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Sample records for enhancing genetic gains

  1. Advances in Maize Genomics and Their Value for Enhancing Genetic Gains from Breeding

    PubMed Central

    Xu, Yunbi; Skinner, Debra J.; Wu, Huixia; Palacios-Rojas, Natalia; Araus, Jose Luis; Yan, Jianbing; Gao, Shibin; Warburton, Marilyn L.; Crouch, Jonathan H.

    2009-01-01

    Maize is an important crop for food, feed, forage, and fuel across tropical and temperate areas of the world. Diversity studies at genetic, molecular, and functional levels have revealed that, tropical maize germplasm, landraces, and wild relatives harbor a significantly wider range of genetic variation. Among all types of markers, SNP markers are increasingly the marker-of-choice for all genomics applications in maize breeding. Genetic mapping has been developed through conventional linkage mapping and more recently through linkage disequilibrium-based association analyses. Maize genome sequencing, initially focused on gene-rich regions, now aims for the availability of complete genome sequence. Conventional insertion mutation-based cloning has been complemented recently by EST- and map-based cloning. Transgenics and nutritional genomics are rapidly advancing fields targeting important agronomic traits including pest resistance and grain quality. Substantial advances have been made in methodologies for genomics-assisted breeding, enhancing progress in yield as well as abiotic and biotic stress resistances. Various genomic databases and informatics tools have been developed, among which MaizeGDB is the most developed and widely used by the maize research community. In the future, more emphasis should be given to the development of tools and strategic germplasm resources for more effective molecular breeding of tropical maize products. PMID:19688107

  2. Enhancing genetic virtue.

    PubMed

    Walker, Mark

    2009-09-01

    The Genetic Virtue Project (GVP) is a proposed interdisciplinary effort between philosophers, psychologists and geneticists to discover and enhance human ethics using biotechnology genetic correlates of virtuous behavior. The empirical plausibility that virtues have biological correlates is based on the claims that (a) virtues are a subset of personality, specifically, personality traits conceived of as "enduring behaviors," and (b) that there is ample evidence that personality traits have a genetic basis. The moral necessity to use the GVP for moral enhancement is based on the claims that we should eliminate evil (as understood generically, not religiously), as some evil is a function of human nature. The GVP is defended against several ethical and political criticisms.

  3. Fundamental limitations to gain enhancement in periodic media and waveguides.

    PubMed

    Grgić, Jure; Ott, Johan Raunkjær; Wang, Fengwen; Sigmund, Ole; Jauho, Antti-Pekka; Mørk, Jesper; Mortensen, N Asger

    2012-05-01

    A common strategy to compensate for losses in optical nanostructures is to add gain material in the system. By exploiting slow-light effects it is expected that the gain may be enhanced beyond its bulk value. Here we show that this route cannot be followed uncritically: inclusion of gain inevitably modifies the underlying dispersion law, and thereby may degrade the slow-light properties underlying the device operation and the anticipated gain enhancement itself. This degradation is generic; we demonstrate it for three different systems of current interest (coupled-resonator optical waveguides, Bragg stacks, and photonic crystal waveguides). Nevertheless, a small amount of added gain may be beneficial.

  4. Gain enhancement of microstrip antennas with overlaying parasitic directors

    NASA Technical Reports Server (NTRS)

    Lee, R. Q.; Lee, K. F.

    1988-01-01

    An experimental study of gain enhancement in microstrip antennas using identical parasitic patch directors is reported. The results indicate that, with two overlying parasitic directors, the gain of a rectangular microstrip antenna is enhanced from 4.7 dB to 10.6 dB, while the 3 dB beamwidth is reduced from 103 deg to 30 deg for the E-plane and from 70 deg to 35 deg for the H-plane. The three-layer electromagnetically coupled patch antenna exhibits similar antenna characteristics to those of the Yagi array, with over 120 dB gain and with about 1 percent bandwidth.

  5. Commissural Gain Control Enhances the Midbrain Representation of Sound Location

    PubMed Central

    Orton, Llwyd David; Papasavvas, Christoforos A.

    2016-01-01

    Accurate localization of sound sources is essential for survival behavior in many species. The inferior colliculi (ICs) are the first point in the auditory pathway where cues used to locate sounds, ie, interaural time differences (ITDs), interaural level differences (ILDs), and pinna spectral cues, are all represented in the same location. These cues are first extracted separately on each side of the midline in brainstem nuclei that project to the ICs. Because of this segregation, each IC predominantly represents stimuli in the contralateral hemifield. We tested the hypothesis that commissural connections between the ICs mediate gain control that enhances sound localization acuity. We recorded IC neurons sensitive to either ITDs or ILDs in anesthetized guinea pig, before, during, and following recovery from deactivation of the contralateral IC by cryoloop cooling or microdialysis of procaine. During deactivation, responses were rescaled by divisive gain change and additive shifts, which reduced the dynamic range of ITD and ILD response functions and the ability of neurons to signal changes in sound location. These data suggest that each IC exerts multiplicative gain control and subtractive shifts over the other IC that enhances the neural representation of sound location. Furthermore, this gain control operates in a similar manner on both ITD- and ILD-sensitive neurons, suggesting a shared mechanism operates across localization cues. Our findings reveal a novel dependence of sound localization on commissural processing. SIGNIFICANCE STATEMENT Sound localization, a fundamental process in hearing, is dependent on bilateral computations in the brainstem. How this information is transmitted from the brainstem to the auditory cortex, through several stages of processing, without loss of signal fidelity, is not clear. We show that the ability of neurons in the auditory midbrain to encode azimuthal sound location is dependent on gain control mediated by the commissure of

  6. Expected genetic contributions and their impact on gene flow and genetic gain.

    PubMed Central

    Woolliams, J A; Bijma, P; Villanueva, B

    1999-01-01

    Long-term genetic contributions (r(i)) measure lasting gene flow from an individual i. By accounting for linkage disequilibrium generated by selection both within and between breeding groups (categories), assuming the infinitesimal model, a general formula was derived for the expected contribution of ancestor i in category q (mu(i)(q)), given its selective advantages (s(i)(q)). Results were applied to overlapping generations and to a variety of modes of inheritance and selection indices. Genetic gain was related to the covariance between r(i) and the Mendelian sampling deviation (a(i)), thereby linking gain to pedigree development. When s(i)(q) includes a(i), gain was related to E[mu(i)(q))a(i)], decomposing it into components attributable to within and between families, within each category, for each element of s(i)(q). The formula for mu(i)(q) was consistent with previous index theory for predicting gain in discrete generations. For overlapping generations, accurate predictions of gene flow were obtained among and within categories in contrast to previous theory that gave qualitative errors among categories and no predictions within. The generation interval was defined as the period for which mu(i)(q), summed over all ancestors born in that period, equaled 1. Predictive accuracy was supported by simulation results for gain and contributions with sib-indices, BLUP selection, and selection with imprinted variation. PMID:10511574

  7. Gain-enhanced hyperbolic metamaterials at telecommunication frequencies (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Smalley, Joseph S. T.; Vallini, Felipe; Kante, Boubacar; Shahin, Shiva; Riley, Conor; Fainman, Yeshaiahu

    2015-09-01

    Using effective medium theory (EMT), Bloch's theorem (BT), and the transfer matrix method (TMM), we analyze the possibility of gain-enhanced transmission in metamaterials with hyperbolic dispersion at telecommunication frequencies. We compare different combinations of dissipative metals and active dielectrics, including noble metals, transparent conducting oxides (TCO), III-V compounds, and solid-state dopants. We find that both indium gallium arsenide phosphide (InGaAsP) and erbium-doped silica (Er:SiO2), when combined with silver, show promise as a platform for demonstration of pump-dependent transmission. On the other hand, when these active dielectrics are combined with aluminum-doped zinc oxide (AZO), a low-loss TCO, gain-enhanced transmission is negligible. Results based on EMT are compared to the more accurate BT and TMM. When losses are ignored, quantitative agreement between these analytical techniques is observed near the center of the first Brillouin zone of a one-dimensional periodic structure. Including realistic levels of loss and gain, however, EMT predictions become overly optimistic compared to BT and TMM. We also discuss the limitations to assumptions inherent to EMT, BT, and TMM, and suggest avenues for future analysis.

  8. Efficient use of hybrid Genetic Algorithms in the gain optimization of distributed Raman amplifiers.

    PubMed

    Neto, B; Teixeira, A L J; Wada, N; André, P S

    2007-12-24

    In this paper, we propose an efficient and accurate method that combines the Genetic Algorithm (GA) with the Nelder-Mead method in order to obtain the gain optimization of distributed Raman amplifiers. By using these two methods together, the advantages of both are combined: the convergence of the GA and the high accuracy of the Nelder-Mead. To enhance the convergence of the GA, several features were examined and correlated with fitting errors. It is also shown that when the right moment to switch between methods is chosen, the computation time can be reduced by a factor of two.

  9. Ejector-Enhanced, Pulsed, Pressure-Gain Combustor

    NASA Technical Reports Server (NTRS)

    Paxson, Daniel E.; Dougherty, Kevin T.

    2009-01-01

    An experimental combination of an off-the-shelf valved pulsejet combustor and an aerodynamically optimized ejector has shown promise as a prototype of improved combustors for gas turbine engines. Despite their name, the constant pressure combustors heretofore used in gas turbine engines exhibit typical pressure losses ranging from 4 to 8 percent of the total pressures delivered by upstream compressors. In contrast, the present ejector-enhanced pulsejet combustor exhibits a pressure rise of about 3.5 percent at overall enthalpy and temperature ratios compatible with those of modern turbomachines. The modest pressure rise translates to a comparable increase in overall engine efficiency and, consequently, a comparable decrease in specific fuel consumption. The ejector-enhanced pulsejet combustor may also offer potential for reducing the emission of harmful exhaust compounds by making it practical to employ a low-loss rich-burn/quench/lean-burn sequence. Like all prior concepts for pressure-gain combustion, the present concept involves an approximation of constant-volume combustion, which is inherently unsteady (in this case, more specifically, cyclic). The consequent unsteadiness in combustor exit flow is generally regarded as detrimental to the performance of downstream turbomachinery. Among other adverse effects, this unsteadiness tends to detract from the thermodynamic benefits of pressure gain. Therefore, it is desirable in any intermittent combustion process to minimize unsteadiness in the exhaust path.

  10. "Genetic Engineering" Gains Momentum (Science/Society Case Study).

    ERIC Educational Resources Information Center

    Moore, John W.; Moore, Elizabeth A., Eds.

    1980-01-01

    Reviews the benefits and hazards of genetic engineering, or "recombinant-DNA" research. Recent federal safety rules issued by NIH which ease the strict prohibitions on recombinant-DNA research are explained. (CS)

  11. Enhancement of stimulated Raman scattering of weak-gain Raman modes in a pendant drop by dye-lasing gain

    NASA Astrophysics Data System (ADS)

    Pu, Xiao-Yun; Yang, Zheng; Lee, Wing-Kee

    2004-02-01

    The enhancement of stimulated Raman scattering (SRS) of weak-gain Raman modes in pendant drops is accomplished by overlapping Stokes wavelengths of the Raman modes with the Rhodamine 640 dye-lasing gain region (called the gain-overlap method). The dye concentration and the pumping intensity of frequency-doubled Nd:YAG lasers determine the efficiency of the enhancement. We apply the gain-overlap technique at optimal dye concentration and pump intensity to probe minority species in pendant drops formed by binary mixtures. The limits of detectable concentrations of the minority species, methanol in methanol-ethanol and ethanol in ethanol-water (dye-doped) mixtures, are much less than those in undoped mixtures. The smooth fluorescence-lasing spectral curves emitted from dye-doped pendant drops reduce complications in distinguishing SRS signals from quasi-periodic fluorescence-lasing spectra in microdroplets.

  12. Genetic causal attributions for weight status and weight loss during a behavioral weight gain prevention intervention

    PubMed Central

    McVay, Megan A.; Steinberg, Dori M.; Askew, Sandy; Kaphingst, Kimberly A.; Bennett, Gary G.

    2015-01-01

    Purpose Emerging evidence suggests that attributing one’s weight to genetics may contribute to the adoption of obesogenic behaviors. We examined if weight-related genetic attributions were associated with weight change during a weight gain prevention intervention. Methods Participants (n=185) were from a randomized clinical trial of a digital health weight gain prevention intervention for Black women age 25–44 with BMI 25.0–34.9kg/m2. Weight-related genetic attributions (weight status attribution and weight loss attributions) were measured at baseline and 12 months. Results Among intervention participants, high genetic attribution for weight loss was associated with greater weight loss at 12 months (−2.7 kg vs 0.5 kg) and 18 months (−3.0 kg vs 0.9 kg). Among usual care participants, high genetic attribution for weight status was associated with greater 18-month weight gain (2.9 kg vs 0.3 kg). The intervention reduced likelihood of high genetic attribution for weight loss at 12 months (p=0.05). Change in likelihood of genetic attribution was not associated with weight change over 12 months. Conclusion Impact of genetic attributions on weight differs for those enrolled and not enrolled in an intervention. However, weight gain prevention intervention may reduce genetic attribution for weight loss. PMID:26291598

  13. Enhanced Decoding for the Galileo Low-Gain Antenna Mission

    NASA Technical Reports Server (NTRS)

    Dolinar, S.; Belongie, M.

    1994-01-01

    Due to a malfunctioning high-gain antenna, the Galileo spacecraft is transmitting all its data through a low-gain antenna, and the data rate will seldom exceed 100 bits per second during its two-year tour of Jupiter's satellites.

  14. High-gain nonlinear observer for simple genetic regulation process

    NASA Astrophysics Data System (ADS)

    Torres, L. A.; Ibarra-Junquera, V.; Escalante-Minakata, P.; Rosu, H. C.

    2007-07-01

    High-gain nonlinear observers occur in the nonlinear automatic control theory and are in standard usage in chemical engineering processes. We apply such a type of analysis in the context of a very simple one-gene regulation circuit. In general, an observer combines an analytical differential-equation-based model with partial measurement of the system in order to estimate the non-measured state variables. We use one of the simplest observers, that of Gauthier et al., which is a copy of the original system plus a correction term which is easy to calculate. For the illustration of this procedure, we employ a biological model, recently adapted from Goodwin's old book by De Jong, in which one plays with the dynamics of the concentrations of the messenger RNA coding for a given protein, the protein itself, and a single metabolite. Using the observer instead of the metabolite, it is possible to rebuild the non-measured concentrations of the mRNA and the protein.

  15. The inevitability of genetic enhancement technologies.

    PubMed

    Baylis, Francoise; Robert, Jason Scott

    2004-01-01

    We outline a number of ethical objections to genetic technologies aimed at enhancing human capacities and traits. We then argue that, despite the persuasiveness of some of these objections, they are insufficient to stop the development and use of genetic enhancement technologies. We contend that the inevitability of the technologies results from a particular guiding worldview of humans as masters of the human evolutionary future, and conclude that recognising this worldview points to new directions for ethical thinking about genetic enhancement technologies. PMID:15168695

  16. Genetic enhancement technologies and the new society.

    PubMed

    Smith, G P

    2000-01-01

    So long as procreation continues to remain a central driving force in a marital relationship, and the family the very core of progressive society, efforts will be undertaken to expand the period of fecundity and combat infertility. Genetic planning and eugenic programming are more rational and humane alternatives to population regulation than death by famine and war. Genetic enhancement technologies and the scientific research undertaken to advance them should be viewed as not only aiding (or, sometimes resolving) the tragedy of infertility in family planning, but as a tool for enhancing the health of a Nation's citizens by engineering man's genetic weaknesses out of the line of inheritance. Put simply, healthier and genetically sound individuals have a much better opportunity for pursuing and achieving the "good life" and making a significant contribution to society's greater well being.

  17. Glycinergic feedback enhances synaptic gain in the distal retina

    PubMed Central

    Jiang, Zheng; Yang, Jinnan; Purpura, Lauren A; Liu, Yufei; Ripps, Harris; Shen, Wen

    2014-01-01

    Glycine input originates with interplexiform cells, a group of neurons situated within the inner retina that transmit signals centrifugally to the distal retina. The effect on visual function of this novel mechanism is largely unknown. Using gramicidin-perforated patch whole cell recordings, intracellular recordings and specific antibody labelling techniques, we examined the effects of the synaptic connections between glycinergic interplexiform cells, photoreceptors and bipolar cells. To confirm that interplexiform cells make centrifugal feedback on bipolar cell dendrites, we recorded the postsynaptic glycine currents from axon-detached bipolar cells while stimulating presynaptic interplexiform cells. The results show that glycinergic interplexiform cells activate bipolar cell dendrites that express the α3 subunit of the glycine receptor, as well as a subclass of unidentified receptors on photoreceptors. By virtue of their synaptic contacts, glycine centrifugal feedback increases glutamate release from photoreceptors and suppresses the uptake of glutamate by the type 2A excitatory amino acid transporter on photoreceptors. The net effect is a significant increase in synaptic gain between photoreceptors and their second-order neurons. PMID:24421349

  18. Genetic diversity and selection gain in the physic nut (Jatropha curcas).

    PubMed

    Brasileiro, B P; Silva, S A; Souza, D R; Santos, P A; Oliveira, R S; Lyra, D H

    2013-01-01

    The use of efficient breeding methods depends on knowledge of genetic control of traits to be improved. We estimated genetic parameters, selection gain, and genetic diversity in physic nut half-sib families, in order to provide information for breeding programs of this important biofuel species. The progeny test included 20 half-sib families in 4 blocks and 10 plants per plot. The mean progeny heritability values were: 50% for number of bunches, 47% for number of fruits, 35% for number of seeds, 6% for stem diameter, 26% for number of primary branches, 14% for number of secondary branches, 66% for plant height, and 25% for survival of the plants, demonstrating good potential for early selection in plant height, number of branches, and number of fruits per plant. In the analysis of genetic diversity, genotypes were divided into 4 groups. Genotypes 18, 19, 20, and 8 clustered together and presented the highest means for the vegetative and production. Lower means were observed in the 17, 12, 13, and 9 genotypes from the same group. We detected genetic variability in this population, with high heritability estimates and accuracy, demonstrating the possibility of obtaining genetic gains for vegetative characters and production at 24 months after planting. PMID:23315871

  19. Distinct developmental genetic mechanisms underlie convergently evolved tooth gain in sticklebacks

    PubMed Central

    Ellis, Nicholas A.; Glazer, Andrew M.; Donde, Nikunj N.; Cleves, Phillip A.; Agoglia, Rachel M.; Miller, Craig T.

    2015-01-01

    Teeth are a classic model system of organogenesis, as repeated and reciprocal epithelial and mesenchymal interactions pattern placode formation and outgrowth. Less is known about the developmental and genetic bases of tooth formation and replacement in polyphyodonts, which are vertebrates with continual tooth replacement. Here, we leverage natural variation in the threespine stickleback fish Gasterosteus aculeatus to investigate the genetic basis of tooth development and replacement. We find that two derived freshwater stickleback populations have both convergently evolved more ventral pharyngeal teeth through heritable genetic changes. In both populations, evolved tooth gain manifests late in development. Using pulse-chase vital dye labeling to mark newly forming teeth in adult fish, we find that both high-toothed freshwater populations have accelerated tooth replacement rates relative to low-toothed ancestral marine fish. Despite the similar evolved phenotype of more teeth and an accelerated adult replacement rate, the timing of tooth number divergence and the spatial patterns of newly formed adult teeth are different in the two populations, suggesting distinct developmental mechanisms. Using genome-wide linkage mapping in marine-freshwater F2 genetic crosses, we find that the genetic basis of evolved tooth gain in the two freshwater populations is largely distinct. Together, our results support a model whereby increased tooth number and an accelerated tooth replacement rate have evolved convergently in two independently derived freshwater stickleback populations using largely distinct developmental and genetic mechanisms. PMID:26062935

  20. Distinct developmental genetic mechanisms underlie convergently evolved tooth gain in sticklebacks.

    PubMed

    Ellis, Nicholas A; Glazer, Andrew M; Donde, Nikunj N; Cleves, Phillip A; Agoglia, Rachel M; Miller, Craig T

    2015-07-15

    Teeth are a classic model system of organogenesis, as repeated and reciprocal epithelial and mesenchymal interactions pattern placode formation and outgrowth. Less is known about the developmental and genetic bases of tooth formation and replacement in polyphyodonts, which are vertebrates with continual tooth replacement. Here, we leverage natural variation in the threespine stickleback fish Gasterosteus aculeatus to investigate the genetic basis of tooth development and replacement. We find that two derived freshwater stickleback populations have both convergently evolved more ventral pharyngeal teeth through heritable genetic changes. In both populations, evolved tooth gain manifests late in development. Using pulse-chase vital dye labeling to mark newly forming teeth in adult fish, we find that both high-toothed freshwater populations have accelerated tooth replacement rates relative to low-toothed ancestral marine fish. Despite the similar evolved phenotype of more teeth and an accelerated adult replacement rate, the timing of tooth number divergence and the spatial patterns of newly formed adult teeth are different in the two populations, suggesting distinct developmental mechanisms. Using genome-wide linkage mapping in marine-freshwater F2 genetic crosses, we find that the genetic basis of evolved tooth gain in the two freshwater populations is largely distinct. Together, our results support a model whereby increased tooth number and an accelerated tooth replacement rate have evolved convergently in two independently derived freshwater stickleback populations using largely distinct developmental and genetic mechanisms.

  1. Realized gain and prediction of yield with genetically improved Pinus radiata in New Zealand

    SciTech Connect

    Carson, S.D.; Hayes, J.D. ); Garcia, O. . Centro de Investigacions Forestais de Lourizan)

    1999-05-01

    Pinus radiata D. Don seedlots of varying genetic quality were compared in block-plot genetic-gain trials at 10 locations representing most of the site types in New Zealand. Permanent sample plots were measured annually for growth from age 6--8 yr from planting to ages 15--17 (midrotation). Seedlots from first-generation open-pollinated seed orchards and a mix of crosses that all involved the top-performing parent were, respectively, on average 4.5 % and 5.3% taller and had 6% and 11% larger mean diameter, 12% and 30% more basal area, and 15% and 34% more stem volume than seedlots originating from mild mass selection in harvested stands (climbing select). The observed growth increases were quantified as changes in the rate of growth from that predicted by pre-existing growth models in order to account for tree size and stocking differences. Seedlots from first-generation seed orchards and crosses of the top clone, respectively, grew 5.1% and 4.5% faster in height, and functions for basal area and stocking changed 13% and 26.4% faster, respectively, than the baseline growth models, which were based on climbing select. This implies that increased basal area growth must be taken into account in order to obtain accurate prediction of gain in stem volume. The incorporation of these observed increases in growth rates into stand growth models as genetic-gain multipliers in order to extrapolate predictions of growth of genetically improved seedlots beyond the sites, silvicultures, and seedlots represented in the genetic gain trials is discussed.

  2. Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations

    PubMed Central

    Saigi-Morgui, Núria; Quteineh, Lina; Bochud, Pierre-Yves; Crettol, Severine; Kutalik, Zoltán; Wojtowicz, Agnieszka; Bibert, Stéphanie; Beckmann, Sonja; Mueller, Nicolas J; Binet, Isabelle; van Delden, Christian; Steiger, Jürg; Mohacsi, Paul; Stirnimann, Guido; Soccal, Paola M.; Pascual, Manuel; Eap, Chin B

    2016-01-01

    Background Polygenic obesity in Solid Organ Transplant (SOT) populations is considered a risk factor for the development of metabolic abnormalities and graft survival. Few studies to date have studied the genetics of weight gain in SOT recipients. We aimed to determine whether weighted genetic risk scores (w-GRS) integrating genetic polymorphisms from GWAS studies (SNP group#1 and SNP group#2) and from Candidate Gene studies (SNP group#3) influence BMI in SOT populations and if they predict ≥10% weight gain (WG) one year after transplantation. To do so, two samples (nA = 995, nB = 156) were obtained from naturalistic studies and three w-GRS were constructed and tested for association with BMI over time. Prediction of 10% WG at one year after transplantation was assessed with models containing genetic and clinical factors. Results w-GRS were associated with BMI in sample A and B combined (BMI increased by 0.14 and 0.11 units per additional risk allele in SNP group#1 and #2, respectively, p-values<0.008). w-GRS of SNP group#3 showed an effect of 0.01 kg/m2 per additional risk allele when combining sample A and B (p-value 0.04). Models with genetic factors performed better than models without in predicting 10% WG at one year after transplantation. Conclusions This is the first study in SOT evaluating extensively the association of w-GRS with BMI and the influence of clinical and genetic factors on 10% of WG one year after transplantation, showing the importance of integrating genetic factors in the final model. Genetics of obesity among SOT recipients remains an important issue and can contribute to treatment personalization and prediction of WG after transplantation. PMID:27788139

  3. Acceleration of genetic gain in cattle by reduction of generation interval

    PubMed Central

    Kasinathan, Poothappillai; Wei, Hong; Xiang, Tianhao; Molina, Jose A.; Metzger, John; Broek, Diane; Kasinathan, Sivakanthan; Faber, David C.; Allan, Mark F.

    2015-01-01

    Genomic selection (GS) approaches, in combination with reproductive technologies, are revolutionizing the design and implementation of breeding programs in livestock species, particularly in cattle. GS leverages genomic readouts to provide estimates of breeding value early in the life of animals. However, the capacity of these approaches for improving genetic gain in breeding programs is limited by generation interval, the average age of an animal when replacement progeny are born. Here, we present a cost-effective approach that combines GS with reproductive technologies to reduce generation interval by rapidly producing high genetic merit calves. PMID:25728468

  4. Low-index-metamaterial for gain enhancement of planar terahertz antenna

    SciTech Connect

    Zhang, Qing-Le; Si, Li-Ming Lv, Xin; Huang, Yongjun; Zhu, Weiren

    2014-03-15

    We theoretically present a high gain planar antenna at terahertz (THz) frequencies by combing a conventional log-periodic antenna (LPA) with a low-index-metamaterial (LIM, |n| < 1). The LIM is realized by properly designing a fishnet metamaterial using full-wave finite-element simulation. Owing to the impedance matching, the LIM can be placed seamlessly on the substrate of the LPA without noticeable reflection. The effectiveness of using LIM for antenna gain enhancement is confirmed by comparing the antenna performance with and without LIM, where significantly improved half-power beam-width (3-dB beam-width) and more than 4 dB gain enhancement are seen within a certain frequency range. The presented LIM-enhanced planar THz antenna is compact, flat, low profile, and high gain, which has extensive applications in THz systems, including communications, radar, and spectroscopy.

  5. Using genetic mouse models to gain insight into glaucoma: Past results and future possibilities.

    PubMed

    Fernandes, Kimberly A; Harder, Jeffrey M; Williams, Pete A; Rausch, Rebecca L; Kiernan, Amy E; Nair, K Saidas; Anderson, Michael G; John, Simon W M; Howell, Gareth R; Libby, Richard T

    2015-12-01

    While all forms of glaucoma are characterized by a specific pattern of retinal ganglion cell death, they are clinically divided into several distinct subclasses, including normal tension glaucoma, primary open angle glaucoma, congenital glaucoma, and secondary glaucoma. For each type of glaucoma there are likely numerous molecular pathways that control susceptibility to the disease. Given this complexity, a single animal model will never precisely model all aspects of all the different types of human glaucoma. Therefore, multiple animal models have been utilized to study glaucoma but more are needed. Because of the powerful genetic tools available to use in the laboratory mouse, it has proven to be a highly useful mammalian system for studying the pathophysiology of human disease. The similarity between human and mouse eyes coupled with the ability to use a combination of advanced cell biological and genetic tools in mice have led to a large increase in the number of studies using mice to model specific glaucoma phenotypes. Over the last decade, numerous new mouse models and genetic tools have emerged, providing important insight into the cell biology and genetics of glaucoma. In this review, we describe available mouse genetic models that can be used to study glaucoma-relevant disease/pathobiology. Furthermore, we discuss how these models have been used to gain insights into ocular hypertension (a major risk factor for glaucoma) and glaucomatous retinal ganglion cell death. Finally, the potential for developing new mouse models and using advanced genetic tools and resources for studying glaucoma are discussed.

  6. Enhanced optical precursors by Doppler effect via active Raman gain process.

    PubMed

    Peng, Yandong; Niu, Yueping; Zhang, Lida; Yang, Aihong; Jiang, Lin; Gong, Shangqing

    2012-08-15

    A scheme for enhancing precursor pulse by Doppler effect is proposed in a room-temperature active-Raman-gain medium. Due to abnormal dispersion between two gain peaks, main fields are advanced and constructively interfere with optical precursors, which leads to enhancement of the transient pulse at the rise edge of the input. Moreover, after Doppler averaging, the abnormal dispersion intensifies and the constructive interference between precursors and main fields is much strengthened, which boosts the transient spike. Simulation results demonstrate that the peak intensity of precursors could be enhanced nearly 20 times larger than that of the input.

  7. Enhanced optical precursors by Doppler effect via active Raman gain process.

    PubMed

    Peng, Yandong; Niu, Yueping; Zhang, Lida; Yang, Aihong; Jiang, Lin; Gong, Shangqing

    2012-08-15

    A scheme for enhancing precursor pulse by Doppler effect is proposed in a room-temperature active-Raman-gain medium. Due to abnormal dispersion between two gain peaks, main fields are advanced and constructively interfere with optical precursors, which leads to enhancement of the transient pulse at the rise edge of the input. Moreover, after Doppler averaging, the abnormal dispersion intensifies and the constructive interference between precursors and main fields is much strengthened, which boosts the transient spike. Simulation results demonstrate that the peak intensity of precursors could be enhanced nearly 20 times larger than that of the input. PMID:23381248

  8. Gain enhancement for wideband end-fire antenna design with artificial material.

    PubMed

    Wei, Min; Sun, Yuanhua; Wu, Xi; Wen, Wu

    2016-01-01

    Gain enhancement wideband end-fire antenna is proposed in this paper. The proposed antenna can achieve gain enhancement by loading novel artificial materials structures (Split-ring Resonators) in the end-fire direction while broad bandwidth is realized by using elliptic dipole elements and a microstrip to coplanar balun. The measurements show that the proposed antenna have around 5-8 dB gain in the working band (5-11 GHz), which is around 2 dB more than the unloaded one. This antenna can be used in target recognition systems for its advantages of end-fire radiation broad bandwidth and high gain. PMID:27652144

  9. A Confucian reflection on genetic enhancement.

    PubMed

    Fan, Ruiping

    2010-04-01

    This essay explores a proper Confucian vision on genetic enhancement. It argues that while Confucians can accept a formal starting point that Michael Sandel proposes in his ethics of giftedness, namely, that children should be taken as gifts, Confucians cannot adopt his generalist strategy. The essay provides a Confucian full ethics of giftedness by addressing a series of relevant questions, such as what kind of gifts children are, where the gifts are from, in which way they are given, and for what purpose they are given. It indicates that Confucians should sort out different types of enhancement and bring them to the test of the Confucian values in terms of both Confucian virtue principles and specific ritual rules. It concludes that Confucians can accept some types of enhancement but must reject others.

  10. Genetic variation and gains in resistance of strawberry to Colletotrichum gloeosporioides.

    PubMed

    Osorio, L F; Pattison, J A; Peres, N A; Whitaker, V M

    2014-01-01

    Anthracnose crown rot is an important disease of strawberry primarily caused by Colletotrichum gloeosporioides in Florida and North Carolina. Information on the magnitude of additive and nonadditive genetic variation is required to define breeding strategies and to estimate potential genetic gains. However, little is known about the genetic control of resistance and its utility in breeding. Our objectives were to obtain estimates of heritabilities and of components of genetic variances, genotype-environment interactions, and gains for resistance, and to examine the effects of locations and transplant types on the estimates. An incomplete diallel mating design generated 42 full-sib families, which were propagated in plugs from seed (seedling tests) and as bare-root runner plants (clonal tests) of different genotypes of the same families. Both seedlings and clones were inoculated with C. gloeosporioides under field conditions in North Carolina and Florida during the 2010-11 season. Narrow-sense heritability (h(2)) and broad-sense heritability (H(2)) for both clones and seedlings were higher at the North Carolina location (h(2) = 0.34 to 0.62 and H(2) = 0.46 to 0.85) than at the Florida location (h(2) = 0.16 to 0.22 and H(2) = 0.37 to 0.46). Likewise, the seedling tests showed higher genetic control than the clonal tests at both locations. Estimates of dominance variance were approximately one-third of the additive variance at North Carolina and were even larger at Florida. Epistasis was negative at both locations and assumed zero for heritability (H(2)) calculations. Genotype-environment interactions were different by transplant type, suggesting rank changes across locations. 'Pelican' was the most resistant parent at both locations, followed by 'NCH09-68' at the NC location and 'Winter Dawn' at the Florida location. Selection and deployment of the most resistant clone within each of the five best families is estimated to produce average genetic gains of 53.0 and 73

  11. Genetic variation and gains in resistance of strawberry to Colletotrichum gloeosporioides.

    PubMed

    Osorio, L F; Pattison, J A; Peres, N A; Whitaker, V M

    2014-01-01

    Anthracnose crown rot is an important disease of strawberry primarily caused by Colletotrichum gloeosporioides in Florida and North Carolina. Information on the magnitude of additive and nonadditive genetic variation is required to define breeding strategies and to estimate potential genetic gains. However, little is known about the genetic control of resistance and its utility in breeding. Our objectives were to obtain estimates of heritabilities and of components of genetic variances, genotype-environment interactions, and gains for resistance, and to examine the effects of locations and transplant types on the estimates. An incomplete diallel mating design generated 42 full-sib families, which were propagated in plugs from seed (seedling tests) and as bare-root runner plants (clonal tests) of different genotypes of the same families. Both seedlings and clones were inoculated with C. gloeosporioides under field conditions in North Carolina and Florida during the 2010-11 season. Narrow-sense heritability (h(2)) and broad-sense heritability (H(2)) for both clones and seedlings were higher at the North Carolina location (h(2) = 0.34 to 0.62 and H(2) = 0.46 to 0.85) than at the Florida location (h(2) = 0.16 to 0.22 and H(2) = 0.37 to 0.46). Likewise, the seedling tests showed higher genetic control than the clonal tests at both locations. Estimates of dominance variance were approximately one-third of the additive variance at North Carolina and were even larger at Florida. Epistasis was negative at both locations and assumed zero for heritability (H(2)) calculations. Genotype-environment interactions were different by transplant type, suggesting rank changes across locations. 'Pelican' was the most resistant parent at both locations, followed by 'NCH09-68' at the NC location and 'Winter Dawn' at the Florida location. Selection and deployment of the most resistant clone within each of the five best families is estimated to produce average genetic gains of 53.0 and 73

  12. Potential benefits of genomic selection on genetic gain of small ruminant breeding programs.

    PubMed

    Shumbusho, F; Raoul, J; Astruc, J M; Palhiere, I; Elsen, J M

    2013-08-01

    In conventional small ruminant breeding programs, only pedigree and phenotype records are used to make selection decisions but prospects of including genomic information are now under consideration. The objective of this study was to assess the potential benefits of genomic selection on the genetic gain in French sheep and goat breeding designs of today. Traditional and genomic scenarios were modeled with deterministic methods for 3 breeding programs. The models included decisional variables related to male selection candidates, progeny testing capacity, and economic weights that were optimized to maximize annual genetic gain (AGG) of i) a meat sheep breeding program that improved a meat trait of heritability (h(2)) = 0.30 and a maternal trait of h(2) = 0.09 and ii) dairy sheep and goat breeding programs that improved a milk trait of h(2) = 0.30. Values of ±0.20 of genetic correlation between meat and maternal traits were considered to study their effects on AGG. The Bulmer effect was accounted for and the results presented here are the averages of AGG after 10 generations of selection. Results showed that current traditional breeding programs provide an AGG of 0.095 genetic standard deviation (σa) for meat and 0.061 σa for maternal trait in meat breed and 0.147 σa and 0.120 σa in sheep and goat dairy breeds, respectively. By optimizing decisional variables, the AGG with traditional selection methods increased to 0.139 σa for meat and 0.096 σa for maternal traits in meat breeding programs and to 0.174 σa and 0.183 σa in dairy sheep and goat breeding programs, respectively. With a medium-sized reference population (nref) of 2,000 individuals, the best genomic scenarios gave an AGG that was 17.9% greater than with traditional selection methods with optimized values of decisional variables for combined meat and maternal traits in meat sheep, 51.7% in dairy sheep, and 26.2% in dairy goats. The superiority of genomic schemes increased with the size of the

  13. Gain enhanced Fano resonance in a coupled photonic crystal cavity-waveguide structure.

    PubMed

    Zhao, Yanhui; Qian, Chenjiang; Qiu, Kangsheng; Tang, Jing; Sun, Yue; Jin, Kuijuan; Xu, Xiulai

    2016-01-01

    Systems with coupled cavities and waveguides have been demonstrated as optical switches and optical sensors. To optimize the functionalities of these optical devices, Fano resonance with asymmetric and steep spectral line shape has been used. We theoretically propose a coupled photonic crystal cavity-waveguide structure to achieve Fano resonance by placing partially reflecting elements in waveguide. To enhance Fano resonance, optical gain material is introduced into the cavity. As the gain increases, the transmission line shape becomes steepened and the transmissivity can be six times enhanced, giving a large contrast by a small frequency shift. It is prospected that the gain enhanced Fano resonance is very useful for optical switches and optical sensors. PMID:27640809

  14. Gain enhanced Fano resonance in a coupled photonic crystal cavity-waveguide structure

    NASA Astrophysics Data System (ADS)

    Zhao, Yanhui; Qian, Chenjiang; Qiu, Kangsheng; Tang, Jing; Sun, Yue; Jin, Kuijuan; Xu, Xiulai

    2016-09-01

    Systems with coupled cavities and waveguides have been demonstrated as optical switches and optical sensors. To optimize the functionalities of these optical devices, Fano resonance with asymmetric and steep spectral line shape has been used. We theoretically propose a coupled photonic crystal cavity-waveguide structure to achieve Fano resonance by placing partially reflecting elements in waveguide. To enhance Fano resonance, optical gain material is introduced into the cavity. As the gain increases, the transmission line shape becomes steepened and the transmissivity can be six times enhanced, giving a large contrast by a small frequency shift. It is prospected that the gain enhanced Fano resonance is very useful for optical switches and optical sensors.

  15. Gain enhanced Fano resonance in a coupled photonic crystal cavity-waveguide structure

    PubMed Central

    Zhao, Yanhui; Qian, Chenjiang; Qiu, Kangsheng; Tang, Jing; Sun, Yue; Jin, Kuijuan; Xu, Xiulai

    2016-01-01

    Systems with coupled cavities and waveguides have been demonstrated as optical switches and optical sensors. To optimize the functionalities of these optical devices, Fano resonance with asymmetric and steep spectral line shape has been used. We theoretically propose a coupled photonic crystal cavity-waveguide structure to achieve Fano resonance by placing partially reflecting elements in waveguide. To enhance Fano resonance, optical gain material is introduced into the cavity. As the gain increases, the transmission line shape becomes steepened and the transmissivity can be six times enhanced, giving a large contrast by a small frequency shift. It is prospected that the gain enhanced Fano resonance is very useful for optical switches and optical sensors. PMID:27640809

  16. Estimate of genetic gain in popcorn after cycles of phenotypic recurrent selection.

    PubMed

    Ematné, H J; Nunes, J A R; Dias, K O G; Prado, P E R; Souza, J C

    2016-01-01

    Popcorn is widely consumed in Brazil, yet there are few breeding programs for this crop. Recurrent selection (RS) is a viable breeding alternative for popcorn; however, the gains achieved must be frequently checked. The aim of this study was to assess the effect of selection for grain type (round and pointed) after four cycles of phenotypic RS on the main agronomic traits of popcorn, to estimate the genetic gain achieved for the trait of expansion volume (EV), and to obtain estimates of phenotypic correlations for the main traits of the crop in the UFLA E and UFLA R populations. The zero, one, two, and three cycles of the UFLA E and UFLA R populations, the fourth cycle, and the controls IAC-112 and IAC-125 were used. The experiments were conducted at the experimental farm of Universidade Federal de Lavras (UFLA; Environment 1) and at the experimental area of the Genetics and Plant Breeding Sector of the Department of Biology at UFLA (Environment 2) in the 2010/11 crop season. Nine agronomic traits were evaluated, including EV and grain yield (GY). The UFLA R and UFLA E populations showed similar behavior for all evaluated traits. The type of grain did not affect the genetic gain for EV, which was 5 and 3.7% in each cycle carried out in the UFLA E and UFLA R population, respectively. Phenotypic selection carried out during recombination for EV is an effective method for increasing expression of the trait. EV and GY did not show a linear association. PMID:27323058

  17. Genetic differences in emotionally enhanced memory.

    PubMed

    Todd, Rebecca M; Palombo, Daniela J; Levine, Brian; Anderson, Adam K

    2011-03-01

    Understanding genetic contributions to individual differences in the capacity for emotional memory has tremendous implications for understanding normal human memory as well as pathological reactions to traumatic stress. Research in the last decade has identified genetic polymorphisms thought to influence cognitive/affective processes that may contribute to emotional memory capacity. In this paper, we review key polymorphisms linked to emotional and mnemonic processing and their influence on neuromodulator activity in the amygdala and other emotion-related structures. We discuss their potential roles in specific cognitive processes involved in memory formation, and review links between these genetic variants, brain activation, and specific patterns of attention, perception, and memory consolidation that may be linked to individual differences in memory vividness. Finally we propose a model predicting an influence of noradrenergic, serotonergic, and dopaminergic processes on emotional perception, as well as on memory consolidation and self-regulation. Outside of the laboratory, it is likely that real-life effects of arousal operate along a continuum that incorporates other "non-emotional" aspects of memory. For this reason we further discuss additional literature on genetic variations that influence general episodic memory processes, rather than being specific to emotional enhancement of memory. We conclude that specific neuromodulators contribute to an amygdala-driven memory system that is relatively involuntary, embodied, and sensorily vivid. PMID:21094178

  18. Undergraduates achieve learning gains in plant genetics through peer teaching of secondary students.

    PubMed

    Chrispeels, H E; Klosterman, M L; Martin, J B; Lundy, S R; Watkins, J M; Gibson, C L; Muday, G K

    2014-01-01

    This study tests the hypothesis that undergraduates who peer teach genetics will have greater understanding of genetic and molecular biology concepts as a result of their teaching experiences. Undergraduates enrolled in a non-majors biology course participated in a service-learning program in which they led middle school (MS) or high school (HS) students through a case study curriculum to discover the cause of a green tomato variant. The curriculum explored plant reproduction and genetic principles, highlighting variation in heirloom tomato fruits to reinforce the concept of the genetic basis of phenotypic variation. HS students were taught additional activities related to mole-cular biology techniques not included in the MS curriculum. We measured undergraduates' learning outcomes using pre/postteaching content assessments and the course final exam. Undergraduates showed significant gains in understanding of topics related to the curriculum they taught, compared with other course content, on both types of assessments. Undergraduates who taught HS students scored higher on questions specific to the HS curriculum compared with undergraduates who taught MS students, despite identical lecture content, on both types of assessments. These results indicate the positive effect of service-learning peer-teaching experiences on undergraduates' content knowledge, even for non-science major students.

  19. Defining desired genetic gains for rainbow trout breeding objective using analytic hierarchy process.

    PubMed

    Sae-Lim, P; Komen, H; Kause, A; van Arendonk, J A M; Barfoot, A J; Martin, K E; Parsons, J E

    2012-06-01

    Distributing animals from a single breeding program to a global market may not satisfy all producers, as they may differ in market objectives and farming environments. Analytic hierarchy process (AHP) is used to estimate preferences, which can be aggregated to consensus preference values using weighted goal programming (WGP). The aim of this study was to use an AHP-WGP based approach to derive desired genetic gains for rainbow trout breeding and to study whether breeding trait preferences vary depending on commercial products and farming environments. Two questionnaires were sent out. Questionnaire-A (Q-A) was distributed to 178 farmers from 5 continents and used to collect information on commercial products and farming environments. In this questionnaire, farmers were asked to rank the 6 most important traits for genetic improvement from a list of 13 traits. Questionnaire B (Q-B) was sent to all farmers who responded to Q-A (53 in total). For Q-B, preferences of the 6 traits were obtained using pairwise comparison. Preference intensity was given to quantify (in % of a trait mean; G%) the degree to which 1 trait is preferred over the other. Individual preferences, social preferences, and consensus preferences (Con-P) were estimated using AHP and WGP. Desired gains were constructed by multiplying Con-P by G%. The analysis revealed that the 6 most important traits were thermal growth coefficient (TGC), survival (Surv), feed conversion ratio (FCR), condition factor (CF), fillet percentage (FIL%), and late maturation (LMat). Ranking of traits based on average Con-P values were Surv (0.271), FCR (0.246), TGC (0.246), LMat (0.090), FIL% (0.081), and CF (0.067). Corresponding desired genetic gains (in % of trait mean) were 1.63, 1.87, 1.67, 1.29, 0.06, and 0.33%, respectively. The results from Con-P values show that trait preferences may vary for different types of commercial production or farming environments. This study demonstrated that combination of AHP and WGP can

  20. Genetic enhancement in sport: just another form of doping?

    PubMed

    Mehlman, Maxwell J

    2012-12-01

    Patented genetic technologies such as the ACTN3 genetic test are adding a new dimension to the types of performance enhancement available to elite athletes. Organized sports organizations and governments are seeking to prevent athletes' use of biomedical enhancements. This paper discusses how these interdiction efforts will affect the use and availability of genetic technologies that can enhance athletic performance. The paper provides a working definition of enhancement, and in light of that definition and the concerns of the sports community, reviews genetic enhancement as a result of varied technologies, including, genetic testing to identify innate athletic ability, performance-enhancing drugs developed with genetic science and technology, pharmacogenetics, enhancement through reproductive technologies, somatic gene transfer, and germ line gene transfer.

  1. Insulin enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in humans.

    PubMed

    Young, Colin N; Deo, Shekhar H; Chaudhary, Kunal; Thyfault, John P; Fadel, Paul J

    2010-09-15

    Recent animal studies indicate that insulin increases arterial baroreflex control of lumbar sympathetic nerve activity; however, the extent to which these findings can be extrapolated to humans is unknown. To begin to address this, muscle sympathetic nerve activity (MSNA) and arterial blood pressure were measured in 19 healthy subjects (27 ± 1 years) before, and for 120 min following, two common methodologies used to evoke sustained increases in plasma insulin: a mixed meal and a hyperinsulinaemic euglycaemic clamp. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. Plasma insulin was significantly elevated within 30 min following meal intake (34 ± 6 uIU ml(1); P < 0.05) and remained above baseline for up to 120 min. Similarly, after meal intake, arterial baroreflex-MSNA gain for burst incidence and total MSNA was increased and remained elevated for the duration of the protocol (e.g. burst incidence gain: 3.29 ± 0.54 baseline vs. 5.64 ± 0.67 bursts (100 heart beats)(1) mmHg(1) at 120 min; P < 0.05). During the hyperinsulinaemic euglycaemic clamp, in which insulin was elevated to postprandial concentrations (42 ± 6 μIU ml(1); P < 0.05), while glucose was maintained constant, arterial baroreflex-MSNA gain was similarly enhanced (e.g. burst incidence gain: 2.44 ± 0.29 baseline vs. 4.74 ± 0.71 bursts (100 heart beats)(1) mmHg(1) at 120 min; P < 0.05). Importantly, during time control experiments, with sustained fasting insulin concentrations, the arterial baroreflex-MSNA gain remained unchanged. These findings demonstrate, for the first time in healthy humans, that increases in plasma insulin enhance the gain of arterial baroreflex control of MSNA.

  2. Genetic Redundancies Enhance Information Transfer in Noisy Regulatory Circuits

    PubMed Central

    Rodrigo, Guillermo; Poyatos, Juan F.

    2016-01-01

    Cellular decision making is based on regulatory circuits that associate signal thresholds to specific physiological actions. This transmission of information is subjected to molecular noise what can decrease its fidelity. Here, we show instead how such intrinsic noise enhances information transfer in the presence of multiple circuit copies. The result is due to the contribution of noise to the generation of autonomous responses by each copy, which are altogether associated with a common decision. Moreover, factors that correlate the responses of the redundant units (extrinsic noise or regulatory cross-talk) contribute to reduce fidelity, while those that further uncouple them (heterogeneity within the copies) can lead to stronger information gain. Overall, our study emphasizes how the interplay of signal thresholding, redundancy, and noise influences the accuracy of cellular decision making. Understanding this interplay provides a basis to explain collective cell signaling mechanisms, and to engineer robust decisions with noisy genetic circuits. PMID:27741249

  3. Fast Ignition Thermonuclear Fusion: Enhancement of the Pellet Gain by the Colossal-Magnetic-Field Shells

    NASA Astrophysics Data System (ADS)

    Stefan, V. Alexander

    2013-10-01

    The fast ignition fusion pellet gain can be enhanced by a laser generated B-field shell. The B-field shell, (similar to Earth's B-field, but with the alternating B-poles), follows the pellet compression in a frozen-in B-field regime. A properly designed laser-pellet coupling can lead to the generation of a B-field shell, (up to 100 MG), which inhibits electron thermal transport and confines the alpha-particles. In principle, a pellet gain of few-100s can be achieved in this manner. Supported in part by Nikola Tesla Labs, Stefan University, 1010 Pearl, La Jolla, CA 92038-1007.

  4. Optimisation of contribution of candidate parents to maximise genetic gain and restricting inbreeding using semidefinite programming (Open Access publication)

    PubMed Central

    Pong-Wong, Ricardo; Woolliams, John A

    2007-01-01

    An approach for optimising genetic contributions of candidates to control inbreeding in the offspring generation using semidefinite programming (SDP) was proposed. Formulations were done for maximising genetic gain while restricting inbreeding to a preset value and for minimising inbreeding without regard of gain. Adaptations to account for candidates with fixed contributions were also shown. Using small but traceable numerical examples, the SDP method was compared with an alternative based upon Lagrangian multipliers (RSRO). The SDP method always found the optimum solution that maximises genetic gain at any level of restriction imposed on inbreeding, unlike RSRO which failed to do so in several situations. For these situations, the expected gains from the solution obtained with RSRO were between 1.5–9% lower than those expected from the optimum solution found with SDP with assigned contributions varying widely. In conclusion SDP is a reliable and flexible method for solving contribution problems. PMID:17212945

  5. Enhancing stimulated Raman scattering of weaker gain Raman modes in microdroplets by seeding and efficient pumping

    NASA Astrophysics Data System (ADS)

    Mazumder, Md. Mohiuddin; Fields, Mitchell H.; Hartings, Justin M.; Pu, Xiaoyun; Kwok, Alfred S.; Schaschek, Karl; Chang, Richard K.

    1996-05-01

    High-Q morphology-dependent resonances (MDR's) in microdroplets provide optical feedback for nonlinear processes such as stimulated Raman scattering (SRS). The SRS signal from weaker gain modes or from the minority species in a binary mixture droplet is small, because of depletion of the pump beam by the strongest-gain Raman mode. We present an effective- average Raman gain formula and discuss the factors that contribute to the enhancement of SRS intensity. Spatial overlap between pump wave and SRS wave is an important factor in determining the SRS intensity. We have observed that in a binary mixture microdroplet, the SRS of the majority species is more efficient (because of good spatial overlap) in pumping the minority species than the input laser itself. Laser-induced distortion can couple light efficiently into a droplet. We have used a variable number (3 - 6) of mode-locked 100-psec laser pulses focused on the droplet rim. The SRS emission from a minority species increases as the number of input pulses is increased, because cumulative laser-induced surface distortion couples more energy into the droplet. SRS signal at the Stokes shift of a weaker gain mode or of the mode of a minority species can be enhanced by seeding light at the SRS wavelengths. The seed signal is obtained from the fluorescence of a dye added to the microdroplet or from external coupling of light into the droplet. A lasing dye (Rhodamine 6G) is added to pure ethanol droplet. By using an excimer-pumped tunable dye laser as the excitation source, the weaker gain C-C-O mode (882 cm-1 Stokes shift) of ethanol is overlapped spectrally with the fluorescence and lasing of R6G. The SRS signal of the C-C-O mode is enhanced, because (1) the fluorescence of R6G at the SRS wavelength adds to the spontaneous SRS emission and (2) the gain from population inversion adds to the Raman gain. We have also observed enhanced SRS emission from a minority species (benzene) in dodecane by using internal dye seeding

  6. Modeling of genetic gain for single traits from marker-assisted seedling selection in clonally propagated crops

    PubMed Central

    Ru, Sushan; Hardner, Craig; Carter, Patrick A; Evans, Kate; Main, Dorrie; Peace, Cameron

    2016-01-01

    Seedling selection identifies superior seedlings as candidate cultivars based on predicted genetic potential for traits of interest. Traditionally, genetic potential is determined by phenotypic evaluation. With the availability of DNA tests for some agronomically important traits, breeders have the opportunity to include DNA information in their seedling selection operations—known as marker-assisted seedling selection. A major challenge in deploying marker-assisted seedling selection in clonally propagated crops is a lack of knowledge in genetic gain achievable from alternative strategies. Existing models based on additive effects considering seed-propagated crops are not directly relevant for seedling selection of clonally propagated crops, as clonal propagation captures all genetic effects, not just additive. This study modeled genetic gain from traditional and various marker-based seedling selection strategies on a single trait basis through analytical derivation and stochastic simulation, based on a generalized seedling selection scheme of clonally propagated crops. Various trait-test scenarios with a range of broad-sense heritability and proportion of genotypic variance explained by DNA markers were simulated for two populations with different segregation patterns. Both derived and simulated results indicated that marker-based strategies tended to achieve higher genetic gain than phenotypic seedling selection for a trait where the proportion of genotypic variance explained by marker information was greater than the broad-sense heritability. Results from this study provides guidance in optimizing genetic gain from seedling selection for single traits where DNA tests providing marker information are available. PMID:27148453

  7. Estimates of genetic parameters for visual scores and daily weight gain in Brangus animals.

    PubMed

    Queiroz, S A; Oliveira, J A; Costa, G Z; Fries, L A

    2011-05-01

    (Co)variance components were estimated for visual scores of conformation (CY), early finishing (PY) and muscling (MY) at 550 days of age (yearling), average daily gain from weaning to yearling (GWY), conformation (CW), early finishing (PW) and muscling (MW) scores at weaning, and average daily gain from birth to weaning (GBW) in animals forming the Brazilian Brangus breed born between 1986 and 2002 from the livestock files of GenSys Consultants Associados S/C Ltda. The data set contained 53 683; 45 136; 52 937; 56 471; 24 531; 21 166; 24 006 and 25 419 records for CW, PW, MW, GBW, CY, PY, MY and GWY, respectively. Data were analyzed by the restricted maximum likelihood method using single- and two-trait animal models. Direct heritability estimates obtained by single-trait analysis were 0.12, 0.14, 0.13 and 0.14 for CY, PY and MY scores and GWY, respectively. A positive association was observed between the same visual scores at weaning and yearling, with correlations ranging from 0.64 to 0.94. Estimated correlations between GBW and weaning and yearling scores ranged from 0.60 to 0.77. The genetic correlation between GBW and GWY was low (0.10), whereas correlations of 0.55, 0.37 and 0.47 were observed between GWY and CY, PY and MY, respectively. Moreover, GWY showed a weak correlation with CW (0.10), PW (-0.08) and MW (-0.03) scores. These results indicate that selection of the traits that was studied would result in a small response. In addition, selection based on average daily gain may have an indirect effect on visual scores as the correlations between GWY and visual scores were generally strong. PMID:22440022

  8. Genetic gains in the UENF-14 popcorn population with recurrent selection.

    PubMed

    Freitas, I L J; do Amaral Júnior, A T; Freitas, S P; Cabral, P D S; Ribeiro, R M; Gonçalves, L S A

    2014-01-01

    The popcorn breeding program of Universidade Estadual do Norte Fluminense Darcy Ribeiro aims to provide farmers a cultivar with desirable agronomic traits, particularly with respect to grain yield (GY) and popping expansion (PE). We evaluated full-sib families from the seventh cycle of recurrent selection and estimated the genetic progress with respect to GY and PE. Eight traits were evaluated in 200 full-sib families that were randomized into blocks with two replicates per set in two contrasting environments, Campos dos Goytacazes and Itaocara, located in north and northwest Rio de Janeiro State, respectively. There were significant differences between sets in families with respect to all traits evaluated, which indicates genetic variability that may be explored in future cycles. Using random economic weights in the selection of superior progenies, the Mulamba and Mock index showed gains for PE and GY of 5.11 and 7.78%, respectively. Significant PE and GY increases were found when comparing the evolution of mean values of these two parameters that were assessed at cycles C₀-C₆ and predicted for C₇. Thus, an advanced-cycle popcorn cultivar with genotypic superiority for the main traits of economic interest can be made available to farmers in Rio de Janeiro State. PMID:24535880

  9. Association between Maternal Fish Consumption and Gestational Weight Gain: Influence of Molecular Genetic Predisposition to Obesity

    PubMed Central

    Larsen, Sofus C.; Ängquist, Lars; Laurin, Charles; Morgen, Camilla S.; Jakobsen, Marianne U.; Paternoster, Lavinia; Smith, George Davey; Olsen, Sjurdur F.; Sørensen, Thorkild I. A.; Nohr, Ellen A.

    2016-01-01

    Background Studies suggest that fish consumption can restrict weight gain. However, little is known about how fish consumption affects gestational weight gain (GWG), and whether this relationship depends on genetic makeup. Objective To examine the association between fish consumption and GWG, and whether this relationship is dependent on molecular genetic predisposition to obesity. Design A nested case-cohort study based on the Danish National Birth Cohort (DNBC) sampling the most obese women (n = 990) and a random sample of the remaining participants (n = 1,128). Replication of statistically significant findings was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4,841). We included 32 body mass index (BMI) associated single nucleotide polymorphisms (SNPs) and 5 SNPs found associated with GWG. BMI associated SNPs were combined in a genetic risk score (GRS). Associations between consumption of fish, GRS or individual variants and GWG were analysed, and interactions between fish and the GRS or individual variants were examined. Results In the DNBC, each portion/week (150 g) of fatty fish was associated with a higher GWG of 0.58 kg (95% CI: 0.16, 0.99, P<0.01). For total fish and lean fish, similar patterns were observed, but these associations were not statistically significant. We found no association between GRS and GWG, and no interactions between GRS and dietary fish on GWG. However, we found an interaction between the PPARG Pro12Ala variant and dietary fish. Each additional Pro12Ala G-allele was associated with a GWG of -0.83 kg (95% CI: -1.29, -0.37, P<0.01) per portion/week of dietary fish, with the same pattern for both lean and fatty fish. In ALSPAC, we were unable to replicate these findings. Conclusion We found no consistent evidence of association between fish consumption and GWG, and our results indicate that the association between dietary fish and GWG has little or no dependency on GRS or individual SNPs. PMID:26930408

  10. Bandwidth enhancement of MgZnO-based MSM photodetectors by inductive gain peaking

    NASA Astrophysics Data System (ADS)

    Wang, Ping; Guo, Xinlu; Guo, Lixin; He, Jingfang; Yang, Yintang; Zhang, Zhiyong

    2016-08-01

    For high-speed optical communication applications, the bandwidth of photodetector would be a key limitation. In this work, the bandwidth property of MgZnO-based Metal-Semiconductor-Metal (MSM) photodetector considering RC and transit limitations is investigated on the basis of the series and enhanced gain peaked photodetector circuits proposed by us with different finger widths. To ensure the accuracy of parameters, the high-filed transportation characteristics of MgZnO are investigated by a three-valley ensemble Monte Carlo simulation combined with first principle calculations. The results show that the gain peaking technique, especially the enhanced gain peaking, can improve the bandwidth of MgZnO MSM photodetector to a maximum value of 61.28 GHz, corresponding to a bandwidth enhancement of 49% without undesired effects. Three-dimensional electromagnetic computation is further performed to design and simulate the on-chip-inductor. The value of the simulated inductor is approximately 0.0529 nH, which is in good agreement with the designed value of 0.0569 nH. This work benefits the development of high speed MgZnO MSM photodetector.

  11. Genomic selection strategies in a small dairy cattle population evaluated for genetic gain and profit.

    PubMed

    Thomasen, J R; Egger-Danner, C; Willam, A; Guldbrandtsen, B; Lund, M S; Sørensen, A C

    2014-01-01

    The objective of this study was to evaluate a genomic breeding scheme in a small dairy cattle population that was intermediate in terms of using both young bulls (YB) and progeny-tested bulls (PB). This scheme was compared with a conventional progeny testing program without use of genomic information and, as the extreme case, a juvenile scheme with genomic information, where all bulls were used before progeny information was available. The population structure, cost, and breeding plan parameters were chosen to reflect the Danish Jersey cattle population, being representative for a small dairy cattle population. The population consisted of 68,000 registered cows. Annually, 1,500 bull dams were screened to produce the 500 genotyped bull calves from which 60 YB were selected to be progeny tested. Two unfavorably correlated traits were included in the breeding goal, a production trait (h(2)=0.30) and a functional trait (h(2)=0.04). An increase in reliability of 5 percentage points for each trait was used in the default genomic scenario. A deterministic approach was used to model the different breeding programs, where the primary evaluation criterion was annual monetary genetic gain (AMGG). Discounted profit was used as an indicator of the economic outcome. We investigated the effect of varying the following parameters: (1) increase in reliability due to genomic information, (2) number of genotyped bull calves, (3) proportion of bull dam sires that are young bulls, and (4) proportion of cow sires that are young bulls. The genomic breeding scheme was both genetically and economically superior to the conventional breeding scheme, even in a small dairy cattle population where genomic information causes a relatively low increase in reliability of breeding values. Assuming low reliabilities of genomic predictions, the optimal breeding scheme according to AMGG was characterized by mixed use of YB and PB as bull sires. Exclusive use of YB for production cows increased AMGG up

  12. Enhanced-gain printed slot antenna using an electric metasurface superstrate

    NASA Astrophysics Data System (ADS)

    Sarkhel, Abhishek; Bhadra Chaudhuri, Sekhar Ranjan

    2016-10-01

    In this article, a method to enhance the radiation characteristics of a slot antenna by using an electric metasurface as a high refractive index superstrate has been presented. The gain enhancement mechanism described here uses the phenomena of enhanced space field by increasing the effective aperture of the antenna, resulting from increase in effective refractive index of the metasurface. As a fundamental constituent of the superstrate, a unit cell of the metasurface composed of symmetrically placed triple pairs of split-ring resonators is introduced. The unit cell of such metasurface has been configured to realize a high refractive index by using the principle of nearest-neighbor coupling. An equivalent circuit model is developed to understand the influence of coupling on the effective refractive index of the metasurface. The presence of the metasurface as a superstrate enhances the broadside gain of the slot by 8.71 dB and the efficiency by 20.35 %. The total height of the proposed configuration is 0.237 λ 0 where λ 0 is the free space wavelength at the resonance frequency of the slot antenna.

  13. Meander-line-based inhomogeneous anisotropic artificial material for gain enhancement of UWB Vivaldi antenna

    NASA Astrophysics Data System (ADS)

    Pandey, Gaurav Kumar; Singh, Hari Shankar; Meshram, Manoj Kumar

    2016-02-01

    An inhomogeneous anisotropic (IA) artificial material (AM) is proposed having epsilon-near-zero (ENZ) characteristics and effective refractive index >1, simultaneously, in the same direction. Further, the proposed IA-AM is utilized for the gain enhancement of Vivaldi antenna for ultra-wideband (UWB) applications. The IA-AM consists of two types of compact meandered line-based anisotropic artificial material with ENZ characteristics in two adjacent narrow bands of 5.5-8.5 and 8-11.5 GHz. However, the non-resonant behavior of the artificial material in other direction appears with high refractive index property in broadband region. The combination of both the unit cells with broadband ENZ and high refractive index property is used to improve the gain of the Vivaldi antenna in broadband. The proposed IA-AM-loaded Vivaldi antenna exhibits a gain enhancement of up to 2 dBi compared to the original antenna in the operating frequency band of 3.1-12 GHz with | S 11| < -10 dB. The proposed antenna shows nearly stable unidirectional radiation patterns with high directivity and nearly flat group delay.

  14. Printed Wide-Slot Antenna Design with Bandwidth and Gain Enhancement on Low-Cost Substrate

    PubMed Central

    Samsuzzaman, M.; Islam, M. T.; Mandeep, J. S.; Misran, N.

    2014-01-01

    This paper presents a printed wide-slot antenna design and prototyping on available low-cost polymer resin composite material fed by a microstrip line with a rotated square slot for bandwidth enhancement and defected ground structure for gain enhancement. An I-shaped microstrip line is used to excite the square slot. The rotated square slot is embedded in the middle of the ground plane, and its diagonal points are implanted in the middle of the strip line and ground plane. To increase the gain, four L-shaped slots are etched in the ground plane. The measured results show that the proposed structure retains a wide impedance bandwidth of 88.07%, which is 20% better than the reference antenna. The average gain is also increased, which is about 4.17 dBi with a stable radiation pattern in the entire operating band. Moreover, radiation efficiency, input impedance, current distribution, axial ratio, and parametric studies of S11 for different design parameters are also investigated using the finite element method-based simulation software HFSS. PMID:24696661

  15. Printed wide-slot antenna design with bandwidth and gain enhancement on low-cost substrate.

    PubMed

    Samsuzzaman, M; Islam, M T; Mandeep, J S; Misran, N

    2014-01-01

    This paper presents a printed wide-slot antenna design and prototyping on available low-cost polymer resin composite material fed by a microstrip line with a rotated square slot for bandwidth enhancement and defected ground structure for gain enhancement. An I-shaped microstrip line is used to excite the square slot. The rotated square slot is embedded in the middle of the ground plane, and its diagonal points are implanted in the middle of the strip line and ground plane. To increase the gain, four L-shaped slots are etched in the ground plane. The measured results show that the proposed structure retains a wide impedance bandwidth of 88.07%, which is 20% better than the reference antenna. The average gain is also increased, which is about 4.17 dBi with a stable radiation pattern in the entire operating band. Moreover, radiation efficiency, input impedance, current distribution, axial ratio, and parametric studies of S11 for different design parameters are also investigated using the finite element method-based simulation software HFSS. PMID:24696661

  16. Brillouin-Erbium fiber laser with enhanced feedback coupling using common Erbium gain section.

    PubMed

    Samsuri, N M; Zamzuri, A K; Al-Mansoori, M H; Ahmad, A; Mahdi, M A

    2008-10-13

    We demonstrate an enhanced architecture of Brillouin-Erbium fiber laser utilizing the reverse-S-shaped fiber section as the coupling mechanism. The enhancement is made by locating a common section of Erbium-doped fiber next to the single-mode fiber to amplify the Brillouin pumps and the oscillating Stokes lines. The requirement of having two Erbium gain sections to enhance the multiple Brillouin Stokes lines generation is neglected by the proposed fiber laser structure. The mode competitions arise from the self-lasing cavity modes of the fiber laser are efficiently suppressed by the stronger pre-amplified Brillouin pump power before entering the single mode fiber section. The maximum output power of 20 mW is obtained from the proposed fiber laser with 10 laser lines that equally separated by 0.089 nm spacing.

  17. Gaining perspective on the allergenicity assessment of genetically modified food crops.

    PubMed

    Goodman, Richard E; Hefle, Sue L

    2005-11-01

    Genetically modified plants are created by the insertion of foreign genes into plant cells followed by the generation of reproductively stable stock plants for rapid and precise improvements in agricultural crops. Current products provide resistance to insect pests, plant viruses or herbicides. Future products include nutritionally enhanced crops, salt and draught tolerant crops and plant produced industrial enzymes or pharmaceuticals. The risk that a newly expressed protein might cause serious allergic reactions is real, but the probability is relatively small. Regulatory agencies require a premarket evaluation of the genetically modified crop to reduce the potential for increased risks of food allergy. While absolute proof of safety is not possible, the major risk - transfer of a potent major allergen or nearly identical crossreactive protein - is minimized by allergen-specific serum immunoglobulin E tests that evaluate proteins taken from major allergenic sources or proteins with sequences highly similar to any allergen. Other tests are performed to identify proteins that are likely to sensitize consumers. Experience indicates the current assessment process is working effectively. However, further guidance on bioinformatics and immunoglobulin E assays could increase the reliability of the assessment. Further development of alternative assays may be needed to assess the next generation of products.

  18. Coherent amplification and noise in gain-enhanced nanoplasmonic metamaterials: a Maxwell-Bloch Langevin approach.

    PubMed

    Pusch, Andreas; Wuestner, Sebastian; Hamm, Joachim M; Tsakmakidis, Kosmas L; Hess, Ortwin

    2012-03-27

    Nanoplasmonic metamaterials are an exciting new class of engineered media that promise a range of important applications, such as subwavelength focusing, cloaking, and slowing/stopping of light. At optical frequencies, using gain to overcome potentially not insignificant losses has recently emerged as a viable solution to ultra-low-loss operation that may lead to next-generation active metamaterials. Maxwell-Bloch models for active nanoplasmonic metamaterials are able to describe the coherent spatiotemporal and nonlinear gain-plasmon dynamics. Here, we extend the Maxwell-Bloch theory to a Maxwell-Bloch Langevin approach-a spatially resolved model that describes the light field and noise dynamics in gain-enhanced nanoplasmonic structures. Using the example of an optically pumped nanofishnet metamaterial with an embedded laser dye (four-level) medium exhibiting a negative refractive index, we demonstrate the transition from loss-compensation to amplification and to nanolasing. We observe ultrafast relaxation oscillations of the bright negative-index mode with frequencies just below the THz regime. The influence of noise on mode competition and the onset and magnitude of the relaxation oscillations is elucidated, and the dynamics and spectra of the emitted light indicate that coherent amplification and lasing are maintained even in the presence of noise and amplified spontaneous emission.

  19. Enhancing speed of pinning synchronizability: low-degree nodes with high feedback gains.

    PubMed

    Zhou, Ming-Yang; Zhuo, Zhao; Liao, Hao; Fu, Zhong-Qian; Cai, Shi-Min

    2015-01-01

    Controlling complex networks is of paramount importance in science and engineering. Despite recent efforts to improve controllability and synchronous strength, little attention has been paid to the speed of pinning synchronizability (rate of convergence in pinning control) and the corresponding pinning node selection. To address this issue, we propose a hypothesis to restrict the control cost, then build a linear matrix inequality related to the speed of pinning controllability. By solving the inequality, we obtain both the speed of pinning controllability and optimal control strength (feedback gains in pinning control) for all nodes. Interestingly, some low-degree nodes are able to achieve large feedback gains, which suggests that they have high influence on controlling system. In addition, when choosing nodes with high feedback gains as pinning nodes, the controlling speed of real systems is remarkably enhanced compared to that of traditional large-degree and large-betweenness selections. Thus, the proposed approach provides a novel way to investigate the speed of pinning controllability and can evoke other effective heuristic pinning node selections for large-scale systems. PMID:26626045

  20. Enhancing speed of pinning synchronizability: low-degree nodes with high feedback gains

    PubMed Central

    Zhou, Ming-Yang; Zhuo, Zhao; Liao, Hao; Fu, Zhong-Qian; Cai, Shi-Min

    2015-01-01

    Controlling complex networks is of paramount importance in science and engineering. Despite recent efforts to improve controllability and synchronous strength, little attention has been paid to the speed of pinning synchronizability (rate of convergence in pinning control) and the corresponding pinning node selection. To address this issue, we propose a hypothesis to restrict the control cost, then build a linear matrix inequality related to the speed of pinning controllability. By solving the inequality, we obtain both the speed of pinning controllability and optimal control strength (feedback gains in pinning control) for all nodes. Interestingly, some low-degree nodes are able to achieve large feedback gains, which suggests that they have high influence on controlling system. In addition, when choosing nodes with high feedback gains as pinning nodes, the controlling speed of real systems is remarkably enhanced compared to that of traditional large-degree and large-betweenness selections. Thus, the proposed approach provides a novel way to investigate the speed of pinning controllability and can evoke other effective heuristic pinning node selections for large-scale systems. PMID:26626045

  1. The wisdom of caution: genetic enhancement and future children.

    PubMed

    Borenstein, Jason

    2009-12-01

    Many scholars predict that the technology to modify unborn children genetically is on the horizon. According to supporters of genetic enhancement, allowing parents to select a child's traits will enable him/her to experience a better life. Following their logic, the technology will not only increase our knowledge base and generate cures for genetic illness, but it may enable us to increase the intelligence, strength, and longevity of future generations as well. Yet it must be examined whether supporters of genetic enhancement, especially libertarians, adequately appreciate the ethical hazards emerging from the technology, including whether its use might violate the harm principle. PMID:19915956

  2. A Cognitive Tutor for Genetics Problem Solving: Learning Gains and Student Modeling

    ERIC Educational Resources Information Center

    Corbett, Albert; Kauffman, Linda; Maclaren, Ben; Wagner, Angela; Jones, Elizabeth

    2010-01-01

    Genetics is a unifying theme of biology that poses a major challenge for students across a wide range of post-secondary institutions, because it entails complex problem solving. This article reports a new intelligent learning environment called the Genetics Cognitive Tutor, which supports genetics problem solving. The tutor presents complex,…

  3. Speech Enhancement, Gain, and Noise Spectrum Adaptation Using Approximate Bayesian Estimation.

    PubMed

    Hao, Jiucang; Attias, Hagai; Nagarajan, Srikantan; Lee, Te-Won; Sejnowski, Terrence J

    2009-01-01

    This paper presents a new approximate Bayesian estimator for enhancing a noisy speech signal. The speech model is assumed to be a Gaussian mixture model (GMM) in the log-spectral domain. This is in contrast to most current models in frequency domain. Exact signal estimation is a computationally intractable problem. We derive three approximations to enhance the efficiency of signal estimation. The Gaussian approximation transforms the log-spectral domain GMM into the frequency domain using minimal Kullback-Leiber (KL)-divergency criterion. The frequency domain Laplace method computes the maximum a posteriori (MAP) estimator for the spectral amplitude. Correspondingly, the log-spectral domain Laplace method computes the MAP estimator for the log-spectral amplitude. Further, the gain and noise spectrum adaptation are implemented using the expectation-maximization (EM) algorithm within the GMM under Gaussian approximation. The proposed algorithms are evaluated by applying them to enhance the speeches corrupted by the speech-shaped noise (SSN). The experimental results demonstrate that the proposed algorithms offer improved signal-to-noise ratio, lower word recognition error rate, and less spectral distortion. PMID:20428253

  4. Physical mechanisms contributing to enhanced bipolar gain degradation at low dose rates

    SciTech Connect

    Fleetwood, D.M.; Reber, R.A. Jr.; Winokur, P.S. ); Kosier, S.L.; Schrimpf, R.D.; Wei, A. . ECE Dept.); Nowlin, R.N. ); DeLaus, M. ); Combs, W.E. ); Pease, R.L. )

    1994-12-01

    The authors have performed capacitance-voltage (C-V) and thermally-stimulated-current (TSC) measurements on non-radiation-hard MOS capacitors simulating screen oxides of modern bipolar technologies. For 0-V irradiation of [approximately]25 C, the net trapped-positive-charge density (N[sub ox]) inferred from midgap C-V shifts is [approximately]25--40% greater for low-dose-rate (< 10 rad(SiO[sub 2])/s) than for high-dose-rate (> 100 rad(SiO[sub 2])/s) exposure. Device modeling shows that such a difference in screen-oxide N[sub ox] is enough to account for the enhanced low-rate gain degradation often observed in bipolar devices, due to the [approximately] exp(N[sub ox][sup 2]) dependence of the excess base current. At the higher rates, TSC measurements reveal a [approximately]10% decrease in trapped-hole density over low rates. Also, at high rates, up to [approximately]2.5-times as many trapped holes are compensated by electrons in border traps than at low rates for these devices and irradiation conditions. Both the reduction in trapped-hole density and increased charge compensation reduce the high-rate midgap shift. A physical model is developed which suggests that both effects are caused by time-dependent space charge in the bulk of these soft oxides associated with slowly transporting and/or metastably trapped holes (e.g., in E[delta][prime] centers). On the basis of this model, bipolar transistors and screen-oxide capacitors were irradiated at 60 C at 200 rad(SiO[sub 2])/s in a successful effort to match low-rate damage. these surprising results provide insight into enhanced low-rate bipolar gain degradation and suggest potentially promising new approaches to bipolar and BiCMOS hardness assurance for space applications.

  5. Genetic Engineering Strategies for Enhanced Biodiesel Production.

    PubMed

    Hegde, Krishnamoorthy; Chandra, Niharika; Sarma, Saurabh Jyoti; Brar, Satinder Kaur; Veeranki, Venkata Dasu

    2015-07-01

    The focus on biodiesel research has shown a tremendous growth over the last few years. Several microbial and plant sources are being explored for the sustainable biodiesel production to replace the petroleum diesel. Conventional methods of biodiesel production have several limitations related to yield and quality, which led to development of new engineering strategies to improve the biodiesel production in plants, and microorganisms. Substantial progress in utilizing algae, yeast, and Escherichia coli for the renewable production of biodiesel feedstock via genetic engineering of fatty acid metabolic pathways has been reported in the past few years. However, in most of the cases, the successful commercialization of such engineering strategies for sustainable biodiesel production is yet to be seen. This paper systematically presents the drawbacks in the conventional methods for biodiesel production and an exhaustive review on the present status of research in genetic engineering strategies for production of biodiesel in plants, and microorganisms. Further, we summarize the technical challenges need to be tackled to make genetic engineering technology economically sustainable. Finally, the need and prospects of genetic engineering technology for the sustainable biodiesel production and the recommendations for the future research are discussed.

  6. GENETIC ENGINEERING OF ENHANCED MICROBIAL NITRIFICATION

    EPA Science Inventory

    Experiments were conducted to introduce genetic information in the form of antibiotic or mercuric ion resistance genes into Nitrobacter hamburgensis strain X14. The resistance genes were either stable components of broad host range plasmids or transposable genes on methods for p...

  7. Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind

    PubMed Central

    Quartier, Pierre

    2015-01-01

    All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any other type of PID. AD PIDs now account for 61 of the 260 known conditions (23%). All known AR PIDs are caused by alleles with some loss-of-function (LOF). A single XR PID is caused by gain-of-function (GOF) mutations (WASP-related neutropenia, 2001). In contrast, only 44 of 61 AD defects are caused by LOF alleles, which exert dominance by haploinsufficiency or negative dominance. Since 2003, up to 17 AD disorders of the third kind, due to GOF alleles, have been described. Remarkably, six of the 17 genes concerned also harbor monoallelic (STAT3), biallelic (C3, CFB, CARD11, PIK3R1) or both monoallelic and biallelic (STAT1) LOF alleles in patients with other clinical phenotypes. Most heterozygous GOF alleles result in auto-inflammation, auto-immunity, or both, with a wide range of immunological and clinical forms. Some also underlie infections and, fewer, allergies, by impairing or enhancing immunity to non-self. Malignancies are also rare. The enormous diversity of immunological and clinical phenotypes is thought provoking and mirrors the diversity and pleiotropy of the underlying genotypes. These experiments of nature provide a unique insight into the quantitative regulation of human immunity. PMID:25645939

  8. Immunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind.

    PubMed

    Boisson, Bertrand; Quartier, Pierre; Casanova, Jean-Laurent

    2015-02-01

    All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any other type of PID. AD PIDs now account for 61 of the 260 known conditions (23%). All known AR PIDs are caused by alleles with some loss-of-function (LOF). A single XR PID is caused by gain-of-function (GOF) mutations (WASP-related neutropenia, 2001). In contrast, only 44 of 61 AD defects are caused by LOF alleles, which exert dominance by haploinsufficiency or negative dominance. Since 2003, up to 17 AD disorders of the third kind, due to GOF alleles, have been described. Remarkably, six of the 17 genes concerned also harbor monoallelic (STAT3), biallelic (C3, CFB, CARD11, PIK3R1) or both monoallelic and biallelic (STAT1) LOF alleles in patients with other clinical phenotypes. Most heterozygous GOF alleles result in auto-inflammation, auto-immunity, or both, with a wide range of immunological and clinical forms. Some also underlie infections and, fewer, allergies, by impairing or enhancing immunity to non-self. Malignancies are also rare. The enormous diversity of immunological and clinical phenotypes is thought provoking and mirrors the diversity and pleiotropy of the underlying genotypes. These experiments of nature provide a unique insight into the quantitative regulation of human immunity. PMID:25645939

  9. Undergraduates Achieve Learning Gains in Plant Genetics through Peer Teaching of Secondary Students

    ERIC Educational Resources Information Center

    Chrispeels, H. E.; Klosterman, M. L.; Martin, J. B.; Lundy, S. R.; Watkins, J. M.; Gibson, C. L.; Muday, G. K.

    2014-01-01

    This study tests the hypothesis that undergraduates who peer teach genetics will have greater understanding of genetic and molecular biology concepts as a result of their teaching experiences. Undergraduates enrolled in a non-majors biology course participated in a service-learning program in which they led middle school (MS) or high school (HS)…

  10. Controlling inbreeding and maximizing genetic gain using semi-definite programming with pedigree-based and genomic relationships.

    PubMed

    Schierenbeck, S; Pimentel, E C G; Tietze, M; Körte, J; Reents, R; Reinhardt, F; Simianer, H; König, S

    2011-12-01

    Because of the relatively high levels of genetic relationships among potential bull sires and bull dams, innovative selection tools should consider both genetic gain and genetic relationships in a long-term perspective. Optimum genetic contribution theory using official estimated breeding values for a moderately heritable trait (production index, Index-PROD), and a lowly heritable functional trait (index for somatic cell score, Index-SCS) was applied to find optimal allocations of bull dams and bull sires. In contrast to previous practical applications using optimizations based on Lagrange multipliers, we focused on semi-definite programming (SDP). The SDP methodology was combined with either pedigree (a(ij)) or genomic relationships (f(ij)) among selection candidates. Selection candidates were 484 genotyped bulls, and 499 preselected genotyped bull dams completing a central test on station. In different scenarios separately for PROD and SCS, constraints on the average pedigree relationships among future progeny were varied from a(ij)=0.08 to a(ij)=0.20 in increments of 0.01. Corresponding constraints for single nucleotide polymorphism-based kinship coefficients were derived from regression analysis. Applying the coefficient of 0.52 with an intercept of 0.14 estimated for the regression pedigree relationship on genomic relationship, the corresponding range to alter genomic relationships varied from f(ij) = 0.18 to f(ij) = 0.24. Despite differences for some bulls in genomic and pedigree relationships, the same trends were observed for constraints on pedigree and corresponding genomic relationships regarding results in genetic gain and achieved coefficients of relationships. Generally, allowing higher values for relationships resulted in an increase of genetic gain for Index-PROD and Index-SCS and in a reduction in the number of selected sires. Interestingly, more sires were selected for all scenarios when restricting genomic relationships compared with restricting

  11. The silencing of Kierkegaard in Habermas' critique of genetic enhancement.

    PubMed

    Christiansen, Karin

    2009-06-01

    The main purpose of this paper is to draw attention to an important part of Habermas' critique of genetic enhancement, which has been largely ignored in the discussion; namely his use of Kierkegaard's reflections on the existential conditions for becoming one-self from Either/or and the Sickness unto Death. It will be argued that, although Habermas presents some valuable and highly significant perspectives on the effect of genetic enhancement on the individual's self-understanding and ability to experience him- or herself as a free and equal individual, he does not succeed in working out a consistent argument. The claim is that he fails to explain how the existential analysis is related to his reflections on the sociological and psychological impacts of genetic enhancement in the realm of communicative action. It is this lack of theoretical clarity, which seems to render Habermas vulnerable to some of the critique which has been raised against his theory from a number of different scientific disciplines and areas of research. Hence, the first part of the paper provides some examples of the nature and variety of this critique, the second part presents Habermas' own critique of genetic enhancement in the context of a dispute between so-called 'liberal' and 'conservative' arguments, and finally, the third part discusses the limits and possibilities of his position in a future debate about genetic enhancement.

  12. Genetic Diversity of Tick-Borne Rickettsial Pathogens; Insights Gained from Distant Strains.

    PubMed

    Pierlé, Sebastián Aguilar; Rosshandler, Ivan Imaz; Kerudin, Ammielle Akim; Sambono, Jacqueline; Lew-Tabor, Ala; Rolls, Peter; Rangel-Escareño, Claudia; Brayton, Kelly A

    2014-01-14

    The ability to capture genetic variation with unprecedented resolution improves our understanding of bacterial populations and their ability to cause disease. The goal of the pathogenomics era is to define genetic diversity that results in disease. Despite the economic losses caused by vector-borne bacteria in the Order Rickettsiales, little is known about the genetic variants responsible for observed phenotypes. The tick-transmitted rickettsial pathogen Anaplasma marginale infects cattle in tropical and subtropical regions worldwide, including Australia. Genomic analysis of North American A. marginale strains reveals a closed core genome defined by high levels of Single Nucleotide Polymorphisms (SNPs). Here we report the first genome sequences and comparative analysis for Australian strains that differ in virulence and transmissibility. A list of genetic differences that segregate with phenotype was evaluated for the ability to distinguish the attenuated strain from virulent field strains. Phylogenetic analyses of the Australian strains revealed a marked evolutionary distance from all previously sequenced strains. SNP analysis showed a strikingly reduced genetic diversity between these strains, with the smallest number of SNPs detected between any two A. marginale strains. The low diversity between these phenotypically distinct bacteria presents a unique opportunity to identify the genetic determinants of virulence and transmission. PMID:25364572

  13. The contribution of migrant breeds to the genetic gain of beef traits of German Vorderwald and Hinterwald cattle.

    PubMed

    Hartwig, S; Wellmann, R; Hamann, H; Bennewitz, J

    2014-12-01

    During the past decades, migrant contributions have accumulated in many local breeds. Cross-breeding was carried out to mitigate the risk of inbreeding depression and to improve the performance of local breeds. However, breeding activities for local breeds were not as intensive and target oriented as for popular high-yielding breeds. Therefore, even if performance improved, the gap between the performance of local and popular breeds increased for many traits. Furthermore, the genetic originality of local breeds declined due to the increasing contributions of migrant breeds. This study examined the importance of migrant breed influences for the realization of breeding progress of beef traits of German Vorderwald and Hinterwald cattle. The results show that there is a high amount of migrant contributions and their effects on performance are substantial for most traits. The effect of the French cattle breed Montbéliard (p-value 0.014) on daily gain of Vorderwald bulls at test station was positive. The effects of Vorderwald ancestors (p-value for daily gain 0.007 and p-value for net gain 0.004) were positive for both traits under consideration in the population of Hinterwald cattle. Additionally, the effect of remaining breeds (p-value 0.030) on net gain of Hinterwald cattle in the field was also positive. The estimated effect of Fleckvieh ancestors on net gain of Hinterwald cattle was even larger but not significant. Breeding values adjusted for the effects of the migrant breeds showed little genetic trend. PMID:24965852

  14. A gain and bandwidth enhanced transimpedance preamplifier for Fourier-transform ion cyclotron resonance mass spectrometry

    PubMed Central

    Lin, Tzu-Yung; Green, Roger J.; O'Connor, Peter B.

    2011-01-01

    The nature of the ion signal from a 12-T Fourier-transform ion cyclotron resonance mass spectrometer and the electronic noise were studied to further understand the electronic detection limit. At minimal cost, a new transimpedance preamplifier was designed, computer simulated, built, and tested. The preamplifier design pushes the electronic signal-to-noise performance at room temperature to the limit, because of its enhanced tolerance of the capacitance of the detection device, lower intrinsic noise, and larger flat mid-band gain (input current noise spectral density of around 1 pA/\\documentclass[12pt]{minimal}\\begin{document}$\\sqrt{\\mbox{Hz}}$\\end{document}Hz when the transimpedance is about 85 dBΩ). The designed preamplifier has a bandwidth of ∼3 kHz to 10 MHz, which corresponds to the mass-to-charge ratio, m/z, of approximately 18 to 61 k at 12 T. The transimpedance and the bandwidth can be easily adjusted by changing the value of passive components. The feedback limitation of the circuit is discussed. With the maximum possible transimpedance of 5.3 MΩ when using an 0402 surface mount resistor, the preamplifier was estimated to be able to detect ∼110 charges in a single scan. PMID:22225232

  15. Colestilan decreases weight gain by enhanced NEFA incorporation in biliary lipids and fecal lipid excretion.

    PubMed

    Sugimoto-Kawabata, Kanami; Shimada, Hiroshi; Sakai, Kaoru; Suzuki, Kazuo; Kelder, Thomas; Pieterman, Elsbet J; Cohen, Louis H; Havekes, Louis M; Princen, Hans M; van den Hoek, Anita M

    2013-05-01

    Bile acid sequestrants (BASs) are cholesterol-lowering drugs that also affect hyperglycemia. The mechanism by which BASs exert these and other metabolic effects beyond cholesterol lowering remains poorly understood. The present study aimed to investigate the effects of a BAS, colestilan, on body weight, energy expenditure, and glucose and lipid metabolism and its mechanisms of action in high-fat-fed hyperlipidemic APOE*3 Leiden (E3L) transgenic mice. Mildly insulin-resistant E3L mice were fed a high-fat diet with or without 1.5% colestilan for 8 weeks. Colestilan treatment decreased body weight, visceral and subcutaneous fat, and plasma cholesterol and triglyceride levels but increased food intake. Blood glucose and plasma insulin levels were decreased, and hyperinsulinemic-euglycemic clamp analysis demonstrated improved insulin sensitivity, particularly in peripheral tissues. In addition, colestilan decreased energy expenditure and physical activity, whereas it increased the respiratory exchange ratio, indicating that colestilan induced carbohydrate catabolism. Moreover, kinetic analysis revealed that colestilan increased [(3)H]NEFA incorporation in biliary cholesterol and phospholipids and increased fecal lipid excretion. Gene expression analysis in liver, fat, and muscle supported the above findings. In summary, colestilan decreases weight gain and improves peripheral insulin sensitivity in high-fat-fed E3L mice by enhanced NEFA incorporation in biliary lipids and increased fecal lipid excretion.

  16. A gain and bandwidth enhanced transimpedance preamplifier for Fourier-transform ion cyclotron resonance mass spectrometry

    SciTech Connect

    Lin, Tzu-Yung; Green, Roger J.; O'Connor, Peter B.

    2011-12-15

    The nature of the ion signal from a 12-T Fourier-transform ion cyclotron resonance mass spectrometer and the electronic noise were studied to further understand the electronic detection limit. At minimal cost, a new transimpedance preamplifier was designed, computer simulated, built, and tested. The preamplifier design pushes the electronic signal-to-noise performance at room temperature to the limit, because of its enhanced tolerance of the capacitance of the detection device, lower intrinsic noise, and larger flat mid-band gain (input current noise spectral density of around 1 pA/{radical}(Hz) when the transimpedance is about 85 dB{Omega}). The designed preamplifier has a bandwidth of {approx}3 kHz to 10 MHz, which corresponds to the mass-to-charge ratio, m/z, of approximately 18 to 61 k at 12 T. The transimpedance and the bandwidth can be easily adjusted by changing the value of passive components. The feedback limitation of the circuit is discussed. With the maximum possible transimpedance of 5.3 M{Omega} when using an 0402 surface mount resistor, the preamplifier was estimated to be able to detect {approx}110 charges in a single scan.

  17. Genetic enhancement of Brassica napus seed quality.

    PubMed

    Hannoufa, Abdelali; Pillai, Bhinu V S; Chellamma, Sreekala

    2014-02-01

    The ultimate value of the Brassica napus (canola) seed is derived from the oil fraction, which has long been recognized for its premium dietary attributes, including its low level of saturated fatty acids, high content of monounsaturated fatty acids, and favorable omega-3 fatty acid profile. However, the protein (meal) portion of the seed has also received favorable attention for its essential amino acids, including abundance of sulfur-containing amino acids, such that B. napus protein is being contemplated for large scale use in livestock and fish feed formulations. Efforts to optimize the composition of B. napus oil and protein fractions are well documented; therefore, this article will review research concerned with optimizing secondary metabolites that affect the quality of seed oil and meal, from undesirable anti-nutritional factors to highl value beneficial products. The biological, agronomic, and economic values attributed to secondary metabolites have brought much needed attention to those in Brassica oilseeds and other crops. This review focuses on increasing levels of beneficial endogenous secondary metabolites (such as carotenoids, choline and tochopherols) and decreasing undesirable antinutritional factors (glucosinolates, sinapine and phytate). Molecular genetic approaches are given emphasis relative to classical breeding.

  18. Gain enhancement in a V-shaped plasmonic slot waveguide for efficient loss compensation at the subwavelength scale

    NASA Astrophysics Data System (ADS)

    Bian, Yusheng; Zheng, Zheng; Zhao, Xin; Yang, Pengfei; Liu, Lei; Zhu, Jinsong; Zhou, Tao

    2013-05-01

    An active plasmonic slot waveguide comprising an inverted triangular metal wedge incorporated inside a V-shaped plasmonic groove with a low-index gain medium embedded between them is presented, and its guiding properties are investigated numerically at the wavelength of 1550 nm. The presented waveguide is shown to be capable of supporting two fundamental plasmonic slot modes with high field localization to the V-shaped low-index slot region. Due to such strong optical confinement and significant field enhancement, the introduced gain in the slot could effectively compensate the propagation loss of the supported plasmonic modes. It is revealed that for the studied channel plasmonic slot and wedge plasmonic slot modes, notable gain enhancements are observable within a wide range of geometric parameters. For the considered structure with a 10-40 nm-wide slot, the enhancements of gain can be as large as 11%-159% for the CPS mode while 43%-174% for the WPS mode. These values could be further improved by adopting even narrower slots. It is shown that, by introducing a gain medium with coefficients around hundreds of cm-1, the modal loss can be largely or even fully compensated, with a subwavelength mode area achievable simultaneously. These unique features of the studied V-shaped plasmonic slot waveguide might be useful for its potential applications in compact, active plasmonic components.

  19. Crop genetic improvement for enhanced human nutrition.

    PubMed

    Toenniessen, Gary H

    2002-09-01

    In the past decade, micronutrient malnutrition has been identified as a major underlying cause of numerous human health problems in developing countries. The international agricultural research system has been highly successful in producing crop varieties with traits desired by farmers, such as higher yield and greater tolerance of poor growing conditions. These improved varieties have spread widely throughout developing countries and now provide the staple foods eaten daily by billions of people, including the poor in many difficult to reach rural areas. Modern plant breeding and biotechnology offer new opportunities to use this same international system to increase the micronutrient content and enhance the nutritional value of these staple foods. Over time, this could be an important complement to the progress that is being made in providing micronutrient supplements and fortified foods and in encouraging people to eat more diversified diets. Nutritionists and agriculturists will need to work together to define the deficiencies, target the right populations and deliver the right products. PMID:12221274

  20. Insights into the biology of Borrelia burgdorferi gained through the application of molecular genetics.

    PubMed

    Groshong, Ashley M; Blevins, Jon S

    2014-01-01

    Borrelia burgdorferi, the vector-borne bacterium that causes Lyme disease, was first identified in 1982. It is known that much of the pathology associated with Lyme borreliosis is due to the spirochete's ability to infect, colonize, disseminate, and survive within the vertebrate host. Early studies aimed at defining the biological contributions of individual genes during infection and transmission were hindered by the lack of adequate tools and techniques for molecular genetic analysis of the spirochete. The development of genetic manipulation techniques, paired with elucidation and annotation of the B. burgdorferi genome sequence, has led to major advancements in our understanding of the virulence factors and the molecular events associated with Lyme disease. Since the dawn of this genetic era of Lyme research, genes required for vector or host adaptation have garnered significant attention and highlighted the central role that these components play in the enzootic cycle of this pathogen. This chapter covers the progress made in the Borrelia field since the application of mutagenesis techniques and how they have allowed researchers to begin ascribing roles to individual genes. Understanding the complex process of adaptation and survival as the spirochete cycles between the tick vector and vertebrate host will lead to the development of more effective diagnostic tools as well as identification of novel therapeutic and vaccine targets. In this chapter, the Borrelia genes are presented in the context of their general biological roles in global gene regulation, motility, cell processes, immune evasion, and colonization/dissemination.

  1. Gain enhancement plasma-loaded FEL in the presence of beat waves

    SciTech Connect

    Shamamian, A.H.; Gevorgian, L.A.

    1995-12-31

    An expression for the dielectric permittivity of underdense plasma interacting with laser beat waves is derived. It is shown that the presence of beat waves in plasma results in an effective growth of the plasma frequency. The FEL Gain is investigated in the case when the frequency of soft photons weakly depending on the electron beam energy and the synchronism condition is maintained. It is shown that the plasma beat waves lead to the essential increase in FEL gain.

  2. Enhanced energy transport in genetically engineered excitonic networks

    NASA Astrophysics Data System (ADS)

    Park, Heechul; Heldman, Nimrod; Rebentrost, Patrick; Abbondanza, Luigi; Iagatti, Alessandro; Alessi, Andrea; Patrizi, Barbara; Salvalaggio, Mario; Bussotti, Laura; Mohseni, Masoud; Caruso, Filippo; Johnsen, Hannah C.; Fusco, Roberto; Foggi, Paolo; Scudo, Petra F.; Lloyd, Seth; Belcher, Angela M.

    2016-02-01

    One of the challenges for achieving efficient exciton transport in solar energy conversion systems is precise structural control of the light-harvesting building blocks. Here, we create a tunable material consisting of a connected chromophore network on an ordered biological virus template. Using genetic engineering, we establish a link between the inter-chromophoric distances and emerging transport properties. The combination of spectroscopy measurements and dynamic modelling enables us to elucidate quantum coherent and classical incoherent energy transport at room temperature. Through genetic modifications, we obtain a significant enhancement of exciton diffusion length of about 68% in an intermediate quantum-classical regime.

  3. Governmentality, biopower, and the debate over genetic enhancement.

    PubMed

    McWhorter, Ladelle

    2009-08-01

    Although Foucault adamantly refused to make moral pronouncements or dictate moral principles or political programs to his readers, his work offers a number of tools and concepts that can help us develop our own ethical views and practices. One of these tools is genealogical analysis, and one of these concepts is "biopower." Specifically, this essay seeks to demonstrate that Foucault's concept of biopower and his genealogical method are valuable as we consider moral questions raised by genetic enhancement technologies. First, it examines contemporary debate over the development, marketing, and application of such technologies, suggesting that what passes for ethical deliberation is often little more than political maneuvering in a field where stakes are very high and public perceptions will play a crucial role in decisions about which technologies will be funded or disallowed. It goes on to argue that genuine ethical deliberation on these issues requires some serious investigation of their historical context. Accordingly, then, it takes up the oft-heard charge from critics that genetic enhancement technologies are continuous with twentieth-century eugenic projects or will usher in a new age of eugenics. Foucault explicitly links twentieth-century eugenics with the rise of biopower. Through review of some aspects of the twentieth-century eugenics movement alongside some of the rhetoric and claims of enhancement's modern-day proponents, the essay shows ways in which deployment of genetic enhancement technologies is and is not continuous with earlier deployments of biopower.

  4. Increased postweaning gain of beef heifers enhances fertility and milk production.

    PubMed

    Buskirk, D D; Faulkner, D B; Ireland, F A

    1995-04-01

    Four hundred fifty-two (452) weanling heifer calves (192 +/- 23 kg) were used to determine the effect of postweaning weight gain on subsequent reproductive performance and lactation. Heifers grazed stockpiled tall fescue pastures and were fed a high (H) or low (L) amount of ground corn supplement (3.68 and 2.99 kg/[animal.d], respectively) during a postweaning treatment period of 136 d. Postweaning gain of heifers receiving L and H was .43 and .62 kg/d, respectively. These treatments resulted in a range of postweaning gain from .07 to 1.17 kg/d. Heifers receiving H were 26 kg heavier (P < .01), had .15 cm more fat thickness (P < .01), 5% greater pelvic area (P < .01), and tended (P = .08) to have greater hip height than heifers receiving L at yearling. More heifers in the H group were pubertal before the start of the breeding season (70.9 vs 61.3%) (P < .05). No significant differences were found in pregnancy rate or first-service calving rate between treatment groups. Mean milk production was 10% greater for H- than for L-fed heifers (P < .01) and resulted in heavier calves at 54, 104, and 153 d of age (P < .05). Regression analysis revealed that as weaning weight and postweaning gain increased, so did the probability for reaching puberty before the breeding season. Increasing weaning weight also increased the probability of calving to the first AI service. As heifer weaning weight and postweaning gain increased, subsequent milk production also increased. Increasing postweaning weight gain of lightweight heifers from .07 to 1.17 kg/d increased both reproductive and lactation performance. PMID:7628970

  5. Experiences gained from implementing mandatory buffer strips in Denmark: how can we enhance their ecosystem services?

    NASA Astrophysics Data System (ADS)

    Kronvang, Brian; Hoffmann, Carl Christian; Baattrup-Pedersen, Annette; Hille, Sandra; Rubæk, Gitte; Heckrath, Goswin; Gertz, Flemming; Jensen, Henning; Feuerback, Peter; Strand, John; Stutter, Marc

    2015-04-01

    along watercourses from ca. 50,000 ha to ca. 25,000 ha and at the same time they reduced the width of the mandatory BSs from 10 m to 9 m. The aim of this presentation is to share the experience gained in Denmark on establishing mandatory BSs. Furthermore, we will show some preliminary results from two newly initiated research projects (BUFFERTECH and BALTICSEA2020) that studies how to enhance the ecosystem services provided by buffer strips. We will show how intelligently to guide managers when establishing BSs along watercourses at catchment scale utilizing a combined P-index model for soil erosion and a statistical model for P retention in BSs as well as results obtained from new 'Engineered' or 'Constructed' BSs that delays tile drainage flow from field to streams thereby increasing nutrient retention. Acknowledgement The work is supported by the Strategic Research Foundation/Innovation Fund Denmark project 'BUFFERTECH - Optimization of Ecosystem Services Provided by Buffer Strips Using Novel Technological Methods' (Grant No. 1305-00017B) and the BalticSea2020 project 'Integrerade skyddszoner (IBZ)'.

  6. Double-maximum enhancement of signal-to-noise ratio gain via stochastic resonance and vibrational resonance.

    PubMed

    Duan, Fabing; Chapeau-Blondeau, François; Abbott, Derek

    2014-08-01

    This paper studies the signal-to-noise ratio (SNR) gain of a parallel array of nonlinear elements that transmits a common input composed of a periodic signal and external noise. Aiming to further enhance the SNR gain, each element is injected with internal noise components or high-frequency sinusoidal vibrations. We report that the SNR gain exhibits two maxima at different values of the internal noise level or of the sinusoidal vibration amplitude. For the addition of internal noise to an array of threshold-based elements, the condition for occurrence of stochastic resonance is analytically investigated in the limit of weak signals. Interestingly, when the internal noise components are replaced by high-frequency sinusoidal vibrations, the SNR gain displays the vibrational multiresonance phenomenon. In both considered cases, there are certain regions of the internal noise intensity or the sinusoidal vibration amplitude wherein the achieved maximal SNR gain can be considerably beyond unity for a weak signal buried in non-Gaussian external noise. Due to the easy implementation of sinusoidal vibration modulation, this approach is potentially useful for improving the output SNR in an array of nonlinear devices. PMID:25215715

  7. Gain enhanced L-band optical fiber amplifiers and tunable fiber lasers with erbium-doped fibers

    NASA Astrophysics Data System (ADS)

    Chen, H.; Leblanc, M.; Schinn, G. W.

    2003-02-01

    We report on the experimental investigation of gain enhanced L-band erbium-doped fiber amplifiers (EDFA) by either recycling residual ASE or using a second C-band wavelength pump laser and on the experimental demonstration of L-band tunable erbium-doped fiber ring lasers. We observed that by reflecting ASE from pumped erbium-doped fiber (EDF) the L-band EDFA gain can be enhanced of 2-15 dB depending on amplifier designs. We also studied wavelength and power dependence of second pump laser on the gain enhanced L-band EDFA and found that an optimum wavelength for second pump laser was between 1550 and 1560 nm. Finally, a L-band tunable erbium-doped fiber laser was also constructed in which lazing oscillation was observed closed to 1624 nm by recycling residual ASE. This L-band tunable laser has a line-width of about 300 MHz, an output power of 1 mW, and a signal to source spontaneous emission ratio of 60 dB.

  8. Can enhancement be distinguished from prevention in genetic medicine?

    PubMed

    Juengst, E T

    1997-04-01

    In discussions of the ethics of human gene therapy, it has become standard to draw a distinction between the use of human gene transfer techniques to treat health problems and their use to enhance or improve normal human traits. Some dispute the normative force of this distinction by arguing that it is undercut by the legitimate medical use of human gene transfer techniques to prevent disease-such as genetic engineering to bolster immune function, improve the efficiency of DNA repair, or add cellular receptors to capture and process cholesterol. If disease prevention is a proper goal of medicine, these critics argue, and the use of gene transfer techniques to enhance human health maintenance capacities will help achieve that goal, then the "treatment/enhancement" distinction cannot define the limits of legitimate gene therapy. In this paper, I argue that a line can be drawn between prevention and enhancement for gene therapy (and thus between properly medical and nonmedical uses of gene therapy), but only if one is willing to accept two rather old-fashioned claims: 1) Some health problems are best understood as if they were entities in their own right, reifiable as processes or parts in a biological system, with at least as much ontological objectivity and theoretical significance as the functions that they inhibit. 2) Legitimate preventive genetic health care should be limited to efforts to defend people from attack by these more robust pathological entities, rather than changing their bodies to evade social injustices. PMID:9186925

  9. Ejector Enhanced Pulsejet Based Pressure Gain Combustors: An Old Idea With a New Twist

    NASA Technical Reports Server (NTRS)

    Paxson, Daniel E.; Dougherty, Kevin T.

    2005-01-01

    An experimental investigation of pressure-gain combustion for gas turbine application is described. The test article consists of an off-the-shelf valved pulsejet, and an optimized ejector, both housed within a shroud. The combination forms an effective can combustor across which there is a modest total pressure rise rather than the usual loss found in conventional combustors. Although the concept of using a pulsejet to affect semi-constant volume (i.e., pressure-gain) combustion is not new, that of combining it with a well designed ejector to efficiently mix the bypass flow is. The result is a device which to date has demonstrated an overall pressure rise of approximately 3.5 percent at an overall temperature ratio commensurate with modern gas turbines. This pressure ratio is substantially higher than what has been previously reported in pulsejet-based combustion experiments. Flow non-uniformities in the downstream portion of the device are also shown to be substantially reduced compared to those within the pulsejet itself. The standard deviation of total pressure fluctuations, measured just downstream of the ejector was only 5.0 percent of the mean. This smoothing aspect of the device is critical to turbomachinery applications since turbine performance is, in general, negatively affected by flow non-uniformities and unsteadiness. The experimental rig will be described and details of the performance measurements will be presented. Analyses showing the thermodynamic benefits from this level of pressure-gain performance in a gas turbine will also be assessed for several engine types. Issues regarding practical development of such a device are discussed, as are potential emissions reductions resulting from the rich burning nature of the pulsejet and the rapid mixing (quenching) associated with unsteady ejectors.

  10. Genetically enhanced cows resist intramammary Staphylococcus aureus infection.

    PubMed

    Wall, Robert J; Powell, Anne M; Paape, Max J; Kerr, David E; Bannerman, Douglas D; Pursel, Vernon G; Wells, Kevin D; Talbot, Neil; Hawk, Harold W

    2005-04-01

    Mastitis, the most consequential disease in dairy cattle, costs the US dairy industry billions of dollars annually. To test the feasibility of protecting animals through genetic engineering, transgenic cows secreting lysostaphin at concentrations ranging from 0.9 to 14 micrograms/ml [corrected] in their milk were produced. In vitro assays demonstrated the milk's ability to kill Staphylococcus aureus. Intramammary infusions of S. aureus were administered to three transgenic and ten nontransgenic cows. Increases in milk somatic cells, elevated body temperatures and induced acute phase proteins, each indicative of infection, were observed in all of the nontransgenic cows but in none of the transgenic animals. Protection against S. aureus mastitis appears to be achievable with as little as 3 micrograms/ml [corrected] of lysostaphin in milk. Our results indicate that genetic engineering can provide a viable tool for enhancing resistance to disease and improve the well-being of livestock.

  11. Enhancing the performance of a high-gain free electron laser operating at millimeter wavelengths

    SciTech Connect

    Barletta, W.A.; Anderson, B.; Fawley, W.M.; Neil, V.K.; Orzechowski, T.J.; Prosnitz, D.; Scharlemann, E.T.; Yarema, S.M.; Paul, A.C.; Hopkins, D.

    1984-10-25

    A high-gain, high extraction efficiency, free electron laser (FEL) amplifier operating at the Experimental Test Accelerator (ETA) at 34.6 GHz has demonstrated a small signal gain of 13.4 dB/m. With a 30 kW input signal, the amplifier has produced a saturated output of 80 MW and a 5% extraction efficiency. Comparison of these results with a linear model at small signal levels indicates that the amplifier can deliver saturated output starting from noise, if the brightness of the electron beam is sufficiently high. The brightness of the ETA is far below that possible with optimized choice of practical design characteristics such as peak voltage, cathode type, gun electrode geometry, and focusing field topology. In particular, the measured brightness of the ETA injector is limited by plasma effects from the present cold, plasma cathode. As part of a coordinated theoretical and experimental effort to improve injector performance, we are using the EBQ gun design code to explore the current limits of gridless, relativistic, Pierce columns with moderate current density (>50 A/cm/sup 2/) at the cathode. The chief component in our experimental effort is a readily modified electron gun that will allow us to test many candidate cathode materials, types, and electrode geometries at field stresses up to 1 MV/cm. 8 references, 5 figures.

  12. Genetic and phenotypic relationships of serum leptin concentration with performance, efficiency of gain, and carcass merit of feedlot cattle.

    PubMed

    Nkrumah, J D; Keisler, D H; Crews, D H; Basarab, J A; Wang, Z; Li, C; Price, M A; Okine, E K; Moore, S S

    2007-09-01

    Leptin is the hormone product of the obese gene that is synthesized and predominantly expressed by adipocytes. This study estimated the genetic variation in serum leptin concentration and evaluated the genetic and phenotypic relationships of serum leptin concentration with performance, efficiency of gain, and carcass merit. There were 464 steers with records for serum leptin concentration, performance, and efficiency of gain and 381 steers with records for carcass traits. The analyses included a total of 813 steers, including those without phenotypic records. Phenotypic and genetic parameter estimates were obtained using SAS and ASREML, respectively. Serum leptin concentration was moderately heritable (h2 = 0.34 +/- 0.13) and averaged 13.91 (SD = 5.74) ng/mL. Sire breed differences in serum leptin concentration correlated well with breed differences in body composition. Specifically, the serum leptin concentration was 20% greater in Angus-sired steers compared with Charolais-sired steers (P < 0.001). Consequently, ultrasound backfat (27%), carcass 12th-rib fat (31%), ultrasound marbling (14%), and carcass marbling (15%) were less in Charolais- than Angus-sired steers (P < 0.001). Conversely, carcass LM area (P = 0.05) and carcass lean meat yield (P < 0.001) were greater in Charolais- compared with Angus-sired steers. Steers with greater serum leptin concentration also had greater DMI (P < 0.001), greater residual feed intake (P = 0.04), and partial efficiency of growth (P = 0.01), but did not differ in feed conversion ratio (P > 0.10). Serum leptin concentration was correlated phenotypically with ultrasound backfat (r = 0.41; P < 0.001), carcass 12th-rib fat (r = 0.42; P < 0.001), ultrasound marbling (r = 0.25; P < 0.01), carcass marbling (r = 0.28; P < 0.01), ultrasound LM area (r = -0.19; P < 0.01), carcass LM area (r = -0.17; P < 0.05), lean meat yield (r = -0.38; P < 0.001), and yield grade (r = 0.32; P < 0.001). The corresponding genetic correlations were

  13. What Do the Participants Gain? Group Counselling to Enhance Agency at Work

    ERIC Educational Resources Information Center

    Vanhalakka-Ruoho, Marjatta; Ruponen, Ritva

    2013-01-01

    Group counselling was carried out in an IT enterprise. The task was to study structured group counselling as a space for enhancing participants' agency at work. The first research question concerned changes the participants reported regarding the group and their collaborative and individual work. The second research question asked what kinds…

  14. Enhancing Integrative Experiences: Evidence of Student Perceptions of Learning Gains from Cross-Course Interactions

    ERIC Educational Resources Information Center

    Wingert, Jason R.; Wasileski, Sally A.; Peterson, Karin; Mathews, Leah Greden; Lanou, Amy Joy; Clarke, David

    2011-01-01

    This article offers food for thought on a strategy used by seven faculty to enhance students' integrative learning by offering cross-course, cross-disciplinary projects and shared activities focused on food. The faculty teach a cluster of ten courses in natural sciences, health sciences, social sciences and humanities that address food themes.…

  15. Enhanced decoding for the Galileo low-gain antenna mission: Viterbi redecoding with four decoding stages

    NASA Technical Reports Server (NTRS)

    Dolinar, S.; Belongie, M.

    1995-01-01

    The Galileo low-gain antenna mission will be supported by a coding system that uses a (14,1/4) inner convolutional code concatenated with Reed-Solomon codes of four different redundancies. Decoding for this code is designed to proceed in four distinct stages of Viterbi decoding followed by Reed-Solomon decoding. In each successive stage, the Reed-Solomon decoder only tries to decode the highest redundancy codewords not yet decoded in previous stages, and the Viterbi decoder redecodes its data utilizing the known symbols from previously decoded Reed-Solomon codewords. A previous article analyzed a two-stage decoding option that was not selected by Galileo. The present article analyzes the four-stage decoding scheme and derives the near-optimum set of redundancies selected for use by Galileo. The performance improvements relative to one- and two-stage decoding systems are evaluated.

  16. Genetic gain and economic values of selection strategies including semen traits in three- and four-way crossbreeding systems for swine production.

    PubMed

    González-Peña, D; Knox, R V; MacNeil, M D; Rodriguez-Zas, S L

    2015-03-01

    Four semen traits: volume (VOL), concentration (CON), progressive motility of spermatozoa (MOT), and abnormal spermatozoa (ABN) provide complementary information on boar fertility. Assessment of the impact of selection for semen traits is hindered by limited information on economic parameters. Objectives of this study were to estimate economic values for semen traits and to evaluate the genetic gain when these traits are incorporated into traditional selection strategies in a 3-tier system of swine production. Three-way (maternal nucleus lines A and B and paternal nucleus line C) and 4-way (additional paternal nucleus line D) crossbreeding schemes were compared. A novel population structure that accommodated selection for semen traits was developed. Three selection strategies were simulated. Selection Strategy I (baseline) encompassed selection for maternal traits: number of pigs born alive (NBA), litter birth weight (LBW), adjusted 21-d litter weight (A21), and number of pigs at 21 d (N21); and paternal traits: number of days to 113.5 kg (D113), backfat (BF), ADG, feed efficiency (FE), and carcass lean % (LEAN). Selection Strategy II included Strategy I and the number of usable semen doses per collection (DOSES), a function of the 4 semen traits. Selection Strategy III included Strategy I and the 4 semen traits individually. The estimated economic values of VOL, CON, MOT, ABN, and DOSES for 7 to 1 collections/wk ranged from $0.21 to $1.44/mL, $0.12 to $0.83/10 spermatozoa/mm, $0.61 to $12.66/%, -$0.53 to -$10.88/%, and $2.01 to $41.43/%, respectively. The decrease in the relative economic values of semen traits and DOSES with higher number of collections per wk was sharper between 1 and 2.33 collections/wk than between 2.33 and 7 collections/wk. The higher economic value of MOT and ABN relative to VOL and CON could be linked to the genetic variances and covariances of these traits. Average genetic gains for the maternal traits were comparable across strategies

  17. Thinking theologically about reproductive and genetic enhancements: the challenge.

    PubMed

    Khushf, George

    1999-08-01

    Current philosophical and legal bioethical reflections on reprogenetics provides little more than a rationalization of the interests of science. There are two reasons for this. First, bioethicists attempt to address ethical issues in a "language of precision" that characterizes science, and this works against analogical and narratological modes of discourse that have traditionally provided guidance for understanding human nature and purpose. Second, the current ethical and legal debate is framed by a public/private distinction that banishes robust norms to the private realm, and leaves a minimalist public discourse of harm avoidance that is insuffucient for regulating the science. In this essay, I argue that Mark Hanson's account of anxiety provides a valuable starting point for addressing deficiencies in the current philosophical and legal debate, and it highlights the need for a theological discourse on genetic enhancements. Through an assessment of Joel Shuman's criticism of the public/private distinction, I show how the needed theological discourse should be situated in the context of robust communities, and how such a communitarian inter-ethic is compatible with a variant of liberalism. Finally, I critically assess James Keenan's account of virtue and perfection, in order to outline what a sufficient discourse on reproductive and genetic enhancements requires.

  18. SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting.

    PubMed

    Boutant, Marie; Kulkarni, Sameer S; Joffraud, Magali; Raymond, Frédéric; Métairon, Sylviane; Descombes, Patrick; Cantó, Carles

    2016-03-01

    Caloric restriction (CR) has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD(+)-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF). Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can be even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different. PMID:26923584

  19. SIRT1 Gain of Function Does Not Mimic or Enhance the Adaptations to Intermittent Fasting.

    PubMed

    Boutant, Marie; Kulkarni, Sameer S; Joffraud, Magali; Raymond, Frédéric; Métairon, Sylviane; Descombes, Patrick; Cantó, Carles

    2016-03-01

    Caloric restriction (CR) has been shown to prevent the onset of insulin resistance and to delay age-related physiological decline in mammalian organisms. SIRT1, a NAD(+)-dependent deacetylase enzyme, has been suggested to mediate the adaptive responses to CR, leading to the speculation that SIRT1 activation could be therapeutically used as a CR-mimetic strategy. Here, we used a mouse model of moderate SIRT1 overexpression to test whether SIRT1 gain of function could mimic or boost the metabolic benefits induced by every-other-day feeding (EODF). Our results indicate that SIRT1 transgenesis does not affect the ability of EODF to decrease adiposity and improve insulin sensitivity. Transcriptomic analyses revealed that SIRT1 transgenesis and EODF promote very distinct adaptations in individual tissues, some of which can be even be metabolically opposite, as in brown adipose tissue. Therefore, whereas SIRT1 overexpression and CR both improve glucose metabolism and insulin sensitivity, the etiologies of these benefits are largely different.

  20. Cumulative gains enhance striatal response to reward opportunities in alcohol-dependent patients

    PubMed Central

    Gilman, Jodi M.; Smith, Ashley R.; Bjork, James M.; Ramchandani, Vijay A.; Momenan, Reza; Hommer, Daniel W.

    2016-01-01

    Substance use disorder is characterized by a transition from volitional to compulsive responding for drug reward. A possible explanation for this transition may be that alcohol-dependent patients (ADP) show a general propensity for a history of rewarded instrumental responses, and these rewarded responses may boost the activation of motivational neurocircuitry for additional reward. Brain imaging studies of decision-making have demonstrated that ADP relative to controls (CON) often show altered neural activation in response to anticipating and receiving rewards, but the majority of studies have not investigated how past performance affects activation. A potential exists for ADP to show increased sensitivity to reward as a function of reward delivery history. In the current study, we used functional magnetic resonance imaging to investigate the neural correlates of risky decision-making in ADP (n = 18) and CON (n = 18) while they played a two-choice monetary risk-taking game. In addition to investigating general neural recruitment by risky decision-making, we also modeled each participant’s running total of monetary earnings in order to determine areas of activation that correlated with cumulative reward. We found that ADP and CON showed few differences in behavior or in mesolimbic activation by choice for, and receipt of, risky gains. However, when including a cumulative-earnings covariate, ADP exhibited heightened striatal activation that correlated with total earnings during the choice event in the task. The heightened contextual sensitivity of striatal responses to cumulative earnings in ADP may represent a general neurobiological affective substrate for development of automatized instrumental behavior. PMID:24754451

  1. Stochasticity enhances the gaining of bet-hedging strategies in contact-process-like dynamics.

    PubMed

    Hidalgo, Jorge; Pigolotti, Simone; Muñoz, Miguel A

    2015-03-01

    In biology and ecology, individuals or communities of individuals living in unpredictable environments often alternate between different evolutionary strategies to spread and reduce risks. Such behavior is commonly referred to as "bet-hedging." Long-term survival probabilities and population sizes can be much enhanced by exploiting such hybrid strategies. Here, we study the simplest possible birth-death stochastic model in which individuals can choose among a poor but safe strategy, a better but risky alternative, or a combination of both. We show analytically and computationally that the benefits derived from bet-hedging strategies are much stronger for higher environmental variabilities (large external noise) and/or for small spatial dimensions (large intrinsic noise). These circumstances are typically encountered by living systems, thus providing us with a possible justification for the ubiquitousness of bet-hedging in nature.

  2. Training leading to repetition failure enhances bench press strength gains in elite junior athletes.

    PubMed

    Drinkwater, Eric J; Lawton, Trent W; Lindsell, Rod P; Pyne, David B; Hunt, Patrick H; McKenna, Michael J

    2005-05-01

    The purpose of this study was to investigate the importance of training leading to repetition failure in the performance of 2 different tests: 6 repetition maximum (6RM) bench press strength and 40-kg bench throw power in elite junior athletes. Subjects were 26 elite junior male basketball players (n = 12; age = 18.6 +/- 0.3 years; height = 202.0 +/- 11.6 cm; mass = 97.0 +/- 12.9 kg; mean +/- SD) and soccer players (n = 14; age = 17.4 +/- 0.5 years; height = 179.0 +/- 7.0 cm; mass = 75.0 +/- 7.1 kg) with a history of greater than 6 months' strength training. Subjects were initially tested twice for 6RM bench press mass and 40-kg Smith machine bench throw power output (in watts) to establish retest reliability. Subjects then undertook bench press training with 3 sessions per week for 6 weeks, using equal volume programs (24 repetitions x 80-105% 6RM in 13 minutes 20 seconds). Subjects were assigned to one of two experimental groups designed either to elicit repetition failure with 4 sets of 6 repetitions every 260 seconds (RF(4 x 6)) or allow all repetitions to be completed with 8 sets of 3 repetitions every 113 seconds (NF(8 x 3)). The RF(4 x 6) treatment elicited substantial increases in strength (7.3 +/- 2.4 kg, +9.5%, p < 0.001) and power (40.8 +/- 24.1 W, +10.6%, p < 0.001), while the NF(8 x 3) group elicited 3.6 +/- 3.0 kg (+5.0%, p < 0.005) and 25 +/- 19.0 W increases (+6.8%, p < 0.001). The improvements in the RF(4 x 6) group were greater than those in the repetition rest group for both strength (p < 0.005) and power (p < 0.05). Bench press training that leads to repetition failure induces greater strength gains than nonfailure training in the bench press exercise for elite junior team sport athletes.

  3. Inner hair cell loss leads to enhanced response amplitudes in auditory cortex of unanesthetized chinchillas: evidence for increased system gain.

    PubMed

    Qiu, C; Salvi, R; Ding, D; Burkard, R

    2000-01-01

    Carboplatin preferentially destroys inner hair cells (IHCs) in the chinchilla inner ear, while retaining a near-normal outer hair cell (OHC) population. The present study investigated the functional consequences of IHC loss on the compound action potential (CAP), inferior colliculus potential (ICP) and auditory cortex potential (ACP) recorded from chronically implanted electrodes. IHC loss led to a reduction in CAP amplitude that was roughly proportional to IHC loss. The ICP amplitude was typically reduced by IHC loss, but the magnitude of this reduction was generally less than that observed for the CAP. In contrast to the CAP and ICP, ACP amplitudes were generally not reduced following IHC loss. In some animals, the ACP amplitude remained at pre-carboplatin values despite substantial IHC loss. However, in other animals, IHC loss led to an increase ('enhancement') of ACP amplitude. ACP enhancement was greatest at 1-2 weeks post-carboplatin, returning towards baseline amplitudes at 5 weeks post-carboplatin. In other animals, the ACP remained enhanced up to 5 weeks post-carboplatin. We interpret the transient and sustained enhancement of ACP amplitude following partial IHC loss as evidence of functional reorganization occurring at or below the level of the auditory cortex. These results suggest that the gain of the central auditory pathway increases following IHC loss to compensate for the reduced input from the cochlea. PMID:10601720

  4. Association genetics, geography and ecophysiology link stomatal patterning in Populus trichocarpa with carbon gain and disease resistance trade-offs.

    PubMed

    McKown, Athena D; Guy, Robert D; Quamme, Linda; Klápště, Jaroslav; La Mantia, Jonathan; Constabel, C P; El-Kassaby, Yousry A; Hamelin, Richard C; Zifkin, Michael; Azam, M S

    2014-12-01

    Stomata are essential for diffusive entry of gases to support photosynthesis, but may also expose internal leaf tissues to pathogens. To uncover trade-offs in range-wide adaptation relating to stomata, we investigated the underlying genetics of stomatal traits and linked variability in these traits with geoclimate, ecophysiology, condensed foliar tannins and pathogen susceptibility in black cottonwood (Populus trichocarpa). Upper (adaxial) and lower (abaxial) leaf stomatal traits were measured from 454 accessions collected throughout much of the species range. We calculated broad-sense heritability (H(2) ) of stomatal traits and, using SNP data from a 34K Populus SNP array, performed a genome-wide association studies (GWAS) to uncover genes underlying stomatal trait variation. H(2) values for stomatal traits were moderate (average H(2) = 0.33). GWAS identified genes associated primarily with adaxial stomata, including polarity genes (PHABULOSA), stomatal development genes (BRASSINOSTEROID-INSENSITIVE 2) and disease/wound-response genes (GLUTAMATE-CYSTEINE LIGASE). Stomatal traits correlated with latitude, gas exchange, condensed tannins and leaf rust (Melampsora) infection. Latitudinal trends of greater adaxial stomata numbers and guard cell pore size corresponded with higher stomatal conductance (gs ) and photosynthesis (Amax ), faster shoot elongation, lower foliar tannins and greater Melampsora susceptibility. This suggests an evolutionary trade-off related to differing selection pressures across the species range. In northern environments, more adaxial stomata and larger pore sizes reflect selection for rapid carbon gain and growth. By contrast, southern genotypes have fewer adaxial stomata, smaller pore sizes and higher levels of condensed tannins, possibly linked to greater pressure from natural leaf pathogens, which are less significant in northern ecosystems.

  5. Genetic parameters related to environmental variability of weight traits in a selection experiment for weight gain in mice; signs of correlated canalised response

    PubMed Central

    Ibáñez-Escriche, Noelia; Moreno, Almudena; Nieto, Blanca; Piqueras, Pepa; Salgado, Concepción; Gutiérrez, Juan Pablo

    2008-01-01

    Data from an experimental mice population selected from 18 generations to increase weight gain were used to estimate the genetic parameters associated with environmental variability. The analysis involved three traits: weight at 21 days, weight at 42 days and weight gain between 21 and 42 days. A dataset of 5273 records for males was studied. Data were analysed using Bayesian procedures by comparing the Deviance Information Criterion (DIC) value of two different models: one assuming homogeneous environmental variances and another assuming them as heterogeneous. The model assuming heterogeneity was better in all cases and also showed higher additive genetic variances and lower common environmental variances. The heterogeneity of residual variance was associated with systematic and additive genetic effects thus making reduction by selection possible. Genetic correlations between the additive genetic effects on mean and environmental variance of the traits analysed were always negative, ranging from -0.19 to -0.38. An increase in the heritability of the traits was found when considering the genetic determination of the environmental variability. A suggested correlated canalised response was found in terms of coefficient of variation but it could be insufficient to compensate for the scale effect associated with an increase of the mean. PMID:18400150

  6. High gain 1.3-μm GaInNAs SOA with fast gain dynamics and enhanced temperature stability

    NASA Astrophysics Data System (ADS)

    Fitsios, D.; Giannoulis, G.; Iliadis, N.; Korpijärvi, V.-M.; Viheriälä, J.; Laakso, A.; Dris, S.; Spyropoulou, M.; Avramopoulos, H.; Kanellos, G. T.; Pleros, N.; Guina, M.

    2014-03-01

    Semiconductor optical amplifiers (SOAs) are a well-established solution of optical access networks. They could prove an enabling technology for DataCom by offering extended range of active optical functionalities. However, in such costand energy-critical applications, high-integration densities increase the operational temperatures and require powerhungry external cooling. Taking a step further towards improving the cost and energy effectiveness of active optical components, we report on the development of a GaInNAs/GaAs (dilute nitride) SOA operating at 1.3μm that exhibits a gain value of 28 dB and combined with excellent temperature stability owing to the large conduction band offset between GaInNAs quantum well and GaAs barrier. Moreover, the characterization results reveal almost no gain variation around the 1320 nm region for a temperature range from 20° to 50° C. The gain recovery time attained values as short as 100 ps, allowing implementation of various signal processing functionalities at 10 Gb/s. The combined parameters are very attractive for application in photonic integrated circuits requiring uncooled operation and thus minimizing power consumption. Moreover, as a result of the insensitivity to heating issues, a higher number of active elements can be integrated on chip-scale circuitry, allowing for higher integration densities and more complex optical on-chip functions. Such component could prove essential for next generation DataCom networks.

  7. Genetic Factors for Enhancement of Nicotine Levels in Cultivated Tobacco.

    PubMed

    Wang, Bingwu; Lewis, Ramsey S; Shi, Junli; Song, Zhongbang; Gao, Yulong; Li, Wenzheng; Chen, Hongxia; Qu, Rongda

    2015-12-02

    Nicotine has practical applications relating to smoking cessation devices and alternative nicotine products. Genetic manipulation for increasing nicotine content in cultivated tobacco (Nicotiana tabacum L.) may be of value for industrial purposes, including the possibility of enhancing the efficiency of nicotine extraction. Biotechnological approaches have been evaluated in connection with this objective, but field-based results are few. Here, we report characterization of two genes encoding basic-helix-loop-helix (bHLH) transcription factors (TFs), NtMYC2a and NtMYC2b from tobacco. Overexpression of NtMYC2a increased leaf nicotine levels in T1 transgenic lines approximately 2.3-fold in greenhouse-grown plants of tobacco cultivar 'NC 95'. Subsequent field testing of T2 and T3 generations of transgenic NtMYC2a overexpression lines showed nicotine concentrations were 76% and 58% higher than control lines, respectively. These results demonstrated that the increased nicotine trait was stably inherited to the T2 and T3 generations, indicating the important role that NtMYC2a plays in regulating nicotine accumulation in N. tabacum and the great potential of NtMYC2a overexpression in tobacco plants for industrial nicotine production. Collected data in this study also indicated a negative feedback inhibition of nicotine biosynthesis. Further enhancement of nicotine accumulation in tobacco leaf may require modification of the processes of nicotine transport and deposition.

  8. Stimulated Raman spectroscopy and nanoscopy of molecules using near field photon induced forces without resonant electronic enhancement gain

    NASA Astrophysics Data System (ADS)

    Tamma, Venkata Ananth; Huang, Fei; Nowak, Derek; Kumar Wickramasinghe, H.

    2016-06-01

    We report on stimulated Raman spectroscopy and nanoscopy of molecules, excited without resonant electronic enhancement gain, and recorded using near field photon induced forces. Photon-induced interaction forces between the sharp metal coated silicon tip of an Atomic Force Microscope (AFM) and a sample resulting from stimulated Raman excitation were detected. We controlled the tip to sample spacing using the higher order flexural eigenmodes of the AFM cantilever, enabling the tip to come very close to the sample. As a result, the detection sensitivity was increased compared with previous work on Raman force microscopy. Raman vibrational spectra of azobenzene thiol and l-phenylalanine were measured and found to agree well with published results. Near-field force detection eliminates the need for far-field optical spectrometer detection. Recorded images show spatial resolution far below the optical diffraction limit. Further optimization and use of ultrafast pulsed lasers could push the detection sensitivity towards the single molecule limit.

  9. Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs

    PubMed Central

    Wang, Yuexiang; Lee, Jang-Won; Oh, Gyeon; Grady, Sharon R.; McIntosh, J. Michael; Brunzell, Darlene H.; Cannon, Jason R.; Drenan, Ryan M.

    2014-01-01

    α6β2* nAChRs in the ventral tegmental area (VTA) to nucleus accumbens (NAc) pathway are implicated in the response to nicotine, and recent work suggests these receptors play a role in the rewarding action of ethanol. Here, we studied mice expressing gain-of-function α6β2* nAChRs (α6L9’S mice) that are hypersensitive to nicotine and endogenous acetylcholine (ACh). Evoked extracellular dopamine (DA) levels were enhanced in α6L9’S NAc slices compared to control, non-transgenic (nonTg) slices. Extracellular DA levels in both nonTg and α6L9’S slices were further enhanced in the presence of GBR12909, suggesting intact DA transporter function in both mouse strains. Ongoing α6β2* nAChR activation by ACh plays a role in enhancing DA levels, as α-conotoxin MII completely abolished evoked DA release in α6L9’S slices and decreased spontaneous DA release from striatal synaptosomes. In HPLC experiments, α6L9’S NAc tissue contained significantly more DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) compared to nonTg NAc tissue. Serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine (NE) were unchanged in α6L9’S compared to nonTg tissue. Western blot analysis revealed increased tyrosine hydroxylase expression in α6L9’S NAc. Overall, these results show that enhanced α6β2* nAChR activity in NAc can stimulate DA production and lead to increased extracellular DA levels. PMID:24266758

  10. Initial genetic diversity enhances population establishment and alters genetic structuring of a newly established Daphnia metapopulation.

    PubMed

    Holmes, Christopher J; Pantel, Jelena H; Schulz, Kimberly L; Cáceres, Carla E

    2016-07-01

    When newly created habitats are initially colonized by genotypes with rapid population growth rates, later arriving colonists may be prevented from establishing. Although these priority effects have been documented in multiple systems, their duration may be influenced by the diversity of the founding population. We conducted a large-scale field manipulation to investigate how initial clonal diversity influences temporal and landscape patterns of genetic structure in a developing metapopulation. Six genotypes of obligately asexual Daphnia pulex were stocked alone (no clonal diversity) or in combination ('high' clonal diversity) into newly created experimental woodland ponds. We also measured the population growth rate of all clones in the laboratory when raised on higher-quality and lower-quality resources. Our predictions were that in the 3 years following stocking, clonally diverse populations would be more likely to persist than nonclonally diverse populations and exhibit evidence for persistent founder effects. We expected that faster growing clones would be found in more pools and comprise a greater proportion of individuals genotyped from the landscape. Genetic composition, both locally and regionally, changed significantly following stocking. Six of 27 populations exhibited evidence for persistent founder effects, and populations stocked with 'high' clonal diversity were more likely to exhibit these effects than nonclonally diverse populations. Performance in the laboratory was not predictive of clonal persistence or overall dominance in the field. Hence, we conclude that although laboratory estimates of fitness did not fully explain metapopulation genetic structure, initial clonal diversity did enhance D. pulex population establishment and persistence in this system.

  11. Lotus tenuis x L. corniculatus interspecific hybridization as a means to breed bloat-safe pastures and gain insight into the genetic control of proanthocyanidin biosynthesis in legumes

    PubMed Central

    2014-01-01

    Background Proanthocyanidins (PAs) are secondary metabolites that strongly affect plant quality traits. The concentration and the structure of these metabolites influence the palatability and nutritional value of forage legumes. Hence, modulating PAs in the leaves of forage legumes is of paramount relevance for forage breeders worldwide. The lack of genetic variation in the leaf PA trait within the most important forage species and the difficulties in engineering this pathway via the ectopic expression of regulatory genes, prompted us to pursue alternative strategies to enhance this trait in forage legumes of agronomic interest. The Lotus genus includes forage species which accumulate PAs in edible organs and can thus be used as potential donor parents in breeding programs. Results We recovered a wild, diploid and PA-rich population of L. corniculatus and crossed with L. tenuis. The former grows in an alkaline-salty area in Spain while the latter is a diploid species, grown extensively in South American pastures, which does not accumulate PAs in the herbage. The resulting interspecific hybrids displayed several traits of outstanding agronomic relevance such as rhizome production, PA levels in edible tissues sufficient to prevent ruminal bloating (around 5 mg of PAs/g DW), biomass production similar to the cultivated parent and potential for adaptability to marginal lands. We show that PA levels correlate with expression levels of the R2R3MYB transcription factor TT2 and, in turn, with those of the key structural genes of the epicatechin and catechin biosynthetic pathways leading to PA biosynthesis. Conclusions The L. tenuis x L. corniculatus hybrids, reported herein, represent the first example of the introgression of the PA trait in forage legumes to levels known to provide nutritional and health benefits to ruminants. Apart from PAs, the hybrids have additional traits which may prove useful to breed forage legumes with increased persistence and adaptability to

  12. Enhanced growth of Juniperus thurifera under a warmer climate is explained by a positive carbon gain under cold and drought.

    PubMed

    Gimeno, Teresa E; Camarero, J Julio; Granda, Elena; Pías, Beatriz; Valladares, Fernando

    2012-03-01

    Juniperus thurifera L. is an endemic conifer of the western Mediterranean Basin where it is subjected to a severe climatic stress characterized by low winter temperatures and summer drought. Given the trend of increased warming-induced drought stress in this area and the climatic sensitivity of this species, we expect a negative impact of climate change on growth and ecophysiological performance of J. thurifera in the harsh environments where it dominates. To evaluate this, we measured long- and short-term radial growth using dendrochronology, photosynthesis and water-use efficiency in males, females and juveniles in three sites in Central Spain. Climate was monitored and completed with historical records. Mean annual temperature has increased +0.2 °C per decade in the study area, and the main warming trends corresponded to spring (+0.2 °C per decade) and summer (+0.3 °C per decade). Radial growth and maximum photosynthesis peaked in spring and autumn. Positive photosynthetic rates were maintained all year long, albeit at reduced rates in winter and summer. Radial growth was enhanced by wet conditions in the previous autumn and by warm springs and high precipitation in summer of the year of tree-ring formation. Cloud cover during the summer increased growth, while cloudy winters led to impaired carbon gain and reduced growth in the long term. We argue that maintenance of carbon gain under harsh conditions (low winter temperatures and dry summer months) and plastic xylogenesis underlie J. thurifera's ability to profit from changing climatic conditions such as earlier spring onset and erratic summer rainfall. Our results highlight that not only the magnitude but also the sign of the impact of climate change on growth and persistence of Mediterranean trees is species specific.

  13. Enhanced growth of Juniperus thurifera under a warmer climate is explained by a positive carbon gain under cold and drought.

    PubMed

    Gimeno, Teresa E; Camarero, J Julio; Granda, Elena; Pías, Beatriz; Valladares, Fernando

    2012-03-01

    Juniperus thurifera L. is an endemic conifer of the western Mediterranean Basin where it is subjected to a severe climatic stress characterized by low winter temperatures and summer drought. Given the trend of increased warming-induced drought stress in this area and the climatic sensitivity of this species, we expect a negative impact of climate change on growth and ecophysiological performance of J. thurifera in the harsh environments where it dominates. To evaluate this, we measured long- and short-term radial growth using dendrochronology, photosynthesis and water-use efficiency in males, females and juveniles in three sites in Central Spain. Climate was monitored and completed with historical records. Mean annual temperature has increased +0.2 °C per decade in the study area, and the main warming trends corresponded to spring (+0.2 °C per decade) and summer (+0.3 °C per decade). Radial growth and maximum photosynthesis peaked in spring and autumn. Positive photosynthetic rates were maintained all year long, albeit at reduced rates in winter and summer. Radial growth was enhanced by wet conditions in the previous autumn and by warm springs and high precipitation in summer of the year of tree-ring formation. Cloud cover during the summer increased growth, while cloudy winters led to impaired carbon gain and reduced growth in the long term. We argue that maintenance of carbon gain under harsh conditions (low winter temperatures and dry summer months) and plastic xylogenesis underlie J. thurifera's ability to profit from changing climatic conditions such as earlier spring onset and erratic summer rainfall. Our results highlight that not only the magnitude but also the sign of the impact of climate change on growth and persistence of Mediterranean trees is species specific. PMID:22427371

  14. Genetic manipulation for enhancing calcium content in potato tuber.

    PubMed

    Park, Sunghun; Kang, Tae-Suk; Kim, Chang-Kil; Han, Jeung-Sul; Kim, Sunggil; Smith, Roberta H; Pike, Leonard M; Hirschi, Kendal D

    2005-07-13

    Increased calcium (Ca) in potatoes may increase the production rate by enhancing tuber quality and storability. Additionally, increased Ca levels in important agricultural crops may help ameliorate the incidence of osteoporosis. However, the capacity to alter Ca levels in potato tubers through genetic manipulations has not been previously addressed. Here we demonstrate that potato tubers expressing the Arabidopsis H+/Ca2+ transporter sCAX1 (N-terminal autoinhibitory domain truncated version of CAtion eXchanger 1) contain up to 3-fold more Ca than wild-type tubers. The increased Ca appears to be distributed throughout the tuber. The sCAX1-expressing potatoes have normally undergone the tuber/plant/tuber cycle for three generations; the trait appeared stable through successive generations. The expression of sCAX1 does not appear to alter potato growth and development. Furthermore, increased Ca levels in sCAX1-expressing tubers do not appear to alter tuber morphology or yield. Given the preponderance of potato consumption worldwide, these transgenic plants may be a means of marginally increasing Ca intake levels in the population. To our knowledge, this study represents the first attempts to use biotechnology to increase the Ca content of potatoes.

  15. Genetic diversity in honey bee colonies enhances productivity and fitness.

    PubMed

    Mattila, Heather R; Seeley, Thomas D

    2007-07-20

    Honey bee queens mate with many males, creating numerous patrilines within colonies that are genetically distinct. The effects of genetic diversity on colony productivity and long-term fitness are unknown. We show that swarms from genetically diverse colonies (15 patrilines per colony) founded new colonies faster than swarms from genetically uniform colonies (1 patriline per colony). Accumulated differences in foraging rates, food storage, and population growth led to impressive boosts in the fitness (i.e., drone production and winter survival) of genetically diverse colonies. These results further our understanding of the origins of polyandry in honey bees and its benefits for colony performance.

  16. Multiple Query Evaluation Based on an Enhanced Genetic Algorithm.

    ERIC Educational Resources Information Center

    Tamine, Lynda; Chrisment, Claude; Boughanem, Mohand

    2003-01-01

    Explains the use of genetic algorithms to combine results from multiple query evaluations to improve relevance in information retrieval. Discusses niching techniques, relevance feedback techniques, and evolution heuristics, and compares retrieval results obtained by both genetic multiple query evaluation and classical single query evaluation…

  17. Genetic (co)variances among birth weight, 200-day weight, and postweaning gain in composites and parental breeds of beef cattle.

    PubMed

    Bennett, G L; Gregory, K E

    1996-11-01

    Genetic and environmental (co)variances for birth weight, adjusted 200-d weight, and postweaning gain were estimated in nine parental and three composite populations of beef cattle. The parental breeds were Angus (A), Braunvieh (B), Charolais (C), Gelbvieh (G), Hereford (H), Limousin (L), Pinzgauer (P), Red Poll (R), and Simmental (S). The composites were MARC I (1/4 B, 1/4 C, 1/4 L, 1/8 H, 1/8 A), MARC II (1/4 G, 1/4 S, 1/4 H, 1/4 A), and MARC III (1/4 R, 1/4 P, 1/4 H, 1/4 A). Heritabilities of additive direct genetic effects for birth weight (.50) and postweaning gain (.49) were greater than for 200-d weight (.32). Heritabilities of additive maternal effects of .09 for birth weight and .10 for 200-d weight were much smaller than direct effect heritabilities. Heritabilities were larger in composites than in parental breeds for additive direct effects of all three traits but smaller for maternal 200-d weight. Correlations were high and positive for direct genetic effects of the three weight traits and higher in composites than in the parental breeds. Correlations between direct and maternal genetic effects for both birth weight and 200-d weight were near zero. Some differences in variances among populations were correlated with differences in weight and milk yield. Heavier populations had larger variances, supporting the use of logarithmic transformation of weights to stabilize variances among genetic groups. Increased average milk yield was correlated with decreased phenotypic variance of 200-d weight. Average milk yield was also implicated in the expression of direct and maternal genetic effects for 200-d weight and their covariance. Comparison of univariate and multivariate estimates of genetic variances suggested that it is important to include birth weight in multivariate analyses of all weight traits to account for increased preweaning mortality of calves with extremely heavy or light birth weights. Based on heritability estimates, within-herd selection in

  18. Thickness-dependent carrier transport and optically enhanced transconductance gain in III-VI multilayer InSe

    NASA Astrophysics Data System (ADS)

    Ho, Ching-Hwa

    2016-06-01

    Multilayer InSe with a thickness above ∼20 nm, is a direct semiconductor with a peak absorption wavelength approaching λ = 1000 nm, which is a promising candidate for solar-energy conversion and 2D optoelectronics devices. We present herein the experimental observations of thickness-dependent conductivity and photoconductive-responsivity spectrum in multilayer InSe as well as optically enhanced transconductance gain in the multilayer InSe metal-semiconductor-field-effect transistor (MESFET) illuminated by a halogen lamp. The voltage-current (V-I) measurement result shows multilayer InSe belongs to a p-type semiconductor, which can form a p-channel FET device. Thickness (t) dependent conductivity (σ) of multilayer InSe reveals about six-order variation from 5076 (Ω-cm)‑1 (t = 5 nm) to 2.56 × 10‑3 (Ω-cm)‑1 (t = 184 μm, bulk) following a relationship of σ ∝ t ‑1.38. The highest conductivity in a thin InSe (e.g. t = 5 nm) is due to the increase of carrier density when the thickness is decreased. The photoresponsivity spectrum of a Ag-InSe-Ag multilayer photoconductor demonstrates a prominent peak absorption at 1.1 ∼ 1.3 eV, matches well with the direct-free-exciton energy of the InSe. A multilayer p-InSe MESFET was tested by V-I measurement. The transconductance was measured and determined to be {g}m={≤ft|\\tfrac{\\partial {{{I}}}{{D}}}{\\partial {{{V}}}{{G}}}\\right|}{{{V}}{{SD}}={{2V}}} = ({1.25 +/- 0.008})× {10}-4≤ft(\\tfrac{{{A}}}{{{V}}}\\right). The gm value will enhance about three times when the MESFET was placed under the illumination of a tungsten halogen lamp of a lower power density ∼0.5 mW · cm‑2. All the experimental results demonstrate multilayer InSe a promising 2D material available for microelectronics and optoelectronics applications.

  19. Thickness-dependent carrier transport and optically enhanced transconductance gain in III-VI multilayer InSe

    NASA Astrophysics Data System (ADS)

    Ho, Ching-Hwa

    2016-06-01

    Multilayer InSe with a thickness above ˜20 nm, is a direct semiconductor with a peak absorption wavelength approaching λ = 1000 nm, which is a promising candidate for solar-energy conversion and 2D optoelectronics devices. We present herein the experimental observations of thickness-dependent conductivity and photoconductive-responsivity spectrum in multilayer InSe as well as optically enhanced transconductance gain in the multilayer InSe metal-semiconductor-field-effect transistor (MESFET) illuminated by a halogen lamp. The voltage-current (V-I) measurement result shows multilayer InSe belongs to a p-type semiconductor, which can form a p-channel FET device. Thickness (t) dependent conductivity (σ) of multilayer InSe reveals about six-order variation from 5076 (Ω-cm)-1 (t = 5 nm) to 2.56 × 10-3 (Ω-cm)-1 (t = 184 μm, bulk) following a relationship of σ ∝ t -1.38. The highest conductivity in a thin InSe (e.g. t = 5 nm) is due to the increase of carrier density when the thickness is decreased. The photoresponsivity spectrum of a Ag-InSe-Ag multilayer photoconductor demonstrates a prominent peak absorption at 1.1 ˜ 1.3 eV, matches well with the direct-free-exciton energy of the InSe. A multilayer p-InSe MESFET was tested by V-I measurement. The transconductance was measured and determined to be {g}m={≤ft|\\tfrac{\\partial {{{I}}}{{D}}}{\\partial {{{V}}}{{G}}}\\right|}{{{V}}{{SD}}={{2V}}} = ({1.25 +/- 0.008})× {10}-4≤ft(\\tfrac{{{A}}}{{{V}}}\\right). The gm value will enhance about three times when the MESFET was placed under the illumination of a tungsten halogen lamp of a lower power density ˜0.5 mW · cm-2. All the experimental results demonstrate multilayer InSe a promising 2D material available for microelectronics and optoelectronics applications.

  20. Investigation of gain enhancement of electrically small antennas using double-negative, single-negative, and double-positive materials.

    PubMed

    Ghosh, B; Ghosh, S; Kakade, A B

    2008-08-01

    In this paper, it is shown that a double-negative or a mu-negative shell can be used to achieve a very high gain for an electrically small loop. It is also seen that together with the high gain, the metamaterial shell can be used to achieve a very uniform gain characteristic with respect to the shell dimensions. This is accomplished by a proper choice of the media parameters of the metamaterial shell and the region surrounding the antenna. This significantly eases the fabrication constraints and the close tolerances on the shell which was a major drawback towards the practical realization of the shell. Also, significant power gain can be obtained when the radiated power from the metamaterial shell is compared to the power radiated by a loop of the same radius as the outer radius of the shell. In addition, it is also found that a double-positive shell of the same dimensions as the metamaterial shell can be used to significantly increase the gain of the infinitesimal antenna. The power gain characteristics show distinct resonant peaks in this case. Excellent matching characteristics are observed corresponding to the radiated power gain.

  1. FAAH genetic variation enhances fronto-amygdala function in mouse and human

    PubMed Central

    Dincheva, Iva; Drysdale, Andrew T.; Hartley, Catherine A.; Johnson, David C.; Jing, Deqiang; King, Elizabeth C.; Ra, Stephen; Gray, Megan; Yang, Ruirong; DeGruccio, Ann Marie; Huang, Chienchun; Cravatt, Benjamin F.; Glatt, Charles E.; Hill, Matthew N.; Casey, B. J.; Lee, Francis S.

    2015-01-01

    Cross-species studies enable rapid translational discovery and produce the broadest impact when both mechanism and phenotype are consistent across organisms. We developed a knock-in mouse that biologically recapitulates a common human mutation in the gene for fatty acid amide hydrolase (FAAH) (C385A; rs324420), the primary catabolic enzyme for the endocannabinoid anandamide. This common polymorphism impacts the expression and activity of FAAH, thereby increasing anandamide levels. Here, we show that the genetic knock-in mouse and human variant allele carriers exhibit parallel alterations in biochemisty, neurocircuitry, and behavior. Specifically, there is reduced FAAH expression associated with the variant allele that selectively enhances fronto-amygdala connectivity and fear extinction learning, and decreases anxiety-like behaviors. These results suggest a gain-of-function in fear regulation and may indicate for whom and for what anxiety symptoms FAAH inhibitors or exposure-based therapies will be most efficacious, bridging an important translational gap between the mouse and human. PMID:25731744

  2. Tapered InAs/InGaAs quantum dot semiconductor optical amplifier design for enhanced gain and beam quality.

    PubMed

    Mesaritakis, Charis; Kapsalis, Alexandros; Simos, Hercules; Simos, Christos; Krakowski, Michel; Krestnikov, Igor; Syvridis, Dimitris

    2013-07-15

    In this Letter, a design for a tapered InAs/InGaAs quantum dot semiconductor optical amplifier is proposed and experimentally evaluated. The amplifier's geometry was optimized in order to reduce gain saturation effects and improve gain efficiency and beam quality. The experimental measurements confirm that the proposed amplifier allows for an elevated optical gain in the saturation regime, whereas a five-fold increase in the coupling efficiency to a standard single mode optical fiber is observed, due to the improvement in the beam quality factor M² of the emitted beam. PMID:23939062

  3. Enhanced genetic tools for engineering multigene traits into green algae.

    PubMed

    Rasala, Beth A; Chao, Syh-Shiuan; Pier, Matthew; Barrera, Daniel J; Mayfield, Stephen P

    2014-01-01

    Transgenic microalgae have the potential to impact many diverse biotechnological industries including energy, human and animal nutrition, pharmaceuticals, health and beauty, and specialty chemicals. However, major obstacles to sophisticated genetic and metabolic engineering in algae have been the lack of well-characterized transformation vectors to direct engineered gene products to specific subcellular locations, and the inability to robustly express multiple nuclear-encoded transgenes within a single cell. Here we validate a set of genetic tools that enable protein targeting to distinct subcellular locations, and present two complementary methods for multigene engineering in the eukaryotic green microalga Chlamydomonas reinhardtii. The tools described here will enable advanced metabolic and genetic engineering to promote microalgae biotechnology and product commercialization. PMID:24710110

  4. Enhanced photo-assisted electrical gating in vanadium dioxide based on saturation-induced gain modulation of erbium-doped fiber amplifier.

    PubMed

    Lee, Yong Wook; Kim, Bong-Jun; Choi, Sungyoul; Lee, Yong Wan; Kim, Hyun-Tak

    2009-10-26

    By incorporating saturation-induced gain modulation of an erbium-doped fiber amplifier (EDFA), we have demonstrated a high-speed photo-assisted electrical gating with considerably enhanced switching characteristics in a two-terminal device fabricated by using vanadium dioxide thin film. The gating operation was performed by illuminating the output light of the EDFA, whose transient gain was modulated by adjusting the chopping frequency of the input light down to 1 kHz, onto the device. In the proposed gating scheme, gated signals with a temporal duration of approximately 40 micros were successively generated at a repetition rate of 1 kHz. PMID:19997180

  5. Genetic Engineering of Algae for Enhanced Biofuel Production ▿

    PubMed Central

    Radakovits, Randor; Jinkerson, Robert E.; Darzins, Al; Posewitz, Matthew C.

    2010-01-01

    There are currently intensive global research efforts aimed at increasing and modifying the accumulation of lipids, alcohols, hydrocarbons, polysaccharides, and other energy storage compounds in photosynthetic organisms, yeast, and bacteria through genetic engineering. Many improvements have been realized, including increased lipid and carbohydrate production, improved H2 yields, and the diversion of central metabolic intermediates into fungible biofuels. Photosynthetic microorganisms are attracting considerable interest within these efforts due to their relatively high photosynthetic conversion efficiencies, diverse metabolic capabilities, superior growth rates, and ability to store or secrete energy-rich hydrocarbons. Relative to cyanobacteria, eukaryotic microalgae possess several unique metabolic attributes of relevance to biofuel production, including the accumulation of significant quantities of triacylglycerol; the synthesis of storage starch (amylopectin and amylose), which is similar to that found in higher plants; and the ability to efficiently couple photosynthetic electron transport to H2 production. Although the application of genetic engineering to improve energy production phenotypes in eukaryotic microalgae is in its infancy, significant advances in the development of genetic manipulation tools have recently been achieved with microalgal model systems and are being used to manipulate central carbon metabolism in these organisms. It is likely that many of these advances can be extended to industrially relevant organisms. This review is focused on potential avenues of genetic engineering that may be undertaken in order to improve microalgae as a biofuel platform for the production of biohydrogen, starch-derived alcohols, diesel fuel surrogates, and/or alkanes. PMID:20139239

  6. Learning about Genetic Inheritance through Technology-Enhanced Instruction

    ERIC Educational Resources Information Center

    Williams, Michelle; Merritt, Joi; Opperman, Amanda; Porter, Jakob; Erlenbeck, Kyle

    2012-01-01

    Genetics is an increasingly important topic in today's society, and one that permeates people's lives on many levels. Students, teachers, and the general public alike are constantly exposed to this topic through popular television shows such as "CSI: Crime Scene Investigation," political issues like voting on stem-cell research, and the…

  7. An Ethical Study on the Uses of Enhancement Genetic Engineering

    NASA Astrophysics Data System (ADS)

    Kawakita, Koji

    A variety of biomedical technologies are being developed that can be used for purposes other than treating diseases. Such “enhancement technologies” can be used to improve our own and future generation's life-chances. While these technologies can help people in many ways, their use raises important ethical issues. Some arguments for anti-enhancement as well as pro-enhancement seem to rest, however, on shaky foundation. Both company engineers and the general public had better learn more from technological, economical and philosophical histories. For such subjects may provide engineers with less opportunities of technological misuses and more powers of self-esteem in addition to self-control.

  8. Genetically enhanced cellulase production in Pseudomonas cellulosa using recombinant DNA technology

    DOEpatents

    Dees, H. Craig

    1999-01-01

    An enhanced strain of Pseudomonas celllulosa was obtained by introducing a recombinant genetic construct comprising a heterologous cellulase gene operably connected to a promoter into ATCC 55702, mutagenizing the transformants by treatment with MNNG, and selecting a high cellulase producing transformant. The transformant, designated Pseudomonas cellulosa ATCC XXXX, exhibits enhanced levels of cellulase production relative to the untransformed Pseudomonas cellulosa strain #142 ATCC 55702.

  9. Genetic improvement of plants for enhanced bio-ethanol production.

    PubMed

    Saha, Sanghamitra; Ramachandran, Srinivasan

    2013-04-01

    The present world energy situation urgently requires exploring and developing alternate, sustainable sources for fuel. Biofuels have proven to be an effective energy source but more needs to be produced to meet energy goals. Whereas first generation biofuels derived from mainly corn and sugarcane continue to be used and produced, the contentious debate between "feedstock versus foodstock" continues. The need for sources that can be grown under different environmental conditions has led to exploring newer sources. Lignocellulosic biomass is an attractive source for production of biofuel, but pretreatment costs to remove lignin are high and the process is time consuming. Genetically modified plants that have increased sugar or starch content, modified lignin content, or produce cellulose degrading enzymes are some options that are being explored and tested. This review focuses on current research on increasing production of biofuels by genetic engineering of plants to have desirable characteristics. Recent patents that have been filed in this area are also discussed.

  10. Allele mining and enhanced genetic recombination for rice breeding.

    PubMed

    Leung, Hei; Raghavan, Chitra; Zhou, Bo; Oliva, Ricardo; Choi, Il Ryong; Lacorte, Vanica; Jubay, Mona Liza; Cruz, Casiana Vera; Gregorio, Glenn; Singh, Rakesh Kumar; Ulat, Victor Jun; Borja, Frances Nikki; Mauleon, Ramil; Alexandrov, Nickolai N; McNally, Kenneth L; Sackville Hamilton, Ruaraidh

    2015-12-01

    Traditional rice varieties harbour a large store of genetic diversity with potential to accelerate rice improvement. For a long time, this diversity maintained in the International Rice Genebank has not been fully used because of a lack of genome information. The publication of the first reference genome of Nipponbare by the International Rice Genome Sequencing Project (IRGSP) marked the beginning of a systematic exploration and use of rice diversity for genetic research and breeding. Since then, the Nipponbare genome has served as the reference for the assembly of many additional genomes. The recently completed 3000 Rice Genomes Project together with the public database (SNP-Seek) provides a new genomic and data resource that enables the identification of useful accessions for breeding. Using disease resistance traits as case studies, we demonstrated the power of allele mining in the 3,000 genomes for extracting accessions from the GeneBank for targeted phenotyping. Although potentially useful landraces can now be identified, their use in breeding is often hindered by unfavourable linkages. Efficient breeding designs are much needed to transfer the useful diversity to breeding. Multi-parent Advanced Generation InterCross (MAGIC) is a breeding design to produce highly recombined populations. The MAGIC approach can be used to generate pre-breeding populations with increased genotypic diversity and reduced linkage drag. Allele mining combined with a multi-parent breeding design can help convert useful diversity into breeding-ready genetic resources.

  11. In sport and social justice, is genetic enhancement a game changer?

    PubMed

    Parker, Lisa S

    2012-12-01

    The possibility of genetic enhancement to increase the likelihood of success in sport and life's prospects raises questions for accounts of sport and theories of justice. These questions obviously include the fairness of such enhancement and its relationship to the goals of sport and demands of justice. Of equal interest, however, is the effect on our understanding of individual effort, merit, and desert of either discovering genetic contributions to components of such effort or recognizing the influence of social factors on the development and exercise of individual effort. This paper analyzes arguments about genetic enhancement with the goal of raising questions about how sport and justice regard unchosen, undeserved inequalities and what is assumed to be their opposite-namely, the exercise and results of individual effort. It is suggested that contemplating enhancement of natural assets previously outside human control may reinforce recognition of responsibility to intervene with regard to social advantages so as to support individual effort and improve individuals' life prospects.

  12. Control of Growth Efficiency in Young Plantation Loblolly Pine and Sweetgum through Irrigation and Fertigation Enhancement of Leaf Carbon Gain

    SciTech Connect

    L. Samuelson

    1999-07-07

    The overall objective of this study was to determine if growth efficiency of young plantation loblolly pine and sweetgum can be maintained by intensive forest management and whether increased carbon gain is the mechanism controlling growth efficiency response to resource augmentation. Key leaf physiological processes were examined over two growing seasons in response to irrigation, fertigation (irrigation with a fertilizer solution), and fertigation plus pest control (pine only). Although irrigation improved leaf net photosynthesis in pine and decreased stomatal sensitivity to vapor pressure deficit in sweetgum, no consistent physiological responses to fertigation were detected in either species. After 4 years of treatment, a 3-fold increase in woody net primary productivity was observed in both species in response to fertigation. Trees supplemented with fertigation and fertigation plus pest control exhibited the largest increases in growth and biomass. Furthermore, growth efficiency was maintained by fertigation and fertigation plus pest control, despite large increases in crown development and self-shading. Greater growth in response to intensive culture was facilitated by significant gains in leaf mass and whole tree carbon gain rather than detectable increases in leaf level processes. Growth efficiency was not maintained by significant increases in leaf level carbon gain but was possibly influenced by changes in carbon allocation to root versus shoot processes.

  13. TERT and AURKA gene copy number gains enhance the detection of acral lentiginous melanomas by fluorescence in situ hybridization.

    PubMed

    Diaz, Alba; Puig-Butillé, Joan Anton; Valera, Alexandra; Muñoz, Concha; Costa, Dolors; Garcia-Herrera, Adriana; Carrera, Cristina; Sole, Francesc; Malvehy, Josep; Puig, Susana; Alos, Llucia

    2014-03-01

    The study of specific chromosomal loci through fluorescence in situ hybridization (FISH) is useful in differential diagnosis of melanocytic tumors. However, sensitivity rates vary, probably because of molecular heterogeneity. Acral lentiginous melanomas are characterized by copy number gains of small genomic regions, including CCND1, TERT, and AURKA. In a series of 58 acral melanocytic lesions, we explored the value of a four-color FISH probe, used in addition to determining MYC gene status, and assessed the potential diagnostic usefulness of newly developed probes targeting TERT and AURKA. Moreover, we tested CCND1, TERT, and AURKA protein expression by immunohistochemistry. The four-color FISH probe detected 85.3% of melanomas and 29.4% of TERT and AURKA copy number gains. Sensitivity was 97% (confidence interval 95%, 82.9% to 99.8%) for the combined results of all probes. No MYC copy number gains were detected. No nevi showed aberrations. Immunohistochemistry revealed a higher percentage of cells positive for CCND1, TERT, and AURKA protein in melanomas than in nevi (P ≤ 0.001). A significant correlation between gene copy number gain and protein expression was found for CCND1 (P = 0.015). Our results indicate that addition of specific FISH probes to the current probe could improve sensitivity for the diagnosis of acral melanomas. Further studies in larger numbers of cases are needed to validate these results.

  14. Evaluation of implant strategies in Angus-sired steers with high or low genetic potential for marbling and gain.

    PubMed

    Black, D N; Neville, B W; Crosswhite, M R; Dahlen, C R

    2015-11-01

    Sixty-nine Angus-sired steer calves (332.3 kg initial BW) were used to determine the effects of single or double implant strategies on steers of high or low genetic potential (GP) determined by the GeneMax (Zoetis, Florham Park, NJ) genetic profiling test. Steers were assigned to treatments in a 2 × 2 factorial design with factors of 1) composite GP score (high, mean GP score of 86.5 [HI]; low, mean GP score of 25.3[LO]) and 2) implant strategy (single, steers implanted on d 70 [1X], or double, steers implanted d 0 and 70 [2X]). All steers were given the same implant (Revalor-S; Merck Animal Health, Summit, NJ), with the 2X group implanted on d 0 and 70 and the 1X group implanted only on d 70. A diet containing 1.38 Mcal NEg/kg DM was fed ad libitum, once daily. Ultrasound was used to measure body composition characteristics on d 0 and 70. Steers were harvested after 140 d on feed. At both the d-0 and d-70 ultrasound, HI steers had greater ( < 0.001) percent intramuscular fat (IMF) than LO steers, but no differences ( ≥ 0.24) were observed in LM area (LMA), rib fat thickness (RF), or rump fat thickness (RMFT). Steers in the 2X group had larger ( = 0.02) LMA and less ( = 0.03) IMF on d 70 than 1X steers and no differences ( ≥ 0.50) in RF or RMFT were observed. From d 0 to 70, HI steers had ADG, DMI, and G:F ( ≥ 0.60) similar to LO steers; however, 2X steers had greater ( < 0.001) ADG and were more ( < 0.001) feed efficient compared with 1X steers during the same interval. Over the entire 140-d feeding period, there were no differences ( ≥ 0.6) in BW, ADG, DMI, or G:F between GP groups; however, 2X steers had greater ( = 0.03) ADG compared with 1X steers and still had similar ( ≥ 0.12) DMI and G:F. Upon slaughter, marbling score tended to be impacted by a GP × implant interaction (499.9 ± 18.5, 545.6 ± 18.5, 487.1 ± 18.5, and 469.8 ± 18.5 for HI and 2X, HI and 1X, LO and 2X, and LO and 1X, respectively; = 0.06). No differences ( ≥ 0.7) were observed

  15. Genetic associations between daily BW gain and live fleshiness of station-tested young bulls and carcass and meat quality traits of commercial intact males in Piemontese cattle.

    PubMed

    Bonfatti, V; Albera, A; Carnier, P

    2013-05-01

    The aim of this study was to investigate genetic relationships between beef traits of station-tested young bulls and carcass and meat quality traits (MQ) of commercial intact males in Piemontese cattle. Phenotypes for daily gain (DG) and live fleshiness traits (width at withers: WW; shoulder muscularity: SM; loin width: LW; loin thickness: LT; thigh muscularity: TM; thigh profile: TP) and thinness of the shin bone (BT) were available for 3,109 and 2,183 performance-tested young bulls, respectively. Carcass daily gain (CDG), carcass conformation (SEUS), pH at 24 h (pH24h) and 8 d after slaughter (pH8d), lightness (L*), redness (a*), yellowness (b*), hue angle (HA), saturation index (SI), drip loss (DL), cooking loss (CL), and shear force (SF) were assessed for 1,208 commercial intact males. (Co) variance components were estimated in a set of twelve 9-traits analyses using REML and linear animal models including all performance-test traits and 1 carcass or MQ trait at a time. Heritabilities ± SE of beef traits ranged from 0.26 ± 0.03 (LW) to 0.47 ± 0.01 (DG), whereas those of carcass traits and MQ from 0.06 ± 0.03 (CL) to 0.63 ± 0.04 (HA). The genetic correlation (rg) between DG and CDG was 0.75 ± 0.10, indicating that DG, as measured at the test station, is a good indicator of the carcass gain achieved by commercial animals under farms conditions. Daily BW gain of station-tested bulls correlated positively with color traits (from 0.11 ± 0.12 to 0.54 ± 0.09), ph8d (rg ± SE = 0.31 ± 0.11), DL (rg ± SE = 0.29 ± 0.17), and CL (rg ± SE = 0.27 ± 0.18). Live fleshiness of station-tested bulls exhibited genetic correlations with MQ of commercial animals that were positive for L* and b* (from 0.13 ± 0.08 to 0.65 ± 0.14) and negative for pH (from -0.27 ± 0.15 to -0.57 ± 0.11), CL (from -0.16 ± 0.23 to -0.43 ± 0.22), and SF (TM: rg ± SE = -0.31 ± 0.15; TP: rg ± SE = -0.41 ± 0.17). The thinness of the shin bone correlated unfavorably with CDG (rg ± SE

  16. Assessing the impact of natural service bulls and genotype by environment interactions on genetic gain and inbreeding in organic dairy cattle genomic breeding programs.

    PubMed

    Yin, T; Wensch-Dorendorf, M; Simianer, H; Swalve, H H; König, S

    2014-06-01

    The objective of the present study was to compare genetic gain and inbreeding coefficients of dairy cattle in organic breeding program designs by applying stochastic simulations. Evaluated breeding strategies were: (i) selecting bulls from conventional breeding programs, and taking into account genotype by environment (G×E) interactions, (ii) selecting genotyped bulls within the organic environment for artificial insemination (AI) programs and (iii) selecting genotyped natural service bulls within organic herds. The simulated conventional population comprised 148 800 cows from 2976 herds with an average herd size of 50 cows per herd, and 1200 cows were assigned to 60 organic herds. In a young bull program, selection criteria of young bulls in both production systems (conventional and organic) were either 'conventional' estimated breeding values (EBV) or genomic estimated breeding values (GEBV) for two traits with low (h 2=0.05) and moderate heritability (h 2=0.30). GEBV were calculated for different accuracies (r mg), and G×E interactions were considered by modifying originally simulated true breeding values in the range from r g=0.5 to 1.0. For both traits (h 2=0.05 and 0.30) and r mg⩾0.8, genomic selection of bulls directly in the organic population and using selected bulls via AI revealed higher genetic gain than selecting young bulls in the larger conventional population based on EBV; also without the existence of G×E interactions. Only for pronounced G×E interactions (r g=0.5), and for highly accurate GEBV for natural service bulls (r mg>0.9), results suggests the use of genotyped organic natural service bulls instead of implementing an AI program. Inbreeding coefficients of selected bulls and their offspring were generally lower when basing selection decisions for young bulls on GEBV compared with selection strategies based on pedigree indices.

  17. Using surface-enhanced Raman spectroscopy to probe for genetic markers on single-stranded DNA

    NASA Astrophysics Data System (ADS)

    Moody, Benjamin; Leotaud, John; McCarty, Gregory S.

    2010-03-01

    Methods capable of quickly and inexpensively collecting genetic information are of increasing importance. We report a method of using surface-enhanced Raman spectroscopy to probe single-stranded DNA for genetic markers. This unique approach is used to analyze unmodified genes of moderate length for genetic markers by hybridizing native test oligonucleotides into a surface-enhanced Raman complex, vastly increasing detection sensitivity as compared to traditional Raman spectroscopy. The Raman complex is formed by sandwiching the test DNA between 40-nm gold nanoparticles and a photolithographically defined gold surface. With this design, we are able to collect characteristic Raman spectra about the test DNA and to detect genetic markers such as single-nucleotide polymorphisms (SNPs) and polymorphic regions. Results show that strands containing one of three different types of polymorphism can be differentiated using statistically significant trends regarding Raman intensity.

  18. Development of genetically enhanced baculovirus pesticides (Chapter 5). Book chapter

    SciTech Connect

    Wood, H.A.

    1991-01-01

    The report describes the assessment of the potential environmental impacts of genetically improved viral pesticides, including an evaluation of the properties of the foreign gene product(s) and the biological properties of the altered virus itself. The current field release studies are collecting much of the information which will be needed to assess the environmental safety of these new pesticides. Of primary concern will be the cost-to-benefit ratios as determined by production costs, stability, application, technology, and field efficacy. Despite the improvements afforded through biotechnology, it is clear that viral and other microbial pesticides will only reduce, not eliminate, the agricultural requirements for synthetic pesticides. Even so, biological pesticides are among the best solutions to reducing crop losses in the absence of ecological disturbances and potential health hazards.

  19. Genetic engineering of stem cells for enhanced therapy.

    PubMed

    Nowakowski, Adam; Andrzejewska, Anna; Janowski, Miroslaw; Walczak, Piotr; Lukomska, Barbara

    2013-01-01

    Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.

  20. Influence of a Small Fraction of Individuals with Enhanced Mutations on a Population Genetic Pool

    NASA Astrophysics Data System (ADS)

    Cebrat, S.; Stauffer, D.

    It has been observed that a higher mutation load could be introduced into the genomes of children conceived by assisted reproduction technology (fertilization in-vitro). This generates two effects — slightly higher mutational pressure on the whole genetic pool of population and inhomogeneity of mutation distributions in the genetic pool. Computer simulations of the Penna ageing model suggest that already a small fraction of births with enhanced number of new mutations can negatively influence the whole population.

  1. GenMin: An enhanced genetic algorithm for global optimization

    NASA Astrophysics Data System (ADS)

    Tsoulos, Ioannis G.; Lagaris, I. E.

    2008-06-01

    A new method that employs grammatical evolution and a stopping rule for finding the global minimum of a continuous multidimensional, multimodal function is considered. The genetic algorithm used is a hybrid genetic algorithm in conjunction with a local search procedure. We list results from numerical experiments with a series of test functions and we compare with other established global optimization methods. The accompanying software accepts objective functions coded either in Fortran 77 or in C++. Program summaryProgram title: GenMin Catalogue identifier: AEAR_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEAR_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 35 810 No. of bytes in distributed program, including test data, etc.: 436 613 Distribution format: tar.gz Programming language: GNU-C++, GNU-C, GNU Fortran 77 Computer: The tool is designed to be portable in all systems running the GNU C++ compiler Operating system: The tool is designed to be portable in all systems running the GNU C++ compiler RAM: 200 KB Word size: 32 bits Classification: 4.9 Nature of problem: A multitude of problems in science and engineering are often reduced to minimizing a function of many variables. There are instances that a local optimum does not correspond to the desired physical solution and hence the search for a better solution is required. Local optimization techniques are frequently trapped in local minima. Global optimization is hence the appropriate tool. For example, solving a nonlinear system of equations via optimization, employing a least squares type of objective, one may encounter many local minima that do not correspond to solutions (i.e. they are far from zero). Solution method: Grammatical evolution and a stopping rule. Running time: Depending on the

  2. Genome-wide association and systems genetic analyses of residual feed intake, daily feed consumption, backfat and weight gain in pigs

    PubMed Central

    2014-01-01

    Background Feed efficiency is one of the major components determining costs of animal production. Residual feed intake (RFI) is defined as the difference between the observed and the expected feed intake given a certain production. Residual feed intake 1 (RFI1) was calculated based on regression of individual daily feed intake (DFI) on initial test weight and average daily gain. Residual feed intake 2 (RFI2) was as RFI1 except it was also regressed with respect to backfat (BF). It has been shown to be a sensitive and accurate measure for feed efficiency in livestock but knowledge of the genomic regions and mechanisms affecting RFI in pigs is lacking. The study aimed to identify genetic markers and candidate genes for RFI and its component traits as well as pathways associated with RFI in Danish Duroc boars by genome-wide associations and systems genetic analyses. Results Phenotypic and genotypic records (using the Illumina Porcine SNP60 BeadChip) were available on 1,272 boars. Fifteen and 12 loci were significantly associated (p < 1.52 × 10-6) with RFI1 and RFI2, respectively. Among them, 10 SNPs were significantly associated with both RFI1 and RFI2 implying the existence of common mechanisms controlling the two RFI measures. Significant QTL regions for component traits of RFI (DFI and BF) were detected on pig chromosome (SSC) 1 (for DFI) and 2 for (BF). The SNPs within MAP3K5 and PEX7 on SSC 1, ENSSSCG00000022338 on SSC 9, and DSCAM on SSC 13 might be interesting markers for both RFI measures. Functional annotation of genes in 0.5 Mb size flanking significant SNPs indicated regulation of protein and lipid metabolic process, gap junction, inositol phosphate metabolism and insulin signaling pathway are significant biological processes and pathways for RFI, respectively. Conclusions The study detected novel genetic variants and QTLs on SSC 1, 8, 9, 13 and 18 for RFI and indicated significant biological processes and metabolic pathways involved in RFI. The

  3. Pre-breeding for diversification of primary gene pool and genetic enhancement of grain legumes

    PubMed Central

    Sharma, Shivali; Upadhyaya, H. D.; Varshney, R. K.; Gowda, C. L. L.

    2013-01-01

    The narrow genetic base of cultivars coupled with low utilization of genetic resources are the major factors limiting grain legume production and productivity globally. Exploitation of new and diverse sources of variation is needed for the genetic enhancement of grain legumes. Wild relatives with enhanced levels of resistance/tolerance to multiple stresses provide important sources of genetic diversity for crop improvement. However, their exploitation for cultivar improvement is limited by cross-incompatibility barriers and linkage drags. Pre-breeding provides a unique opportunity, through the introgression of desirable genes from wild germplasm into genetic backgrounds readily used by the breeders with minimum linkage drag, to overcome this. Pre-breeding activities using promising landraces, wild relatives, and popular cultivars have been initiated at International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) to develop new gene pools in chickpea, pigeonpea, and groundnut with a high frequency of useful genes, wider adaptability, and a broad genetic base. The availability of molecular markers will greatly assist in reducing linkage drags and increasing the efficiency of introgression in pre-breeding programs. PMID:23970889

  4. Genetic dissection of the α-globin super-enhancer in vivo.

    PubMed

    Hay, Deborah; Hughes, Jim R; Babbs, Christian; Davies, James O J; Graham, Bryony J; Hanssen, Lars L P; Kassouf, Mira T; Oudelaar, A Marieke; Sharpe, Jacqueline A; Suciu, Maria C; Telenius, Jelena; Williams, Ruth; Rode, Christina; Li, Pik-Shan; Pennacchio, Len A; Sloane-Stanley, Jacqueline A; Ayyub, Helena; Butler, Sue; Sauka-Spengler, Tatjana; Gibbons, Richard J; Smith, Andrew J H; Wood, William G; Higgs, Douglas R

    2016-08-01

    Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. These super-enhancers have been proposed to manifest higher-order properties important in development and disease. Here we report a comprehensive functional dissection of one of the strongest putative super-enhancers in erythroid cells. By generating a series of mouse models, deleting each of the five regulatory elements of the α-globin super-enhancer individually and in informative combinations, we demonstrate that each constituent enhancer seems to act independently and in an additive fashion with respect to hematological phenotype, gene expression, chromatin structure and chromosome conformation, without clear evidence of synergistic or higher-order effects. Our study highlights the importance of functional genetic analyses for the identification of new concepts in transcriptional regulation.

  5. Enhancing the Internationalisation of Distance Education in the Biological Sciences: The DUNE Project and Genetic Engineering.

    ERIC Educational Resources Information Center

    Leach, C. K.; And Others

    1997-01-01

    Describes the Distance Educational Network of Europe (DUNE) project that aims at enhancing the development of distance education in an international context. Highlights issues relating to the delivery of distance-learning courses in a transnational forum. Describes the genetic engineering course that aims at explaining the core techniques of…

  6. Analyzing and Quantifying the Gain-of-Function Enhancement of IP3 Receptor Gating by Familial Alzheimer’s Disease-Causing Mutants in Presenilins

    PubMed Central

    Mak, Don-On Daniel; Cheung, King-Ho; Toglia, Patrick; Foskett, J. Kevin; Ullah, Ghanim

    2015-01-01

    Familial Alzheimer’s disease (FAD)-causing mutant presenilins (PS) interact with inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) Ca2+ release channels resulting in enhanced IP3R channel gating in an amyloid beta (Aβ) production-independent manner. This gain-of-function enhancement of IP3R activity is considered to be the main reason behind the upregulation of intracellular Ca2+ signaling in the presence of optimal and suboptimal stimuli and spontaneous Ca2+ signals observed in cells expressing mutant PS. In this paper, we employed computational modeling of single IP3R channel activity records obtained under optimal Ca2+ and multiple IP3 concentrations to gain deeper insights into the enhancement of IP3R function. We found that in addition to the high occupancy of the high-activity (H) mode and the low occupancy of the low-activity (L) mode, IP3R in FAD-causing mutant PS-expressing cells exhibits significantly longer mean life-time for the H mode and shorter life-time for the L mode, leading to shorter mean close-time and hence high open probability of the channel in comparison to IP3R in cells expressing wild-type PS. The model is then used to extrapolate the behavior of the channel to a wide range of IP3 and Ca2+ concentrations and quantify the sensitivity of IP3R to its two ligands. We show that the gain-of-function enhancement is sensitive to both IP3 and Ca2+ and that very small amount of IP3 is required to stimulate IP3R channels in the presence of FAD-causing mutant PS to the same level of activity as channels in control cells stimulated by significantly higher IP3 concentrations. We further demonstrate with simulations that the relatively longer time spent by IP3R in the H mode leads to the observed higher frequency of local Ca2+ signals, which can account for the more frequent global Ca2+ signals observed, while the enhanced activity of the channel at extremely low ligand concentrations will lead to spontaneous Ca2+ signals in cells expressing FAD

  7. A fast-evolving human NPAS3 enhancer gained reporter expression in the developing forebrain of transgenic mice

    PubMed Central

    Kamm, Gretel B.; López-Leal, Rodrigo; Lorenzo, Juan R.; Franchini, Lucía F.

    2013-01-01

    The developmental brain gene NPAS3 stands out as a hot spot in human evolution because it contains the largest number of human-specific, fast-evolving, conserved, non-coding elements. In this paper we studied 2xHAR142, one of these elements that is located in the fifth intron of NPAS3. Using transgenic mice, we show that the mouse and chimp 2xHAR142 orthologues behave as transcriptional enhancers driving expression of the reporter gene lacZ to a similar NPAS3 expression subdomain in the mouse central nervous system. Interestingly, the human 2xHAR142 orthologue drives lacZ expression to an extended expression pattern in the nervous system. Thus, molecular evolution of 2xHAR142 provides the first documented example of human-specific heterotopy in the forebrain promoted by a transcriptional enhancer and suggests that it may have contributed to assemble the unique properties of the human brain. PMID:24218632

  8. Mycobacterial Phylogenomics: An Enhanced Method for Gene Turnover Analysis Reveals Uneven Levels of Gene Gain and Loss among Species and Gene Families

    PubMed Central

    Librado, Pablo; Vieira, Filipe G.; Sánchez-Gracia, Alejandro; Kolokotronis, Sergios-Orestis; Rozas, Julio

    2014-01-01

    Species of the genus Mycobacterium differ in several features, from geographic ranges, and degree of pathogenicity, to ecological and host preferences. The recent availability of several fully sequenced genomes for a number of these species enabled the comparative study of the genetic determinants of this wide lifestyle diversity. Here, we applied two complementary phylogenetic-based approaches using information from 19 Mycobacterium genomes to obtain a more comprehensive view of the evolution of this genus. First, we inferred the phylogenetic relationships using two new approaches, one based on a Mycobacterium-specific amino acid substitution matrix and the other on a gene content dissimilarity matrix. Then, we utilized our recently developed gain-and-death stochastic models to study gene turnover dynamics in this genus in a maximum-likelihood framework. We uncovered a scenario that differs markedly from traditional 16S rRNA data and improves upon recent phylogenomic approaches. We also found that the rates of gene gain and death are high and unevenly distributed both across species and across gene families, further supporting the utility of the new models of rate heterogeneity applied in a phylogenetic context. Finally, the functional annotation of the most expanded or contracted gene families revealed that the transposable elements and the fatty acid metabolism-related gene families are the most important drivers of gene content evolution in Mycobacterium. PMID:24904011

  9. In sport and social justice, is genetic enhancement a game changer?

    PubMed

    Parker, Lisa S

    2012-12-01

    The possibility of genetic enhancement to increase the likelihood of success in sport and life's prospects raises questions for accounts of sport and theories of justice. These questions obviously include the fairness of such enhancement and its relationship to the goals of sport and demands of justice. Of equal interest, however, is the effect on our understanding of individual effort, merit, and desert of either discovering genetic contributions to components of such effort or recognizing the influence of social factors on the development and exercise of individual effort. This paper analyzes arguments about genetic enhancement with the goal of raising questions about how sport and justice regard unchosen, undeserved inequalities and what is assumed to be their opposite-namely, the exercise and results of individual effort. It is suggested that contemplating enhancement of natural assets previously outside human control may reinforce recognition of responsibility to intervene with regard to social advantages so as to support individual effort and improve individuals' life prospects. PMID:22983765

  10. Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9.

    PubMed

    Korkmaz, Gozde; Lopes, Rui; Ugalde, Alejandro P; Nevedomskaya, Ekaterina; Han, Ruiqi; Myacheva, Ksenia; Zwart, Wilbert; Elkon, Ran; Agami, Reuven

    2016-02-01

    Systematic identification of noncoding regulatory elements has, to date, mainly relied on large-scale reporter assays that do not reproduce endogenous conditions. We present two distinct CRISPR-Cas9 genetic screens to identify and characterize functional enhancers in their native context. Our strategy is to target Cas9 to transcription factor binding sites in enhancer regions. We identified several functional enhancer elements and characterized the role of two of them in mediating p53 (TP53) and ERα (ESR1) gene regulation. Moreover, we show that a genomic CRISPR-Cas9 tiling screen can precisely map functional domains within enhancer elements. Our approach expands the utility of CRISPR-Cas9 to elucidate the functions of the noncoding genome.

  11. Performance enhancement for crystallization unit of a sugar plant using genetic algorithm technique

    NASA Astrophysics Data System (ADS)

    Tewari, P. C.; Khanduja, Rajiv; Gupta, Mahesh

    2012-05-01

    This paper deals with the performance enhancement for crystallization unit of a sugar plant using genetic algorithm. The crystallization unit of a sugar industry has three main subsystems arranged in series. Considering exponential distribution for the probable failures and repairs, the mathematical formulation of the problem is done using probabilistic approach, and differential equations are developed on the basis of Markov birth-death process. These equations are then solved using normalizing conditions so as to determine the steady-state availability of the crystallization unit. The performance of each subsystem of crystallization unit in a sugar plant has also been optimized using genetic algorithm. Thus, the findings of the present paper will be highly useful to the plant management for the timely execution of proper maintenance decisions and, hence, to enhance the system performance.

  12. Genetic diversity enhanced by ancient introgression and secondary contact in East Pacific black mangroves.

    PubMed

    Nettel, Alejandro; Dodd, Richard S; Afzal-Rafii, Zara; Tovilla-Hernández, Cristian

    2008-06-01

    Regional distribution of genetic diversity in widespread species may be influenced by hybridization with locally restricted, closely related species. Previous studies have shown that Central American East Pacific populations of the wide-ranged Avicennia germinans, the black mangrove, harbour higher genetic diversity than the rest of its range. Genetic diversity in this region might be enhanced by introgression with the locally restricted Avicennia bicolor. We tested the hypotheses of ancient hybridization using phylogenetic analysis of the internal transcribed spacer region (ITS) of the nuclear ribosomal DNA and intergenic chloroplast DNA; we also tested for current hybridization by population level analysis of nuclear microsatellites. Our results unveiled ancient ITS introgression between a northern Pacific Central American A. germinans lineage and A. bicolor. However, microsatellite data revealed contemporary isolation between the two species. Polymorphic ITS sequences from Costa Rica and Panama are consistent with a zone of admixture between the introgressant ITS A. germinans lineage and a southern Central American lineage of A. germinans. Interspecific introgression influenced lineage diversity and divergence at the nuclear ribosomal DNA; intraspecific population differentiation and secondary contact are more likely to have enhanced regional genetic diversity in Pacific Central American populations of the widespread A. germinans.

  13. Enhanced biofilm formation and multi-host transmission evolve from divergent genetic backgrounds in Campylobacter jejuni.

    PubMed

    Pascoe, Ben; Méric, Guillaume; Murray, Susan; Yahara, Koji; Mageiros, Leonardos; Bowen, Ryan; Jones, Nathan H; Jeeves, Rose E; Lappin-Scott, Hilary M; Asakura, Hiroshi; Sheppard, Samuel K

    2015-11-01

    Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as Campylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype with different genetic backgrounds. Our approach combines genome-wide association studies with traditional microbiology techniques to investigate the genetic basis of biofilm formation in 102 Campylobacter jejuni isolates. We quantified biofilm formation among the isolates and identified hotspots of genetic variation in homologous sequences that correspond to variation in biofilm phenotypes. Thirteen genes demonstrated a statistically robust association including those involved in adhesion, motility, glycosylation, capsule production and oxidative stress. The genes associated with biofilm formation were different in the host generalist ST-21 and ST-45 clonal complexes, which are frequently isolated from multiple host species and clinical samples. This suggests the evolution of enhanced biofilm from different genetic backgrounds and a possible role in colonization of multiple hosts and transmission to humans.

  14. Genetic enhancement, social justice, and welfare-oriented patterns of distribution.

    PubMed

    Etieyibo, Edwin

    2012-07-01

    The debate over the host of moral issues that genetic enhancement technology (GET) raises has been significant. One argument that has been advanced to impugn its moral legitimacy is the 'unfair advantage argument' (UAA), which states: allowing access to GET to be determined by socio-economic status would lead to unjust outcomes, namely, create a genetic caste system, and with it the exacerbation and perpetuation of existing socio-economic inequalities. Fritz Allhoff has recently objected to the argument, the kernel of which is that it conflates the use of the technology with its distribution. GET, he argues, would generate unjust outcomes only if it is distributed according to principles of an unjust pattern of distribution; for if we can determine what constitutes a 'just' distributive scheme, then the technology can be allocated according to the principles of that scheme. In this paper I argue the following cluster of related claims: (1) both UAA and Allhoff's proposed distributive schemes ignore the importance of non-genetic factors in the development of an individual's characteristics and capacities; (2) if we accept the view that it is good to prevent unjust outcomes that arise because some have exclusive access to GET, then we have to accept wide-ranging distributive schemes; (3) by tracking genetic and non-genetic factors wide-ranging schemes do violate in some sense the widely shared value of neutrality in liberal democracies.

  15. Gain-of-function of mutant p53: mutant p53 enhances cancer progression by inhibiting KLF17 expression in invasive breast carcinoma cells.

    PubMed

    Ali, Amjad; Shah, Abdus Saboor; Ahmad, Ayaz

    2014-11-01

    Kruppel-like-factor 17 (KLF17) is a negative regulator of metastasis and epithelial-mesenchymal-transition (EMT). However, its expression is downregulated in metastatic breast cancer that contains p53 mutations. Here, we show that mutant-p53 plays a key role to suppress KLF17 and thereby enhances cancer progression, which defines novel gain-of-function (GOF) of mutant-p53. Mutant-p53 interacts with KLF17 and antagonizes KLF17 mediated EMT genes transcription. Depletion of KLF17 promotes cell viability, decreases apoptosis and induces drug resistance in metastatic breast cancer cells. KLF17 suppresses cell migration and invasion by decreasing CD44, PAI-1 and Cyclin-D1 expressions. Taken together, our results show that KLF17 is important for the suppression of metastasis and could be a potential therapeutic target during chemotherapy.

  16. Genetics

    MedlinePlus

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  17. Enhanced vascularization of cultured skin substitutes genetically modified to overexpress vascular endothelial growth factor.

    PubMed

    Supp, D M; Supp, A P; Bell, S M; Boyce, S T

    2000-01-01

    Cultured skin substitutes have been used as adjunctive therapies in the treatment of burns and chronic wounds, but they are limited by lack of a vascular plexus. This deficiency leads to greater time for vascularization compared with native skin autografts and contributes to graft failure. Genetic modification of cultured skin substitutes to enhance vascularization could hypothetically lead to improved wound healing. To address this hypothesis, human keratinocytes were genetically modified by transduction with a replication incompetent retrovirus to overexpress vascular endothelial growth factor, a specific and potent mitogen for endothelial cells. Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates inoculated with human fibroblasts and either vascular endothelial growth factor-modified or control keratinocytes were prepared, and were cultured in vitro for 21 d. Northern blot analysis demonstrated enhanced expression of vascular endothelial growth factor mRNA in genetically modified keratinocytes and in cultured skin substitutes prepared with modified cells. Furthermore, the vascular endothelial growth factor-modified cultured skin substitutes secreted greatly elevated levels of vascular endothelial growth factor protein throughout the entire culture period. The bioactivity of vascular endothelial growth factor protein secreted by the genetically modified cultured skin substitutes was demonstrated using a microvascular endothelial cell growth assay. Vascular endothelial growth factor-modified and control cultured skin substitutes were grafted to full-thickness wounds on athymic mice, and elevated vascular endothelial growth factor mRNA expression was detected in the modified grafts for at least 2 wk after surgery. Vascular endothelial growth factor-modified grafts exhibited increased numbers of dermal blood vessels and decreased time to vascularization compared with controls. These results indicate that genetic modification of

  18. Giant enhancement of optical high-order sideband generation and their control in a dimer of two cavities with gain and loss

    NASA Astrophysics Data System (ADS)

    Li, Jiahui; Li, Jiahua; Xiao, Qian; Wu, Ying

    2016-06-01

    Parity-time (PT ) symmetric systems, which rely on the balanced gain-loss condition and render the Hamiltonian non-Hermitian, have provided a new platform to engineer effective light-matter interactions in recent years. Here we explore the high-order sideband features of the output fields obtained from a PT -symmetric optical system consisting of a passive nonlinear cavity coupled to an active linear cavity. By employing a perturbation technique, we derive analytic formulas used to determine the nonlinear transmission coefficient of optical second-order sideband in this structure. Using experimentally achievable parameters, it is clearly shown that the efficiency of the second-order sideband generation can be greatly enhanced in the PT -symmetric dimer, extremely in the vicinity of the transition point from unbroken- to broken-PT regimes. Moreover, we further analyzed the influences of the system parameters, including the photon-tunneling rate between two cavities, Kerr nonlinearity strength, and optical detuning, on the second-order sideband generation. Subsequently we investigate the higher-order sideband output spectrum by numerical simulations, where the sideband amplitude also is largely enhanced in the PT -symmetric arrangement, compared with the passive-passive double-cavity system. Our obtained results provide a new avenue for acquiring optical high-order sidebands and operating light, which may inspire further applications in chip-scale optical communications and optical frequency combs.

  19. Enhancing livestock through genetic engineering--recent advances and future prospects.

    PubMed

    Laible, G

    2009-03-01

    Transgenic technology allows for the stable introduction of exogenous genetic information into livestock genomes. With its ability to enhance existing or introduce entirely novel characteristics at unprecedented magnitude and speed this emerging technology is expected to have a profound impact on the genetic improvement of livestock in the future. The continual advances in animal genomics towards the identification of genes that influence livestock production traits and impact on human health will increase its ability and versatility for the purposeful modification of livestock animals to enhance their welfare, produce superior quality food and biomedical products and reduce the environmental impact of farming. In contrast to biomedicine, which has so far been the main driver for this technology platform, the potential opportunities for animal agriculture are more challenging because of the greater demands on cost, efficiency, consumer acceptance and relative value of the product. While various transgenic concepts for the genetic improvement of livestock animals for agriculture are being evaluated the integration of this technology into practical farming systems remains some distance in the future. PMID:18243310

  20. Enhancing livestock through genetic engineering--recent advances and future prospects.

    PubMed

    Laible, G

    2009-03-01

    Transgenic technology allows for the stable introduction of exogenous genetic information into livestock genomes. With its ability to enhance existing or introduce entirely novel characteristics at unprecedented magnitude and speed this emerging technology is expected to have a profound impact on the genetic improvement of livestock in the future. The continual advances in animal genomics towards the identification of genes that influence livestock production traits and impact on human health will increase its ability and versatility for the purposeful modification of livestock animals to enhance their welfare, produce superior quality food and biomedical products and reduce the environmental impact of farming. In contrast to biomedicine, which has so far been the main driver for this technology platform, the potential opportunities for animal agriculture are more challenging because of the greater demands on cost, efficiency, consumer acceptance and relative value of the product. While various transgenic concepts for the genetic improvement of livestock animals for agriculture are being evaluated the integration of this technology into practical farming systems remains some distance in the future.

  1. Enhanced killing of antibiotic-resistant bacteria enabled by massively parallel combinatorial genetics.

    PubMed

    Cheng, Allen A; Ding, Huiming; Lu, Timothy K

    2014-08-26

    New therapeutic strategies are needed to treat infections caused by drug-resistant bacteria, which constitute a major growing threat to human health. Here, we use a high-throughput technology to identify combinatorial genetic perturbations that can enhance the killing of drug-resistant bacteria with antibiotic treatment. This strategy, Combinatorial Genetics En Masse (CombiGEM), enables the rapid generation of high-order barcoded combinations of genetic elements for high-throughput multiplexed characterization based on next-generation sequencing. We created ∼ 34,000 pairwise combinations of Escherichia coli transcription factor (TF) overexpression constructs. Using Illumina sequencing, we identified diverse perturbations in antibiotic-resistance phenotypes against carbapenem-resistant Enterobacteriaceae. Specifically, we found multiple TF combinations that potentiated antibiotic killing by up to 10(6)-fold and delivered these combinations via phagemids to increase the killing of highly drug-resistant E. coli harboring New Delhi metallo-beta-lactamase-1. Moreover, we constructed libraries of three-wise combinations of transcription factors with >4 million unique members and demonstrated that these could be tracked via next-generation sequencing. We envision that CombiGEM could be extended to other model organisms, disease models, and phenotypes, where it could accelerate massively parallel combinatorial genetics studies for a broad range of biomedical and biotechnology applications, including the treatment of antibiotic-resistant infections.

  2. Wild Help for Enhancing Genetic Resistance in Lentil Against Fungal Diseases.

    PubMed

    Bhadauria, Vijai; Wong, Melissa M L; Bett, Kirstin E; Banniza, Sabine

    2016-01-01

    Lentil (Lens culinaris) is one of the cool season grain legume crops and an important source of dietary proteins and fibre. Fungal diseases are main constraints to lentil production and account for significant yield and quality losses. Lentil has a narrow genetic base presumably due to a bottleneck during domestication and as a result, any resistance to fungal diseases in the cultivated genepool is gradually eroded and overcome by pathogens. New sources of resistance have been identified in wild lentil (Lens ervoides). This article provides an overview of harnessing resistance potential of wild germplasm to enhance genetic resistance in lentil cultivars using next-generation sequencing-based genotyping, comparative genomics and marker-assisted selection breeding. PMID:26363611

  3. Genetic diversity enhances the resistance of a seagrass ecosystem to disturbance

    PubMed Central

    Hughes, A. Randall; Stachowicz, John J.

    2004-01-01

    Motivated by recent global reductions in biodiversity, empirical and theoretical research suggests that more species-rich systems exhibit enhanced productivity, nutrient cycling, or resistance to disturbance or invasion relative to systems with fewer species. In contrast, few data are available to assess the potential ecosystem-level importance of genetic diversity within species known to play a major functional role. Using a manipulative field experiment, we show that increasing genotypic diversity in a habitat-forming species (the seagrass Zostera marina) enhances community resistance to disturbance by grazing geese. The time required for recovery to near predisturbance densities also decreases with increasing eelgrass genotypic diversity. However, there is no effect of diversity on resilience, measured as the rate of shoot recovery after the disturbance, suggesting that more rapid recovery in diverse plots is due solely to differences in disturbance resistance. Genotypic diversity did not affect ecosystem processes in the absence of disturbance. Thus, our results suggest that genetic diversity, like species diversity, may be most important for enhancing the consistency and reliability of ecosystems by providing biological insurance against environmental change. PMID:15184681

  4. Enhancing cellulose utilization for fuels and chemicals by genetic modification of plant cell wall architecture.

    PubMed

    Vermerris, Wilfred; Abril, Alejandra

    2015-04-01

    Cellulose from plant biomass can serve as a sustainable feedstock for fuels, chemicals and polymers that are currently produced from petroleum. In order to enhance economic feasibility, the efficiency of cell wall deconstruction needs to be enhanced. With the use of genetic and biotechnological approaches cell wall composition can be modified in such a way that interactions between the major cell wall polymers—cellulose, hemicellulosic polysaccharides and lignin—are altered. Some of the resulting plants are compromised in their growth and development, but this may be caused in part by the plant's overcompensation for metabolic perturbances. In other cases novel structures have been introduced in the cell wall without negative effects. The first field studies with engineered bioenergy crops look promising, while detailed structural analyses of cellulose synthase offer new opportunities to modify cellulose itself.

  5. Owning genetic information and gene enhancement techniques: why privacy and property rights may undermine social control of the human genome.

    PubMed

    Moore, A D

    2000-04-01

    In this article I argue that the proper subjects of intangible property claims include medical records, genetic profiles, and gene enhancement techniques. Coupled with a right to privacy these intangible property rights allow individuals a zone of control that will, in most cases, justifiably exclude governmental or societal invasions into private domains. I argue that the threshold for overriding privacy rights and intangible property rights is higher, in relation to genetic enhancement techniques and sensitive personal information, than is commonly suggested. Once the bar is raised, so-to-speak, the burden of overriding it is formidable. Thus many policy decisions that have been recently proposed or enacted--citywide audio and video surveillance, law enforcement DNA sweeps, genetic profiling, national bans on genetic testing and enhancement of humans, to name a few--will have to be backed by very strong arguments. PMID:11765764

  6. Genetic conjugation of components in two pneumococcal fusion protein vaccines enhances paediatric mucosal immune responses.

    PubMed

    Pope, Caroline; Oliver, Elizabeth H; Ma, Jiangtao; Langton Hewer, Claire; Mitchell, Tim J; Finn, Adam

    2015-03-30

    Streptococcus pneumoniae colonises the upper respiratory tract and can cause pneumonia, meningitis and otitis media. Existing pneumococcal conjugate vaccines are expensive to produce and only protect against 13 of the 90+ pneumococcal serotypes; hence there is an urgent need for the development of new vaccines. We have shown previously in mice that pneumolysin (Ply) and a non-toxic variant (Δ6Ply) enhance antibody responses when genetically fused to pneumococcal surface adhesin A (PsaA), a potentially valuable effect for future vaccines. We investigated this adjuvanticity in human paediatric mucosal primary immune cell cultures. Adenoidal mononuclear cells (AMNC) from children aged 0-15 years (n=46) were stimulated with conjugated, admixed or individual proteins, cell viability and CD4+ T-cell proliferative responses were assessed using flow cytometry and cytokine secretion was measured using multiplex technology. Proliferation of CD4+ T-cells in response to PsaAPly, was significantly higher than responses to individual or admixed proteins (p=0.002). In contrast, an enhanced response to PsaAΔ6Ply compared to individual or admixed proteins only occurred at higher concentrations (p<0.01). Evaluation of cytotoxicity suggested that responses occurred when Ply-induced cytolysis was inhibited, either by fusion or mutation, but importantly an additional toxicity independent immune enhancing effect was also apparent as a result of fusion. Responses were MHC class II dependent and had a Th1/Th17 profile. Genetic fusion of Δ6Ply to PsaA significantly modulates and enhances pro-inflammatory CD4+ T-cell responses without the cytolytic effects of some other pneumolysoids. Membrane binding activity of such proteins may confer valuable adjuvant properties as fusion may assist Δ6Ply to deliver PsaA to the APC surface effectively, contributing to the initiation of anti-pneumococcal CD4+ T-cell immunity.

  7. Enhancing Neurobehavioral Gains with the Aid of Games and Exercise (ENGAGE): Initial open trial of a novel early intervention fostering the development of preschoolers' self-regulation.

    PubMed

    Healey, Dione M; Halperin, Jeffrey M

    2015-01-01

    Poor self-regulation during the preschool years predicts a wide array of adverse adult outcomes and, as such, is an important treatment target. We assessed the efficacy of a novel early intervention aimed at fostering the development of preschoolers' self-regulation. Enhancing Neurobehavioral Gains with the Aid of Games and Exercise (ENGAGE) involves parents and children playing a wide range of games targeting self-regulation on a daily basis over a 5-week period. Twenty-five New Zealand families, in whom parents identified their children as difficult to manage, took part in this study. Parent hyperactivity, aggression, and attention problems ratings on the BASC-2 were used to assess improvements in behavioral self-regulation, and subtests of the Stanford Binet-5 and NEPSY-2 were used to assess improvements in cognitive control. Improvements in parent-rated hyperactivity, aggression, and attention problems were maintained throughout the 12-month follow-up. In addition, improvements were found in two neurocognitive areas associated with self-regulation. While more rigorous randomized controlled trials are necessary, ENGAGE shows promise as a novel intervention for developing self-regulation in at-risk preschoolers.

  8. Enhancing Neurobehavioral Gains with the Aid of Games and Exercise (ENGAGE): Initial open trial of a novel early intervention fostering the development of preschoolers' self-regulation.

    PubMed

    Healey, Dione M; Halperin, Jeffrey M

    2015-01-01

    Poor self-regulation during the preschool years predicts a wide array of adverse adult outcomes and, as such, is an important treatment target. We assessed the efficacy of a novel early intervention aimed at fostering the development of preschoolers' self-regulation. Enhancing Neurobehavioral Gains with the Aid of Games and Exercise (ENGAGE) involves parents and children playing a wide range of games targeting self-regulation on a daily basis over a 5-week period. Twenty-five New Zealand families, in whom parents identified their children as difficult to manage, took part in this study. Parent hyperactivity, aggression, and attention problems ratings on the BASC-2 were used to assess improvements in behavioral self-regulation, and subtests of the Stanford Binet-5 and NEPSY-2 were used to assess improvements in cognitive control. Improvements in parent-rated hyperactivity, aggression, and attention problems were maintained throughout the 12-month follow-up. In addition, improvements were found in two neurocognitive areas associated with self-regulation. While more rigorous randomized controlled trials are necessary, ENGAGE shows promise as a novel intervention for developing self-regulation in at-risk preschoolers. PMID:24735230

  9. Dilute nitride resonant cavity enhanced photodetector with internal gain for the λ ∼ 1.3 μm optical communications window

    NASA Astrophysics Data System (ADS)

    Balkan, N.; Erol, A.; Sarcan, F.; Al-Ghuraibawi, L. F. F.; Nordin, M. S.

    2015-10-01

    We report on a novel dilute nitride-based resonant cavity enhanced photodetector (RCEPD) operating at 1.286 μm. The RCEPD was fabricated using 21 pairs top and 24 pairs bottom GaAs/AlGaAs distributed Bragg reflectors for mirrors and 7 nm thick nine GaAs/Ga0.65In0.35N0.02 As0.98 quantum wells as the absorption region. For a 15 μm diameter window, the photocurrent at 1.286 μm is 27 μA and 42 μA, at V = 0 and -1 V, respectively, whereas the dark current is as low as 1.7 nA at -1 V. At the operating wavelength, an excellent wavelength selectivity with a full width at half maximum (FWHM) of 5 nm, and a high quantum efficiency of 43% are demonstrated. The device exhibits significant internal gain at very small reverse bias voltages of V ⩾ -2 V with an overall quantum efficiency of 67%. These are the best ever recorded values for a dilute nitride RCEPD.

  10. Genetic modification of plant cell walls to enhance biomass yield and biofuel production in bioenergy crops.

    PubMed

    Wang, Yanting; Fan, Chunfen; Hu, Huizhen; Li, Ying; Sun, Dan; Wang, Youmei; Peng, Liangcai

    2016-01-01

    Plant cell walls represent an enormous biomass resource for the generation of biofuels and chemicals. As lignocellulose property principally determines biomass recalcitrance, the genetic modification of plant cell walls has been posed as a powerful solution. Here, we review recent progress in understanding the effects of distinct cell wall polymers (cellulose, hemicelluloses, lignin, pectin, wall proteins) on the enzymatic digestibility of biomass under various physical and chemical pretreatments in herbaceous grasses, major agronomic crops and fast-growing trees. We also compare the main factors of wall polymer features, including cellulose crystallinity (CrI), hemicellulosic Xyl/Ara ratio, monolignol proportion and uronic acid level. Furthermore, the review presents the main gene candidates, such as CesA, GH9, GH10, GT61, GT43 etc., for potential genetic cell wall modification towards enhancing both biomass yield and enzymatic saccharification in genetic mutants and transgenic plants. Regarding cell wall modification, it proposes a novel groove-like cell wall model that highlights to increase amorphous regions (density and depth) of the native cellulose microfibrils, providing a general strategy for bioenergy crop breeding and biofuel processing technology.

  11. Genetic modification of plant cell walls to enhance biomass yield and biofuel production in bioenergy crops.

    PubMed

    Wang, Yanting; Fan, Chunfen; Hu, Huizhen; Li, Ying; Sun, Dan; Wang, Youmei; Peng, Liangcai

    2016-01-01

    Plant cell walls represent an enormous biomass resource for the generation of biofuels and chemicals. As lignocellulose property principally determines biomass recalcitrance, the genetic modification of plant cell walls has been posed as a powerful solution. Here, we review recent progress in understanding the effects of distinct cell wall polymers (cellulose, hemicelluloses, lignin, pectin, wall proteins) on the enzymatic digestibility of biomass under various physical and chemical pretreatments in herbaceous grasses, major agronomic crops and fast-growing trees. We also compare the main factors of wall polymer features, including cellulose crystallinity (CrI), hemicellulosic Xyl/Ara ratio, monolignol proportion and uronic acid level. Furthermore, the review presents the main gene candidates, such as CesA, GH9, GH10, GT61, GT43 etc., for potential genetic cell wall modification towards enhancing both biomass yield and enzymatic saccharification in genetic mutants and transgenic plants. Regarding cell wall modification, it proposes a novel groove-like cell wall model that highlights to increase amorphous regions (density and depth) of the native cellulose microfibrils, providing a general strategy for bioenergy crop breeding and biofuel processing technology. PMID:27269671

  12. Genetic engineering of crops: a ray of hope for enhanced food security.

    PubMed

    Gill, Sarvajeet Singh; Gill, Ritu; Tuteja, Renu; Tuteja, Narendra

    2014-01-01

    Crop improvement has been a basic and essential chase since organized cultivation of crops began thousands of years ago. Abiotic stresses as a whole are regarded as the crucial factors restricting the plant species to reach their full genetic potential to deliver desired productivity. The changing global climatic conditions are making them worse and pointing toward food insecurity. Agriculture biotechnology or genetic engineering has allowed us to look into and understand the complex nature of abiotic stresses and measures to improve the crop productivity under adverse conditions. Various candidate genes have been identified and transformed in model plants as well as agriculturally important crop plants to develop abiotic stress-tolerant plants for crop improvement. The views presented here are an attempt toward realizing the potential of genetic engineering for improving crops to better tolerate abiotic stresses in the era of climate change, which is now essential for global food security. There is great urgency in speeding up crop improvement programs that can use modern biotechnological tools in addition to current breeding practices for providing enhanced food security.

  13. Ethical Reflections on Genetic Enhancement with the Aim of Enlarging Altruism.

    PubMed

    DeGrazia, David

    2016-09-01

    When it comes to caring about and helping those in need, our imaginations tend to be weak and our motivation tends to be parochial. This is a major moral problem in view of how much unmet need there is in the world and how much material capacity there is to address that need. With this problem in mind, the present paper will focus on genetic means to the enhancement of a moral capacity-a disposition to altruism-and of a cognitive capacity that facilitates use of the moral capacity: the ability to grasp vividly the needs of individuals who are unknown and not present. I will address two questions, with more extensive attention to the first question. First, assuming we had excellent reason to believe that the enhancements were safe, effective, and available to all who desired them, would seeking these enhancements be inherently morally acceptable-that is, free of inherent wrongness? Second, would it be wise for a society to pursue these enhancements? I will defend an affirmative answer to the first question while leaving the second question open. PMID:26246070

  14. Genetic or pharmacological blockade of noradrenaline synthesis enhances the neurochemical, behavioural, and neurotoxic effects of methamphetamine

    PubMed Central

    Weinshenker, David; Ferrucci, Michela; Busceti, Carla L.; Biagioni, Francesca; Lazzeri, Gloria; Liles, L. Cameron; Lenzi, Paola; Murri, Luigi; Paparelli, Antonio; Fornai, Francesco

    2008-01-01

    N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) lesions of the locus coeruleus (LC), the major brain noradrenergic nucleus, exacerbate the damage to nigrostriatal dopamine (DA) terminals caused by the psychostimulant methamphetamine (METH). However, because noradrenergic terminals contain other neuromodulators and the noradrenaline (NA) transporter, which may act as a neuroprotective buffer, it was unclear whether this enhancement of METH neurotoxicity was caused by the loss of noradrenergic innervation or the loss of NA itself. We addressed the specific role of NA by comparing the effects of METH in mice with noradrenergic lesions (DSP-4) and those with intact noradrenergic terminals but specifically lacking NA (genetic or acute pharmacological blockade of the NA biosynthetic enzyme dopamine β-hydroxylase; DBH). We found that genetic deletion of DBH (DBH −/− mice) and acute treatment of wild-type mice with a DBH inhibitor (fusaric acid) recapitulated the effects of DSP-4 lesions on METH responses. All three methods of NA depletion enhanced striatal DA release, extracellular oxidative stress (as measured by in vivo microdialysis of DA and 2,3-dihydroxybenzoic acid), and behavioural stereotypies following repeated METH administration. These effects accompanied a worsening of the striatal DA neuron terminal damage and ultrastructural changes to medium spiny neurons. We conclude that NA itself is neuroprotective and plays a fundamental role in the sensitivity of striatal DA terminals to the neurochemical, behavioural, and neurotoxic effects of METH. PMID:18042179

  15. A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies.

    PubMed

    Bodea, Corneliu A; Neale, Benjamin M; Ripke, Stephan; Daly, Mark J; Devlin, Bernie; Roeder, Kathryn

    2016-05-01

    One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data. PMID:27087321

  16. A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies.

    PubMed

    Bodea, Corneliu A; Neale, Benjamin M; Ripke, Stephan; Daly, Mark J; Devlin, Bernie; Roeder, Kathryn

    2016-05-01

    One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data.

  17. Enhanced genetic analysis of single human bioparticles recovered by simplified micromanipulation from forensic 'touch DNA' evidence.

    PubMed

    Farash, Katherine; Hanson, Erin K; Ballantyne, Jack

    2015-03-09

    DNA profiles can be obtained from 'touch DNA' evidence, which comprises microscopic traces of human biological material. Current methods for the recovery of trace DNA employ cotton swabs or adhesive tape to sample an area of interest. However, such a 'blind-swabbing' approach will co-sample cellular material from the different individuals, even if the individuals' cells are located in geographically distinct locations on the item. Thus, some of the DNA mixtures encountered in touch DNA samples are artificially created by the swabbing itself. In some instances, a victim's DNA may be found in significant excess thus masking any potential perpetrator's DNA. In order to circumvent the challenges with standard recovery and analysis methods, we have developed a lower cost, 'smart analysis' method that results in enhanced genetic analysis of touch DNA evidence. We describe an optimized and efficient micromanipulation recovery strategy for the collection of bio-particles present in touch DNA samples, as well as an enhanced amplification strategy involving a one-step 5 µl microvolume lysis/STR amplification to permit the recovery of STR profiles from the bio-particle donor(s). The use of individual or few (i.e., "clumps") bioparticles results in the ability to obtain single source profiles. These procedures represent alternative enhanced techniques for the isolation and analysis of single bioparticles from forensic touch DNA evidence. While not necessary in every forensic investigation, the method could be highly beneficial for the recovery of a single source perpetrator DNA profile in cases involving physical assault (e.g., strangulation) that may not be possible using standard analysis techniques. Additionally, the strategies developed here offer an opportunity to obtain genetic information at the single cell level from a variety of other non-forensic trace biological material.

  18. Genetic analysis of an enhancer of the NKX2-5 gene in ventricular septal defects.

    PubMed

    Qin, Xianyun; Xing, Qining; Ma, Liming; Meng, Haihong; Liu, Yumei; Pang, Shuchao; Yan, Bo

    2012-10-15

    Congenital heart disease (CHD) is one of the most common birth defects in humans. Mutations in cardiac transcription factor genes, such as GATA4, NKX2-5 and TBX5 genes, have been associated to a small portion of familial and isolated CHD cases. NKX2-5, a highly conserved homeobox gene, is expressed in the developing heart. During embryonic development, NKX2-5 plays pivotal roles in specifying cardiac progenitors, cardiac morphogenesis, cardiomyocyte differentiation and conduction system development. Numerous mutations in NKX2-5 gene have been reported in CHD patients, including atrial septal defect, ventricular septal defect (VSD) and tetrology of Fallot. We have previously identified the sequence variants within the NKX2-5 gene promoter in VSD patients. As several studies have revealed that the NKX2-5 gene is regulated by a complex module involving promoter and multiple independent cardiac enhancers, one of which is located between -3500 bp and -2500 bp upstream to the transcription start site, we hypothesized that the variants within the cardiac enhancer may contribute to CHD. In this study, we genetically analyzed the enhancer of NKX2-5 gene in large cohorts of VSD patients (n=322) and controls (n=336). The results showed that three novel variants, g.1467G>A, g.1487 Ins with a 13 bp insertion and g.1515 Ins with a 6 bp insertion, were identified within the enhancer element in both VSD patients and controls with similar frequencies (P>0.05). Therefore, our data suggested that the enhancer of NKX2-5 gene may not be a contributor to the VSD etiology. Other regulatory elements of the NKX2-5 gene will be further analyzed in CHD patients.

  19. Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics

    PubMed Central

    Kuo, Szu-Yu; Castoreno, Adam B.; Aldrich, Leslie N.; Lassen, Kara G.; Goel, Gautam; Dančík, Vlado; Kuballa, Petric; Latorre, Isabel; Conway, Kara L.; Sarkar, Sovan; Maetzel, Dorothea; Jaenisch, Rudolf; Clemons, Paul A.; Schreiber, Stuart L.; Shamji, Alykhan F.; Xavier, Ramnik J.

    2015-01-01

    Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to study how modulation of autophagy affects disease-associated phenotypes. Here, we describe the discovery of the small-molecule probe BRD5631 that is derived from diversity-oriented synthesis and enhances autophagy through an mTOR-independent pathway. We demonstrate that BRD5631 affects several cellular disease phenotypes previously linked to autophagy, including protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in the context of cellular homeostasis and disease. PMID:26195741

  20. Genetic Screens for Floral Mutants in Arabidopsis thaliana: Enhancers and Suppressors

    PubMed Central

    Dinh, Thanh Theresa; Luscher, Elizabeth; Li, Shaofang; Liu, Xigang; Won, So Youn; Chen, Xuemei

    2015-01-01

    The flower is a hallmark feature that has contributed to the evolutionary success of land plants. Diverse mutagenic agents have been employed as a tool to genetically perturb flower development and identify genes involved in floral patterning and morphogenesis. Since the initial studies to identify genes governing processes such as floral organ specification, mutagenesis in sensitized backgrounds has been used to isolate enhancers and suppressors to further probe the molecular basis of floral development. Here, we first describe two commonly employed methods for mutagenesis (using ethyl methanesulfonate (EMS) or T-DNAs as mutagens), and then describe three methods for identifying a mutation that leads to phenotypic alterations—traditional map-based cloning, TAIL-PCR, and deep sequencing in the plant model Arabidopsis thaliana. PMID:24395255

  1. Global Wild Annual Lens Collection: A Potential Resource for Lentil Genetic Base Broadening and Yield Enhancement

    PubMed Central

    Singh, Mohar; Bisht, Ishwari Singh; Kumar, Sandeep; Dutta, Manoranjan; Bansal, Kailash Chander; Karale, Moreshwar; Sarker, Ashutosh; Amri, Ahmad; Kumar, Shiv; Datta, Swapan Kumar

    2014-01-01

    Crop wild relatives (CWRs) are invaluable gene sources for various traits of interest, yet these potential resources are themselves increasingly threatened by the impact of climate change as well as other anthropogenic and socio-economic factors. The prime goal of our research was to cover all aspects of wild Lens genetic resource management like species characterization, agro-morphological evaluation, diversity assessment, and development of representative sets for its enhanced utilization in lentil base broadening and yield improvement initiatives. We characterized and evaluated extensively, the global wild annual Lens taxa, originating from twenty seven counties under two agro-climatic conditions of India consecutively for three cropping seasons. Results on various qualitative and quantitative characters including two foliar diseases showed wide variations for almost all yield attributing traits including multiple disease resistance in the wild species, L. nigricans and L. ervoides accessions. The core set developed from the entire Lens taxa had maximum representation from Turkey and Syria, indicating rich diversity in accessions originating from these regions. Diversity analysis also indicated wide geographical variations across genepool as was reflected in the core set. Potential use of core set, as an initial starting material, for genetic base broadening of cultivated lentil was also suggested. PMID:25254552

  2. Global wild annual Lens collection: a potential resource for lentil genetic base broadening and yield enhancement.

    PubMed

    Singh, Mohar; Bisht, Ishwari Singh; Kumar, Sandeep; Dutta, Manoranjan; Bansal, Kailash Chander; Karale, Moreshwar; Sarker, Ashutosh; Amri, Ahmad; Kumar, Shiv; Datta, Swapan Kumar

    2014-01-01

    Crop wild relatives (CWRs) are invaluable gene sources for various traits of interest, yet these potential resources are themselves increasingly threatened by the impact of climate change as well as other anthropogenic and socio-economic factors. The prime goal of our research was to cover all aspects of wild Lens genetic resource management like species characterization, agro-morphological evaluation, diversity assessment, and development of representative sets for its enhanced utilization in lentil base broadening and yield improvement initiatives. We characterized and evaluated extensively, the global wild annual Lens taxa, originating from twenty seven counties under two agro-climatic conditions of India consecutively for three cropping seasons. Results on various qualitative and quantitative characters including two foliar diseases showed wide variations for almost all yield attributing traits including multiple disease resistance in the wild species, L. nigricans and L. ervoides accessions. The core set developed from the entire Lens taxa had maximum representation from Turkey and Syria, indicating rich diversity in accessions originating from these regions. Diversity analysis also indicated wide geographical variations across genepool as was reflected in the core set. Potential use of core set, as an initial starting material, for genetic base broadening of cultivated lentil was also suggested.

  3. Global wild annual Lens collection: a potential resource for lentil genetic base broadening and yield enhancement.

    PubMed

    Singh, Mohar; Bisht, Ishwari Singh; Kumar, Sandeep; Dutta, Manoranjan; Bansal, Kailash Chander; Karale, Moreshwar; Sarker, Ashutosh; Amri, Ahmad; Kumar, Shiv; Datta, Swapan Kumar

    2014-01-01

    Crop wild relatives (CWRs) are invaluable gene sources for various traits of interest, yet these potential resources are themselves increasingly threatened by the impact of climate change as well as other anthropogenic and socio-economic factors. The prime goal of our research was to cover all aspects of wild Lens genetic resource management like species characterization, agro-morphological evaluation, diversity assessment, and development of representative sets for its enhanced utilization in lentil base broadening and yield improvement initiatives. We characterized and evaluated extensively, the global wild annual Lens taxa, originating from twenty seven counties under two agro-climatic conditions of India consecutively for three cropping seasons. Results on various qualitative and quantitative characters including two foliar diseases showed wide variations for almost all yield attributing traits including multiple disease resistance in the wild species, L. nigricans and L. ervoides accessions. The core set developed from the entire Lens taxa had maximum representation from Turkey and Syria, indicating rich diversity in accessions originating from these regions. Diversity analysis also indicated wide geographical variations across genepool as was reflected in the core set. Potential use of core set, as an initial starting material, for genetic base broadening of cultivated lentil was also suggested. PMID:25254552

  4. Dehydroepiandrosterone-enhanced dual specificity protein phosphatase (DDSP) prevents diet-induced and genetic obesity.

    PubMed

    Watanabe, Tetsuhiro; Ashida, Kenji; Goto, Kiminobu; Nawata, Hajime; Takayanagi, Ryoichi; Yanase, Toshihiko; Nomura, Masatoshi

    Dehydroepiandrosterone (DHEA) exerts a wide variety of therapeutic effects against medical disorders, such as diabetes and obesity. However, the molecular basis of DHEA action remains to be clarified. Previously, we reported that DHEA-enhanced dual specificity protein phosphatase, designated DDSP, is one of the target molecules of DHEA. To examine the role of DDSP in DHEA signaling, we generated mice that carry a DDSP transgene in which expression is driven by the CAG promoter (DDSP-Tg). DDSP-Tg mice weighed significantly less than wild-type (WT) control mice when a high fat diet was supplied (p < 0.01). No difference in food-intake or locomotor activity was found between DDSP-Tg and WT mice. Oxygen consumption of DDSP-Tg mice was higher than that of WT mice (p < 0.01), which suggested an increase in basal metabolism in DDSP-Tg mice. To further investigate the role of DDSP in genetic obese mice, DDSP-Tg mice with a db/db background were generated (DDSP-Tg db/db). We observed cancellation of obesity by the db/db mutation and development of a cachexic phenotype in DDSP-Tg db/db mice. In conclusion, our study shows that expression of DDSP leads to prevention of diet-induced and genetic (db/db) obesity. Anti-obese effects of DHEA might be mediated through DDSP, which might be a therapeutic target for intervention of obesity.

  5. Pharmacologic and genetic strategies to enhance cell therapy for cardiac regeneration.

    PubMed

    Kanashiro-Takeuchi, Rosemeire M; Schulman, Ivonne Hernandez; Hare, Joshua M

    2011-10-01

    Cell-based therapy is emerging as an exciting potential therapeutic approach for cardiac regeneration following myocardial infarction (MI). As heart failure (HF) prevalence increases over time, development of new interventions designed to aid cardiac recovery from injury are crucial and should be considered more broadly. In this regard, substantial efforts to enhance the efficacy and safety of cell therapy are continuously growing along several fronts, including modifications to improve the reprogramming efficiency of inducible pluripotent stem cells (iPS), genetic engineering of adult stem cells, and administration of growth factors or small molecules to activate regenerative pathways in the injured heart. These interventions are emerging as potential therapeutic alternatives and/or adjuncts based on their potential to promote stem cell homing, proliferation, differentiation, and/or survival. Given the promise of therapeutic interventions to enhance the regenerative capacity of multipotent stem cells as well as specifically guide endogenous or exogenous stem cells into a cardiac lineage, their application in cardiac regenerative medicine should be the focus of future clinical research. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

  6. Genetic disruption of KSHV major latent nuclear antigen LANA enhances viral lytic transcriptional program

    SciTech Connect

    Li Qiuhua; Zhou Fuchun; Ye Fengchun; Gao Shoujiang

    2008-09-30

    Following primary infection, KSHV establishes a lifelong persistent latent infection in the host. The mechanism of KSHV latency is not fully understood. The latent nuclear antigen (LANA or LNA) encoded by ORF73 is one of a few viral genes expressed during KSHV latency, and is consistently detected in all KSHV-related malignancies. LANA is essential for KSHV episome persistence, and regulates the expression of viral lytic genes through epigenetic silencing, and inhibition of the expression and transactivation function of the key KSHV lytic replication initiator RTA (ORF50). In this study, we used a genetic approach to examine the role of LANA in regulating KSHV lytic replication program. Deletion of LANA did not affect the expression of its adjacent genes vCyclin (ORF72) and vFLIP (ORF71). In contrast, the expression levels of viral lytic genes including immediate-early gene RTA, early genes MTA (ORF57), vIL-6 (ORF-K2) and ORF59, and late gene ORF-K8.1 were increased before and after viral lytic induction with 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate. This enhanced expression of viral lytic genes was also observed following overexpression of RTA with or without simultaneous chemical induction. Consistent with these results, the LANA mutant cells produced more infectious virions than the wild-type virus cells did. Furthermore, genetic repair of the mutant virus reverted the phenotypes to those of wild-type virus. Together, these results have demonstrated that, in the context of viral genome, LANA contributes to KSHV latency by regulating the expression of RTA and its downstream genes.

  7. Genetic Disruption of KSHV Major Latent Nuclear Antigen LANA Enhances Viral Lytic 2 Transcriptional Program

    PubMed Central

    Li, Qiuhua; Zhou, Fuchun; Ye, Fengchun; Gao, Shou-Jiang

    2008-01-01

    Following primary infection, KSHV establishes a lifelong persistent latent infection in the host. The mechanism of KSHV latency is not fully understood. The latent nuclear antigen (LANA or LNA) encoded by ORF73 is one of a few viral genes expressed during KSHV latency, and is consistently detected in all KSHV-related malignancies. LANA is essential for KSHV episome persistence, and regulates the expression of viral lytic genes through epigenetic silencing, and inhibition of the expression and transactivation function of the key KSHV lytic replication initiator RTA (ORF50). In this study, we used a genetic approach to examine the role of LANA in regulating KSHV lytic replication program. Deletion of LANA did not affect the expression of its adjacent genes vCyclin (ORF72) and vFLIP (ORF71). In contrast, the expression levels of viral lytic genes including immediate-early gene RTA, early genes MTA (ORF57), vIL-6 (ORF-K2) and ORF59, and late gene ORF-K8.1 were increased before and after viral lytic induction with 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate. This enhanced expression of viral lytic genes was also observed following overexpression of RTA with or without simultaneous chemical induction. Consistent with these results, the LANA mutant cells produced more infectious virions than the wild-type virus cells did. Furthermore, genetic repair of the mutant virus reverted the phenotypes to those of wild-type virus. Together, these results have demonstrated that, in the context of viral genome, LANA contributes to KSHV latency by regulating the expression of RTA and its downstream genes. PMID:18684478

  8. Genetic delivery of an immunoRNase by an oncolytic adenovirus enhances anticancer activity.

    PubMed

    Fernández-Ulibarri, Inés; Hammer, Katharina; Arndt, Michaela A E; Kaufmann, Johanna K; Dorer, Dominik; Engelhardt, Sarah; Kontermann, Roland E; Hess, Jochen; Allgayer, Heike; Krauss, Jürgen; Nettelbeck, Dirk M

    2015-05-01

    Antibody therapy of solid cancers is well established, but suffers from unsatisfactory tumor penetration of large immunoglobulins or from low serum retention of antibody fragments. Oncolytic viruses are in advanced clinical development showing excellent safety, but suboptimal potency due to limited virus spread within tumors. Here, by developing an immunoRNase-encoding oncolytic adenovirus, we combine viral oncolysis with intratumoral genetic delivery of a small antibody-fusion protein for targeted bystander killing of tumor cells (viro-antibody therapy). Specifically, we explore genetic delivery of a small immunoRNase consisting of an EGFR-binding scFv antibody fragment fused to the RNase Onconase (ONC(EGFR)) that induces tumor cell death by RNA degradation after cellular internalization. Onconase is a frog RNase that combines lack of immunogenicity and excellent safety in patients with high tumor killing potency due to its resistance to the human cytosolic RNase inhibitor. We show that ONC(EGFR) expression by oncolytic adenoviruses is feasible with an optimized, replication-dependent gene expression strategy. Virus-encoded ONC(EGFR) induces potent and EGFR-dependent bystander killing of tumor cells. Importantly, the ONC(EGFR)-encoding oncolytic adenovirus showed dramatically increased cytotoxicity specifically to EGFR-positive tumor cells in vitro and significantly enhanced therapeutic activity in a mouse xenograft tumor model. The latter demonstrates that ONC(EGFR) is expressed at levels sufficient to trigger tumor cell killing in vivo. The established ONC(EGFR)-encoding oncolytic adenovirus represents a novel agent for treatment of EGFR-positive tumors. This viro-antibody therapy platform can be further developed for targeted/personalized cancer therapy by exploiting antibody diversity to target further established or emerging tumor markers or combinations thereof.

  9. Light-extraction enhancement for light-emitting diodes: a firefly-inspired structure refined by the genetic algorithm

    NASA Astrophysics Data System (ADS)

    Bay, Annick; Mayer, Alexandre

    2014-09-01

    The efficiency of light-emitting diodes (LED) has increased significantly over the past few years, but the overall efficiency is still limited by total internal reflections due to the high dielectric-constant contrast between the incident and emergent media. The bioluminescent organ of fireflies gave incentive for light-extraction enhance-ment studies. A specific factory-roof shaped structure was shown, by means of light-propagation simulations and measurements, to enhance light extraction significantly. In order to achieve a similar effect for light-emitting diodes, the structure needs to be adapted to the specific set-up of LEDs. In this context simulations were carried out to determine the best geometrical parameters. In the present work, the search for a geometry that maximizes the extraction of light has been conducted by using a genetic algorithm. The idealized structure considered previously was generalized to a broader variety of shapes. The genetic algorithm makes it possible to search simultaneously over a wider range of parameters. It is also significantly less time-consuming than the previous approach that was based on a systematic scan on parameters. The results of the genetic algorithm show that (1) the calculations can be performed in a smaller amount of time and (2) the light extraction can be enhanced even more significantly by using optimal parameters determined by the genetic algorithm for the generalized structure. The combination of the genetic algorithm with the Rigorous Coupled Waves Analysis method constitutes a strong simulation tool, which provides us with adapted designs for enhancing light extraction from light-emitting diodes.

  10. Genetic deletion of MT₁/MT₂ melatonin receptors enhances murine cognitive and motor performance.

    PubMed

    O'Neal-Moffitt, G; Pilli, J; Kumar, S S; Olcese, J

    2014-09-26

    Melatonin, an indoleamine hormone secreted into circulation at night primarily by the brain's pineal gland, has been shown to have a wide variety of actions on the development and physiology of neurons in the CNS. Acting via two G-protein-coupled membrane receptors (MT1 and MT2), melatonin modulates neurogenesis, synaptic functions, neuronal cytoskeleton and gene expression. In the present studies, we sought to characterize the behavior and neuronal biology of transgenic mice lacking both of these melatonin receptors as a way to understand the hormone's receptor versus non-receptor-mediated actions in CNS-dependent activities, such as learning and memory, anxiety, general motor performance and circadian rhythmicity. Assessment of these behaviors was complemented by molecular analyses of gene expression in the brain. Our results demonstrate mild behavioral hyperactivity and a lengthened circadian period of free-running motor activity in melatonin receptor-deficient mice as compared to receptor-intact control mice beginning at an early age. Significant improvement in cognitive performance was found using the Barnes Maze and the Y-Maze. No behavioral changes in anxiety levels were found. Electrophysiological measures in hippocampal slices revealed a clear enhancement of long-term potentiation in mice lacking melatonin receptors with no significant differences in paired-pulse facilitation. Quantitative analysis of brain protein expression levels of phosphoCREB and phosphoERK1/2 and key markers of synaptic activity (synapsin, glutamate receptor 1, spinophilin, and glutamic acid decarboxylase 1) revealed significant differences between the double-knockout and wild-type animals, consistent with the behavioral findings. Thus, genetic deletion of melatonin receptors produces mice with enhanced cognitive and motor performance, supporting the view that these receptors play an important role in neurobehavioral development.

  11. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The genus Capsicum represents one of several well characterized Solanaceous genera. A wealth of classical and molecular genetics research is available for the genus. Information gleaned from its cultivated relatives, tomato and potato, provide further insight for basic and applied studies. Early ...

  12. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  13. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

    PubMed Central

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-01-01

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481–486, 682–687, 1018–1034, 1313–1323, 1450–1459 and 1582–1587 cm−1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood. PMID:25947114

  14. Characterization and noninvasive diagnosis of bladder cancer with serum surface enhanced Raman spectroscopy and genetic algorithms

    NASA Astrophysics Data System (ADS)

    Li, Shaoxin; Li, Linfang; Zeng, Qiuyao; Zhang, Yanjiao; Guo, Zhouyi; Liu, Zhiming; Jin, Mei; Su, Chengkang; Lin, Lin; Xu, Junfa; Liu, Songhao

    2015-05-01

    This study aims to characterize and classify serum surface-enhanced Raman spectroscopy (SERS) spectra between bladder cancer patients and normal volunteers by genetic algorithms (GAs) combined with linear discriminate analysis (LDA). Two group serum SERS spectra excited with nanoparticles are collected from healthy volunteers (n = 36) and bladder cancer patients (n = 55). Six diagnostic Raman bands in the regions of 481-486, 682-687, 1018-1034, 1313-1323, 1450-1459 and 1582-1587 cm-1 related to proteins, nucleic acids and lipids are picked out with the GAs and LDA. By the diagnostic models built with the identified six Raman bands, the improved diagnostic sensitivity of 90.9% and specificity of 100% were acquired for classifying bladder cancer patients from normal serum SERS spectra. The results are superior to the sensitivity of 74.6% and specificity of 97.2% obtained with principal component analysis by the same serum SERS spectra dataset. Receiver operating characteristic (ROC) curves further confirmed the efficiency of diagnostic algorithm based on GA-LDA technique. This exploratory work demonstrates that the serum SERS associated with GA-LDA technique has enormous potential to characterize and non-invasively detect bladder cancer through peripheral blood.

  15. Toward responsible stock enhancement: broadcast spawning dynamics and adaptive genetic management in white seabass aquaculture.

    PubMed

    Gruenthal, Kristen M; Drawbridge, Mark A

    2012-06-01

    The evolutionary effects captive-bred individuals that can have on wild conspecifics are necessary considerations for stock enhancement programs, but breeding protocols are often developed without the knowledge of realized reproductive behavior. To help fill that gap, parentage was assigned to offspring produced by a freely mating group of 50 white seabass (Atractoscion nobilis), a representative broadcast spawning marine finfish cultured for conservation. Similar to the well-known and closely related red drum (Sciaenops ocellatus), A. nobilis exhibited large variation in reproductive success. More males contributed and contributed more equally than females within and among spawns in a mating system best described as lottery polygyny. Two females produced 27% of the seasonal offspring pool and female breeding effective size averaged 1.85 per spawn and 12.38 seasonally, whereas male breeding effective size was higher (6.42 and 20.87, respectively), with every male contributing 1-7% of offspring. Further, females batch spawned every 1-5 weeks, while males displayed continuous reproductive readiness. Sex-specific mating strategies resulted in multiple successful mate pairings and a breeding effective to census size ratio of ≥0.62. Understanding a depleted species' mating system allowed management to more effectively utilize parental genetic variability for culture, but the fitness consequences of long-term stocking can be difficult to address. PMID:25568060

  16. Enhanced efficiency of genetic programming toward cardiomyocyte creation through topographical cues.

    PubMed

    Morez, Constant; Noseda, Michela; Paiva, Marta Abreu; Belian, Elisa; Schneider, Michael D; Stevens, Molly M

    2015-11-01

    Generation of de novo cardiomyocytes through viral over-expression of key transcription factors represents a highly promising strategy for cardiac muscle tissue regeneration. Although the feasibility of cell reprogramming has been proven possible both in vitro and in vivo, the efficiency of the process remains extremely low. Here, we report a chemical-free technique in which topographical cues, more specifically parallel microgrooves, enhance the directed differentiation of cardiac progenitors into cardiomyocyte-like cells. Using a lentivirus-mediated direct reprogramming strategy for expression of Myocardin, Tbx5, and Mef2c, we showed that the microgrooved substrate provokes an increase in histone H3 acetylation (AcH3), known to be a permissive environment for reprogramming by "stemness" factors, as well as stimulation of myocardin sumoylation, a post-translational modification essential to the transcriptional function of this key co-activator. These biochemical effects mimicked those of a pharmacological histone deacetylase inhibitor, valproic acid (VPA), and like VPA markedly augmented the expression of cardiomyocyte-specific proteins by the genetically engineered cells. No instructive effect was seen in cells unresponsive to VPA. In addition, the anisotropy resulting from parallel microgrooves induced cellular alignment, mimicking the native ventricular myocardium and augmenting sarcomere organization.

  17. Enhanced efficiency of genetic programming toward cardiomyocyte creation through topographical cues

    PubMed Central

    Morez, Constant; Noseda, Michela; Paiva, Marta Abreu; Belian, Elisa; Schneider, Michael D.; Stevens, Molly M.

    2015-01-01

    Generation of de novo cardiomyocytes through viral over-expression of key transcription factors represents a highly promising strategy for cardiac muscle tissue regeneration. Although the feasibility of cell reprogramming has been proven possible both in vitro and in vivo, the efficiency of the process remains extremely low. Here, we report a chemical-free technique in which topographical cues, more specifically parallel microgrooves, enhance the directed differentiation of cardiac progenitors into cardiomyocyte-like cells. Using a lentivirus-mediated direct reprogramming strategy for expression of Myocardin, Tbx5, and Mef2c, we showed that the microgrooved substrate provokes an increase in histone H3 acetylation (AcH3), known to be a permissive environment for reprogramming by “stemness” factors, as well as stimulation of myocardin sumoylation, a post-translational modification essential to the transcriptional function of this key co-activator. These biochemical effects mimicked those of a pharmacological histone deacetylase inhibitor, valproic acid (VPA), and like VPA markedly augmented the expression of cardiomyocyte-specific proteins by the genetically engineered cells. No instructive effect was seen in cells unresponsive to VPA. In addition, the anisotropy resulting from parallel microgrooves induced cellular alignment, mimicking the native ventricular myocardium and augmenting sarcomere organization. PMID:26302234

  18. Toward responsible stock enhancement: broadcast spawning dynamics and adaptive genetic management in white seabass aquaculture

    PubMed Central

    Gruenthal, Kristen M; Drawbridge, Mark A

    2012-01-01

    The evolutionary effects captive-bred individuals that can have on wild conspecifics are necessary considerations for stock enhancement programs, but breeding protocols are often developed without the knowledge of realized reproductive behavior. To help fill that gap, parentage was assigned to offspring produced by a freely mating group of 50 white seabass (Atractoscion nobilis), a representative broadcast spawning marine finfish cultured for conservation. Similar to the well-known and closely related red drum (Sciaenops ocellatus), A. nobilis exhibited large variation in reproductive success. More males contributed and contributed more equally than females within and among spawns in a mating system best described as lottery polygyny. Two females produced 27% of the seasonal offspring pool and female breeding effective size averaged 1.85 per spawn and 12.38 seasonally, whereas male breeding effective size was higher (6.42 and 20.87, respectively), with every male contributing 1–7% of offspring. Further, females batch spawned every 1–5 weeks, while males displayed continuous reproductive readiness. Sex-specific mating strategies resulted in multiple successful mate pairings and a breeding effective to census size ratio of ≥0.62. Understanding a depleted species’ mating system allowed management to more effectively utilize parental genetic variability for culture, but the fitness consequences of long-term stocking can be difficult to address. PMID:25568060

  19. The Impact of PNPLA3 rs738409 Genetic Polymorphism and Weight Gain ≥10 kg after Age 20 on Non-Alcoholic Fatty Liver Disease in Non-Obese Japanese Individuals.

    PubMed

    Nishioji, Kenichi; Mochizuki, Naomi; Kobayashi, Masao; Kamaguchi, Mai; Sumida, Yoshio; Nishimura, Takeshi; Yamaguchi, Kanji; Kadotani, Hiroshi; Itoh, Yoshito

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals is inadequately elucidated. We aim to investigate the impact of known genetic polymorphisms on NAFLD and the interaction between genetic risks and weight gain on NAFLD in obese and non-obese Japanese individuals. A total of 1164 participants who received health checkups were included. Participants with excessive alcohol consumption, with viral hepatitis or other inappropriate cases were excluded. Fatty liver was diagnosed by ultrasonography. Participants with a body mass index (BMI) of <18.5 kg/m2, 18.5-22.9 kg/m2, 23.0-24.9 kg/m2 and ≥25 kg/m2 were classified underweight, normal weight, overweight and obese, respectively. Self-administered questionnaire for lifestyle was assessed and a total of 8 previously reported genetic polymorphisms were chosen and examined. In all, 824 subjects were enrolled. The overall prevalence of NAFLD was 33.0%: 0% in underweight, 15.3% in normal weight, 41.1% in overweight and 71.7% in obese individuals. The prevalence of NAFLD is more affected by the G allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 in normal weight (odds ratio (OR) 3.52; 95%-CI: 1.42-8.71; P = 0.0063) and in overweight individuals (OR 2.60; 95%-CI: 1.14-5.91; P = 0.0225) than in obese individuals (not significant). Moreover, the G allele of PNPLA3 rs738409 and weight gain ≥10 kg after age 20 had a joint effect on the risk of NAFLD in the normal weight (OR 12.00; 95% CI: 3.71-38.79; P = 3.3×10-5) and the overweight individuals (OR 13.40; 95% CI: 2.92-61.36; P = 0.0008). The G allele of PNPLA3 rs738409 is a prominent risk factor for NAFLD and the interaction between the PNPLA3 rs738409 and weight gain ≥10 kg after age 20 plays a crucial role in the pathogenesis of NAFLD, especially in non-obese Japanese individuals.

  20. The Impact of PNPLA3 rs738409 Genetic Polymorphism and Weight Gain ≥10 kg after Age 20 on Non-Alcoholic Fatty Liver Disease in Non-Obese Japanese Individuals

    PubMed Central

    Nishioji, Kenichi; Mochizuki, Naomi; Kobayashi, Masao; Kamaguchi, Mai; Sumida, Yoshio; Nishimura, Takeshi; Yamaguchi, Kanji; Kadotani, Hiroshi; Itoh, Yoshito

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) in non-obese individuals is inadequately elucidated. We aim to investigate the impact of known genetic polymorphisms on NAFLD and the interaction between genetic risks and weight gain on NAFLD in obese and non-obese Japanese individuals. A total of 1164 participants who received health checkups were included. Participants with excessive alcohol consumption, with viral hepatitis or other inappropriate cases were excluded. Fatty liver was diagnosed by ultrasonography. Participants with a body mass index (BMI) of <18.5 kg/m2, 18.5–22.9 kg/m2, 23.0–24.9 kg/m2 and ≥25 kg/m2 were classified underweight, normal weight, overweight and obese, respectively. Self-administered questionnaire for lifestyle was assessed and a total of 8 previously reported genetic polymorphisms were chosen and examined. In all, 824 subjects were enrolled. The overall prevalence of NAFLD was 33.0%: 0% in underweight, 15.3% in normal weight, 41.1% in overweight and 71.7% in obese individuals. The prevalence of NAFLD is more affected by the G allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 in normal weight (odds ratio (OR) 3.52; 95%-CI: 1.42–8.71; P = 0.0063) and in overweight individuals (OR 2.60; 95%-CI: 1.14–5.91; P = 0.0225) than in obese individuals (not significant). Moreover, the G allele of PNPLA3 rs738409 and weight gain ≥10 kg after age 20 had a joint effect on the risk of NAFLD in the normal weight (OR 12.00; 95% CI: 3.71–38.79; P = 3.3×10−5) and the overweight individuals (OR 13.40; 95% CI: 2.92–61.36; P = 0.0008). The G allele of PNPLA3 rs738409 is a prominent risk factor for NAFLD and the interaction between the PNPLA3 rs738409 and weight gain ≥10 kg after age 20 plays a crucial role in the pathogenesis of NAFLD, especially in non-obese Japanese individuals. PMID:26485523

  1. Exploring the Role of Plant Genetics to Enhance Soil Carbon Sequestration in Hybrid Poplar Plantations

    NASA Astrophysics Data System (ADS)

    Wullschleger, S. D.; Garten, C. T.; Classen, A. T.

    2008-12-01

    Atmospheric CO2 concentrations have increased in recent decades and are projected to increase even further during the coming century. These projections have prompted scientists and policy-makers to consider how plants and soils can be used to stabilize CO2 concentrations. Although storing carbon in terrestrial ecosystems represents an attractive near-term option for mitigating rising atmospheric CO2 concentrations, enhancing the sequestration potential of managed systems will require advancements in understanding the fundamental mechanisms that control rates of carbon transfer and turnover in plants and soils. To address this challenge, a mathematical model was constructed to evaluate how changes in particular plant traits and management practices could affect soil carbon storage beneath hybrid poplar (Populus) plantations. The model was built from four sub-models that describe aboveground biomass, root biomass, soil carbon dynamics, and soil nitrogen transformations for trees growing throughout a user-defined rotation. Simulations could be run over one or multiple rotations. A sensitivity analysis of the model indicated changes in soil carbon storage were affected by variables that could be linked to hybrid poplar traits like rates of aboveground production, partitioning of carbon to coarse and fine roots, and rates of root decomposition. A higher ratio of belowground to aboveground production was especially important and correlated directly with increased soil carbon storage. Faster decomposition rates for coarse and fine dead roots resulted in a greater loss of carbon to the atmosphere as CO2 and less residual organic carbon for transfer to the fast soil carbon pool. Hence, changes in root chemistry that prolonged dead root decomposition rates, a trait that is under potential genetic control, were predicted to increase soil carbon storage via higher soil carbon inputs. Nitrogen limitation of both aboveground biomass production and soil carbon sequestration was

  2. Genetic Enhancement of Limb Defects in a Mouse Model of Cornelia de Lange Syndrome

    PubMed Central

    LOPEZ-BURKS, MARTHA E.; SANTOS, ROSAYSELA; KAWAUCHI, SHIMAKO; CALOF, ANNE L.; LANDER, ARTHUR D.

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is characterized by a wide variety of structural and functional abnormalities in almost every organ system of the body. CdLS is now known to be caused by mutations that disrupt the function of the cohesin complex or its regulators, and studies of animal models and cell lines tell us that the effect of these mutations is to produce subtle yet pervasive dysregulation of gene expression. With many hundreds of mostly small gene expression changes occurring in every cell type and tissue, identifying the etiology of any particular birth defect is very challenging. Here we focus on limb abnormalities, which are commonly seen in CdLS. In the limb buds of the Nipbl-haploinsufficient mouse (Nipbl+/− mouse), a model for the most common form of CdLS, modest gene expression changes are observed in several candidate pathways whose disruption is known to cause limb abnormalities, yet the limbs of Nipbl+/− mice develop relatively normally. We hypothesized that further impairment of candidate pathways might produce limb defects similar to those seen in CdLS, and performed genetic experiments to test this. Focusing on Sonic hedgehog (Shh), Bone morphogenetic protein (Bmp), and Hox gene pathways, we show that decreasing Bmp or Hox function (but not Shh function) enhances polydactyly in Nipbl+/− mice, and in some cases produces novel skeletal phenotypes. However, frank limb reductions, as are seen in a subset of individuals with CdLS, do not occur, suggesting that additional signaling and/or gene regulatory pathways are involved in producing such dramatic changes. PMID:27120109

  3. Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability.

    PubMed

    Greenbury, Sam F; Schaper, Steffen; Ahnert, Sebastian E; Louis, Ard A

    2016-03-01

    Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps-a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure-to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so

  4. Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability

    PubMed Central

    Greenbury, Sam F.; Schaper, Steffen; Ahnert, Sebastian E.; Louis, Ard A.

    2016-01-01

    Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps—a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure—to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so

  5. Genetically Determined Susceptibility to Tuberculosis in Mice Causally Involves Accelerated and Enhanced Recruitment of Granulocytes

    PubMed Central

    Keller, Christine; Hoffmann, Reinhard; Lang, Roland; Brandau, Sven; Hermann, Corinna; Ehlers, Stefan

    2006-01-01

    Classical twin studies and recent linkage analyses of African populations have revealed a potential involvement of host genetic factors in susceptibility or resistance to Mycobacterium tuberculosis infection. In order to identify the candidate genes involved and test their causal implication, we capitalized on the mouse model of tuberculosis, since inbred mouse strains also differ substantially in their susceptibility to infection. Two susceptible and two resistant mouse strains were aerogenically infected with 1,000 CFU of M. tuberculosis, and the regulation of gene expression was examined by Affymetrix GeneChip U74A array with total lung RNA 2 and 4 weeks postinfection. Four weeks after infection, 96 genes, many of which are involved in inflammatory cell recruitment and activation, were regulated in common. One hundred seven genes were differentially regulated in susceptible mouse strains, whereas 43 genes were differentially expressed only in resistant mice. Data mining revealed a bias towards the expression of genes involved in granulocyte pathophysiology in susceptible mice, such as an upregulation of those for the neutrophil chemoattractant LIX (CXCL5), interleukin 17 receptor, phosphoinositide kinase 3 delta, or gamma interferon-inducible protein 10. Following M. tuberculosis challenge in both airways or peritoneum, granulocytes were recruited significantly faster and at higher numbers in susceptible than in resistant mice. When granulocytes were efficiently depleted by either of two regimens at the onset of infection, only susceptible mice survived aerosol challenge with M. tuberculosis significantly longer than control mice. We conclude that initially enhanced recruitment of granulocytes contributes to susceptibility to tuberculosis. PMID:16790804

  6. Genetic enhancement of limb defects in a mouse model of Cornelia de Lange syndrome.

    PubMed

    Lopez-Burks, Martha E; Santos, Rosaysela; Kawauchi, Shimako; Calof, Anne L; Lander, Arthur D

    2016-06-01

    Cornelia de Lange Syndrome (CdLS) is characterized by a wide variety of structural and functional abnormalities in almost every organ system of the body. CdLS is now known to be caused by mutations that disrupt the function of the cohesin complex or its regulators, and studies of animal models and cell lines tell us that the effect of these mutations is to produce subtle yet pervasive dysregulation of gene expression. With many hundreds of mostly small gene expression changes occurring in every cell type and tissue, identifying the etiology of any particular birth defect is very challenging. Here we focus on limb abnormalities, which are commonly seen in CdLS. In the limb buds of the Nipbl-haploinsufficient mouse (Nipbl(+/-) mouse), a model for the most common form of CdLS, modest gene expression changes are observed in several candidate pathways whose disruption is known to cause limb abnormalities, yet the limbs of Nipbl(+/-) mice develop relatively normally. We hypothesized that further impairment of candidate pathways might produce limb defects similar to those seen in CdLS, and performed genetic experiments to test this. Focusing on Sonic hedgehog (Shh), Bone morphogenetic protein (Bmp), and Hox gene pathways, we show that decreasing Bmp or Hox function (but not Shh function) enhances polydactyly in Nipbl(+/-) mice, and in some cases produces novel skeletal phenotypes. However, frank limb reductions, as are seen in a subset of individuals with CdLS, do not occur, suggesting that additional signaling and/or gene regulatory pathways are involved in producing such dramatic changes. © 2016 Wiley Periodicals, Inc.

  7. Genetic enhancement of limb defects in a mouse model of Cornelia de Lange syndrome.

    PubMed

    Lopez-Burks, Martha E; Santos, Rosaysela; Kawauchi, Shimako; Calof, Anne L; Lander, Arthur D

    2016-06-01

    Cornelia de Lange Syndrome (CdLS) is characterized by a wide variety of structural and functional abnormalities in almost every organ system of the body. CdLS is now known to be caused by mutations that disrupt the function of the cohesin complex or its regulators, and studies of animal models and cell lines tell us that the effect of these mutations is to produce subtle yet pervasive dysregulation of gene expression. With many hundreds of mostly small gene expression changes occurring in every cell type and tissue, identifying the etiology of any particular birth defect is very challenging. Here we focus on limb abnormalities, which are commonly seen in CdLS. In the limb buds of the Nipbl-haploinsufficient mouse (Nipbl(+/-) mouse), a model for the most common form of CdLS, modest gene expression changes are observed in several candidate pathways whose disruption is known to cause limb abnormalities, yet the limbs of Nipbl(+/-) mice develop relatively normally. We hypothesized that further impairment of candidate pathways might produce limb defects similar to those seen in CdLS, and performed genetic experiments to test this. Focusing on Sonic hedgehog (Shh), Bone morphogenetic protein (Bmp), and Hox gene pathways, we show that decreasing Bmp or Hox function (but not Shh function) enhances polydactyly in Nipbl(+/-) mice, and in some cases produces novel skeletal phenotypes. However, frank limb reductions, as are seen in a subset of individuals with CdLS, do not occur, suggesting that additional signaling and/or gene regulatory pathways are involved in producing such dramatic changes. © 2016 Wiley Periodicals, Inc. PMID:27120109

  8. Genetically Engineered Immunomodulatory Streptococcus thermophilus Strains Producing Antioxidant Enzymes Exhibit Enhanced Anti-Inflammatory Activities

    PubMed Central

    del Carmen, Silvina; de Moreno de LeBlanc, Alejandra; Martin, Rebeca; Chain, Florian; Langella, Philippe; Bermúdez-Humarán, Luis G.

    2014-01-01

    The aims of this study were to develop strains of lactic acid bacteria (LAB) having both immunomodulatory and antioxidant properties and to evaluate their anti-inflammatory effects both in vitro, in different cellular models, and in vivo, in a mouse model of colitis. Different Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains were cocultured with primary cultures of mononuclear cells. Analysis of the pro- and anti-inflammatory cytokines secreted by these cells after coincubation with candidate bacteria revealed that L. delbrueckii subsp. bulgaricus CRL 864 and S. thermophilus CRL 807 display the highest anti-inflammatory profiles in vitro. Moreover, these results were confirmed in vivo by the determination of the cytokine profiles in large intestine samples of mice fed with these strains. S. thermophilus CRL 807 was then transformed with two different plasmids harboring the genes encoding catalase (CAT) or superoxide dismutase (SOD) antioxidant enzymes, and the anti-inflammatory effects of recombinant streptococci were evaluated in a mouse model of colitis induced by trinitrobenzenesulfonic acid (TNBS). Our results showed a decrease in weight loss, lower liver microbial translocation, lower macroscopic and microscopic damage scores, and modulation of the cytokine production in the large intestines of mice treated with either CAT- or SOD-producing streptococci compared to those in mice treated with the wild-type strain or control mice without any treatment. Furthermore, the greatest anti-inflammatory activity was observed in mice receiving a mixture of both CAT- and SOD-producing streptococci. The addition of L. delbrueckii subsp. bulgaricus CRL 864 to this mixture did not improve their beneficial effects. These findings show that genetically engineering a candidate bacterium (e.g., S. thermophilus CRL 807) with intrinsic immunomodulatory properties by introducing a gene expressing an antioxidant enzyme enhances its anti

  9. Adaptive allocation of attentional gain

    PubMed Central

    Scolari, Miranda; Serences, John T.

    2009-01-01

    Humans are adept at distinguishing between stimuli that are very similar, an ability that is particularly crucial when the outcome is of serious consequence (e.g. for a surgeon or air traffic controller). Traditionally, selective attention was thought to facilitate perception by increasing the gain of sensory neurons tuned to the defining features of a behaviorally relevant object (e.g. color, orientation, etc.). In contrast, recent mathematical models counter-intuitively suggest that in many cases attentional gain should be applied to neurons that are tuned away from relevant features, especially when discriminating highly similar stimuli. Here we used psychophysical methods to critically evaluate these ‘ideal observer’ models. The data demonstrate that attention enhances the gain of the most informative sensory neurons, even when these neurons are tuned away from the behaviorally relevant target feature. Moreover, the degree to which an individual adopted optimal attentional gain settings by the end of testing predicted success rates on a difficult visual discrimination task, as well as the amount of task improvement that occurred across repeated testing sessions (learning). Contrary to most traditional accounts, these observations suggest that the primary function of attentional gain is not simply to enhance the representation of target features, but to optimize performance on the current perceptual task. Additionally, individual differences in gain suggest that the operating characteristics of low-level attentional phenomena are not stable trait-like attributes and that variability in how attention is deployed may play an important role in determining perceptual abilities. PMID:19776279

  10. Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE

    PubMed Central

    Bekris, L.M.; Lutz, F.; Yu, C.E.

    2011-01-01

    Genetic variation within the apolipoprotein E gene (APOE) locus is associated with late-onset Alzheimer's disease risk and quantitative traits as well as apoE expression in multiple tissues. The aim of this investigation was to explore the influence of APOE locus cis-regulatory element enhancer region genetic variation on regional gene promoter activity. Luciferase reporter constructs containing haplotypes of APOE locus gene promoters; APOE, APOC1, and TOMM40, and regional putative enhancers; TOMM40 IVS2-4, TOMM40 IVS6 poly-T, as well as previously described enhancers; ME1, or BCR, were evaluated for their effects on luciferase activity in 3 human cell lines. Results of this investigation demonstrate that in SHSY5Y cells, the APOE promoter is significantly influenced by the TOMM40 IVS2-4 and ME1 and the TOMM40 promoter is significantly influenced by the TOMM40 IVS6 poly-T, ME1 and BCR. In HepG2 cells, theTOMM40 promoter is significantly influenced by all four enhancers, whereas the APOE promoter is not influenced by any of the enhancers. The main novel finding of this investigation was that multiple APOE locus cis-elements influence both APOE and TOMM40 promoter activity according to haplotype and cell type suggesting that a complex transcriptional regulatory structure modulates regional expression. PMID:22089642

  11. Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study.

    PubMed

    Zhang, Wei; Li, Qizhai

    2016-03-01

    The conventional method to examine whether genetic variants are associated with the ordinal traits is the proportional odds model. Such analyses are often conducted by assuming an additive genetic mode of inheritance. However, how the genetic variants influence the risk of occurrence of a disease is impossible to know in practice. Using an improper model might result in a low-power test, thus it reduces the probability of detecting the deleterious genetic markers. To address these concerns, we propose a two-phase procedure (TPP) for ordinal trait genetic studies. In the first phase, we used a linear combination to weight the Hardy-Weinberg equilibrium tests in case groups and formed an omnibus test to classify the genetic models. Then based on the chosen model, the corresponding score test was used to identify the associations. To control the false positive rate, we derived the joint distribution of the test used for selecting the genetic model and that used for identifying the associations. We also obtained the closed forms of two other robust tests, MAX3 and CHI2. Extensive computer simulations were carried out and the results showed that the true selection rates of genetic models are satisfactory and the proposed TPP is more robust than MAX3 and CHI2. Finally, we demonstrated the advantage of our proposed method by applying it to analyse the antibody reactivity to cyclic citrullinated peptides data.

  12. Incorporating Hardy-Weinberg Equilibrium Law to Enhance the Association Strength for Ordinal Trait Genetic Study.

    PubMed

    Zhang, Wei; Li, Qizhai

    2016-03-01

    The conventional method to examine whether genetic variants are associated with the ordinal traits is the proportional odds model. Such analyses are often conducted by assuming an additive genetic mode of inheritance. However, how the genetic variants influence the risk of occurrence of a disease is impossible to know in practice. Using an improper model might result in a low-power test, thus it reduces the probability of detecting the deleterious genetic markers. To address these concerns, we propose a two-phase procedure (TPP) for ordinal trait genetic studies. In the first phase, we used a linear combination to weight the Hardy-Weinberg equilibrium tests in case groups and formed an omnibus test to classify the genetic models. Then based on the chosen model, the corresponding score test was used to identify the associations. To control the false positive rate, we derived the joint distribution of the test used for selecting the genetic model and that used for identifying the associations. We also obtained the closed forms of two other robust tests, MAX3 and CHI2. Extensive computer simulations were carried out and the results showed that the true selection rates of genetic models are satisfactory and the proposed TPP is more robust than MAX3 and CHI2. Finally, we demonstrated the advantage of our proposed method by applying it to analyse the antibody reactivity to cyclic citrullinated peptides data. PMID:26626859

  13. Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer.

    PubMed

    van den Boogaard, Malou; Wong, L Y Elaine; Tessadori, Federico; Bakker, Martijn L; Dreizehnter, Lisa K; Wakker, Vincent; Bezzina, Connie R; 't Hoen, Peter A C; Bakkers, Jeroen; Barnett, Phil; Christoffels, Vincent M

    2012-07-01

    The contraction pattern of the heart relies on the activation and conduction of the electrical impulse. Perturbations of cardiac conduction have been associated with congenital and acquired arrhythmias as well as cardiac arrest. The pattern of conduction depends on the regulation of heterogeneous gene expression by key transcription factors and transcriptional enhancers. Here, we assessed the genome-wide occupation of conduction system-regulating transcription factors TBX3, NKX2-5, and GATA4 and of enhancer-associated coactivator p300 in the mouse heart, uncovering cardiac enhancers throughout the genome. Many of the enhancers colocalized with ion channel genes repressed by TBX3, including the clustered sodium channel genes Scn5a, essential for cardiac function, and Scn10a. We identified 2 enhancers in the Scn5a/Scn10a locus, which were regulated by TBX3 and its family member and activator, TBX5, and are functionally conserved in humans. We also provided evidence that a SNP in the SCN10A enhancer associated with alterations in cardiac conduction patterns in humans disrupts TBX3/TBX5 binding and reduces the cardiac activity of the enhancer in vivo. Thus, the identification of key regulatory elements for cardiac conduction helps to explain how genetic variants in noncoding regulatory DNA sequences influence the regulation of cardiac conduction and the predisposition for cardiac arrhythmias. PMID:22706305

  14. Fluorescent genetic barcoding in mammalian cells for enhanced multiplexing capabilities in flow cytometry.

    PubMed

    Smurthwaite, Cameron A; Hilton, Brett J; O'Hanlon, Ryan; Stolp, Zachary D; Hancock, Bryan M; Abbadessa, Darin; Stotland, Aleksandr; Sklar, Larry A; Wolkowicz, Roland

    2014-01-01

    The discovery of the green fluorescent protein from Aequorea victoria has revolutionized the field of cell and molecular biology. Since its discovery a growing panel of fluorescent proteins, fluorophores and fluorescent-coupled staining methodologies, have expanded the analytical capabilities of flow cytometry. Here, we exploit the power of genetic engineering to barcode individual cells with genes encoding fluorescent proteins. For genetic engineering, we utilize retroviral technology, which allows for the expression of ectopic genetic information in a stable manner in mammalian cells. We have genetically barcoded both adherent and nonadherent cells with different fluorescent proteins. Multiplexing power was increased by combining both the number of distinct fluorescent proteins, and the fluorescence intensity in each channel. Moreover, retroviral expression has proven to be stable for at least a 6-month period, which is critical for applications such as biological screens. We have shown the applicability of fluorescent barcoded multiplexing to cell-based assays that rely themselves on genetic barcoding, or on classical staining protocols. Fluorescent genetic barcoding gives the cell an inherited characteristic that distinguishes it from its counterpart. Once cell lines are developed, no further manipulation or staining is required, decreasing time, nonspecific background associated with staining protocols, and cost. The increasing number of discovered and/or engineered fluorescent proteins with unique absorbance/emission spectra, combined with the growing number of detection devices and lasers, increases multiplexing versatility, making fluorescent genetic barcoding a powerful tool for flow cytometry-based analysis.

  15. Accuracy of whole-genome prediction using a genetic architecture-enhanced variance-covariance matrix.

    PubMed

    Zhang, Zhe; Erbe, Malena; He, Jinlong; Ober, Ulrike; Gao, Ning; Zhang, Hao; Simianer, Henner; Li, Jiaqi

    2015-02-09

    Obtaining accurate predictions of unobserved genetic or phenotypic values for complex traits in animal, plant, and human populations is possible through whole-genome prediction (WGP), a combined analysis of genotypic and phenotypic data. Because the underlying genetic architecture of the trait of interest is an important factor affecting model selection, we propose a new strategy, termed BLUP|GA (BLUP-given genetic architecture), which can use genetic architecture information within the dataset at hand rather than from public sources. This is achieved by using a trait-specific covariance matrix ( T: ), which is a weighted sum of a genetic architecture part ( S: matrix) and the realized relationship matrix ( G: ). The algorithm of BLUP|GA (BLUP-given genetic architecture) is provided and illustrated with real and simulated datasets. Predictive ability of BLUP|GA was validated with three model traits in a dairy cattle dataset and 11 traits in three public datasets with a variety of genetic architectures and compared with GBLUP and other approaches. Results show that BLUP|GA outperformed GBLUP in 20 of 21 scenarios in the dairy cattle dataset and outperformed GBLUP, BayesA, and BayesB in 12 of 13 traits in the analyzed public datasets. Further analyses showed that the difference of accuracies for BLUP|GA and GBLUP significantly correlate with the distance between the T: and G: matrices. The new strategy applied in BLUP|GA is a favorable and flexible alternative to the standard GBLUP model, allowing to account for the genetic architecture of the quantitative trait under consideration when necessary. This feature is mainly due to the increased similarity between the trait-specific relationship matrix ( T: matrix) and the genetic relationship matrix at unobserved causal loci. Applying BLUP|GA in WGP would ease the burden of model selection.

  16. Accuracy of Whole-Genome Prediction Using a Genetic Architecture-Enhanced Variance-Covariance Matrix

    PubMed Central

    Zhang, Zhe; Erbe, Malena; He, Jinlong; Ober, Ulrike; Gao, Ning; Zhang, Hao; Simianer, Henner; Li, Jiaqi

    2015-01-01

    Obtaining accurate predictions of unobserved genetic or phenotypic values for complex traits in animal, plant, and human populations is possible through whole-genome prediction (WGP), a combined analysis of genotypic and phenotypic data. Because the underlying genetic architecture of the trait of interest is an important factor affecting model selection, we propose a new strategy, termed BLUP|GA (BLUP-given genetic architecture), which can use genetic architecture information within the dataset at hand rather than from public sources. This is achieved by using a trait-specific covariance matrix (T), which is a weighted sum of a genetic architecture part (S matrix) and the realized relationship matrix (G). The algorithm of BLUP|GA (BLUP-given genetic architecture) is provided and illustrated with real and simulated datasets. Predictive ability of BLUP|GA was validated with three model traits in a dairy cattle dataset and 11 traits in three public datasets with a variety of genetic architectures and compared with GBLUP and other approaches. Results show that BLUP|GA outperformed GBLUP in 20 of 21 scenarios in the dairy cattle dataset and outperformed GBLUP, BayesA, and BayesB in 12 of 13 traits in the analyzed public datasets. Further analyses showed that the difference of accuracies for BLUP|GA and GBLUP significantly correlate with the distance between the T and G matrices. The new strategy applied in BLUP|GA is a favorable and flexible alternative to the standard GBLUP model, allowing to account for the genetic architecture of the quantitative trait under consideration when necessary. This feature is mainly due to the increased similarity between the trait-specific relationship matrix (T matrix) and the genetic relationship matrix at unobserved causal loci. Applying BLUP|GA in WGP would ease the burden of model selection. PMID:25670771

  17. Genetic Transformation of Artemisia carvifolia Buch with rol Genes Enhances Artemisinin Accumulation

    PubMed Central

    Dilshad, Erum; Cusido, Rosa Maria; Estrada, Karla Ramirez; Bonfill, Mercedes; Mirza, Bushra

    2015-01-01

    The potent antimalarial drug artemisinin has a high cost, since its only viable source to date is Artemisia annua (0.01–0.8% DW). There is therefore an urgent need to design new strategies to increase its production or to find alternative sources. In the current study, Artemisia carvifolia Buch was selected with the aim of detecting artemisinin and then enhancing the production of the target compound and its derivatives. These metabolites were determined by LC-MS in the shoots of A. carvifolia wild type plants at the following concentrations: artemisinin (8μg/g), artesunate (2.24μg/g), dihydroartemisinin (13.6μg/g) and artemether (12.8μg/g). Genetic transformation of A. carvifolia was carried out with Agrobacterium tumefaciens GV3101 harboring the rol B and rol C genes. Artemisinin content increased 3-7-fold in transgenics bearing the rol B gene, and 2.3-6-fold in those with the rol C gene. A similar pattern was observed for artemisinin analogues. The dynamics of artemisinin content in transgenics and wild type A.carvifolia was also correlated with the expression of genes involved in its biosynthesis. Real time qPCR analysis revealed the differential expression of genes involved in artemisinin biosynthesis, i.e. those encoding amorpha-4, 11 diene synthase (ADS), cytochrome P450 (CYP71AV1), and aldehyde dehydrogenase 1 (ALDH1), with a relatively higher transcript level found in transgenics than in the wild type plant. Also, the gene related to trichome development and sesquiterpenoid biosynthesis (TFAR1) showed an altered expression in the transgenics compared to wild type A.carvifolia, which was in accordance with the trichome density of the respective plants. The trichome index was significantly higher in the rol B and rol C gene-expressing transgenics with an increased production of artemisinin, thereby demonstrating that the rol genes are effective inducers of plant secondary metabolism. PMID:26444558

  18. Genetic Transformation of Artemisia carvifolia Buch with rol Genes Enhances Artemisinin Accumulation.

    PubMed

    Dilshad, Erum; Cusido, Rosa Maria; Ramirez Estrada, Karla; Bonfill, Mercedes; Mirza, Bushra

    2015-01-01

    The potent antimalarial drug artemisinin has a high cost, since its only viable source to date is Artemisia annua (0.01-0.8% DW). There is therefore an urgent need to design new strategies to increase its production or to find alternative sources. In the current study, Artemisia carvifolia Buch was selected with the aim of detecting artemisinin and then enhancing the production of the target compound and its derivatives. These metabolites were determined by LC-MS in the shoots of A. carvifolia wild type plants at the following concentrations: artemisinin (8μg/g), artesunate (2.24μg/g), dihydroartemisinin (13.6μg/g) and artemether (12.8μg/g). Genetic transformation of A. carvifolia was carried out with Agrobacterium tumefaciens GV3101 harboring the rol B and rol C genes. Artemisinin content increased 3-7-fold in transgenics bearing the rol B gene, and 2.3-6-fold in those with the rol C gene. A similar pattern was observed for artemisinin analogues. The dynamics of artemisinin content in transgenics and wild type A.carvifolia was also correlated with the expression of genes involved in its biosynthesis. Real time qPCR analysis revealed the differential expression of genes involved in artemisinin biosynthesis, i.e. those encoding amorpha-4, 11 diene synthase (ADS), cytochrome P450 (CYP71AV1), and aldehyde dehydrogenase 1 (ALDH1), with a relatively higher transcript level found in transgenics than in the wild type plant. Also, the gene related to trichome development and sesquiterpenoid biosynthesis (TFAR1) showed an altered expression in the transgenics compared to wild type A.carvifolia, which was in accordance with the trichome density of the respective plants. The trichome index was significantly higher in the rol B and rol C gene-expressing transgenics with an increased production of artemisinin, thereby demonstrating that the rol genes are effective inducers of plant secondary metabolism. PMID:26444558

  19. Incorporation of genetic technologies associated with applied reproductive technologies to enhance world food production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Animal breeding and reproductive physiology have been closely related throughout the history of animal production science. Artificial insemination provides the best method of increasing the influence of sires with superior genetics to improve production traits. Multiple ovulation embryo transfer (MO...

  20. Expression of recombinant human α-lactalbumin in milk of transgenic cloned pigs is sufficient to enhance intestinal growth and weight gain of suckling piglets.

    PubMed

    Ma, Jin; Li, Qiuyan; Li, Yan; Wen, Xiao; Li, Zhiyuan; Zhang, Zaihu; Zhang, Jiuming; Yu, Zhengquan; Li, Ning

    2016-06-10

    Human α-lactalbumin (HLA) has very high nutritional value and important physiological functions during the neonatal period. The peptides derived from HLA provide diverse health benefits including antimicrobial, antiviral, immune-modulating, and antihypertensive effects. Thus, it is worth investigating the effects on offspring development of increasing HLA in milk. In this study, we found that recombinant human α-lactalbumin (rHLA) exhibits efficient inhibition of dipeptidyl peptidase-IV (DPP-IV) activity in an in vitro simulated gastrointestinal digestion system. Using a BAC clone containing the complete HLA gene as a candidate vector, we generated two lines of transgenic cloned sows via somatic cell nuclear transfer that over-expressed rHLA. The average concentrations of rHLA in milk from the two lines of transgenic cloned sows were 2.24 ± 0.71 mg/ml and 2.67 ± 1.29 mg/ml. The feeding experiments revealed that rHLA represses dipeptidyl peptidase-IV (DPP-IV) activity in vivo. Furthermore, the piglets reared by rHLA transgenic cloned sows exhibit better performance in gain of body weight and intestine growth than the control piglets reared by non-transgenic sows. Therefore, these findings indicate that rHLA could serve as a natural precursor for a DPP-IV inhibitor, and the transgenic technology that produced the over-expression of rHLA could be a useful method for pig breeders to improve lactation performance.

  1. Expression of recombinant human α-lactalbumin in milk of transgenic cloned pigs is sufficient to enhance intestinal growth and weight gain of suckling piglets.

    PubMed

    Ma, Jin; Li, Qiuyan; Li, Yan; Wen, Xiao; Li, Zhiyuan; Zhang, Zaihu; Zhang, Jiuming; Yu, Zhengquan; Li, Ning

    2016-06-10

    Human α-lactalbumin (HLA) has very high nutritional value and important physiological functions during the neonatal period. The peptides derived from HLA provide diverse health benefits including antimicrobial, antiviral, immune-modulating, and antihypertensive effects. Thus, it is worth investigating the effects on offspring development of increasing HLA in milk. In this study, we found that recombinant human α-lactalbumin (rHLA) exhibits efficient inhibition of dipeptidyl peptidase-IV (DPP-IV) activity in an in vitro simulated gastrointestinal digestion system. Using a BAC clone containing the complete HLA gene as a candidate vector, we generated two lines of transgenic cloned sows via somatic cell nuclear transfer that over-expressed rHLA. The average concentrations of rHLA in milk from the two lines of transgenic cloned sows were 2.24 ± 0.71 mg/ml and 2.67 ± 1.29 mg/ml. The feeding experiments revealed that rHLA represses dipeptidyl peptidase-IV (DPP-IV) activity in vivo. Furthermore, the piglets reared by rHLA transgenic cloned sows exhibit better performance in gain of body weight and intestine growth than the control piglets reared by non-transgenic sows. Therefore, these findings indicate that rHLA could serve as a natural precursor for a DPP-IV inhibitor, and the transgenic technology that produced the over-expression of rHLA could be a useful method for pig breeders to improve lactation performance. PMID:26899869

  2. Welfare Gains from Financial Liberalization

    PubMed Central

    Townsend, Robert M.; Ueda, Kenichi

    2010-01-01

    Financial liberalization has been a controversial issue, as empirical evidence for growth enhancing effects is mixed. Here, we find sizable welfare gains from liberalization (cost to repression), though the gain in economic growth is ambiguous. We take the view that financial liberalization is a government policy that alters the path of financial deepening, while financial deepening is endogenously chosen by agents given a policy and occurs in transition towards a distant steady state. This history-dependent view necessitates the use of simulation analysis based on a growth model. Our application is a specific episode: Thailand from 1976 to 1996. PMID:20806055

  3. Impact of demographic, genetic, and bioimpedance factors on gestational weight gain and birth weight in a Romanian population: A cross-sectional study in mothers and their newborns: the Monebo study (STROBE-compliant article).

    PubMed

    Mărginean, Claudiu; Mărginean, Cristina Oana; Bănescu, Claudia; Meliţ, Lorena; Tripon, Florin; Iancu, Mihaela

    2016-07-01

    The present study had 2 objectives, first, to investigate possible relationships between increased gestational weight gain and demographic, clinical, paraclinical, genetic, and bioimpedance (BIA) characteristics of Romanian mothers, and second, to identify the influence of predictors (maternal and newborns characteristics) on our outcome birth weight (BW).We performed a cross-sectional study on 309 mothers and 309 newborns from Romania, divided into 2 groups: Group I-141 mothers with high gestational weight gain (GWG) and Group II-168 mothers with normal GWG, that is, control group.The groups were evaluated regarding demographic, anthropometric (body mass index [BMI], middle upper arm circumference, tricipital skinfold thickness, weight, height [H]), clinical, paraclinical, genetic (interleukin 6 [IL-6]: IL-6 -174G>C and IL-6 -572C>G gene polymorphisms), and BIA parameters.We noticed that fat mass (FM), muscle mass (MM), bone mass (BM), total body water (TBW), basal metabolism rate (BMR) and metabolic age (P < 0.001), anthropometric parameters (middle upper arm circumference, tricipital skinfold thickness; P < 0.001/P = 0.001) and hypertension (odds ratio = 4.65, 95% confidence interval: 1.27-17.03) were higher in mothers with high GWG. BW was positively correlated with mothers' FM (P < 0.001), TBW (P = 0.001), BMR (P = 0.02), while smoking was negatively correlated with BW (P = 0.04). Variant genotype (GG+GC) of the IL-6 -572C>G polymorphism was higher in the control group (P = 0.042).We observed that high GWG may be an important predictor factor for the afterward BW, being positively correlated with FM, TBW, BMR, metabolic age of the mothers, and negatively with the mother's smoking status. Variant genotype (GG+GC) of the IL-6 -572C>G gene polymorphism is a protector factor against obesity in mothers. All the variables considered explained 14.50% of the outcome variance. PMID:27399105

  4. High-gain 1.3  μm GaInNAs semiconductor optical amplifier with enhanced temperature stability for all-optical signal processing at 10  Gb/s.

    PubMed

    Fitsios, D; Giannoulis, G; Korpijärvi, V-M; Viheriälä, J; Laakso, A; Iliadis, N; Dris, S; Spyropoulou, M; Avramopoulos, H; Kanellos, G T; Pleros, N; Guina, M

    2015-01-01

    We report on the complete experimental evaluation of a GaInNAs/GaAs (dilute nitride) semiconductor optical amplifier that operates at 1.3 μm and exhibits 28 dB gain and a gain recovery time of 100 ps. Successful wavelength conversion operation is demonstrated using pseudorandom bit sequence 27-1 non-return-to-zero bit streams at 5 and 10  Gb/s, yielding error-free performance and showing feasibility for implementation in various signal processing functionalities. The operational credentials of the device are analyzed in various operational regimes, while its nonlinear performance is examined in terms of four-wave mixing. Moreover, characterization results reveal enhanced temperature stability with almost no gain variation around the 1320 nm region for a temperature range from 20°C to 50°C. The operational characteristics of the device, along with the cost and energy benefits of dilute nitride technology, make it very attractive for application in optical access networks and dense photonic integrated circuits. PMID:25967005

  5. High-gain 1.3  μm GaInNAs semiconductor optical amplifier with enhanced temperature stability for all-optical signal processing at 10  Gb/s.

    PubMed

    Fitsios, D; Giannoulis, G; Korpijärvi, V-M; Viheriälä, J; Laakso, A; Iliadis, N; Dris, S; Spyropoulou, M; Avramopoulos, H; Kanellos, G T; Pleros, N; Guina, M

    2015-01-01

    We report on the complete experimental evaluation of a GaInNAs/GaAs (dilute nitride) semiconductor optical amplifier that operates at 1.3 μm and exhibits 28 dB gain and a gain recovery time of 100 ps. Successful wavelength conversion operation is demonstrated using pseudorandom bit sequence 27-1 non-return-to-zero bit streams at 5 and 10  Gb/s, yielding error-free performance and showing feasibility for implementation in various signal processing functionalities. The operational credentials of the device are analyzed in various operational regimes, while its nonlinear performance is examined in terms of four-wave mixing. Moreover, characterization results reveal enhanced temperature stability with almost no gain variation around the 1320 nm region for a temperature range from 20°C to 50°C. The operational characteristics of the device, along with the cost and energy benefits of dilute nitride technology, make it very attractive for application in optical access networks and dense photonic integrated circuits.

  6. Weight gain - unintentional

    MedlinePlus

    ... as much as 25 to 30 pounds. This weight gain is not simply due to eating more. ... or a dietitian about how to make a healthy eating plan and set ... be causing the weight gain without talking with your provider.

  7. Improved adherence with PTH(1–84) in an extension trial for 24 months results in enhanced BMD gains in the treatment of postmenopausal women with osteoporosis

    PubMed Central

    Bilezikian, J. P.; Greenspan, S. L.; Wüster, C.; Muñoz-Torres, M.; Bone, H. G.; Rosen, C. J.; Andersen, H. S.; Hanley, D. A.

    2016-01-01

    Summary The purpose of this study is to examine the effect of PTH(1–84) treatment over 24 months followed by 12 months discontinuation on BMD, bone turnover markers, fractures and the impact of adherence on efficacy. Introduction There is limited information about the effect of PTH(1-84) after 18 months and limited data about the impact of compliance on response to anabolic therapy. Methods Seven hundred and eighty-one subjects who received active PTH(1–84) in the Treatment of Osteoporosis with Parathyroid hormone trial for approximately 18 months were entered into a 6-month open-label extension. Thereafter, they were followed for 12 additional months after discontinuation of treatment. Endpoints examined included changes in BMD and biochemical markers. Results PTH(1–84) treatment over 24 months increased BMD at the lumbar spine by 6.8 % above baseline (p < 0.05). The total corresponding BMD increases at the hip and femoral neck were 1.1 and 2.2% above baseline. Larger increases in spine BMD were observed in participants with ≥80 % adherence to daily injections of PTH(1–84) (8.3% in adherent vs 4.9 % in poorly adherent patients). Total hip BMD gains were 1.7 % in adherent vs 0.6 % in poorly adherent participants. Markers of bone turnover (BSAP and NTx) peaked 6 months after starting PTH(1–84) treatment and declined slowly but remained above baseline at 24 months. After discontinuation of PTH(1–84) treatment (at 24 months), bone turnover markers returned to near baseline levels by 30 months. The adherent group sustained significantly fewer fractures than the poorly adherent group. Conclusions PTH(1–84) treatment over 24 months results in continued increases in lumbar spine BMD. Adherence to treatment with PTH(1–84) for up to 24 months is also associated with greater efficacy. PMID:22930240

  8. Genetic analysis of stress responses in soil bacteria for enhanced bioremediation of mixed contaminants. 1998 annual progress report

    SciTech Connect

    Wong, K.K.

    1998-06-01

    'To realize the full potential of bioremediation, the individual bacterial responses to the stresses (lack of nutrients or oxygen; mixed pollutants) encountered at contaminated sites must be understood. This information can then be extrapolated to field applications using indigenous bacteria or genetically engineered micro-organisms. Studying bacterial response to stresses presents an opportunity for improving bioremediation strategies, both with indigenous populations and genetically engineered microbes, and should contribute to environmental management and restoration goals. Enhancing in-situ removal of hazardous wastes by stimulating the growth of indigenous bacteria with nutrients has been demonstrated. But how much and how often to apply these supplements has been difficult to determine, and controlled and reproducible degradation of pollutants in the environment has not yet been achieved. As of May 31st 1998, this report summarizes work after 17 months of a 36 month project.'

  9. Genetically determined resistance to listeriosis is associated with increased accumulation of inflammatory neutrophils and macrophages which have enhanced listericidal activity.

    PubMed Central

    Czuprynski, C J; Canono, B P; Henson, P M; Campbell, P A

    1985-01-01

    The C57BL/6 and A/J inbred strains of mice differ markedly in their resistance to the facultative intracellular bacterium Listeria monocytogenes. One possible explanation for this genetically determined resistance is that phagocytes from Listeria-resistant strains of mice can kill L. monocytogenes more effectively than phagocytes from Listeria-susceptible strains of mice. We report here that inflammatory neutrophils and macrophages from Listeria-resistant mice (C57BL/6) exhibit a slight but significantly enhanced ability to kill L. monocytogenes in vitro as compared to inflammatory phagocytes from Listeria-susceptible mice (A/J). More importantly, however, Listeria-resistant mice recruited more inflammatory neutrophils and macrophages to the peritoneal cavity in response to i.p. injection of heat-killed Listeria than did Listeria-susceptible mice. These data suggest that genetically determined resistance to listeriosis is dependent on the enhanced inflammatory responsiveness of Listeria-resistant mice. Further support for this hypothesis was provided by experiments in which the passive transfer to A/J mice (C5-deficient) of plasma from C57BL/6 mice (C5-sufficient) enhanced the ability of the recipient A/J mice both to recruit inflammatory neutrophils to the peritoneal cavity in response to i.p. injection of heat-killed Listeria, and to clear L. monocytogenes from the spleen after a sublethal challenge of viable Listeria. PMID:4018836

  10. Central Gain Control in Tinnitus and Hyperacusis

    PubMed Central

    Auerbach, Benjamin D.; Rodrigues, Paulo V.; Salvi, Richard J.

    2014-01-01

    Sensorineural hearing loss induced by noise or ototoxic drug exposure reduces the neural activity transmitted from the cochlea to the central auditory system. Despite a reduced cochlear output, neural activity from more central auditory structures is paradoxically enhanced at suprathreshold intensities. This compensatory increase in the central auditory activity in response to the loss of sensory input is referred to as central gain enhancement. Enhanced central gain is hypothesized to be a potential mechanism that gives rise to hyperacusis and tinnitus, two debilitating auditory perceptual disorders that afflict millions of individuals. This review will examine the evidence for gain enhancement in the central auditory system in response to cochlear damage. Further, it will address the potential cellular and molecular mechanisms underlying this enhancement and discuss the contribution of central gain enhancement to tinnitus and hyperacusis. Current evidence suggests that multiple mechanisms with distinct temporal and spectral profiles are likely to contribute to central gain enhancement. Dissecting the contributions of these different mechanisms at different levels of the central auditory system is essential for elucidating the role of central gain enhancement in tinnitus and hyperacusis and, most importantly, the development of novel treatments for these disorders. PMID:25386157

  11. Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery.

    PubMed

    Scott, Eric M; Halees, Anason; Itan, Yuval; Spencer, Emily G; He, Yupeng; Azab, Mostafa Abdellateef; Gabriel, Stacey B; Belkadi, Aziz; Boisson, Bertrand; Abel, Laurent; Clark, Andrew G; Alkuraya, Fowzan S; Casanova, Jean-Laurent; Gleeson, Joseph G

    2016-09-01

    The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia, has resulted in an elevated burden of recessive disease. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized 'genetic purging'. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics. PMID:27428751

  12. Characterization of Greater Middle Eastern genetic variation for enhanced disease gene discovery.

    PubMed

    Scott, Eric M; Halees, Anason; Itan, Yuval; Spencer, Emily G; He, Yupeng; Azab, Mostafa Abdellateef; Gabriel, Stacey B; Belkadi, Aziz; Boisson, Bertrand; Abel, Laurent; Clark, Andrew G; Alkuraya, Fowzan S; Casanova, Jean-Laurent; Gleeson, Joseph G

    2016-09-01

    The Greater Middle East (GME) has been a central hub of human migration and population admixture. The tradition of consanguinity, variably practiced in the Persian Gulf region, North Africa, and Central Asia, has resulted in an elevated burden of recessive disease. Here we generated a whole-exome GME variome from 1,111 unrelated subjects. We detected substantial diversity and admixture in continental and subregional populations, corresponding to several ancient founder populations with little evidence of bottlenecks. Measured consanguinity rates were an order of magnitude above those in other sampled populations, and the GME population exhibited an increased burden of runs of homozygosity (ROHs) but showed no evidence for reduced burden of deleterious variation due to classically theorized 'genetic purging'. Applying this database to unsolved recessive conditions in the GME population reduced the number of potential disease-causing variants by four- to sevenfold. These results show variegated genetic architecture in GME populations and support future human genetic discoveries in Mendelian and population genetics.

  13. Expression of human beta defensin 4 in genetically modified keratinocytes enhances antimicrobial activity.

    PubMed

    Smiley, Andrea K; Gardner, Jason; Klingenberg, Jennifer M; Neely, Alice N; Supp, Dorothy M

    2007-01-01

    Defensins are cationic peptides of the innate host defense system with antimicrobial activity against many of the microorganisms commonly found in burn units. Beta defensins are variably expressed in the epithelia of skin and other organs. Human beta defensin 4 reportedly has antimicrobial activity against Pseudomonas aeruginosa and is not normally expressed in intact skin. Genetic modification was used to ectopically express human beta defensin 4 in cultured primary epidermal keratinocytes. Keratinocytes expressing human beta defensin 4 showed significantly elevated antimicrobial activity against clinically-isolated P. aeruginosa compared with controls. These results suggest that genetic modification of keratinocytes can increase their resistance to microbial contamination. Bioengineered skin replacements containing human beta defensin 4-modified keratinocytes may be useful for transplantation to contaminated burn wounds.

  14. [Genetic variance in Vicia cracca cenopopulation inhabiting site with enhanced level of natural radioactivity].

    PubMed

    Evseeva, T I; Maĭstrenko, T A; Geras'kin, S A; Belykh, E S

    2007-01-01

    The contribution of low dose rate ionizing radiation into genetic variance in Vicia cracca L. cenopopulation inhabiting high natural background territories more then 40 years quantity estimation was made. Incorporated in the aboveground parts of Vicia cracca 230Th determine both the level of intrapopulation genetic variance and the adaptive possibility. Significantly increased frequency of double fragments was revealed in root tips of plants inhabiting all experimental plots. This type of damages depends on 226Ra concentrations accumulated in the aboveground parts of Vicia cracca. External irradiation influences the embryonic lethals. It was found that the relative contribution on mutagenesis induced by ionizing radiation was significant and was about 3-5% of the total variance.

  15. An enhanced algorithm for multiple sequence alignment of protein sequences using genetic algorithm

    PubMed Central

    Kumar, Manish

    2015-01-01

    One of the most fundamental operations in biological sequence analysis is multiple sequence alignment (MSA). The basic of multiple sequence alignment problems is to determine the most biologically plausible alignments of protein or DNA sequences. In this paper, an alignment method using genetic algorithm for multiple sequence alignment has been proposed. Two different genetic operators mainly crossover and mutation were defined and implemented with the proposed method in order to know the population evolution and quality of the sequence aligned. The proposed method is assessed with protein benchmark dataset, e.g., BALIBASE, by comparing the obtained results to those obtained with other alignment algorithms, e.g., SAGA, RBT-GA, PRRP, HMMT, SB-PIMA, CLUSTALX, CLUSTAL W, DIALIGN and PILEUP8 etc. Experiments on a wide range of data have shown that the proposed algorithm is much better (it terms of score) than previously proposed algorithms in its ability to achieve high alignment quality. PMID:27065770

  16. Can genetic risk information enhance motivation for smoking cessation? An analogue study.

    PubMed

    Wright, Alison J; French, David P; Weinman, John; Marteau, Theresa M

    2006-11-01

    Protection motivation theory and the extended parallel processing model are used to predict the motivational impact of information regarding a genetic susceptibility to heart disease. One hundred ninety-eight smokers read 1 of 3 vignettes: gene positive, gene negative, or standard smoking risk information. Analyses examined whether the impact of type of risk information was moderated by smokers' self-efficacy (SE) levels. Key outcomes were intention to quit and intention to attend an information session about quitting. There were significant main effects of SE and of receiving gene-positive risk information on intentions to quit. There was a significant Risk x SE interaction on intentions to attend an information session. SE was not associated with intentions to attend the information session for smokers in the gene-positive group. Intentions to attend the session were negatively associated with SE for smokers in the lower risk groups. Implications for using genetic risk information to motivate smoking cessation are discussed.

  17. Gain weighted eigenspace assignment

    NASA Technical Reports Server (NTRS)

    Davidson, John B.; Andrisani, Dominick, II

    1994-01-01

    This report presents the development of the gain weighted eigenspace assignment methodology. This provides a designer with a systematic methodology for trading off eigenvector placement versus gain magnitudes, while still maintaining desired closed-loop eigenvalue locations. This is accomplished by forming a cost function composed of a scalar measure of error between desired and achievable eigenvectors and a scalar measure of gain magnitude, determining analytical expressions for the gradients, and solving for the optimal solution by numerical iteration. For this development the scalar measure of gain magnitude is chosen to be a weighted sum of the squares of all the individual elements of the feedback gain matrix. An example is presented to demonstrate the method. In this example, solutions yielding achievable eigenvectors close to the desired eigenvectors are obtained with significant reductions in gain magnitude compared to a solution obtained using a previously developed eigenspace (eigenstructure) assignment method.

  18. Genetic manipulation of iron biomineralization enhances MR relaxivity in a ferritin-M6A chimeric complex

    PubMed Central

    Radoul, Marina; Lewin, Limor; Cohen, Batya; Oren, Roni; Popov, Stanislav; Davidov, Geula; Vandsburger, Moriel H.; Harmelin, Alon; Bitton, Ronit; Greneche, Jean-Marc; Neeman, Michal; Zarivach, Raz

    2016-01-01

    Ferritin has gained significant attention as a potential reporter gene for in vivo imaging by magnetic resonance imaging (MRI). However, due to the ferritin ferrihydrite core, the relaxivity and sensitivity for detection of native ferritin is relatively low. We report here on a novel chimeric magneto-ferritin reporter gene – ferritin-M6A – in which the magnetite binding peptide from the magnetotactic bacteria magnetosome-associated Mms6 protein was fused to the C-terminal of murine h-ferritin. Biophysical experiments showed that purified ferritin-M6A assembled into a stable protein cage with the M6A protruding into the cage core, enabling magnetite biomineralisation. Ferritin-M6A-expressing C6-glioma cells showed enhanced (per iron) r2 relaxivity. MRI in vivo studies of ferritin-M6A-expressing tumour xenografts showed enhanced R2 relaxation rate in the central hypoxic region of the tumours. Such enhanced relaxivity would increase the sensitivity of ferritin as a reporter gene for non-invasive in vivo MRI-monitoring of cell delivery and differentiation in cellular or gene-based therapies. PMID:27211820

  19. Plasmonics: Loss and gain

    NASA Astrophysics Data System (ADS)

    Oulton, Rupert F.

    2012-04-01

    Providing sufficient gain to overcome loss remains a fundamental challenge for light amplification in miniaturized plasmonic devices. Ongoing research gives hope for a cautious but optimistic outlook.

  20. CRISPR/Cas9 system as an innovative genetic engineering tool: Enhancements in sequence specificity and delivery methods.

    PubMed

    Jo, Young-Il; Suresh, Bharathi; Kim, Hyongbum; Ramakrishna, Suresh

    2015-12-01

    While human gene therapy has gained significant attention for its therapeutic promise, CRISPR/Cas9 technology has made a breakthrough as an efficient genome editing tool by emulating prokaryotic immune defense mechanisms. Although many studies have found that CRISPR/Cas9 technology is more efficient, specific and manipulable than previous generations of gene editing tools, it can be further improved by elevating its overall efficiency in a higher frequency of genome modifications and reducing its off-target effects. Here, we review the development of CRISPR/Cas9 technology, focusing on enhancement of its sequence specificity, reduction of off-target effects and delivery systems. Moreover, we describe recent successful applications of CRISPR/Cas9 technology in laboratory and clinical studies.

  1. CRISPR/Cas9 system as an innovative genetic engineering tool: Enhancements in sequence specificity and delivery methods.

    PubMed

    Jo, Young-Il; Suresh, Bharathi; Kim, Hyongbum; Ramakrishna, Suresh

    2015-12-01

    While human gene therapy has gained significant attention for its therapeutic promise, CRISPR/Cas9 technology has made a breakthrough as an efficient genome editing tool by emulating prokaryotic immune defense mechanisms. Although many studies have found that CRISPR/Cas9 technology is more efficient, specific and manipulable than previous generations of gene editing tools, it can be further improved by elevating its overall efficiency in a higher frequency of genome modifications and reducing its off-target effects. Here, we review the development of CRISPR/Cas9 technology, focusing on enhancement of its sequence specificity, reduction of off-target effects and delivery systems. Moreover, we describe recent successful applications of CRISPR/Cas9 technology in laboratory and clinical studies. PMID:26434948

  2. Enhanced Genetic Analysis of Single Human Bioparticles Recovered by Simplified Micromanipulation from Forensic ‘Touch DNA’ Evidence

    PubMed Central

    Farash, Katherine; Hanson, Erin K.; Ballantyne, Jack

    2015-01-01

    DNA profiles can be obtained from ‘touch DNA’ evidence, which comprises microscopic traces of human biological material. Current methods for the recovery of trace DNA employ cotton swabs or adhesive tape to sample an area of interest. However, such a ‘blind-swabbing’ approach will co-sample cellular material from the different individuals, even if the individuals’ cells are located in geographically distinct locations on the item. Thus, some of the DNA mixtures encountered in touch DNA samples are artificially created by the swabbing itself. In some instances, a victim’s DNA may be found in significant excess thus masking any potential perpetrator’s DNA. In order to circumvent the challenges with standard recovery and analysis methods, we have developed a lower cost, ‘smart analysis’ method that results in enhanced genetic analysis of touch DNA evidence. We describe an optimized and efficient micromanipulation recovery strategy for the collection of bio-particles present in touch DNA samples, as well as an enhanced amplification strategy involving a one-step 5 µl microvolume lysis/STR amplification to permit the recovery of STR profiles from the bio-particle donor(s). The use of individual or few (i.e., “clumps”) bioparticles results in the ability to obtain single source profiles. These procedures represent alternative enhanced techniques for the isolation and analysis of single bioparticles from forensic touch DNA evidence. While not necessary in every forensic investigation, the method could be highly beneficial for the recovery of a single source perpetrator DNA profile in cases involving physical assault (e.g., strangulation) that may not be possible using standard analysis techniques. Additionally, the strategies developed here offer an opportunity to obtain genetic information at the single cell level from a variety of other non-forensic trace biological material. PMID:25867046

  3. Invention and Gain Analysis.

    ERIC Educational Resources Information Center

    Weber, Robert J.; Dixon, Stacey

    1989-01-01

    Gain analysis is applied to the invention of the sewing needle as well as different sewing implements and modes of sewing. The analysis includes a two-subject experiment. To validate the generality of gain heuristics and underlying switching processes, the invention of the assembly line is also analyzed. (TJH)

  4. An Enhanced Genetic Approach to Composing Cooperative Learning Groups for Multiple Grouping Criteria

    ERIC Educational Resources Information Center

    Hwang, Gwo-Jen; Yin, Peng-Yeng; Hwang, Chi-Wei; Tsai, Chin-Chung

    2008-01-01

    Cooperative learning is known to be an effective educational strategy in enhancing the learning performance of students. The goal of a cooperative learning group is to maximize all members' learning efficacy. This is accomplished via promoting each other's success, through assisting, sharing, mentoring, explaining, and encouragement. To achieve…

  5. Increasing public involvement in enriching our fish stocks through genetic enhancement.

    PubMed

    Halvorson, H O; Quezada, F

    1999-11-01

    A total of 70%, of the world's conventional commercial fish species are now fully exploited, overexploited, depleted or recovering from depletion. This dramatic crash in the capture world fisheries production has led to problems in foods distribution, balance of payments, employment, and ecological depletion. Public support for breeding programs with terrestrial farm animals and plants in agriculture have revolutionized this industry over the past few hundred years. However, new genetic rearing technologies to improve marine animal production through aquaculture that utilize modern biology to obtain sustainable aquaculture and preserve biodiversity provide a promise to address these problems. However aquaculture has not been subject to public discussion and approval. Public involvement, not necessarily acquiescence, provide value added in the decision making process. Public understanding and involvement involves three stages. (i) Public concern over the pool of genetic information; (ii) if aquaculture is to respond to the fisheries crises with innovation, the knowledge gap between public understanding and scientific information must be bridged; and (iii) strategies must be developed for achieving this. Release of recombinant DNA to the environment, and handling exotic species, are useful case studies. Illustrations will be given of communication bridges to the public and ways to involve the public in making policy decisions.

  6. Enhanced heterotetrameric assembly of potato ADP-glucose pyrophosphorylase using reverse genetics.

    PubMed

    Seferoglu, A Bengisu; Koper, Kaan; Can, F Betul; Cevahir, Gul; Kavakli, I Halil

    2014-08-01

    ADP-glucose pyrophosphorylase (AGPase) is a key allosteric enzyme in plant starch biosynthesis. Plant AGPase is a heterotetrameric enzyme that consists of large (LS) and small subunits (SS), which are encoded by two different genes. Computational and experimental studies have revealed that the heterotetrameric assembly of AGPase is thermodynamically weak. Modeling studies followed by the mutagenesis of the LS of the potato AGPase identified a heterotetramer-deficient mutant, LS(R88A). To enhance heterotetrameric assembly, LS(R88A) cDNA was subjected to error-prone PCR, and second-site revertants were identified according to their ability to restore glycogen accumulation, as assessed with iodine staining. Selected mutations were introduced into the wild-type (WT) LS and co-expressed with the WT SS in Escherichia coli glgC(-). The biochemical characterization of revertants revealed that LS(I90V)SS(WT), LS(Y378C)SS(WT) and LS(D410G)SS(WT) mutants displayed enhanced heterotetrameric assembly with the WT SS. Among these mutants, LS(Y378C)SS(WT) AGPase displayed increased heat stability compared with the WT enzyme. Kinetic characterization of the mutants indicated that the LS(I90V)SS(WT) and LS(Y378C)SS(WT) AGPases have comparable allosteric and kinetic properties. However, the LS(D410G)SS(WT) mutant exhibited altered allosteric properties of being less responsive and more sensitive to 3-phosphoglyceric acid activation and inorganic phosphate inhibition. This study not only enhances our understanding of the interaction between the SS and the LS of AGPase but also enables protein engineering to obtain enhanced assembled heat-stable variants of AGPase, which can be used for the improvement of plant yields.

  7. Enhanced heterotetrameric assembly of potato ADP-glucose pyrophosphorylase using reverse genetics.

    PubMed

    Seferoglu, A Bengisu; Koper, Kaan; Can, F Betul; Cevahir, Gul; Kavakli, I Halil

    2014-08-01

    ADP-glucose pyrophosphorylase (AGPase) is a key allosteric enzyme in plant starch biosynthesis. Plant AGPase is a heterotetrameric enzyme that consists of large (LS) and small subunits (SS), which are encoded by two different genes. Computational and experimental studies have revealed that the heterotetrameric assembly of AGPase is thermodynamically weak. Modeling studies followed by the mutagenesis of the LS of the potato AGPase identified a heterotetramer-deficient mutant, LS(R88A). To enhance heterotetrameric assembly, LS(R88A) cDNA was subjected to error-prone PCR, and second-site revertants were identified according to their ability to restore glycogen accumulation, as assessed with iodine staining. Selected mutations were introduced into the wild-type (WT) LS and co-expressed with the WT SS in Escherichia coli glgC(-). The biochemical characterization of revertants revealed that LS(I90V)SS(WT), LS(Y378C)SS(WT) and LS(D410G)SS(WT) mutants displayed enhanced heterotetrameric assembly with the WT SS. Among these mutants, LS(Y378C)SS(WT) AGPase displayed increased heat stability compared with the WT enzyme. Kinetic characterization of the mutants indicated that the LS(I90V)SS(WT) and LS(Y378C)SS(WT) AGPases have comparable allosteric and kinetic properties. However, the LS(D410G)SS(WT) mutant exhibited altered allosteric properties of being less responsive and more sensitive to 3-phosphoglyceric acid activation and inorganic phosphate inhibition. This study not only enhances our understanding of the interaction between the SS and the LS of AGPase but also enables protein engineering to obtain enhanced assembled heat-stable variants of AGPase, which can be used for the improvement of plant yields. PMID:24891561

  8. Genetic engineering of cyanobacteria to enhance biohydrogen production from sunlight and water.

    PubMed

    Masukawa, Hajime; Kitashima, Masaharu; Inoue, Kazuhito; Sakurai, Hidehiro; Hausinger, Robert P

    2012-01-01

    To mitigate global warming caused by burning fossil fuels, a renewable energy source available in large quantity is urgently required. We are proposing large-scale photobiological H(2) production by mariculture-raised cyanobacteria where the microbes capture part of the huge amount of solar energy received on earth's surface and use water as the source of electrons to reduce protons. The H(2) production system is based on photosynthetic and nitrogenase activities of cyanobacteria, using uptake hydrogenase mutants that can accumulate H(2) for extended periods even in the presence of evolved O(2). This review summarizes our efforts to improve the rate of photobiological H(2) production through genetic engineering. The challenges yet to be overcome to further increase the conversion efficiency of solar energy to H(2) also are discussed.

  9. Genetically engineered charge modifications to enhance protein separation in aqueous two-phase systems: Electrochemical partitioning

    SciTech Connect

    Luther, J.R.; Glatz, C.E. . Dept. of Chemical Engineering)

    1994-06-20

    The authors examined the effect of genetically engineered charge modifications on the partitioning behavior of proteins in dextran/polyethylene glycol two-phase systems containing potassium phosphate. By genetically altering a protein's charge, the role of charge on partitioning can be assessed directly without the need to modify the phase system. The charge modifications used are of two types: charged tails of polyaspartic acid fused to [beta]-galactosidase and charge-change point mutations of T4 lysozyme which replace positive lysine residues with negative glutamic acids. The partition coefficient K[sub p] for these proteins was related to measured interfacial potential differences [Delta][phi] using the simple thermodynamic model, In K[sub p] = In K, + (FIRT)Z[sub p] [Delta][phi]. The protein net charge Z[sub p] was determined using the Henderson-Hasselbalch relationship with modifications based on experimentally determined titration and isoelectric point data. It was found that when the electropartitioning term Z[sub p] [Delta][phi] was varied by changing the pH, the partitioning of T4 lysozyme was quantitatively described by the thermodynamic model. The [beta]-galactosidase fusions displayed qualitative agreement, and although less than predicted, the partitioning increased more than two orders of magnitude for the pH range examined. Changes in the partitioning of lysozyme due to the various mutations agreed qualitatively with the thermodynamic model, but with a smaller than expected dependence on the estimated charge differences. The [beta]-galactosidase fusions, on the other hand, did not display a consistent charge based trend, which is likely due either to the enzyme's large size and complexity or to nonelectrostatic contributions from the tails. The lack of quantitative fit with the model described above suggests that the assumptions made in developing this model are oversimplified.

  10. Enhanced characteristics of genetically modified switchgrass (Panicum virgatum L.) for high biofuel production

    PubMed Central

    2013-01-01

    Background Lignocellulosic biomass is one of the most promising renewable and clean energy resources to reduce greenhouse gas emissions and dependence on fossil fuels. However, the resistance to accessibility of sugars embedded in plant cell walls (so-called recalcitrance) is a major barrier to economically viable cellulosic ethanol production. A recent report from the US National Academy of Sciences indicated that, “absent technological breakthroughs”, it was unlikely that the US would meet the congressionally mandated renewable fuel standard of 35 billion gallons of ethanol-equivalent biofuels plus 1 billion gallons of biodiesel by 2022. We here describe the properties of switchgrass (Panicum virgatum) biomass that has been genetically engineered to increase the cellulosic ethanol yield by more than 2-fold. Results We have increased the cellulosic ethanol yield from switchgrass by 2.6-fold through overexpression of the transcription factor PvMYB4. This strategy reduces carbon deposition into lignin and phenolic fermentation inhibitors while maintaining the availability of potentially fermentable soluble sugars and pectic polysaccharides. Detailed biomass characterization analyses revealed that the levels and nature of phenolic acids embedded in the cell-wall, the lignin content and polymer size, lignin internal linkage levels, linkages between lignin and xylans/pectins, and levels of wall-bound fucose are all altered in PvMYB4-OX lines. Genetically engineered PvMYB4-OX switchgrass therefore provides a novel system for further understanding cell wall recalcitrance. Conclusions Our results have demonstrated that overexpression of PvMYB4, a general transcriptional repressor of the phenylpropanoid/lignin biosynthesis pathway, can lead to very high yield ethanol production through dramatic reduction of recalcitrance. MYB4-OX switchgrass is an excellent model system for understanding recalcitrance, and provides new germplasm for developing switchgrass cultivars as

  11. Developmental and genetic components explain enhanced pulmonary volumes of female Peruvian Quechua.

    PubMed

    Kiyamu, Melisa; Bigham, Abigail; Parra, Esteban; León-Velarde, Fabiola; Rivera-Chira, María; Brutsaert, Tom D

    2012-08-01

    High altitude natives have enlarged vital capacities and residual volumes (RV). Because pulmonary volumes are an indication of functionally relevant traits, such as diffusion capacity, the understanding of the factors (genetic/developmental) that influence lung volumes provides insight into the adaptive responses of highlanders. In order to test for the effect of growth and development at high altitude on lung volumes, we obtained forced vital capacities (FVC), RV, and total lung capacities (TLC) for a sample of 65 Peruvian females of mostly Quechua origins (18-34 years) who were sub-divided into two well-matched groups: 1) sea-level born and raised females (BSL, n = 34) from Lima, Peru (150 m), and 2) high-altitude born and raised females (BHA, n = 31) from Cerro de Pasco, Peru (4,338 m). To determine Quechua origins, Native American ancestry proportion (NAAP) for each individual was assessed using a panel of 70 ancestry informative markers. NAAP was similar between groups (BSL = 91.71%; BHA = 89.93%; P = 0.240), and the analysis confirmed predominantly Quechua origins. After adjusting for body size and NAAP, BHA females had significantly higher FVC (3.79 ± 0.06 l; P < 0.001), RV (0.98 ± 0.03 l; P < 0.001) and TLC (4.80 ± 0.07 l; P < 0.001) compared to BSL females (FVC = 3.33 ± 0.05 l; RV = 0.69 ± 0.03 l; TLC = 4.02 ± 0.06 l). NAAP was not associated with FVC (P = 0.352) or TLC (P = 0.506). However, NAAP was positively associated with RV (P = 0.004). In summary, results indicate that developmental exposure to high altitude in females constitutes an important factor for all lung volumes, whereas both genetic and developmental factors seem to be important for RV.

  12. Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampus-dependent long-term memory.

    PubMed

    Wang, Wenbin; Pan, Yung-Wei; Zou, Junhui; Li, Tan; Abel, Glen M; Palmiter, Richard D; Storm, Daniel R; Xia, Zhengui

    2014-02-01

    Recent studies have shown that inhibition of adult neurogenesis impairs the formation of hippocampus-dependent memory. However, it is not known whether increasing adult neurogenesis affects the persistence of hippocampus-dependent long-term memory. Furthermore, signaling mechanisms that regulate adult neurogenesis are not fully defined. We recently reported that the conditional and targeted knock-out of ERK5 MAP kinase in adult neurogenic regions of the mouse brain attenuates adult neurogenesis in the hippocampus and disrupts several forms of hippocampus-dependent memory. Here, we developed a gain-of-function knock-in mouse model to specifically activate endogenous ERK5 in the neurogenic regions of the adult brain. We report that the selective and targeted activation of ERK5 increases adult neurogenesis in the dentate gyrus by enhancing cell survival, neuronal differentiation, and dendritic complexity. Conditional ERK5 activation also improves the performance of challenging forms of spatial learning and memory and extends hippocampus-dependent long-term memory. We conclude that enhancing signal transduction of a single signaling pathway within adult neural stem/progenitor cells is sufficient to increase adult neurogenesis and improve the persistence of hippocampus-dependent memory. Furthermore, activation of ERK5 may provide a novel therapeutic target to improve long-term memory.

  13. Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming.

    PubMed

    Islam, Mohammed M; Smith, Derek K; Niu, Wenze; Fang, Sanhua; Iqbal, Nida; Sun, Guoqiang; Shi, Yanhong; Zhang, Chun-Li

    2015-11-10

    The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming. PMID:26607952

  14. Enhancer Analysis Unveils Genetic Interactions between TLX and SOX2 in Neural Stem Cells and In Vivo Reprogramming

    PubMed Central

    Islam, Mohammed M.; Smith, Derek K.; Niu, Wenze; Fang, Sanhua; Iqbal, Nida; Sun, Guoqiang; Shi, Yanhong; Zhang, Chun-Li

    2015-01-01

    Summary The orphan nuclear receptor TLX is a master regulator of postnatal neural stem cell (NSC) self-renewal and neurogenesis; however, it remains unclear how TLX expression is precisely regulated in these tissue-specific stem cells. Here, we show that a highly conserved cis-element within the Tlx locus functions to drive gene expression in NSCs. We demonstrate that the transcription factors SOX2 and MYT1 specifically interact with this genomic element to directly regulate Tlx enhancer activity in vivo. Knockdown experiments further reveal that SOX2 dominantly controls endogenous expression of TLX, whereas MYT1 only plays a modulatory role. Importantly, TLX is essential for SOX2-mediated in vivo reprogramming of astrocytes and itself is also sufficient to induce neurogenesis in the adult striatum. Together, these findings unveil functional genetic interactions among transcription factors that are critical to NSCs and in vivo cell reprogramming. PMID:26607952

  15. Estimates of epistatic and pleiotropic effects of () and () genetic markers on beef heifer performance traits enhanced by selection.

    PubMed

    Tait, R G; Cushman, R A; McNeel, A K; Casas, E; Smith, T P L; Freetly, H C; Bennett, G L

    2016-03-01

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for 2 yr to equalize and genetic marker frequencies to evaluate the epistatic and pleiotropic effects of these markers on BW, reproduction, and first calf performance traits in replacement beef females ( = 171) managed under 2 postweaning development protocols. Traits evaluated on the heifers were birth BW, weaning BW, 11-mo BW, 12-mo BW, 13-mo BW, first breeding season pregnancy evaluation BW, first calving season BW, 11-mo puberty, 12-mo puberty, 13-mo puberty, first breeding season pregnancy, and first calf weaning rate. Additionally, heifer's first calf performance traits of ordinal calving date, first calf birth BW, and first calf weaning BW (with and without age adjustment) were analyzed. Selection to increase minor allele frequencies and balanced sampling across genotype classes enhanced the ability to detect all genetic effects except dominance × dominance epistasis. The × genotype effect was significant ( < 0.05) for 11-mo BW and 12-mo BW and tended to be significant ( = 0.08) for 13-mo BW. Consistently, for all 3 traits, the most significant effect among epistatic × genotype effects was the additive effect, with the G allele decreasing BW. There were no associations between × genotype and fertility related traits ( ≥ 0.46) in this study. Additionally, there were no × genotype associations with first progeny performance traits ( ≥ 0.14). The large effect of the additive × additive interaction on first calf weaning BW was imprecisely estimated, which may warrant further investigation. PMID:27065254

  16. Genetic variation at the 8q24.21 renal cancer susceptibility locus affects HIF binding to a MYC enhancer

    PubMed Central

    Grampp, Steffen; Platt, James L.; Lauer, Victoria; Salama, Rafik; Kranz, Franziska; Neumann, Viviana K.; Wach, Sven; Stöhr, Christine; Hartmann, Arndt; Eckardt, Kai-Uwe; Ratcliffe, Peter J.; Mole, David R.; Schödel, Johannes

    2016-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by loss of function of the von Hippel–Lindau tumour suppressor (VHL) and unrestrained activation of hypoxia-inducible transcription factors (HIFs). Genetic and epigenetic determinants have an impact on HIF pathways. A recent genome-wide association study on renal cancer susceptibility identified single-nucleotide polymorphisms (SNPs) in an intergenic region located between the oncogenes MYC and PVT1. Here using assays of chromatin conformation, allele-specific chromatin immunoprecipitation and genome editing, we show that HIF binding to this regulatory element is necessary to trans-activate MYC and PVT1 expression specifically in cells of renal tubular origins. Moreover, we demonstrate that the risk-associated polymorphisms increase chromatin accessibility and activity as well as HIF binding to the enhancer. These findings provide further evidence that genetic variation at HIF-binding sites modulates the oncogenic transcriptional output of the VHL–HIF axis and provide a functional explanation for the disease-associated effects of SNPs in ccRCC. PMID:27774982

  17. An improved ARS2-derived nuclear reporter enhances the efficiency and ease of genetic engineering in Chlamydomonas.

    PubMed

    Specht, Elizabeth A; Nour-Eldin, Hussam Hassan; Hoang, Kevin T D; Mayfield, Stephen P

    2015-03-01

    The model alga Chlamydomonas reinhardtii has been used to pioneer genetic engineering techniques for high-value protein and biofuel production from algae. To date, most studies of transgenic Chlamydomonas have utilized the chloroplast genome due to its ease of engineering, with a sizeable suite of reporters and well-characterized expression constructs. The advanced manipulation of algal nuclear genomes has been hampered by limited strong expression cassettes, and a lack of high-throughput reporters. We have improved upon an endogenous reporter gene - the ARS2 gene encoding an arylsulfatase enzyme - that was first cloned and characterized decades ago but has not been used extensively. The new construct, derived from ARS2 cDNA, expresses significantly higher levels of reporter protein and transforms more efficiently, allowing qualitative and quantitative screening using a rapid, inexpensive 96-well assay. The improved arylsulfatase expression cassette was used to screen a new transgene promoter from the ARG7 gene, and found that the ARG7 promoter can express the ARS2 reporter as strongly as the HSP70-RBCS2 chimeric promoter that currently ranks as the best available promoter, thus adding to the list of useful nuclear promoters. This enhanced arylsulfatase reporter construct improves the efficiency and ease of genetic engineering within the Chlamydomonas nuclear genome, with potential application to other algal strains.

  18. Enhanced genetic modification of adult growth factor mobilized peripheral blood hematopoietic stem and progenitor cells with rapamycin.

    PubMed

    Li, Lijing; Torres-Coronado, Mónica; Gu, Angel; Rao, Anitha; Gardner, Agnes M; Epps, Elizabeth W; Gonzalez, Nancy; Tran, Chy-Anh; Wu, Xiwei; Wang, Jin-Hui; DiGiusto, David L

    2014-10-01

    Genetic modification of adult human hematopoietic stem and progenitor cells (HSPCs) with lentiviral vectors leads to long-term gene expression in the progeny of the HSPCs and has been used to successfully treat several monogenic diseases. In some cases, the gene-modified cells have a selective growth advantage over nonmodified cells and eventually are the dominant engrafted population. However, in disease indications for which the gene-modified cells do not have a selective advantage, optimizing transduction of HSPC is paramount to successful stem cell-based gene therapy. We demonstrate here that transduction of adult CD34+ HSPCs with lentiviral vectors in the presence of rapamycin, a widely used mTORC1 inhibitor, results in an approximately threefold increase in stable gene marking with minimal effects on HSPC growth and differentiation. Using this approach, we have demonstrated that we can enhance the frequency of gene-modified HSPCs that give rise to clonogenic progeny in vitro without excessive increases in the number of vector copies per cell or changes in integration pattern. The genetic marking of HSPCs and expression of transgenes is durable, and transplantation of gene-modified HSPCs into immunodeficient mice results in high levels of gene marking of the lymphoid and myeloid progeny in vivo. The prior safe clinical history of rapamycin in other applications supports the use of this compound to generate gene-modified autologous HSPCs for our HIV gene therapy clinical trials.

  19. Preventing Weight Gain

    MedlinePlus

    ... If this is the case, preventing further weight gain is a worthy goal. As people age, their body composition gradually shifts — the proportion of muscle decreases and the proportion of fat increases. This ...

  20. Dominant Enhancers of Egfr in Drosophila Melanogaster: Genetic Links between the Notch and Egfr Signaling Pathways

    PubMed Central

    Price, J. V.; Savenye, E. D.; Lum, D.; Breitkreutz, A.

    1997-01-01

    The Drosophila epidermal growth factor receptor (EGFR) is a key component of a complex signaling pathway that participates in multiple developmental processes. We have performed an F(1) screen for mutations that cause dominant enhancement of wing vein phenotypes associated with mutations in Egfr. With this screen, we have recovered mutations in Hairless (H), vein, groucho (gro), and three apparently novel loci. All of the E(Egfr)s we have identified show dominant interactions in transheterozygous combinations with each other and with alleles of N or Su(H), suggesting that they are involved in cross-talk between the N and EGFR signaling pathways. Further examination of the phenotypic interactions between Egfr, H, and gro revealed that reductions in Egfr activity enhanced both the bristle loss associated with H mutations, and the bristle hyperplasia and ocellar hypertrophy associated with gro mutations. Double mutant combinations of Egfr and gro hypomorphic alleles led to the formation of ectopic compound eyes in a dosage sensitive manner. Our findings suggest that these E(Egfr)s represent links between the Egfr and Notch signaling pathways, and that Egfr activity can either promote or suppress Notch signaling, depending on its developmental context. PMID:9383058

  1. A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening

    PubMed Central

    Diao, Yarui; Li, Bin; Meng, Zhipeng; Jung, Inkyung; Lee, Ah Young; Dixon, Jesse; Maliskova, Lenka; Guan, Kun-liang; Shen, Yin; Ren, Bing

    2016-01-01

    With <2% of the human genome coding for proteins, a major challenge is to interpret the function of the noncoding DNA. Millions of regulatory sequences have been predicted in the human genome through analysis of DNA methylation, chromatin modification, hypersensitivity to nucleases, and transcription factor binding, but few have been shown to regulate transcription in their native contexts. We have developed a high-throughput CRISPR/Cas9-based genome-editing strategy and used it to interrogate 174 candidate regulatory sequences within the 1-Mbp POU5F1 locus in human embryonic stem cells (hESCs). We identified two classical regulatory elements, including a promoter and a proximal enhancer, that are essential for POU5F1 transcription in hESCs. Unexpectedly, we also discovered a new class of enhancers that contribute to POU5F1 transcription in an unusual way: Disruption of such sequences led to a temporary loss of POU5F1 transcription that is fully restored after a few rounds of cell division. These results demonstrate the utility of high-throughput screening for functional characterization of noncoding DNA and reveal a previously unrecognized layer of gene regulation in human cells. PMID:26813977

  2. Argument-predicate distance as a filter for enhancing precision in extracting predications on the genetic etiology of disease

    PubMed Central

    Masseroli, Marco; Kilicoglu, Halil; Lang, François-Michel; Rindflesch, Thomas C

    2006-01-01

    Background Genomic functional information is valuable for biomedical research. However, such information frequently needs to be extracted from the scientific literature and structured in order to be exploited by automatic systems. Natural language processing is increasingly used for this purpose although it inherently involves errors. A postprocessing strategy that selects relations most likely to be correct is proposed and evaluated on the output of SemGen, a system that extracts semantic predications on the etiology of genetic diseases. Based on the number of intervening phrases between an argument and its predicate, we defined a heuristic strategy to filter the extracted semantic relations according to their likelihood of being correct. We also applied this strategy to relations identified with co-occurrence processing. Finally, we exploited postprocessed SemGen predications to investigate the genetic basis of Parkinson's disease. Results The filtering procedure for increased precision is based on the intuition that arguments which occur close to their predicate are easier to identify than those at a distance. For example, if gene-gene relations are filtered for arguments at a distance of 1 phrase from the predicate, precision increases from 41.95% (baseline) to 70.75%. Since this proximity filtering is based on syntactic structure, applying it to the results of co-occurrence processing is useful, but not as effective as when applied to the output of natural language processing. In an effort to exploit SemGen predications on the etiology of disease after increasing precision with postprocessing, a gene list was derived from extracted information enhanced with postprocessing filtering and was automatically annotated with GFINDer, a Web application that dynamically retrieves functional and phenotypic information from structured biomolecular resources. Two of the genes in this list are likely relevant to Parkinson's disease but are not associated with this disease

  3. Genetic design of enhanced valley splitting towards a spin qubit in silicon.

    PubMed

    Zhang, Lijun; Luo, Jun-Wei; Saraiva, Andre; Koiller, Belita; Zunger, Alex

    2013-01-01

    The long spin coherence time and microelectronics compatibility of Si makes it an attractive material for realizing solid-state qubits. Unfortunately, the orbital (valley) degeneracy of the conduction band of bulk Si makes it difficult to isolate individual two-level spin-1/2 states, limiting their development. This degeneracy is lifted within Si quantum wells clad between Ge-Si alloy barrier layers, but the magnitude of the valley splittings achieved so far is small--of the order of 1 meV or less--degrading the fidelity of information stored within such a qubit. Here we combine an atomistic pseudopotential theory with a genetic search algorithm to optimize the structure of layered-Ge/Si-clad Si quantum wells to improve this splitting. We identify an optimal sequence of multiple Ge/Si barrier layers that more effectively isolates the electron ground state of a Si quantum well and increases the valley splitting by an order of magnitude, to ~9 meV. PMID:24013452

  4. Cryptococcus neoformans Virulence Is Enhanced after Growth in the Genetically Malleable Host Dictyostelium discoideum

    PubMed Central

    Steenbergen, Judith N.; Nosanchuk, Joshua D.; Malliaris, Stephanie D.; Casadevall, Arturo

    2003-01-01

    Cryptococcus neoformans is an encapsulated, environmental fungus that can cause life-threatening meningitis. Pathogenicity of C. neoformans for macrophages and vertebrate hosts may be a mechanism selected in evolution for protection against environmental predators. In this study, we investigated whether Dictyostelium discoideum could serve as an alternate host for C. neoformans. D. discoideum has a defined genetic system which provides significant advantages for the study of fungus-amoeba interactions. Our results show that D. discoideum is susceptible to infection with C. neoformans and that the interactions are similar to those described previously for this fungus with macrophages and Acanthamoeba castellanii. Acapsular C. neoformans cells did not replicate when coincubated with D. discoideum. However, incubation of acapsular C. neoformans with D. discoideum mutants defective in myosin VII synthesis resulted in infection, validating the concept that avirulent organisms can be virulent in impaired hosts even at the unicellular level. Phagocytosis of C. neoformans by D. discoideum could be inhibited with capsule-specific antibodies and various sugars. Passage of an encapsulated C. neoformans strain through D. discoideum cultures increased virulence and was accompanied by larger capsules and faster time to melanization. These results add to the evidence implicating soil ameboid predators as important factors for the maintenance of C. neoformans virulence in the environment and suggest that D. discoideum promises to be an extremely useful system for studying the interaction of C. neoformans with phagocytic cells. PMID:12933827

  5. Genetic design of enhanced valley splitting towards a spin qubit in silicon.

    PubMed

    Zhang, Lijun; Luo, Jun-Wei; Saraiva, Andre; Koiller, Belita; Zunger, Alex

    2013-01-01

    The long spin coherence time and microelectronics compatibility of Si makes it an attractive material for realizing solid-state qubits. Unfortunately, the orbital (valley) degeneracy of the conduction band of bulk Si makes it difficult to isolate individual two-level spin-1/2 states, limiting their development. This degeneracy is lifted within Si quantum wells clad between Ge-Si alloy barrier layers, but the magnitude of the valley splittings achieved so far is small--of the order of 1 meV or less--degrading the fidelity of information stored within such a qubit. Here we combine an atomistic pseudopotential theory with a genetic search algorithm to optimize the structure of layered-Ge/Si-clad Si quantum wells to improve this splitting. We identify an optimal sequence of multiple Ge/Si barrier layers that more effectively isolates the electron ground state of a Si quantum well and increases the valley splitting by an order of magnitude, to ~9 meV.

  6. Anti-Apoptotic NF-κB and “Gain of Function” mutp53 in Concert Act Pro-Apoptotic in Response to UVB+IL-1 via Enhanced TNF Production

    PubMed Central

    Müller, Ines; Beissert, Stefan; Kulms, Dagmar

    2015-01-01

    In response to genotoxic stress, including UVB radiation, transcription factors NF-κB and p53 inevitably influence the cellular fate. Loss of p53 function has been attributed to malignant transformation and interferes with therapeutic interventions, whereas “gain of function” mutants even enhance tumor promotion. Constitutive NF-κB activation is linked to tumor maintenance and resistance against chemotherapy. The cross talk between p53 and NF-κB, however, is still under debate. Using the non-transformed keratinocyte cell line HaCaT, we shed light on the interplay between p53 and NF-κB by providing clear evidence that chronically activated NF-κB together with designated “gain of function” mutp53 promotes apoptosis via cooperative tumor necrosis factor (TNF) production in response to UVB+IL-1. Performing chromatin immunoprecipitation analysis we demonstrate that both transcription factors bind to the TNF promoter, whereas UVB-induced inhibition of Ser-Thr-phosphatase protein phosphatase 2A facilitates prolonged phosphorylation of NF-κB and the transcriptional cofactor cAMP response element–binding protein, both being required for extended TNF transcription. Thus, two major anti-apoptotic factors, NF-κB and mutp53, in concert may generate pro-apoptotic responses. As human skin is constantly exposed to UVB, causing IL-1 production as well, we hypothesize that the remarkable amount of hotspot p53 mutations within the epidermis (4%) may serve a protective function to eliminate precancerous cells at an early stage. PMID:25380350

  7. Genetic enhancement of behavioral itch responses in mice lacking phosphoinositide 3-kinase-γ (PI3Kγ)

    PubMed Central

    2011-01-01

    Phosphoinositide 3-kinases (PI3Ks) are important for synaptic plasticity and various brain functions. The only class IB isoform of PI3K, PI3Kγ, has received the most attention due to its unique roles in synaptic plasticity and cognition. However, the potential role of PI3Kγ in sensory transmission, such as pain and itch has not been examined. In this study, we present the evidence for the first time, that genetic deletion of PI3Kγ enhanced scratching behaviours in histamine-dependent and protease-activated receptor 2 (PAR-2)-dependent itch. In contrast, PI3Kγ-deficient mice did not exhibit enhanced scratching in chloroquine-induced itch, suggesting that PI3Kγ selectively contributes to certain types of behavioal itch response. Furthermore, PI3Kγ-deficient mice exhibited normal acute nociceptive responses to thermal and mechanical noxious stimuli. Behavioral licking responses to intraplantar injections of formalin and mechanical allodynia in a chronic inflammatory pain model (CFA) were also not affected by PI3Kγ gene deletion. Our findings indicate that PI3Kγ selectively contributes to behavioral itching induced by histamine and PAR-2 agonist, but not chloroquine agonist. PMID:22168443

  8. Enhanced flight performance by genetic manipulation of wing shape in Drosophila

    PubMed Central

    Ray, Robert P.; Nakata, Toshiyuki; Henningsson, Per; Bomphrey, Richard J.

    2016-01-01

    Insect wing shapes are remarkably diverse and the combination of shape and kinematics determines both aerial capabilities and power requirements. However, the contribution of any specific morphological feature to performance is not known. Using targeted RNA interference to modify wing shape far beyond the natural variation found within the population of a single species, we show a direct effect on flight performance that can be explained by physical modelling of the novel wing geometry. Our data show that altering the expression of a single gene can significantly enhance aerial agility and that the Drosophila wing shape is not, therefore, optimized for certain flight performance characteristics that are known to be important. Our technique points in a new direction for experiments on the evolution of performance specialities in animals. PMID:26926954

  9. Genetic Signatures for Enhanced Olfaction in the African Mole-Rats

    PubMed Central

    Stathopoulos, Sofia; Bishop, Jacqueline M.; O’Ryan, Colleen

    2014-01-01

    The Olfactory Receptor (OR) superfamily, the largest in the vertebrate genome, is responsible for vertebrate olfaction and is traditionally subdivided into 17 OR families. Recent studies characterising whole-OR subgenomes revealed a ‘birth and death’ model of evolution for a range of species, however little is known about fine-scale evolutionary dynamics within single-OR families. This study reports the first assessment of fine-scale OR evolution and variation in African mole-rats (Bathyergidae), a family of subterranean rodents endemic to sub-Saharan Africa. Because of the selective pressures of life underground, enhanced olfaction is proposed to be fundamental to the evolutionary success of the Bathyergidae, resulting in a highly diversified OR gene-repertoire. Using a PCR-sequencing approach, we analysed variation in the OR7 family across 14 extant bathyergid species, which revealed enhanced levels of functional polymorphisms concentrated across the receptors’ ligand-binding region. We propose that mole-rats are able to recognise a broad range of odorants and that this diversity is reflected throughout their OR7 gene repertoire. Using both classic tests and tree-based methods to test for signals of selection, we investigate evolutionary forces across the mole-rat OR7 gene tree. Four well-supported clades emerged in the OR phylogeny, with varying signals of selection; from neutrality to positive and purifying selection. Bathyergid life-history traits and environmental niche-specialisation are explored as possible drivers of adaptive OR evolution, emerging as non-exclusive contributors to the positive selection observed at OR7 genes. Our results reveal unexpected complexity of evolutionary mechanisms acting within a single OR family, providing insightful perspectives into OR evolutionary dynamics. PMID:24699281

  10. Genetic Regulation of Fate Decisions in Therapeutic T Cells to Enhance Tumor Protection and Memory Formation.

    PubMed

    Veliça, Pedro; Zech, Mathias; Henson, Sian; Holler, Angelika; Manzo, Teresa; Pike, Rebecca; Santos E Sousa, Pedro; Zhang, Lei; Heinz, Niels; Schiedlmeier, Bernhard; Pule, Martin; Stauss, Hans; Chakraverty, Ronjon

    2015-07-01

    A key challenge in the field of T-cell immunotherapy for cancer is creating a suitable platform for promoting differentiation of effector cells while at the same time enabling self-renewal needed for long-term memory. Although transfer of less differentiated memory T cells increases efficacy through greater expansion and persistence in vivo, the capacity of such cells to sustain effector functions within immunosuppressive tumor microenvironments may still be limiting. We have therefore directly compared the impact of effector versus memory differentiation of therapeutic T cells in tumor-bearing mice by introducing molecular switches that regulate cell fate decisions via mTOR. Ectopic expression of RAS homolog enriched in brain (RHEB) increased mTORC1 signaling, promoted a switch to aerobic glycolysis, and increased expansion of effector T cells. By rapidly infiltrating tumors, RHEB-transduced T cells significantly reduced the emergence of immunoedited escape variants. In contrast, expression of proline-rich Akt substrate of 40 kDa (PRAS40) inhibited mTORC1, promoted quiescence, and blocked tumor infiltration. Fate mapping studies following transient expression of PRAS40 demonstrated that mTORC1(low) T cells made no contribution to initial tumor control but instead survived to become memory cells proficient in generating recall immunity. Our data support the design of translational strategies for generating heterogeneous T-cell immunity against cancer, with the appropriate balance between promoting effector differentiation and self-renewal. Unlike pharmacologic inhibitors, the genetic approach described here allows for upregulation as well as inhibition of the mTORC1 pathway and is highly selective for the therapeutic T cells without affecting systemic mTORC1 functions.

  11. Non-genetic benefits of mate choice: fecundity enhancement and sexy sons.

    PubMed

    M

    1998-05-01

    I compared reproductive success (lifetime number of fertilized eggs) as a function of mate choice among females of the stink bug, Nezara viridula L. (Hemiptera: Pentatomidae). 'Choosing' (C) females were placed with one of two males on alternate days. CI females chose between inexperienced males while CR females chose between males previously rejected by CI females. 'Non-choosing' (N) females were placed with the same male every day. Non-choosing NI, NR and NA females encountered, respectively, inexperienced males, previously rejected males, or previously accepted and mated males. Reproductive success was highest for CI females, showing direct selection on mate preferences. Reproductive success did not differ between CR and NR females, indicating that male quality, not the act of choosing a mate, affects fitness. CI females preferred males with longer antennae and their fecundity (lifetime number of eggs) was correlated with male antenna length, consistent with antenna length as an indicator of male ability to transfer nutritive sperm produced in paired harlequin lobes of the testes. Harlequin lobes were smaller in rejected than chosen males. In second-generation mate choice trials, sons of NR females competed well against sons of NA females but not against sons of CI females. This suggests that non-genetic paternal contributions that decline with prior mating account for the attractiveness of sons because sons of CI and NA females shared the same fathers. Sons experiencing mating success came from larger eggs and egg size was greatest for CI females, perhaps as a consequence of paternal nutritional contributions. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.

  12. Assessing and enhancing the introductory science course in physics and biology: Peer instruction, classroom demonstrations, and genetics vocabulary

    NASA Astrophysics Data System (ADS)

    Fagen, Adam Paul

    Most introductory college science courses in the United States are taught in large lectures with students rarely having the opportunity to think critically about the material being presented nor to participate actively. Further, many classes focus on teaching rather than learning, that is, the transfer of information as opposed to actual student understanding. This thesis focuses on three studies about the assessment and enhancement of learning in undergraduate science courses. We describe the results of an international survey on the implementation of Peer Instruction (PI), a collaborative learning pedagogy in which lectures are interspersed with short conceptual questions designed to challenge students to think about the material as it is being presented. We present a portrait of the many instructors teaching with PI and the settings in which it is being used as well as data on the effectiveness of PI in enhancing student learning in diverse settings. The wide variety of implementations suggests that PI is a highly adaptable strategy that can work successfully in almost any environment. We also provide recommendations for those considering adopting PI in their classes. Classroom demonstrations are an important aspect of many introductory science courses, but there is little evidence supporting their educational effectiveness. We explore the effect of different modes of presentation on enhancing student learning from demonstrations. Our results show that students who actively engage with a demonstration by predicting the outcome before it is conducted are better able to recall and explain the scenario posed by that demonstration. As preliminary work for the creation of an inventory of conceptual understanding in introductory biology, we discuss results from a survey of vocabulary familiarity and understanding in an undergraduate genetics course. Students begin introductory classes with significant gaps in their understanding, some of which are retained beyond

  13. Control of the olive fruit fly using genetics-enhanced sterile insect technique

    PubMed Central

    2012-01-01

    Background The olive fruit fly, Bactrocera oleae, is the major arthropod pest of commercial olive production, causing extensive damage to olive crops worldwide. Current control techniques rely on spraying of chemical insecticides. The sterile insect technique (SIT) presents an alternative, environmentally friendly and species-specific method of population control. Although SIT has been very successful against other tephritid pests, previous SIT trials on olive fly have produced disappointing results. Key problems included altered diurnal mating rhythms of the laboratory-reared insects, resulting in asynchronous mating activity between the wild and released sterile populations, and low competitiveness of the radiation-sterilised mass-reared flies. Consequently, the production of competitive, male-only release cohorts is considered an essential prerequisite for successful olive fly SIT. Results We developed a set of conditional female-lethal strains of olive fly (named Release of Insects carrying a Dominant Lethal; RIDL®), providing highly penetrant female-specific lethality, dominant fluorescent marking, and genetic sterility. We found that males of the lead strain, OX3097D-Bol, 1) are strongly sexually competitive with wild olive flies, 2) display synchronous mating activity with wild females, and 3) induce appropriate refractoriness to wild female re-mating. Furthermore, we showed, through a large proof-of-principle experiment, that weekly releases of OX3097D-Bol males into stable populations of caged wild-type olive fly could cause rapid population collapse and eventual eradication. Conclusions The observed mating characteristics strongly suggest that an approach based on the release of OX3097D-Bol males will overcome the key difficulties encountered in previous olive fly SIT attempts. Although field confirmation is required, the proof-of-principle suppression and elimination of caged wild-type olive fly populations through OX3097D-Bol male releases provides

  14. Enhancement of the nitrogen fixation efficiency of genetically-engineered Rhizobium with high catalase activity.

    PubMed

    Orikasa, Yoshitake; Nodasaka, Yoshinobu; Ohyama, Takuji; Okuyama, Hidetoshi; Ichise, Nobutoshi; Yumoto, Isao; Morita, Naoki; Wei, Min; Ohwada, Takuji

    2010-10-01

    The vktA catalase gene, which had been cloned from Vibrio rumoiensis S-1T having extraordinarily high catalase activity, was introduced into the root nodule bacterium, Rhizobium leguminosarum bv. phaseoli USDA 2676. The catalase activity of the vktA-transformed R. leguminosarum cells (free-living) was three orders in magnitude higher than that of the parent cells and this transformant could grow in a higher concentration of exogenous hydrogen peroxide (H2O2). The vktA-transformant was inoculated to the host plant (Phaseolus vulgaris L.) and the nodulation efficiency was evaluated. The results showed that the nitrogen-fixing activity of nodules was increased 1.7 to 2.3 times as compared to the parent. The levels of H2O2 in nodules formed by the vktA-transformant were decreased by around 73%, while those of leghemoglobins (Lba and Lbb) were increased by 1.2 (Lba) and 2.1 (Lbb) times compared with the parent. These results indicated that the increase of catalase activity in rhizobia could be useful to improve the nitrogen-fixing efficiency of nodules by the reduction of H2O2 content concomitantly with the enhancement of leghemoglobins contents.

  15. Massive sorghum collection genotyped with SSR markers to enhance use of global genetic resources.

    PubMed

    Billot, Claire; Ramu, Punna; Bouchet, Sophie; Chantereau, Jacques; Deu, Monique; Gardes, Laetitia; Noyer, Jean-Louis; Rami, Jean-François; Rivallan, Ronan; Li, Yu; Lu, Ping; Wang, Tianyu; Folkertsma, Rolf T; Arnaud, Elizabeth; Upadhyaya, Hari D; Glaszmann, Jean-Christophe; Hash, C Thomas

    2013-01-01

    Large ex situ collections require approaches for sampling manageable amounts of germplasm for in-depth characterization and use. We present here a large diversity survey in sorghum with 3367 accessions and 41 reference nuclear SSR markers. Of 19 alleles on average per locus, the largest numbers of alleles were concentrated in central and eastern Africa. Cultivated sorghum appeared structured according to geographic regions and race within region. A total of 13 groups of variable size were distinguished. The peripheral groups in western Africa, southern Africa and eastern Asia were the most homogeneous and clearly differentiated. Except for Kafir, there was little correspondence between races and marker-based groups. Bicolor, Caudatum, Durra and Guinea types were each dispersed in three groups or more. Races should therefore better be referred to as morphotypes. Wild and weedy accessions were very diverse and scattered among cultivated samples, reinforcing the idea that large gene-flow exists between the different compartments. Our study provides an entry to global sorghum germplasm collections. Our reference marker kit can serve to aggregate additional studies and enhance international collaboration. We propose a core reference set in order to facilitate integrated phenotyping experiments towards refined functional understanding of sorghum diversity. PMID:23565161

  16. Massive Sorghum Collection Genotyped with SSR Markers to Enhance Use of Global Genetic Resources

    PubMed Central

    Bouchet, Sophie; Chantereau, Jacques; Deu, Monique; Gardes, Laetitia; Noyer, Jean-Louis; Rami, Jean-François; Rivallan, Ronan; Li, Yu; Lu, Ping; Wang, Tianyu; Folkertsma, Rolf T.; Arnaud, Elizabeth; Upadhyaya, Hari D.; Glaszmann, Jean-Christophe; Hash, C. Thomas

    2013-01-01

    Large ex situ collections require approaches for sampling manageable amounts of germplasm for in-depth characterization and use. We present here a large diversity survey in sorghum with 3367 accessions and 41 reference nuclear SSR markers. Of 19 alleles on average per locus, the largest numbers of alleles were concentrated in central and eastern Africa. Cultivated sorghum appeared structured according to geographic regions and race within region. A total of 13 groups of variable size were distinguished. The peripheral groups in western Africa, southern Africa and eastern Asia were the most homogeneous and clearly differentiated. Except for Kafir, there was little correspondence between races and marker-based groups. Bicolor, Caudatum, Durra and Guinea types were each dispersed in three groups or more. Races should therefore better be referred to as morphotypes. Wild and weedy accessions were very diverse and scattered among cultivated samples, reinforcing the idea that large gene-flow exists between the different compartments. Our study provides an entry to global sorghum germplasm collections. Our reference marker kit can serve to aggregate additional studies and enhance international collaboration. We propose a core reference set in order to facilitate integrated phenotyping experiments towards refined functional understanding of sorghum diversity. PMID:23565161

  17. Receiver Gain Modulation Circuit

    NASA Technical Reports Server (NTRS)

    Jones, Hollis; Racette, Paul; Walker, David; Gu, Dazhen

    2011-01-01

    A receiver gain modulation circuit (RGMC) was developed that modulates the power gain of the output of a radiometer receiver with a test signal. As the radiometer receiver switches between calibration noise references, the test signal is mixed with the calibrated noise and thus produces an ensemble set of measurements from which ensemble statistical analysis can be used to extract statistical information about the test signal. The RGMC is an enabling technology of the ensemble detector. As a key component for achieving ensemble detection and analysis, the RGMC has broad aeronautical and space applications. The RGMC can be used to test and develop new calibration algorithms, for example, to detect gain anomalies, and/or correct for slow drifts that affect climate-quality measurements over an accelerated time scale. A generalized approach to analyzing radiometer system designs yields a mathematical treatment of noise reference measurements in calibration algorithms. By treating the measurements from the different noise references as ensemble samples of the receiver state, i.e. receiver gain, a quantitative description of the non-stationary properties of the underlying receiver fluctuations can be derived. Excellent agreement has been obtained between model calculations and radiometric measurements. The mathematical formulation is equivalent to modulating the gain of a stable receiver with an externally generated signal and is the basis for ensemble detection and analysis (EDA). The concept of generating ensemble data sets using an ensemble detector is similar to the ensemble data sets generated as part of ensemble empirical mode decomposition (EEMD) with exception of a key distinguishing factor. EEMD adds noise to the signal under study whereas EDA mixes the signal with calibrated noise. It is mixing with calibrated noise that permits the measurement of temporal-functional variability of uncertainty in the underlying process. The RGMC permits the evaluation of EDA by

  18. Genetic improvement of Saccharomyces cerevisiae wine strains for enhancing cell viability after desiccation stress.

    PubMed

    López-Martínez, Gema; Pietrafesa, Rocchina; Romano, Patrizia; Cordero-Otero, Ricardo; Capece, Angela

    2013-08-01

    In the last few decades spontaneous grape must fermentations have been replaced by inoculated fermentation with Saccharomyces cerevisiae strains as active dry yeast (ADY). Among the essential genes previously characterized to overcome the cell-drying/rehydration process, six belong to the group of very hydrophilic proteins known as hydrophilins. Among them, only SIP18 has shown early transcriptional response during dehydration stress. In fact, the overexpression in S. cerevisiae of gene SIP18 increases cell viability after the dehydration process. The purpose of this study was to characterize dehydration stress tolerance of three wild and one commercial S. cerevisiae strains of wine origin. The four strains were submitted to transformation by insertion of the gene SIP18. Selected transformants were submitted to the cell-drying-rehydration process and yeast viability was evaluated by both viable cell count and flow cytometry. The antioxidant capacity of SIP18p was illustrated by ROS accumulation reduction after H2 O2 attack. Growth data as cellular duplication times and lag times were calculated to estimate cell vitality after the cell rehydration process. The overexpressing SIP18 strains showed significantly longer time of lag phase despite less time needed to stop the leakage of intracellular compounds during the rehydration process. Subsequently, the transformants were tested in inoculated grape must fermentation at laboratory scale in comparison to untransformed strains. Chemical analyses of the resultant wines indicated that no significant change for the content of secondary compounds was detected. The obtained data showed that the transformation enhances the viability of ADY without affecting fermentation efficiency and metabolic behaviour.

  19. Genetics- and genomics-based interventions for nutritional enhancement of grain legume crops: status and outlook.

    PubMed

    Bohra, Abhishek; Sahrawat, Kanwar L; Kumar, Shiv; Joshi, Rohit; Parihar, Ashok K; Singh, Ummed; Singh, Deepak; Singh, Narendra P

    2015-05-01

    Meeting the food demands and ensuring nutritional security of the ever increasing global population in the face of degrading natural resource base and impending climate change is the biggest challenge of the twenty first century. The consequences of mineral/micronutrient deficiencies or the hidden hunger in the developing world are indeed alarming and need urgent attention. In addressing the problems associated with mineral/micronutrient deficiency, grain legumes as an integral component of the farming systems in the developing world have to play a crucial role. For resource-poor populations, a strategy based on selecting and/or developing grain legume cultivars with grains denser in micronutrients, by biofortification, seems the most appropriate and attractive approach to address the problem. This is evident from the on-going global research efforts on biofortification to provide nutrient-dense grains for use by the poorest of the poor in the developing countries. Towards this end, rapidly growing genomics technologies hold promise to hasten the progress of breeding nutritious legume crops. In conjunction with the myriad of expansions in genomics, advances in other 'omics' technologies particularly plant ionomics or ionome profiling open up novel opportunities to comprehensively examine the elemental composition and mineral networks of an organism in a rapid and cost-effective manner. These emerging technologies would effectively guide the scientific community to enrich the edible parts of grain legumes with bio-available minerals and enhancers/promoters. We believe that the application of these new-generation tools in turn would provide crop-based solutions to hidden hunger worldwide for achieving global nutritional security. PMID:25592547

  20. Phenotypic and Marker-Assisted Genetic Enhancement of Parental Lines of Rajalaxmi, an Elite Rice Hybrid

    PubMed Central

    Dash, Amit K.; Rao, Ravi N.; Rao, G. J. N.; Verma, Ram L.; Katara, Jawahar L.; Mukherjee, Arup K.; Singh, Onkar N.; Bagchi, Torit B.

    2016-01-01

    The cytoplasmic male sterile line system comprising CRMS 32A and its maintainer line CRMS 32B is a popular choice for the development of new hybrids in India as CRMS 32A, having Kalinga 1 cytoplasm (other than WA), is a viable alternative to WA cytoplasm. However, both lines are susceptible to bacterial blight (BB), a major disease on rice. As enhancement of host plant resistance is the most effective and economical strategy to control this disease, four resistance genes (Xa4, xa5, xa13, and Xa21) were transferred from a BB pyramid line of IR64, into the A and B lines using a marker-assisted backcrossing (MAB) breeding strategy. During the transfer of genes into CRMS 32B, foreground selection was applied using markers associated with the genes, and plants having resistance alleles of the donor, are selected. Selection for morphological and quality traits was practiced to select plants similar to the recurrent parent. The four gene and three gene pyramid lines exhibited high levels of resistance against the BB pathogen when challenged with eight virulent isolates. Using genome wide based SSR markers for background selection, pyramids having >95% of the recurrent parent genome were identified. With CRMS 32B gene pyramid as donor, the four resistance genes were transferred into the A line through repeated backcrosses and the A line pyramids also exhibited high level of resistance against BB. Through a combination of selection at phenotypic and molecular levels, four BB resistance genes were successfully introduced into two parental lines (CRMS 32 B and A) of Rajalaxmi, an elite popular hybrid. The pyramided B lines did exhibit high levels of resistance against BB. Selection for morphological and quality traits and background selection hastened the recovery of the recurrent parent genome in the recombinants. Through repeated backcrosses, all the four resistance genes were transferred to CRMS 32A and test crosses suggest that the maintenance ability of the improved CRMS

  1. Enhanced production of Thermomyces lanuginosus lipase in Pichia pastoris via genetic and fermentation strategies.

    PubMed

    Fang, Zhonggang; Xu, Li; Pan, Dujie; Jiao, Liangcheng; Liu, Ziming; Yan, Yunjun

    2014-10-01

    This study attempted to enhance the expression level of Thermomyces lanuginosus lipase (TLL) in Pichia pastoris using a series of strategies. The tll gene was first inserted into the expression vector pPIC9 K and transformed into P. pastoris strain GS115. The maximum hydrolytic activity of TLL reached 4,350 U/mL under the optimal culture conditions of a 500 mL shaking flask containing 20 mL culture medium with the addition of 1.2 % (w/v) methanol, cultivation for 144 h at pH 7.0 and 27 °C. To further increase the TLL expression and copy number, strains containing two plasmids were obtained by sequential electroporation into GS115/9k-TLL #3 with a second vector, either pGAPZαA-TLL, pFZα-TLL, or pPICZαA-TLL. The maximum activity of the resultant strains GS115/9KTLL-ZαATLL #40, GS115/9KTLL-FZαATLL #46 and GS115/9KTLL-GAPTLL #45 was 6,600 U/mL, 6,000 U/mL and 4,800 U/mL, respectively. The tll copy number in these strains, as assessed by real-time quantitative PCR, was demonstrated to be seven, five, and three, respectively, versus two copies in GS115/9k-TLL #3. When a co-feeding strategy of sorbitol/methanol was adopted in a 3-L fermenter, the maximum TLL activity of GS115/9k-TLL #3 increased to 27,000 U/mL after 130 h of fed-batch fermentation, whereas, the maximum TLL activity was 19,500 U/mL after 145 h incubation when methanol was used as the sole carbon source.

  2. Phenotypic and Marker-Assisted Genetic Enhancement of Parental Lines of Rajalaxmi, an Elite Rice Hybrid.

    PubMed

    Dash, Amit K; Rao, Ravi N; Rao, G J N; Verma, Ram L; Katara, Jawahar L; Mukherjee, Arup K; Singh, Onkar N; Bagchi, Torit B

    2016-01-01

    The cytoplasmic male sterile line system comprising CRMS 32A and its maintainer line CRMS 32B is a popular choice for the development of new hybrids in India as CRMS 32A, having Kalinga 1 cytoplasm (other than WA), is a viable alternative to WA cytoplasm. However, both lines are susceptible to bacterial blight (BB), a major disease on rice. As enhancement of host plant resistance is the most effective and economical strategy to control this disease, four resistance genes (Xa4, xa5, xa13, and Xa21) were transferred from a BB pyramid line of IR64, into the A and B lines using a marker-assisted backcrossing (MAB) breeding strategy. During the transfer of genes into CRMS 32B, foreground selection was applied using markers associated with the genes, and plants having resistance alleles of the donor, are selected. Selection for morphological and quality traits was practiced to select plants similar to the recurrent parent. The four gene and three gene pyramid lines exhibited high levels of resistance against the BB pathogen when challenged with eight virulent isolates. Using genome wide based SSR markers for background selection, pyramids having >95% of the recurrent parent genome were identified. With CRMS 32B gene pyramid as donor, the four resistance genes were transferred into the A line through repeated backcrosses and the A line pyramids also exhibited high level of resistance against BB. Through a combination of selection at phenotypic and molecular levels, four BB resistance genes were successfully introduced into two parental lines (CRMS 32 B and A) of Rajalaxmi, an elite popular hybrid. The pyramided B lines did exhibit high levels of resistance against BB. Selection for morphological and quality traits and background selection hastened the recovery of the recurrent parent genome in the recombinants. Through repeated backcrosses, all the four resistance genes were transferred to CRMS 32A and test crosses suggest that the maintenance ability of the improved CRMS

  3. Positive genetic correlation between female preference and offspring fitness.

    PubMed

    Hine, Emma; Lachish, Shelly; Higgie, Megan; Blows, Mark W

    2002-11-01

    In many species, females display preferences for extreme male signal traits, but it has not been determined if such preferences evolve as a consequence of females gaining genetic benefits from exercising choice. If females prefer extreme male traits because they indicate male genetic quality that will enhance the fitness of offspring, a genetic correlation will evolve between female preference genes and genes that confer offspring fitness. We show that females of Drosophila serrata prefer extreme male cuticular hydrocarbon (CHC) blends, and that this preference affects offspring fitness. Female preference is positively genetically correlated with offspring fitness, indicating that females have gained genetic benefits from their choice of males. Despite male CHCs experiencing strong sexual selection, the genes underlying attractive CHCs also conferred lower offspring fitness, suggesting a balance between sexual selection and natural selection may have been reached in this population.

  4. Achieving yield gains in wheat.

    PubMed

    Reynolds, Matthew; Foulkes, John; Furbank, Robert; Griffiths, Simon; King, Julie; Murchie, Erik; Parry, Martin; Slafer, Gustavo

    2012-10-01

    Wheat provides 20% of calories and protein consumed by humans. Recent genetic gains are <1% per annum (p.a.), insufficient to meet future demand. The Wheat Yield Consortium brings expertise in photosynthesis, crop adaptation and genetics to a common breeding platform. Theory suggest radiation use efficiency (RUE) of wheat could be increased ~50%; strategies include modifying specificity, catalytic rate and regulation of Rubisco, up-regulating Calvin cycle enzymes, introducing chloroplast CO(2) concentrating mechanisms, optimizing light and N distribution of canopies while minimizing photoinhibition, and increasing spike photosynthesis. Maximum yield expression will also require dynamic optimization of source: sink so that dry matter partitioning to reproductive structures is not at the cost of the roots, stems and leaves needed to maintain physiological and structural integrity. Crop development should favour spike fertility to maximize harvest index so phenology must be tailored to different photoperiods, and sensitivity to unpredictable weather must be modulated to reduce conservative responses that reduce harvest index. Strategic crossing of complementary physiological traits will be augmented with wide crossing, while genome-wide selection and high throughput phenotyping and genotyping will increase efficiency of progeny screening. To ensure investment in breeding achieves agronomic impact, sustainable crop management must also be promoted through crop improvement networks.

  5. Expression of Rice Chitinase Gene in Genetically Engineered Tomato Confers Enhanced Resistance to Fusarium Wilt and Early Blight.

    PubMed

    Jabeen, Nyla; Chaudhary, Zubeda; Gulfraz, Muhammad; Rashid, Hamid; Mirza, Bushra

    2015-09-01

    This is the first study reporting the evaluation of transgenic lines of tomato harboring rice chitinase (RCG3) gene for resistance to two important fungal pathogens Fusarium oxysporum f. sp. lycopersici (Fol) causing fusarium wilt and Alternaria solani causing early blight (EB). In this study, three transgenic lines TL1, TL2 and TL3 of tomato Solanum lycopersicum Mill. cv. Riogrande genetically engineered with rice chitinase (RCG 3) gene and their R1 progeny was tested for resistance to Fol by root dip method and A. solani by detached leaf assay. All the R0 transgenic lines were highly resistant to these fungal pathogens compared to non-transgenic control plants. The pattern of segregation of three independent transformant for Fol and A. solani was also studied. Mendelian segregation was observed in transgenic lines 2 and 3 while it was not observed in transgenic line 1. It was concluded that introduction of chitinase gene in susceptible cultivar of tomato not only enhanced the resistance but was stably inherited in transgenic lines 2 and 3. PMID:26361473

  6. Biochemical, genetic, and metabolic engineering strategies to enhance coproduction of 1-propanol and ethanol in engineered Escherichia coli.

    PubMed

    Srirangan, Kajan; Liu, Xuejia; Westbrook, Adam; Akawi, Lamees; Pyne, Michael E; Moo-Young, Murray; Chou, C Perry

    2014-11-01

    We recently reported the heterologous production of 1-propanol in Escherichia coli via extended dissimilation of succinate under anaerobic conditions through expression of the endogenous sleeping beauty mutase (Sbm) operon. In the present work, we demonstrate high-level coproduction of 1-propanol and ethanol by developing novel engineered E. coli strains with effective cultivation strategies. Various biochemical, genetic, metabolic, and physiological factors affecting relative levels of acidogenesis and solventogenesis during anaerobic fermentation were investigated. In particular, CPC-PrOH3, a plasmid-free propanogenic E. coli strain derived by activating the Sbm operon on the genome, showed high levels of solventogenesis accounting for up to 85 % of dissimilated carbon. Anaerobic fed-batch cultivation of CPC-PrOH3 with glycerol as the major carbon source produced high titers of nearly 7 g/L 1-propanol and 31 g/L ethanol, implying its potential industrial applicability. The activated Sbm pathway served as an ancillary channel for consuming reducing equivalents upon anaerobic dissimilation of glycerol, resulting in an enhanced glycerol dissimilation and a major metabolic shift from acidogenesis to solventogenesis. PMID:25301579

  7. Expression of Rice Chitinase Gene in Genetically Engineered Tomato Confers Enhanced Resistance to Fusarium Wilt and Early Blight

    PubMed Central

    Jabeen, Nyla; Chaudhary, Zubeda; Gulfraz, Muhammad; Rashid, Hamid; Mirza, Bushra

    2015-01-01

    This is the first study reporting the evaluation of transgenic lines of tomato harboring rice chitinase (RCG3) gene for resistance to two important fungal pathogens Fusarium oxysporum f. sp. lycopersici (Fol) causing fusarium wilt and Alternaria solani causing early blight (EB). In this study, three transgenic lines TL1, TL2 and TL3 of tomato Solanum lycopersicum Mill. cv. Riogrande genetically engineered with rice chitinase (RCG 3) gene and their R1 progeny was tested for resistance to Fol by root dip method and A. solani by detached leaf assay. All the R0 transgenic lines were highly resistant to these fungal pathogens compared to non-transgenic control plants. The pattern of segregation of three independent transformant for Fol and A. solani was also studied. Mendelian segregation was observed in transgenic lines 2 and 3 while it was not observed in transgenic line 1. It was concluded that introduction of chitinase gene in susceptible cultivar of tomato not only enhanced the resistance but was stably inherited in transgenic lines 2 and 3. PMID:26361473

  8. Development of Genetically Modified Chinese Hamster Ovary Host Cells for the Enhancement of Recombinant Tissue Plasminogen Activator Expression

    PubMed Central

    Rahimpour, Azam; Ahani, Roshanak; Najaei, Azita; Adeli, Ahmad; Barkhordari, Farzaneh; Mahboudi, Fereidoun

    2016-01-01

    Background Chinese hamster ovary (CHO) cells are the most commonly used host system for the expression of high quality recombinant proteins. However, the development of stable, high-yielding CHO cell lines is a major bottleneck in the industrial manufacturing of therapeutic proteins. Therefore, different strategies such as the generation of more efficient expression vectors and establishment of genetically engineered host cells have been employed to increase the efficiency of cell line development. In order to examine the possibility of generating improved CHO host cells, cell line engineering approaches were developed based on ceramide transfer protein (CERT), and X-box binding protein 1s (XBP1s). Methods CHO cells were transfected with CERT S132A, a mutant variant of CERT which is resistant to phosphorylation, or XBP1s expression plasmids, and then stable cell pools were generated. Transient expression of t-PA was examined in engineered cell pools in comparison to un-modified CHO host cells. Results Overexpression of CERT S132A led to the enhancement of recombinant tissue plasminogen activator (t-PA) expression in transient expression by 50%. On the other hand, it was observed that the ectopic expression of the XBP1s, did not improve the t-PA expression level. Conclusion The results obtained in this study indicate successful development of the improved CHO host cells through CERT S132A overexpression. PMID:27547109

  9. Biochemical, genetic, and metabolic engineering strategies to enhance coproduction of 1-propanol and ethanol in engineered Escherichia coli.

    PubMed

    Srirangan, Kajan; Liu, Xuejia; Westbrook, Adam; Akawi, Lamees; Pyne, Michael E; Moo-Young, Murray; Chou, C Perry

    2014-11-01

    We recently reported the heterologous production of 1-propanol in Escherichia coli via extended dissimilation of succinate under anaerobic conditions through expression of the endogenous sleeping beauty mutase (Sbm) operon. In the present work, we demonstrate high-level coproduction of 1-propanol and ethanol by developing novel engineered E. coli strains with effective cultivation strategies. Various biochemical, genetic, metabolic, and physiological factors affecting relative levels of acidogenesis and solventogenesis during anaerobic fermentation were investigated. In particular, CPC-PrOH3, a plasmid-free propanogenic E. coli strain derived by activating the Sbm operon on the genome, showed high levels of solventogenesis accounting for up to 85 % of dissimilated carbon. Anaerobic fed-batch cultivation of CPC-PrOH3 with glycerol as the major carbon source produced high titers of nearly 7 g/L 1-propanol and 31 g/L ethanol, implying its potential industrial applicability. The activated Sbm pathway served as an ancillary channel for consuming reducing equivalents upon anaerobic dissimilation of glycerol, resulting in an enhanced glycerol dissimilation and a major metabolic shift from acidogenesis to solventogenesis.

  10. AAV8-mediated in vivo overexpression of miR-155 enhances the protective capacity of genetically attenuated malarial parasites.

    PubMed

    Hentzschel, Franziska; Hammerschmidt-Kamper, Christiane; Börner, Kathleen; Heiss, Kirsten; Knapp, Bettina; Sattler, Julia M; Kaderali, Lars; Castoldi, Mirco; Bindman, Julia G; Malato, Yann; Willenbring, Holger; Mueller, Ann-Kristin; Grimm, Dirk

    2014-12-01

    Malaria, caused by protozoan Plasmodium parasites, remains a prevalent infectious human disease due to the lack of an efficient and safe vaccine. This is directly related to the persisting gaps in our understanding of the parasite's interactions with the infected host, especially during the clinically silent yet essential liver stage of Plasmodium development. Previously, we and others showed that genetically attenuated parasites (GAP) that arrest in the liver induce sterile immunity, but only upon multiple administrations. Here, we comprehensively studied hepatic gene and miRNA expression in GAP-injected mice, and found both a broad activation of IFNγ-associated pathways and a significant increase of murine microRNA-155 (miR-155), that was especially pronounced in non-parenchymal cells including liver-resident macrophages (Kupffer cells). Remarkably, ectopic upregulation of this miRNA in the liver of mice using robust hepatotropic adeno-associated virus 8 (AAV8) vectors enhanced GAP's protective capacity substantially. In turn, this AAV8-mediated miR-155 expression permitted a reduction of GAP injections needed to achieve complete protection against infectious parasite challenge from previously three to only one. Our study highlights a crucial role of mammalian miRNAs in Plasmodium liver infection in vivo and concurrently implies their great potential as future immune-augmenting agents in improved vaccination regimes against malaria and other diseases.

  11. A rapid method for detection of genetically modified organisms based on magnetic separation and surface-enhanced Raman scattering.

    PubMed

    Guven, Burcu; Boyacı, İsmail Hakkı; Tamer, Ugur; Çalık, Pınar

    2012-01-01

    In this study, a new method combining magnetic separation (MS) and surface-enhanced Raman scattering (SERS) was developed to detect genetically modified organisms (GMOs). An oligonucleotide probe which is specific for 35 S DNA target was immobilized onto gold coated magnetic nanospheres to form oligonucleotide-coated nanoparticles. A self assembled monolayer was formed on gold nanorods using 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) and the second probe of the 35 S DNA target was immobilized on the activated nanorod surfaces. Probes on the nanoparticles were hybridized with the target oligonucleotide. Optimization parameters for hybridization were investigated by high performance liquid chromatography. Optimum hybridization parameters were determined as: 4 μM probe concentration, 20 min immobilization time, 30 min hybridization time, 55 °C hybridization temperature, 750 mM buffer salt concentration and pH: 7.4. Quantification of the target concentration was performed via SERS spectra of DTNB on the nanorods. The correlation between the target concentration and the SERS signal was found to be linear within the range of 25-100 nM. The analyses were performed with only one hybridization step in 40 min. Real sample analysis was conducted using Bt-176 maize sample. The results showed that the developed MS-SERS assay is capable of detecting GMOs in a rapid and selective manner.

  12. Amoco technique gains support

    SciTech Connect

    1995-10-01

    Amoco Corp.`s low-cost horizontal drilling technique and equipment are gaining acceptance in the oilpatch after five years of design and fine-tuning work. The system is purely mechanical, and it`s designed to operate with a workover rig instead of a drilling rig. It`s engineered to drill short-radius horizontal wells with lateral sup to 1,000 feet, so far.

  13. Helicopter high gain control

    NASA Technical Reports Server (NTRS)

    Cunningham, T. B.; Nunn, E. C.

    1979-01-01

    High gain control is explored through a design study of the CH-47B helicopter. The plans are designed to obtain the maximum bandwidth possible given the hardware constraints. Controls are designed with modal control theory to specific bandwidths and closed loop mode shapes. Comparisons are made to an earlier complementary filter approach. Bandwidth improvement by removal of limitations is explored in order to establish hardware and mechanization options. Improvements in the pitch axis control system and in the rate gyro sensor noise characteristics in all axes are discussed. The use of rotor state feedback is assessed.

  14. Collapsible high gain antenna

    NASA Technical Reports Server (NTRS)

    Cribb, H. E. (Inventor)

    1973-01-01

    A lightweight small high gain antenna which is capable of being packaged in a collapsed form and automatically expanded when in use is described. The antenna includes a cylindrical housing having a rod with a piston adjacent to one end extending through it. Attached to the outer end of the rod in a normally collapsed state is a helical wire coil. When the gas producing means is activated the piston and rod are shifted outwardly to expand the wire coil. A latch is provided for holding the helical coil in the expanded position.

  15. Smoking Cessation and Weight Gain.

    ERIC Educational Resources Information Center

    Hall, Sharon M.; And Others

    1986-01-01

    Investigated determinants of weight gain after quitting smoking in two smoking treatment outcome studies. Results indicated abstinence resulted in weight gain, and postquitting weight gain was predicted by pretreatment tobacco use, a history of weight problems, and eating patterns. Relapse to smoking did not follow weight gain. (Author/BL)

  16. Stock enhancement or sea ranching? Insights from monitoring the genetic diversity, relatedness and effective population size in a seeded great scallop population (Pecten maximus).

    PubMed

    Morvezen, R; Boudry, P; Laroche, J; Charrier, G

    2016-09-01

    The mass release of hatchery-propagated stocks raises numerous questions concerning its efficiency in terms of local recruitment and effect on the genetic diversity of wild populations. A seeding program, consisting of mass release of hatchery-produced juveniles in the local naturally occurring population of great scallops (Pecten maximus L.), was initiated in the early 1980s in the Bay of Brest (France). The present study aims at evaluating whether this seeding program leads to actual population enhancement, with detectable effects on genetic diversity and effective population size, or consists of sea ranching with limited genetic consequences on the wild stock. To address this question, microsatellite-based genetic monitoring of three hatchery-born and naturally recruited populations was conducted over a 5-year period. Results showed a limited reduction in allelic richness but a strong alteration of allelic frequencies in hatchery populations, while genetic diversity appeared very stable over time in the wild populations. A temporal increase in relatedness was observed in both cultured stock and wild populations. Effective population size (Ne) estimates were low and variable in the wild population. Moreover, the application of the Ryman-Laikre model suggested a high contribution of hatchery-born scallops to the reproductive output of the wild population. Overall, the data suggest that the main objective of the seeding program, which is stock enhancement, is fulfilled. Moreover, gene flow from surrounding populations and/or the reproductive input of undetected sub-populations within the bay may buffer the Ryman-Laikre effect and ensure the retention of the local genetic variability.

  17. Private Gain, Public Loss.

    ERIC Educational Resources Information Center

    Lapp, David, Ed.; Ruben, Barbara, Ed.

    1994-01-01

    Corporations contribute curricular materials to schools. Argues that the goal of these materials is to initiate the school-age population to their products, enhance their public image, and increase visibility of their products. Cites examples of corporate activity with these goals. (MDH)

  18. FEL gain optimisation and spontaneous radiation

    SciTech Connect

    Bali, L.M.; Srivastava, A.; Pandya, T.P.

    1995-12-31

    Colson have evaluated FEL gains for small deviations from perfect electron beam injection, with radiation of the same polarisation as that of the wiggler fields. We find that for optimum gain the polarisation of the optical field should be the same as that of the spontaneous emission under these conditions. With a helical wiggler the axial oscillations resulting from small departures from perfect electron beam injection lead to injection dependent unequal amplitudes and phases of the spontaneous radiation in the two transverse directions. Viewed along the axis therefore the spontaneous emission is elliptically polarised. The azimuth of the ellipse varies with the difference of phase of the two transverse components of spontaneous emission but the eccentricity remains the same. With planar wigglers the spontaneous emission viewed in the axial direction is linearly polarised, again with an injection dependent azimuth. For optimum coherent gain of a radiation field its polarisation characteristics must be the same as those of the spontaneous radiation with both types of wiggler. Thus, with a helical wiggler and the data reported earlier, an increase of 10% in the FEL gain at the fundamental frequency and of 11% at the fifth harmonic has been calculated in the small gain per pass limit. Larger enhancements in gain may result from more favourable values of input parameters.

  19. Managing price, gaining profit.

    PubMed

    Marn, M V; Rosiello, R L

    1992-01-01

    The fastest and most effective way for a company to realize maximum profit is to get its pricing right. The right price can boost profit faster than increasing volume will; the wrong price can shrink it just as quickly. Yet many otherwise tough-minded managers miss out on significant profits because they shy away from pricing decisions for fear that they will alienate their customers. Worse, if management isn't controlling its pricing policies, there's a good chance that the company's clients are manipulating them to their own advantage. McKinsey & Company's Michael Marn and Robert Rosiello show managers how to gain control of the pricing puzzle and capture untapped profit potential by using two basic concepts: the pocket price waterfall and the pocket price band. The pocket price waterfall reveals how price erodes between a company's invoice figure and the actual amount paid by the customer--the transaction price. It tracks the volume purchase discounts, early payment bonuses, and frequent customer incentives that squeeze a company's profits. The pocket price band plots the range of pocket prices over which any given unit volume of a single product sells. Wide price bands are commonplace: some manufacturers' transaction prices for a given product range 60%; one fastener supplier's price band ranged up to 500%. Managers who study their pocket price waterfalls and bands can identify unnecessary discounting at the transaction level, low-performance accounts, and misplaced marketing efforts. The problems, once identified, are typically easy and inexpensive to remedy. PMID:10121318

  20. Acting to gain information

    NASA Technical Reports Server (NTRS)

    Rosenchein, Stanley J.; Burns, J. Brian; Chapman, David; Kaelbling, Leslie P.; Kahn, Philip; Nishihara, H. Keith; Turk, Matthew

    1993-01-01

    This report is concerned with agents that act to gain information. In previous work, we developed agent models combining qualitative modeling with real-time control. That work, however, focused primarily on actions that affect physical states of the environment. The current study extends that work by explicitly considering problems of active information-gathering and by exploring specialized aspects of information-gathering in computational perception, learning, and language. In our theoretical investigations, we analyzed agents into their perceptual and action components and identified these with elements of a state-machine model of control. The mathematical properties of each was developed in isolation and interactions were then studied. We considered the complexity dimension and the uncertainty dimension and related these to intelligent-agent design issues. We also explored active information gathering in visual processing. Working within the active vision paradigm, we developed a concept of 'minimal meaningful measurements' suitable for demand-driven vision. We then developed and tested an architecture for ongoing recognition and interpretation of visual information. In the area of information gathering through learning, we explored techniques for coping with combinatorial complexity. We also explored information gathering through explicit linguistic action by considering the nature of conversational rules, coordination, and situated communication behavior.

  1. Managing price, gaining profit.

    PubMed

    Marn, M V; Rosiello, R L

    1992-01-01

    The fastest and most effective way for a company to realize maximum profit is to get its pricing right. The right price can boost profit faster than increasing volume will; the wrong price can shrink it just as quickly. Yet many otherwise tough-minded managers miss out on significant profits because they shy away from pricing decisions for fear that they will alienate their customers. Worse, if management isn't controlling its pricing policies, there's a good chance that the company's clients are manipulating them to their own advantage. McKinsey & Company's Michael Marn and Robert Rosiello show managers how to gain control of the pricing puzzle and capture untapped profit potential by using two basic concepts: the pocket price waterfall and the pocket price band. The pocket price waterfall reveals how price erodes between a company's invoice figure and the actual amount paid by the customer--the transaction price. It tracks the volume purchase discounts, early payment bonuses, and frequent customer incentives that squeeze a company's profits. The pocket price band plots the range of pocket prices over which any given unit volume of a single product sells. Wide price bands are commonplace: some manufacturers' transaction prices for a given product range 60%; one fastener supplier's price band ranged up to 500%. Managers who study their pocket price waterfalls and bands can identify unnecessary discounting at the transaction level, low-performance accounts, and misplaced marketing efforts. The problems, once identified, are typically easy and inexpensive to remedy.

  2. On Comparing Transition Rate Gains.

    ERIC Educational Resources Information Center

    Reuterberg, Sven-Eric

    This report is about the problem of making transition or enrollment rate gains comparable. It is shown that measures based on the proportions themselves, i.e. the difference between proportions, the proportion ratio and the residual gain ratio do not make the gains comparable. Instead a non-linear transformation has to be done. Two such…

  3. Airflow models gaining clout

    SciTech Connect

    Post, N.M.

    1994-10-10

    Move over, mock-ups. So long, smoke bombs. Take a walk, wind tunnels. Computational fluid dynamics, a spaceage simulation technique, is gaining velocity in the building community. And the design of inner spaces may never be the same. CFD is an equation-intensive computer modeling method that can simulate transient and steady-state airflow patterns and temperature gradients, indoors or out. CFD is used to downsize heating, ventilating and air conditioning systems, locate air outlets, and in general, create spaces that offer creature comfort, provide quality air and use less energy. The method is good for new construction, retrofits and forensic work, for example to investigate a building fire or a contaminant. In a room, CFD helps engineers consider, over a period of time, the combined impacts of ventilation, size, shape, contents, weather, even fenestration. For its first decade or two, CFD stayed the near-exclusive domain of aerospace, defense and electronics. With few exceptions, the building community could not afford the supercomputers that were needed to run the tens of thousands of equations involved. However, in the past few years, thanks to the increasing power and decreasing cost of computers, CFD simulation became practical. Curtain wall designers are even using it, though not without some controversy. Indoor air quality specialists, smoke and fire-spread researchers, laboratory designers, energy engineers, code writers, architects, and plant and building engineers are uncharacteristically upbeat about the tool. {open_quotes}CFD modeling is so many light years ahead of design tools that exist,{close_quotes} says Mariano Rodriguez, director of research and development for architect The Hillier Group, Princeton, N.J. {open_quotes}It`s the next step up from a wind tunnel test, and you don`t need a $300,000 wind tunnel.{close_quotes}

  4. Monitoring substrate and products in a bioprocess with FTIR spectroscopy coupled to artificial neural networks enhanced with a genetic-algorithm-based method for wavelength selection.

    PubMed

    Franco, Vanina G; Perín, Juan C; Mantovani, Víctor E; Goicoechea, Héctor C

    2006-01-15

    An experiment was developed as a simple alternative to existing analytical methods for the simultaneous quantitation of glucose (substrate) and glucuronic acid (main product) in the bioprocesses Kombucha by using FTIR spectroscopy coupled to multivariate calibration (partial least-squares, PLS-1 and artificial neural networks, ANNs). Wavelength selection through a novel ranked regions genetic algorithm (RRGA) was used to enhance the predictive ability of the chemometric models. Acceptable results were obtained by using the ANNs models considering the complexity of the sample and the speediness and simplicity of the method. The accuracy on the glucuronic acid determination was calculated by analysing spiked real fermentation samples (recoveries ca. 115%).

  5. Runaway sexual selection without genetic correlations: social environments and flexible mate choice initiate and enhance the Fisher process.

    PubMed

    Bailey, Nathan W; Moore, Allen J

    2012-09-01

    Female mating preferences are often flexible, reflecting the social environment in which they are expressed. Associated indirect genetic effects (IGEs) can affect the rate and direction of evolutionary change, but sexual selection models do not capture these dynamics. We incorporate IGEs into quantitative genetic models to explore how variation in social environments and mate choice flexibility influence Fisherian sexual selection. The importance of IGEs is that runaway sexual selection can occur in the absence of a genetic correlation between male traits and female preferences. Social influences can facilitate the initiation of the runaway process and increase the rate of trait elaboration. Incorporating costs to choice do not alter the main findings. Our model provides testable predictions: (1) genetic covariances between male traits and female preferences may not exist, (2) social flexibility in female choice will be common in populations experiencing strong sexual selection, (3) variation in social environments should be associated with rapid sexual trait divergence, and (4) secondary sexual traits will be more elaborate than previously predicted. Allowing feedback from the social environment resolves discrepancies between theoretical predictions and empirical data, such as why indirect selection on female preferences, theoretically weak, might be sufficient for preferences to become elaborated.

  6. RUNAWAY SEXUAL SELECTION WITHOUT GENETIC CORRELATIONS: SOCIAL ENVIRONMENTS AND FLEXIBLE MATE CHOICE INITIATE AND ENHANCE THE FISHER PROCESS

    PubMed Central

    Bailey, Nathan W; Moore, Allen J

    2012-01-01

    Female mating preferences are often flexible, reflecting the social environment in which they are expressed. Associated indirect genetic effects (IGEs) can affect the rate and direction of evolutionary change, but sexual selection models do not capture these dynamics. We incorporate IGEs into quantitative genetic models to explore how variation in social environments and mate choice flexibility influence Fisherian sexual selection. The importance of IGEs is that runaway sexual selection can occur in the absence of a genetic correlation between male traits and female preferences. Social influences can facilitate the initiation of the runaway process and increase the rate of trait elaboration. Incorporating costs to choice do not alter the main findings. Our model provides testable predictions: (1) genetic covariances between male traits and female preferences may not exist, (2) social flexibility in female choice will be common in populations experiencing strong sexual selection, (3) variation in social environments should be associated with rapid sexual trait divergence, and (4) secondary sexual traits will be more elaborate than previously predicted. Allowing feedback from the social environment resolves discrepancies between theoretical predictions and empirical data, such as why indirect selection on female preferences, theoretically weak, might be sufficient for preferences to become elaborated. PMID:22946795

  7. A Model Inquiry-Based Genetics Experiment for Introductory Biology Students: Screening for Enhancers & Suppressors of Ptpmeg

    ERIC Educational Resources Information Center

    Setty, Sumana; Kosinski-Collins, Melissa S.

    2015-01-01

    It has been noted that undergraduate project-based laboratories lead to increased interest in scientific research and student understanding of biological concepts. We created a novel, inquiry-based, multiweek genetics research project studying Ptpmeg, for the Introductory Biology Laboratory course at Brandeis University. Ptpmeg is a protein…

  8. Potential gains in lifetime net merit from genomic testing of cows, heifers, and calves on commercial dairy farms.

    PubMed

    Weigel, K A; Hoffman, P C; Herring, W; Lawlor, T J

    2012-04-01

    The objective of this study was to quantify the gains in genetic potential of replacement females that could be achieved by using genomic testing to facilitate selection and culling decisions on commercial dairy farms. Data were simulated for 100 commercial dairy herds, each with 1,850 cows, heifers, and calves. Parameters of the simulation were based on the US Holstein population, and assumed reliabilities of traditional and genomic predictions matched reliabilities of animals that have been genotyped to date. Selection of the top 10, 20, 30, …, 90% of animals within each age group was based on parent averages and predicted transmitting abilities with or without genomic testing of all animals or subsets of animals that had been presorted by traditional predictions. Average gains in lifetime net merit breeding value of selected females due to genomic testing, minus prorated costs of genotyping the animals and their unselected contemporaries, ranged from $28 (top 90% selected) to $259 (top 20% selected) for heifer calves with no pedigrees, $14 (top 90% selected) to $121 (top 10% selected) for heifer calves with known sires, and $7 (top 90% selected) to $87 (top 20% selected) for heifer calves with full pedigrees. In most cases, gains in genetic merit of selected heifer calves far exceeded prorated genotyping costs, and gains were greater for animals with missing or incomplete pedigree information. Gains in genetic merit due to genomic testing were smaller for lactating cows that had phenotypic records, and in many cases, these gains barely exceeded or failed to exceed genotyping costs. Strategies based on selective genotyping of the top, middle, or bottom 50% of animals after presorting by traditional parent averages or predicted transmitting abilities were cost effective, particularly when pedigrees or phenotypes were available and a relatively small proportion of animals were to be selected or culled. Based on these results, it appears that routine genotyping of

  9. Simultaneous expression of growth hormone releasing hormone (GHRH) and hepatitis B surface antigen/somatostatin (HBsAg/SS) fusion genes in a construct in the skeletal muscle enhances rabbit weight gain.

    PubMed

    Dai, Jian-wei; Liu, Song-cai; Hao, Lin-lin; Zhang, Yong-liang; Zhang, Qianqian; Ren, Xiao-hui; Jiang, Qing-yan

    2008-01-01

    Somatostatin (SS) and growth hormone-releasing hormone (GHRH) are synthesized and secreted by the hypothalamus, which can control the synthesis and secretion of the growth hormone (GH) from the hypophysis as well as regulate the GH concentrations in animals and humans. In this article, we describe the regulation of animal growth using plasmid DNA encoding both the GHRH gene and the SS gene fused with the hepatitis B surface antigen (HBsAg) gene. We constructed a series of expression plasmids to express the GHRH and HBsAg-SS fusion genes individually as well as collectively. The fusion gene and GHRH were successfully expressed in Chinese hamster ovary (CHO) cells, as proven by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting tests. Poly D, L-lactide-co-glycolic acid (PLGA) plasmid-encapsulating microspheres were prepared and injected intramuscularly into the leg skeletal muscles of rabbits. Weight gain/day and the levels of insulinlike growth factor-I (IGF-I), SS, and hepatitis B surface antibody (HBsAb) were monitored. During days 30 postinjection, increase in weight gain/day and IGF- I concentration and decrease in SS were observed in treatment groups. From days 15 to 30 postinjection, the weight gain/day significantly increased (P < 0.05) by 129.13%, 106.8%, and 72.82% relative to the control group in the co-expression GHRH and fusion gene (named P-G-HS), fusion gene (named P-HS), and GHRH (named P-G) groups, respectively. And most importantly, the P-G-HS group showed significant weight gain/day (P < 0.05) relative to the P-G and P-HS groups. A significant increase in the IGF-I concentration and decrease in the SS level relative to the control group were also observed. The results indicated that the combination of plasmid-mediated GHRH supplementation and positive immunization against SS led to more robust weight gain/day in rabbits.

  10. Nature's loss, Immunologists gain?

    PubMed

    Aluvihare

    2000-01-01

    Nature Reviews Molecular Cell Biology Nature Publishing Group (2000). ISSN 1471-0072. Monthly First there was Annual Reviews, then came the monthly Elsevier Trends Journals, both of which try to identify hot topics in their chosen fields. The Current Opinion journals followed several years later, and Current Opinion in Cell Biology is presently one of the highest 'impact factor' review journals, with a distinguished board of editors and advisors and a systematic approach to regular coverage of the major fields of cell biology. Important topics are visited once a year, whether or not something specially exciting happened in the last 12 months. Add to this list Seminars in Cell and Developmental Biology, the FASEB journal and the countless minireviews in 'real' journals, and you begin to wonder how anyone finds any time for doing experiments, or indeed reading the primary literature. So, into this already crowded field arrive three important newcomers: Nature Reviews in Molecular Cell Biology, Genetics, and Neurosciences, of which the first two will probably interest readers of Journal of Cell Science the most. Backed by the name and money of Nature and edited by experienced Nature staff, it is hard to see how these publications can possibly do other than succeed with writers and readers alike. What's inside the first issue? The cover of Nature Reviews in Molecular Cell Biology presents a 3-colour montage of a blue cell nucleus surrounded by splotches of green GPI-anchored GFP overlaid by orange actin stress fibres that seem to come from somewhere else. This image trails a comprehensive review from Kai Simons and Derek Toomre about Lipid Rafts. There are another five major review articles: calcium puffs and sparks, rings around DNA, HIV inhibitors, kinesin and the circadian clock provide a rich and varied mix of topics from authors who know what they're talking about. Surrounding this core is an entertaining mixture of 'highlights' at the front: news and views about

  11. Nature's loss, Immunologists gain?

    PubMed

    Aluvihare

    2000-01-01

    Nature Reviews Molecular Cell Biology Nature Publishing Group (2000). ISSN 1471-0072. Monthly First there was Annual Reviews, then came the monthly Elsevier Trends Journals, both of which try to identify hot topics in their chosen fields. The Current Opinion journals followed several years later, and Current Opinion in Cell Biology is presently one of the highest 'impact factor' review journals, with a distinguished board of editors and advisors and a systematic approach to regular coverage of the major fields of cell biology. Important topics are visited once a year, whether or not something specially exciting happened in the last 12 months. Add to this list Seminars in Cell and Developmental Biology, the FASEB journal and the countless minireviews in 'real' journals, and you begin to wonder how anyone finds any time for doing experiments, or indeed reading the primary literature. So, into this already crowded field arrive three important newcomers: Nature Reviews in Molecular Cell Biology, Genetics, and Neurosciences, of which the first two will probably interest readers of Journal of Cell Science the most. Backed by the name and money of Nature and edited by experienced Nature staff, it is hard to see how these publications can possibly do other than succeed with writers and readers alike. What's inside the first issue? The cover of Nature Reviews in Molecular Cell Biology presents a 3-colour montage of a blue cell nucleus surrounded by splotches of green GPI-anchored GFP overlaid by orange actin stress fibres that seem to come from somewhere else. This image trails a comprehensive review from Kai Simons and Derek Toomre about Lipid Rafts. There are another five major review articles: calcium puffs and sparks, rings around DNA, HIV inhibitors, kinesin and the circadian clock provide a rich and varied mix of topics from authors who know what they're talking about. Surrounding this core is an entertaining mixture of 'highlights' at the front: news and views about

  12. Recent and Projected Increases in Atmospheric CO2 Concentration Can Enhance Gene Flow between Wild and Genetically Altered Rice (Oryza sativa)

    PubMed Central

    Ziska, Lewis H.; Gealy, David R.; Tomecek, Martha B.; Jackson, Aaron K.; Black, Howard L.

    2012-01-01

    Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO2 between genetically modified crops and wild, weedy relatives increase the spread of novel genes, potentially altering evolutionary fitness? Here we show that increasing CO2 from an early 20th century concentration (300 µmol mol−1) to current (400 µmol mol−1) and projected, mid-21st century (600 µmol mol−1) values, enhanced the flow of genes from wild, weedy rice to the genetically altered, herbicide resistant, cultivated population, with outcrossing increasing from 0.22% to 0.71% from 300 to 600 µmol mol−1. The increase in outcrossing and gene transfer was associated with differential increases in plant height, as well as greater tiller and panicle production in the wild, relative to the cultivated population. In addition, increasing CO2 also resulted in a greater synchronicity in flowering times between the two populations. The observed changes reported here resulted in a subsequent increase in rice dedomestication and a greater number of weedy, herbicide-resistant hybrid progeny. Overall, these data suggest that differential phenological responses to rising atmospheric CO2 could result in enhanced flow of novel genes and greater success of feral plant species in agroecosystems. PMID:22649533

  13. Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

    PubMed Central

    Arama, Charles; Skinner, Jeff; Doumtabe, Didier; Portugal, Silvia; Tran, Tuan M.; Jain, Aarti; Traore, Boubacar; Doumbo, Ogobara K.; Davies, David Huw; Troye-Blomberg, Marita; Dolo, Amagana; Felgner, Philip L.; Crompton, Peter D.

    2015-01-01

    Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection. PMID:26361633

  14. Optimum Reliability of Gain Scores.

    ERIC Educational Resources Information Center

    Sharma, K. K.; Gupta, J. K.

    1986-01-01

    This paper gives a mathematical treatment to findings of Zimmerman and Williams and establishes a minimum reliability for gain scores when the pretest and posttest have equal reliabilities and equal standard deviations. It discusses the behavior of the reliability of gain scores in terms of variations in other test parameters. (Author/LMO)

  15. Computer algorithm for coding gain

    NASA Technical Reports Server (NTRS)

    Dodd, E. E.

    1974-01-01

    Development of a computer algorithm for coding gain for use in an automated communications link design system. Using an empirical formula which defines coding gain as used in space communications engineering, an algorithm is constructed on the basis of available performance data for nonsystematic convolutional encoding with soft-decision (eight-level) Viterbi decoding.

  16. How aluminum adjuvants could promote and enhance non-target IgE synthesis in a genetically-vulnerable sub-population.

    PubMed

    Terhune, Todd D; Deth, Richard C

    2013-01-01

    Aluminum-containing adjuvants increase the effectiveness of vaccination, but their ability to augment immune responsiveness also carries the risk of eliciting non-target responses, especially in genetically susceptible individuals. This study reviews the relevant actions of aluminum adjuvants and sources of genetic risk that can combine to adversely affect a vulnerable sub-population. Aluminum adjuvants promote oxidative stress and increase inflammasome activity, leading to the release of IL-1β, IL-18, and IL-33, but not the important regulatory cytokine IL-12. In addition, they stimulate macrophages to produce PGE₂, which also has a role in regulating immune responses. This aluminum-induced cytokine context leads to a T(H)2 immune response, characterized by the further release of IL-3, IL-4, IL-5, IL-9, IL-13, and IgE-potentiating factors such as sCD23. Genetic variants in cytokine genes, such as IL-4, IL-13, IL-33, and IL-18 influence the response to vaccines in children and are also associated with atopy. These genetic factors may therefore define a genetically-vulnerable sub-population, children with a family history of atopy, who may experience an exaggerated T(H)2 immune response to aluminum-containing vaccines. IL-4, sCD23, and IgE are common factors for both atopy and the immune-stimulating properties of aluminum adjuvants. IL-4 is critical in the production of IgE and total IgE up-regulation. IL-4 has also been reported to induce the production of sCD23 and trigger resting sIgM+, sIgD+ B-cells to switch to sIgE+ B-cells, making them targets for IgE-potentiating factors. Further, the actions of IgE-potentiating factors on sIgE+ B-cells are polyclonal and unrestricted, triggering their differentiation into IgE-forming plasma cells. These actions provide a mechanism for aluminum-adjuvant promotion and enhancement of non-target IgE in a genetically vulnerable sub-population. Identification of these individuals may decrease the risk of adverse events

  17. Theory of noise in high-gain surface plasmon-polariton amplifiers incorporating dipolar gain media.

    PubMed

    De Leon, Israel; Berini, Pierre

    2011-10-10

    A theoretical analysis of noise in high-gain surface plasmon-polariton amplifiers incorporating dipolar gain media is presented. An expression for the noise figure is obtained in terms of the spontaneous emission rate into the amplified surface plasmon-polariton taking into account the different energy decay channels experienced by dipoles in close proximity to the metallic surface. Two amplifier structures are examined: a single-interface between a metal and a gain medium and a thin metal film bounded by identical gain media on both sides. A realistic configuration is considered where the surface plasmon-polariton undergoing amplification has a Gaussian field profile in the plane of the metal and paraxial propagation along the amplifier's length. The noise figure of these plasmonic amplifiers is studied considering three prototypical gain media with different permittivities. It is shown that the noise figure exhibits a strong dependance on the real part of the permittivities of the metal and gain medium, and that its minimum value is 4/π(∼3.53 dB). The origin of this minimum value is discussed. It is also shown that amplifier configurations supporting strongly confined surface plasmon-polaritons suffer from a large noise figure, which follows from an enhanced spontaneous emission rate due to the Purcell effect.

  18. The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data

    PubMed Central

    Chen, Gary K.; Millikan, Robert C.; John, Esther M.; Ambrosone, Christine B.; Bernstein, Leslie; Zheng, Wei; Hu, Jennifer J.; Chanock, Stephen J.; Ziegler, Regina G.; Bandera, Elisa V.; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.

    2010-01-01

    We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study. PMID:20824062

  19. Genetic Enhancement as Care or as Domination? The Ethics of Asymmetrical Relationships in the Upbringing of Children

    ERIC Educational Resources Information Center

    Junker-Kenny, Maureen

    2005-01-01

    Should a society oriented towards justice provide parents with the possibility of enhancing their children's genes? The opposing arguments of authors in the Rawls School and of the theorist of communicative action, Jurgen Habermas, are analysed in terms of their key concepts. Their positions are then assessed from the point of view of the…

  20. A Web-based database of genetic association studies in cutaneous melanoma enhanced with network-driven data exploration tools

    PubMed Central

    Athanasiadis, Emmanouil I.; Antonopoulou, Kyriaki; Chatzinasiou, Foteini; Lill, Christina M.; Bourdakou, Marilena M.; Sakellariou, Argiris; Kypreou, Katerina; Stefanaki, Irene; Evangelou, Evangelos; Ioannidis, John P.A.; Bertram, Lars; Stratigos, Alexander J.; Spyrou, George M.

    2014-01-01

    The publicly available online database MelGene provides a comprehensive, regularly updated, collection of data from genetic association studies in cutaneous melanoma (CM), including random-effects meta-analysis results of all eligible polymorphisms. The updated database version includes data from 192 publications with information on 1114 significantly associated polymorphisms across 280 genes, along with new front-end and back-end capabilities. Various types of relationships between data are calculated and visualized as networks. We constructed 13 different networks containing the polymorphisms and the genes included in MelGene. We explored the derived network representations under the following questions: (i) are there nodes that deserve consideration regarding their network connectivity characteristics? (ii) What is the relation of either the genome-wide or nominally significant CM polymorphisms/genes with the ones highlighted by the network representation? We show that our network approach using the MelGene data reveals connections between statistically significant genes/ polymorphisms and other genes/polymorphisms acting as ‘hubs’ in the reconstructed networks. To the best of our knowledge, this is the first database containing data from a comprehensive field synopsis and systematic meta-analyses of genetic polymorphisms in CM that provides user-friendly tools for in-depth molecular network visualization and exploration. The proposed network connections highlight potentially new loci requiring further investigation of their relation to melanoma risk. Database URL: http://www.melgene.org. PMID:25380778

  1. Genetic Deletion of the Transcriptional Repressor NFIL3 Enhances Axon Growth In Vitro but Not Axonal Repair In Vivo

    PubMed Central

    van der Kallen, Loek R.; Eggers, Ruben; Ehlert, Erich M.; Verhaagen, Joost; Smit, August B.; van Kesteren, Ronald E.

    2015-01-01

    Axonal regeneration after injury requires the coordinated expression of genes in injured neurons. We previously showed that either reducing expression or blocking function of the transcriptional repressor NFIL3 activates transcription of regeneration-associated genes Arg1 and Gap43 and strongly promotes axon outgrowth in vitro. Here we tested whether genetic deletion or dominant-negative inhibition of NFIL3 could promote axon regeneration and functional recovery after peripheral nerve lesion in vivo. Contrary to our expectations, we observed no changes in the expression of regeneration-associated genes and a significant delay in functional recovery following genetic deletion of Nfil3. When NFIL3 function was inhibited specifically in dorsal root ganglia prior to sciatic nerve injury, we observed a decrease in regenerative axon growth into the distal nerve segment rather than an increase. Finally, we show that deletion of Nfil3 changes sciatic nerve lesion-induced expression in dorsal root ganglia of genes that are not typically involved in regeneration, including several olfactory receptors and developmental transcription factors. Together our findings show that removal of NFIL3 in vivo does not recapitulate the regeneration-promoting effects that were previously observed in vitro, indicating that in vivo transcriptional control of regeneration is probably more complex and more robust against perturbation than in vitro data may suggest. PMID:25993115

  2. The potential for modification in cloning and vitrification technology to enhance genetic progress in beef cattle in Northern Australia.

    PubMed

    Taylor-Robinson, Andrew W; Walton, Simon; Swain, David L; Walsh, Kerry B; Vajta, Gábor

    2014-08-01

    Recent advances in embryology and related research offer considerable possibilities to accelerate genetic improvement in cattle breeding. Such progress includes optimization and standardization of laboratory embryo production (in vitro fertilization - IVF), introduction of a highly efficient method for cryopreservation (vitrification), and dramatic improvement in the efficiency of somatic cell nuclear transfer (cloning) in terms of required effort, cost, and overall outcome. Handmade cloning (HMC), a simplified version of somatic cell nuclear transfer, offers the potential for relatively easy and low-cost production of clones. A potentially modified method of vitrification used at a centrally located laboratory facility could result in cloned offspring that are economically competitive with elite animals produced by more traditional means. Apart from routine legal and intellectual property issues, the main obstacle that hampers rapid uptake of these technologies by the beef cattle industry is a lack of confidence from scientific and commercial sources. Once stakeholder support is increased, the combined application of these methods makes a rapid advance toward desirable traits (rapid growth, high-quality beef, optimized reproductive performance) a realistic goal. The potential impact of these technologies on genetic advancement in beef cattle herds in which improvement of stock is sought, such as in northern Australia, is hard to overestimate.

  3. Genetic Deletion of the Transcriptional Repressor NFIL3 Enhances Axon Growth In Vitro but Not Axonal Repair In Vivo.

    PubMed

    van der Kallen, Loek R; Eggers, Ruben; Ehlert, Erich M; Verhaagen, Joost; Smit, August B; van Kesteren, Ronald E

    2015-01-01

    Axonal regeneration after injury requires the coordinated expression of genes in injured neurons. We previously showed that either reducing expression or blocking function of the transcriptional repressor NFIL3 activates transcription of regeneration-associated genes Arg1 and Gap43 and strongly promotes axon outgrowth in vitro. Here we tested whether genetic deletion or dominant-negative inhibition of NFIL3 could promote axon regeneration and functional recovery after peripheral nerve lesion in vivo. Contrary to our expectations, we observed no changes in the expression of regeneration-associated genes and a significant delay in functional recovery following genetic deletion of Nfil3. When NFIL3 function was inhibited specifically in dorsal root ganglia prior to sciatic nerve injury, we observed a decrease in regenerative axon growth into the distal nerve segment rather than an increase. Finally, we show that deletion of Nfil3 changes sciatic nerve lesion-induced expression in dorsal root ganglia of genes that are not typically involved in regeneration, including several olfactory receptors and developmental transcription factors. Together our findings show that removal of NFIL3 in vivo does not recapitulate the regeneration-promoting effects that were previously observed in vitro, indicating that in vivo transcriptional control of regeneration is probably more complex and more robust against perturbation than in vitro data may suggest.

  4. Genetically engineered charge modifications to enhance protein separation in aqueous two-phase systems: Charge directed partitioning

    SciTech Connect

    Luther, J.R.; Glatz, C.E.

    1995-04-05

    This report continues the authors` examination of the effect of genetically engineered charge modifications on the partitioning behavior of proteins in aqueous two-phase extraction. The genetic modifications consisted of the fusion of charged peptide tails to {beta}-galactosidase and charge-change point mutations to T4 lysozyme. In this study, they examined charge directed partitioning behavior in PEG/dextran systems containing small amounts of the charged polymers diethylaminoethyl-dextran (DEAE-dextran) or dextran sulfate. The best results were obtained when attractive forces between the protein and polymer were present. Nearly 100% of the {beta}-galactosidase, which carries a net negative charge, partitioned to the DEAE-dextran-rich phase regardless of whether the phase was dextran or PEG. In these cases, cloudiness of the protein-rich phases suggest that strong charge interactions resulted in protein/polymer aggregation, which may have contribution to the extreme partitioning. Unlike the potential-driven partitioning reported previously, consistent partitioning trends were observed as a result of the fusion tails, with observed shifts in partition coefficient (K{sub p}) of up to 37-fold. However, these changes could not be solely attributed to charge-based interactions.

  5. A Web-based database of genetic association studies in cutaneous melanoma enhanced with network-driven data exploration tools.

    PubMed

    Athanasiadis, Emmanouil I; Antonopoulou, Kyriaki; Chatzinasiou, Foteini; Lill, Christina M; Bourdakou, Marilena M; Sakellariou, Argiris; Kypreou, Katerina; Stefanaki, Irene; Evangelou, Evangelos; Ioannidis, John P A; Bertram, Lars; Stratigos, Alexander J; Spyrou, George M

    2014-01-01

    The publicly available online database MelGene provides a comprehensive, regularly updated, collection of data from genetic association studies in cutaneous melanoma (CM), including random-effects meta-analysis results of all eligible polymorphisms. The updated database version includes data from 192 publications with information on 1114 significantly associated polymorphisms across 280 genes, along with new front-end and back-end capabilities. Various types of relationships between data are calculated and visualized as networks. We constructed 13 different networks containing the polymorphisms and the genes included in MelGene. We explored the derived network representations under the following questions: (i) are there nodes that deserve consideration regarding their network connectivity characteristics? (ii) What is the relation of either the genome-wide or nominally significant CM polymorphisms/genes with the ones highlighted by the network representation? We show that our network approach using the MelGene data reveals connections between statistically significant genes/ polymorphisms and other genes/polymorphisms acting as 'hubs' in the reconstructed networks. To the best of our knowledge, this is the first database containing data from a comprehensive field synopsis and systematic meta-analyses of genetic polymorphisms in CM that provides user-friendly tools for in-depth molecular network visualization and exploration. The proposed network connections highlight potentially new loci requiring further investigation of their relation to melanoma risk. Database URL: http://www.melgene.org. PMID:25380778

  6. Sabbatical leave: who gains and how much?

    PubMed

    Davidson, Oranit B; Eden, Dov; Westman, Mina; Cohen-Charash, Yochi; Hammer, Leslie B; Kluger, Avraham N; Krausz, Moshe; Maslach, Christina; O'Driscoll, Michael; Perrewé, Pamela L; Quick, James Campbell; Rosenblatt, Zehava; Spector, Paul E

    2010-09-01

    A rigorous quasi-experiment tested the ameliorative effects of a sabbatical leave, a special case of respite from routine work. We hypothesized that (a) respite increases resource level and well-being and (b) individual differences and respite features moderate respite effects. A sample of 129 faculty members on sabbatical and 129 matched controls completed measures of resource gain, resource loss, and well-being before, during, and after the sabbatical. Among the sabbatees, resource loss declined and resource gain and well-being rose during the sabbatical. The comparison group showed no change. Moderation analysis revealed that those who reported higher respite self-efficacy and greater control, were more detached, had a more positive sabbatical experience, and spent their sabbatical outside their home country enjoyed more enhanced well-being than others.

  7. Gaining approval for clinical research.

    PubMed

    Cobb, Vanessa; Srinivasan, Neil; Lambiase, Pier

    2016-07-01

    Set-up and delivery of a clinical research project can be complicated and difficult. This article introduces the regulatory processes involved in gaining approval for clinical research and discusses the obstacles that may be encountered. PMID:27388381

  8. Hitchhiking selection is driving intron gain in a pathogenic fungus.

    PubMed

    Brunner, Patrick C; Torriani, Stefano F F; Croll, Daniel; Stukenbrock, Eva H; McDonald, Bruce A

    2014-07-01

    The variability of intron density among eukaryotes is puzzling and still debated. Most previous studies have been limited because of the near absence of intron presence-absence polymorphism (IPAP) within species or because comparisons could be made only between distantly related species. We conducted population genetic analyses on eight loci showing IPAP to investigate the effect of natural selection on intron dynamics in a global collection of the panmictic fungal plant pathogen Zymoseptoria tritici and its very close relatives. Five of these loci likely represent recent intron gains because their absence is fixed among the closest relatives of Z. tritici, and three likely represent recent intron losses because their presence is fixed among the close relatives. We analyzed signatures of selection by comparing allele frequencies, nucleotide diversities, and rates of recombination and found compelling evidence that at least two out of the five intron-gain loci, a SWIM zinc-finger gene and a sugar transporter, are under directional selection favoring alleles that gained the intron. Our results suggest that the intron-present alleles of these loci are sweeping to fixation, providing a genetic hitchhiking mechanism to explain rapid intron gain in Z. tritici. The overall findings are consistent with the hypothesis that intron gains are more likely to be driven by selection while intron losses are more likely to be due to neutral processes such as genetic drift.

  9. Developmental gains in visuospatial memory predict gains in mathematics achievement.

    PubMed

    Li, Yaoran; Geary, David C

    2013-01-01

    Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning. PMID:23936154

  10. Developmental Gains in Visuospatial Memory Predict Gains in Mathematics Achievement

    PubMed Central

    Li, Yaoran; Geary, David C.

    2013-01-01

    Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning. PMID:23936154

  11. Developmental gains in visuospatial memory predict gains in mathematics achievement.

    PubMed

    Li, Yaoran; Geary, David C

    2013-01-01

    Visuospatial competencies are related to performance in mathematical domains in adulthood, but are not consistently related to mathematics achievement in children. We confirmed the latter for first graders and demonstrated that children who show above average first-to-fifth grade gains in visuospatial memory have an advantage over other children in mathematics. The study involved the assessment of the mathematics and reading achievement of 177 children in kindergarten to fifth grade, inclusive, and their working memory capacity and processing speed in first and fifth grade. Intelligence was assessed in first grade and their second to fourth grade teachers reported on their in-class attentive behavior. Developmental gains in visuospatial memory span (d = 2.4) were larger than gains in the capacity of the central executive (d = 1.6) that in turn were larger than gains in phonological memory span (d = 1.1). First to fifth grade gains in visuospatial memory and in speed of numeral processing predicted end of fifth grade mathematics achievement, as did first grade central executive scores, intelligence, and in-class attentive behavior. The results suggest there are important individual differences in the rate of growth of visuospatial memory during childhood and that these differences become increasingly important for mathematics learning.

  12. Information Gain Based Dimensionality Selection for Classifying Text Documents

    SciTech Connect

    Dumidu Wijayasekara; Milos Manic; Miles McQueen

    2013-06-01

    Selecting the optimal dimensions for various knowledge extraction applications is an essential component of data mining. Dimensionality selection techniques are utilized in classification applications to increase the classification accuracy and reduce the computational complexity. In text classification, where the dimensionality of the dataset is extremely high, dimensionality selection is even more important. This paper presents a novel, genetic algorithm based methodology, for dimensionality selection in text mining applications that utilizes information gain. The presented methodology uses information gain of each dimension to change the mutation probability of chromosomes dynamically. Since the information gain is calculated a priori, the computational complexity is not affected. The presented method was tested on a specific text classification problem and compared with conventional genetic algorithm based dimensionality selection. The results show an improvement of 3% in the true positives and 1.6% in the true negatives over conventional dimensionality selection methods.

  13. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction.

    PubMed

    Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

    2015-01-01

    Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  14. Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice

    PubMed Central

    Danilov, Camelia A.; Steward, Oswald

    2015-01-01

    Previous studies indicate that conditional genetic deletion of phosphatase and tensin homolog (PTEN) in neonatal mice enhances the ability of axons to regenerate following spinal cord injury (SCI) in adults. Here, we assessed whether deleting PTEN in adult neurons post-SCI is also effective, and whether enhanced regenerative growth is accompanied by enhanced recovery of voluntary motor function. PTENloxP/loxP mice received moderate contusion injuries at cervical level 5 (C5). One group received unilateral injections of adeno-associated virus expressing CRE (AAV-CRE) into the sensorimotor cortex; controls received a vector expressing green fluorescent protein (AAV-GFP) or injuries only (no vector injections). Forelimb function was tested for 14 weeks post-SCI using a grip strength meter (GSM) and a hanging task. The corticospinal tract (CST) was traced by injecting mini-ruby BDA into the sensorimotor cortex. Forelimb gripping ability was severely impaired immediately post-SCI but recovered slowly over time. The extent of recovery was significantly greater in PTEN-deleted mice in comparison to either the AAV-GFP group or the injury only group. BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups. In addition, in the PTEN-deleted group, there were exuberant collaterals extending from the main tract rostral to the lesion, into and around the scar tissue at the injury site. These results indicate that PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons and forelimb motor function recovery. PMID:25704959

  15. Enhanced cell surface expression, immunogenicity and genetic stability resulting from a spontaneous truncation of HIV Env expressed by a recombinant MVA

    SciTech Connect

    Wyatt, Linda S. Belyakov, Igor M.; Earl, Patricia L.; Berzofsky, Jay A.; Moss, Bernard

    2008-03-15

    During propagation of modified vaccinia virus Ankara (MVA) encoding HIV 89.6 Env, a few viral foci stained very prominently. Virus cloned from such foci replicated to higher titers than the parent and displayed enhanced genetic stability on passage. Sequence analysis showed a single nucleotide deletion in the 89.6 env gene of the mutant that caused a frame shift and truncation of 115 amino acids from the cytoplasmic domain. The truncated Env was more highly expressed on the cell surface, induced higher antibody responses than the full-length Env, reacted with HIV neutralizing monoclonal antibodies and mediated CD4/co-receptor-dependent fusion. Intramuscular (IM), intradermal (ID) needleless, and intrarectal (IR) catheter inoculations gave comparable serum IgG responses. However, intraoral (IO) needleless injector route gave the highest IgA in lung washings and IR gave the highest IgA and IgG responses in fecal extracts. Induction of CTL responses in the spleens of individual mice as assayed by intracellular cytokine staining was similar with both the full-length and truncated Env constructs. Induction of acute and memory CTL in the spleens of mice immunized with the truncated Env construct by ID, IO, and IR routes was comparable and higher than by the IM route, but only the IR route induced CTL in the gut-associated lymphoid tissue. Thus, truncation of Env enhanced genetic stability as well as serum and mucosal antibody responses, suggesting the desirability of a similar modification in MVA-based candidate HIV vaccines.

  16. The enhanced locating performance of an integrated cross-correlation and genetic algorithm for radio monitoring systems.

    PubMed

    Chang, Yao-Tang; Wu, Chi-Lin; Cheng, Hsu-Chih

    2014-01-01

    The rapid development of wireless broadband communication technology has affected the location accuracy of worldwide radio monitoring stations that employ time-difference-of-arrival (TDOA) location technology. In this study, TDOA-based location technology was implemented in Taiwan for the first time according to International Telecommunications Union Radiocommunication (ITU-R) recommendations regarding monitoring and location applications. To improve location accuracy, various scenarios, such as a three-dimensional environment (considering an unequal locating antenna configuration), were investigated. Subsequently, the proposed integrated cross-correlation and genetic algorithm was evaluated in the metropolitan area of Tainan. The results indicated that the location accuracy at a circular error probability of 50% was less than 60 m when a multipath effect was present in the area. Moreover, compared with hyperbolic algorithms that have been applied in conventional TDOA-based location systems, the proposed algorithm yielded 17-fold and 19-fold improvements in the mean difference when the location position of the interference station was favorable and unfavorable, respectively. Hence, the various forms of radio interference, such as low transmission power, burst and weak signals, and metropolitan interference, was proved to be easily identified, located, and removed. PMID:24763254

  17. The Enhanced Locating Performance of an Integrated Cross-Correlation and Genetic Algorithm for Radio Monitoring Systems

    PubMed Central

    Chang, Yao-Tang; Wu, Chi-Lin; Cheng, Hsu-Chih

    2014-01-01

    The rapid development of wireless broadband communication technology has affected the location accuracy of worldwide radio monitoring stations that employ time-difference-of-arrival (TDOA) location technology. In this study, TDOA-based location technology was implemented in Taiwan for the first time according to International Telecommunications Union Radiocommunication (ITU-R) recommendations regarding monitoring and location applications. To improve location accuracy, various scenarios, such as a three-dimensional environment (considering an unequal locating antenna configuration), were investigated. Subsequently, the proposed integrated cross-correlation and genetic algorithm was evaluated in the metropolitan area of Tainan. The results indicated that the location accuracy at a circular error probability of 50% was less than 60 m when a multipath effect was present in the area. Moreover, compared with hyperbolic algorithms that have been applied in conventional TDOA-based location systems, the proposed algorithm yielded 17-fold and 19-fold improvements in the mean difference when the location position of the interference station was favorable and unfavorable, respectively. Hence, the various forms of radio interference, such as low transmission power, burst and weak signals, and metropolitan interference, was proved to be easily identified, located, and removed. PMID:24763254

  18. Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton

    NASA Technical Reports Server (NTRS)

    Judex, Stefan; Donahue, Leah-Rae; Rubin, Clinton

    2002-01-01

    The structure of the adult skeleton is determined, in large part, by its genome. Whether genetic variations may influence the effectiveness of interventions to combat skeletal diseases remains unknown. The differential response of trabecular bone to an anabolic (low-level mechanical vibration) and a catabolic (disuse) mechanical stimulus were evaluated in three strains of adult mice. In low bone-mineral-density C57BL/6J mice, the low-level mechanical signal caused significantly larger bone formation rates (BFR) in the proximal tibia, but the removal of functional weight bearing did not significantly alter BFR. In mid-density BALB/cByJ mice, mechanical stimulation also increased BFR, whereas disuse significantly decreased BFR. In contrast, neither anabolic nor catabolic mechanical signals influenced any index of bone formation in high-density C3H/HeJ mice. Together, data from this study indicate that the sensitivity of trabecular tissue to both anabolic and catabolic stimuli is influenced by the genome. Extrapolated to humans, these results may explain in part why prophylaxes for low bone mass are not universally effective, yet also indicate that there may be a genotypic indication of people who are at reduced risk of suffering from bone loss.

  19. Loss/gain-induced ultrathin antireflection coatings.

    PubMed

    Luo, Jie; Li, Sucheng; Hou, Bo; Lai, Yun

    2016-01-01

    Tradional antireflection coatings composed of dielectric layers usually require the thickness to be larger than quarter wavelength. Here, we demonstrate that materials with permittivity or permeability dominated by imaginary parts, i.e. lossy or gain media, can realize non-resonant antireflection coatings in deep sub-wavelength scale. Interestingly, while the reflected waves are eliminated as in traditional dielectric antireflection coatings, the transmitted waves can be enhanced or reduced, depending on whether gain or lossy media are applied, respectively. We provide a unified theory for the design of such ultrathin antireflection coatings, showing that under different polarizations and incident angles, different types of ultrathin coatings should be applied. Especially, under transverse magnetic polarization, the requirement shows a switch between gain and lossy media at Brewster angle. As a proof of principle, by using conductive films as a special type of lossy antireflection coatings, we experimentally demonstrate the suppression of Fabry-Pérot resonances in a broad frequency range for microwaves. This valuable functionality can be applied to remove undesired resonant effects, such as the frequency-dependent side lobes induced by resonances in dielectric coverings of antennas. Our work provides a guide for the design of ultrathin antireflection coatings as well as their applications in broadband reflectionless devices. PMID:27349750

  20. Loss/gain-induced ultrathin antireflection coatings

    PubMed Central

    Luo, Jie; Li, Sucheng; Hou, Bo; Lai, Yun

    2016-01-01

    Tradional antireflection coatings composed of dielectric layers usually require the thickness to be larger than quarter wavelength. Here, we demonstrate that materials with permittivity or permeability dominated by imaginary parts, i.e. lossy or gain media, can realize non-resonant antireflection coatings in deep sub-wavelength scale. Interestingly, while the reflected waves are eliminated as in traditional dielectric antireflection coatings, the transmitted waves can be enhanced or reduced, depending on whether gain or lossy media are applied, respectively. We provide a unified theory for the design of such ultrathin antireflection coatings, showing that under different polarizations and incident angles, different types of ultrathin coatings should be applied. Especially, under transverse magnetic polarization, the requirement shows a switch between gain and lossy media at Brewster angle. As a proof of principle, by using conductive films as a special type of lossy antireflection coatings, we experimentally demonstrate the suppression of Fabry-Pérot resonances in a broad frequency range for microwaves. This valuable functionality can be applied to remove undesired resonant effects, such as the frequency-dependent side lobes induced by resonances in dielectric coverings of antennas. Our work provides a guide for the design of ultrathin antireflection coatings as well as their applications in broadband reflectionless devices. PMID:27349750

  1. Enhancement of antitumor activity of gammaretrovirus carrying IL-12 gene through genetic modification of envelope targeting HER2 receptor: a promising strategy for bladder cancer therapy.

    PubMed

    Tsai, Y-S; Shiau, A-L; Chen, Y-F; Tsai, H-T; Tzai, T-S; Wu, C-L

    2010-01-01

    The objective of this study was to develop an HER2-targeted, envelope-modified Moloney murine leukemia virus (MoMLV)-based gammaretroviral vector carrying interleukin (IL)-12 gene for bladder cancer therapy. It displayed a chimeric envelope protein containing a single-chain variable fragment (scFv) antibody to the HER2 receptor and carried the mouse IL-12 gene. The fragment of anti-erbB2scFv was constructed into the proline-rich region of the viral envelope of the packaging vector lacking a transmembrane subunit of the carboxyl terminal region of surface subunit. As compared with envelope-unmodified gammaretroviruses, envelope-modified ones had extended viral tropism to human HER2-expressing bladder cancer cell lines, induced apoptosis, and affected cell cycle progression despite lower viral titers. Moreover, animal studies showed that envelope-modified gammaretroviruses carrying IL-12 gene exerted higher antitumor activity in terms of retarding tumor growth and prolonging the survival of tumor-bearing mice than unmodified ones, which were associated with enhanced tumor cell apoptosis as well as increased intratumoral levels of IL-12, interferon-gamma, IL-1beta, and tumor necrosis factor-alpha proteins. Therefore, the antitumor activity of gammaretroviruses carrying the IL-12 gene was enhanced through genetic modification of the envelope targeting HER2 receptor, which may be a promising strategy for bladder cancer therapy.

  2. High current gain transistor laser.

    PubMed

    Liang, Song; Qiao, Lijun; Zhu, Hongliang; Wang, Wei

    2016-06-10

    A transistor laser (TL), having the structure of a transistor with multi-quantum wells near its base region, bridges the functionality gap between lasers and transistors. However, light emission is produced at the expense of current gain for all the TLs reported up to now, leading to a very low current gain. We propose a novel design of TLs, which have an n-doped InP layer inserted in the emitter ridge. Numerical studies show that a current flow aperture for only holes can be formed in the center of the emitter ridge. As a result, the common emitter current gain can be as large as 143.3, which is over 15 times larger than that of a TL without the aperture. Besides, the effects of nonradiative recombination defects can be reduced greatly because the flow of holes is confined in the center region of the emitter ridge.

  3. Commutated automatic gain control system

    NASA Technical Reports Server (NTRS)

    Yost, S. R.

    1981-01-01

    A commutated automatic gain control system (AGC) was designed and constructed for the prototype Loran C receiver. The AGC is designed to improve the signal-to-signal ratio of the received Loran signals. The AGC design does not require any analog to digital conversion and it utilizes commonly available components. The AGC consists of: (1) a circuit which samples the peak of the envelope of the Loran signal to obtain an AGC voltage for each of three Loran stations, (2) a dc gain circuit to control the overall gain of the AGC system, and (3) an AGC amplification of the input RF signal. The performance of the AGC system was observed in bench and flight tests; it has improved the overall accuracy of the receiver. Improvements in the accuracy of the time difference calculations to within approx. + or - 1.5 microseconds of the observed time differnces for a given position are reported.

  4. High current gain transistor laser

    NASA Astrophysics Data System (ADS)

    Liang, Song; Qiao, Lijun; Zhu, Hongliang; Wang, Wei

    2016-06-01

    A transistor laser (TL), having the structure of a transistor with multi-quantum wells near its base region, bridges the functionality gap between lasers and transistors. However, light emission is produced at the expense of current gain for all the TLs reported up to now, leading to a very low current gain. We propose a novel design of TLs, which have an n-doped InP layer inserted in the emitter ridge. Numerical studies show that a current flow aperture for only holes can be formed in the center of the emitter ridge. As a result, the common emitter current gain can be as large as 143.3, which is over 15 times larger than that of a TL without the aperture. Besides, the effects of nonradiative recombination defects can be reduced greatly because the flow of holes is confined in the center region of the emitter ridge.

  5. High current gain transistor laser

    PubMed Central

    Liang, Song; Qiao, Lijun; Zhu, Hongliang; Wang, Wei

    2016-01-01

    A transistor laser (TL), having the structure of a transistor with multi-quantum wells near its base region, bridges the functionality gap between lasers and transistors. However, light emission is produced at the expense of current gain for all the TLs reported up to now, leading to a very low current gain. We propose a novel design of TLs, which have an n-doped InP layer inserted in the emitter ridge. Numerical studies show that a current flow aperture for only holes can be formed in the center of the emitter ridge. As a result, the common emitter current gain can be as large as 143.3, which is over 15 times larger than that of a TL without the aperture. Besides, the effects of nonradiative recombination defects can be reduced greatly because the flow of holes is confined in the center region of the emitter ridge. PMID:27282466

  6. Triticale development in Algeria: genetic gains through decades.

    PubMed

    Abdelkader, Benbelkacem; Fatiha, Sadli

    2014-01-01

    Algeria started working on triticale since the late seventies, it was first as a scientific curiosity (1974-1980), the production of this crop began in the early eighties and expanded well for a decade (10.000ha) then decreased for another decade due to lack of subsidies and serious interest from decision makers putting all their effort in wheat production which is the predominant crop in the country. Since the 1990s up to date, it is developing again mainly based on feed market requirements (20.500ha in 2001) and a better consideration by stakeholders. Triticale is now developed by the informal seed system. Triticale is grown in Algeria under a wide range of soil and climatic conditions, including dryland and marginal soils. Under high input and rainfall environments, the best triticale cultivars have comparable grain yield with wheat but slightly lower to barley. This advantage is larger under dry conditions. Our study was dealing with an evaluation of the progress made in time since their introduction and selection of triticale varieties. The study was conducted on twenty five varieties and advanced lines, selected in the different phases of triticale development, during the three last seasons (2009 - 2012) in two contrasting regions (semi arid and high input environment) showed very interesting results and a linear improvement in grain yield and its components, and also in the feeding quality traits. The improvement was apparent in both sites; although result data was higher in number in the high input environment, the increase rate was larger in the semi arid area of study. In the favorable area, grain yield increased from 2.94t/ha for the varieties developed in the early phase (late 1970s), to 3.98t/ha for the varieties released in the second phase (1990s) up to 5.45t/ha for the latest varieties developed in the 2000s. Grain yield increased in the dry area from 2.42t/ha to 4.92t/ha. The trend is almost the same for all yield components and even for forage quality traits.

  7. Triticale development in Algeria: genetic gains through decades.

    PubMed

    Abdelkader, Benbelkacem; Fatiha, Sadli

    2014-01-01

    Algeria started working on triticale since the late seventies, it was first as a scientific curiosity (1974-1980), the production of this crop began in the early eighties and expanded well for a decade (10.000ha) then decreased for another decade due to lack of subsidies and serious interest from decision makers putting all their effort in wheat production which is the predominant crop in the country. Since the 1990s up to date, it is developing again mainly based on feed market requirements (20.500ha in 2001) and a better consideration by stakeholders. Triticale is now developed by the informal seed system. Triticale is grown in Algeria under a wide range of soil and climatic conditions, including dryland and marginal soils. Under high input and rainfall environments, the best triticale cultivars have comparable grain yield with wheat but slightly lower to barley. This advantage is larger under dry conditions. Our study was dealing with an evaluation of the progress made in time since their introduction and selection of triticale varieties. The study was conducted on twenty five varieties and advanced lines, selected in the different phases of triticale development, during the three last seasons (2009 - 2012) in two contrasting regions (semi arid and high input environment) showed very interesting results and a linear improvement in grain yield and its components, and also in the feeding quality traits. The improvement was apparent in both sites; although result data was higher in number in the high input environment, the increase rate was larger in the semi arid area of study. In the favorable area, grain yield increased from 2.94t/ha for the varieties developed in the early phase (late 1970s), to 3.98t/ha for the varieties released in the second phase (1990s) up to 5.45t/ha for the latest varieties developed in the 2000s. Grain yield increased in the dry area from 2.42t/ha to 4.92t/ha. The trend is almost the same for all yield components and even for forage quality traits. PMID:26072575

  8. Agrobacterium-mediated genetic transformation of Coffea arabica (L.) is greatly enhanced by using established embryogenic callus cultures

    PubMed Central

    2011-01-01

    Background Following genome sequencing of crop plants, one of the main challenges today is determining the function of all the predicted genes. When gene validation approaches are used for woody species, the main obstacle is the low recovery rate of transgenic plants from elite or commercial cultivars. Embryogenic calli have frequently been the target tissue for transformation, but the difficulty in producing or maintaining embryogenic tissues is one of the main problems encountered in genetic transformation of many woody plants, including Coffea arabica. Results We identified the conditions required for successful long-term proliferation of embryogenic cultures in C. arabica and designed a highly efficient and reliable Agrobacterium tumefaciens-mediated transformation method based on these conditions. The transformation protocol with LBA1119 harboring pBin 35S GFP was established by evaluating the effect of different parameters on transformation efficiency by GFP detection. Using embryogenic callus cultures, co-cultivation with LBA1119 OD600 = 0.6 for five days at 20 °C enabled reproducible transformation. The maintenance conditions for the embryogenic callus cultures, particularly a high auxin to cytokinin ratio, the age of the culture (optimum for 7-10 months of proliferation) and the use of a yellow callus phenotype, were the most important factors for achieving highly efficient transformation (> 90%). At the histological level, successful transformation was related to the number of proembryogenic masses present. All the selected plants were proved to be transformed by PCR and Southern blot hybridization. Conclusion Most progress in increasing transformation efficiency in coffee has been achieved by optimizing the production conditions of embryogenic cultures used as target tissues for transformation. This is the first time that a strong positive effect of the age of the culture on transformation efficiency was demonstrated. Our results make Agrobacterium

  9. Genetic expression programming-based DBA for enhancing peer-assisted music-on-demand service in EPON

    NASA Astrophysics Data System (ADS)

    Liem, Andrew Tanny; Hwang, I.-Shyan; Nikoukar, AliAkbar; Lee, Jhong-Yue

    2015-03-01

    Today, the popularity of peer-assisted music-on-demand (MoD) has increased significantly worldwide. This service allows users to access large music library tracks, listen to music, and share their playlist with other users. Unlike the conventional voice traffic, such an application maintains music quality that ranges from 160 kbps to 320 kbps, which most likely consumes more bandwidth than other traffics. In the access network, Ethernet passive optical network (EPON) is one of the best candidates for delivering such a service because of being cost-effective and with high bandwidth. To maintain music quality, a stutter needs to be prevented because of either network effects or when the due user was not receiving enough resources to play in a timely manner. Therefore, in this paper, we propose two genetic expression programming (GEP)-based dynamic bandwidth allocations (DBAs). The first DBA is a generic DBA that aims to find an optimum formula for voice, video, and data services. The second DBA aims to find optimum formulas so that Optical Line Terminal (OLT) can satisfy not only the voice and Peer-to-Peer (P2P) MoD traffics but also reduce the stutter. Optical Network Unit (ONU) traits such as REPORT and GATE messages, cycle time, and mean packet delay are set to be predictor variables. Simulation results show that our proposed DBAs can satisfy the voice and P2P MoD services packet delay and monitor other overall system performances such as expedited forwarding (EF) jitter, packet loss, bandwidth waste, and system throughputs.

  10. Thalamocortical neurons display suppressed burst-firing due to an enhanced Ih current in a genetic model of absence epilepsy.

    PubMed

    Cain, Stuart M; Tyson, John R; Jones, Karen L; Snutch, Terrance P

    2015-06-01

    Burst-firing in distinct subsets of thalamic relay (TR) neurons is thought to be a key requirement for the propagation of absence seizures. However, in the well-regarded Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model as yet there has been no link described between burst-firing in TR neurons and spike-and-wave discharges (SWDs). GAERS ventrobasal (VB) neurons are a specific subset of TR neurons that do not normally display burst-firing during absence seizures in the GAERS model, and here, we assessed the underlying relationship of VB burst-firing with Ih and T-type calcium currents between GAERS and non-epileptic control (NEC) animals. In response to 200-ms hyperpolarizing current injections, adult epileptic but not pre-epileptic GAERS VB neurons displayed suppressed burst-firing compared to NEC. In response to longer duration 1,000-ms hyperpolarizing current injections, both pre-epileptic and epileptic GAERS VB neurons required significantly more hyperpolarizing current injection to burst-fire than those of NEC animals. The current density of the Hyperpolarization and Cyclic Nucleotide-activated (HCN) current (Ih) was found to be increased in GAERS VB neurons, and the blockade of Ih relieved the suppressed burst-firing in both pre-epileptic P15-P20 and adult animals. In support, levels of HCN-1 and HCN-3 isoform channel proteins were increased in GAERS VB thalamic tissue. T-type calcium channel whole-cell currents were found to be decreased in P7-P9 GAERS VB neurons, and also noted was a decrease in CaV3.1 mRNA and protein levels in adults. Z944, a potent T-type calcium channel blocker with anti-epileptic properties, completely abolished hyperpolarization-induced VB burst-firing in both NEC and GAERS VB neurons.

  11. High gain photoconductive semiconductor switching

    SciTech Connect

    Zutavern, F.J.; Loubriel, G.M.; O'Malley, M.W.; Helgeson, W.D.; McLaughlin, D.L.

    1991-01-01

    Switching properties are reported for high gain photoconductive semiconductor switches (PCSS). A 200 ps pulse width laser was used in tests to examine the relations between electric field, rise time, delay, and minimum optical trigger energy for switches which reached 80 kV in a 50 {Omega} transmission line with rise times as short as 600 ps. Infrared photoluminescence was imaged during high gain switching providing direct evidence for current filamentation. Implications of these measurements for the theoretical understanding and practical development of these switches are discussed. 16 refs., 10 figs.

  12. Gain lever characterization in monolithically integrated diode lasers

    NASA Astrophysics Data System (ADS)

    Pocha, Michael; Bond, Tiziana; Welty, Rebecca; Vernon, Stephen; Kallman, Jeffrey; Behymer, Elaine

    2005-04-01

    Gain Lever, an effect for enhancing amplitude modulation (AM) efficiency in multisection laser diodes1, has been characterized in InGaAs DQW edge emitting lasers that are integrated with passive waveguides. Specifically designed structures which give a range of split ratios from 1:1 to 9:1 have been fabricated and measured to fully characterize the parameter space for operation in the gain lever mode. Additionally the experimental results are compared to a hybrid 3-D simulation involving effective index method (EIM) reduction to 2-D. Gains greater than 6 dB in the AM efficiency can be achieved within the appropriate operating range, but this gain drops rapidly as the parameter range is exceeded. High speed RF modulation with significant gain is, in principle, possible if proper biasing and modulation conditions are used. This phenomenon can also be useful for high-speed digital information transmission.

  13. Approximate reversibility in the context of entropy gain, information gain, and complete positivity

    NASA Astrophysics Data System (ADS)

    Buscemi, Francesco; Das, Siddhartha; Wilde, Mark M.

    2016-06-01

    There are several inequalities in physics which limit how well we can process physical systems to achieve some intended goal, including the second law of thermodynamics, entropy bounds in quantum information theory, and the uncertainty principle of quantum mechanics. Recent results provide physically meaningful enhancements of these limiting statements, determining how well one can attempt to reverse an irreversible process. In this paper, we apply and extend these results to give strong enhancements to several entropy inequalities, having to do with entropy gain, information gain, entropic disturbance, and complete positivity of open quantum systems dynamics. Our first result is a remainder term for the entropy gain of a quantum channel. This result implies that a small increase in entropy under the action of a subunital channel is a witness to the fact that the channel's adjoint can be used as a recovery map to undo the action of the original channel. We apply this result to pure-loss, quantum-limited amplifier, and phase-insensitive quantum Gaussian channels, showing how a quantum-limited amplifier can serve as a recovery from a pure-loss channel and vice versa. Our second result regards the information gain of a quantum measurement, both without and with quantum side information. We find here that a small information gain implies that it is possible to undo the action of the original measurement if it is efficient. The result also has operational ramifications for the information-theoretic tasks known as measurement compression without and with quantum side information. Our third result shows that the loss of Holevo information caused by the action of a noisy channel on an input ensemble of quantum states is small if and only if the noise can be approximately corrected on average. We finally establish that the reduced dynamics of a system-environment interaction are approximately completely positive and trace preserving if and only if the data processing

  14. Enhancement of Experimental Cutaneous Leishmaniasis by Leishmania Molecules Is Dependent on Interleukin-4, Serine Protease/Esterase Activity, and Parasite and Host Genetic Backgrounds ▿

    PubMed Central

    Silva, Virgínia M. G.; Larangeira, Daniela F.; Oliveira, Pablo R. S.; Sampaio, Romina B.; Suzart, Paula; Nihei, Jorge S.; Teixeira, Márcia C. A.; Mengel, José O.; dos-Santos, Washington L. C.; Pontes-de-Carvalho, Lain

    2011-01-01

    Most inbred strains of mice, like the BALB/c strain, are susceptible to Leishmania amazonensis infections and resistant to Leishmania braziliensis infections. This parasite-related difference could result from the activity of an L. amazonensis-specific virulence factor. In agreement with this hypothesis, it is shown here that the intravenous injection of BALB/c mice with L. amazonensis amastigote extract (LaE) but not the L. braziliensis extract confers susceptibility to L. braziliensis infection. This effect was associated with high circulating levels of IgG1 anti-L. amazonensis antibodies and with an increase in interleukin-4 (IL-4) production and a decrease in gamma interferon production by draining lymph node cells. Moreover, the effect was absent in IL-4-knockout mice. The biological activity in the LaE was not mediated by amphiphilic molecules and was inhibited by pretreatment of the extract with irreversible serine protease inhibitors. These findings indicate that the LaE contains a virulence-related factor that (i) enhances the Leishmania infection by promoting Th2-type immune responses, (ii) is not one of the immunomodulatory Leishmania molecules described so far, and (iii) is either a serine protease or has an effect that depends on that protease activity. In addition to being Leishmania species specific, the infection-enhancing activity was also shown to depend on the host genetic makeup, as LaE injections did not affect the susceptibility of C57BL/6 mice to L. braziliensis infection. The identification of Leishmania molecules with infection-enhancing activity could be important for the development of a vaccine, since the up- or downmodulation of the immune response against a virulence factor could well contribute to controlling the infection. PMID:21173308

  15. The Gains from Vertical Scaling

    ERIC Educational Resources Information Center

    Briggs, Derek C.; Domingue, Ben

    2013-01-01

    It is often assumed that a vertical scale is necessary when value-added models depend upon the gain scores of students across two or more points in time. This article examines the conditions under which the scale transformations associated with the vertical scaling process would be expected to have a significant impact on normative interpretations…

  16. 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)

  17. Gain compression effect on the modulation dynamics of an optically injection-locked semiconductor laser using gain lever

    NASA Astrophysics Data System (ADS)

    Sarraute, J.-M.; Schires, K.; LaRochelle, S.; Grillot, F.

    2016-03-01

    The modulation response of an optically-injected gain lever semiconductor laser is studied and calculations show that a gain-lever laser operating under medium to strong optical injection provides a unique and robust configuration for ultra large bandwidth enhancement. Modulation bandwidths above nine times the relaxation oscillation frequency of the free-running laser can be reached using injection-locking conditions that are reasonable for practical applications. The impact of the gain compression on the modulation dynamic is discussed for the first time. This work is of prime importance for the development of directly-modulated broadband optical sources for high-speed operation at 40 Gbps and beyond.

  18. Enhanced In Vivo Tumor Detection by Active Tumor Cell Targeting Using Multiple Tumor Receptor-Binding Peptides Presented on Genetically Engineered Human Ferritin Nanoparticles.

    PubMed

    Kwon, Koo Chul; Ko, Ho Kyung; Lee, Jiyun; Lee, Eun Jung; Kim, Kwangmeyung; Lee, Jeewon

    2016-08-01

    Human ferritin heavy-chain nanoparticle (hFTH) is genetically engineered to present tumor receptor-binding peptides (affibody and/or RGD-derived cyclic peptides, named 4CRGD here) on its surface. The affibody and 4CRGD specifically and strongly binds to human epidermal growth factor receptor I (EGFR) and human integrin αvβ3, respectively, which are overexpressed on various tumor cells. Through in vitro culture of EGFR-overexpressing adenocarcinoma (MDA-MB-468) and integrin-overexpressing glioblastoma cells (U87MG), it is clarified that specific interactions between receptors on tumor cells and receptor-binding peptides on engineered hFTH is critical in active tumor cell targeting. After labeling with the near-infrared fluorescence dye (Cy5.5) and intravenouse injection into MDA-MB-468 or U87MG tumor-bearing mice, the recombinant hFTHs presenting either peptide or both of affibody and 4CRGD are successfully delivered to and retained in the tumor for a prolonged period of time. In particular, the recombinant hFTH presenting both affibody and 4CRGD notably enhances in vivo detection of U87MG tumors that express heterogeneous receptors, integrin and EGFR, compared to the other recombinant hFTHs presenting either affibody or 4CRGD only. Like affibody and 4CRGD used in this study, other multiple tumor receptor-binding peptides can be also genetically introduced to the hFTH surface for actively targeting of in vivo tumors with heterogenous receptors. PMID:27356892

  19. NPY1-36 and PYY1-36 activate cardiac fibroblasts: an effect enhanced by genetic hypertension and inhibition of dipeptidyl peptidase 4.

    PubMed

    Zhu, Xiao; Gillespie, Delbert G; Jackson, Edwin K

    2015-11-01

    Cardiac sympathetic nerves release neuropeptide Y (NPY)1-36, and peptide YY (PYY)1-36 is a circulating peptide; therefore, these PP-fold peptides could affect cardiac fibroblasts (CFs). We examined the effects of NPY1-36 and PYY1-36 on the proliferation of and collagen production ([(3)H]proline incorporation) by CFs isolated from Wistar-Kyoto (WKY) normotensive rats and spontaneously hypertensive rats (SHRs). Experiments were performed with and without sitagliptin, an inhibitor of dipeptidyl peptidase 4 [DPP4; an ectoenzyme that metabolizes NPY1-36 and PYY1-36 (Y1 receptor agonists) to NPY3-36 and PYY3-36 (inactive at Y1 receptors), respectively]. NPY1-36 and PYY1-36, but not NPY3-36 or PYY3-36, stimulated proliferation of CFs, and these effects were more potent than ANG II, enhanced by sitagliptin, blocked by BIBP3226 (Y1 receptor antagonist), and greater in SHR CFs. SHR CF membranes expressed more receptor for activated C kinase (RACK)1 [which scaffolds the Gi/phospholipase C (PLC)/PKC pathway] compared with WKY CF membranes. RACK1 knockdown (short hairpin RNA) and inhibition of Gi (pertussis toxin), PLC (U73122), and PKC (GF109203X) blocked the proliferative effects of NPY1-36. NPY1-36 and PYY1-36 stimulated collagen production more potently than did ANG II, and this was enhanced by sitagliptin and greater in SHR CFs. In conclusion, 1) NPY1-36 and PYY1-36, via the Y1 receptor/Gi/PLC/PKC pathway, activate CFs, and this pathway is enhanced in SHR CFs due to increased localization of RACK1 in membranes; and 2) DPP4 inhibition enhances the effects of NPY1-36 and PYY1-36 on CFs, likely by inhibiting the metabolism of NPY1-36 and PYY1-36. The implications are that endogenous NPY1-36 and PYY1-36 could adversely affect cardiac structure/function by activating CFs, and this may be exacerbated in genetic hypertension and by DPP4 inhibitors.

  20. Photomultiplier tube gain regulating system

    DOEpatents

    Johnson, Wayne F.

    1976-01-01

    This invention relates to an improved system for regulating the gain of a photomultiplier tube, and was designed for use with the photomultiplier tubes of a GeMSAEC fast analyzers. It has the following advantages over the prior system: noise is virtually eliminated; sample analysis can begin after 3 to 4 revolutions of the rotor; fluorescent and light scattering solutions can be used as a reference; and the reference solution can be in any cuvette on the rotor.

  1. Cassegrain-Antenna Gain Improvement

    NASA Technical Reports Server (NTRS)

    Galindo, V.; Cha, A. G.; Mittra, R.

    1986-01-01

    Modified antenna feed with dual-shaped subreflectors yields 10-to20-percent improvement in efficiency of existing large-aperture paraboloidal or Cassegrainian antennas. Such offset dual-shaped subreflector (DSS) feed brings gain of existing paraboloid or Cassegrain antennas up to that of reflector antennas of more recent design at cost considerably lower than for reshaping existing reflecting surfaces. Mathematical procedures developed for synthesizing nearly optimum shapes for DSS elements of new feeds.

  2. Maternal Prenatal Weight Gain and Autism Spectrum Disorders

    PubMed Central

    Bakian, Amanda V.; Viskochil, Joseph; Clark, Erin A.S.; Botts, Elizabeth L.; Smith, Ken R.; Pimentel, Richard; McMahon, William M.; Coon, Hilary

    2013-01-01

    BACKGROUND: The rising population of individuals identified with an autism spectrum disorder (ASD) calls for further investigation of its underlying etiology. A disturbance in the fetal steroid hormone environment may be a mechanism in which environmental and genetic risk factors interact. The mother, fetus, and placenta collectively create the fetal steroid environment. Prepregnancy BMI and pregnancy weight gain have served as markers for fetal steroid hormone exposure in other disease states. This study’s objective is to determine whether prepregnancy BMI and pregnancy weight gain are associated with increased ASD risk across study designs and cohorts while controlling for important confounding variables. METHODS: A population-based Utah ASD cohort (n = 128) was ascertained in a 3-county surveillance area and gender- and age-matched to 10 920 control subjects. A second, research-based ASD cohort of Utah children (n = 288) and their unaffected siblings (n = 493) were ascertained through participation in an ASD genetics study. Prenatal variables were obtained from birth certificate records. RESULTS: ASD risk was significantly associated with pregnancy weight gain (adjusted odds ratio = 1.10, 95% confidence interval: 1.03 to 1.17; adjusted odds ratio = 1.17, 95% confidence interval: 1.01 to 1.35 for each 5 pounds of weight gained), but not prepregnancy BMI, in population and research-based cohorts, respectively. When analyses were restricted to ASD cases with normal IQ, these associations remained significant. CONCLUSIONS: ASD risk associated with a modest yet consistent increase in pregnancy weight gain suggests that pregnancy weight gain may serve as an important marker for autism’s underlying gestational etiology. This justifies an investigation into phenomena that link pregnancy weight gain and ASD independent of prepregnancy BMI. PMID:24167172

  3. PDGFRA gain in low-grade diffuse gliomas.

    PubMed

    Motomura, Kazuya; Mittelbronn, Michel; Paulus, Werner; Brokinkel, Benjamin; Keyvani, Kathy; Sure, Ulrich; Wrede, Karsten; Nakazato, Yoichi; Tanaka, Yuko; Nonoguchi, Naosuke; Pierscianek, Daniela; Kim, Young-Ho; Mariani, Luigi; Vital, Anne; Perry, Arie; Ohgaki, Hiroko

    2013-01-01

    Glioblastomas with a proneural expression signature are characterized by frequent IDH1 mutations (i.e. genetic hallmarks of secondary glioblastomas) and PDGFRA (platelet-derived growth factor receptor-α) amplification. Mutations in IDH1/2 are frequent and early genetic events in diffuse astrocytomas (World Health Organization grade II), precursor to secondary glioblastomas, but little is known about the role and timing of PDGFRA amplification in these tumors. We assessed PDGFRA gain in 342 low-grade diffuse gliomas by quantitative polymerase chain reaction. Gain in PDGFRA was detected in 27 (16.3%) of 166 diffuse astrocytomas, significantly more frequent than in oligodendrogliomas (3 [2.6%] of 115, p < 0.0001). Analyses using previously published data from our laboratory showed an inverse correlation between PDGFRA gain and IDH1/2 mutations (p = 0.018) or 1p/19q loss (p < 0.0001). The vast majority of diffuse astrocytomas showed IDH1/2 mutations and/or PDGFRA gain (154 [93%] of 166). Mean survival of diffuse astrocytoma patients with PDGFRA gain was 8.8 ± 1.6 years, similar to that with IDH1/2 mutations (7.8 ± 0.5 years) or TP53 mutations (7.6 ± 0.6 years) but significantly longer than those with MET gain (4.4 ± 0.7 years). Dual-color fluorescence in situ hybridization in 6 diffuse astrocytomas with PDGFRA/MET co-gain identified by quantitative polymerase chain reaction revealed that PDGFRA and MET were typically amplified in different tumor cell populations. Tumor cells with coamplification were also focally observed, suggesting intratumoral heterogeneity, even in diffuse astrocytomas.

  4. Engineering genetic injustice.

    PubMed

    Wenz, Peter

    2005-02-01

    In their jointly written book, From Chance to Choice: Genetics and Justice, Allen Buchanan, Dan Brock, Norman Daniels and Daniel Wikler defend 'the development and deployment of genetic intervention technologies..', including genetic enhancements, against charges that they exacerbate injustice. The present paper examines some of their arguments. The first section shows that the authors confuse real societies with just societies. The second shows that without this confusion, their arguments reveal the enormous justice-impairing potential of deploying genetic enhancements in such societies as the United States.

  5. Enhanced genetic algorithm optimization model for a single reservoir operation based on hydropower generation: case study of Mosul reservoir, northern Iraq.

    PubMed

    Al-Aqeeli, Yousif H; Lee, T S; Abd Aziz, S

    2016-01-01

    Achievement of the optimal hydropower generation from operation of water reservoirs, is a complex problems. The purpose of this study was to formulate and improve an approach of a genetic algorithm optimization model (GAOM) in order to increase the maximization of annual hydropower generation for a single reservoir. For this purpose, two simulation algorithms were drafted and applied independently in that GAOM during 20 scenarios (years) for operation of Mosul reservoir, northern Iraq. The first algorithm was based on the traditional simulation of reservoir operation, whilst the second algorithm (Salg) enhanced the GAOM by changing the population values of GA through a new simulation process of reservoir operation. The performances of these two algorithms were evaluated through the comparison of their optimal values of annual hydropower generation during the 20 scenarios of operating. The GAOM achieved an increase in hydropower generation in 17 scenarios using these two algorithms, with the Salg being superior in all scenarios. All of these were done prior adding the evaporation (Ev) and precipitation (Pr) to the water balance equation. Next, the GAOM using the Salg was applied by taking into consideration the volumes of these two parameters. In this case, the optimal values obtained from the GAOM were compared, firstly with their counterpart that found using the same algorithm without taking into consideration of Ev and Pr, secondly with the observed values. The first comparison showed that the optimal values obtained in this case decreased in all scenarios, whilst maintaining the good results compared with the observed in the second comparison. The results proved the effectiveness of the Salg in increasing the hydropower generation through the enhanced approach of the GAOM. In addition, the results indicated to the importance of taking into account the Ev and Pr in the modelling of reservoirs operation.

  6. High-level hemicellulosic arabinose predominately affects lignocellulose crystallinity for genetically enhancing both plant lodging resistance and biomass enzymatic digestibility in rice mutants.

    PubMed

    Li, Fengcheng; Zhang, Mingliang; Guo, Kai; Hu, Zhen; Zhang, Ran; Feng, Yongqing; Yi, Xiaoyan; Zou, Weihua; Wang, Lingqiang; Wu, Changyin; Tian, Jinshan; Lu, Tiegang; Xie, Guosheng; Peng, Liangcai

    2015-05-01

    Rice is a major food crop with enormous biomass residue for biofuels. As plant cell wall recalcitrance basically decides a costly biomass process, genetic modification of plant cell walls has been regarded as a promising solution. However, due to structural complexity and functional diversity of plant cell walls, it becomes essential to identify the key factors of cell wall modifications that could not much alter plant growth, but cause an enhancement in biomass enzymatic digestibility. To address this issue, we performed systems biology analyses of a total of 36 distinct cell wall mutants of rice. As a result, cellulose crystallinity (CrI) was examined to be the key factor that negatively determines either the biomass enzymatic saccharification upon various chemical pretreatments or the plant lodging resistance, an integrated agronomic trait in plant growth and grain production. Notably, hemicellulosic arabinose (Ara) was detected to be the major factor that negatively affects cellulose CrI probably through its interlinking with β-1,4-glucans. In addition, lignin and G monomer also exhibited the positive impact on biomass digestion and lodging resistance. Further characterization of two elite mutants, Osfc17 and Osfc30, showing normal plant growth and high biomass enzymatic digestion in situ and in vitro, revealed the multiple GH9B candidate genes for reducing cellulose CrI and XAT genes for increasing hemicellulosic Ara level. Hence, the results have suggested the potential cell wall modifications for enhancing both biomass enzymatic digestibility and plant lodging resistance by synchronically overexpressing GH9B and XAT genes in rice.

  7. Enhanced genetic algorithm optimization model for a single reservoir operation based on hydropower generation: case study of Mosul reservoir, northern Iraq.

    PubMed

    Al-Aqeeli, Yousif H; Lee, T S; Abd Aziz, S

    2016-01-01

    Achievement of the optimal hydropower generation from operation of water reservoirs, is a complex problems. The purpose of this study was to formulate and improve an approach of a genetic algorithm optimization model (GAOM) in order to increase the maximization of annual hydropower generation for a single reservoir. For this purpose, two simulation algorithms were drafted and applied independently in that GAOM during 20 scenarios (years) for operation of Mosul reservoir, northern Iraq. The first algorithm was based on the traditional simulation of reservoir operation, whilst the second algorithm (Salg) enhanced the GAOM by changing the population values of GA through a new simulation process of reservoir operation. The performances of these two algorithms were evaluated through the comparison of their optimal values of annual hydropower generation during the 20 scenarios of operating. The GAOM achieved an increase in hydropower generation in 17 scenarios using these two algorithms, with the Salg being superior in all scenarios. All of these were done prior adding the evaporation (Ev) and precipitation (Pr) to the water balance equation. Next, the GAOM using the Salg was applied by taking into consideration the volumes of these two parameters. In this case, the optimal values obtained from the GAOM were compared, firstly with their counterpart that found using the same algorithm without taking into consideration of Ev and Pr, secondly with the observed values. The first comparison showed that the optimal values obtained in this case decreased in all scenarios, whilst maintaining the good results compared with the observed in the second comparison. The results proved the effectiveness of the Salg in increasing the hydropower generation through the enhanced approach of the GAOM. In addition, the results indicated to the importance of taking into account the Ev and Pr in the modelling of reservoirs operation. PMID:27390638

  8. The hitchhiker's guide to Xenopus genetics.

    PubMed

    Abu-Daya, Anita; Khokha, Mustafa K; Zimmerman, Lyle B

    2012-03-01

    A decade after the human genome sequence, most vertebrate gene functions remain poorly understood, limiting benefits to human health from rapidly advancing genomic technologies. Systematic in vivo functional analysis is ideally suited to the experimentally accessible Xenopus embryo, which combines embryological accessibility with a broad range of transgenic, biochemical, and gain-of-function assays. The diploid X. tropicalis adds loss-of-function genetics and enhanced genomics to this repertoire. In the last decade, diverse phenotypes have been recovered from genetic screens, mutations have been cloned, and reverse genetics in the form of TILLING and targeted gene editing have been established. Simple haploid genetics and gynogenesis and the very large number of embryos produced streamline screening and mapping. Improved genomic resources and the revolution in high-throughput sequencing are transforming mutation cloning and reverse genetic approaches. The combination of loss-of-function mutant backgrounds with the diverse array of conventional Xenopus assays offers a uniquely flexible platform for analysis of gene function in vertebrate development. PMID:22344745

  9. Commutated automatic gain control system

    NASA Technical Reports Server (NTRS)

    Yost, S. R.

    1982-01-01

    A commutated automatic gain control (AGC) system was designed and built for a prototype Loran C receiver. The receiver uses a microcomputer to control a memory aided phase-locked loop (MAPLL). The microcomputer also controls the input/output, latitude/longitude conversion, and the recently added AGC system. The circuit designed for the AGC is described, and bench and flight test results are presented. The AGC circuit described actually samples starting at a point 40 microseconds after a zero crossing determined by the software lock pulse ultimately generated by a 30 microsecond delay and add network in the receiver front end envelope detector.

  10. Scalar gain interpretation of large order filters

    NASA Technical Reports Server (NTRS)

    Mason, Paul A. C.; Mook, D. Joseph

    1993-01-01

    A technique is developed which demonstrates how to interpret a large fully-populated filter gain matrix as a set of scalar gains. The inverse problem is also solved, namely, how to develop a large-order filter gain matrix from a specified set of scalar gains. Examples are given to illustrate the method.

  11. A gain-coefficient switched Alexandrite laser

    NASA Astrophysics Data System (ADS)

    Lee, Chris J.; van der Slot, Peter J. M.; Boller, Klaus-J.

    2013-01-01

    We report on a gain-coefficient switched Alexandrite laser. An electro-optic modulator is used to switch between high and low gain states by making use of the polarization dependent gain of Alexandrite. In gain-coefficient switched mode, the laser produces 85 ns pulses with a pulse energy of 240 mJ at a repetition rate of 5 Hz.

  12. Pharmacological management of atypical antipsychotic-induced weight gain.

    PubMed

    Baptista, Trino; ElFakih, Yamily; Uzcátegui, Euderruh; Sandia, Ignacio; Tálamo, Eduardo; Araujo de Baptista, Enma; Beaulieu, Serge

    2008-01-01

    Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p<0.001). Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics. In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate. More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient's personal and family history of bodyweight gain and metabolic dysfunction.

  13. [Genetics and genetic counseling].

    PubMed

    Izzi, Claudia; Liut, Francesca; Dallera, Nadia; Mazza, Cinzia; Magistroni, Riccardo; Savoldi, Gianfranco; Scolari, Francesco

    2016-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic disease, characterized by progressive development of bilateral renal cysts. Two causative genes have been identified: PKD1 and PKD2. ADPKD phenotype is highly variable. Typically, ADPKD is an adult onset disease. However, occasionally, ADPKD manifests as very early onset disease. The phenotypic variability of ADPKD can be explained at three genetic levels: genic, allelic and gene modifier effects. Recent advances in molecular screening for PKD gene mutations and the introduction of the new next generation sequencing (NGS)- based genotyping approach have generated considerable improvement regarding the knowledge of genetic basis of ADPKD. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, focusing on new insights in genotype-phenotype correlation and exploring novel clinical approach to genetic testing. Evaluation of these new genetic information requires a multidisciplinary approach involving a nephrologist and a clinical geneticist. PMID:27067213

  14. Unidirectional high gain brake stop

    NASA Technical Reports Server (NTRS)

    Lang, David J. (Inventor)

    1987-01-01

    This invention relates to a unidirectional high gain brake arrangement that includes in combination a shaft mounted for rotation within a housing. The shaft is rotatable in either direction. A brake is selectively releasably coupled to the housing and to the shaft. The brake has a first member. An intermittent motion device is respectively coupled through the first member to the housing and through a one-way clutch to the shaft. The brake also has a second member that is mechanically coupled to the first brake member and to the housing. The intermittent motion device causes the brake to be activated by movement imparted to the first brake member after a preset number of revolutions of the shaft in one direction. The brake is released by rotation of the shaft in an opposite direction whereby torque transmitted through the one-way clutch to the first brake member is removed.

  15. High-gain antenna & terrain

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Areas of rocky Martian terrain are seen in this image, taken by the Imager for Mars Pathfinder (IMP) on Sol 2. Portions of a lander petal and deflated airbag are at lower left. The dark disk at center is the high-gain antenna, and the silver cylindrical objects at upper right are part of the antenna's mechanism. An area of relatively smooth terrain is seen at upper right, which may offer clues to how this area was formed, and may be a future target for Sojourner's studies. The black area at lower right and small strip at top center is missing data.

    Mars Pathfinder was developed and managed by the Jet Propulsion Laboratory (JPL) for the National Aeronautics and Space Administration. The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  16. Sudden gains in behavioural activation for depression.

    PubMed

    Masterson, Ciara; Ekers, David; Gilbody, Simon; Richards, David; Toner-Clewes, Benjamin; McMillan, Dean

    2014-09-01

    Sudden gains have been linked to improved outcomes in cognitive behaviour therapy for depression. The relationship between sudden gains and outcome is less clear in other treatment modalities, including interpersonal psychotherapy and supportive expressive therapy, which may indicate different mechanisms of change between treatment modalities. The current study examined sudden gains in adults meeting diagnostic criteria for depression (N = 40) offered up to 12 sessions of behavioural activation treatment. Sudden gains were found in 42.5% of the sample. Sudden gains occurred early (median pre-gain session 2) and were related to outcome: those who experienced a sudden gain had significantly lower post-treatment scores on the PHQ-9. Furthermore, the proportion meeting the reliable and clinically significant change criteria at end of treatment was higher in the sudden gain group. These findings highlight the importance of understanding the mechanisms by which sudden gains relate to therapy outcome in behavioural activation.

  17. Are videogame training gains specific or general?

    PubMed

    Oei, Adam C; Patterson, Michael D

    2014-01-01

    Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the "common demands" hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements.

  18. Are videogame training gains specific or general?

    PubMed

    Oei, Adam C; Patterson, Michael D

    2014-01-01

    Many recent studies using healthy adults document enhancements in perception and cognition from playing commercial action videogames (AVGs). Playing action games (e.g., Call of Duty, Medal of Honor) is associated with improved bottom-up lower-level information processing skills like visual-perceptual and attentional processes. One proposal states a general improvement in the ability to interpret and gather statistical information to predict future actions which then leads to better performance across different perceptual/attentional tasks. Another proposal claims all the tasks are separately trained in the AVGs because the AVGs and laboratory tasks contain similar demands. We review studies of action and non-AVGs to show support for the latter proposal. To explain transfer in AVGs, we argue that the perceptual and attention tasks share common demands with the trained videogames (e.g., multiple object tracking (MOT), rapid attentional switches, and peripheral vision). In non-AVGs, several studies also demonstrate specific, limited transfer. One instance of specific transfer is the specific enhancement to mental rotation after training in games with a spatial emphasis (e.g., Tetris). In contrast, the evidence for transfer is equivocal where the game and task do not share common demands (e.g., executive functioning). Thus, the "common demands" hypothesis of transfer not only characterizes transfer effects in AVGs, but also non-action games. Furthermore, such a theory provides specific predictions, which can help in the selection of games to train human cognition as well as in the design of videogames purposed for human cognitive and perceptual enhancement. Finally this hypothesis is consistent with the cognitive training literature where most post-training gains are for tasks similar to the training rather than general, non-specific improvements. PMID:24782722

  19. Estimates of epistatic and pleiotropic effects of casein alpha s1 (CSN1S1) and thyroglobulin (TG) genetic markers on beef heifer performance traits enhanced by selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for two years to equalize CSN1S1 and TG genetic marker frequencies to evaluate the epista...

  20. Cognitive Enhancement and Education

    ERIC Educational Resources Information Center

    Buchanan, Allen

    2011-01-01

    Cognitive enhancement--augmenting normal cognitive capacities--is not new. Literacy, numeracy, computers, and the practices of science are all cognitive enhancements. Science is now making new cognitive enhancements possible. Biomedical cognitive enhancements (BCEs) include the administration of drugs, implants of genetically engineered or…

  1. A gain-of-function mutation in the ROC1 gene alters plant architecture in Arabidopsis.

    PubMed

    Ma, Xiqing; Song, Li; Yang, Yaxuan; Liu, Dong

    2013-02-01

    Plant architecture is an important agronomic trait and is useful for identification of plant species. The molecular basis of plant architecture, however, is largely unknown. Forward genetics was used to identify an Arabidopsis mutant with altered plant architecture. Using genetic and molecular approaches, we analyzed the roles of a mutated cyclophilin in the control of plant architecture. The Arabidopsis mutant roc1 has reduced stem elongation and increased shoot branching, and the mutant phenotypes are strongly affected by temperature and photoperiod. Map-based cloning and transgenic experiments demonstrated that the roc1 mutant phenotypes are caused by a gain-of-function mutation in a cyclophilin gene, ROC1. Besides, application of the plant hormone gibberellic acid (GA) further suppresses stem elongation in the mutant. GA treatment enhances the accumulation of mutated but not of wildtype (WT) ROC1 proteins. The roc1 mutation does not seem to interfere with GA biosynthesis or signaling. GA signaling, however, antagonizes the effect of the roc1 mutation on stem elongation. The altered plant architecture may result from the activation of an R gene by the roc1 protein. We also present a working model for the interaction between the roc1 mutation and GA signaling in regulating stem elongation. PMID:23206262

  2. Medical genetics

    SciTech Connect

    Nora, J.J.; Fraser, F.C.

    1989-01-01

    This book presents a discussion of medical genetics for the practitioner treating or counseling patients with genetic disease. It includes a discussion of the relationship of heredity and diseases, the chromosomal basis for heredity, gene frequencies, and genetics of development and maldevelopment. The authors also focus on teratology, somatic cell genetics, genetics and cancer, genetics of behavior.

  3. Forward ramp & low gain antenna

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Mars Pathfinder's forward rover ramp can be seen successfully unfurled in this color image, taken by the Imager for Mars Pathfinder (IMP) on Sol 3. This ramp was not used for the deployment of the microrover Sojourner, which occurred at the end of Sol 2. When this image was taken, Sojourner was still latched to one of the lander's petals, waiting for the command sequence that would execute its descent off of the lander's petal. The image helped Pathfinder scientists determine whether to deploy the rover using the forward or backward ramps and the nature of the first rover traverse. The metallic object at the lower part of the image is the lander's low-gain antenna. The square at the end of the ramp is one of the spacecraft's magnetic targets. Dust that accumulates on the magnetic targets will later be examined by Sojourner's Alpha Proton X-Ray Spectrometer instrument for chemical analysis. At center, a lander petal is visible.

    spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The Imager for Mars Pathfinder (IMP) was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal Investigator.

  4. Human T-lymphotropic virus type 1 peptides in chimeric and multivalent constructs with promiscuous T-cell epitopes enhance immunogenicity and overcome genetic restriction.

    PubMed Central

    Lairmore, M D; DiGeorge, A M; Conrad, S F; Trevino, A V; Lal, R B; Kaumaya, P T

    1995-01-01

    contrast, the chimeric constructs MVF-SP2 and SP4a-measles virus F protein were highly immunogenic, producing elevated ELISA titers after only two immunizations. Elicited antibodies recognized native forms of gp46 in ELISAs and radioimmunoprecipitation assays, as well as inhibited HTLV-1-mediated syncytium formation. In addition, chimeric constructs were effective at induction of lymphocyte proliferation to the T-cell epitope, SP4a, in each strain of immunized mice. Our data demonstrate that the antibody response to retroviral peptides is enhanced by promiscuous peptide constructs, in part because of the ability of such constructs to promote appropriate secondary structural forms of viral epitopes. In addition, these constructs promote virus-specific helper T-cell responses, thereby overcoming genetically restricted immune responses to the synthetic peptides. PMID:7545241

  5. Nicotine Replacement: Effects on Postcessation Weight Gain.

    ERIC Educational Resources Information Center

    Gross, Janet; And Others

    1989-01-01

    Examined nicotine replacement effects on postcessation weight gain in smoking cessation volunteers. Randomly assigned abstinent subjects to active nicotine or placebo gum conditions for 10 weeks. Analyses revealed strong evidence for gum effect on weight gain, with active gum users gaining mean total of 3.8 pounds compared with 7.8 pounds for…

  6. STADAN antenna gain calibration using radio stars

    NASA Technical Reports Server (NTRS)

    Taylor, R. E.

    1972-01-01

    An antenna gain measurement method was developed which utilizes a signal emitted from a radio star to determine absolute antenna gain at 136 MHz and 400 MHz for antennas in the STADAN network. An error analysis of the radio star method shows that the overall standard deviation uncertainty in antenna gain is + or - 0.6 db (1 sigma).

  7. Determination of optimal gains for constrained controllers

    SciTech Connect

    Kwan, C.M.; Mestha, L.K.

    1993-08-01

    In this report, we consider the determination of optimal gains, with respect to a certain performance index, for state feedback controllers where some elements in the gain matrix are constrained to be zero. Two iterative schemes for systematically finding the constrained gain matrix are presented. An example is included to demonstrate the procedures.

  8. Electrical and Optical Gain Lever Effects in InGaAs Double Quantum Well Diode Lasers

    SciTech Connect

    Pocha, M D; Goddard, L L; Bond, T C; Nikolic, R J; Vernon, S P; Kallman, J S; Behymer, E M

    2007-01-03

    In multisection laser diodes, the amplitude or frequency modulation (AM or FM) efficiency can be improved using the gain lever effect. To study gain lever, InGaAs double quantum well (DQW) edge emitting lasers have been fabricated with integrated passive waveguides and dual sections providing a range of split ratios from 1:1 to 9:1. Both the electrical and the optical gain lever have been examined. An electrical gain lever with greater than 7 dB enhancement of AM efficiency was achieved within the range of appropriate DC biasing currents, but this gain dropped rapidly outside this range. We observed a 4 dB gain in the optical AM efficiency under non-ideal biasing conditions. This value agreed with the measured gain for the electrical AM efficiency under similar conditions. We also examined the gain lever effect under large signal modulation for digital logic switching applications. To get a useful gain lever for optical gain quenched logic, a long control section is needed to preserve the gain lever strength and a long interaction length between the input optical signal and the lasing field of the diode must be provided. The gain lever parameter space has been fully characterized and validated against numerical simulations of a semi-3D hybrid beam propagation method (BPM) model for the coupled electron-photon rate equation. We find that the optical gain lever can be treated using the electrical injection model, once the absorption in the sample is known.

  9. Genomic-Based Optimum Contribution in Conservation and Genetic Improvement Programs with Antagonistic Fitness and Productivity Traits

    PubMed Central

    Sánchez-Molano, Enrique; Pong-Wong, Ricardo; Banos, Georgios

    2016-01-01

    Animal selection for genetic improvement of productivity may lead to an increase in inbreeding through the use of techniques that enhance the reproductive capability of selected animals. Therefore, breeding strategies aim to balance maintaining genetic variability and acceptable fitness levels with increasing productivity. The present study demonstrates the effectiveness of genomic-based optimum contribution strategies at addressing this objective when fitness and productivity are genetically antagonistic traits. Strategies are evaluated in directional selection (increasing productivity) or conservation (maintaining fitness) scenarios. In the former case, substantial rates of genetic gain can be achieved while greatly constraining the rate of increase in inbreeding. Under a conservation approach, inbreeding depression can be effectively halted while also achieving a modest rate of genetic gain for productivity. Furthermore, the use of optimum contribution strategies when combined with a simple non-random mating scheme (minimum kinship method) showed an additional delay in the increase of inbreeding in the short term. In conclusion, genomic-based optimum contribution methods can be effectively used to control inbreeding and inbreeding depression, and still allow genetic gain for productivity traits even when fitness and productivity are antagonistically correlated. PMID:26941779

  10. Gestational weight gain among Hispanic women.

    PubMed

    Sangi-Haghpeykar, Haleh; Lam, Kim; Raine, Susan P

    2014-01-01

    To describe gestational weight gain among Hispanic women and to examine psychological, social, and cultural contexts affecting weight gain. A total of 282 Hispanic women were surveyed post-partum before leaving the hospital. Women were queried about their prepregnancy weight and weight gained during pregnancy. Adequacy of gestational weight gain was based on guidelines set by the Institute of Medicine in 2009. Independent risk factors for excessive or insufficient weight gain were examined by logistic regression. Most women were unmarried (59 %), with a mean age of 28.4 ± 6.6 years and an average weight gain of 27.9 ± 13.3 lbs. Approximately 45 % of women had gained too much, 32 % too little, and only 24 % had an adequate amount of weight gain. The mean birth weight was 7.3, 7.9, and 6.8 lbs among the adequate, excessive, and insufficient weight gain groups. Among women who exercised before pregnancy, two-thirds continued to do so during pregnancy; the mean gestational weight gain of those who continued was lower than those who stopped (26.8 vs. 31.4 lbs, p = 0.04). Independent risk factors for excessive weight gain were being unmarried, U.S. born, higher prepregnancy body mass index, and having indifferent or negative views about weight gain. Independent risk factors for insufficient weight gain were low levels of support and late initiation of prenatal care. Depression, stress, and a woman's or her partner's happiness regarding pregnancy were unrelated to weight gain. The results of this study can be used by prenatal programs to identify Hispanic women at risk for excessive or insufficient gestational weight gain.

  11. Additional solar/load ratio correlations for direct gain buildings

    SciTech Connect

    Wray, W.O.

    1980-01-01

    Solar/load ratio (SLR) correlations have been developed for two new reference direct gain designs. The new reference designs are identical to the originals except that the glazing air gap has been increased from 1/4 in. to 1/2 in. and a vector average of the local hourly windspeed was used in the thermal network calculations rather than an assumed average value of 15 m.p.h. Both of these modifications are realistic and enhance the predicted performance of direct gain buildings. A comprehensive set of mass sensitivity calculations has been performed in order to provide information needed to select an appropriate set of parameters for new lightweight direct gain designs for which additional SLR correlations will be developed. Representative results are reported.

  12. Ethereal and material gain: unanticipated opportunity with illness or disability.

    PubMed

    O'Mahony, Seamus; Shanahan, Fergus

    2014-02-01

    When caregivers address the positive aspects of illness or disability, there is a risk of patronising the sufferer. It is equally problematic when secondary gain is judged in a negative light and impedes an effective doctor-patient relationship. Changing attitudes, and particularly the negative perception of a patient's gain from illness, are reflected in biographies of artists, philosophers and other creative individuals. In contrast, some memoirs about illness feature a retrospective discussion of the positive features of the experience - from one who is now free from the ordeal. The experience of continual sufferers may be more instructive. We examine contemporary examples of unanticipated advantage or gain arising from ongoing disability or illness. The contribution of disability/illness to remarkable achievement promotes enhanced self-appreciation for patients and may foster in others a better understanding of what it means to suffer and live with disability. PMID:24532744

  13. Small signal gain in DPAL systems

    NASA Astrophysics Data System (ADS)

    Galbally-Kinney, Kristin L.; Maser, Daniel L.; Kessler, William J.; Rawlins, Wilson T.; Davis, Steven J.

    2011-03-01

    In this paper we describe a platform for small signal gain measurements for alkali atom laser systems based on the DPAL excitation method. We present initial results that clearly show the transition from absorption on the alkali atom D1 lines in Cs and Rb to optical transparency and positive gain. The achievement of optical gain is critically dependent upon alkali cell conditions and collision partners. We also present the first spatially resolved gain measurements in a DPAL system. The small signal gain methods described will be valuable tools for power scaling of these laser systems.

  14. Proprioceptive feedback determines visuomotor gain in Drosophila

    PubMed Central

    Bartussek, Jan; Lehmann, Fritz-Olaf

    2016-01-01

    Multisensory integration is a prerequisite for effective locomotor control in most animals. Especially, the impressive aerial performance of insects relies on rapid and precise integration of multiple sensory modalities that provide feedback on different time scales. In flies, continuous visual signalling from the compound eyes is fused with phasic proprioceptive feedback to ensure precise neural activation of wing steering muscles (WSM) within narrow temporal phase bands of the stroke cycle. This phase-locked activation relies on mechanoreceptors distributed over wings and gyroscopic halteres. Here we investigate visual steering performance of tethered flying fruit flies with reduced haltere and wing feedback signalling. Using a flight simulator, we evaluated visual object fixation behaviour, optomotor altitude control and saccadic escape reflexes. The behavioural assays show an antagonistic effect of wing and haltere signalling on visuomotor gain during flight. Compared with controls, suppression of haltere feedback attenuates while suppression of wing feedback enhances the animal’s wing steering range. Our results suggest that the generation of motor commands owing to visual perception is dynamically controlled by proprioception. We outline a potential physiological mechanism based on the biomechanical properties of WSM and sensory integration processes at the level of motoneurons. Collectively, the findings contribute to our general understanding how moving animals integrate sensory information with dynamically changing temporal structure. PMID:26909184

  15. Characterization of newly gained introns in Daphnia populations.

    PubMed

    Li, Wenli; Kuzoff, Robert; Wong, Chen Khuan; Tucker, Abraham; Lynch, Michael

    2014-08-14

    As one of the few known species in an active phase of intron proliferation, the microcrustacean Daphnia pulex is an especially attractive system for interrogating the gain and loss of introns in natural populations. In this study, we used a comparative population-genomic approach to identify and characterize 90 recently gained introns in this species. Molecular clock analyses indicate that these introns arose between 3.9 × 10(5) and 1.45 × 10(4) years ago, with a spike in intron proliferation approximately 5.2 × 10(4) to 1.22 × 10(5) years ago. Parallel gains at homologous positions contribute to 47.8% (43/90) of discovered new introns. A disproportionally large number of new introns were found in historically isolated populations in Oregon. Nonetheless, derived, intron-bearing alleles were also identified in a wide range of geographic locations, suggesting intron gain and, to a lesser degree, intron loss are important sources of genetic variation in natural populations of Daphnia. A majority (55/90 or 61.1%) of the identified neointrons have associated internal direct repeats with lengths and compositions that are unlikely to occur by chance, suggesting repeated bouts of staggered double-strand breaks (DSBs) during their evolution. Accordingly, internal, staggered DSBs may contribute to a passive trend toward increased length and sequence diversity in nascent introns.

  16. Nitrogen incorporation effects on gain properties of GaInNAs lasers : experiment and theory.

    SciTech Connect

    Thranhardt, A.; Mawst, L. J.; Hader, J.; Schlichenmaier, C.; Tansu, N.; Yeh, J. -Y.; Belenky, G.; Chow, Weng Wah; Shterengas, L.; Moloney, Jerome V.; Koch, S. W.; Kuznetsova, I.

    2005-05-01

    Gain properties of GaInNAs lasers with different nitrogen concentrations in the quantum wells are investigated experimentally and theoretically. Whereas nitrogen incorporation induces appreciable modifications in the spectral extension and the carrier density dependence of the gain, it is found that the linewidth enhancement factor is reduced by inclusion of nitrogen, but basically unaffected by different nitrogen content due to the balancing between gain and index changes.

  17. Optimum wavelet based masking for the contrast enhancement of medical images using enhanced cuckoo search algorithm.

    PubMed

    Daniel, Ebenezer; Anitha, J

    2016-04-01

    Unsharp masking techniques are a prominent approach in contrast enhancement. Generalized masking formulation has static scale value selection, which limits the gain of contrast. In this paper, we propose an Optimum Wavelet Based Masking (OWBM) using Enhanced Cuckoo Search Algorithm (ECSA) for the contrast improvement of medical images. The ECSA can automatically adjust the ratio of nest rebuilding, using genetic operators such as adaptive crossover and mutation. First, the proposed contrast enhancement approach is validated quantitatively using Brain Web and MIAS database images. Later, the conventional nest rebuilding of cuckoo search optimization is modified using Adaptive Rebuilding of Worst Nests (ARWN). Experimental results are analyzed using various performance matrices, and our OWBM shows improved results as compared with other reported literature.

  18. Optimum wavelet based masking for the contrast enhancement of medical images using enhanced cuckoo search algorithm.

    PubMed

    Daniel, Ebenezer; Anitha, J

    2016-04-01

    Unsharp masking techniques are a prominent approach in contrast enhancement. Generalized masking formulation has static scale value selection, which limits the gain of contrast. In this paper, we propose an Optimum Wavelet Based Masking (OWBM) using Enhanced Cuckoo Search Algorithm (ECSA) for the contrast improvement of medical images. The ECSA can automatically adjust the ratio of nest rebuilding, using genetic operators such as adaptive crossover and mutation. First, the proposed contrast enhancement approach is validated quantitatively using Brain Web and MIAS database images. Later, the conventional nest rebuilding of cuckoo search optimization is modified using Adaptive Rebuilding of Worst Nests (ARWN). Experimental results are analyzed using various performance matrices, and our OWBM shows improved results as compared with other reported literature. PMID:26945462

  19. Medical genetics

    SciTech Connect

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  20. Genetic algorithms

    NASA Technical Reports Server (NTRS)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  1. Wavelets meet genetic imaging

    NASA Astrophysics Data System (ADS)

    Wang, Yu-Ping

    2005-08-01

    Genetic image analysis is an interdisciplinary area, which combines microscope image processing techniques with the use of biochemical probes for the detection of genetic aberrations responsible for cancers and genetic diseases. Recent years have witnessed parallel and significant progress in both image processing and genetics. On one hand, revolutionary multiscale wavelet techniques have been developed in signal processing and applied mathematics in the last decade, providing sophisticated tools for genetic image analysis. On the other hand, reaping the fruit of genome sequencing, high resolution genetic probes have been developed to facilitate accurate detection of subtle and cryptic genetic aberrations. In the meantime, however, they bring about computational challenges for image analysis. In this paper, we review the fruitful interaction between wavelets and genetic imaging. We show how wavelets offer a perfect tool to address a variety of chromosome image analysis problems. In fact, the same word "subband" has been used in the nomenclature of cytogenetics to describe the multiresolution banding structure of the chromosome, even before its appearance in the wavelet literature. The application of wavelets to chromosome analysis holds great promise in addressing several computational challenges in genetics. A variety of real world examples such as the chromosome image enhancement, compression, registration and classification will be demonstrated. These examples are drawn from fluorescence in situ hybridization (FISH) and microarray (gene chip) imaging experiments, which indicate the impact of wavelets on the diagnosis, treatments and prognosis of cancers and genetic diseases.

  2. Optical antenna gain. I - Transmitting antennas

    NASA Technical Reports Server (NTRS)

    Klein, B. J.; Degnan, J. J.

    1974-01-01

    The gain of centrally obscured optical transmitting antennas is analyzed in detail. The calculations, resulting in near- and far-field antenna gain patterns, assume a circular antenna illuminated by a laser operating in the TEM-00 mode. A simple polynomial equation is derived for matching the incident source distribution to a general antenna configuration for maximum on-axis gain. An interpretation of the resultant gain curves allows a number of auxiliary design curves to be drawn that display the losses in antenna gain due to pointing errors and the cone angle of the beam in the far field as a function of antenna aperture size and its central obscuration. The results are presented in a series of graphs that allow the rapid and accurate evaluation of the antenna gain which may then be substituted into the conventional range equation.

  3. Random lasing with spatially nonuniform gain

    NASA Astrophysics Data System (ADS)

    Fan, Ting; Lü, Jiantao

    2016-07-01

    Spatial and spectral properties of random lasing with spatially nonuniform gain were investigated in two-dimensional (2D) disordered medium. The pumping light was described by an individual electric field and coupled into the rate equations by using the polarization equation. The spatially nonuniform gain comes from the multiple scattering of this pumping light. Numerical simulation of the random system with uniform and nonuniform gain were performed both in weak and strong scattering regime. In weak scattering sample, all the lasing modes correspond to those of the passive system whether the nonuniform gain is considered. However, in strong scattering regime, new lasing modes appear with nonuniform gain as the localization area changes. Our results show that it is more accurate to describe the random lasing behavior with introducing the nonuniform gain origins from the multiple light scattering.

  4. New Genetics

    MedlinePlus

    ... human genome, behavioral genetics, pharmacogenetics, drug resistance, biofilms, computer modeling. » more Chapter 5: 21st-Century Genetics Covers systems biology, GFP, genetic testing, privacy concerns, DNA forensics, ...

  5. Genetic Counseling

    MedlinePlus

    Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A ... meets with you to discuss genetic risks. The counseling may be for yourself or a family member. ...

  6. Genetic Counseling

    MedlinePlus

    ... Articles Genetic Counseling Information For... Media Policy Makers Genetic Counseling Language: English Español (Spanish) Recommend on Facebook ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

  7. Unstable resonators with a distributed focusing gain.

    PubMed

    Ferguson, T R

    1994-08-20

    The geometrical optics approximation is used to form a model of axisymmetric unstable resonators having distributed focus, gain, and loss. A tapered reflectivity feedback mirror is included. The rate equations for propagation through the focusing gain medium are derived. A unique grid is found for propagation without interpolation along eigenrays in each direction. Numerical examples show the effects of distributed gain and focus on the axial and transverse intensity distributions. PMID:20935986

  8. Gestational weight gain trajectories in primary care

    PubMed Central

    Piccinini-Vallis, Helena; Lee-Baggley, Dayna; Stewart, Moira; Ryan, Bridget

    2016-01-01

    Objective To identify gestational weight gain trajectories, stratified by prepregnancy body mass index (BMI), of women with singleton pregnancies who received prenatal care in a primary care setting, and to compare these trajectories with the 2009 Institute of Medicine gestational weight gain recommendations. Design Retrospective cohort study. Setting Halifax, NS. Participants Women who received prenatal care at the Dalhousie Family Medicine clinics in Halifax from 2009 to 2013. Main outcome measures For each prenatal visit, gestational age and weight measurements were obtained. Multilevel modeling was used to analyze the gestational weight gain trajectories. The upper limit of the guideline-recommended weekly gestational weight gain was compared with the 95% CI of the observed mean weekly gestational weight gain for each prepregnancy BMI category. Results A total of 280 women were included in the analyses. There was a significant interaction between prepregnancy BMI category and gestational weight gain over time (P < .001), with gestational weight gain being significantly lower among women with prepregnancy BMI of 30.0 kg/m2 or greater compared with those with BMI of 18.5 to less than 25.0 kg/m2 and 25.0 to less than 30.0 kg/m2. When comparing women’s weight gain with the recommendations, women with prepregnancy BMI of 25.0 to less than 30.0 kg/m2 had the most guideline discordance, deviating from the weight gain recommendations at 20 weeks’ gestation. Conclusion These results are relevant and of benefit to women and clinicians wishing to address excess gestational weight gain, and to researchers and policy makers developing interventions aimed at curbing gestational weight gain in primary care. Although our results showed women with prepregnancy BMI of 25.0 to less than 30.0 kg/m2 gained the most excess, guideline-discordant weight, interventions should target all women planning or experiencing a pregnancy.

  9. Measurement of Antenna Bore-Sight Gain

    NASA Technical Reports Server (NTRS)

    Fortinberry, Jarrod; Shumpert, Thomas

    2016-01-01

    The absolute or free-field gain of a simple antenna can be approximated using standard antenna theory formulae or for a more accurate prediction, numerical methods may be employed to solve for antenna parameters including gain. Both of these methods will result in relatively reasonable estimates but in practice antenna gain is usually verified and documented via measurements and calibration. In this paper, a relatively simple and low-cost, yet effective means of determining the bore-sight free-field gain of a VHF/UHF antenna is proposed by using the Brewster angle relationship.

  10. Error margin for antenna gain measurements

    NASA Technical Reports Server (NTRS)

    Cable, V.

    2002-01-01

    The specification of measured antenna gain is incomplete without knowing the error of the measurement. Also, unless gain is measured many times for a single antenna or over many identical antennas, the uncertainty or error in a single measurement is only an estimate. In this paper, we will examine in detail a typical error budget for common antenna gain measurements. We will also compute the gain uncertainty for a specific UHF horn test that was recently performed on the Jet Propulsion Laboratory (JPL) antenna range. The paper concludes with comments on these results and how they compare with the 'unofficial' JPL range standard of +/- ?.

  11. Very high gain Nd:YLF amplifiers

    SciTech Connect

    Knights, M.G.; Thomas, M.D.; Chicklis, E.P.; Rines, G.A.; Seka, W.

    1988-05-01

    The authors report on high gain Nd:YLF rod amplifiers in which single-pass, small signal gains of over 1700 have been obtained along with stored energy densitiesgreater than or equal to0.4J/cm/sup 3/. The ability of Nd:YLF amplifiers to support such gains is a result of high parasitic oscillation thresholds, due primarily to the low refractive index of the material. These results suggest that Nd:YLF is an excellent candidate for amplifiers where high specific stored energies and/or very high gains are required.

  12. Quantitative analysis of serum neutralization of human immunodeficiency virus type 1 from subtypes A, B, C, D, E, F, and I: lack of direct correlation between neutralization serotypes and genetic subtypes and evidence for prevalent serum-dependent infectivity enhancement.

    PubMed Central

    Kostrikis, L G; Cao, Y; Ngai, H; Moore, J P; Ho, D D

    1996-01-01

    Human immunodeficiency virus type 1 (HIV-1) M group strains have been assigned to date to nine distinct genetic subtypes, designated A through I, according to phylogenetic analyses of nucleotide sequences of their env or gag genes. Whether there is any relationship between phylogenetic subtypes and the neutralization serotypes is not clear, yet defining the nature of any such relationship by mathematical means would be of major importance for the development of globally effective HIV-1 vaccines. We have therefore developed a quantitative method to analyze serum neutralization of HIV-1 isolates and to identify HIV-1 neutralization serotypes. This method involves calculations of the neutralization index, N(i), a newly defined parameter derived from plots generated from in vitro neutralization assays, calculations of pairwise serum-virus vector distances, and cluster analyses. We have applied this approach to analyze three independent neutralization matrices involving primary HIV-1 strains and sera from genetic subtypes A, B, C, D, E, F, and I. Detailed serum and HIV-1 isolate cluster analyses have shown that in general, the identified neutralization serotypes do not directly correlate with HIV-1 genetic subtypes. These results suggest that neutralization serotypes do not during natural HIV-1 infection are not governed by antibodies directed against simple epitopes within gp120 monomers. A significant proportion (28%) of 1,213 combinations of sera and HIV-1 isolates caused serum-dependent infectivity enhancement [negative N(i) values] rather than neutralization. We also noted that negative N(i) values tended to correlate better with certain HIV-1 isolates rather than with HIV-1-positive sera. Syncytium-inducing variants of HIV-1 were slightly more likely than non-syncytium-inducing variants to undergo serum-dependent infectivity enhancement, although the latter variants could clearly be susceptible to enhancement. PMID:8523557

  13. Enhanced Classification of Brugada Syndrome–Associated and Long-QT Syndrome–Associated Genetic Variants in the SCN5A-Encoded Nav1.5 Cardiac Sodium Channel

    PubMed Central

    Kapplinger, Jamie D.; Giudicessi, John R.; Ye, Dan; Tester, David J.; Callis, Thomas E.; Valdivia, Carmen R.; Makielski, Jonathan C.; Wilde, Arthur A.; Ackerman, Michael J.

    2016-01-01

    Background A 2% to 5% background rate of rare SCN5A nonsynonymous single nucleotide variants (nsSNVs) among healthy individuals confounds clinical genetic testing. Therefore, the purpose of this study was to enhance interpretation of SCN5A nsSNVs for clinical genetic testing using estimated predictive values derived from protein-topology and 7 in silico tools. Methods and Results Seven in silico tools were used to assign pathogenic/benign status to nsSNVs from 2888 long-QT syndrome cases, 2111 Brugada syndrome cases, and 8975 controls. Estimated predictive values were determined for each tool across the entire SCN5A-encoded Nav1.5 channel as well as for specific topographical regions. In addition, the in silico tools were assessed for their ability to correlate with cellular electrophysiology studies. In long-QT syndrome, transmembrane segments S3−S5+S6 and the DIII/DIV linker region were associated with high probability of pathogenicity. For Brugada syndrome, only the transmembrane spanning domains had a high probability of pathogenicity. Although individual tools distinguished case- and control-derived SCN5A nsSNVs, the composite use of multiple tools resulted in the greatest enhancement of interpretation. The use of the composite score allowed for enhanced interpretation for nsSNVs outside of the topological regions that intrinsically had a high probability of pathogenicity, as well as within the transmembrane spanning domains for Brugada syndrome nsSNVs. Conclusions We have used a large case/control study to identify regions of Nav1.5 associated with a high probability of pathogenicity. Although topology alone would leave the variants outside these identified regions in genetic purgatory, the synergistic use of multiple in silico tools may help promote or demote a variant's pathogenic status. PMID:25904541

  14. Genetic test reporting enhances understanding of risk information and acceptance of prevention recommendations compared to family history-based counseling alone

    PubMed Central

    Taber, Jennifer M.; Aspinwall, Lisa G.; Stump, Tammy K.; Kohlmann, Wendy; Champine, Marjan; Leachman, Sancy A.

    2015-01-01

    It is unknown whether or why genetic test reporting confers benefits in the understanding and management of cancer risk beyond what patients learn from counseling based on family history. A prospective nonexperimental control group study compared participants from melanoma-prone families who underwent CDKN2A/p16 (p16) genetic testing (27 carriers, 38 noncarriers) to participants from equivalently melanoma-prone families known not to carry a deleterious p16 mutation (31 no-test controls). All participants received equivalent counseling concerning elevated lifetime melanoma risk and corresponding recommendations for prevention and screening. Both immediately and one month after counseling, participants receiving a genetic test result reported greater understanding of their risk, decreased derogation of the risk information, and greater personal applicability of prevention recommendations than no-test controls. Decreased derogation of risk information after test reporting predicted further increases in understanding of melanoma risk and applicability of prevention recommendations one month later. Results suggest unique benefits of genetic test reporting in promoting understanding and acceptance of information about hereditary cancer risk and its management. PMID:26178773

  15. Genetic Modification of Stem Cells for Transplantation

    PubMed Central

    Phillips, M. Ian; Tang, Yao Liang

    2009-01-01

    Gene modification of cells for prior to their transplantation, especially stem cells, enhances their survival and increases their function in cell therapy. Like the Trojan horse, the gene modified cell has to gain entrance inside the host’s walls and survive and deliver its transgene products Using cellular, molecular and gene manipulation techniques the transplanted cell can be protected in a hostile environment from immune rejection, inflammation, hypoxia and apoptosis. Genetic engineering to modify cells involves constructing modules of functional gene sequences. They can be simple reporter genes or complex cassettes with gene switches, cell specific promoters and multiple transgenes. We discuss methods to deliver and construct gene cassettes with viral and non viral delivery, siRNA, and conditional Cre/Lox P. We review the current uses of gene modified stem cells in cardiovascular disease, diabetes, neurological diseases,( including Parkinson’s, Alzheimer’s and spinal cord injury repair), bone defects, hemophilia, and cancer. PMID:18031863

  16. Why Research on the Pharmacogenetics of Atypical Antipsychotic-Induced Weight Gain in Individuals with Intellectual Disabilities Is Warranted

    ERIC Educational Resources Information Center

    Sleister, Heidi M.; Valdovinos, Maria Gabriela

    2011-01-01

    Weight gain is an often-observed side effect of atypical antipsychotics (AAPs) and is particularly significant in individuals with intellectual disabilities (ID). The majority of individuals treated with AAPs will gain at least 10% of their initial body weight over the course of therapy (Umbricht & Kane, 1996). One's genetic constitution is an…

  17. Correcting the Normalized Gain for Guessing

    ERIC Educational Resources Information Center

    Stewart, John; Stewart, Gay

    2010-01-01

    The normalized gain, "g", has been an important tool for the characterization of conceptual improvement in physics courses since its use in Hake's extensive study on conceptual learning in introductory physics. The normalized gain is calculated from the score on a pre-test administered before instruction and a post-test administered after…

  18. Sudden Gains During Therapy of Social Phobia

    PubMed Central

    Hofmann, Stefan G.; Schulz, Stefan M.; Meuret, Alicia E.; Moscovitch, David A.; Suvak, Michael

    2007-01-01

    The present study investigated the phenomenon of sudden gains in 107 participants with social phobia (social anxiety disorder) who received either cognitive–behavioral group therapy or exposure group therapy without explicit cognitive interventions, which primarily used public speaking situations as exposure tasks. Twenty-two out of 967 session-to-session intervals met criteria for sudden gains, which most frequently occurred in Session 5. Individuals with sudden gains showed similar improvements in the 2 treatment groups. Although cognitive–behavioral therapy was associated with more cognitive changes than exposure therapy, cognitive changes did not precede sudden gains. In general, the results of this study question the clinical significance of sudden gains in social phobia treatment. PMID:16881776

  19. The Hitchhiker’s Guide to Xenopus Genetics

    PubMed Central

    Abu-Daya, Anita; Khokha, Mustafa K.; Zimmerman, Lyle B.

    2012-01-01

    Summary A decade after the human genome sequence, most vertebrate gene functions remain poorly understood, limiting benefits to human health from rapidly advancing genomic technologies. Systematic in vivo functional analysis is ideally suited to the experimentally accessible Xenopus embryo, which combines embryological accessibility with a broad range of transgenic, biochemical and gain-of-function assays. The diploid X. tropicalis adds loss-of-function genetics and enhanced genomics to this repertoire. In the last decade diverse phenotypes have been recovered from genetic screens, mutations have been cloned, and reverse genetics in the form of TILLING and targeted gene editing have been established. Simple haploid genetics and gynogenesis and the very large number of embryos produced streamline screening and mapping. Improved genomic resources and the revolution in high-throughput sequencing are transforming mutation cloning and reverse genetic approaches. The combination of loss-of-function mutant backgrounds with the diverse array of conventional Xenopus assays offers a uniquely flexible platform for analysis of gene function in vertebrate development. PMID:22344745

  20. Genetic characterization of Chikungunya virus in the Central African Republic.

    PubMed

    Desdouits, Marion; Kamgang, Basile; Berthet, Nicolas; Tricou, Vianney; Ngoagouni, Carine; Gessain, Antoine; Manuguerra, Jean-Claude; Nakouné, Emmanuel; Kazanji, Mirdad

    2015-07-01

    Chikungunya virus (CHIKV) is an alphavirus transmitted by the bite of mosquito vectors. Over the past 10 years, the virus has gained mutations that enhance its transmissibility by the Aedes albopictus vector, resulting in massive outbreaks in the Indian Ocean, Asia and Central Africa. Recent introduction of competent A. albopictus vectors into the Central African Republic (CAR) pose a threat of a Chikungunya fever (CHIKF) epidemic in this region. We undertook this study to assess the genetic diversity and background of CHIKV strains isolated in the CAR between 1975 and 1984 and also to estimate the ability of local strains to adapt to A. albopictus. Our results suggest that, local CHIKV strains have a genetic background compatible with quick adaptation to A. albopictus, as previously observed in other Central African countries. Intense surveillance of the human and vector populations is necessary to prevent or anticipate the emergence of a massive CHIKF epidemic in the CAR.

  1. SATIETY MECHANISMS IN GENETIC RISK OF OBESITY

    PubMed Central

    van Jaarsveld, Cornelia Hendrika Maria; Plomin, Robert; Wardle, Jane

    2014-01-01

    % CI, 1.98 to 4.25). Associations between the PRS and adiposity were significantly mediated by satiety responsiveness (BMI-SDS: P = 0.006; waist-SDS: P = 0.005). CONCLUSIONS AND RELEVANCE These results support the hypothesis that low satiety responsiveness is one of the mechanisms through which genetic predisposition leads to weight gain in an environment rich with food. Strategies to enhance satiety responsiveness could help prevent weight gain in genetically at-risk children. PMID:24535189

  2. Phenotypic H-Antigen Typing by Mass Spectrometry Combined with Genetic Typing of H Antigens, O Antigens, and Toxins by Whole-Genome Sequencing Enhances Identification of Escherichia coli Isolates

    PubMed Central

    Chui, Huixia; Domish, Larissa; Sloan, Angela; Hernandez, Drexler; McCorrister, Stuart; Robinson, Alyssia; Walker, Matthew; Peterson, Lorea A. M.; Majcher, Miles; Ratnam, Sam; Haldane, David J. M.; Bekal, Sadjia; Wylie, John; Chui, Linda; Tyler, Shaun; Xu, Bianli; Reimer, Aleisha; Nadon, Celine; Knox, J. David

    2016-01-01

    Mass spectrometry-based phenotypic H-antigen typing (MS-H) combined with whole-genome-sequencing-based genetic identification of H antigens, O antigens, and toxins (WGS-HOT) was used to type 60 clinical Escherichia coli isolates, 43 of which were previously identified as nonmotile, H type undetermined, or O rough by serotyping or having shown discordant MS-H and serotyping results. Whole-genome sequencing confirmed that MS-H was able to provide more accurate data regarding H antigen expression than serotyping. Further, enhanced and more confident O antigen identification resulted from gene cluster based typing in combination with conventional typing based on the gene pair comprising wzx and wzy and that comprising wzm and wzt. The O antigen was identified in 94.6% of the isolates when the two genetic O typing approaches (gene pair and gene cluster) were used in conjunction, in comparison to 78.6% when the gene pair database was used alone. In addition, 98.2% of the isolates showed the existence of genes for various toxins and/or virulence factors, among which verotoxins (Shiga toxin 1 and/or Shiga toxin 2) were 100% concordant with conventional PCR based testing results. With more applications of mass spectrometry and whole-genome sequencing in clinical microbiology laboratories, this combined phenotypic and genetic typing platform (MS-H plus WGS-HOT) should be ideal for pathogenic E. coli typing. PMID:27307455

  3. Analysis of optical amplifier gain competition attack in a point-to-point WDM link

    NASA Astrophysics Data System (ADS)

    Deng, Tao; Subramaniam, Suresh

    2002-07-01

    Gain competition in an optical amplifier can result in a performance-degrading reduction in the gain of a channel if the overall input power of the amplifier is increased. A gain competition attack may be realized by one or more attackers (pretending to be legitimate users) increasing their source powers in order to degrade the quality of service seen by other users. In this paper, we study the effect of an optical amplifier gain competition attack in a point-to-point WDM link. By looking at the relative OSNR degradation ratio of the attacked channels, we show that Automatic Gain Control mechanisms can alleviate the absolute OSNR degradation to a significant extent, but cannot immunize the system from performance deterioration if the attacking user's power is strong enough. Adding more amplifiers to a link will enhance the service quality as well as the system's robustness against a gain competition attack at the price of higher network cost.

  4. High gain holmium-doped fibre amplifiers.

    PubMed

    Simakov, Nikita; Li, Zhihong; Jung, Yongmin; Daniel, Jae M O; Barua, Pranabesh; Shardlow, Peter C; Liang, Sijing; Sahu, Jayanta K; Hemming, Alexander; Clarkson, W Andrew; Alam, Shaif-Ul; Richardson, David J

    2016-06-27

    We investigate the operation of holmium-doped fibre amplifiers (HDFAs) in the 2.1 µm spectral region. For the first time we demonstrate a diode-pumped HDFA. This amplifier provides a peak gain of 25 dB at 2040 nm with a 15 dB gain window spanning the wavelength range 2030 - 2100 nm with an external noise figure (NF) of 4-6 dB. We also compare the operation of HDFAs when pumped at 1950 nm and 2008 nm. The 1950 nm pumped HDFA provides 41 dB peak gain at 2060 nm with 15 dB of gain spanning the wavelength range 2050 - 2120 nm and an external NF of 7-10 dB. By pumping at the longer wavelength of 2008 nm the gain bandwidth of the amplifier is shifted to longer wavelengths and using this architecture a HDFA was demonstrated with a peak gain of 39 dB at 2090 nm and 15 dB of gain spanning the wavelength range 2050 - 2150 nm. The external NF over this wavelength range was 8-14 dB. PMID:27410557

  5. Temporal evolution of "automatic gain-scaling".

    PubMed

    Pruszynski, J Andrew; Kurtzer, Isaac; Lillicrap, Timothy P; Scott, Stephen H

    2009-08-01

    The earliest neural response to a mechanical perturbation, the short-latency stretch response (R1: 20-45 ms), is known to exhibit "automatic gain-scaling" whereby its magnitude is proportional to preperturbation muscle activity. Because gain-scaling likely reflects an intrinsic property of the motoneuron pool (via the size-recruitment principle), counteracting this property poses a fundamental challenge for the nervous system, which must ultimately counter the absolute change in load regardless of the initial muscle activity (i.e., show no gain-scaling). Here we explore the temporal evolution of gain-scaling in a simple behavioral task where subjects stabilize their arm against different background loads and randomly occurring torque perturbations. We quantified gain-scaling in four elbow muscles (brachioradialis, biceps long, triceps lateral, triceps long) over the entire sequence of muscle activity following perturbation onset-the short-latency response, long-latency response (R2: 50-75 ms; R3: 75-105 ms), early voluntary corrections (120-180 ms), and steady-state activity (750-1250 ms). In agreement with previous observations, we found that the short-latency response demonstrated substantial gain-scaling with a threefold increase in background load resulting in an approximately twofold increase in muscle activity for the same perturbation. Following the short-latency response, we found a rapid decrease in gain-scaling starting in the long-latency epoch ( approximately 75-ms postperturbation) such that no significant gain-scaling was observed for the early voluntary corrections or steady-state activity. The rapid decrease in gain-scaling supports our recent suggestion that long-latency responses and voluntary control are inherently linked as part of an evolving sensorimotor control process through similar neural circuitry.

  6. Active rc filter permits easy trade-off of amplifier gain and sensitivity to gain

    NASA Technical Reports Server (NTRS)

    Kerwin, W. J.; Shaffer, C. V.

    1968-01-01

    Passive RC network was designed with zeros of transmission in the right half of the complex frequency plane in the feedback loop of a simple negative-gain amplifier. The proper positioning provides any desired trade-off between amplifier gain and sensitivity to amplifier gain.

  7. Provider advice about pregnancy weight gain and adequacy of weight gain.

    PubMed

    Ferrari, Renée M; Siega-Riz, Anna Maria

    2013-02-01

    To explore the association between health care provider advice about weight gain and gestational weight gain. Using data from a prospective cohort study, we explored the association between provider advice about weight gain in pregnancy with weight gain adequacy among 1,454 pregnant women. Provider advice was measured by maternal self-report at 27-30 weeks' gestation. Linear and Poisson regression were used to explore associations. Seventy-eight percent of the women gained outside current recommendations. Fifty-one percent reported receiving weight gain advice from a health care provider. Adjusted Generalized Linear Model (GLM) estimates showed weak effect of provider advice on inadequate or excessive gain (Relative Risk (RR) 0.96, 95% CI 0.74, 1.26 for inadequate gain and RR 1.01, 95% CI 0.97, 1.06 for excessive gain). There is a need for more women to hear about their targeted weight gains during pregnancy and the present advice that exists does little to influence actual gains. Further studies are warranted to find better strategies for providers to motivate their patients to gain weight within the appropriate ranges.

  8. TCAD simulation of Low Gain Avalanche Detectors

    NASA Astrophysics Data System (ADS)

    Dalal, Ranjeet; Jain, Geetika; Bhardwaj, Ashutosh; Ranjan, Kirti

    2016-11-01

    In the present work, detailed simulation using Technology Computer Aided Design (TCAD) tool, Silvaco for non-irradiated and irradiated LGAD (Low Gain Avalanche Detector) devices has been carried out. The effects of different design parameters and proton irradiation on LGAD operation are discussed in detail. An already published effective two trap bulk damage model is used to simulate the radiation damage without implementing any acceptor removal term. The TCAD simulation for irradiated LGAD devices produce decreasing gain with increasing fluence, similar to the measurement results. The space charge density and electric field distribution are used to illustrate the possible reasons for the degradation of gain of the irradiated LGAD devices.

  9. Optical properties of nanowire metamaterials with gain

    NASA Astrophysics Data System (ADS)

    Lima, Joaquim; Adam, Jost; Rego, Davi; Esquerre, Vitaly; Bordo, Vladimir

    2016-11-01

    The transmittance, reflectance and absorption of a nanowire metamaterial with optical gain are numerically simulated and investigated. It is assumed that the metamaterial is represented by aligned silver nanowires embedded into a semiconductor matrix, made of either silicon or gallium phosphide. The gain in the matrix is modeled by adding a negative imaginary part to the dielectric function of the semiconductor. It is found that the optical coefficients of the metamaterial depend on the gain magnitude in a non-trivial way: they can both increase and decrease with gain depending on the lattice constant of the metamaterial. This peculiar behavior is explained by the field redistribution between the lossy metal nanowires and the amplifying matrix material. These findings are significant for a proper design of nanowire metamaterials with low optical losses for diverse applications.

  10. Adolescent drug addiction treatment and weight gain.

    PubMed

    Hodgkins, Candace C; Cahill, Kevin S; Seraphine, Anne E; Frost-Pineda, Kimberly; Gold, Mark S

    2004-01-01

    Neurotransmitter release in the nucleus accumbens use has been linked to self-administration and learning following drug use. This endogenous reward system is also activated following food intake or sex. Therefore, rebound hyperphagia following abstinence may be a mechanism to replenish the release of neurotransmitters in this reward system, leading to increased weight gain and a rise in body mass index during recovery from substance abuse. In this report, we examined the relationship between supervised drug abstinence and increased weight gain among adolescents at a residential substance abuse treatment center. Mean weight change over time was followed by repeated analysis of weight and body mass index. Significant weight gain and body mass index increase was observed during supervised and confirmed abstinence from drug use. Furthermore, significant interactions between tobacco use and primary substance use disorder with weight gain was demonstrated by multivariate analysis of variance.

  11. Organic Causes of Weight Gain and Obesity

    MedlinePlus

    ... Issues Listen Español Text Size Email Print Share Organic Causes of Weight Gain and Obesity Page Content ... as children, before they became heavy. Still other organic factors partly determine which kids can eat anything ...

  12. Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity

    PubMed Central

    Ooi, Wen Fong; Xing, Manjie; Xu, Chang; Yao, Xiaosai; Ramlee, Muhammad Khairul; Lim, Mei Chee; Cao, Fan; Lim, Kevin; Babu, Deepak; Poon, Lai-Fong; Lin Suling, Joyce; Qamra, Aditi; Irwanto, Astrid; Qu Zhengzhong, James; Nandi, Tannistha; Lee-Lim, Ai Ping; Chan, Yang Sun; Tay, Su Ting; Lee, Ming Hui; Davies, James O. J.; Wong, Wai Keong; Soo, Khee Chee; Chan, Weng Hoong; Ong, Hock Soo; Chow, Pierce; Wong, Chow Yin; Rha, Sun Young; Liu, Jianjun; Hillmer, Axel M.; Hughes, Jim R.; Rozen, Steve; Teh, Bin Tean; Fullwood, Melissa Jane; Li, Shang; Tan, Patrick

    2016-01-01

    Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, we highlight 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively. Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments. Somatic gain super-enhancers are associated with complex chromatin interaction profiles, expression patterns correlated with patient outcome and dense co-occupancy of the transcription factors CDX2 and HNF4α. Somatic super-enhancers are also enriched in genetic risk SNPs associated with cancer predisposition. Our results reveal a genome-wide reprogramming of the GC enhancer and super-enhancer landscape during tumorigenesis, contributing to dysregulated local and regional cancer gene expression. PMID:27677335

  13. The Galileo high gain antenna deployment anomaly

    NASA Technical Reports Server (NTRS)

    Johnson, Michael R.

    1994-01-01

    On April 11, 1991, the Galileo spacecraft executed a sequence that would open the spacecraft's High Gain Antenna. The Antenna's launch restraint had been released just after deployment sequence, the antenna, which opens like an umbrella, never reached the fully deployed position. The analyses and tests that followed allowed a conclusive determination of the likely failure mechanisms and pointed to some strategies to use for recovery of the high gain antenna.

  14. The relationship between parental genetic or phenotypic divergence and progeny variation in the maize nested association mapping population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The choice of populations for quantitative genetics experiments impacts inferences about genetic architecture and prospective selection gains. Plant breeding and quantitative genetics studies are often conducted in one or a few among many possible biparental families. Trait genotypic variation withi...

  15. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome

    PubMed Central

    de Jorge, Elena Goicoechea; Harris, Claire L.; Esparza-Gordillo, Jorge; Carreras, Luis; Arranz, Elena Aller; Garrido, Cynthia Abarrategui; López-Trascasa, Margarita; Sánchez-Corral, Pilar; Morgan, B. Paul; de Córdoba, Santiago Rodríguez

    2007-01-01

    Hemolytic uremic syndrome (HUS) is an important cause of acute renal failure in children. Mutations in one or more genes encoding complement-regulatory proteins have been reported in approximately one-third of nondiarrheal, atypical HUS (aHUS) patients, suggesting a defect in the protection of cell surfaces against complement activation in susceptible individuals. Here, we identified a subgroup of aHUS patients showing persistent activation of the complement alternative pathway and found within this subgroup two families with mutations in the gene encoding factor B (BF), a zymogen that carries the catalytic site of the complement alternative pathway convertase (C3bBb). Functional analyses demonstrated that F286L and K323E aHUS-associated BF mutations are gain-of-function mutations that result in enhanced formation of the C3bBb convertase or increased resistance to inactivation by complement regulators. These data expand our understanding of the genetic factors conferring predisposition to aHUS, demonstrate the critical role of the alternative complement pathway in the pathogenesis of aHUS, and provide support for the use of complement-inhibition therapies to prevent or reduce tissue damage caused by dysregulated complement activation. PMID:17182750

  16. Optimal Takagi-Sugeno Fuzzy Gain-Scheduler Design Using Taguchi-MHGA Method

    NASA Astrophysics Data System (ADS)

    Hsieh, Chen-Huei; Chou, Jyh-Horng; Wu, Ying-Jeng

    The fuzzy gain scheduling (FGS) control scheme based on TS (Takagi-Sugeno) fuzzy model is an effective approach to control nonlinear systems whose dynamics change with different operating condition. However, when the TS-model-based FGS control scheme is adopted to the stabilization/tracking control problem, a considerable amount of approximation errors between the nonlinear system and fuzzy approximation system apparently affect the control performance. Besides, when the LQR (linear quadratic regulator) method is employed to design local linear controllers, it is necessary to adjust the weighting matrices in performance index of the LQR for getting minimum performance index. Hence, in order to reduce the aforementioned approximation errors and enhance the dynamic performance of the TS-model-based FGS control scheme, a systematic and optimal reasoning method, named as Taguchi-MHGA (Taguchi-modified-hierarchical-genetic-algorithm) approach, is proposed in this paper to search for the optimal fuzzy centers (the linearization points) of the fuzzy regions, the optimal set of membership functions, and the weighting matrices of the LQR method. Furthermore, for ensuring that the closed-loop FGS system at any arbitrary operating point is asymptotically stable, two new sufficient conditions are presented. Finally, computer simulations are performed to demonstrate the effectiveness of the TS-model-based FGS control scheme designed by Taguchi-MHGA method. It is shown that the satisfactory performances have been achieved by such designed optimal TS-model-based FGS control scheme.

  17. Can LENR Energy Gains Exceed 1000?

    NASA Astrophysics Data System (ADS)

    Nagel, David J.

    2011-03-01

    Energy gain is defined as the energy realized from reactions divided by the energy required to produce those reactions. Low Energy Nuclear Reactions (LENR) have already been measured to significantly exceed the energy gain of 10 projected from ITER,possibly 15 years from now. Electrochemical experiments using the Pd-D system have shown energy gains exceeding 10. Gas phase experiments with the Ni-H system were reported to yield energy gains of over 100. Neither of these reports has been adequately verified or reproduced. However, the question in the title still deserves consideration. If, as thought by many, it is possible to trigger nuclear reactions that yield MeV energies with chemical energies of the order of eV, then the most optimistic expectation is that LENR gains could approach one million. Hence, the very tentative answer to the question above is yes. However, if LENR could be initiated with some energy cost, and then continue to ``burn,'' very high energy gains might be realized. Consider a match and a pile of dry logs. The phenomenon termed ``heat after death'' will be examined to see if it might be the initial evidence for nuclear ``burning.''

  18. Context-specific adaptation of saccade gain

    NASA Technical Reports Server (NTRS)

    Shelhamer, Mark; Clendaniel, Richard A.

    2002-01-01

    Previous studies established that vestibular reflexes can have two adapted states (e.g., gain) simultaneously, and that a context cue (e.g., vertical eye position) can switch between the two states. The present study examined this phenomenon of context-specific adaptationfor horizontal saccades, using a variety of contexts. Our overall goal was to assess the efficacy of different context cues in switching between adapted states. A standard double-step paradigm was used to adapt saccade gain. In each experiment, we asked for a simultaneous gain decrease in one context and gain increase in another context, and then determined if a change in the context would invoke switching between the adapted states. Horizontal eye position worked well as a context cue: saccades with the eyes deviated to the right could be made to have higher gains while saccades with the eyes deviated to the left could be made to have lower gains. Vertical eye position was less effective. This suggests that the more closely related a context cue is to the response being adapted, the more effective it is. Roll tilt of the head, and upright versus supine orientations, were somewhat effective in context switching; these paradigms contain orientation of gravity with respect to the head as part of the context.

  19. High hyperdiploid childhood acute lymphoblastic leukemia: Chromosomal gains as the main driver event.

    PubMed

    Paulsson, Kajsa

    2016-01-01

    High hyperdiploid childhood acute lymphoblastic leukemia is characterized by multiple chromosomal gains. Recent results show that this subtype harbors relatively few genetic abnormalities besides the extra chromosomes, which appear to arise early and are likely the main driver event. Secondary hits primarily target genes in the rat sarcoma (RAS) signaling pathway and histone modifiers. PMID:27308574

  20. Genetic Base Changes for January 2010

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic bases were updated previously in the United States in 1965, 1974, 1984, 1989, 1995, 2000, and 2005, and the next base change is scheduled for January 2010. Changing the base every 5 years subtracts accumulated genetic gain so that all animals are compared with a more recent cow population, w...

  1. New Results in Astrodynamics Using Genetic Algorithms

    NASA Technical Reports Server (NTRS)

    Coverstone-Carroll, V.; Hartmann, J. W.; Williams, S. N.; Mason, W. J.

    1998-01-01

    Generic algorithms have gained popularity as an effective procedure for obtaining solutions to traditionally difficult space mission optimization problems. In this paper, a brief survey of the use of genetic algorithms to solve astrodynamics problems is presented and is followed by new results obtained from applying a Pareto genetic algorithm to the optimization of low-thrust interplanetary spacecraft missions.

  2. Assessing the Permeability of Landscape Features to Animal Movement: Using Genetic Structure to Infer Functional Connectivity

    PubMed Central

    Anderson, Sara J.; Kierepka, Elizabeth M.; Swihart, Robert K.; Latch, Emily K.; Rhodes, Olin E.

    2015-01-01

    Human-altered environments often challenge native species with a complex spatial distribution of resources. Hostile landscape features can inhibit animal movement (i.e., genetic exchange), while other landscape attributes facilitate gene flow. The genetic attributes of organisms inhabiting such complex environments can reveal the legacy of their movements through the landscape. Thus, by evaluating landscape attributes within the context of genetic connectivity of organisms within the landscape, we can elucidate how a species has coped with the enhanced complexity of human altered environments. In this research, we utilized genetic data from eastern chipmunks (Tamias striatus) in conjunction with spatially explicit habitat attribute data to evaluate the realized permeability of various landscape elements in a fragmented agricultural ecosystem. To accomplish this we 1) used logistic regression to evaluate whether land cover attributes were most often associated with the matrix between or habitat within genetically identified populations across the landscape, and 2) utilized spatially explicit habitat attribute data to predict genetically-derived Bayesian probabilities of population membership of individual chipmunks in an agricultural ecosystem. Consistency between the results of the two approaches with regard to facilitators and inhibitors of gene flow in the landscape indicate that this is a promising new way to utilize both landscape and genetic data to gain a deeper understanding of human-altered ecosystems. PMID:25719366

  3. Genetics & sport: bioethical concerns.

    PubMed

    Miah, Andy

    2012-12-01

    This paper provides an overview of the ethical issues pertaining to the use of genetic insights and techniques in sport. Initially, it considers a range of scientific findings that have stimulated debate about the ethical issues associated with genetics applied to sport. It also outlines some of the early policy responses to these discoveries from world leading sports organizations, along with knowledge about actual use of gene technologies in sport. Subsequently, it considers the challenges with distinguishing between therapeutic use and human enhancement within genetic science, which is a particularly important issue for the world of sport. Next, particular attention is given to the use of genetic information, which raises questions about the legitimacy and reliability of genetic tests, along with the potential public value of having DNA databanks to economize in health care. Finally, the ethics of gene transfer are considered, inviting questions into the values of sport and humanity. It argues that, while gene modification may seem conceptually similar to other forms of doping, the requirements upon athletes are such that new forms of enhancement become increasingly necessary to discover. Insofar as genetic science is able to create safer, more effective techniques of human modification, then it may be an appealing route through which to modify athletes to safeguard the future of elite sports as enterprises of human excellence. PMID:22830450

  4. Genetics & sport: bioethical concerns.

    PubMed

    Miah, Andy

    2012-12-01

    This paper provides an overview of the ethical issues pertaining to the use of genetic insights and techniques in sport. Initially, it considers a range of scientific findings that have stimulated debate about the ethical issues associated with genetics applied to sport. It also outlines some of the early policy responses to these discoveries from world leading sports organizations, along with knowledge about actual use of gene technologies in sport. Subsequently, it considers the challenges with distinguishing between therapeutic use and human enhancement within genetic science, which is a particularly important issue for the world of sport. Next, particular attention is given to the use of genetic information, which raises questions about the legitimacy and reliability of genetic tests, along with the potential public value of having DNA databanks to economize in health care. Finally, the ethics of gene transfer are considered, inviting questions into the values of sport and humanity. It argues that, while gene modification may seem conceptually similar to other forms of doping, the requirements upon athletes are such that new forms of enhancement become increasingly necessary to discover. Insofar as genetic science is able to create safer, more effective techniques of human modification, then it may be an appealing route through which to modify athletes to safeguard the future of elite sports as enterprises of human excellence.

  5. Effect of body weight gain on insulin sensitivity after retirement from exercise training

    NASA Technical Reports Server (NTRS)

    Dolkas, Constantine B.; Rodnick, Kenneth J.; Mondon, Carl E.

    1990-01-01

    The effect of the body-weight gain after retirement from an exercise-training program on the retained increase in insulin sensitivity elicited by the training was investigated in exercise-trained (ET) rats. Insulin sensitivity was assessed by oral glucose tolerance and insulin suppression tests immediately after training and during retirement. Results show that, compared with sedentary controls, exercise training enhanced insulin-induced glucose uptake, but the enhanced sensitivity was gradually lost with the end of running activity until after seven days of retirement, when it became equal to that of controls. This loss of enhanced sensitivity to insulin was associated with an accelerated gain in body weight beginning one day after the start of retirement. However, those animals that gained weight only at rates similar to those of control rats, retained their enhanced sensitivity to insulin.

  6. Clinical Genetic Testing in Epilepsy

    PubMed Central

    2015-01-01

    New technologies for mutation detection in the human genome have greatly increased our understanding of epilepsy genetics. Application of genomic technologies in the clinical setting allows for more efficient genetic diagnosis in some patients; therefore, it is important to understand the types of tests available and the types of mutations that can be detected. Making a genetic diagnosis improves overall patient care by enhancing prognosis and recurrence risk counseling and informing treatment decisions. PMID:26316867

  7. Genetically modified human placenta‑derived mesenchymal stem cells with FGF‑2 and PDGF‑BB enhance neovascularization in a model of hindlimb ischemia.

    PubMed

    Yin, Tao; He, Sisi; Su, Chao; Chen, Xiancheng; Zhang, Dongmei; Wan, Yang; Ye, Tinghong; Shen, Guobo; Wang, Yongsheng; Shi, Huashan; Yang, Li; Wei, Yuquan

    2015-10-01

    Ischemic diseases represent a challenging worldwide health burden. The current study investigated the therapeutic potential of genetically modified human placenta‑derived mesenchymal stem cells (hPDMSCs) with basic fibroblast growth factor (FGF2) and platelet‑derived growth factor‑BB (PDGF‑BB) genes in hindlimb ischemia. Mesenchymal stem cells obtained from human term placenta were transfected ex vivo with adenoviral bicistronic vectors carrying the FGF2 and PDGF‑BB genes (Ad‑F‑P). Unilateral hindlimb ischemia was surgically induced by excision of the right femoral artery in New Zealand White rabbits. Ad‑F‑P genetically modified hPDMSCs, Ad‑null (control vector)‑modified hPDMSCs, unmodified hPDMSCs or media were intramuscularly implanted into the ischemic limbs 7 days subsequent to the induction of ischemia. Four weeks after cell therapy, angiographic analysis revealed significantly increased collateral vessel formation in the Ad‑F‑P‑hPDMSC group compared with the control group. Histological examination revealed markedly increased capillary and arteriole density in the Ad‑F‑P‑hPDMSC group. The xenografted hPDMSCs survived in the ischemic tissue for at least 4 weeks subsequent to cell therapy. The current study demonstrated that the combination of hPDMSC therapy with FGF2 and PDGF‑BB gene therapy effectively induced collateral vessel formation and angiogenesis, suggesting a novel strategy for therapeutic angiogenesis. PMID:26239842

  8. Genetically modified human placenta-derived mesenchymal stem cells with FGF-2 and PDGF-BB enhance neovascularization in a model of hindlimb ischemia

    PubMed Central

    YIN, TAO; HE, SISI; SU, CHAO; CHEN, XIANCHENG; ZHANG, DONGMEI; WAN, YANG; YE, TINGHONG; SHEN, GUOBO; WANG, YONGSHENG; SHI, HUASHAN; YANG, LI; WEI, YUQUAN

    2015-01-01

    Ischemic diseases represent a challenging worldwide health burden. The current study investigated the therapeutic potential of genetically modified human placenta-derived mesenchymal stem cells (hPDMSCs) with basic fibroblast growth factor (FGF2) and platelet-derived growth factor-BB (PDGF-BB) genes in hindlimb ischemia. Mesenchymal stem cells obtained from human term placenta were transfected ex vivo with adenoviral bicistronic vectors carrying the FGF2 and PDGF-BB genes (Ad-F-P). Unilateral hindlimb ischemia was surgically induced by excision of the right femoral artery in New Zealand White rabbits. Ad-F-P genetically modified hPDMSCs, Ad-null (control vector)-modified hPDMSCs, unmodified hPDMSCs or media were intramuscularly implanted into the ischemic limbs 7 days subsequent to the induction of ischemia. Four weeks after cell therapy, angiographic analysis revealed significantly increased collateral vessel formation in the Ad-F-P-hPDMSC group compared with the control group. Histological examination revealed markedly increased capillary and arteriole density in the Ad-F-P-hPDMSC group. The xenografted hPDMSCs survived in the ischemic tissue for at least 4 weeks subsequent to cell therapy. The current study demonstrated that the combination of hPDMSC therapy with FGF2 and PDGF-BB gene therapy effectively induced collateral vessel formation and angiogenesis, suggesting a novel strategy for therapeutic angiogenesis. PMID:26239842

  9. Genetic variance and covariance components for feed intake, average daily gain, and postweaning gain in growing beef cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Feed is the single most expensive cost related to a beef cattle production enterprise. Data collection to determine feed efficient animals is also costly. Currently a 70 d performance test is recommended for accurate calculation of efficiency. Previous research has suggested intake tests can be l...

  10. A Case Report of a Breastfed Infant's Excessive Weight Gains over 14 Months.

    PubMed

    Perrella, Sharon Lisa; Geddes, Donna Tracy

    2016-05-01

    High infant weight gain is associated with subsequent overweight and obesity and so may contribute to related comorbidities such as metabolic syndrome and cardiovascular disease. The growth acceleration hypothesis proposes that early and rapid growth in infancy can shape the metabolic profile to increase susceptibility to obesity. Although breastfeeding reduces the infant's risk of subsequent overweight and obesity, high infant weight gains are observed in this population. We report the case of an infant with excessive weight gains that persisted throughout 6 months of exclusive breastfeeding. The mother chose to continue breastfeeding despite medical advice to wean, and high weight gains continued for a further 8 months of breastfeeding and complementary foods. This is the first reported case of an exclusively breastfed infant with excessive weight gains (> 97th percentile) with contemporaneous measures of 24-hour breast milk intake and doses and concentrations of protein, fat, and energy. We found a high breast milk protein dose, which is associated with increased weight gain and lean body mass but not necessarily adiposity. It is likely that other influences also contributed to the high infant weight gain. High infant weight gain is multifactorial, with evolving evidence for the role of adipokines and genetic markers. Advice to replace breast milk with formula affects the dose-dependent protection from noncommunicable diseases afforded by breast milk and may not be an effective strategy for reducing adiposity. PMID:26470877

  11. A Case Report of a Breastfed Infant's Excessive Weight Gains over 14 Months.

    PubMed

    Perrella, Sharon Lisa; Geddes, Donna Tracy

    2016-05-01

    High infant weight gain is associated with subsequent overweight and obesity and so may contribute to related comorbidities such as metabolic syndrome and cardiovascular disease. The growth acceleration hypothesis proposes that early and rapid growth in infancy can shape the metabolic profile to increase susceptibility to obesity. Although breastfeeding reduces the infant's risk of subsequent overweight and obesity, high infant weight gains are observed in this population. We report the case of an infant with excessive weight gains that persisted throughout 6 months of exclusive breastfeeding. The mother chose to continue breastfeeding despite medical advice to wean, and high weight gains continued for a further 8 months of breastfeeding and complementary foods. This is the first reported case of an exclusively breastfed infant with excessive weight gains (> 97th percentile) with contemporaneous measures of 24-hour breast milk intake and doses and concentrations of protein, fat, and energy. We found a high breast milk protein dose, which is associated with increased weight gain and lean body mass but not necessarily adiposity. It is likely that other influences also contributed to the high infant weight gain. High infant weight gain is multifactorial, with evolving evidence for the role of adipokines and genetic markers. Advice to replace breast milk with formula affects the dose-dependent protection from noncommunicable diseases afforded by breast milk and may not be an effective strategy for reducing adiposity.

  12. Genetic Mapping

    MedlinePlus

    ... Genetic Education Resources for Teachers Genomic Careers National DNA Day Online Education Kit Online Genetics Education Resources ... prevalent. Using various laboratory techniques, the scientists isolate DNA from these samples and examine it for unique ...

  13. Genetic Disorders

    MedlinePlus

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  14. An assessment of wheat breeding gains in hot environments

    NASA Astrophysics Data System (ADS)

    Gourdji, S. M.; Mathews, K.; Reynolds, M.; Crossa, J.; Lobell, D. B.

    2012-12-01

    Wheat, a critical crop for ensuring global food security, has the lowest optimum temperatures among the major cereals, and is already grown in many heat stress areas, thereby increasing risks to production from a warming climate. Historical spring wheat trial data from the International Maize and Wheat Improvement Center (CIMMYT) was used to investigate the relationship between environmental conditions and yield in major wheat-growing areas, assess the response to future warming, and identify different rates of genetic gains due to variety improvement across environments and breeding nurseries. Results were compared for two nurseries: 1) the Elite Spring Wheat Yield Trial (ESWYT), which aims to improve yield potential under optimal environmental conditions, and 2) the Semi-Arid Wheat Yield Trial (SAWYT), where improvements are targeted in semi-arid, rainfed environments, frequently subject to heat and water stress. Yields from 25 years of trial data were paired with reconstructed daily weather data in an empirical model with environmental variables averaged by growth stage. Temperature, radiation, day length and interaction terms between temperature and vapor pressure deficit (VPD) were all determined to be significant terms in the model. Results show a detrimental response to warming across all temperatures in the grain-filling, or final growth stage, particularly under low VPD/ humid conditions. A negative response to warming was also observed in the reproductive stage after ~14C, although high VPD conferred no additional benefit, perhaps due to a higher sensitivity and/or exposure to water stress during this period. A projected 2C season average warming was seen to have differential effects between ESWYT and SAWYT, with SAWYT germplasm less sensitive to warming up until ~21C, but an equally negative response to further warming for both nurseries. The regions where wheat is already grown under hot, and sometimes humid, conditions, particularly in south and south

  15. Quantitative genetics of disease traits.

    PubMed

    Wray, N R; Visscher, P M

    2015-04-01

    John James authored two key papers on the theory of risk to relatives for binary disease traits and the relationship between parameters on the observed binary scale and an unobserved scale of liability (James Annals of Human Genetics, 1971; 35: 47; Reich, James and Morris Annals of Human Genetics, 1972; 36: 163). These two papers are John James' most cited papers (198 and 328 citations, November 2014). They have been influential in human genetics and have recently gained renewed popularity because of their relevance to the estimation of quantitative genetics parameters for disease traits using SNP data. In this review, we summarize the two early papers and put them into context. We show recent extensions of the theory for ascertained case-control data and review recent applications in human genetics.

  16. Genetic modification and genetic determinism

    PubMed Central

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  17. Genetic principles.

    PubMed

    Abuelo, D

    1987-01-01

    The author discusses the basic principles of genetics, including the classification of genetic disorders and a consideration of the rules and mechanisms of inheritance. The most common pitfalls in clinical genetic diagnosis are described, with emphasis on the problem of the negative or misleading family history.

  18. Imaging Genetics

    ERIC Educational Resources Information Center

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  19. Genetic Testing

    MedlinePlus

    ... genetic tests for several reasons. These include Finding genetic diseases in unborn babies Finding out if people carry a gene for a disease and might pass it on to their children Screening embryos for disease Testing for genetic diseases in adults before they cause ...

  20. Legal issues associated with genetics.

    PubMed

    Carson, W Y

    2000-09-01

    With the evolution of genetic research, legal issues have emerged related to the health care delivery industry and the protection of patient information. The use of genetics or genetic enhancement expands the role of the nurse and also brings a new perspective to the nurse-patient relationship. Nurses now must discern their role in relation to patient privacy and confidentiality. In addition to reviewing the ethical and legal dilemmas of registered nurses in clinical practice, the nursing profession must review the level of responsibility appropriate when using genetic and or experimental treatments, especially when the nurse is not the primary care provider or the leader of the research team. Nurses will have to delve into privacy and confidentiality issues associated with genetic research. Although little case law exists on the relationship of nursing to genetic research and treatments, the implications of experimental research and policy associated with genetics must be analyzed to better understand their impact on the scope of nursing practice.

  1. Production of D-lactic acid in a continuous membrane integrated fermentation reactor by genetically modified Saccharomyces cerevisiae: enhancement in D-lactic acid carbon yield.

    PubMed

    Mimitsuka, Takashi; Sawai, Kenji; Kobayashi, Koji; Tsukada, Takeshi; Takeuchi, Norihiro; Yamada, Katsushige; Ogino, Hiroyasu; Yonehara, Tetsu

    2015-01-01

    Poly d-lactic acid is an important polymer because it improves the thermostability of poly l-lactic acid by stereo complex formation. To demonstrate potency of continuous fermentation using a membrane-integrated fermentation reactor (MFR) system, continuous fermentation using genetically modified Saccharomyces cerevisiae which produces d-lactic acid was performed at the low pH and microaerobic conditions. d-Lactic acid continuous fermentation using the MFR system by genetically modified yeast increased production rate by 11-fold compared with batch fermentation. In addition, the carbon yield of d-lactic acid in continuous fermentation was improved to 74.6 ± 2.3% compared to 39.0 ± 1.7% with batch fermentation. This dramatic improvement in carbon yield could not be explained by a reduction in carbon consumption to form cells compared to batch fermentation. Further detailed analysis at batch fermentation revealed that the carbon yield increased to 76.8% at late stationary phase. S. cerevisiae, which exhibits the Crabtree-positive effect, demonstrated significant changes in metabolic activities at low sugar concentrations (Rossignol et al., Yeast, 20, 1369-1385, 2003). Moreover, lactate-producing S. cerevisiae requires ATP supplied not only from the glycolytic pathway but also from the TCA cycle (van Maris et al., Appl. Environ. Microbiol., 70, 2898-2905, 2004). Our finding was revealed that continuous fermentation, which can maintain the conditions of both a low sugar concentration and air supply, results in Crabtree-positive and lactate-producing S. cerevisiae for suitable conditions of d-lactic acid production with respect to redox balance and ATP generation because of releasing the yeast from the Crabtree effect.

  2. From genetic improvement to commercial-scale mass culture of a Chilean strain of the green microalga Haematococcus pluvialis with enhanced productivity of the red ketocarotenoid astaxanthin

    PubMed Central

    Gómez, Patricia I.; Inostroza, Ingrid; Pizarro, Mario; Pérez, Jorge

    2013-01-01

    Astaxanthin is a red ketocarotenoid, widely used as a natural red colourant in marine fish aquaculture and poultry and, recently, as an antioxidant supplement for humans and animals. The green microalga Haematococcus pluvialis is one of the richest natural sources of this pigment. However, its slow growth rate and complex life cycle make mass culture difficult for commercial purposes. The aims of this research were (i) to standardize and apply a genetic improvement programme to a Chilean strain of H. pluvialis in order to improve its carotenogenic capacity and (ii) to evaluate the performance of a selected mutant strain in commercial-sized (125 000 L) open ponds in the north of Chile. Haematococcus pluvialis strain 114 was mutated by ethyl methanesulfonate. The level of mutagen dose (exposure time and concentration) was one that induced at least 90 % mortality. Surviving colonies were screened for resistance to the carotenoid biosynthesis inhibitor diphenylamine (25 µM). Resistant mutants were grown in a 30-mL volume for 30 days, after which the total carotenoid content was determined by spectrophotometry. Tens of mutants with improved carotenogenic capacity compared with the wild-type strain were isolated by the application of these standardized protocols. Some mutants exhibited curious morphological features such as spontaneous release of astaxanthin and loss of flagella. One of the mutants was grown outdoors in commercial-sized open ponds of 125 000 L in the north of Chile. Grown under similar conditions, the mutant strain accumulated 30 % more astaxanthin than the wild-type strain on a per dry weight basis and 72 % more on a per culture volume basis. We show that random mutagenesis/selection is an effective strategy for genetically improving strains of H. pluvialis and that improved carotenogenic capacity is maintained when the volume of the cultures is scaled up to a commercial size. PMID:23789055

  3. Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors.

    PubMed

    Maroni, Paola; Brini, Anna Teresa; Arrigoni, Elena; de Girolamo, Laura; Niada, Stefania; Matteucci, Emanuela; Bendinelli, Paola; Desiderio, Maria Alfonsina

    2012-11-16

    The human adipose-tissue derived stem/stromal cells (hASCs) are an interesting source for bone-tissue engineering applications. Our aim was to clarify in hASCs the role of acetylation in the control of Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator activated receptor (PPAR) γ. These key osteogenic and adipogenic transcription factors are oppositely involved in osteo-differentiation. The hASCs, committed or not towards bone lineage with osteoinductive medium, were exposed to HDACs chemical blockade with Trichostatin A (TSA) or were genetically silenced for HDACs. Alkaline phosphatase (ALP) and collagen/calcium deposition, considered as early and late osteogenic markers, were evaluated concomitantly as index of osteo-differentiation. TSA pretreatment, useful experimental protocol to analyse pan-HDAC-chemical inhibition, and switch to osteogenic medium induced early-osteoblast maturation gene Runx2, while transiently decreased PPARγ and scarcely affected late-differentiation markers. Time-dependent effects were observed after knocking-down of HDAC1 and 3: Runx2 and ALP underwent early activation, followed by late-osteogenic markers increase and by PPARγ/ALP activity diminutions mostly after HDAC3 silencing. HDAC1 and 3 genetic blockade increased and decreased Runx2 and PPARγ target genes, respectively. Noteworthy, HDACs knocking-down favoured the commitment effect of osteogenic medium. Our results reveal a role for HDACs in orchestrating osteo-differentiation of hASCs at transcriptional level, and might provide new insights into the modulation of hASCs-based regenerative therapy. PMID:23085045

  4. Intron loss and gain in Drosophila.

    PubMed

    Coulombe-Huntington, Jasmin; Majewski, Jacek

    2007-12-01

    Although introns were first discovered almost 30 years ago, their evolutionary origin remains elusive. In this work, we used multispecies whole-genome alignments to map Drosophila melanogaster introns onto 10 other fully sequenced Drosophila genomes. We were able to find 1,944 sites where an intron was missing in one or more species. We show that for most (>80%) of these cases, there is no leftover intronic sequence or any missing exonic sequence, indicating exact intron loss or gain events. We used parsimony to classify these differences as 1,754 intron loss events and 213 gain events. We show that lost and gained introns are significantly shorter than average and flanked by longer than average exons. They also display quite distinct phase distributions and show greater than average similarity between the 5' splice site and its 3' partner splice site. Introns that have been lost in one or more species evolve faster than other introns, occur in slowly evolving genes, and are found adjacent to each other more often than would be expected for independent single losses. Our results support the cDNA recombination mechanism of intron loss, suggest that selective pressures affect site-specific loss rates, and show conclusively that intron gain has occurred within the Drosophila lineage, solidifying the "introns-middle" hypothesis and providing some hints about the gain mechanism.

  5. Gain and energy storage in holmium YLF

    NASA Technical Reports Server (NTRS)

    Storm, Mark E.; Deyst, John P.

    1991-01-01

    It is demonstrated that Q-switched holmium lasers are capable of high-gain and high-energy operation at 300 K. Small-signal gain coefficients of 0.50 and 0.12/cm have been measured in YLF and YAG, respectively. Small-signal gains of 0.50/cm are comparable to those achievable in Nd:YAG and are not typical of low-gain materials. This large gain in the Ho:YLF material is made possible by operating the amplifier in the ground state depletion mode. The amplifier performance data and associated analysis presented demonstrate that efficient energy storage is possible with very high excited state ion densities of the Ho 5I7 upper laser level. This is an important result since upconversion can limit the 5I7 population. Although upconversion was still present in this experiment, it was possible to achieve efficient energy storage, demonstrating that the problem is manageable even at high excitation densities in YLF.

  6. Edemagenic gain and interstitial fluid volume regulation.

    PubMed

    Dongaonkar, R M; Quick, C M; Stewart, R H; Drake, R E; Cox, C S; Laine, G A

    2008-02-01

    Under physiological conditions, interstitial fluid volume is tightly regulated by balancing microvascular filtration and lymphatic return to the central venous circulation. Even though microvascular filtration and lymphatic return are governed by conservation of mass, their interaction can result in exceedingly complex behavior. Without making simplifying assumptions, investigators must solve the fluid balance equations numerically, which limits the generality of the results. We thus made critical simplifying assumptions to develop a simple solution to the standard fluid balance equations that is expressed as an algebraic formula. Using a classical approach to describe systems with negative feedback, we formulated our solution as a "gain" relating the change in interstitial fluid volume to a change in effective microvascular driving pressure. The resulting "edemagenic gain" is a function of microvascular filtration coefficient (K(f)), effective lymphatic resistance (R(L)), and interstitial compliance (C). This formulation suggests two types of gain: "multivariate" dependent on C, R(L), and K(f), and "compliance-dominated" approximately equal to C. The latter forms a basis of a novel method to estimate C without measuring interstitial fluid pressure. Data from ovine experiments illustrate how edemagenic gain is altered with pulmonary edema induced by venous hypertension, histamine, and endotoxin. Reformulation of the classical equations governing fluid balance in terms of edemagenic gain thus yields new insight into the factors affecting an organ's susceptibility to edema.

  7. Edemagenic gain and interstitial fluid volume regulation.

    PubMed

    Dongaonkar, R M; Quick, C M; Stewart, R H; Drake, R E; Cox, C S; Laine, G A

    2008-02-01

    Under physiological conditions, interstitial fluid volume is tightly regulated by balancing microvascular filtration and lymphatic return to the central venous circulation. Even though microvascular filtration and lymphatic return are governed by conservation of mass, their interaction can result in exceedingly complex behavior. Without making simplifying assumptions, investigators must solve the fluid balance equations numerically, which limits the generality of the results. We thus made critical simplifying assumptions to develop a simple solution to the standard fluid balance equations that is expressed as an algebraic formula. Using a classical approach to describe systems with negative feedback, we formulated our solution as a "gain" relating the change in interstitial fluid volume to a change in effective microvascular driving pressure. The resulting "edemagenic gain" is a function of microvascular filtration coefficient (K(f)), effective lymphatic resistance (R(L)), and interstitial compliance (C). This formulation suggests two types of gain: "multivariate" dependent on C, R(L), and K(f), and "compliance-dominated" approximately equal to C. The latter forms a basis of a novel method to estimate C without measuring interstitial fluid pressure. Data from ovine experiments illustrate how edemagenic gain is altered with pulmonary edema induced by venous hypertension, histamine, and endotoxin. Reformulation of the classical equations governing fluid balance in terms of edemagenic gain thus yields new insight into the factors affecting an organ's susceptibility to edema. PMID:18056984

  8. An assessment of wheat yield sensitivity and breeding gains in hot environments.

    PubMed

    Gourdji, Sharon M; Mathews, Ky L; Reynolds, Matthew; Crossa, José; Lobell, David B

    2013-02-01

    Genetic improvements in heat tolerance of wheat provide a potential adaptation response to long-term warming trends, and may also boost yields in wheat-growing areas already subject to heat stress. Yet there have been few assessments of recent progress in breeding wheat for hot environments. Here, data from 25 years of wheat trials in 76 countries from the International Maize and Wheat Improvement Center (CIMMYT) are used to empirically model the response of wheat to environmental variation and assess the genetic gains over time in different environments and for different breeding strategies. Wheat yields exhibited the most sensitivity to warming during the grain-filling stage, typically the hottest part of the season. Sites with high vapour pressure deficit (VPD) exhibited a less negative response to temperatures during this period, probably associated with increased transpirational cooling. Genetic improvements were assessed by using the empirical model to correct observed yield growth for changes in environmental conditions and management over time. These 'climate-corrected' yield trends showed that most of the genetic gains in the high-yield-potential Elite Spring Wheat Yield Trial (ESWYT) were made at cooler temperatures, close to the physiological optimum, with no evidence for genetic gains at the hottest temperatures. In contrast, the Semi-Arid Wheat Yield Trial (SAWYT), a lower-yielding nursery targeted at maintaining yields under stressed conditions, showed the strongest genetic gains at the hottest temperatures. These results imply that targeted breeding efforts help us to ensure progress in building heat tolerance, and that intensified (and possibly new) approaches are needed to improve the yield potential of wheat in hot environments in order to maintain global food security in a warmer climate.

  9. Purified herpes simplex type 1 glycoprotein D (gD) genetically fused with the type 16 human papillomavirus E7 oncoprotein enhances antigen-specific CD8+ T cell responses and confers protective antitumor immunity.

    PubMed

    Porchia, Bruna F M M; Diniz, Mariana O; Cariri, Francisco A M O; Santana, Vinícius C; Amorim, Jaime H; Balan, Andrea; Braga, Catarina J M; Ferreira, Luís Carlos S

    2011-12-01

    Type 1 herpes virus (HSV-1) glycoprotein D (gD) enhances antigen-specific immune responses, particularly CD8(+) T cell responses, in mice immunized with DNA vaccines encoding hybrid proteins genetically fused with the target antigen at a site near the C-terminal end. These effects are attributed to the interaction of gD with the herpes virus entry mediator (HVEM) and the concomitant blockade of a coinhibitory mechanism mediated by the B- and T-lymphocyte attenuator (BTLA). However, questions concerning the requirement for endogenous synthesis of the antigen or the adjuvant/antigen fusion itself have not been addressed so far. In the present study, we investigated these points using purified recombinant gDs, genetically fused or not with type 16 papilloma virus (HPV-16) E7 oncoprotein. Soluble recombinant gDs, but not denatured forms, retained the ability to bind surface-exposed cellular receptors of HVEM-expressing U937 cells. In addition, in vivo administration of the recombinant proteins, particularly gD genetically fused with E7 (gDE7), promoted the activation of dendritic cells (DC) and antigen-specific cytotoxic CD8(+) T cells. More relevantly, mice immunized with the gDE7 protein developed complete preventive and partial therapeutic antitumor protection, as measured in mice following the implantation of TC-1 cells expressing HPV-16 oncoproteins. Collectively, these results demonstrate that the T cell adjuvant effects of the HSV-1 gD protein did not require endogenous synthesis and could be demonstrated in mice immunized with purified recombinant proteins.

  10. Gain-of-function mutations in sodium channel Na(v)1.9 in painful neuropathy.

    PubMed

    Huang, Jianying; Han, Chongyang; Estacion, Mark; Vasylyev, Dymtro; Hoeijmakers, Janneke G J; Gerrits, Monique M; Tyrrell, Lynda; Lauria, Giuseppe; Faber, Catharina G; Dib-Hajj, Sulayman D; Merkies, Ingemar S J; Waxman, Stephen G

    2014-06-01

    Sodium channel Nav1.9 is expressed in peripheral nociceptive neurons, as well as visceral afferents, and has been shown to act as a threshold channel. Painful peripheral neuropathy represents a significant public health challenge and may involve gain-of-function variants in sodium channels that are preferentially expressed in peripheral sensory neurons. Although gain-of-function variants of peripheral sodium channels Nav1.7 and Nav1.8 have recently been found in painful small fibre neuropathy, the aetiology of peripheral neuropathy in many cases remains unknown. We evaluated 459 patients who were referred for possible painful peripheral neuropathy, and confirmed the diagnosis of small fibre neuropathy in a cohort of 393 patients (369 patients with pure small fibre neuropathy, and small fibre neuropathy together with large fibre involvement in an additional 24 patients). From this cohort of 393 patients with peripheral neuropathy, we sequenced SCN11A in 345 patients without mutations in SCN9A and SCN10A, and found eight variants in 12 patients. Functional profiling by electrophysiological recordings showed that these Nav1.9 mutations confer gain-of-function attributes to the channel, depolarize resting membrane potential of dorsal root ganglion neurons, enhance spontaneous firing, and increase evoked firing of these neurons. Our data show, for the first time, missense mutations of Nav1.9 in individuals with painful peripheral neuropathy. These genetic and functional observations identify missense mutations of Nav1.9 as a cause of painful peripheral neuropathy. PMID:24776970

  11. Cascade amps for increased subsystem gain

    NASA Astrophysics Data System (ADS)

    Galla, Timothy J.

    1990-05-01

    Selecting cascadable TO-8 amplifiers integrated onto microstrip circuit boards is considered from the point of view of cascaded circuit design techniques and performance characteristics. Cascaded assemblies and circuit boards used in cascaded-amplifier applications are presented. It is noted that TO-8 package constrains allow as many as three transistor stages per housing, utilizing either passive or active biasing with choke decoupling; these configurations can achieve broadband performance with small-signal gain of 15 to 20 dB. Where higher gain levels are required, TO-8 amplifiers can be cascaded as gain blocks and assembled into aluminum housing with connectors. Increased reflection losses resulting in a higher voltage standing wave ratio are analyzed, along with noise minimization techniques. A model showing how to find a TO-8 amplifier's noise figure, input power, and third-order intercept point is described.

  12. High fat diet causes rebound weight gain.

    PubMed

    McNay, David E G; Speakman, John R

    2012-01-01

    Obesity is at epidemic proportions but treatment options remain limited. Treatment of obesity by calorie restriction (CR) despite having initial success often fails due to rebound weight gain. One possibility is that this reflects an increased body weight (BW) set-point. Indeed, high fat diets (HFD) reduce adult neurogenesis altering hypothalamic neuroarchitecture. However, it is uncertain if these changes are associated with weight rebound or if long-term weight management is associated with reversing this. Here we show that obese mice have an increased BW set-point and lowering this set-point is associated with rescuing hypothalamic remodelling. Treating obesity by CR using HFD causes weight loss, but not rescued remodelling resulting in rebound weight gain. However, treating obesity by CR using non-HFD causes weight loss, rescued remodelling and attenuates rebound weight gain. We propose that these phenomena may explain why successful short-term weight loss improves obesity in some people but not in others.

  13. Aromatic Gain in a Supramolecular Polymer.

    PubMed

    Saez Talens, Victorio; Englebienne, Pablo; Trinh, Thuat T; Noteborn, Willem E M; Voets, Ilja K; Kieltyka, Roxanne E

    2015-09-01

    The synergy of aromatic gain and hydrogen bonding in a supramolecular polymer is explored. Partially aromatic bis(squaramide) bolaamphiphiles were designed to self-assemble through a combination of hydrophobic, hydrogen-bonding, and aromatic effects into stiff, high-aspect-ratio fibers. UV and IR spectroscopy show electron delocalization and geometric changes within the squaramide ring indicative of strong hydrogen bonding and aromatic gain of the monomer units. The aromatic contribution to the interaction energy was further supported computationally by nucleus-independent chemical shift (NICS) and harmonic oscillator model of aromaticity (HOMA) indices, demonstrating greater aromatic character upon polymerization: at least 30% in a pentamer. The aromatic gain-hydrogen bonding synergy results in a significant increase in thermodynamic stability and a striking difference in aggregate morphology of the bis(squaramide) bolamphiphile compared to isosteres that cannot engage in this effect. PMID:26179942

  14. Image formation using stimulated raman scattering gain

    NASA Astrophysics Data System (ADS)

    Bespalov, V. G.; Makarov, E. A.; Stasel'ko, D. I.

    2016-07-01

    Theoretical analysis of the spatial, noise, and energy characteristics of an amplifier has been performed in the mode of spectral and time selection using subnanosecond stimulated Raman Scattering gain of weak echo signals in crystalline active media that are known for high (up to 10-1 cm/MW) gain coefficients. The possibility to reach high gain values has been demonstrated for weak signals from objects at acceptable angular sizes of the field of vision of an amplifier. To provide a signal-to-noise ratio that exceeds unity over the entire field of vision, the number of photons at the input to an amplifier that is required has to exceed the number of its resolution elements. Accurate determination of the possibilities of recording of weak echo signals and quality of images of targets that are obtained using amplifiers under stimulated Raman Scattering requires additional special experiments.

  15. Relating weight gain and feed:gain of male and female broilers to rearing temperature.

    PubMed

    May, J D; Lott, B D

    2001-05-01

    The effects of environmental temperature on growth and feed:gain were studied in three trials each for male and female broilers. Chicks were reared in a common environment to 21 d of age. At 21 d, they were randomly allocated to 10 environmental chambers. Each chamber was maintained at a constant temperature; the chambers ranged from 12 to 30 C in two-degree increments. The dewpoint was maintained at 18 C, except that relative humidity was not permitted to exceed 82.9%. Body weight was determined at 21 d. Weight gain and feed:gain were determined at 28, 35, 42, and 49 d. The data were analyzed statistically, and regression equations were obtained for weight gain and feed:gain for each sex. Equations were based on body weight and temperature, and the body weight equations were plotted as grams gained per bird per day. Feed:gain increased with increasing weight. The temperature that resulted in the most favorable feed:gain decreased with increasing weight. These results support lower rearing temperatures for optimum growth and feed:gain by large broilers than those of other reports in the literature.

  16. Enhancement of immunogenicity of a therapeutic cervical cancer DNA-based vaccine by co-application of sequence-optimized genetic adjuvants.

    PubMed

    Ohlschläger, Peter; Quetting, Michael; Alvarez, Gerardo; Dürst, Matthias; Gissmann, Lutz; Kaufmann, Andreas M

    2009-07-01

    Treatment of patients with cervical cancer by conventional methods (mainly surgery, but also radiotherapy and chemotherapy) results in a significant loss in quality of life. A therapeutic DNA vaccine directed to tumor-specific antigens of the human papilloma virus (HPV) could be an attractive treatment option. We have developed a nontransforming HPV-16 E7-based DNA vaccine containing all putative T cell epitopes (HPV-16 E7SH). DNA vaccines, however, are less immunogenic than protein- or peptide-based vaccines in larger animals and humans. In this study, we have investigated an adjuvant gene support of the HPV-16 E7SH therapeutic cervical cancer vaccine. DNA encoded cytokines (IL-2, IL-12, GM-CSF, IFN-gamma) and the chemokine MIP1-alpha were co-applied either simultaneously or at different time points pre- or post-E7SH vaccination. In addition, sequence-optimized adjuvant genes were compared to wild type genes. Three combinations investigated lead to an enhanced IFN-gamma response of the induced T cells in mice. Interestingly, IFN-gamma secretion of splenocytes did not strictly correlate with tumor response in tumor regression experiments. Gene-encoded MIP-1alpha applied 5 days prior to E7SH-immunization combined with IFN-gamma or IL-12 (3 days) or IL-2 (5 days) postimmunization lead to a significantly enhanced tumor response that was clearly associated with granzyme B secretion and target cells lysis. Our results suggest that a conditioning application and combination with adjuvant genes may be a promising strategy to enhance synergistically immune responses by DNA immunization for the treatment of cervical cancer. PMID:19358269

  17. Analytic gain in probabilistic decompression sickness models.

    PubMed

    Howle, Laurens E

    2013-11-01

    Decompression sickness (DCS) is a disease known to be related to inert gas bubble formation originating from gases dissolved in body tissues. Probabilistic DCS models, which employ survival and hazard functions, are optimized by fitting model parameters to experimental dive data. In the work reported here, I develop methods to find the survival function gain parameter analytically, thus removing it from the fitting process. I show that the number of iterations required for model optimization is significantly reduced. The analytic gain method substantially improves the condition number of the Hessian matrix which reduces the model confidence intervals by more than an order of magnitude. PMID:24209920

  18. Reducing gain shifts in photomultiplier tubes

    DOEpatents

    Cohn, Charles E.

    1976-01-01

    A means is provided for reducing gain shifts in multiplier tubes due to varying event count rates. It includes means for limiting the number of cascaded, active dynodes of the multiplier tube to a predetermined number with the last of predetermined number of dynodes being the output terminal of the tube. This output is applied to an amplifier to make up for the gain sacrificed by not totally utilizing all available active stages of the tube. Further reduction is obtained by illuminating the predetermined number of dynodes with a light source of such intensity that noise appearing at the output dynode associated with the illumination is negligible.

  19. Analytic gain in probabilistic decompression sickness models.

    PubMed

    Howle, Laurens E

    2013-11-01

    Decompression sickness (DCS) is a disease known to be related to inert gas bubble formation originating from gases dissolved in body tissues. Probabilistic DCS models, which employ survival and hazard functions, are optimized by fitting model parameters to experimental dive data. In the work reported here, I develop methods to find the survival function gain parameter analytically, thus removing it from the fitting process. I show that the number of iterations required for model optimization is significantly reduced. The analytic gain method substantially improves the condition number of the Hessian matrix which reduces the model confidence intervals by more than an order of magnitude.

  20. Varactor-diode modulator yields conversion gain

    NASA Astrophysics Data System (ADS)

    Breitkopf, K.

    1980-05-01

    It is shown that varactor diodes used as modulator elements can make a balanced diode mixer yield conversion gain when employed in an upconverter. Replacing the normal mixer diodes with varactor diodes and inserting the IF and LO voltages at a level that drives the diodes into their nonlinear voltage-capacitance region produces a parametric amplifying effect. This modification results in conversion gain rather than loss, and brings the desired output power up to the 0.1-1.0 W level. The use of this technique in a lower-sideband UHF TV upconverter is considered.

  1. Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors

    SciTech Connect

    Maroni, Paola; Brini, Anna Teresa; Arrigoni, Elena; Girolamo, Laura de; Niada, Stefania; Matteucci, Emanuela; Bendinelli, Paola; Desiderio, Maria Alfonsina

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Acetylation affected hASCs osteodifferentiation through Runx2-PPAR{gamma}. Black-Right-Pointing-Pointer HDACs knocking-down favoured the commitment effect of osteogenic medium. Black-Right-Pointing-Pointer HDACs silencing early activated Runx2 and ALP. Black-Right-Pointing-Pointer PPAR{gamma} reduction and calcium/collagen deposition occurred later. Black-Right-Pointing-Pointer Runx2/PPAR{gamma} target genes were modulated in line with HDACs role in osteo-commitment. -- Abstract: The human adipose-tissue derived stem/stromal cells (hASCs) are an interesting source for bone-tissue engineering applications. Our aim was to clarify in hASCs the role of acetylation in the control of Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator activated receptor (PPAR) {gamma}. These key osteogenic and adipogenic transcription factors are oppositely involved in osteo-differentiation. The hASCs, committed or not towards bone lineage with osteoinductive medium, were exposed to HDACs chemical blockade with Trichostatin A (TSA) or were genetically silenced for HDACs. Alkaline phosphatase (ALP) and collagen/calcium deposition, considered as early and late osteogenic markers, were evaluated concomitantly as index of osteo-differentiation. TSA pretreatment, useful experimental protocol to analyse pan-HDAC-chemical inhibition, and switch to osteogenic medium induced early-osteoblast maturation gene Runx2, while transiently decreased PPAR{gamma} and scarcely affected late-differentiation markers. Time-dependent effects were observed after knocking-down of HDAC1 and 3: Runx2 and ALP underwent early activation, followed by late-osteogenic markers increase and by PPAR{gamma}/ALP activity diminutions mostly after HDAC3 silencing. HDAC1 and 3 genetic blockade increased and decreased Runx2 and PPAR{gamma} target genes, respectively. Noteworthy, HDACs knocking-down favoured the commitment effect of osteogenic medium. Our results reveal

  2. Gain-Bandwidth Product Optimization of Heterostructure Avalanche Photodiodes

    NASA Astrophysics Data System (ADS)

    Kwon, Oh-Hyun; Hayat, Majeed M.; Campbell, Joe C.; Saleh, Bahaa E. A.; Teich, Malvin C.

    2005-05-01

    A generalized history-dependent recurrence theory for the time-response analysis is derived for avalanche photodiodes with multilayer, heterojunction multiplication regions. The heterojunction multiplication region considered consists of two layers: a high-bandgap Al_0.6 Ga_0.4 As energy-buildup layer, which serves to heat up the primary electrons, and a GaAs layer, which serves as the primary avalanching layer. The model is used to optimize the gain-bandwidth product (GBP) by appropriate selection of the width of the energy-buildup layer for a given width of the avalanching layer. The enhanced GBP is a direct consequence of the heating of primary electrons in the energy-buildup layer, which results in a reduced first dead space for the carriers that are injected into the avalanche-active GaAs layer. This effect is akin to the initial-energy effect previously shown to enhance the excess-noise factor characteristics in thin avalanche photodiodes (APDs). Calculations show that the GBP optimization is insensitive to the operational gain and the optimized APD also minimizes the excess-noise factor.

  3. Ribose Accelerates Gut Motility and Suppresses Mouse Body Weight Gaining

    PubMed Central

    Liu, Yan; Li, Tong-Ruei R; Xu, Cong; Xu, Tian

    2016-01-01

    The increasing prevalence of obesity is closely related to excessive energy consumption. Clinical intervention of energy intake is an attractive strategy to fight obesity. However, the current FDA-approved weight-loss drugs all have significant side effects. Here we show that ribose upregulates gut motility and suppresses mice body weight gain. Ribokinase, which is encoded by Rbks gene, is the first enzyme for ribose metabolism in vivo. Rbks mutation resulted in ribose accumulation in the small intestine, which accelerated gut movement. Ribose oral treatment in wild type mice also enhanced bowel motility and rendered mice resistance to high fat diets. The suppressed weight gain was resulted from enhanced ingested food excretion. In addition, the effective dose of ribose didn't cause any known side effects (i.e. diarrhea and hypoglycemia). Overall, our results show that ribose can regulate gut motility and energy homeostasis in mice, and suggest that administration of ribose and its analogs could regulate gastrointestinal motility, providing a novel therapeutic approach for gastrointestinal dysfunction and weight control. PMID:27194947

  4. Many human accelerated regions are developmental enhancers

    PubMed Central

    Capra, John A.; Erwin, Genevieve D.; McKinsey, Gabriel; Rubenstein, John L. R.; Pollard, Katherine S.

    2013-01-01

    The genetic changes underlying the dramatic differences in form and function between humans and other primates are largely unknown, although it is clear that gene regulatory changes play an important role. To identify regulatory sequences with potentially human-specific functions, we and others used comparative genomics to find non-coding regions conserved across mammals that have acquired many sequence changes in humans since divergence from chimpanzees. These regions are good candidates for performing human-specific regulatory functions. Here, we analysed the DNA sequence, evolutionary history, histone modifications, chromatin state and transcription factor (TF) binding sites of a combined set of 2649 non-coding human accelerated regions (ncHARs) and predicted that at least 30% of them function as developmental enhancers. We prioritized the predicted ncHAR enhancers using analysis of TF binding site gain and loss, along with the functional annotations and expression patterns of nearby genes. We then tested both the human and chimpanzee sequence for 29 ncHARs in transgenic mice, and found 24 novel developmental enhancers active in both species, 17 of which had very consistent patterns of activity in specific embryonic tissues. Of these ncHAR enhancers, five drove expression patterns suggestive of different activity for the human and chimpanzee sequence at embryonic day 11.5. The changes to human non-coding DNA in these ncHAR enhancers may modify the complex patterns of gene expression necessary for proper development in a human-specific manner and are thus promising candidates for understanding the genetic basis of human-specific biology. PMID:24218637

  5. Human midbrain precursors activate the expected developmental genetic program and differentiate long-term to functional A9 dopamine neurons in vitro. Enhancement by Bcl-X(L).

    PubMed

    Seiz, Emma G; Ramos-Gómez, Milagros; Courtois, Elise T; Tønnesen, Jan; Kokaia, Merab; Liste Noya, Isabel; Martínez-Serrano, Alberto

    2012-11-15

    Understanding the molecular programs of the generation of human dopaminergic neurons (DAn) from their ventral mesencephalic (VM) precursors is of key importance for basic studies, progress in cell therapy, drug screening and pharmacology in the context of Parkinson's disease. The nature of human DAn precursors in vitro is poorly understood, their properties unstable, and their availability highly limited. Here we present positive evidence that human VM precursors retaining their genuine properties and long-term capacity to generate A9 type Substantia nigra human DAn (hVM1 model cell line) can be propagated in culture. During a one month differentiation, these cells activate all key genes needed to progress from pro-neural and pro-dopaminergic precursors to mature and functional DAn. For the first time, we demonstrate that gene cascades are correctly activated during differentiation, resulting in the generation of mature DAn. These DAn have morphological and functional properties undistinguishable from those generated by VM primary neuronal cultures. In addition, we have found that the forced expression of Bcl-X(L) induces an increase in the expression of key developmental genes (MSX1, NGN2), maintenance of PITX3 expression temporal profile, and also enhances genes involved in DAn long-term function, maintenance and survival (EN1, LMX1B, NURR1 and PITX3). As a result, Bcl-X(L) anticipates and enhances DAn generation.

  6. Alcohol gains access to appetitive learning through adolescent heavy drinking

    PubMed Central

    DiLeo, Alyssa; Wright, Kristina M.; Mangone, Elizabeth; McDannald, Michael A.

    2015-01-01

    Adolescent heavy alcohol drinking increases the risk for alcohol use disorders in adulthood, yet mechanisms conferring increased risk are not well understood. We propose that adolescent alcohol drinking shapes alcohol’s aversive or appetitive properties in adulthood. Alcohol normally drives aversive learning and alcohol-predictive cues are avoided. We hypothesize that through adolescent heavy drinking alcohol gains access to appetitive learning. A primary consequence is that alcohol-predictive cues become valued and sought out. To test this hypothesis, we gave genetically heterogeneous, male Long Evans rats voluntary, chronic intermittent access to water or alcohol throughout adolescence and then identified moderate and heavy alcohol drinkers. After a short abstinence period, we assessed the aversive or appetitive properties of alcohol using flavor learning procedures. We compared alcohol to the known appetitive properties of sugar. Flavor learning in adult rats who were alcohol-naïve or adolescent moderate alcohol drinkers revealed alcohol to be aversive and sugar to be appetitive. The same flavor learning procedures revealed both alcohol and sugar to be appetitive in adult rats who were adolescent heavy drinkers. The results demonstrate that alcohol gains access to neurobehavioral circuits for appetitive learning through adolescent heavy alcohol drinking. PMID:26052793

  7. Alcohol gains access to appetitive learning through adolescent heavy drinking.

    PubMed

    DiLeo, Alyssa; Wright, Kristina M; Mangone, Elizabeth; McDannald, Michael A

    2015-08-01

    Adolescent heavy alcohol drinking increases the risk for alcohol use disorders in adulthood, yet mechanisms conferring increased risk are not well understood. We propose that adolescent alcohol drinking shapes alcohol's aversive or appetitive properties in adulthood. Alcohol normally drives aversive learning and alcohol-predictive cues are avoided. We hypothesize that through adolescent heavy drinking alcohol gains access to appetitive learning. A primary consequence is that alcohol-predictive cues become valued and sought out. To test this hypothesis, we gave genetically heterogeneous, male Long Evans rats voluntary, chronic intermittent access to water or alcohol throughout adolescence and then identified moderate and heavy alcohol drinkers. After a short abstinence period, we assessed the aversive or appetitive properties of alcohol using flavor learning procedures. We compared alcohol to the known appetitive properties of sugar. Flavor learning in adult rats who were alcohol-naïve or adolescent moderate alcohol drinkers revealed alcohol to be aversive and sugar to be appetitive. The same flavor learning procedures revealed both alcohol and sugar to be appetitive in adult rats who were adolescent heavy drinkers. The results demonstrate that alcohol gains access to neurobehavioral circuits for appetitive learning through adolescent heavy alcohol drinking.

  8. Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2

    PubMed Central

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Ni, Qu-Bo; Pan, Zheng-Qi; Wang, Hui; Chen, Liao-Bin

    2016-01-01

    Many strategies, including various growth factors and gene transfer, have been used to augment healing after anterior cruciate ligament (ACL) reconstruction. The biological environment regulated by the growth factors during the stage of tendon-bone healing was considered important in controlling the integrating process. The purpose of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) on healing after ACL reconstruction. BMSCs were infected with an adenoviral vector encoding BMP2 (AdBMP2) or bFGF (AdbFGF). Then, the infected BMSCs were surgically implanted into the tendon-bone interface. At 12 weeks postoperatively, the formation of abundant cartilage-like cells, smaller tibial bone tunnel and significantly higher ultimate load and stiffness levels, through histological analysis, micro-computed tomography and biomechanical testing, were observed. In addition, the AdBMP2-plus-AdbFGF group had the smallest bone tunnel and the best mechanical properties among all the groups. The addition of BMP2 or bFGF by gene transfer resulted in better cellularity, new bone formation and higher mechanical property, which contributed to the healing process after ACL reconstruction. Furthermore, the co-application of these two genes was more powerful and efficient than either single gene therapy. PMID:27173013

  9. Invasive blue mussels threaten regional scale genetic diversity in mainland and remote offshore locations: the need for baseline data and enhanced protection in the Southern Ocean.

    PubMed

    Gardner, Jonathan P A; Zbawicka, Małgorzata; Westfall, Kristen M; Wenne, Roman

    2016-09-01

    Human-mediated biological transfers of species have substantially modified many ecosystems with profound environmental and economic consequences. However, in many cases, invasion events are very hard to identify because of the absence of an appropriate baseline of information for receiving sites/regions. In this study, use of high-resolution genetic markers (single nucleotide polymorphisms - SNPs) highlights the threat of introduced Northern Hemisphere blue mussels (Mytilus galloprovincialis) at a regional scale to Southern Hemisphere lineages of blue mussels via hybridization and introgression. Analysis of a multispecies SNP dataset reveals hotspots of invasive Northern Hemisphere blue mussels in some mainland New Zealand locations, as well as the existence of unique native lineages of blue mussels on remote oceanic islands in the Southern Ocean that are now threatened by invasive mussels. Samples collected from an oil rig that has moved between South Africa, Australia, and New Zealand were identified as invasive Northern Hemisphere mussels, revealing the relative ease with which such non-native species may be moved from region to region. In combination, our results highlight the existence of unique lineages of mussels (and by extension, presumably of other taxa) on remote offshore islands in the Southern Ocean, the need for more baseline data to help identify bioinvasion events, the ongoing threat of hybridization and introgression posed by invasive species, and the need for greater protection of some of the world's last great remote areas.

  10. Enhancement of tendon-to-bone healing after anterior cruciate ligament reconstruction using bone marrow-derived mesenchymal stem cells genetically modified with bFGF/BMP2.

    PubMed

    Chen, Biao; Li, Bin; Qi, Yong-Jian; Ni, Qu-Bo; Pan, Zheng-Qi; Wang, Hui; Chen, Liao-Bin

    2016-01-01

    Many strategies, including various growth factors and gene transfer, have been used to augment healing after anterior cruciate ligament (ACL) reconstruction. The biological environment regulated by the growth factors during the stage of tendon-bone healing was considered important in controlling the integrating process. The purpose of this study was to evaluate the effects of bone marrow-derived mesenchymal stem cells (BMSCs) genetically modified with bone morphogenetic protein 2 (BMP2) and basic fibroblast growth factor (bFGF) on healing after ACL reconstruction. BMSCs were infected with an adenoviral vector encoding BMP2 (AdBMP2) or bFGF (AdbFGF). Then, the infected BMSCs were surgically implanted into the tendon-bone interface. At 12 weeks postoperatively, the formation of abundant cartilage-like cells, smaller tibial bone tunnel and significantly higher ultimate load and stiffness levels, through histological analysis, micro-computed tomography and biomechanical testing, were observed. In addition, the AdBMP2-plus-AdbFGF group had the smallest bone tunnel and the best mechanical properties among all the groups. The addition of BMP2 or bFGF by gene transfer resulted in better cellularity, new bone formation and higher mechanical property, which contributed to the healing process after ACL reconstruction. Furthermore, the co-application of these two genes was more powerful and efficient than either single gene therapy. PMID:27173013

  11. A systematic analysis of TCA Escherichia coli mutants reveals suitable genetic backgrounds for enhanced hydrogen and ethanol production using glycerol as main carbon source.

    PubMed

    Valle, Antonio; Cabrera, Gema; Muhamadali, Howbeer; Trivedi, Drupad K; Ratray, Nicholas J W; Goodacre, Royston; Cantero, Domingo; Bolivar, Jorge

    2015-09-01

    Biodiesel has emerged as an environmentally friendly alternative to fossil fuels; however, the low price of glycerol feed-stocks generated from the biodiesel industry has become a burden to this industry. A feasible alternative is the microbial biotransformation of waste glycerol to hydrogen and ethanol. Escherichia coli, a microorganism commonly used for metabolic engineering, is able to biotransform glycerol into these products. Nevertheless, the wild type strain yields can be improved by rewiring the carbon flux to the desired products by genetic engineering. Due to the importance of the central carbon metabolism in hydrogen and ethanol synthesis, E. coli single null mutant strains for enzymes of the TCA cycle and other related reactions were studied in this work. These strains were grown anaerobically in a glycerol-based medium and the concentrations of ethanol, glycerol, succinate and hydrogen were analysed by HPLC and GC. It was found that the reductive branch is the more relevant pathway for the aim of this work, with malate playing a central role. It was also found that the putative C4-transporter dcuD mutant improved the target product yields. These results will contribute to reveal novel metabolic engineering strategies for improving hydrogen and ethanol production by E. coli.

  12. Reward Region Responsivity Predicts Future Weight Gain and Moderating Effects of the TaqIA Allele

    PubMed Central

    Burger, Kyle S.; Yokum, Sonja

    2015-01-01

    Because no large prospective study has investigated neural vulnerability factors that predict future weight gain, we tested whether neural response to receipt and anticipated receipt of palatable food and monetary reward predicted body fat gain over a 3-year follow-up in healthy-weight adolescent humans and whether the TaqIA polymorphism moderates these relations. A total of 153 adolescents completed fMRI paradigms assessing response to these events; body fat was assessed annually over follow-up. Elevated orbitofrontal cortex response to cues signaling impending milkshake receipt predicted future body fat gain (r = 0.32), which is a novel finding that provides support for the incentive sensitization theory of obesity. Neural response to receipt and anticipated receipt of monetary reward did not predict body fat gain, which has not been tested previously. Replicating an earlier finding (Stice et al., 2008a), elevated caudate response to milkshake receipt predicted body fat gain for adolescents with a genetic propensity for greater dopamine signaling by virtue of possessing the TaqIA A2/A2 allele, but lower caudate response predicted body fat gain for adolescents with a genetic propensity for less dopamine signaling by virtue of possessing a TaqIA A1 allele, though this interaction was only marginal [p-value <0.05 corrected using voxel-level familywise error rate (pFWE) = 0.06]. Parental obesity, which correlated with TaqIA allele status (odds ratio = 2.7), similarly moderated the relation of caudate response to milkshake receipt to future body fat gain, which is another novel finding. The former interaction implies that too much or too little dopamine signaling and reward region responsivity increases risk for overeating, suggesting qualitatively distinct reward surfeit and reward deficit pathways to obesity. SIGNIFICANCE STATEMENT Because no large prospective study has investigated neural vulnerability factors that predict future weight gain we tested whether

  13. Measurement of Information Gain from Written Discourse.

    ERIC Educational Resources Information Center

    Mosberg, Ludwig

    A pretest/post-test procedure for measuring information gain from discourse was investigated together with several other aspects of discourse processing. The main purpose was to determine the effect of a pretest on discourse learning as measured by post-test performance. The study also investigated (1) serial position effects in learning from…

  14. Electromagnetically induced gain in molecular systems

    NASA Astrophysics Data System (ADS)

    Mukherjee, Nandini; Patel, C. Kumar N.

    2009-12-01

    We report electromagnetically induced gain in a highly degenerate two-level rotational vibrational molecular system. Using two photon (Raman-type) interaction with right and left circularly polarized pump and probe waves, the Zeeman coherence is established within the manifold of degenerate sublevels belonging to a rotational vibrational eigenstate. We analytically and numerically calculate the third-order nonlinear optical susceptibility for a Doppler-broadened molecular transition for an arbitrary high rotational angular momentum (J≥20) . It is shown that for a Q -type open transition, a weak probe will experience an electromagnetically induced gain in presence of a strong copropagating pump wave. The inversionless gain originates due to cancellation of absorption from the interference of the coupled Λ - and V-type excitation channels in an N -type configuration. A detailed analysis of the optical susceptibility as a function of Doppler detuning explains how the gain bands are generated in a narrow transparency window from the overlapping contributions of different velocity groups. It is shown that the orientation dependent coherent interaction in presence of a strong pump induces narrow resonances for the probe susceptibility. The locations, intensity, and sign (positive or negative susceptibility) of these resonances are decided by the frequency detuning of the Doppler group and the strength of the coupling field. The availability of high power tunable quantum cascade lasers covering a spectral region from about 4 to 12μm opens up the possibility of investigating the molecular vibrational rotational transitions for a variety of coherent effects.

  15. Project GAIN Evaluation: 1969-70.

    ERIC Educational Resources Information Center

    Biller, Julian

    Project GAIN was designed to meet the special needs of the academically retarded junior high school student. This federally funded project has been on-going in Broward County (Florida) since January 1966. The project was conceived of as a means to motivate and educate those students whose "dull normal" intellectual ability might otherwise doom…

  16. Net Photorefractive Gain In Gallium Arsenide

    NASA Technical Reports Server (NTRS)

    Liu, Tsuen-Hsi; Cheng, Li-Jen

    1990-01-01

    Prerequisite includes applied electric field. Electric field applied to GaAs crystal in which two infrared beams interfere. Depending on quality of sample and experimental conditions, net photorefractive gain obtained. Results offer possibility of new developments in real-time optical processing of signals by use of near-infrared lasers of low power.

  17. X chromosome gain in male breast cancer.

    PubMed

    Di Oto, Enrico; Monti, Valentina; Cucchi, Maria C; Masetti, Riccardo; Varga, Zsuzsanna; Foschini, Maria P

    2015-12-01

    Male breast cancer (MBC) is an uncommon disease whose molecular profile is not well known. X chromosome gain has been described as a marker of aggressive behavior in female breast cancer. The aim of this study is to investigate the role of the X chromosome in male breast cancer. Twenty cases of male breast invasive ductal carcinoma were retrieved and compared with 10 cases of gynecomastia. Cases were tested by fluorescence in situ hybridization to assess a cytogenetic profile for the X chromosome. The X chromosome status was compared with histopathologic features and stage at presentation. All MBC cases harbored an X chromosome gain (100%) in a variable percentage of neoplastic cells, ranging from 31% to 85% (mean, 59%). On the contrary, all cases of gynecomastia showed wild X chromosome asset. The patients' age at surgery and tumor grading showed a statistically significant correlation (P = .0188-.04), with the percentages of neoplastic cells showing an X chromosome gain. These data suggest that this X chromosome gain plays a role in the neoplastic transformation of male breast epithelial cells.

  18. Dimensions of Compliance-Gaining Situations.

    ERIC Educational Resources Information Center

    Cody, Michael J.; And Others

    1983-01-01

    Tested a seven-factor model of situation perception to develop a set of valid and reliable situation perception factors for use in compliance-gaining research. (Factors included personal benefits, intimacy, rights, resistance, dominance, situation apprehension, and relational consequences.) Found that the model fit the data well and was superior…

  19. Pleasure Reading and Reading Rate Gains

    ERIC Educational Resources Information Center

    Beglar, David; Hunt, Alan

    2014-01-01

    This study investigated the effects of (a) the amount of pleasure reading completed, (b) the type of texts read (i.e., simplified or unsimplified books), and (c) the level of simplified texts read by 14 Japanese university students who made the largest reading rate gains over one academic year. The findings indicated that the participants who made…

  20. GAIN Appraisal Program IV. Fourth Report.

    ERIC Educational Resources Information Center

    Simon, June; And Others

    The Greater Avenues for Independence (GAIN) legislation in California mandated a full range of employment-related training and supportive services designed to provide welfare program applicants and recipients with the skills needed to acquire unsubsidized employment through education and training. Tests to assess the basic reading, mathematics,…