were also similar, providing support for a general model for the mutations associated with VNTRs. Finally, we use two small sets of Y. pestis isolates to show how this general model and our estimated mutation rates can be used to compare alternate phylogenies, and to evaluate the significance of genotype matches, near-matches, and mismatches found in empirical comparisons with a reference database. PMID:17161849

  7. 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.

  8. 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)

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. TERT Promoter Mutations in Thyroid Cancer.

    PubMed

    Alzahrani, Ali S; Alsaadi, Rawan; Murugan, Avaniyapuram Kannan; Sadiq, Bakr Bin

    2016-06-01

    Two mutations (C228T and C250T) in the promoter region of the telomerase reverse transcriptase (TERT) have recently been described in different types of cancer including follicular cell-derived thyroid cancer (TC). In this paper, we reviewed the rates of these mutations in different types and subtypes of TC, their association with a number of clinical and histopathological features and outcome of TC, and their potential diagnostic and prognostic roles in TC. The overall rate of these mutations in TC is about 14 % with least prevalence in the well-differentiated subtypes of papillary thyroid cancer (10-13 %). Their rates increase significantly with increasing aggressiveness of TC reaching about 40 % in the undifferentiated and anaplastic thyroid cancers. There is also clear association with increasing age of patients at the time of diagnosis of TC. The evidence is compelling but with some conflicting results for associations between TERT promoter mutations and tumor size, extrathyroidal invasion, distant metastases, high tumor TNM stage, BRAF (V600E) mutation, recurrence, and mortality. A couple of studies reported a potential diagnostic role for TERT promoter mutations in thyroid nodules with indeterminate cytology of fine needle aspiration biopsy. These studies showed 100 % specificity but very low sensitivity of 7-10 %. The sensitivity increases significantly when TERT promoter mutation testing is combined with other gene mutations, particularly BRAF (V600E) and RAS mutations. Although TERT promoter mutations seem to play significant roles in the pathogenesis of TC, the mechanisms by which they contribute to carcinogenesis remain elusive and future work is needed to fully assess the roles, interactions, and impact of these mutations on the pathogenesis, diagnosis, prognosis, and therapeutics of TC. PMID:26902827

  14. 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. PMID:20624042

  15. 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. PMID:16846117

  16. FAST - Five hundred meter Aperture Spherical radio Telescope

    NASA Astrophysics Data System (ADS)

    Nan, Ren-Dong

    2009-01-01

    The idea of sitting a large spherical dish in Karst depression is rooted in Arecibo telescope hosted by the NAIC of Cornell University. FAST is an Arecibo-type antenna with 3 outstanding aspects: the unique karst depression as the site; the active main reflector which corrects spherical aberration on the ground to achieve full polarization and wide band without involving complex feed system; and the light focus cabin driven by cables and servomechanism plus a parallel robot as secondary adjustable system to carry the most precise parts of the receivers. These design features will enable FAST to jumpstart many of science goals, such as HI neutral hydrogen line survey, pulsar survey, largest station in VLBI network, spectral line observations and Search for alien's technologies. The feasibility studies for FAST have been carried out for 14 years, being supported by Chinese and world astronomical communities. Funding for Project FAST has been approved by the National Development and Reform commission NDRC in July of 2007 with a capital budget 600 millions RMB and a project time of 5.5 years from the foundation. The first light is expected to be in early 2014. This work is supported by the Chinese Academy of Sciences and the National Natural Science Foundation of China (Grant No. 10433020). More than a hundred research personnel from over thirty research teams were involved in this research. On behalf of project FAST, I wish to make special recognition to their diligent work and great contribution to the project.

  17. Fast Flux Test Facility Closure Project - Project Management Plan

    SciTech Connect

    BEACH, R.R.

    2002-09-26

    The Fast Flux Test Facility (FFTF) Closure Project, Project Management Plan, Revision 5, provides the scope, cost, and schedule to achieve the most cost effective and expeditious closure of the FFTF to an assumed final end-state with the reactor vessel and the containment building, below the 5504 grade level, being entombed in place. Closure will be completed by December 2009 at a cost of $547 million.

  18. Fast sampling algorithm for Lie-Trotter products.

    PubMed

    Predescu, Cristian

    2005-04-01

    A fast algorithm for path sampling in path-integral Monte Carlo simulations is proposed. The algorithm utilizes the Lévy-Ciesielski implementation of Lie-Trotter products to achieve a mathematically proven computational cost of n log2(n) with the number of time slices n, despite the fact that each path variable is updated separately, for reasons of optimality. In this respect, we demonstrate that updating a group of random variables simultaneously results in loss of efficiency. PMID:15903719

  19. Fast adaptive interferometer with a photorefractive GaP crystal

    NASA Astrophysics Data System (ADS)

    Kamshilin, Alexei A.; Prokofiev, Victor V.

    2002-10-01

    The performance of an adaptive interferometer based on mixing of light waves with different polarization states in a photorefractive GaP crystal at λ = 0.633 μm is described. Both high sensitivity and fast response time are achieved with a low-power He-Ne laser. The parameters of the interferometer are appropriate for remote ultrasound detection in an industrial environment.

  20. A Compact, Fast, Wide-Field Imaging Spectrometer System

    NASA Technical Reports Server (NTRS)

    Mouroulis, Pantazis; VanGorp, Byron E.; White, Victor E.; Mumolo, Jason M.; Hebert, Daniel; Feldman, Martin

    2011-01-01

    We present test results from a compact, fast (F/1.4) imaging spectrometer system with a 33 degree field of view, operating in the 450-1650 nm wavelength region with an extended response InGaAs detector array. The system incorporates a simple two-mirror telescope and a steeply concave bilinear groove diffraction grating made with gray scale x-ray lithography techniques. High degree of spectral and spatial uniformity (97%) is achieved.

  1. [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. PMID:25443866

  2. Fast generation of stereolithographic models.

    PubMed

    Raic, K; Jansen, T; von Rymon-Lipinski, B; Tille, C; Seitz, H; Keeve, E

    2002-01-01

    In this paper we present a work-in-progress method for fast and efficient generation of stereolithographic models. The overall approach is embedded in our general software framework Julius, which runs on high-end-graphic systems as well as on low-level PCs. The design of the support structures needed for the stereolithographic process will allow semiautomatic generation of the model. We did produce support structures for stereolithographic models with this fast data processing pipeline and will show future perspectives in this paper. PMID:12451779

  3. The Sacramento Peak fast microphotometer

    NASA Technical Reports Server (NTRS)

    Arrambide, M. R.; Dunn, R. B.; Healy, A. W.; Porter, R.; Widener, A. L.; November, L. J.; Spence, G. E.

    1984-01-01

    The Sacramento Peak Observatory Fast Microphotometer translates an optical system that includes a laser and photodiode detector across the film to scan the Y direction. A stepping motor moves the film gate in the X direction. This arrangement affords high positional accuracy, low noise (0.002 RMS density units), modest speed (5000 points/second), large dynamic range (4.5 density units), high stability (0.005 density units), and low scattered light. The Fast Microphotometer is interfaced to the host computer by a 6502 microprocessor.

  4. Efficiency of carcinogenesis: is the mutator phenotype inevitable?

    PubMed

    Beckman, Robert A

    2010-10-01

    Cancer development requires multiple oncogenic mutations. Pathogenic mechanisms which accelerate this process may be favored carcinogenic pathways. Mutator mutations are mutations in genetic stability genes, and increase the mutation rate, speeding up the accumulation of oncogenic mutations. The mutator hypothesis states that mutator mutations play a critical role in carcinogenesis. Alternatively, tumors might arise by mutations occurring at the normal rate followed by selection and expansion of various premalignant lineages on the path to cancer. This alternative pathway is a significant argument against the mutator hypothesis. Mutator mutations may also lead to accumulation of deleterious mutations, which could lead to extinction of premalignant lineages before they become cancerous, another argument against the mutator hypothesis. Finally, the need for acquisition of a mutator mutation imposes an additional step on the carcinogenic process. Accordingly, the mutator hypothesis has been a seminal but controversial idea for several decades despite considerable experimental and theoretical work. To resolve this debate, the concept of efficiency has been introduced as a metric for comparing carcinogenic mechanisms, and a new theoretical approach of focused quantitative modeling has been applied. The results demonstrate that, given what is already known, the predominance of mutator mechanisms is likely inevitable, as they overwhelm less efficient non-mutator pathways to cancer. PMID:20934514

  5. Basic Skills Achievement, 1981-82.

    ERIC Educational Resources Information Center

    Austin Independent School District, TX. Office of Research and Evaluation.

    The Austin Independent School District (AISD) office of Research and Evaluation presents Basic Skills Achievement, 1981-82 (BSA). The BSA answers the following questions: (1) How does AISD student achievement compare to student achievement nationwide? (2) How does AISD's 1981-82 student achievement compare to the achievement of students in past…

  6. Studies of human mutation rates

    SciTech Connect

    Neel, J.V.

    1990-01-01

    November 1989, marked the beginning of a new three-year cycle of DOE grant support, in connection with which the program underwent a major reorganization. This document presents the progress on the three objectives of the present program which are: to isolate by the technique of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), proteins of special interest because of the relative mutability of the corresponding gene, establish the identity of the protein, and, for selected proteins, move to a characterization of the corresponding gene; to develop a more efficient approach, based on 2-D PAGE, for the detection of variants in DNA, with special reference to the identification of mutations in the parents of the individual whose DNA is being examined; and, to continue an effective interface with the genetic studies on the children of atomic bomb survivors in Japan, with reference to both the planning and implementation of new studies at the molecular level.

  7. Fast cost-volume filtering for visual correspondence and beyond.

    PubMed

    Hosni, Asmaa; Rhemann, Christoph; Bleyer, Michael; Rother, Carsten; Gelautz, Margrit

    2013-02-01

    Many computer vision tasks can be formulated as labeling problems. The desired solution is often a spatially smooth labeling where label transitions are aligned with color edges of the input image. We show that such solutions can be efficiently achieved by smoothing the label costs with a very fast edge-preserving filter. In this paper, we propose a generic and simple framework comprising three steps: 1) constructing a cost volume, 2) fast cost volume filtering, and 3) Winner-Takes-All label selection. Our main contribution is to show that with such a simple framework state-of-the-art results can be achieved for several computer vision applications. In particular, we achieve 1) disparity maps in real time whose quality exceeds those of all other fast (local) approaches on the Middlebury stereo benchmark, and 2) optical flow fields which contain very fine structures as well as large displacements. To demonstrate robustness, the few parameters of our framework are set to nearly identical values for both applications. Also, competitive results for interactive image segmentation are presented. With this work, we hope to inspire other researchers to leverage this framework to other application areas. PMID:22848130

  8. Coincidence electron/ion imaging with a fast frame camera

    NASA Astrophysics Data System (ADS)

    Li, Wen; Lee, Suk Kyoung; Lin, Yun Fei; Lingenfelter, Steven; Winney, Alexander; Fan, Lin

    2015-05-01

    A new time- and position- sensitive particle detection system based on a fast frame CMOS camera is developed for coincidence electron/ion imaging. The system is composed of three major components: a conventional microchannel plate (MCP)/phosphor screen electron/ion imager, a fast frame CMOS camera and a high-speed digitizer. The system collects the positional information of ions/electrons from a fast frame camera through real-time centroiding while the arrival times are obtained from the timing signal of MCPs processed by a high-speed digitizer. Multi-hit capability is achieved by correlating the intensity of electron/ion spots on each camera frame with the peak heights on the corresponding time-of-flight spectrum. Efficient computer algorithms are developed to process camera frames and digitizer traces in real-time at 1 kHz laser repetition rate. We demonstrate the capability of this system by detecting a momentum-matched co-fragments pair (methyl and iodine cations) produced from strong field dissociative double ionization of methyl iodide. We further show that a time resolution of 30 ps can be achieved when measuring electron TOF spectrum and this enables the new system to achieve a good energy resolution along the TOF axis.

  9. Significance of duon mutations in cancer genomes.

    PubMed

    Yadav, Vinod Kumar; Smith, Kyle S; Flinders, Colin; Mumenthaler, Shannon M; De, Subhajyoti

    2016-01-01

    Functional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed "duon mutations" due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types, and integrating allelic expression, overall mRNA expression, regulatory motif perturbation, and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures. PMID:27272679

  10. Analyzing effects of naturally occurring missense mutations.

    PubMed

    Zhang, Zhe; Miteva, Maria A; Wang, Lin; Alexov, Emil

    2012-01-01

    Single-point mutation in genome, for example, single-nucleotide polymorphism (SNP) or rare genetic mutation, is the change of a single nucleotide for another in the genome sequence. Some of them will produce an amino acid substitution in the corresponding protein sequence (missense mutations); others will not. This paper focuses on genetic mutations resulting in a change in the amino acid sequence of the corresponding protein and how to assess their effects on protein wild-type characteristics. The existing methods and approaches for predicting the effects of mutation on protein stability, structure, and dynamics are outlined and discussed with respect to their underlying principles. Available resources, either as stand-alone applications or webservers, are pointed out as well. It is emphasized that understanding the molecular mechanisms behind these effects due to these missense mutations is of critical importance for detecting disease-causing mutations. The paper provides several examples of the application of 3D structure-based methods to model the effects of protein stability and protein-protein interactions caused by missense mutations as well. PMID:22577471

  11. Model for Mutation in Bacterial Populations

    NASA Astrophysics Data System (ADS)

    Donangelo, R.; Fort, H.

    2002-07-01

    We describe the evolution of E. coli populations through a Bak-Sneppen-type model which incorporates random mutations. We show that, for a value of the mutation level which coincides with the one estimated from experiments, this model reproduces the measures of mean fitness relative to that of a common ancestor, performed for over 10 000 bacterial generations.

  12. Spectrum of mutations in alpha-mannosidosis.

    PubMed Central

    Berg, T; Riise, H M; Hansen, G M; Malm, D; Tranebjaerg, L; Tollersrud, O K; Nilssen, O

    1999-01-01

    alpha-Mannosidosis is an autosomal recessive disorder caused by deficiency of lysosomal alpha-mannosidase (LAMAN). The resulting intracellular accumulation of mannose-containing oligosaccharides leads to mental retardation, hearing impairment, skeletal changes, and immunodeficiency. Recently, we reported the first alpha-mannosidosis-causing mutation affecting two Palestinian siblings. In the present study 21 novel mutations and four polymorphic amino acid positions were identified by the screening of 43 patients, from 39 families, mainly of European origin. Disease-causing mutations were identified in 72% of the alleles and included eight splicing, six missense, and three nonsense mutations, as well as two small insertions and two small deletions. In addition, Southern blot analysis indicated rearrangements in some alleles. Most mutations were private or occurred in two or three families, except for a missense mutation resulting in an R750W substitution. This mutation was found in 13 patients, from different European countries, and accounted for 21% of the disease alleles. Although there were clinical variations among the patients, no significant LAMAN activity could be detected in any of the fibroblast cultures. In addition, no correlation between the types of mutations and the clinical manifestations was evident. PMID:9915946

  13. De novo mutations in epileptic encephalopathies.

    PubMed

    Allen, Andrew S; Berkovic, Samuel F; Cossette, Patrick; Delanty, Norman; Dlugos, Dennis; Eichler, Evan E; Epstein, Michael P; Glauser, Tracy; Goldstein, David B; Han, Yujun; Heinzen, Erin L; Hitomi, Yuki; Howell, Katherine B; Johnson, Michael R; Kuzniecky, Ruben; Lowenstein, Daniel H; Lu, Yi-Fan; Madou, Maura R Z; Marson, Anthony G; Mefford, Heather C; Esmaeeli Nieh, Sahar; O'Brien, Terence J; Ottman, Ruth; Petrovski, Slavé; Poduri, Annapurna; Ruzzo, Elizabeth K; Scheffer, Ingrid E; Sherr, Elliott H; Yuskaitis, Christopher J; Abou-Khalil, Bassel; Alldredge, Brian K; Bautista, Jocelyn F; Berkovic, Samuel F; Boro, Alex; Cascino, Gregory D; Consalvo, Damian; Crumrine, Patricia; Devinsky, Orrin; Dlugos, Dennis; Epstein, Michael P; Fiol, Miguel; Fountain, Nathan B; French, Jacqueline; Friedman, Daniel; Geller, Eric B; Glauser, Tracy; Glynn, Simon; Haut, Sheryl R; Hayward, Jean; Helmers, Sandra L; Joshi, Sucheta; Kanner, Andres; Kirsch, Heidi E; Knowlton, Robert C; Kossoff, Eric H; Kuperman, Rachel; Kuzniecky, Ruben; Lowenstein, Daniel H; McGuire, Shannon M; Motika, Paul V; Novotny, Edward J; Ottman, Ruth; Paolicchi, Juliann M; Parent, Jack M; Park, Kristen; Poduri, Annapurna; Scheffer, Ingrid E; Shellhaas, Renée A; Sherr, Elliott H; Shih, Jerry J; Singh, Rani; Sirven, Joseph; Smith, Michael C; Sullivan, Joseph; Lin Thio, Liu; Venkat, Anu; Vining, Eileen P G; Von Allmen, Gretchen K; Weisenberg, Judith L; Widdess-Walsh, Peter; Winawer, Melodie R

    2013-09-12

    Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders. PMID:23934111

  14. 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

  15. Core binding factor acute myeloid leukaemia and c-KIT mutations.

    PubMed

    Riera, Ludovica; Marmont, Filippo; Toppino, Daniela; Frairia, Chiara; Sismondi, Francesca; Audisio, Ernesta; Di Bello, Cristiana; D'Ardia, Stefano; Di Celle, Paola Francia; Messa, Emanuela; Inghirami, Giorgio; Vitolo, Umberto; Pich, Achille

    2013-05-01

    Core binding factor (CBF) acute myeloid leukaemia (AML) represents 5-8% of all AMLs and has a relatively favourable prognosis. However, activating c-KIT mutations are reported to be associated with higher risk of relapse and shorter survival. To verify the incidence and prognostic value of c-KIT mutations in CBF AML, we retrospectively analysed bone marrow samples of 23 consecutive adult patients with de novo CBF AML [14 inv(16) and 9 t(8;21)] treated at a single institution from 2000 to 2011. All patients received standard induction chemotherapy with cytarabine, idarubicin and etoposide; 13 underwent allogeneic stem cell transplantation. c-KIT mutations in exons 8, 9, 10, 11, 13, 14 and 17 were assessed by PCR amplification in combination with direct sequencing. c-KIT mutations (3 in exon 10 and 4 in exon 17) were detected in 7/23 (30.4%) patients, 3 with t(8;21) and 4 with inv(16). No difference in c-KIT mutation status was observed between cases with inv(16) or t(8;21) alone and cases with additional cytogenetic abnormalities. No association between gender, age, white blood cell and platelet count, peripheral blood and bone marrow blast cells at diagnosis, achievement of complete remission, cytogenetic risk groups and Wilms tumour gene 1 (WT1) levels was found. On the contrary, lactate dehydrogenase (LDH) values were higher in mutated than in non-mutated patients (p=0.01). Overall survival (OS) rates were longer in CBF compared to the other types of AML and disease-free survival (DFS) was longer in inv(16) than in t(8;21) AML. OS and DFS were similar in mutated and non-mutated CBF AML patients. Our results confirm a better prognosis for CBF AML than all other AML categories, and for inv(16) than t(8;21) AML. However, no prognostic value for c-KIT mutational status was found in our series. The association between LDH levels and c-KIT mutation would indicate a more active proliferation for mutated CBF AML. PMID:23467883

  16. Hotspot-Mutation Analysis of the EGFR/KRAS/BRAF Pathway Using Mutation Surveyor® Software

    PubMed Central

    Hulce, D.; LeVan, K.; Shouyong, N.; Liu, J.

    2011-01-01

    Hotspot-mutation analysis of the EGFR/KRAS/BRAF pathway (or other clinically relevant pathway) can quickly genotype patients as candidates who may respond favorably to specific drug treatments and therapies or into other groups where treatment options are limited and less favorable. Sanger sequencing analysis using Mutation Surveyor software provides high-throughput, high-sensitivity variation detection. Increased efficiency can be achieved using flexible and customizable reporting-sequencing results can be organized by patient identifiers, variation type (reported or unreported, pathogenic or benign or drug sensitive), by gene/exon/amplicon, or quality metrics, and other options. GenBank sequence files from NCBI for EGFR exons 18, 19, 20, and 21; KRAS exons 2 and 3; and BRAF exon 15 were edited to contain reported variations. These reported variations included polymorphisms from dbSNP (downloaded with the GenBank file), pathogenic and drug-sensitivity variations for EGFR (obtained from http://www.egfr.org/), activating mutations for KRAS, and constitutive mutations for BRAF. Bidirectional sequencing data for twelve, simulated (mutations obtained from sequencing reports in the scientific literature), patients were developed and compared to the customized GenBank sequences. Sequencing analysis results were grouped by patient-specific identifiers. Any unmatched or low quality data files are identified in the report, indicating which samples require resequencing. Mutations that match reported variations added to the GenBank sequences are highlighted-SNP identifiers or color coding of SNP type quickly indicate which variations are pathogenic or drug-sensitive or reported in dbSNP. Unreported variations are not highlighted and may be benign or variations of unknown significance. The gene column displays the gene and accession number for that gene used for the analysis. The exon column displays the exon number of the gene, and accession numbers of the mRNA and protein

  17. Validation of Deleterious Mutations in Vorderwald Cattle

    PubMed Central

    Reinartz, Sina; Distl, Ottmar

    2016-01-01

    In Montbéliarde cattle two candidate mutations on bovine chromosomes 19 and 29 responsible for embryonic lethality have been detected. Montbéliarde bulls have been introduced into Vorderwald cattle to improve milk and fattening performance. Due to the small population size of Vorderwald cattle and the wide use of a few Montbéliarde bulls through artificial insemination, inbreeding on Montbéliarde bulls in later generations was increasing. Therefore, we genotyped an aborted fetus which was inbred on Montbéliarde as well as Vorderwald x Montbéliarde crossbred bulls for both deleterious mutations. The abortion was observed in an experimental herd of Vorderwald cattle. The objectives of the present study were to prove if one or both lethal mutations may be assumed to have caused this abortion and to show whether these deleterious mutations have been introduced into the Vorderwald cattle population through Montbéliarde bulls. The aborted fetus was homozygous for the SLC37A2:g.28879810C>T mutation (ss2019324563) on BTA29 and both parents as well as the paternal and maternal grandsire were heterozygous for this mutation. In addition, the parents and the paternal grandsire were carriers of the MH2-haplotype linked with the T-allele of the SLC37A2:g.28879810C>T mutation. For the SHBG:g.27956790C>T mutation (rs38377500) on BTA19 (MH1), the aborted fetus and its sire were heterozygous. Among all further 341 Vorderwald cattle genotyped we found 27 SLC37A2:g.28879810C>T heterozygous animals resulting in an allele frequency of 0.0396. Among the 120 male Vorderwald cattle, there were 12 heterozygous with an allele frequency of 0.05. The SLC37A2:g.28879810C>T mutation could not be found in further nine cattle breeds nor in Vorderwald cattle with contributions from Ayrshire bulls. In 69 Vorderwald cattle without genes from Montbéliarde bulls the mutated allele of SLC37A2:g.28879810C>T could not be detected. The SHBG:g.27956790C>T mutation appeared unlikely to be responsible

  18. Validation of Deleterious Mutations in Vorderwald Cattle.

    PubMed

    Reinartz, Sina; Distl, Ottmar

    2016-01-01

    In Montbéliarde cattle two candidate mutations on bovine chromosomes 19 and 29 responsible for embryonic lethality have been detected. Montbéliarde bulls have been introduced into Vorderwald cattle to improve milk and fattening performance. Due to the small population size of Vorderwald cattle and the wide use of a few Montbéliarde bulls through artificial insemination, inbreeding on Montbéliarde bulls in later generations was increasing. Therefore, we genotyped an aborted fetus which was inbred on Montbéliarde as well as Vorderwald x Montbéliarde crossbred bulls for both deleterious mutations. The abortion was observed in an experimental herd of Vorderwald cattle. The objectives of the present study were to prove if one or both lethal mutations may be assumed to have caused this abortion and to show whether these deleterious mutations have been introduced into the Vorderwald cattle population through Montbéliarde bulls. The aborted fetus was homozygous for the SLC37A2:g.28879810C>T mutation (ss2019324563) on BTA29 and both parents as well as the paternal and maternal grandsire were heterozygous for this mutation. In addition, the parents and the paternal grandsire were carriers of the MH2-haplotype linked with the T-allele of the SLC37A2:g.28879810C>T mutation. For the SHBG:g.27956790C>T mutation (rs38377500) on BTA19 (MH1), the aborted fetus and its sire were heterozygous. Among all further 341 Vorderwald cattle genotyped we found 27 SLC37A2:g.28879810C>T heterozygous animals resulting in an allele frequency of 0.0396. Among the 120 male Vorderwald cattle, there were 12 heterozygous with an allele frequency of 0.05. The SLC37A2:g.28879810C>T mutation could not be found in further nine cattle breeds nor in Vorderwald cattle with contributions from Ayrshire bulls. In 69 Vorderwald cattle without genes from Montbéliarde bulls the mutated allele of SLC37A2:g.28879810C>T could not be detected. The SHBG:g.27956790C>T mutation appeared unlikely to be responsible

  19. 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

  20. 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.