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Sample records for achieve fast mutation

  1. 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

  2. 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.

  3. 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.

  4. 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

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

    PubMed

    Logan, Ian S

    2016-03-18

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

  6. 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.

  7. 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

  8. The Compact Mutation of Myostatin Causes a Glycolytic Shift in the Phenotype of Fast Skeletal Muscles

    PubMed Central

    Baán, Júlia Aliz; Kocsis, Tamás; Keller-Pintér, Anikó; Müller, Géza; Zádor, Ernö; Dux, László

    2013-01-01

    Myostatin is an important negative regulator of skeletal muscle growth. The hypermuscular Compact (Cmpt) mice carry a 12-bp natural mutation in the myostatin propeptide, with additional modifier genes being responsible for the phenotype. Muscle cellularity of the fast-type tibialis anterior (TA) and extensor digitorum longus (EDL) as well as the mixed-type soleus (SOL) muscles of Cmpt and wild-type mice was examined by immunohistochemical staining of the myosin heavy chain (MHC) proteins. In addition, transcript levels of MHC isoforms were quantified by qPCR. Based on our results, all investigated muscles of Cmpt mice were significantly larger compared with that of wild-type mice, as characterized by fiber hyperplasia of different grades. Fiber hypertrophy was not present in TA; however, EDL muscles showed specific IIB fiber hypertrophy while the (I and IIA) fibers of SOL muscles were generally hypertrophied. Both the fast TA and EDL muscles of Cmpt mice contained significantly more glycolytic IIB fibers accompanied by a decreased number of IIX and IIA fibers; however, this was not the case for SOL muscles. In summary, despite the variances found in muscle cellularity between the different myostatin mutant mice, similar glycolytic shifts were observed in Cmpt fast muscles as in muscles from myostatin knockout mice. PMID:23979839

  9. Achievement of Cure with Gefitinib in Advanced Lung Adenocarcinoma Harboring an Activating EGFR Mutation: A Case Report

    PubMed Central

    Kuwata, Taiji; Yoneda, Kazue; Kobayashi, Kenichi; Oyama, Rintarou; Matumiya, Hiroki; Shinohara, Shuichi; Takenaka, Masaru; Oka, Soichi; Chikaishi, Yasuhiro; Imanishi, Naoko; Kuroda, Koji; Tanaka, Fumihiro

    2016-01-01

    Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) may achieve long-term survival in selected cases with advanced non-small cell lung cancer harboring activating mutations in the EGFR gene, but a cured case has not been reported yet. Here, we present the first case of EGFR-mutated lung adenocarcinoma cured with an EGFR-TKI, as the 75-year-old Japanese man has achieved complete response with gefitinib treatment and has survived without tumor 10 years after termination of gefitinib treatment.

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

    PubMed

    Keogh, Louise A; Otlowski, Margaret F A

    2013-09-01

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

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

    PubMed

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

    2008-09-01

    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 approximately 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 (approximately 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.

  12. The High-Potential Fast-Flying Achiever: Themes from the English Language Literature 1976-1995.

    ERIC Educational Resources Information Center

    Altman, Yochanan

    1997-01-01

    Review of business management literature from the United States, United Kingdom, and Canada identified the following: the images of high flyer, fast track, and high achiever; the meaning of success; emphasis on performance; corporate rites of passage; and opportunities for women to be high flyers. (SK)

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  15. 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

  16. 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…

  17. 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

  18. 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

  19. 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.

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

    PubMed

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

    2015-11-01

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

  1. A Comparison of "Reading Mastery Fast Cycle" and "Horizons Fast Track A-B" on the Reading Achievement of Students with Mild Disabilities

    ERIC Educational Resources Information Center

    Cooke, Nancy L.; Gibbs, Susan L.; Campbell, Monica L.; Shalvis, Shawnna L.

    2004-01-01

    This study examined the reading gains of students with mild disabilities who were taught with one of two programs: "Horizons Fast Track A-B" (Engelmann, Engelmann, & Seitz-Davis, 1997) or "Reading Mastery Fast Cycle" (Engelmann & Bruner, 1995). A quasi-experimental design with preexisting groups was used to examine changes from pretest to…

  2. Fast side chain replacement in proteins using a coarse-grained approach for evaluating the effects of mutation during evolution.

    PubMed

    Grahnen, Johan A; Kubelka, Jan; Liberles, David A

    2011-08-01

    For high-throughput structural genomic and evolutionary bioinformatics approaches, there is a clear need for fast methods to evaluate substitutions structurally. Coarse-grained methods are both powerful and fast, and a coarse-grained approach to position the substituted side chains is presented. Through the application of a coarse-grained method, a speed-up on the single- residue replacement, of at least sevenfold is achieved compared with modern all-atom approaches. At the same time, this approach maintains a small median RMSD from the leading all-atom approach (as measured in coarse-grained space), and predicts the conformation of point mutants with similar accuracy and generates biologically realistic side chain angles. This method is also substantially more predictable in its run time, making it useful for high-throughput studies of protein structural evolution. To demonstrate the utility of this method, it has been implemented in a forward simulation of sequences threaded through the SH2 domains, with selective pressures to fold and bind specifically. The relative substitution rates across the protein structure and at the binding interface are reflective of those observed in SH2 domain evolution. The algorithm has been implemented in C++, with the source code and binaries (currently supported for Linux systems) freely available as SARA at http://www.wyomingbioinformatics.org/LiberlesGroup/SARA .

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

    PubMed

    Nicholas, Frank W; Hobbs, Matthew

    2014-04-01

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

  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. 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

  6. The Domain II S4-S5 Linker in Nav1.9: A Missense Mutation Enhances Activation, Impairs Fast Inactivation, and Produces Human Painful Neuropathy.

    PubMed

    Han, Chongyang; Yang, Yang; de Greef, Bianca T A; Hoeijmakers, Janneke G J; Gerrits, Monique M; Verhamme, Camiel; Qu, Jian; Lauria, Giuseppe; Merkies, Ingemar S J; Faber, Catharina G; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2015-06-01

    Painful small fiber neuropathy is a challenging medical condition with no effective treatment. Non-genetic causes can be identified in one half of the subjects. Gain-of-function variants of sodium channels Nav1.7 and Nav1.8 have recently been associated with painful small fiber neuropathy. More recently, mutations of sodium channel Nav1.9 have been linked to human pain disorders, with two gain-of-function mutations found in patients with painful small fiber neuropathy. Here we report a novel Nav1.9 mutation, a glycine 699 substitution by arginine (G699R) in the domain II S4-S5 linker, identified in a patient with painful small fiber neuropathy. In this study, we assayed the mutant channels by voltage-clamp in superior cervical ganglion neurons, which do not produce endogenous Nav1.8 or Nav1.9 currents, and provide a novel platform where Nav1.9 is expressed at relatively high levels. Voltage-clamp analysis showed that the mutation hyperpolarizes (-10.1 mV) channel activation, depolarizes (+6.3 mV) steady-state fast inactivation, slows deactivation, and enhances ramp responses compared with wild-type Nav1.9 channels. Current-clamp analysis showed that the G699R mutant channels render dorsal root ganglion neurons hyperexcitable, via depolarized resting membrane potential, reduced current threshold and increased evoked firing. These observations show that the domain II S4-S5 linker plays an important role in the gating of Nav1.9 and demonstrates that a mutation in this linker is linked to a common pain disorder. PMID:25791876

  7. The Domain II S4-S5 Linker in Nav1.9: A Missense Mutation Enhances Activation, Impairs Fast Inactivation, and Produces Human Painful Neuropathy.

    PubMed

    Han, Chongyang; Yang, Yang; de Greef, Bianca T A; Hoeijmakers, Janneke G J; Gerrits, Monique M; Verhamme, Camiel; Qu, Jian; Lauria, Giuseppe; Merkies, Ingemar S J; Faber, Catharina G; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2015-06-01

    Painful small fiber neuropathy is a challenging medical condition with no effective treatment. Non-genetic causes can be identified in one half of the subjects. Gain-of-function variants of sodium channels Nav1.7 and Nav1.8 have recently been associated with painful small fiber neuropathy. More recently, mutations of sodium channel Nav1.9 have been linked to human pain disorders, with two gain-of-function mutations found in patients with painful small fiber neuropathy. Here we report a novel Nav1.9 mutation, a glycine 699 substitution by arginine (G699R) in the domain II S4-S5 linker, identified in a patient with painful small fiber neuropathy. In this study, we assayed the mutant channels by voltage-clamp in superior cervical ganglion neurons, which do not produce endogenous Nav1.8 or Nav1.9 currents, and provide a novel platform where Nav1.9 is expressed at relatively high levels. Voltage-clamp analysis showed that the mutation hyperpolarizes (-10.1 mV) channel activation, depolarizes (+6.3 mV) steady-state fast inactivation, slows deactivation, and enhances ramp responses compared with wild-type Nav1.9 channels. Current-clamp analysis showed that the G699R mutant channels render dorsal root ganglion neurons hyperexcitable, via depolarized resting membrane potential, reduced current threshold and increased evoked firing. These observations show that the domain II S4-S5 linker plays an important role in the gating of Nav1.9 and demonstrates that a mutation in this linker is linked to a common pain disorder.

  8. 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

  9. 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.

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

    PubMed

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

    2000-08-01

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

  11. Coupling between fast and slow inactivation revealed by analysis of a point mutation (F1304Q) in mu 1 rat skeletal muscle sodium channels.

    PubMed Central

    Nuss, H B; Balser, J R; Orias, D W; Lawrence, J H; Tomaselli, G F; Marban, E

    1996-01-01

    1. We sought to elucidate the mechanism of the defective inactivation that characterizes sodium channels containing mutations in the cytoplasmic loop between the third and fourth domains (the III-IV linker). Specifically, we measured whole-cell and single-channel currents through wild-type and F1304Q mutant mu 1 rat skeletal muscle Na+ channels expressed in Xenopus laevis oocytes. 2. In wild-type channels, inactivation is complete and the faster of two decay components predominates. In F1304Q, inactivation is incomplete; the slow decay component is larger in amplitude and slower than in wild-type. The fraction of non-inactivating current is substantial (37 +/- 2% of peak current at -20 mV) in F1304Q. 3. Cell-attached patch recordings confirmed the profound kinetic differences and indicated that permeation was not altered by the F1304Q mutation. The F1304Q phenotype must be conferred entirely by changes in gating properties and is not remedied by coexpression with the beta 1-subunit. 4. Recovery from inactivation of F1304Q channels is faster than for wild-type channels and three exponentials are required to describe recovery adequately following long (5 s) depolarizations. Thus, there are three inactivated states even in 'inactivation-deficient' F1304Q channels. 5. The steady-state voltage dependence of F1304Q inactivation is right-shifted by 26 +/- 2 mV. 6. A gating model incorporating three inactivated states, all directly accessible from multiple closed states or the open state, was constrained to fit wild-type and F1304Q inactivation (h infinitive) data and repriming data simultaneously. While it was necessary to alter the rate constants entering and exiting all three inactivated states, the model accounted for the F1304Q-induced rightward shift in steady-state inactivation without imposing voltage dependence on the inactivation rate constants. 7. We conclude that the F1304Q mutation in mu 1 sodium channels modifies several inactivation processes simultaneously

  12. 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.

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

    PubMed

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

    2015-12-22

    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 BRAF(V600E) and BRAF(V600K) 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.

  14. 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

  15. The Effects of Fast Start Reading: A Fluency-Based Home Involvement Reading Program, on the Reading Achievement of Beginning Readers

    ERIC Educational Resources Information Center

    Rasinski, Timothy; Stevenson, Bruce

    2005-01-01

    This study tested the effects of a fluency-based home reading program called Fast Start. Thirty beginning first-grade students, representing a wide range of early reading abilities, were randomly assigned to experimental or control conditions for a period of 11 weeks. Parents and students in the experimental group received Fast Start training,…

  16. Preventing the transmission of pathogenic mitochondrial DNA mutations: can we achieve long-term benefits from germ-line gene transfer?

    PubMed Central

    Samuels, David C.; Wonnapinij, Passorn; Chinnery, Patrick F.

    2013-01-01

    Mitochondrial medicine is one of the few areas of genetic disease where germ-line transfer is being actively pursued as a treatment option. All of the germ-line transfer methods currently under development involve some carry-over of the maternal mitochondrial DNA (mtDNA) heteroplasmy, potentially delivering the pathogenic mutation to the offspring. Rapid changes in mtDNA heteroplasmy have been observed within a single generation, and so any ‘leakage’ of mutant mtDNA could lead to mtDNA disease in future generations, compromising the reproductive health of the first generation, and leading to repeated interventions in subsequent generations. To determine whether this is a real concern, we developed a model of mtDNA heteroplasmy inheritance by studying 87 mother–child pairs, and predicted the likely outcome of different levels of ‘mutant mtDNA leakage’ on subsequent maternal generations. This showed that, for a clinical threshold of 60%, reducing the proportion of mutant mtDNA to <5% dramatically reduces the chance of disease recurrence in subsequent generations, but transmitting >5% mutant mtDNA was associated with a significant chance of disease recurrence. Mutations with a lower clinical threshold were associated with a higher risk of recurrence. Our findings provide reassurance that, at least from an mtDNA perspective, methods currently under development have the potential to effectively eradicate pathogenic mtDNA mutations from subsequent generations. PMID:23297368

  17. Preventing the transmission of pathogenic mitochondrial DNA mutations: Can we achieve long-term benefits from germ-line gene transfer?

    PubMed

    Samuels, David C; Wonnapinij, Passorn; Chinnery, Patrick F

    2013-03-01

    Mitochondrial medicine is one of the few areas of genetic disease where germ-line transfer is being actively pursued as a treatment option. All of the germ-line transfer methods currently under development involve some carry-over of the maternal mitochondrial DNA (mtDNA) heteroplasmy, potentially delivering the pathogenic mutation to the offspring. Rapid changes in mtDNA heteroplasmy have been observed within a single generation, and so any 'leakage' of mutant mtDNA could lead to mtDNA disease in future generations, compromising the reproductive health of the first generation, and leading to repeated interventions in subsequent generations. To determine whether this is a real concern, we developed a model of mtDNA heteroplasmy inheritance by studying 87 mother-child pairs, and predicted the likely outcome of different levels of 'mutant mtDNA leakage' on subsequent maternal generations. This showed that, for a clinical threshold of 60%, reducing the proportion of mutant mtDNA to <5% dramatically reduces the chance of disease recurrence in subsequent generations, but transmitting >5% mutant mtDNA was associated with a significant chance of disease recurrence. Mutations with a lower clinical threshold were associated with a higher risk of recurrence. Our findings provide reassurance that, at least from an mtDNA perspective, methods currently under development have the potential to effectively eradicate pathogenic mtDNA mutations from subsequent generations.

  18. Fast and reliable screening of mutations in human tumors: use of multiple fluorescence-based long linker arm nucleotides assay (mf-LLA).

    PubMed

    Marcelino, L A; Galvin, M; Martins, G M; Proença, M J; Mayrand, E; Rueff, J A; Monteiro, C J

    1999-06-01

    Human tumor samples were screened for point mutations by adapting a mobility-shift assay to automated DNA sizing. This screen identifies the type of point mutation and relative amount of mutated DNA sequences present in a sample. Test samples having known hypoxanthine-guanine phosphoribosyl transferase (hprt)/exon-3 sequence mutations were characterized by: (i) PCR amplification, (ii) fluorescent dye-primer extension with 36-atom linker derived deoxycytosine or deoxyuridine triphosphate and the remaining three natural nucleotides and (iii) sizing of the resulting fluorescently labeled modified strands, using an automated DNA sequencer. Routinely, a range of sizes is observed among the sequence variants of a single DNA target sequence. This is because nucleotide analogs are incorporated into DNA strands in a sequence-dependent manner, resulting in composition-dependent electrophoretic mobility. Thus, point mutations are identified as shifts in mobility between the fluorescently labeled modified strands of the control and test samples. The twenty different hprt/exon-3 single-base substitution mutations tested were easily identified, even at fourfold dilution with control DNA.

  19. 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.

  20. 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)

  1. Do mutator mutations fuel tumorigenesis?

    PubMed

    Fox, Edward J; Prindle, Marc J; Loeb, Lawrence A

    2013-12-01

    The mutator phenotype hypothesis proposes that the mutation rate of normal cells is insufficient to account for the large number of mutations found in human cancers. Consequently, human tumors exhibit an elevated mutation rate that increases the likelihood of a tumor acquiring advantageous mutations. The hypothesis predicts that tumors are composed of cells harboring hundreds of thousands of mutations, as opposed to a small number of specific driver mutations, and that malignant cells within a tumor therefore constitute a highly heterogeneous population. As a result, drugs targeting specific mutated driver genes or even pathways of mutated driver genes will have only limited anticancer potential. In addition, because the tumor is composed of such a diverse cell population, tumor cells harboring drug-resistant mutations will exist prior to the administration of any chemotherapeutic agent. We present recent evidence in support of the mutator phenotype hypothesis, major arguments against this concept, and discuss the clinical consequences of tumor evolution fueled by an elevated mutation rate. We also consider the therapeutic possibility of altering the rate of mutation accumulation. Most significantly, we contend that there is a need to fundamentally reconsider current approaches to personalized cancer therapy. We propose that targeting cellular pathways that alter the rate of mutation accumulation in tumors will ultimately prove more effective than attempting to identify and target mutant driver genes or driver pathways.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Neighborhood fast food availability and fast food consumption

    PubMed Central

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

    2015-01-01

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

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Sex and deleterious mutations.

    PubMed

    Gordo, Isabel; Campos, Paulo R A

    2008-05-01

    The evolutionary advantage of sexual reproduction has been considered as one of the most pressing questions in evolutionary biology. While a pluralistic view of the evolution of sex and recombination has been suggested by some, here we take a simpler view and try to quantify the conditions under which sex can evolve given a set of minimal assumptions. Since real populations are finite and also subject to recurrent deleterious mutations, this minimal model should apply generally to all populations. We show that the maximum advantage of recombination occurs for an intermediate value of the deleterious effect of mutations. Furthermore we show that the conditions under which the biggest advantage of sex is achieved are those that produce the fastest fitness decline in the corresponding asexual population and are therefore the conditions for which Muller's ratchet has the strongest effect. We also show that the selective advantage of a modifier of the recombination rate depends on its strength. The quantification of the range of selective effects that favors recombination then leads us to suggest that, if in stressful environments the effect of deleterious mutations is enhanced, a connection between sex and stress could be expected, as it is found in several species.

  12. Driver Missense Mutation Identification Using Feature Selection and Model Fusion.

    PubMed

    Soliman, Ahmed T; Meng, Tao; Chen, Shu-Ching; Iyengar, S S; Iyengar, Puneeth; Yordy, John; Shyu, Mei-Ling

    2015-12-01

    Driver mutations propel oncogenesis and occur much less frequently than passenger mutations. The need for automatic and accurate identification of driver mutations has increased dramatically with the exponential growth of mutation data. Current computational solutions to identify driver mutations rely on sequence homology. Here we construct a machine learning-based framework that does not rely on sequence homology or domain knowledge to predict driver missense mutations. A windowing approach to represent the local environment of the sequence around the mutation point as a mutation sample is applied, followed by extraction of three sequence-level features from each sample. After selecting the most significant features, the support vector machine and multimodal fusion strategies are employed to give final predictions. The proposed framework achieves relatively high performance and outperforms current state-of-the-art algorithms. The ease of deploying the proposed framework and the relatively accurate performance make this solution applicable to large-scale mutation data analyses. PMID:26402258

  13. Fasting - the ultimate diet?

    PubMed

    Johnstone, A M

    2007-05-01

    Adult humans often undertake acute fasts for cosmetic, religious or medical reasons. For example, an estimated 14% of US adults have reported using fasting as a means to control body weight and this approach has long been advocated as an intermittent treatment for gross refractory obesity. There are unique historical data sets on extreme forms of food restriction that give insight into the consequences of starvation or semi-starvation in previously healthy, but usually non-obese subjects. These include documented medical reports on victims of hunger strike, famine and prisoners of war. Such data provide a detailed account on how the body adapts to prolonged starvation. It has previously been shown that fasting for the biblical period of 40 days and 40 nights is well within the overall physiological capabilities of a healthy adult. However, the specific effects on the human body and mind are less clearly documented, either in the short term (hours) or in the longer term (days). This review asks the following three questions, pertinent to any weight-loss therapy, (i) how effective is the regime in achieving weight loss, (ii) what impact does it have on psychology? and finally, (iii) does it work long-term? PMID:17444963

  14. A fluorescent multiplex-DGGE screening test for mutations in the BRCA1 gene.

    PubMed

    Kuperstein, Graciela; Jack, Elaine; Narod, Steven A

    2006-01-01

    Screening for mutations in the BRCA1 gene is challenging because of the wide spectrum of mutations found in this large gene. As the extensive exon 11 is commonly screened by the protein truncation test (PTT), here a fluorescent multiplex denaturing gradient gel electrophoresis (FMD) mutation screening technique was developed to test the remaining numerous small exons and splice sites of the gene. The method is based upon the use of an efficient multiplex polymerase chain reaction (PCR) amplification of the target regions, followed by denaturing gradient gel electrophoresis (DGGE) separation of the amplicon mixture, and the immediate achievement of results by wet gel scanning. The technique was applied to screen 16 samples with different BRCA1 sequence variants distributed over 12 exons. All variants were detected. In addition, 188 DNA samples from ovarian cancer patients were screened, identifying 22 new sequence variants (11.7% of the samples) and 243 common polymorphisms in the BRCA1 locus. Variants included 16 single nucleotide substitutions, 3 deletions of 2 nucleotides, 1 deletion of 4 nucleotides, and 2 insertions of 1 nucleotide. The FMD test provides an accurate, fast, nonradioactive and cost-efficient way to scan the BRCA1 gene with high sensitivity and an ease of result interpretation. This technique may prove to be a useful research tool for the detection of mutations and polymorphisms in the BRCA1 gene and for large-scale epidemiologic studies. PMID:16544996

  15. Mitochondrial DNA mutations in human cancer.

    PubMed

    Chatterjee, A; Mambo, E; Sidransky, D

    2006-08-01

    Somatic mitochondrial DNA (mtDNA) mutations have been increasingly observed in primary human cancers. As each cell contains many mitochondria with multiple copies of mtDNA, it is possible that wild-type and mutant mtDNA can co-exist in a state called heteroplasmy. During cell division, mitochondria are randomly distributed to daughter cells. Over time, the proportion of the mutant mtDNA within the cell can vary and may drift toward predominantly mutant or wild type to achieve homoplasmy. Thus, the biological impact of a given mutation may vary, depending on the proportion of mutant mtDNAs carried by the cell. This effect contributes to the various phenotypes observed among family members carrying the same pathogenic mtDNA mutation. Most mutations occur in the coding sequences but few result in substantial amino acid changes raising questions as to their biological consequence. Studies reveal that mtDNA play a crucial role in the development of cancer but further work is required to establish the functional significance of specific mitochondrial mutations in cancer and disease progression. The origin of somatic mtDNA mutations in human cancer and their potential diagnostic and therapeutic implications in cancer are discussed. This review article provides a detailed summary of mtDNA mutations that have been reported in various types of cancer. Furthermore, this review offers some perspective as to the origin of these of mutations, their functional consequences in cancer development, and possible therapeutic implications.

  16. 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…

  17. Automated extraction and semantic analysis of mutation impacts from the biomedical literature

    PubMed Central

    2012-01-01

    Background Mutations as sources of evolution have long been the focus of attention in the biomedical literature. Accessing the mutational information and their impacts on protein properties facilitates research in various domains, such as enzymology and pharmacology. However, manually curating the rich and fast growing repository of biomedical literature is expensive and time-consuming. As a solution, text mining approaches have increasingly been deployed in the biomedical domain. While the detection of single-point mutations is well covered by existing systems, challenges still exist in grounding impacts to their respective mutations and recognizing the affected protein properties, in particular kinetic and stability properties together with physical quantities. Results We present an ontology model for mutation impacts, together with a comprehensive text mining system for extracting and analysing mutation impact information from full-text articles. Organisms, as sources of proteins, are extracted to help disambiguation of genes and proteins. Our system then detects mutation series to correctly ground detected impacts using novel heuristics. It also extracts the affected protein properties, in particular kinetic and stability properties, as well as the magnitude of the effects and validates these relations against the domain ontology. The output of our system can be provided in various formats, in particular by populating an OWL-DL ontology, which can then be queried to provide structured information. The performance of the system is evaluated on our manually annotated corpora. In the impact detection task, our system achieves a precision of 70.4%-71.1%, a recall of 71.3%-71.5%, and grounds the detected impacts with an accuracy of 76.5%-77%. The developed system, including resources, evaluation data and end-user and developer documentation is freely available under an open source license at http://www.semanticsoftware.info/open-mutation-miner. Conclusion We present

  18. 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

  19. 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.

  20. Mutational landscape of yeast mutator strains.

    PubMed

    Serero, Alexandre; Jubin, Claire; Loeillet, Sophie; Legoix-Né, Patricia; Nicolas, Alain G

    2014-02-01

    The acquisition of mutations is relevant to every aspect of genetics, including cancer and evolution of species on Darwinian selection. Genome variations arise from rare stochastic imperfections of cellular metabolism and deficiencies in maintenance genes. Here, we established the genome-wide spectrum of mutations that accumulate in a WT and in nine Saccharomyces cerevisiae mutator strains deficient for distinct genome maintenance processes: pol32Δ and rad27Δ (replication), msh2Δ (mismatch repair), tsa1Δ (oxidative stress), mre11Δ (recombination), mec1Δ tel1Δ (DNA damage/S-phase checkpoints), pif1Δ (maintenance of mitochondrial genome and telomere length), cac1Δ cac3Δ (nucleosome deposition), and clb5Δ (cell cycle progression). This study reveals the diversity, complexity, and ultimate unique nature of each mutational spectrum, composed of punctual mutations, chromosomal structural variations, and/or aneuploidies. The mutations produced in clb5Δ/CCNB1, mec1Δ/ATR, tel1Δ/ATM, and rad27Δ/FEN1 strains extensively reshape the genome, following a trajectory dependent on previous events. It comprises the transmission of unstable genomes that lead to colony mosaicisms. This comprehensive analytical approach of mutator defects provides a model to understand how genome variations might accumulate during clonal evolution of somatic cell populations, including tumor cells.

  1. Mutation accumulation and fitness in mutator subpopulations of Escherichia coli.

    PubMed

    Maharjan, Ram P; Liu, Bin; Li, Yang; Reeves, Peter R; Wang, Lei; Ferenci, Thomas

    2013-02-23

    Bacterial populations in clinical and laboratory settings contain a significant proportion of mutants with elevated mutation rates (mutators). Mutators have a particular advantage when multiple beneficial mutations are needed for fitness, as in antibiotic resistance. Nevertheless, high mutation rates potentially lead to increasing numbers of deleterious mutations and subsequently to the decreased fitness of mutators. To test how fitness changed with mutation accumulation, genome sequencing and fitness assays of nine Escherichia coli mutY mutators were undertaken in an evolving chemostat population at three time points. Unexpectedly, the fitness in members of the mutator subpopulation became constant despite a growing number of mutations over time. To test if the accumulated mutations affected fitness, we replaced each of the known beneficial mutations with wild-type alleles in a mutator isolate. We found that the other 25 accumulated mutations were not deleterious. Our results suggest that isolates with deleterious mutations are eliminated by competition in a continuous culture, leaving mutators with mostly neutral mutations. Interestingly, the mutator-non-mutator balance in the population reversed after the fitness plateau of mutators was reached, suggesting that the mutator-non-mutator ratio in populations has more to do with competition between members of the population than the accumulation of deleterious mutations.

  2. 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

  3. 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.

  4. [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

  5. [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.

  6. Physical studies of fast ignition in China

    NASA Astrophysics Data System (ADS)

    He, X. T.; Cai, Hong-bo; Wu, Si-zhong; Cao, Li-hua; Zhang, Hua; He, Ming-qing; Chen, Mo; Wu, Jun-feng; Zhou, Cang-tao; Zhou, Wei-Min; Shan, Lian-qiang; Wang, Wei-wu; Zhang, Feng; Bi, Bi; Zhao, Zong-qing; Gu, Yu-qiu; Zhang, Bao-han; Wang, Wei; Fang, Zhi-heng; Lei, An-le; Wang, Chen; Pei, Wen-bing; Fu, Si-zu

    2015-06-01

    Fast ignition approach to inertial confinement fusion is one of the important goals today, in addition to central hot spot ignition in China. The SG-IIU and PW laser facilities are coupled to investigate the hot spot formation for fast ignition. The SG-III laser facility is almost completed and will be coupled with tens kJ PW lasers for the demonstration of fast ignition. In recent years, for physical studies of fast ignition, we have been focusing on the experimental study of implosion symmetry, M-band radiation preheating and mixing, advanced fast ignition target design, and so on. In addition, the modeling capabilities and code developments enhanced our ability to perform the hydro-simulation of the compression implosion, and the particle-in-cell (PIC) and hybrid-PIC simulation of the generation, transport and deposition of relativistic electron beams. Considerable progress has been achieved in understanding the critical issues of fast ignition.

  7. 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.

  8. 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.

  9. New Mutations in NEB Gene Discovered by Targeted Next-Generation Sequencing in Nemaline Myopathy Italian Patients.

    PubMed

    Piga, Daniela; Magri, Francesca; Ronchi, Dario; Corti, Stefania; Cassandrini, Denise; Mercuri, Eugenio; Tasca, Giorgio; Bertini, Enrico; Fattori, Fabiana; Toscano, Antonio; Messina, Sonia; Moroni, Isabella; Mora, Marina; Moggio, Maurizio; Colombo, Irene; Giugliano, Teresa; Pane, Marika; Fiorillo, Chiara; D'Amico, Adele; Bruno, Claudio; Nigro, Vincenzo; Bresolin, Nereo; Comi, Giacomo Pietro

    2016-07-01

    Nemaline myopathy represents a group of clinically and genetically heterogeneous neuromuscular disorders. Different clinical-genetic entities have been characterized in the last few years, with implications for diagnostics and genetic counseling. Fifty percent of nemaline myopathy forms are due to NEB mutations, but genetic analysis of this large and complex gene by Sanger sequencing is time consuming and expensive. We selected 10 Italian patients with clinical and biopsy features suggestive for nemaline myopathy and negative for ACTA1, TPM2 and TPM3 mutations. We applied a targeted next-generation sequencing strategy designed to analyse NEB coding regions, the relative full introns and the promoter. We also evaluated copy number variations (by CGH array) and transcriptional changes by RNA Sanger sequencing, whenever possible. This combined strategy revealed 11 likely pathogenic variants in 8 of 10 patients. The molecular diagnosis was fully achieved in 3 of 8 patients, while only one heterozygous mutation was observed in 5 subjects. This approach revealed to be a fast and cost-effective way to analyse the large NEB gene in a small group of patients and might be promising for the detection of pathological variants of other genes featuring large coding regions and lacking mutational hotspots. PMID:27105866

  10. Kras gene codon 12 mutation detection enabled by gold nanoparticles conducted in a nanobioarray chip.

    PubMed

    Sedighi, Abootaleb; Li, Paul C H

    2014-03-01

    This study employs a nanobioarray (NBA) chip for multiple biodetection of single base pair mutations at the Kras gene codon 12. To distinguish between the mutant and wild-type target DNAs, current bioarray methods use high-temperature hybridization of the targets to the allele-specific probes. However, these techniques need prior temperature optimization and become harder to implement in the case of the detection of multiple mutations. We aimed to detect these mutations at a single temperature (room temperature), enabled by the use of gold nanoparticles (AuNPs) on the bioarray created within nanofluidic channels. In this method, a low amount of target oligonucleotides (5fmol) and polymerase chain reaction (PCR) products (300pg) were first loaded on the AuNP surface, and then these AuNP-bound targets were introduced into the channels of a polydimethylsiloxane (PDMS) glass chip. The targets hybridized to their complementary probes at the intersection of the target channels to the pre-printed oligonucleotide probe lines on the glass surface, creating a bioarray. Using this technique, fast and high-throughput multiple discrimination of the Kras gene codon 12 were achieved at room temperature using the NBA chip, and the specificity of the method was proved to be as high as that with the temperature stringency method.

  11. 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

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

    PubMed

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

    2015-04-01

    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.

  13. 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.

  14. Estimation of the RNU2 macrosatellite mutation rate by BRCA1 mutation tracing

    PubMed Central

    Tessereau, Chloé; Lesecque, Yann; Monnet, Nastasia; Buisson, Monique; Barjhoux, Laure; Léoné, Mélanie; Feng, Bingjian; Goldgar, David E.; Sinilnikova, Olga M.; Mousset, Sylvain; Duret, Laurent; Mazoyer, Sylvie

    2014-01-01

    Large tandem repeat sequences have been poorly investigated as severe technical limitations and their frequent absence from the genome reference hinder their analysis. Extensive allelotyping of this class of variation has not been possible until now and their mutational dynamics are still poorly known. In order to estimate the mutation rate of a macrosatellite, we analysed in detail the RNU2 locus, which displays at least 50 different alleles containing 5-82 copies of a 6.1 kb repeat unit. Mining data from the 1000 Genomes Project allowed us to precisely estimate copy numbers of the RNU2 repeat unit using read depth of coverage. This further revealed significantly different mean values in various recent modern human populations, favoring a scenario of fast evolution of this locus. Its proximity to a disease gene with numerous founder mutations, BRCA1, within the same linkage disequilibrium block, offered the unique opportunity to trace RNU2 arrays over a large timescale. Analysis of the transmission of RNU2 arrays associated with one ‘private’ mutation in an extended kindred and four founder mutations in multiple kindreds gave an estimation by maximum likelihood of 5 × 10−3 mutations per generation, which is close to that of microsatellites. PMID:25034697

  15. 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 ...

  16. 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, ...

  17. 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

  18. Mutation and premating isolation.

    PubMed

    Woodruff, R C; Thompson, J N

    2002-11-01

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

  19. Multiplex detection of mutations.

    PubMed

    Perlin, David S; Balashov, Sergey; Park, Steven

    2008-01-01

    Rapid and reliable detection of mutations at the genetic level is an integral part of modern molecular diagnostics. These mutations can range from dominant single nucleotide polymorphisms within specific loci to codominant heterozygotic insertions and they present considerable challenges to investigators in developing rapid nucleic acid-based amplification assays that can distinguish wild-type from mutant alleles. The recent improvements of real-time polymerase chain reaction (PCR) using self-reporting fluorescence probes have given researchers a powerful tool in developing assays for mutation detection that can be multiplexed for high-throughput screening of multiple mutations and cost effectiveness. Here we describe an application of a multiplexed real-time PCR assay using Molecular Beacon probes for the detection of mutations in codon 54 of the CYP51A gene in Aspergillus fumigatus conferring triazole resistance.

  20. 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.

  1. 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.

  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. 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.

  4. 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.…

  5. 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…

  6. Fast food: friendly?

    PubMed

    Rice, S; McAllister, E J; Dhurandhar, N V

    2007-06-01

    Fast food is routinely blamed for the obesity epidemic and consequentially excluded from professional dietary recommendations. However, several sections of society including senior citizens, low-income adult and children, minority and homeless children, or those pressed for time appear to rely on fast food as an important source of meals. Considering the dependence of these nutritionally vulnerable population groups on fast food, we examined the possibility of imaginative selection of fast food, which would attenuate the potentially unfavorable nutrient composition. We present a sample menu to demonstrate that it is possible to design a fast food menu that provides reasonable level of essential nutrients without exceeding the caloric recommendations. We would like to alert health-care professionals that fast food need not be forbidden under all circumstances, and that a fresh look at the role of fast food may enable its inclusion in meal planning for those who depend on it out of necessity, while adding flexibility.

  7. 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

  8. Fast ignition breakeven scaling.

    SciTech Connect

    Slutz, Stephen A.; Vesey, Roger Alan

    2005-01-01

    A series of numerical simulations have been performed to determine scaling laws for fast ignition break even of a hot spot formed by energetic particles created by a short pulse laser. Hot spot break even is defined to be when the fusion yield is equal to the total energy deposited in the hot spot through both the initial compression and the subsequent heating. In these simulations, only a small portion of a previously compressed mass of deuterium-tritium fuel is heated on a short time scale, i.e., the hot spot is tamped by the cold dense fuel which surrounds it. The hot spot tamping reduces the minimum energy required to obtain break even as compared to the situation where the entire fuel mass is heated, as was assumed in a previous study [S. A. Slutz, R. A. Vesey, I. Shoemaker, T. A. Mehlhorn, and K. Cochrane, Phys. Plasmas 7, 3483 (2004)]. The minimum energy required to obtain hot spot break even is given approximately by the scaling law E{sub T} = 7.5({rho}/100){sup -1.87} kJ for tamped hot spots, as compared to the previously reported scaling of E{sub UT} = 15.3({rho}/100){sup -1.5} kJ for untamped hotspots. The size of the compressed fuel mass and the focusability of the particles generated by the short pulse laser determines which scaling law to use for an experiment designed to achieve hot spot break even.

  9. 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)

  10. 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.

  11. 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.

  12. 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.

  13. 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

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

    PubMed Central

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

    2013-01-01

    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

  15. 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.

  16. 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.

  17. 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.

  18. Fast robust correlation.

    PubMed

    Fitch, Alistair J; Kadyrov, Alexander; Christmas, William J; Kittler, Josef

    2005-08-01

    A new, fast, statistically robust, exhaustive, translational image-matching technique is presented: fast robust correlation. Existing methods are either slow or non-robust, or rely on optimization. Fast robust correlation works by expressing a robust matching surface as a series of correlations. Speed is obtained by computing correlations in the frequency domain. Computational cost is analyzed and the method is shown to be fast. Speed is comparable to conventional correlation and, for large images, thousands of times faster than direct robust matching. Three experiments demonstrate the advantage of the technique over standard correlation.

  19. General Achievement Trends: Oklahoma

    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: Georgia

    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: 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…

  2. 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…

  3. 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…

  4. General Achievement Trends: Maine

    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: 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…

  6. 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…

  7. 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…

  8. General Achievement Trends: Kansas

    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…

  9. 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…

  10. General Achievement Trends: Massachusetts

    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: 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…

  12. General Achievement Trends: Alabama

    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…

  13. 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…

  14. General Achievement Trends: Michigan

    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: 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…

  16. 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…

  17. 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…

  18. School Effects on Achievement.

    ERIC Educational Resources Information Center

    Nichols, Robert C.

    The New York State Education Department conducts a Pupil Evaluation Program (PEP) in which each year all third, sixth, and ninth grade students in the state are given a series of achievement tests in reading and mathematics. The data accumulated by the department includes achievement test scores, teacher characteristics, building and curriculum…

  19. 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…

  20. 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…

  1. 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…

  2. [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

  3. 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

  4. Somatic mitochondrial DNA mutations do not increase neuronal vulnerability to MPTP in young POLG mutator mice.

    PubMed

    Dai, Ying; Clark, Joanne; Zheng, Kangni; Kujoth, Gregory C; Prolla, Tomas A; Simon, David K

    2014-01-01

    Mitochondrial DNA (mtDNA) mutations are hypothesized to play a pathogenic role in aging and age-related neurodegenerative diseases such as Parkinson's disease (PD). In support of this, high levels of somatic mtDNA mutations in “POLG mutator” mice carrying a proofreading-deficient form of mtDNA polymerase ã (Polg(D257A)) lead to a premature aging phenotype. However, the relevance of this finding to the normal aging process has been questioned as the number of mutations is greater even in young POLG mutator mice, which shows no overt phenotype, than levels achieved during normal aging in mice. Vulnerability of dopaminergic neurons to 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) increases with age, and we hypothesized that this may result in part from the accumulation with age of somatic mtDNA mutations. If correct, then levels of mutations in young (2–3 month old) POLG mutator mice should be sufficient to increase vulnerability to MPTP. In contrast, we find that susceptibility to MPTP in both heterozygous and homozygous POLG mutator mice at this young age is not different from that of wild type littermate controls as measured by levels of tyrosine hydroxylase positive (TH+) striatal terminals, striatal dopamine and its metabolites, a marker of oxidative damage, or stereological counts of TH+ and total substantia nigra neurons. These unexpected results do not support the hypothesis that somatic mtDNA mutations contribute to the age-related vulnerability of dopaminergic neurons to MPTP. It remains possible that somatic mtDNA mutations influence vulnerability to other stressors, or require additional time for the deleterious consequences to manifest. Furthermore, the impact of the higher levels of mutations present at older ages in these mice was not assessed in our study, although a prior study also failed to detect an increase in vulnerability to MPTP in older mice. With these caveats, the current data do not provide evidence for a role of somatic mt

  5. Mutational spectrum drives the rise of mutator bacteria.

    PubMed

    Couce, Alejandro; Guelfo, Javier R; Blázquez, Jesús

    2013-01-01

    Understanding how mutator strains emerge in bacterial populations is relevant both to evolutionary theory and to reduce the threat they pose in clinical settings. The rise of mutator alleles is understood as a result of their hitchhiking with linked beneficial mutations, although the factors that govern this process remain unclear. A prominent but underappreciated fact is that each mutator allele increases only a specific spectrum of mutational changes. This spectrum has been speculated to alter the distribution of fitness effects of beneficial mutations, potentially affecting hitchhiking. To study this possibility, we analyzed the fitness distribution of beneficial mutations generated from different mutator and wild-type Escherichia coli strains. Using antibiotic resistance as a model system, we show that mutational spectra can alter these distributions substantially, ultimately determining the competitive ability of each strain across environments. Computer simulation showed that the effect of mutational spectrum on hitchhiking dynamics follows a non-linear function, implying that even slight spectrum-dependent fitness differences are sufficient to alter mutator success frequency by several orders of magnitude. These results indicate an unanticipated central role for the mutational spectrum in the evolution of bacterial mutation rates. At a practical level, this study indicates that knowledge of the molecular details of resistance determinants is crucial for minimizing mutator evolution during antibiotic therapy.

  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. 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

  8. 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.

  9. 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

  10. 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

  11. Fast-ion D{alpha} measurements of the fast-ion distribution (invited)

    SciTech Connect

    Heidbrink, W. W.

    2010-10-15

    The fast-ion D{alpha} (FIDA) diagnostic is an application of charge-exchange recombination spectroscopy. Fast ions that neutralize in an injected neutral beam emit Balmer-{alpha} light with a large Doppler shift. The spectral shift is exploited to distinguish the FIDA emission from other bright sources of D{alpha} light. Background subtraction is the main technical challenge. A spectroscopic diagnostic typically achieves temporal, energy, and transverse spatial resolution of {approx}1 ms, {approx}10 keV, and {approx}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 {approx}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.

  12. 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.

  13. 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)

  14. 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.

  15. 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

  16. Reusable fast opening switch

    DOEpatents

    Van Devender, John P.; Emin, David

    1986-01-01

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

  17. 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.

  18. 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

  19. 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.

  20. Fast interceptors for theater boost-phase intercept

    SciTech Connect

    Canavan, G.H.

    1993-04-01

    Boost-phase theater intercept concepts are needed for known and existing countermeasures to current systems. Fast kinetic energy interceptors could be developed from existing and improved propulsion technology and miniaturized sensors to provide that capability. High velocity interceptors with achievable acceleration could achieve the ranges needed for protection of bases and populations, addressing most theater threats. Propulsion requires development. Drag and heating are largely predictable and controllable. Fast interceptors would also have useful applications in national and global missile defense.

  1. Impact of Fast Ignition on Laser Fusion Energy Development

    NASA Astrophysics Data System (ADS)

    Mirna, Kunioki

    2016-10-01

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

  2. 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

  3. Prevention of avoidable mutational diseases: Memorandum from a WHO Meeting*

    PubMed Central

    1986-01-01

    About 1% of children are born with a serious disorder which is the direct result of a mutational event in a parent or a more distant ancestor. These disorders, of which several thousand are known, mainly afflict the blood, bone, brain, ear, eye or muscle and the changes are usually irrevocable by the time of diagnosis. Another 1% of individuals will develop a serious genetic disease some time after birth. In addition to these direct consequences of a mutant event, far higher proportions will suffer from the indirect effects of one or several mutations. In view of their chronic and severe nature most of these disorders impose a burden disproportionate to their frequency, and it is sound public health policy to avoid the birth of babies known to have the established mutations and prevent further cases in the immediate or distant future by minimizing the exposure of people at risk to known mutagens. The advantages in permitting certain mutagenic exposures must be assessed against the later costs. Owing to the natural mutation rate and the vast backlog of previous mutations, the prospects of prevention are limited to preventing an increase, rather than to achieving any substantial decrease. This Memorandum describes progress in the ability to dissect and interpret the mutational process, to identify populations at risk, and to evaluate the consequences of the various types of mutational event and emphasizes that the current approach to prevention of mutational disease must involve improving our ability to study populations that appear to be at increased risk. PMID:3488837

  4. 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.

  5. FOMA: A Fast Optical Multichannel Analyzer

    NASA Astrophysics Data System (ADS)

    Haskovec, J. S.; Bramson, G.; Brooks, N. H.; Perry, M.

    1989-12-01

    A Fast Optical Multichannel Analyzer (FOMA) was built for spectroscopic measurements with fast time resolution on the DIII-D tokamak. The FOMA utilizes a linear photodiode array (RETICON RL 1024 SA) as the detector sensor. An external recharge switch and ultrafast operational amplifiers permit a readout time per pixel of 300 ns. In conjunction with standard CAMAC digitizer and timing modules, a readout time of 500 microns is achieved for the full 1024-element array. Data acquired in bench tests and in actual spectroscopic measurements on the DIII-D tokamak is presented to illustrate the camera's capability.

  6. 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.

  7. 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…

  8. 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,…

  9. 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…

  10. 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,…

  11. Leadership Issues: Raising Achievement.

    ERIC Educational Resources Information Center

    Horsfall, Chris, Ed.

    This document contains five papers examining the meaning and operation of leadership as a variable affecting student achievement in further education colleges in the United Kingdom. "Introduction" (Chris Horsfall) discusses school effectiveness studies' findings regarding the relationship between leadership and effective schools, distinguishes…

  12. 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)

  13. Achieving True Consensus.

    ERIC Educational Resources Information Center

    Napier, Rod; Sanaghan, Patrick

    2002-01-01

    Uses the example of Vermont's Middlebury College to explore the challenges and possibilities of achieving consensus about institutional change. Discusses why, unlike in this example, consensus usually fails, and presents four demands of an effective consensus process. Includes a list of "test" questions on successful collaboration. (EV)

  14. 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…

  15. 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…

  16. Assessing Handwriting Achievement.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Teachers in the school setting need to emphasize quality handwriting across the curriculum. Quality handwriting means that the written content is easy to read in either manuscript or cursive form. Handwriting achievement can be assessed, but not compared to the precision of assessing basic addition, subtraction, multiplication, and division facts.…

  17. 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…

  18. 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.

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. 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…

  4. 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.

  5. Mutator and MULE Transposons.

    PubMed

    Lisch, Damon

    2015-04-01

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

  6. 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

  7. First results on fast baking

    NASA Astrophysics Data System (ADS)

    Visentin, B.; Gasser, Y.; Charrier, J. P.

    2006-07-01

    High gradient performances of bulk niobium cavities go through a low-temperature baking during one or two days, the temperature parameter is adjusted in a narrow tuning range around 110 or 120 °C. With such treatment, the intrinsic quality factor Q0 is improved at high fields. Assuming the oxygen diffusion is involved in this phenomenon, we have developed the “fast baking” (145 °C/3 h) as an alternative method. Similar results have been achieved with this method compared to standard baking. Consequently, for the first time, a link between oxygen diffusion and high field Q-slope has been demonstrated. Furthermore, this method open the way to a simpler and better baking procedure for the large-scale cavity production due to: time reduction and possibility to combine baking and drying during cavity preparation.

  8. Fast Randomized STDMA Link Scheduling

    NASA Astrophysics Data System (ADS)

    Gomez, Sergio; Gras, Oriol; Friderikos, Vasilis

    In this paper a fast randomized parallel link swap based packing (RSP) algorithm for timeslot allocation in a spatial time division multiple access (STDMA) wireless mesh network is presented. The proposed randomized algorithm extends several greedy scheduling algorithms that utilize the physical interference model by applying a local search that leads to a substantial improvement in the spatial timeslot reuse. Numerical simulations reveal that compared to previously scheduling schemes the proposed randomized algorithm can achieve a performance gain of up to 11%. A significant benefit of the proposed scheme is that the computations can be parallelized and therefore can efficiently utilize commoditized and emerging multi-core and/or multi-CPU processors.

  9. Fast Intersection Algorithms for Sorted Sequences

    NASA Astrophysics Data System (ADS)

    Baeza-Yates, Ricardo; Salinger, Alejandro

    This paper presents and analyzes a simple intersection algorithm for sorted sequences that is fast on average. It is related to the multiple searching problem and to merging. We present the worst and average case analysis, showing that in the former, the complexity nicely adapts to the smallest list size. In the latter case, it performs less comparisons than the total number of elements on both inputs, n and m, when n = αm (α> 1), achieving O(m log(n/m)) complexity. The algorithm is motivated by its application to fast query processing in Web search engines, where large intersections, or differences, must be performed fast. In this case we experimentally show that the algorithm is faster than previous solutions.

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

    PubMed

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

    2010-08-01

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

  11. 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

  12. Does achievement motivation mediate the semantic achievement priming effect?

    PubMed

    Engeser, Stefan; Baumann, Nicola

    2014-10-01

    The aim of our research was to understand the processes of the prime-to-behavior effects with semantic achievement primes. We extended existing models with a perspective from achievement motivation theory and additionally used achievement primes embedded in the running text of excerpts of school textbooks to simulate a more natural priming condition. Specifically, we proposed that achievement primes affect implicit achievement motivation and conducted pilot experiments and 3 main experiments to explore this proposition. We found no reliable positive effect of achievement primes on implicit achievement motivation. In light of these findings, we tested whether explicit (instead of implicit) achievement motivation is affected by achievement primes and found this to be the case. In the final experiment, we found support for the assumption that higher explicit achievement motivation implies that achievement priming affects the outcome expectations. The implications of the results are discussed, and we conclude that primes affect achievement behavior by heightening explicit achievement motivation and outcome expectancies. PMID:24820250

  13. 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

  14. A Fast Hermite Transform★

    PubMed Central

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

    2008-01-01

    We present algorithms for fast and stable approximation of the Hermite transform of a compactly supported function on the real line, attainable via an application of a fast algebraic algorithm for computing sums associated with a three-term relation. Trade-offs between approximation in bandlimit (in the Hermite sense) and size of the support region are addressed. Numerical experiments are presented that show the feasibility and utility of our approach. Generalizations to any family of orthogonal polynomials are outlined. Applications to various problems in tomographic reconstruction, including the determination of protein structure, are discussed. PMID:20027202

  15. Fast Overcurrent Tripping Circuit

    NASA Technical Reports Server (NTRS)

    Sullender, Craig C.; Davies, Bryan L.; Osborn, Stephen H.

    1993-01-01

    Fast overcurrent tripping circuit designed for incorporation into power metal oxide/semiconductor field-effect transistor (MOSFET) switching circuit. Serves as fast electronic circuit breaker by sensing voltage across MOSFET's during conduction and switching MOSFET's off within 1 microsecond after voltage exceeds reference value corresponding to tripping current. Acts more quickly than Hall-effect current sensor and, in comparison with shunt current-measuring circuits, smaller and consumes less power. Also ignores initial transient overcurrents during first 5 microseconds of switching cycle.

  16. Germline PTPRD mutations in Ewing sarcoma: biologic and clinical implications.

    PubMed

    Jiang, Yunyun; Janku, Filip; Subbiah, Vivek; Angelo, Laura S; Naing, Aung; Anderson, Peter M; Herzog, Cynthia E; Fu, Siqing; Benjamin, Robert S; Kurzrock, Razelle

    2013-06-01

    Ewing sarcoma occurs in children, adolescents and young adults. High STAT3 levels have been reported in approximately 50% of patients with Ewing sarcoma, and may be important in tumorigenesis. Protein tyrosine phosphatase delta (PTPRD) is a tumor suppressor that inhibits STAT3 activation. To date, while somatic mutations in PTPRD have been reported in diverse tumors, germline mutations of PTPRD have not been investigated in Ewing sarcoma or other cancers. We identified a novel germline mutation in the PTPRD gene in three of eight patients (37.5%) with metastatic Ewing sarcoma. Although the functional impact in two of the patients is unclear, in one of them the aberration was annotated as a W775stop germline mutation, and would be expected to lead to gene truncation and, hence, loss of the STAT3 dephosphorylation function of PTPRD. Since STAT3 is phosphorylated after being recruited to the insulin growth factor receptor (IGF-1R), suppression of IGF-1R could attenuate the enhanced STAT3 activation expected in the presence of PTPRD mutations. Of interest, two of three patients with germline PTPRD mutations achieved durable complete responses following treatment with IGF-1R monoclonal antibody-based therapies. Our pilot data suggest that PTPRD germline mutations may play a role in the development of Ewing sarcoma, a disease of young people, and their presence may have implications for therapy.

  17. Trapped ion scaling with pulsed fast gates

    NASA Astrophysics Data System (ADS)

    Bentley, C. D. B.; Carvalho, A. R. R.; Hope, J. J.

    2015-10-01

    Fast entangling gates for trapped ion pairs offer vastly improved gate operation times relative to implemented gates, as well as approaches to trap scaling. Gates on a neighbouring ion pair only involve local ions when performed sufficiently fast, and we find that even a fast gate between a pair of distant ions with few degrees of freedom restores all the motional modes given more stringent gate speed conditions. We compare pulsed fast gate schemes, defined by a timescale faster than the trap period, and find that our proposed scheme has less stringent requirements on laser repetition rate for achieving arbitrary gate time targets and infidelities well below 10-4. By extending gate schemes to ion crystals, we explore the effect of ion number on gate fidelity for coupling two neighbouring ions in large crystals. Inter-ion distance determines the gate time, and a factor of five increase in repetition rate, or correspondingly the laser power, reduces the infidelity by almost two orders of magnitude. We also apply our fast gate scheme to entangle the first and last ions in a crystal. As the number of ions in the crystal increases, significant increases in the laser power are required to provide the short gate times corresponding to fidelity above 0.99.

  18. Fast focus field calculations

    NASA Astrophysics Data System (ADS)

    Leutenegger, Marcel; Geissbuehler, Matthias; Märki, Iwan; Leitgeb, Rainer A.; Lasser, Theo

    2008-02-01

    We present a method for fast calculation of the electromagnetic field near the focus of an objective with a high numerical aperture (NA). Instead of direct integration, the vectorial Debye diffraction integral is evaluated with the fast Fourier transform for calculating the electromagnetic field in the entire focal region. We generalize this concept with the chirp z transform for obtaining a flexible sampling grid and an additional gain in computation speed. Under the conditions for the validity of the Debye integral representation, our method yields the amplitude, phase and polarization of the focus field for an arbitrary paraxial input field in the aperture of the objective. Our fast calculation method is particularly useful for engineering the point-spread function or for fast image deconvolution. We present several case studies by calculating the focus fields of high NA oil immersion objectives for various amplitude, polarization and phase distributions of the input field. In addition, the calculation of an extended polychromatic focus field generated by a Bessel beam is presented. This extended focus field is of particular interest for Fourier domain optical coherence tomography because it preserves a lateral resolution of a few micrometers over an axial distance in the millimeter range.

  19. Fast ForWord.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO.

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

  20. 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.

  1. Filaggrin mutations and the skin.

    PubMed

    De, Dipankar; Handa, Sanjeev

    2012-01-01

    Filaggrin is very important in the terminal differentiation of the skin and the formation of cornified envelope in the stratum corneum. Several mutations in the filaggrin gene have been identified in the last decade, mostly from the European countries. Loss of function mutations in the filaggrin gene results in reduced production of filaggrin, depending on the type and site of mutation. Such mutations in the filaggrin gene have been shown to be the most significant genetic risk factor for development of atopic dermatitis and undoubtedly has a role in the pathogenesis of ichthyosis vulgaris. Though there is theoretical possibility of association with hand eczema and allergic contact dermatitis; in clinical studies, the strength of these associations was not significantly strong. In this review, we have discussed the structure and function of filaggrin, basic genetics, type of mutations in filaggrin gene, and association of such mutations with different dermatoses.

  2. 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.

  3. 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…

  4. 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.

  5. From molecular genetics to phylodynamics: evolutionary relevance of mutation rates across viruses.

    PubMed

    Sanjuán, Rafael

    2012-01-01

    Although evolution is a multifactorial process, theory posits that the speed of molecular evolution should be directly determined by the rate at which spontaneous mutations appear. To what extent these two biochemical and population-scale processes are related in nature, however, is largely unknown. Viruses are an ideal system for addressing this question because their evolution is fast enough to be observed in real time, and experimentally-determined mutation rates are abundant. This article provides statistically supported evidence that the mutation rate determines molecular evolution across all types of viruses. Properties of the viral genome such as its size and chemical composition are identified as major determinants of these rates. Furthermore, a quantitative analysis reveals that, as expected, evolution rates increase linearly with mutation rates for slowly mutating viruses. However, this relationship plateaus for fast mutating viruses. A model is proposed in which deleterious mutations impose an evolutionary speed limit and set an extinction threshold in nature. The model is consistent with data from replication kinetics, selection strength and chemical mutagenesis studies.

  6. Magnetically assisted fast ignition.

    PubMed

    Wang, W-M; Gibbon, P; Sheng, Z-M; Li, Y-T

    2015-01-01

    Fast ignition (FI) is investigated via integrated particle-in-cell simulation including both generation and transport of fast electrons, where petawatt ignition lasers of 2 ps and compressed targets of a peak density of 300  g cm(-3) and areal density of 0.49  g cm(-2) at the core are taken. When a 20 MG static magnetic field is imposed across a conventional cone-free target, the energy coupling from the laser to the core is enhanced by sevenfold and reaches 14%. This value even exceeds that obtained using a cone-inserted target, suggesting that the magnetically assisted scheme may be a viable alternative for FI. With this scheme, it is demonstrated that two counterpropagating, 6 ps, 6 kJ lasers along the magnetic field transfer 12% of their energy to the core, which is then heated to 3 keV. PMID:25615473

  7. 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.

  8. Fast Ion Conductors

    NASA Astrophysics Data System (ADS)

    Chadwick, Alan V.

    Fast ion conductors, sometimes referred to as superionic conductors or solid electrolytes, are solids with ionic conductivities that are comparable to those found in molten salts and aqueous solutions of strong electrolytes, i.e., 10-2-10 S cm-1. Such materials have been known of for a very long time and some typical examples of the conductivity are shown in Fig. 1, along with sodium chloride as the archetypal normal ionic solid. Faraday [1] first noted the high conductivity of solid lead fluoride (PbF2) and silver sulphide (Ag2S) in the 1830s and silver iodide was known to be unusually high ionic conductor to the German physicists early in the 1900s. However, the materials were regarded as anomalous until the mid 1960s when they became the focus of intense interest to academics and technologists and they have remained at the forefront of materials research [2-4]. The academic aim is to understand the fundamental origin of fast ion behaviour and the technological goal is to utilize the properties in applications, particularly in energy applications such as the electrolyte membranes in solid-state batteries and fuel cells, and in electrochemical sensors. The last four decades has seen an expansion of the types of material that exhibit fast ion behaviour that now extends beyond simple binary ionic crystals to complex solids and even polymeric materials. Over this same period computer simulations of solids has also developed (in fact these methods and the interest in fast ion conductors were almost coincidental in their time of origin) and the techniques have played a key role in this area of research.

  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. Fast track evaluation methodology.

    PubMed

    Duke, J R

    1991-06-01

    Evaluating hospital information systems has taken a variety of forms since the initial development and use of automation. The process itself has moved from a hardware-based orientation controlled by data processing professionals to systems solutions and a user-driven process overseen by management. At Harbor Hospital Center in Baltimore, a fast track methodology has been introduced to shorten system evaluation time to meet the rapid changes that constantly affect the healthcare industry.

  11. 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.

  12. 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…

  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. 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…

  16. 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

  17. 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

  18. 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.

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

    ERIC Educational Resources Information Center

    Veloo, Arsaythamby; Nor, Rahimah; Khalid, Rozalina

    2015-01-01

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

  20. The Impact of Reading Achievement on Overall Academic Achievement

    ERIC Educational Resources Information Center

    Churchwell, Dawn Earheart

    2009-01-01

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

  1. High frequency of W1327X mutation in glycogen storage disease type III patients from central Tunisia.

    PubMed

    Cherif, Wafa; Ben Rhouma, Faten; Messai, Habib; Mili, Amira; Gribaa, Moez; Kefi, Rym; Ayadi, Abdelkarim; Boughamoura, Lamia; Chemli, Jelel; Saad, Ali; Kaabachi, Naziha; Sfar, Mohamed Tahar; Ben Dridi, Marie-Françoise; Tebib, Neji; Abdelhak, Sonia

    2012-01-01

    Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by the deficiency of glycogen debranching enzyme (AGL). It is characterized by hepatomegaly, progressive myopathy, cardiomyopathy and fasting hypoglycemia. Several mutations in AGL gene have been described in different populations. The W1327X mutation was reported in one Tunisian patient resident in Italy. We looked in this report to determine the frequency of W1327X mutation among Tunisian patients. The W1327X mutation was screening in 26 GSD III patients originated from various geographic locations in Tunisia. The sequence analysis revealed that among nine patients carried the W1327X mutation. Eight of them were from six unrelated families and they were originated from Mahdia (centre of Tunisia) suggesting the existence of a founder effect in this region. Taking into account historical migratory waves, screening for this mutation should be performed in priority for molecular diagnosis confirmation of GSD III in North African populations.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Mutational landscape and underlying mutational processes in chronic lymphocytic leukemia.

    PubMed

    Kasar, S; Brown, J R

    2016-07-01

    Sequencing studies have been instrumental in understanding the genetic basis of chronic lymphocytic leukemia (CLL). Our recent whole-genome sequencing study focusing on lower cytogenetic risk CLL demonstrated that CLL mutations can be attributed to 3 key mutational processes-2 types of activation induced-cytidine deaminase (AID) signatures and an aging signature-that operate at different times throughout CLL evolution. PMID:27652313

  15. 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.

  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 Fourier transform telescope

    SciTech Connect

    Tegmark, Max; Zaldarriaga, Matias

    2009-04-15

    We propose an all-digital telescope for 21 cm tomography, which combines key advantages of both single dishes and interferometers. The electric field is digitized by antennas on a rectangular grid, after which a series of fast Fourier transforms recovers simultaneous multifrequency images of up to half the sky. Thanks to Moore's law, the bandwidth up to which this is feasible has now reached about 1 GHz, and will likely continue doubling every couple of years. The main advantages over a single dish telescope are cost and orders of magnitude larger field-of-view, translating into dramatically better sensitivity for large-area surveys. The key advantages over traditional interferometers are cost (the correlator computational cost for an N-element array scales as Nlog{sub 2}N rather than N{sup 2}) and a compact synthesized beam. We argue that 21 cm tomography could be an ideal first application of a very large fast Fourier transform telescope, which would provide both massive sensitivity improvements per dollar and mitigate the off-beam point source foreground problem with its clean beam. Another potentially interesting application is cosmic microwave background polarization.

  18. 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…

  19. 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

  20. 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.

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

    PubMed Central

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

    2016-01-01

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

  2. 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

  3. Nucleotide sequence determines the accelerated rate of point mutations.

    PubMed

    Kini, R Manjunatha; Chinnasamy, Arunkumar

    2010-09-01

    Although the theory of evolution was put forth about 150 years ago our understanding of how molecules drive evolution remains poor. It is well-established that proteins evolve at different rates, essentially based on their functional role and three-dimensional structure. However, the highly variable rates of evolution of different proteins - especially the rapidly evolving ones - within a single organism are poorly understood. Using examples of genes for fast-evolving toxins and human hereditary diseases, we show for the first time that specific nucleotide sequences appear to determine point mutation rates. Based on mutation rates, we have classified triplets (not just codons) into stable, unstable and intermediate groups. Toxin genes contain a relatively higher percentage of unstable triplets in their exons compared to introns, whereas non-toxin genes contain a higher percentage of unstable triplets in their introns. Thus the distribution of stable and unstable triplets is correlated with and may explain the accelerated evolution of point mutations in toxins. Similarly, at the genomic level, lower organisms with genes that evolve faster contain a higher percentage of unstable triplets compared to higher organisms. These findings show that mutation rates of proteins, and hence of the organisms, are DNA sequence-dependent and thus provide a proximate mechanism of evolution at the molecular level. PMID:20362603

  4. 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

  5. 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.

  6. 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…

  7. Clinical Outcomes of TP53 Mutations in Cancers.

    PubMed

    Robles, Ana I; Jen, Jin; Harris, Curtis C

    2016-01-01

    High-throughput sequencing of cancer genomes is increasingly becoming an essential tool of clinical oncology that facilitates target identification and targeted therapy within the context of precision medicine. The cumulative profiles of somatic mutations in cancer yielded by comprehensive molecular studies also constitute a fingerprint of historical exposures to exogenous and endogenous mutagens, providing insight into cancer evolution and etiology. Mutational signatures that were first established by inspection of the TP53 gene somatic landscape have now been confirmed and expanded by comprehensive sequencing studies. Further, the degree of granularity achieved by deep sequencing allows detection of low-abundance mutations with clinical relevance. In tumors, they represent the emergence of small aggressive clones; in normal tissues, they signal a mutagenic exposure related to cancer risk; and, in blood, they may soon become effective surveillance tools for diagnostic purposes and for monitoring of cancer prognosis and recurrence. PMID:27449973

  8. PPARγ mutations, lipodystrophy and diabetes.

    PubMed

    Astapova, Olga; Leff, Todd

    2014-11-01

    The focus of this review is the lipodystrophy syndrome caused by mutation in the PPARγ nuclear receptor - partial familial lipodystrophy FPLD3. To provide a broader context for how these mutations act to generate the clinical features of partial lipodystrophy we will review the basic biology of PPARγ and also survey the set PPARγ genetic variants that do not cause lipodystrophy, but are nonetheless associated with clinically related syndromes, specifically type 2 diabetes.

  9. 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

  10. 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

  11. 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.

  12. Mutations in cardiovascular connexin genes.

    PubMed

    Molica, Filippo; Meens, Merlijn J P; Morel, Sandrine; Kwak, Brenda R

    2014-09-01

    Connexins (Cxs) form a family of transmembrane proteins comprising 21 members in humans. Cxs differ in their expression patterns, biophysical properties and ability to combine into homomeric or heteromeric gap junction channels between neighbouring cells. The permeation of ions and small metabolites through gap junction channels or hemichannels confers a crucial role to these proteins in intercellular communication and in maintaining tissue homeostasis. Among others, Cx37, Cx40, Cx43, Cx45 and Cx47 are found in heart, blood and lymphatic vessels. Mutations or polymorphisms in the genes coding for these Cxs have not only been implicated in cardiovascular pathologies but also in a variety of other disorders. While mutations in Cx43 are mostly linked to oculodentodigital dysplasia, Cx47 mutations are associated with Pelizaeus-Merzbacher-like disease and lymphoedema. Cx40 mutations are principally linked to atrial fibrillation. Mutations in Cx37 have not yet been described, but polymorphisms in the Cx37 gene have been implicated in the development of arterial disease. This review addresses current knowledge on gene mutations in cardiovascular Cxs systematically and links them to alterations in channel properties and disease.

  13. 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,…

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  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 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.

  18. 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)

  19. Fast-switching bistable cholesteric intensity modulator.

    PubMed

    Hsiao, Yu-Cheng; Tang, Chen-Yu; Lee, Wei

    2011-05-01

    A fast-switching bistable optical intensity modulator is demonstrated. Using a dual-frequency cholesteric liquid crystal, the direct switching is achieved from the scattering focal conic state to the transparent long-pitch planar state. In comparison with the bistable cholesteric devices proposed previously, our device, characterized by its capability of direct two-way transitions between the two bistable states, possesses a very short transition time from the focal conic state to the planar state as short as 10 ms. No voltage has to be applied to sustain the optical states, making the device low energy consuming. Potential applications of this device are addressed.

  20. Direct Energy Conversion for Fast Reactors

    NASA Astrophysics Data System (ADS)

    Brown, N. W.; Vogt, D.; Cooper, J.; Chapline, G.; Turchi, P.

    2000-07-01

    Thermoelectric generators (TEG) are a well-established technology for compact low power output long-life applications. Solid state TEGs are the technology of choice for many space missions and remote earth-based applications. Use of solid state TEGs in these applications requires engineering designs that minimize the weight and volume of the device. Thermal to electric conversion efficiency, while an important design consideration, is not the principal design factor. However, design of a TEG for a fast reactor nuclear power plant requires higher thermal efficiencies in order to achieve competitive power generation costs.

  1. Fast-switching bistable cholesteric intensity modulator.

    PubMed

    Hsiao, Yu-Cheng; Tang, Chen-Yu; Lee, Wei

    2011-05-01

    A fast-switching bistable optical intensity modulator is demonstrated. Using a dual-frequency cholesteric liquid crystal, the direct switching is achieved from the scattering focal conic state to the transparent long-pitch planar state. In comparison with the bistable cholesteric devices proposed previously, our device, characterized by its capability of direct two-way transitions between the two bistable states, possesses a very short transition time from the focal conic state to the planar state as short as 10 ms. No voltage has to be applied to sustain the optical states, making the device low energy consuming. Potential applications of this device are addressed. PMID:21643231

  2. 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

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

    PubMed

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

    2014-02-01

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

  4. 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

  5. The androgen receptor gene mutations database.

    PubMed

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

    1994-09-01

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

  6. Mutator Dynamics on a Smooth Evolutionary Landscape

    NASA Astrophysics Data System (ADS)

    Kessler, David A.; Levine, Herbert

    1998-03-01

    We investigate a model of evolutionary dynamics on a smooth landscape which features a ``mutator'' allele which increases the mutation rate. We show that when the fitness is far from its equilibrium value the expected proportion of mutators approaches a value governed solely by the transition rates into and out of the mutator state, resulting in a much faster fitness increase than would be the case without the mutator allele. Near the fitness equilibrium, the mutators are severely suppressed, due to the detrimental effects of a large mutation rate near the fitness maximum. We discuss the results of a recent experiment on natural selection of E. coli in the light of our model.

  7. Three novel mutations responsible for Cockayne syndrome group A.

    PubMed

    Ren, Yan; Saijo, Masafumi; Nakatsu, Yoshimichi; Nakai, Hiroshi; Yamaizumi, Masaru; Tanaka, Kiyoji

    2003-02-01

    Cockayne syndrome (CS) is a rare autosomal recessive disease, which shows diverse clinical symptoms such as photosensitivity, severe mental retardation and developmental defects. CS cells are hypersensitive to killing by UV-irradiation and defective in transcription-coupled repair. Two genetic complementation groups in CS (CS-A and CS-B) have been identified. We analyzed mutations of the CSA gene in 5 CS-A patients and identified 3 types of mutations. Four unrelated CS-A patients (CS2OS, CS2AW, Nps2 and CS2SE) had a deletion including exon 4, suggesting that there is a founder effect on the CSA mutation in Japanese CS-A patients. Patient CS2SE was a compound heterozygote for this deletion and an amino acid substitution at the 106th glutamine to proline (Q106P) in the WD-40 repeat motif of the CSA protein, which resulted in a defective nucleotide excision repair. Patient Mps1 had a large deletion in the upstream region including exon 1 of the CSA gene. Our results indicate that a rapid and reliable diagnosis of CSA mutations could be achieved in CS-A patients by PCR or PCR-RFLP and that the Q106P mutation could alter the propeller structure of the CSA protein which is important for the formation of the CSA protein complex. PMID:12655141

  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 Central

    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. 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

  11. 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…

  12. 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

  13. HFE mutations in the elderly.

    PubMed

    Willis, Gavin; Wimperis, Jennie Z; Smith, Katy; Fellows, Ian W; Jennings, Barbara A

    2003-01-01

    Most individuals diagnosed with hereditary hemochromatosis have mutations in both copies of the HFE gene, with such mutations being common in populations of north European origin. The number of individuals currently diagnosed and treated for hemochromatosis is small relative to the number carrying two HFE mutations. Studies searching for undiagnosed hemochromatosis cases among disease cohorts have generally failed to find the number of cases that would be expected if disease were the commonest outcome for individuals with two C282Y HFE mutations. Our aim was to test the hypothesis that individuals with two HFE mutations would be under-represented in an elderly population because many would have died from disease caused by hemochromatosis before they reached old age. This is a cross-sectional study of elderly patients referred for full blood counts at the Norfolk and Norwich University Hospital. We screened blood samples from 1,000 elderly men (aged 85 and over) and women (aged 89 and over) for the C282Y, H63D, and S65C mutations of the HFE gene. We also analyzed any recent laboratory data relevant to signs of hemochromatosis. None of the ten possible genotypes was significantly under- or over-represented compared to the expected frequency calculated from the Hardy-Weinberg equation. Four C282Y homozygotes were found. There were few significant differences in the laboratory findings between the genotypes. Our data suggest that most people with HFE mutations survive to old age and do not suffer from signs of iron overload and hemochromatosis. PMID:12972032

  14. 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.

  15. 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.

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

    PubMed

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

    2015-01-01

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

  17. 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%.

  18. A Single Mutation in the Acetylcholine Receptor δ-Subunit Causes Distinct Effects in Two Types of Neuromuscular Synapses

    PubMed Central

    Park, Jee-Young; Mott, Meghan; Williams, Tory; Ikeda, Hiromi; Wen, Hua; Linhoff, Michael

    2014-01-01

    Mutations in AChR subunits, expressed as pentamers in neuromuscular junctions (NMJs), cause various types of congenital myasthenic syndromes. In AChR pentamers, the adult ε subunit gradually replaces the embryonic γ subunit as the animal develops. Because of this switch in subunit composition, mutations in specific subunits result in synaptic phenotypes that change with developmental age. However, a mutation in any AChR subunit is considered to affect the NMJs of all muscle fibers equally. Here, we report a zebrafish mutant of the AChR δ subunit that exhibits two distinct NMJ phenotypes specific to two muscle fiber types: slow or fast. Homozygous fish harboring a point mutation in the δ subunit form functional AChRs in slow muscles, whereas receptors in fast muscles are nonfunctional. To test the hypothesis that different subunit compositions in slow and fast muscles underlie distinct phenotypes, we examined the presence of ε/γ subunits in NMJs using specific antibodies. Both wild-type and mutant larvae lacked ε/γ subunits in slow muscle synapses. These findings in zebrafish suggest that some mutations in human congenital myasthenic syndromes may affect slow and fast muscle fibers differently. PMID:25080583

  19. 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.

  20. 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

  1. FABRICATION AND CHARACTERIZATION OF FAST IGNITION TARGETS

    SciTech Connect

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

    2003-06-01

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

  2. Fast pitch softball injuries.

    PubMed

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

    2001-01-01

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

  3. Fast pitch softball injuries.

    PubMed

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

    2001-01-01

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

  4. 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

  5. [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.

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

    PubMed

    Jasmin, Jean-Nicolas; Lenormand, Thomas

    2016-02-01

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

  7. 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

  8. Parallel fast gauss transform

    SciTech Connect

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

    2010-01-01

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

  9. Fast 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)).

  10. 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…

  11. Poor Results for High Achievers

    ERIC Educational Resources Information Center

    Bui, Sa; Imberman, Scott; Craig, Steven

    2012-01-01

    Three million students in the United States are classified as gifted, yet little is known about the effectiveness of traditional gifted and talented (G&T) programs. In theory, G&T programs might help high-achieving students because they group them with other high achievers and typically offer specially trained teachers and a more advanced…

  12. 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…

  13. 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…

  14. 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…

  15. 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);…

  16. Family Status and School Achievement.

    ERIC Educational Resources Information Center

    Chalker, Rhoda N.; Horns, Virginia

    This study tested the hypothesis that there is no significant difference in reading achievement among children in grades 2 through 5 related to family structure. Researchers administered the Stanford Achievement Test to 119 students in an Alabama city suburban school system. Of the sample, 69 children lived in intact families and 50 lived in…

  17. 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…

  18. Classroom Composition and Achievement Gains.

    ERIC Educational Resources Information Center

    Leiter, Jeffrey

    1983-01-01

    Third-grade students in high ability groups in mathematics achieved greater gains than students in low ability groups. The opposite results occurred in reading achievement. Possible reasons for this difference include different instructional techniques for reading and math and the effect of home environment on learning. (IS)

  19. 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…

  20. 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…

  1. 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…

  2. Fasting of mice: a review.

    PubMed

    Jensen, T L; Kiersgaard, M K; Sørensen, D B; Mikkelsen, L F

    2013-10-01

    Fasting of mice is a common procedure performed in association with many different types of experiments mainly in order to reduce variability in investigatory parameters or to facilitate surgical procedures. However, the effects of fasting not directly related to the investigatory parameters are often ignored. The aim of this review is to present and summarize knowledge about the effects of fasting of mice to facilitate optimization of the fasting procedure for any given study and thereby maximize the scientific outcome and minimize the discomfort for the mice and hence ensure high animal welfare. The results are presented from a number of experimental studies, providing evidence for fasting-induced changes in hormone balance, body weight, metabolism, hepatic enzymes, cardiovascular parameters, body temperature and toxicological responses. A description of relevant normal behaviour and standard physiological parameters is given, concluding that mice are primarily nocturnal and consume two-thirds of their total food intake during the night. It is argued that overnight fasting of mice is not comparable with overnight fasting of humans because the mouse has a nocturnal circadian rhythm and a higher metabolic rate. It is suggested that because many physiological parameters are regulated by circadian rhythms, fasting initiated at different points in the circadian rhythm has different impacts and produces different results.

  3. 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…

  4. Fast-Polynomial-Transform Program

    NASA Technical Reports Server (NTRS)

    Truong, T. K.; Hsu, I. S.; Chu, Y. F.

    1987-01-01

    Computer program uses fast-polynomial-transformation (FPT) algorithm applicable to two-dimensional mathematical convolutions. Two-dimensional cyclic convolutions converted to one-dimensional convolutions in polynomial rings. Program decomposes cyclic polynomials into polynomial convolutions of same length. Only FPT's and fast Fourier transforms of same length required. Modular approach saves computional resources. Program written in C.

  5. 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.

  6. 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.

  7. 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

  8. The FAST (FRC Acceleration Space Thruster) Experiment

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  9. 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.

  10. Fast causal multicast

    NASA Technical Reports Server (NTRS)

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

    1990-01-01

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

  11. 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

  12. Phenotypic clustering in MPZ mutations.

    PubMed

    Shy, Michael E; Jáni, Agnes; Krajewski, Karen; Grandis, Marina; Lewis, Richard A; Li, Jun; Shy, Rosemary R; Balsamo, Janne; Lilien, Jack; Garbern, James Y; Kamholz, John

    2004-02-01

    Myelin protein zero (MPZ) is a member of the immunoglobulin gene superfamily with single extracellular, transmembrane and cytoplasmic domains. Homotypic interactions between extracellular domains of MPZ adhere adjacent myelin wraps to each other. MPZ is also necessary for myelin compaction since mice which lack MPZ develop severe dysmyelinating neuropathies in which compaction is dramatically disrupted. MPZ mutations in humans cause the inherited demyelinating neuropathy CMT1B. Some mutations cause the severe neuropathies of infancy designated as Dejerine-Sottas disease, while others cause a 'classical' Charcot-Marie-Tooth (CMT) disease Type 1B (CMT1B) phenotype with normal early milestones but development of disability during the first two decades of life. Still other mutations cause a neuropathy that presents in adults, with normal nerve conduction velocities, designated as a 'CMT2' form of CMT1B. To correlate the phenotype of patients with MPZ mutations with their genotype, we identified and evaluated 13 patients from 12 different families with eight different MPZ mutations. In addition, we re-analysed the clinical data from 64 cases of CMT1B from the literature. Contrary to our expectations, we found that most patients presented with either an early onset neuropathy with signs and symptoms prior to the onset of walking or a late onset neuropathy with signs and symptoms at around age 40 years. Only occasional patients presented with a 'classical' CMT phenotype. Correlation of specific MPZ mutations with their phenotypes demonstrated that addition of either a charged amino acid or altering a cysteine residue in the extracellular domain caused a severe early onset neuropathy. Severe neuropathy was also caused by truncation of the cytoplasmic domain or alteration of an evolutionarily conserved amino acid. Taken together, these data suggest that early onset neuropathy is caused by MPZ mutations that significantly disrupt the tertiary structure of MPZ and thus

  13. Mutations in pseudohypoparathyroidism 1a and pseudopseudohypoparathyroidism in ethnic Chinese.

    PubMed

    Wu, Yi-Lei; Hwang, Daw-Yang; Hsiao, Hui-Pin; Ting, Wei-Hsin; Huang, Chi-Yu; Tsai, Wen-Yu; Chen, Hung-Chun; Chao, Mei-Chyn; Lo, Fu-Sung; Tsai, Jeng-Daw; Yang, Stone; Shih, Shin-Lin; Lin, Shuan-Pei; Lin, Chiung-Ling; Lee, Yann-Jinn

    2014-01-01

    An inactivating mutation in the GNAS gene causes either pseudohypoparathyroidism 1a (PHP1A) when it is maternally inherited or pseudopseudohypoparathyroidism (PPHP) when it is paternally inherited. We investigated clinical manifestations and mutations of the GNAS gene in ethnic Chinese patients with PHP1A or PPHP. Seven patients from 5 families including 4 girls and 2 boys with PHP1A and 1 girl with PPHP were studied. All PHP1A patients had mental retardation. They were treated with calcitriol and CaCO3 with regular monitoring of serum Ca levels, urinary Ca/Cr ratios, and renal sonography. Among them, 5 patients also had primary hypothyroidism suggesting TSH resistance. One female patient had a renal stone which was treated with extracorporeal shockwave lithotripsy. She had an increased urinary Ca/Cr ratio of 0.481 mg/mg when the stone was detected. We detected mutations using PCR and sequencing as well as analysed a splice acceptor site mutation using RT-PCR, sequencing, and minigene construct. We detected 5 mutations: c.85C>T (Q29*), c.103C>T (Q35*), c.840-2A>G (R280Sfs*21), c.1027_1028delGA (D343*), and c.1174G>A (E392K). Mutations c.840-2A>G and c.1027_1028delGA were novel. The c.840-2A>G mutation at the splice acceptor site of intron 10 caused retention of intron 10 in the minigene construct but skipping of exon 11 in the peripheral blood cells. The latter was the most probable mechanism which caused a frameshift, changing Arg to Ser at residue 280 and invoking a premature termination of translation at codon 300 (R280Sfs*21). Five GNAS mutations in ethnic Chinese with PHP1A and PPHP were reported. Two of them were novel. Mutation c.840-2A>G destroyed a spice acceptor site and caused exon skipping. Regular monitoring and adjustment in therapy are mandatory to achieve optimal therapeutic effects and avoid nephrolithiasis in patients with PHP1A.

  14. Mathematics anxiety and mathematics achievement

    NASA Astrophysics Data System (ADS)

    Sherman, Brian F.; Wither (Post.), David P.

    2003-09-01

    This paper is a distillation of the major result from the 1998 Ph.D. thesis of the late David Wither. It details a longitudinal study over five years of the relationship between mathematics anxiety and mathematics achievement. It starts from the already well documented negative correlation between the two, and seeks to establish one of the three hypotheses—that mathematics anxiety causes an impairment of mathematics achievement; that lack of mathematics achievement causes mathematics anxiety; or that there is a third underlying cause of the two.

  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. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  18. 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

  19. Identification of a recently active Prunus-specific non-autonomous Mutator element with considerable genome shaping force.

    PubMed

    Halász, Júlia; Kodad, Ossama; Hegedűs, Attila

    2014-07-01

    Miniature inverted-repeat transposable elements (MITEs) are known to contribute to the evolution of plants, but only limited information is available for MITEs in the Prunus genome. We identified a MITE that has been named Falling Stones, FaSt. All structural features (349-bp size, 82-bp terminal inverted repeats and 9-bp target site duplications) are consistent with this MITE being a putative member of the Mutator transposase superfamily. FaSt showed a preferential accumulation in the short AT-rich segments of the euchromatin region of the peach genome. DNA sequencing and pollination experiments have been performed to confirm that the nested insertion of FaSt into the S-haplotype-specific F-box gene of apricot resulted in the breakdown of self-incompatibility (SI). A bioinformatics-based survey of the known Rosaceae and other genomes and a newly designed polymerase chain reaction (PCR) assay verified the Prunoideae-specific occurrence of FaSt elements. Phylogenetic analysis suggested a recent activity of FaSt in the Prunus genome. The occurrence of a nested insertion in the apricot genome further supports the recent activity of FaSt in response to abiotic stress conditions. This study reports on a presumably active non-autonomous Mutator element in Prunus that exhibits a major indirect genome shaping force through inducing loss-of-function mutation in the SI locus.

  20. 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....

  1. 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

  2. Mastery Achievement of Intellectual Skills.

    ERIC Educational Resources Information Center

    Trembath, Richard J.; White, Richard T.

    1979-01-01

    Mastery learning techniques were improved through mathematics instruction based on a validated learning hierarchy, presenting tasks in a sequence consistent with the requirements of the hierarchy, and requiring learners to demonstrate achievement before being allowed to proceed. (Author/GDC)

  3. Achieving Standards through Environmental Education.

    ERIC Educational Resources Information Center

    Kaspar, Mike

    1999-01-01

    Most states do not have the time or resources to develop environmental education standards from scratch. Highlights the role that environmental education and its interdisciplinary nature can play in helping students achieve. (DDR)

  4. 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.

  5. Fast Ignition Experimental and Theoretical Studies

    SciTech Connect

    Akli, Kramer Ugerthen

    2006-01-01

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

  6. Intragenic single nucleotide polymorphism haplotype analysis of SUR1 mutations in familial hyperinsulinism.

    PubMed

    Glaser, B; Furth, J; Stanley, C A; Baker, L; Thornton, P S; Landau, H; Permutt, M A

    1999-01-01

    Familial hyperinsulinism (HI; MIM# 256450) is an autosomal recessive disorder of pancreatic beta-cell function, characterized by inadequate suppression of insulin secretion despite severe recurrent fasting hypoglycemia. Subtotal pancreatectomy is frequently required to prevent permanent neurologic sequelae. The incidence of HI in the Caucasian population is estimated at 1:50,000, however an apparent increased incidence among Ashkenazi Jews and Saudi Arabian Arabs has been reported. A locus for HI was assigned by linkage analyses to human chromosome 11p15.1. The sulfonylurea receptor (MIM# 600509, SUR1) and the potassium channel, inwardly rectifying, subfamily J member 11 (MIM# 600937, KIR6.2) genes, 2 components of the beta-cell K(ATP) channel, are clustered in this chromosomal region, and mutations in these genes have been implicated in HI. We previously demonstrated that two mutations in the SUR1 gene are present on approximately 88% of HI-associated chromosomes in Ashkenazi Jewish patients. Haplotype analysis with microsatellite markers flanking the gene revealed that one mutation (delF1388), reported only in Ashkenazi probands, occurred on two related extended haplotypes. By contrast, the second, more common mutation (3992-9g-->a) was associated with nine different intergenic haplotypes and has been reported in non-Jewish HI patients as well. In this study, we evaluated disease-associated chromosomes from 41 Ashkenazi Jewish and 2 non-Jewish HI patients carrying the 3992-9g-->a mutation by assessing haplotypes defined by nine common single nucleotide polymorphisms (SNPs), six in the SUR1 gene, and three in the KIR6.2 gene. Our results indicate that all 54 chromosomes carrying the 3992-9g-->a mutation in the Jewish patients appear to have originated from one founder mutation, whereas the same mutation on chromosomes from non-Jewish patients originated independently. Furthermore, our findings have implications concerning the HI-associated chromosomes on which no

  7. 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.

  8. Signatures of mutational processes in human cancer

    PubMed Central

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

    2013-01-01

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

  9. Signatures of mutational processes in human cancer.

    PubMed

    Alexandrov, Ludmil B; Nik-Zainal, Serena; Wedge, David C; Aparicio, Samuel A J R; Behjati, Sam; Biankin, Andrew V; Bignell, Graham R; Bolli, Niccolò; 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; Imielinski, Marcin; 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

    2013-08-22

    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 cancer 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 aetiology, prevention and therapy.

  10. Genetic heterogeneity of pseudoxanthoma elasticum: the Chinese signature profile of ABCC6 and ENPP1 mutations.

    PubMed

    Jin, Liang; Jiang, Qiujie; Wu, Zhengsheng; Shao, Changxia; Zhou, Yong; Yang, Luting; Uitto, Jouni; Wang, Gang

    2015-05-01

    Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them being, to our knowledge, previously unreported, including 5 frameshift and 10 missense variants. In addition, a missense mutation in combination with a recurrent nonsense mutation in ENPP1 was discovered in a pediatric PXE case. No cases with p.R1141X or del23-29 mutations, common in Caucasian patient populations, were identified. The 10 missense mutations in ABCC6 were expressed in the mouse liver via hydrodynamic tail-vein injections. One mutant protein showed cytoplasmic accumulation indicating abnormal subcellular trafficking, while the other nine mutants showed correct plasma membrane location. These nine mutations were further investigated for their pathogenicity using a recently developed zebrafish mRNA rescue assay. Minimal rescue of the morpholino-induced phenotype was achieved with eight of the nine mutant human ABCC6 mRNAs tested, implying pathogenicity. This study demonstrates that the Chinese PXE population harbors unique ABCC6 mutations. These genetic data have implications for allele-specific therapy currently being developed for PXE. PMID:25615550

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Psychophysiological study on fasting therapy.

    PubMed

    Yamamoto, H; Suzuki, J; Yamauchi, Y

    1979-01-01

    The Tohoku University method of fasting therapy was performed on 380 patients. The clinical results revealed an efficacy rate of 87%. With regard to psychosomatic diseases, irritable colon syndrome, neurocirculatory asthenia, mild diabetes mellitus, obesity and borderline hypertension were good indications for this therapy. In order to clarify the therapeutic mechanism, several clinical examinations were administered before, during and after therapy. EEG data was analysed according to the power spectral method. The peak frequency decreased as fasting progressed, while it increased as re-fed continued. Percent energy of alpha waves after fasting therapy was significantly higher than that of the pre-fasting stage. The dexamethasone suppression rate of urine 17-OHCS after fasting therapy was significantly lower than that of the pre-fasting stage. It seems that ketone nutrition may work as a strong stressor in the brain cell, temporarily placing all biological mechanisms in a stress state and then activating the natural healing power inherent to the human body, thereby bringing about homeostasis.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. Mutation rate evolution in replicator dynamics.

    PubMed

    Allen, Benjamin; Rosenbloom, Daniel I Scholes

    2012-11-01

    The mutation rate of an organism is itself evolvable. In stable environments, if faithful replication is costless, theory predicts that mutation rates will evolve to zero. However, positive mutation rates can evolve in novel or fluctuating environments, as analytical and empirical studies have shown. Previous work on this question has focused on environments that fluctuate independently of the evolving population. Here we consider fluctuations that arise from frequency-dependent selection in the evolving population itself. We investigate how the dynamics of competing traits can induce selective pressure on the rates of mutation between these traits. To address this question, we introduce a theoretical framework combining replicator dynamics and adaptive dynamics. We suppose that changes in mutation rates are rare, compared to changes in the traits under direct selection, so that the expected evolutionary trajectories of mutation rates can be obtained from analysis of pairwise competition between strains of different rates. Depending on the nature of frequency-dependent trait dynamics, we demonstrate three possible outcomes of this competition. First, if trait frequencies are at a mutation-selection equilibrium, lower mutation rates can displace higher ones. Second, if trait dynamics converge to a heteroclinic cycle-arising, for example, from "rock-paper-scissors" interactions-mutator strains succeed against non-mutators. Third, in cases where selection alone maintains all traits at positive frequencies, zero and nonzero mutation rates can coexist indefinitely. Our second result suggests that relatively high mutation rates may be observed for traits subject to cyclical frequency-dependent dynamics.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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…

  10. 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…

  11. Scheduling and Achievement. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2006-01-01

    To use a block schedule or a traditional schedule? Which structure will produce the best and highest achievement rates for students? The research is mixed on this due to numerous variables such as: (1) socioeconomic levels; (2) academic levels; (3) length of time a given schedule has been in operation; (4) strategies being used in the classrooms;…

  12. 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…

  13. 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…

  14. 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…

  15. 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…

  16. Game Addiction and Academic Achievement

    ERIC Educational Resources Information Center

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

    2016-01-01

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

  17. 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…

  18. Achieving Results in MBA Communication.

    ERIC Educational Resources Information Center

    Barrett, Deborah J.

    2002-01-01

    Describes how Rice University's Jones Graduate School of Management achieves their mission for the communication program. Discusses three keys to the success of the program: individual coaching, integrated team instruction, and constant assessment of the students and the program. Presents an overview of the program. (SG)

  19. Attribution Theory in Science Achievement

    ERIC Educational Resources Information Center

    Craig, Martin

    2013-01-01

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

  20. Graders' Mathematics Achievement

    ERIC Educational Resources Information Center

    Bond, John B.; Ellis, Arthur K.

    2013-01-01

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

  1. 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…

  2. 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.

  3. Achievement in Two School Cultures.

    ERIC Educational Resources Information Center

    Borth, Audrey M.

    The purpose of the study was to assess non-intellective correlates of achievement in a lower-class, all black, urban elementary school. These students were compared with a University school population which was different in many dimensions. There were residual similarities relative to the general role of the elementary school student. In neither…

  4. Literacy Achievement in Nongraded Classrooms

    ERIC Educational Resources Information Center

    Kreide, Anita Therese

    2011-01-01

    This longitudinal quantitative study compared literacy achievement of students from second through sixth grade based on two organizational systems: graded (traditional) and nongraded (multiage) classrooms. The California Standards Test (CST) scaled and proficiency scores for English-Language Arts (ELA) were used as the study's independent variable…

  5. PREDICTING ACHIEVEMENT FOR DEAF CHILDREN.

    ERIC Educational Resources Information Center

    BONHAM, S.J., JR.

    THIS STUDY WAS DONE TO DETERMINE THE PREDICTIVE VALUE OF INDIVIDUAL AND GROUP ACHIEVEMENT TESTS WHEN USED TO EVALUATE DEAF CHILDREN. THE 36 CHILDREN SELECTED FOR THIS STUDY WERE IN GRADES 2, 4, AND 6 IN THE KENNEDY SCHOOL IN DAYTON, OHIO. ALL HAD SEVERE AUDITORY HANDICAPS AND WERE 10 TO 16 YEARS OLD. FOUR PSYCHOLOGISTS ADMINISTERED THE FOLLOWING…

  6. 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…

  7. Perlman receives Sustained Achievement Award

    NASA Astrophysics Data System (ADS)

    Petit, Charles; Perlman, David

    David Perlman was awarded the Sustained Achievement Award at the AGU Fall Meeting Honors Ceremony, which was held on December 10, 1997, in San Francisco, California. The award recognizes a journalist who has made significant, lasting, and consistent contributions to accurate reporting or writing on the geophysical sciences for the general public.

  8. Great achievements by dedicated nurses.

    PubMed

    Whyte, Alison

    2016-04-27

    Like many nurses, those featured here are motivated by a desire to do everything they can to give high quality care to their patients. Nurses are often reluctant to seek recognition for their achievements, but by talking publicly about the difference they have made, Gillian Elwood, Anja Templin and Sandra Wood are helping to share good practice. PMID:27191295

  9. 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…

  10. 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…

  11. Helping Rural Schools Achieve Success.

    ERIC Educational Resources Information Center

    Collins, Susan

    2003-01-01

    Senator Collins of Maine plans to fight for proper federal funding of the Rural Education Achievement Program (REAP) that allows rural schools to combine federal funding sources. Collins, and Senator Dianne Feinstein, will soon introduce legislation that will eliminate inequities in the current Social Security law that penalize teachers and other…

  12. 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…

  13. 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…

  14. 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…

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

    PubMed

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

    2014-08-27

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

  16. 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.

  17. Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype.

    PubMed

    Worgan, Lisa C; Niles, Kirsten; Tirone, Jamie C; Hofmann, Adam; Verner, Andrei; Sammak, Alya'a; Kucic, Terrence; Lepage, Pierre; Rosenblatt, David S

    2006-01-01

    Cobalamin nonresponsive methylmalonic acidemia (MMA, mut complementation class) results from mutations in the nuclear gene MUT, which codes for the mitochondrial enzyme methylmalonyl CoA mutase (MCM). To better elucidate the spectrum of mutations that cause MMA, the MUT gene was sequenced in 160 patients with mut MMA. Sequence analysis identified mutations in 96% of disease alleles. Mutations were found in all coding exons, but predominantly in exons 2, 3, 6, and 11. A total of 116 different mutations, 68 of which were novel, were identified. Of the 116 different mutations, 53% were missense mutations, 22% were deletions, duplications or insertions, 16% were nonsense mutations, and 9% were splice-site mutations. Sixty-one of the mutations have only been identified in one family. A novel mutation in exon 2, c.322C>T (p.R108C), was identified in 16 of 27 Hispanic patients. SNP genotyping data demonstrated that Hispanic patients with this mutation share a common haplotype. Three other mutations were seen exclusively in Hispanic patients: c.280G>A (p.G94R), c.1022dupA, and c.970G>A (p.A324T). Seven mutations were seen almost exclusively in black patients, including the previously reported c.2150G>T (p.G717V) mutation, which was identified in 12 of 29 black patients. Two mutations were seen only in Asian patients. Some frequently identified mutations were not population-specific and were identified in patients of various ethnic backgrounds. Some of these mutations were found in mutation clusters in exons 2, 3, 6, and 11, suggesting a recurrent mutation.

  18. Tailoring the metabolism against mutations

    NASA Astrophysics Data System (ADS)

    Gulbahce, Natali; Motter, Adilson E.; Almaas, Eivind; Barabasi, Albert Laszlo

    2008-03-01

    In the post-genomic era, organisms can be modelled at the whole-cell level in silico via steady state methods to describe their metabolic capabilities. We use two such methods, Flux Balance Analysis and Minimization of Metabolic Adjustment to explore the behavior of cells (of E. coli and S. cerevisiae) after severe mutations. We propose experimentally feasible ways of modifying the underlying biochemical reaction network of a mutant cell such that cell functionality, in particular growth rate, is significantly improved.

  19. [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

  20. Somatic mutation, genomic variation, and neurological disease.

    PubMed

    Poduri, Annapurna; Evrony, Gilad D; Cai, Xuyu; Walsh, Christopher A

    2013-07-01

    Genetic mutations causing human disease are conventionally thought to be inherited through the germ line from one's parents and present in all somatic (body) cells, except for most cancer mutations, which arise somatically. Increasingly, somatic mutations are being identified in diseases other than cancer, including neurodevelopmental diseases. Somatic mutations can arise during the course of prenatal brain development and cause neurological disease-even when present at low levels of mosaicism, for example-resulting in brain malformations associated with epilepsy and intellectual disability. Novel, highly sensitive technologies will allow more accurate evaluation of somatic mutations in neurodevelopmental disorders and during normal brain development.

  1. Somatic Mutation, Genomic Variation, and Neurological Disease

    PubMed Central

    Poduri, Annapurna; Evrony, Gilad D.; Cai, Xuyu; Walsh, Christopher A.

    2014-01-01

    Genetic mutations causing human disease are conventionally thought to be inherited through the germ line from one’s parents and present in all somatic (body) cells, except for most cancer mutations, which arise somatically. Increasingly, somatic mutations are being identified in diseases other than cancer, including neurodevelopmental diseases. Somatic mutations can arise during the course of prenatal brain development and cause neurological disease—even when present at low levels of mosaicism, for example—resulting in brain malformations associated with epilepsy and intellectual disability. Novel, highly sensitive technologies will allow more accurate evaluation of somatic mutations in neurodevelopmental disorders and during normal brain development. PMID:23828942

  2. Integrated Fast-Ignition Experiments on OMEGA

    NASA Astrophysics Data System (ADS)

    Theobald, W.; Stoeckl, C.; Glebov, V. Yu.; Marshall, F. J.; Anderson, K. S.; Betti, R.; Craxton, R. S.; Meyerhofer, D. D.; Nilson, P. M.; Sangster, T. C.; Solodov, A. A.; Frenje, J. A.; Petrasso, R. D.; Hey, D.; Patel, P. K.; Stephens, R. B.; Lauck, R.; Norreys, P. A.

    2009-11-01

    Integrated fast-ignition experiments using room-temperature cone-in-shell targets have begun at the Omega/Omega EP Laser Facility. Empty 40-μm-thick CD shells are imploded using 54 UV beams. At the time of peak compression, a short-pulse (˜10 ps) IR laser with energy >1 kJ is focused into the tip of the hollow cone. A three-fold increase in time-integrated 2- to 7-keV x-ray emission was observed, indicating that fast-electron energy is coupled into the core. Neutron detectors are strongly affected by the emission of an intense γ-ray pulse, making it challenging to measure neutron yield. Significant reduction of the γ-ray background has been achieved by gating the MCP detector and using a liquid scintillator to suppress the afterglow. The D2 neutron yield is being measured. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement Nos. DE-FC52-08NA28302, DE-FC02-04ER54789, and DE-FG02-05ER54839.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. LHON: Mitochondrial Mutations and More.

    PubMed

    Kirches, E

    2011-03-01

    Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of the electron transport chain. It was thus obvious to accuse neuronal energy depletion as the most probable mediator of neuronal death. The group of Valerio Carelli and other authors have nicely shown that energy depletion shapes the cell fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma cells, which do not fully model neuronal energy metabolism. Although complex I mutations may cause oxidative stress, a potential pathogenetic role of the latter was less taken into focus. The hypothesis of bioenergetic failure does not provide a simple explanation for the relatively late disease onset and for the incomplete penetrance, which differs remarkably between genders. It is assumed that other genetic and environmental factors are needed in addition to the 'primary LHON mutations' to elicit RGC death. Relevant nuclear modifier genes have not been identified so far. The review discusses the unresolved problems of a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in RGCs.

  8. Fast training algorithms for multilayer neural nets.

    PubMed

    Brent, R P

    1991-01-01

    An algorithm that is faster than back-propagation and for which it is not necessary to specify the number of hidden units in advance is described. The relationship with other fast pattern-recognition algorithms, such as algorithms based on k-d trees, is discussed. The algorithm has been implemented and tested on artificial problems, such as the parity problem, and on real problems arising in speech recognition. Experimental results, including training times and recognition accuracy, are given. Generally, the algorithm achieves accuracy as good as or better than nets trained using back-propagation. Accuracy is comparable to that for the nearest-neighbor algorithm, which is slower and requires more storage space.

  9. 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).

  10. Fast Photochromic Molecules toward Realization of Photosynergetic Effects.

    PubMed

    Kobayashi, Yoichi; Mutoh, Katsuya; Abe, Jiro

    2016-09-15

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

  11. Fast Photochromic Molecules toward Realization of Photosynergetic Effects.

    PubMed

    Kobayashi, Yoichi; Mutoh, Katsuya; Abe, Jiro

    2016-09-15

    There has been a growing interest toward the development of advanced photofunctional materials whose photoresponses involve multiple photons and molecules because these materials show the photoresponses which cannot be achieved by a one-photon reaction of a single chromophore. These cooperative interactions of multiple photons and molecules are recently termed as the "photosynergetic" effects, and the understanding and utilization of these effects are becoming important research topics. In this Perspective, we overview the recent progress of the fast T-type photochromic molecules involving the stepwise two-photon absorption processes. Although high power pulse lasers were necessary to induce conventional simultaneous and stepwise two-photon absorption processes, the stepwise two-photon absorption process with the fast photochromic compound can be initiated by extremely weak continuous wave (CW) LEDs. The basic concept and future outlook of the fast photochromism involving the stepwise two-photon absorption process will be discussed. PMID:27585058

  12. The evolution of low mutation rates in experimental mutator populations of Saccharomyces cerevisiae.

    PubMed

    McDonald, Michael J; Hsieh, Yu-Ying; Yu, Yen-Hsin; Chang, Shang-Lin; Leu, Jun-Yi

    2012-07-10

    Mutation is the source of both beneficial adaptive variation and deleterious genetic load, fueling the opposing selective forces than shape mutation rate evolution. This dichotomy is well illustrated by the evolution of the mutator phenotype, a genome-wide 10- to 100-fold increase in mutation rate. This phenotype has often been observed in clonally expanding populations exposed to novel or frequently changing conditions. Although studies of both experimental and natural populations have shed light on the evolutionary forces that lead to the spread of the mutator allele through a population, significant gaps in our understanding of mutator evolution remain. Here we use an experimental evolution approach to investigate the conditions required for the evolution of a reduction in mutation rate and the mechanisms by which populations tolerate the accumulation of deleterious mutations. We find that after ∼6,700 generations, four out of eight experimental mutator lines had evolved a decreased mutation rate. We provide evidence that the accumulation of deleterious mutations leads to selection for reduced mutation rate clones in populations of mutators. Finally, we test the long-term consequences of the mutator phenotype, finding that mutator lines follow different evolutionary trajectories, some of which lead to drug resistance.

  13. 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...

  14. Myopathies associated with β-tropomyosin mutations.

    PubMed

    Tajsharghi, H; Ohlsson, M; Palm, L; Oldfors, A

    2012-11-01

    Mutations in TPM2, encoding β-tropomyosin, have recently been found to cause a range of muscle disorders. We review the clinical and morphological expression of the previously reported mutations illustrating the heterogeneity of β-tropomyosin-associated diseases and describe an additional case with a novel mutation. The manifestations of mutations in TPM2 include non-specific congenital myopathy with type 1 fibre predominance, nemaline myopathy, cap disease and distal arthrogryposis. In addition, Escobar syndrome with nemaline myopathy is a manifestation of homozygous truncating β-tropomyosin mutation. Cap disease appears to be the most common morphological manifestation. A coarse intermyofibrillar network and jagged Z lines are additional frequent changes. The dominant β-tropomyosin mutations manifest either as congenital myopathy or distal arthrogryposis. The various congenital myopathies are usually associated with moderate muscle weakness and no congenital joint contractures. The distal arthrogryposis syndromes associated with TPM2 mutations include the less severe forms, with congenital contractures mainly of the hands and feet and mild or no muscle weakness. The dominant TPM2 mutations include amino acid deletions/insertions and missense mutations. There is no clear relation between the type of mutations or the localisation of the mutated residue in the β-tropomyosin molecule and the clinical and morphological phenotype. PMID:22749895

  15. 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

  16. KRAS mutation testing in clinical practice.

    PubMed

    Perincheri, Sudhir; Hui, Pei

    2015-03-01

    Activating mutation of KRAS plays a significant role in the pathogenesis of common human malignancies and molecular testing of KRAS mutation has emerged as an essential biomarker in the current practice of clinical oncology. The presence of KRAS mutation is generally associated with clinical aggressiveness of the cancer and reduced survival of the patient. Therapeutically, KRAS mutation testing has maximum utility in stratifying metastatic colorectal carcinoma and lung cancer patients for treatment with targeted therapy. Diagnostically, KRAS mutation testing is useful in the workup of pancreaticobiliary and thyroid cancers, particularly using cytological specimens. In the era of precision medicine, the role of KRAS mutation testing is poised to expand, likely in a setting of combinatorial therapeutic strategy and requiring additional mutation testing of its upstream and/or downstream effectors.

  17. Androgen receptor gene mutation, rearrangement, polymorphism.

    PubMed

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

    2013-09-01

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

  18. [Applications of microchip electrophoresis and capillary electrophoresis for screening FLT3-ITD gene mutation in acute myeloid leukemia].

    PubMed

    Leng, Xin; Li, Ling-Di; Li, Jin-Lan; Huang, Xiao-Jun; Ruan, Guo-Rui

    2014-02-01

    The purpose of the present study was to compare the reliability of microchip electrophoresis and capillary electrophoresis for screening FLT3-ITD gene mutation in acute myeloid leukemia. The FLT3-ITD mutation in the genomic DNA samples from 214 untreated AML patients were separately detected by PCR-microchip electrophoresis and PCR-capillary electrophoresis, then the DNA direct sequencing analysis was carried out. The results from PCR-microchip electrophoresis showed that there were 151 FLT3-ITD mutation negative, 58 FLT3-ITD mutation positive (58/214, 27.1%) and 5 FLT3-ITD mutation doubtful positive (5/214, 2.3%), while the outcomes from PCR-capillary electrophoresis displayed that there were 147 FLT3-ITD mutation negative and 67 FLT3-ITD mutation positive (67/214, 31.3%) without doubtful positive. In the 67 FLT3-ITD mutation positive samples detected by using PCR-capillary electrophoresis, 4 samples were detected as the negative while 5 samples were measured as the doubtful positive by using PCR-microchip electrophoresis. The followed sequencing analysis demonstrated that the above 9 samples were all FLT3-ITD mutation positive, indicating that PCR-capillary electrophoresis was more accurate and sensitive in screening the FLT3-ITD mutation, although statistic analysis showed that there were no significant differences in the detected results between PCR-microchip electrophoresis and PCR-capillary electrophoresis groups (Pearson Chi-squared Test, P > 0.05). It is concluded that both PCR-microchip electrophoresis and PCR-capillary electrophoresis were convenient and fast for screening FLT3-ITD mutation, but the accuracy of PCR-microchip electrophoresis awaits further improvement.

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

    PubMed

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

    2015-01-01

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

  20. 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

  1. A novel diagnostic biosensor for distinguishing immunoglobulin mutated and unmutated types of chronic lymphocytic leukemia.

    PubMed

    Ensafi, Ali A; Amini, Maryam; Rezaei, Behzad; Talebi, Majid

    2016-03-15

    In chronic lymphocytic leukemia (CLL), the immunoglobulin heavy-chain variable (IgVH) region may be mutated (Ig-mutated CLL) or unmutated (Ig-unmutated CLL); and the presence or absence of mutations in this region of CLL cells distinguishes two clinically distinct forms. It is important for physicians to distinguish between patients with Ig-unmutated CLL, where typically have more indolent disease with median survivals close to 25 years, and Ig-mutated CLL, where have more aggressive disease with median survivals around eight years. In this work, a biosensor capable of diagnosis and distinguishing between these two types of CLL was reported. The biosensor was fabricated by modifying a gold electrode with gold nanoparticles (AuNPS) followed by coating of ZAP70 oligonucleotide probe on the surface to detect specific sequence of ZAP70 gene. ZAP70 could predict the IgVH mutation status and is a good marker for differentiating Ig-mutated and Ig-unmutated CLL and serve as prognostic marker. First, we focused on achieving hybridization between probe and its complementary sequence. Hybridization between probe and target was determined with electrochemical impedance spectroscopy (EIS). Then, our efforts turned to optimize the conditions for the detection of any point mutation and also to maximize the selectivity. Under optimal conditions, the biosensor has a good calibration range between 2.0 × 10(-14) and 1.0 × 10(-9)molL(-1), with ZAP70 DNA sequence detection limit of 4.0 × 10(-15)molL(-1). We successfully detect hybridization first in synthetic samples, and ultimately in blood samples from patients. Experimental results illustrated that the nanostructured biosensor clearly discriminates between mutated and non-mutated CLL and predict the IgVH mutation status, which it has been considered as the single most informative stage independent prognostic factor in CLL.

  2. Selectivity profile of afatinib for EGFR-mutated non-small-cell lung cancer.

    PubMed

    Wang, Debby D; Lee, Victor H F; Zhu, Guangyu; Zou, Bin; Ma, Lichun; Yan, Hong

    2016-04-26

    EGFR-mutated non-small-cell lung cancer (NSCLC) has long been a research focus in lung cancer studies. Besides reversible tyrosine kinase inhibitors (TKIs), new-generation irreversible inhibitors, such as afatinib, embark on playing an important role in NSCLC treatment. To achieve an optimal application of these inhibitors, the correlation between the EGFR mutation status and the potency of such an inhibitor should be decoded. In this study, the correlation was profiled for afatinib, based on a cohort of patients with the EGFR-mutated NSCLC. Relying on extracted DNAs from the paraffin-embedded tumor samples, EGFR mutations were detected by direct sequencing. Progression-free survival (PFS) and the response level were recorded as study endpoints. These PFS and response values were analyzed and correlated to different mutation types, implying a higher potency of afatinib to classic activation mutations (L858R and deletion 19) and a lower one to T790M-related mutations. To further bridge the mutation status with afatinib-related response or PFS, we conducted a computational study to estimate the binding affinity in a mutant-afatinib system, based on molecular structural modeling and dynamics simulations. The derived binding affinities were well in accordance with the clinical response or PFS values. At last, these computational binding affinities were successfully mapped to the patient response or PFS according to linear models. Consequently, a detailed mutation-response or mutation-PFS profile was drafted for afatinib, implying the selective nature of afatinib to various EGFR mutants and further encouraging the design of specialized therapies or innovative drugs. PMID:26961138

  3. 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

  4. 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.

  5. 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)

  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. 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.

  8. Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability.

    PubMed

    Raimondo, Anne; Chakera, Ali J; Thomsen, Soren K; Colclough, Kevin; Barrett, Amy; De Franco, Elisa; Chatelas, Alisson; Demirbilek, Huseyin; Akcay, Teoman; Alawneh, Hussein; Flanagan, Sarah E; Van De Bunt, Martijn; Hattersley, Andrew T; Gloyn, Anna L; Ellard, Sian

    2014-12-15

    Mutations in glucokinase (GCK) cause a spectrum of glycemic disorders. Heterozygous loss-of-function mutations cause mild fasting hyperglycemia irrespective of mutation severity due to compensation from the unaffected allele. Conversely, homozygous loss-of-function mutations cause permanent neonatal diabetes requiring lifelong insulin treatment. This study aimed to determine the relationship between in vitro mutation severity and clinical phenotype in a large international case series of patients with homozygous GCK mutations. Clinical characteristics for 30 patients with diabetes due to homozygous GCK mutations (19 unique mutations, including 16 missense) were compiled and assigned a clinical severity grade (CSG) based on birth weight and age at diagnosis. The majority (28 of 30) of subjects were diagnosed before 9 months, with the remaining two at 9 and 15 years. These are the first two cases of a homozygous GCK mutation diagnosed outside infancy. Recombinant mutant GCK proteins were analyzed for kinetic and thermostability characteristics and assigned a relative activity index (RAI) or relative stability index (RSI) value. Six of 16 missense mutations exhibited severe kinetic defects (RAI ≤ 0.01). There was no correlation between CSG and RAI (r(2) = 0.05, P = 0.39), indicating that kinetics alone did not explain the phenotype. Eighty percent of the remaining mutations showed reduced thermostability, the exceptions being the two later-onset mutations which exhibited increased thermostability. Comparison of CSG with RSI detected a highly significant correlation (r(2) = 0.74, P = 0.002). We report the largest case series of homozygous GCK mutations to date and demonstrate that they can cause childhood-onset diabetes, with protein instability being the major determinant of mutation severity. PMID:25015100

  9. Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability.

    PubMed

    Raimondo, Anne; Chakera, Ali J; Thomsen, Soren K; Colclough, Kevin; Barrett, Amy; De Franco, Elisa; Chatelas, Alisson; Demirbilek, Huseyin; Akcay, Teoman; Alawneh, Hussein; Flanagan, Sarah E; Van De Bunt, Martijn; Hattersley, Andrew T; Gloyn, Anna L; Ellard, Sian

    2014-12-15

    Mutations in glucokinase (GCK) cause a spectrum of glycemic disorders. Heterozygous loss-of-function mutations cause mild fasting hyperglycemia irrespective of mutation severity due to compensation from the unaffected allele. Conversely, homozygous loss-of-function mutations cause permanent neonatal diabetes requiring lifelong insulin treatment. This study aimed to determine the relationship between in vitro mutation severity and clinical phenotype in a large international case series of patients with homozygous GCK mutations. Clinical characteristics for 30 patients with diabetes due to homozygous GCK mutations (19 unique mutations, including 16 missense) were compiled and assigned a clinical severity grade (CSG) based on birth weight and age at diagnosis. The majority (28 of 30) of subjects were diagnosed before 9 months, with the remaining two at 9 and 15 years. These are the first two cases of a homozygous GCK mutation diagnosed outside infancy. Recombinant mutant GCK proteins were analyzed for kinetic and thermostability characteristics and assigned a relative activity index (RAI) or relative stability index (RSI) value. Six of 16 missense mutations exhibited severe kinetic defects (RAI ≤ 0.01). There was no correlation between CSG and RAI (r(2) = 0.05, P = 0.39), indicating that kinetics alone did not explain the phenotype. Eighty percent of the remaining mutations showed reduced thermostability, the exceptions being the two later-onset mutations which exhibited increased thermostability. Comparison of CSG with RSI detected a highly significant correlation (r(2) = 0.74, P = 0.002). We report the largest case series of homozygous GCK mutations to date and demonstrate that they can cause childhood-onset diabetes, with protein instability being the major determinant of mutation severity.

  10. Phenotypic severity of homozygous GCK mutations causing neonatal or childhood-onset diabetes is primarily mediated through effects on protein stability

    PubMed Central

    Raimondo, Anne; Chakera, Ali J.; Thomsen, Soren K.; Colclough, Kevin; Barrett, Amy; De Franco, Elisa; Chatelas, Alisson; Demirbilek, Huseyin; Akcay, Teoman; Alawneh, Hussein; Flanagan, Sarah E.; Van De Bunt, Martijn; Hattersley, Andrew T.; Gloyn, Anna L.; Ellard, Sian; Abduljabbar, Mohammad A.; Al-Zyoud, Mahmoud; Aman, Syed; Bath, Louise; De, Parijat; Deshpande, Neeta; Durmaz, Erdem; Eickmeier, Frank; Elbarbary, Nancy Samir; Fillion, Marc; Jagadeesh, Sujatha M.; Kershaw, Melanie; Khan, Waqas I.; Mlynarski, Wojciech; Noyes, Kathryn; Peters, Catherine J.; Shaw, Nick; Tiron, Irina; Turkkahraman, Doga; Turner, Lesley; Eltonbary, Khadiga Y.; Yuksel, Bilgin

    2014-01-01

    Mutations in glucokinase (GCK) cause a spectrum of glycemic disorders. Heterozygous loss-of-function mutations cause mild fasting hyperglycemia irrespective of mutation severity due to compensation from the unaffected allele. Conversely, homozygous loss-of-function mutations cause permanent neonatal diabetes requiring lifelong insulin treatment. This study aimed to determine the relationship between in vitro mutation severity and clinical phenotype in a large international case series of patients with homozygous GCK mutations. Clinical characteristics for 30 patients with diabetes due to homozygous GCK mutations (19 unique mutations, including 16 missense) were compiled and assigned a clinical severity grade (CSG) based on birth weight and age at diagnosis. The majority (28 of 30) of subjects were diagnosed before 9 months, with the remaining two at 9 and 15 years. These are the first two cases of a homozygous GCK mutation diagnosed outside infancy. Recombinant mutant GCK proteins were analyzed for kinetic and thermostability characteristics and assigned a relative activity index (RAI) or relative stability index (RSI) value. Six of 16 missense mutations exhibited severe kinetic defects (RAI ≤ 0.01). There was no correlation between CSG and RAI (r2 = 0.05, P = 0.39), indicating that kinetics alone did not explain the phenotype. Eighty percent of the remaining mutations showed reduced thermostability, the exceptions being the two later-onset mutations which exhibited increased thermostability. Comparison of CSG with RSI detected a highly significant correlation (r2 = 0.74, P = 0.002). We report the largest case series of homozygous GCK mutations to date and demonstrate that they can cause childhood-onset diabetes, with protein instability being the major determinant of mutation severity. PMID:25015100

  11. Molecular characterization of antithrombin III (ATIII) variants using polymerase chain reaction. Identification of the ATIII Charleville as an Ala 384 Pro mutation.

    PubMed Central

    Molho-Sabatier, P; Aiach, M; Gaillard, I; Fiessinger, J N; Fischer, A M; Chadeuf, G; Clauser, E

    1989-01-01

    The genes of seven structural mutants of antithrombin III (ATIII), presenting either defective serine protease reactivity or abnormal heparin binding, were analyzed. The polymerase chain reaction (PCR) was used to amplify the corresponding gene exon and the mutation was identified by either dot blot analysis using a battery of allele-specific oligonucleotide probes or sequencing. Variants Paris and Paris 2 were identified as Arg 47 Cys mutations, and Clichy, Clichy 2, and Franconville were found to be Pro 41 Leu mutations. All five are heparin binding-site variants. ATIII Avranches is an Arg 393 His mutation and ATIII Charleville is an Ala 384 Pro mutation. These two mutations impair the reactive site of the molecule. ATIII Charleville is a new mutation of the reactive center, as predicted by previous biochemical data. The position of this new mutation, together with the other previously described mutations of the reactive center, sheds light on the molecular function of this site in inhibiting thrombin. Finally, genomic amplification by PCR is a powerful technique for the fast identification of antithrombin III mutations and their homozygous/heterozygous status, and should be useful for predicting thrombotic risk. Images PMID:2794060

  12. 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.

  13. [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.

  14. 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

  15. A fast spectrum heat pipe cooled thermionic power system

    NASA Astrophysics Data System (ADS)

    Mills, Joseph C.; Determan, William R.; Van Hagan, Thomas H.; Wuchte, Thomas, Captain

    1992-01-01

    This paper summarizes the design and performance characteristics of a heat pipe cooled thermionic (HPTI) power system being developed by a team headed by Rockwell International and General Atomics (GA). The design utilizes multicell, in-core thermionic fuel elements (TFEs) in a fast spectrum reactor core that is passively cooled by in-core heat pipes. The fast spectrum promotes competitive mass scalability over the power range of interest for future military application of 10 to 100 kWe without changing basic components or technologies. The number of TFEs and companion uranium nitride fuel elements are merely varied to achieve the critical mass requirements for each power level. The redundant in-core heat pipes in conjunction with an internally redundant heat pipe radiator help assure meeting key design goals for no single point failures and high survivability to both natural and hostile threats. These attractive attributes are achieved using already developed or under development technology.

  16. 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.

  17. 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.

  18. Fast response pyroelectric detector-preamplifier assembled device

    NASA Astrophysics Data System (ADS)

    Bai, PiJi; Tai, Yunjian; Liu, Huiping

    2008-03-01

    The pyroelectric detector is wide used for its simple structure and high performance to price ratio. It has been used in thermal detecting, infrared spectrum and laser testing. When the pyroelectric detector was applied in practice, fast reponse speed is need. For improving the response speed of the pyroelectric detector some specific technology has been used in the preamplifier schematic. High sense and fast response character of the pyroelectric detector-preamplifier assembled device had been achieved. When the device is applied in acute concussion condition, it must survive from the acute concussion condition testing. For it reliability some specific technology was used in the device fabricating procedure. At last the performance parameter testing result and simulation application condition result given in this paper show the performance of the pyroelectric detector-preamplifier assembled device had achieved the advance goal.

  19. Fast Ignition Realization Experiments (FIREX) and Beyond

    NASA Astrophysics Data System (ADS)

    Azechi, Hiroshi

    2010-11-01

    After 50 years journey from the innovation of lasers, controlled ignition and subsequent burn will be demonstrated within a couple of years at the US National Ignition Facility (NIF). Fast ignition has the high potential to ignite a fuel using only about one tenth of laser energy of NIF [1]. One of the most advanced fast ignition programs is the Fast Ignition Realization Experiment (FIREX) [2]. The goal of its first phase is to demonstrate ignition temperature of 5 keV, followed by the second phase to demonstrate the ignition-and-burn. The first experiment of FIREX-I, reported here, gives a confidence that one can achieve ignition temperature at the heating laser energy of 10 kJ. One beam of LFEX laser was equipped with a pair of tiled gratings and successfully compressed to 1.2 ps with the energy of 1 kJ, providing about 1 PW laser power. The first experiment with the LFEX laser was performed using deuterated polystyrene shells with a gold cone. Ion temperatures of the core plasmas were deduced from the observed neutron yield, fuel density and the fuel mass. The result gives a confidence that ion temperature will increase up to the 5-keV level with using sharp rising rectangular laser pulse. Given the demonstrations of the ignition temperature at FIREX-I and the ignition-and-burn at NIF, the inertial fusion research would then shift from the plasma physics era to electric power era. Success of the high power short pulse laser system LFEX also makes us envisage future ultra high intensity lasers, such as, GEKKO-EXA and ELI [3] with sub exa Watt power. Extremely high intensity achieved in such facilities will open up ultra high-field physics. [4pt] [1] E.I. Moses, Nucl. Fusion 49(2009)104022. [0pt] [2] H. Azechi et al., Nucl. Fusion 49 (2009) 104024. [0pt] [3] http://www.extreme-light-infrastructure.eu/what-is-eli.php

  20. 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.

  1. Cone-guided fast ignition with no imposed magnetic fields

    NASA Astrophysics Data System (ADS)

    Strozzi, D.; Tabak, M.; Larson, D.; Marinak, M.; Key, M.; Divol, L.; Kemp, A.; Bellei, C.; Shay, H.

    2013-11-01

    Simulations are presented of ignition-scale fast ignition targets with the integrated Zuma-Hydra PIC-hydrodynamic capability. We consider a spherical DT fuel assembly with a carbon cone, and an artificially-collimated fast electron source. We study the role of E and B fields and the fast electron energy spectrum. For mono-energetic 1.5 MeV fast electrons, without E and B fields, ignition can be achieved with fast electron energy Efig = 30kJ. This is 3.5× the minimal deposited ignition energy of 8.7 kJ for our fuel density of 450 g/cm3. Including E and B fields with the resistive Ohm's law E = ηJb gives Efig = 20kJ, while using the full Ohm's law gives Efig > 40 kJ. This is due to magnetic self-guiding in the former case, and ∇n ×∇T magnetic fields in the latter. Using a realistic, quasi two-temperature energy spectrum derived from PIC laser-plasma simulations increases Efig to (102, 81, 162) kJ for (no E/B, E = ηJb, full Ohm's law). Such electrons are too energetic to stop in the optimal hot spot depth.

  2. 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

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

    PubMed

    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

    2016-01-25

    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.

  4. 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

  5. [Treatment of two chronic myeloid leukemia patients with V299L mutation by using nilotinib].

    PubMed

    Yang, Xiang-Chou; Qiu, Hong-Xia; Zhang, Su-Jiang; Wang, Ju-Juan; Ouyang, Yuan; Pan, Liang-Qin; Qiao, Chun; Li, Jian-Yong

    2014-06-01

    This study was aimed to enhance clinical understanding the effect of nilotinib on CML patients with V299L mutation who were resistant to imatinib. Bone marrow specimens from 2 cases of CML with V299L mutation were collected before and after the treatment with nilotinib. ABL mutation was detected by nested reverse transcription polymerase chain reaction (PCR) followed by direct sequencing. The clinical characteristics of the two cases were analyzed. The results showed that both cases were resistant to imatinib presented V299L mutation. Out of them 1 case achieved complete haematological response (CHR) after treatment with nilotinib for 6 months and another case abstained obvious molecular response after using nilotinib for 7 month. V299L mutation of both cases was turned into negative after the treatment with nilotinib. It is concluded that the nilotinib can safely and effectively override tyrosine kinase inhibitor (TKI) resistance mediated by the V299L mutation. The safety and efficacy of nilotinib for treatment of CML patients with TKI resistance and V299L mutation are satisfactory.

  6. 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

  7. 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.

  8. Mutations affecting enzymatic activity in liver arginase

    SciTech Connect

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

    1994-09-01

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

  9. Generation of a monkey with MECP2 mutations by TALEN-based gene targeting.

    PubMed

    Liu, Zhen; Zhou, Xue; Zhu, Ying; Chen, Zhi-Fang; Yu, Bin; Wang, Yan; Zhang, Chen-Chen; Nie, Yan-Hong; Sang, Xiao; Cai, Yi-Jun; Zhang, Yue-Fang; Zhang, Chen; Zhou, Wen-Hao; Sun, Qiang; Qiu, Zilong

    2014-06-01

    Gene editing in model organisms has provided critical insights into brain development and diseases. Here, we report the generation of a cynomolgus monkey (Macaca fascicularis) carrying MECP2 mutations using transcription activator-like effector nucleases (TALENs)-mediated gene targeting. After injecting TALENs mRNA into monkey zygotes achieved by in vitro fertilization and embryo transplantation into surrogate monkeys, we obtained one male newborn monkey with an MECP2 deletion caused by frameshifting mutation in various tissues. The monkey carrying the MECP2 mutation failed to survive after birth, due to either the toxicity of TALENs or the critical requirement of MECP2 for neural development. The level of MeCP2 protein was essentially depleted in the monkey's brain. This study demonstrates the feasibility of introducing genetic mutations in non-human primates by site-specific gene-editing methods.

  10. 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.

  11. 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

  12. Fast-response cloud chamber

    NASA Technical Reports Server (NTRS)

    Fogal, G. L.

    1977-01-01

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

  13. Fast Detector Simulation Using Lelaps

    SciTech Connect

    Langeveld, W

    2004-08-20

    Lelaps is a fast detector simulation program which reads StdHep generator files and produces SIO or LCIO output files. It swims particles through detectors taking into account magnetic fields, multiple scattering and dE/dx energy loss. It simulates parameterized showers in EM and hadronic calorimeters and supports gamma conversions and decays.

  14. Fast Facts 26-42.

    ERIC Educational Resources Information Center

    Florida State Board of Community Colleges, Tallahassee.

    The document is a compilation of Fast Facts on a wide range of issues affecting the Florida Community College System (FCCS) and higher education in general. It uses data extracted from a federal publication entitled "Answers in the Tool Box." Some of the topics that are addressed are as follows: important variables for student baccalaureate…

  15. Fast and Easy Website Tuneups

    ERIC Educational Resources Information Center

    Wisniewski, Jeff

    2008-01-01

    This article presents fast, easy and helpful hints for making web sites that people will want to use over and over again. These tips include: (1) Making sure that the website's copyright statement is up-to-date; (2) Adding "last updated" code to each webpage at the site; (3) Adding photos to the site's contact information; (4) Turning boring old…

  16. Fast superconducting magnetic field switch

    SciTech Connect

    Goren, Y.; Mahale, N.K.

    1995-12-31

    The superconducting magnetic switch or fast kicker magnet is employed with an electron stream or a bunch of electrons to rapidly change the direction of flow of the electron stream or bunch of electrons. The apparatus employs a beam tube which is coated with a film of superconducting material. The tube is cooled to a temperature below the superconducting transition temperature and is subjected to a constant magnetic field which is produced by an external dc magnet. The magnetic field produced by the dc magnet is less than the critical field for the superconducting material, thus, creating a Meissner Effect condition. A controllable fast electromagnet is used to provide a magnetic field which supplements that of the dc magnet so that when the fast magnet is energized the combined magnetic field is now greater than the critical field and the superconducting material returns to its normal state allowing the magnetic field to penetrate the tube. This produces an internal field which effects the direction of motion and of the electron stream or electron bunch. The switch can also operate as a switching mechanism for charged particles. Magnetic switches and particularly fast kicker magnets are used in the accelerator industry to quickly deflect particle beams into and out of various transport lines, storage rings, dumps, and specifically to differentially route individual bunches of particles from a train of bunches which are injected or ejected from a given ring.

  17. Fast Atom Bombardment Mass Spectrometry.

    ERIC Educational Resources Information Center

    Rinehart, Kenneth L., Jr.

    1982-01-01

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

  18. 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.

  19. Expanding the mutation spectrum in 130 probands with ARPKD: identification of 62 novel PKHD1 mutations by sanger sequencing and MLPA analysis.

    PubMed

    Melchionda, Salvatore; Palladino, Teresa; Castellana, Stefano; Giordano, Mario; Benetti, Elisa; De Bonis, Patrizia; Zelante, Leopoldo; Bisceglia, Luigi

    2016-09-01

    Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe genetic disorder arising in the perinatal period, although a late-onset presentation of the disease has been described. Pulmonary hypoplasia is the major cause of morbidity and mortality in the newborn period. ARPKD is caused by mutations in the PKHD1 (polycystic kidney and hepatic disease 1) gene that is among the largest human genes. To achieve a molecular diagnosis of the disease, a large series of Italian affected subjects were recruited. Exhaustive mutation analysis of PKHD1 gene was carried out by Sanger sequencing and multiple ligation probe amplification (MLPA) technique in 110 individuals. A total of 173 mutations resulting in a detection rate of 78.6% were identified. Additional 20 unrelated patients, in whom it was not possible to analyze the whole coding sequence, have been included in this study. Taking into account the total number (n=130) of this cohort of patients, 107 different types of mutations have been detected in 193 mutated alleles. Out of 107 mutations, 62 were novel: 11 nonsense, 6 frameshift, 7 splice site mutations, 2 in-frame deletions and 2 multiexon deletion detected by MLPA. Thirty-four were missense variants. In conclusion, our report expands the spectrum of PKHD1 mutations and confirms the heterogeneity of this disorder. The population under study represents the largest Italian ARPKD cohort reported to date. The estimated costs and the time invested for molecular screening of genes with large size and allelic heterogeneity such as PKHD1 demand the use of next-generation sequencing (NGS) technologies for a faster and cheaper screening of the affected subjects. PMID:27225849

  20. Expanding the mutation spectrum in 130 probands with ARPKD: identification of 62 novel PKHD1 mutations by sanger sequencing and MLPA analysis.

    PubMed

    Melchionda, Salvatore; Palladino, Teresa; Castellana, Stefano; Giordano, Mario; Benetti, Elisa; De Bonis, Patrizia; Zelante, Leopoldo; Bisceglia, Luigi

    2016-09-01

    Autosomal recessive polycystic kidney disease (ARPKD) is a rare severe genetic disorder arising in the perinatal period, although a late-onset presentation of the disease has been described. Pulmonary hypoplasia is the major cause of morbidity and mortality in the newborn period. ARPKD is caused by mutations in the PKHD1 (polycystic kidney and hepatic disease 1) gene that is among the largest human genes. To achieve a molecular diagnosis of the disease, a large series of Italian affected subjects were recruited. Exhaustive mutation analysis of PKHD1 gene was carried out by Sanger sequencing and multiple ligation probe amplification (MLPA) technique in 110 individuals. A total of 173 mutations resulting in a detection rate of 78.6% were identified. Additional 20 unrelated patients, in whom it was not possible to analyze the whole coding sequence, have been included in this study. Taking into account the total number (n=130) of this cohort of patients, 107 different types of mutations have been detected in 193 mutated alleles. Out of 107 mutations, 62 were novel: 11 nonsense, 6 frameshift, 7 splice site mutations, 2 in-frame deletions and 2 multiexon deletion detected by MLPA. Thirty-four were missense variants. In conclusion, our report expands the spectrum of PKHD1 mutations and confirms the heterogeneity of this disorder. The population under study represents the largest Italian ARPKD cohort reported to date. The estimated costs and the time invested for molecular screening of genes with large size and allelic heterogeneity such as PKHD1 demand the use of next-generation sequencing (NGS) technologies for a faster and cheaper screening of the affected subjects.

  1. Fast Neutron Sensitivity with HPGe

    SciTech Connect

    Seifert, Allen; Hensley, Walter K.; Siciliano, Edward R.; Pitts, W. K.

    2008-01-22

    In addition to being excellent gamma-ray detectors, germanium detectors are also sensitive to fast neutrons. Incident neutrons undergo inelastic scattering {Ge(n,n')Ge*} off germanium nuclei and the resulting excited states emit gamma rays or conversion electrons. The response of a standard 140% high-purity germanium (HPGe) detector with a bismuth germanate (BGO) anti-coincidence shield was measured for several neutron sources to characterize the ability of the HPGe detector to detect fast neutrons. For a sensitivity calculation performed using the characteristic fast neutron response peak that occurs at 692 keV, the 140% germanium detector system exhibited a sensitivity of ~175 counts / kg of WGPumetal in 1000 seconds at a source-detector distance of 1 meter with 4 in. of lead shielding between source and detector. Theoretical work also indicates that it might be possible to use the shape of the fast-neutron inelastic scattering signatures (specifically, the end-point energy of the long high energy tail of the resulting asymmetric peak) to gain additional information about the energy distribution of the incident neutron spectrum. However, the experimentally observed end-point energies appear to be almost identical for each of the fast neutron sources counted. Detailed MCNP calculations show that the neutron energy distributions impingent on the detector for these sources are very similar in this experimental configuration, due to neutron scattering in a lead shield (placed between the neutron source and HPGe detector to reduce the gamma ray flux), the BGO anti-coincidence detector, and the concrete floor.

  2. How mutation affects evolutionary games on graphs.

    PubMed

    Allen, Benjamin; Traulsen, Arne; Tarnita, Corina E; Nowak, Martin A

    2012-04-21

    Evolutionary dynamics are affected by population structure, mutation rates and update rules. Spatial or network structure facilitates the clustering of strategies, which represents a mechanism for the evolution of cooperation. Mutation dilutes this effect. Here we analyze how mutation influences evolutionary clustering on graphs. We introduce new mathematical methods to evolutionary game theory, specifically the analysis of coalescing random walks via generating functions. These techniques allow us to derive exact identity-by-descent (IBD) probabilities, which characterize spatial assortment on lattices and Cayley trees. From these IBD probabilities we obtain exact conditions for the evolution of cooperation and other game strategies, showing the dual effects of graph topology and mutation rate. High mutation rates diminish the clustering of cooperators, hindering their evolutionary success. Our model can represent either genetic evolution with mutation, or social imitation processes with random strategy exploration.

  3. DCDC2 Mutations Cause Neonatal Sclerosing Cholangitis.

    PubMed

    Girard, Muriel; Bizet, Albane A; Lachaux, Alain; Gonzales, Emmanuel; Filhol, Emilie; Collardeau-Frachon, Sophie; Jeanpierre, Cécile; Henry, Charline; Fabre, Monique; Viremouneix, Loic; Galmiche, Louise; Debray, Dominique; Bole-Feysot, Christine; Nitschke, Patrick; Pariente, Danièle; Guettier, Catherine; Lyonnet, Stanislas; Heidet, Laurence; Bertholet, Aurelia; Jacquemin, Emmanuel; Henrion-Caude, Alexandra; Saunier, Sophie

    2016-10-01

    Neonatal sclerosing cholangitis (NSC) is a rare biliary disease leading to liver transplantation in childhood. Patients with NSC and ichtyosis have already been identified with a CLDN1 mutation, encoding a tight-junction protein. However, for the majority of patients, the molecular basis of NSC remains unknown. We identified biallelic missense mutations or in-frame deletion in DCDC2 in four affected children. Mutations involve highly conserved amino acids in the doublecortin domains of the protein. In cholangiocytes, DCDC2 protein is normally located in the cytoplasm and cilia, whereas in patients the mutated protein is accumulated in the cytoplasm, absent from cilia, and associated with ciliogenesis defect. This is the first report of DCDC2 mutations in NSC. This data expands the molecular spectrum of NSC, that can be considered as a ciliopathy and also expands the clinical spectrum of the DCDC2 mutations, previously reported in dyslexia, deafness, and nephronophtisis. PMID:27319779

  4. DCDC2 Mutations Cause Neonatal Sclerosing Cholangitis.

    PubMed

    Girard, Muriel; Bizet, Albane A; Lachaux, Alain; Gonzales, Emmanuel; Filhol, Emilie; Collardeau-Frachon, Sophie; Jeanpierre, Cécile; Henry, Charline; Fabre, Monique; Viremouneix, Loic; Galmiche, Louise; Debray, Dominique; Bole-Feysot, Christine; Nitschke, Patrick; Pariente, Danièle; Guettier, Catherine; Lyonnet, Stanislas; Heidet, Laurence; Bertholet, Aurelia; Jacquemin, Emmanuel; Henrion-Caude, Alexandra; Saunier, Sophie

    2016-10-01

    Neonatal sclerosing cholangitis (NSC) is a rare biliary disease leading to liver transplantation in childhood. Patients with NSC and ichtyosis have already been identified with a CLDN1 mutation, encoding a tight-junction protein. However, for the majority of patients, the molecular basis of NSC remains unknown. We identified biallelic missense mutations or in-frame deletion in DCDC2 in four affected children. Mutations involve highly conserved amino acids in the doublecortin domains of the protein. In cholangiocytes, DCDC2 protein is normally located in the cytoplasm and cilia, whereas in patients the mutated protein is accumulated in the cytoplasm, absent from cilia, and associated with ciliogenesis defect. This is the first report of DCDC2 mutations in NSC. This data expands the molecular spectrum of NSC, that can be considered as a ciliopathy and also expands the clinical spectrum of the DCDC2 mutations, previously reported in dyslexia, deafness, and nephronophtisis.

  5. Achieving urinary continence in children.

    PubMed

    Wu, Hsi-Yang

    2010-07-01

    Achievement of urinary continence is an important developmental step that most children attain with the assistance of their parents and caregivers. Debate continues as to the best time to toilet train; in some Asian and African cultures children are trained as infants, while training at age 2-3 years is more typical in Western cultures. Infant voiding is not merely a spinal reflex, as the sensation of bladder filling is relayed to the brain. However, the ability of the brain to inhibit bladder contractions, and to achieve coordinated bladder contraction with sphincter relaxation, matures over time. While there is a concern that later toilet training may be responsible for an increase in urinary incontinence in children, no controlled studies on early versus late toilet training exist to evaluate this hypothesis. A number of medical conditions such as spina bifida, posterior urethral valves, cerebral palsy and autism can cause incontinence and difficulties in toilet training. The decision to start toilet training a child should take into account both the parents' expectation of how independent the child will be in terms of toileting, and the child's developmental readiness, so that a realistic time course for toilet training can be implemented.

  6. 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.

  7. 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.

  8. Spliceosome mutations exhibit specific associations with epigenetic modifiers and proto-oncogenes mutated in myelodysplastic syndrome.

    PubMed

    Mian, Syed A; Smith, Alexander E; Kulasekararaj, Austin G; Kizilors, Aytug; Mohamedali, Azim M; Lea, Nicholas C; Mitsopoulos, Konstantinos; Ford, Kevin; Nasser, Erick; Seidl, Thomas; Mufti, Ghulam J

    2013-07-01

    The recent identification of acquired mutations in key components of the spliceosome machinery strongly implicates abnormalities of mRNA splicing in the pathogenesis of myelodysplastic syndromes. However, questions remain as to how these aberrations functionally combine with the growing list of mutations in genes involved in epigenetic modification and cell signaling/transcription regulation identified in these diseases. In this study, amplicon sequencing was used to perform a mutation screen in 154 myelodysplastic syndrome patients using a 22-gene panel, including commonly mutated spliceosome components (SF3B1, SRSF2, U2AF1, ZRSR2), and a further 18 genes known to be mutated in myeloid cancers. Sequencing of the 22-gene panel revealed that 76% (n=117) of the patients had mutations in at least one of the genes, with 38% (n=59) having splicing gene mutations and 49% (n=75) patients harboring more than one gene mutation. Interestingly, single and specific epigenetic modifier mutations tended to coexist with SF3B1 and SRSF2 mutations (P<0.03). Furthermore, mutations in SF3B1 and SRSF2 were mutually exclusive to TP53 mutations both at diagnosis and at the time of disease transformation. Moreover, mutations in FLT3, NRAS, RUNX1, CCBL and C-KIT were more likely to co-occur with splicing factor mutations generally (P<0.02), and SRSF2 mutants in particular (P<0.003) and were significantly associated with disease transformation (P<0.02). SF3B1 and TP53 mutations had varying impacts on overall survival with hazard ratios of 0.2 (P<0.03, 95% CI, 0.1-0.8) and 2.1 (P<0.04, 95% CI, 1.1-4.4), respectively. Moreover, patients with splicing factor mutations alone had a better overall survival than those with epigenetic modifier mutations, or cell signaling/transcription regulator mutations with and without coexisting mutations of splicing factor genes, with worsening prognosis (P<0.001). These findings suggest that splicing factor mutations are maintained throughout disease

  9. 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

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

    NASA Astrophysics Data System (ADS)

    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.

  11. 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.

  12. Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring.

    PubMed

    Stark, Zornitza; Storen, Rebecca; Bennetts, Bruce; Savarirayan, Ravi; Jamieson, Robyn V

    2011-07-01

    Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment.

  13. 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

  14. 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

  15. LHON: Mitochondrial Mutations and More

    PubMed Central

    Kirches, E

    2011-01-01

    Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to severe visual impairment or even blindness by death of retinal ganglion cells (RGCs). The primary cause of the disease is usually a mutation of the mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of the electron transport chain. It was thus obvious to accuse neuronal energy depletion as the most probable mediator of neuronal death. The group of Valerio Carelli and other authors have nicely shown that energy depletion shapes the cell fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma cells, which do not fully model neuronal energy metabolism. Although complex I mutations may cause oxidative stress, a potential pathogenetic role of the latter was less taken into focus. The hypothesis of bioenergetic failure does not provide a simple explanation for the relatively late disease onset and for the incomplete penetrance, which differs remarkably between genders. It is assumed that other genetic and environmental factors are needed in addition to the ‘primary LHON mutations’ to elicit RGC death. Relevant nuclear modifier genes have not been identified so far. The review discusses the unresolved problems of a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in RGCs. PMID:21886454

  16. 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.

  17. 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.

  18. 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…

  19. Point mutation instability (PIN) mutator phenotype as model for true back mutations seen in hereditary tyrosinemia type 1 - a hypothesis.

    PubMed

    van Dyk, Etresia; Pretorius, Pieter J

    2012-05-01

    Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disorder affecting fumarylacetoacetate hydrolase (FAH), the last enzyme in the tyrosine catabolism pathway. The liver mosaicism observed in HT1 patients is due to the reversion to the wild type of one allele of the original point mutation in fah. It is generally accepted that these reversions are true back mutations; however, the mechanism is still unresolved. Previous reports excluded intragenic recombination, mitotic recombination, or homologous recombination with a pseudogene as possible mechanisms of mutation reversion in HT1. Sequence analysis did not reveal DNA motifs, tandem repeats or other sequence peculiarities that may be involved in mutation reversion. We propose the hypothesis that a point mutation instability mutator (PIN) phenotype brought about by the sustained stress environment created by the accumulating metabolites in the cell is the driver of the true back mutations in HT1. The metabolites accumulating in HT1 create a sustained stress environment by activating the extracellular signal-regulated kinase (ERK) and AKT survival pathways, inducing aberrant mitosis and development of death resistant cells, depleting glutathione, and impairing DNA ligase IV and possibly DNA polymerases δ and ε. This continual production of proliferative and stress-related survival signals in the cellular environment coupled with the mutagenicity of FAA, may instigate a mutator phenotype and could end in tumorigenesis and/or mutation reversion. The establishment of a PIN-mutator phenotype therefore not only seems to be a possible mechanism underlying the true back mutations, but also contributes to explaining the clinical heterogeneity seen in hereditary tyrosinemia type 1.

  20. 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.

  1. Novel PORCN mutations in focal dermal hypoplasia.

    PubMed

    Froyen, G; Govaerts, K; Van Esch, H; Verbeeck, J; Tuomi, M-L; Heikkilä, H; Torniainen, S; Devriendt, K; Fryns, J-P; Marynen, P; Järvelä, I; Ala-Mello, S

    2009-12-01

    Focal dermal hypoplasia (FDH), Goltz or Goltz-Gorlin syndrome, is an X-linked dominant multisystem disorder characterized primarily by involvement of the skin, skeletal system and eyes. We screened for mutations in the PORCN gene in eight patients of Belgian and Finnish origin with firm clinical suspicion of FDH. First, we performed quantitative PCR (qPCR) analysis to define the copy number at this locus. Next, we sequenced the coding regions and flanking intronic sequences of the PORCN gene. Three de novo mutations were identified in our patients with FDH: a 150-kb deletion removing six genes including PORCN, as defined by qPCR and X-array-CGH, and two heterozygous missense mutations; c.992T>G (p.L331R) in exon 11 and c.1094G>A (p.R365Q) in exon 13 of the gene. Both point mutations changed highly conserved amino acids and were not found in 300 control X chromosomes. The three patients in whom mutations were identified all present with characteristic dermal findings together with limb manifestations, which were not seen in our mutation-negative patients. The clinical characteristics of our patients with PORCN mutations were compared with the previously reported mutation-positive cases. In this report, we summarize the literature on PORCN mutations and associated phenotypes.

  2. Repair-Resistant Mutation in Neurospora

    PubMed Central

    Stadler, David; Macleod, Helen; Loo, Melanie

    1987-01-01

    Chronic UV treatment produces severalfold fewer mutations in Neurospora conidia than does the same total dose of acute UV. Experiments were designed to determine the conditions required for chronic UV mutagenesis. Measurement of the coincidence frequency for two independent mutations revealed the existence of a subset of cells which are mutable by chronic UV. Analysis of forward mutation at the mtr locus showed that the genetic alterations produced by chronic UV were virtually all point mutants, even though the assay system could detect alterations or deletions extending into neighboring genes. A significant fraction of the mutants produced by acute UV were multigenic deletions. The size of the dose-rate effect (acute UV mutation frequency divided by chronic UV mutation frequency) was compared for several different mutation assay systems. Forward mutations (recessive lethals and mtr) gave values ranging from four to nine. For events which were restricted to specific molecular sites (specific reversions and nonsense suppressor mutations), there was a wider range of dose-rate ratios. This suggests that chronic UV mutation may be restricted to certain molecular sequences or configurations. PMID:3609724

  3. 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

  4. Gene mutations in chronic lymphocytic leukemia.

    PubMed

    Amin, Nisar A; Malek, Sami N

    2016-04-01

    The recent discovery of genes mutated in chronic lymphocytic leukemia (CLL) has stimulated new research into the role of these genes in CLL pathogenesis. CLL cases carry approximately 5-20 mutated genes per exome, a lower number than detected in many human tumors. Of the recurrently mutated genes in CLL, all are mutated in 10% or less of patients when assayed in unselected CLL cohorts at diagnosis. Mutations in TP53 are of major clinical relevance, are often associated with del17p and gain in frequency over time. TP53 mutated and associated del17p states substantially lower response rates, remission duration, and survival in CLL. Mutations in NOTCH1 and SF3B1 are recurrent, often associated with progressive CLL that is also IgVH unmutated and ZAP70-positive and are under investigation as targets for novel therapies and as factors influencing CLL outcome. There are an estimated 20-50 additional mutated genes with frequencies of 1%-5% in CLL; more work is needed to identify these and to study their significance. Finally, of the major biological aberration categories influencing CLL as a disease, gene mutations will need to be placed into context with regard to their ultimate role and importance. Such calibrated appreciation necessitates studies incorporating multiple CLL driver aberrations into biological and clinical analyses. PMID:27040699

  5. 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

  6. 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

  7. Regular systems of inbreeding with mutation.

    PubMed

    Campbell, R B

    1988-08-01

    Probability of identity by type is studied for regular systems of inbreeding in the presence of mutation. Analytic results are presented for half-sib mating, first cousin mating, and half nth cousin mating under both infinite allele and two allele (back mutation) models. Reasonable rates of mutation do not provide significantly different results from probability of identity by descent in the absence of mutation. Homozygosity is higher under half-sib mating than under first cousin mating, but the expected number of copies of a gene in the population is higher under first cousin mating than under half-sib mating.

  8. 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.

  9. 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

  10. High accuracy mutation detection in leukemia on a selected panel of cancer genes.

    PubMed

    Kalender Atak, Zeynep; De Keersmaecker, Kim; Gianfelici, Valentina; Geerdens, Ellen; Vandepoel, Roel; Pauwels, Daphnie; Porcu, Michaël; Lahortiga, Idoya; Brys, Vanessa; Dirks, Willy G; Quentmeier, Hilmar; Cloos, Jacqueline; Cuppens, Harry; Uyttebroeck, Anne; Vandenberghe, Peter; Cools, Jan; Aerts, Stein

    2012-01-01

    With the advent of whole-genome and whole-exome sequencing, high-quality catalogs of recurrently mutated cancer genes are becoming available for many cancer types. Increasing access to sequencing technology, including bench-top sequencers, provide the opportunity to re-sequence a limited set of cancer genes across a patient cohort with limited processing time. Here, we re-sequenced a set of cancer genes in T-cell acute lymphoblastic leukemia (T-ALL) using Nimblegen sequence capture coupled with Roche/454 technology. First, we investigated how a maximal sensitivity and specificity of mutation detection can be achieved through a benchmark study. We tested nine combinations of different mapping and variant-calling methods, varied the variant calling parameters, and compared the predicted mutations with a large independent validation set obtained by capillary re-sequencing. We found that the combination of two mapping algorithms, namely BWA-SW and SSAHA2, coupled with the variant calling algorithm Atlas-SNP2 yields the highest sensitivity (95%) and the highest specificity (93%). Next, we applied this analysis pipeline to identify mutations in a set of 58 cancer genes, in a panel of 18 T-ALL cell lines and 15 T-ALL patient samples. We confirmed mutations in known T-ALL drivers, including PHF6, NF1, FBXW7, NOTCH1, KRAS, NRAS, PIK3CA, and PTEN. Interestingly, we also found mutations in several cancer genes that had not been linked to T-ALL before, including JAK3. Finally, we re-sequenced a small set of 39 candidate genes and identified recurrent mutations in TET1, SPRY3 and SPRY4. In conclusion, we established an optimized analysis pipeline for Roche/454 data that can be applied to accurately detect gene mutations in cancer, which led to the identification of several new candidate T-ALL driver mutations.

  11. 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

  12. Feature-based multiple models improve classification of mutation-induced stability changes

    PubMed Central

    2014-01-01

    Background Reliable prediction of stability changes in protein variants is an important aspect of computational protein design. A number of machine learning methods that allow a classification of stability changes knowing only the sequence of the protein emerged. However, their performance on amino acid substitutions of previously unseen non-homologous proteins is rather limited. Moreover, the performance varies for different types of mutations based on the secondary structure or accessible surface area of the mutation site. Results We proposed feature-based multiple models with each model designed for a specific type of mutations. The new method is composed of five models trained for mutations in exposed, buried, helical, sheet, and coil residues. The classification of a mutation as stabilising or destabilising is made as a consensus of two models, one selected based on the predicted accessible surface area and the other based on the predicted secondary structure of the mutation site. We refer to our new method as Evolutionary, Amino acid, and Structural Encodings with Multiple Models (EASE-MM). Cross-validation results show that EASE-MM provides a notable improvement to our previous work reaching a Matthews correlation coefficient of 0.44. EASE-MM was able to correctly classify 73% and 75% of stabilising and destabilising protein variants, respectively. Using an independent test set of 238 mutations, we confirmed our results in a comparison with related work. Conclusions EASE-MM not only outperformed other related methods but achieved more balanced results for different types of mutations based on the accessible surface area, secondary structure, or magnitude of stability changes. This can be attributed to using multiple models with the most relevant features selected for the given type of mutations. Therefore, our results support the presumption that different interactions govern stability changes in the exposed and buried residues or in residues with a

  13. WRN mutations in Werner syndrome patients: genomic rearrangements, unusual intronic mutations and ethnic-specific alterations

    PubMed Central

    Friedrich, Katrin; Lee, Lin; Leistritz, Dru F.; Nürnberg, Gudrun; Saha, Bidisha; Hisama, Fuki M.; Eyman, Daniel K.; Lessel, Davor; Nürnberg, Peter; Li, Chumei; Garcia-F-Villalta, María J.; Kets, Carolien M.; Schmidtke, Joerg; Cruz, Vítor Tedim; Van den Akker, Peter C.; Boak, Joseph; Peter, Dincy; Compoginis, Goli; Cefle, Kivanc; Ozturk, Sukru; López, Norberto; Wessel, Theda; Poot, Martin; Ippel, P. F.; Groff-Kellermann, Birgit; Hoehn, Holger; Martin, George M.; Kubisch, Christian; Oshima, Junko

    2015-01-01

    Werner syndrome (WS) is an autosomal recessive segmental progeroid syndrome caused by null mutations at the WRN locus, which codes for a member of the RecQ family of DNA helicases. Since 1988, the International Registry of Werner syndrome had enrolled 130 molecularly confirmed WS cases from among 110 worldwide pedigrees. We now report 18 new mutations, including two genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and two rare missense mutations. We also review evidence for founder mutations among various ethnic/geographic groups. Founder WRN mutations had been previously reported in Japan and Northern Sardinia. Our Registry now suggests characteristic mutations originated in Morocco, Turkey, The Netherlands and elsewhere. PMID:20443122

  14. Mudi, a web tool for identifying mutations by bioinformatics analysis of whole-genome sequence.

    PubMed

    Iida, Naoko; Yamao, Fumiaki; Nakamura, Yasukazu; Iida, Tetsushi

    2014-06-01

    In forward genetics, identification of mutations is a time-consuming and laborious process. Modern whole-genome sequencing, coupled with bioinformatics analysis, has enabled fast and cost-effective mutation identification. However, for many experimental researchers, bioinformatics analysis is still a difficult aspect of whole-genome sequencing. To address this issue, we developed a browser-accessible and easy-to-use bioinformatics tool called Mutation discovery (Mudi; http://naoii.nig.ac.jp/mudi_top.html), which enables 'one-click' identification of causative mutations from whole-genome sequence data. In this study, we optimized Mudi for pooled-linkage analysis aimed at identifying mutants in yeast model systems. After raw sequencing data are uploaded, Mudi performs sequential analysis, including mapping, detection of variant alleles, filtering and removal of background polymorphisms, prioritization, and annotation. In an example study of suppressor mutants of ptr1-1 in the fission yeast Schizosaccharomyces pombe, pooled-linkage analysis with Mudi identified mip1(+) , a component of Target of Rapamycin Complex 1 (TORC1), as a novel component involved in RNA interference (RNAi)-related cell-cycle control. The accessibility of Mudi will accelerate systematic mutation analysis in forward genetics.

  15. Music training and mathematics achievement.

    PubMed

    Cheek, J M; Smith, L R

    1999-01-01

    Iowa Tests of Basic Skills (ITBS) mathematics scores of eighth graders who had received music instruction were compared according to whether the students were given private lessons. Comparisons also were made between students whose lessons were on the keyboard versus other music lessons. Analyses indicated that students who had private lessons for two or more years performed significantly better on the composite mathematics portion of the ITBS than did students who did not have private lessons. In addition, students who received lessons on the keyboard had significantly higher ITBS mathematics scores than did students whose lessons did not involve the keyboard. These results are discussed in relation to previous research on music training and mathematics achievement.

  16. 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.

  17. Learning environment, motivation, and achievement in high school science

    NASA Astrophysics Data System (ADS)

    Bobbitt Nolen, Susan

    2003-04-01

    In a study of the relationship between high school students' perceptions of their science learning environments and their motivation, learning strategies, and achievement, 377 students in 22 introductory science classrooms completed surveys in the fall and spring of their ninth-grade year. Hierarchical linear regression was used to model the effects of variables at both the classroom and individual level simultaneously. High intraclass agreement (indicated by high parameter reliability) on all classroom environment measures indicated that students shared perceptions of the classroom learning environment. Controlling for other factors, shared perceptions that only the most able could succeed in science classrooms and that instruction was fast-paced and focused on correct answers negatively predicted science achievement, as measured on a districtwide curriculum-linked test. Shared perceptions that classrooms focused on understanding and independent thinking positively predicted students' self-reported satisfaction with learning. Implications of these results for both teaching and research into classroom environments are discussed.

  18. Extreme-longevity mutations orchestrate silencing of multiple signaling pathways.

    PubMed

    Shmookler Reis, Robert J; Bharill, Puneet; Tazearslan, Cagdas; Ayyadevara, Srinivas

    2009-10-01

    Long-lived mutants provide unique insights into the genetic factors that limit lifespan in wild-type animals. Most mutants and RNA interference targets found to extend life, typically by 1.5- to 2.5-fold, were discovered in C. elegans. Several longevity-assurance pathways are conserved across widely divergent taxa, indicating that mechanisms of lifespan regulation evolved several hundred million years ago. Strong mutations to the C. elegans gene encoding AGE-1/PI3KCS achieve unprecedented longevity by orchestrating the modulation (predominantly silencing) of multiple signaling pathways. This is evident in a profound attenuation of total kinase activity, leading to reduced phosphoprotein content. Mutations to the gene encoding the catalytic subunit of PI3K (phosphatidylinositol 3-kinase) have the potential to modulate all enzymes that depend on its product, PIP3, for membrane tethering or activation by other kinases. Remarkably, strong mutants inactivating PI3K also silence multiple signaling pathways at the transcript level, partially but not entirely mediated by the DAF-16/FOXO transcription factor. Mammals have a relatively large proportion of somatic cells, and survival depends on their replication, whereas somatic cell divisions in nematodes are limited to development and reproductive tissues. Thus, translation of longevity gains from nematodes to mammals requires disentangling the downstream consequences of signaling mutations, to avoid their deleterious consequences.

  19. '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

  20. 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

  1. Improved detection of mutated human cytomegalovirus UL97 by pyrosequencing.

    PubMed

    Schindele, Birgit; Apelt, Luise; Hofmann, Jörg; Nitsche, Andreas; Michel, Detlef; Voigt, Sebastian; Mertens, Thomas; Ehlers, Bernhard

    2010-12-01

    Ganciclovir (GCV) resistance frequently occurs upon prolonged treatment of ongoing active human cytomegalovirus (HCMV) infection in individuals with immature or compromised immune functions (e.g., recipients of solid-organ and hematopoietic stem cell transplants). Using pyrosequencing (PSQ), we established fast and sensitive detection of GCV resistance-associated mutations occurring in the HCMV open reading frame UL97. These mutations have been repeatedly associated with clinical treatment failure. We designed four PSQ assays and evaluated them by analyzing mixtures of plasmids or bacterial artificial chromosome-derived viruses containing UL97 wild-type and mutant sequences. A minimum level of 6% mutant sequence variants could be detected in these mixtures. In order to further evaluate the novel PSQ assays, we tested clinical specimens from patients with active HCMV infections. The results were compared with those obtained by conventional dideoxy chain terminator sequencing. As the PSQ method was more sensitive in detecting minor HCMV mutant fractions in a wild-type population, it is suggested that pyrosequencing is a useful tool for the early detection of emerging GCV-resistant HCMV in GCV-treated patients.

  2. LFR "Lead-Cooled Fast Reactor"

    SciTech Connect

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

    2006-05-11

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

  3. Fast Reactor Fuel Type and Reactor Safety Performance

    SciTech Connect

    R. Wigeland; J. Cahalan

    2009-09-01

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

  4. Design of a tapered stripline fast Faraday cup for measurements on heavy ion beams: problems and solutions

    SciTech Connect

    Marcellini, F.; Poggi, M.

    1998-12-10

    The design of a tapered stripline fast Faraday cup (TSFFC) to perform the impedance matching between the fast cup itself and the signal line (connector, cable, and amplifier) is reported here. The frequency response of the TSFFC as a high-pass filter is analyzed from a theoretical point of view and some solutions to achieve a broadband response are given.

  5. Identification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patients.

    PubMed

    Vindas-Smith, Rebeca; Fiore, Michele; Vásquez, Melissa; Cuenca, Patricia; Del Valle, Gerardo; Lagostena, Laura; Gaitán-Peñas, Héctor; Estevez, Raúl; Pusch, Michael; Morales, Fernando

    2016-01-01

    Mutations in the gene coding for the skeletal muscle Cl(-) channel (CLCN1) lead to dominant or recessive myotonia. Here, we identified and characterized CLCN1 mutations in Costa Rican patients, who had been clinically diagnosed with myotonic dystrophy type 1 but who were negative for DM1 mutations. CLCN1 mutations c.501C>G, p.F167L and c.1235A>C, p.Q412P appeared to have recessive inheritance but patients had atypical clinical phenotypes; c.313C>T, p.R105C was found in combination with c.501C>G, p.F167L in an apparently recessive family and the c.461A>G, p.Q154R variant was associated with a less clear clinical picture. In Xenopus oocytes, none of the mutations exhibited alterations of fast or slow gating parameters or single channel conductance, and mutations p.R105C, p.Q154R, and p.F167L were indistinguishable from wild-type (WT). p.Q412P displayed a dramatically reduced current density, surface expression and exerted no dominant negative effect in the context of the homodimeric channel. Fluorescently tagged constructs revealed that p.Q412P is expressed inefficiently. Our study confirms p.F167L and p.R105C as myotonia mutations in the Costa Rican population, whereas p.Q154R may be a benign variant. p.Q412P most likely induces a severe folding defect, explaining the lack of dominance in patients and expression systems, but has WT properties once expressed in the plasma membrane.

  6. Can robots patch-clamp as well as humans? Characterization of a novel sodium channel mutation

    PubMed Central

    Estacion, M; Choi, J S; Eastman, E M; Lin, Z; Li, Y; Tyrrell, L; Yang, Y; Dib-Hajj, S D; Waxman, S G

    2010-01-01

    Ion channel missense mutations cause disorders of excitability by changing channel biophysical properties. As an increasing number of new naturally occurring mutations have been identified, and the number of other mutations produced by molecular approaches such as in situ mutagenesis has increased, the need for functional analysis by patch-clamp has become rate limiting. Here we compare a patch-clamp robot using planar-chip technology with human patch-clamp in a functional assessment of a previously undescribed Nav1.7 sodium channel mutation, S211P, which causes erythromelalgia. This robotic patch-clamp device can increase throughput (the number of cells analysed per day) by 3- to 10-fold. Both modes of analysis show that the mutation hyperpolarizes activation voltage dependence (−8 mV by manual profiling, −11 mV by robotic profiling), alters steady-state fast inactivation so that it requires an additional Boltzmann function for a second fraction of total current (∼20% manual, ∼40% robotic), and enhances slow inactivation (hyperpolarizing shift −15 mV by human, −13 mV robotic). Manual patch-clamping demonstrated slower deactivation and enhanced (∼2-fold) ramp response for the mutant channel while robotic recording did not, possibly due to increased temperature and reduced signal-to-noise ratio on the robotic platform. If robotic profiling is used to screen ion channel mutations, we recommend that each measurement or protocol be validated by initial comparison to manual recording. With this caveat, we suggest that, if results are interpreted cautiously, robotic patch-clamp can be used with supervision and subsequent confirmation from human physiologists to facilitate the initial profiling of a variety of electrophysiological parameters of ion channel mutations. PMID:20123784

  7. 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

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

    PubMed

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

    2016-06-01

    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 [Formula: see text] (=[Formula: see text]) from intraspecific DNA polymorphism data. When [Formula: see text] and the number of sampled diploid individuals is large enough ([Formula: see text]), the variance of [Formula: see text] remains slightly smaller than that of [Formula: see text] The new estimate [Formula: see text] (calculated by averaging [Formula: see text] and [Formula: see text]) has the smallest variance of all cases. When estimating [Formula: see text], 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 [Formula: see text] and [Formula: see text] 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

  9. 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

  10. A fast meteor detection algorithm

    NASA Astrophysics Data System (ADS)

    Gural, P.

    2016-01-01

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

  11. Causes of Extremely Fast CMEs

    NASA Technical Reports Server (NTRS)

    Feynman, Joan; Ruzmaikin, Alexander

    2006-01-01

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

  12. Electron Beams for Fast Ignition

    NASA Astrophysics Data System (ADS)

    Fonseca, R. A.; Davies, J. R.; Silva, L. O.

    2004-11-01

    In the fast ignitor scenario an intense relativistic electron beam is used to deposit energy inside the fuel target and trigger the thermonuclear reaction. This electron beam is produced on the outer plasma layer of the target by the interaction of an ultra-intense laser. The energy transfer from the laser to the electron beam, and the stability of the propagation of the electron beam are crucial for a successful fast ignitor scheme. We have used three-dimensional particle-in-cell simulations using the OSIRIS.framework [1] to explore the self-consistent generation of high current electron beams by ultra intense lasers. Novel laser pulse configurations are explored in order to generate electron beams transporting more energy, and capable of avoiding the deleterious effects of collisionless instabilities in the plasma corona. [1] R. A. Fonseca et al., LNCS 2331, 342-351, (Springer, Heidelberg, 2002);

  13. 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

  14. 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.

  15. Fast, comprehensive two-dimensional liquid chromatography

    PubMed Central

    Stoll, Dwight R.; Li, Xiaoping; Wang, Xiaoli; Carr, Peter W.; Porter, Sarah E. G.; Rutan, Sarah C.

    2011-01-01

    The absolute need to improve the separating power of liquid chromatography, especially for multi-constituent biological samples, is becoming increasingly evident. In response, over the past few years, there has been a great deal of interest in the development of two dimension liquid chromatography (2DLC). Just as 1DLC is preferred to 1DGC based on its compatibility with biological materials we believe that ultimately 2DLC will be preferred to the much more highly developed 2DGC for such samples. The huge advantage of 2D chromatographic techniques over 1D methods is inherent in the tremendous potential increase in peak capacity (resolving power). This is especially true of comprehensive 2D chromatography wherein it is possible, under ideal conditions, to obtain a total peak capacity equal to the product of the peak capacities of the first and second dimension separations. However, the very long timescale (typically several hours to tens of hours) of comprehensive 2DLC is clearly its chief drawback. Recent advances in the use of higher temperatures to speed up isocratic and gradient elution liquid chromatography have been used to decrease the time needed to do the second dimension LC separation of 2DLC to about 20 seconds for a full gradient elution run. Thus fast, high temperature LC is becoming a very promising technique. Peak capacities of over 2000 and rates of peak capacity production of nearly 1 peak/s have been achieved. In consequence, many real samples showing more than 200 peaks with signal to noise ratios of better than 10:1 have been run in total times of under 30 minutes. This report is not intended to be a comprehensive review of 2DLC, but is deliberately focused on the issues involved in doing fast 2DLC by means of elevating the column temperature; however, many issues of broader applicability will be discussed. PMID:17888443

  16. Fast quench reactor and method

    DOEpatents

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

    2002-01-01

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

  17. Fast quench reactor and method

    DOEpatents

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

    2002-09-24

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

  18. Fast quench reactor and method

    DOEpatents

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

    1998-01-01

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

  19. Fast track to 340B.

    PubMed

    Gricius, Robert F; Wong, Douglas

    2016-01-01

    Hospitals that are newly qualified for the 340B Drug Pricing Program may have an opportunity for fast-track approval to participate in the program. Three steps are required to seize this opportunity: Use data analytics to assess current and future percentages of Medicaid utilization and eligibility for federal SSI cash benefits. Determine the feasibility of early cost report filing. Prepare appropriate documentation and undertake the initial enrollment process. PMID:26863836

  20. Fast track to 340B.

    PubMed

    Gricius, Robert F; Wong, Douglas

    2016-01-01

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

  1. Fast quench reactor and method

    DOEpatents

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

    1998-05-12

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

  2. A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0

    PubMed Central

    2010-01-01

    Background Glycogen storage disease type 0 is an autosomal recessive disease presenting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia. Sixteen different mutations have been identified to date in the gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen storage in the liver. Case Presentation Biochemical evaluation as well as direct sequencing of exons and exon-intron boundary regions of the GYS2 gene were performed in a patient presenting fasting hypoglycemia and postprandial hyperglycemia and her parents. The patient was found to be compound heterozygous for one previously reported nonsense mutation (c.736 C>T; R243X) and a novel frameshift mutation (966_967delGA/insC) which introduces a stop codon 21 aminoacids downstream from the site of the mutation that presumably leads to loss of 51% of the COOH-terminal part of the protein. The glycemia and lactatemia of the parents after an oral glucose tolerance test were evaluated to investigate a possible impact of the carrier status on the metabolic profile. The mother, who presented a positive family history of type 2 diabetes, was classified as glucose intolerant and the father, who did not exhibit metabolic changes after the glucose overload, had an antecedent history of hypoglycemia after moderate alcohol ingestion. Conclusion The current results expand the spectrum of known mutations in GYS2 and suggest that haploinsufficiency could explain metabolic abnormalities in heterozygous carriers in presence of predisposing conditions. PMID:20051115

  3. Fast wave current drive on DIII-D

    SciTech Connect

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

    1995-07-01

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

  4. A repeating fast radio burst.

    PubMed

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

    2016-03-10

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star. PMID:26934226

  5. Diagnostics for Fast Ignition Science

    SciTech Connect

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

    2008-05-06

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

  6. Fast superconducting magnetic field switch

    DOEpatents

    Goren, Yehuda; Mahale, Narayan K.

    1996-01-01

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

  7. Heterogeneous Transmutation Sodium Fast Reactor

    SciTech Connect

    S. E. Bays

    2007-09-01

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

  8. A repeating fast radio burst.

    PubMed

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

    2016-03-10

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

  9. Fast superconducting magnetic field switch

    DOEpatents

    Goren, Y.; Mahale, N.K.

    1996-08-06

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

  10. Leiomodin-3-deficient mice display nemaline myopathy with fast-myofiber atrophy

    PubMed Central

    Tian, Lei; Ding, Sheng; You, Yun; Li, Tong-ruei; Liu, Yan; Wu, Xiaohui; Sun, Ling; Xu, Tian

    2015-01-01

    ABSTRACT Nemaline myopathy (NM) is one of the most common forms of congenital myopathy, and affects either fast myofibers, slow myofibers, or both. However, an animal model for congenital myopathy with fast-myofiber-specific atrophy is not available. Furthermore, mutations in the leiomodin-3 (LMOD3) gene have recently been identified in a group of individuals with NM. However, it is not clear how loss of LMOD3 leads to NM. Here, we report a mouse mutant in which the piggyBac (PB) transposon is inserted into the Lmod3 gene and disrupts its expression. Lmod3PB/PB mice show severe muscle weakness and postnatal growth retardation. Electron microscopy and immunofluorescence studies of the mutant skeletal muscles revealed the presence of nemaline bodies, a hallmark of NM, and disorganized sarcomeric structures. Interestingly, Lmod3 deficiency caused muscle atrophy specific to the fast fibers. Together, our results show that Lmod3 is required in the fast fibers for sarcomere integrity, and this study offers the first NM mouse model with muscle atrophy that is specific to fast fibers. This model could be a valuable resource for interrogating myopathy pathogenesis and developing therapeutics for NM as well as other pathophysiological conditions with preferential atrophy of fast fibers, including cancer cachexia and sarcopenia. PMID:26035871

  11. Leiomodin-3-deficient mice display nemaline myopathy with fast-myofiber atrophy.

    PubMed

    Tian, Lei; Ding, Sheng; You, Yun; Li, Tong-ruei; Liu, Yan; Wu, Xiaohui; Sun, Ling; Xu, Tian

    2015-06-01

    Nemaline myopathy (NM) is one of the most common forms of congenital myopathy, and affects either fast myofibers, slow myofibers, or both. However, an animal model for congenital myopathy with fast-myofiber-specific atrophy is not available. Furthermore, mutations in the leiomodin-3 (LMOD3) gene have recently been identified in a group of individuals with NM. However, it is not clear how loss of LMOD3 leads to NM. Here, we report a mouse mutant in which the piggyBac (PB) transposon is inserted into the Lmod3 gene and disrupts its expression. Lmod3(PB/PB) mice show severe muscle weakness and postnatal growth retardation. Electron microscopy and immunofluorescence studies of the mutant skeletal muscles revealed the presence of nemaline bodies, a hallmark of NM, and disorganized sarcomeric structures. Interestingly, Lmod3 deficiency caused muscle atrophy specific to the fast fibers. Together, our results show that Lmod3 is required in the fast fibers for sarcomere integrity, and this study offers the first NM mouse model with muscle atrophy that is specific to fast fibers. This model could be a valuable resource for interrogating myopathy pathogenesis and developing therapeutics for NM as well as other pathophysiological conditions with preferential atrophy of fast fibers, including cancer cachexia and sarcopenia. PMID:26035871

  12. Boosted Fast Flux Loop Final Report

    SciTech Connect

    Boosted Fast Flux Loop Project Staff

    2009-09-01

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

  13. Fast response dual frequency liquid crystal materials

    NASA Astrophysics Data System (ADS)

    Song, Qiong

    Dual frequency liquid crystal (DFLC) exhibits a positive dielectric anisotropy at low frequencies and negative dielectric anisotropy at high frequencies. The frequency where dielectric anisotropy is zero is called crossover frequency. DFLC can achieve fast rise time and fast decay time with the assistance of applied voltage. However, one drawback of DFLC is that it has dielectric heating effect when driven at a high frequency. Thus, the first part of this dissertation is to develop low crossover frequency DFLC materials. The dielectric relaxation and physical properties of some single- and double-ester compounds were investigated. Experimental results indicate that the double-ester compound exhibits a ˜3X lower dielectric relaxation frequencies and larger dielectric anisotropy than the single ester, but its viscosity is also higher. More generally, ten groups of dual frequency liquid crystals were compared in terms of dielectric relaxation frequency and dielectric anisotropy. The dielectric relaxation theory was discussed at last. To realize fast response time, high birefringence and low viscosity LC are required. From these two aspects, firstly four new high birefringence laterally difluoro phenyl tolane liquid crystals with a negative dielectric anisotropy were studied. These materials are used to enhance the birefringence of DFLC. They have a fairly small heat fusion enthalpy (˜3000 cal/mol) which improves their solubility in a host. We dope 10 wt% of each compound into a commercial negative mixture N1 and measured their birefringence, viscoelastic constant and figure of merit. Birefringence varies very little among homologues while viscoelastic constant increases as alkyl chain length increases. Secondly, we studied the effects of six diluters for lowering the viscosity while stabilizing the vertical alignment (VA) of the laterally difluoro terphenyl host mixture at elevated temperatures. The pros and cons of each diluter are analyzed. These lateral difluoro

  14. 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.

  15. 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

  16. 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.

  17. A low thermal mass fast gas chromatograph and its implementation in fast gas chromatography mass spectrometry with supersonic molecular beams.

    PubMed

    Fialkov, Alexander B; Moragn, Mati; Amirav, Aviv

    2011-12-30

    A new type of low thermal mass (LTM) fast gas chromatograph (GC) was designed and operated in combination with gas chromatography mass spectrometry (GC-MS) with supersonic molecular beams (SMB), including GC-MS-MS with SMB, thereby providing a novel combination with unique capabilities. The LTM fast GC is based on a short capillary column inserted inside a stainless steel tube that is resistively heated. It is located and mounted outside the standard GC oven on its available top detector port, while the capillary column is connected as usual to the standard GC injector and supersonic molecular beam interface transfer line. This new type of fast GC-MS with SMB enables less than 1 min full range temperature programming and cooling down analysis cycle time. The operation of the fast GC-MS with SMB was explored and 1 min full analysis cycle time of a mixture of 16 hydrocarbons in the C(10)H(22) up to C(44)H(90) range was achieved. The use of 35 mL/min high column flow rate enabled the elution of C(44)H(90) in less than 45 s while the SMB interface enabled splitless acceptance of this high flow rate and the provision of dominant molecular ions. A novel compound 9-benzylazidanthracene was analyzed for its purity and a synthetic chemistry process was monitored for the optimization of the chemical reaction yield. Biodiesel was analyzed in jet fuel (by both GC-MS and GC-MS-MS) in under 1 min as 5 ppm fatty acid methyl esters. Authentic iprodion and cypermethrin pesticides were analyzed in grapes extract in both full scan mode and fast GC-MS-MS mode in under 1 min cycle time and explosive mixture including TATP, TNT and RDX was analyzed in under 1 min combined with exhibiting dominant molecular ion for TATP. Fast GC-MS with SMB is based on trading GC separation for speed of analysis while enhancing the separation power of the MS via the enhancement of the molecular ion in the electron ionization of cold molecules in the SMB. This paper further discusses several features of

  18. The digital backend of FAST

    NASA Astrophysics Data System (ADS)

    Yu, Xinying; Zhang, Xia; Duan, Ran; li, di; Hao, Jie

    2015-08-01

    The receiver system is an important part of FAST (Five-hundred-meter Aperture Spherical Radio Telescope) and plays a key role in determining the performance of the telescope.This research covers three major aspects: establishment of system synchronization and timestamps, field-programmable gate array (FPGA)-based data transmission and analysis, and the rear receiver monitoring system. We intend to combine the use of GPS and a frequency standard instrument with network access to Unix timestamps to form actual timestamps. The data are stored with timestamps that contain integer and fractional seconds to be precise and headers, which are primarily intended to distinguish the data from each other.The data analysis procedures includes converting the timestamp information to real-time information, and merging the 8 channels’ data conversion results into frequency and energy data using corresponding conversion formulae. We must develop tailored monitoring software for the FAST receiver to customize the data format and perform data transmission. Signals on the front-end and back-end of the receiver can be monitored and controlled by adjusting the parameters on the software to increase the flexibility of the receiver.Most operations are performed on FPGA board, which can be shown from the figure, including the analog-to-digital conversion (ADC), fast Fourier transform (FFT), and pulse per second (1PPS) and Unix timestamp access operations.When analog data arrive, we initialize two ADCs at a sampling rate of 3Gsps, following by 8-channel FFT parallel processing.In collaboration with the Institute of Automation, we have developed a custom FPGA board which we call "FDB"("FAST Digital Backend"). The board is integrated with two Virtex-6 and one Virtex-5 high-speed Xilinx chips. The main function of the two Virtex-6 devices is to run the FFT and PFB programs, whereas the main function of Virtex-5 is configuration of the board.This research is indispensable for realizing the

  19. Seismic responses of a pool-type fast reactor with different core support designs

    SciTech Connect

    Wu, Ting-shu; Seidensticker, R.W. )

    1989-01-01

    In designing the core support system for a pool-type fast reactor, there are many issues which must be considered in order to achieve an optimum and balanced design. These issues include safety, reliability, as well as costs. Several design options are possible to support the reactor core. Different core support options yield different frequency ranges and responses. Seismic responses of a large pool-type fast reactor incorporated with different core support designs have been investigated. 4 refs., 3 figs.

  20. Competency-Based Achievement System

    PubMed Central

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

    2011-01-01

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