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Sample records for encodes guidance molecules

  1. Guidance molecules in lung cancer

    PubMed Central

    Nasarre, Patrick; Potiron, Vincent; Drabkin, Harry

    2010-01-01

    Guidance molecules were first described in the nervous system to control axon outgrowth direction. They are also widely expressed outside the nervous system where they control cell migration, tissue development and establishment of the vascular network. In addition, they are involved in cancer development, tumor angiogenesis and metastasis. This review is primarily focused on their functions in lung cancer and their involvement in lung development is also presented. Five guidance molecule families and their corresponding receptors are described, including the semaphorins/neuropilins/plexins, ephrins and Eph receptors, netrin/DCC/UNC5, Slit/Robo and Notch/Delta. In addition, the possibility to target these molecules as a therapeutic approach in cancer is discussed. PMID:20139699

  2. Pollen tube guidance by attractant molecules: LUREs.

    PubMed

    Okuda, Satohiro; Higashiyama, Tetsuya

    2010-01-01

    Sexual reproduction in flowering plants requires pollen-tube guidance, which is thought to be mediated by chemoattractants derived from target ovules. To date, however, no convincing evidence has been reported of a particular molecule being the true attractant. Emerging data indicate that two synergid cells, which are on either side of the egg cell, emit a diffusible, species-specific signal to attract the pollen tube at the last step of pollen-tube guidance. Recently, it was demonstrated that LUREs (LURE1 and LURE2), cysteine-rich polypeptides secreted from the synergid cell, are the key molecules in pollen-tube guidance. In this review, we summarize the mechanism of pollen-tube guidance, with special focus on gametophytic guidance and the attractants.

  3. Geranyl diphosphate synthase molecules, and nucleic acid molecules encoding same

    DOEpatents

    Croteau, Rodney Bruce; Burke, Charles Cullen

    2008-06-24

    In one aspect, the present invention provides isolated nucleic acid molecules that each encode a geranyl diphosphate synthase protein, wherein each isolated nucleic acid molecule hybridizes to a nucleic acid molecule consisting of the sequence set forth in SEQ ID NO:1 under conditions of 5.times.SSC at 45.degree. C. for one hour. The present invention also provides isolated geranyl diphosphate synthase proteins, and methods for altering the level of expression of geranyl diphosphate synthase protein in a host cell.

  4. Isolated menthone reductase and nucleic acid molecules encoding same

    DOEpatents

    Croteau, Rodney B; Davis, Edward M; Ringer, Kerry L

    2013-04-23

    The present invention provides isolated menthone reductase proteins, isolated nucleic acid molecules encoding menthone reductase proteins, methods for expressing and isolating menthone reductase proteins, and transgenic plants expressing elevated levels of menthone reductase protein.

  5. Small-molecule discovery from DNA-encoded chemical libraries.

    PubMed

    Kleiner, Ralph E; Dumelin, Christoph E; Liu, David R

    2011-12-01

    Researchers seeking to improve the efficiency and cost effectiveness of the bioactive small-molecule discovery process have recently embraced selection-based approaches, which in principle offer much higher throughput and simpler infrastructure requirements compared with traditional small-molecule screening methods. Since selection methods benefit greatly from an information-encoding molecule that can be readily amplified and decoded, several academic and industrial groups have turned to DNA as the basis for library encoding and, in some cases, library synthesis. The resulting DNA-encoded synthetic small-molecule libraries, integrated with the high sensitivity of PCR and the recent development of ultra high-throughput DNA sequencing technology, can be evaluated very rapidly for binding or bond formation with a target of interest while consuming minimal quantities of material and requiring only modest investments of time and equipment. In this tutorial review we describe the development of two classes of approaches for encoding chemical structures and reactivity with DNA: DNA-recorded library synthesis, in which encoding and library synthesis take place separately, and DNA-directed library synthesis, in which DNA both encodes and templates library synthesis. We also describe in vitro selection methods used to evaluate DNA-encoded libraries and summarize successful applications of these approaches to the discovery of bioactive small molecules and novel chemical reactivity.

  6. Small-Molecule Discovery from DNA-Encoded Chemical Libraries†

    PubMed Central

    Kleiner, Ralph E.; Dumelin, Christoph E.; Liu, David R.

    2015-01-01

    Researchers seeking to improve the efficiency and cost effectiveness of the bioactive small-molecule discovery process have recently embraced selection-based approaches, which in principle offer much higher throughput and simpler infrastructure requirements compared with traditional small-molecule screening methods. Since selection methods benefit greatly from an information-encoding molecule that can be readily amplified and decoded, several academic and industrial groups have turned to DNA as the basis for library encoding and, in some cases, library synthesis. The resulting DNA-encoded synthetic small-molecule libraries, integrated with the high sensitivity of PCR and the recent development of ultra high-throughput DNA sequencing technology, can be evaluated very rapidly for binding or bond formation with a target of interest while consuming minimal quantities of material and requiring only modest investments of time and equipment. In this review we describe the development of two classes of approaches for encoding chemical structures and reactivity with DNA: DNA-recorded library synthesis, in which encoding and library synthesis take place separately, and DNA-directed library synthesis, in which DNA both encodes and templates library synthesis. We also describe in vitro selection methods used to evaluate DNA-encoded libraries and summarize successful applications of these approaches to the discovery of bioactive small molecules and novel chemical reactivity. PMID:21674077

  7. Coevolution of axon guidance molecule Slit and its receptor Robo.

    PubMed

    Yu, Qi; Li, Xiao-Tong; Zhao, Xiao; Liu, Xun-Li; Ikeo, Kazuho; Gojobori, Takashi; Liu, Qing-Xin

    2014-01-01

    Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

  8. Cellular encoding of Cy dyes for single-molecule imaging

    PubMed Central

    Leisle, Lilia; Chadda, Rahul; Lueck, John D; Infield, Daniel T; Galpin, Jason D; Krishnamani, Venkatramanan; Robertson, Janice L; Ahern, Christopher A

    2016-01-01

    A general method is described for the site-specific genetic encoding of cyanine dyes as non-canonical amino acids (Cy-ncAAs) into proteins. The approach relies on an improved technique for nonsense suppression with in vitro misacylated orthogonal tRNA. The data show that Cy-ncAAs (based on Cy3 and Cy5) are tolerated by the eukaryotic ribosome in cell-free and whole-cell environments and can be incorporated into soluble and membrane proteins. In the context of the Xenopus laevis oocyte expression system, this technique yields ion channels with encoded Cy-ncAAs that are trafficked to the plasma membrane where they display robust function and distinct fluorescent signals as detected by TIRF microscopy. This is the first demonstration of an encoded cyanine dye as a ncAA in a eukaryotic expression system and opens the door for the analysis of proteins with single-molecule resolution in a cellular environment. DOI: http://dx.doi.org/10.7554/eLife.19088.001 PMID:27938668

  9. Visual Map Development: Bidirectional Signaling, Bifunctional Guidance Molecules, and Competition

    PubMed Central

    Feldheim, David A.; O’Leary, Dennis D. M.

    2010-01-01

    Topographic maps are a two-dimensional representation of one neural structure within another and serve as the main strategy to organize sensory information. The retina’s projection via axons of retinal ganglion cells to midbrain visual centers, the optic tectum/superior colliculus, is the leading model to elucidate mechanisms of topographic map formation. Each axis of the retina is mapped independently using different mechanisms and sets of axon guidance molecules expressed in gradients to achieve the goal of representing a point in the retina onto a point within the target. An axon’s termination along the temporal-nasal mapping axis is determined by opposing gradients of EphAs and ephrin-As that act through their forward and reverse signaling, respectively, within the projecting axons, each of which inhibits interstitial branching, cooperating with a branch-promoting activity, to generate topographic specific branching along the shaft of the parent axons that overshoot their correct termination zone along the anterior-posterior axis of the target. The dorsal-ventral termination position is then determined using a gradient of ephrin-B that can act as a repellent or attractant depending on the ephrin-B concentration relative to EphB levels on the interstitial branches to guide them along the medial-lateral axis of the target to their correct termination zone, where they arborize. In both cases, axon-axon competition results in axon mapping based on relative rather than absolute levels of repellent or attractant activity. The map is subsequently refined through large-scale pruning driven in large part by patterned retinal activity. PMID:20880989

  10. Surgical Guidance in Prostate Cancer: "From Molecule to Man" Translations.

    PubMed

    van Leeuwen, Fijs W B; van der Poel, Henk G

    2016-03-15

    Given the frequency of the disease and the difficulty of tumor resections, image-guided surgery technologies may aid the surgical management of prostate cancer patients. The "from molecule to man" translation of such approaches is, however, complex and depends on many different features, both from a technical and a practical perspective. ©2015 American Association for Cancer Research.

  11. Levodopa increases oxidative stress and repulsive guidance molecule A levels: a pilot study in patients with Parkinson's disease.

    PubMed

    Müller, Thomas; Trommer, Isabel; Muhlack, Siegfried; Mueller, Bernhard K

    2016-04-01

    Exposure to free radicals influences synthesis, degradation and function of proteins, such as repulsive guidance molecule A. Decay of this protein is essential for neuronal maintenance and recovery. Levodopa elevates oxidative stress. Therefore levodopa may impact repulsive guidance molecule A metabolism. Objectives were to investigate plasma concentrations of repulsive guidance molecule A, levodopa, cysteine and cysteinyl-glycine before and 1 h after levodopa application in patients with Parkinson's disease. Cysteine and cysteinyl-glycine as biomarkers for oxidative stress exposure decreased, repulsive guidance molecule A and levodopa rose. Repulsive guidance molecule A remained unchanged in levodopa naïve patients, but particularly went up in patients on a prior chronic levodopa regimen. Decay of cysteine specifically cysteinyl-glycine results from an elevated glutathione generation with rising cysteine consumption respectively from the alternative glutathione transformation to its oxidized form glutathione disulfide after free radical scavenging. Repulsive guidance molecule A rise may inhibit physiologic mechanisms for neuronal survival.

  12. [Current progress in functions of axon guidance molecule Robo and underlying molecular mechanism].

    PubMed

    Li, Xiao-Tong; Zhou, Qi-Sheng; Yu, Qi; Zhao, Xiao; Liu, Qing-Xin

    2014-06-25

    The axon guidance molecule Robo is a transmembrane protein which is conserved during evolution. Robo and its ligand, Slit, have been implicated in regulating many developmental processes, such as axon guidance, neuronal migration, tumor metastasis, angiogenesis, lung morphogenesis, kidney morphogenesis, heart morphogenesis, ovary development and gonad development. Robo function mainly depends on the binding of its Ig1 domain to the LRR-2 domain of Slit ligand. Meanwhile, Robo function is also mediated by binding to some signaling molecules, including the heparan sulfate proteoglycans (HSPGs), GTPase-activating proteins (GAPs) and tyrosine kinase Abelson. Several transcription factors, including Hox, Midline and Nkx2.9, were shown to regulate robo expression. In addition, alternative splicing and transport regulation also affect Robo function. In this review, we summarized the studies on the molecular structure, functions and molecular mechanism of Robo, which would propose a novel strategy for the research of neural development, as well as prevention and treatment of nervous system diseases and cancers.

  13. The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system

    PubMed Central

    Mueller, Bernhard K; Yamashita, Toshihide; Schaffar, Gregor; Mueller, Reinhold

    2006-01-01

    During the development of the nervous system, outgrowing axons often have to travel long distances to reach their target neurons. In this process, outgrowing neurites tipped with motile growth cones rely on guidance cues present in their local environment. These cues are detected by specific receptors expressed on growth cones and neurites and influence the trajectory of the growing fibres. Neurite growth, guidance, target innervation and synapse formation and maturation are the processes that occur predominantly but not exclusively during embryonic or early post-natal development in vertebrates. As a result, a functional neural network is established, which is usually remarkably stable. However, the stability of the neural network in higher vertebrates comes at an expensive price, i.e. the loss of any significant ability to regenerate injured or damaged neuronal connections in their central nervous system (CNS). Most importantly, neurite growth inhibitors prevent any regenerative growth of injured nerve fibres. Some of these inhibitors are associated with CNS myelin, others are found at the lesion site and in the scar tissue. Traumatic injuries in brain and spinal cord of mammals induce upregulation of embryonic inhibitory or repulsive guidance cues and their receptors on the neurites. An example for embryonic repulsive directional cues re-expressed at lesion sites in both the rat and human CNS is provided with repulsive guidance molecules, a new family of directional guidance cues. PMID:16939972

  14. Design, synthesis and selection of DNA-encoded small-molecule libraries.

    PubMed

    Clark, Matthew A; Acharya, Raksha A; Arico-Muendel, Christopher C; Belyanskaya, Svetlana L; Benjamin, Dennis R; Carlson, Neil R; Centrella, Paolo A; Chiu, Cynthia H; Creaser, Steffen P; Cuozzo, John W; Davie, Christopher P; Ding, Yun; Franklin, G Joseph; Franzen, Kurt D; Gefter, Malcolm L; Hale, Steven P; Hansen, Nils J V; Israel, David I; Jiang, Jinwei; Kavarana, Malcolm J; Kelley, Michael S; Kollmann, Christopher S; Li, Fan; Lind, Kenneth; Mataruse, Sibongile; Medeiros, Patricia F; Messer, Jeffrey A; Myers, Paul; O'Keefe, Heather; Oliff, Matthew C; Rise, Cecil E; Satz, Alexander L; Skinner, Steven R; Svendsen, Jennifer L; Tang, Lujia; van Vloten, Kurt; Wagner, Richard W; Yao, Gang; Zhao, Baoguang; Morgan, Barry A

    2009-09-01

    Biochemical combinatorial techniques such as phage display, RNA display and oligonucleotide aptamers have proven to be reliable methods for generation of ligands to protein targets. Adapting these techniques to small synthetic molecules has been a long-sought goal. We report the synthesis and interrogation of an 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide. The library was assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection. We describe methods for the selection and deconvolution of the chemical display library, and the discovery of inhibitors for two enzymes: Aurora A kinase and p38 MAP kinase.

  15. Novel Roles of the Chemorepellent Axon Guidance Molecule RGMa in Cell Migration and Adhesion

    PubMed Central

    Lah, Grace J.

    2012-01-01

    The repulsive guidance molecule A (RGMa) is a contact-mediated axon guidance molecule that has significant roles in central nervous system (CNS) development. Here we have examined whether RGMa has novel roles in cell migration and cell adhesion outside the nervous system. RGMa was found to stimulate cell migration from Xenopus animal cap explants in a neogenin-dependent and BMP-independent manner. RGMa also stimulated the adhesion of Xenopus animal cap cells, and this adhesion was dependent on neogenin and independent of calcium. To begin to functionally characterize the role of specific domains in RGMa, we assessed the migratory and adhesive activities of deletion mutants. RGMa lacking the partial von Willebrand factor type D (vWF) domain preferentially perturbed cell adhesion, while mutants lacking the RGD motif affected cell migration. We also revealed that manipulating the levels of RGMa in vivo caused major migration defects during Xenopus gastrulation. We have revealed here novel roles of RGMa in cell migration and adhesion and demonstrated that perturbations to the homeostasis of RGMa expression can severely disrupt major morphogenetic events. These results have implications for understanding the role of RGMa in both health and disease. PMID:22215618

  16. Expression of structurally diverse Qa-2-encoded molecules on the surface of cloned cytotoxic T lymphocytes

    PubMed Central

    1984-01-01

    Extracts of 125I-labeled cloned murine cytotoxic T lymphocytes (CTL) were immunoprecipitated with alloantisera to the cloned CTL and rabbit antisera to beta-2 microglobulin. Polyacrylamide gel electrophoresis (PAGE) of the specific precipitates revealed, as expected, 125I-labeled components that corresponded to products of class I genes of the major histocompatibility complex (MHC). However, additional class I gene products of relatively low apparent molecular weight (Mr) were also observed. Similar analyses of spleen cells from a variety of MHC- congenic mouse strains suggested that the class I molecules of relatively low Mr are encoded in the Qa-2 region of the MHC, and this was confirmed by immunoprecipitation with a monoclonal antibody to Qa- 2. Surprisingly, however, the cell surface Qa-2 molecules of different CTL clones differed in Mr, in isoelectric focusing (IEF) pattern, and in the number of distinguishable molecules expressed per clone: some clones seemed to express only a single Qa-2-encoded molecule while others expressed two distinct ones. Treatment of the immunoprecipitated Qa-2 with endoglycosidase F (Endo F) resulted in a decrease in Mr of approximately 5,000-6,000, corresponding to the expected loss of N- linked oligosaccharides, but the decrease did not eliminate structural variability among the clones. Structural diversity of the Qa-2-encoded molecules expressed on CTL could arise because CTL clones differ (a) in the particular Qa-2 genes they express, (b) in the way they splice Qa-2 gene transcripts or, perhaps, (c) in Endo F-resistant oligosaccharides on their Qa-2 molecules. PMID:6333483

  17. Discovery of small-molecule interleukin-2 inhibitors from a DNA-encoded chemical library.

    PubMed

    Leimbacher, Markus; Zhang, Yixin; Mannocci, Luca; Stravs, Michael; Geppert, Tim; Scheuermann, Jörg; Schneider, Gisbert; Neri, Dario

    2012-06-18

    Libraries of chemical compounds individually coupled to encoding DNA tags (DNA-encoded chemical libraries) hold promise to facilitate exceptionally efficient ligand discovery. We constructed a high-quality DNA-encoded chemical library comprising 30,000 drug-like compounds; this was screened in 170 different affinity capture experiments. High-throughput sequencing allowed the evaluation of 120 million DNA codes for a systematic analysis of selection strategies and statistically robust identification of binding molecules. Selections performed against the tumor-associated antigen carbonic anhydrase IX (CA IX) and the pro-inflammatory cytokine interleukin-2 (IL-2) yielded potent inhibitors with exquisite target specificity. The binding mode of the revealed pharmacophore against IL-2 was confirmed by molecular docking. Our findings suggest that DNA-encoded chemical libraries allow the facile identification of drug-like ligands principally to any protein of choice, including molecules capable of disrupting high-affinity protein-protein interactions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Inhibition of Repulsive Guidance Molecule, RGMa, Increases Afferent Synapse Formation with Auditory Hair Cells

    PubMed Central

    Brugeaud, Aurore; Tong, Mingjie; Luo, Li; Edge, Albert S.B.

    2017-01-01

    The peripheral fibers that extend from auditory neurons to hair cells are sensitive to damage, and replacement of the fibers and their afferent synapse with hair cells would be of therapeutic interest. Here, we show that RGMa, a repulsive guidance molecule previously shown to play a role in the development of the chick visual system, is expressed in the developing, newborn, and mature mouse inner ear. The effect of RGMa on synaptogenesis between afferent neurons and hair cells, from which afferent connections had been removed, was assessed. Contact of neural processes with hair cells and elaboration of postsynaptic densities at sites of the ribbon synapse were increased by treatment with a blocking antibody to RGMa, and pruning of auditory fibers to achieve the mature branching pattern of afferent neurons was accelerated. Inhibition by RGMa could thus explain why auditory neurons have a low capacity to regenerate peripheral processes: postnatal spiral ganglion neurons retain the capacity to send out processes that respond to signals for synapse formation, but expression of RGMa postnatally appears to be detrimental to regeneration of afferent hair cell innervation and antagonizes synaptogenesis. Increased synaptogenesis after inhibition of RGMa suggests that manipulation of guidance or inhibitory factors may provide a route to increase formation of new synapses at deafferented hair cells. PMID:24123853

  19. Capturing Single Molecules of Immunoglobulin and Ricin with an Aptamer-Encoded Glass Nanopore

    PubMed Central

    Ding, Shu; Gao, Changlu; Gu, Li-Qun

    2010-01-01

    Nanopore-based single-molecule biosensors have been extensively studied. Protein pores that have receptors attached to them are target-selective, but their real-time applications are limited by the fragility of the lipid membrane into which the protein pores are embedded. Synthetic nanopores are more stable and provide flexible pore sizes, but the selectivity is low when detecting in the translocation mode. In spite of modifications with probing molecules, such as antibodies, to potentiate specific targeting, these nanopores fail to bind individual target molecules. Distinguishing between binding and translocation blocks remains unsolved. Here, we propose an aptamer-encoded nanopore that overcomes these challenges. Aptamers are well-known probing oligonucleotides that have high sensitivity and selectivity. In contrast to antibodies, aptamers are much smaller than their targets, rendering target blockades in the nanopore much more distinguishable. We used aptamer-encoded nanopores to detect single molecules of immunoglobulin E and the bioterrorist agent ricin, sequentially captured by the immobilized aptamer in the sensing zone of the pore. The functional nanopore also probed sequence-dependent aptamer-protein interactions. These findings will facilitate the development of a universal nanopore for multitarget detection. PMID:19627120

  20. Spatiotemporal Expression of Repulsive Guidance Molecules (RGMs) and Their Receptor Neogenin in the Mouse Brain

    PubMed Central

    van den Heuvel, Dianne M. A.; Hellemons, Anita J. C. G. M.; Pasterkamp, R. Jeroen

    2013-01-01

    Neogenin has been implicated in a variety of developmental processes such as neurogenesis, neuronal differentiation, apoptosis, migration and axon guidance. Binding of repulsive guidance molecules (RGMs) to Neogenin inhibits axon outgrowth of different neuronal populations. This effect requires Neogenin to interact with co-receptors of the uncoordinated locomotion-5 (Unc5) family to activate downstream Rho signaling. Although previous studies have reported RGM, Neogenin, and/or Unc5 expression, a systematic comparison of RGM and Neogenin expression in the developing nervous system is lacking, especially at later developmental stages. Furthermore, information on RGM and Neogenin expression at the protein level is limited. To fill this void and to gain further insight into the role of RGM-Neogenin signaling during mouse neural development, we studied the expression of RGMa, RGMb, Neogenin and Unc5A-D using in situ hybridization, immunohistochemistry and RGMa section binding. Expression patterns in the primary olfactory system, cortex, hippocampus, habenula, and cerebellum were studied in more detail. Characteristic cell layer-specific expression patterns were detected for RGMa, RGMb, Neogenin and Unc5A-D. Furthermore, strong expression of RGMa, RGMb and Neogenin protein was found on several major axon tracts such as the primary olfactory projections, anterior commissure and fasciculus retroflexus. These data not only hint at a role for RGM-Neogenin signaling during the development of different neuronal systems, but also suggest that Neogenin partners with different Unc5 family members in different systems. Overall, the results presented here will serve as a framework for further dissection of the role of RGM-Neogenin signaling during neural development. PMID:23457482

  1. Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library

    PubMed Central

    Ahn, Seungkirl; Kahsai, Alem W.; Pani, Biswaranjan; Wang, Qin-Ting; Zhao, Shuai; Wall, Alissa L.; Strachan, Ryan T.; Staus, Dean P.; Wingler, Laura M.; Sun, Lillian D.; Sinnaeve, Justine; Choi, Minjung; Cho, Ted; Xu, Thomas T.; Hansen, Gwenn M.; Burnett, Michael B.; Lamerdin, Jane E.; Bassoni, Daniel L.; Gavino, Bryant J.; Husemoen, Gitte; Olsen, Eva K.; Franch, Thomas; Costanzi, Stefano; Chen, Xin; Lefkowitz, Robert J.

    2017-01-01

    The β2-adrenergic receptor (β2AR) has been a model system for understanding regulatory mechanisms of G-protein–coupled receptor (GPCR) actions and plays a significant role in cardiovascular and pulmonary diseases. Because all known β-adrenergic receptor drugs target the orthosteric binding site of the receptor, we set out to isolate allosteric ligands for this receptor by panning DNA-encoded small-molecule libraries comprising 190 million distinct compounds against purified human β2AR. Here, we report the discovery of a small-molecule negative allosteric modulator (antagonist), compound 15 [([4-((2S)-3-(((S)-3-(3-bromophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-2-(2-cyclohexyl-2-phenylacetamido)-3-oxopropyl)benzamide], exhibiting a unique chemotype and low micromolar affinity for the β2AR. Binding of 15 to the receptor cooperatively enhances orthosteric inverse agonist binding while negatively modulating binding of orthosteric agonists. Studies with a specific antibody that binds to an intracellular region of the β2AR suggest that 15 binds in proximity to the G-protein binding site on the cytosolic surface of the β2AR. In cell-signaling studies, 15 inhibits cAMP production through the β2AR, but not that mediated by other Gs-coupled receptors. Compound 15 also similarly inhibits β-arrestin recruitment to the activated β2AR. This study presents an allosteric small-molecule ligand for the β2AR and introduces a broadly applicable method for screening DNA-encoded small-molecule libraries against purified GPCR targets. Importantly, such an approach could facilitate the discovery of GPCR drugs with tailored allosteric effects. PMID:28130548

  2. Allosteric "beta-blocker" isolated from a DNA-encoded small molecule library.

    PubMed

    Ahn, Seungkirl; Kahsai, Alem W; Pani, Biswaranjan; Wang, Qin-Ting; Zhao, Shuai; Wall, Alissa L; Strachan, Ryan T; Staus, Dean P; Wingler, Laura M; Sun, Lillian D; Sinnaeve, Justine; Choi, Minjung; Cho, Ted; Xu, Thomas T; Hansen, Gwenn M; Burnett, Michael B; Lamerdin, Jane E; Bassoni, Daniel L; Gavino, Bryant J; Husemoen, Gitte; Olsen, Eva K; Franch, Thomas; Costanzi, Stefano; Chen, Xin; Lefkowitz, Robert J

    2017-02-14

    The β2-adrenergic receptor (β2AR) has been a model system for understanding regulatory mechanisms of G-protein-coupled receptor (GPCR) actions and plays a significant role in cardiovascular and pulmonary diseases. Because all known β-adrenergic receptor drugs target the orthosteric binding site of the receptor, we set out to isolate allosteric ligands for this receptor by panning DNA-encoded small-molecule libraries comprising 190 million distinct compounds against purified human β2AR. Here, we report the discovery of a small-molecule negative allosteric modulator (antagonist), compound 15 [([4-((2S)-3-(((S)-3-(3-bromophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-2-(2-cyclohexyl-2-phenylacetamido)-3-oxopropyl)benzamide], exhibiting a unique chemotype and low micromolar affinity for the β2AR. Binding of 15 to the receptor cooperatively enhances orthosteric inverse agonist binding while negatively modulating binding of orthosteric agonists. Studies with a specific antibody that binds to an intracellular region of the β2AR suggest that 15 binds in proximity to the G-protein binding site on the cytosolic surface of the β2AR. In cell-signaling studies, 15 inhibits cAMP production through the β2AR, but not that mediated by other Gs-coupled receptors. Compound 15 also similarly inhibits β-arrestin recruitment to the activated β2AR. This study presents an allosteric small-molecule ligand for the β2AR and introduces a broadly applicable method for screening DNA-encoded small-molecule libraries against purified GPCR targets. Importantly, such an approach could facilitate the discovery of GPCR drugs with tailored allosteric effects.

  3. Repulsive Guidance Molecule is a structural bridge between Neogenin and Bone Morphogenetic Protein

    PubMed Central

    Healey, Eleanor G.; Bishop, Benjamin; Elegheert, Jonathan; Bell, Christian H.; Padilla-Parra, Sergi; Siebold, Christian

    2015-01-01

    Repulsive guidance molecules (RGMs) control crucial processes spanning cell motility, adhesion, immune cell regulation and systemic iron metabolism. RGMs signal via two fundamental signaling cascades: the Neogenin (NEO1) and the Bone Morphogenetic Protein (BMP) pathways. Here, we report crystal structures of the N-terminal domains of all human RGM family members in complex with the BMP ligand BMP2, revealing a novel protein fold and a conserved BMP-binding mode. Our structural and functional data suggest a pH-linked mechanism for RGM-activated BMP signaling and offer a rationale for RGM mutations causing juvenile hemochromatosis. We also determined the ternary BMP2–RGM–NEO1 complex crystal structure, which combined with solution scattering and live-cell super-resolution fluorescence microscopy, indicates BMP-induced clustering of the RGM–NEO1 complex. Our results show how RGM acts as the central hub linking BMP and NEO1 and physically connecting these fundamental signaling pathways. PMID:25938661

  4. Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth

    PubMed Central

    Shi, Ying; Chen, Guo-Bin; Huang, Xiao-Xiao; Xiao, Chuan-Xing; Wang, Huan-Huan; Li, Ye-Sen; Zhang, Jin-Fang; Li, Shao; Xia, Yin; Ren, Jian-Lin; Guleng, Bayasi

    2015-01-01

    Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment. PMID:26029998

  5. Dragon (repulsive guidance molecule b, RGMb) is a novel gene that promotes colorectal cancer growth.

    PubMed

    Shi, Ying; Chen, Guo-Bin; Huang, Xiao-Xiao; Xiao, Chuan-Xing; Wang, Huan-Huan; Li, Ye-Sen; Zhang, Jin-Fang; Li, Shao; Xia, Yin; Ren, Jian-Lin; Guleng, Bayasi

    2015-08-21

    Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment.

  6. Dragon (repulsive guidance molecule b) inhibits IL-6 expression in macrophages.

    PubMed

    Xia, Yin; Cortez-Retamozo, Virna; Niederkofler, Vera; Salie, Rishard; Chen, Shanzhuo; Samad, Tarek A; Hong, Charles C; Arber, Silvia; Vyas, Jatin M; Weissleder, Ralph; Pittet, Mikael J; Lin, Herbert Y

    2011-02-01

    Repulsive guidance molecule (RGM) family members RGMa, RGMb/Dragon, and RGMc/hemojuvelin were found recently to act as bone morphogenetic protein (BMP) coreceptors that enhance BMP signaling activity. Although our previous studies have shown that hemojuvelin regulates hepcidin expression and iron metabolism through the BMP pathway, the role of the BMP signaling mediated by Dragon remains largely unknown. We have shown previously that Dragon is expressed in neural cells, germ cells, and renal epithelial cells. In this study, we demonstrate that Dragon is highly expressed in macrophages. Studies with RAW264.7 and J774 macrophage cell lines reveal that Dragon negatively regulates IL-6 expression in a BMP ligand-dependent manner via the p38 MAPK and Erk1/2 pathways but not the Smad1/5/8 pathway. We also generated Dragon knockout mice and found that IL-6 is upregulated in macrophages and dendritic cells derived from whole lung tissue of these mice compared with that in respective cells derived from wild-type littermates. These results indicate that Dragon is an important negative regulator of IL-6 expression in immune cells and that Dragon-deficient mice may be a useful model for studying immune and inflammatory disorders.

  7. DNA-encoded chemical libraries: advancing beyond conventional small-molecule libraries.

    PubMed

    Franzini, Raphael M; Neri, Dario; Scheuermann, Jörg

    2014-04-15

    DNA-encoded chemical libraries (DECLs) represent a promising tool in drug discovery. DECL technology allows the synthesis and screening of chemical libraries of unprecedented size at moderate costs. In analogy to phage-display technology, where large antibody libraries are displayed on the surface of filamentous phage and are genetically encoded in the phage genome, DECLs feature the display of individual small organic chemical moieties on DNA fragments serving as amplifiable identification barcodes. The DNA-tag facilitates the synthesis and allows the simultaneous screening of very large sets of compounds (up to billions of molecules), because the hit compounds can easily be identified and quantified by PCR-amplification of the DNA-barcode followed by high-throughput DNA sequencing. Several approaches have been used to generate DECLs, differing both in the methods used for library encoding and for the combinatorial assembly of chemical moieties. For example, DECLs can be used for fragment-based drug discovery, displaying a single molecule on DNA or two chemical moieties at the extremities of complementary DNA strands. DECLs can vary substantially in the chemical structures and the library size. While ultralarge libraries containing billions of compounds have been reported containing four or more sets of building blocks, also smaller libraries have been shown to be efficient for ligand discovery. In general, it has been found that the overall library size is a poor predictor for library performance and that the number and diversity of the building blocks are rather important indicators. Smaller libraries consisting of two to three sets of building blocks better fulfill the criteria of drug-likeness and often have higher quality. In this Account, we present advances in the DECL field from proof-of-principle studies to practical applications for drug discovery, both in industry and in academia. DECL technology can yield specific binders to a variety of target

  8. Characterization of the gene encoding the polymorphic immunodominant molecule, a neutralizing antigen of Theileria parva

    SciTech Connect

    Toye, P.G.; Metzelaar, M.J.; Wijngaard, P.L.J.

    1995-08-01

    Theileria parva, a tick-transmitted protozoan parasite related to Plasmodium spp., causes the disease East Coast fever, an acute and usually fatal lymphoproliferative disorder of cattle in Africa. Previous studies using sera from cattle that have survived infection identified a polymorphic immunodominant molecule (PIM) that is expressed by both the infective sporozoite stage of the parasite and the intracellular schizont. Here we show that mAb specific for the PIM Ag can inhibit sporozoite invasion of lymphocytes in vitro. A cDNA clone encoding the PIM Ag of the T. parva (Muguga) stock was obtained by using these mAb in a novel eukaryotic expression cloning system that allows isolation of cDNA encoding cytoplasmic or surface Ags. To establish the molecular basis of the polymorphism of PIM, the cDNA of the PIM Ag from a buffalo-derived T. parva stock was isolated and its sequence was compared with that of the cattle-derived Muguga PIM. The two cDNAs showed considerable identity in both the 5{prime} and 3{prime} regions, but there was substantial sequence divergence in the central regions. Several types of repeated sequences were identified in the variant regions. In the Muguga form of the molecule, there were five tandem repeats of the tetrapeptide, QPEP, that were shown, by transfection of a deleted version of the PIM gene, not to react with several anti-PIM mAbs. By isolating and sequencing the genomic version of the gene, we identified two small introns in the 3{prime} region of the gene. Finally, we showed that polyclonal rat Abs against recombinant PIM neutralize sporozoite infectivity in vitro, suggesting that the PIM Ag should be evaluated for its capacity to immunize cattle against East Coast Fever.

  9. Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome.

    PubMed

    Brancati, Francesco; Fortugno, Paola; Bottillo, Irene; Lopez, Marc; Josselin, Emmanuelle; Boudghene-Stambouli, Omar; Agolini, Emanuele; Bernardini, Laura; Bellacchio, Emanuele; Iannicelli, Miriam; Rossi, Alfredo; Dib-Lachachi, Amina; Stuppia, Liborio; Palka, Giandomenico; Mundlos, Stefan; Stricker, Sigmar; Kornak, Uwe; Zambruno, Giovanna; Dallapiccola, Bruno

    2010-08-13

    Ectodermal dysplasias form a large disease family with more than 200 members. The combination of hair and tooth abnormalities, alopecia, and cutaneous syndactyly is characteristic of ectodermal dysplasia-syndactyly syndrome (EDSS). We used a homozygosity mapping approach to map the EDSS locus to 1q23 in a consanguineous Algerian family. By candidate gene analysis, we identified a homozygous mutation in the PVRL4 gene that not only evoked an amino acid change but also led to exon skipping. In an Italian family with two siblings affected by EDSS, we further detected a missense and a frameshift mutation. PVRL4 encodes for nectin-4, a cell adhesion molecule mainly implicated in the formation of cadherin-based adherens junctions. We demonstrated high nectin-4 expression in hair follicle structures, as well as in the separating digits of murine embryos, the tissues mainly affected by the EDSS phenotype. In patient keratinocytes, mutated nectin-4 lost its capability to bind nectin-1. Additionally, in discrete structures of the hair follicle, we found alterations of the membrane localization of nectin-afadin and cadherin-catenin complexes, which are essential for adherens junction formation, and we found reorganization of actin cytoskeleton. Together with cleft lip and/or palate ectodermal dysplasia (CLPED1, or Zlotogora-Ogur syndrome) due to an impaired function of nectin-1, EDSS is the second known "nectinopathy" caused by mutations in a nectin adhesion molecule.

  10. Bacterial Biosynthetic Gene Clusters Encoding the Anti-cancer Haterumalide Class of Molecules

    PubMed Central

    Matilla, Miguel A.; Stöckmann, Henning; Leeper, Finian J.; Salmond, George P. C.

    2012-01-01

    Haterumalides are halogenated macrolides with strong antitumor properties, making them attractive targets for chemical synthesis. Unfortunately, current synthetic routes to these molecules are inefficient. The potent haterumalide, oocydin A, was previously identified from two plant-associated bacteria through its high bioactivity against plant pathogenic fungi and oomycetes. In this study, we describe oocydin A (ooc) biosynthetic gene clusters identified by genome sequencing, comparative genomics, and chemical analysis in four plant-associated enterobacteria of the Serratia and Dickeya genera. Disruption of the ooc gene cluster abolished oocydin A production and bioactivity against fungi and oomycetes. The ooc gene clusters span between 77 and 80 kb and encode five multimodular polyketide synthase (PKS) proteins, a hydroxymethylglutaryl-CoA synthase cassette and three flavin-dependent tailoring enzymes. The presence of two free-standing acyltransferase proteins classifies the oocydin A gene cluster within the growing family of trans-AT PKSs. The amino acid sequences and organization of the PKS domains are consistent with the chemical predictions and functional peculiarities associated with trans-acyltransferase PKS. Based on extensive in silico analysis of the gene cluster, we propose a biosynthetic model for the production of oocydin A and, by extension, for other members of the haterumalide family of halogenated macrolides exhibiting anti-cancer, anti-fungal, and other interesting biological properties. PMID:23012376

  11. Digitally encoded DNA nanostructures for multiplexed, single-molecule protein sensing with nanopores

    NASA Astrophysics Data System (ADS)

    Bell, Nicholas A. W.; Keyser, Ulrich F.

    2016-07-01

    The simultaneous detection of a large number of different analytes is important in bionanotechnology research and in diagnostic applications. Nanopore sensing is an attractive method in this regard as the approach can be integrated into small, portable device architectures, and there is significant potential for detecting multiple sub-populations in a sample. Here, we show that highly multiplexed sensing of single molecules can be achieved with solid-state nanopores by using digitally encoded DNA nanostructures. Based on the principles of DNA origami, we designed a library of DNA nanostructures in which each member contains a unique barcode; each bit in the barcode is signalled by the presence or absence of multiple DNA dumbbell hairpins. We show that a 3-bit barcode can be assigned with 94% accuracy by electrophoretically driving the DNA structures through a solid-state nanopore. Select members of the library were then functionalized to detect a single, specific antibody through antigen presentation at designed positions on the DNA. This allows us to simultaneously detect four different antibodies of the same isotype at nanomolar concentration levels.

  12. Selection of DNA-encoded small molecule libraries against unmodified and non-immobilized protein targets.

    PubMed

    Zhao, Peng; Chen, Zitian; Li, Yizhou; Sun, Dawei; Gao, Yuan; Huang, Yanyi; Li, Xiaoyu

    2014-09-15

    The selection of DNA-encoded libraries against biological targets has become an important discovery method in chemical biology and drug discovery, but the requirement of modified and immobilized targets remains a significant disadvantage. With a terminal protection strategy and ligand-induced photo-crosslinking, we show that iterated selections of DNA-encoded libraries can be realized with unmodified and non-immobilized protein targets.

  13. Secretion of a soluble class I molecule encoded by the Q10 gene of the C57BL/10 mouse.

    PubMed Central

    Devlin, J J; Lew, A M; Flavell, R A; Coligan, J E

    1985-01-01

    The DNA sequence of the Q10 genes appears to be highly conserved amongst strains of mice and has only been found to be transcribed in the liver. An examination of the nucleotide sequence of the exon that normally encodes the transmembrane domain of class I molecules suggested that the Q10 gene encodes a secreted protein. We have established this by showing that L cells transformed with an expression vector containing the Q10 gene secrete a class I molecule which was identified with an antiserum raised against a peptide predicted by the Q10 transmembrane exon. Both the L cell-derived Q10 molecule and a class I protein immunoprecipitated from serum with this anti-peptide antiserum have mol. wts. of approximately 38 000; the Q10 molecule secreted by L cells is heterogeneous in mol. wt. This heterogeneity was drastically reduced after endoglycosidase F treatment, suggesting that Q10 molecules secreted into the serum by the liver may be glycosylated differently from those secreted by L cells. Endoglycosidase F treatment of both the L cell and serum forms of the soluble molecule yielded two products with mol. wts. of approximately 32 000 and 35 000; this is consistent with the observation that the predicted Q10 protein sequence has two potential glycosylation sites. In contrast to previous published results, the Q10 molecule reacted with rabbit anti-H-2 antisera which is consistent with its greater than 80% homology to the classical transplantation antigens. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:4018029

  14. The Caenorhabditis elegans NF2/Merlin Molecule NFM-1 Nonautonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit.

    PubMed

    Josephson, Matthew P; Aliani, Rana; Norris, Megan L; Ochs, Matthew E; Gujar, Mahekta; Lundquist, Erik A

    2017-02-01

    During nervous system development, neurons and their progenitors migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tumor suppressor in humans. Mutations in NF2 lead to neurofibromatosis type II, characterized by benign tumors of glial tissues. Here we demonstrate that in C. elegans, nfm-1 is required for the ability of Q cells and their descendants to extend protrusions and to migrate, but is not required for direction of migration. Using a combination of mosaic analysis and cell-specific expression, we show that NFM-1 is required nonautonomously, possibly in muscles, to promote Q lineage migrations. We also show a genetic interaction between nfm-1 and the C. elegans Slit homolog slt-1, which encodes a conserved secreted guidance cue. Our results suggest that NFM-1 might be involved in the generation of an extracellular cue that promotes Q neuroblast protrusion and migration that acts with or in parallel to SLT-1 In vertebrates, NF2 and Slit2 interact in axon pathfinding, suggesting a conserved interaction of NF2 and Slit2 in regulating migratory events.

  15. Universal strategies for the DNA-encoding of libraries of small molecules using the chemical ligation of oligonucleotide tags

    PubMed Central

    Litovchick, Alexander; Clark, Matthew A; Keefe, Anthony D

    2014-01-01

    The affinity-mediated selection of large libraries of DNA-encoded small molecules is increasingly being used to initiate drug discovery programs. We present universal methods for the encoding of such libraries using the chemical ligation of oligonucleotides. These methods may be used to record the chemical history of individual library members during combinatorial synthesis processes. We demonstrate three different chemical ligation methods as examples of information recording processes (writing) for such libraries and two different cDNA-generation methods as examples of information retrieval processes (reading) from such libraries. The example writing methods include uncatalyzed and Cu(I)-catalyzed alkyne-azide cycloadditions and a novel photochemical thymidine-psoralen cycloaddition. The first reading method “relay primer-dependent bypass” utilizes a relay primer that hybridizes across a chemical ligation junction embedded in a fixed-sequence and is extended at its 3′-terminus prior to ligation to adjacent oligonucleotides. The second reading method “repeat-dependent bypass” utilizes chemical ligation junctions that are flanked by repeated sequences. The upstream repeat is copied prior to a rearrangement event during which the 3′-terminus of the cDNA hybridizes to the downstream repeat and polymerization continues. In principle these reading methods may be used with any ligation chemistry and offer universal strategies for the encoding (writing) and interpretation (reading) of DNA-encoded chemical libraries. PMID:25483841

  16. Universal strategies for the DNA-encoding of libraries of small molecules using the chemical ligation of oligonucleotide tags.

    PubMed

    Litovchick, Alexander; Clark, Matthew A; Keefe, Anthony D

    2014-01-01

    The affinity-mediated selection of large libraries of DNA-encoded small molecules is increasingly being used to initiate drug discovery programs. We present universal methods for the encoding of such libraries using the chemical ligation of oligonucleotides. These methods may be used to record the chemical history of individual library members during combinatorial synthesis processes. We demonstrate three different chemical ligation methods as examples of information recording processes (writing) for such libraries and two different cDNA-generation methods as examples of information retrieval processes (reading) from such libraries. The example writing methods include uncatalyzed and Cu(I)-catalyzed alkyne-azide cycloadditions and a novel photochemical thymidine-psoralen cycloaddition. The first reading method "relay primer-dependent bypass" utilizes a relay primer that hybridizes across a chemical ligation junction embedded in a fixed-sequence and is extended at its 3'-terminus prior to ligation to adjacent oligonucleotides. The second reading method "repeat-dependent bypass" utilizes chemical ligation junctions that are flanked by repeated sequences. The upstream repeat is copied prior to a rearrangement event during which the 3'-terminus of the cDNA hybridizes to the downstream repeat and polymerization continues. In principle these reading methods may be used with any ligation chemistry and offer universal strategies for the encoding (writing) and interpretation (reading) of DNA-encoded chemical libraries.

  17. Fidelity by design: Yoctoreactor and binder trap enrichment for small-molecule DNA-encoded libraries and drug discovery.

    PubMed

    Blakskjaer, Peter; Heitner, Tara; Hansen, Nils Jakob Vest

    2015-06-01

    DNA-encoded small-molecule library (DEL) technology allows vast drug-like small molecule libraries to be efficiently synthesized in a combinatorial fashion and screened in a single tube method for binding, with an assay readout empowered by advances in next generation sequencing technology. This approach has increasingly been applied as a viable technology for the identification of small-molecule modulators to protein targets and as precursors to drugs in the past decade. Several strategies for producing and for screening DELs have been devised by both academic and industrial institutions. This review highlights some of the most significant and recent strategies along with important results. A special focus on the production of high fidelity DEL technologies with the ability to eliminate screening noise and false positives is included: using a DNA junction called the Yoctoreactor, building blocks (BBs) are spatially confined at the center of the junction facilitating both the chemical reaction between BBs and encoding of the synthetic route. A screening method, known as binder trap enrichment, permits DELs to be screened robustly in a homogeneous manner delivering clean data sets and potent hits for even the most challenging targets.

  18. Structure-Activity Relation of AMOR Sugar Molecule That Activates Pollen-Tubes for Ovular Guidance.

    PubMed

    Jiao, Jiao; Mizukami, Akane G; Sankaranarayanan, Subramanian; Yamguchi, Junichiro; Itami, Kenichiro; Higashiyawma, Tetsuya

    2017-01-01

    Successful fertilization in flowering plants depends on the precise directional growth control of pollen tube through the female pistil tissue toward the female gametophyte contained in the ovule for delivery of nonmotile sperm cells. Cys-rich peptides LUREs secreted from the synergid cells on either side of the egg cell act as ovular attractants of pollen tubes. Competency control by the pistil is crucial for the response of pollen tubes to these ovular attractants. We recently reported that ovular 4-O-methyl-glucuronosyl arabinogalactan (AMOR) induces competency of the pollen tube to respond to ovular attractant LURE peptides in Torenia fournieri. The beta isomer of the terminal disaccharide 4-O-methyl-glucuronosyl galactose was essential and sufficient for the competency induction. However, critical and noncritical structures in the disaccharide have not been dissected deeply. Herein, we report the synthesis of new AMOR analogs and the structure-activity relationships for AMOR activity in the presence of these synthesized analogs. Removal of 4-O-methyl group or -COOH from the glucuronosyl residue of the disaccharide dramatically reduces AMOR activity. The pyranose backbone of the second sugar of disaccharide is essential for the activity but not hydroxy groups. The role of beta isomer of the disaccharide 4-Me-GlcA-β(1,6)-Gal is very specific for competency control, as there was no difference in effect among the sugar analogs tested for pollen germination. This study represents the first structure-activity relationship study, to our knowledge, of a sugar molecule involved in plant reproduction, which opens a way for modification of the molecule without loss of activity. © 2017 American Society of Plant Biologists. All Rights Reserved.

  19. Aptamer-Encoded Nanopore for Ultrasensitive Detection of Bioterrorist Agent Ricin at Single-Molecule Resolution

    PubMed Central

    Gu, Li-Qun; Ding, Shu; Gao, Changlu

    2011-01-01

    The molecular-scale pore structure, called nanopore, can be formed from protein ion channels by genetic engineering or fabricated on solid substrates using fashion nanotechnology. Target molecules in interaction with the functionalized lumen of nanopore, can produce characteristic changes in the pore conductance, which act as fingerprints, allowing us to identify single molecules and simultaneously quantify each target species in the mixture. Nanopore sensors have been created for tremendous biomedical detections, with targets ranging from metal ions, drug compounds and cellular second messengers, to proteins and DNAs. Here we will review our recent discoveries with a lab-in-hand glass nanopore: single-molecule discrimination of chiral enantiomers with a trapped cyclodextrin, and sensing of bioterrorist agent ricin. PMID:19964179

  20. Nucleic acid molecules encoding isopentenyl monophosphate kinase, and methods of use

    DOEpatents

    Croteau, Rodney B.; Lange, Bernd M.

    2001-01-01

    A cDNA encoding isopentenyl monophosphate kinase (IPK) from peppermint (Mentha x piperita) has been isolated and sequenced, and the corresponding amino acid sequence has been determined. Accordingly, an isolated DNA sequence (SEQ ID NO:1) is provided which codes for the expression of isopentenyl monophosphate kinase (SEQ ID NO:2), from peppermint (Mentha x piperita). In other aspects, replicable recombinant cloning vehicles are provided which code for isopentenyl monophosphate kinase, or for a base sequence sufficiently complementary to at least a portion of isopentenyl monophosphate kinase DNA or RNA to enable hybridization therewith. In yet other aspects, modified host cells are provided that have been transformed, transfected, infected and/or injected with a recombinant cloning vehicle and/or DNA sequence encoding isopentenyl monophosphate kinase. Thus, systems and methods are provided for the recombinant expression of the aforementioned recombinant isopentenyl monophosphate kinase that may be used to facilitate its production, isolation and purification in significant amounts. Recombinant isopentenyl monophosphate kinase may be used to obtain expression or enhanced expression of isopentenyl monophosphate kinase in plants in order to enhance the production of isopentenyl monophosphate kinase, or isoprenoids derived therefrom, or may be otherwise employed for the regulation or expression of isopentenyl monophosphate kinase, or the production of its products.

  1. A virus-like molecule in the early stage of encoded molecular evolution

    NASA Astrophysics Data System (ADS)

    Nemoto, Naoto; Yanagawa, Hiroshi; Husimi, Yuzuru

    1996-10-01

    The recent advances of the evolutionary molecular engineering revealed the effectiveness of bonding strategy for assignment of the phenotype to its genotype, which non-enveloped viruses such as simple bacteriophages adopt. On the other hand, cellular organisms adopt another kind of the strategy, namely the compartmentalzation of both genotype and phenotype molecules in a single compartment enclosed with a cell membrane. The simplest strategy is that adopted by ribozymes in the RNA world. A single molecule carries both genotype and its phenotype. Based on the definition of “virus”-type and “cell”-type of the assignment strategy, we propose a virus-early/cell-late model of the history of life.

  2. Fastigial nucleus electrostimulation reduces the expression of repulsive guidance molecule, improves axonal growth following focal cerebral ischemia.

    PubMed

    Jiang, Fan; Yin, Honglei; Qin, Xinyue

    2012-09-01

    The role of repulsive guidance molecule A (RGMa) in cerebral ischemia remains unclear. In the study, we examined the expression of RGMa in ischemic brain tissues following focal cerebral ischemia/reperfusion (IR) in rats. An established middle cerebral artery suture occlusion model was employed. A dipolar electrode was placed into the cerebellum to stimulate the cerebellar fastigial nucleus for 1 h at 2 h after ischemia. Reverse transcription-polymerase chain reaction was used to measure the mRNA RGMa and its downstream mediator, Ras homolog A (RhoA). Immunohistochemistry was applied to detect RGMa and RhoA expressions and to evaluate axonal regeneration by optical density analysis of 200 kDa neurofilaments. We found that both mRNA and protein levels of RGMa and RhoA were increased in the ischemic cortex and hippocampus 48 h following cerebral IR and these elevated levels were maintained for 2 weeks. Electrostimulation of the fastigial nucleus reduced the expression of RGMa and RhoA at 24 h and 2 weeks following cerebral IR. In addition, axonal growth was enhanced in the fastigial nucleus electrostimulated group compared to non-stimulated ischemic animals (P < 0.05). RGMa/RhoA expression was negatively correlated with the growth of axons (P < 0.05). Therefore, we concluded that RGMa and RhoA could be another key molecule and might inhibit axonal regeneration during cerebral IR injury. Electrostimulation of the fastigial nucleus enhances axonal growth, possibly by reducing the expression of RGMa and RhoA after cerebral IR.

  3. The guidance molecule Semaphorin3A is differentially involved in the arealization of the mouse and primate neocortex.

    PubMed

    Homman-Ludiye, Jihane; Bourne, James A

    2014-11-01

    The visual cortex is organized into discrete domains characterized by their specific function, connectivity, chemoarchitecture, and cytoarchitecture. Gradients of transcription factors across the anteroposterior and mediolateral axes of the neocortex have previously been demonstrated to specify the main sensory regions. However, they do not account for the establishment of multiple areas in the primate visual cortex, which occupies approximately 50% of the neocortical surface. We demonstrate that the guidance molecule Semaphorin3A (Sema3A) is initially secreted in the cortical plate of the embryonic marmoset monkey and acts as an intrinsic cue to control the migration of subpopulations of neuronal progenitors and projection neurons expressing the receptor Neuropilin 1 (Npn1). During the first 2 postnatal weeks, Sema3A expression becomes primarily associated with ventral visual cortical areas, leading to the specific migration of Npn1+ neurons in the late maturing visual areas. In the mouse, Sema3A distribution is not arealized, but Npn1 expression becomes restricted to the posterior neocortex at embryonic day 16.5. The selective reduction in the striate cortex we observe in Sema3A-/- animals potentially results from the differential distribution of Npn1+ cells. Therefore, the Sema3A/Npn1 pathway participates to the parcellation of the visual neocortex in both the mouse and the marmoset, however, through different regulatory processes.

  4. The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors.

    PubMed

    Bollard, Julien; Massoma, Patrick; Vercherat, Cécile; Blanc, Martine; Lepinasse, Florian; Gadot, Nicolas; Couderc, Christophe; Poncet, Gilles; Walter, Thomas; Joly, Marie-Odile; Hervieu, Valérie; Scoazec, Jean-Yves; Roche, Colette

    2015-11-03

    Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs.SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways.This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy.

  5. Recurrent RNA motifs as scaffolds for genetically encodable small-molecule biosensors.

    PubMed

    Porter, Ely B; Polaski, Jacob T; Morck, Makenna M; Batey, Robert T

    2017-03-01

    Allosteric RNA devices are increasingly being viewed as important tools capable of monitoring enzyme evolution, optimizing engineered metabolic pathways, facilitating gene discovery and regulators of nucleic acid-based therapeutics. A key bottleneck in the development of these platforms is the availability of small-molecule-binding RNA aptamers that robustly function in the cellular environment. Although aptamers can be raised against nearly any desired target through in vitro selection, many cannot easily be integrated into devices or do not reliably function in a cellular context. Here, we describe a new approach using secondary- and tertiary-structural scaffolds derived from biologically active riboswitches and small ribozymes. When applied to the neurotransmitter precursors 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine, this approach yielded easily identifiable and characterizable aptamers predisposed for coupling to readout domains to allow engineering of nucleic acid-sensory devices that function in vitro and in the cellular context.

  6. Dragon (repulsive guidance molecule RGMb) inhibits E-cadherin expression and induces apoptosis in renal tubular epithelial cells.

    PubMed

    Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y; Xia, Yin

    2013-11-01

    Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45-66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo.

  7. Localization and action of Dragon (repulsive guidance molecule b), a novel bone morphogenetic protein coreceptor, throughout the reproductive axis.

    PubMed

    Xia, Yin; Sidis, Yisrael; Mukherjee, Abir; Samad, Tarek A; Brenner, Gary; Woolf, Clifford J; Lin, Herbert Y; Schneyer, Alan

    2005-08-01

    Bone morphogenetic proteins (BMPs) play important roles in reproduction including primordial germ cell formation, follicular development, spermatogenesis, and FSH secretion. Dragon, a recently identified glycosylphosphatidylinositol-anchored member of the repulsive guidance molecule family, is also a BMP coreceptor. In the present study, we determined the tissue and cellular localization of Dragon in reproductive organs using immunohistochemistry and in situ hybridization. Among reproductive organs, Dragon was expressed in testis, epididymis, ovary, uterus, and pituitary. In the testis of early postnatal mice, Dragon was found in gonocytes and spermatogonia, whereas in immature testes, Dragon was only weakly expressed in spermatogonia. Interestingly, pregnant mare serum gonadotropin treatment of immature mice robustly induced Dragon production in spermatocytes. In adult testis, Dragon was found in spermatocytes and round spermatids. In the ovary, Dragon was detected exclusively within oocytes and primarily those within secondary follicles. In the pituitary, Dragon-expressing cells overlapped FSH-expressing cells. Dragon was also expressed in a number of cell lines originating from reproductive tissues including Ishikawa, Hela, LbetaT2, MCF-7, and JEG3 cells. Immunocytochemistry and gradient sucrose ultracentrifugation studies showed Dragon was localized in lipid rafts within the plasma membrane. In reproductive cell lines, Dragon expression enhanced signaling of exogenous BMP2 or BMP4. The present studies demonstrate that Dragon expression is dynamically regulated throughout the reproductive tract and that Dragon protein modulates BMP signaling in cells from reproductive tissues. The overlap between Dragon expression and the functional BMP signaling system suggests that Dragon may play a role in mammalian reproduction.

  8. Site-specific labeling of genetically encoded azido groups for multicolor, single-molecule fluorescence imaging of GPCRs.

    PubMed

    Tian, He; Sakmar, Thomas P; Huber, Thomas

    2013-01-01

    Heptahelical G protein-coupled receptors (GPCRs) mediate transmembrane signal transduction to facilitate intercellular communication. GPCRs assemble in the membrane bilayer with a variety of cytoplasmic adapter and scaffold proteins to form molecular machines, or "signalosomes," which undergo complex dynamic assembly and disassembly reactions. Despite significant recent advances in structural studies of GPCRs and their associated cytoplasmic components, understanding transmembrane signaling in four dimensions with chemical precision requires new approaches. One promising approach to study allosteric effects involved in signalosome reaction pathways is to use multicolor single-molecule detection (SMD) fluorescence experiments in biochemically defined systems. We describe here the methodological foundation for automated, multicolor, single-molecule fluorescence studies of the structural and compositional dynamics of macromolecular complexes involved in signal transduction. We present a general, simple, and robust method for stoichiometric, site-specific fluorescence labeling of expressed GPCRs. The method is based on bioorthogonal conjugation of a fluorescent reporter group to a genetically encoded azido group introduced into expressed GPCRs using amber codon suppression. We then present a strategy to reconstitute labeled GPCRs in native-like membranes and to tether-oriented samples onto surfaces amenable for interrogation by total internal reflectance fluorescence (TIRF) spectroscopy. We describe how to assemble an automated four-color epifluorescence microscope with SMD-TIRF optics. Finally, we discuss how to adapt engineered samples for high-throughput imaging with the aim of understanding the kinetic relationships between ligand binding and the dynamic regulation of the GPCR signalosome.

  9. Predicting Electrophoretic Mobility of Protein-Ligand Complexes for Ligands from DNA-Encoded Libraries of Small Molecules.

    PubMed

    Bao, Jiayin; Krylova, Svetlana M; Cherney, Leonid T; Hale, Robert L; Belyanskaya, Svetlana L; Chiu, Cynthia H; Shaginian, Alex; Arico-Muendel, Christopher C; Krylov, Sergey N

    2016-05-17

    Selection of target-binding ligands from DNA-encoded libraries of small molecules (DELSMs) is a rapidly developing approach in drug-lead discovery. Methods of kinetic capillary electrophoresis (KCE) may facilitate highly efficient homogeneous selection of ligands from DELSMs. However, KCE methods require accurate prediction of electrophoretic mobilities of protein-ligand complexes. Such prediction, in turn, requires a theory that would be applicable to DNA tags of different structures used in different DELSMs. Here we present such a theory. It utilizes a model of a globular protein connected, through a single point (small molecule), to a linear DNA tag containing a combination of alternating double-stranded and single-stranded DNA (dsDNA and ssDNA) regions of varying lengths. The theory links the unknown electrophoretic mobility of protein-DNA complex with experimentally determined electrophoretic mobilities of the protein and DNA. Mobility prediction was initially tested by using a protein interacting with 18 ligands of various combinations of dsDNA and ssDNA regions, which mimicked different DELSMs. For all studied ligands, deviation of the predicted mobility from the experimentally determined value was within 11%. Finally, the prediction was tested for two proteins and two ligands with a DNA tag identical to those of DELSM manufactured by GlaxoSmithKline. Deviation between the predicted and experimentally determined mobilities did not exceed 5%. These results confirm the accuracy and robustness of our model, which makes KCE methods one step closer to their practical use in selection of drug leads, and diagnostic probes from DELSMs.

  10. Mechanical strain stimulates vasculogenesis and expression of angiogenesis guidance molecules of embryonic stem cells through elevation of intracellular calcium, reactive oxygen species and nitric oxide generation.

    PubMed

    Sharifpanah, Fatemeh; Behr, Sascha; Wartenberg, Maria; Sauer, Heinrich

    2016-12-01

    Differentiation of embryonic stem (ES) cells may be regulated by mechanical strain. Herein, signaling molecules underlying mechanical stimulation of vasculogenesis and expression of angiogenesis guidance cues were investigated in ES cell-derived embryoid bodies. Treatment of embryoid bodies with 10% static mechanical strain using a Flexercell strain system significantly increased CD31-positive vascular structures and the angiogenesis guidance molecules plexinB1, ephrin B2, neuropilin1 (NRP1), semaphorin 4D (sem4D) and robo4 as well as vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-BB (PDGF-BB) as evaluated by Western blot and real time RT-PCR. In contrast ephrin type 4 receptor B (EphB4) expression was down-regulated upon mechanical strain, indicating an arterial-type differentiation. Robo1 protein expression was modestly increased with no change in mRNA expression. Mechanical strain increased intracellular calcium as well as reactive oxygen species (ROS) and nitric oxide (NO). Mechanical strain-induced vasculogenesis was abolished by the NOS inhibitor L-NAME, the NADPH oxidase inhibitor VAS2870, upon chelation of intracellular calcium by BAPTA as well as upon siRNA inactivation of ephrin B2, NRP1 and robo4. BAPTA blunted the strain-induced expression of angiogenic growth factors, the increase in NO and ROS as well as the expression of NRP1, sem4D and plexinB1, whereas ephrin B2, EphB4 as well as robo1 and robo4 expression were not impaired. Mechanical strain stimulates vasculogenesis of ES cells by the intracellular messengers ROS, NO and calcium as well as by upregulation of angiogenesis guidance molecules and the angiogenic growth factors VEGF, FGF-2 and PDGF-BB. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Dual roles of the chemorepellent axon guidance molecule RGMa in establishing pioneering axon tracts and neural fate decisions in embryonic vertebrate forebrain.

    PubMed

    Lah, Grace J; Key, Brian

    2012-11-01

    Repulsive guidance molecule A (RGMa) is a glycosylphosphatidylinositol-anchored plasma membrane protein that was originally identified based on its chemorepulsive activity during axon navigation in the developing nervous system. Knock down of RGMa has previously shown to perturb axon navigation in the developing Xenopus forebrain (Wilson and Key, 2006). In order to further understand the in vivo role of RGMa in axon guidance, we have adopted an in vivo gain-of-function approach. RGMa was mosaically overexpressed in the developing Xenopus embryo by the injection of mRNA into single blastomeres. Ectopic expression of RGMa affected the morphology and the topography of developing axon tracts in vivo. Pioneer axons misrouted or aberrantly projected in response to ectopic RGMa in the developing Xenopus forebrain, confirming the in vivo chemorepulsive activity of this ligand. In addition, we show here for the first time that overexpression of RGMa acts cell-autonomously to generate ectopic neurons in the developing embryonic brain. Taken together, the current study reveals a pleiotropic role of RGMa in early vertebrate embryonic brain in the spatial organization of axon tracts, pioneer axon guidance, and neural cell differentiation.

  12. Development of hydrogel TentaGel shell-core beads for ultrahigh throughput solution-phase screening of encoded OBOC combinatorial small molecule libraries.

    PubMed

    Baek, Hyoung Gee; Liu, Ruiwu; Lam, Kit S

    2009-01-01

    The one-bead one-compound (OBOC) combinatorial library method enables the rapid generation and screening of millions of discrete chemical compounds on beads. Most of the OBOC screening methods require the library compounds to remain tethered to the bead during screening process. Methods have also been developed to release library compounds from immobilized beads for in situ solution phase or "lawn" assays. However, this latter approach, while extremely powerful, is severely limited by the lack of suitable solid supports for such assays. Here, we report on the development of a novel hydrogel TentaGel shell-core (HTSC) bead in which hydrogel is grafted onto the polystyrene-based TentaGel (TG) bead as an outer shell (5-80 mum thick) via free radical surface-initiated polymerization. This novel shell-core bilayer resin enables the preparation of encoded OBOC combinatorial small molecule libraries, such that the library compounds reside on the highly hydrophilic outer layer and the coding tags reside in the polystyrene-based TG core. Using fluorescein as a model small molecule compound, we have demonstrated that fluorescein molecules that have been linked covalently to the hydrogel shell via a disulfide bond could readily diffuse out of the hydrogel layer into the bead surrounding after reduction with dithiothreitol. In contrast, under identical condition, the released fluorescein molecules remained bound to unmodified TG bead. We have prepared an encoded OBOC small molecule library on the novel shell-core beads and demonstrated that the beads can be readily decoded.

  13. Development of Hydrogel TentaGel Shell-Core Beads for Ultra-high Throughput Solution Phase Screening of Encoded OBOC Combinatorial Small Molecule Libraries

    PubMed Central

    Gee Baek, Hyoung; Liu, Ruiwu; Lam, Kit S.

    2009-01-01

    The one-bead one-compound (OBOC) combinatorial library method enables the rapid generation and screening of millions of discrete chemical compounds on beads. Most of the OBOC screening methods require the library compounds to remain tethered to the bead during screening process. Methods have also been developed to release library compounds from immobilized beads for in situ solution phase or “lawn” assays. However, this latter approach, while extremely powerful, is severely limited by the lack of suitable solid supports for such assays. Here we report on the development of a novel hydrogel TentaGel shell-core (HTSC) bead in which hydrogel is grafted onto the polystyrene-based TentaGel® (TG) bead as an outer shell (5–80 µm thick), via free radical surface-initiated polymerization. This novel shell-core bilayer resin enables the preparation of encoded OBOC combinatorial small molecule libraries such that the library compounds reside on the highly hydrophilic outer layer and the coding tags reside in the polystyrene-based TG core. Using fluorescein as a model small molecule compound, we have demonstrated that fluorescein molecules that have been linked covalently to the hydrogel shell via a disulfide bond, could readily diffuse out of the hydrogel layer into the bead surrounding after reduction with dithiothreitol. In contrast, under identical condition, the released fluorescein molecules remained bound to unmodified TG bead. We have prepared an encoded OBOC small molecule library on the novel shell-core beads and demonstrated that the beads can be readily decoded. PMID:19061339

  14. Structure-Activity Relation of AMOR Sugar Molecule That Activates Pollen-Tubes for Ovular Guidance1[OPEN

    PubMed Central

    Mizukami, Akane G.; Yamguchi, Junichiro

    2017-01-01

    Successful fertilization in flowering plants depends on the precise directional growth control of pollen tube through the female pistil tissue toward the female gametophyte contained in the ovule for delivery of nonmotile sperm cells. Cys-rich peptides LUREs secreted from the synergid cells on either side of the egg cell act as ovular attractants of pollen tubes. Competency control by the pistil is crucial for the response of pollen tubes to these ovular attractants. We recently reported that ovular 4-O-methyl-glucuronosyl arabinogalactan (AMOR) induces competency of the pollen tube to respond to ovular attractant LURE peptides in Torenia fournieri. The beta isomer of the terminal disaccharide 4-O-methyl-glucuronosyl galactose was essential and sufficient for the competency induction. However, critical and noncritical structures in the disaccharide have not been dissected deeply. Herein, we report the synthesis of new AMOR analogs and the structure-activity relationships for AMOR activity in the presence of these synthesized analogs. Removal of 4-O-methyl group or –COOH from the glucuronosyl residue of the disaccharide dramatically reduces AMOR activity. The pyranose backbone of the second sugar of disaccharide is essential for the activity but not hydroxy groups. The role of beta isomer of the disaccharide 4-Me-GlcA-β(1,6)-Gal is very specific for competency control, as there was no difference in effect among the sugar analogs tested for pollen germination. This study represents the first structure-activity relationship study, to our knowledge, of a sugar molecule involved in plant reproduction, which opens a way for modification of the molecule without loss of activity. PMID:27913739

  15. Peripheral T Cell Survival Requires Continual Ligation of the T Cell Receptor to Major Histocompatibility Complex–Encoded Molecules

    PubMed Central

    Kirberg, Jörg; Berns, Anton; Boehmer, Harald von

    1997-01-01

    In the thymus, T cells are selected according to their T cell receptor (TCR) specificity. After positive selection, mature cells are exported from primary lymphoid organs to seed the secondary lymphoid tissue. An important question is whether survival of mature T cells is an intrinsic property or requires continuous survival signals, i.e., engagement of the TCR by major histocompatibility complex (MHC) molecules in the periphery, perhaps in a similar way as occurring during thymic positive selection. To address this issue we used recombination-activating gene (Rag)-deficient H-2b mice expressing a transgenic TCR restricted by I-Ed class II MHC molecules. After engraftment with Rag−/− H-2d fetal thymi, CD4+8− peripheral T cells emerged. These cells were isolated and transferred into immunodeficient hosts of H-2b or H-2d haplotype, some of the latter being common cytokine receptor γ chain deficient to exclude rejection of H-2b donor cells by host natural killer cells. Our results show that in the absence, but not in the presence, of selecting MHC molecules, peripheral mature T cells are short lived and disappear within 7 wk, indicating that continuous contact of the TCR with selecting MHC molecules is required for survival of T cells. PMID:9334366

  16. Cloning and characterization of the 2B4 gene encoding a molecule associated with non-MHC-restricted killing mediated by activated natural killer cells and T cells

    SciTech Connect

    Mathew, P.A.; Garni-Wagner, B.A.; Land, K.; Takashima, A.; Stoneman, E.; Bennett, M.; Kumar, V. )

    1993-11-15

    The authors have recently described a signal transducing molecule, 2B4, expressed on all NK and T cells that mediate non-MHC-restricted killing. The gene encoding this molecule was cloned and its nucleotide sequence determined. The encoded protein of 398 amino acids has a leader peptide of 18 amino acids and a transmembrane region of 24 amino acids. The predicted protein has eight N-linked glycosylation sites, suggesting that it is highly glycosylated. Comparison of 2B4 with sequences in the databanks indicates that 2B4 is a member of the Ig supergene family, and it shows homology to murine and rat CD48 and human LFA-3. Northern blot analysis has shown at least three transcripts for 2B4 in adherent lymphokine-activated killer cells of several mouse strains and TCR-[gamma]/[delta] dendritic epidermal T cell lines but not in allospecific T cell clones. These three mRNA are the products of differential splicing of heterogeneous nuclear RNA. Southern blot analysis of genomic DNA from several mouse strains revealed that 2B4 belongs to a family of closely related genes. The 2B4 gene has been mapped to mouse chromosome 1 by analysis of 2B4 expression in recombinant inbred mouse strains. 48 refs., 6 figs., 2 tabs.

  17. Genomic clone encoding the. cap alpha. chain of the OKM1, LFA-1, and platelet glycoprotein IIb-IIIa molecules

    SciTech Connect

    Cosgrove, L.J.; Sandrin, M.S.; Rajasekariah, P.; McKenzie, I.F.C.

    1986-02-01

    LFA-1, an antigen involved in cytolytic T lymphocyte-mediated killing, and Mac-1, the receptor for complement component C3bi, constitute a family of structurally and functionally related cell surface glycoproteins involved in cellular interactions. In both mouse and man, Mac-1 (OKM1) and LFA-1 share a common 95-kDa ..beta.. subunit but are distinguished by their ..cap alpha.. chains, which have different cellular distributions, apparent molecular masses (165 and 177 kDa, respectively), and peptide maps. The authors report the isolation of a genomic clone from a human genomic library that on transfection into mouse fibroblasts produced a molecule(s) reactive with monoclonal antibodies to OKM1, to LFA-1, and to platelet glycoprotein IIb-IIIa. This gene was cloned by several cycles of transfection of L cells with a human genomic library cloned in lambda phase Charon 4A and subsequent rescue of the lambda phage. Transfection with the purified recombinant lambda DNA yielded a transfectant that expressed the three human ..cap alpha.. chains of OKM1, LFA-1, and glycoprotein IIb-IIIa, presumably in association with the murine ..beta.. chain.

  18. Apparent HLA DR triplet due to the coexpression of a DRB5-encoded molecule on a DR1 haplotype.

    PubMed

    Gebuhrer, L; Tiercy, J M; Freidel, A C; Labonne, M P; Lambert, J; Jeannet, M; Betuel, H

    1992-06-01

    HLA DR1 molecules are coded by a single polymorphic DRB1 gene. We have observed rare DR1 cells in one Caucasoid family and three unrelated individuals that also reacted with some anti-DR2 sera. Since the second DR antigen was normally expressed, these cells appeared as triplets. Contrary to serology, the cells were not typed by HTCs defining Dw2, Dw12, and Dw21. Further investigations on these unusual DR1+2* haplotypes were conducted by DNA oligotyping and by sequencing of the DRB first-domain exon. The results showed that these DR1 haplotypes, besides their DRB1*0101 allele, carried also a DRB5*0101 allele.

  19. A pAD1-Encoded Small RNA Molecule, mD, Negatively Regulates Enterococcus faecalis Pheromone Response by Enhancing Transcription Termination

    PubMed Central

    Tomita, Haruyoshi; Clewell, Don B.

    2000-01-01

    pAD1 is a 60-kb hemolysin-bacteriocin plasmid in Enterococcus faecalis that encodes a conjugative mating response to a peptide sex pheromone, cAD1, secreted by plasmid-free bacteria. The pheromone response is regulated by two proteins: TraE1, which positively regulates all or most conjugative structural genes, and TraA, which negatively regulates traE1. TraA binds to pAD1 DNA at the iad (encoding the inhibitor peptide iAD1) promoter but is released upon binding to imported pheromone. This leads to enhanced transcription through two closely spaced downstream terminators (t1 and t2) into traE1. TraE1 is believed to then upregulate itself from a site located within t2; thus, a small amount of transcription through t1-t2 could lead to overall induction. It is important therefore that the t1-t2 terminators be tightly controlled to keep the response shut down in the absence of pheromone. A small (200-nucleotide) RNA molecule designated mD is encoded just upstream of t1 by a determinant (traD) oriented in the direction opposite to that of transcripts utilizing t1. mD is expressed at high levels in the uninduced state, but it decreases significantly upon induction. Here we present results of genetic studies relating to the activity of t1-t2 and show that mD strongly enhances transcriptional termination at t1. The mD activity is shown to influence transcription well downstream and can affect the determinant for aggregation substance asa1. The phenomenon is specific in that there is no effect of mD on the unrelated pheromone-responding plasmids pPD1 and pCF10. PMID:10648533

  20. Discovery of highly potent and selective small molecule ADAMTS-5 inhibitors that inhibit human cartilage degradation via encoded library technology (ELT).

    PubMed

    Deng, Hongfeng; O'Keefe, Heather; Davie, Christopher P; Lind, Kenneth E; Acharya, Raksha A; Franklin, G Joseph; Larkin, Jonathan; Matico, Rosalie; Neeb, Michael; Thompson, Monique M; Lohr, Thomas; Gross, Jeffrey W; Centrella, Paolo A; O'Donovan, Gary K; Bedard, Katie L Sargent; van Vloten, Kurt; Mataruse, Sibongile; Skinner, Steven R; Belyanskaya, Svetlana L; Carpenter, Tiffany Y; Shearer, Todd W; Clark, Matthew A; Cuozzo, John W; Arico-Muendel, Christopher C; Morgan, Barry A

    2012-08-23

    The metalloprotease ADAMTS-5 is considered a potential target for the treatment of osteoarthritis. To identify selective inhibitors of ADAMTS-5, we employed encoded library technology (ELT), which enables affinity selection of small molecule binders from complex mixtures by DNA tagging. Selection of ADAMTS-5 against a four-billion member ELT library led to a novel inhibitor scaffold not containing a classical zinc-binding functionality. One exemplar, (R)-N-((1-(4-(but-3-en-1-ylamino)-6-(((2-(thiophen-2-yl)thiazol-4-yl)methyl)amino)-1,3,5-triazin-2-yl)pyrrolidin-2-yl)methyl)-4-propylbenzenesulfonamide (8), inhibited ADAMTS-5 with IC(50) = 30 nM, showing >50-fold selectivity against ADAMTS-4 and >1000-fold selectivity against ADAMTS-1, ADAMTS-13, MMP-13, and TACE. Extensive SAR studies showed that potency and physicochemical properties of the scaffold could be further improved. Furthermore, in a human osteoarthritis cartilage explant study, compounds 8 and 15f inhibited aggrecanase-mediated (374)ARGS neoepitope release from aggrecan and glycosaminoglycan in response to IL-1β/OSM stimulation. This study provides the first small molecule evidence for the critical role of ADAMTS-5 in human cartilage degradation.

  1. Cell-Based Selection Expands the Utility of DNA-Encoded Small-Molecule Library Technology to Cell Surface Drug Targets: Identification of Novel Antagonists of the NK3 Tachykinin Receptor.

    PubMed

    Wu, Zining; Graybill, Todd L; Zeng, Xin; Platchek, Michael; Zhang, Jean; Bodmer, Vera Q; Wisnoski, David D; Deng, Jianghe; Coppo, Frank T; Yao, Gang; Tamburino, Alex; Scavello, Genaro; Franklin, G Joseph; Mataruse, Sibongile; Bedard, Katie L; Ding, Yun; Chai, Jing; Summerfield, Jennifer; Centrella, Paolo A; Messer, Jeffrey A; Pope, Andrew J; Israel, David I

    2015-12-14

    DNA-encoded small-molecule library technology has recently emerged as a new paradigm for identifying ligands against drug targets. To date, this technology has been used with soluble protein targets that are produced and used in a purified state. Here, we describe a cell-based method for identifying small-molecule ligands from DNA-encoded libraries against integral membrane protein targets. We use this method to identify novel, potent, and specific inhibitors of NK3, a member of the tachykinin family of G-protein coupled receptors (GPCRs). The method is simple and broadly applicable to other GPCRs and integral membrane proteins. We have extended the application of DNA-encoded library technology to membrane-associated targets and demonstrate the feasibility of selecting DNA-tagged, small-molecule ligands from complex combinatorial libraries against targets in a heterogeneous milieu, such as the surface of a cell.

  2. Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM.

    PubMed Central

    Hemperly, J J; Murray, B A; Edelman, G M; Cunningham, B A

    1986-01-01

    Purified fractions of the neural cell-adhesion molecule N-CAM from embryonic chicken brain contain two similar polypeptides (Mr, 160,000 and 130,000), each containing an amino-terminal external binding region, a carbohydrate-rich central region, and a carboxyl-terminal region that is associated with the cell. Previous studies indicate that the two polypeptides arise by alternative splicing of mRNAs transcribed from a single gene. We report here the 3556-nucleotide sequence of a cDNA clone (pEC208) that encodes 964 amino acids from the carbohydrate and cell-associated domains of the larger N-CAM polypeptide followed by 664 nucleotides of 3' untranslated sequence. The predicted protein sequence contains attachment sites for polysialic acid-containing oligosaccharides, four tandem homologous regions of polypeptide resembling those seen in the immunoglobulin superfamily, and a single hydrophobic sequence that appears to be the membrane-spanning segment. The cytoplasmic domain carboxyl terminal to this segment includes a block of approximately equal to 250 amino acids present in the larger but not in the smaller N-CAM polypeptide. We designate these the ld (large domain) polypeptide and the sd (small domain) polypeptide. The intracellular domains of the ld and sd polypeptides are likely to be critical for cell-surface modulation of N-CAM by interacting in a differential fashion with other intrinsic proteins or with the cytoskeleton. PMID:3458261

  3. Policy & Guidance

    EPA Pesticide Factsheets

    Policy documents represent EPA's official interpretation or view of specific issues. Guidance documents are published to further clarify regulations and to assist in implementation of environmental regulations.

  4. A microfluidics-based turning assay reveals complex growth cone responses to integrated gradients of substrate-bound ECM molecules and diffusible guidance cues.

    PubMed

    Joanne Wang, C; Li, Xiong; Lin, Benjamin; Shim, Sangwoo; Ming, Guo-Li; Levchenko, Andre

    2008-02-01

    Neuronal growth cones contain sophisticated molecular machinery precisely regulating their migration in response to complex combinatorial gradients of diverse external cues. The details of this regulation are still largely unknown, in part due to limitations of the currently available experimental techniques. Microfluidic devices have been shown to be capable of generating complex, stable and precisely controlled chemical gradients, but their use in studying growth cone migration has been limited in part due to the effects of shear stress. Here we describe a microfluidics-based turning-assay chip designed to overcome this issue. In addition to generating precise gradients of soluble guidance cues, the chip can also fabricate complex composite gradients of diffusible and surface-bound guidance cues that mimic the conditions the growth cones realistically counter in vivo. Applying this assay to Xenopus embryonic spinal neurons, we demonstrate that the presence of a surface-bound laminin gradient can finely tune the polarity of growth cone responses (repulsion or attraction) to gradients of brain-derived neurotrophic factor (BDNF), with the guidance outcome dependent on the mean BDNF concentration. The flexibility inherent in this assay holds significant potential for refinement of our understanding of nervous system development and regeneration, and can be extended to elucidate other cellular processes involving chemotaxis of shear sensitive cells.

  5. A Role of Staphyococcus aureus, Interleukin-18, Nerve Growth Factor and Semaphorin 3A, an Axon Guidance Molecule, in Pathogenesis and Treatment of Atopic Dermatitis

    PubMed Central

    Komori, Junko; Ikezawa, Yuko; Inoue, Yusuke; Kirino, Mio; Katsuyama, Masako; Aihara, Michiko

    2010-01-01

    (F) and xylitol (X) synergistically inhibited biofilm formation by SA, and indeed the ratio of SA in total bacteria at sites to which the FX cream containing F and X had been applied was significantly decreased 1 week later, accompanied with improvement of AD, when compared with that before application and at placebo sites. Therefore, the FX cream is a useful skin-care agent for atopic dry skin colonized by SA. The nerve growth factor (NGF) in the horny layer (the horn NGF) of skin lesions on the cubital fossa was collected by tape stripping and measured using ELISA in AD patients before and after 2 and 4 weeks treatments. Simultaneously, the itch and eruptions on the whole body and on the lesions, in which the horn NGF was measured, were recorded, and also the peripheral blood eosinophil count, serum LDH level and serum total IgE level were examined. The level of NGF was significantly higher in AD patients than in healthy controls, correlated with the severity of itch, erythema, scale/xerosis, the eosinophil count and LDH level, and also significantly decreased after treatments with olopatadine and/or steroid ointment for 2 and 4 weeks. Therefore, the measurement of the NGF by this harmless method seems to be useful to assess the severity of AD and the therapeutic effects on AD. In AD patients, C-fiber in the epidermis increase and sprout, inducing hypersensitivity, which is considered to aggravate the disease. Semaphorin 3A (Sema3A), an axon guidance molecule, is a potent inhibitor of neurite outgrowth of sensory neurons. We administered recombinant Sema3A intracutaneously into the skin lesions of NC/Nga mice, an animal model of AD, and investigated the effect of Sema3A on the skin lesions and their itch. Sema3A dose-dependently improved skin lesions and attenuated the scratching behavior in NC/Nga mice. Histological examinations revealed a decrease in the epidermal thickness, the density of invasive nerve fibers in the epidermis, inflammatory infiltrate including

  6. Image Guidance

    EPA Pesticide Factsheets

    Guidance that explains the process for getting images approved in One EPA Web microsites and resource directories. includes an appendix that shows examples of what makes some images better than others, how some images convey meaning more than others

  7. Differences defined by bone marrow transplantation suggest that lpr and gld are mutations of genes encoding an interacting pair of molecules.

    PubMed

    Allen, R D; Marshall, J D; Roths, J B; Sidman, C L

    1990-11-01

    Homozygosity for either of the lymphoproliferation (lpr) or generalized lymphoproliferative disease (gld) mutations of mice causes the development of systemic lupus erythematosus-like autoimmune syndromes that are characterized by severe lymphadenopathy and highly elevated serum immunoglobulin levels. Although the mutations are nonallelic, analysis of homozygous lpr/lpr and gld/gld mice on the same strain background has indicated that the pathology and severity of the autoimmune syndromes induced by these mutations are indistinguishable. To explain this, it has previously been suggested that lpr and gld may represent mutations in molecules involved in sequential steps of an intracellular metabolic pathway of T cells. We have now investigated the behavior of both lpr and gld in a variety of bone marrow chimeras and have found that functional differences between lpr and gld become apparent after bone marrow transfer. Transfer of lpr/lpr bone marrow to irradiated congenic +/+ recipients caused the development of a graft-vs.-host-like lymphoid wasting syndrome, whereas transfer of gld/gld bone marrow to +/+ recipients resulted in development of a gld-like autoimmune syndrome. Additionally, gld/gld hosts behaved like +/+ hosts irrespective of the genotype of the donor bone marrow, whereas lpr/lpr hosts behaved unlike +/+ hosts when reconstituted with either lpr/lpr, gld/gld, or +/+ bone marrow. These are the first clear differences between these two mutations yet described. Our studies indicate that the molecule altered by the gld mutation is expressed only by bone marrow-derived cells, whereas the molecule altered by the lpr mutation is expressed by both bone marrow-derived cells and by one or more peripheral radioresistant cell populations. To reconcile these differences with the fact that homozygous lpr/lpr and gld/gld mice are indistinguishable, we suggest an alternative model for the relationship between the lpr and gld mutations in which the two molecules affected

  8. Mitochondrial genome of the moon jelly Aurelia aurita (Cnidaria, Scyphozoa): A linear DNA molecule encoding a putative DNA-dependent DNA polymerase.

    PubMed

    Shao, Zhiyong; Graf, Shannon; Chaga, Oleg Y; Lavrov, Dennis V

    2006-10-15

    The 16,937-nuceotide sequence of the linear mitochondrial DNA (mt-DNA) molecule of the moon jelly Aurelia aurita (Cnidaria, Scyphozoa) - the first mtDNA sequence from the class Scypozoa and the first sequence of a linear mtDNA from Metazoa - has been determined. This sequence contains genes for 13 energy pathway proteins, small and large subunit rRNAs, and methionine and tryptophan tRNAs. In addition, two open reading frames of 324 and 969 base pairs in length have been found. The deduced amino-acid sequence of one of them, ORF969, displays extensive sequence similarity with the polymerase [but not the exonuclease] domain of family B DNA polymerases, and this ORF has been tentatively identified as dnab. This is the first report of dnab in animal mtDNA. The genes in A. aurita mtDNA are arranged in two clusters with opposite transcriptional polarities; transcription proceeding toward the ends of the molecule. The determined sequences at the ends of the molecule are nearly identical but inverted and lack any obvious potential secondary structures or telomere-like repeat elements. The acquisition of mitochondrial genomic data for the second class of Cnidaria allows us to reconstruct characteristic features of mitochondrial evolution in this animal phylum.

  9. The T cell response to allelic determinants on Igh-1-encoded IgG2a antibodies: dual recognition examined by using antigenic antibodies with binding affinity for Ia molecules.

    PubMed

    Hedrick, S M; Schwartz, R H

    1983-04-01

    In this report we examine the effects of binding antigen directly to Ia molecules during immunization and stimulation of T cells in culture. To accomplish this we characterize the T cell response to Igh-1j-encoded IgG2a antibodies in C57BL/10 H-2 congenic mice. In contrast to the response to the closely related Igh-1a-encoded IgG2a antibodies, high responder mice were (C57BL/10 X B10.A)F1 hybrids, and the important alleles appeared to map to I-Ab and I-Ak. C57BL/10 and B10.A(5R) strains were low responders (I-Ab), and B10.A and B10.A(4R) strains were nonresponders (I-Ak). The interest in using monoclonal IgG2a antibodies as T cell antigens was that different V-region-encoded binding specificities could be associated with the same IgG2a antigenic determinant. In our interpretation of the Langman and Cohn dual binding site model of the T cell receptor, the response to anti-Ia antibody should have some of the same characteristics as that to an allogeneic Ia molecule; in particular, it should be non-H-2-restricted. Although the response to anti-Ia antibody had several interesting properties, no difference in the restriction specificity was found for the T cell response to anti-Ia antibodies relative to unreactive IgG2a antibodies. Our conclusion is that T cell receptors must bind both Ia and antigen molecules for activation to occur. In a separate set of experiments, the T cell response resulting from immunization with anti-Ia antibody was examined. Because the antigen was shown to be associated with the Ia molecule during immunization, experiments were designed to detect an alteration or lack of H-2 restriction in the resulting T cell population. A long-term T cell line induced after such immunization showed no qualitative differences from a T cell line produced with unreactive IgG2a antibody. These results demonstrate that simply attaching a foreign antigen to a restriction element is not sufficient to lead to unrestricted T cell activation. This in turn suggests the

  10. A molecule in teleost fish, related with human MHC-encoded G6F, has a cytoplasmic tail with ITAM and marks the surface of thrombocytes and in some fishes also of erythrocytes.

    PubMed

    Ohashi, Ken; Takizawa, Fumio; Tokumaru, Norihiro; Nakayasu, Chihaya; Toda, Hideaki; Fischer, Uwe; Moritomo, Tadaaki; Hashimoto, Keiichiro; Nakanishi, Teruyuki; Dijkstra, Johannes Martinus

    2010-08-01

    In teleost fish, a novel gene G6F-like was identified, encoding a type I transmembrane molecule with four extracellular Ig-like domains and a cytoplasmic tail with putative tyrosine phosphorylation motifs including YxN and an immunoreceptor tyrosine-based activation motif (ITAM). G6F-like maps to a teleost genomic region where stretches corresponding to human chromosomes 6p (with the MHC), 12p (with CD4 and LAG-3), and 19q are tightly linked. This genomic organization resembles the ancestral "Ur-MHC" proposed for the jawed vertebrate ancestor. The deduced G6F-like molecule shows sequence similarity with members of the CD4/LAG-3 family and with the human major histocompatibility complex-encoded thrombocyte marker G6F. Despite some differences in molecular organization, teleost G6F-like and tetrapod G6F seem orthologous as they map to similar genomic location, share typical motifs in transmembrane and cytoplasmic regions, and are both expressed by thrombocytes/platelets. In the crucian carps goldfish (Carassius auratus auratus) and ginbuna (Carassius auratus langsdorfii), G6F-like was found expressed not only by thrombocytes but also by erythrocytes, supporting that erythroid and thromboid cells in teleost fish form a hematopoietic lineage like they do in mammals. The ITAM-bearing of G6F-like suggests that the molecule plays an important role in cell activation, and G6F-like expression by erythrocytes suggests that these cells have functional overlap potential with thrombocytes.

  11. Polymorphisms in host genes encoding NOSII, C-reactive protein, and adhesion molecules thrombospondin and E-selectin are risk factors for Plasmodium falciparum malaria in India.

    PubMed

    Kanchan, K; Pati, S S; Mohanty, S; Mishra, S K; Sharma, S K; Awasthi, S; Venkatesh, V; Habib, S

    2015-10-01

    Cytoadherence of Plasmodium falciparum-infected red blood cells (RBCs) in host microvasculature and complex regulation of the immune response are important contributors to the clinical outcome of disease. We tested the association of 23 single nucleotide polymorphisms (SNPs) and a microsatellite repeat in adhesion molecule genes THBS1 and ESEL, and immune regulatory molecule genes NOSII, CRP, and MBL2 with falciparum malaria in populations residing in a malaria-endemic and a non-endemic region of India. The THBS1 haplotype CCCCA (rs1478604, rs7170682, rs2664141, rs12912082, rs3743125) was a risk factor in the endemic region (relative risk = 3.78) and an ESEL SNP (rs5368, His468Tyr) associated with cerebral malaria (CM) [CM vs. non-cerebral malaria (NCM), odds ratio (OR) = 2.23, p = 0.03]. In the non-endemic region, an ESEL 3'UTR SNP (rs5359) associated with enhanced risk of disease (OR = 3.62, p = 1 × 10(-4)) and the CT genotype of the CRP promoter SNP (C/T/A) strongly associated with protection (severe vs. control, OR = 0.29, p = 6 × 10(-5)). Long repeat alleles of the NOSII promoter microsatellite (CCTTT)n exhibited strong association with protection and the NOSII ATG haplotype (rs3729508, rs2297520, rs9282801) was strongly protective against severe malaria in both regions (endemic, severe vs. control, OR = 0.05, p = 0.0001; non-endemic, severe vs. control, OR = 0.3, p = 1 × 10(-5)). Our results suggest differential contribution of variants of the investigated genes in determining the outcome of malaria in Indian populations.

  12. HLA-DQA2 and HLA-DQB2 genes are specifically expressed in human Langerhans cells and encode a new HLA class II molecule.

    PubMed

    Lenormand, Cedric; Bausinger, Huguette; Gross, Florence; Signorino-Gelo, Francois; Koch, Susanne; Peressin, Maryse; Fricker, Dominique; Cazenave, Jean-Pierre; Bieber, Thomas; Hanau, Daniel; de la Salle, Henri; Tourne, Sylvie

    2012-04-15

    The precise role of human epidermal Langerhans cells (LCs) in immune response is highly controversial. While studying the gene expression profile of these cells, we were intrigued to identify the HLA-DQB2 gene as potentially expressed in LCs. Despite a strong evolutionary conservation of their sequences, the concomitant expression of the poorly polymorphic HLA-DQA2/HLA-DQB2 genes, paralogous to the HLA-DQA1/HLA-DQB1 genes, has never been detected in any cell type. We confirmed by RT-PCR that the HLA-DQA2 and -DQB2 genes are both expressed in LCs, but not in monocyte-derived dendritic cells, or in blood CD1c(+) or plasmacytoid dendritic cells. The presence of the HLA-DQβ2 chain in LCs could be demonstrated by Western blotting, whereas immunofluorescence revealed its localization in early endosomes. As in the case of other HLA class II molecules, the HLA-DQα2 and -DQβ2 chains formed heterodimers that had to associate with the invariant chain to reach endosomal compartments. HLA-DQα2/β2 heterodimers were expressed at the cell surface, where they could mediate staphylococcal superantigen stimulation of T cells. Interestingly, HLA-DQα2 and HLA-DQβ1 chains formed mixed heterodimers which efficiently left the endoplasmic reticulum. These observations strongly suggest that the poorly polymorphic HLA-DQA2 and -DQB2 genes should be considered to be of immunological importance. The HLA-DQα2/β2 molecules could influence the complexity of the repertoire of Ags presented by LCs.

  13. Where does axon guidance lead us?

    PubMed Central

    Stoeckli, Esther

    2017-01-01

    During neural circuit formation, axons need to navigate to their target cells in a complex, constantly changing environment. Although we most likely have identified most axon guidance cues and their receptors, we still cannot explain the molecular background of pathfinding for any subpopulation of axons. We lack mechanistic insight into the regulation of interactions between guidance receptors and their ligands. Recent developments in the field of axon guidance suggest that the regulation of surface expression of guidance receptors comprises transcriptional, translational, and post-translational mechanisms, such as trafficking of vesicles with specific cargos, protein-protein interactions, and specific proteolysis of guidance receptors. Not only axon guidance molecules but also the regulatory mechanisms that control their spatial and temporal expression are involved in synaptogenesis and synaptic plasticity. Therefore, it is not surprising that genes associated with axon guidance are frequently found in genetic and genomic studies of neurodevelopmental disorders. PMID:28163913

  14. Molecular cloning and cold shock induced overexpression of the DNA encoding phor sensor domain from Mycobacterium tuberculosis as a target molecule for novel anti-tubercular drugs

    NASA Astrophysics Data System (ADS)

    Langi, Gladys Emmanuella Putri; Moeis, Maelita R.; Ihsanawati, Giri-Rachman, Ernawati Arifin

    2014-03-01

    Mycobacterium tuberculosis (Mtb), the sole cause of Tuberculosis (TB), is still a major global problem. The discovery of new anti-tubercular drugs is needed to face the increasing TB cases, especially to prevent the increase of cases with resistant Mtb. A potential novel drug target is the Mtb PhoR sensor domain protein which is the histidine kinase extracellular domain for receiving environmental signals. This protein is the initial part of the two-component system PhoR-PhoP regulating 114 genes related to the virulence of Mtb. In this study, the gene encoding PhoR sensor domain (SensPhoR) was subcloned from pGEM-T SensPhoR from the previous study (Suwanto, 2012) to pColdII. The construct pColdII SensPhoR was confirmed through restriction analysis and sequencing. Using the construct, SensPhoR was overexpressed at 15°C using Escherichia coli BL21 (DE3). Low temperature was chosen because according to the solubility prediction program of recombinant proteins from The University of Oklahama, the PhoR sensor domain has a chance of 79.8% to be expressed as insoluble proteins in Escherichia coli's (E. coli) cytoplasm. This prediction is also supported by other similar programs: PROSO and PROSO II. The SDS PAGE result indicated that the PhoR sensor domain recombinant protein was overexpressed. For future studies, this protein will be purified and used for structure analysis which can be used to find potential drugs through rational drug design.

  15. Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule

    SciTech Connect

    Dunne, P. Owen, M.J.; Hanby, A.M.; Poulsom, R.

    1995-11-20

    FAT, a new member of the human cadherin super-family, has been isolated from the T-leukemia cell line J6. The predicted protein closely resembles the Drosophila tumor suppressor fat, which is essential for controlling cell proliferation during Drosophila development. The gene has the potential to encode a large transmembrane protein of nearly 4600 residues with 34 tandem cadherin repeats, five EGF-like repeats, and a laminin A-G domain. The cytoplasmic sequence contains two domains with distant homology to the cadherin catenin-binding region. Northern blotting analysis of J6 mRNA demonstrated full-length, approximately 15-kb, FAT message in addition to several 5{prime}-truncated transcripts. In addition to its presence in J6 cells, in situ hybridization revealed FAT mRNA expression in epithelia and in some mesenchymal compartments. Furthermore, higher levels of expression were observed in fetal, as opposed to adult, tissue, suggesting that its expression may be developmentally regulated in these tissues. FAT shows homologies with a number of proteins important in developmental decisions and cell:cell communication and is the first fat-like protein reported in vertebrates. The gene encoding FAT was located by in situ hybridization on chromosome 4q34-q35. We propose that this family of molecules is likely to be important in mammalian developmental processes and cell communication. 80 refs., 10 figs., 1 tab.

  16. Forward Genetic Screening Identifies a Small Molecule That Blocks Toxoplasma gondii Growth by Inhibiting Both Host- and Parasite-Encoded Kinases

    PubMed Central

    Brown, Kevin M.; Suvorova, Elena; Farrell, Andrew; McLain, Aaron; Dittmar, Ashley; Wiley, Graham B.; Marth, Gabor; Gaffney, Patrick M.; Gubbels, Marc Jan; White, Michael; Blader, Ira J.

    2014-01-01

    The simultaneous targeting of host and pathogen processes represents an untapped approach for the treatment of intracellular infections. Hypoxia-inducible factor-1 (HIF-1) is a host cell transcription factor that is activated by and required for the growth of the intracellular protozoan parasite Toxoplasma gondii at physiological oxygen levels. Parasite activation of HIF-1 is blocked by inhibiting the family of closely related Activin-Like Kinase (ALK) host cell receptors ALK4, ALK5, and ALK7, which was determined in part by use of an ALK4,5,7 inhibitor named SB505124. Besides inhibiting HIF-1 activation, SB505124 also potently blocks parasite replication under normoxic conditions. To determine whether SB505124 inhibition of parasite growth was exclusively due to inhibition of ALK4,5,7 or because the drug inhibited a second kinase, SB505124-resistant parasites were isolated by chemical mutagenesis. Whole-genome sequencing of these mutants revealed mutations in the Toxoplasma MAP kinase, TgMAPK1. Allelic replacement of mutant TgMAPK1 alleles into wild-type parasites was sufficient to confer SB505124 resistance. SB505124 independently impacts TgMAPK1 and ALK4,5,7 signaling since drug resistant parasites could not activate HIF-1 in the presence of SB505124 or grow in HIF-1 deficient cells. In addition, TgMAPK1 kinase activity is inhibited by SB505124. Finally, mice treated with SB505124 had significantly lower tissue burdens following Toxoplasma infection. These data therefore identify SB505124 as a novel small molecule inhibitor that acts by inhibiting two distinct targets, host HIF-1 and TgMAPK1. PMID:24945800

  17. Functional diversity of Robo receptor immunoglobulin domains promotes distinct axon guidance decisions.

    PubMed

    Evans, Timothy A; Bashaw, Greg J

    2010-03-23

    Recognition molecules of the immunoglobulin (Ig) superfamily control axon guidance in the developing nervous system. Ig-like domains are among the most widely represented protein domains in the human genome, and the number of Ig superfamily proteins is strongly correlated with cellular complexity. In Drosophila, three Roundabout (Robo) Ig superfamily receptors respond to their common Slit ligand to regulate axon guidance at the midline: Robo and Robo2 mediate midline repulsion, Robo2 and Robo3 control longitudinal pathway selection, and Robo2 can promote midline crossing. How these closely related receptors mediate distinct guidance functions is not understood. We report that the differential functions of Robo2 and Robo3 are specified by their ectodomains and do not reflect differences in cytoplasmic signaling. Functional modularity of Robo2's ectodomain facilitates multiple guidance decisions: Ig1 and Ig3 of Robo2 confer lateral positioning activity, whereas Ig2 confers promidline crossing activity. Robo2's distinct functions are not dependent on greater Slit affinity but are instead due in part to differences in multimerization and receptor-ligand stoichiometry conferred by Robo2's Ig domains. Together, our findings suggest that diverse responses to the Slit guidance cue are imparted by intrinsic structural differences encoded in the extracellular Ig domains of the Robo receptors.

  18. Molecular mechanisms of optic axon guidance

    NASA Astrophysics Data System (ADS)

    Inatani, Masaru

    2005-12-01

    Axon guidance is one of the critical processes during vertebrate central nervous system (CNS) development. The optic nerve, which contains the axons of retinal ganglion cells, has been used as a powerful model to elucidate some of the mechanisms underlying axon guidance because it is easily manipulated experimentally, and its function is well understood. Recent molecular biology studies have revealed that numerous guidance molecules control the development of the visual pathway. This review introduces the molecular mechanisms involved in each critical step during optic axon guidance. Axonal projections to the optic disc are thought to depend on adhesion molecules and inhibitory extracellular matrices such as chondroitin sulfate. The formation of the head of the optic nerve and the optic chiasm require ligand-receptor interactions between netrin-1 and the deleted in colorectal cancer receptor, and Slit proteins and Robo receptors, respectively. The gradient distributions of ephrin ligands and Eph receptors are essential for correct ipsilateral projections at the optic chiasm and the topographic mapping of axons in the superior colliculus/optic tectum. The precise gradient is regulated by transcription factors determining the retinal dorso-ventral and nasal-temporal polarities. Moreover, the axon guidance activities by Slit and semaphorin 5A require the existence of heparan sulfate, which binds to numerous guidance molecules. Recent discoveries about the molecular mechanisms underlying optic nerve guidance will facilitate progress in CNS developmental biology and axon-regeneration therapy.

  19. An ankyrin-related gene (unc-44) is necessary for proper axonal guidance in Caenorhabditis elegans

    PubMed Central

    1995-01-01

    Caenorhabditis elegans unc-44 mutations result in aberrant axon guidance and fasciculation with inappropriate partners. The unc-44 gene was cloned by transposon tagging, and verified by genetic and molecular analyses of six transposon-induced alleles and their revertants. Nucleotide sequence analyses demonstrated that unc-44 encodes a series of putative ankyrin-related proteins, including AO49 ankyrin (1815 aa, 198.8 kD), AO66 ankyrin (1867 aa, 204 kD), and AO13 ankyrin (< or = 4700 aa, < or = 517 kD). In addition to the major set of approximately 6 kb alternatively spliced transcripts, minor transcripts were observed at approximately 3, 5, 7, and 14 kb. Evidence is provided that mutations in the approximately 14-kb AO13 ankyrin transcript are responsible for the neuronal defects. These molecular studies provide the first evidence that ankyrin-related molecules are required for axonal guidance. PMID:7744957

  20. Recombinant DNA encoding a desulfurization biocatalyst

    DOEpatents

    Rambosek, John; Piddington, Chris S.; Kovacevich, Brian R.; Young, Kevin D.; Denome, Sylvia A.

    1994-01-01

    This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous.

  1. Recombinant DNA encoding a desulfurization biocatalyst

    DOEpatents

    Rambosek, J.; Piddington, C.S.; Kovacevich, B.R.; Young, K.D.; Denome, S.A.

    1994-10-18

    This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous. 13 figs.

  2. Unified powered flight guidance

    NASA Technical Reports Server (NTRS)

    Brand, T. J.; Brown, D. W.; Higgins, J. P.

    1973-01-01

    A complete revision of the orbiter powered flight guidance scheme is presented. A unified approach to powered flight guidance was taken to accommodate all phases of exo-atmospheric orbiter powered flight, from ascent through deorbit. The guidance scheme was changed from the previous modified version of the Lambert Aim Point Maneuver Mode used in Apollo to one that employs linear tangent guidance concepts. This document replaces the previous ascent phase equation document.

  3. DNA encoding a DNA repair protein

    DOEpatents

    Petrini, John H.; Morgan, William Francis; Maser, Richard Scott; Carney, James Patrick

    2006-08-15

    An isolated and purified DNA molecule encoding a DNA repair protein, p95, is provided, as is isolated and purified p95. Also provided are methods of detecting p95 and DNA encoding p95. The invention further provides p95 knock-out mice.

  4. Less than 5 Netrin-1 molecules initiate attraction but 200 Sema3A molecules are necessary for repulsion

    PubMed Central

    Pinato, Giulietta; Cojoc, Dan; Lien, Linh Thuy; Ansuini, Alessio; Ban, Jelena; D’Este, Elisa; Torre, Vincent

    2012-01-01

    Guidance molecules, such as Sema3A or Netrin-1, induce growth cone (GC) repulsion or attraction. In order to determine the speed of action and efficiency of these guidance cues we developed an experimental procedure to deliver controlled amounts of these molecules. Lipid vesicles encapsulating 10–104 molecules of Sema3A or Netrin-1 were manipulated with high spatial and temporal resolution by optical tweezers and their photolysis triggered by laser pulses. Guidance molecules released from the vesicles diffused and reached the GC membrane in a few seconds. Following their arrival, GCs retracted or grew in 20–120 s. By determining the number of guidance molecules trapped inside vesicles and estimating the fraction of guidance molecules reaching the GC, we show that the arrival of less than 5 Netrin-1 molecules on the GC membrane is sufficient to induce growth. In contrast, the arrival of about 200 Sema3A molecules is necessary to induce filopodia repulsion. PMID:22997549

  5. Corporate information management guidance

    SciTech Connect

    1997-08-01

    At the request of the Department of Energy`s (DOE) Information Management (IM) Council, IM representatives from nearly all Headquarters (HQ) organizations have been meeting over the past year as the Corporate Guidance Group (CGG) to develop useful and sound corporate information management (IM) guidance. The ability of the Department`s IM community to develop such unified guidance continues to be critical to the success of future Departmental IM planning processes and the establishment of a well-coordinated IM environment between Headquarters and field organizations. This report, with 26 specific corporate IM guidance items documented and unanimously agreed to, as well as 12 items recommended for further development and 3 items deferred for future consideration, represents a highly successful effort by the IM community. The effort has proven that the diverse DOE organizations can put aside individual preferences and work together towards a common and mutually beneficial goal. In examining most areas and issues associated with information management in the Department, they have developed specific, far-reaching, and useful guidance. The IM representatives recommend that the documented guidance items provided in this report and approved by the DOE IM Council be followed by all IM organizations. The representatives also strongly recommend that the guidance process developed by the CGG be the single process for developing corporate IM guidance.

  6. Aiding Vertical Guidance Understanding

    NASA Technical Reports Server (NTRS)

    Feary, Michael; McCrobie, Daniel; Alkin, Martin; Sherry, Lance; Polson, Peter; Palmer, Everett; McQuinn, Noreen

    1998-01-01

    A two-part study was conducted to evaluate modern flight deck automation and interfaces. In the first part, a survey was performed to validate the existence of automation surprises with current pilots. Results indicated that pilots were often surprised by the behavior of the automation. There were several surprises that were reported more frequently than others. An experimental study was then performed to evaluate (1) the reduction of automation surprises through training specifically for the vertical guidance logic, and (2) a new display that describes the flight guidance in terms of aircraft behaviors instead of control modes. The study was performed in a simulator that was used to run a complete flight with actual airline pilots. Three groups were used to evaluate the guidance display and training. In the training, condition, participants went through a training program for vertical guidance before flying the simulation. In the display condition, participants ran through the same training program and then flew the experimental scenario with the new Guidance-Flight Mode Annunciator (G-FMA). Results showed improved pilot performance when given training specifically for the vertical guidance logic and greater improvements when given the training and the new G-FMA. Using actual behavior of the avionics to design pilot training and FMA is feasible, and when the automated vertical guidance mode of the Flight Management System is engaged, the display of the guidance mode and targets yields improved pilot performance.

  7. Ascent Guidance Comparisons

    NASA Technical Reports Server (NTRS)

    Hanson, John M.; Shrader, M. Wade; Cruzen, Craig A.

    1995-01-01

    This paper contains results from ascent guidance studies conducted at the NASA Marshall Space Flight Center. The studies include investigation of different guidance schemes for a variety of potential launch vehicles. Criteria of a successful ascent guidance scheme are low operations cost, satisfaction of load indicator constraints, and maximization of performance. Results show that open-loop designs as a function of altitude or velocity are preferable to designs that are functions of time. Optimized open-loop trajectories can increase performance while maintaining load indicators within limits. Closed-loop atmospheric schemes that involve linear tangent steering or feedback of velocity terms for trajectory modification did not yield any improvement. Early release of vacuum closed-loop guidance, including use during solid rocket booster operation, yields some improvements. Evaluation of a closed-loop optimization scheme for flying through the atmosphere shows no advantages over open-loop optimization. Dispersion study results for several potential guidance schemes and launch vehicles are included in the paper and are not a discriminator between guidance schemes. The primary cost driver is mission operations philosophy, not choice of guidance scheme. More autonomous guidance schemes can help in movement towards a philosophy that would reduce operations costs.

  8. astray, a zebrafish roundabout homolog required for retinal axon guidance.

    PubMed

    Fricke, C; Lee, J S; Geiger-Rudolph, S; Bonhoeffer, F; Chien, C B

    2001-04-20

    As growing retinotectal axons navigate from the eye to the tectum, they sense guidance molecules distributed along the optic pathway. Mutations in the zebrafish astray gene severely disrupt retinal axon guidance, causing anterior-posterior pathfinding defects, excessive midline crossing, and defasciculation of the retinal projection. Eye transplantation experiments show that astray function is required in the eye. We identify astray as zebrafish robo2, a member of the Roundabout family of axon guidance receptors. Retinal ganglion cells express robo2 as they extend axons. Thus, robo2 is required for multiple axon guidance decisions during establishment of the vertebrate visual projection.

  9. Shuttle entry guidance revisited

    NASA Technical Reports Server (NTRS)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-01-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  10. Shuttle entry guidance

    NASA Technical Reports Server (NTRS)

    Harpold, J. C.; Graves, C. A., Jr.

    1978-01-01

    This paper describes the design of the entry guidance for the Space Shuttle Orbiter. This guidance provides the steering commands for trajectory control from initial penetration of the earth's atmosphere until the terminal area guidance is activated at an earth-relative speed of 2500 fps. At this point, the Orbiter is at a distance of about 50 nmi from the runway threshold, and at an altitude of about 80,000 ft. The entry guidance design is based on an analytic solution of the equations of motion defining the drag acceleration profile that meets the terminal criteria of the entry flight while maintaining the flight within systems and operational constraints. Guidance commands, which are based on a control law that ensures damping of oscillatory type trajectory motion, are computed to steer the Orbiter to this drag acceleration profile.

  11. Shuttle entry guidance revisited

    NASA Astrophysics Data System (ADS)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-08-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  12. Shuttle entry guidance revisited

    NASA Technical Reports Server (NTRS)

    Mease, Kenneth D.; Kremer, Jean-Paul

    1992-01-01

    The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

  13. Federal Guidance for Radiation Protection

    EPA Pesticide Factsheets

    EPA produces federal guidance technical reports, which standardize dose and risk assessment and issues radiation protection guidance to federal agencies. This page provides links to federal guidance policy recommendations and technical reports.

  14. Atoms-in-molecules study of the genetically encoded amino acids. III. Bond and atomic properties and their correlations with experiment including mutation-induced changes in protein stability and genetic coding.

    PubMed

    Matta, Chérif F; Bader, Richard F W

    2003-08-15

    This article presents a study of the molecular charge distributions of the genetically encoded amino acids (AA), one that builds on the previous determination of their equilibrium geometries and the demonstrated transferability of their common geometrical parameters. The properties of the charge distributions are characterized and given quantitative expression in terms of the bond and atomic properties determined within the quantum theory of atoms-in-molecules (QTAIM) that defines atoms and bonds in terms of the observable charge density. The properties so defined are demonstrated to be remarkably transferable, a reflection of the underlying transferability of the charge distributions of the main chain and other groups common to the AA. The use of the atomic properties in obtaining an understanding of the biological functions of the AA, whether free or bound in a polypeptide, is demonstrated by the excellent statistical correlations they yield with experimental physicochemical properties. A property of the AA side chains of particular importance is the charge separation index (CSI), a quantity previously defined as the sum of the magnitudes of the atomic charges and which measures the degree of separation of positive and negative charges in the side chain of interest. The CSI values provide a correlation with the measured free energies of transfer of capped side chain analogues, from the vapor phase to aqueous solution, yielding a linear regression equation with r2 = 0.94. The atomic volume is defined by the van der Waals isodensity surface and it, together with the CSI, which accounts for the electrostriction of the solvent, yield a linear regression (r2 = 0.98) with the measured partial molar volumes of the AAs. The changes in free energies of transfer from octanol to water upon interchanging 153 pairs of AAs and from cyclohexane to water upon interchanging 190 pairs of AAs, were modeled using only three calculated parameters (representing electrostatic and

  15. Laser beam riding artillery missiles guidance device is designed

    NASA Astrophysics Data System (ADS)

    Yan, Mingliang; Huo, Zhicheng; Chen, Wei

    2014-09-01

    Laser driving gun missile guidance type beam of laser information field formed by any link failure or reduced stability will directly lead to ballistic or miss out of control, and based on this, this paper designed the driving beam of laser guided missile guidance beam type forming device modulation and zoom mechanism, in order to make the missile can recognize its position in the laser beam, laser beam gun missile, by means of spatial encoding of the laser beam laser beam into information after forming device, a surface to achieve the purpose of precision guidance.

  16. EPA Policy and Guidance

    EPA Pesticide Factsheets

    The policy establishes the principles for accessible Electronic and Information Technology (EIT) and complying with Section 508 requirements. The guidance defines EIT and the technical and functional performance criteria necessary for compliance.

  17. Pollinator Risk Assessment Guidance

    EPA Pesticide Factsheets

    This Guidance is part of a long-term strategy to advance the science of assessing the risks posed by pesticides to honey bees, giving risk managers the means to further improve pollinator protection in our regulatory decisions.

  18. Isotopomer-selective spectra of a single intact H2O molecule in the Cs+(D2O)5H2O isotopologue: Going beyond pattern recognition to harvest the structural information encoded in vibrational spectra

    SciTech Connect

    Wolke, Conrad T.; Fournier, Joseph A.; Miliordos, Evangelos; Kathmann, Shawn M.; Xantheas, Sotiris S.; Johnson, Mark A.

    2016-02-21

    We report the vibrational signatures of a single H2O water molecule occupying distinct sites of the hydration network in the Cs+(H2O)6 cluster. This is accomplished using isotopomer selective IR-IR hole-burning on the Cs+(D2O)5(H2O) clusters formed by gas-phase exchange of a single, intact H2O molecule for D2O in the Cs+(D2O)6 ion. The OH stretching pattern of the Cs+(H2O)6 isotopologue is accurately recovered by superposition of the isotopomer spectra, thus establishing that the H2O incorporation is random and that the OH stretching manifold is largely due to contributions from decoupled water molecules. This behavior enables a powerful new way to extract structural information from vibrational spectra of size-selected clusters by explicitly identifying the local environments responsible for specific infrared features. The Cs+(H2O)6 structure was unambiguously assigned to the 4.1.1 isomer (a homodromic water tetramer with two additional flanking water molecules) from the fact that its computed IR spectrum matches the observed overall pattern and recovers the embedded correlations in the two OH stretching bands of the water molecule in the Cs+(D2O)5(H2O) isotopomers. The 4.1.1 isomer is the lowest in energy among other candidate networks at advanced (e.g., CCSD(T)) levels of theoretical treatment after corrections for (anharmonic) zero-point energy (ZPE). With the structure in hand, we then explore the mechanical origin of the various band locations using a local electric field formalism. This approach promises to provide a transferrable scheme for the prediction of the OH stretching fundamentals displayed by water networks in close proximity to solute ions.

  19. Isotopomer-selective spectra of a single intact H2O molecule in the Cs+(D2O)5H2O isotopologue: Going beyond pattern recognition to harvest the structural information encoded in vibrational spectra

    NASA Astrophysics Data System (ADS)

    Wolke, Conrad T.; Fournier, Joseph A.; Miliordos, Evangelos; Kathmann, Shawn M.; Xantheas, Sotiris S.; Johnson, Mark A.

    2016-02-01

    We report the vibrational signatures of a single H2O molecule occupying distinct sites of the hydration network in the Cs+(H2O)6 cluster. This is accomplished using isotopomer-selective IR-IR hole-burning on the Cs+(D2O)5(H2O) clusters formed by gas-phase exchange of a single, intact H2O molecule for D2O in the Cs+(D2O)6 ion. The OH stretching pattern of the Cs+(H2O)6 isotopologue is accurately recovered by superposition of the isotopomer spectra, thus establishing that the H2O incorporation is random and that the OH stretching manifold is largely due to contributions from decoupled water molecules. This behavior enables a powerful new way to extract structural information from vibrational spectra of size-selected clusters by explicitly identifying the local environments responsible for specific infrared features. The Cs+(H2O)6 structure was unambiguously assigned to the 4.1.1 isomer (a homodromic water tetramer with two additional flanking water molecules) from the fact that its computed IR spectrum matches the observed overall pattern and recovers the embedded correlations in the two OH stretching bands of the water molecule in the Cs+(D2O)5(H2O) isotopomers. The 4.1.1 isomer is the lowest in energy among other candidate networks at advanced (e.g., CCSD(T)) levels of theoretical treatment after corrections for (anharmonic) zero-point energy. With the structure in hand, we then explore the mechanical origin of the various band locations using a local electric field formalism. This approach promises to provide a transferrable scheme for the prediction of the OH stretching fundamentals displayed by water networks in close proximity to solute ions.

  20. Comprehensive Guidance Programs That Work.

    ERIC Educational Resources Information Center

    Gysbers, Norman C.; And Others

    This monograph describes how the comprehensive guidance model is transforming elementary-secondary school guidance and counseling programs in schools across the country. It incorporates the ideas and experiences of 12 guidance program developers in the actual use of the comprehensive guidance model in diverse school and cultural settings. The book…

  1. Anticipatory guidance through DVD.

    PubMed

    Franz, Sandra; McMahon, Pamela M; Calongne, Laurinda; Steele-Moses, Susan K

    2014-03-01

    The major purpose of the study was to determine if a 5-minute DVD is an effective method for communicating anticipatory guidance to parents at their child's 4-month well-child visit. A total of 84 caregivers were randomly assigned to receive anticipatory guidance through standard care (written anticipatory guidance handout and free talk) or DVD (DVD format + standard care). Participants completed a brief questionnaire immediately before and after their visit. As anticipated, knowledge scores improved significantly from pre-test to post-test. There was also a significant interaction between format used for anticipatory guidance and time. Specifically, there was greater improvement in knowledge over time for parents in the DVD group as compared with the standard care group. Additionally, the mean knowledge level of those in the DVD group as compared with those in the standard care group trended toward significance. Finally, visit length was shortened by nearly 3 minutes in the DVD group, and close to 100% of all respondents, regardless of anticipatory guidance format, indicated that they were very satisfied with their visit and amount of information learned.

  2. Guidance publication proves timely.

    PubMed

    Baillie, Jonathan

    2011-05-01

    The importance of properly identifying, assessing, and managing risk in all areas of engineering practice, the fact that genuine innovation is almost impossible without a certain element of risk-taking, and the need to acknowledge and respond to public concerns, however much some may be ill-founded, over the risks inherent in technological and engineering advances, are highlighted in a new risk guidance document, Guidance on Risk for the Engineering Profession, published by the Engineering Council in London last month. HEJ editor Jonathan Baillie reports.

  3. Annual Compliance Certification Guidance

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  4. Cell-Cell Interactions during pollen tube guidance

    SciTech Connect

    Daphne Preuss

    2009-03-31

    The long-term goal of this research is to identify the signaling molecules that mediate plant cell-cell interactions during pollination. The immediate goals of this project are to perform genetic and molecular analysis of pollen tube guidance. Specifically, we proposed to: 1. Characterize the pistil components that direct pollen tube navigation using the Arabidopsis thaliana in vitro pollen tube guidance system 2. Identify pistil signals that direct pollen tube guidance by a) using microarrays to profile gene expression in developing pistils, and b) employing proteomics and metabolomics to isolate pollen tube guidance signals. 3. Explore the genetic basis of natural variation in guidance signals, comparing the in vitro interactions between pollen and pistils from A. thaliana and its close relatives.

  5. Guidance on lobbying restrictions

    EPA Pesticide Factsheets

    The purpose of this guidance is to remind nonprofit organizations, universities, and other non-government recipients of EPA grants that, with very limited exceptions, you may not use Federal grant funds or cost-sharing funds to conduct lobbying activities.

  6. Vocational Guidance for Everyone

    ERIC Educational Resources Information Center

    Holland, John L.

    1974-01-01

    Describes some of the current problems of vocational guidance, summarizes relevant knowledge and theory in the field, and offers some practical plans for a coordinated, theoretically compatible group of vocational programs, services, and experiences for a high school. (Author/JM)

  7. PIV Logon Configuration Guidance

    SciTech Connect

    Lee, Glen Alan

    2016-03-04

    This document details the configurations and enhancements implemented to support the usage of federal Personal Identity Verification (PIV) Card for logon on unclassified networks. The guidance is a reference implementation of the configurations and enhancements deployed at the Los Alamos National Laboratory (LANL) by Network and Infrastructure Engineering – Core Services (NIE-CS).

  8. Click Here for Guidance.

    ERIC Educational Resources Information Center

    Trotter, Andrew

    2003-01-01

    School guidance counselors can use computers to enhance students' abilities to get into top colleges. One high school counselor has established a Web site with online forms requesting that transcripts be sent to colleges and search tools for finding financial assistance; an Internet discussion forum for seniors to discuss college admissions; and…

  9. Vocational Development and Guidance.

    ERIC Educational Resources Information Center

    Tennyson, W. Wesley; And Others

    The vocational education volume considers questions of career development, the role of guidance in the school, vocational training, the relation of self-concept to vocational choice, and occupational information. Twenty-six papers deal with theories of vocational behavior, the success of vocational education programs, and testing information.…

  10. Regulatory guidance document

    SciTech Connect

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  11. The Counseling & Guidance Curriculum.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    Counseling and guidance services are vital in any school curriculum. Counselors may themselves be dealing with students of diverse abilities and handicaps. Counselors may have to work with students affected by drug addiction, fetal alcohol syndrome, homelessness, poverty, Acquired Immune Deficiency Syndrome (AIDS) and divorce. Students may present…

  12. Foundations of Career Guidance.

    ERIC Educational Resources Information Center

    Ruff, Eldon E.

    The paper traces the evolution of career guidance from 1909 to the present. The predominant views before 1950 were almost entirely nondevelopmental, but in response to questions raised at a series of major national conferences in the 1960's and the national impact of the career education concept, the 1970's have seen a flurry of writings and…

  13. Guidelines for Guidance Services.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education and Training, Winnipeg.

    The purpose of this booklet is to provide direction and assistance to school divisions as they develop responsive, effective, and accountable guidance services and programs at the school level. The guidelines presented provide a broad conceptual framework of definitions and goals and outline expectations for service standards. Models and…

  14. Vocational Development and Guidance.

    ERIC Educational Resources Information Center

    Tennyson, W. Wesley; And Others

    The vocational education volume considers questions of career development, the role of guidance in the school, vocational training, the relation of self-concept to vocational choice, and occupational information. Twenty-six papers deal with theories of vocational behavior, the success of vocational education programs, and testing information.…

  15. Quality in Careers Guidance.

    ERIC Educational Resources Information Center

    Plant, Peter

    This paper examines quality issues in career guidance, counseling, and information services in Europe and elsewhere from a range of different perspectives related to economic, ethical, and/or effectiveness criteria. Selected examples from the European Union member states, Canada, and the United States are used to illustrate how quality is…

  16. Secondary Guidance Manual.

    ERIC Educational Resources Information Center

    Bennett, Charlotte; And Others

    This manual outlines the philosophy and organization of the secondary counseling program of the Moore Public Schools (Oklahoma). The school district has made efforts in counseling American Indian students. This document presents the goals and objectives for secondary guidance programs that provide such services as orientation, information,…

  17. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex, E [Brookfield, IL; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL; Diaz, Rocio [Chicago, IL; Vukovic, Lela [Westchester, IL

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  18. ENCODE data at the ENCODE portal

    PubMed Central

    Sloan, Cricket A.; Chan, Esther T.; Davidson, Jean M.; Malladi, Venkat S.; Strattan, J. Seth; Hitz, Benjamin C.; Gabdank, Idan; Narayanan, Aditi K.; Ho, Marcus; Lee, Brian T.; Rowe, Laurence D.; Dreszer, Timothy R.; Roe, Greg; Podduturi, Nikhil R.; Tanaka, Forrest; Hong, Eurie L.; Cherry, J. Michael

    2016-01-01

    The Encyclopedia of DNA Elements (ENCODE) Project is in its third phase of creating a comprehensive catalog of functional elements in the human genome. This phase of the project includes an expansion of assays that measure diverse RNA populations, identify proteins that interact with RNA and DNA, probe regions of DNA hypersensitivity, and measure levels of DNA methylation in a wide range of cell and tissue types to identify putative regulatory elements. To date, results for almost 5000 experiments have been released for use by the scientific community. These data are available for searching, visualization and download at the new ENCODE Portal (www.encodeproject.org). The revamped ENCODE Portal provides new ways to browse and search the ENCODE data based on the metadata that describe the assays as well as summaries of the assays that focus on data provenance. In addition, it is a flexible platform that allows integration of genomic data from multiple projects. The portal experience was designed to improve access to ENCODE data by relying on metadata that allow reusability and reproducibility of the experiments. PMID:26527727

  19. Vocational Guidance and Human Development.

    ERIC Educational Resources Information Center

    Herr, Edwin L., Ed.

    New knowledge and practices in the area of vocational guidance and human growth and development that have occurred since 1964 as well as future directions for guidance, both nationally and internationally, are covered in this second volume of a decennial volume series sponsored by the National Vocational Guidance Association to up-date the…

  20. When Instructional Guidance is Needed

    ERIC Educational Resources Information Center

    Chen, Ouhao; Kalyuga, Slava; Sweller, John

    2016-01-01

    Studying worked examples providing problem solutions to learners usually leads to better test performance than solving the equivalent problems without guidance, demonstrating the worked-example effect. The generation effect occurs when learners who generate answers without guidance learn better than those who read answers that provide guidance.…

  1. When Instructional Guidance is Needed

    ERIC Educational Resources Information Center

    Chen, Ouhao; Kalyuga, Slava; Sweller, John

    2016-01-01

    Studying worked examples providing problem solutions to learners usually leads to better test performance than solving the equivalent problems without guidance, demonstrating the worked-example effect. The generation effect occurs when learners who generate answers without guidance learn better than those who read answers that provide guidance.…

  2. Employee commute options guidance

    SciTech Connect

    Not Available

    1992-12-01

    The Clean Air Act Amendments of 1990 (CAAA) require severe and extreme ozone nonattainment areas and serious carbon monoxide nonattainment areas to establish programs aimed at reducing commute trips to the worksites of large employers. The concerns that lead to the inclusion of the Employee Commute Options (ECO) provision in the Act are that more people are driving than ever before and they are driving longer distances. The purpose of the guidance is to inform the affected State and local jurisdictions of the Clean Air Act requirement, to provide guidance on preparing an approvable State Implementation Plan (SIP) revision, and to discuss various approaches which may help areas achieve Clean Air Act targets through implementation strategies that are the least burdensome and costly to both affected employers and employees.

  3. Environmental guidance regulatory bulletin

    SciTech Connect

    1997-01-31

    This document describes the background on expanding public participation in the Resource Conservation and Recovery Act and DOE`s response. The bulletin also describes the changes made by the final rule to existing regulations, guidance provided by EPA in the preamble and in the revised RCRA Public Participation Manual, the relationship between public participation and environmental justice, and DOE`s recent public participation and environmental justice initiatives.

  4. CDER photosafety guidance for industry.

    PubMed

    Jacobs, Abigail C; Brown, Paul C; Chen, Conrad; Ellis, Amy; Farrelly, James; Osterberg, Robert

    2004-01-01

    In the Federal Register of January 10, 2000 (65 FR 1399), FDA published a draft guidance entitled "Photosafety Testing." The notice gave interested persons an opportunity to submit comments. As a result of the comments, certain sections of the guidance were reworded to improve clarity. A final guidance was published in May 2003. The final guidance further emphasizes that a flexible approach can be used to address adverse photoeffects and that specific assays are not required. Moreover, it encourages the development of methods that can efficiently be used to evaluate human safety. The guidance describes a consistent, science-based approach for testing of topically and systemically administered drug products.

  5. Shuttle ascent guidance and control.

    NASA Technical Reports Server (NTRS)

    Lovingood, J. A.; Blair, J. C.; Geissler, E. O.

    1972-01-01

    The requirements of a unified optimal guidance scheme are discussed, giving attention to a general formulation, aspects of self-targeting, problems of optimum guidance within the atmosphere, and a unified concept for all flight phases. Since no previous guidance scheme meets these requirements, the shuttle demands a fundamentally new approach. A new unified optimal guidance scheme, called Mascot, was developed. The capabilities of Mascot include the real-time solution of general trajectory-optimization problems and the unification of guidance for all flight phases.

  6. Interstellar molecules

    NASA Technical Reports Server (NTRS)

    Townes, C. H.

    1976-01-01

    Progress in the discovery and study of interstellar molecules is summarized. The 36 molecular species thus far identified in interstellar space are listed in several groups which include simple hydrides, oxides, and sulfides, various derivatives of ammonia, molecules involving linear carbon chains, cyanides, and molecules related in structure to formaldehyde, alcohols, or ethers. Several free radicals are described, the discovery of molecules in external galaxies is discussed, and possible mechanisms for molecular formation are noted. Methods for examining relative isotopic abundances by measuring molecules in interstellar clouds are outlined, mechanisms for the excitation of interstellar molecules are reviewed, and values are presented for the C-12/C-13 abundance ratio in a number of interstellar clouds. The detection of interstellar masers is discussed along with pumping mechanisms and masing transitions in H2CO, CH, OH, and SiO. The nature of dense interstellar clouds is examined in terms of several simple and complex cloud models, with emphasis on multiple condensation models.

  7. Chemical Space of DNA-Encoded Libraries.

    PubMed

    Franzini, Raphael M; Randolph, Cassie

    2016-07-28

    In recent years, DNA-encoded chemical libraries (DECLs) have attracted considerable attention as a potential discovery tool in drug development. Screening encoded libraries may offer advantages over conventional hit discovery approaches and has the potential to complement such methods in pharmaceutical research. As a result of the increased application of encoded libraries in drug discovery, a growing number of hit compounds are emerging in scientific literature. In this review we evaluate reported encoded library-derived structures and identify general trends of these compounds in relation to library design parameters. We in particular emphasize the combinatorial nature of these libraries. Generally, the reported molecules demonstrate the ability of this technology to afford hits suitable for further lead development, and on the basis of them, we derive guidelines for DECL design.

  8. Wavelet encoding and variable resolution progressive transmission

    NASA Technical Reports Server (NTRS)

    Blanford, Ronald P.

    1993-01-01

    Progressive transmission is a method of transmitting and displaying imagery in stages of successively improving quality. The subsampled lowpass image representations generated by a wavelet transformation suit this purpose well, but for best results the order of presentation is critical. Candidate data for transmission are best selected using dynamic prioritization criteria generated from image contents and viewer guidance. We show that wavelets are not only suitable but superior when used to encode data for progressive transmission at non-uniform resolutions. This application does not preclude additional compression using quantization of highpass coefficients, which to the contrary results in superior image approximations at low data rates.

  9. PSD Increment Consumption Guidance

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  10. Hypervelocity Orbital Intercept Guidance

    DTIC Science & Technology

    1988-04-14

    Professor Charles E. Fosha, Jr. Terminal guidance of a hypervelocity exo-atmospheric orbital interceptor with free end-time is examined. The pursuer is...stochastic nonlinear systems with free end-time was developed by Tse and 29 Bar-Shalom [5]. This method differs from the optimal control formulation...Vol. AC-18, No. 2, April 1973, pp. 98-108. 5. Tse, E., and Y. Bar-Shalom, "Adaptive Dual Control For Stochastic Nonlinear Systems with Free End- Time

  11. Guidance on Determining LAER

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  12. PSD Guidance Document

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  13. NSR Program Transitional Guidance

    EPA Pesticide Factsheets

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  14. Controls and guidance: Aeronautics

    NASA Technical Reports Server (NTRS)

    Dibattista, John D.

    1988-01-01

    The overall objective is to provide a validated technology base leading to the development and exploitation of new concepts, analysis and design methodologies, and flight systems for future civil and military aircraft. This will provide increased efficiency, effectiveness, reliability, and safety. The program is organized into generic elements and vehicle-specific elements. The generic elements are control theory, guidance and display concepts, and flight crucial systems. Vehicle-specific elements are generic hypersonics, subsonic transport/commuter/general aviation, rotorcraft, and fighter/attack. Research in the control theory element is directed toward the improved flight control analysis and design methodologies for highly integrated, robust flight control designs. Flight Crucial Systems research is directed toward the development of design, assessment, and validation methodologies for flight crucial systems. The generic hypersonics research concentrates on the integration of flight control, propulsion control, sensors, and displays. The Aeronautical Controls and Guidance Program involves analytical and experimental research by in-house, university, and industry personnel. Extensive use of ground-based simulation is a characteristic of the program with selected flight experiments in a variety of aircraft.

  15. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  16. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  17. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  18. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  19. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  20. Enumerating molecules.

    SciTech Connect

    Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  1. Comprehensive Career Guidance. Career Guidance Curriculum. Staff Development K-6.

    ERIC Educational Resources Information Center

    Straub, Vicki W.; Moore, Earl J.

    One of six staff development training manuals for career guidance infusion in the elementary school curriculum (K-6), this manual focuses on the curriculum design of a comprehensive career guidance program. It is divided into the following five major sections: (1) a list of the major goals and activities covered in the manual; (2) an overview…

  2. Endangerment assessment guidance

    SciTech Connect

    Not Available

    1985-11-22

    The directive clarifies the requirement that an endangerment assessment be developed to support all administrative and judicial enforcement actions under Section 106 of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and Section 7003 of the Resource Conservation and Recovery Act (RCRA). Before taking enforcement action under these provisions to abate the hazards or potential hazards at a site, the Environmental Protection Agency (EPA) must be able to properly document and justify its assertion that an imminent and substantial endangerment to public health or welfare or the environment may exist. The endangerment assessment provides this documentation and justification. The endangerment assessment is not necessary to support Section 104 actions. It also provides guidance on the content, timing, level of detail, format, and resources required for the preparation of endangerment assessments.

  3. microRNAs in axon guidance

    PubMed Central

    Iyer, Archana N.; Bellon, Anaïs; Baudet, Marie-Laure

    2014-01-01

    Brain wiring is a highly intricate process in which trillions of neuronal connections are established. Its initial phase is particularly crucial in establishing the general framework of neuronal circuits. During this early step, differentiating neurons extend axons, which reach their target by navigating through a complex environment with extreme precision. Research in the past 20 years has unraveled a vast and complex array of chemotropic cues that guide the leading tip of axons, the growth cone, throughout its journey. Tight regulation of these cues, and of their receptors and signaling pathways, is necessary for the high degree of accuracy required during circuit formation. However, little is known about the nature of regulatory molecules or mechanisms fine-tuning axonal cue response. Here we review recent, and somewhat fragmented, research on the possibility that microRNAs (miRNAs) could be key fine-tuning regulatory molecules in axon guidance. miRNAs appear to shape long-range axon guidance, fasciculation and targeting. We also present several lines of evidence suggesting that miRNAs could have a compartmentalized and differential action at the cell soma, and within axons and growth cones. PMID:24672429

  4. Miniaturised optical encoder

    NASA Astrophysics Data System (ADS)

    Carr, John; Desmulliez, Marc P. Y.; Weston, Nick; McKendrick, David; Cunningham, Graeme; McFarland, Geoff; Meredith, Wyn; McKee, Andrew; Langton, Conrad; Eddie, Iain

    2008-08-01

    Optical encoders are pervasive in many sectors of industry including metrology, motion systems, electronics, medical, scanning/ printing, scientific instruments, space research and specialist machine tools. The precision of automated manufacture and assembly has been revolutionised by the adoption of optical diffractive measurement methods. Today's optical encoders comprise discrete components: light source(s), reference and analyser gratings, and a photodiode array that utilise diffractive optic methods to achieve high resolution. However the critical alignment requirements between the optical gratings and to the photodiode array, the bulky nature of the encoder devices and subsequent packaging mean that optical encoders can be prohibitively expensive for many applications and unsuitable for others. We report here on the design, manufacture and test of a miniaturised optical encoder to be used in precision measurement systems. Microsystems manufacturing techniques facilitate the monolithic integration of the traditional encoder components onto a single compound semiconductor chip, radically reducing the size, cost and set-up time. Fabrication of the gratings at the wafer level, by standard photo-lithography, allows for the simultaneous alignment of many devices in a single process step. This development coupled with a unique photodiode configuration not only provides increased performance but also significantly improves the alignment tolerances in both manufacture and set-up. A National Research and Development Corporation type optical encoder chip has been successfully demonstrated under test conditions on both amplitude and phase scales with pitches of 20 micron, 8 micron and 4 micron, showing significantly relaxed alignment tolerances with signal-to-noise ratios greater than 60:1. Various reference mark schemes have also been investigated. Results are presented here.

  5. Innovative Approaches to Career Guidance.

    ERIC Educational Resources Information Center

    Freeman, Andrew R.

    A key part of a broad-based approach to career education in Australian schools is vocational/career guidance. Various vocational guidance programs have been developed for specific groups in Australian society, including work experience, caravans, and micrographics technology for the handicapped; pre-employment courses and a family education center…

  6. Discussing Diverse Perspectives on Guidance

    ERIC Educational Resources Information Center

    Gonzalez-Mena, Janet; Shareef, Intisar

    2005-01-01

    Ideas about discipline and guidance get extremely complex when they intersect with culture and oppression. Some groups of people who are targets of racism have to protect their children from the oppressive practices of racist individuals and institutions. Their methods of guidance and discipline may be different from those of groups for whom…

  7. Restructuring Guidance and Counseling Programs.

    ERIC Educational Resources Information Center

    Snyder, Beverly A.; Daly, Timothy P.

    1993-01-01

    Briefly reviews counseling profession's call for revitalization and transformation in school counseling and guidance programs. Summarizes one school system's efforts during late 1980s and early 1990s to transform its program from services and crisis orientation into a comprehensive developmental model based on Myrick's developmental guidance and…

  8. Guidance Services in Spanish Universities

    ERIC Educational Resources Information Center

    Vidal, Javier; Diez, Gloria; Vieira, Maria J.

    2003-01-01

    Since the 80s, higher education in Spain has undergone important modifications such as greater autonomy, expansion in the number of students and the introduction of more flexible programmes. In this context, guidance services have proliferated in an unstructured way. This paper presents a description of guidance services in Spanish universities…

  9. Automated Guidance for Student Inquiry

    ERIC Educational Resources Information Center

    Gerard, Libby F.; Ryoo, Kihyun; McElhaney, Kevin W.; Liu, Ou Lydia; Rafferty, Anna N.; Linn, Marcia C.

    2016-01-01

    In 4 classroom experiments we investigated uses for technologies that automatically score student generated essays, concept diagrams, and drawings in inquiry curricula. We used the automatic scores to assign typical and research-based guidance and studied the impact of the guidance on student progress. Seven teachers and their 897 students…

  10. Guidance for the New Millenium?

    ERIC Educational Resources Information Center

    McLaren, David J.

    1996-01-01

    Reviews the "Guidance Arrangements" consultation document issued with "Higher Still" (proposed new Scottish upper secondary curricula). Argues that the paper ignores the full implications for educational change in Higher Still and misses the opportunity for timely modernization of school guidance. Advocates a cross-curricular…

  11. Characterizing Guidance in Visual Analytics.

    PubMed

    Ceneda, Davide; Gschwandtner, Theresia; May, Thorsten; Miksch, Silvia; Schulz, Hans-Jorg; Streit, Marc; Tominski, Christian

    2017-01-01

    Visual analytics (VA) is typically applied in scenarios where complex data has to be analyzed. Unfortunately, there is a natural correlation between the complexity of the data and the complexity of the tools to study them. An adverse effect of complicated tools is that analytical goals are more difficult to reach. Therefore, it makes sense to consider methods that guide or assist users in the visual analysis process. Several such methods already exist in the literature, yet we are lacking a general model that facilitates in-depth reasoning about guidance. We establish such a model by extending van Wijk's model of visualization with the fundamental components of guidance. Guidance is defined as a process that gradually narrows the gap that hinders effective continuation of the data analysis. We describe diverse inputs based on which guidance can be generated and discuss different degrees of guidance and means to incorporate guidance into VA tools. We use existing guidance approaches from the literature to illustrate the various aspects of our model. As a conclusion, we identify research challenges and suggest directions for future studies. With our work we take a necessary step to pave the way to a systematic development of guidance techniques that effectively support users in the context of VA.

  12. Automated Guidance for Student Inquiry

    ERIC Educational Resources Information Center

    Gerard, Libby F.; Ryoo, Kihyun; McElhaney, Kevin W.; Liu, Ou Lydia; Rafferty, Anna N.; Linn, Marcia C.

    2016-01-01

    In 4 classroom experiments we investigated uses for technologies that automatically score student generated essays, concept diagrams, and drawings in inquiry curricula. We used the automatic scores to assign typical and research-based guidance and studied the impact of the guidance on student progress. Seven teachers and their 897 students…

  13. Guidance in the Secondary School

    ERIC Educational Resources Information Center

    Kumar, V. Jurist Lional

    2010-01-01

    Secondary School Students face a lot of problems in their body as well as in mind due to puberty that tends to adolescence stage. Adolescence has peculiar characters of their own. They need proper Guidance and Counselling to tackle their own problems. Guidance is described as a counselling service to assist the individual in achieving self…

  14. GUIDANCE AWARENESS IN ELEMENTARY EDUCATION.

    ERIC Educational Resources Information Center

    MOREAU, GEORGE H., ED.

    THE PURPOSE OF THE WORKSHOP IN ELEMENTARY SCHOOL GUIDANCE WAS TWOFOLD--(1) TO SHOW HOW GUIDANCE PROCEDURES AND TECHNIQUES CENTER ABOUT AND INVOLVE THE CHILD AS HE ADAPTS TO A NEW TYPE OF SCHOOL SETTING AND LEARNING PROCESS, AND (2) TO CREATE AN AWARENESS OF THE NEED FOR ALL AREAS OF COUNSELING AT THE ELEMENTARY SCHOOL LEVEL. OF THE ELEVEN PAPERS…

  15. Marxist Guidance: A Dialectic Lesson

    ERIC Educational Resources Information Center

    Drapela, Victor J.

    1971-01-01

    Based on primary sources published in the Soviet Bloc, this article compares the stated goals of Marxist guidance with actual outcomes, and identifies the foundations of guidance in the Soviet Bloc in terms of Marxist philosophy and social doctrine. Current symptoms of ideological unrest in socialist society as exemplified by the suppressed reform…

  16. Asymmetric synthesis using chiral-encoded metal

    NASA Astrophysics Data System (ADS)

    Yutthalekha, Thittaya; Wattanakit, Chularat; Lapeyre, Veronique; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

    2016-08-01

    The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity.

  17. Asymmetric synthesis using chiral-encoded metal

    PubMed Central

    Yutthalekha, Thittaya; Wattanakit, Chularat; Lapeyre, Veronique; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

    2016-01-01

    The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity. PMID:27562028

  18. Storing data encoded DNA in living organisms

    DOEpatents

    Wong; Pak C. , Wong; Kwong K. , Foote; Harlan P.

    2006-06-06

    Current technologies allow the generation of artificial DNA molecules and/or the ability to alter the DNA sequences of existing DNA molecules. With a careful coding scheme and arrangement, it is possible to encode important information as an artificial DNA strand and store it in a living host safely and permanently. This inventive technology can be used to identify origins and protect R&D investments. It can also be used in environmental research to track generations of organisms and observe the ecological impact of pollutants. Today, there are microorganisms that can survive under extreme conditions. As well, it is advantageous to consider multicellular organisms as hosts for stored information. These living organisms can provide as memory housing and protection for stored data or information. The present invention provides well for data storage in a living organism wherein at least one DNA sequence is encoded to represent data and incorporated into a living organism.

  19. RH Packaging Program Guidance

    SciTech Connect

    Washington TRU Solutions LLC

    2006-11-07

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: "...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." It further states: "...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with 10 Code of Federal Regulations (CFR) §71.8, "Deliberate Misconduct." Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. In accordance with 10 CFR Part 71, "Packaging and Transportation of Radioactive Material," certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, "Reporting of Defects and Noncompliance," regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a conspicuous location where the activities subject to

  20. RH Packaging Program Guidance

    SciTech Connect

    Washington TRU Solutions LLC

    2008-01-12

    The purpose of this program guidance document is to provide the technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package (also known as the "RH-TRU 72-B cask") and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the C of C shall govern. The C of C states: "...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, Operating Procedures, of the application." It further states: "...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, Acceptance Tests and Maintenance Program of the Application." Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) Contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC-approved, users need to be familiar with Title 10 Code of Federal Regulations (CFR) §71.8, "Deliberate Misconduct." Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the U.S. Department of Energy (DOE) Carlsbad Field Office (CBFO) shall be notified immediately. The CBFO will evaluate the issue and notify the NRC if required.In accordance with 10 CFR Part 71, "Packaging and Transportation of Radioactive Material," certificate holders, packaging users, and contractors or subcontractors who use, design, fabricate, test, maintain, or modify the packaging shall post copies of (1) 10 CFR Part 21, "Reporting of Defects and Noncompliance," regulations, (2) Section 206 of the Energy Reorganization Act of 1974, and (3) NRC Form 3, Notice to Employees. These documents must be posted in a

  1. Polarization encoded color camera.

    PubMed

    Schonbrun, Ethan; Möller, Guðfríður; Di Caprio, Giuseppe

    2014-03-15

    Digital cameras would be colorblind if they did not have pixelated color filters integrated into their image sensors. Integration of conventional fixed filters, however, comes at the expense of an inability to modify the camera's spectral properties. Instead, we demonstrate a micropolarizer-based camera that can reconfigure its spectral response. Color is encoded into a linear polarization state by a chiral dispersive element and then read out in a single exposure. The polarization encoded color camera is capable of capturing three-color images at wavelengths spanning the visible to the near infrared.

  2. Autonomous landing guidance program

    NASA Astrophysics Data System (ADS)

    Brown, John A.

    1996-05-01

    The Autonomous Landing Guidance program is partly funded by the US Government under the Technology Reinvestment Project. The program consortium consists of avionics and other equipment vendors, airlines and the USAF. A Sextant Avionique HUD is used to present flight symbology in cursive form as well as millimeter wave radar imagery from Lear Astronics equipment and FLIR Systems dual-channel, forward-looking, infrared imagery. All sensor imagery is presented in raster form. A future aim is to fuse all imagery data into a single presentation. Sensor testing has been accomplished in a Cessna 402 operated by the Maryland Advanced Development Laboratory. Development testing is under way in a Northwest Airlines simulator equipped with HUD and image simulation. Testing is also being carried out using United Airlines Boeing 727 and USAF C-135C (Boeing 707) test aircraft. The paper addresses the technology utilized in sensory and display systems as well as modifications made to accommodate the elements in the aircraft. Additions to the system test aircraft include global positioning systems, inertial navigation systems and extensive data collection equipment. Operational philosophy and benefits for both civil and military users are apparent. Approach procedures have been developed allowing use of Category 1 ground installations in Category 3 conditions.

  3. Pandemic influenza guidance for corporations.

    PubMed

    2011-06-01

    The purpose of this guidance document is to assist members of the American College of Occupational and Environmental Medicine (ACOEM), and the organizations for which they work, in managing the impact of a pandemic of influenza or other contagious respiratory disease on patients, employees, and business. This guidance document outlines actions to take before and during an influenza pandemic on the basis of two main strategies: (1) reducing the spread of the virus within facilities; and (2) providing medical care and medical surveillance to client/patient populations. Facilities in which ACOEM members serve include government agencies and the military, universities, and corporations, which generally have multiple locations/sites and their own medical staff, with members responsible for medical care and disease control. This guidance is for organizations with outpatient occupational medicine services, to be used as appropriate. Medical centers should also use guidance that addresses additional employee and external patient care needs.1–3 The ACOEM fully supports implementation of occupational influenza programs that conform with guidance from the Centers for Disease Control and Prevention (CDC), with other guidance from the US Department of Health and Human Services (DHHS), and Occupational Safety and Health Administration (OSHA) regulations and guidance.

  4. General RMP Guidance - Appendix D: OSHA Guidance on PSM

    EPA Pesticide Factsheets

    OSHA's Process Safety Management (PSM) Guidance on providing complete and accurate written information concerning process chemicals, process technology, and process equipment; including process hazard analysis and material safety data sheets.

  5. Video time encoding machines.

    PubMed

    Lazar, Aurel A; Pnevmatikakis, Eftychios A

    2011-03-01

    We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value.

  6. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  7. Genetically-encoded Reporters

    NASA Astrophysics Data System (ADS)

    Isacoff, Ehud

    2002-03-01

    One of the principle goals of neuroscience has been to understand the cellular basis of information processing and the plasticity that underlies learning and memory. Efforts in this area have mainly relied on electrical recording and optical imaging with chemical dyes. Over the last few years we and others have begun to develop genetically-encoded optical reporter "dyes" which should provide several important advantages over the classical methods for monitoring signal transmission in the nervous system. The advantages are that genetically-encoded reporters can be molecularly targeted a) to specific cell types via cell-specific promoters, and b) to specific subcellular compartments by peptides that are recognized by the protein sorting machinery of the cell. This makes it possible, in principle, to exclude signals from non-neuronal cells and to visualize selectively, in a brain region that contains many cell types with numerous kinds of synaptic connections, the activity of specific types of neurons (e.g. GABAergic interneurons) and specific synaptic elements (e.g. nerve terminals or dendrites), something that has hitherto not been possible. An additional advantage is that protein reporters may be rationally and irrationally "tuned" with mutations in functional domains known to control their dynamic range of operation. The general idea behind genetically-encoded reporters of cell signaling is to encode a protein that is either intrinsically fluorescent, or that can be labeled orthogonally with a fluorescent probe, and where the physiological signal changes fluorescence emission. I will describe recent progress employing both kinds of approaches.

  8. Time-Encoded Imagers.

    SciTech Connect

    Marleau, Peter; Brubaker, Erik

    2014-11-01

    This report provides a short overview of the DNN R&D funded project, Time-Encoded Imagers. The project began in FY11 and concluded in FY14. The Project Description below provides the overall motivation and objectives for the project as well as a summary of programmatic direction. It is followed by a short description of each task and the resulting deliverables.

  9. Uprated fine guidance sensor study

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Future orbital observatories will require star trackers of extremely high precision. These sensors must maintain high pointing accuracy and pointing stability simultaneously with a low light level signal from a guide star. To establish the fine guidance sensing requirements and to evaluate candidate fine guidance sensing concepts, the Space Telescope Optical Telescope Assembly was used as the reference optical system. The requirements review was separated into three areas: Optical Telescope Assembly (OTA), Fine Guidance Sensing and astrometry. The results show that the detectors should be installed directly onto the focal surface presented by the optics. This would maximize throughput and minimize point stability error by not incoporating any additional optical elements.

  10. RH Packaging Program Guidance

    SciTech Connect

    Washington TRU Solutions, LLC

    2003-08-25

    The purpose of this program guidance document is to provide technical requirements for use, operation, inspection, and maintenance of the RH-TRU 72-B Waste Shipping Package and directly related components. This document complies with the requirements as specified in the RH-TRU 72-B Safety Analysis Report for Packaging (SARP), and Nuclear Regulatory Commission (NRC) Certificate of Compliance (C of C) 9212. If there is a conflict between this document and the SARP and/or C of C, the SARP and/or C of C shall govern. The C of C states: ''...each package must be prepared for shipment and operated in accordance with the procedures described in Chapter 7.0, ''Operating Procedures,'' of the application.'' It further states: ''...each package must be tested and maintained in accordance with the procedures described in Chapter 8.0, ''Acceptance Tests and Maintenance Program of the Application.'' Chapter 9.0 of the SARP tasks the Waste Isolation Pilot Plant (WIPP) Management and Operating (M&O) contractor with assuring the packaging is used in accordance with the requirements of the C of C. Because the packaging is NRC approved, users need to be familiar with 10 CFR {section} 71.11, ''Deliberate Misconduct.'' Any time a user suspects or has indications that the conditions of approval in the C of C were not met, the Carlsbad Field Office (CBFO) shall be notified immediately. CBFO will evaluate the issue and notify the NRC if required. This document details the instructions to be followed to operate, maintain, and test the RH-TRU 72-B packaging. This Program Guidance standardizes instructions for all users. Users shall follow these instructions. Following these instructions assures that operations are safe and meet the requirements of the SARP. This document is available on the Internet at: ttp://www.ws/library/t2omi/t2omi.htm. Users are responsible for ensuring they are using the current revision and change notices. Sites may prepare their own document using the word

  11. SPLC Sustainable Purchasing Guidance Profile

    EPA Pesticide Factsheets

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  12. Inert Ingredients Overview and Guidance

    EPA Pesticide Factsheets

    This Web page provides information on inert ingredients approved for use in pesticide products and the guidance documents that are available to assist in obtaining approval for a new inert ingredient.

  13. Enforcement Response Policies and Guidance

    EPA Pesticide Factsheets

    EPA's Enforcement Response Policies relating to violations or noncompliance with the environmental statutes and regulations. The listing is not inclusive of all policy and guidance that may be relied upon in developing enforcement actions.

  14. Chesapeake Bay Program Grant Guidance

    EPA Pesticide Factsheets

    Grant Guidance and appendices for the Chesapeake Bay Program that describes how the U.S. Environmental Protection Agency’s (EPA) Region 3’s Chesapeake Bay Program Office (CBPO) administers grant and cooperative agreement funds.

  15. Guidance Documents for Marine Fuel

    EPA Pesticide Factsheets

    The following guidance documents apply to marine fuel used in ocean-going vessels. All vessels that operate in the North American Emission Control Area (ECA) must generally use fuel with 1,000 ppm sulfur or less.

  16. TSCA Inventory Policy and Guidance

    EPA Pesticide Factsheets

    A list of numerous policy statements and guidance documents on how to identify certain chemical substances for the purpose of assigning unique and unambiguous descriptions tor each substance listed on the Inventory.

  17. Guidance Documents for Inert Ingredients

    EPA Pesticide Factsheets

    These guidance documents provide information on various inert ingredient issues, including the general process for submitting petitions or requests, adding trade names to our database, and doing searches related to inert ingredients.

  18. BASINS User Information and Guidance

    EPA Pesticide Factsheets

    This page provides links to guidance on how to use BASINS, including the User’s Manual, tutorials and training, technical notes, case studies, and publications that highlight the use of BASINS in various watershed analyses.

  19. Metagenomic small molecule discovery methods

    PubMed Central

    Charlop-Powers, Zachary; Milshteyn, Aleksandr; Brady, Sean F.

    2014-01-01

    Metagenomic approaches to natural product discovery provide the means of harvesting bioactive small molecules synthesized by environmental bacteria without the requirement of first culturing these organisms. Advances in sequencing technologies and general metagenomic methods are beginning to provide the tools necessary to unlock the unexplored biosynthetic potential encoded by the genomes of uncultured environmental bacteria. Here, we highlight recent advances in sequence- and functional- based metagenomic approaches that promise to facilitate antibiotic discovery from diverse environmental microbiomes. PMID:25000402

  20. Optical highlighter molecules in neurobiology

    PubMed Central

    Datta, Sandeep Robert; Patterson, George H.

    2011-01-01

    The development of advanced optical methods has played a key role in propelling progress in neurobiology. Genetically-encoded fluorescent molecules found in nature have enabled labeling of individual neurons to study their physiology and anatomy. Here we discuss the recent use of both native and synthetic optical highlighter proteins to address key problems in neurobiology, including questions relevant to synaptic function, neuroanatomy, and the organization of neural circuits. PMID:22129781

  1. Optical highlighter molecules in neurobiology.

    PubMed

    Datta, Sandeep Robert; Patterson, George H

    2012-02-01

    The development of advanced optical methods has played a key role in propelling progress in neurobiology. Genetically-encoded fluorescent molecules found in nature have enabled labeling of individual neurons to study their physiology and anatomy. Here we discuss the recent use of both native and synthetic optical highlighter proteins to address key problems in neurobiology, including questions relevant to synaptic function, neuroanatomy, and the organization of neural circuits. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Time-Encoded Imagers

    SciTech Connect

    Marleau, Peter; Brubaker, Erik; Brennan, James S.; Nowack, Aaron

    2014-09-01

    We have developed two neutron detector systems based on time-encoded imaging and demonstrated their applicability toward non-proliferation missions. The 1D-TEI system was designed for and evaluated against the ability to detect Special Nuclear Material (SNM) in very low signal to noise environments; in particular, very large stand-off and/or weak sources that may be shielded. We have demonstrated significant detection (>5 sigma) of a 2.8e5 n/s neutron fission source at 100 meters stand-off in 30 min. If scaled to an IAEA significant quantity of Pu, we estimate that this could be reduced to as few as ~5 minutes. In contrast to simple counting detectors, this was accomplished without the need of previous background measurements. The 2D-TEI system was designed for high resolution spatial mapping of distributions of SNM and proved feasibility of twodimensional fast neutron imaging using the time encoded modulation of rates on a single pixel detector. Because of the simplicity of the TEI design, there is much lower systematic uncertainty in the detector response typical coded apertures. Other imaging methods require either multiple interactions (e.g. neutron scatter camera or Compton imagers), leading to intrinsically low efficiencies, or spatial modulation of the signal (e.g., Neutron Coded Aperture Imager (Hausladen, 2012)), which requires a complicated, high channel count, and expensive position sensitive detector. In contrast, a single detector using a time-modulated collimator can encode directional information in the time distribution of detected events. This is the first investigation of time-encoded imaging for nuclear nonproliferation applications.

  3. Guidelines for Comprehensive Guidance and Counseling Services.

    ERIC Educational Resources Information Center

    Stefkovich, Jacqueline; And Others

    These guidelines are designed to assist local school districts and their Boards of Education in developing and implementing comprehensive guidance and counseling services in thier school systems. The components of the comprehensive guidance program are comprehensive guidance services, certified personnel, and comprehensive guidance facilities.…

  4. Guidance on submitting quality system information.

    PubMed

    Donawa, Maria E

    2004-03-01

    The Food and Drug Administration's final guidance document on the type of quality system information that should be submitted in some types of premarket submissions was published in February 2003. The final guidance replaces previous draft guidance. This article discusses the final guidance document.

  5. Resources for Guidance Program Improvement. Volume 2.

    ERIC Educational Resources Information Center

    Frenza, Mary C., Comp.; and Others

    This guide, for guidance personnel and teachers, is designed to provide ready access to current, practical programs, activities, and references for improving guidance programs. The resources are organized in four sections representing areas of basic concern for guidance personnel. Section 1 presents selected portions of guidance programs from…

  6. Resources for Guidance Program Improvement. Volume I.

    ERIC Educational Resources Information Center

    Walz, Garry R., Comp.; And Others

    Designed for use by counselors, guidance directors, school administrators, school board members, and anyone interested in the improvement of school guidance programs, this resource book provides a collection of over 100 guidance program models and individual guidance practices. The format consists of references (bibliographic information with…

  7. Haptic Guidance Improves the Visuo-Manual Tracking of Trajectories

    PubMed Central

    Bluteau, Jérémy; Coquillart, Sabine; Payan, Yohan; Gentaz, Edouard

    2008-01-01

    Background Learning to perform new movements is usually achieved by following visual demonstrations. Haptic guidance by a force feedback device is a recent and original technology which provides additional proprioceptive cues during visuo-motor learning tasks. The effects of two types of haptic guidances-control in position (HGP) or in force (HGF)–on visuo-manual tracking (“following”) of trajectories are still under debate. Methodology/Principals Findings Three training techniques of haptic guidance (HGP, HGF or control condition, NHG, without haptic guidance) were evaluated in two experiments. Movements produced by adults were assessed in terms of shapes (dynamic time warping) and kinematics criteria (number of velocity peaks and mean velocity) before and after the training sessions. Trajectories consisted of two Arabic and two Japanese-inspired letters in Experiment 1 and ellipses in Experiment 2. We observed that the use of HGF globally improves the fluency of the visuo-manual tracking of trajectories while no significant improvement was found for HGP or NHG. Conclusion/Significance These results show that the addition of haptic information, probably encoded in force coordinates, play a crucial role on the visuo-manual tracking of new trajectories. PMID:18335049

  8. Spectrally encoded confocal microscopy

    SciTech Connect

    Tearney, G.J.; Webb, R.H.; Bouma, B.E.

    1998-08-01

    An endoscope-compatible, submicrometer-resolution scanning confocal microscopy imaging system is presented. This approach, spectrally encoded confocal microscopy (SECM), uses a quasi-monochromatic light source and a transmission diffraction grating to detect the reflectivity simultaneously at multiple points along a transverse line within the sample. Since this method does not require fast spatial scanning within the probe, the equipment can be miniaturized and incorporated into a catheter or endoscope. Confocal images of an electron microscope grid were acquired with SECM to demonstrate the feasibility of this technique. {copyright} {ital 1998} {ital Optical Society of America}

  9. Core needle biopsy guidance based on EMOCT imaging (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Iftimia, Nicusor V.; Park, Jesung; Maguluri, Gopi

    2016-03-01

    We present a novel method, based on encoder mapping OCT imaging, for real-time guidance of core biopsy procedures. This method provides real-time feedback to the interventional radiologist, such that he/she can reorient the needle during the biopsy and sample the most representative area of the suspicious mass that is being investigated. This aspect is very important for tailoring therapy to the specific cancer based on biomarker analysis, which will become one of the next big advances in our search for the optimal cancer therapy. To enable individualized treatment, the genetic constitution and the DNA repair status in the affected areas is needed for each patient. Thus, representative sampling of the tumor is needed for analyzing various biomarkers, which are used as a tool to personalize cancer therapy. The encoder-based OCT enables samping of large size masses and provides full control on the imaging probe, which is passed through the bore of the biopsy guidance needle. The OCT image is built gradually, based on the feedback of an optical encoder which senses the incremental movement of the needle with a few microns resolution. Tissue mapping is independent of the needle speed, while it is advanced through the tissue. The OCT frame is analyzed in real-time and tissue cellularity is reported in a very simple manner (pie chart). Our preliminary study on a rabbit model of cancer has demonstrated the capability of this technology for accurately differentiating between viable cancer and heterogeneous or necrotic tissue.

  10. Information architecture. Volume 3: Guidance

    SciTech Connect

    1997-04-01

    The purpose of this document, as presented in Volume 1, The Foundations, is to assist the Department of Energy (DOE) in developing and promulgating information architecture guidance. This guidance is aimed at increasing the development of information architecture as a Departmentwide management best practice. This document describes departmental information architecture principles and minimum design characteristics for systems and infrastructures within the DOE Information Architecture Conceptual Model, and establishes a Departmentwide standards-based architecture program. The publication of this document fulfills the commitment to address guiding principles, promote standard architectural practices, and provide technical guidance. This document guides the transition from the baseline or defacto Departmental architecture through approved information management program plans and budgets to the future vision architecture. This document also represents another major step toward establishing a well-organized, logical foundation for the DOE information architecture.

  11. Autonomous Guidance, Navigation and Control

    NASA Technical Reports Server (NTRS)

    Bordano, A. J.; Mcswain, G. G.; Fernandes, S. T.

    1991-01-01

    The NASA Autonomous Guidance, Navigation and Control (GN&C) Bridging program is reviewed to demonstrate the program plan and GN&C systems for the Space Shuttle. The ascent CN&C system is described in terms of elements such as the general-purpose digital computers, sensors for the navigation subsystem, the guidance-system software, and the flight-control subsystem. Balloon-based and lidar wind soundings are used for operations assessment on the day of launch, and the guidance software is based on dedicated units for atmospheric powered flight, vacuum powered flight, and abort-specific situations. Optimization of the flight trajectories is discussed, and flight-control responses are illustrated for wavelengths of 500-6000 m. Alternate sensors are used for load relief, and adaptive GN&C systems based on alternate gain synthesis are used for systems failures.

  12. Ultrasound guidance for vascular access.

    PubMed

    Abboud, Paul-André C; Kendall, John L

    2004-08-01

    The evidence that supports the general application of US guidance for venous access in the ED has reached a critical mass. The increasing familiarity of emergency physicians with US and the recent focus on patient safety and clinical outcomes has intensified attention on the capacity for US to improve patient care in the ED. US guidance can increase the safety and efficiency of venous access procedures and offers improved outcomes. The potential for these improvements is compelling, especially among certain types of ED patients such as those with difficult or complicated access. Varying levels of evidence support the use of US guidance over the traditional landmark approach for venous access in adult and pediatric populations and for central and peripheral veins. Many different techniques may be applied, depending on the clinical situation and equipment available.

  13. BmRobo2/3 is required for axon guidance in the silkworm Bombyx mori.

    PubMed

    Li, Xiao-Tong; Yu, Qi; Zhou, Qi-Sheng; Zhao, Xiao; Liu, Zhao-Yang; Cui, Wei-Zheng; Liu, Qing-Xin

    2016-02-15

    Axon guidance is critical for proper wiring of the nervous system. During the neural development, the axon guidance molecules play a key role and direct axons to choose the correct way to reach the target. Robo, as the receptor of axon guidance molecule Slit, is evolutionarily conserved from planarians to humans. However, the function of Robo in the silkworm, Bombyx mori, remained unknown. In this study, we cloned robo2/3 from B. mori (Bmrobo2/3), a homologue of robo2/3 in Tribolium castaneum. Moreover, BmRobo2/3 was localized in the neuropil, and RNAi-mediated knockdown of Bmrobo2/3 resulted in the longitudinal connectives forming closer to the midline. These data demonstrate that BmRobo2/3 is required for axon guidance in the silkworm. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Guidance for state attainment plans

    SciTech Connect

    Strait, R.

    1994-06-01

    Title I of the Clean Air act Amendments of 1990 significantly changed requirements for regulatory agencies to prepare state implementation plans that demonstrate attainment of the ozone National Ambient Air Quality Standards. State agencies now are required to submit plans that show how they will meet the standards by their attainment date. EPA has published a series of guidance documents to assist states in preparing their plans. In addition, the agency is developing software to assist states in projecting emissions and tracking reductions. This article summarizes the guidance documents and software program.

  15. Guidance on Annual Compliance Certifications

    EPA Pesticide Factsheets

    This document may be of assistance in applying the Title V air operating permit regulations. This document is part of the Title V Policy and Guidance Database available at www2.epa.gov/title-v-operating-permits/title-v-operating-permit-policy-and-guidance-document-index. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  16. Signaling mechanisms of non-conventional axon guidance cues: the Shh, BMP and Wnt morphogens.

    PubMed

    Yam, Patricia T; Charron, Frédéric

    2013-12-01

    During nervous system development, axons, led by the growth cone, must navigate to their destinations. Axon guidance cues are molecules in the extracellular environment that attract or repel axons to guide them along their correct trajectory. The non-conventional axon guidance cues include morphogens of the Hedgehog, TGF-β/BMP, and Wnt/Wgl families. Canonical signaling by morphogens regulates transcription in the nucleus to specify cell fate. Recent studies have begun to elucidate how these morphogens can also direct growth cone turning, using signaling mechanisms that diverge from their canonical signaling pathways. Furthermore, in addition to directly guiding axons, some non-conventional guidance cues such as Sonic hedgehog also modulate the response of axons to other guidance cues, adding another level of regulation to axon guidance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. 78 FR 56752 - Interim Staff Guidance Specific Environmental Guidance for Integral Pressurized Water Reactors...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-13

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Interim Staff Guidance Specific Environmental Guidance for Integral Pressurized Water Reactors... and operate integral pressurized water reactors (iPWR). This guidance applies to environmental reviews...

  18. Mind Molecules

    PubMed Central

    Snyder, Solomon H.

    2011-01-01

    Scientific styles vary tremendously. For me, research is largely about the unfettered pursuit of novel ideas and experiments that can test multiple ideas in a day, not a year, an approach that I learned from my mentor Julius “Julie” Axelrod. This focus on creative conceptualizations has been my métier since working in the summers during medical school at the National Institutes of Health, during my two years in the Axelrod laboratory, and throughout my forty-five years at Johns Hopkins University School of Medicine. Equally important has been the “high” that emerges from brainstorming with my students. Nothing can compare with the eureka moments when, together, we sense new insights and, better yet, when high-risk, high-payoff experiments succeed. Although I have studied many different questions over the years, a common theme emerges: simple biochemical approaches to understanding molecular messengers, usually small molecules. Equally important has been identifying, purifying, and cloning the messengers' relevant biosynthetic, degradative, or target proteins, at all times seeking potential therapeutic relevance in the form of drugs. In the interests of brevity, this Reflections article is highly selective, and, with a few exceptions, literature citations are only of findings of our laboratory that illustrate notable themes. PMID:21543333

  19. The TL region gene 37 encodes a Qa-1 antigen

    PubMed Central

    1990-01-01

    Of all the biochemically defined mouse MHC class I molecules, the Qa-1 antigens are the only ones for which a gene has not been identified. Recent evidence has suggested that Qa-1 antigens are functional class I molecules and can function as restriction elements for gamma/delta T cells. We have examined the relationship between Qa-1 and the product of gene 37, a presumed novel class I antigen encoded within the TL region. Immunoprecipitation and polyacrylamide gel electrophoresis analysis of the molecules reactive with anti-Qa-1 and anti-37 sera show that the Qa-1 molecule of Qa-1b (Qa-1.2) mouse strains is identical to the product of gene 37 on the basis of molecular weight, pI, and strain distribution. Immunodepletion, biosynthetic labeling, and tunicamycin treatment confirm that the protein encoded by gene 37 in Qa-1b mice is Qa-1.2. In contrast, the anti-37 serum was unable to recognize the Qa-1 molecule in Qa-1a strains. Given the fact that the only allele to gene 37 thus far identified in a Qa-1a strain (A/J) has a termination codon in the alpha 3 domain, our data lead us to conclude that the Qa-1 molecule expressed in Qa-1a mice is not a true allelic product of the gene 37 encoded antigen of Qa-1b mouse strains. PMID:2258708

  20. EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans

    PubMed Central

    Dong, Bingyun; Moseley-Alldredge, Melinda; Schwieterman, Alicia A.; Donelson, Cory J.; McMurry, Jonathan L.; Hudson, Martin L.; Chen, Lihsia

    2016-01-01

    During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. In C. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for the C. elegans ephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with the C. elegans divergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. We also show that EFN-4 probably functions as a diffusible factor because EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal. PMID:26903502

  1. Time Encoded Radiation Imaging

    SciTech Connect

    Marleau, Peter; Brubaker, Erik; Gerling, Mark D.; Schuster, Patricia Frances; Steele, John T.

    2011-09-01

    Passive detection of special nuclear material (SNM) at long range or under heavy shielding can only be achieved by observing the penetrating neutral particles that it emits: gamma rays and neutrons in the MeV energy range. The ultimate SNM standoff detector system would have sensitivity to both gamma and neutron radiation, a large area and high efficiency to capture as many signal particles as possible, and good discrimination against background particles via directional and energy information. Designing such a system is a daunting task. Using timemodulated collimators could be a transformative technique leading to practical gamma-neutron imaging detector systems that are highly efficient with the potential to exhibit simultaneously high angular and energy resolution. A new technique using time encoding to make a compact, high efficiency imaging detector was conceived. Design considerations using Monte Carlo modeling and the construction and demonstration of a prototype imager are described.

  2. Time encoded radiation imaging

    SciTech Connect

    Marleau, Peter; Brubaker, Erik; Kiff, Scott

    2014-10-21

    The various technologies presented herein relate to detecting nuclear material at a large stand-off distance. An imaging system is presented which can detect nuclear material by utilizing time encoded imaging relating to maximum and minimum radiation particle counts rates. The imaging system is integrated with a data acquisition system that can utilize variations in photon pulse shape to discriminate between neutron and gamma-ray interactions. Modulation in the detected neutron count rates as a function of the angular orientation of the detector due to attenuation of neighboring detectors is utilized to reconstruct the neutron source distribution over 360 degrees around the imaging system. Neutrons (e.g., fast neutrons) and/or gamma-rays are incident upon scintillation material in the imager, the photons generated by the scintillation material are converted to electrical energy from which the respective neutrons/gamma rays can be determined and, accordingly, a direction to, and the location of, a radiation source identified.

  3. Rotary encoding device

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B. (Inventor)

    1993-01-01

    A device for position encoding of a rotating shaft in which a polygonal mirror having a number of facets is mounted to the shaft and a light beam is directed towards the facets is presented. The facets of the polygonal mirror reflect the light beam such that a light spot is created on a linear array detector. An analog-to-digital converter is connected to the linear array detector for reading the position of the spot on the linear array detector. A microprocessor with memory is connected to the analog-to-digital converter to hold and manipulate the data provided by the analog-to-digital converter on the position of the spot and to compute the position of the shaft based upon the data from the analog-to-digital converter.

  4. Linear encoding device

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B. (Inventor)

    1993-01-01

    A Linear Motion Encoding device for measuring the linear motion of a moving object is disclosed in which a light source is mounted on the moving object and a position sensitive detector such as an array photodetector is mounted on a nearby stationary object. The light source emits a light beam directed towards the array photodetector such that a light spot is created on the array. An analog-to-digital converter, connected to the array photodetector is used for reading the position of the spot on the array photodetector. A microprocessor and memory is connected to the analog-to-digital converter to hold and manipulate data provided by the analog-to-digital converter on the position of the spot and to compute the linear displacement of the moving object based upon the data from the analog-to-digital converter.

  5. Consensus standard requirements and guidance

    SciTech Connect

    Putman, V.L.

    1995-12-01

    This report presents information from the ANS Criticality Alarm System Workshop relating to the consensus standard requirements and guidance. Topics presented include: definition; nomenclature; requirements and recommendations; purpose of criticality alarms; design criteria; signal characteristics; reliability, dependability and durability; tests; and emergency preparedness and planning.

  6. Project Inspire: Vocational Guidance Institute.

    ERIC Educational Resources Information Center

    National Alliance of Businessmen, Washington, DC.

    Two introductory speeches suggest the general social and interracial climate in the United States. It is against this backdrop that Project Inspire is described. Its purpose is the development of a vocational guidance component within the broader school curriculum. Its major objective is elevating the awareness level of students to the work world…

  7. Reading Guidance: Death and Grief.

    ERIC Educational Resources Information Center

    Smith, Alice Gullen

    1989-01-01

    Gives guidelines for the librarian using reading guidance (similar to bibliotherapy). Provides a nine-item annotated bibliography of novels for children and adolescents on the subject of death and grief. Appends an embryo list of categories suitable for content analysis of any file librarians might wish to keep on books suitable for use in this…

  8. Elementary Guidance Program. Navajo Area.

    ERIC Educational Resources Information Center

    Bureau of Indian Affairs (Dept. of Interior), Window Rock, AZ.

    A program designed to assist guidance staff in working with Navajo elementary school students, particularly boarding school students, is presented in this booklet with emphasis directed toward meeting both individual and group needs in the areas of home living, student activities, and counseling. The first section gives 14 separate functions of…

  9. DOE Waste Treatability Group Guidance

    SciTech Connect

    Kirkpatrick, T.D.

    1995-01-01

    This guidance presents a method and definitions for aggregating U.S. Department of Energy (DOE) waste into streams and treatability groups based on characteristic parameters that influence waste management technology needs. Adaptable to all DOE waste types (i.e., radioactive waste, hazardous waste, mixed waste, sanitary waste), the guidance establishes categories and definitions that reflect variations within the radiological, matrix (e.g., bulk physical/chemical form), and regulated contaminant characteristics of DOE waste. Beginning at the waste container level, the guidance presents a logical approach to implementing the characteristic parameter categories as part of the basis for defining waste streams and as the sole basis for assigning streams to treatability groups. Implementation of this guidance at each DOE site will facilitate the development of technically defined, site-specific waste stream data sets to support waste management planning and reporting activities. Consistent implementation at all of the sites will enable aggregation of the site-specific waste stream data sets into comparable national data sets to support these activities at a DOE complex-wide level.

  10. Research Bulletin: Bayesian Guidance Technology.

    ERIC Educational Resources Information Center

    Novick, Melvin R.; Jackson, Paul H.

    This paper presents a discussion of the use of educational tests in guidance services as seen in the light of modern developments in statistical theory and computer technology, and of the increasing demands for such services. A focus and vocabulary for this discussion is found in Turnbull's recent article on "Relevance in Testing." Following an…

  11. Reading Guidance: Death and Grief.

    ERIC Educational Resources Information Center

    Smith, Alice Gullen

    1989-01-01

    Gives guidelines for the librarian using reading guidance (similar to bibliotherapy). Provides a nine-item annotated bibliography of novels for children and adolescents on the subject of death and grief. Appends an embryo list of categories suitable for content analysis of any file librarians might wish to keep on books suitable for use in this…

  12. Developing Local Lifelong Guidance Strategies.

    ERIC Educational Resources Information Center

    Watts, A. G.; Hawthorn, Ruth; Hoffbrand, Jill; Jackson, Heather; Spurling, Andrea

    1997-01-01

    Outlines the background, rationale, methodology, and outcomes of developing local lifelong guidance strategies in four geographic areas. Analyzes the main components of the strategies developed and addresses a number of issues relating to the process of strategy development. Explores implications for parallel work in other localities. (RJM)

  13. THE STRESSOR IDENTIFICATION GUIDANCE DOCUMENT

    EPA Science Inventory

    THE STRESSOR IDENTIFICATION GUIDANCE DOCUMENT

    Susan M. Cormier, ORD/NRMRL, Susan B. Norton, ORD/NCEA, Glenn W. Suter, II ORD/NCEA, William Swietlik, OW lOST

    Science Question(s):

    MYP Science Question: How can multiple and possibly related causes of biological ...

  14. Guidance: Interim Municipal Settlement Policy

    EPA Pesticide Factsheets

    Interim guidance and fact sheets regarding settlements involving municipalities or municipal waste under Section 122 CERCLA as amended by SARA. Interim policy sets forth the criteria by which EPA generally determines whether to exercise enforcement discretion to pursue MSW generators and transporters as PRPs.

  15. THE STRESSOR IDENTIFICATION GUIDANCE DOCUMENT

    EPA Science Inventory

    THE STRESSOR IDENTIFICATION GUIDANCE DOCUMENT

    Susan M. Cormier, ORD/NRMRL, Susan B. Norton, ORD/NCEA, Glenn W. Suter, II ORD/NCEA, William Swietlik, OW lOST

    Science Question(s):

    MYP Science Question: How can multiple and possibly related causes of biological ...

  16. Abortion Information: A Guidance Viewpoint

    ERIC Educational Resources Information Center

    Wolleat, Patricia L.

    1975-01-01

    A number of questions relating to providing abortion information to teenagers can be raised from legal, ethical and philosophical standpoints. The purpose of this article is to examine abortion information-giving from the perspective of counseling and guidance theory and practice. (Author)

  17. Child Development, Care, and Guidance.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin. Dept. of Occupational Education and Technology.

    This teacher's guide on child development, care, and guidance is one of seven subject area guides developed for use in consumer and homemaking education in secondary schools in Texas. The guide is correlated with the "Conceptual Framework for Consumer and Homemaking Education in Texas." Content is based on the competencies needed by…

  18. Theater As A Guidance Technique

    ERIC Educational Resources Information Center

    Wolpert, William

    1973-01-01

    Guidance-drama activity provides (a) crisp definitions of selected issues; (b) potent modeling from the characters in the play, the students actively engaged in the play, and the students involved in the discussions that follow the play; and (c) a technique for peer-led discussions on sensitive issues. This article gives precise definition to the…

  19. GUIDANCE FOR CONDUCTING HEALTH RISK ...

    EPA Pesticide Factsheets

    While some potential environmental hazards involve significant exposure to only a single compound, most instances of environmental contamination involve concurrent or sequential exposures to a mixture of compounds that may induce similar or dissimilar effects over exposure periods ranging from short-term to lifetime. Multichemical exposures are ubiquitous, including air and soil pollution from municipal incinerators, leakage from hazardous waste facilities and uncontrolled waste sites, and drinking water containing chemical substances formed during disinfection. To address concerns over health risks from multichemical exposures, EPA issued Guidelines for Health Risk from Exposure to Chemical Mixtures in 1986. Those Guidelines described broad concepts related to mixtures exposure and toxicity and included few specific procedures. Since then, EPA has published additional mixtures guidance documents such as 1989 guidance for the Superfund program on hazardous waste and the 1990 Technical Support Document on Health Risk Assessment of Chemical Mixtures. Because the science of environmental risk assessment continues to evolve, EPA's Risk Assessment Forum established a Technical Work Panel to ensure that the advances in the area of chemical mixtures health risk assessment are reflected in the Agency's guidance materials. This document has been developed by the Technical Work Panel to supplement the earlier guidances and is organized according to the type of data avail

  20. Atmospheric guidance techniques and performance

    NASA Technical Reports Server (NTRS)

    Harpold, J. C.; Gavert, D. E.

    1982-01-01

    The Orbiter entry guidance system controls the Space Shuttle Orbiter from the initial atmospheric penetration point to the point at which an earth relative velocity of 2500 feet/second is reached. At the latter point, control of the Orbiter is transferred to the terminal area energy management system. The entry guidance system is based on the concept that the range to be flown during entry is a unique function of the drag deceleration profile flown throughout the entry. The range prediction during entry is based on analytic equations which are simple drag deceleration functions of earth relative velocity above Mach 10.5 and energy with respect to the earth below Mach 10.5. Flight through the entry corridor is accomplished by linking these simple drag deceleration functions together in series in order to define a drag deceleration reference profile. The results of the first three Space Shuttle missions have not only verified the entry guidance concept but have also demonstrated the stability of the guidance system.

  1. Imaging Futuristic Career Guidance Programs.

    ERIC Educational Resources Information Center

    Miller, Juliet V; And Others

    This Module is directed toward guidance personnel in school (K-adult) and agency settings such as counselors, teachers, students and administrators. It is also designed for students in pre-service education programs who have had previous exposure to career development theories and to sources of educational-occupational information. The Module…

  2. Imaging Futuristic Career Guidance Goals.

    ERIC Educational Resources Information Center

    Miller, Juliet V.; and Others

    This module is directed toward guidance personnel in school (k-adult) and agency settings such as counselors, teachers, students and administrators. It is also designed for students in pre-service education programs who are familiar with career development theories and information. The Module assumes that the participant is not familiar with the…

  3. Guidance for Supporting School Counselors

    ERIC Educational Resources Information Center

    Light, Carolyn

    2005-01-01

    School counselors need the assistance of principals and other administrators to improve guidance and school counseling services in schools. Principals and other administrators are the leaders in education, and it is important that they know how to create the best school counseling programs possible. This article provides 12 suggestions that can…

  4. Educational Guidance and Curriculum Change.

    ERIC Educational Resources Information Center

    Oakeshott, Martin

    A project conducted by Britain's Further Education Unit: (1) identified and evaluated strategies used by Educational Guidance Services for Adults (EGSAs) to feed back to providers of learning opportunities the unmet needs of adult clients with particular reference to the unemployed and unwaged; (2) identified and evaluated mechanisms used by…

  5. A new paradigm in optimal missile guidance

    NASA Astrophysics Data System (ADS)

    Morgan, Robert W.

    2007-12-01

    This dissertation investigates advanced concepts in terminal missile guidance. The terminal phase of missile guidance usually lasts less than ten seconds and calls for very accurate maneuvering to ensure intercept. Technological advancements have produced increasingly sophisticated threats that greatly reduce the effectiveness of traditional approaches to missile guidance. Because of this, terminal missile guidance is, and will remain, an important and active area of research. The complexity of the problem and the desire for an optimal solution has resulted in researchers focusing on simplistic, usually linear, models. The fruit of these endeavors has resulted in some of the world's most advanced weapons systems. Even so, the resulting guidance schemes cannot possibly counter the evolving threats that will push the system outside the linear envelope for which they were designed. The research done in this dissertation greatly extends previous research in the area of optimal missile guidance. Herein it is shown that optimal missile guidance is fundamentally a pairing of an optimal guidance strategy and an optimal control strategy. The optimal guidance strategy is determined from a missile's information constraints, which are themselves largely determined from the missile's sensors. The optimal control strategy is determined by the missile's control constraints, and works to achieve a specified guidance strategy. This dichotomy of missile guidance is demonstrated by showing that missiles having different control constraints utilize the same guidance strategy so long as the information constraints are the same. This concept has hitherto been unrecognized because of the difficulty in developing an optimal control for the nonlinear set of equations that result from control constraints. Having overcome this difficulty by indirect means, evidence of the guidance strategy paradigm emerged. The guidance strategy paradigm is used to develop two advanced guidance laws. The new

  6. DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis

    PubMed Central

    2015-01-01

    The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the “structure elucidation problem”: the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded solid-phase synthesis (DESPS), comprising parallel compound synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length <100 bases for facile sequencing. Ligation is efficient (70% yield), specific, and directional over 6 encoding positions. A series of isomers served as a testbed for DESPS’s utility in split-and-pool diversification. Single-bead quantitative PCR detected 9 × 104 molecules/bead and sequencing allowed for elucidation of each compound’s synthetic history. We applied DESPS to the combinatorial synthesis of a 75 645-member OBOC library containing scaffold, stereochemical and regiochemical diversity using mixed-scale resin (160-μm quality control beads and 10-μm screening beads). Tandem DNA sequencing/MALDI-TOF MS analysis of 19 quality control beads showed excellent agreement (<1 ppt) between DNA sequence-predicted mass and the observed mass. DESPS synergistically unites the advantages of solid-phase synthesis and DNA encoding, enabling single-bead structural elucidation of complex compounds and synthesis using reactions normally considered incompatible with unprotected DNA. The widespread availability of inexpensive oligonucleotide synthesis, enzymes, DNA sequencing, and

  7. DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis.

    PubMed

    MacConnell, Andrew B; McEnaney, Patrick J; Cavett, Valerie J; Paegel, Brian M

    2015-09-14

    The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the "structure elucidation problem": the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded solid-phase synthesis (DESPS), comprising parallel compound synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length <100 bases for facile sequencing. Ligation is efficient (70% yield), specific, and directional over 6 encoding positions. A series of isomers served as a testbed for DESPS's utility in split-and-pool diversification. Single-bead quantitative PCR detected 9 × 10(4) molecules/bead and sequencing allowed for elucidation of each compound's synthetic history. We applied DESPS to the combinatorial synthesis of a 75,645-member OBOC library containing scaffold, stereochemical and regiochemical diversity using mixed-scale resin (160-μm quality control beads and 10-μm screening beads). Tandem DNA sequencing/MALDI-TOF MS analysis of 19 quality control beads showed excellent agreement (<1 ppt) between DNA sequence-predicted mass and the observed mass. DESPS synergistically unites the advantages of solid-phase synthesis and DNA encoding, enabling single-bead structural elucidation of complex compounds and synthesis using reactions normally considered incompatible with unprotected DNA. The widespread availability of inexpensive oligonucleotide synthesis, enzymes, DNA sequencing, and PCR

  8. Genetic analysis of a Drosophila neural cell adhesion molecule: interaction of fasciclin I and Abelson tyrosine kinase mutations.

    PubMed

    Elkins, T; Zinn, K; McAllister, L; Hoffmann, F M; Goodman, C S

    1990-02-23

    Drosophila fasciclin I is a homophilic cell adhesion molecule expressed in the developing embryo on the surface of a subset of fasciculating CNS axons, all PNS axons, and some nonneuronal cells. We have identified protein-null mutations in the fasciclin I (fas I) gene, and show that these mutants are viable and do not display gross defects in nervous system morphogenesis. The Drosophila Abelson (abl) proto-oncogene homolog encodes a cytoplasmic tyrosine kinase that is expressed during embryogenesis primarily in developing CNS axons; abl mutants show no gross defects in CNS morphogenesis. However, embryos doubly mutant for fas I and abl display major defects in CNS axon pathways, particularly in the commissural tracts where expression of these two proteins normally overlaps. The double mutant shows a clear defect in growth cone guidance; for example, the RP1 growth cone (normally fas I positive) does not follow its normal path across the commissure.

  9. Semaphorins: a new class of immunoregulatory molecules

    PubMed Central

    Takegahara, Noriko; Kumanogoh, Atsushi; Kikutani, Hitoshi

    2005-01-01

    The immune and nervous systems play distinct roles in maintaining physiological homeostasis. Recent data indicates that these systems influence one another and share many proteins and pathways that are essential for their normal function and development. Molecules originally shown to be critical for the development of proper immune responses have recently been found to function in the nervous system. Conversely, neuronal guidance cues can modulate immune functions. Although semaphorins were originally identified as axon guidance factors active during neuronal development, several recent studies have identified indispensable functions for these molecules in the immune system. This review provides an overview of the rapidly emerging functions of semaphorins and their receptors in the immune system. PMID:16147531

  10. Twenty-five Years of DNA-Encoded Chemical Libraries.

    PubMed

    Neri, Dario

    2017-05-04

    Reference library: The availability of DNA-encoded chemical libraries containing billions of compounds facilitates the discovery of binding molecules for pharmaceutical applications and for investigating biological processes. This Special Issue highlights the use of this library technology and some of the latest developments in the field. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Maladjusted Children and the Child Guidance Service

    ERIC Educational Resources Information Center

    Tizard, Jack

    1973-01-01

    Argues that the child guidance clinic, linchpin of the child guidance service, is an expensive, ineffective, and wrongly conceived institution. Does not discuss the needs of preschoolers, services by special classes, nor special schools for maladjusted pupils. (RJ)

  12. Guidance: CERCLA Section 106 Judicial Actions

    EPA Pesticide Factsheets

    This guidance provides criteria for consideration in selecting and initiating Section 106 judicial actions. The guidance also identifies and discusses issues that should be considered in preparation of a Section 106 referral.

  13. Space vehicle onboard command encoder

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A flexible onboard encoder system was designed for the space shuttle. The following areas were covered: (1) implementation of the encoder design into hardware to demonstrate the various encoding algorithms/code formats, (2) modulation techniques in a single hardware package to maintain comparable reliability and link integrity of the existing link systems and to integrate the various techniques into a single design using current technology. The primary function of the command encoder is to accept input commands, generated either locally onboard the space shuttle or remotely from the ground, format and encode the commands in accordance with the payload input requirements and appropriately modulate a subcarrier for transmission by the baseband RF modulator. The following information was provided: command encoder system design, brassboard hardware design, test set hardware and system packaging, and software.

  14. N-Consecutive-Phase Encoder

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Lee, Ho-Kyoung; Weber, Charles

    1995-01-01

    N-consecutive-phase encoder (NCPE) is conceptual encoder for generating alphabet of N consecutive full-response continuous-phase-modulation (CPM) signals. Enables use of binary preencoder of higher rate than used with simple continuous-phase encoder (CPE). NCPE makes possible to achieve power efficiencies and bandwidth efficiencies greater than conventional trellis coders with continuous-phase frequency-shift keying (CPFSK).

  15. A guidance concept for hypersonic aerospacecrafts

    NASA Astrophysics Data System (ADS)

    Ishimoto, Shinji

    In this paper a guidance concept for hypersonic re-entry flights is presented. The method uses a closed-form guidance technique based on a drag acceleration reference profile. A guidance law for range control is developed. It employs a physical relation between vehicle energy and range instead of a prediction-correction technique used for Shuttle entry guidance. Simulation results show that the algorithm provides good performance.

  16. Genetically encoding new bioreactivity.

    PubMed

    Wang, Lei

    2017-09-25

    The genetic code can be expanded to include unnatural amino acids (Uaas) by engineering orthogonal components involved in protein translation. To be compatible with live cells, side chains of Uaas have been limited to either chemically inert or bio-orthogonal (i.e., nonreactive toward biomolecules) functionalities. To introduce bioreactivity into live systems, the genetic code has recently been engineered to encode a new class of Uaas, the bioreactive Uaas. These Uaas, after being incorporated into proteins, specifically react with target natural amino acid residues via proximity-enabled bioreactivity, enabling the selective formation of new covalent linkages within and between proteins both in vitro and in live systems. The new covalent bonding ability has been harnessed within proteins to enhance photostability, increase thermostability, staple proteins recombinantly, and build optical nano-switches, and between proteins to pinpoint ligand-receptor interaction, target native receptors irreversibly, and generate covalent macromolecular inhibitors. These diverse bioreactivities, inaccessible to natural proteins, thus open doors to novel protein engineering and provide new avenues for biological studies, biotherapeutics and synthetic biology. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Encoded libraries of chemically modified peptides.

    PubMed

    Heinis, Christian; Winter, Greg

    2015-06-01

    The use of powerful technologies for generating and screening DNA-encoded protein libraries has helped drive the development of proteins as pharmaceutical ligands. However the development of peptides as pharmaceutical ligands has been more limited. Although encoded peptide libraries are typically several orders of magnitude larger than classical chemical libraries, can be more readily screened, and can give rise to higher affinity ligands, their use as pharmaceutical ligands is limited by their intrinsic properties. Two of the intrinsic limitations include the rotational flexibility of the peptide backbone and the limited number (20) of natural amino acids. However these limitations can be overcome by use of chemical modification. For example, the libraries can be modified to introduce topological constraints such as cyclization linkers, or to introduce new chemical entities such as small molecule ligands, fluorophores and photo-switchable compounds. This article reviews the chemistry involved, the properties of the peptide ligands, and the new opportunities offered by chemical modification of DNA-encoded peptide libraries.

  18. Career Guidance in England: Retrospect and Prospect

    ERIC Educational Resources Information Center

    Mulvey, M. Rachel

    2006-01-01

    This paper tackles three challenges: first, to sketch the history of career guidance provision in England over the last 25 years; second, to identify what the current structure of career guidance in England is; and finally, to analyse the key issues and challenges which career guidance in England now faces. Whilst its earlier history in this field…

  19. 75 FR 76079 - Sound Incentive Compensation Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-07

    ... Office of Thrift Supervision Sound Incentive Compensation Guidance AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Sound Incentive Compensation Guidance. OMB Number: 1550-0129. Form Number: N/A... principles and the guidance are consistent with the Principles for Sound Compensation Practices adopted...

  20. 75 FR 22679 - Sound Incentive Compensation Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... Office of Thrift Supervision Sound Incentive Compensation Guidance AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Sound Incentive Compensation Guidance. OMB Number: 1550-0NEW. Form Number: N/A... principles and the guidance are consistent with the Principles for Sound Compensation Practices adopted...

  1. 75 FR 53023 - Sound Incentive Compensation Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-30

    ... Office of Thrift Supervision Sound Incentive Compensation Guidance AGENCY: Office of Thrift Supervision... collection. Title of Proposal: Sound Incentive Compensation Guidance. OMB Number: 1550-0129. Form Number: N/A... principles and the guidance are consistent with the Principles for Sound Compensation Practices adopted...

  2. Quality Assurance in University Guidance Services

    ERIC Educational Resources Information Center

    Simon, Alexandra

    2014-01-01

    In Europe there is no common quality assurance framework for the delivery of guidance in higher education. Using a case study approach in four university career guidance services in England, France and Spain, this article aims to study how quality is implemented in university career guidance services in terms of strategy, standards and models,…

  3. Space Shuttle ascent guidance, navigation, and control

    NASA Technical Reports Server (NTRS)

    Mchenry, R. L.; Long, A. D.; Cockrell, B. F.; Thibodeau, J. R., III; Brand, T. J.

    1979-01-01

    The factors leading to the particular design of the Shuttle guidance, navigation and control software are discussed. The derivation of explicit guidance equations satisfying a wide range of different maneuver constraints and steering equations that create attitude steering errors from the guidance solutions is presented, as are navigation equations, and equations for identifying faulty instruments from sets of redundant instrument measurements.

  4. Providing Career Guidance for Young Women.

    ERIC Educational Resources Information Center

    Colby, Pamela G.

    This module is directed at personnel working or planning to work in the areas of guidance, counseling, placement and follow-through in junior and senior high school settings, grades 7-12. The module topic is career guidance for young women of junior and senior high school age, aand the focus will be on providing nonbiased career guidance which…

  5. Quality Assurance in University Guidance Services

    ERIC Educational Resources Information Center

    Simon, Alexandra

    2014-01-01

    In Europe there is no common quality assurance framework for the delivery of guidance in higher education. Using a case study approach in four university career guidance services in England, France and Spain, this article aims to study how quality is implemented in university career guidance services in terms of strategy, standards and models,…

  6. On the Efficiency of Career Guidance.

    ERIC Educational Resources Information Center

    Pellerano, Jean

    1988-01-01

    Explores the question of how guidance and job-finding services can be improved. Notes that guidance has the underlying goals of efficient use of human resources and the insurance of equity in access to opportunities. Examines methods, accessibility of services, new technologies, and community support relative to guidance activities. (KO)

  7. Teleautonomous guidance for mobile robots

    NASA Technical Reports Server (NTRS)

    Borenstein, J.; Koren, Y.

    1990-01-01

    Teleautonomous guidance (TG), a technique for the remote guidance of fast mobile robots, has been developed and implemented. With TG, the mobile robot follows the general direction prescribed by an operator. However, if the robot encounters an obstacle, it autonomously avoids collision with that obstacle while trying to match the prescribed direction as closely as possible. This type of shared control is completely transparent and transfers control between teleoperation and autonomous obstacle avoidance gradually. TG allows the operator to steer vehicles and robots at high speeds and in cluttered environments, even without visual contact. TG is based on the virtual force field (VFF) method, which was developed earlier for autonomous obstacle avoidance. The VFF method is especially suited to the accommodation of inaccurate sensor data (such as that produced by ultrasonic sensors) and sensor fusion, and allows the mobile robot to travel quickly without stopping for obstacles.

  8. Microfluidic control of axonal guidance

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Black, Bryan; Ordonez, Simon; Mondal, Argha; Jain, Ankur; Mohanty, Samarendra

    2014-10-01

    The precision of axonal pathfinding and the accurate formation of functional neural circuitry are crucial for an organism during development as well as during adult central and peripheral nerve regeneration. While chemical cues are believed to be primarily responsible for axonal pathfinding, we hypothesize that forces due to localized fluid flow may directly affect neuronal guidance during early organ development. Here, we report direct evidence of fluid flow influencing axonal migration, producing turning angles of up to 90°. Microfluidic flow simulations indicate that an axon may experience significant bending force due to cross-flow, which may contribute to the observed axonal turning. This method of flow-based guidance was successfully used to fasciculate one advancing axon onto another, showcasing the potential of this technique to be used for the formation of in vitro neuronal circuits.

  9. Reentry guidance for Space Shuttle

    NASA Technical Reports Server (NTRS)

    Causey, W.; Sohoni, V.

    1973-01-01

    An explicit guidance scheme is outlined which provides the appropriate energy management in order for the shuttle orbiter to reach any location within the required footprint. Considering the orbiter as entering the earth's atmosphere, expressions for the downrange, crossrange, and the time of the termination of the entry phase as functions of the control variables are developed. Performing an order-of-magnitude analysis of the terms in these expressions, only dominant terms are retained. Analytical expressions for the elements of the sensitivity matrix which represents the partial derivatives of the desired range with respect to control variables are formulated. Using the Gauss-Jordan inversion technique, the required change in guidance commands as a function of the deviations in the downrange and crossrange are explicitly computed.

  10. Reentry guidance for Space Shuttle

    NASA Technical Reports Server (NTRS)

    Causey, W.; Sohoni, V.

    1973-01-01

    An explicit guidance scheme is outlined which provides the appropriate energy management in order for the shuttle orbiter to reach any location within the required footprint. Considering the orbiter as entering the earth's atmosphere, expressions for the downrange, crossrange, and the time of the termination of the entry phase as functions of the control variables are developed. Performing an order-of-magnitude analysis of the terms in these expressions, only dominant terms are retained. Analytical expressions for the elements of the sensitivity matrix which represents the partial derivatives of the desired range with respect to control variables are formulated. Using the Gauss-Jordan inversion technique, the required change in guidance commands as a function of the deviations in the downrange and crossrange are explicitly computed.

  11. Optical guidance vidicon test program

    NASA Technical Reports Server (NTRS)

    Eiseman, A. R.; Stanton, R. H.; Voge, C. C.

    1976-01-01

    A laboratory and field test program was conducted to quantify the optical navigation parameters of the Mariner vidicons. A scene simulator and a camera were designed and built for vidicon tests under a wide variety of conditions. Laboratory tests characterized error sources important to the optical navigation process and field tests verified star sensitivity and characterized comet optical guidance parameters. The equipment, tests and data reduction techniques used are described. Key test results are listed. A substantial increase in the understanding of the use of selenium vidicons as detectors for spacecraft optical guidance was achieved, indicating a reduction in residual offset errors by a factor of two to four to the single pixel level.

  12. 2011 Army Strategic Planning Guidance

    DTIC Science & Technology

    2011-03-25

    TESI ) of 22,000 Soldiers, the Army’s total force by the end of the mid-term period is programmed to be 520K (AC). We will achieve a more...dwell ratios, extending TESI authority to adequately man deploying units and sustain the All-Volunteer Force, right-sizing the generating force, and... TESI Temporary End-Strength Increase WMD Weapons of Mass Destruction 2011 ARMY STRATEGIC PLANNING GUIDANCE Page 19 2011

  13. BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

    EPA Pesticide Factsheets

    The U.S. EPA conducts risk assessments for an array of health effects that may result from exposure to environmental agents, and that require an analysis of the relationship between exposure and health-related outcomes. The dose-response assessment is essentially a two-step process, the first being the definition of a point of departure (POD), and the second extrapolation from the POD to low environmentally-relevant exposure levels. The benchmark dose (BMD) approach provides a more quantitative alternative to the first step in the dose-response assessment than the current NOAEL/LOAEL process for noncancer health effects, and is similar to that for determining the POD proposed for cancer endpoints. As the Agency moves toward harmonization of approaches for human health risk assessment, the dichotomy between cancer and noncancer health effects is being replaced by consideration of mode of action and whether the effects of concern are likely to be linear or nonlinear at low doses. Thus, the purpose of this project is to provide guidance for the Agency and the outside community on the application of the BMD approach in determining the POD for all types of health effects data, whether a linear or nonlinear low dose extrapolation is used. A guidance document is being developed under the auspices of EPA's Risk Assessment Forum. The purpose of this project is to provide guidance for the Agency and the outside community on the application of the benchmark dose (BMD) appr

  14. Mars Science Laboratory Entry Guidance

    NASA Technical Reports Server (NTRS)

    Mendeck, Gavin F.

    2011-01-01

    The Mars Science Laboratory will be the first Mars mission to attempt a guided entry with the objective of safely delivering the entry vehicle to a survivable parachute deploy state within 12.5 km of the pre-designated parachute deploy coordinates. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control range based on deviations in range, altitude rate, and drag acceleration from a reference trajectory. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last nine years. Performance tradeoffs between ellipse size and deploy altitude will be presented, along with imposed constraints of entry acceleration and heating. Performance sensitivities to the bank reversal deadbands, heading alignment, attitude initialization error, and entry delivery errors are presented.

  15. Prosodic Encoding in Silent Reading.

    ERIC Educational Resources Information Center

    Wilkenfeld, Deborah

    In silent reading, short-memory tasks, such as semantic and syntactic processing, require a stage of phonetic encoding between visual representation and the actual extraction of meaning, and this encoding includes prosodic as well as segmental features. To test for this suprasegmental coding, an experiment was conducted in which subjects were…

  16. Prosodic Encoding in Silent Reading.

    ERIC Educational Resources Information Center

    Wilkenfeld, Deborah

    In silent reading, short-memory tasks, such as semantic and syntactic processing, require a stage of phonetic encoding between visual representation and the actual extraction of meaning, and this encoding includes prosodic as well as segmental features. To test for this suprasegmental coding, an experiment was conducted in which subjects were…

  17. Peri-encoding predictors of memory encoding and consolidation.

    PubMed

    Cohen, Noga; Pell, Liat; Edelson, Micah G; Ben-Yakov, Aya; Pine, Alex; Dudai, Yadin

    2015-03-01

    We review reports of brain activations that occur immediately prior to the onset or following the offset of to-be-remembered information and can predict subsequent mnemonic success. Memory-predictive pre-encoding processes, occurring from fractions of a second to minutes prior to event onset, are mainly associated with activations in the medial temporal lobe (MTL), amygdala and midbrain, and with enhanced theta oscillations. These activations may be considered as the neural correlates of one or more cognitive operations, including contextual processing, attention, and the engagement of distinct computational modes associated with prior encoding or retrieval. Post-encoding activations that correlate with subsequent memory performance are mainly observed in the MTL, sensory cortices and frontal regions. These activations may reflect binding of elements of the encoded information and initiation of memory consolidation. In all, the findings reviewed here illustrate the importance of brain states in the immediate peri-encoding time windows in determining encoding success. Understanding these brain states and their specific effects on memory may lead to optimization of the encoding of desired memories and mitigation of undesired ones. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Superresolution Imaging using Single-Molecule Localization

    PubMed Central

    Patterson, George; Davidson, Michael; Manley, Suliana; Lippincott-Schwartz, Jennifer

    2013-01-01

    Superresolution imaging is a rapidly emerging new field of microscopy that dramatically improves the spatial resolution of light microscopy by over an order of magnitude (∼10–20-nm resolution), allowing biological processes to be described at the molecular scale. Here, we discuss a form of superresolution microscopy based on the controlled activation and sampling of sparse subsets of photoconvertible fluorescent molecules. In this single-molecule based imaging approach, a wide variety of probes have proved valuable, ranging from genetically encodable photoactivatable fluorescent proteins to photoswitchable cyanine dyes. These have been used in diverse applications of superresolution imaging: from three-dimensional, multicolor molecule localization to tracking of nanometric structures and molecules in living cells. Single-molecule-based superresolution imaging thus offers exciting possibilities for obtaining molecular-scale information on biological events occurring at variable timescales. PMID:20055680

  19. Peptide Sharing Between Influenza A H1N1 Hemagglutinin and Human Axon Guidance Proteins

    PubMed Central

    Kanduc, Darja

    2014-01-01

    Epidemiologic data suggest that maternal microbial infections may cause fetal neurodevelopmental disorders, potentially increasing susceptibility to heavy psychopathologies such as schizophrenia, schizophreniform disorder, autism, pervasive developmental disorders, bipolar disorders, psychosis, epilepsy, language and speech disorders, and cognitive impairment in adult offspring. However, the molecular pathomechanisms underlying such a relationship are not clear. Here we analyze the potential role of the maternal immune response to viral infection in determining fetal brain injuries that increase the risk of neurological disorders in the adult. We use influenza infection as a disease model and human axon guidance pathway, a key process in the formation of neural network during midgestation, as a potential fetal target of immune insults. Specifically, we examined influenza A H1N1 hemagglutinin (HA), an antigenic viral protein, for amino acid sequence similarity to a random library of 188 axon guidance proteins. We obtain the results that (1) contrary to any theoretical expectations, 45 viral pentapeptide matches are distributed throughout a subset of 36 guidance molecules; (2) in 24 guidance proteins, the peptide sharing with HA antigen involves already experimentally validated influenza HA epitopes; and (3) most of the axon guidance vs HA peptide overlap is conserved among influenza A viral strains and subsets. Taken together, our data indicate that immune cross-reactivity between influenza HA and axon guidance molecules is possible and may well represent a pathologic mechanism capable of determining neurodevelopmental disruption in the fetus. PMID:23378012

  20. Information encoder/decoder using chaotic systems

    DOEpatents

    Miller, S.L.; Miller, W.M.; McWhorter, P.J.

    1997-10-21

    The present invention discloses a chaotic system-based information encoder and decoder that operates according to a relationship defining a chaotic system. Encoder input signals modify the dynamics of the chaotic system comprising the encoder. The modifications result in chaotic, encoder output signals that contain the encoder input signals encoded within them. The encoder output signals are then capable of secure transmissions using conventional transmission techniques. A decoder receives the encoder output signals (i.e., decoder input signals) and inverts the dynamics of the encoding system to directly reconstruct the original encoder input signals. 32 figs.

  1. Information encoder/decoder using chaotic systems

    DOEpatents

    Miller, Samuel Lee; Miller, William Michael; McWhorter, Paul Jackson

    1997-01-01

    The present invention discloses a chaotic system-based information encoder and decoder that operates according to a relationship defining a chaotic system. Encoder input signals modify the dynamics of the chaotic system comprising the encoder. The modifications result in chaotic, encoder output signals that contain the encoder input signals encoded within them. The encoder output signals are then capable of secure transmissions using conventional transmission techniques. A decoder receives the encoder output signals (i.e., decoder input signals) and inverts the dynamics of the encoding system to directly reconstruct the original encoder input signals.

  2. Multiplexed Sequence Encoding: A Framework for DNA Communication

    PubMed Central

    Zakeri, Bijan; Carr, Peter A.; Lu, Timothy K.

    2016-01-01

    Synthetic DNA has great propensity for efficiently and stably storing non-biological information. With DNA writing and reading technologies rapidly advancing, new applications for synthetic DNA are emerging in data storage and communication. Traditionally, DNA communication has focused on the encoding and transfer of complete sets of information. Here, we explore the use of DNA for the communication of short messages that are fragmented across multiple distinct DNA molecules. We identified three pivotal points in a communication—data encoding, data transfer & data extraction—and developed novel tools to enable communication via molecules of DNA. To address data encoding, we designed DNA-based individualized keyboards (iKeys) to convert plaintext into DNA, while reducing the occurrence of DNA homopolymers to improve synthesis and sequencing processes. To address data transfer, we implemented a secret-sharing system—Multiplexed Sequence Encoding (MuSE)—that conceals messages between multiple distinct DNA molecules, requiring a combination key to reveal messages. To address data extraction, we achieved the first instance of chromatogram patterning through multiplexed sequencing, thereby enabling a new method for data extraction. We envision these approaches will enable more widespread communication of information via DNA. PMID:27050646

  3. Biomolecular screening with encoded porous-silicon photonic crystals

    NASA Astrophysics Data System (ADS)

    Cunin, Frédérique; Schmedake, Thomas A.; Link, Jamie R.; Li, Yang Yang; Koh, Jennifer; Bhatia, Sangeeta N.; Sailor, Michael J.

    2002-09-01

    Strategies to encode or label small particles or beads for use in high-throughput screening and bioassay applications focus on either spatially differentiated, on-chip arrays or random distributions of encoded beads. Attempts to encode large numbers of polymeric, metallic or glass beads in random arrays or in fluid suspension have used a variety of entities to provide coded elements (bits)-fluorescent molecules, molecules with specific vibrational signatures, quantum dots, or discrete metallic layers. Here we report a method for optically encoding micrometre-sized nanostructured particles of porous silicon. We generate multilayered porous films in crystalline silicon using a periodic electrochemical etch. This results in photonic crystals with well-resolved and narrow optical reflectivity features, whose wavelengths are determined by the etching parameters. Millions of possible codes can be prepared this way. Micrometre-sized particles are then produced by ultrasonic fracture, mechanical grinding or by lithographic means. A simple antibody-based bioassay using fluorescently tagged proteins demonstrates the encoding strategy in biologically relevant media.

  4. Biomolecular screening with encoded porous-silicon photonic crystals.

    PubMed

    Cunin, Frédérique; Schmedake, Thomas A; Link, Jamie R; Li, Yang Yang; Koh, Jennifer; Bhatia, Sangeeta N; Sailor, Michael J

    2002-09-01

    Strategies to encode or label small particles or beads for use in high-throughput screening and bioassay applications focus on either spatially differentiated, on-chip arrays or random distributions of encoded beads. Attempts to encode large numbers of polymeric, metallic or glass beads in random arrays or in fluid suspension have used a variety of entities to provide coded elements (bits)--fluorescent molecules, molecules with specific vibrational signatures, quantum dots, or discrete metallic layers. Here we report a method for optically encoding micrometre-sized nanostructured particles of porous silicon. We generate multilayered porous films in crystalline silicon using a periodic electrochemical etch. This results in photonic crystals with well-resolved and narrow optical reflectivity features, whose wavelengths are determined by the etching parameters. Millions of possible codes can be prepared this way. Micrometre-sized particles are then produced by ultrasonic fracture, mechanical grinding or by lithographic means. A simple antibody-based bioassay using fluorescently tagged proteins demonstrates the encoding strategy in biologically relevant media.

  5. Orthobiologic Interventions Using Ultrasound Guidance.

    PubMed

    Malanga, Gerard; Abdelshahed, Dena; Jayaram, Prathap

    2016-08-01

    The application of regenerative therapies for the treatment of musculoskeletal conditions has emerged over the last decade with recent acceleration. These include prolotherapy, platelet-rich plasma, and mesenchymal stem cell therapy. These strategies augment the body's innate physiology to heal pathologic processes. This article presents an overview of platelet-rich plasma and mesenchymal stem cell therapy for the treatment of musculoskeletal injuries. A brief literature review is included, as are techniques for the use of ultrasound guidance to assist with these procedures.

  6. Precision optical navigation guidance system

    NASA Astrophysics Data System (ADS)

    Starodubov, D.; McCormick, K.; Nolan, P.; Johnson, D.; Dellosa, M.; Volfson, L.; Fallahpour, A.; Willner, A.

    2016-05-01

    We present the new precision optical navigation guidance system approach that provides continuous, high quality range and bearing data to fixed wing aircraft during landing approach to an aircraft carrier. The system uses infrared optical communications to measure range between ship and aircraft with accuracy and precision better than 1 meter at ranges more than 7.5 km. The innovative receiver design measures bearing from aircraft to ship with accuracy and precision better than 0.5 mRad. The system provides real-time range and bearing updates to multiple aircraft at rates up to several kHz, and duplex data transmission between ship and aircraft.

  7. The Hedgehog Signalling Pathway in Cell Migration and Guidance: What We Have Learned from Drosophila melanogaster

    PubMed Central

    Araújo, Sofia J.

    2015-01-01

    Cell migration and guidance are complex processes required for morphogenesis, the formation of tumor metastases, and the progression of human cancer. During migration, guidance molecules induce cell directionality and movement through complex intracellular mechanisms. Expression of these molecules has to be tightly regulated and their signals properly interpreted by the receiving cells so as to ensure correct navigation. This molecular control is fundamental for both normal morphogenesis and human disease. The Hedgehog (Hh) signaling pathway is evolutionarily conserved and known to be crucial for normal cellular growth and differentiation throughout the animal kingdom. The relevance of Hh signaling for human disease is emphasized by its activation in many cancers. Here, I review the current knowledge regarding the involvement of the Hh pathway in cell migration and guidance during Drosophila development and discuss its implications for human cancer origin and progression. PMID:26445062

  8. The Hedgehog Signalling Pathway in Cell Migration and Guidance: What We Have Learned from Drosophila melanogaster.

    PubMed

    Araújo, Sofia J

    2015-10-02

    Cell migration and guidance are complex processes required for morphogenesis, the formation of tumor metastases, and the progression of human cancer. During migration, guidance molecules induce cell directionality and movement through complex intracellular mechanisms. Expression of these molecules has to be tightly regulated and their signals properly interpreted by the receiving cells so as to ensure correct navigation. This molecular control is fundamental for both normal morphogenesis and human disease. The Hedgehog (Hh) signaling pathway is evolutionarily conserved and known to be crucial for normal cellular growth and differentiation throughout the animal kingdom. The relevance of Hh signaling for human disease is emphasized by its activation in many cancers. Here, I review the current knowledge regarding the involvement of the Hh pathway in cell migration and guidance during Drosophila development and discuss its implications for human cancer origin and progression.

  9. Endothelial Expression of Guidance Cues in Vessel Wall Homeostasis: Dysregulation under pro-atherosclerotic conditions

    PubMed Central

    van Gils, Janine M.; Ramkhelawon, Bhama; Fernandes, Luciana; Stewart, Merran C.; Guo, Liang; Seibert, Tara; Menezes, Gustavo B.; Cara, Denise C.; Chow, Camille; Kinane, T. Bernard; Fisher, Edward A.; Balcells, Mercedes; Alvarez-Leite, Jacqueline; Moore, Kathryn J.

    2013-01-01

    Objective Emerging evidence suggests that neuronal guidance cues, typically expressed during development, are involved in both physiological and pathological immune responses. We hypothesized that endothelial expression of such guidance cues may regulate leukocyte trafficking into the vascular wall during atherogenesis. Approach/Results We demonstrate that members of the Netrin, Semaphorin and Ephrin family of guidance molecules are differentially regulated under conditions that promote or protect from atherosclerosis. Netrin-1 and Semaphorin3A are expressed by coronary artery endothelial cells and potently inhibit chemokine-directed migration of human monocytes. Endothelial expression of these negative guidance cues is down-regulated by pro-atherogenic factors, including oscillatory shear stress and pro-inflammatory cytokines associated with monocyte entry into the vessel wall. Furthermore, we show using intravital microscopy that inhibition of Netrin-1 or Semaphorin3A using blocking peptides increases leukocyte adhesion to the endothelium. Unlike Netrin-1 and Semaphorin3A, the guidance cue EphrinB2 is up-regulated under pro-atherosclerotic flow conditions and functions as a chemoattractant, increasing leukocyte migration in the absence of additional chemokines. Conclusions The concurrent regulation of negative and positive guidance cues may facilitate leukocyte infiltration of the endothelium through a balance between chemoattraction and chemorepulsion. These data indicate a previously unappreciated role for axonal guidance cues in maintaining the endothelial barrier and regulating leukocyte trafficking during atherogenesis. PMID:23430612

  10. PNA-encoded chemical libraries.

    PubMed

    Zambaldo, Claudio; Barluenga, Sofia; Winssinger, Nicolas

    2015-06-01

    Peptide nucleic acid (PNA)-encoded chemical libraries along with DNA-encoded libraries have provided a powerful new paradigm for library synthesis and ligand discovery. PNA-encoding stands out for its compatibility with standard solid phase synthesis and the technology has been used to prepare libraries of peptides, heterocycles and glycoconjugates. Different screening formats have now been reported including selection-based and microarray-based methods that have yielded specific ligands against diverse target classes including membrane receptors, lectins and challenging targets such as Hsp70.

  11. Flamingo, a seven-pass transmembrane cadherin, cooperates with Netrin/Frazzled in Drosophila midline guidance.

    PubMed

    Organisti, Cristina; Hein, Irina; Grunwald Kadow, Ilona C; Suzuki, Takashi

    2015-01-01

    During central nervous system development, several guidance cues and receptors, as well as cell adhesion molecules, are required for guiding axons across the midline and along the anterior-posterior axis. In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors. Despite their importance, lack of Net or fra affects only some commissures, suggesting that additional molecules can fulfill this function. Recently, planar cell polarity (PCP) proteins have been implicated in midline axon guidance in both vertebrate and invertebrate systems. Here, we report that the atypical cadherin and PCP molecule Flamingo/Starry night (Fmi/Stan) acts jointly with Net/Fra signaling during midline development. Additional removal of fmi strongly increases the guidance defects in Net/fra mutants. Rescue and domain deletion experiments suggest that Fmi signaling facilitates commissural pathfinding potentially by mediating axonal fasciculation in a partly homophilic manner. Altogether, our results indicate that contact-mediated cell adhesion via Fmi acts in addition to the Net/Fra guidance system during axon pathfinding across the midline, underlining the importance of PCP molecules during vertebrates and invertebrates midline development.

  12. Aerocapture Guidance Algorithm Comparison Campaign

    NASA Technical Reports Server (NTRS)

    Rousseau, Stephane; Perot, Etienne; Graves, Claude; Masciarelli, James P.; Queen, Eric

    2002-01-01

    The aerocapture is a promising technique for the future human interplanetary missions. The Mars Sample Return was initially based on an insertion by aerocapture. A CNES orbiter Mars Premier was developed to demonstrate this concept. Mainly due to budget constraints, the aerocapture was cancelled for the French orbiter. A lot of studies were achieved during the three last years to develop and test different guidance algorithms (APC, EC, TPC, NPC). This work was shared between CNES and NASA, with a fruitful joint working group. To finish this study an evaluation campaign has been performed to test the different algorithms. The objective was to assess the robustness, accuracy, capability to limit the load, and the complexity of each algorithm. A simulation campaign has been specified and performed by CNES, with a similar activity on the NASA side to confirm the CNES results. This evaluation has demonstrated that the numerical guidance principal is not competitive compared to the analytical concepts. All the other algorithms are well adapted to guaranty the success of the aerocapture. The TPC appears to be the more robust, the APC the more accurate, and the EC appears to be a good compromise.

  13. Flight Guidance System Requirements Specification

    NASA Technical Reports Server (NTRS)

    Miller, Steven P.; Tribble, Alan C.; Carlson, Timothy M.; Danielson, Eric J.

    2003-01-01

    This report describes a requirements specification written in the RSML-e language for the mode logic of a Flight Guidance System of a typical regional jet aircraft. This model was created as one of the first steps in a five-year project sponsored by the NASA Langley Research Center, Rockwell Collins Inc., and the Critical Systems Research Group of the University of Minnesota to develop new methods and tools to improve the safety of avionics designs. This model will be used to demonstrate the application of a variety of methods and techniques, including safety analysis of system and subsystem requirements, verification of key properties using theorem provers and model checkers, identification of potential sources mode confusion in system designs, partitioning of applications based on the criticality of system hazards, and autogeneration of avionics quality code. While this model is representative of the mode logic of a typical regional jet aircraft, it does not describe an actual or planned product. Several aspects of a full Flight Guidance System, such as recovery from failed sensors, have been omitted, and no claims are made regarding the accuracy or completeness of this specification.

  14. Guidance assistance, autonomous guidance and assisted distance guidance in precision agriculture

    NASA Astrophysics Data System (ADS)

    Gomez Gil, Jaime

    The present doctoral thesis analyses the potential of technological advances in electronics, telematics and communications for their application in agriculture. Research has been carried out and some prototypes have been developed in four stages: In a first phase, it has been carried out the analysis and development of guidance assistance devices. It has been carried out the development of a microcontroller based device which has been patented by the author of this thesis and later, has been developed and commercialized by the company GMV Sistemas. In a second phase, it has been developed a module of distance guidance which allows the remote driving of an agricultural tractor. There have been made the mechanical modifications in a tractor and the necessary hardware has been installed in order to allow the remote control of the tractor steering. The laptop receives the guidance instructions by means of wireless communication from the computer installed in the base. In a third phase, there have been developed two autonomous guidance systems, one by means of GPS and the other by means of Computer Vision, using as base the platform developed in the previous phase. It is incorporated a module of path generation from the plot outline. With this trajectory, the tractor is able to do most of the farming work in a plot without the participation of the driver. The last phase has been developed at the same time than the previous ones and it is located in Precision Agriculture. In this phase it has been carried out the performance of a centrifugal spreader of fertilizer and it has been developed an application for the generation in a precise way of fertilizer maps. The carried out studies have produced real developments implanted on the machinery of the author's farm. The development of the work has been carried out on a software platform with modules which are intercommunicated between them, because a large part of the developed applications have a common base of work. This

  15. Encoding color information for visual tracking: Algorithms and benchmark.

    PubMed

    Liang, Pengpeng; Blasch, Erik; Ling, Haibin

    2015-12-01

    While color information is known to provide rich discriminative clues for visual inference, most modern visual trackers limit themselves to the grayscale realm. Despite recent efforts to integrate color in tracking, there is a lack of comprehensive understanding of the role color information can play. In this paper, we attack this problem by conducting a systematic study from both the algorithm and benchmark perspectives. On the algorithm side, we comprehensively encode 10 chromatic models into 16 carefully selected state-of-the-art visual trackers. On the benchmark side, we compile a large set of 128 color sequences with ground truth and challenge factor annotations (e.g., occlusion). A thorough evaluation is conducted by running all the color-encoded trackers, together with two recently proposed color trackers. A further validation is conducted on an RGBD tracking benchmark. The results clearly show the benefit of encoding color information for tracking. We also perform detailed analysis on several issues, including the behavior of various combinations between color model and visual tracker, the degree of difficulty of each sequence for tracking, and how different challenge factors affect the tracking performance. We expect the study to provide the guidance, motivation, and benchmark for future work on encoding color in visual tracking.

  16. Collective cell migration: guidance principles and hierarchies.

    PubMed

    Haeger, Anna; Wolf, Katarina; Zegers, Mirjam M; Friedl, Peter

    2015-09-01

    Collective cell migration results from the establishment and maintenance of collective polarization, mechanocoupling, and cytoskeletal kinetics. The guidance of collective cell migration depends on a reciprocal process between cell-intrinsic multicellular organization with leader-follower cell behavior and results in mechanosensory integration of extracellular guidance cues. Important guidance mechanisms include chemotaxis, haptotaxis, durotaxis, and strain-induced mechanosensing to move cell groups along interfaces and paths of least resistance. Additional guidance mechanisms steering cell groups during specialized conditions comprise electrotaxis and passive drift. To form higher-order cell and tissue structures during morphogenesis and cancer invasion, these guidance principles act in parallel and are integrated for collective adaptation to and shaping of varying tissue environments. We review mechanochemical and electrical inputs and multiparameter signal integration underlying collective guidance, decision making, and outcome.

  17. Energy angular momentum closed-loop guidance

    NASA Astrophysics Data System (ADS)

    Patera, Russell P.

    2015-03-01

    A novel guidance algorithm for launch vehicle ascent to the desired mission orbit is proposed. The algorithm uses total specific energy and orbital angular momentum as new state vector parameters. These parameters are ideally suited for the ascent guidance task, since the guidance algorithm steers the launch vehicle along a pre-flight optimal trajectory in energy angular momentum space. The guidance algorithm targets apogee, perigee, inclination and right ascension of ascending node. Computational complexities are avoided by eliminating time in the guidance computation and replacing it with angular momentum magnitude. As a result, vehicle acceleration, mass, thrust, length of motor burns, and staging times are also eliminated from the pitch plane guidance calculations. The algorithm does not involve launch vehicle or target state propagation, which results in minimal computational effort. Proof of concept of the new algorithm is presented using several numerical examples that illustrate performance results.

  18. DNA sequences encoding osteoinductive products

    SciTech Connect

    Wang, E.A.; Wozney, J.M.; Rosen, V.

    1991-05-07

    This patent describes an isolated DNA sequence encoding an osteoinductive protein the DNA sequence comprising a coding sequence. It comprises: nucleotide No.1 through nucleotide No.387, nucleotide No.356 through nucleotide No.1543, nucleotide $402 through nucleotide No.1626, naturally occurring allelic sequences and equivalent degenerative codon sequences and sequences which hybridize to any of sequences under stringent hybridization conditions; and encode a protein characterized by the ability to induce the formation of bone and/or cartilage.

  19. Encoding and decoding time in neural development.

    PubMed

    Toma, Kenichi; Wang, Tien-Cheng; Hanashima, Carina

    2016-01-01

    The development of a multicellular organism involves time-dependent changes in molecular and cellular states; therefore 'time' is an indispensable mathematical parameter of ontogenesis. Regardless of their inextricable relationship, there is a limited number of events for which the output of developmental phenomena primarily uses temporal cues that are generated through multilevel interactions between molecules, cells, and tissues. In this review, we focus on neural stem cells, which serve as a faithful decoder of temporal cues to transmit biological information and generate specific output in the developing nervous system. We further explore the identity of the temporal information that is encoded in neural development, and how this information is decoded into various cellular fate decisions. © 2016 The Authors Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.

  20. Axon Guidance Mechanisms for Establishment of Callosal Connections

    PubMed Central

    Nishikimi, Mitsuaki; Oishi, Koji; Nakajima, Kazunori

    2013-01-01

    Numerous studies have investigated the formation of interhemispheric connections which are involved in high-ordered functions of the cerebral cortex in eutherian animals, including humans. The development of callosal axons, which transfer and integrate information between the right/left hemispheres and represent the most prominent commissural system, must be strictly regulated. From the beginning of their growth, until reaching their targets in the contralateral cortex, the callosal axons are guided mainly by two environmental cues: (1) the midline structures and (2) neighboring? axons. Recent studies have shown the importance of axona guidance by such cues and the underlying molecular mechanisms. In this paper, we review these guidance mechanisms during the development of the callosal neurons. Midline populations express and secrete guidance molecules, and “pioneer” axons as well as interactions between the medial and lateral axons are also involved in the axon pathfinding of the callosal neurons. Finally, we describe callosal dysgenesis in humans and mice, that results from a disruption of these navigational mechanisms. PMID:23533817

  1. Axon guidance mechanisms for establishment of callosal connections.

    PubMed

    Nishikimi, Mitsuaki; Oishi, Koji; Nakajima, Kazunori

    2013-01-01

    Numerous studies have investigated the formation of interhemispheric connections which are involved in high-ordered functions of the cerebral cortex in eutherian animals, including humans. The development of callosal axons, which transfer and integrate information between the right/left hemispheres and represent the most prominent commissural system, must be strictly regulated. From the beginning of their growth, until reaching their targets in the contralateral cortex, the callosal axons are guided mainly by two environmental cues: (1) the midline structures and (2) neighboring? axons. Recent studies have shown the importance of axona guidance by such cues and the underlying molecular mechanisms. In this paper, we review these guidance mechanisms during the development of the callosal neurons. Midline populations express and secrete guidance molecules, and "pioneer" axons as well as interactions between the medial and lateral axons are also involved in the axon pathfinding of the callosal neurons. Finally, we describe callosal dysgenesis in humans and mice, that results from a disruption of these navigational mechanisms.

  2. Simulation of low thrust guidance problems

    NASA Technical Reports Server (NTRS)

    Dawkins, G. S.; Long, D.

    1974-01-01

    The determination of optimal rocket control profiles and the guidance procedures used to approximate these profiles have received much attention. Simple guidance procedures have sufficed for the Apollo flights. A modified version of the linear tangent guidance law is developed which can be used for a low-thrust orbital maneuvering system such as the space shuttle. The modification allows the estimation of gravity over long thrusting arcs which is necessary for low thrust systems.

  3. Simulation of low thrust guidance problems

    NASA Technical Reports Server (NTRS)

    Dawkins, G. S.; Long, D.

    1974-01-01

    The determination of optimal rocket control profiles and the guidance procedures used to approximate these profiles have received much attention. Simple guidance procedures have sufficed for the Apollo flights. A modified version of the linear tangent guidance law is developed which can be used for a low-thrust orbital maneuvering system such as the space shuttle. The modification allows the estimation of gravity over long thrusting arcs which is necessary for low thrust systems.

  4. Virtual Ultrasound Guidance for Inexperienced Operators

    NASA Technical Reports Server (NTRS)

    Caine, Timothy; Martin, Davis

    2012-01-01

    Medical ultrasound or echocardiographic studies are highly operator-dependent and generally require lengthy training and internship to perfect. To obtain quality echocardiographic images in remote environments, such as on-orbit, remote guidance of studies has been employed. This technique involves minimal training for the user, coupled with remote guidance from an expert. When real-time communication or expert guidance is not available, a more autonomous system of guiding an inexperienced operator through an ultrasound study is needed. One example would be missions beyond low Earth orbit, in which the time delay inherent with communication will make remote guidance impractical.

  5. Septic Systems Guidance, Policy, and Regulations

    EPA Pesticide Factsheets

    EPA has developed several documents outlining its mission, priorities and regulatory authorities as well as guidance and technical information to help communities establish comprehensive septic (onsite) management programs.

  6. Genetically Encoded Libraries of Nonstandard Peptides

    PubMed Central

    Kawakami, Takashi; Murakami, Hiroshi

    2012-01-01

    The presence of a nonproteinogenic moiety in a nonstandard peptide often improves the biological properties of the peptide. Non-standard peptide libraries are therefore used to obtain valuable molecules for biological, therapeutic, and diagnostic applications. Highly diverse non-standard peptide libraries can be generated by chemically or enzymatically modifying standard peptide libraries synthesized by the ribosomal machinery, using posttranslational modifications. Alternatively, strategies for encoding non-proteinogenic amino acids into the genetic code have been developed for the direct ribosomal synthesis of non-standard peptide libraries. In the strategies for genetic code expansion, non-proteinogenic amino acids are assigned to the nonsense codons or 4-base codons in order to add these amino acids to the universal genetic code. In contrast, in the strategies for genetic code reprogramming, some proteinogenic amino acids are erased from the genetic code and non-proteinogenic amino acids are reassigned to the blank codons. Here, we discuss the generation of genetically encoded non-standard peptide libraries using these strategies and also review recent applications of these libraries to the selection of functional non-standard peptides. PMID:23097693

  7. Physics of Molecules

    NASA Astrophysics Data System (ADS)

    Williams, D.; Murdin, P.

    2000-11-01

    Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

  8. Memo Transmitting the Technical Guidance on the FY 2014 National Program Manager Guidance

    EPA Pesticide Factsheets

    This memo transmits OCFO’s Technical Guidance for developing the FY 2014 National Program Manager (NPM) Guidances and complements the policy memorandum issued by Barbara J. Bennett on October 25, 2012.

  9. Federal Guidance Report No. 8: Guidance for the Control of Radiation Hazards in Uranium Mining

    EPA Pesticide Factsheets

    This report contains background material used in the development of guidance concerning radiation protection in the mining of uranium ore, and seeks to provide guidance for long-term radiation protection in uranium mining.

  10. Orion Cislunar Guidance and Navigation

    NASA Technical Reports Server (NTRS)

    D'Souza, Christopher; Crain, Timothy; Clark, Fred C.

    2007-01-01

    The Orion vehicle is being designed to provide nominal crew transport to the lunar transportation stack in low Earth orbit, crew abort prior during transit to the moon, and crew return to Earth once lunar orbit is achieved. Design of guidance and navigation algorithms to perform maneuvers in support of these functions is dependent on the support provided by navigation infrastructure, the performance of the onboard GN&C system, and the choice of trajectory maneuver methodology for outbound and return mission phases. This paper documents the preliminary integrated analyses performed by members of the Orion Orbit GN&C System team investigating the navigation update accuracy of a modern equivalent to the Apollo era ground tracking network and the expected onboard dispersion and navigation errors during a lunar mission using a linear covariance error analysis technique.

  11. Aerocapture - Guidance, navigation, and control

    NASA Astrophysics Data System (ADS)

    Mease, K. D.; Weidner, R. J.; Kechichian, J. A.; Wood, L. J.; Cruz, M. I.

    1982-08-01

    Aerocapture is a concept for inserting a spacecraft into orbit about a target planet. The energy required for orbit insertion is obtained from natural resources present at or near the target body, thereby reducing the amount of propellant which must be carried onboard. Specifically, the transfer from a hyperbolic flyby trajectory to a desired bound orbit is effected by aerodynamic lift and drag forces acting on the spacecraft during controlled flight through the atmosphere of either the target planet or a nearby satellite. A survey is provided of the trajectory guidance, navigation, and control aspects of aerocapture, and a summary is given of the results of a number of preliminary studies concerning certain of these aspects. The investigation has additional significance in connection with the current interest in aeroassisted orbital transfer vehicles, which may be used in conjunction with the Space Shuttle.

  12. Aerocapture - Guidance, navigation, and control

    NASA Technical Reports Server (NTRS)

    Mease, K. D.; Weidner, R. J.; Kechichian, J. A.; Wood, L. J.; Cruz, M. I.

    1982-01-01

    Aerocapture is a concept for inserting a spacecraft into orbit about a target planet. The energy required for orbit insertion is obtained from natural resources present at or near the target body, thereby reducing the amount of propellant which must be carried onboard. Specifically, the transfer from a hyperbolic flyby trajectory to a desired bound orbit is effected by aerodynamic lift and drag forces acting on the spacecraft during controlled flight through the atmosphere of either the target planet or a nearby satellite. A survey is provided of the trajectory guidance, navigation, and control aspects of aerocapture, and a summary is given of the results of a number of preliminary studies concerning certain of these aspects. The investigation has additional significance in connection with the current interest in aeroassisted orbital transfer vehicles, which may be used in conjunction with the Space Shuttle.

  13. Can coffee improve image guidance?

    NASA Astrophysics Data System (ADS)

    Wirz, Raul; Lathrop, Ray A.; Godage, Isuru S.; Burgner-Kahrs, Jessica; Russell, Paul T.; Webster, Robert J.

    2015-03-01

    Anecdotally, surgeons sometimes observe large errors when using image guidance in endonasal surgery. We hypothesize that one contributing factor is the possibility that operating room personnel might accidentally bump the optically tracked rigid body attached to the patient after registration has been performed. In this paper we explore the registration error at the skull base that can be induced by simulated bumping of the rigid body, and find that large errors can occur when simulated bumps are applied to the rigid body. To address this, we propose a new fixation method for the rigid body based on granular jamming (i.e. using particles like ground coffee). Our results show that our granular jamming fixation prototype reduces registration error by 28%-68% (depending on bump direction) in comparison to a standard Brainlab reference headband.

  14. Longwall Guidance and Control Development

    NASA Technical Reports Server (NTRS)

    1982-01-01

    The longwall guidance and control (G&C) system was evaluated to determine which systems and subsystems lent themselves to automatic control in the mining of coal. The upper coal/shale interface was identified as the reference for a vertical G&C system, with two sensors (the natural backgound and the sensitized pick) being used to locate and track this boundary. In order to insure a relatively smooth recession surface (roof and floor of the excavated seam), a last and present cut measuring instrument (acoustic sensor) was used. Potentiometers were used to measure elevations of the shearer arms. The intergration of these components comprised the vertical control system (pitch control). Yaw and roll control were incorporated into a face alignment system which was designed to keep the coal face normal to its external boundaries. Numerous tests, in the laboratory and in the field, have confirmed the feasibility of automatic horizon control, as well as determining the face alignment.

  15. Endangerment assessment guidance. Final report

    SciTech Connect

    Not Available

    1985-10-21

    The directive clarifies the requirement that an endangerment assessment be developed to support all administrative and judicial enforcement actions under Section 106 of the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) and Section 7003 of the Resource Conservation and Recovery Act (RCRA). Before taking enforcement action under these provisions to abate the hazards or potential hazards at a site, the Environmental Protection Agency (EPA) must be able to properly document and justify its assertion that an imminent and substantial endangerment to public health or welfare or the environment may exist. The endangerment assessment provides the documentation and justification. The endangerment assessment is not necessary to support Section 104 actions. It also provides guidance on the content, timing, level of detail, format, and resources required for the preparation of endangerment assessments.

  16. Biological mechanisms, one molecule at a time.

    PubMed

    Tinoco, Ignacio; Gonzalez, Ruben L

    2011-06-15

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome.

  17. Biological mechanisms, one molecule at a time

    PubMed Central

    Tinoco, Ignacio; Gonzalez, Ruben L.

    2011-01-01

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome. PMID:21685361

  18. Guidance, Navigation, and Control Program

    NASA Technical Reports Server (NTRS)

    Hinkel, Heather; Tamblyn, Scott; Jackson, William L.; Foster, Chris; Brazzel, Jack; Manning, Thomas R.; Clark, Fred; Spehar, Pete; Barrett, Jim D.; Milenkovic, Zoran

    2011-01-01

    The Rendezvous and Proximity Operations Program (RPOP) is real-time guidance, navigation, and control (GN&C) domain piloting-aid software that provides 3D Orbiter graphics and runs on the Space Shuttle's Criticality-3 Payload and General Support Computer (PGSC) in the crew cockpit. This software provides the crew with Situational Awareness during the rendezvous and proximity operations phases of flight. RPOP can be configured from flight to flight, accounting for mission-specific flight scenarios and target vehicles, via initialization load (I-load) data files. The software provides real-time, automated, closed-loop guidance recommendations and the capability to integrate the crew s manual backup techniques. The software can bring all relative navigation sensor data, including the Orbiter's GPC (general purpose computer) data, into one central application to provide comprehensive situational awareness of the rendezvous and proximity operations trajectory. RPOP also can separately maintain trajectory estimates (past, current, and predicted) based on certain data types and co-plot them, in order to show how the various navigation solutions compare. RPOP s best estimate of the relative trajectory is determined by a relative Kalman filter processing data provided by the sensor suite s most accurate sensor, the trajectory control sensor (TCS). Integrated with the Kalman filter is an algorithm that identifies the reflector that the TCS is tracking. Because RPOP runs on PC laptop computers, the development and certification lifecycles are more agile, flexible, and cheaper than those that govern the Orbiter FSW (flight software) that runs in the GPC. New releases of RPOP can be turned around on a 3- to 6-month template, from new Change Request (CR) to certification, depending on the complexity of the changes.

  19. Nucleic acids encoding antifungal polypeptides and uses thereof

    DOEpatents

    Altier, Daniel J.; Ellanskaya, I. A.; Gilliam, Jacob T.; Hunter-Cevera, Jennie; Presnail, James K; Schepers, Eric; Simmons, Carl R.; Torok, Tamas; Yalpani, Nasser

    2010-11-02

    Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include an amino acid sequence, and variants and fragments thereof, for an antipathogenic polypeptide that was isolated from a fungal fermentation broth. Nucleic acid molecules that encode the antipathogenic polypeptides of the invention, and antipathogenic domains thereof, are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention are also disclosed.

  20. 78 FR 38683 - Availability of Guidance: Establishments Guidance for the Selection of a Commercial or Private...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-27

    ... that meet the guidance provided in the International Organization for Standardization (ISO) 17025... laboratories seeking to implement the ISO 17025 standards. FSIS has developed its guidance to assist industry... an explanation that laboratories that meet the guidance provided in the ISO 17025 accreditation...

  1. 78 FR 48175 - Retrospective Review of Draft Guidance Documents Issued Before 2010; Withdrawal of Guidances

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-07

    ... are no longer up to date, and for which more current information is available, will be withdrawn... guidances that are no longer up to date. CDER is also actively reviewing the draft guidances to determine... this process as transparent as possible. DATES: General comments on Agency guidance documents...

  2. Multidimensionally encoded magnetic resonance imaging.

    PubMed

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. Copyright © 2012 Wiley Periodicals, Inc.

  3. Using Xenopus laevis retinal and spinal neurons to study mechanisms of axon guidance in vivo and in vitro.

    PubMed

    Erdogan, Burcu; Ebbert, Patrick T; Lowery, Laura Anne

    2016-03-01

    The intricate and precise establishment of neuronal connections in the developing nervous system relies on accurate navigation of growing axons. Since Ramón y Cajal's discovery of the growth cone, the phenomenon of axon guidance has been revealed as a coordinated operation of guidance molecules, receptors, secondary messengers, and responses driven by the dynamic cytoskeleton within the growth cone. With the advent of new and accelerating techniques, Xenopus laevis emerged as a robust model to investigate neuronal circuit formation during development. We present here the advantages of the Xenopus nervous system to our growing understanding of axon guidance.

  4. Oligonucleotide and Long Polymeric DNA Encoding

    SciTech Connect

    Miller, E; Mariella Jr., R P; Christian, A T; Gardner, S N; Williams, J M

    2003-11-24

    This report summarizes the work done at Lawrence Livermore National Laboratory for the Oligonucleotide and Long Polymeric DNA Encoding project, part of the Microelectronic Bioprocesses Program at DARPA. The goal of the project was to develop a process by which long (circa 10,000 base-pair) synthetic DNA molecules could be synthesized in a timely and economic manner. During construction of the long molecule, errors in DNA sequence occur during hybridization and/or the subsequent enzymatic process. The work done on this project has resulted in a novel synthesis scheme that we call the parallel pyramid synthesis protocol, the development of a suit of computational tools to minimize and quantify errors in the synthesized DNA sequence, and experimental proof of this technique. The modeling consists of three interrelated modules: the bioinformatics code which determines the specifics of parallel pyramid synthesis for a given chain of long DNA, the thermodynamics code which tracks the products of DNA hybridization and polymerase extension during the later steps in the process, and the kinetics model which examines the temporal and spatial processes during one thermocycle. Most importantly, we conducted the first successful syntheses of a gene using small starting oligomers (tetramers). The synthesized sequence, 813 base pairs long, contained a 725 base pair gene, modified green fluorescent protein (mGFP), which has been shown to be a functional gene by cloning into cells and observing its green fluorescent product.

  5. SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) Function Interdependently to Promote Axon Guidance by Regulating the MIG-2 GTPase

    PubMed Central

    Xu, Yan; Taru, Hidenori; Jin, Yishi; Quinn, Christopher C.

    2015-01-01

    During development, axons must integrate directional information encoded by multiple guidance cues and their receptors. Axon guidance receptors, such as UNC-40 (DCC) and SAX-3 (Robo), can function individually or combinatorially with other guidance receptors to regulate downstream effectors. However, little is known about the molecular mechanisms that mediate combinatorial guidance receptor signaling. Here, we show that UNC-40, SAX-3 and the SYD-1 RhoGAP-like protein function interdependently to regulate the MIG-2 (Rac) GTPase in the HSN axon of C. elegans. We find that SYD-1 mediates an UNC-6 (netrin) independent UNC-40 activity to promote ventral axon guidance. Genetic analysis suggests that SYD-1 function in axon guidance requires both UNC-40 and SAX-3 activity. Moreover, the cytoplasmic domains of UNC-40 and SAX-3 bind to SYD-1 and SYD-1 binds to and negatively regulates the MIG-2 (Rac) GTPase. We also find that the function of SYD-1 in axon guidance is mediated by its phylogenetically conserved C isoform, indicating that the role of SYD-1 in guidance is distinct from its previously described roles in synaptogenesis and axonal specification. Our observations reveal a molecular mechanism that can allow two guidance receptors to function interdependently to regulate a common downstream effector, providing a potential means for the integration of guidance signals. PMID:25876065

  6. SYD-1C, UNC-40 (DCC) and SAX-3 (Robo) function interdependently to promote axon guidance by regulating the MIG-2 GTPase.

    PubMed

    Xu, Yan; Taru, Hidenori; Jin, Yishi; Quinn, Christopher C

    2015-04-01

    During development, axons must integrate directional information encoded by multiple guidance cues and their receptors. Axon guidance receptors, such as UNC-40 (DCC) and SAX-3 (Robo), can function individually or combinatorially with other guidance receptors to regulate downstream effectors. However, little is known about the molecular mechanisms that mediate combinatorial guidance receptor signaling. Here, we show that UNC-40, SAX-3 and the SYD-1 RhoGAP-like protein function interdependently to regulate the MIG-2 (Rac) GTPase in the HSN axon of C. elegans. We find that SYD-1 mediates an UNC-6 (netrin) independent UNC-40 activity to promote ventral axon guidance. Genetic analysis suggests that SYD-1 function in axon guidance requires both UNC-40 and SAX-3 activity. Moreover, the cytoplasmic domains of UNC-40 and SAX-3 bind to SYD-1 and SYD-1 binds to and negatively regulates the MIG-2 (Rac) GTPase. We also find that the function of SYD-1 in axon guidance is mediated by its phylogenetically conserved C isoform, indicating that the role of SYD-1 in guidance is distinct from its previously described roles in synaptogenesis and axonal specification. Our observations reveal a molecular mechanism that can allow two guidance receptors to function interdependently to regulate a common downstream effector, providing a potential means for the integration of guidance signals.

  7. Drug discovery with DNA-encoded chemical libraries.

    PubMed

    Buller, Fabian; Mannocci, Luca; Scheuermann, Jörg; Neri, Dario

    2010-09-15

    DNA-encoded chemical libraries represent a novel avenue for the facile discovery of small molecule ligands against target proteins of biological or pharmaceutical importance. Library members consist of small molecules covalently attached to unique DNA fragments that serve as amplifiable identification barcodes. This encoding allows the in vitro selection of ligands at subpicomolar concentrations from large library populations by affinity capture on a target protein of interest, in analogy to established technologies for the selection of binding polypeptides (e.g., antibodies). Different library formats have been explored by various groups, allowing the construction of chemical libraries comprising up to millions of DNA-encoded compounds. Libraries before and after selection have been characterized by PCR amplification of the DNA codes and subsequent relative quantification of library members using high-throughput sequencing. The most enriched compounds have then been further analyzed in biological assays, in the presence or in the absence of linked DNA. This article reviews experimental strategies used for the construction of DNA-encoded chemical libraries, revealing how selection, decoding, and hit validation technologies have been used for drug discovery programs.

  8. Guidance trajectories for aeroassisted orbital transfer

    NASA Technical Reports Server (NTRS)

    Miele, A.

    1990-01-01

    Research on aerobraking guidance schemes is presented. The intent is to produce aerobraking guidance trajectories exhibiting many of the desirable characteristics of optimal aerobraking trajectories. Both one-control schemes and two-control schemes are studied. The research is in the interest of aeroassisted flight experiment vehicles (AFE) and aeroassisted orbital transfer (AOT) vehicles.

  9. SPACE VEHICLE NAVIGATION, GUIDANCE, AND CONTROL

    DTIC Science & Technology

    The report contains a summary of space vehicle guidance and control plus an extensive bibliography of the subject area. This report is intended to...encompass only the interplanetary portion of the space vehicle flight. Launch vehicle guidance and control is covered in RSIC-494, entitled Methods of

  10. Vocational Guidance and Career Development. Selected Readings.

    ERIC Educational Resources Information Center

    Peters, Herman J.; Hansen, James C.

    This compilation of readings pertaining to vocational guidance is designed to provide counselors in a number of settings with access to articles that will complement standard information sources. Part 1 explores various approaches to the nature of work, while Part 2 focuses on society's dimensions of work with consequent implications for guidance.…

  11. Foundations for Policy in Guidance and Counseling.

    ERIC Educational Resources Information Center

    Herr, Edwin L., Ed.; Pinson, Nancy M., Ed.

    This book provides educators, counselors, policy makers, and community members with information about the state of the art of federal and state policy in guidance and counseling. The two chapters in part 1, Overview, are: "Foundations for Policy in Guidance and Counseling: An Introduction", by Edwin L. Herr and Nancy M. Pinson; and "A Counselor…

  12. Guidance Counsellor Strategies for Handling Bullying

    ERIC Educational Resources Information Center

    Power-Elliott, Michleen; Harris, Gregory E.

    2012-01-01

    The purpose of this exploratory-descriptive study was to examine how guidance counsellors in the province of Newfoundland and Labrador would handle a specific verbal-relational bullying incident. Also of interest was guidance counsellor involvement and training in bullying programmes and Positive Behaviour Supports. Data for this study was…

  13. Guidance for performing preliminary assessments under CERCLA

    SciTech Connect

    1991-09-01

    EPA headquarters and a national site assessment workgroup produced this guidance for Regional, State, and contractor staff who manage or perform preliminary assessments (PAs). EPA has focused this guidance on the types of sites and site conditions most commonly encountered. The PA approach described in this guidance is generally applicable to a wide variety of sites. However, because of the variability among sites, the amount of information available, and the level of investigative effort required, it is not possible to provide guidance that is equally applicable to all sites. PA investigators should recognize this and be aware that variation from this guidance may be necessary for some sites, particularly for PAs performed at Federal facilities, PAs conducted under EPA`s Environmental Priorities Initiative (EPI), and PAs at sites that have previously been extensively investigated by EPA or others. The purpose of this guidance is to provide instructions for conducting a PA and reporting results. This guidance discusses the information required to evaluate a site and how to obtain it, how to score a site, and reporting requirements. This document also provides guidelines and instruction on PA evaluation, scoring, and the use of standard PA scoresheets. The overall goal of this guidance is to assist PA investigators in conducting high-quality assessments that result in correct site screening or further action recommendations on a nationally consistent basis.

  14. Career Guidance in Wales: Retrospect and Prospect

    ERIC Educational Resources Information Center

    Clark, Mike; Talbot, John

    2006-01-01

    Deregulation of the LEA Careers Service followed by the establishment of the National Assembly for Wales in 1999 led, through consultation, to the establishment of a bi-lingual all-age career guidance service under the banner of Careers Wales. The article traces the history of career guidance in Wales from 1974, showing how it has taken a very…

  15. The Internationalization of Educational and Vocational Guidance

    ERIC Educational Resources Information Center

    Savickas, Mark L.; Van Esbroeck, Raoul; Herr, Edwin L.

    2005-01-01

    The authors identify and discuss the main themes from the discourse on the internationalization of educational and vocational guidance at the 2004 "Symposium on International Perspectives on Career Development," co sponsored by the International Association for Educational and Vocational Guidance and the National Career Development Association.…

  16. Career Guidance and Public Mental Health

    ERIC Educational Resources Information Center

    Robertson, Peter J.

    2013-01-01

    Career guidance may have the potential to promote public health by contributing positively to both the prevention of mental health conditions and to population level well-being. The policy implications of this possibility have received little attention. Career guidance agencies are well placed to reach key target groups. Producing persuasive…

  17. Elementary School Guidance Work Conference. Conference Report.

    ERIC Educational Resources Information Center

    Herr, Edwin L.; Hershberger, James K.

    In October, 1967, 100 invited participants representing all aspects of guidance, education, school administration, counselor education, psychology, and interested government agencies in Pennsylvania met for three days to listen, think, discuss, and hopefully develop some recommendations for those who want a better program of elementary guidance.…

  18. 77 FR 48591 - State Rail Plan Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    ... Federal Railroad Administration State Rail Plan Guidance AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Request for Public Comment on Proposed State Rail Plan Guidance..., submission, and acceptance of State rail plans. State rail plans are documents that are required...

  19. 48 CFR 427.104 - General guidance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false General guidance. 427.104 Section 427.104 Federal Acquisition Regulations System DEPARTMENT OF AGRICULTURE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 427.104 General guidance. As used in FAR part 27, the...

  20. 48 CFR 27.102 - General guidance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false General guidance. 27.102 Section 27.102 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 27.102 General guidance. (a) The Government encourages...

  1. 48 CFR 27.102 - General guidance.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false General guidance. 27.102 Section 27.102 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 27.102 General guidance. (a) The Government encourages...

  2. 48 CFR 27.102 - General guidance.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false General guidance. 27.102 Section 27.102 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 27.102 General guidance. (a) The Government encourages...

  3. Guidance in Adult and Continuing Education.

    ERIC Educational Resources Information Center

    McNamara, Gerry

    The provision of guidance in adult and continuing education in Ireland was examined. First, policy in Ireland regarding guidance for adults in education is discussed in the context of the proposals adopted by the European Union (EU) Commission and EU Member States pursuant to the EU Year of Lifelong Learning in 1996. Recent literature on career…

  4. Career Guidance and Public Mental Health

    ERIC Educational Resources Information Center

    Robertson, Peter J.

    2013-01-01

    Career guidance may have the potential to promote public health by contributing positively to both the prevention of mental health conditions and to population level well-being. The policy implications of this possibility have received little attention. Career guidance agencies are well placed to reach key target groups. Producing persuasive…

  5. Social Benefits of Career Guidance. NICEC Briefing.

    ERIC Educational Resources Information Center

    Killeen, John; Watts, Tony; Kidd, Jenny

    Social benefits can be thought of as aggregates of individual benefits, though with possible "snowball" effects. Potential social benefits of career guidance fall into the following two main categories: reducing social exclusion and enhancing social development. Guidance is a way of making the structure of society work, by linking…

  6. Consultant Directory for Rural Career Guidance.

    ERIC Educational Resources Information Center

    Donaldson, Kloyd N.; Edington, Everett D.

    The National Rural Career Guidance Project for Rural and Small Schools was designed to promote active exchange of information among rural schools and to provide services to administrators, counselors, and teachers wishing to implement or upgrade career guidance activities in their schools. The directory was developed for the purpose of providing…

  7. HANDBOOK: HAZARDOUS WASTE INCINERATION MEASUREMENT GUIDANCE

    EPA Science Inventory

    This publication, Volume III of the Hazardous Waste Incineration Guidance Series, contains general guidance to permit writers in reviewing hazardous waste incineration permit applications and trial burn plans. he handbook is a how-to document dealing with how incineration measure...

  8. Gifted Child Development and Guidance Study.

    ERIC Educational Resources Information Center

    Virginia Beach City Public Schools, VA.

    The Gifted Child Development and Guidance Program of Virginia Beach City (Virginia) Public Schools was developed to interest gifted college-bound students in a vocational class in child development and guidance that might lead to further career interest in child-related professions. This report briefly describes program promotion; student…

  9. Fly Photoreceptors Encode Phase Congruency

    PubMed Central

    Friederich, Uwe; Billings, Stephen A.; Hardie, Roger C.; Juusola, Mikko; Coca, Daniel

    2016-01-01

    More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli. PMID:27336733

  10. Synaptic encoding of temporal contiguity

    PubMed Central

    Ostojic, Srdjan; Fusi, Stefano

    2013-01-01

    Often we need to perform tasks in an environment that changes stochastically. In these situations it is important to learn the statistics of sequences of events in order to predict the future and the outcome of our actions. The statistical description of many of these sequences can be reduced to the set of probabilities that a particular event follows another event (temporal contiguity). Under these conditions, it is important to encode and store in our memory these transition probabilities. Here we show that for a large class of synaptic plasticity models, the distribution of synaptic strengths encodes transitions probabilities. Specifically, when the synaptic dynamics depend on pairs of contiguous events and the synapses can remember multiple instances of the transitions, then the average synaptic weights are a monotonic function of the transition probabilities. The synaptic weights converge to the distribution encoding the probabilities also when the correlations between consecutive synaptic modifications are considered. We studied how this distribution depends on the number of synaptic states for a specific model of a multi-state synapse with hard bounds. In the case of bistable synapses, the average synaptic weights are a smooth function of the transition probabilities and the accuracy of the encoding depends on the learning rate. As the number of synaptic states increases, the average synaptic weights become a step function of the transition probabilities. We finally show that the information stored in the synaptic weights can be read out by a simple rate-based neural network. Our study shows that synapses encode transition probabilities under general assumptions and this indicates that temporal contiguity is likely to be encoded and harnessed in almost every neural circuit in the brain. PMID:23641210

  11. Approach guidance for outer planet pioneer missions

    NASA Technical Reports Server (NTRS)

    Bejczy, A. K.

    1975-01-01

    Onboard optical approach guidance measurements for spin-stabilized Pioneer-type spacecraft are discussed. Approach guidance measurement accuracy requirements are outlined. The application concept and operation principle of the V-slit star tracker are discussed within the context of approach guidance measurements and measurables. It is shown that the accuracy of onboard optical approach guidance measurements is inherently coupled to the stability characteristics of the spacecraft spin axis. Geometrical and physical measurement parameters are presented for Pioneer entry probe missions to Uranus via Jupiter or Saturn flyby. The impact of these parameters on both sensor instrumentation and measurement system design is discussed. The need for sensing extended objects is shown. The feasibility of implementing an onboard approach guidance measurement system for Pioneer-type spacecraft is indicated. Two Pioneer 10 onboard measurement experiments performed in May-June 1974 are described.

  12. Holographically Encoded Volume Phase Masks

    DTIC Science & Technology

    2015-07-13

    yÞAg; (6) where à and B̃ are the Fourier transforms of A and B, respec- tively, and fx and fy are the spatial frequencies along the x and y axes...collimated and directed onto a reflecting spatial light modulator (SLM). Applying the SLM encoding technique by Arrizón et al.,42 the incident beam was...converted into the LP11 and LP21 HOMs. These modes were selected because their spatial phase pattern match the HPM with the encoded four-sector binary

  13. Entry Guidance for the Reusable Launch Vehicle

    NASA Technical Reports Server (NTRS)

    Lu, Ping

    1999-01-01

    The X-33 Advanced Technology Demonstrator is a half-scale prototype developed to test the key technologies needed for a full-scale single-stage reusable launch vehicle (RLV). The X-33 is a suborbital vehicle that will be launched vertically, and land horizontally. The goals of this research were to develop an alternate entry guidance scheme for the X-33 in parallel to the actual X-33 entry guidance algorithms, provide comparative and complementary study, and identify potential new ways to improve entry guidance performance. Toward these goals, the nominal entry trajectory is defined by a piecewise linear drag-acceleration-versus-energy profile, which is in turn obtained by the solution of a semi-analytical parameter optimization problem. The closed-loop guidance is accomplished by tracking the nominal drag profile with primarily bank-angle modulation on-board. The bank-angle is commanded by a single full-envelope nonlinear trajectory control law. Near the end of the entry flight, the guidance logic is switched to heading control in order to meet strict conditions at the terminal area energy management interface. Two methods, one on ground-track control and the other on heading control, were proposed and examined for this phase of entry guidance where lateral control is emphasized. Trajectory dispersion studies were performed to evaluate the effectiveness of the entry guidance algorithms against a number of uncertainties including those in propulsion system, atmospheric properties, winds, aerodynamics, and propellant loading. Finally, a new trajectory-regulation method is introduced at the end as a promising precision entry guidance method. The guidance principle is very different and preliminary application in X-33 entry guidance simulation showed high precision that is difficult to achieve by existing methods.

  14. 78 FR 67442 - Congestion Mitigation and Air Quality Improvement Program Interim Guidance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ... Federal Highway Administration Congestion Mitigation and Air Quality Improvement Program Interim Guidance... Mitigation and Air Quality Improvement (CMAQ) Program (Interim Guidance). The Interim Guidance revises CMAQ....gov/environment/air_quality/cmaq/policy_and_guidance/2008_guidance/ guidance/. DATES: This...

  15. Survey, analysis and genetic organization of genes encoding eukaryotic-like signaling proteins on a cyanobacterial genome.

    PubMed Central

    Zhang, C C; Gonzalez, L; Phalip, V

    1998-01-01

    Bacteria usually use two-component systems for signal transduction, while eukaryotic organisms employ Ser/Thr and Tyr kinases and phosphatases for the same purpose. Many prokaryotes turn out to harbor Ser/Thr and Tyr kinases, Ser/Thr and Tyr phosphatases, and their accessory components as well. The sequence determination of the genome of the cyanobacterium Synechocystis sp. strain PCC 6803 offers the possibility to survey the extent of such molecules in a prokaryotic organism. This cyanobacterium possesses seven Ser/Thr kinases, seven Ser/Thr and Tyr phosphatases, one protein kinase interacting protein, one protein kinase regulatory subunit and several WD40-repeat-containing proteins. The majority of the protein phosphatases presented in this study were previously reported as hypothetical proteins. We analyze here the structure and genetic organization of these ORFs in the hope of providing a guidance for their functional analysis. Unlike their eukaryotic counterparts, many of these genes are clustered on the chromosome, and this genetic organization offers the opportunity to study their possible interaction. In several cases, genes of two-component transducers are found within the same cluster as those encoding a Ser/Thr kinase or a Ser/Thr phosphatase; the implication for signal transduction mechanism will be discussed. PMID:9685474

  16. Space shuttle guidance, navigation, and control design equations. Volume 3: Guidance

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Space shuttle guidance, navigation, and control design equations are presented. The space-shuttle mission includes three relatively distinct guidance phases which are discussed; atmospheric boost, which is characterized by an adaptive guidance law; extra-atmospheric activities; and re-entry activities, where aerodynamic surfaces are the principal effectors. Guidance tasks include pre-maneuver targeting and powered flight guidance, where powered flight is defined to include the application of aerodynamic forces as well as thruster forces. A flow chart which follows guidance activities throughout the mission from the pre-launch phase through touchdown is presented. The main guidance programs and subroutines used in each phase of a typical rendezvous mission are listed. Detailed software requirements are also presented.

  17. Quantum simulation with cold molecules

    NASA Astrophysics Data System (ADS)

    Rey, Ana Maria

    2014-03-01

    Recent experimental developments on cooling, trapping, manipulating and loading ultra-cold ground state molecules in an optical lattice have opened the door for the exploration of quantum magnetism and the observation of complex quantum dynamics. In this talk I will discuss recent developments towards the implementation of controllable spin lattice models in polar molecules with the spin degrees of freedom encoded in rotational states. The spin-spin couplings are generated by direct dipolar interactions and can be fully controlled by dc electromagnetic fields and microwaves. The spin models realized in this way are long range, anisotropic and can even feature direction-dependent spin interactions. They can emulate Hamiltonians ranging from the Heisenberg spin model, to Hamiltonians with symmetry protected topological phases to Hamiltonians without solid state counterpart. At JILA we have been able to realize for the first time a lattice spin model with fermionic KRb molecules pinned in a 3D lattice. We observe clear manifestation of dipolar exchange interactions in Ramsey spectroscopy even at substantially less than unit lattice filling. I will describe the new theoretical methods that we developed to model the spin dynamics and show that those reproduce the experimental observations. Even though so far the spin dynamics has been restricted to pinned molecules, in part to prevent chemical reactions, I will finish by presenting theoretical calculations supported by experimental measurement at JILA that demonstrate that the continuous quantum Zeno mechanism can actually suppress loss in this highly reactive system. This finding opens the exciting possibility of observing itinerant quantum magnetism in near term experiments. This work is supported by ARO, ARO-DARPA-OLE, NSF-PFC and NSF-PIF

  18. How Infants Encode Spatial Extent

    ERIC Educational Resources Information Center

    Duffy, Sean; Huttenlocher, Janellen; Levine, Susan; Duffy, Renee

    2005-01-01

    This study explores how infants encode an object's spatial extent. We habituated 6.5-month-old infants to a dowel inside a container and then tested whether they dishabituate to a change in absolute size when the relation between dowel and container is held constant (by altering the size of both container and dowel) and when the relation changes…

  19. Encoding Standards for Linguistic Corpora.

    ERIC Educational Resources Information Center

    Ide, Nancy

    The demand for extensive reusability of large language text collections for natural languages processing research requires development of standardized encoding formats. Such formats must be capable of representing different kinds of information across the spectrum of text types and languages, capable of representing different levels of…

  20. Encoding Ownership Types in Java

    NASA Astrophysics Data System (ADS)

    Cameron, Nicholas; Noble, James

    Ownership types systems organise the heap into a hierarchy which can be used to support encapsulation properties, effects, and invariants. Ownership types have many applications including parallelisation, concurrency, memory management, and security. In this paper, we show that several flavours and extensions of ownership types can be entirely encoded using the standard Java type system.

  1. Spectrally-encoded color imaging

    PubMed Central

    Kang, DongKyun; Yelin, Dvir; Bouma, Brett E.; Tearney, Guillermo J.

    2010-01-01

    Spectrally-encoded endoscopy (SEE) is a technique for ultraminiature endoscopy that encodes each spatial location on the sample with a different wavelength. One limitation of previous incarnations of SEE is that it inherently creates monochromatic images, since the spectral bandwidth is expended in the spatial encoding process. Here we present a spectrally-encoded imaging system that has color imaging capability. The new imaging system utilizes three distinct red, green, and blue spectral bands that are configured to illuminate the grating at different incident angles. By careful selection of the incident angles, the three spectral bands can be made to overlap on the sample. To demonstrate the method, a bench-top system was built, comprising a 2400-lpmm grating illuminated by three 525-μm-diameter beams with three different spectral bands. Each spectral band had a bandwidth of 75 nm, producing 189 resolvable points. A resolution target, color phantoms, and excised swine small intestine were imaged to validate the system's performance. The color SEE system showed qualitatively and quantitatively similar color imaging performance to that of a conventional digital camera. PMID:19688002

  2. Numerical Skip-Entry Guidance

    NASA Technical Reports Server (NTRS)

    Tigges, Michael; Crull, Timothy; Rea, Jeremy; Johnson, Wyatt

    2006-01-01

    This paper assesses a preliminary guidance and targeting strategy for accomplishing Skip-Entry (SE) flight during a lunar return-capsule entry flight. One of the primary benefits of flying a SE trajectory is to provide the crew with continuous Continental United States (CONUS) landing site access throughout the lunar month. Without a SE capability, the capsule must land either in water or at one of several distributed land sites in the Southern Hemisphere for a significant portion of a lunar month using a landing and recovery scenario similar to that employed during the Apollo program. With a SE trajectory, the capsule can land either in water at a site in proximity to CONUS or at one of several distributed landing sites within CONUS, thereby simplifying the operational requirements for crew retrieval and vehicle recovery, and possibly enabling a high degree of vehicle reusability. Note that a SE capability does not require that the vehicle land on land. A SE capability enables a longer-range flight than a direct-entry flight, which permits the vehicle to land at a much greater distance from the Entry Interface (EI) point. This does not exclude using this approach to push the landing point to a water location in proximity of CONUS and utilizing water or airborne recovery forces.

  3. Optofluidic control of axonal guidance

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Ordonez, Simon; Black, Bryan; Mohanty, Samarendra K.

    2013-03-01

    Significant efforts are being made for control on axonal guidance due to its importance in nerve regeneration and in the formation of functional neuronal circuitry in-vitro. These include several physical (topographic modification, optical force, and electric field), chemical (surface functionalization cues) and hybrid (electro-chemical, photochemical etc) methods. Here, we report comparison of the effect of linear flow versus microfluidic flow produced by an opticallydriven micromotor in guiding retinal ganglion axons. A circularly polarized laser tweezers was used to hold, position and spin birefringent calcite particle near growth cone, which in turn resulted in microfluidic flow. The flow rate and resulting shear-force on axons could be controlled by a varying the power of the laser tweezers beam. The calcite particles were placed separately in one chamber and single particle was transported through microfluidic channel to another chamber containing the retina explant. In presence of flow, the turning of axons was found to strongly correlate with the direction of flow. Turning angle as high as 90° was achieved. Optofluidic-manipulation can be applied to other types of mammalian neurons and also can be extended to stimulate mechano-sensing neurons.

  4. Evaluation of genotoxicity testing of FDA approved large molecule therapeutics.

    PubMed

    Sawant, Satin G; Fielden, Mark R; Black, Kurt A

    2014-10-01

    Large molecule therapeutics (MW>1000daltons) are not expected to enter the cell and thus have reduced potential to interact directly with DNA or related physiological processes. Genotoxicity studies are therefore not relevant and typically not required for large molecule therapeutic candidates. Regulatory guidance supports this approach; however there are examples of marketed large molecule therapeutics where sponsors have conducted genotoxicity studies. A retrospective analysis was performed on genotoxicity studies of United States FDA approved large molecule therapeutics since 1998 identified through the Drugs@FDA website. This information was used to provide a data-driven rationale for genotoxicity evaluations of large molecule therapeutics. Fifty-three of the 99 therapeutics identified were tested for genotoxic potential. None of the therapeutics tested showed a positive outcome in any study except the peptide glucagon (GlucaGen®) showing equivocal in vitro results, as stated in the product labeling. Scientific rationale and data from this review indicate that testing of a majority of large molecule modalities do not add value to risk assessment and support current regulatory guidance. Similarly, the data do not support testing of peptides containing only natural amino acids. Peptides containing non-natural amino acids and small molecules in conjugated products may need to be tested.

  5. Optimal guidance law in quantum mechanics

    SciTech Connect

    Yang, Ciann-Dong Cheng, Lieh-Lieh

    2013-11-15

    Following de Broglie’s idea of a pilot wave, this paper treats quantum mechanics as a problem of stochastic optimal guidance law design. The guidance scenario considered in the quantum world is that an electron is the flight vehicle to be guided and its accompanying pilot wave is the guidance law to be designed so as to guide the electron to a random target driven by the Wiener process, while minimizing a cost-to-go function. After solving the stochastic optimal guidance problem by differential dynamic programming, we point out that the optimal pilot wave guiding the particle’s motion is just the wavefunction Ψ(t,x), a solution to the Schrödinger equation; meanwhile, the closed-loop guidance system forms a complex state–space dynamics for Ψ(t,x), from which quantum operators emerge naturally. Quantum trajectories under the action of the optimal guidance law are solved and their statistical distribution is shown to coincide with the prediction of the probability density function Ψ{sup ∗}Ψ. -- Highlights: •Treating quantum mechanics as a pursuit-evasion game. •Reveal an interesting analogy between guided flight motion and guided quantum motion. •Solve optimal quantum guidance problem by dynamic programming. •Gives a formal proof of de Broglie–Bohm’s idea of a pilot wave. •The optimal pilot wave is shown to be a wavefunction solved from Schrödinger equation.

  6. 76 FR 411 - Regulatory Guidance Concerning Electronic Signatures and Documents

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... Federal Motor Carrier Safety Administration Regulatory Guidance Concerning Electronic Signatures and... guidance. SUMMARY: FMCSA issues regulatory guidance concerning the use of electronic signatures and... information regarding FMCSA's acceptance of electronic signature on documents required by the Federal Motor...

  7. The Development of Vocational Guidance in the USSR.

    ERIC Educational Resources Information Center

    Kostin, L. A.

    1986-01-01

    The author defines the scope and importance of vocational guidance in the Soviet Union. He states that such guidance is primarily for youth. He discusses the institutional framework of vocational guidance programs and new developments in the Soviet Union. (CH)

  8. Standard generalized markup language: A guide for transmitting encoded bibliographic records

    SciTech Connect

    Not Available

    1994-09-01

    This document provides the guidance necessary to transmit to DOE`s Office of Scientific and Technical Information (OSTI) an encoded bibliographic record that conforms to International Standard ISO 8879, Information Processing -- Text and office systems -- Standard Generalized Markup Language (SGML). Included in this document are element and attribute tag definitions, sample bibliographic records, the bibliographic document type definition, and instructions on how to transmit a bibliographic record electronically to OSTI.

  9. 76 FR 29251 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls; Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-20

    ...; Class II Special Controls; Guidance Document: Topical Oxygen Chamber for Extremities; Availability... Drug Administration Staff; Class II Special Controls Guidance Documents: Topical Oxygen Chamber for... Guidance Document: Topical Oxygen Chamber for Extremities'' to the Division of Small...

  10. 76 FR 43690 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... Administration (FDA) is announcing the availability of the guidance entitled ``Class II Special Controls Guidance Document: Electrocardiograph Electrodes.'' The special controls identify the following risks to health... Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph...

  11. Guidance of magnetic space tug

    NASA Astrophysics Data System (ADS)

    Fabacher, Emilien; Lizy-Destrez, Stéphanie; Alazard, Daniel; Ankersen, Finn; Profizi, Alexandre

    2017-07-01

    Magnetic tugging of a target satellite without thrust capacity can be interesting in various contexts, as for example End-Of-Life management, or to complete launchers capabilities. The aim is to gradually modify the orbit of the target by constantly exerting on it a magnetic force. To do so, the chaser is assumed equipped with a steerable magnetic dipole, able to create both forces and torques on the magnetic torque rods carried by the target. The chaser is also supposed to carry electric thrusters, creating a continuous force which modifies the orbit of the whole formation composed of chaser and target. The relative motions of both satellites are derived, in order to assess the feasibility of such a concept. Relative configuration (attitudes and position) trajectories are derived, which are compliant with the dynamics, and enable the chaser to tug the target. Considering targets in Low Earth Orbit (LEO), the magnetic field of the Earth is taken into account, modeled by the International Geomagnetic Reference Field (IGRF). The position of the magnetic torque rod of the target may not be located at its center of mass. This lever-arm is taken into account in the dynamics. As for every Electro-Magnetic Formation Flight concept developed in the literature, satellites involved in magnetic tugging are constantly subjected to torques, created by the Earth magnetic field and by the magnetic fields created by the other satellites in the formation. In this study, the solution chosen to face this problem is to take into account the attitude equilibrium of the satellites early in the guidance phase, in order to avoid having to wave the dipole, as it is generally done. Promising results are presented for different types of orbit, showing that the concept could be feasible in many different scenarios.

  12. The Title V guidance notebook

    SciTech Connect

    Powell, R.D.; McCutchen, G.D.

    1998-12-31

    In October 1997, the Air and Waste Management Association (A and WMA) made available a notebook consisting of documents pertaining to implementation of the operating permits program required by title V of the Clean Air Act and the Environmental Protection Agency`s (EPA) part 70 operating permits regulations. The documents include guidance memos/letters, questions/answers, several specialty documents, and related Federal Register notices that have been produced by EPA since inception of the program with the Clean Air Act amendments of 1990. The notebook contents were made available by EPA and the project was carried out under an EPA contract to A and WMA. The work was performed by RTP Environmental Associates Inc. of Raleigh, North Carolina. The notebook contains more than 75 documents; all the materials EPA believes relevant to implementation of the part 70 program by States, local agencies, territories, and Indian tribes. The documents that comprise the notebook are organized by subject matter and each is given a reference number for purposes of referring to the document. The part 70 operating permits regulations are annotated with document reference numbers to indicate where a document relates to a specific section of the regulations. In addition, documents are indexed four ways; by date, by author, alphabetically by title, and by reference number. Abstracts of each document are included in the notebook to allow the user to determine if the document is of interest. The notebook user, therefore, should be able to readily locate documents and be aware of all materials that affect any area of interest the user may have. The notebook will periodically be updated to add any new materials generated since the last update. The notebook should also be of interest to sources who must obtain a part 70 operating permit and to the general public interested in following implementation of the program. Notebooks may be purchased from A and WMA.

  13. Autonomous landing guidance system validation

    NASA Astrophysics Data System (ADS)

    Bui, Long Q.; Franklin, Michael R.; Taylor, Christopher; Neilson, Graham

    1997-06-01

    ALG is a combination of raster imaging sensor, head-up displays, flight guidance and procedures which allow pilots to perform hand flown aircraft maneuvers in adverse weather, at night, or in low visibility conditions at facilities with minimal or no ground aids. Maneuvers in the context of ALG relate to takeoff, landing, rollout, taxi and terminal parking. Commercial needs are driven by potential revenue savings since today only 43 Type III and 80 Type II instrumented landing system (ILS) runway ends in the United States are equipped for lower minimum flight operations. Additionally, most of these ILS facilities are clustered at major gateway airports which further impacts on dispatch authority and general ATC regional delays. Infrastructure consists to upgrade additional runways must not only account for the high integrity ground instrumentation, but also the installation of lights and markers mandated for Cat III operations. The military services ability to train under realistic battlefield conditions, to project power globally in support of national interests, while providing humanitarian aid, is significantly impaired by the inability to conduct precision approaches and landings in low visibility conditions to either instrumented runways or to a more tactical environment with operations into and out of unprepared landing strips, particularly when time does not permit deployment of ground aids and the verification of their integrity. Recently, Lear Astronics, in cooperation with Consortium members of the ALG Program, concluded a flight test program which evaluated the utility of the ALG system in meeting both civil and military needs. Those results are the subject of this paper.

  14. Travel guidance system for vehicles

    SciTech Connect

    Takanabe, K.; Yamamoto, M.; Ito, K.; Fujinami, H.

    1987-02-24

    A travel guidance system is described for vehicles including: a heading sensor for detecting a direction of movement of a vehicle; a distance sensor for detecting a distance traveled by the vehicle; a map data storage medium preliminarily storing map data; a control unit for receiving a heading signal from the heading sensor and a distance signal from the distance sensor to successively compute a present position of the vehicle and for generating video signals corresponding to display data including map data from the map data storage medium and data of the present position; and a display having first and second display portions and responsive to the video signals from the control unit to display on the first display portion a map and a present portion mark, in which: the map data storage medium comprises means for preliminarily storing administrative division name data and landmark data; and the control unit comprises: landmark display means for: (1) determining a landmark closest to the present position, (2) causing a position of the landmark to be displayed on the map and (3) retrieving a landmark massage concerning the landmark from the storage medium to cause the display to display the landmark message on the second display portion; division name display means for retrieving the name of an administrative division to which the present position belongs from the storage medium and causing the display to display a division name message on the second display portion; and selection means for selectively actuating at least one of the landmark display means and the division name display means.

  15. Encoding information into precipitation structures

    NASA Astrophysics Data System (ADS)

    Martens, Kirsten; Bena, Ioana; Droz, Michel; Rácz, Zoltan

    2008-12-01

    Material design at submicron scales would be profoundly affected if the formation of precipitation patterns could be easily controlled. It would allow the direct building of bulk structures, in contrast to traditional techniques which consist of removing material in order to create patterns. Here, we discuss an extension of our recent proposal of using electrical currents to control precipitation bands which emerge in the wake of reaction fronts in A+ + B- → C reaction-diffusion processes. Our main result, based on simulating the reaction-diffusion-precipitation equations, is that the dynamics of the charged agents can be guided by an appropriately designed time-dependent electric current so that, in addition to the control of the band spacing, the width of the precipitation bands can also be tuned. This makes straightforward the encoding of information into precipitation patterns and, as an amusing example, we demonstrate the feasibility by showing how to encode a musical rhythm.

  16. Practice Greenhealth Sustainable Purchasing Guidance Profile

    EPA Pesticide Factsheets

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  17. Responsible Purchasing Network - Sustainable Purchasing Guidance Profile

    EPA Pesticide Factsheets

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  18. Surface Water Treatment Rules State Implementation Guidance

    EPA Pesticide Factsheets

    These documents provide guidance to states, tribes and U.S. EPA Regions exercising primary enforcement responsibility under the Safe Drinking Water Act. The documents contain EPA’s recommendations for implementation of the Surface Water Treatment Rules.

  19. Guidance: Treatment of Insurers Under Superfund

    EPA Pesticide Factsheets

    Guidance provides EPA Regional offices with the appropriate procedures to follow in issuing notice letters, developing referrals, and tracking CERCLA enforcement cases that may include insurers as third party defendants.

  20. Tests and Guidance: What Students Need.

    ERIC Educational Resources Information Center

    Krumboltz, John D.

    1982-01-01

    Innovations in testing and guidance which can integrate assessment to facilitate learning, help develop practical wisdom in behavior, and correct students' faulty cognitions in career decisions are described. (CM)

  1. Delta launch vehicle inertial guidance system (DIGS)

    NASA Technical Reports Server (NTRS)

    Duck, K. I.

    1973-01-01

    The Delta inertial guidance system, part of the Delta launch vehicle improvement effort, has been flown on three launches and was found to perform as expected for a variety of mission profiles and vehicle configurations.

  2. Beam envelope matching for beam guidance systems

    SciTech Connect

    Brown, K.L.

    1980-08-01

    Ray optics and phase ellipse optics are developed as tools for designing charged particle beam guidance systems. Specific examples of basic optical systems and of phase ellipse matching are presented as illustrations of these mathematical techniques.

  3. General RMP Guidance - Table of Contents

    EPA Pesticide Factsheets

    The Risk Management Programs for Chemical Accident Prevention (40 CFR Part 68) guidance is in chapters; each covering topics such as applicability of the rule, and requirements for reporting five-year accident history and offsite consequence analysis.

  4. The Industrial User Permitting Guidance Manual

    EPA Pesticide Factsheets

    Provides guidance for control authorities to effectively develop and issue control mechanisms to IUs discharging to the POTW and covers developing and implementing control mechanisms for both SIUs and non-SIUs.

  5. European Union Sustainable Purchasing Guidance Profile

    EPA Pesticide Factsheets

    To help you find the resource that is right for your organization, EPA conducted a scan of the landscape and developed summary profiles of some of the leading sources of sustainable purchasing guidance around the globe.

  6. Much more than just another guidance document.

    PubMed

    Kulkarni, K

    2016-11-01

    As a pediatric hematologist oncologist with clinical and research interests in thrombosis in high-risk pediatric populations, and also as a member of the ISTH Early Career Task Force, I had the opportunity to develop a guidance document on 'Thromboprophylaxis for central venous catheters in the pediatric population' for the 'Guidelines and Guidance Documents' committee. In this communication, I share my experiences to date; I discuss my excitement and initial success, the steep learning curve required to build research acumen, the lessons learnt, and the opportunities and challenges faced. My experience with preparing the guidance document was much more than writing 'just another guidance document'. © 2016 International Society on Thrombosis and Haemostasis.

  7. Beyond Black: An Alternative to Ethnocentric Guidance

    ERIC Educational Resources Information Center

    Goldman, Robert C.

    1977-01-01

    This article is a clarification of the author's personal philosophy in the guidance and counseling of youth and adults, and clarification of commonalities that form the raison d'etre of all student personnel services. (Author)

  8. Safe abortion: WHO technical and policy guidance.

    PubMed

    Cook, R J; Dickens, B M; Horga, M

    2004-07-01

    In 2003, the World Health Organization published its well referenced handbook Safe Abortion: Technical and Policy Guidance for Health Systems to address the estimated almost 20 million induced abortions each year that are unsafe, imposing a burden of approximately 67 thousand deaths annually. It is a global injustice that 95% of unsafe abortions occur in developing countries. The focus of guidance is on abortion procedures that are lawful within the countries in which they occur, noting that in almost all countries, the law permits abortion to save a woman's life. The guidance treats unsafe abortion as a public health challenge, and responds to the problem through strategies concerning improved clinical care for women undergoing procedures, and the appropriate placement of necessary services. Legal and policy considerations are explored, and annexes present guidance to further reading, international consensus documents on safe abortion, and on manual vacuum aspiration and post-abortion contraception.

  9. POTW Sludge Sampling and Analysis Guidance Document

    EPA Pesticide Factsheets

    In view of the variability of municipal sludge quality,appropriate procedures must be followed to collect and analyze samples that accurately represent each POTW's sludge quality.This manual was developed to provide that guidance to POTW operators, engin

  10. Guidance for Developing TMDLs in California

    EPA Pesticide Factsheets

    This document provides guidance to the State of California concerning its responsibility under section 303(d) of the Clean Water Act concerning the development of TMDLs for water quality-limited segments listed under section 303(d).

  11. Moisture Control Guidance for Commercial and Public ...

    EPA Pesticide Factsheets

    This document provides guidance to designers, construction mangers, and building operation/maintenance managers to improve IEQ and reduce risks of encountering IEQ problems due to insufficient moisture control. EPA will be producing a document entitled

  12. Optimal guidance for the space shuttle transition.

    NASA Technical Reports Server (NTRS)

    Stengel, R. F.

    1972-01-01

    A guidance method for the space shuttle's transition from hypersonic entry to subsonic cruising flight is presented. The method evolves from a numerical trajectory optimization technique in which kinetic energy and total energy (per unit weight) replace velocity and time in the dynamic equations. This allows the open end-time problem to be transformed to one of fixed terminal energy. In its ultimate form, 'E-Guidance' obtains energy balance (including dynamic-pressure-rate damping) and path length control by angle-of-attack modulation and cross-range control by roll angle modulation. The guidance functions also form the basis for a pilot display of instantaneous maneuver limits and destination. Numerical results illustrate the E-Guidance concept and the optimal trajectories on which it is based.

  13. Optimal guidance for the space shuttle transition

    NASA Technical Reports Server (NTRS)

    Stengel, R. F.

    1974-01-01

    A guidance method for the space shuttle's transition from hypersonic entry to subsonic cruising flight is presented. The method evolves from a numerical trajectory optimization technique in which kinetic energy and total energy (per unit weight) replace velocity and time in the dynamic equations. This allows the open end-time problem to be transformed to one of fixed terminal energy. In its ultimate form, E-Guidance obtains energy balance (including dynamic-pressure-rate damping) and path length control by angle-of-attack modulation and cross-range control by roll angle modulation. The guidance functions also form the basis for a pilot display of instantaneous maneuver limits and destination. Numerical results illustrate the E-Guidance concept and the optimal trajectories on which it is based.

  14. Optimal guidance for the space shuttle transition

    NASA Technical Reports Server (NTRS)

    Stengel, R. F.

    1972-01-01

    A guidance method for the space shuttle's transition from hypersonic entry to subsonic cruising flight is presented. The method evolves from a numerical trajectory optimization technique in which kinetic energy and total energy (per unit weight) replace velocity and time in the dynamic equations. This allows the open end-time problem to be transformed to one of fixed terminal energy. In its ultimate form, E-Guidance obtains energy balance (including dynamic-pressure-rate damping) and path length control by angle-of-attack modulation and cross-range control by roll angle modulation. The guidance functions also form the basis for a pilot display of instantaneous maneuver limits and destination. Numerical results illustrate the E-Guidance concept and the optimal trajectories on which it is based.

  15. The Work of the Guidance Administrator

    ERIC Educational Resources Information Center

    Biggers, Julian L.; Mangusso, David J.

    1972-01-01

    The results of this survey suggest that there is basic agreement in the fundamental duties performed by the director of guidance, although a great deal of variation exists in the title given that post. (Author)

  16. RMP Guidance for Warehouses - Table of Contents

    EPA Pesticide Factsheets

    This Risk Management Program (40 CFR Part 68) Guidance is organized into chapters, each covering a topic such as applicability of the rule, requirements for the five-year accident history and offsite consequence analysis, and emergency response.

  17. 36 CFR 1290.7 - Additional guidance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ASSASSINATION RECORDS GUIDANCE FOR INTERPRETATION AND IMPLEMENTATION OF THE PRESIDENT JOHN F. KENNEDY..., committees, and meetings that possess or created records relating to the assassination of President John F...

  18. 36 CFR 1290.7 - Additional guidance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ASSASSINATION RECORDS GUIDANCE FOR INTERPRETATION AND IMPLEMENTATION OF THE PRESIDENT JOHN F. KENNEDY..., committees, and meetings that possess or created records relating to the assassination of President John F...

  19. GUIDANCE MANUAL FOR SOURCE WATER MONITORING ...

    EPA Pesticide Factsheets

    The manual explains the source water monitoring requirements of LT2ESWTR; provides guidance on how to collect samples for Cryptosporidium and E. coli and on how to establish and manage a Cryptosporidium laboratory contract; and explains how to use and interpret source water monitoring data. Utilities and regulatory agencies will use the guidance for implementing the source water Cryptosporidium and E. coli monitoring requirements of the LT2ESWTR.

  20. Soil screening guidance: User`s guide

    SciTech Connect

    1996-04-01

    The Soil Screening Guidance is a tool that the U.S. Environmental Protection Agency (EPA) developed to help standardize and accelerate the evaluation and cleanup of contaminated soils at sites on the National Priorities List (NPL) with future residential land use. This guidance provides a methodology for environmental science/engineering professionals to calculate risk-based, site-specific, soil screening levels (SSLs) for contaminants in soil that may be used to identify areas needing further investigation at NPL sites.

  1. UV DISINFECTION GUIDANCE MANUAL FOR THE ...

    EPA Pesticide Factsheets

    Provides technical information on selection, design and operation of UV systems; provides regulatory agencies with guidance and the necessary tools to assess UV systems at the design, start-up, and routine operation phase; provides manufacturers with the testing and performance standards for UV components and systems for treating drinking water. Provide guidance to water systems, regulators and manufacturers on UV disinfection of drinking water.

  2. Vector Encoding in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Potter, Garrett; Sun, Bo

    Encoding of environmental cues via biochemical signaling pathways is of vital importance in the transmission of information for cells in a network. The current literature assumes a single cell state is used to encode information, however, recent research suggests the optimal strategy utilizes a vector of cell states sampled at various time points. To elucidate the optimal sampling strategy for vector encoding, we take an information theoretic approach and determine the mutual information of the calcium signaling dynamics obtained from fibroblast cells perturbed with different concentrations of ATP. Specifically, we analyze the sampling strategies under the cases of fixed and non-fixed vector dimension as well as the efficiency of these strategies. Our results show that sampling with greater frequency is optimal in the case of non-fixed vector dimension but that, in general, a lower sampling frequency is best from both a fixed vector dimension and efficiency standpoint. Further, we find the use of a simple modified Ornstein-Uhlenbeck process as a model qualitatively captures many of our experimental results suggesting that sampling in biochemical networks is based on a few basic components.

  3. A study on sound guidance for evacuation: Effect of megaphoned evacuation guidance in smoke

    NASA Astrophysics Data System (ADS)

    Watanabe, Y.

    Tests conducted to determine the effectiveness of megaphone evacuation guidance for people lost in smoke are discussed. Two types of voice guidance were used: a direct live voice, instructing the subject to go left or right as he was watched; and a taped voice mechanically broadcasted every five seconds. The subjects' response to obstacles was also observed. Guidance with a live voice resulted in less smoothness of walking than the tape recording, but was more effective owing to its reassuring nature.

  4. Formation of Ultracold Molecules

    SciTech Connect

    Cote, Robin

    2016-01-28

    Advances in our ability to slow down and cool atoms and molecules to ultracold temperatures have paved the way to a revolution in basic research on molecules. Ultracold molecules are sensitive of very weak interactions, even when separated by large distances, which allow studies of the effect of those interactions on the behavior of molecules. In this program, we have explored ways to form ultracold molecules starting from pairs of atoms that have already reached the ultracold regime. We devised methods that enhance the efficiency of ultracold molecule production, for example by tuning external magnetic fields and using appropriate laser excitations. We also investigates the properties of those ultracold molecules, especially their de-excitation into stable molecules. We studied the possibility of creating new classes of ultra-long range molecules, named macrodimers, thousand times more extended than regular molecules. Again, such objects are possible because ultra low temperatures prevent their breakup by collision. Finally, we carried out calculations on how chemical reactions are affected and modified at ultracold temperatures. Normally, reactions become less effective as the temperature decreases, but at ultracold temperatures, they can become very effective. We studied this counter-intuitive behavior for benchmark chemical reactions involving molecular hydrogen.

  5. Ergonomic concerns with lightbar guidance displays.

    PubMed

    Ima, C S; Mann, D D

    2004-05-01

    This article reviews some ergonomic factors associated with agricultural guidance displays. Any technology or management decision that improves the efficiency of an agricultural operation can be considered an aspect of precision farming. Agricultural guidance displays are one such tool because they help to reduce guidance error (i.e., skipping and overlapping of implements within the field), which result in improper application of crop inputs at increased cost. Although each of the guidance displays currently available functions using a different principle, their key objective is to communicate useful guidance information to the operator of the agricultural machine. The case with which the operator obtains the required information depends on a number of ergonomic factors, such as color perceptibility, flash rate, attentional demand, display size, viewing distance, and height of placement of the display in the cab. Ergonomics can be defined as the application of knowledge to create a safe, comfortable, and effective work environment. Consequently, it is critical to consider ergonomics when designing guidance displays or when locating a display in the tractor cab. Without considering ergonomics, it is unlikely that the efficiency of the human-machine system can be optimized.

  6. Application of image guidance in pituitary surgery

    PubMed Central

    de Lara, Danielle; Filho, Leo F. S. Ditzel; Prevedello, Daniel M.; Otto, Bradley A.; Carrau, Ricardo L.

    2012-01-01

    Background: Surgical treatment of pituitary pathologies has evolved along the years, adding safety and decreasing morbidity related to the procedure. Advances in the field of radiology, coupled with stereotactic technology and computer modeling, have culminated in the contemporary and widespread use of image guidance systems, as we know them today. Image guidance navigation has become a frequently used technology that provides continuous three-dimensional information for the accurate performance of neurosurgical procedures. We present a discussion about the application of image guidance in pituitary surgeries. Methods: Major indications for image guidance neuronavigation application in pituitary surgery are presented and demonstrated with illustrative cases. Limitations of this technology are also presented. Results: Patients presenting a history of previous transsphenoidal surgeries, anatomical variances of the sphenoid sinus, tumors with a close relation to the internal carotid arteries, and extrasellar tumors are the most important indications for image guidance in pituitary surgeries. The high cost of the equipment, increased time of surgery due to setup time, and registration and the need of specific training for the operating room personnel could be pointed as limitations of this technology. Conclusion: Intraoperative image guidance systems provide real-time images, increasing surgical accuracy and enabling safe, minimally invasive interventions. However, the use of intraoperative navigation is not a replacement for surgical experience and a systematic knowledge of regional anatomy. It must be recognized as a tool by which the neurosurgeon can reduce the risk associated with surgical approach and treatment of pituitary pathologies. PMID:22826819

  7. Nerve guidance channels as drug delivery vehicles.

    PubMed

    Piotrowicz, Alexandra; Shoichet, Molly S

    2006-03-01

    Nerve guidance channels (NGCs) have been shown to facilitate regeneration after transection injury to the peripheral nerve or spinal cord. Various therapeutic molecules, including neurotrophic factors, have improved regeneration and functional recovery after injury when combined with NGCs; however, their impact has not been maximized partly due to the lack of an appropriate drug delivery system. To address this limitation, nerve growth factor (NGF) was incorporated into NGCs of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate), P(HEMA-co-MMA). The NGCs were synthesized by a liquid-liquid centrifugal casting process and three different methods of protein incorporation were compared in terms of protein distribution and NGF release profile: (1) NGF was encapsulated (with BSA) in biodegradable poly(d,l-lactide-co-glycolide) 85/15 microspheres, which were combined with a PHEMA polymerization formulation and coated on the inside of pre-formed NGCs by a second liquid-liquid centrifugal casting technique; (2) pre-formed NGCs were imbibed with a solution of NGF/BSA and (3) NGF/BSA alone was combined with a PHEMA formulation and coated on the inside of pre-formed NGCs by a second liquid-liquid centrifugal casting technique. Using a fluorescently labelled model protein, the distribution of proteins in NGCs prepared with a coating of either protein-loaded microspheres or protein alone was found to be confined to the inner PHEMA layer. Sustained release of NGF was achieved from NGCs with either NGF-loaded microspheres or NGF alone incorporated into the inner layer, but not from channels imbibed with NGF. By day 28, NGCs with microspheres released a total of 220 pg NGF/cm of channel whereas those NGCs imbibed with NGF released 1040 pg/cm and those NGCs with NGF incorporated directly in a PHEMA layer released 8624 pg/cm. The release of NGF from NGCs with microspheres was limited by a slow-degrading microsphere formulation and by the maximum amount of microspheres that

  8. General RMP Guidance - Appendix E: Supplemental Risk Management Program Guidance for Ammonia Refrigeration Facilities

    EPA Pesticide Factsheets

    Additional information for food processors, food distributors, refrigerated warehouses, and any other facility with ammonia refrigeration system. Includes guidance on exemptions, threshold quantity, offsite consequence analysis.

  9. The status of molecules

    SciTech Connect

    Barnes, T. :

    1994-10-01

    This report summarizes the experimental and theoretical status of hadronic molecules, which are weakly-bound states of two or more hadrons. We begin with a brief history of the subject and discuss a few good candidates, and then abstract some signatures for molecules which may be of interest in the classification of possible molecule states. Next we argue that a more general understanding of 2 {yields} 2 hadron-hadron scattering amplitudes will be crucial for molecule searches, and discuss some of our recent work in this area. We conclude with a discussion of a few more recent molecule candidates (notably the f{sub o}(1710)) which are not well established as molecules but satisfy some of the expected signatures.

  10. Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions

    PubMed Central

    Dong, Xintong; Chiu, Hui; Park, Yeonhee Jenny; Zou, Wei; Zou, Yan; Özkan, Engin; Chang, Chieh; Shen, Kang

    2016-01-01

    Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis. DOI: http://dx.doi.org/10.7554/eLife.11008.001 PMID:26974341

  11. Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions.

    PubMed

    Dong, Xintong; Chiu, Hui; Park, Yeonhee Jenny; Zou, Wei; Zou, Yan; Özkan, Engin; Chang, Chieh; Shen, Kang

    2016-03-14

    Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis.

  12. A Network of HSPG Core Proteins and HS Modifying Enzymes Regulates Netrin-Dependent Guidance of D-Type Motor Neurons in Caenorhabditis elegans

    PubMed Central

    Gysi, Stephan; Rhiner, Christa; Flibotte, Stephane; Moerman, Donald G.; Hengartner, Michael O.

    2013-01-01

    Heparan sulfate proteoglycans (HSPGs) are proteins with long covalently attached sugar side chains of the heparan sulfate (HS) type. Depending on the cellular context HS chains carry multiple structural modifications such as sulfate residues or epimerized sugars allowing them to bind to a wide range of molecules. HSPGs have been found to play extremely diverse roles in animal development and were shown to interact with certain axon guidance molecules. In this study we describe the role of the Caenorhabditis elegans HSPG core proteins Syndecan (SDN-1) and Glypican (LON-2) and the HS modifying enzymes in the dorsal guidance of D-type motor axons, a process controlled mainly by the conserved axon guidance molecule UNC-6/Netrin. Our genetic analysis established the specific HS code relevant for this axon guidance event. Using two sensitized genetic backgrounds, we isolated novel components influencing D-type motor axon guidance with a link to HSPGs, as well as new alleles of several previously characterized axon guidance genes. Interestingly, the dorsal axon guidance defects induced by mutations in zfp-1 or lin-35 depended on the transgene oxIs12 used to visualize the D-type motor neurons. oxIs12 is a large multi-copy transgene that enlarges the X chromosome by approximately 20%. In a search for genes with a comparable phenotype we found that a mutation in the known dosage compensation gene dpy-21 showed similar axon guidance defects as zfp-1 or lin-35 mutants. Thus, derepression of genes on X, where many genes relevant for HS dependent axon guidance are located, might also influence axon guidance of D-type motor neurons. PMID:24066155

  13. [Endothelial cell adhesion molecules].

    PubMed

    Ivanov, A N; Norkin, I A; Puchin'ian, D M; Shirokov, V Iu; Zhdanova, O Iu

    2014-01-01

    The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

  14. Evolutionary Genomics of Immunoglobulin-Encoding Loci in Vertebrates

    PubMed Central

    Das, Sabyasachi; Hirano, Masayuki; Tako, Rea; McCallister, Chelsea; Nikolaidis, Nikolas

    2012-01-01

    Immunoglobulins (or antibodies) are an essential element of the jawed vertebrate adaptive immune response system. These molecules have evolved over the past 500 million years and generated highly specialized proteins that recognize an extraordinarily large number of diverse substances, collectively known as antigens. During vertebrate evolution the diversification of the immunoglobulin-encoding loci resulted in differences in the genomic organization, gene content, and ratio of functional genes and pseudogenes. The tinkering process in the immunoglobulin-encoding loci often gave rise to lineage-specific characteristics that were formed by selection to increase species adaptation and fitness. Immunoglobulin loci and their encoded antibodies have been shaped repeatedly by contrasting evolutionary forces, either to conserve the prototypic structure and mechanism of action or to generate alternative and diversified structures and modes of function. Moreover, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, which are used by different species to effectively generate an almost infinite collection of diverse antibody types. This review summarizes our current knowledge on the genomics and evolution of the immunoglobulin-encoding loci and their protein products in jawed vertebrates. PMID:23024601

  15. Designing Automated Guidance for Concept Diagrams in Inquiry Instruction

    ERIC Educational Resources Information Center

    Ryoo, Kihyun; Linn, Marcia C.

    2016-01-01

    Advances in automated scoring technologies have the potential to support student learning during inquiry instruction by providing timely and adaptive guidance on individual students' responses. To identify which forms of automated guidance can be beneficial for inquiry learning, we compared reflective guidance to directive guidance for…

  16. The Development of a Lifelong Guidance System in Hungary

    ERIC Educational Resources Information Center

    Watts, A. G.; Borbely-Pecze, Bors Tibor

    2011-01-01

    The development of a lifelong guidance system in Hungary Systematic work is currently being undertaken in Hungary to develop a lifelong guidance system, in line with principles outlined by leading international organisations. The origins of career guidance in Hungary, and the nature of the current career guidance system, are outlined. The main…

  17. Constituent Aspects of Workplace Guidance in Secondary VET

    ERIC Educational Resources Information Center

    Swager, Robert; Klarus, Ruud; van Merriënboer, Jeroen J. G.; Nieuwenhuis, Loek F. M.

    2015-01-01

    Purpose: This paper aims to present an integrated model of workplace guidance to enhance awareness of what constitutes good guidance, to improve workplace guidance practices in vocational education and training. Design/methodology/approach: To identify constituent aspects of workplace guidance, a systematic search of Web of Science was conducted,…

  18. Non-Participation in Guidance: An Opportunity for Development?

    ERIC Educational Resources Information Center

    Thomsen, Rie

    2014-01-01

    This article discusses how new opportunities for guidance can emerge from an analysis of the interplay between the participation (or lack of participation) of the individuals in career guidance, and the career guidance practitioner's response. The article suggests critical psychology as a framework for career guidance research and presents…

  19. Constituent Aspects of Workplace Guidance in Secondary VET

    ERIC Educational Resources Information Center

    Swager, Robert; Klarus, Ruud; van Merriënboer, Jeroen J. G.; Nieuwenhuis, Loek F. M.

    2015-01-01

    Purpose: This paper aims to present an integrated model of workplace guidance to enhance awareness of what constitutes good guidance, to improve workplace guidance practices in vocational education and training. Design/methodology/approach: To identify constituent aspects of workplace guidance, a systematic search of Web of Science was conducted,…

  20. Designing Automated Guidance for Concept Diagrams in Inquiry Instruction

    ERIC Educational Resources Information Center

    Ryoo, Kihyun; Linn, Marcia C.

    2016-01-01

    Advances in automated scoring technologies have the potential to support student learning during inquiry instruction by providing timely and adaptive guidance on individual students' responses. To identify which forms of automated guidance can be beneficial for inquiry learning, we compared reflective guidance to directive guidance for…

  1. The Development of a Lifelong Guidance System in Hungary

    ERIC Educational Resources Information Center

    Watts, A. G.; Borbely-Pecze, Bors Tibor

    2011-01-01

    The development of a lifelong guidance system in Hungary Systematic work is currently being undertaken in Hungary to develop a lifelong guidance system, in line with principles outlined by leading international organisations. The origins of career guidance in Hungary, and the nature of the current career guidance system, are outlined. The main…

  2. DNA-Encoded Compound Libraries as Open Source: A Powerful Pathway to New Drugs.

    PubMed

    Lerner, Richard A; Brenner, Sydney

    2017-01-24

    "… We envisioned an iterative system where a unique DNA tag identifier that encoded the event was appended to each newly formed molecule. These vast collections of molecules are known today as DNA- encoded chemical libraries (DECLs), and allow scientists to do selections on the benchtop that previously required access to large and complex high-throughput screening centers …" Read more in the Guest Editorial by Richard A. Lerner and Sydney Brenner. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Hall effect encoding of brushless dc motors

    NASA Technical Reports Server (NTRS)

    Berard, C. A.; Furia, T. J.; Goldberg, E. A.; Greene, R. C.

    1970-01-01

    Encoding mechanism integral to the motor and using the permanent magnets embedded in the rotor eliminates the need for external devices to encode information relating the position and velocity of the rotating member.

  4. NRZ Data Asymmetry Corrector and Convolutional Encoder

    NASA Technical Reports Server (NTRS)

    Pfiffner, H. J.

    1983-01-01

    Circuit compensates for timing, amplitude and symmetry perturbations. Data asymmetry corrector and convolutional encoder regenerate data and clock signals in spite of signal variations such as data or clock asymmetry, phase errors, and amplitude variations, then encode data for transmission.

  5. Novel optical encoder for harsh environments

    NASA Astrophysics Data System (ADS)

    Kress, Bernard; Mueller, Ulrich; Brac-de-la-Perriere, Vincent

    2014-09-01

    We are presenting a new optical encoder architecture for shaft encoding, both in incremental and absolute modes. This encoder is based on a diffractive optics technology platform. We have developed various disk based rotary diffractive encoders previously. This encoder is different in the way it is not a disk composed of successive gratings or computer generated holograms, but rather composed of a single element placed on the shaft. It is thus best suited for hollow shaft or end of shaft applications such as in encoder controlled electrical motors. This new architecture aims at solving some of the problems encountered with previous implementations of diffractive encoders such as disk wobble, disk to shaft centering and also encoding in harsh environments.

  6. Terahertz wavelength encoding compressive imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Qiong; Wang, Xinke; Zhang, Yan

    2016-11-01

    Terahertz (THz) compressive imaging can obtain two dimensional image with a single or linear detector, which can overcome the bottleneck problem of lacking of THz two dimensional detectors. In this presentation, we propose a method to obtain two dimensional images using a linear detector. A plano-convex cylindrical lens is employed to perform Fourier transform and to encode one dimensional information of an object into wavelengths. After recording, both amplitude and phase information for different frequency at each pixel of the line detector are extracted, two dimensional image of the object can be reconstructed. Numerical simulation demonstrates the validity of the proposed method.

  7. Launch flexibility using NLP guidance and remote wind sensing

    NASA Technical Reports Server (NTRS)

    Cramer, Evin J.; Bradt, Jerre E.; Hardtla, John W.

    1990-01-01

    This paper examines the use of lidar wind measurements in the implementation of a guidance strategy for a nonlinear programming (NLP) launch guidance algorithm. The NLP algorithm uses B-spline command function representation for flexibility in the design of the guidance steering commands. Using this algorithm, the guidance system solves a two-point boundary value problem at each guidance update. The specification of different boundary value problems at each guidance update provides flexibility that can be used in the design of the guidance strategy. The algorithm can use lidar wind measurements for on pad guidance retargeting and for load limiting guidance steering commands. Examples presented in the paper use simulated wind updates to correct wind induced final orbit errors and to adjust the guidance steering commands to limit the product of the dynamic pressure and angle-of-attack for launch vehicle load alleviation.

  8. A Qualitative Investigation of Undergraduate Chemistry Students' Macroscopic Interpretations of the Submicroscopic Structure of Molecules.

    ERIC Educational Resources Information Center

    Nicoll, Gayle

    2003-01-01

    Reports research that investigates the encoding that students use to develop molecular models at the undergraduate level. Focuses on the translation between symbolic and subatomic representations of molecules. (Contains 31 references.) (DDR)

  9. Megaplasmids encode differing combinations of lantibiotics in Streptococcus salivarius.

    PubMed

    Wescombe, Philip A; Burton, Jeremy P; Cadieux, Peter A; Klesse, Nikolai A; Hyink, Otto; Heng, Nicholas C K; Chilcott, Chris N; Reid, Gregor; Tagg, John R

    2006-10-01

    Streptococcus salivarius strains commonly produce bacteriocins as putative anti-competitor or signalling molecules. Here we report that bacteriocin production by the oral probiotic strain S. salivarius K12 is encoded by a large (ca. 190 kb) plasmid. Oral cavity transmission of the plasmid from strain K12 to a plasmid-negative variant of this bacterium was demonstrated in two subjects. Tests of additional S. salivarius strains showed large (up to ca. 220 kb) plasmids present in bacteriocin-producing isolates. Various combinations (up to 3 per plasmid) of loci encoding the known streptococcal lantibiotics salivaricin A, salivaricin B, streptin and SA-FF22 were localised to these plasmids. Since all bacteriocin-producing strains of S. salivarius tested to date appear to harbour plasmids, it appears that they may function as mobile repositories for bacteriocin loci, especially those of the lantibiotic class.

  10. Human jagged polypeptide, encoding nucleic acids and methods of use

    DOEpatents

    Li, Linheng; Hood, Leroy

    2000-01-01

    The present invention provides an isolated polypeptide exhibiting substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the polypeptide does not have the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. The invention further provides an isolated nucleic acid molecule containing a nucleotide sequence encoding substantially the same amino acid sequence as JAGGED, or an active fragment thereof, provided that the nucleotide sequence does not encode the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:6. Also provided herein is a method of inhibiting differentiation of hematopoietic progenitor cells by contacting the progenitor cells with an isolated JAGGED polypeptide, or active fragment thereof. The invention additionally provides a method of diagnosing Alagille Syndrome in an individual. The method consists of detecting an Alagille Syndrome disease-associated mutation linked to a JAGGED locus.

  11. Novel selection methods for DNA-encoded chemical libraries.

    PubMed

    Chan, Alix I; McGregor, Lynn M; Liu, David R

    2015-06-01

    Driven by the need for new compounds to serve as biological probes and leads for therapeutic development and the growing accessibility of DNA technologies including high-throughput sequencing, many academic and industrial groups have begun to use DNA-encoded chemical libraries as a source of bioactive small molecules. In this review, we describe the technologies that have enabled the selection of compounds with desired activities from these libraries. These methods exploit the sensitivity of in vitro selection coupled with DNA amplification to overcome some of the limitations and costs associated with conventional screening methods. In addition, we highlight newer techniques with the potential to be applied to the high-throughput evaluation of DNA-encoded chemical libraries.

  12. Elementary School Guidance Curriculum Grades K-6. Georgia Comprehensive Guidance Series.

    ERIC Educational Resources Information Center

    Gunderson, Margaret S.; Moore, Earl J.

    This manual provides a framework, to be used by elementary program developers and teachers, for creating or improving guidance curriculum programs. The manual is based on the Georgia Comprehensive Guidance Model, which is appended for reference. The materials in the manual represent a competency-based approach that is designed to provide a…

  13. Radiation Protection Guidance for Diagnostic and Interventional X-Ray Procedures; Federal Guidance Report No. 14

    EPA Science Inventory

    Federal Guidance Report No. 14 provides federal facilities that use diagnostic and interventional x-ray equipment with updated recommendations for keeping doses as low as reasonably achievable without compromising the quality of patient care, This guidance is an update of Federal...

  14. Radiation Protection Guidance for Diagnostic and Interventional X-Ray Procedures; Federal Guidance Report No. 14

    EPA Science Inventory

    Federal Guidance Report No. 14 provides federal facilities that use diagnostic and interventional x-ray equipment with updated recommendations for keeping doses as low as reasonably achievable without compromising the quality of patient care, This guidance is an update of Federal...

  15. Raising the Profile of Career Guidance: Educational and Vocational Guidance Practitioner

    ERIC Educational Resources Information Center

    Hiebert, Bryan

    2009-01-01

    In 2007 the International Association for Educational and Vocational Guidance (IAEVG) launched the Educational and Vocational Guidance Practitioner credential (EVGP) as one means of formally acknowledging the knowledge, skills, and personal attributes that practitioners need in order to provide quality career development services to clients. This…

  16. 78 FR 37231 - Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug Substances and Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing...

  17. Enzymatic DNA molecules

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor); Breaker, Ronald R. (Inventor)

    1998-01-01

    The present invention discloses deoxyribonucleic acid enzymes--catalytic or enzymatic DNA molecules--capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

  18. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

  19. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

  20. Schematic driven layout of Reed Solomon encoders

    NASA Technical Reports Server (NTRS)

    Arave, Kari; Canaris, John; Miles, Lowell; Whitaker, Sterling

    1992-01-01

    Two Reed Solomon error correcting encoders are presented. Schematic driven layout tools were used to create the encoder layouts. Special consideration had to be given to the architecture and logic to provide scalability of the encoder designs. Knowledge gained from these projects was used to create a more flexible schematic driven layout system.

  1. Time Course of Grammatical Encoding in Agrammatism

    ERIC Educational Resources Information Center

    Lee, Jiyeon

    2011-01-01

    Producing a sentence involves encoding a preverbal message into a grammatical structure by retrieving lexical items and integrating them into a functional (semantic-to-grammatical) structure. Individuals with agrammatism are impaired in this grammatical encoding process. However, it is unclear what aspect of grammatical encoding is impaired and…

  2. VMT forecasting and tracking guidance, Section 187

    SciTech Connect

    Not Available

    1992-01-01

    The guidance is required by Section 187 (a) of the Clean Air Act Amendments of 1990. It offers the Environmental Protection Agency's (EPA's) recommendations on how to forecast and track vehicle miles traveled (VMT) in Moderate and Serious carbon monoxide (CO) non-attainment areas with design values greater than 12.7 ppm at the time of classification. The purpose of the guidance is to help states prepare State Implementation Plan (SIP) revisions that EPA can readily propose to approve as meeting the requirements of the Clean Air Act Amendments. If a state adheres to the guidance, EPA will propose approval of its SIP. A state intending to depart from the guidance, however, should show that the alternative approach it proposes is technically sound and adequate to meet the requirements of the Clean Air Act Amendments. EPA will review SIP submittals from such states on a case-by-case basis to determine whether they do in fact comply with the Clean Air Act Amendment requirements. States are encouraged to obtain EPA approval before using methods other than those specified in the guidance, in order to avoid later problems.

  3. Safety of magnetic fusion facilities: Guidance

    SciTech Connect

    1996-05-01

    This document provides guidance for the implementation of the requirements identified in DOE-STD-6002-96, Safety of Magnetic Fusion Facilities: Requirements. This guidance is intended for the managers, designers, operators, and other personnel with safety responsibilities for facilities designated as magnetic fusion facilities. While the requirements in DOE-STD-6002-96 are generally applicable to a wide range of fusion facilities, this Standard, DOE-STD-6003-96, is concerned mainly with the implementation of those requirements in large facilities such as the International Thermonuclear Experimental Reactor (ITER). Using a risk-based prioritization, the concepts presented here may also be applied to other magnetic fusion facilities. This Standard is oriented toward regulation in the Department of Energy (DOE) environment as opposed to regulation by other regulatory agencies. As the need for guidance involving other types of fusion facilities or other regulatory environments emerges, additional guidance volumes should be prepared. The concepts, processes, and recommendations set forth here are for guidance only. They will contribute to safety at magnetic fusion facilities.

  4. Fine Guidance Sensing for Coronagraphic Observatories

    NASA Technical Reports Server (NTRS)

    Brugarolas, Paul; Alexander, James W.; Trauger, John T.; Moody, Dwight C.

    2011-01-01

    Three options have been developed for Fine Guidance Sensing (FGS) for coronagraphic observatories using a Fine Guidance Camera within a coronagraphic instrument. Coronagraphic observatories require very fine precision pointing in order to image faint objects at very small distances from a target star. The Fine Guidance Camera measures the direction to the target star. The first option, referred to as Spot, was to collect all of the light reflected from a coronagraph occulter onto a focal plane, producing an Airy-type point spread function (PSF). This would allow almost all of the starlight from the central star to be used for centroiding. The second approach, referred to as Punctured Disk, collects the light that bypasses a central obscuration, producing a PSF with a punctured central disk. The final approach, referred to as Lyot, collects light after passing through the occulter at the Lyot stop. The study includes generation of representative images for each option by the science team, followed by an engineering evaluation of a centroiding or a photometric algorithm for each option. After the alignment of the coronagraph to the fine guidance system, a "nulling" point on the FGS focal point is determined by calibration. This alignment is implemented by a fine alignment mechanism that is part of the fine guidance camera selection mirror. If the star images meet the modeling assumptions, and the star "centroid" can be driven to that nulling point, the contrast for the coronagraph will be maximized.

  5. Guidance Trade-off for Aerocapture Missions

    NASA Astrophysics Data System (ADS)

    Vernis, P.; Gelly, G.; Ferreira, E.; da Costa, R.; Ortega, G.

    In the very late 90's, EADS-ST began home funded studies on aerocapture problems. The objectives of these studies were at that time to prepare a possible cooperation within the NASA/Cnes MSR-Orbiter program by investigating this new orbital insertion technique studying different algorithmic solutions from a guidance point of view. According to these preliminary studies, EADS-ST was retained in 2002 by ESA to study insertion techniques such as aerocapture, aero-gravity assist or aerobraking techniques within the frame of Technological Research Program able to bring solutions to Aurora program. In the frame of the ATPE (Aeroassist Technologies for Planetary Exploration) TRP program, EADS-ST, led by Astrium-Gmbh (now part of EADS-ST), developed and implemented an efficient and simple guidance scheme able to cope with mission requirements for aerocapture on Mars, Venus or the Earth: the Feedback Trajectory Control, or FTC. The development of this guidance scheme was made according to a preliminary trade-off analysis using different guidance schemes. Among those ones was an original predictor-corrector guidance scheme, already analyzed within the frame of the MSR-O mission. But, the FTC algoritm was prefered because of its good results and high simplicity. This paper presents an upgrade of the original Apoapsis Predictor, or AP, with the improvement of its robustness woth respect to off-nomonal flight conditions and its process simplification. A new trade-off analysis is then detailed on a Mars Sample return mission.

  6. Measuring Integrated Socioemotional Guidance at School: Factor Structure and Reliability of the Socioemotional Guidance Questionnaire (SEG-Q)

    ERIC Educational Resources Information Center

    Jacobs, Karen; Struyf, Elke

    2013-01-01

    Socioemotional guidance of students has recently become an integral part of education, however no instrument exists to measure integrated socioemotional guidance. This study therefore examines the factor structure and reliability of the Socioemotional Guidance Questionnaire. Psychometric properties of the Socioemotional Guidance Questionnaire and…

  7. Guidance and control, 1993; Annual Rocky Mountain Guidance and Control Conference, 16th, Keystone, CO, Feb. 6-10, 1993

    NASA Technical Reports Server (NTRS)

    Culp, Robert D. (Editor); Bickley, George (Editor)

    1993-01-01

    Papers from the sixteenth annual American Astronautical Society Rocky Mountain Guidance and Control Conference are presented. The topics covered include the following: advances in guidance, navigation, and control; control system videos; guidance, navigation and control embedded flight control systems; recent experiences; guidance and control storyboard displays; and applications of modern control, featuring the Hubble Space Telescope (HST) performance enhancement study.

  8. Measuring Integrated Socioemotional Guidance at School: Factor Structure and Reliability of the Socioemotional Guidance Questionnaire (SEG-Q)

    ERIC Educational Resources Information Center

    Jacobs, Karen; Struyf, Elke

    2013-01-01

    Socioemotional guidance of students has recently become an integral part of education, however no instrument exists to measure integrated socioemotional guidance. This study therefore examines the factor structure and reliability of the Socioemotional Guidance Questionnaire. Psychometric properties of the Socioemotional Guidance Questionnaire and…

  9. Automated low-thrust guidance for the orbital maneuvering vehicle

    NASA Technical Reports Server (NTRS)

    Rose, Richard E.; Schmeichel, Harry; Shortwell, Charles P.; Werner, Ronald A.

    1988-01-01

    This paper describes the highly autonomous OMV Guidance Navigation and Control system. Emphasis is placed on a key feature of the design, the low thrust guidance algorithm. The two guidance modes, orbit change guidance and rendezvous guidance, are discussed in detail. It is shown how OMV will automatically transfer from its initial orbit to an arbitrary target orbit and reach a specified rendezvous position relative to the target vehicle.

  10. [Neurons that encode sound direction].

    PubMed

    Peña, J L

    In the auditory system, the inner ear breaks down complex signals into their spectral components, and encodes the amplitude and phase of each. In order to infer sound direction in space, a computation on each frequency component of the sound must be performed. Space specific neurons in the owl s inferior colliculus respond only to sounds coming from a particular direction and represent the results of this computation. The interaural time difference (ITD) and interaural level difference (ILD define the auditory space for the owl and are processed in separate neural pathways. The parallel pathways that process these cues merge in the external nucleus of the inferior colliculus where the space specific neurons are selective to combinations of ITD and ILD. How do inputs from the two sources interact to produce combination selectivity to ITD ILD pairs? A multiplication of postsynaptic potentials tuned to ITD and ILD can account for the subthreshold responses of these neurons to ITD ILD pairs. Examples of multiplication by neurons or neural circuits are scarce, but many computational models assume the existence of this basic operation. The owl s auditory system uses such operation to create a 2 dimensional map of auditory space. The map of space in the owl s auditory system shows important similarities with representations of space in the cerebral cortex and other sensory systems. In encoding space or other stimulus features, individual neurons appear to possess analogous functional properties related to the synthesis of high order receptive fields.

  11. Porous organic molecules

    NASA Astrophysics Data System (ADS)

    Holst, James R.; Trewin, Abbie; Cooper, Andrew I.

    2010-11-01

    Most synthetic materials that show molecular-scale porosity consist of one-, two- or three-dimensional networks. Porous metal-organic frameworks in particular have attracted a lot of recent attention. By contrast, discrete molecules tend to pack efficiently in the solid state, leaving as little empty space as possible, which leads to non-porous materials. This Perspective discusses recent developments with discrete organic molecules that are porous in the solid state. Such molecules, which may be either crystalline or amorphous, can be categorized as either intrinsically porous (containing permanent covalent cavities) or extrinsically porous (inefficiently packed). We focus on the possible advantages of organic molecules over inorganic or hybrid systems in terms of molecular solubility, choice of components and functionalities, and structural mobility and responsiveness in non-covalent extended solids. We also highlight the potential for 'undiscovered' porous systems among the large number of cage-like organic molecules that are already known.

  12. Single molecule electronic devices.

    PubMed

    Song, Hyunwook; Reed, Mark A; Lee, Takhee

    2011-04-12

    Single molecule electronic devices in which individual molecules are utilized as active electronic components constitute a promising approach for the ultimate miniaturization and integration of electronic devices in nanotechnology through the bottom-up strategy. Thus, the ability to understand, control, and exploit charge transport at the level of single molecules has become a long-standing desire of scientists and engineers from different disciplines for various potential device applications. Indeed, a study on charge transport through single molecules attached to metallic electrodes is a very challenging task, but rapid advances have been made in recent years. This review article focuses on experimental aspects of electronic devices made with single molecules, with a primary focus on the characterization and manipulation of charge transport in this regime. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila

    PubMed Central

    Cate, Marie-Sophie; Gajendra, Sangeetha; Alsbury, Samantha; Raabe, Thomas; Tear, Guy; Mitchell, Kevin J.

    2016-01-01

    The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance. PMID:26893348

  14. HUMAN FACTORS GUIDANCE FOR CONTROL ROOM EVALUATION

    SciTech Connect

    OHARA,J.; BROWN,W.; STUBLER,W.; HIGGINS,J.; WACHTEL,J.; PERSENSKY,J.J.

    2000-07-30

    The Human-System Interface Design Review Guideline (NUREG-0700, Revision 1) was developed by the US Nuclear Regulatory Commission (NRC) to provide human factors guidance as a basis for the review of advanced human-system interface technologies. The guidance consists of three components: design review procedures, human factors engineering guidelines, and a software application to provide design review support called the ``Design Review Guideline.'' Since it was published in June 1996, Rev. 1 to NUREG-0700 has been used successfully by NRC staff, contractors and nuclear industry organizations, as well as by interested organizations outside the nuclear industry. The NRC has committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool in the face of emerging and rapidly changing technology. This paper addresses the current research to update of NUREG-0700 based on the substantial work that has taken place since the publication of Revision 1.

  15. VTOL shipboard letdown guidance system analysis

    NASA Technical Reports Server (NTRS)

    Phatak, A. V.; Karmali, M. S.

    1983-01-01

    Alternative letdown guidance strategies are examined for landing of a VTOL aircraft onboard a small aviation ship under adverse environmental conditions. Off line computer simulation of shipboard landing task is utilized for assessing the relative merits of the proposed guidance schemes. The touchdown performance of a nominal constant rate of descent (CROD) letdown strategy serves as a benchmark for ranking the performance of the alternative letdown schemes. Analysis of ship motion time histories indicates the existence of an alternating sequence of quiescent and rough motions called lulls and swells. A real time algorithms lull/swell classification based upon ship motion pattern features is developed. The classification algorithm is used to command a go/no go signal to indicate the initiation and termination of an acceptable landing window. Simulation results show that such a go/no go pattern based letdown guidance strategy improves touchdown performance.

  16. The handling of causality in SEA guidance

    SciTech Connect

    Perdicoulis, A. . E-mail: tasso@utad.pt; Hanusch, M. . E-mail: marie.hanusch@ufz.de; Kasperidus, H.D. . E-mail: hans.kasperidus@ufz.de; Weiland, U. . E-mail: ulrike.weiland@ufz.de

    2007-03-15

    Causality, or the relation of cause and effect, is a fundamental notion in science, planning, and management. It is also a fundamental notion in impact assessment, as it relates action proposals with environmental impacts. Building on recent research about causality in impact assessment, this article turns to Strategic Environmental Assessment (SEA) and examines eleven guidance documents to see whether and how they handle causality. The findings of this research, in line with results from similar research in EIA, indicate a weak handling of causality with regards to instruction, obligation, and theoretical support. The recommendations are to investigate the reasons for the observed trend, as there is no evidence in the guidance documents themselves, and to have the fundamental premise of causality in impact assessment safeguarded in future SEA guidance.

  17. Cloning and expression of three zebrafish roundabout homologs suggest roles in axon guidance and cell migration.

    PubMed

    Lee, J S; Ray, R; Chien, C B

    2001-06-01

    We report the cloning and expression patterns of three novel zebrafish Roundabout homologs. The Roundabout (robo) gene encodes a transmembrane receptor that is essential for axon guidance in Drosophila and Robo family members have been implicated in cell migration. Analysis of extracellular domains and conserved cytoplasmic motifs shows that zebrafish Robo1 and Robo2 are orthologs of mammalian Robo1 and Robo2, respectively, while zebrafish Robo3 is likely to be an ortholog of mouse Rig-1. The three zebrafish robos are expressed in distinct but overlapping patterns during embryogenesis. They are highly expressed in the developing nervous system, including the olfactory system, visual system, hindbrain, cranial ganglia, spinal cord, and posterior lateral line primordium. They are also expressed in several nonneuronal tissues, including somites and fin buds. The timing and patterns of expression suggest roles for zebrafish robos in axon guidance and cell migration. Wiley-Liss, Inc.

  18. Plexin A is a neuronal semaphorin receptor that controls axon guidance.

    PubMed

    Winberg, M L; Noordermeer, J N; Tamagnone, L; Comoglio, P M; Spriggs, M K; Tessier-Lavigne, M; Goodman, C S

    1998-12-23

    The Semaphorins comprise a large family of secreted and transmembrane proteins, some of which function as repellents during axon guidance. Semaphorins fall into seven subclasses. Neuropilins are neuronal receptors for class III Semaphorins. In the immune system, VESPR, a member of the Plexin family, is a receptor for a viral-encoded Semaphorin. Here, we identify two Drosophila Plexins, both of which are expressed in the developing nervous system. We present evidence that Plexin A is a neuronal receptor for class I Semaphorins (Sema 1a and Sema 1b) and show that Plexin A controls motor and CNS axon guidance. Plexins, which themselves contain complete Semaphorin domains, may be both the ancestors of classical Semaphorins and binding partners for Semaphorins.

  19. Dynamics of Activated Molecules

    SciTech Connect

    Mullin, Amy S.

    2016-11-16

    Experimental studies have been performed to investigate the collisional energy transfer processes of gas-phase molecules that contain large amounts of internal energy. Such molecules are prototypes for molecules under high temperature conditions relevant in combustion and information about their energy transfer mechanisms is needed for a detailed understanding and modeling of the chemistry. We use high resolution transient IR absorption spectroscopy to measure the full, nascent product distributions for collisions of small bath molecules that relax highly vibrationally excited pyrazine molecules with E=38000 cm-1 of vibrational energy. To perform these studies, we developed new instrumentation based on modern IR light sources to expand our experimental capabilities to investigate new molecules as collision partners. This final report describes our research in four areas: the characterization of a new transient absorption spectrometer and the results of state-resolved collision studies of pyrazine(E) with HCl, methane and ammonia. Through this research we have gained fundamental new insights into the microscopic details of relatively large complex molecules at high energy as they undergo quenching collisions and redistribute their energy.

  20. Guidance accuracy considerations for realtime GPS interferometry

    NASA Technical Reports Server (NTRS)

    Braasch, Michael S.; Van Graas, Frank

    1991-01-01

    During April and May of 1991, the Avionics Engineering Center at Ohio University completed the first set of realtime flight tests of a GPS interferometric attitude and heading determination system. This technique has myriad applications for aircraft and spacecraft guidance and control. However, before these applications can be further developed, a number of guidance accuracy issues must be considered. Among these are: signal derogation due to multipath and shadowing, effects of structural flexures, and system robustness during loss of phase lock. This paper addresses these issues with special emphasis on the information content of the GPS signal, and characterization and mitigation of multipath encountered while in flight.

  1. Virtual Ultrasound Guidance for Inexperienced Operators

    NASA Technical Reports Server (NTRS)

    Caine, Timothy; Martin, David

    2012-01-01

    Medical ultrasound or echocardiographic studies are highly operator-dependent and generally require lengthy training and internship to perfect. To obtain quality echocardiographic images in remote environments, such as on-orbit, remote guidance of studies has been employed. This technique involves minimal training for the user, coupled with remote guidance from an expert. When real-time communication or expert guidance is not available, a more autonomous system of guiding an inexperienced operator through an ultrasound study is needed. One example would be missions beyond low Earth orbit in which the time delay inherent with communication will make remote guidance impractical. The Virtual Ultrasound Guidance system is a combination of hardware and software. The hardware portion includes, but is not limited to, video glasses that allow hands-free, full-screen viewing. The glasses also allow the operator a substantial field of view below the glasses to view and operate the ultrasound system. The software is a comprehensive video program designed to guide an inexperienced operator through a detailed ultrasound or echocardiographic study without extensive training or guidance from the ground. The program contains a detailed description using video and audio to demonstrate equipment controls, ergonomics of scanning, study protocol, and scanning guidance, including recovery from sub-optimal images. The components used in the initial validation of the system include an Apple iPod Classic third-generation as the video source, and Myvue video glasses. Initially, the program prompts the operator to power-up the ultrasound and position the patient. The operator would put on the video glasses and attach them to the video source. After turning on both devices and the ultrasound system, the audio-video guidance would then instruct on patient positioning and scanning techniques. A detailed scanning protocol follows with descriptions and reference video of each view along with

  2. Aeroassist flight experiment guidance, navigation and control

    NASA Technical Reports Server (NTRS)

    Brand, Timothy J.; Engel, Albert G.

    1986-01-01

    The Aeroassist Flight Experiment scheduled for the early 1990's will demonstrate the use of a low L/D lifting brake using aerodynamic drag to return a spacecraft from a high energy to a low earth orbit. The experimental vehicle will be deployed and retrieved by the Shuttle Orbiter. This paper reviews some of the challenges, problems, and solutions encountered to date during guidance system development, with emphasis on technology advances which will benefit an operational Orbit Transfer Vehicle (OTV). Key factors to be discussed include guidance alternatives, aerodynamic modeling, navigation requirements, the impact of atmospheric uncertainties, and flight profile alternatives considered during initial planning.

  3. Overcoming consumer inertia to dietary guidance.

    PubMed

    Webb, Densie; Byrd-Bredbenner, Carol

    2015-07-01

    Despite 35 y of dietary guidance, there has been no substantial shift in consumer compliance. Consumers report that they seek information on nutrition and healthy eating, but most are not paying attention to dietary recommendations. For guidance to be effective, it must be realistic. Even with increasingly detailed nutrition information and evidence that diet affects health outcomes, convenience and taste remain the strongest determinants of food choices. It is up to health educators to clear up confusion and give consumers control with nutrition messages that are realistic, positive, easy to understand, and actionable without an expectation that consumers will surrender foods they love.

  4. Development of mining guidance and control systems

    NASA Technical Reports Server (NTRS)

    1979-01-01

    New fundamental interface sensor concepts were identified and investigated including tabulation of the physical and performance characteristics of two new interface detector concepts: - natural background radiation and magnetic spin resonance. Studies of guidance and control techniques for the longwall miner identified three basic systems for use in automated/remote controlled longwall mining. The following projects were initiated: system study which will more completely define the longwall guidance and control system design concepts; integration of the various control functions (vertical, yaw, and roll); and hardware technical requirements.

  5. Ascent guidance algorithm using lidar wind measurements

    NASA Technical Reports Server (NTRS)

    Cramer, Evin J.; Bradt, Jerre E.; Hardtla, John W.

    1990-01-01

    The formulation of a general nonlinear programming guidance algorithm that incorporates wind measurements in the computation of ascent guidance steering commands is discussed. A nonlinear programming (NLP) algorithm that is designed to solve a very general problem has the potential to address the diversity demanded by future launch systems. Using B-splines for the command functional form allows the NLP algorithm to adjust the shape of the command profile to achieve optimal performance. The algorithm flexibility is demonstrated by simulation of ascent with dynamic loading constraints through a set of random wind profiles with and without wind sensing capability.

  6. Ascent guidance algorithm using lidar wind measurements

    NASA Technical Reports Server (NTRS)

    Cramer, Evin J.; Bradt, Jerre E.; Hardtla, John W.

    1990-01-01

    The formulation of a general nonlinear programming guidance algorithm that incorporates wind measurements in the computation of ascent guidance steering commands is discussed. A nonlinear programming (NLP) algorithm that is designed to solve a very general problem has the potential to address the diversity demanded by future launch systems. Using B-splines for the command functional form allows the NLP algorithm to adjust the shape of the command profile to achieve optimal performance. The algorithm flexibility is demonstrated by simulation of ascent with dynamic loading constraints through a set of random wind profiles with and without wind sensing capability.

  7. Finite-time intercept-angle guidance

    NASA Astrophysics Data System (ADS)

    Lu, Kunfeng; Xia, Yuanqing; Yu, Chunmei; Chen, Rongfang

    2015-02-01

    In this paper, new nonsingular terminal sliding mode control guidance laws (NTSMCGLs) to unknown maneuvering target intercept are proposed and their finite-time convergences are proved. A novel nonsingular terminal sliding mode surface based on a predefined angle is designed to improve intercept performance and avoid singularity problem. The presented guidance law requires no information on maneuvering target that is estimated and compensated by extended state observer (ESO), and it can be used in practical systems where the target can evade freely. Also, undesired chattering is restrained effectively by real-time estimation and compensation of ESO. Simulation results show that the NTSMCGLs can achieve exact interception.

  8. Aerospace plane guidance using geometric control theory

    NASA Technical Reports Server (NTRS)

    Van Buren, Mark A.; Mease, Kenneth D.

    1990-01-01

    A reduced-order method employing decomposition, based on time-scale separation, of the 4-D state space in a 2-D slow manifold and a family of 2-D fast manifolds is shown to provide an excellent approximation to the full-order minimum-fuel ascent trajectory. Near-optimal guidance is obtained by tracking the reduced-order trajectory. The tracking problem is solved as regulation problems on the family of fast manifolds, using the exact linearization methodology from nonlinear geometric control theory. The validity of the overall guidance approach is indicated by simulation.

  9. CNES Approaching Guidance Experiment within FFIORD

    NASA Technical Reports Server (NTRS)

    Berges, Jean-Claude; Cayeux, Philippe; Gaudel-Vacaresse, Angelique; Meyssignac, Benoit

    2007-01-01

    This article outlines the relative orbit control (guidance algorithm and its preliminary performance tests evaluation) that will be tested by the CNES Team on FFIORD (Formation Flying In Orbit Ranging Demonstration) onboard PRISMA mission. After a brief summary of the PRISMA mission context, the paper provides a full description of the rendezvous function involved in the approaching guidance experiment. This FFIORD onboard function is detailed in terms of on-board algorithmic method (basic algorithm and enhanced alternative), sensibility analysis used to construct maneuver plans and preliminary tests results.

  10. Atmospheric guidance law for planar skip trajectories

    NASA Technical Reports Server (NTRS)

    Mease, K. D.; Mccreary, F. A.

    1985-01-01

    The applicability of an approximate, closed-form, analytical solution to the equations of motion, as a basis for a deterministic guidance law for controlling the in-plane motion during a skip trajectory, is investigated. The derivation of the solution by the method of matched asymptotic expansions is discussed. Specific issues that arise in the application of the solution to skip trajectories are addressed. Based on the solution, an explicit formula for the approximate energy loss due to an atmospheric pass is derived. A guidance strategy is proposed that illustrates the use of the approximate solution. A numerical example shows encouraging performance.

  11. Overcoming Consumer Inertia to Dietary Guidance12

    PubMed Central

    Webb, Densie; Byrd-Bredbenner, Carol

    2015-01-01

    Despite 35 y of dietary guidance, there has been no substantial shift in consumer compliance. Consumers report that they seek information on nutrition and healthy eating, but most are not paying attention to dietary recommendations. For guidance to be effective, it must be realistic. Even with increasingly detailed nutrition information and evidence that diet affects health outcomes, convenience and taste remain the strongest determinants of food choices. It is up to health educators to clear up confusion and give consumers control with nutrition messages that are realistic, positive, easy to understand, and actionable without an expectation that consumers will surrender foods they love. PMID:26178023

  12. Molecular mechanisms for protein-encoded inheritance.

    PubMed

    Wiltzius, Jed J W; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R; Apostol, Marcin I; Goldschmidt, Lukasz; Soriaga, Angela B; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

    2009-09-01

    In prion inheritance and transmission, strains are phenotypic variants encoded by protein 'conformations'. However, it is unclear how a protein conformation can be stable enough to endure transmission between cells or organisms. Here we describe new polymorphic crystal structures of segments of prion and other amyloid proteins, which offer two structural mechanisms for the encoding of prion strains. In packing polymorphism, prion strains are encoded by alternative packing arrangements (polymorphs) of beta-sheets formed by the same segment of a protein; in segmental polymorphism, prion strains are encoded by distinct beta-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring conformations capable of encoding strains. These molecular mechanisms for transfer of protein-encoded information into prion strains share features with the familiar mechanism for transfer of nucleic acid-encoded information into microbial strains, including sequence specificity and recognition by noncovalent bonds.

  13. Molecular mechanisms for protein-encoded inheritance

    SciTech Connect

    Wiltzius, Jed J.W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

    2009-12-01

    In prion inheritance and transmission, strains are phenotypic variants encoded by protein 'conformations'. However, it is unclear how a protein conformation can be stable enough to endure transmission between cells or organisms. Here we describe new polymorphic crystal structures of segments of prion and other amyloid proteins, which offer two structural mechanisms for the encoding of prion strains. In packing polymorphism, prion strains are encoded by alternative packing arrangements (polymorphs) of {beta}-sheets formed by the same segment of a protein; in segmental polymorphism, prion strains are encoded by distinct {beta}-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring conformations capable of encoding strains. These molecular mechanisms for transfer of protein-encoded information into prion strains share features with the familiar mechanism for transfer of nucleic acid-encoded information into microbial strains, including sequence specificity and recognition by noncovalent bonds.

  14. Heavy exotic molecules

    NASA Astrophysics Data System (ADS)

    Liu, Yizhuang; Zahed, Ismail

    We briefly review the formation of pion-mediated heavy-light exotic molecules with both charm and bottom, under the general structures of chiral and heavy quark symmetries. The charm isosinglet exotic molecules with JPC = 1++ binds, which we identify as the reported neutral X(3872). The bottom isotriplet exotic with JPC = 1+- binds, and is identified as a mixed state of the reported charged exotics Zb+(10610) and Zb+(10650). The bound bottom isosinglet molecule with JPC = 1++ is a possible neutral Xb(10532) to be observed.

  15. Heavy exotic molecules

    NASA Astrophysics Data System (ADS)

    Liu, Yizhuang; Zahed, Ismail

    We briefly review the formation of pion-mediated heavy-light exotic molecules with both charm and bottom, under the general structures of chiral and heavy quark symmetries. The charm isosinglet exotic molecules with JPC = 1++ binds, which we identify as the reported neutral X(3872). The bottom isotriplet exotic with JPC = 1+1 binds, and is identified as a mixed state of the reported charged exotics Zb+(10610) and Zb-(10650). The bound bottom isosinglet molecule with JPC = 1++ is a possible neutral Xb(10532) to be observed.

  16. Photolithographic Encoding of Metal Complexes.

    PubMed

    Lang, Christiane; Bestgen, Sebastian; Welle, Alexander; Müller, Rouven; Roesky, Peter W; Barner-Kowollik, Christopher

    2015-10-12

    A platform technology for the creation of spatially resolved surfaces encoded with a monolayer consisting of different metal complexes was developed. The concept entails the light-triggered activation of a self- assembled monolayer (SAM) of UV-labile anchors, that is, phenacylsulfides, and the subsequent cycloaddition of selected diene-functionalized metal complexes at defined areas on the surface. The synthesis and characterization of the metal complexes for the UV-light assisted anchoring on the surface and a detailed study of a short-chain oligomer model system in solution confirm the high efficiency of the photoreaction. The hybrid materials obtained by this concept can potentially be utilized for the design of highly valuable catalytic or (opto-)electronic devices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Engineering Genetically Encoded FRET Sensors

    PubMed Central

    Lindenburg, Laurens; Merkx, Maarten

    2014-01-01

    Förster Resonance Energy Transfer (FRET) between two fluorescent proteins can be exploited to create fully genetically encoded and thus subcellularly targetable sensors. FRET sensors report changes in energy transfer between a donor and an acceptor fluorescent protein that occur when an attached sensor domain undergoes a change in conformation in response to ligand binding. The design of sensitive FRET sensors remains challenging as there are few generally applicable design rules and each sensor must be optimized anew. In this review we discuss various strategies that address this shortcoming, including rational design approaches that exploit self-associating fluorescent domains and the directed evolution of FRET sensors using high-throughput screening. PMID:24991940

  18. A Rebeccamycin Analog Provides Plasmid-Encoded Niche Defense.

    PubMed

    Van Arnam, Ethan B; Ruzzini, Antonio C; Sit, Clarissa S; Currie, Cameron R; Clardy, Jon

    2015-11-18

    Bacterial symbionts of fungus-growing ants occupy a highly specialized ecological niche and face the constant existential threat of displacement by another strain of ant-adapted bacteria. As part of a systematic study of the small molecules underlying this fraternal competition, we discovered an analog of the antitumor agent rebeccamycin, a member of the increasingly important indolocarbazole family. While several gene clusters consistent with this molecule's newly reported modification had previously been identified in metagenomic studies, the metabolite itself has been cryptic. The biosynthetic gene cluster for 9-methoxyrebeccamycin is encoded on a plasmid in a manner reminiscent of plasmid-derived peptide antimicrobials that commonly mediate antagonism among closely related Gram-negative bacteria.

  19. Wnt/Calcium Signaling Mediates Axon Growth and Guidance in the Developing Corpus Callosum

    PubMed Central

    Hutchins, B Ian; Li, Li; Kalil, Katherine

    2011-01-01

    It has been shown in vivo that Wnt5a gradients surround the corpus callosum and guide callosal axons after the midline (postcrossing) by Wnt5a-induced repulsion via Ryk receptors. In dissociated cortical cultures we showed that Wnt5a simultaneously promotes axon outgrowth and repulsion by calcium signaling. Here to test the role of Wnt5a/calcium signaling in a complex in vivo environment we used sensorimotor cortical slices containing the developing corpus callosum. Plasmids encoding the cytoplasmic marker DsRed and the genetically encoded calcium indicator GCaMP2 were electroporated into one cortical hemisphere. Postcrossing callosal axons grew 50% faster than pre-crossing axons and higher frequencies of calcium transients in axons and growth cones correlated well with outgrowth. Application of pharmacological inhibitors to the slices showed that signaling pathways involving calcium release through IP3 receptors and calcium entry through TRP channels regulate post-crossing axon outgrowth and guidance. Co-electroporation of Ryk siRNA and DsRed revealed that knock down of the Ryk receptor reduced outgrowth rates of postcrossing but not precrossing axons by 50% and caused axon misrouting. Guidance errors in axons with Ryk knockdown resulted from reduced calcium activity. In the corpus callosum CaMKII inhibition reduced the outgrowth rate of postcrossing (but not precrossing) axons and caused severe guidance errors which resulted from reduced CaMKII-dependent repulsion downstream of Wnt/calcium. We show for the first time that Wnt/Ryk calcium signaling mechanisms regulating axon outgrowth and repulsion in cortical cultures are also essential for the proper growth and guidance of postcrossing callosal axons which involve axon repulsion through CaMKII. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 269–283, 2011. PMID:20936661

  20. Genetically Encoded Sensors for Metabolites

    PubMed Central

    Deuschle, Karen; Fehr, Marcus; Hilpert, Melanie; Lager, Ida; Lalonde, Sylvie; Looger, Loren L.; Okumoto, Sakiko; Persson, Jörgen; Schmidt, Anja; Frommer, Wolf B.

    2009-01-01

    Background Metabolomics, i.e., the multiparallel analysis of metabolite changes occurring in a cell or an organism, has become feasible with the development of highly efficient mass spectroscopic technologies. Functional genomics as a standard tool helped to identify the function of many of the genes that encode important transporters and metabolic enzymes over the past few years. Advanced expression systems and analysis technologies made it possible to study the biochemical properties of the corresponding proteins in great detail. We begin to understand the biological functions of the gene products by systematic analysis of mutants using systematic PTGS/RNAi, knockout and TILLING approaches. However, one crucial set of data especially relevant in the case of multicellular organisms is lacking: the knowledge of the spatial and temporal profiles of metabolite levels at cellular and subcellular levels. Methods We therefore developed genetically encoded nanosensors for several metabolites to provide a basic set of tools for the determination of cytosolic and subcellular metabolite levels in real time by using fluorescence microscopy. Results Prototypes of these sensors were successfully used in vitro and also in vivo, i.e., to measure sugar levels in fungal and animal cells. Conclusions One of the future goals will be to expand the set of sensors to a wider spectrum of substrates by using the natural spectrum of periplasmic binding proteins from bacteria and by computational design of proteins with altered binding pockets in conjunction with mutagenesis. This toolbox can then be applied for four-dimensional imaging of cells and tissues to elucidate the spatial and temporal distribution of metabolites as a discovery tool in functional genomics, as a tool for high-throughput, high-content screening for drugs, to test metabolic models, and to analyze the interplay of cells in a tissue or organ. PMID:15688353

  1. Of Molecules and Models.

    ERIC Educational Resources Information Center

    Brinner, Bonnie

    1992-01-01

    Presents an activity in which models help students visualize both the DNA process and transcription. After constructing DNA, RNA messenger, and RNA transfer molecules; students model cells, protein synthesis, codons, and RNA movement. (MDH)

  2. Single-Molecule Enzymology

    SciTech Connect

    Xie, Xiaoliang; Lu, H PETER.

    1999-06-04

    Viewing a movie of an enzyme molecule made from molecular dynamics (MD) simulation, we see incredible details of molecular motions, be it a change of the conformation or the action of a chemical reaction.

  3. Of Molecules and Models.

    ERIC Educational Resources Information Center

    Brinner, Bonnie

    1992-01-01

    Presents an activity in which models help students visualize both the DNA process and transcription. After constructing DNA, RNA messenger, and RNA transfer molecules; students model cells, protein synthesis, codons, and RNA movement. (MDH)

  4. Apollo experience report guidance and control systems: Primary guidance, navigation, and control system development

    NASA Technical Reports Server (NTRS)

    Holley, M. D.; Swingle, W. L.; Bachman, S. L.; Leblanc, C. J.; Howard, H. T.; Biggs, H. M.

    1976-01-01

    The primary guidance, navigation, and control systems for both the lunar module and the command module are described. Development of the Apollo primary guidance systems is traced from adaptation of the Polaris Mark II system through evolution from Block I to Block II configurations; the discussion includes design concepts used, test and qualification programs performed, and major problems encountered. The major subsystems (inertial, computer, and optical) are covered. Separate sections on the inertial components (gyroscopes and accelerometers) are presented because these components represent a major contribution to the success of the primary guidance, navigation, and control system.

  5. Polyatomic molecule vibrations

    NASA Technical Reports Server (NTRS)

    1976-01-01

    Polyatomic molecule vibrations are analyzed as harmonic vibrations along normal coordinates. The energy eigenvalues are found for linear and nonlinear symmetric triatomic molecules for valence bond models of the potential function with arbitrary coupling coefficients; such models can usually be fitted to observed energy levels with reasonably good accuracy. Approximate normal coordinates for the H2O molecule are discussed. Degenerate vibrational modes such as occur in CO2 are analyzed and expressions for Fermi resonance between close-lying states of the same symmetry are developed. The bending modes of linear triatomic molecules are expressed in terms of Laguerre polynomials in cylindrical coordinates as well as in terms of Hermite polynomials in Cartesian coordinates. The effects of large-amplitude bending such as occur in the C3 molecule are analyzed, along with anharmonic effects, which split the usually degenerate bending mode energy levels. Finally, the vibrational frequencies, degeneracies, and symmetry properties of XY3, X2Y2, and XY4 type molecules are discussed.

  6. Computer-Based Vocational Guidance Systems.

    ERIC Educational Resources Information Center

    Gallagher, James J., Ed.

    Job and educational opportunities are increasing dramatically. School guidance counselors can no longer cope adequately with the available information, nor can they help all students to see the complex range of alternative life styles. Computers are now programed to give students information. They can also provide for students' decision-making…

  7. Computer Applications in Guidance and Counseling.

    ERIC Educational Resources Information Center

    Havens, Robert I.

    The purpose of this discussion is to acquaint pupil personnel workers with some of the applications of computer based information processing systems for pupil services and also to consider some of the legal and ethical concerns relative to data processing in counseling and guidance. Some of the uses discussed are: (1) scheduling; (2) student…

  8. Guidance Program Evaluation: What's Out There?

    ERIC Educational Resources Information Center

    Miller, Juliet V.; Grisdale, George A.

    1975-01-01

    This article reviews a number of guidance evaluation materials and programs presently in use in terms of Stufflebeam's CIPP model. Some materials were simple evaluation instruments; others were as comprehensive as process guides for the planning, development, and application of a complete systems approach evaluation. (Author)

  9. Designing Schoolwide Programs. Non-Regulatory Guidance

    ERIC Educational Resources Information Center

    US Department of Education, 2006

    2006-01-01

    This guidance offers a renewed vision for the use of the schoolwide program, both as a reform strategy and as a means of realizing the high standards for student achievement envisioned by the No Child Left Behind Act of 2001 (NCLB). It is intended to be used as a companion document to the statute and regulations, as well as a technical assistance…

  10. Pointers on Guidance and Counseling Programs.

    ERIC Educational Resources Information Center

    Williams, Calvin E.

    This paper assumes five basic functions for the community college guidance and counseling program: (1) applicant consulting (interpreting test results, introducing career planning, aiding the student in course selection, and explaining curricular requirements); (2) student advisement (scheduling students, explaining Senior College requirements and…

  11. ICS: An Intelligent Vocational Guidance Counseling System.

    ERIC Educational Resources Information Center

    Lorton, Paul, Jr.; And Others

    Computerized career guidance systems hold the promise of providing a breadth and depth of information for which counselors are not suited. At the Institute for Mathematical Studies in the Social Sciences, Stanford University, an individualized counseling system (ICS) is being developed which integrates advanced techniques from comptuer assisted…

  12. Organization and Administration of Guidance Services.

    ERIC Educational Resources Information Center

    Ryan, T. Antoinette; Zeran, Franklin R.

    The organization and administration of guidance services must be person-oriented and future-directed, utilizing a systems approach for developmental planning and evaluation in order to satisfy demands for accountability in education. Focusing specifically upon systems analysis, ST-benefit analysis, computer-assisted counseling and related…

  13. Guidance for performing site inspections under CERCLA

    SciTech Connect

    Not Available

    1992-09-01

    This guidance presents EPA`s site inspection (SI) strategy. The strategy discusses procedural guidelines to investigate potential Superfund (CERCLA) sites for evaluation pursuant to the Hazard Ranking System (HRS), revised in accordance with the Superfund Amendments and Reauthorization Act of 1986. The HRS is the primary means by which EPA evaluates sites for superfund`s National Priorities List (NPL).

  14. Guidance and Control strategies for aerospace vehicles

    NASA Technical Reports Server (NTRS)

    Hibey, J. L.; Naidu, D. S.; Charalambous, C. D.

    1989-01-01

    A neighboring optimal guidance scheme was devised for a nonlinear dynamic system with stochastic inputs and perfect measurements as applicable to fuel optimal control of an aeroassisted orbital transfer vehicle. For the deterministic nonlinear dynamic system describing the atmospheric maneuver, a nominal trajectory was determined. Then, a neighboring, optimal guidance scheme was obtained for open loop and closed loop control configurations. Taking modelling uncertainties into account, a linear, stochastic, neighboring optimal guidance scheme was devised. Finally, the optimal trajectory was approximated as the sum of the deterministic nominal trajectory and the stochastic neighboring optimal solution. Numerical results are presented for a typical vehicle. A fuel-optimal control problem in aeroassisted noncoplanar orbital transfer is also addressed. The equations of motion for the atmospheric maneuver are nonlinear and the optimal (nominal) trajectory and control are obtained. In order to follow the nominal trajectory under actual conditions, a neighboring optimum guidance scheme is designed using linear quadratic regulator theory for onboard real-time implementation. One of the state variables is used as the independent variable in reference to the time. The weighting matrices in the performance index are chosen by a combination of a heuristic method and an optimal modal approach. The necessary feedback control law is obtained in order to minimize the deviations from the nominal conditions.

  15. 21 CFR 312.145 - Guidance documents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE INVESTIGATIONAL NEW DRUG APPLICATION Miscellaneous § 312.145 Guidance documents. (a) FDA has... for a copy of the CDER list should be directed to the Office of Training and Communications, Division...

  16. Self-Awareness. Level One. Career Guidance.

    ERIC Educational Resources Information Center

    Fiendach, Nancy; And Others

    Materials contained in this career guidance unit are designed to develop in five-and six-year-old children an awareness of their senses and the related body organs, likenesses and differences, and self-control. The nineteen activities included in the unit vary in length from twenty to sixty minutes; the entire unit requires approximately ten hours…

  17. 2008 Rapanos Guidance and Related Documents

    EPA Pesticide Factsheets

    This memo provides guidance to EPA regions and Corps districts implementing the Supreme Court's decision in the consolidated cases Rapanos v. US and Carabell v. US which address the jurisdiction over waters of the U.S. under the Clean Water Act.

  18. Advisory List of Instructional Media Guidance.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh.

    A bibliography of materials relevant to the competency-based guidance curriculum of the North Carolina State Department of Public Instruction is presented in this document. Books for students, books for teacher/counselor use, filmstrips (sound), and videocassettes are listed. Grade ranges are provided for each item, although use of the materials…

  19. Child Guidance for Child Caregivers: Instructor's Guide.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This instructor guide is designed for use by postsecondary child development instructors in courses that have both lecture and laboratory sections. The guide is organized into five units covering the following subject matter: foundations and assumptions about child caregiving, development of young children, indirect guidance of children's…

  20. 40 CFR 1506.7 - Further guidance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Further guidance. 1506.7 Section 1506.7 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.7...) Publication of the Council's Memoranda to Heads of Agencies. (c) In conjunction with the Environmental...

  1. 40 CFR 1506.7 - Further guidance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 33 2014-07-01 2014-07-01 false Further guidance. 1506.7 Section 1506.7 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.7...) Publication of the Council's Memoranda to Heads of Agencies. (c) In conjunction with the Environmental...

  2. 40 CFR 1506.7 - Further guidance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 33 2011-07-01 2011-07-01 false Further guidance. 1506.7 Section 1506.7 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.7...) Publication of the Council's Memoranda to Heads of Agencies. (c) In conjunction with the Environmental...

  3. 40 CFR 1506.7 - Further guidance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Further guidance. 1506.7 Section 1506.7 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.7...) Publication of the Council's Memoranda to Heads of Agencies. (c) In conjunction with the Environmental...

  4. 40 CFR 1506.7 - Further guidance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Further guidance. 1506.7 Section 1506.7 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY OTHER REQUIREMENTS OF NEPA § 1506.7...) Publication of the Council's Memoranda to Heads of Agencies. (c) In conjunction with the Environmental...

  5. "Telling Tales": Using Narrative in Career Guidance

    ERIC Educational Resources Information Center

    Reid, Hazel; West, Linden

    2011-01-01

    In this article the authors argue for the importance of narrative-based approaches in career guidance work in an uncertain, unpredictable world. This requires a paradigmatic shift in thinking that can be too difficult, at present, for some practitioners. The article reports on the first phase of a collaborative project with a group of…

  6. Career Guidance in Scotland: Retrospect and Prospect

    ERIC Educational Resources Information Center

    Howieson, Cathy; Semple, Sheila

    2006-01-01

    Devolution of powers to Scotland has accentuated pre-existing divergence from the rest of the UK with respect to education, training and career guidance provision. Scotland now has an all-age national careers service--Careers Scotland. It is suggested that it is unlikely that a national, publicly-funded careers agency would have been established…

  7. From the Church to the Guidance Department.

    ERIC Educational Resources Information Center

    Fraser, Bruce W.

    1979-01-01

    The religious instituations seem to be experiencing an exodus of young people from active participation, but those who leave are not rejecting life, they are simply looking for answers from different sources. Guidance counselors have opportunities to assist the young people who come to them in several ways. (Author)

  8. The Guidance Counselor and the Reading Curriculum.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    There are many ways guidance counselors can help teachers achieve more optimal reading instruction. Counselors first may have to ascertain the kinds of problems faced by a student in learning to read. Assessing a student's ability to use picture clues to decipher words may be necessary with primary grade students. Knowledge about phonics, using…

  9. The Spanish Family Guidance Center of Miami.

    ERIC Educational Resources Information Center

    Hispanic Research Center: Research Bulletin, 1979

    1979-01-01

    Two major programs of the Spanish Family Guidance Center, a facility that addresses the mental health needs of Hispanics in the Greater Miami (Florida) area, are described in this report. One program, the Spanish Drug Rehabilitation Project (completed in 1977), compared a series of activities including: (1) research on the characteristics of…

  10. Assessing Enterprise Capability: Guidance for Schools

    ERIC Educational Resources Information Center

    National Foundation for Educational Research, 2007

    2007-01-01

    This document offers guidance to schools on how assessment can support enterprise education. It presents the interim findings from research carried out by the National Foundation for Educational Research (NFER) for the Department for Education and Skills (DfES) in secondary schools in England. Enterprise capability is the key outcome of enterprise…

  11. Museum Personnel's Opinions on Mobile Guidance Systems

    ERIC Educational Resources Information Center

    Yoshimura, Hirokazu; Sekiguchi, Hiromi; Yabumoto, Yoshitaka

    2007-01-01

    While opinions from the general public are certainly important, opinions from the museum staff are also necessary to improve user service systems. this article introduces two groups of museum staff who have evaluated the usability of mobile guidance systems in Japanese museums. One group is the research team who used the PDA system in the National…

  12. Hypermedia Authoring with Writing Process Guidance

    ERIC Educational Resources Information Center

    Chang, Kuo-En; Sung, Yao-Ting; Zheng, Jie-Wen

    2007-01-01

    A writing process of five stages, setting the topic and goals, planning the outline, organising the structure, building the content, and reviewing, is proposed to guide hypermedia authoring. To explore the effects of the system designed with writing-process guidance, this study enrolled 108 seventh graders at a junior high school as experimental…

  13. Laser radar for spacecraft guidance applications

    NASA Technical Reports Server (NTRS)

    Liebe, C. C.; Abramovici, A.; Bartman, R. K.; Bunker, R. L.; Chapsky, J.; Chu, C. C.; Clouse, D.; Dillon, J. W.; Hausmann, B.; Hemmati, H.; hide

    2003-01-01

    A flight qualified laser radar called LAMP (LAser MaPper) is under development at JPL. LAMP is a guidance and control sensor that can form 3 dimensional images of its field of regard. This paper describes the detailed design of the LAMP sensor.

  14. Stressor Identification Guidance Document | Science Inventory ...

    EPA Pesticide Factsheets

    EPA has made availabile the Stressor Identification Guidance Document (EPA 822-B-00-025) published under the authority of Section 304(a)(2) of the Clean Water Act (CWA). This technical guidance document is designed to assist water quality managers in identifying unknown causes of biological impairments in any type of water body. Section 101(a) of the Clean Water Act states that it is the objective of the Act to restore and maintain the chemical, physical and biological integrity of the Nation's waters. To achieve this objective, numerous States and Tribes are using biological assessments and biocriteria to help protect the Nation's waters. Using these tools, State and Tribal water quality experts are finding water bodies where the fish, invertebrate, algae or plant communities (or other aquatic life) have been detrimentally impacted by different singular or multiple causes. In many cases, the cause, or causes, of these biological impairments have not yet been identified. The Stressor Identification Guidance Document provides a logical, scientific process by which State, Tribal, and other water quality experts can evaluate available information to identify the stressor(s) causing the biological impairments. The process has three main steps: (1) List candidate causes of impairment, (2) analyze the evidence, and (3) characterize the causes. When evidence is adequate, using this guidance, investigators should be able to successfully identify the likely cause, or ca

  15. Money, Money, Money: A Developmental Guidance Approach.

    ERIC Educational Resources Information Center

    Allan, John; Klassen, Garry

    1992-01-01

    Describes developmental guidance unit on topic of money for grades six and seven. Describes class discussion format used to conduct two sessions helping students explore, understand, and develop coping skills regarding money issues. Notes that students worried about money, understood why people overspend, and developed ways of earning and saving…

  16. Online guidance updates using neural networks

    NASA Astrophysics Data System (ADS)

    Filici, Cristian; Sánchez Peña, Ricardo S.

    2010-02-01

    The aim of this article is to present a method for the online guidance update for a launcher ascent trajectory that is based on the utilization of a neural network approximator. Generation of training patterns and selection of the input and output spaces of the neural network are presented, and implementation issues are discussed. The method is illustrated by a 2-dimensional launcher simulation.

  17. 33 CFR 385.5 - Guidance memoranda.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Guidance memoranda. 385.5 Section 385.5 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions...

  18. 33 CFR 385.5 - Guidance memoranda.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Guidance memoranda. 385.5 Section 385.5 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions...

  19. 33 CFR 385.5 - Guidance memoranda.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Guidance memoranda. 385.5 Section 385.5 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions...

  20. 33 CFR 385.5 - Guidance memoranda.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Guidance memoranda. 385.5 Section 385.5 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions...