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.

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

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. Copyright © 2017 by the Genetics Society of America.

Expression of the repulsive guidance molecule RGM and it receptor Neogenin after spinal cord injury in sea lamprey

PubMed Central

Shifman, Michael I.; Yumul, Rae Eden; Laramore, Cindy; Selzer, Michael E.

2009-01-01

The sea lamprey recovers normal-appearing locomotion after spinal cord transection and its spinal axons regenerate selectively in their correct paths. However, among identified reticulospinal neurons some are consistently bad regenerators and only about 50% of severed reticulospinal axons regenerate through the site of injury. We previously suggested (Shifman and Selzer, 2000) that selective chemorepulsion might explain why some neurons are bad regenerators and others not. To explore the role of additional chemorepulsive axonal guidance molecules during regeneration, we examined the expression of the repulsive guidance molecule (RGM) and its receptor neogenin by in situ hybridization and quantitative PCR. RGM mRNA was expressed in the spinal cord, primarily in neurons of the lateral gray matter and in dorsal cells. Following spinal cord transection, RGM message was downregulated in neurons close (within 10 mm) to the transection at 2 and 4 weeks, although it was upregulated in reactive microglia at 2 weeks post-transection. Neogenin mRNA expression was unchanged in the brainstem after spinal cord transection, and among the identified reticulospinal neurons, was detected only in “bad regenerators, Neurons that are known to regenerate well never expressed neogenin. The downregulation of RGM expression in neurons near the transection may increase the probability that regenerating axons will regenerate through the site of injury and entered caudal spinal cord. PMID:19268666

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

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.

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 eukaryoticmore » 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.« less

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.

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.

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.

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.

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

PubMed

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.

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.

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

Cell-Cell Interactions during pollen tube guidance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daphne Preuss

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 variationmore » in guidance signals, comparing the in vitro interactions between pollen and pistils from A. thaliana and its close relatives.« less

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

Multiplexed Sequence Encoding: A Framework for DNA Communication.

PubMed

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.

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.

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.

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

Solving traveling salesman problems with DNA molecules encoding numerical values.

PubMed

Lee, Ji Youn; Shin, Soo-Yong; Park, Tai Hyun; Zhang, Byoung-Tak

2004-12-01

We introduce a DNA encoding method to represent numerical values and a biased molecular algorithm based on the thermodynamic properties of DNA. DNA strands are designed to encode real values by variation of their melting temperatures. The thermodynamic properties of DNA are used for effective local search of optimal solutions using biochemical techniques, such as denaturation temperature gradient polymerase chain reaction and temperature gradient gel electrophoresis. The proposed method was successfully applied to the traveling salesman problem, an instance of optimization problems on weighted graphs. This work extends the capability of DNA computing to solving numerical optimization problems, which is contrasted with other DNA computing methods focusing on logical problem solving.

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

Visual search guidance is best after a short delay

PubMed Central

Schmidt, Joseph; Zelinsky, Gregory J.

2011-01-01

Search displays are typically presented immediately after a target cue, but in the real-world, delays often exist between target designation and search. Experiments 1 and 2 asked how search guidance changes with delay. Targets were cued using a picture or text label, each for 3000ms, followed by a delay up to 9000ms before the search display. Search stimuli were realistic objects, and guidance was quantified using multiple eye movement measures. Text-based cues showed a non-significant trend towards greater guidance following any delay relative to a no-delay condition. However, guidance from a pictorial cue increased sharply 300–600 msec after preview offset. Experiment 3 replicated this guidance enhancement using shorter preview durations while equating the time from cue onset to search onset, demonstrating that the guidance benefit is linked to preview offset rather than a more complete encoding of the target. Experiment 4 showed that enhanced guidance persists even with a mask flashed at preview offset, suggesting an explanation other than visual priming. We interpret our findings as evidence for the rapid consolidation of target information into a guiding representation, which attains its maximum effectiveness shortly after preview offset. PMID:21295053

Cheating, facilitation and cooperation regulate the effectiveness of phage-encoded exotoxins as antipredator molecules.

PubMed

Aijaz, Iqbal; Koudelka, Gerald B

2018-04-19

Temperate phage encoded Shiga toxin (Stx) kills the bacterivorous predator, Tetrahymena thermophila, providing Stx + Escherichia coli with a survival advantage over Stx - cells. Although bacterial death accompanies Stx release, since bacteria grow clonally the fitness benefits of predator killing accrue to the kin of the sacrificed organism, meaning Stx-mediated protist killing is a form of self-destructive cooperation. We show here that the fitness benefits of Stx production are not restricted to the kin of the phage-encoding bacteria. Instead, nearby "free loading" bacteria, irrespective of their genotype, also reap the benefit of Stx-mediated predator killing. This finding indicates that the phage-borne Stx exotoxin behaves as a public good. Stx is encoded by a mobile phage. We find that Stx-encoding phage can use susceptible bacteria in the population as surrogates to enhance toxin and phage production. Moreover, our findings also demonstrate that engulfment and concentration of Stx-encoding and susceptible Stx - bacteria in the Tetrahymena phagosome enhances the transfer of Stx-encoding temperate phage from the host to the susceptible bacteria. This transfer increases the population of cooperating bacteria within the community. Since these bacteria now encode Stx, the predation-stimulated increase in phage transfer increases the population of toxin encoding bacteria in the environment. © 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

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. © 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

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.

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.

Visual search guidance is best after a short delay.

PubMed

Schmidt, Joseph; Zelinsky, Gregory J

2011-03-25

Search displays are typically presented immediately after a target cue, but in the real-world, delays often exist between target designation and search. Experiments 1 and 2 asked how search guidance changes with delay. Targets were cued using a picture or text label, each for 3000ms, followed by a delay up to 9000ms before the search display. Search stimuli were realistic objects, and guidance was quantified using multiple eye movement measures. Text-based cues showed a non-significant trend towards greater guidance following any delay relative to a no-delay condition. However, guidance from a pictorial cue increased sharply 300-600ms after preview offset. Experiment 3 replicated this guidance enhancement using shorter preview durations while equating the time from cue onset to search onset, demonstrating that the guidance benefit is linked to preview offset rather than a more complete encoding of the target. Experiment 4 showed that enhanced guidance persists even with a mask flashed at preview offset, suggesting an explanation other than visual priming. We interpret our findings as evidence for the rapid consolidation of target information into a guiding representation, which attains its maximum effectiveness shortly after preview offset. Copyright © 2011 Elsevier Ltd. All rights reserved.

Neuronal clues to vascular guidance.

PubMed

Suchting, Steven; Bicknell, Roy; Eichmann, Anne

2006-03-10

The development of the vertebrate vascular system into a highly ordered and stereotyped network requires precise control over the branching and growth of new vessels. Recent research has highlighted the important role of genetic programs in regulating vascular patterning and in particular has established a crucial role for families of molecules previously described in controlling neuronal guidance. Like neurons, new vessels are guided along the correct path by integrating attractive and repulsive cues from the external environment. This is achieved by specialised endothelial cells at the leading tip of vessel sprouts which express receptor proteins that couple extracellular guidance signals with the cytoskeletal changes necessary to alter cell direction. Here, we review the genetic and in vitro evidence implicating four families of ligand-receptor signalling systems common to both neuronal and vessel guidance: the Ephrins and Eph receptors; Semaphorins, Neuropilins and Plexin receptors; Netrin and Unc5 receptors; and Slits and Robo receptors.

The Yersinia pestis gcvB gene encodes two small regulatory RNA molecules

PubMed Central

McArthur, Sarah D; Pulvermacher, Sarah C; Stauffer, George V

2006-01-01

Background In recent years it has become clear that small non-coding RNAs function as regulatory elements in bacterial virulence and bacterial stress responses. We tested for the presence of the small non-coding GcvB RNAs in Y. pestis as possible regulators of gene expression in this organism. Results In this study, we report that the Yersinia pestis KIM6 gcvB gene encodes two small RNAs. Transcription of gcvB is activated by the GcvA protein and repressed by the GcvR protein. The gcvB-encoded RNAs are required for repression of the Y. pestis dppA gene, encoding the periplasmic-binding protein component of the dipeptide transport system, showing that the GcvB RNAs have regulatory activity. A deletion of the gcvB gene from the Y. pestis KIM6 chromosome results in a decrease in the generation time of the organism as well as a change in colony morphology. Conclusion The results of this study indicate that the Y. pestis gcvB gene encodes two small non-coding regulatory RNAs that repress dppA expression. A gcvB deletion is pleiotropic, suggesting that the sRNAs are likely involved in controlling genes in addition to dppA. PMID:16768793

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.

Influence of incident angle on the decoding in laser polarization encoding guidance

NASA Astrophysics Data System (ADS)

Zhou, Muchun; Chen, Yanru; Zhao, Qi; Xin, Yu; Wen, Hongyuan

2009-07-01

Dynamic detection of polarization states is very important for laser polarization coding guidance systems. In this paper, a set of dynamic polarization decoding and detection system used in laser polarization coding guidance was designed. Detection process of the normal incident polarized light is analyzed with Jones Matrix; the system can effectively detect changes in polarization. Influence of non-normal incident light on performance of polarization decoding and detection system is studied; analysis showed that changes in incident angle will have a negative impact on measure results, the non-normal incident influence is mainly caused by second-order birefringence and polarization sensitivity effect generated in the phase delay and beam splitter prism. Combined with Fresnel formula, decoding errors of linearly polarized light, elliptically polarized light and circularly polarized light with different incident angles into the detector are calculated respectively, the results show that the decoding errors increase with increase of incident angle. Decoding errors have relations with geometry parameters, material refractive index of wave plate, polarization beam splitting prism. Decoding error can be reduced by using thin low-order wave-plate. Simulation of detection of polarized light with different incident angle confirmed the corresponding conclusions.

Time to Guide: Evidence for Delayed Attentional Guidance in Contextual Cueing

PubMed Central

Kunar, Melina A.; Flusberg, Stephen J.; Wolfe, Jeremy M.

2008-01-01

Contextual cueing experiments show that, when displays are repeated, reaction times (RTs) to find a target decrease over time even when the observers are not aware of the repetition. Recent evidence suggests that this benefit in standard contextual cueing tasks is not likely to be due to an improvement in attentional guidance (Kunar, Flusberg, Horowitz & Wolfe, 2007). Nevertheless, we ask whether guidance can help participants find the target in a repeated display, if they are given sufficient time to encode the display. In Experiment 1 we increased the display complexity so that it took participants longer to find the target. Here we found a larger effect of guidance than in a condition with shorter RTs. Experiment 2 gave participants prior exposure to the display context. The data again showed that with more time participants could implement guidance to help find the target, provided that there was something in the search stimuli locations to guide attention to. The data suggest that although the benefit in a standard contextual cueing task is unlikely to be a result of guidance, guidance can play a role if it is given time to develop. PMID:18846248

Time to Guide: Evidence for Delayed Attentional Guidance in Contextual Cueing.

PubMed

Kunar, Melina A; Flusberg, Stephen J; Wolfe, Jeremy M

2008-01-01

Contextual cueing experiments show that, when displays are repeated, reaction times (RTs) to find a target decrease over time even when the observers are not aware of the repetition. Recent evidence suggests that this benefit in standard contextual cueing tasks is not likely to be due to an improvement in attentional guidance (Kunar, Flusberg, Horowitz & Wolfe, 2007). Nevertheless, we ask whether guidance can help participants find the target in a repeated display, if they are given sufficient time to encode the display. In Experiment 1 we increased the display complexity so that it took participants longer to find the target. Here we found a larger effect of guidance than in a condition with shorter RTs. Experiment 2 gave participants prior exposure to the display context. The data again showed that with more time participants could implement guidance to help find the target, provided that there was something in the search stimuli locations to guide attention to. The data suggest that although the benefit in a standard contextual cueing task is unlikely to be a result of guidance, guidance can play a role if it is given time to develop.

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. Copyright © 2014 Elsevier Inc. All rights reserved.

Design and Synthesis of Biaryl DNA-Encoded Libraries.

PubMed

Ding, Yun; Franklin, G Joseph; DeLorey, Jennifer L; Centrella, Paolo A; Mataruse, Sibongile; Clark, Matthew A; Skinner, Steven R; Belyanskaya, Svetlana

2016-10-10

DNA-encoded library technology (ELT) is a powerful tool for the discovery of new small-molecule ligands to various protein targets. Here we report the design and synthesis of biaryl DNA-encoded libraries based on the scaffold of 5-formyl 3-iodobenzoic acid. Three reactions on DNA template, acylation, Suzuki-Miyaura coupling and reductive amination, were applied in the library synthesis. The three cycle library of 3.5 million diversity has delivered potent hits for phosphoinositide 3-kinase α (PI3Kα).

Storing data encoded DNA in living organisms

DOEpatents

Wong,; Pak C. , Wong; Kwong K. , Foote; Harlan, P [Richland, WA

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.

In vitro efficacy of a gene-activated nerve guidance conduit incorporating non-viral PEI-pDNA nanoparticles carrying genes encoding for NGF, GDNF and c-Jun.

PubMed

Lackington, William A; Raftery, Rosanne M; O'Brien, Fergal J

2018-06-07

Despite the success of tissue engineered nerve guidance conduits (NGCs) for the treatment of small peripheral nerve injuries, autografts remain the clinical gold standard for larger injuries. The delivery of neurotrophic factors from conduits might enhance repair for more effective treatment of larger injuries but the efficacy of such systems is dependent on a safe, effective platform for controlled and localised therapeutic delivery. Gene therapy might offer an innovative approach to control the timing, release and level of neurotrophic factor production by directing cells to transiently sustain therapeutic protein production in situ. In this study, a gene-activated NGC was developed by incorporating non-viral polyethyleneimine-plasmid DNA (PEI-pDNA) nanoparticles (N/P 7 ratio, 2μg dose) with the pDNA encoding for nerve growth factor (NGF), glial derived neurotrophic factor (GDNF) or the transcription factor c-Jun. The physicochemical properties of PEI-pDNA nanoparticles, morphology, size and charge, were shown to be suitable for gene delivery and demonstrated high Schwann cell transfection efficiency (60±13%) in vitro. While all three genes showed therapeutic potential in terms of enhancing neurotrophic cytokine production while promoting neurite outgrowth, delivery of the gene encoding for c-Jun showed the greatest capacity to enhance regenerative cellular processes in vitro. Ultimately, this gene-activated NGC construct was shown to be capable of transfecting both Schwann cells (S42 cells) and neuronal cells (PC12 and dorsal root ganglia) in vitro, demonstrating potential for future therapeutic applications in vivo. The basic requirements of biomaterial-based nerve guidance conduits have now been well established and include being able to bridge a nerve injury to support macroscopic guidance between nerve stumps, while being strong enough to withstand longitudinal tension and circumferential compression, in addition to being mechanically sound to facilitate

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

Method for accurate determination of dissociation constants of optical ratiometric systems: chemical probes, genetically encoded sensors, and interacting molecules.

PubMed

Pomorski, Adam; Kochańczyk, Tomasz; Miłoch, Anna; Krężel, Artur

2013-12-03

Ratiometric chemical probes and genetically encoded sensors are of high interest for both analytical chemists and molecular biologists. Their high sensitivity toward the target ligand and ability to obtain quantitative results without a known sensor concentration have made them a very useful tool in both in vitro and in vivo assays. Although ratiometric sensors are widely used in many applications, their successful and accurate usage depends on how they are characterized in terms of sensing target molecules. The most important feature of probes and sensors besides their optical parameters is an affinity constant toward analyzed molecules. The literature shows that different analytical approaches are used to determine the stability constants, with the ratio approach being most popular. However, oversimplification and lack of attention to detail results in inaccurate determination of stability constants, which in turn affects the results obtained using these sensors. Here, we present a new method where ratio signal is calibrated for borderline values of intensities of both wavelengths, instead of borderline ratio values that generate errors in many studies. At the same time, the equation takes into account the cooperativity factor or fluorescence artifacts and therefore can be used to characterize systems with various stoichiometries and experimental conditions. Accurate determination of stability constants is demonstrated utilizing four known optical ratiometric probes and sensors, together with a discussion regarding other, currently used methods.

Chemical Biology Probes from Advanced DNA-encoded Libraries.

PubMed

Salamon, Hazem; Klika Škopić, Mateja; Jung, Kathrin; Bugain, Olivia; Brunschweiger, Andreas

2016-02-19

The identification of bioactive compounds is a crucial step toward development of probes for chemical biology studies. Screening of DNA-encoded small molecule libraries (DELs) has emerged as a validated technology to interrogate vast chemical space. DELs consist of chimeric molecules composed of a low-molecular weight compound that is conjugated to a DNA identifier tag. They are screened as pooled libraries using selection to identify "hits." Screening of DELs has identified numerous bioactive compounds. Some of these molecules were instrumental in gaining a deeper understanding of biological systems. One of the main challenges in the field is the development of synthesis methodology for DELs.

Genetically Encoded Biosensors in Plants: Pathways to Discovery.

PubMed

Walia, Ankit; Waadt, Rainer; Jones, Alexander M

2018-04-29

Genetically encoded biosensors that directly interact with a molecule of interest were first introduced more than 20 years ago with fusion proteins that served as fluorescent indicators for calcium ions. Since then, the technology has matured into a diverse array of biosensors that have been deployed to improve our spatiotemporal understanding of molecules whose dynamics have profound influence on plant physiology and development. In this review, we address several types of biosensors with a focus on genetically encoded calcium indicators, which are now the most diverse and advanced group of biosensors. We then consider the discoveries in plant biology made by using biosensors for calcium, pH, reactive oxygen species, redox conditions, primary metabolites, phytohormones, and nutrients. These discoveries were dependent on the engineering, characterization, and optimization required to develop a successful biosensor; they were also dependent on the methodological developments required to express, detect, and analyze the readout of such biosensors.

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

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.

Development and Synthesis of DNA-Encoded Benzimidazole Library.

PubMed

Ding, Yun; Chai, Jing; Centrella, Paolo A; Gondo, Chenaimwoyo; DeLorey, Jennifer L; Clark, Matthew A

2018-04-25

Encoded library technology (ELT) is an effective approach to the discovery of novel small-molecule ligands for biological targets. A key factor for the success of the technology is the chemical diversity of the libraries. Here we report the development of DNA-conjugated benzimidazoles. Using 4-fluoro-3-nitrobenzoic acid as a key synthon, we synthesized a 320 million-member DNA-encoded benzimidazole library using Fmoc-protected amino acids, amines and aldehydes as diversity elements. Affinity selection of the library led to the discovery of a novel, potent and specific antagonist of the NK3 receptor.

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

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.

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.

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. Copyright © 2015. Published by Elsevier Ltd.

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.

Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas

PubMed Central

Navari, Mohsen; Etebari, Maryam; Ibrahimi, Mostafa; Leoncini, Lorenzo

2018-01-01

Epstein–Barr virus (EBV) is a human γ-herpesvirus implicated in several human malignancies, including a wide range of lymphomas. Several molecules encoded by EBV in its latent state are believed to be related to EBV-induced lymphomagenesis, among which microRNAs—small RNAs with a posttranscriptional regulating role—are of great importance. The genome of EBV encodes 44 mature microRNAs belonging to two different classes, including BamHI-A rightward transcript (BART) and Bam HI fragment H rightward open reading frame 1 (BHRF1), with different expression levels in different EBV latency types. These microRNAs might contribute to the pathogenetic effects exerted by EBV through targeting self mRNAs and host mRNAs and interfering with several important cellular mechanisms such as immunosurveillance, cell proliferation, and apoptosis. In addition, EBV microRNAs can regulate the surrounding microenvironment of the infected cells through exosomal transportation. Moreover, these small molecules could be potentially used as molecular markers. In this review, we try to present an updated and extensive view of the role of EBV-encoded miRNAs in human lymphomas. PMID:29649101

Novel selection methods for DNA-encoded chemical libraries

PubMed Central

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

2015-01-01

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. PMID:25723146

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.

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.

Guidance of vascular development: lessons from the nervous system.

PubMed

Larrivée, Bruno; Freitas, Catarina; Suchting, Steven; Brunet, Isabelle; Eichmann, Anne

2009-02-27

The vascular system of vertebrates consists of an organized, branched network of arteries, veins, and capillaries that penetrates all the tissues of the body. One of the most striking features of the vascular system is that its branching pattern is highly stereotyped, with major and secondary branches forming at specific sites and developing highly conserved organ-specific vascular patterns. The factors controlling vascular patterning are not yet completely understood. Recent studies have highlighted the anatomic and structural similarities between blood vessels and nerves. The 2 networks are often aligned, with nerve fibers and blood vessels following parallel routes. Furthermore, both systems require precise control over their guidance and growth. Several molecules with attractive and repulsive properties have been found to modulate the proper guidance of both nerves and blood vessels. These include the Semaphorins, the Slits, and the Netrins and their receptors. In this review, we describe the molecular mechanisms by which blood vessels and axons achieve proper path finding and the molecular cues that are involved in their guidance.

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.

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

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optoporation of impermeable molecules and genes for visualization and activation of cells

NASA Astrophysics Data System (ADS)

Dhakal, Kamal; Batbyal, Subrata; Kim, Young-Tae; Mohanty, Samarendra

2015-03-01

Visualization, activation, and detection of the cell(s) and their electrical activity require delivery of exogenous impermeable molecules and targeted expression of genes encoding labeling proteins, ion-channels and voltage indicators. While genes can be delivered by viral vector to cells, delivery of other impermeable molecules into the cytoplasm of targeted cells requires microinjection by mechanical needle or microelectrodes, which pose significant challenge to the viability of the cells. Further, it will be useful to localize the expression of the targeted molecules not only in specific cell types, but to specific cells in restricted spatial regions. Here, we report use of focused near-infrared (NIR) femtosecond laser beam to transiently perforate targeted cell membrane to insert genes encoding blue light activatable channelrhodopsin-2 (ChR2) and red-shifted opsin (ReachR). Optoporation of nanomolar concentrations of rhodamine phalloidin (an impermeable dye molecule for staining filamentous actin) into targeted living mammalian cells (both HEK and primary cortical neurons) is also achieved allowing imaging of dynamics and intact morphology of cellular structures without requiring fixation.

Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.

PubMed

Kollmann, Christopher S; Bai, Xiaopeng; Tsai, Ching-Hsuan; Yang, Hongfang; Lind, Kenneth E; Skinner, Steven R; Zhu, Zhengrong; Israel, David I; Cuozzo, John W; Morgan, Barry A; Yuki, Koichi; Xie, Can; Springer, Timothy A; Shimaoka, Motomu; Evindar, Ghotas

2014-04-01

The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein. Copyright © 2014 Elsevier Ltd. All rights reserved.

Microtechnologies for studying the role of mechanics in axon growth and guidance

PubMed Central

Kilinc, Devrim; Blasiak, Agata; Lee, Gil U.

2015-01-01

The guidance of axons to their proper targets is not only a crucial event in neurodevelopment, but also a potential therapeutic target for neural repair. Axon guidance is mediated by various chemo- and haptotactic cues, as well as the mechanical interactions between the cytoskeleton and the extracellular matrix (ECM). Axonal growth cones, dynamic ends of growing axons, convert external stimuli to biochemical signals, which, in turn, are translated into behavior, e.g., turning or retraction, via cytoskeleton–matrix linkages. Despite the inherent mechanical nature of the problem, the role of mechanics in axon guidance is poorly understood. Recent years has witnessed the application of a range of microtechnologies in neurobiology, from microfluidic circuits to single molecule force spectroscopy. In this mini-review, we describe microtechnologies geared towards dissecting the mechanical aspects of axon guidance, divided into three categories: controlling the growth cone microenvironment, stimulating growth cones with externally applied forces, and measuring forces exerted by the growth cones. A particular emphasis is given to those studies that combine multiple techniques, as dictated by the complexity of the problem. PMID:26283918

Microtechnologies for studying the role of mechanics in axon growth and guidance.

PubMed

Kilinc, Devrim; Blasiak, Agata; Lee, Gil U

2015-01-01

The guidance of axons to their proper targets is not only a crucial event in neurodevelopment, but also a potential therapeutic target for neural repair. Axon guidance is mediated by various chemo- and haptotactic cues, as well as the mechanical interactions between the cytoskeleton and the extracellular matrix (ECM). Axonal growth cones, dynamic ends of growing axons, convert external stimuli to biochemical signals, which, in turn, are translated into behavior, e.g., turning or retraction, via cytoskeleton-matrix linkages. Despite the inherent mechanical nature of the problem, the role of mechanics in axon guidance is poorly understood. Recent years has witnessed the application of a range of microtechnologies in neurobiology, from microfluidic circuits to single molecule force spectroscopy. In this mini-review, we describe microtechnologies geared towards dissecting the mechanical aspects of axon guidance, divided into three categories: controlling the growth cone microenvironment, stimulating growth cones with externally applied forces, and measuring forces exerted by the growth cones. A particular emphasis is given to those studies that combine multiple techniques, as dictated by the complexity of the problem.

Dragon (Repulsive Guidance Molecule RGMb) Inhibits E-cadherin Expression and Induces Apoptosis in Renal Tubular Epithelial Cells*

PubMed Central

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

2013-01-01

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. PMID:24052264

Second-generation DNA-templated macrocycle libraries for the discovery of bioactive small molecules.

PubMed

Usanov, Dmitry L; Chan, Alix I; Maianti, Juan Pablo; Liu, David R

2018-07-01

DNA-encoded libraries have emerged as a widely used resource for the discovery of bioactive small molecules, and offer substantial advantages compared with conventional small-molecule libraries. Here, we have developed and streamlined multiple fundamental aspects of DNA-encoded and DNA-templated library synthesis methodology, including computational identification and experimental validation of a 20 × 20 × 20 × 80 set of orthogonal codons, chemical and computational tools for enhancing the structural diversity and drug-likeness of library members, a highly efficient polymerase-mediated template library assembly strategy, and library isolation and purification methods. We have integrated these improved methods to produce a second-generation DNA-templated library of 256,000 small-molecule macrocycles with improved drug-like physical properties. In vitro selection of this library for insulin-degrading enzyme affinity resulted in novel insulin-degrading enzyme inhibitors, including one of unusual potency and novel macrocycle stereochemistry (IC 50  = 40 nM). Collectively, these developments enable DNA-templated small-molecule libraries to serve as more powerful, accessible, streamlined and cost-effective tools for bioactive small-molecule discovery.

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.

Nucleic Acid Encoding A Lectin-Derived Progenitor Cell Preservation Factor

DOEpatents

Colucci, M. Gabriella; Chrispeels, Maarten J.; Moore, Jeffrey G.

2001-10-30

The invention relates to an isolated nucleic acid molecule that encodes a protein that is effective to preserve progenitor cells, such as hematopoietic progenitor cells. The nucleic acid comprises a sequence defined by SEQ ID NO:1, a homolog thereof, or a fragment thereof. The encoded protein has an amino acid sequence that comprises a sequence defined by SEQ ID NO:2, a homolog thereof, or a fragment thereof that contains an amino acid sequence TNNVLQVT. Methods of using the encoded protein for preserving progenitor cells in vitro, ex vivo, and in vivo are also described. The invention, therefore, include methods such as myeloablation therapies for cancer treatment wherein myeloid reconstitution is facilitated by means of the specified protein. Other therapeutic utilities are also enabled through the invention, for example, expanding progenitor cell populations ex vivo to increase chances of engraftation, improving conditions for transporting and storing progenitor cells, and facilitating gene therapy to treat and cure a broad range of life-threatening hematologic diseases.

An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening

PubMed Central

2017-01-01

DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distribution into picoliter-scale assay reagent droplets, photochemical cleavage of compound from the bead, assay incubation, laser-induced fluorescence-based assay detection, and fluorescence-activated droplet sorting to isolate hits. DNA-encoded compound beads (10-μm diameter) displaying a photocleavable positive control inhibitor pepstatin A were mixed (1920 beads, 729 encoding sequences) with negative control beads (58 000 beads, 1728 encoding sequences) and screened for cathepsin D inhibition using a biochemical enzyme activity assay. The circuit sorted 1518 hit droplets for collection following 18 min incubation over a 240 min analysis. Visual inspection of a subset of droplets (1188 droplets) yielded a 24% false discovery rate (1166 pepstatin A beads; 366 negative control beads). Using template barcoding strategies, it was possible to count hit collection beads (1863) using next-generation sequencing data. Bead-specific barcodes enabled replicate counting, and the false discovery rate was reduced to 2.6% by only considering hit-encoding sequences that were observed on >2 beads. This work represents a complete distributable small molecule discovery platform, from microfluidic miniaturized automation to ultrahigh-throughput hit deconvolution by sequencing. PMID:28199790

An Integrated Microfluidic Processor for DNA-Encoded Combinatorial Library Functional Screening.

PubMed

MacConnell, Andrew B; Price, Alexander K; Paegel, Brian M

2017-03-13

DNA-encoded synthesis is rekindling interest in combinatorial compound libraries for drug discovery and in technology for automated and quantitative library screening. Here, we disclose a microfluidic circuit that enables functional screens of DNA-encoded compound beads. The device carries out library bead distribution into picoliter-scale assay reagent droplets, photochemical cleavage of compound from the bead, assay incubation, laser-induced fluorescence-based assay detection, and fluorescence-activated droplet sorting to isolate hits. DNA-encoded compound beads (10-μm diameter) displaying a photocleavable positive control inhibitor pepstatin A were mixed (1920 beads, 729 encoding sequences) with negative control beads (58 000 beads, 1728 encoding sequences) and screened for cathepsin D inhibition using a biochemical enzyme activity assay. The circuit sorted 1518 hit droplets for collection following 18 min incubation over a 240 min analysis. Visual inspection of a subset of droplets (1188 droplets) yielded a 24% false discovery rate (1166 pepstatin A beads; 366 negative control beads). Using template barcoding strategies, it was possible to count hit collection beads (1863) using next-generation sequencing data. Bead-specific barcodes enabled replicate counting, and the false discovery rate was reduced to 2.6% by only considering hit-encoding sequences that were observed on >2 beads. This work represents a complete distributable small molecule discovery platform, from microfluidic miniaturized automation to ultrahigh-throughput hit deconvolution by sequencing.

Room-temperature ultrafast nonlinear spectroscopy of a single molecule

NASA Astrophysics Data System (ADS)

Liebel, Matz; Toninelli, Costanza; van Hulst, Niek F.

2018-01-01

Single-molecule spectroscopy aims to unveil often hidden but potentially very important contributions of single entities to a system's ensemble response. Albeit contributing tremendously to our ever growing understanding of molecular processes, the fundamental question of temporal evolution, or change, has thus far been inaccessible, thus painting a static picture of a dynamic world. Here, we finally resolve this dilemma by performing ultrafast time-resolved transient spectroscopy on a single molecule. By tracing the femtosecond evolution of excited electronic state spectra of single molecules over hundreds of nanometres of bandwidth at room temperature, we reveal their nonlinear ultrafast response in an effective three-pulse scheme with fluorescence detection. A first excitation pulse is followed by a phase-locked de-excitation pulse pair, providing spectral encoding with 25 fs temporal resolution. This experimental realization of true single-molecule transient spectroscopy demonstrates that two-dimensional electronic spectroscopy of single molecules is experimentally within reach.

The mitochondrial gene encoding ribosomal protein S12 has been translocated to the nuclear genome in Oenothera.

PubMed Central

Grohmann, L; Brennicke, A; Schuster, W

1992-01-01

The Oenothera mitochondrial genome contains only a gene fragment for ribosomal protein S12 (rps12), while other plants encode a functional gene in the mitochondrion. The complete Oenothera rps12 gene is located in the nucleus. The transit sequence necessary to target this protein to the mitochondrion is encoded by a 5'-extension of the open reading frame. Comparison of the amino acid sequence encoded by the nuclear gene with the polypeptides encoded by edited mitochondrial cDNA and genomic sequences of other plants suggests that gene transfer between mitochondrion and nucleus started from edited mitochondrial RNA molecules. Mechanisms and requirements of gene transfer and activation are discussed. Images PMID:1454526

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

PubMed Central

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

2015-01-01

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. PMID:26447612

Discovering Drugs with DNA-Encoded Library Technology: From Concept to Clinic with an Inhibitor of Soluble Epoxide Hydrolase.

PubMed

Belyanskaya, Svetlana L; Ding, Yun; Callahan, James F; Lazaar, Aili L; Israel, David I

2017-05-04

DNA-encoded chemical library technology was developed with the vision of its becoming a transformational platform for drug discovery. The hope was that a new paradigm for the discovery of low-molecular-weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information-encoding attributes of DNA, the power of molecular biology, and a streamlined selection-based discovery process. Here, we describe the discovery and early clinical development of GSK2256294, an inhibitor of soluble epoxide hydrolase (sEH, EPHX2), by using encoded-library technology (ELT). GSK2256294 is an orally bioavailable, potent and selective inhibitor of sEH that has a long half life and produced no serious adverse events in a first-time-in-human clinical study. To our knowledge, GSK2256294 is the first molecule discovered from this technology to enter human clinical testing and represents a realization of the vision that DNA-encoded chemical library technology can efficiently yield molecules with favorable properties that can be readily progressed into high-quality drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Commensal bacteria produce GPCR ligands that mimic human signaling molecules

PubMed Central

Cohen, Louis J.; Esterhazy, Daria; Kim, Seong-Hwan; Lemetre, Christophe; Aguilar, Rhiannon R.; Gordon, Emma A.; Pickard, Amanda J.; Cross, Justin R.; Emiliano, Ana B.; Han, Sun M.; Chu, John; Vila-Farres, Xavier; Kaplitt, Jeremy; Rogoz, Aneta; Calle, Paula Y.; Hunter, Craig; Bitok, J. Kipchirchir; Brady, Sean F.

2017-01-01

Summary Statement Commensal bacteria are believed to play important roles in human health. The mechanisms by which they affect mammalian physiology are poorly understood; however, bacterial metabolites are likely to be key components of host interactions. Here, we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands although future studies are needed to define their potential physiologic role in humans. This work suggests that chemical mimicry of eukaryotic signaling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a new small molecule therapeutic modality (microbiome-biosynthetic-gene-therapy). PMID:28854168

The Differential Expression of Adhesion Molecule and Extracellular Matrix Genes in Mesenchymal Stromal Cells after Interaction with Cord Blood Hematopoietic Progenitors.

PubMed

Buravkova, L B; Andreeva, E R; Lobanova, M V; Cotnezova, E V; Grigoriev, A I

2018-03-01

The dynamics of the expression of genes encoding adhesion molecules, molecules of the connective tissue matrix, and its remodeling enzymes was studied in multipotent mesenchymal stromal cells (MSCs) from human adipose tissue after interaction with cord blood hematopoietic progenitors (HSPCs). An upregulation of ICAM1 and VCAM1, directly proportional to the coculture time (24-72 h), was found. After 72 h of culturing, a downregulation of the genes encoding the majority of matrix molecules (SPP1; COL6A2,7A1; MMP1,3; TIMP1,3; and HAS1) and cell-matrix adhesion molecules (ITGs) was revealed. The detected changes may ensure the realization of the stromal MSC function due to improvement of adhesion and transmigration of HSPCs into the subcellular space.

Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance

PubMed Central

Tischfield, Max A.; Baris, Hagit N.; Wu, Chen; Rudolph, Guenther; Van Maldergem, Lionel; He, Wei; Chan, Wai-Man; Andrews, Caroline; Demer, Joseph L.; Robertson, Richard L.; Mackey, David A.; Ruddle, Jonathan B.; Bird, Thomas D.; Gottlob, Irene; Pieh, Christina; Traboulsi, Elias I.; Pomeroy, Scott L.; Hunter, David G.; Soul, Janet S.; Newlin, Anna; Sabol, Louise J.; Doherty, Edward J.; de Uzcátegui, Clara E.; de Uzcátegui, Nicolas; Collins, Mary Louise Z.; Sener, Emin C.; Wabbels, Bettina; Hellebrand, Heide; Meitinger, Thomas; de Berardinis, Teresa; Magli, Adriano; Schiavi, Costantino; Pastore-Trossello, Marco; Koc, Feray; Wong, Agnes M.; Levin, Alex V.; Geraghty, Michael T.; Descartes, Maria; Flaherty, Maree; Jamieson, Robyn V.; Møller, H. U.; Meuthen, Ingo; Callen, David F.; Kerwin, Janet; Lindsay, Susan; Meindl, Alfons; Gupta, Mohan L.; Pellman, David; Engle, Elizabeth C.

2011-01-01

We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific β-tubulin isotype III, result in a spectrum of human nervous system disorders we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves, and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate normal TUBB3 is required for axon guidance and maintenance in mammals. PMID:20074521

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.

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

SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata.

PubMed

Hitz, Benjamin C; Rowe, Laurence D; Podduturi, Nikhil R; Glick, David I; Baymuradov, Ulugbek K; Malladi, Venkat S; Chan, Esther T; Davidson, Jean M; Gabdank, Idan; Narayana, Aditi K; Onate, Kathrina C; Hilton, Jason; Ho, Marcus C; Lee, Brian T; Miyasato, Stuart R; Dreszer, Timothy R; Sloan, Cricket A; Strattan, J Seth; Tanaka, Forrest Y; Hong, Eurie L; Cherry, J Michael

2017-01-01

The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package.

SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata

PubMed Central

Podduturi, Nikhil R.; Glick, David I.; Baymuradov, Ulugbek K.; Malladi, Venkat S.; Chan, Esther T.; Davidson, Jean M.; Gabdank, Idan; Narayana, Aditi K.; Onate, Kathrina C.; Hilton, Jason; Ho, Marcus C.; Lee, Brian T.; Miyasato, Stuart R.; Dreszer, Timothy R.; Sloan, Cricket A.; Strattan, J. Seth; Tanaka, Forrest Y.; Hong, Eurie L.; Cherry, J. Michael

2017-01-01

The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package. PMID:28403240

FRET-based genetically-encoded sensors for quantitative monitoring of metabolites.

PubMed

Mohsin, Mohd; Ahmad, Altaf; Iqbal, Muhammad

2015-10-01

Neighboring cells in the same tissue can exist in different states of dynamic activities. After genomics, proteomics and metabolomics, fluxomics is now equally important for generating accurate quantitative information on the cellular and sub-cellular dynamics of ions and metabolite, which is critical for functional understanding of organisms. Various spectrometry techniques are used for monitoring ions and metabolites, although their temporal and spatial resolutions are limited. Discovery of the fluorescent proteins and their variants has revolutionized cell biology. Therefore, novel tools and methods targeting sub-cellular compartments need to be deployed in specific cells and targeted to sub-cellular compartments in order to quantify the target-molecule dynamics directly. We require tools that can measure cellular activities and protein dynamics with sub-cellular resolution. Biosensors based on fluorescence resonance energy transfer (FRET) are genetically encoded and hence can specifically target sub-cellular organelles by fusion to proteins or targetted sequences. Since last decade, FRET-based genetically encoded sensors for molecules involved in energy production, reactive oxygen species and secondary messengers have helped to unravel key aspects of cellular physiology. This review, describing the design and principles of sensors, presents a database of sensors for different analytes/processes, and illustrate examples of application in quantitative live cell imaging.

Genetically encoded fluorescent tags

PubMed Central

Thorn, Kurt

2017-01-01

Genetically encoded fluorescent tags are protein sequences that can be fused to a protein of interest to render it fluorescent. These tags have revolutionized cell biology by allowing nearly any protein to be imaged by light microscopy at submicrometer spatial resolution and subsecond time resolution in a live cell or organism. They can also be used to measure protein abundance in thousands to millions of cells using flow cytometry. Here I provide an introduction to the different genetic tags available, including both intrinsically fluorescent proteins and proteins that derive their fluorescence from binding of either endogenous or exogenous fluorophores. I discuss their optical and biological properties and guidelines for choosing appropriate tags for an experiment. Tools for tagging nucleic acid sequences and reporter molecules that detect the presence of different biomolecules are also briefly discussed. PMID:28360214

Apollo lunar descent guidance

NASA Technical Reports Server (NTRS)

Klumpp, A. R.

1974-01-01

Apollo lunar-descent guidance transfers the Lunar Module from a near-circular orbit to touchdown, traversing a 17 deg central angle and a 15 km altitude in 11 min. A group of interactive programs in an onboard computer guide the descent, controlling altitude and the descent propulsion system throttle. A ground-based program pre-computes guidance targets. The concepts involved in this guidance are described. Explicit and implicit guidance are discussed, guidance equations are derived, and the earlier Apollo explicit equation is shown to be an inferior special case of the later implicit equation. Interactive guidance, by which the two-man crew selects a landing site in favorable terrain and directs the trajectory there, is discussed. Interactive terminal-descent guidance enables the crew to control the essentially vertical descent rate in order to land in minimum time with safe contact speed. The altitude maneuver routine uses concepts that make gimbal lock inherently impossible.

Polymers mediate a one-pot route for functionalized quantum dot barcodes with a large encoding capacity.

PubMed

Zhang, Ding Sheng-Zi; Jiang, Yang; Wei, Dan; Wei, Xunbin; Xu, Hong; Gu, Hongchen

2018-06-21

With the increasing demands for high-throughput multiplexed bioassays, quantum dot (QD)-encoded microbeads as biocarriers for various bioreactions have attracted considerable attention. However, three key requirements for these biocarriers are still longstanding issues: a stable fluorescence intensity, a large encoding capacity and abundant surface functional groups. Here, a novel one-pot strategy is developed, generating functionalized QD-encoded microspheres with a strong fluorescence intensity and optical stability. With poly(styrene-co-maleic anhydride) (PSMA) molecules as mediators, the encapsulation of QDs and carboxylation of the bead surface are integrated together, greatly improving the preparation efficiency and guaranteeing their potential application in biodetection. Moreover, the mechanism for preparing QD-doped beads is further proposed, which helps to precisely manipulate the preparation process and accurately encode the beads. Through this approach, a single- and dual-color barcode library of QD-encoded microspheres has been successfully established, which demonstrates their great potential in suspension arrays.

Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology

PubMed Central

Kotlikoff, Michael I

2007-01-01

This article reviews genetically encoded Ca2+ indicators (GECIs), with a focus on the use of these novel molecules in the context of understanding complex cell signalling in mammals, in vivo. The review focuses on the advantages and limitations of specific GECI design strategies and the results of experiments in which these molecules have been expressed in transgenic mice, concentrating particularly on recent experiments from our laboratory in which physiological signalling could be monitored in vivo. Finally, newer strategies for effective genetic specification of GECIs are briefly reviewed. PMID:17038427

DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic Compounds with Amplifiable Information.

PubMed

Neri, Dario; Lerner, Richard A

2018-06-20

The discovery of organic ligands that bind specifically to proteins is a central problem in chemistry, biology, and the biomedical sciences. The encoding of individual organic molecules with distinctive DNA tags, serving as amplifiable identification bar codes, allows the construction and screening of combinatorial libraries of unprecedented size, thus facilitating the discovery of ligands to many different protein targets. Fundamentally, one links powers of genetics and chemical synthesis. After the initial description of DNA-encoded chemical libraries in 1992, several experimental embodiments of the technology have been reduced to practice. This review provides a historical account of important milestones in the development of DNA-encoded chemical libraries, a survey of relevant ongoing research activities, and a glimpse into the future.

The Text Encoding Initiative: Flexible and Extensible Document Encoding.

ERIC Educational Resources Information Center

Barnard, David T.; Ide, Nancy M.

1997-01-01

The Text Encoding Initiative (TEI), an international collaboration aimed at producing a common encoding scheme for complex texts, examines the requirement for generality versus the requirement to handle specialized text types. Discusses how documents and users tax the limits of fixed schemes requiring flexible extensible encoding to support…

Click strategies for single-molecule protein fluorescence.

PubMed

Milles, Sigrid; Tyagi, Swati; Banterle, Niccolò; Koehler, Christine; VanDelinder, Virginia; Plass, Tilman; Neal, Adrian P; Lemke, Edward A

2012-03-21

Single-molecule methods have matured into central tools for studies in biology. Foerster resonance energy transfer (FRET) techniques, in particular, have been widely applied to study biomolecular structure and dynamics. The major bottleneck for a facile and general application of these studies arises from the need to label biological samples site-specifically with suitable fluorescent dyes. In this work, we present an optimized strategy combining click chemistry and the genetic encoding of unnatural amino acids (UAAs) to overcome this limitation for proteins. We performed a systematic study with a variety of clickable UAAs and explored their potential for high-resolution single-molecule FRET (smFRET). We determined all parameters that are essential for successful single-molecule studies, such as accessibility of the probes, expression yield of proteins, and quantitative labeling. Our multiparameter fluorescence analysis allowed us to gain new insights into the effects and photophysical properties of fluorescent dyes linked to various UAAs for smFRET measurements. This led us to determine that, from the extended tool set that we now present, genetically encoding propargyllysine has major advantages for state-of-the-art measurements compared to other UAAs. Using this optimized system, we present a biocompatible one-step dual-labeling strategy of the regulatory protein RanBP3 with full labeling position freedom. Our technique allowed us then to determine that the region encompassing two FxFG repeat sequences adopts a disordered but collapsed state. RanBP3 serves here as a prototypical protein that, due to its multiple cysteines, size, and partially disordered structure, is not readily accessible to any of the typical structure determination techniques such as smFRET, NMR, and X-ray crystallography.

Optimized Reaction Conditions for Amide Bond Formation in DNA-Encoded Combinatorial Libraries.

PubMed

Li, Yizhou; Gabriele, Elena; Samain, Florent; Favalli, Nicholas; Sladojevich, Filippo; Scheuermann, Jörg; Neri, Dario

2016-08-08

DNA-encoded combinatorial libraries are increasingly being used as tools for the discovery of small organic binding molecules to proteins of biological or pharmaceutical interest. In the majority of cases, synthetic procedures for the formation of DNA-encoded combinatorial libraries incorporate at least one step of amide bond formation between amino-modified DNA and a carboxylic acid. We investigated reaction conditions and established a methodology by using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide, 1-hydroxy-7-azabenzotriazole and N,N'-diisopropylethylamine (EDC/HOAt/DIPEA) in combination, which provided conversions greater than 75% for 423/543 (78%) of the carboxylic acids tested. These reaction conditions were efficient with a variety of primary and secondary amines, as well as with various types of amino-modified oligonucleotides. The reaction conditions, which also worked efficiently over a broad range of DNA concentrations and reaction scales, should facilitate the synthesis of novel DNA-encoded combinatorial libraries.

Nucleic acid encoding DS-CAM proteins and products related thereto

DOEpatents

Korenberg, Julie R.

2005-11-01

In accordance with the present invention, there are provided Down Syndrome-Cell Adhesion Molecule (DS-CAM) proteins. Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention DS-CAM proteins can be employed in a variety of ways, for example, for the production of anti-DS-CAM antibodies thereto, in therapeutic compositions and methods employing such proteins and/or antibodies. DS-CAM proteins are also useful in bioassays to identify agonists and antagonists thereto.

How Water’s Properties Are Encoded in Its Molecular Structure and Energies

PubMed Central

2017-01-01

How are water’s material properties encoded within the structure of the water molecule? This is pertinent to understanding Earth’s living systems, its materials, its geochemistry and geophysics, and a broad spectrum of its industrial chemistry. Water has distinctive liquid and solid properties: It is highly cohesive. It has volumetric anomalies—water’s solid (ice) floats on its liquid; pressure can melt the solid rather than freezing the liquid; heating can shrink the liquid. It has more solid phases than other materials. Its supercooled liquid has divergent thermodynamic response functions. Its glassy state is neither fragile nor strong. Its component ions—hydroxide and protons—diffuse much faster than other ions. Aqueous solvation of ions or oils entails large entropies and heat capacities. We review how these properties are encoded within water’s molecular structure and energies, as understood from theories, simulations, and experiments. Like simpler liquids, water molecules are nearly spherical and interact with each other through van der Waals forces. Unlike simpler liquids, water’s orientation-dependent hydrogen bonding leads to open tetrahedral cage-like structuring that contributes to its remarkable volumetric and thermal properties. PMID:28949513

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.

Chondroitin sulfates and their binding molecules in the central nervous system.

PubMed

Djerbal, L; Lortat-Jacob, H; Kwok, Jcf

2017-06-01

Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases.

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)

Small-molecule control of protein function through Staudinger reduction

NASA Astrophysics Data System (ADS)

Luo, Ji; Liu, Qingyang; Morihiro, Kunihiko; Deiters, Alexander

2016-11-01

Using small molecules to control the function of proteins in live cells with complete specificity is highly desirable, but challenging. Here we report a small-molecule switch that can be used to control protein activity. The approach uses a phosphine-mediated Staudinger reduction to activate protein function. Genetic encoding of an ortho-azidobenzyloxycarbonyl amino acid using a pyrrolysyl transfer RNA synthetase/tRNACUA pair in mammalian cells enables the site-specific introduction of a small-molecule-removable protecting group into the protein of interest. Strategic placement of this group renders the protein inactive until deprotection through a bioorthogonal Staudinger reduction delivers the active wild-type protein. This developed methodology was applied to the conditional control of several cellular processes, including bioluminescence (luciferase), fluorescence (enhanced green fluorescent protein), protein translocation (nuclear localization sequence), DNA recombination (Cre) and gene editing (Cas9).

Optimizing the 391-nm lasing intensity from ionized nitrogen molecules in 800-nm femtosecond laser fields

NASA Astrophysics Data System (ADS)

Zhong, Xunqi; Miao, Zhiming; Zhang, Linlin; Jiang, Hongbing; Liu, Yunquan; Gong, Qihuang; Wu, Chengyin

2018-03-01

We investigate the 391-nm lasing dynamics from ionized nitrogen molecules in 800-nm femtosecond laser fields. By comparing the radiation intensity, spectrum shape, and temporal profile of the 391-nm lasing at various experimental conditions, we conclude that the lasing dynamics contains not only the generation and the decay of ionized nitrogen molecules, but also the seed-built coherence among emitters as well as the propagation effect in the plasma filamentation. These results provide reliable guidance for optimizing the 391-nm lasing from ionized nitrogen molecules in 800-nm femtosecond laser fields, which have potential applications for remote sensing in the atmosphere.

Generation of Gene-Engineered Chimeric DNA Molecules for Specific Therapy of Autoimmune Diseases

PubMed Central

Gesheva, Vera; Szekeres, Zsuzsanna; Mihaylova, Nikolina; Dimitrova, Iliyana; Nikolova, Maria; Erdei, Anna; Prechl, Jozsef

2012-01-01

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the development of self-reactive B and T cells and autoantibody production. In particular, double-stranded DNA-specific B cells play an important role in lupus progression, and their selective elimination is a reasonable approach for effective therapy of SLE. DNA-based vaccines aim at the induction of immune response against the vector-encoded antigen. Here, we are exploring, as a new DNA-based therapy of SLE, a chimeric DNA molecule encoding a DNA-mimotope peptide, and the Fv but not the immunogenic Fc fragment of an FcγRIIb-specific monoclonal antibody. This DNA construct was inserted in the expression vector pNut and used as a naked DNA vaccine in a mouse model of lupus. The chimeric DNA molecule can be expressed in eukaryotic cells and cross-links cell surface receptors on DNA-specific B cells, delivering an inhibitory intracellular signal. Intramuscular administration of the recombinant DNA molecule to lupus-prone MRL/lpr mice prevented increase in IgG anti-DNA antibodies and was associated with a low degree of proteinuria, modulation of cytokine profile, and suppression of lupus nephritis. PMID:23075110

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.

Monitoring Phosphatidic Acid Signaling in Breast Cancer Cells Using Genetically Encoded Biosensors.

PubMed

Lu, Maryia; Tay, Li Wei Rachel; He, Jingquan; Du, Guangwei

2016-01-01

Phospholipids are important signaling molecules that regulate cell proliferation, death, migration, and metabolism. Many phospholipid signaling cascades are altered in breast cancer. To understand the functions of phospholipid signaling molecules, genetically encoded phospholipid biosensors have been developed to monitor their spatiotemporal dynamics. Compared to other phospholipids, much less is known about the subcellular production and cellular functions of phosphatidic acid (PA), partially due to the lack of a specific and sensitive PA biosensor in the past. This chapter describes the use of a newly developed PA biosensor, PASS, in two applications: regular fluorescent microscopy and fluorescence lifetime imaging microscopy-Förster/fluorescence resonance energy transfer (FLIM-FRET). These protocols can be also used with other phospholipid biosensors.

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.

The use and manipulation of insect reproductive molecules for controlling insect populations

USDA-ARS?s Scientific Manuscript database

The use and manipulation of insect reproductive molecules, and the genes that encode them, provides a variety of methods to control insect fertility and thus a means of population control for insect pests. Towards this end, we first studied the yolk polypeptide gene from the caribfly, Anastrepha su...

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.

Novel Roles for Immune Molecules in Neural Development: Implications for Neurodevelopmental Disorders

PubMed Central

Garay, Paula A.; McAllister, A. Kimberley

2010-01-01

Although the brain has classically been considered “immune-privileged”, current research suggests an extensive communication between the immune and nervous systems in both health and disease. Recent studies demonstrate that immune molecules are present at the right place and time to modulate the development and function of the healthy and diseased central nervous system (CNS). Indeed, immune molecules play integral roles in the CNS throughout neural development, including affecting neurogenesis, neuronal migration, axon guidance, synapse formation, activity-dependent refinement of circuits, and synaptic plasticity. Moreover, the roles of individual immune molecules in the nervous system may change over development. This review focuses on the effects of immune molecules on neuronal connections in the mammalian central nervous system – specifically the roles for MHCI and its receptors, complement, and cytokines on the function, refinement, and plasticity of geniculate, cortical and hippocampal synapses, and their relationship to neurodevelopmental disorders. These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD) and schizophrenia. PMID:21423522

Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT).

PubMed

Yang, Hongfang; Medeiros, Patricia F; Raha, Kaushik; Elkins, Patricia; Lind, Kenneth E; Lehr, Ruth; Adams, Nicholas D; Burgess, Joelle L; Schmidt, Stanley J; Knight, Steven D; Auger, Kurt R; Schaber, Michael D; Franklin, G Joseph; Ding, Yun; DeLorey, Jennifer L; Centrella, Paolo A; Mataruse, Sibongile; Skinner, Steven R; Clark, Matthew A; Cuozzo, John W; Evindar, Ghotas

2015-05-14

In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein.

Single Molecule Sensing by Nanopores and Nanopore Devices

PubMed Central

Gu, Li-Qun; Shim, Ji Wook

2010-01-01

Molecular-scale pore structures, called nanopores, can be assembled by protein ion channels through genetic engineering or be artificially fabricated on solid substrates using fashion nanotechnology. When target molecules interact with the functionalized lumen of a nanopore, they characteristically block the ion pathway. The resulting conductance changes allow for identification of single molecules and quantification of target species in the mixture. In this review, we first overview nanopore-based sensory techniques that have been created for the detection of myriad biomedical targets, from metal ions, drug compounds, and cellular second messengers to proteins and DNA. Then we introduce our recent discoveries in nanopore single molecule detection: (1) using the protein nanopore to study folding/unfolding of the G-quadruplex aptamer; (2) creating a portable and durable biochip that is integrated with a single-protein pore sensor (this chip is compared with recently developed protein pore sensors based on stabilized bilayers on glass nanopore membranes and droplet interface bilayer); and (3) creating a glass nanopore-terminated probe for single-molecule DNA detection, chiral enantiomer discrimination, and identification of the bioterrorist agent ricin with an aptamer-encoded nanopore. PMID:20174694

ERP Correlates of Encoding Success and Encoding Selectivity in Attention Switching

PubMed Central

Yeung, Nick

2016-01-01

Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (EEG) data by studying event-related potential (ERP) subsequent memory effects. The current study investigated ERP correlates of memory success operationalised with two different measures—memory selectivity and global memory—to assess whether previously observed ERP subsequent memory effects reflect focused encoding of task-relevant information (memory selectivity), general encoding success (global memory), or both. Building on previous work, the present study combined an attention switching paradigm—in which participants were presented with compound object-word stimuli and switched between attending to the object or the word across trials—with a later recognition memory test for those stimuli, while recording their EEG. Our results provided clear evidence that subsequent memory effects resulted from selective attentional focusing and effective top-down control (memory selectivity) in contrast to more general encoding success effects (global memory). Further analyses addressed the question of whether successful encoding depended on similar control mechanisms to those involved in attention switching. Interestingly, differences in the ERP correlates of attention switching and successful encoding, particularly during the poststimulus period, indicated that variability in encoding success occurred independently of prestimulus demands for top-down cognitive control. These results suggest that while effects of selective attention and selective encoding co-occur behaviourally their ERP correlates are at least partly dissociable. PMID:27907075

Rational Design of Small Molecules Targeting Oncogenic Noncoding RNAs from Sequence.

PubMed

Disney, Matthew D; Angelbello, Alicia J

2016-12-20

The discovery of RNA catalysis in the 1980s and the dissemination of the human genome sequence at the start of this century inspired investigations of the regulatory roles of noncoding RNAs in biology. In fact, the Encyclopedia of DNA Elements (ENCODE) project has shown that only 1-2% of the human genome encodes protein, yet 75% is transcribed into RNA. Functional studies both preceding and following the ENCODE project have shown that these noncoding RNAs have important roles in regulating gene expression, developmental timing, and other critical functions. RNA's diverse roles are often a consequence of the various folds that it adopts. The single-stranded nature of the biopolymer enables it to adopt intramolecular folds with noncanonical pairings to lower its free energy. These folds can be scaffolds to bind proteins or to form frameworks to interact with other RNAs. Not surprisingly, dysregulation of certain noncoding RNAs has been shown to be causative of disease. Given this as the background, it is easy to see why it would be useful to develop methods that target RNA and manipulate its biology in rational and predictable ways. The antisense approach has afforded strategies to target RNAs via Watson-Crick base pairing and has typically focused on targeting partially unstructured regions of RNA. Small molecule strategies to target RNA would be desirable not only because compounds could be lead optimized via medicinal chemistry but also because structured regions within an RNA of interest could be targeted to directly interfere with RNA folds that contribute to disease. Additionally, small molecules have historically been the most successful drug candidates. Until recently, the ability to design small molecules that target non-ribosomal RNAs has been elusive, creating the perception that they are "undruggable". In this Account, approaches to demystify targeting RNA with small molecules are described. Rather than bulk screening for compounds that bind to singular

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.

Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library

NASA Astrophysics Data System (ADS)

Litovchick, Alexander; Dumelin, Christoph E.; Habeshian, Sevan; Gikunju, Diana; Guié, Marie-Aude; Centrella, Paolo; Zhang, Ying; Sigel, Eric A.; Cuozzo, John W.; Keefe, Anthony D.; Clark, Matthew A.

2015-06-01

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase.

Accurate Encoding and Decoding by Single Cells: Amplitude Versus Frequency Modulation

PubMed Central

Micali, Gabriele; Aquino, Gerardo; Richards, David M.; Endres, Robert G.

2015-01-01

Cells sense external concentrations and, via biochemical signaling, respond by regulating the expression of target proteins. Both in signaling networks and gene regulation there are two main mechanisms by which the concentration can be encoded internally: amplitude modulation (AM), where the absolute concentration of an internal signaling molecule encodes the stimulus, and frequency modulation (FM), where the period between successive bursts represents the stimulus. Although both mechanisms have been observed in biological systems, the question of when it is beneficial for cells to use either AM or FM is largely unanswered. Here, we first consider a simple model for a single receptor (or ion channel), which can either signal continuously whenever a ligand is bound, or produce a burst in signaling molecule upon receptor binding. We find that bursty signaling is more accurate than continuous signaling only for sufficiently fast dynamics. This suggests that modulation based on bursts may be more common in signaling networks than in gene regulation. We then extend our model to multiple receptors, where continuous and bursty signaling are equivalent to AM and FM respectively, finding that AM is always more accurate. This implies that the reason some cells use FM is related to factors other than accuracy, such as the ability to coordinate expression of multiple genes or to implement threshold crossing mechanisms. PMID:26030820

Multimodal ophthalmic imaging using swept source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

Malone, Joseph D.; El-Haddad, Mohamed T.; Tye, Logan A.; Majeau, Lucas; Godbout, Nicolas; Rollins, Andrew M.; Boudoux, Caroline; Tao, Yuankai K.

2016-03-01

Scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) benefit clinical diagnostic imaging in ophthalmology by enabling in vivo noninvasive en face and volumetric visualization of retinal structures, respectively. Spectrally encoding methods enable confocal imaging through fiber optics and reduces system complexity. Previous applications in ophthalmic imaging include spectrally encoded confocal scanning laser ophthalmoscopy (SECSLO) and a combined SECSLO-OCT system for image guidance, tracking, and registration. However, spectrally encoded imaging suffers from speckle noise because each spectrally encoded channel is effectively monochromatic. Here, we demonstrate in vivo human retinal imaging using a swept source spectrally encoded scanning laser ophthalmoscope and OCT (SSSESLO- OCT) at 1060 nm. SS-SESLO-OCT uses a shared 100 kHz Axsun swept source, shared scanner and imaging optics, and are detected simultaneously on a shared, dual channel high-speed digitizer. SESLO illumination and detection was performed using the single mode core and multimode inner cladding of a double clad fiber coupler, respectively, to preserve lateral resolution while improving collection efficiency and reducing speckle contrast at the expense of confocality. Concurrent en face SESLO and cross-sectional OCT images were acquired with 1376 x 500 pixels at 200 frames-per-second. Our system design is compact and uses a shared light source, imaging optics, and digitizer, which reduces overall system complexity and ensures inherent co-registration between SESLO and OCT FOVs. En face SESLO images acquired concurrent with OCT cross-sections enables lateral motion tracking and three-dimensional volume registration with broad applications in multivolume OCT averaging, image mosaicking, and intraoperative instrument tracking.

Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT)

PubMed Central

2015-01-01

In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein. PMID:26005528

Engineered kinesin motor proteins amenable to small-molecule inhibition

PubMed Central

Engelke, Martin F.; Winding, Michael; Yue, Yang; Shastry, Shankar; Teloni, Federico; Reddy, Sanjay; Blasius, T. Lynne; Soppina, Pushpanjali; Hancock, William O.; Gelfand, Vladimir I.; Verhey, Kristen J.

2016-01-01

The human genome encodes 45 kinesin motor proteins that drive cell division, cell motility, intracellular trafficking and ciliary function. Determining the cellular function of each kinesin would benefit from specific small-molecule inhibitors. However, screens have yielded only a few specific inhibitors. Here we present a novel chemical-genetic approach to engineer kinesin motors that can carry out the function of the wild-type motor yet can also be efficiently inhibited by small, cell-permeable molecules. Using kinesin-1 as a prototype, we develop two independent strategies to generate inhibitable motors, and characterize the resulting inhibition in single-molecule assays and in cells. We further apply these two strategies to create analogously inhibitable kinesin-3 motors. These inhibitable motors will be of great utility to study the functions of specific kinesins in a dynamic manner in cells and animals. Furthermore, these strategies can be used to generate inhibitable versions of any motor protein of interest. PMID:27045608

Encoded Library Synthesis Using Chemical Ligation and the Discovery of sEH Inhibitors from a 334-Million Member Library

PubMed Central

Litovchick, Alexander; Dumelin, Christoph E.; Habeshian, Sevan; Gikunju, Diana; Guié, Marie-Aude; Centrella, Paolo; Zhang, Ying; Sigel, Eric A.; Cuozzo, John W.; Keefe, Anthony D.; Clark, Matthew A.

2015-01-01

A chemical ligation method for construction of DNA-encoded small-molecule libraries has been developed. Taking advantage of the ability of the Klenow fragment of DNA polymerase to accept templates with triazole linkages in place of phosphodiesters, we have designed a strategy for chemically ligating oligonucleotide tags using cycloaddition chemistry. We have utilized this strategy in the construction and selection of a small molecule library, and successfully identified inhibitors of the enzyme soluble epoxide hydrolase. PMID:26061191

Orientation to determine quality attributes of flavoring excipients containing volatile molecules.

PubMed

Kiene, Florian E; Pein, Miriam; Thommes, Markus

2015-06-10

Pharmaceutical excipients containing volatile odor-active molecules can be used in pharmaceutical development to increase patients' compliance. However, capturing the molecular composition of these odor-active substances is challenging. Therefore, guidance for the analytical investigation of these excipients should be developed. Using a model flavor, lead molecules were chosen and a gas chromatographic method was validated according to pharmaceutical guidelines. Changes during storage as well as batch homogeneity and conformity were investigated. The knowledge gained could be used to understand molecular differences between batches caused by aging. A suitable attempt to capture the volatile molecular composition of flavoring substance was presented and the found results could be used for the determination and interpretation of quality attributes. Copyright © 2015 Elsevier B.V. All rights reserved.

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…

Contextual cueing improves attentional guidance, even when guidance is supposedly optimal.

PubMed

Harris, Anthony M; Remington, Roger W

2017-05-01

Visual search through previously encountered contexts typically produces reduced reaction times compared with search through novel contexts. This contextual cueing benefit is well established, but there is debate regarding its underlying mechanisms. Eye-tracking studies have consistently shown reduced number of fixations with repetition, supporting improvements in attentional guidance as the source of contextual cueing. However, contextual cueing benefits have been shown in conditions in which attentional guidance should already be optimal-namely, when attention is captured to the target location by an abrupt onset, or under pop-out conditions. These results have been used to argue for a response-related account of contextual cueing. Here, we combine eye tracking with response time to examine the mechanisms behind contextual cueing in spatially cued and pop-out conditions. Three experiments find consistent response time benefits with repetition, which appear to be driven almost entirely by a reduction in number of fixations, supporting improved attentional guidance as the mechanism behind contextual cueing. No differences were observed in the time between fixating the target and responding-our proxy for response related processes. Furthermore, the correlation between contextual cueing magnitude and the reduction in number of fixations on repeated contexts approaches 1. These results argue strongly that attentional guidance is facilitated by familiar search contexts, even when guidance is near-optimal. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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.

Nucleic acids encoding plant glutamine phenylpyruvate transaminase (GPT) and uses thereof

DOEpatents

Unkefer, Pat J.; Anderson, Penelope S.; Knight, Thomas J.

2016-03-29

Glutamine phenylpyruvate transaminase (GPT) proteins, nucleic acid molecules encoding GPT proteins, and uses thereof are disclosed. Provided herein are various GPT proteins and GPT gene coding sequences isolated from a number of plant species. As disclosed herein, GPT proteins share remarkable structural similarity within plant species, and are active in catalyzing the synthesis of 2-hydroxy-5-oxoproline (2-oxoglutaramate), a powerful signal metabolite which regulates the function of a large number of genes involved in the photosynthesis apparatus, carbon fixation and nitrogen metabolism.

Quantum-Sequencing: Fast electronic single DNA molecule sequencing

NASA Astrophysics Data System (ADS)

Casamada Ribot, Josep; Chatterjee, Anushree; Nagpal, Prashant

2014-03-01

A major goal of third-generation sequencing technologies is to develop a fast, reliable, enzyme-free, high-throughput and cost-effective, single-molecule sequencing method. Here, we present the first demonstration of unique ``electronic fingerprint'' of all nucleotides (A, G, T, C), with single-molecule DNA sequencing, using Quantum-tunneling Sequencing (Q-Seq) at room temperature. We show that the electronic state of the nucleobases shift depending on the pH, with most distinct states identified at acidic pH. We also demonstrate identification of single nucleotide modifications (methylation here). Using these unique electronic fingerprints (or tunneling data), we report a partial sequence of beta lactamase (bla) gene, which encodes resistance to beta-lactam antibiotics, with over 95% success rate. These results highlight the potential of Q-Seq as a robust technique for next-generation sequencing.

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.

Micro guidance and control technology overview

NASA Technical Reports Server (NTRS)

Kissel, Glen J.; Hadaegh, Fred Y.

1993-01-01

This paper gives an overview of micro-guidance and control technologies and in the process previews of the technology/user and systems issues presented in the guidance and control session at the workshop. We first present a discussion of the advantages of using micro-guidance and control components and then detail six micro-guidance and control thrusts that could have a revolutionary impact on space missions and systems. Specific technologies emerging in the micro-guidance and control field will be examined. These technologies fall into two broad categories: micro-attitude determination (inertial and celestial) and micro-actuation, control and sensing. Finally, the scope of the workshop's guidance and control panel are presented.

A Liquid Array Platform For the Multiplexed Analysis of Synthetic Molecule-Protein Interactions

PubMed Central

Doran, Todd M.; Kodadek, Thomas

2014-01-01

Synthetic molecule microarrays, consisting of many different compounds spotted onto a planar surface such as modified glass or cellulose, have proven to be useful tools for the multiplexed analysis of small molecule- and peptide-protein interactions. However, these arrays are technically difficult to manufacture and use with high reproducibility and require specialized equipment. Here we report a more convenient alternative comprised of color-encoded beads that display a small molecule protein ligand on the surface. Quantitative, multiplexed assay of protein binding to up to 24 different ligands can be achieved using a common flow cytometer for the readout. This technology should be useful for evaluating hits from library screening efforts, the determination of structure activity relationships and for certain types of serological analyses. PMID:24245981

A review of the FDA draft guidance document for software validation: guidance for industry.

PubMed

Keatley, K L

1999-01-01

A Draft Guidance Document (Version 1.1) was issued by the United States Food and Drug Administration (FDA) to address the software validation requirement of the Quality System Regulation, 21 CFR Part 820, effective June 1, 1997. The guidance document outlines validation considerations that the FDA regards as applicable to both medical device software and software used to "design, develop or manufacture" medical devices. The Draft Guidance is available at the FDA web site http:@www.fda.gov/cdrh/comps/swareval++ +.html. Presented here is a review of the main features of the FDA document for Quality System Regulation (QSR), and some guidance for its implementation in industry.

Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.

PubMed

Jamain, Stéphane; Quach, Hélène; Betancur, Catalina; Råstam, Maria; Colineaux, Catherine; Gillberg, I Carina; Soderstrom, Henrik; Giros, Bruno; Leboyer, Marion; Gillberg, Christopher; Bourgeron, Thomas

2003-05-01

Many studies have supported a genetic etiology for autism. Here we report mutations in two X-linked genes encoding neuroligins NLGN3 and NLGN4 in siblings with autism-spectrum disorders. These mutations affect cell-adhesion molecules localized at the synapse and suggest that a defect of synaptogenesis may predispose to autism.

Roundabout geometric design guidance.

DOT National Transportation Integrated Search

2007-06-01

This research report is intended to examine the geometric standards, guidelines, and practices used nationally and by other states to develop recommendations on roundabout design guidance for California. This research serves as a guidance tool in sup...

Electric-field-driven electron-transfer in mixed-valence molecules.

PubMed

Blair, Enrique P; Corcelli, Steven A; Lent, Craig S

2016-07-07

Molecular quantum-dot cellular automata is a computing paradigm in which digital information is encoded by the charge configuration of a mixed-valence molecule. General-purpose computing can be achieved by arranging these compounds on a substrate and exploiting intermolecular Coulombic coupling. The operation of such a device relies on nonequilibrium electron transfer (ET), whereby the time-varying electric field of one molecule induces an ET event in a neighboring molecule. The magnitude of the electric fields can be quite large because of close spatial proximity, and the induced ET rate is a measure of the nonequilibrium response of the molecule. We calculate the electric-field-driven ET rate for a model mixed-valence compound. The mixed-valence molecule is regarded as a two-state electronic system coupled to a molecular vibrational mode, which is, in turn, coupled to a thermal environment. Both the electronic and vibrational degrees-of-freedom are treated quantum mechanically, and the dissipative vibrational-bath interaction is modeled with the Lindblad equation. This approach captures both tunneling and nonadiabatic dynamics. Relationships between microscopic molecular properties and the driven ET rate are explored for two time-dependent applied fields: an abruptly switched field and a linearly ramped field. In both cases, the driven ET rate is only weakly temperature dependent. When the model is applied using parameters appropriate to a specific mixed-valence molecule, diferrocenylacetylene, terahertz-range ET transfer rates are predicted.

Electric-field-driven electron-transfer in mixed-valence molecules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blair, Enrique P., E-mail: enrique-blair@baylor.edu; Corcelli, Steven A., E-mail: scorcell@nd.edu; Lent, Craig S., E-mail: lent@nd.edu

2016-07-07

Molecular quantum-dot cellular automata is a computing paradigm in which digital information is encoded by the charge configuration of a mixed-valence molecule. General-purpose computing can be achieved by arranging these compounds on a substrate and exploiting intermolecular Coulombic coupling. The operation of such a device relies on nonequilibrium electron transfer (ET), whereby the time-varying electric field of one molecule induces an ET event in a neighboring molecule. The magnitude of the electric fields can be quite large because of close spatial proximity, and the induced ET rate is a measure of the nonequilibrium response of the molecule. We calculate themore » electric-field-driven ET rate for a model mixed-valence compound. The mixed-valence molecule is regarded as a two-state electronic system coupled to a molecular vibrational mode, which is, in turn, coupled to a thermal environment. Both the electronic and vibrational degrees-of-freedom are treated quantum mechanically, and the dissipative vibrational-bath interaction is modeled with the Lindblad equation. This approach captures both tunneling and nonadiabatic dynamics. Relationships between microscopic molecular properties and the driven ET rate are explored for two time-dependent applied fields: an abruptly switched field and a linearly ramped field. In both cases, the driven ET rate is only weakly temperature dependent. When the model is applied using parameters appropriate to a specific mixed-valence molecule, diferrocenylacetylene, terahertz-range ET transfer rates are predicted.« less

Cloud-based uniform ChIP-Seq processing tools for modENCODE and ENCODE.

PubMed

Trinh, Quang M; Jen, Fei-Yang Arthur; Zhou, Ziru; Chu, Kar Ming; Perry, Marc D; Kephart, Ellen T; Contrino, Sergio; Ruzanov, Peter; Stein, Lincoln D

2013-07-22

Funded by the National Institutes of Health (NIH), the aim of the Model Organism ENCyclopedia of DNA Elements (modENCODE) project is to provide the biological research community with a comprehensive encyclopedia of functional genomic elements for both model organisms C. elegans (worm) and D. melanogaster (fly). With a total size of just under 10 terabytes of data collected and released to the public, one of the challenges faced by researchers is to extract biologically meaningful knowledge from this large data set. While the basic quality control, pre-processing, and analysis of the data has already been performed by members of the modENCODE consortium, many researchers will wish to reinterpret the data set using modifications and enhancements of the original protocols, or combine modENCODE data with other data sets. Unfortunately this can be a time consuming and logistically challenging proposition. In recognition of this challenge, the modENCODE DCC has released uniform computing resources for analyzing modENCODE data on Galaxy (https://github.com/modENCODE-DCC/Galaxy), on the public Amazon Cloud (http://aws.amazon.com), and on the private Bionimbus Cloud for genomic research (http://www.bionimbus.org). In particular, we have released Galaxy workflows for interpreting ChIP-seq data which use the same quality control (QC) and peak calling standards adopted by the modENCODE and ENCODE communities. For convenience of use, we have created Amazon and Bionimbus Cloud machine images containing Galaxy along with all the modENCODE data, software and other dependencies. Using these resources provides a framework for running consistent and reproducible analyses on modENCODE data, ultimately allowing researchers to use more of their time using modENCODE data, and less time moving it around.

Cloud-based uniform ChIP-Seq processing tools for modENCODE and ENCODE

PubMed Central

2013-01-01

Background Funded by the National Institutes of Health (NIH), the aim of the Model Organism ENCyclopedia of DNA Elements (modENCODE) project is to provide the biological research community with a comprehensive encyclopedia of functional genomic elements for both model organisms C. elegans (worm) and D. melanogaster (fly). With a total size of just under 10 terabytes of data collected and released to the public, one of the challenges faced by researchers is to extract biologically meaningful knowledge from this large data set. While the basic quality control, pre-processing, and analysis of the data has already been performed by members of the modENCODE consortium, many researchers will wish to reinterpret the data set using modifications and enhancements of the original protocols, or combine modENCODE data with other data sets. Unfortunately this can be a time consuming and logistically challenging proposition. Results In recognition of this challenge, the modENCODE DCC has released uniform computing resources for analyzing modENCODE data on Galaxy (https://github.com/modENCODE-DCC/Galaxy), on the public Amazon Cloud (http://aws.amazon.com), and on the private Bionimbus Cloud for genomic research (http://www.bionimbus.org). In particular, we have released Galaxy workflows for interpreting ChIP-seq data which use the same quality control (QC) and peak calling standards adopted by the modENCODE and ENCODE communities. For convenience of use, we have created Amazon and Bionimbus Cloud machine images containing Galaxy along with all the modENCODE data, software and other dependencies. Conclusions Using these resources provides a framework for running consistent and reproducible analyses on modENCODE data, ultimately allowing researchers to use more of their time using modENCODE data, and less time moving it around. PMID:23875683

HERMES: Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy

PubMed Central

Chan, Kimberly L.; Puts, Nicolaas A. J.; Schär, Michael; Barker, Peter B.; Edden, Richard A. E.

2017-01-01

Purpose To investigate a novel Hadamard-encoded spectral editing scheme and evaluate its performance in simultaneously quantifying N-acetyl aspartate (NAA) and N-acetyl aspartyl glutamate (NAAG) at 3 Tesla. Methods Editing pulses applied according to a Hadamard encoding scheme allow the simultaneous acquisition of multiple metabolites. The method, called HERMES (Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy), was optimized to detect NAA and NAAG simultaneously using density-matrix simulations and validated in phantoms at 3T. In vivo data were acquired in the centrum semiovale of 12 normal subjects. The NAA:NAAG concentration ratio was determined by modeling in vivo data using simulated basis functions. Simulations were also performed for potentially coedited molecules with signals within the detected NAA/NAAG region. Results Simulations and phantom experiments show excellent segregation of NAA and NAAG signals into the intended spectra, with minimal crosstalk. Multiplet patterns show good agreement between simulations and phantom and in vivo data. In vivo measurements show that the relative peak intensities of the NAA and NAAG spectra are consistent with a NAA:NAAG concentration ratio of 4.22:1 in good agreement with literature. Simulations indicate some coediting of aspartate and glutathione near the detected region (editing efficiency: 4.5% and 78.2%, respectively, for the NAAG reconstruction and 5.1% and 19.5%, respectively, for the NAA reconstruction). Conclusion The simultaneous and separable detection of two otherwise overlapping metabolites using HERMES is possible at 3T. PMID:27089868

The Midline Protein Regulates Axon Guidance by Blocking the Reiteration of Neuroblast Rows within the Drosophila Ventral Nerve Cord

PubMed Central

Manavalan, Mary Ann; Gaziova, Ivana; Bhat, Krishna Moorthi

2013-01-01

Guiding axon growth cones towards their targets is a fundamental process that occurs in a developing nervous system. Several major signaling systems are involved in axon-guidance, and disruption of these systems causes axon-guidance defects. However, the specific role of the environment in which axons navigate in regulating axon-guidance has not been examined in detail. In Drosophila, the ventral nerve cord is divided into segments, and half-segments and the precursor neuroblasts are formed in rows and columns in individual half-segments. The row-wise expression of segment-polarity genes within the neuroectoderm provides the initial row-wise identity to neuroblasts. Here, we show that in embryos mutant for the gene midline, which encodes a T-box DNA binding protein, row-2 neuroblasts and their neuroectoderm adopt a row-5 identity. This reiteration of row-5 ultimately creates a non-permissive zone or a barrier, which prevents the extension of interneuronal longitudinal tracts along their normal anterior-posterior path. While we do not know the nature of the barrier, the axon tracts either stall when they reach this region or project across the midline or towards the periphery along this zone. Previously, we had shown that midline ensures ancestry-dependent fate specification in a neuronal lineage. These results provide the molecular basis for the axon guidance defects in midline mutants and the significance of proper specification of the environment to axon-guidance. These results also reveal the importance of segmental polarity in guiding axons from one segment to the next, and a link between establishment of broad segmental identity and axon guidance. PMID:24385932

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.

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.

Polymeric peptide pigments with sequence-encoded properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lampel, Ayala; McPhee, Scott A.; Park, Hang-Ah

Melanins are a family of heterogeneous polymeric pigments that provide ultraviolet (UV) light protection, structural support, coloration, and free radical scavenging. Formed by oxidative oligomerization of catecholic small molecules, the physical properties of melanins are influenced by covalent and noncovalent disorder. We report the use of tyrosine-containing tripeptides as tunable precursors for polymeric pigments. In these structures, phenols are presented in a (supra-)molecular context dictated by the positions of the amino acids in the peptide sequence. Oxidative polymerization can be tuned in a sequence-dependent manner, resulting in peptide sequence–encoded properties such as UV absorbance, morphology, coloration, and electrochemical properties overmore » a considerable range. Short peptides have low barriers to application and can be easily scaled, suggesting near-term applications in cosmetics and biomedicine.« less

Effects of Functional Groups in Redox-Active Organic Molecules: A High-Throughput Screening Approach

DOE PAGES

Pelzer, Kenley M.; Cheng, Lei; Curtiss, Larry A.

2016-12-08

Nonaqueous redox flow batteries have attracted recent attention with their potential for high electrochemical storage capacity, with organic electrolytes serving as solvents with a wide electrochemical stability window. Organic molecules can also serve as electroactive species, where molecules with low reduction potentials or high oxidation potentials can provide substantial chemical energy. To identify promising electrolytes in a vast chemical space, high-throughput screening (HTS) of candidate molecules plays an important role, where HTS is used to calculate properties of thousands of molecules and identify a few organic molecules worthy of further attention in battery research. Here, in this work, we presentmore » reduction and oxidation potentials obtained from HTS of 4178 molecules. The molecules are composed of base groups of five- or six-membered rings with one or two functional groups attached, with the set of possible functional groups including both electron-withdrawing and electron-donating groups. In addition to observing the trends in potentials that result from differences in organic base groups and functional groups, we analyze the effects of molecular characteristics such as multiple bonds, Hammett parameters, and functional group position. In conclusion, this work provides useful guidance in determining how the identities of the base groups and functional groups are correlated with desirable reduction and oxidation potentials.« less

Effects of Functional Groups in Redox-Active Organic Molecules: A High-Throughput Screening Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pelzer, Kenley M.; Cheng, Lei; Curtiss, Larry A.

Nonaqueous redox flow batteries have attracted recent attention with their potential for high electrochemical storage capacity, with organic electrolytes serving as solvents with a wide electrochemical stability window. Organic molecules can also serve as electroactive species, where molecules with low reduction potentials or high oxidation potentials can provide substantial chemical energy. To identify promising electrolytes in a vast chemical space, high-throughput screening (HTS) of candidate molecules plays an important role, where HTS is used to calculate properties of thousands of molecules and identify a few organic molecules worthy of further attention in battery research. Here, in this work, we presentmore » reduction and oxidation potentials obtained from HTS of 4178 molecules. The molecules are composed of base groups of five- or six-membered rings with one or two functional groups attached, with the set of possible functional groups including both electron-withdrawing and electron-donating groups. In addition to observing the trends in potentials that result from differences in organic base groups and functional groups, we analyze the effects of molecular characteristics such as multiple bonds, Hammett parameters, and functional group position. In conclusion, this work provides useful guidance in determining how the identities of the base groups and functional groups are correlated with desirable reduction and oxidation potentials.« less

2017 White Paper on recent issues in bioanalysis: aren't BMV guidance/guidelines 'Scientific'? (Part 1 - LCMS: small molecules, peptides and small molecule biomarkers).

PubMed

Welink, Jan; Yang, Eric; Hughes, Nicola; Rago, Brian; Woolf, Eric; Sydor, Jens; Coppola, Laura; Ackermann, Brad; Li, Wenkui; Alley, Stephen C; Arnold, Mark; Berger, Isabella; Briscoe, Chad; Buonarati, Michael; Bustard, Mark; Cancilla, Mark; Cho, Seongeun Julia; Duggan, Jeff; Fraier, Daniela; Garofolo, Fabio; Green, Rachel; Haidar, Sam; Hittle, Lucinda; Ishii-Watabe, Akiko; Islam, Rafiq; Jenkins, Rand; Jones, Barry; Kadavil, John; Kassim, Sean; Kavetska, Olga; Blaye, Olivier Le; Lee, Anita; Liu, Hanlan; Mehl, John; Lima Santos, Gustavo Mendes; Musuku, Adrien; Ramanathan, Ragu; Saito, Yoshiro; Savoie, Natasha; Summerfield, Scott; Surapaneni, Sekhar; Szapacs, Matthew; Tampal, Nilufer; Verhaeghe, Tom; Vinter, Stephen; Whale, Emma

2017-11-01

The 2017 11th Workshop on Recent Issues in Bioanalysis (11th WRIB) took place in Los Angeles/Universal City, California from 3 April 2017 to 7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event - A Full Immersion Week of Bioanalysis, Biomarkers and Immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid LBA/LCMS and ligand-binding assay (LBA) approaches. This 2017 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1) covers the recommendations for Small Molecules, Peptides and Small Molecule Biomarkers using LCMS. Part 2 (Biotherapeutics, Biomarkers and Immunogenicity Assays using Hybrid LBA/LCMS and Regulatory Agencies' Inputs) and Part 3 (LBA: Immunogenicity, Biomarkers and PK Assays) are published in volume 9 of Bioanalysis, issues 23 and 24 (2017), respectively.

A comprehensive study of sampling-based optimum signal detection in concentration-encoded molecular communication.

PubMed

Mahfuz, Mohammad U; Makrakis, Dimitrios; Mouftah, Hussein T

2014-09-01

In this paper, a comprehensive analysis of the sampling-based optimum signal detection in ideal (i.e., free) diffusion-based concentration-encoded molecular communication (CEMC) system has been presented. A generalized amplitude-shift keying (ASK)-based CEMC system has been considered in diffusion-based noise and intersymbol interference (ISI) conditions. Information is encoded by modulating the amplitude of the transmission rate of information molecules at the TN. The critical issues involved in the sampling-based receiver thus developed are addressed in detail, and its performance in terms of the number of samples per symbol, communication range, and transmission data rate is evaluated. ISI produced by the residual molecules deteriorates the performance of the CEMC system significantly, which further deteriorates when the communication range and/or the transmission data rate increase(s). In addition, the performance of the optimum receiver depends on the receiver's ability to compute the ISI accurately, thus providing a trade-off between receiver complexity and achievable bit error rate (BER). Exact and approximate detection performances have been derived. Finally, it is found that the sampling-based signal detection scheme thus developed can be applied to both binary and multilevel (M-ary) ASK-based CEMC systems, although M-ary systems suffer more from higher BER.

The EGF and FGF receptors mediate neuroglian function to control growth cone decisions during sensory axon guidance in Drosophila.

PubMed

García-Alonso, L; Romani, S; Jiménez, F

2000-12-01

Cell adhesion molecules (CAMs) implement the process of axon guidance by promoting specific selection and attachment to substrates. We show that, in Drosophila, loss-of-function conditions of either the Neuroglian CAM, the FGF receptor coded by the gene heartless, or the EGF receptor coded by DER display a similar phenotype of abnormal substrate selection and axon guidance by peripheral sensory neurons. Moreover, neuroglian loss-of-function phenotype can be suppressed by the expression of gain-of-function conditions of heartless or DER. The results are consistent with a scenario where the activity of these receptor tyrosine kinases is controlled by Neuroglian at choice points where sensory axons select between alternative substrates for extension.

Lab-on-a-chip platform for high throughput drug discovery with DNA-encoded chemical libraries

NASA Astrophysics Data System (ADS)

Grünzner, S.; Reddavide, F. V.; Steinfelder, C.; Cui, M.; Busek, M.; Klotzbach, U.; Zhang, Y.; Sonntag, F.

2017-02-01

The fast development of DNA-encoded chemical libraries (DECL) in the past 10 years has received great attention from pharmaceutical industries. It applies the selection approach for small molecular drug discovery. Because of the limited choices of DNA-compatible chemical reactions, most DNA-encoded chemical libraries have a narrow structural diversity and low synthetic yield. There is also a poor correlation between the ranking of compounds resulted from analyzing the sequencing data and the affinity measured through biochemical assays. By combining DECL with dynamical chemical library, the resulting DNA-encoded dynamic library (EDCCL) explores the thermodynamic equilibrium of reversible reactions as well as the advantages of DNA encoded compounds for manipulation/detection, thus leads to enhanced signal-to-noise ratio of the selection process and higher library quality. However, the library dynamics are caused by the weak interactions between the DNA strands, which also result in relatively low affinity of the bidentate interaction, as compared to a stable DNA duplex. To take advantage of both stably assembled dual-pharmacophore libraries and EDCCLs, we extended the concept of EDCCLs to heat-induced EDCCLs (hi-EDCCLs), in which the heat-induced recombination process of stable DNA duplexes and affinity capture are carried out separately. To replace the extremely laborious and repetitive manual process, a fully automated device will facilitate the use of DECL in drug discovery. Herein we describe a novel lab-on-a-chip platform for high throughput drug discovery with hi-EDCCL. A microfluidic system with integrated actuation was designed which is able to provide a continuous sample circulation by reducing the volume to a minimum. It consists of a cooled and a heated chamber for constant circulation. The system is capable to generate stable temperatures above 75 °C in the heated chamber to melt the double strands of the DNA and less than 15 °C in the cooled chamber

76 FR 43332 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

...: Focused Ultrasound Stimulator System for Aesthetic Use; Availability AGENCY: Food and Drug Administration... the guidance entitled, ``Class II Special Controls Guidance Document: Focused Ultrasound Stimulator System for Aesthetic Use.'' This guidance document describes a means by which focused ultrasound...

Plasmonic Encoding

DTIC Science & Technology

2014-10-06

The nanosheets, like many SERS platforms, are ideally suited for encoding schemes based on the SERS signal from a variety of thiolated small...counterfeiting purposes. The nanosheets, like many SERS platforms, are ideally suited for encoding schemes based on the SERS signal from a variety of...environments ( like the surface of human hair). 2. Nanoflares In 2007, we first introduced the concept of nanoflares. Nanoflares are a new class of

Encoding processes during retrieval tasks.

PubMed

Buckner, R L; Wheeler, M E; Sheridan, M A

2001-04-01

Episodic memory encoding is pervasive across many kinds of task and often arises as a secondary processing effect in tasks that do not require intentional memorization. To illustrate the pervasive nature of information processing that leads to episodic encoding, a form of incidental encoding was explored based on the "Testing" phenomenon: The incidental-encoding task was an episodic memory retrieval task. Behavioral data showed that performing a memory retrieval task was as effective as intentional instructions at promoting episodic encoding. During fMRI imaging, subjects viewed old and new words and indicated whether they remembered them. Relevant to encoding, the fate of the new words was examined using a second, surprise test of recognition after the imaging session. fMRI analysis of those new words that were later remembered revealed greater activity in left frontal regions than those that were later forgotten - the same pattern of results as previously observed for traditional incidental and intentional episodic encoding tasks. This finding may offer a partial explanation for why repeated testing improves memory performance. Furthermore, the observation of correlates of episodic memory encoding during retrieval tasks challenges some interpretations that arise from direct comparisons between "encoding tasks" and "retrieval tasks" in imaging data. Encoding processes and their neural correlates may arise in many tasks, even those nominally labeled as retrieval tasks by the experimenter.

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…

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.

What Can Interfacial Water Molecules Tell Us About Solute Structure?

NASA Astrophysics Data System (ADS)

Willard, Adam

The molecular structure of bulk liquid water reflects a molecular tendency to engage in tetrahedrally coordinated hydrogen bonding. At a solute interface waters preferred three-dimensional hydrogen bonding network must conform to a locally anisotropy interfacial environment. Interfacial water molecules adopt configurations that balance water-solute and water-water interactions. The arrangements of interfacial water molecules, therefore encode information about the effective solute-water interactions. This solute-specific information is difficult to extract, however, because interfacial structure also reflects waters collective response to an anisotropic hydrogen bonding environment. Here I present a methodology for characterizing the molecular-level structure of liquid water interface from simulation data. This method can be used to explore waters static and/or dynamic response to a wide range of chemically and topologically heterogeneous solutes such as proteins.

Recent advances on the encoding and selection methods of DNA-encoded chemical library.

PubMed

Shi, Bingbing; Zhou, Yu; Huang, Yiran; Zhang, Jianfu; Li, Xiaoyu

2017-02-01

DNA-encoded chemical library (DEL) has emerged as a powerful and versatile tool for ligand discovery in chemical biology research and in drug discovery. Encoding and selection methods are two of the most important technological aspects of DEL that can dictate the performance and utilities of DELs. In this digest, we have summarized recent advances on the encoding and selection strategies of DEL and also discussed the latest developments on DNA-encoded dynamic library, a new frontier in DEL research. Copyright © 2016 Elsevier Ltd. All rights reserved.

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).

Regulatory Forum Opinion Piece: Review of FDA Draft Guidance Testicular Toxicity-Evaluation during Drug Development Guidance for Industry.

PubMed

Hukkanen, Renee R; Halpern, Wendy G; Vidal, Justin D

2016-10-01

In July 2015, the U.S. Food and Drug Administration (FDA) posted a new draft guidance entitled "Testicular Toxicity: Evaluation during Drug Development Guidance for Industry," with a 90-day public comment period. As the nonclinical assessment of testicular toxicity often relies on the expert interpretation of pathology affecting the male reproductive tract, this draft guidance is considered directly relevant to the toxicologic pathology community. Therefore, a working group was formed through the Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathologists (STPs) to provide a detailed review of the draft guidance. Specific comments on the guidance were submitted to the FDA by the STP. The draft guidance and all comments received are currently under review with the FDA. This commentary provides a summary of the components of the draft guidance and the comments submitted by the STP with acknowledgment of different perspectives reflected in comments from other respondents. © The Author(s) 2016.

28 CFR 77.4 - Guidance.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., gives advice or guidance to another Department attorney about the other attorney's ethical obligations... good faith provides legal advice or guidance upon request to an investigative agent should not be...

28 CFR 77.4 - Guidance.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., gives advice or guidance to another Department attorney about the other attorney's ethical obligations... good faith provides legal advice or guidance upon request to an investigative agent should not be...

Built-in adjuvanticity of genetically and protein-engineered chimeric molecules for targeting of influenza A peptide epitopes.

PubMed

Kerekov, Nikola S; Ivanova, Iva I; Mihaylova, Nikolina M; Nikolova, Maria; Prechl, Jozsef; Tchorbanov, Andrey I

2014-10-01

Highly purified, subunit, or synthetic viral antigens are known to be weakly immunogenic and potentate only the antibody, rather than cell-mediated immune responses. An alternative approach for inducing protective immunity with small viral peptides would be the direct targeting of viral epitopes to the immunocompetent cells by DNA vaccines encoding antibody fragments specific to activating cell surface co-receptor molecules. Here, we are exploring as a new genetic vaccine, a DNA chimeric molecule encoding a T and B cell epitope-containing influenza A virus hemagglutinin peptide joined to sequences encoding a single-chain variable fragment antibody fragment specific for the costimulatory B cell complement receptors 1 and 2. This recombinant DNA molecule was inserted into eukaryotic expression vector and used as a naked DNA vaccine in WT and CR1/2 KO mice. The intramuscular administration of the DNA construct resulted in the in vivo expression of an immunogenic chimeric protein, which cross-links cell surface receptors on influenza-specific B cells. The DNA vaccination was followed by prime-boosting with the protein-engineered replica of the DNA construct, thus delivering an activation intracellular signal. Immunization with an expression vector containing the described construct and boosting with the protein chimera induced a strong anti-influenza cytotoxic response, modulation of cytokine profile, and a weak antibody response in Balb/c mice. The same immunization scheme did not result in generation of influenza-specific response in mice lacking the target receptor, underlining the molecular adjuvant effect of receptor targeting.

Stressor Identification Guidance Document

EPA Science Inventory

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 doc...

Guidance and New Education for Schools.

ERIC Educational Resources Information Center

Sprinthall, Norman A.

1980-01-01

Details rationale for broad-based school reform including examination of old guidance. General curriculum of schools must include psychological growth as direct object of classroom instruction. Effective guidance role can alter classroom teaching strategies and curriculum content. Guidance theory and practice should lead in seeking school reforms.…

NASP guidance design for vehicle autonomy

NASA Astrophysics Data System (ADS)

Wagner, E. A.; Li, I.; Nguyen, D. D.; Nguyen, P. L.

1990-10-01

Vehicle guidance for General Dynamics' NASP vehicle is planned to be self-contained onboard the vehicle, and independent of any ground support during the mission. It will include real-time onboard abort and ascent trajectory optimization capability. Although these features should be considered a natural outgrowth of research in guidance and trajectory optimization and advances in computation, facilitating full vehicle autonomy for NASP represents a significant advance relative to any flight-demonstrated guidance. Algorithms and processing requirements for autonomous NASP vehicle guidance are considered.

Lifelong guidance: How guidance and counselling support lifelong learning in the contrasting contexts of China and Denmark

NASA Astrophysics Data System (ADS)

Zhang, Zhixin

2016-10-01

Due to the effects of globalisation and rapid technological development, traditional linear life course patterns of the past are gradually disappearing, and this affects education and learning systems as well as labour markets. Individuals are forced to develop lifestyles and survival strategies to manage job insecurity and make their skills and interests meet labour market needs. In modern attempts to develop and implement institutional provision for lifelong learning, guidance and counselling play an important role. The current Danish guidance system is well-organised, highly structured and professionalised. By contrast, Chinese guidance is still fragmented and "sectorisational". This paper explores whether elements of the highly structured and professionalised Danish guidance system and practice might be applicable to the Chinese context. The author begins by outlining international and national factors which are affecting citizens' life and career planning. She then presents and discusses the evolution of guidance and the different elements of provision in each of the two countries. Next, She compares the concepts and goals of "lifelong guidance" in Denmark and China, pointing out their similarities and differences and their respective strengths and weaknesses. The paper concludes with some suggestions for the further development of guidance in China.

Video-Guidance Design for the DART Rendezvous Mission

NASA Technical Reports Server (NTRS)

Ruth, Michael; Tracy, Chisholm

2004-01-01

NASA's Demonstration of Autonomous Rendezvous Technology (DART) mission will validate a number of different guidance technologies, including state-differenced GPS transfers and close-approach video guidance. The video guidance for DART will employ NASA/Marshall s Advanced Video Guidance Sensor (AVGS). This paper focuses on the terminal phase of the DART mission that includes close-approach maneuvers under AVGS guidance. The closed-loop video guidance design for DART is driven by a number of competing requirements, including a need for maximizing tracking bandwidths while coping with measurement noise and the need to minimize RCS firings. A range of different strategies for attitude control and docking guidance have been considered for the DART mission, and design decisions are driven by a goal of minimizing both the design complexity and the effects of video guidance lags. The DART design employs an indirect docking approach, in which the guidance position targets are defined using relative attitude information. Flight simulation results have proven the effectiveness of the video guidance design.

76 FR 20992 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-14

...: Low Level Laser System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS... guidance entitled ``Class II Special Controls Guidance Document: Low Level Laser System for Aesthetic Use.'' This guidance document describes a means by which low level laser systems for aesthetic use may comply...

Live-cell imaging of cell signaling using genetically encoded fluorescent reporters.

PubMed

Ni, Qiang; Mehta, Sohum; Zhang, Jin

2018-01-01

Synergistic advances in fluorescent protein engineering and live-cell imaging techniques in recent years have fueled the concurrent development and application of genetically encoded fluorescent reporters that are tailored for tracking signaling dynamics in living systems over multiple length and time scales. These biosensors are uniquely suited for this challenging task, owing to their specificity, sensitivity, and versatility, as well as to the noninvasive and nondestructive nature of fluorescence and the power of genetic encoding. Over the past 10 years, a growing number of fluorescent reporters have been developed for tracking a wide range of biological signals in living cells and animals, including second messenger and metabolite dynamics, enzyme activation and activity, and cell cycle progression and neuronal activity. Many of these biosensors are gaining wide use and are proving to be indispensable for unraveling the complex biological functions of individual signaling molecules in their native environment, the living cell, shedding new light on the structural and molecular underpinnings of cell signaling. In this review, we highlight recent advances in protein engineering that are likely to help expand and improve the design and application of these valuable tools. We then turn our focus to specific examples of live-cell imaging using genetically encoded fluorescent reporters as an important platform for advancing our understanding of G protein-coupled receptor signaling and neuronal activity. © 2017 Federation of European Biochemical Societies.

Small molecules targeting LapB protein prevent Listeria attachment to catfish muscle

PubMed Central

Das, Bhaskar; Lawrence, Mark

2017-01-01

Listeria monocytogenes is a Gram-positive foodborne pathogen and the causative agent of listeriosis. L. monocytogenes lapB gene encodes a cell wall surface anchor protein, and mutation of this gene causes Listeria attenuation in mice. In this work, the potential role of Listeria LapB protein in catfish fillet attachment was investigated. To achieve this, boron-based small molecules designed to interfere with the active site of the L. monocytogenes LapB protein were developed, and their ability to prevent L. monocytogenes attachment to fish fillet was tested. Results indicated that seven out of nine different small molecules were effective in reducing the Listeria attachment to catfish fillets. Of these, three small molecules (SM3, SM5, and SM7) were highly effective in blocking Listeria attachment to catfish fillets. This study suggests an alternative strategy for reduction of L. monocytogenes contamination in fresh and frozen fish products. PMID:29253892

Genetic analysis of an overlapping functional requirement for L1- and NCAM-type proteins during sensory axon guidance in Drosophila.

PubMed

Kristiansen, Lars V; Velasquez, Emma; Romani, Susana; Baars, Sigrid; Berezin, Vladimir; Bock, Elisabeth; Hortsch, Michael; Garcia-Alonso, Luis

2005-01-01

L1- and NCAM-type cell adhesion molecules represent distinct protein families that function as specific receptors for different axon guidance cues. However, both L1 and NCAM proteins promote axonal growth by inducing neuronal tyrosine kinase activity and are coexpressed in subsets of axon tracts in arthropods and vertebrates. We have studied the functional requirements for the Drosophila L1- and NCAM-type proteins, Neuroglian (Nrg) and Fasciclin II (FasII), during postembryonic sensory axon guidance. The rescue of the Neuroglian loss-of-function (LOF) phenotype by transgenically expressed L1- and NCAM-type proteins demonstrates a functional interchangeability between these proteins in Drosophila photoreceptor pioneer axons, where both proteins are normally coexpressed. In contrast, the ectopic expression of Fasciclin II in mechanosensory neurons causes a strong enhancement of the axonal misguidance phenotype. Moreover, our findings demonstrate that this functionally redundant specificity to mediate axon guidance has been conserved in their vertebrate homologs, L1-CAM and NCAM.

47 CFR 11.32 - EAS Encoder.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false EAS Encoder. 11.32 Section 11.32....32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol described... must additionally provide the following minimum specifications: (1) Encoder programming. Access to...

Guidance Program Assessment Procedures for Elementary and Secondary Schools. Georgia Comprehensive Guidance Series.

ERIC Educational Resources Information Center

Gunderson, Margaret S.; Moore, Earl J.

This manual provides a series of assessment instruments that guidance program planners may adopt or adapt to provide a basis for defining the guidance program, educating others about the program, or planning needed program changes. The assessment procedures are designed to gather information about students' needs and progress from the students,…

Treating aerophagia with contingent physical guidance.

PubMed

Garcia, D; Starin, S; Churchill, R M

2001-01-01

Contingent physical guidance was used to treat chronic aerophagia. This consisted of guiding the participant's hand over her mouth following each attempt to engage in aerophagia. A wristwatch was then correlated with the contingent physical guidance procedure. Responding remained low in the presence of the wristwatch, even after contingent physical guidance was withdrawn.

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.

A Formal Investigation of the Organization of Guidance Behavior: Implications for Humans and Autonomous Guidance

NASA Astrophysics Data System (ADS)

Kong, Zhaodan

Guidance behavior generated either by artificial agents or humans has been actively studied in the fields of both robotics and cognitive science. The goals of these two fields are different. The former is the automatic generation of appropriate or even optimal behavior, while the latter is the understanding of the underlying mechanism. Their challenges, though, are closely related, the most important one being the lack of a unified, formal and grounded framework where the guidance behavior can be modeled and studied. This dissertation presents such a framework. In this framework, guidance behavior is analyzed as the closed-loop dynamics of the whole agent-environment system. The resulting dynamics give rise to interaction patterns. The central points of this dissertation are that: first of all, these patterns, which can be explained in terms of symmetries that are inherent to the guidance behavior, provide building blocks for the organization of behavior; second, the existence of these patterns and humans' organization of their guidance behavior based on these patterns are the reasons that humans can generate successful behavior in spite of all the complexities involved in the planning and control. This dissertation first gives an overview of the challenges existing in both scientific endeavors, such as human and animal spatial behavior study, and engineering endeavors, such as autonomous guidance system design. It then lays out the foundation for our formal framework, which states that guidance behavior should be interpreted as the collection of the closed-loop dynamics resulting from the agent's interaction with the environment. The following, illustrated by examples of three different UAVs, shows that the study of the closed-loop dynamics should not be done without the consideration of vehicle dynamics, as is the common practice in some of the studies in both autonomous guidance and human behavior analysis. The framework, the core concepts of which are

76 FR 44594 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0465] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document... guidance document will serve as the special control for rTMS systems. Section 513(f)(2) of the Federal Food...

The Elementary School Guidance Counselor: A Developmental Model.

ERIC Educational Resources Information Center

Gum, Moy F.

The position taken is that elementary schools need a guidance program and an elementary school guidance counselor who is a regular member of a given school staff. However, it is advocated that elementary guidance should not be merely an extension of the secondary guidance program. The viewpoint taken here is that elementary guidance should be…

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,…

Treating aerophagia with contingent physical guidance.

PubMed Central

Garcia, D; Starin, S; Churchill, R M

2001-01-01

Contingent physical guidance was used to treat chronic aerophagia. This consisted of guiding the participant's hand over her mouth following each attempt to engage in aerophagia. A wristwatch was then correlated with the contingent physical guidance procedure. Responding remained low in the presence of the wristwatch, even after contingent physical guidance was withdrawn. PMID:11317995

Genetic interaction of Neuroglian and Semaphorin1a during guidance and synapse formation.

PubMed

Godenschwege, Tanja A; Murphey, Rodney K

2009-01-01

We have previously demonstrated a function for Neuroglian and Semaphorin1a in Drosophila giant fiber circuit formation. Both molecules are required for guiding the giant fibers out of the brain and have distinct functions during giant synapse formation. In this study we characterized the effects of various combinations of Neuroglian and Semaphorin1a gain and loss of function backgrounds on giant fiber circuitry formation. We found that Neuroglian and Semaphorin1a genetically interact with each other during axon guidance as well as during synapse formation. Our experiments revealed that during pathfinding of the giant fibers out of the brain, Neuroglian function seems to be dependent on Semaphorin1a. In contrast, during giant fiber synapse formation we observed that Semaphorin1a signaling as a receptor can be altered by Neuroglian in the same cell. In summary, our findings suggest that Neuroglian and Semaphorin1a can regulate each other's function in cis and that the resultant signaling output is possibly different during guidance and synapse formation.

Genetic Interaction of Neuroglian and Semaphorin1a during Guidance and Synapse Formation

PubMed Central

Godenschwege, Tanja A.; Murphey, Rodney K.

2009-01-01

We have previously demonstrated a function for Neuroglian and Semaphorin1a in Drosophila giant fiber circuit formation. Both molecules are required for guiding the giant fibers out of the brain and have distinct functions during giant synapse formation. In this study we characterized the effects of various combinations of Neuroglian and Semaphorin1a gain and loss of function backgrounds on giant fiber circuitry formation. We found that Neuroglian and Semaphorin1a genetically interact with each other during axon guidance as well as during synapse formation. Our experiments revealed that during pathfinding of the giant fibers out of the brain, Neuroglian function seems to be dependent on Semaphorin1a. In contrast, during giant fiber synapse formation we observed that Semaphorin1a signaling as a receptor can be altered by Neuroglian in the same cell. In summary, our findings suggest that Neuroglian and Semaphorin1a can regulate each other’s function in cis and that the resultant signaling output is possibly different during guidance and synapse formation. PMID:19052954

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.

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.

Is Career Guidance for the Individual or for the Market? Implications of EU Policy for Career Guidance

ERIC Educational Resources Information Center

Bergmo-Prvulovic, Ingela

2014-01-01

This paper explores the essential understanding and underlying perspectives of career implicit in EU career guidance policy in the twenty-first century, as well as the possible implications of these for the future mission of guidance. Career theories, models and concepts that serve career guidance are shaped on the twentieth-century industrial…

BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

EPA Pesticide Factsheets

The purpose of this document is to provide guidance for the Agency on the application of the benchmark dose approach in determining the point of departure (POD) for health effects data, whether a linear or nonlinear low dose extrapolation is used. The guidance includes discussion on computation of benchmark doses and benchmark concentrations (BMDs and BMCs) and their lower confidence limits, data requirements, dose-response analysis, and reporting requirements. This guidance is based on today's knowledge and understanding, and on experience gained in using this approach.

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…

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.

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.

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.

Molecular Determinants of Peptide Binding to Two Common Rhesus Macaque Major Histocompatibility Complex Class II Molecules

PubMed Central

Dzuris, John L.; Sidney, John; Horton, Helen; Correa, Rose; Carter, Donald; Chesnut, Robert W.; Watkins, David I.; Sette, Alessandro

2001-01-01

Major histocompatibility complex class II molecules encoded by two common rhesus macaque alleles Mamu-DRB1*0406 and Mamu-DRB*w201 have been purified, and quantitative binding assays have been established. The structural requirements for peptide binding to each molecule were characterized by testing panels of single-substitution analogs of the two previously defined epitopes HIV Env242 (Mamu-DRB1*0406 restricted) and HIV Env482 (Mamu-DRB*w201 restricted). Anchor positions of both macaque DR molecules were spaced following a position 1 (P1), P4, P6, P7, and P9 pattern. The specific binding motif associated with each molecule was distinct, but largely overlapping, and was based on crucial roles of aromatic and/or hydrophobic residues at P1, P6, and P9. Based on these results, a tentative Mamu class II DR supermotif was defined. This pattern is remarkably similar to a previously defined human HLA-DR supermotif. Similarities in binding motifs between human HLA and macaque Mamu-DR molecules were further illustrated by testing a panel of more than 60 different single-substitution analogs of the HLA-DR-restricted HA 307–319 epitope for binding to Mamu-DRB*w201 and HLA-DRB1*0101. The Mamu-DRB1*0406 and -DRB*w201 binding capacity of a set of 311 overlapping peptides spanning the entire simian immunodeficiency virus (SIV) genome was also evaluated. Ten peptides capable of binding both molecules were identified, together with 19 DRB1*0406 and 43 DRB*w201 selective binders. The Mamu-DR supermotif was found to be present in about 75% of the good binders and in 50% of peptides binding with intermediate affinity but only in approximately 25% of the peptides which did not bind either Mamu class II molecule. Finally, using flow cytometric detection of antigen-induced intracellular gamma interferon, we identify a new CD4+ T-lymphocyte epitope encoded within the Rev protein of SIV. PMID:11602736

32 CFR 2001.16 - Fundamental classification guidance review.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 6 2010-07-01 2010-07-01 false Fundamental classification guidance review. 2001... INFORMATION Classification § 2001.16 Fundamental classification guidance review. (a) Performance of fundamental classification guidance reviews. An initial fundamental classification guidance review shall be...

Phytosulfokine peptide signaling controls pollen tube growth and funicular pollen tube guidance in Arabidopsis thaliana.

PubMed

Stührwohldt, Nils; Dahlke, Renate I; Kutschmar, Anke; Peng, Xiongbo; Sun, Meng-Xiang; Sauter, Margret

2015-04-01

Phytosulfokine (PSK) is a peptide growth factor that requires tyrosine sulfation carried out by tyrosylprotein sulfotransferase (TPST) for its activity. PSK is processed from precursor proteins encoded by five genes in Arabidopsis thaliana and perceived by receptor kinases encoded by two genes in Arabidopsis. pskr1-3 pskr2-1 and tpst-1 knockout mutants displayed reduced seed production, indicative of a requirement for PSK peptide signaling in sexual plant reproduction. Expression analysis revealed PSK precursor and PSK receptor gene activity in reproductive organs with strong expression of PSK2 in pollen. In support of a role for PSK signaling in pollen, in vitro pollen tube (PT) growth was enhanced by exogenously added PSK while PTs of pskr1-3 pskr2-1 and of tpst-1 were shorter. In planta, growth of wild-type pollen in pskr1-3 pskr2-1 and tpst-1 flowers appeared slower than growth in wild-type flowers. But PTs did eventually reach the base of the style, suggesting that PT elongation rate may not be responsible for the reduced fertility. Detailed analysis of anthers, style and ovules did not reveal obvious developmental defects. By contrast, a high percentage of unfertilized ovules in pskr1-3 pskr2-1 and in tpst-1 siliques displayed loss of funicular PT guidance, suggesting that PSK signaling is required to guide the PT from the transmitting tract to the embryo sac. Cross-pollination experiments with wild-type, pskr1-3 pskr2-1 and tpst-1 male and female parents revealed that both the PT and the female sporophytic tissue and/or female gametophyte contribute to successful PT guidance via PSK signaling and to fertilization success. © 2014 Scandinavian Plant Physiology Society.

GET-SERF, a new gradient encoded SERF experiment for the trivial edition of 1H-19F couplings

NASA Astrophysics Data System (ADS)

Di Pietro, Maria Enrica; Aroulanda, Christie; Merlet, Denis

2013-09-01

A new spatially encoded heteronuclear 1H-19F selective refocusing NMR experiment (GET-SERF) is proposed. This sequence allows editing in one single 2D experiment all couplings between a selected fluorine site and all the proton nuclei of the molecule. Its efficiency is illustrated in the case of diflunisal, a difluorinated anti-inflammatory drug, in isotropic and anisotropic media.

Design, Optimization and Application of Small Molecule Biosensor in Metabolic Engineering.

PubMed

Liu, Yang; Liu, Ye; Wang, Meng

2017-01-01

The development of synthetic biology and metabolic engineering has painted a great future for the bio-based economy, including fuels, chemicals, and drugs produced from renewable feedstocks. With the rapid advance of genome-scale modeling, pathway assembling and genome engineering/editing, our ability to design and generate microbial cell factories with various phenotype becomes almost limitless. However, our lack of ability to measure and exert precise control over metabolite concentration related phenotypes becomes a bottleneck in metabolic engineering. Genetically encoded small molecule biosensors, which provide the means to couple metabolite concentration to measurable or actionable outputs, are highly promising solutions to the bottleneck. Here we review recent advances in the design, optimization and application of small molecule biosensor in metabolic engineering, with particular focus on optimization strategies for transcription factor (TF) based biosensors.

Design, Optimization and Application of Small Molecule Biosensor in Metabolic Engineering

PubMed Central

Liu, Yang; Liu, Ye; Wang, Meng

2017-01-01

The development of synthetic biology and metabolic engineering has painted a great future for the bio-based economy, including fuels, chemicals, and drugs produced from renewable feedstocks. With the rapid advance of genome-scale modeling, pathway assembling and genome engineering/editing, our ability to design and generate microbial cell factories with various phenotype becomes almost limitless. However, our lack of ability to measure and exert precise control over metabolite concentration related phenotypes becomes a bottleneck in metabolic engineering. Genetically encoded small molecule biosensors, which provide the means to couple metabolite concentration to measurable or actionable outputs, are highly promising solutions to the bottleneck. Here we review recent advances in the design, optimization and application of small molecule biosensor in metabolic engineering, with particular focus on optimization strategies for transcription factor (TF) based biosensors. PMID:29089935

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.

Final OSWER Vapor Intrusion Guidance

EPA Science Inventory

EPA is preparing to finalize its guidance on assessing and addressing vapor intrusion, which is defined as migration of volatile constituents from contaminated media in the subsurface (soil or groundwater) into the indoor environment. In November 2002, EPA issued draft guidance o...

fMRI differences in encoding and retrieval of pictures due to encoding strategy in the elderly.

PubMed

Mandzia, Jennifer L; Black, Sandra E; McAndrews, Mary Pat; Grady, Cheryl; Graham, Simon

2004-01-01

Functional MRI (fMRI) was used to examine the neural correlates of depth of processing during encoding and retrieval of photographs in older normal volunteers (n = 12). Separate scans were run during deep (natural vs. man-made decision) and shallow (color vs. black-and-white decision) encoding and during old/new recognition of pictures initially presented in one of the two encoding conditions. A baseline condition consisting of a scrambled, color photograph was used as a contrast in each scan. Recognition accuracy was greater for the pictures on which semantic decisions were made at encoding, consistent with the expected levels of processing effect. A mixed-effects model was used to compare fMRI differences between conditions (deep-baseline vs. shallow-baseline) in both encoding and retrieval. For encoding, this contrast revealed greater activation associated with deep encoding in several areas, including the left parahippocampal gyrus (PHG), left middle temporal gyrus, and left anterior thalamus. Increased left hippocampal, right dorsolateral, and inferior frontal activations were found for recognition of items that had been presented in the deep relative to the shallow encoding condition. We speculate that the modulation of activity in these regions by the depth of processing manipulation shows that these regions support effective encoding and successful retrieval. A direct comparison between encoding and retrieval revealed greater activation during retrieval in the medial temporal (right hippocampus and bilateral PHG), anterior cingulate, and bilateral prefrontal (inferior and dorsolateral). Most notably, greater right posterior PHG was found during encoding compared to recognition. Focusing on the medial temporal lobe (MTL) region, our results suggest a greater involvement of both anterior MTL and prefrontal regions in retrieval compared to encoding. Copyright 2003 Wiley-Liss, Inc.

FACILITATING LEARNING AND INDIVIDUAL DEVELOPMENT, TOWARD A THEORY FOR ELEMENTARY GUIDANCE. MINNESOTA GUIDANCE SERIES.

ERIC Educational Resources Information Center

GRAMS, ARMIN

A THEORY UPON WHICH ELEMENTARY GUIDANCE PROGRAMS CAN BE SOUNDLY DESIGNED IS PRESENTED. A MAJOR THEME IS THAT PSYCHOLOGICAL WELL-BEING OR GOOD ADJUSTMENT IS RELATED TO LEARNED, INDIVIDUAL COMPETENCIES SUCH AS COMMUNICATION AND INTERACTION IN DEPTH WITH OTHERS. THE APPROPRIATE CONCERN OF GUIDANCE THEN BECOMES TO FOSTER THESE COMPETENCIES, THUS…

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

NASA Astrophysics Data System (ADS)

Culp, Robert D.; Bickley, George

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. For individual titles, see A95-80390 through A95-80436.

Examining the implementation of NICE guidance: cross-sectional survey of the use of NICE interventional procedures guidance by NHS Trusts.

PubMed

Lowson, Karin; Jenks, Michelle; Filby, Alexandra; Carr, Louise; Campbell, Bruce; Powell, John

2015-06-30

In the UK, NHS hospitals receive large amounts of evidence-based recommendations for care delivery from the National Institute for Health and Care Excellence (NICE) and other organisations. Little is known about how NHS organisations implement such guidance and best practice for doing so. This study was therefore designed to examine the dissemination, decision-making, and monitoring processes for NICE interventional procedures (IP) guidance and to investigate the barriers and enablers to the implementation of such guidance. A cross-sectional survey questionnaire was developed and distributed to individuals responsible for managing the processes around NICE guidance in all 181 acute NHS hospitals in England, Scotland, Wales and Northern Ireland. A review of acute NHS hospital policies for implementing NICE guidance was also undertaken using information available in the public domain and from organisations' websites. The response rate to the survey was 75 % with 135 completed surveys received. Additionally, policies from 25 % of acute NHS hospitals were identified and analysed. NHS acute hospitals typically had detailed processes in place to implement NICE guidance, although organisations recognised barriers to implementation including organisational process barriers, clinical engagement and poor targeting with a large number of guidance issued. Examples of enablers to, and good practice for, implementation of guidance were found, most notably the value of shared learning experiences between NHS hospitals. Implications for NICE were also identified. These included making improvements to the layout of guidance, signposting on the website and making better use of their shared learning platform. Most organisations have robust processes in place to deal with implementing guidance. However, resource limitations and the scope of guidance received by organisations create barriers relating to organisational processes, clinician engagement and financing of new procedures

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...

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.

Development and potential applications of microarrays based on fluorescent nanocrystal-encoded beads for multiplexed cancer diagnostics

NASA Astrophysics Data System (ADS)

Brazhnik, Kristina; Grinevich, Regina; Efimov, Anton E.; Nabiev, Igor; Sukhanova, Alyona

2014-05-01

Advanced multiplexed assays have recently become an indispensable tool for clinical diagnostics. These techniques provide simultaneous quantitative determination of multiple biomolecules in a single sample quickly and accurately. The development of multiplex suspension arrays is currently of particular interest for clinical applications. Optical encoding of microparticles is the most available and easy-to-use technique. This technology uses fluorophores incorporated into microbeads to obtain individual optical codes. Fluorophore-encoded beads can be rapidly analyzed using classical flow cytometry or microfluidic techniques. We have developed a new generation of highly sensitive and specific diagnostic systems for detection of cancer antigens in human serum samples based on microbeads encoded with fluorescent quantum dots (QDs). The designed suspension microarray system was validated for quantitative detection of (1) free and total prostate specific antigen (PSA) in the serum of patients with prostate cancer and (2) carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) in the serum of patients with breast cancer. The serum samples from healthy donors were used as a control. The antigen detection is based on the formation of an immune complex of a specific capture antibody (Ab), a target antigen (Ag), and a detector Ab on the surface of the encoded particles. The capture Ab is bound to the polymer shell of microbeads via an adapter molecule, for example, protein A. Protein A binds a monoclonal Ab in a highly oriented manner due to specific interaction with the Fc-region of the Ab molecule. Each antigen can be recognized and detected due to a specific microbead population carrying the unique fluorescent code. 100 and 231 serum samples from patients with different stages of prostate cancer and breast cancer, respectively, and those from healthy donors were examined using the designed suspension system. The data were validated by comparing with the results of

Signaling Lymphocytic Activation Molecule Family Receptor Homologs in New World Monkey Cytomegaloviruses.

PubMed

Pérez-Carmona, Natàlia; Farré, Domènec; Martínez-Vicente, Pablo; Terhorst, Cox; Engel, Pablo; Angulo, Ana

2015-11-01

Throughout evolution, large DNA viruses have been usurping genes from their hosts to equip themselves with proteins that restrain host immune defenses. Signaling lymphocytic activation molecule (SLAM) family (SLAMF) receptors are involved in the regulation of both innate and adaptive immunity, which occurs upon engagement with their ligands via homotypic or heterotypic interactions. Here we report a total of seven SLAMF genes encoded by the genomes of two cytomegalovirus (CMV) species, squirrel monkey CMV (SMCMV) and owl monkey CMV (OMCMV), that infect New World monkeys. Our results indicate that host genes were captured by retrotranscription at different stages of the CMV-host coevolution. The most recent acquisition led to S1 in SMCMV. S1 is a SLAMF6 homolog with an amino acid sequence identity of 97% to SLAMF6 in its ligand-binding N-terminal Ig domain. We demonstrate that S1 is a cell surface glycoprotein capable of binding to host SLAMF6. Furthermore, the OMCMV genome encodes A33, an LY9 (SLAMF3) homolog, and A43, a CD48 (SLAMF2) homolog, two soluble glycoproteins which recognize their respective cellular counterreceptors and thus are likely to be viral SLAMF decoy receptors. In addition, distinct copies of further divergent CD48 homologs were found to be encoded by both CMV genomes. Remarkably, all these molecules display a number of unique features, including cytoplasmic tails lacking characteristic SLAMF signaling motifs. Taken together, our findings indicate a novel immune evasion mechanism in which incorporation of host SLAMF receptors that retain their ligand-binding properties enables viruses to interfere with SLAMF functions and to supply themselves with convenient structural molds for expanding their immunomodulatory repertoires. The way in which viruses shape their genomes under the continual selective pressure exerted by the host immune system is central for their survival. Here, we report that New World monkey cytomegaloviruses have broadly

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.

RESEARCH VISIBILITY. VOCATIONAL EDUCATION IS SERVICE--VOCATIONAL GUIDANCE.

ERIC Educational Resources Information Center

LAW, GORDON F.

NINETEEN REVIEWS IN THIS ISSUE PERTAIN TO VOCATIONAL GUIDANCE AND ARE ORGANIZED BY TOPICS--(1) "SYSTEMS TECHNOLOGY IN GUIDANCE" REVIEWS AN EXPLORATORY STUDY OF INFORMATION PROCESSING PROCEDURES AND COMPUTER APPLICATIONS IN GUIDANCE, AND A CONFERENCE ON SYSTEMS DEVELOPMENT FOR VOCATIONAL GUIDANCE, (2) "CAREER DEVELOPMENT THEORY AND PRACTICE" TREATS…

ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia.

PubMed

Landt, Stephen G; Marinov, Georgi K; Kundaje, Anshul; Kheradpour, Pouya; Pauli, Florencia; Batzoglou, Serafim; Bernstein, Bradley E; Bickel, Peter; Brown, James B; Cayting, Philip; Chen, Yiwen; DeSalvo, Gilberto; Epstein, Charles; Fisher-Aylor, Katherine I; Euskirchen, Ghia; Gerstein, Mark; Gertz, Jason; Hartemink, Alexander J; Hoffman, Michael M; Iyer, Vishwanath R; Jung, Youngsook L; Karmakar, Subhradip; Kellis, Manolis; Kharchenko, Peter V; Li, Qunhua; Liu, Tao; Liu, X Shirley; Ma, Lijia; Milosavljevic, Aleksandar; Myers, Richard M; Park, Peter J; Pazin, Michael J; Perry, Marc D; Raha, Debasish; Reddy, Timothy E; Rozowsky, Joel; Shoresh, Noam; Sidow, Arend; Slattery, Matthew; Stamatoyannopoulos, John A; Tolstorukov, Michael Y; White, Kevin P; Xi, Simon; Farnham, Peggy J; Lieb, Jason D; Wold, Barbara J; Snyder, Michael

2012-09-01

Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals.

ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia

PubMed Central

Landt, Stephen G.; Marinov, Georgi K.; Kundaje, Anshul; Kheradpour, Pouya; Pauli, Florencia; Batzoglou, Serafim; Bernstein, Bradley E.; Bickel, Peter; Brown, James B.; Cayting, Philip; Chen, Yiwen; DeSalvo, Gilberto; Epstein, Charles; Fisher-Aylor, Katherine I.; Euskirchen, Ghia; Gerstein, Mark; Gertz, Jason; Hartemink, Alexander J.; Hoffman, Michael M.; Iyer, Vishwanath R.; Jung, Youngsook L.; Karmakar, Subhradip; Kellis, Manolis; Kharchenko, Peter V.; Li, Qunhua; Liu, Tao; Liu, X. Shirley; Ma, Lijia; Milosavljevic, Aleksandar; Myers, Richard M.; Park, Peter J.; Pazin, Michael J.; Perry, Marc D.; Raha, Debasish; Reddy, Timothy E.; Rozowsky, Joel; Shoresh, Noam; Sidow, Arend; Slattery, Matthew; Stamatoyannopoulos, John A.; Tolstorukov, Michael Y.; White, Kevin P.; Xi, Simon; Farnham, Peggy J.; Lieb, Jason D.; Wold, Barbara J.; Snyder, Michael

2012-01-01

Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals. PMID:22955991

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…

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,…

Comparative performance of a genetically-encoded voltage indicator and a blue voltage sensitive dye for large scale cortical voltage imaging

PubMed Central

Mutoh, Hiroki; Mishina, Yukiko; Gallero-Salas, Yasir; Knöpfel, Thomas

2015-01-01

Traditional small molecule voltage sensitive dye indicators have been a powerful tool for monitoring large scale dynamics of neuronal activities but have several limitations including the lack of cell class specific targeting, invasiveness and difficulties in conducting longitudinal studies. Recent advances in the development of genetically-encoded voltage indicators have successfully overcome these limitations. Genetically-encoded voltage indicators (GEVIs) provide sufficient sensitivity to map cortical representations of sensory information and spontaneous network activities across cortical areas and different brain states. In this study, we directly compared the performance of a prototypic GEVI, VSFP2.3, with that of a widely used small molecule voltage sensitive dye (VSD), RH1691, in terms of their ability to resolve mesoscopic scale cortical population responses. We used three synchronized CCD cameras to simultaneously record the dual emission ratiometric fluorescence signal from VSFP2.3 and RH1691 fluorescence. The results show that VSFP2.3 offers more stable and less invasive recording conditions, while the signal-to-noise level and the response dynamics to sensory inputs are comparable to RH1691 recordings. PMID:25964738

Molecules and mechanisms involved in the generation and migration of cortical interneurons

PubMed Central

Hernández-Miranda, Luis R; Parnavelas, John G; Chiara, Francesca

2010-01-01

The GABA (γ-aminobutyric acid)-containing interneurons of the neocortex are largely derived from the ganglionic eminences in the subpallium. Numerous studies have previously defined the migratory paths travelled by these neurons from their origins to their destinations in the cortex. We review here results of studies that have identified many of the genes expressed in the subpallium that are involved in the specification of the subtypes of cortical interneurons, and the numerous transcription factors, motogenic factors and guidance molecules that are involved in their migration. PMID:20360946

Unconscious relational encoding depends on hippocampus

PubMed Central

Duss, Simone B.; Reber, Thomas P.; Hänggi, Jürgen; Schwab, Simon; Wiest, Roland; Müri, René M.; Brugger, Peter; Gutbrod, Klemens

2014-01-01

Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998

Stress as a mnemonic filter: Interactions between medial temporal lobe encoding processes and post-encoding stress

PubMed Central

Ritchey, Maureen; McCullough, Andrew M.; Ranganath, Charan; Yonelinas, Andrew P.

2016-01-01

Acute stress has been shown to modulate memory for recently learned information, an effect attributed to the influence of stress hormones on medial temporal lobe (MTL) consolidation processes. However, little is known about which memories will be affected when stress follows encoding. One possibility is that stress interacts with encoding processes to selectively protect memories that had elicited responses in the hippocampus and amygdala, two MTL structures important for memory formation. There is limited evidence for interactions between encoding processes and consolidation effects in humans, but recent studies of consolidation in rodents have emphasized the importance of encoding “tags” for determining the impact of consolidation manipulations on memory. Here, we used fMRI in humans to test the hypothesis that the effects of post-encoding stress depend on MTL processes observed during encoding. We found that changes in stress hormone levels were associated with an increase in the contingency of memory outcomes on hippocampal and amygdala encoding responses. That is, for participants showing high cortisol reactivity, memories became more dependent on MTL activity observed during encoding, thereby shifting the distribution of recollected events toward those that had elicited relatively high activation. Surprisingly, this effect was generally larger for neutral, compared to emotionally negative, memories. The results suggest that stress does not uniformly enhance memory, but instead selectively preserves memories tagged during encoding, effectively acting as mnemonic filter. PMID:27774683

Nucleic acid molecules conferring enhanced ethanol tolerance and microorganisms having enhanced tolerance to ethanol

DOEpatents

Brown, Steven; Guss, Adam; Yang, Shihui; Karpinets, Tatiana; Lynd, Lee; Shao, Xiongjun

2014-01-14

The present invention provides isolated nucleic acid molecules which encode a mutant acetaldehyde-CoA/alcohol dehydrogenase or mutant alcohol dehydrogenase and confer enhanced tolerance to ethanol. The invention also provides related expression vectors, genetically engineered microorganisms having enhanced tolerance to ethanol, as well as methods of making and using such genetically modified microorganisms for production of biofuels based on fermentation of biomass materials.

Identification and characterization of the gltK gene encoding a membrane-associated glucose transport protein of pseudomonas aeruginosa.

PubMed

Adewoye, L O; Worobec, E A

2000-08-08

The Pseudomonas aeruginosa oprB gene encodes the carbohydrate-selective OprB porin, which translocates substrate molecules across the outer membrane to the periplasmic glucose-binding protein. We identified and cloned two open reading frames (ORFs) flanking the oprB gene but are not in operonic arrangement with the oprB gene. The downstream ORF encodes a putative polypeptide homologous to members of a family of transcriptional repressors, whereas the oprB gene is preceded by an ORF encoding a putative product, which exhibits strong homology to several carbohydrate transport ATP-binding cassette (ABC) proteins. The genomic copy of the upstream ORF was mutagenized by homologous recombination. Analysis of the deletion mutant in comparison with the wild type revealed a significant reduction in [14C] glucose transport activity in the mutant strain, suggesting that this ORF likely encodes the inner membrane component of the glucose ABC transporter. It is thus designated gltK gene to reflect its homology to the Pseudomona fluorescens mtlK and its involvement in the high-affinity glucose transport system. Multiple alignment analysis revealed that the P. aeruginosa gltK gene product is a member of the MalK subfamily of ABC proteins.

The continuum of behavior guidance.

PubMed

Nelson, Travis

2013-01-01

Behavior guidance is a continuum of techniques, basic and advanced, fundamental to the provision of quality dental care for pediatric patients. This practice must be individualized, pairing the correct method of behavior guidance with each child. To select the appropriate technique, the clinician must have a thorough understanding of each aspect of the continuum and anticipate parental expectations, child temperament, and the technical procedures necessary to complete care. By effectively using techniques within the continuum of behavior guidance, a healing relationship with the family is maintained while addressing dental disease and empowering the child to receive dental treatment throughout their lifetime. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Development of B cells expressing surface immunoglobulin molecules that lack V(D)J-encoded determinants in the avian embryo bursa of Fabricius

PubMed Central

Sayegh, Camil E.; Demaries, Sandra L.; Iacampo, Sandra; Ratcliffe, Michael J. H.

1999-01-01

Immunoglobulin gene rearrangement in avian B cell precursors generates surface Ig receptors of limited diversity. It has been proposed that specificities encoded by these receptors play a critical role in B lineage development by recognizing endogenous ligands within the bursa of Fabricius. To address this issue directly we have introduced a truncated surface IgM, lacking variable region domains, into developing B precursors by retroviral gene transfer in vivo. Cells expressing this truncated receptor lack endogenous surface IgM, and the low level of endogenous Ig rearrangements that have occurred within this population of cells has not been selected for having a productive reading frame. Such cells proliferate rapidly within bursal epithelial buds of normal morphology. In addition, despite reduced levels of endogenous light chain rearrangement, those light chain rearrangements that have occurred have undergone variable region diversification by gene conversion. Therefore, although surface expression of an Ig receptor is required for bursal colonization and the induction of gene conversion, the specificity encoded by the prediversified receptor is irrelevant and, consequently, there is no obligate ligand for V(D)J-encoded determinants of prediversified avian cell surface IgM receptor. PMID:10485907

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…

Guidance in the Middle Schools.

ERIC Educational Resources Information Center

New York City Board of Education, Brooklyn, NY. Bureau of Curriculum Development.

This publication is designed to assist the guidance counselor, the administrator, the supervisors, and other members of the school staff to integrate a developmental guidance program into the total educational process of the preadolescent in an urban society. Special attention is devoted to appropriate topics and techniques for use in individual…

Landscape Encodings Enhance Optimization

PubMed Central

Klemm, Konstantin; Mehta, Anita; Stadler, Peter F.

2012-01-01

Hard combinatorial optimization problems deal with the search for the minimum cost solutions (ground states) of discrete systems under strong constraints. A transformation of state variables may enhance computational tractability. It has been argued that these state encodings are to be chosen invertible to retain the original size of the state space. Here we show how redundant non-invertible encodings enhance optimization by enriching the density of low-energy states. In addition, smooth landscapes may be established on encoded state spaces to guide local search dynamics towards the ground state. PMID:22496860

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

21 CFR 7.59 - General industry guidance.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false General industry guidance. 7.59 Section 7.59 Food... POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry Responsibilities § 7.59 General industry guidance. A recall can be disruptive of a firm's operation and business...

21 CFR 7.59 - General industry guidance.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false General industry guidance. 7.59 Section 7.59 Food... POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry Responsibilities § 7.59 General industry guidance. A recall can be disruptive of a firm's operation and business...

21 CFR 7.59 - General industry guidance.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false General industry guidance. 7.59 Section 7.59 Food... POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry Responsibilities § 7.59 General industry guidance. A recall can be disruptive of a firm's operation and business...

21 CFR 7.59 - General industry guidance.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false General industry guidance. 7.59 Section 7.59 Food... POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry Responsibilities § 7.59 General industry guidance. A recall can be disruptive of a firm's operation and business...

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

New FDA draft guidance on immunogenicity.

PubMed

Parenky, Ashwin; Myler, Heather; Amaravadi, Lakshmi; Bechtold-Peters, Karoline; Rosenberg, Amy; Kirshner, Susan; Quarmby, Valerie

2014-05-01

A "Late Breaking" session was held on May 20 at the 2013 American Association of Pharmaceutical Scientists-National Biotech Conference (AAPS-NBC) to discuss the US Food and Drug Administration's (FDA) 2013 draft guidance on Immunogenicity Assessment for Therapeutic Protein Products. The session was initiated by a presentation from the FDA which highlighted several key aspects of the 2013 draft guidance pertaining to immunogenicity risk, the potential impact on patient safety and product efficacy, and risk mitigation. This was followed by an open discussion on the draft guidance which enabled delegates from biopharmaceutical companies to engage the FDA on topics that had emerged from their review of the draft guidance. The multidisciplinary audience fostered an environment that was conducive to scientific discussion on a broad range of topics such as clinical impact, immune mitigation strategies, immune prediction and the role of formulation, excipients, aggregates, and degradation products in immunogenicity. This meeting report highlights several key aspects of the 2013 draft guidance together with related dialog from the session.

A neural net approach to space vehicle guidance

NASA Technical Reports Server (NTRS)

Caglayan, Alper K.; Allen, Scott M.

1990-01-01

The space vehicle guidance problem is formulated using a neural network approach, and the appropriate neural net architecture for modeling optimum guidance trajectories is investigated. In particular, an investigation is made of the incorporation of prior knowledge about the characteristics of the optimal guidance solution into the neural network architecture. The online classification performance of the developed network is demonstrated using a synthesized network trained with a database of optimum guidance trajectories. Such a neural-network-based guidance approach can readily adapt to environment uncertainties such as those encountered by an AOTV during atmospheric maneuvers.

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.

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…

Career Guidance in Five English Independent Schools

ERIC Educational Resources Information Center

Hutchinson, Jo

2018-01-01

English independent schools are not required to follow government statutory guidance in a number of aspects including career education and guidance, and yet many are actively engaged in careers work and this has caught the attention of policymakers. State schools are subject to statutory guidance but, according to Ofsted and other authorities, the…

Meet Guidance Needs of Older Adults. Module CG C-16 of Category C--Implementing. Competency-Based Career Guidance Modules.

ERIC Educational Resources Information Center

Cook, Patricia; Stewart, Ellen

This learning module, one in a series of competency-based guidance program training packages focusing upon professional and paraprofessional competencies of guidance personnel, deals with meeting the guidance needs of older adults. Addressed in the module are the following topics: describing a negative and a positive bias, stereotype, or attitude…

Visual encoding and fixation target selection in free viewing: presaccadic brain potentials

PubMed Central

Nikolaev, Andrey R.; Jurica, Peter; Nakatani, Chie; Plomp, Gijs; van Leeuwen, Cees

2013-01-01

In scrutinizing a scene, the eyes alternate between fixations and saccades. During a fixation, two component processes can be distinguished: visual encoding and selection of the next fixation target. We aimed to distinguish the neural correlates of these processes in the electrical brain activity prior to a saccade onset. Participants viewed color photographs of natural scenes, in preparation for a change detection task. Then, for each participant and each scene we computed an image heat map, with temperature representing the duration and density of fixations. The temperature difference between the start and end points of saccades was taken as a measure of the expected task-relevance of the information concentrated in specific regions of a scene. Visual encoding was evaluated according to whether subsequent change was correctly detected. Saccades with larger temperature difference were more likely to be followed by correct detection than ones with smaller temperature differences. The amplitude of presaccadic activity over anterior brain areas was larger for correct detection than for detection failure. This difference was observed for short “scrutinizing” but not for long “explorative” saccades, suggesting that presaccadic activity reflects top-down saccade guidance. Thus, successful encoding requires local scanning of scene regions which are expected to be task-relevant. Next, we evaluated fixation target selection. Saccades “moving up” in temperature were preceded by presaccadic activity of higher amplitude than those “moving down”. This finding suggests that presaccadic activity reflects attention deployed to the following fixation location. Our findings illustrate how presaccadic activity can elucidate concurrent brain processes related to the immediate goal of planning the next saccade and the larger-scale goal of constructing a robust representation of the visual scene. PMID:23818877

DOE Waste Treatability Group Guidance

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 solemore » 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.« less

MHC2NNZ: A novel peptide binding prediction approach for HLA DQ molecules

NASA Astrophysics Data System (ADS)

Xie, Jiang; Zeng, Xu; Lu, Dongfang; Liu, Zhixiang; Wang, Jiao

2017-07-01

The major histocompatibility complex class II (MHC-II) molecule plays a crucial role in immunology. Computational prediction of MHC-II binding peptides can help researchers understand the mechanism of immune systems and design vaccines. Most of the prediction algorithms for MHC-II to date have made large efforts in human leukocyte antigen (HLA, the name of MHC in Human) molecules encoded in the DR locus. However, HLA DQ molecules are equally important and have only been made less progress because it is more difficult to handle them experimentally. In this study, we propose an artificial neural network-based approach called MHC2NNZ to predict peptides binding to HLA DQ molecules. Unlike previous artificial neural network-based methods, MHC2NNZ not only considers sequence similarity features but also captures the chemical and physical properties, and a novel method incorporating these properties is proposed to represent peptide flanking regions (PFR). Furthermore, MHC2NNZ improves the prediction accuracy by combining with amino acid preference at more specific positions of the peptides binding core. By evaluating on 3549 peptides binding to six most frequent HLA DQ molecules, MHC2NNZ is demonstrated to outperform other state-of-the-art MHC-II prediction methods.

A DNA-Encoded Library of Chemical Compounds Based on Common Scaffolding Structures Reveals the Impact of Ligand Geometry on Protein Recognition.

PubMed

Favalli, Nicholas; Biendl, Stefan; Hartmann, Marco; Piazzi, Jacopo; Sladojevich, Filippo; Gräslund, Susanne; Brown, Peter J; Näreoja, Katja; Schüler, Herwig; Scheuermann, Jörg; Franzini, Raphael; Neri, Dario

2018-06-01

A DNA-encoded chemical library (DECL) with 1.2 million compounds was synthesized by combinatorial reaction of seven central scaffolds with two sets of 343×492 building blocks. Library screening by affinity capture revealed that for some target proteins, the chemical nature of building blocks dominated the selection results, whereas for other proteins, the central scaffold also crucially contributed to ligand affinity. Molecules based on a 3,5-bis(aminomethyl)benzoic acid core structure were found to bind human serum albumin with a K d value of 6 nm, while compounds with the same substituents on an equidistant but flexible l-lysine scaffold showed 140-fold lower affinity. A 18 nm tankyrase-1 binder featured l-lysine as linking moiety, while molecules based on d-Lysine or (2S,4S)-amino-l-proline showed no detectable binding to the target. This work suggests that central scaffolds which predispose the orientation of chemical building blocks toward the protein target may enhance the screening productivity of encoded libraries. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nucleotide sequencing and characterization of the genes encoding benzene oxidation enzymes of Pseudomonas putida.

PubMed Central

Irie, S; Doi, S; Yorifuji, T; Takagi, M; Yano, K

1987-01-01

The nucleotide sequence of the genes from Pseudomonas putida encoding oxidation of benzene to catechol was determined. Five open reading frames were found in the sequence. Four corresponding protein molecules were detected by a DNA-directed in vitro translation system. Escherichia coli cells containing the fragment with the four open reading frames transformed benzene to cis-benzene glycol, which is an intermediate of the oxidation of benzene to catechol. The relation between the product of each cistron and the components of the benzene oxidation enzyme system is discussed. Images PMID:3667527

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…

Localization of Action of the Is50-Encoded Transposase Protein

PubMed Central

Phadnis, Suhas H.; Sasakawa, Chihiro; Berg, Douglas E.

1986-01-01

The movement of the bacterial insertion sequence IS50 and of composite elements containing direct terminal repeats of IS50 involves the two ends of IS50, designated O (outside) and I (inside), which are weakly matched in DNA sequence, and an IS50 encoded protein, transposase, which recognizes the O and I ends and acts preferentially in cis. Previous data had suggested that, initially, transposase interacts preferentially with the O end sequence and then, in a second step, with either an O or an I end. To better understand the cis action of transposase and how IS50 ends are selected, we generated a series of composite transposons which contain direct repeats of IS50 elements. In each transposon, one IS50 element encoded transposase (tnp +), and the other contained a null (tnp-) allele. In each of the five sets of composite transposons studied, the transposon for which the tnp+ IS50 element contained its O end was more active than a complementary transposon for which the tnp - IS50 element contained its O end. This pattern of O end use suggests models in which the cis action of transposase and its choice of ends is determined by protein tracking along DNA molecules. PMID:3007274

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.

Ultrasound Guidance for Botulinum Neurotoxin Chemodenervation Procedures.

PubMed

Alter, Katharine E; Karp, Barbara I

2017-12-28

Injections of botulinum neurotoxins (BoNTs) are prescribed by clinicians for a variety of disorders that cause over-activity of muscles; glands; pain and other structures. Accurately targeting the structure for injection is one of the principle goals when performing BoNTs procedures. Traditionally; injections have been guided by anatomic landmarks; palpation; range of motion; electromyography or electrical stimulation. Ultrasound (US) based imaging based guidance overcomes some of the limitations of traditional techniques. US and/or US combined with traditional guidance techniques is utilized and or recommended by many expert clinicians; authors and in practice guidelines by professional academies. This article reviews the advantages and disadvantages of available guidance techniques including US as well as technical aspects of US guidance and a focused literature review related to US guidance for chemodenervation procedures including BoNTs injection.

Guidance and control 1989; Proceedings of the Annual Rocky Mountain Guidance and Control Conference, Keystone, CO, Feb. 4-8, 1989

NASA Astrophysics Data System (ADS)

Culp, Robert D.; Lewis, Robert A.

1989-05-01

Papers are presented on advances in guidance, navigation, and control; guidance and control storyboard displays; attitude referenced pointing systems; guidance, navigation, and control for specialized missions; and recent experiences. Other topics of importance to support the application of guidance and control to the space community include concept design and performance test of a magnetically suspended single-gimbal control moment gyro; design, fabrication and test of a prototype double gimbal control moment gyroscope for the NASA Space Station; the Circumstellar Imaging Telescope Image Motion Compensation System providing ultra-precise control on the Space Station platform; pinpointing landing concepts for the Mars Rover Sample Return mission; and space missile guidance and control simulation and flight testing.

Surface Movement Guidance and Control System

DOT National Transportation Integrated Search

1996-12-12

This Advisory Circular (AC) describes the standards and provides guidance in the : development of a Surface Movement Guidance and Control System (SMGCS) plan for : U.S. airports where scheduled Air Carriers are authorized to conduct operations : when...

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.

Plasmids encoding therapeutic agents

DOEpatents

Keener, William K [Idaho Falls, ID

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.

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.

The discovery of the growth cone and its influence on the study of axon guidance

PubMed Central

Tamariz, Elisa; Varela-Echavarría, Alfredo

2015-01-01

For over a century, there has been a great deal of interest in understanding how neural connectivity is established during development and regeneration. Interest in the latter arises from the possibility that knowledge of this process can be used to re-establish lost connections after lesion or neurodegeneration. At the end of the XIX century, Santiago Ramón y Cajal discovered that the distal tip of growing axons contained a structure that he called the growth cone. He proposed that this structure enabled the axon’s oriented growth in response to attractants, now known as chemotropic molecules. He further proposed that the physical properties of the surrounding tissues could influence the growth cone and the direction of growth. This seminal discovery afforded a plausible explanation for directed axonal growth and has led to the discovery of axon guidance mechanisms that include diffusible attractants and repellants and guidance cues anchored to cell membranes or extracellular matrix. In this review the major events in the development of this field are discussed. PMID:26029056

European Lifelong Guidance Policy Network Representatives' Conceptions of the Role of Information and Communication Technologies Related to National Guidance Policies

ERIC Educational Resources Information Center

Kettunen, Jaana; Vuorinen, Raimo; Ruusuvirta, Outi

2016-01-01

This article reports findings from a phenomenographic investigation into European Lifelong Guidance Policy Network representatives' conceptions of the role of information and communication technologies (ICT) related to national lifelong guidance policies. The role of ICT in relation to national lifelong guidance policies was conceived as (1)…

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0938] Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug Substances....'' Because of increases in the number and complexity of ANDAs and FDA's desire to standardize generic drug...

Online thesis guidance management information system

NASA Astrophysics Data System (ADS)

Nasution, T. H.; Pratama, F.; Tanjung, K.; Siregar, I.; Amalia, A.

2018-03-01

The development of internet technology in education is still not maximized, especially in the process of thesis guidance between students and lecturers. Difficulties met the lecturers to help students during thesis guidance is the limited communication time and the compatibility of schedule between students and lecturer. To solve this problem, we designed an online thesis guidance management information system that helps students and lecturers to do thesis tutoring process anytime, anywhere. The system consists of a web-based admin app for usage management and an android-based app for students and lecturers.

Navigating through 'a labyrinth' of guidance.

PubMed

Pearson, Susan

2014-09-01

Devising a strategy to deliver safe water to thousands of outlets spread across numerous buildings is always going to be a challenge, so how do you navigate your way through a bewildering labyrinth of sometimes contradictory guidance documents? Is there, in fact, simply too much guidance? Posing this question at a recent one-day conference on waterborne infections in healthcare facilities, Paul Nolan, authorised water engineer (AE), and operations manager for PFI provider, Lend Lease, took delegates through a review of the latest guidance and regulations, as Susan Pearson reports.

3D single-molecule super-resolution microscopy with a tilted light sheet.

PubMed

Gustavsson, Anna-Karin; Petrov, Petar N; Lee, Maurice Y; Shechtman, Yoav; Moerner, W E

2018-01-09

Tilted light sheet microscopy with 3D point spread functions (TILT3D) combines a novel, tilted light sheet illumination strategy with long axial range point spread functions (PSFs) for low-background, 3D super-localization of single molecules as well as 3D super-resolution imaging in thick cells. Because the axial positions of the single emitters are encoded in the shape of each single-molecule image rather than in the position or thickness of the light sheet, the light sheet need not be extremely thin. TILT3D is built upon a standard inverted microscope and has minimal custom parts. The result is simple and flexible 3D super-resolution imaging with tens of nm localization precision throughout thick mammalian cells. We validate TILT3D for 3D super-resolution imaging in mammalian cells by imaging mitochondria and the full nuclear lamina using the double-helix PSF for single-molecule detection and the recently developed tetrapod PSFs for fiducial bead tracking and live axial drift correction.

Provide Career Guidance to Girls and Women. Module CG C-13 of Category C--Implementing. Competency-Based Career Guidance Modules.

ERIC Educational Resources Information Center

Birk, Janice M.; Colby, Pamela G.

This learning module, one in a series of competency-based guidance program training packages focusing upon professional and paraprofessional competencies of guidance personnel, deals with providing career guidance to girls and women. Addressed in the module are the following topics: society's influence on shaping differential roles and behaviors…

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…

33 CFR 385.5 - Guidance memoranda.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Water Management District shall, in consultation with the Department of the Interior, the Environmental... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.5 Guidance memoranda. (a) General. (1) Technical guidance for internal management of Corps of...

33 CFR 385.5 - Guidance memoranda.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Water Management District shall, in consultation with the Department of the Interior, the Environmental... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.5 Guidance memoranda. (a) General. (1) Technical guidance for internal management of Corps of...

33 CFR 385.5 - Guidance memoranda.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Water Management District shall, in consultation with the Department of the Interior, the Environmental... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.5 Guidance memoranda. (a) General. (1) Technical guidance for internal management of Corps of...

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...

On the design of fuzzified trajectory shaping guidance law.

PubMed

Lin, Chun-Liang; Lin, Yu-Ping; Chen, Kai-Ming

2009-04-01

Midcourse guidance is commonly designed to save as much energy as possible so that the missile's final speed can be maximized while entering the homing stage. For this purpose, a competitive guidance design should be able to generate an admissible flight trajectory as to bring the interceptor to a superior altitude for a favorable target engagement. In this paper, a new adaptive trajectory shaping guidance scheme based on the adaptive fuzzy inference system, which is capable of generating a variety of trajectories for efficient target interception, is presented. The guidance law is developed with the aim of saving the interceptor's energy conservation while improving performance robustness. Applications of the presented approach have included a variety of mission oriented guidance, such as cruise missile guidance, anti-ballistic missile guidance, etc.

Differential Game Theory Application to Intelligent Missile Guidance

DTIC Science & Technology

2013-06-01

guidance (OG) and game theoretic guidance ( GTG ). One reason for this development is the fact that the implementation hardware for the guidance system has...state estimation techniques such as the Kalman Filter and others, it is now feasible to implement the OG, GTG and GTG +AI ‘intelligent’ guidance on...both PN and APN as special cases of OG and GTG ; this connection is further explored in this report. The desire to reduce weapon life-cycle cost

Encoder: A Connectionist Model of How Learning to Visually Encode Fixated Text Images Improves Reading Fluency

ERIC Educational Resources Information Center

Martin, Gale L.

2004-01-01

This article proposes that visual encoding learning improves reading fluency by widening the span over which letters are recognized from a fixated text image so that fewer fixations are needed to cover a text line. Encoder is a connectionist model that learns to convert images like the fixated text images human readers encode into the…

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.

Video Time Encoding Machines

PubMed Central

Lazar, Aurel A.; Pnevmatikakis, Eftychios A.

2013-01-01

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. PMID:21296708

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

75 FR 68364 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-05

... European Protocol for the Quality Control of the Physical and Technical Aspects of Mammography Screening... entitled ``Physical Laboratory Testing, Breast Compression System'' to follow the Mammography Quality...] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

77 FR 14403 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0167] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Norovirus Serological Reagents; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

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

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0149] (Formerly 2007D-0309) Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document: Electrocardiograph Electrodes; Availability AGENCY: Food and Drug...

76 FR 22906 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-25

...: Topical Oxygen Chamber for Extremities; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled, ``Class II Special Controls Guidance Document: Topical Oxygen Chamber for Extremities.'' This guidance document was developed as a special control to support the reclassification of the topical oxygen...

The Status of Career Guidance in Michigan Schools. An Opinion Research Study of Career Guidance Professionals.

ERIC Educational Resources Information Center

Michigan State Dept. of Education, Lansing.

Project Outreach, the opinion research division of the Michigan State Board of Education, conducted a study on the current status of career guidance in Michigan public schools, using in-depth telephone interviews with career guidance professionals (N=445) in November and December of 1989. The interview questionnaire, developed with the advice of…

Comprehensive Career Guidance. Methods Guide. K-6 Career.

ERIC Educational Resources Information Center

Moore, Earl J.; And Others

This methods guide is intended to assist elementary school guidance workers in implementing a comprehensive career guidance program. Three major areas are considered. First, the life career development perspective is examined as a framework for organizing guidance objectives and practices so that there is a developmental, integrative…

Encoders for block-circulant LDPC codes

NASA Technical Reports Server (NTRS)

Andrews, Kenneth; Dolinar, Sam; Thorpe, Jeremy

2005-01-01

In this paper, we present two encoding methods for block-circulant LDPC codes. The first is an iterative encoding method based on the erasure decoding algorithm, and the computations required are well organized due to the block-circulant structure of the parity check matrix. The second method uses block-circulant generator matrices, and the encoders are very similar to those for recursive convolutional codes. Some encoders of the second type have been implemented in a small Field Programmable Gate Array (FPGA) and operate at 100 Msymbols/second.

Along the Central Dogma-Controlling Gene Expression with Small Molecules.

PubMed

Schneider-Poetsch, Tilman; Yoshida, Minoru

2018-05-04

The central dogma of molecular biology, that DNA is transcribed into RNA and RNA translated into protein, was coined in the early days of modern biology. Back in the 1950s and 1960s, bacterial genetics first opened the way toward understanding life as the genetically encoded interaction of macromolecules. As molecular biology progressed and our knowledge of gene control deepened, it became increasingly clear that expression relied on many more levels of regulation. In the process of dissecting mechanisms of gene expression, specific small-molecule inhibitors played an important role and became valuable tools of investigation. Small molecules offer significant advantages over genetic tools, as they allow inhibiting a process at any desired time point, whereas mutating or altering the gene of an important regulator would likely result in a dead organism. With the advent of modern sequencing technology, it has become possible to monitor global cellular effects of small-molecule treatment and thereby overcome the limitations of classical biochemistry, which usually looks at a biological system in isolation. This review focuses on several molecules, especially natural products, that have played an important role in dissecting gene expression and have opened up new fields of investigation as well as clinical venues for disease treatment. Expected final online publication date for the Annual Review of Biochemistry Volume 87 is June 20, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

76 FR 61098 - Guidance for 1-Hour SO2

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-03

...Notice is hereby given that the EPA has posted its draft non- binding guidance titled, ``Guidance for 1-Hour SO2 NAAQS SIP Submissions'' on its Web site. The EPA invites public comments on this guidance document during the comment period specified below, and plans to issue an updated version of the guidance after reviewing timely submitted comments.

Child Guidance for Child Caregivers: Student Laboratory Manual.

ERIC Educational Resources Information Center

Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

Designed to enhance student knowledge of and skills in child guidance in group care settings, this manual provides 50 laboratory experiences for five units. Units cover foundations and assumptions (2 laboratory experiences), developmental factors (8), indirect guidance (14), direct guidance (14), and strategies (12). Each unit includes performance…

Mapping the Future: Young People and Career Guidance.

ERIC Educational Resources Information Center

St. John-Brooks, Caroline

This report examines the strengths and weaknesses of educational and career guidance in seven Organisation for Economic Development (OECD) countries. Chapter 1 defines educational and career guidance as embracing three key elements: educational, career, and personal/social guidance. Described in chapter 2 is the role of educational and career…

Emotional arousal and memory after deep encoding.

PubMed

Leventon, Jacqueline S; Camacho, Gabriela L; Ramos Rojas, Maria D; Ruedas, Angelica

2018-05-22

Emotion often enhances long-term memory. One mechanism for this enhancement is heightened arousal during encoding. However, reducing arousal, via emotion regulation (ER) instructions, has not been associated with reduced memory. In fact, the opposite pattern has been observed: stronger memory for emotional stimuli encoded with an ER instruction to reduce arousal. This pattern may be due to deeper encoding required by ER instructions. In the current research, we examine the effects of emotional arousal and deep-encoding on memory across three studies. In Study 1, adult participants completed a writing task (deep-encoding) for encoding negative, neutral, and positive picture stimuli, whereby half the emotion stimuli had the ER instruction to reduce the emotion. Memory was strong across conditions, and no memory enhancement was observed for any condition. In Study 2, adult participants completed the same writing task as Study 1, as well as a shallow-encoding task for one-third of negative, neutral, and positive trials. Memory was strongest for deep vs. shallow encoding trials, with no effects of emotion or ER instruction. In Study 3, adult participants completed a shallow-encoding task for negative, neutral, and positive stimuli, with findings indicating enhanced memory for negative emotional stimuli. Findings suggest that deep encoding must be acknowledged as a source of memory enhancement when examining manipulations of emotion-related arousal. Copyright © 2018. Published by Elsevier B.V.

European Universities' Guidance on Research Integrity and Misconduct.

PubMed

Aubert Bonn, Noémie; Godecharle, Simon; Dierickx, Kris

2017-02-01

Research integrity is imperative to good science. Nonetheless, many countries and institutions develop their own integrity guidance, thereby risking incompatibilities with guidance of collaborating institutions. We retrieved guidance for academic integrity and misconduct of 18 universities from 10 European countries and investigated accessibility, general content, principles endorsed, and definitions of misconduct. Accessibility and content differ substantially between institutions. There are general trends of common principles of integrity and definitions of misconduct, yet differences remain. Parallel with previous research, we distinguish different approaches in integrity guidance; one emphasizes broad values of integrity, and the other details negative behaviors of misconduct. We propose that a balance between both approaches is necessary to preserve trust, meaning, and realism of guidance on research integrity.

76 FR 6622 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-07

...: Contact Cooling System for Aesthetic Use; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled ``Class II Special Controls Guidance Document: Contact Cooling System for Aesthetic Use.'' This guidance document describes a means by which contact cooling systems for aesthetic use may comply with the...

76 FR 48870 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-09

... selection inclusion and exclusion criteria section. The revisions define and differentiate the required... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0428] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

Coral Reef Guidance

EPA Pesticide Factsheets

Guidance prepared by EPA and Army Corps of Engineers concerning coral reef protection under the Clean Water Act, Marine Protection, Research, and Sanctuaries Act, Rivers and Harbors Act, and Federal Project Authorities.

Pulse Vector-Excitation Speech Encoder

NASA Technical Reports Server (NTRS)

Davidson, Grant; Gersho, Allen

1989-01-01

Proposed pulse vector-excitation speech encoder (PVXC) encodes analog speech signals into digital representation for transmission or storage at rates below 5 kilobits per second. Produces high quality of reconstructed speech, but with less computation than required by comparable speech-encoding systems. Has some characteristics of multipulse linear predictive coding (MPLPC) and of code-excited linear prediction (CELP). System uses mathematical model of vocal tract in conjunction with set of excitation vectors and perceptually-based error criterion to synthesize natural-sounding speech.

Pneumatic binary encoder replaces multiple solenoid system

NASA Technical Reports Server (NTRS)

1966-01-01

Pneumatic binary encoder replaces solenoid system in the pilot stage of a digital actuator. The encoder operates in flip-flop manner to valve gas at either high or low pressures. By rotating the disk in a pinion-to-encoding gear ratio, six to eight adder circuits may be operated from single encoder.

RMP Guidance for Chemical Distributors - Appendix D: OSHA Guidance on PSM

EPA Pesticide Factsheets

Guidance on the Process Safety Management standard says information (including MSDS) about chemicals, including process intermediates, must enable accurate assessment of fire/explosion characteristics, reactivity hazards, and corrosing/erosion effects.

28 CFR 36.608 - Guidance concerning model codes.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Guidance concerning model codes. 36.608... Codes § 36.608 Guidance concerning model codes. Upon application by an authorized representative of a... relevant model code and issue guidance concerning whether and in what respects the model code is consistent...

High-throughput Identification of DNA-Encoded IgG Ligands that Distinguish Active and Latent Mycobacterium Tuberculosis Infections

PubMed Central

Ndungu, John Maina; Suponitsky-Kroyter, Irena; Cavett, Valerie J.; McEnaney, Patrick J.; MacConnell, Andrew B.; Doran, Todd. M.; Ronacher, Katharina; Stanley, Kim; Utset, Ofelia; Walzl, Gerhard; Paegel, Brian M.; Kodadek, Thomas

2017-01-01

The circulating antibody repertoire encodes a patient's health status and pathogen exposure history, but identifying antibodies with diagnostic potential usually requires knowledge of the antigen(s). We previously circumvented this problem by screening libraries of bead-displayed small molecules against case and control serum samples to discover “epitope surrogates” (ligands of IgGs enriched in the case sample). Here, we describe an improved version of this technology that employs DNA-encoded libraries and high-throughput FACS-based screening to discover epitope surrogates that differentiate noninfectious/latent (LTB) patients from infectious/active TB (ATB) patients, which is imperative for proper treatment selection and antibiotic stewardship. Normal control/LTB (10 patients each, NCL) and ATB (10 patients) serum pools were screened against a library (5 × 106 beads, 448k unique compounds) using fluorescent anti-human IgG to label hit compound beads for FACS. Deep sequencing decoded all hit structures and each hit's occurrence frequencies. ATB hits were pruned of NCL hits and prioritized for resynthesis based on occurrence and homology. Several structurally homologous families were identified and 16/21 resynthesized representative hits validated as selective ligands of ATB serum IgGs (p < 0.005). The native secreted TB protein Ag85B (though not the E. coli recombinant form) competed with one of the validated ligands for binding to antibodies, suggesting that it mimics a native Ag85B epitope. The use of DNA-encoded libraries and FACS-based screening in epitope surrogate discovery reveals thousands of potential hit structures. Distilling this list down to several consensus chemical structures yielded a diagnostic panel for ATB composed of thermally stable and economically produced small molecule ligands in place of protein antigens. PMID:27957856

Three-dimensional vectorial multifocal arrays created by pseudo-period encoding

NASA Astrophysics Data System (ADS)

Zeng, Tingting; Chang, Chenliang; Chen, Zhaozhong; Wang, Hui-Tian; Ding, Jianping

2018-06-01

Multifocal arrays have been attracting considerable attention recently owing to their potential applications in parallel optical tweezers, parallel single-molecule orientation determination, parallel recording and multifocal multiphoton microscopy. However, the generation of vectorial multifocal arrays with a tailorable structure and polarization state remains a great challenge, and reports on multifocal arrays have hitherto been restricted either to scalar focal spots without polarization versatility or to regular arrays with fixed spacing. In this work, we propose a specific pseudo-period encoding technique to create three-dimensional (3D) vectorial multifocal arrays with the ability to manipulate the position, polarization state and intensity of each focal spot. We experimentally validated the flexibility of our approach in the generation of 3D vectorial multiple spots with polarization multiplicity and position tunability.

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…

Career Guidance for Special Needs Learners.

ERIC Educational Resources Information Center

White, Francis A., Jr.

1982-01-01

A career guidance institute for educators working with handicapped and disadvantaged learners included 10 hours of seminar/classroom guidance experiences devoted to theory. Each participant then undertook a 40-hour work internship designed to provide experiences and information about entry-level jobs that special needs learners could perform. (SK)

Educational Guidance for Adults. Identifying Competences.

ERIC Educational Resources Information Center

Oakeshott, Martin

A brief study conducted for the Further Education Unit, Great Britain, defined the competencies associated with educational guidance for adults. The objective was to develop a qualification for educational guidance workers with adults. The project provided an example of applying a competence model to a "higher level" interpersonal field…

Robot-assisted endoscope guidance versus manual endoscope guidance in functional endonasal sinus surgery (FESS).

PubMed

Eichhorn, Klaus Wolfgang; Westphal, Ralf; Rilk, Markus; Last, Carsten; Bootz, Friedrich; Wahl, Friedrich; Jakob, Mark; Send, Thorsten

2017-10-01

Having one hand occupied with the endoscope is the major disadvantage for the surgeon when it comes to functional endoscopic sinus surgery (FESS). Only the other hand is free to use the surgical instruments. Tiredness or frequent instrument changes can thus lead to shaky endoscopic images. We collected the pose data (position and orientation) of the rigid 0° endoscope and all the instruments used in 16 FESS procedures with manual endoscope guidance as well as robot-assisted endoscope guidance. In combination with the DICOM CT data, we tracked the endoscope poses and workspaces using self-developed tracking markers. All surgeries were performed once with the robot and once with the surgeon holding the endoscope. Looking at the durations required, we observed a decrease in the operating time because one surgeon doing all the procedures and so a learning curve occurred what we expected. The visual inspection of the specimens showed no damages to any of the structures outside the paranasal sinuses. Robot-assisted endoscope guidance in sinus surgery is possible. Further CT data, however, are desirable for the surgical analysis of a tracker-based navigation within the anatomic borders. Our marker-based tracking of the endoscope as well as the instruments makes an automated endoscope guidance feasible. On the subjective side, we see that RASS brings a relief for the surgeon.

Experiments in encoding multilevel images as quadtrees

NASA Technical Reports Server (NTRS)

Lansing, Donald L.

1987-01-01

Image storage requirements for several encoding methods are investigated and the use of quadtrees with multigray level or multicolor images are explored. The results of encoding a variety of images having up to 256 gray levels using three schemes (full raster, runlength and quadtree) are presented. Although there is considerable literature on the use of quadtrees to store and manipulate binary images, their application to multilevel images is relatively undeveloped. The potential advantage of quadtree encoding is that an entire area with a uniform gray level may be encoded as a unit. A pointerless quadtree encoding scheme is described. Data are presented on the size of the quadtree required to encode selected images and on the relative storage requirements of the three encoding schemes. A segmentation scheme based on the statistical variation of gray levels within a quadtree quadrant is described. This parametric scheme may be used to control the storage required by an encoded image and to preprocess a scene for feature identification. Several sets of black and white and pseudocolor images obtained by varying the segmentation parameter are shown.

75 FR 6209 - Guidance for Industry and Food and Drug Administration; Guidance for the Use of Bayesian...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2006-D-0410] (formerly Docket No. 2006D-0191) Guidance for Industry and Food and Drug Administration; Guidance for the Use of Bayesian Statistics in Medical Device Clinical Trials; Availability AGENCY: Food and Drug...

The clinical spectrum of mutations in L1, a neuronal cell adhesion molecule

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fransen, E.; Vits, L.; Van Camp, G.

1996-07-12

Mutations in the gene encoding the neuronal cell adhesion molecule L1 are responsible for several syndromes with clinical overlap, including X-linked hydrocephalus (XLH, HSAS), MASA (mental retardation, aphasia, shuffling gait, adducted thumbs) syndrome, complicated X-linked spastic paraplegia (SP 1), X-linked mental retardation-clasped thumb (MR-CT) syndrome, and some forms of X-linked agenesis of the corpus callosum (ACC). We review 34 L1 mutations in patients with these phenotypes. 22 refs., 3 figs., 4 tabs.

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.

Comparison of H.265/HEVC encoders

NASA Astrophysics Data System (ADS)

Trochimiuk, Maciej

2016-09-01

The H.265/HEVC is the state-of-the-art video compression standard, which allows the bitrate reduction up to 50% compared with its predecessor, H.264/AVC, maintaining equal perceptual video quality. The growth in coding efficiency was achieved by increasing the number of available intra- and inter-frame prediction features and improvements in existing ones, such as entropy encoding and filtering. Nevertheless, to achieve real-time performance of the encoder, simplifications in algorithm are inevitable. Some features and coding modes shall be skipped, to reduce time needed to evaluate modes forwarded to rate-distortion optimisation. Thus, the potential acceleration of the encoding process comes at the expense of coding efficiency. In this paper, a trade-off between video quality and encoding speed of various H.265/HEVC encoders is discussed.

Guidance and Counseling Personnel and Programs in Nevada.

ERIC Educational Resources Information Center

Nevada Univ., Reno. Research and Educational Planning Center.

Data were collected on guidance and counseling programs and guidance personnel in Nevada schools. Questionnaires were mailed to all 309 practicing school counselors in Nevada; the response rate was 72%. Guidance counselors in Nevada were primarily female, Caucasian, and middle-aged. Mean number of years as a counselor was 9 years, and most…

Simulated Administration of a Regular Guidance Operation (SARGO).

ERIC Educational Resources Information Center

Fredrickson, Ronald H.; Popken, Charles F.

Simulated Administration of a Regular Guidance Operation (SARGO) is a program for the training of directors of guidance and pupil personnel services. The objective of SARGO is to prepare directors of guidance services to: (1) prepare a written description of a pupil personnel program; (2) interact with a school administrator to clarify role…

Quality Guidance: A Sectoral Analysis. NICEC Project Report.

ERIC Educational Resources Information Center

Watts, A. G.; Sadler, Jackie

This report reviews the structure of the guidance field and provides a sector-by-sector analysis of current quality assurance arrangements in the United Kingdom. Part 1 presents an outline of the guidance sector, including some key concepts, structures, and roles. It defines guidance and other terms; discusses the three main categories…

VLSI chips for vision-based vehicle guidance

NASA Astrophysics Data System (ADS)

Masaki, Ichiro

1994-02-01

Sensor-based vehicle guidance systems are gathering rapidly increasing interest because of their potential for increasing safety, convenience, environmental friendliness, and traffic efficiency. Examples of applications include intelligent cruise control, lane following, collision warning, and collision avoidance. This paper reviews the research trends in vision-based vehicle guidance with an emphasis on VLSI chip implementations of the vision systems. As an example of VLSI chips for vision-based vehicle guidance, a stereo vision system is described in detail.

PredGuid+A: Orion Entry Guidance Modified for Aerocapture

NASA Technical Reports Server (NTRS)

Lafleur, Jarret

2013-01-01

PredGuid+A software was developed to enable a unique numerical predictor-corrector aerocapture guidance capability that builds on heritage Orion entry guidance algorithms. The software can be used for both planetary entry and aerocapture applications. Furthermore, PredGuid+A implements a new Delta-V minimization guidance option that can take the place of traditional targeting guidance and can result in substantial propellant savings. PredGuid+A allows the user to set a mode flag and input a target orbit's apoapsis and periapsis. Using bank angle control, the guidance will then guide the vehicle to the appropriate post-aerocapture orbit using one of two algorithms: Apoapsis Targeting or Delta-V Minimization (as chosen by the user). Recently, the PredGuid guidance algorithm was adapted for use in skip-entry scenarios for NASA's Orion multi-purpose crew vehicle (MPCV). To leverage flight heritage, most of Orion's entry guidance routines are adapted from the Apollo program.

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

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…

The vision guidance and image processing of AGV

NASA Astrophysics Data System (ADS)

Feng, Tongqing; Jiao, Bin

2017-08-01

Firstly, the principle of AGV vision guidance is introduced and the deviation and deflection angle are measured by image coordinate system. The visual guidance image processing platform is introduced. In view of the fact that the AGV guidance image contains more noise, the image has already been smoothed by a statistical sorting. By using AGV sampling way to obtain image guidance, because the image has the best and different threshold segmentation points. In view of this situation, the method of two-dimensional maximum entropy image segmentation is used to solve the problem. We extract the foreground image in the target band by calculating the contour area method and obtain the centre line with the least square fitting algorithm. With the help of image and physical coordinates, we can obtain the guidance information.

Integrating mechanisms of visual guidance in naturalistic language production.

PubMed

Coco, Moreno I; Keller, Frank

2015-05-01

Situated language production requires the integration of visual attention and linguistic processing. Previous work has not conclusively disentangled the role of perceptual scene information and structural sentence information in guiding visual attention. In this paper, we present an eye-tracking study that demonstrates that three types of guidance, perceptual, conceptual, and structural, interact to control visual attention. In a cued language production experiment, we manipulate perceptual (scene clutter) and conceptual guidance (cue animacy) and measure structural guidance (syntactic complexity of the utterance). Analysis of the time course of language production, before and during speech, reveals that all three forms of guidance affect the complexity of visual responses, quantified in terms of the entropy of attentional landscapes and the turbulence of scan patterns, especially during speech. We find that perceptual and conceptual guidance mediate the distribution of attention in the scene, whereas structural guidance closely relates to scan pattern complexity. Furthermore, the eye-voice span of the cued object and its perceptual competitor are similar; its latency mediated by both perceptual and structural guidance. These results rule out a strict interpretation of structural guidance as the single dominant form of visual guidance in situated language production. Rather, the phase of the task and the associated demands of cross-modal cognitive processing determine the mechanisms that guide attention.

The axonal guidance cue semaphorin 3C contributes to alveolar growth and repair.

PubMed

Vadivel, Arul; Alphonse, Rajesh S; Collins, Jennifer J P; van Haaften, Tim; O'Reilly, Megan; Eaton, Farah; Thébaud, Bernard

2013-01-01

Lung diseases characterized by alveolar damage such as bronchopulmonary dysplasia (BPD) in premature infants and emphysema lack efficient treatments. Understanding the mechanisms contributing to normal and impaired alveolar growth and repair may identify new therapeutic targets for these lung diseases. Axonal guidance cues are molecules that guide the outgrowth of axons. Amongst these axonal guidance cues, members of the Semaphorin family, in particular Semaphorin 3C (Sema3C), contribute to early lung branching morphogenesis. The role of Sema3C during alveolar growth and repair is unknown. We hypothesized that Sema3C promotes alveolar development and repair. In vivo Sema3C knock down using intranasal siRNA during the postnatal stage of alveolar development in rats caused significant air space enlargement reminiscent of BPD. Sema3C knock down was associated with increased TLR3 expression and lung inflammatory cells influx. In a model of O2-induced arrested alveolar growth in newborn rats mimicking BPD, air space enlargement was associated with decreased lung Sema3C mRNA expression. In vitro, Sema3C treatment preserved alveolar epithelial cell viability in hyperoxia and accelerated alveolar epithelial cell wound healing. Sema3C preserved lung microvascular endothelial cell vascular network formation in vitro under hyperoxic conditions. In vivo, Sema3C treatment of hyperoxic rats decreased lung neutrophil influx and preserved alveolar and lung vascular growth. Sema3C also preserved lung plexinA2 and Sema3C expression, alveolar epithelial cell proliferation and decreased lung apoptosis. In conclusion, the axonal guidance cue Sema3C promotes normal alveolar growth and may be worthwhile further investigating as a potential therapeutic target for lung repair.

Modulation-frequency encoded multi-color fluorescent DNA analysis in an optofluidic chip.

PubMed

Dongre, Chaitanya; van Weerd, Jasper; Besselink, Geert A J; Vazquez, Rebeca Martinez; Osellame, Roberto; Cerullo, Giulio; van Weeghel, Rob; van den Vlekkert, Hans H; Hoekstra, Hugo J W M; Pollnau, Markus

2011-02-21

We introduce a principle of parallel optical processing to an optofluidic lab-on-a-chip. During electrophoretic separation, the ultra-low limit of detection achieved with our set-up allows us to record fluorescence from covalently end-labeled DNA molecules. Different sets of exclusively color-labeled DNA fragments-otherwise rendered indistinguishable by spatio-temporal coincidence-are traced back to their origin by modulation-frequency-encoded multi-wavelength laser excitation, fluorescence detection with a single ultrasensitive, albeit color-blind photomultiplier, and Fourier analysis decoding. As a proof of principle, fragments obtained by multiplex ligation-dependent probe amplification from independent human genomic segments, associated with genetic predispositions to breast cancer and anemia, are simultaneously analyzed.

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.

75 FR 48973 - Draft Guidance for Industry: Prevention of Salmonella

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-12

...] Draft Guidance for Industry: Prevention of Salmonella Enteritidis in Shell Eggs During Production... entitled ``Prevention of Salmonella Enteritidis in Shell Eggs During Production, Storage, and Transportation'' (the draft guidance). The draft guidance, when finalized, will provide guidance to egg producers...

48 CFR 427.104 - General guidance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false General guidance. 427.104... REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS General 427.104 General guidance. As used in FAR part 27, the agency head or agency head designee is the Senior Procurement Executive, except under FAR 27.306(a) and (b...

33 CFR 385.5 - Guidance memoranda.

Code of Federal Regulations, 2010 CFR

2010-07-01

... sources of water will occur as a result of implementation of the Plan (§ 385.36(b)). (b) Special processes..., implementation, and management of one specific individual feature of the Plan, this section does not require... § 385.5 Guidance memoranda. (a) General. (1) Technical guidance for internal management of Corps of...

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.

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors

PubMed Central

Naganathan, Saranga; Grunbeck, Amy; Tian, He; Huber, Thomas; Sakmar, Thomas P.

2013-01-01

To facilitate structural and dynamic studies of G protein-coupled receptor (GPCR) signaling complexes, new approaches are required to introduce informative probes or labels into expressed receptors that do not perturb receptor function. We used amber codon suppression technology to genetically-encode the unnatural amino acid, p-azido-L-phenylalanine (azF) at various targeted positions in GPCRs heterologously expressed in mammalian cells. The versatility of the azido group is illustrated here in different applications to study GPCRs in their native cellular environment or under detergent solubilized conditions. First, we demonstrate a cell-based targeted photocrosslinking technology to identify the residues in the ligand-binding pocket of GPCR where a tritium-labeled small-molecule ligand is crosslinked to a genetically-encoded azido amino acid. We then demonstrate site-specific modification of GPCRs by the bioorthogonal Staudinger-Bertozzi ligation reaction that targets the azido group using phosphine derivatives. We discuss a general strategy for targeted peptide-epitope tagging of expressed membrane proteins in-culture and its detection using a whole-cell-based ELISA approach. Finally, we show that azF-GPCRs can be selectively tagged with fluorescent probes. The methodologies discussed are general, in that they can in principle be applied to any amino acid position in any expressed GPCR to interrogate active signaling complexes. PMID:24056801

Target identification for small bioactive molecules: finding the needle in the haystack.

PubMed

Ziegler, Slava; Pries, Verena; Hedberg, Christian; Waldmann, Herbert

2013-03-04

Identification and confirmation of bioactive small-molecule targets is a crucial, often decisive step both in academic and pharmaceutical research. Through the development and availability of several new experimental techniques, target identification is, in principle, feasible, and the number of successful examples steadily grows. However, a generic methodology that can successfully be applied in the majority of the cases has not yet been established. Herein we summarize current methods for target identification of small molecules, primarily for a chemistry audience but also the biological community, for example, the chemist or biologist attempting to identify the target of a given bioactive compound. We describe the most frequently employed experimental approaches for target identification and provide several representative examples illustrating the state-of-the-art. Among the techniques currently available, protein affinity isolation using suitable small-molecule probes (pulldown) and subsequent mass spectrometric analysis of the isolated proteins appears to be most powerful and most frequently applied. To provide guidance for rapid entry into the field and based on our own experience we propose a typical workflow for target identification, which centers on the application of chemical proteomics as the key step to generate hypotheses for potential target proteins. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Live-cell imaging of endogenous mRNAs with a small molecule.

PubMed

Sato, Shin-ichi; Watanabe, Mizuki; Katsuda, Yousuke; Murata, Asako; Wang, Dan Ohtan; Uesugi, Motonari

2015-02-02

Determination of subcellular localization and dynamics of mRNA is increasingly important to understanding gene expression. A new convenient and versatile method is reported that permits spatiotemporal imaging of specific non-engineered RNAs in living cells. The method uses transfection of a plasmid encoding a gene-specific RNA aptamer, combined with a cell-permeable synthetic small molecule, the fluorescence of which is restored only when the RNA aptamer hybridizes with its cognitive mRNA. The method was validated by live-cell imaging of the endogenous mRNA of β-actin. Application of the technology to mRNAs of a total of 84 human cytoskeletal genes allowed us to observe cellular dynamics of several endogenous mRNAs including arfaptin-2, cortactin, and cytoplasmic FMR1-interacting protein 2. The RNA-imaging technology and its further optimization might permit live-cell imaging of any RNA molecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Guidance concepts for time-based flight operations

NASA Technical Reports Server (NTRS)

Vicroy, Dan D.

1990-01-01

Airport congestion and the associated delays are severe in today's airspace system and are expected to increase. NASA and the FAA is investigating various methods of alleviating this problem through new technology and operational procedures. One concept for improving airspace productivity is time-based control of aircraft. Research to date has focused primarily on the development of time-based flight management systems and Air Traffic Control operational procedures. Flight operations may, however, require special onboard guidance in order to satisfy the Air Traffic Control imposed time constraints. The results are presented of a simulation study aimed at evaluating several time-based guidance concepts in terms of tracking performance, pilot workload, and subjective preference. The guidance concepts tested varied in complexity from simple digital time-error feedback to an advanced time-referenced-energy guidance scheme.

Enabling technologies for Chinese Mars lander guidance system

NASA Astrophysics Data System (ADS)

Jiang, Xiuqiang; Li, Shuang

2017-04-01

Chinese first Mars exploration activity, orbiting landing and roaming collaborative mission, has been programmed and started. As a key technology, Mars lander guidance system is intended to serve atmospheric entry, descent and landing (EDL) phases. This paper is to report the formation process of enabling technology road map for Chinese Mars lander guidance system. First, two scenarios of the first-stage of the Chinese Mars exploration project are disclosed in detail. Second, mission challenges and engineering needs of EDL guidance, navigation, and control (GNC) are presented systematically for Chinese Mars exploration program. Third, some useful related technologies developed in China's current aerospace projects are pertinently summarized, especially on entry guidance, parachute descent, autonomous hazard avoidance and safe landing. Finally, an enabling technology road map of Chinese Mars lander guidance is given through technological inheriting and improving.

Contact guidance is cell cycle-dependent.

PubMed

Pourfarhangi, Kamyar Esmaeili; De La Hoz, Edgar Cardenas; Cohen, Andrew R; Gligorijevic, Bojana

2018-09-01

Cancer cell migration is essential for metastasis, during which cancer cells move through the tumor and reach the blood vessels. In vivo , cancer cells are exposed to contact guidance and chemotactic cues. Depending on the strength of such cues, cells will migrate in a random or directed manner. While similar cues may also stimulate cell proliferation, it is not clear whether cell cycle progression affects migration of cancer cells and whether this effect is different in random versus directed migration. In this study, we tested the effect of cell cycle progression on contact guided migration in 2D and 3D environments, in the breast carcinoma cell line, FUCCI-MDA-MB-231. The results were quantified from live cell microscopy images using the open source lineage editing and validation image analysis tools (LEVER). In 2D, cells were placed inside 10 μ m-wide microchannels to stimulate contact guidance, with or without an additional chemotactic gradient of the soluble epidermal growth factor. In 3D, contact guidance was modeled by aligned collagen fibers. In both 2D and 3D, contact guidance was cell cycle-dependent, while the addition of the chemo-attractant gradient in 2D increased cell velocity and persistence in directionally migrating cells, regardless of their cell cycle phases. In both 2D and 3D contact guidance, cells in the G1 phase of the cell cycle outperformed cells in the S/G2 phase in terms of migration persistence and instantaneous velocity. These data suggest that in the presence of contact guidance cues in vivo , breast carcinoma cells in the G1 phase of the cell cycle may be more efficient in reaching the neighboring vasculature.

Guidance, Gender Equity and Technology Education.

ERIC Educational Resources Information Center

Silverman, Suzanne; Pritchard, Alice M.

A study examined the role of guidance in girls' decisions about whether or not to take technology education as an elective in high school and to consider future careers in technological fields. The researchers reviewed the literature on guidance and looked at the results of interventions designed to attract girls to nontraditional fields. Eighteen…

Molecular Rotation Signals: Molecule Chemistry and Particle Physics

NASA Astrophysics Data System (ADS)

Grabow, Jens-Uwe

2015-06-01

Molecules - large or small - are attractive academic resources, with numerous questions on their chemical behaviour as well as problems in fundamental physics now (or still) waiting to be answered: Targeted by high-resolution spectroscopy, a rotating molecular top can turn into a laboratory for molecule chemistry or a laboratory for particle physics. Once successfully entrained (many species - depending on size and chemical composition - have insufficient vapour pressures or are of transient nature, such that specifically designed pulsed-jet sources are required for their transfer into the gas phase or in-situ generation) into the collision-free environment of a supersonic-jet expansion, each molecular top comes with its own set of challenges, theoretically and experimentally: Multiple internal interactions are causing complicated energy level schemes and the resulting spectra will be rather difficult to predict theoretically. Experimentally, these spectra are difficult to assess and assign. With today's broad-banded chirp microwave techniques, finding and identifying such spectral features have lost their major drawback of being very time consuming for many molecules. For other molecules, the unrivalled resolution and sensitivity of the narrow-banded impulse microwave techniques provide a window to tackle - at the highest precision available to date - fundamental questions in physics, even particle physics - potentially beyond the standard model. Molecular charge distribution, properties of the chemical bond, details on internal dynamics and intermolecular interaction, the (stereo-chemical) molecular structure (including the possibility of their spatial separation) as well as potential evidence for tiny yet significant interactions encode their signature in pure molecular rotation subjected to time-domain microwave spectroscopic techniques. Ongoing exciting technical developments promise rapid progress. We present recent examples from Hannover, new directions, and

Autonomous Guidance Strategy for Spacecraft Formations and Reconfiguration Maneuvers

NASA Astrophysics Data System (ADS)

Wahl, Theodore P.

A guidance strategy for autonomous spacecraft formation reconfiguration maneuvers is presented. The guidance strategy is presented as an algorithm that solves the linked assignment and delivery problems. The assignment problem is the task of assigning the member spacecraft of the formation to their new positions in the desired formation geometry. The guidance algorithm uses an auction process (also called an "auction algorithm''), presented in the dissertation, to solve the assignment problem. The auction uses the estimated maneuver and time of flight costs between the spacecraft and targets to create assignments which minimize a specific "expense'' function for the formation. The delivery problem is the task of delivering the spacecraft to their assigned positions, and it is addressed through one of two guidance schemes described in this work. The first is a delivery scheme based on artificial potential function (APF) guidance. APF guidance uses the relative distances between the spacecraft, targets, and any obstacles to design maneuvers based on gradients of potential fields. The second delivery scheme is based on model predictive control (MPC); this method uses a model of the system dynamics to plan a series of maneuvers designed to minimize a unique cost function. The guidance algorithm uses an analytic linearized approximation of the relative orbital dynamics, the Yamanaka-Ankersen state transition matrix, in the auction process and in both delivery methods. The proposed guidance strategy is successful, in simulations, in autonomously assigning the members of the formation to new positions and in delivering the spacecraft to these new positions safely using both delivery methods. This guidance algorithm can serve as the basis for future autonomous guidance strategies for spacecraft formation missions.

State Indoor Radon Grants Guidance and Tools

EPA Pesticide Factsheets

This guidance explains the standardized state template for SIRG measures,as required by the OMB and answers questions about the template. The Program guidance is intended to reconcile all legal, policy and programmatic changes that affected SIRG.

The revised HSE fatigue guidance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stacey, A.; Sharp, J.V.

1995-12-31

Fatigue cracking has been a principal cause of damage to North Sea structures and consequently considerable attention has been given to the development of guidance for the prediction of fatigue performance. The fatigue guidance of the Offshore Safety Division of the Health and Safety Executive (HSE) was recently revised and published, following a significant offshore industry review in the period 1987 to 1990, and is based on the results of a considerable amount of research and development work on the fatigue behavior of welded tubular and plated joints. As a result of this review, the revised fatigue guidance incorporates severalmore » new clauses and recommendations. The revised recommendations apply to joint classification, basic design S-N curves for welded joints and cast or forged steel components, the thickness effect, the effects of environment and the treatment of low and high stress ranges. Additionally, a new appendix on the derivation of stress concentration factors is included. The new clauses cover high strength steels, bolts and threaded connectors, moorings, repaired joints and the use of fracture mechanics analysis. This paper presents an overview of the revisions to the fatigue guidance, the associated background technical information and aspects of the fatigue behavior of offshore structures which are considered to require further investigation. 67 refs., 7 figs., 8 tabs.« less

Case Studies in Practical Career Guidance, Number 7: Developmental Career Guidance Project Detroit Public Schools, Detroit, Michigan.

ERIC Educational Resources Information Center

Scott, Thelma J.

The Developmental Career Guidance (DCG) project is a K-12 career guidance demonstration project operating at three high schools and 18 feeder schools in the Detroit Public School District. Directed from Wayne State University, DCG has centers at the high schools and each of the feeder schools. From the centers, students voluntarily can draw…

Development of a gene synthesis platform for the efficient large scale production of small genes encoding animal toxins.

PubMed

Sequeira, Ana Filipa; Brás, Joana L A; Guerreiro, Catarina I P D; Vincentelli, Renaud; Fontes, Carlos M G A

2016-12-01

Gene synthesis is becoming an important tool in many fields of recombinant DNA technology, including recombinant protein production. De novo gene synthesis is quickly replacing the classical cloning and mutagenesis procedures and allows generating nucleic acids for which no template is available. In addition, when coupled with efficient gene design algorithms that optimize codon usage, it leads to high levels of recombinant protein expression. Here, we describe the development of an optimized gene synthesis platform that was applied to the large scale production of small genes encoding venom peptides. This improved gene synthesis method uses a PCR-based protocol to assemble synthetic DNA from pools of overlapping oligonucleotides and was developed to synthesise multiples genes simultaneously. This technology incorporates an accurate, automated and cost effective ligation independent cloning step to directly integrate the synthetic genes into an effective Escherichia coli expression vector. The robustness of this technology to generate large libraries of dozens to thousands of synthetic nucleic acids was demonstrated through the parallel and simultaneous synthesis of 96 genes encoding animal toxins. An automated platform was developed for the large-scale synthesis of small genes encoding eukaryotic toxins. Large scale recombinant expression of synthetic genes encoding eukaryotic toxins will allow exploring the extraordinary potency and pharmacological diversity of animal venoms, an increasingly valuable but unexplored source of lead molecules for drug discovery.

Architecture for VLSI design of Reed-Solomon encoders

NASA Technical Reports Server (NTRS)

Liu, K. Y.

1981-01-01

The logic structure of a universal VLSI chip called the symbol-slice Reed-Solomon (RS) encoder chip is discussed. An RS encoder can be constructed by cascading and properly interconnecting a group of such VLSI chips. As a design example, it is shown that a (255,223) RD encoder requiring around 40 discrete CMOS ICs may be replaced by an RS encoder consisting of four identical interconnected VLSI RS encoder chips. Besides the size advantage, the VLSI RS encoder also has the potential advantages of requiring less power and having a higher reliability.

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.

Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa.

PubMed

Kishnani, Priya S; Rush, Eric T; Arundel, Paul; Bishop, Nick; Dahir, Kathryn; Fraser, William; Harmatz, Paul; Linglart, Agnès; Munns, Craig F; Nunes, Mark E; Saal, Howard M; Seefried, Lothar; Ozono, Keiichi

2017-09-01

Hypophosphatasia (HPP) is a rare, inherited, systemic, metabolic disorder caused by autosomal recessive mutations or a single dominant-negative mutation in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). The disease is associated with a broad range of signs, symptoms, and complications, including impaired skeletal mineralization, altered calcium and phosphate metabolism, recurrent fractures, pain, respiratory problems, impaired growth and mobility, premature tooth loss, developmental delay, and seizures. Asfotase alfa is a human, recombinant enzyme replacement therapy that is approved in many countries for the treatment of patients with HPP. To address the unmet need for guidance in the monitoring of patients receiving asfotase alfa, an international panel of physicians with experience in diagnosing and managing HPP convened in May 2016 to discuss treatment monitoring parameters. The panel discussions focused on recommendations for assessing and monitoring patients after the decision to treat with asfotase alfa had been made and did not include recommendations for whom to treat. Based on the consensus of panel members, this review provides guidance on the monitoring of patients with HPP during treatment with asfotase alfa, including recommendations for laboratory, efficacy, and safety assessments and the frequency with which these should be performed during the course of treatment. Recommended assessments are based on patient age and include regular monitoring of biochemistry, skeletal radiographs, respiratory function, growth, pain, mobility and motor function, and quality of life. Because of the systemic presentation of HPP, a coordinated, multidisciplinary, team-based, patient-focused approach is recommended in the management of patients receiving asfotase alfa. Monitoring of efficacy and safety outcomes must be tailored to the individual patient, depending on medical history, clinical manifestations, availability of resources in the clinical

Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

PubMed Central

Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan

2016-01-01

Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion. PMID:27367541

Immunoglobulin superfamily members encoded by viruses and their multiple roles in immune evasion.

PubMed

Farré, Domènec; Martínez-Vicente, Pablo; Engel, Pablo; Angulo, Ana

2017-05-01

Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily, whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions. The flexible structural nature of the immunoglobulin domains makes them appealing targets for viral capture due to their capacity to generate high functional diversity. Here, we present an up-to-date review of immunoglobulin superfamily gene homologs encoded by herpesviruses, poxviruses, and adenoviruses, that include CD200, CD47, Fc receptors, interleukin-1 receptor 2, interleukin-18 binding protein, CD80, carcinoembryonic antigen-related cell adhesion molecules, and signaling lymphocyte activation molecules. We discuss their distinct structural attributes, binding properties, and functions, shaped by evolutionary pressures to disarm specific immune pathways. We include several novel genes identified from extensive genome database surveys. An understanding of the properties and modes of action of these viral proteins may guide the development of novel immune-modulatory therapeutic tools. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

75 FR 76079 - Sound Incentive Compensation Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision Sound Incentive Compensation Guidance... on the following information collection. Title of Proposal: Sound Incentive Compensation Guidance... Sound Compensation Practices adopted by the Financial Stability Board (FSB) in April 2009, as well as...

Automation practices in large molecule bioanalysis: recommendations from group L5 of the global bioanalytical consortium.

PubMed

Ahene, Ago; Calonder, Claudio; Davis, Scott; Kowalchick, Joseph; Nakamura, Takahiro; Nouri, Parya; Vostiar, Igor; Wang, Yang; Wang, Jin

2014-01-01

In recent years, the use of automated sample handling instrumentation has come to the forefront of bioanalytical analysis in order to ensure greater assay consistency and throughput. Since robotic systems are becoming part of everyday analytical procedures, the need for consistent guidance across the pharmaceutical industry has become increasingly important. Pre-existing regulations do not go into sufficient detail in regard to how to handle the use of robotic systems for use with analytical methods, especially large molecule bioanalysis. As a result, Global Bioanalytical Consortium (GBC) Group L5 has put forth specific recommendations for the validation, qualification, and use of robotic systems as part of large molecule bioanalytical analyses in the present white paper. The guidelines presented can be followed to ensure that there is a consistent, transparent methodology that will ensure that robotic systems can be effectively used and documented in a regulated bioanalytical laboratory setting. This will allow for consistent use of robotic sample handling instrumentation as part of large molecule bioanalysis across the globe.

A gain-of-function screen for genes that influence axon guidance identifies the NF-kappaB protein dorsal and reveals a requirement for the kinase Pelle in Drosophila photoreceptor axon targeting.

PubMed

Mindorff, Elizabeth N; O'Keefe, David D; Labbé, Alain; Yang, Jennie Ping; Ou, Yimiao; Yoshikawa, Shingo; van Meyel, Donald J

2007-08-01

To identify novel regulators of nervous system development, we used the GAL4-UAS misexpression system in Drosophila to screen for genes that influence axon guidance in developing embryos. We mobilized the Gene Search (GS) P element and identified 42 lines with insertions in unique loci, including leak/roundabout2, which encodes an axon guidance receptor and confirms the utility of our screen. The genes we identified encode proteins of diverse classes, some acting near the cell surface and others in the cytoplasm or nucleus. We found that one GS line drove misexpression of the NF-kappaB transcription factor Dorsal, causing motor axons to bypass their correct termination sites. In the developing visual system, Dorsal misexpression also caused photoreceptor axons to reach incorrect positions within the optic lobe. This mistargeting occurred without observable changes of cell fate and correlated with localization of ectopic Dorsal in distal axons. We found that Dorsal and its inhibitor Cactus are expressed in photoreceptors, though neither was required for axon targeting. However, mutation analyses of genes known to act upstream of Dorsal revealed a requirement for the interleukin receptor-associated kinase family kinase Pelle for layer-specific targeting of photoreceptor axons, validating our screen as a means to identify new molecular determinants of nervous system development in vivo.

78 FR 53792 - Draft Guidance for Reciprocity

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-30

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0186] Draft Guidance for Reciprocity AGENCY: Nuclear... Commission (NRC) is revising its licensing guidance for reciprocity. The NRC is requesting public comment on... Work in Agreement State Jurisdiction (Reciprocity).'' The document has been updated from the previous...

40 CFR 56.6 - Dissemination of policy and guidance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) REGIONAL CONSISTENCY § 56.6 Dissemination of policy and guidance. The Assistant Administrators of... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Dissemination of policy and guidance... to disseminate policy and guidance. They shall distribute material under foregoing systems to the...

40 CFR 56.6 - Dissemination of policy and guidance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) REGIONAL CONSISTENCY § 56.6 Dissemination of policy and guidance. The Assistant Administrators of... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Dissemination of policy and guidance... to disseminate policy and guidance. They shall distribute material under foregoing systems to the...

OECD Review of Career Guidance Policies. Norway: Country Note.

ERIC Educational Resources Information Center

Organisation for Economic Cooperation and Development, Paris (France).

Norway's career guidance system and policies were evaluated. The review team met with policymakers and guidance practitioners in the public and private sectors, analyzed data from a national questionnaire, and reviewed pertinent documentation. The evaluation focused on the following areas: splitting educational/vocational guidance from personal…

Concurrent encoding of frequency and amplitude modulation in human auditory cortex: encoding transition.

PubMed

Luo, Huan; Wang, Yadong; Poeppel, David; Simon, Jonathan Z

2007-12-01

Complex natural sounds (e.g., animal vocalizations or speech) can be characterized by specific spectrotemporal patterns the components of which change in both frequency (FM) and amplitude (AM). The neural coding of AM and FM has been widely studied in humans and animals but typically with either pure AM or pure FM stimuli. The neural mechanisms employed to perceptually unify AM and FM acoustic features remain unclear. Using stimuli with simultaneous sinusoidal AM (at rate f(AM) = 37 Hz) and FM (with varying rates f(FM)), magnetoencephalography (MEG) is used to investigate the elicited auditory steady-state response (aSSR) at relevant frequencies (f(AM), f(FM), f(AM) + f(FM)). Previous work demonstrated that for sounds with slower FM dynamics (f(FM) < 5 Hz), the phase of the aSSR at f(AM) tracked the FM; in other words, AM and FM features were co-tracked and co-represented by "phase modulation" encoding. This study explores the neural coding mechanism for stimuli with faster FM dynamics (< or =30 Hz), demonstrating that at faster rates (f(FM) > 5 Hz), there is a transition from pure phase modulation encoding to a single-upper-sideband (SSB) response (at frequency f(AM) + f(FM)) pattern. We propose that this unexpected SSB response can be explained by the additional involvement of subsidiary AM encoding responses simultaneously to, and in quadrature with, the ongoing phase modulation. These results, using MEG to reveal a possible neural encoding of specific acoustic properties, demonstrate more generally that physiological tests of encoding hypotheses can be performed noninvasively on human subjects, complementing invasive, single-unit recordings in animals.

Guidance strategies and analysis for low thrust navigation

NASA Technical Reports Server (NTRS)

Jacobson, R. A.

1973-01-01

A low-thrust guidance algorithm suitable for operational use was formulated. A constrained linear feedback control law was obtained using a minimum terminal miss criterion and restricting control corrections to constant changes for specified time periods. Both fixed- and variable-time-of-arrival guidance were considered. The performance of the guidance law was evaluated by applying it to the approach phase of the 1980 rendezvous mission with the comet Encke.

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.

Genomic structure and chromosomal localization of GML (GPI-anchored molecule-like protein), a gene induced by p53

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimura, Yasutoshi; Furuhata, Tomohisa; Nakamura, Yusuke

1997-05-01

Among its known functions, tumor suppressor gene p53 serves as a transcriptional regulator and mediates various signals through activation of downstream genes. We recently identified a novel gene, GML (glycosylphosphatidylinositol (GPI)-anchored molecule-like protein), whose expression is specifically induced by wildtype p53. To characterize the GML gene further, we determined 35.8 kb of DNA sequence that included a consensus binding sequence for p53 and the entire GML gene. The GML gene consists of four exons, and the p53-binding sequence is present in the 5{prime}-flanking region. In genomic organization this gene resembles genes encoding murine Ly-6 glycoproteins, a human homologue of themore » Ly-6 family called RIG-E, and CD59; products of these genes, known as GPI-anchored proteins, are variously involved in signal transduction, cell-cell adhesion, and cell-matrix attachment. FISH analysis revealed that the GML gene is located on human chromosome 8q24.3. Genes encoding at least two other GPI-anchored molecules, E48 and RIG-E, are also located in this region. 20 refs., 2 figs., 1 tab.« less

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

Programmable Pulse-Position-Modulation Encoder

NASA Technical Reports Server (NTRS)

Zhu, David; Farr, William

2006-01-01

A programmable pulse-position-modulation (PPM) encoder has been designed for use in testing an optical communication link. The encoder includes a programmable state machine and an electronic code book that can be updated to accommodate different PPM coding schemes. The encoder includes a field-programmable gate array (FPGA) that is programmed to step through the stored state machine and code book and that drives a custom high-speed serializer circuit board that is capable of generating subnanosecond pulses. The stored state machine and code book can be updated by means of a simple text interface through the serial port of a personal computer.

[Process of institutional child guidance counseling reflected by the Central Continuing Education of the Federal Conference for Child Guidance Counseling].

PubMed

Pfeifer, W K

2000-12-01

The Bundeskonferenz für Erziehungsberatung (bke) is the federation for child guidance and family-counseling in Germany. Members are the working groups for child guidance and family-counseling of the Länder, where the employees of the child guidance are organized. The federation was founded in 1962. It is sponsored by the Federal Ministry for Family, Seniors, Women and Youth. Further education for professional youth workers is central mission of bke. The constitution of the federation lais down these contents. Every autumn the bke publishes the program for further education for the following year in a brochure called Zentrale Weiterbildung--the program for child guidance, family counseling and youth counseling. A special Kommission Zentrale Weiterbildung acquires the contents of the program for further education und selects the referents. Since 1968 the Zentrale Weiterbildung of Bundeskonferenz für Erziehungsberatung offers events for professional youth workers in child guidance, family counseling. The program for further education contributes the quality of the institution of child guidance. After a time with above average use of the program for further education with therapeutical focal point, the orientation of the program changes to child and youth services. A constant number of counselors use the program. Beside the change of contents there was a change to effectiveness of contents and a reduction of participants.

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…

Concept development of automatic guidance for rotorcraft obstacle avoidance

NASA Technical Reports Server (NTRS)

Cheng, Victor H. L.

1990-01-01

The automatic guidance of rotorcraft for obstacle avoidance in nap-of-the-earth flight is studied. A hierarchical breakdown of the guidance components is used to identify the functional requirements. These requirements and anticipated sensor capabilities lead to a preliminary guidance concept, which has been evaluated via computer simulations.

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 3 2012-01-01 2012-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 3 2014-01-01 2014-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 3 2011-01-01 2011-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

10 CFR 420.32 - Program guidance/solicitation.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 3 2013-01-01 2013-01-01 false Program guidance/solicitation. 420.32 Section 420.32 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION STATE ENERGY PROGRAM Implementation of Special Projects... more project(s) under the special projects financial assistance with a detailed program guidance...

Guidance of Nonlinear Nonminimum-Phase Dynamic Systems

NASA Technical Reports Server (NTRS)

Devasia, Santosh

1997-01-01

The first two years research work has advanced the inversion-based guidance theory for: (1) systems with non-hyperbolic internal dynamics; (2) systems with parameter jumps; (3) systems where a redesign of the output trajectory is desired; and (4) the generation of recovery guidance maneuvers.

77 FR 48591 - State Rail Plan Guidance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Plan Guidance AGENCY: Federal Railroad Administration (FRA), Department of Transportation (DOT). ACTION: Request for Public Comment on Proposed State Rail Plan Guidance. SUMMARY: FRA is publishing this notice to... plans. State rail plans are documents that are required under Section 303 of the Passenger Rail...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

21 CFR 10.115 - Good guidance practices.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., journal articles and editorials, media interviews, press materials, warning letters, memoranda of... document “Guidance Document Submission” and submit it to Division of Dockets Management (HFA-305), 5630... review. (iv) After providing an opportunity for public comment on a Level 1 guidance document, FDA will...

Electron-Molecule Col1isions: Quantitative Approaches, and the Legacy of Aaron Temkin

NASA Technical Reports Server (NTRS)

Schneider, B.I.

2007-01-01

This article, on electron-molecule collisions, is dedicated to the legacy of my good friend and sometime collaborator, Aaron Temkin on his retirement from the NASA-Goddard Space Flight Center after many years of work at the highest intellectual level in the theoretical treatment of electron-atom and electron-molecule scattering. Aaron's contributions to the manner in which we think about electron-molecule collisions is clear to all of us who have worked in this field. I doubt that the great progress that has occurred in the computational treatment of such complex collision problems could have happened without these contributions. For a brief historical account, see the discussion of Temkin's contribution to electron-molecule scattering in the first article of this volume by Dr. A. K. Bhatia. In this article, I will concentrate on the application of the so called, non-adiabatic R-matrix theory, to vibrational excitation and dissociative attachment, although I will also present some results applying the Linear Algebraic and Kohn-Variational methods to vibrational excitation. As a starting point for almost all computationally effective approaches to electron-molecule collisions, is the fixed nuclei approximation. That is, one recognizes, just as one does with molecular bound states, that there is a separation of electronic(fast) and nuclear(s1ow) degrees of freedom. This separation makes it possible to "freeze" the nuclei in space, calculate the collision parameters for the frozen molecule and then, somehow to add back the vibrations and rotations. The manner in which this is done, depends on the details of the collision problem. It is the work of Aaron and a number of other researchers that has provided the guidance necessary to resolve these issues.

Multicore-based 3D-DWT video encoder

NASA Astrophysics Data System (ADS)

Galiano, Vicente; López-Granado, Otoniel; Malumbres, Manuel P.; Migallón, Hector

2013-12-01

Three-dimensional wavelet transform (3D-DWT) encoders are good candidates for applications like professional video editing, video surveillance, multi-spectral satellite imaging, etc. where a frame must be reconstructed as quickly as possible. In this paper, we present a new 3D-DWT video encoder based on a fast run-length coding engine. Furthermore, we present several multicore optimizations to speed-up the 3D-DWT computation. An exhaustive evaluation of the proposed encoder (3D-GOP-RL) has been performed, and we have compared the evaluation results with other video encoders in terms of rate/distortion (R/D), coding/decoding delay, and memory consumption. Results show that the proposed encoder obtains good R/D results for high-resolution video sequences with nearly in-place computation using only the memory needed to store a group of pictures. After applying the multicore optimization strategies over the 3D DWT, the proposed encoder is able to compress a full high-definition video sequence in real-time.

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.

An Investigation of the Guidance Counselling Needs of Adults with Dyslexia in the Adult Educational Guidance Initiative (AEGI)

ERIC Educational Resources Information Center

Elftorp, Petra; Hearne, Lucy

2014-01-01

The experiences of adult learners with dyslexia is an under-researched area in Ireland at present. This article will discuss the findings from phase one of a mixed methods research study, which is investigating the guidance counselling needs of clients with dyslexia within the Adult Education Guidance Initiative (AEGI). The research is underpinned…

River City High School Guidance Services: A Conceptual Model.

ERIC Educational Resources Information Center

American Coll. Testing Program, Iowa City, IA.

This model describes how the guidance staff at a hypothetical high school communicated the effectiveness of the guidance program to students, parents, teachers, and administrators. A description of the high school is presented, and guidance services and personnel are described. A conceptual model responding to student needs is outlined along with…

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.

Halon 1301 management planning guidance

NASA Astrophysics Data System (ADS)

1995-05-01

This ETL provides guidance to help the Base Civil Engineer (BCE) and other users manage inventories of Halon 1301, an ozone depleting substance used in many facility fire protection systems. This guidance will allow Halon 1301 users to develop the transition plans necessary to implement the DOD and Air Force policies on ozone depleting substances. Attachment 3 to this ETL contains detailed instructions on how to develop a Base Halon 1 301 Management Plan and comply with Air Force policies and regulations designed to minimize dependency on Halon 1301.

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…

Architecture for VLSI design of Reed-Solomon encoders

NASA Technical Reports Server (NTRS)

Liu, K. Y.

1982-01-01

A description is given of the logic structure of the universal VLSI symbol-slice Reed-Solomon (RS) encoder chip, from a group of which an RS encoder may be constructed through cascading and proper interconnection. As a design example, it is shown that an RS encoder presently requiring approximately 40 discrete CMOS ICs may be replaced by an RS encoder consisting of four identical, interconnected VLSI RS encoder chips, offering in addition to greater compactness both a lower power requirement and greater reliability.

Architecture for VLSI design of Reed-Solomon encoders

NASA Astrophysics Data System (ADS)

Liu, K. Y.

1982-02-01

A description is given of the logic structure of the universal VLSI symbol-slice Reed-Solomon (RS) encoder chip, from a group of which an RS encoder may be constructed through cascading and proper interconnection. As a design example, it is shown that an RS encoder presently requiring approximately 40 discrete CMOS ICs may be replaced by an RS encoder consisting of four identical, interconnected VLSI RS encoder chips, offering in addition to greater compactness both a lower power requirement and greater reliability.

Single-molecule fluorimetry and gating currents inspire an improved optical voltage indicator

PubMed Central

Treger, Jeremy S; Priest, Michael F; Bezanilla, Francisco

2015-01-01

Voltage-sensing domains (VSDs) underlie the movement of voltage-gated ion channels, as well as the voltage-sensitive fluorescent responses observed from a common class of genetically encoded voltage indicators (GEVIs). Despite the widespread use and potential utility of these GEVIs, the biophysical underpinnings of the relationship between VSD movement and fluorophore response remain unclear. We investigated the recently developed GEVI ArcLight, and its close variant Arclight', at both the single-molecule and macroscopic levels to better understand their characteristics and mechanisms of activity. These studies revealed a number of previously unobserved features of ArcLight's behavior, including millisecond-scale fluorescence fluctuations in single molecules as well as a previously unreported delay prior to macroscopic fluorescence onset. Finally, these mechanistic insights allowed us to improve the optical response of ArcLight to fast or repetitive pulses with the development of ArcLightning, a novel GEVI with improved kinetics. DOI: http://dx.doi.org/10.7554/eLife.10482.001 PMID:26599732

21 CFR 7.59 - General industry guidance.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false General industry guidance. 7.59 Section 7.59 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENFORCEMENT POLICY Recalls (Including Product Corrections)-Guidance on Policy, Procedures, and Industry...

Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

PubMed Central

van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

1992-01-01

Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

Effortful Retrieval Reduces Hippocampal Activity and Impairs Incidental Encoding

PubMed Central

Reas, Emilie T.; Brewer, James B.

2014-01-01

Functional imaging studies frequently report that the hippocampus is engaged by successful episodic memory retrieval. However, considering that concurrent encoding of the background environment occurs during retrieval and influences medial temporal lobe activity, it is plausible that hippocampal encoding functions are reduced with increased attentional engagement during effortful retrieval. Expanding upon evidence that retrieval efforts suppress activity in hippocampal regions implicated in encoding, this study examines the influence of retrieval effort on encoding performance and the interactive effects of encoding and retrieval on hippocampal and neocortical activity. Functional magnetic resonance imaging was conducted while subjects performed a word recognition task with incidental picture encoding. Both lower memory strength and increased search duration were associated with encoding failure and reduced hippocampal and default network activity. Activity in the anterior hippocampus tracked encoding, which was more strongly deactivated when incidental encoding was unsuccessful. These findings highlight potential contributions from background encoding processes to hippocampal activations during neuroimaging studies of episodic memory retrieval. PMID:23378272

USAF Development Of Optical Correlation Missile Guidance

NASA Astrophysics Data System (ADS)

Kaehr, Ronald; Spector, Marvin

1980-12-01

In 1965, the Advanced Development Program (ADP)-679A of the Avionics Laboratory initiated development of guidance systems for stand-off tactical missiles. Employing project engineering support from the Aeronautical Systems Division, WPAFB, the Avionics Laboratory funded multiple terminal guidance concepts and related midcourse navigation technology. Optical correlation techniques which utilize prestored reference information for autonomous target acquisition offered the best near-term opportunity for meeting mission goals. From among the systems studied and flight tested, Aimpoint* optical area guidance provided the best and most consistent performance. Funded development by the Air Force ended in 1974 with a MK-84 guided bomb drop test demonstration at White Sands Missile Range and the subsequent transfer of the tactical missile guidance development charter to the Air Force Armament Laboratory, Eglin AFB. A historical review of optical correlation development within the Avionics Laboratory is presented. Evolution of the Aimpoint system is specifically addressed. Finally, a brief discussion of trends in scene matching technology is presented.

Molecules Without Atoms

NASA Astrophysics Data System (ADS)

Ruth, Anthony; Collins, Laura; Gomes, Kenjiro; Janko, Boldizsar

We present a real-space representation of molecules which results in the normal bonding rules and electronic structure of chemistry without atom-centered coulomb potentials. Using a simple mapping, we can generate atomless molecules from the structure of real molecules. Additionally, molecules without atoms show similar covalent bonding energies and transfer of charge in ionic bonds as real molecules. The atomless molecules contain only the valence and conduction electronic structure of the real molecule. Using the framework of the Atoms in Molecules (AIM) theory of Bader, we prove that the topological features of the valence charge distribution of molecules without atoms are identical to that of real molecules. In particular, the charge basins of atomless molecules show identical location and quantities of representative charge. We compare the accuracy, computational cost, and intuition gained from electronic structure calculations of molecules without atoms with the use of pseudopotentials to represent atomic cores in density functional theory. A. R. acknowledges support from a NASA Space Technology Research Fellowship.

Key Performance Indicators for the Assessment of Pediatric Pharmacotherapeutic Guidance

PubMed Central

Barrett, Jeffrey S.; Patel, Dimple; Jayaraman, Bhuvana; Narayan, Mahesh; Zuppa, Athena

2008-01-01

Given the paucity of actual guidance provided for managing pediatric drug therapy, prescribing caregivers must be able to draw on the limited published information in pediatrics and/or guidance provided in adults with some account for expected pediatric response. Guidance for managing drug therapy in children is clearly desirable. Our objectives were to construct key performance indicators (KPIs) for pediatric pharmacotherapy guidance to identify drugs where pharmacotherapy guidance would be most beneficial. A pilot survey to assess variation in caregiver appreciation for pediatric dosing guidance has also been constructed to provide a complementary subjective assessment. Three KPI categories, drug utilization (based on hospital admission and billing data collected from 2001 through 2006), medical need, and guidance outcome value along with a KPI composite score have been proposed. Low scores are favored with respect to prioritization for pharmacotherapy guidance. The pilot survey consisted of 15 questions to assess 1) physician knowledge regarding dosing guidance, 2) attitudes toward dose modification and patient individualization, 3) the accessibility, ease of use and appropriateness of existing data stores, and 4) frequency of dosing modification, consultation of dosing compendiums and estimate of success rate in dosing guidance. Pilot results suggest that dosing guidance is generally viewed as important and that the existing resources are insufficient to guide recommendations for all drugs. While the majority of respondents check more than one resource less than 25% of the time, at least 25% of the respondents check more than one resource 25–50% of the time. The majority viewed the relevance of dosing guidance very important to the management of drug therapy. The questionnaire is being extended to the primary care centers, the Kids First Network and specialty care centers. Results will guide the development of decision support systems (DSS) that provide

Key performance indicators for the assessment of pediatric pharmacotherapeutic guidance.

PubMed

Barrett, Jeffrey S; Patel, Dimple; Jayaraman, Bhuvana; Narayan, Mahesh; Zuppa, Athena

2008-07-01

Given the paucity of actual guidance provided for managing pediatric drug therapy, prescribing caregivers must be able to draw on the limited published information in pediatrics and/or guidance provided in adults with some account for expected pediatric response. Guidance for managing drug therapy in children is clearly desirable. Our objectives were to construct key performance indicators (KPIs) for pediatric pharmacotherapy guidance to identify drugs where pharmacotherapy guidance would be most beneficial. A pilot survey to assess variation in caregiver appreciation for pediatric dosing guidance has also been constructed to provide a complementary subjective assessment. Three KPI categories, drug utilization (based on hospital admission and billing data collected from 2001 through 2006), medical need, and guidance outcome value along with a KPI composite score have been proposed. Low scores are favored with respect to prioritization for pharmacotherapy guidance. The pilot survey consisted of 15 questions to assess 1) physician knowledge regarding dosing guidance, 2) attitudes toward dose modification and patient individualization, 3) the accessibility, ease of use and appropriateness of existing data stores, and 4) frequency of dosing modification, consultation of dosing compendiums and estimate of success rate in dosing guidance. Pilot results suggest that dosing guidance is generally viewed as important and that the existing resources are insufficient to guide recommendations for all drugs. While the majority of respondents check more than one resource less than 25% of the time, at least 25% of the respondents check more than one resource 25-50% of the time. The majority viewed the relevance of dosing guidance very important to the management of drug therapy. The questionnaire is being extended to the primary care centers, the Kids First Network and specialty care centers. Results will guide the development of decision support systems (DSS) that provide patient

Getting Closer: Workplace Guidance for Lifelong Learning

ERIC Educational Resources Information Center

Plant, Peter; Turner, Bob

2005-01-01

The purposes of this article are twofold. First, it considers the policy links between guidance and lifelong learning, highlighting in particular the implications of findings from a recent study by the Organisation for Economic Co-operation and Development (OECD). Secondly, it critically compares two approaches to workplace guidance about…

Middle School Developmental Guidance. "Steps to Success."

ERIC Educational Resources Information Center

Orange County Public Schools, Orlando, FL.

This document articulates the goals and objectives of the middle school guidance program in Orange County, Florida Public Schools system. Professional roles and responsibilities are discussed, as well as program implementation. These goals to assist students are listed for the middle school guidance program: (1) understanding the school…

Absolute angular encoder based on optical diffraction

NASA Astrophysics Data System (ADS)

Wu, Jian; Zhou, Tingting; Yuan, Bo; Wang, Liqiang

2015-08-01

A new encoding method for absolute angular encoder based on optical diffraction was proposed in the present study. In this method, an encoder disc is specially designed that a series of elements are uniformly spaced in one circle and each element is consisted of four diffraction gratings, which are tilted in the directions of 30°, 60°, -60° and -30°, respectively. The disc is illuminated by a coherent light and the diffractive signals are received. The positions of diffractive spots are used for absolute encoding and their intensities are for subdivision, which is different from the traditional optical encoder based on transparent/opaque binary principle. Since the track's width in the disc is not limited in the diffraction pattern, it provides a new way to solve the contradiction between the size and resolution, which is good for minimization of encoder. According to the proposed principle, the diffraction pattern disc with a diameter of 40 mm was made by lithography in the glass substrate. A prototype of absolute angular encoder with a resolution of 20" was built up. Its maximum error was tested as 78" by comparing with a small angle measuring system based on laser beam deflection.

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.

Highly Effective Photonic Cue for Repulsive Axonal Guidance

PubMed Central

Black, Bryan J.; Gu, Ling; Mohanty, Samarendra K.

2014-01-01

In vivo nerve repair requires not only the ability to regenerate damaged axons, but most importantly, the ability to guide developing or regenerating axons along paths that will result in functional connections. Furthermore, basic studies in neuroscience and neuro-electronic interface design require the ability to construct in vitro neural circuitry. Both these applications require the development of a noninvasive, highly effective tool for axonal growth-cone guidance. To date, a myriad of technologies have been introduced based on chemical, electrical, mechanical, and hybrid approaches (such as electro-chemical, optofluidic flow and photo-chemical methods). These methods are either lacking in desired spatial and temporal selectivity or require the introduction of invasive external factors. Within the last fifteen years however, several attractive guidance cues have been developed using purely light based cues to achieve axonal guidance. Here, we report a novel, purely optical repulsive guidance technique that uses low power, near infrared light, and demonstrates the guidance of primary goldfish retinal ganglion cell axons through turns of up to 120 degrees and over distances of ∼90 µm. PMID:24717339

Highly effective photonic cue for repulsive axonal guidance.

PubMed

Black, Bryan J; Gu, Ling; Mohanty, Samarendra K

2014-01-01

In vivo nerve repair requires not only the ability to regenerate damaged axons, but most importantly, the ability to guide developing or regenerating axons along paths that will result in functional connections. Furthermore, basic studies in neuroscience and neuro-electronic interface design require the ability to construct in vitro neural circuitry. Both these applications require the development of a noninvasive, highly effective tool for axonal growth-cone guidance. To date, a myriad of technologies have been introduced based on chemical, electrical, mechanical, and hybrid approaches (such as electro-chemical, optofluidic flow and photo-chemical methods). These methods are either lacking in desired spatial and temporal selectivity or require the introduction of invasive external factors. Within the last fifteen years however, several attractive guidance cues have been developed using purely light based cues to achieve axonal guidance. Here, we report a novel, purely optical repulsive guidance technique that uses low power, near infrared light, and demonstrates the guidance of primary goldfish retinal ganglion cell axons through turns of up to 120 degrees and over distances of ∼90 µm.

Diverse circular replication-associated protein encoding viruses circulating in invertebrates within a lake ecosystem.

PubMed

Dayaram, Anisha; Galatowitsch, Mark L; Argüello-Astorga, Gerardo R; van Bysterveldt, Katherine; Kraberger, Simona; Stainton, Daisy; Harding, Jon S; Roumagnac, Philippe; Martin, Darren P; Lefeuvre, Pierre; Varsani, Arvind

2016-04-01

Over the last five years next-generation sequencing has become a cost effective and efficient method for identifying known and unknown microorganisms. Access to this technique has dramatically changed the field of virology, enabling a wide range of environmental viral metagenome studies to be undertaken of organisms and environmental samples from polar to tropical regions. These studies have led to the discovery of hundreds of highly divergent single stranded DNA (ssDNA) virus-like sequences encoding replication-associated proteins. Yet, few studies have explored how viruses might be shared in an ecosystem through feeding relationships. Here we identify 169 circular molecules (160 CRESS DNA molecules, nine circular molecules) recovered from a New Zealand freshwater lake, that we have tentatively classified into 51 putatively novel species and five previously described species (DflaCV-3, -5, -6, -8, -10). The CRESS DNA viruses identified in this study were recovered from molluscs (Echyridella menzeisii, Musculium novaezelandiae, Potamopyrgus antipodarum and Physella acuta) and insect larvae (Procordulia grayi, Xanthocnemis zealandica, and Chironomus zealandicus) collected from Lake Sarah, as well as from the lake water and benthic sediments. Extensive diversity was observed across most CRESS DNA molecules recovered. The putative capsid protein of one viral species was found to be most similar to those of members of the Tombusviridae family, thus expanding the number of known RNA-DNA hybrid viruses in nature. We noted a strong association between the CRESS DNA viruses and circular molecules identified in the water and browser organisms (C. zealandicus, P. antipodarum and P. acuta), and between water sediments and undefended prey species (C. zealandicus). However, we were unable to find any significant correlation of viral assemblages to the potential feeding relationships of the host aquatic invertebrates. Copyright © 2016 Elsevier B.V. All rights reserved.

Automatic guidance and control laws for helicopter obstacle avoidance

NASA Technical Reports Server (NTRS)

Cheng, Victor H. L.; Lam, T.

1992-01-01

The authors describe the implementation of a full-function guidance and control system for automatic obstacle avoidance in helicopter nap-of-the-earth (NOE) flight. The guidance function assumes that the helicopter is sufficiently responsive so that the flight path can be readily adjusted at NOE speeds. The controller, basically an autopilot for following the derived flight path, was implemented with parameter values to control a generic helicopter model used in the simulation. Evaluation of the guidance and control system with a 3-dimensional graphical helicopter simulation suggests that the guidance has the potential for providing good and meaningful flight trajectories.

Waypoints Following Guidance for Surface-to-Surface Missiles

NASA Astrophysics Data System (ADS)

Zhou, Hao; Khalil, Elsayed M.; Rahman, Tawfiqur; Chen, Wanchun

2018-04-01

The paper proposes waypoints following guidance law. In this method an optimal trajectory is first generated which is then represented through a set of waypoints that are distributed from the starting point up to the final target point using a polynomial. The guidance system then works by issuing guidance command needed to move from one waypoint to the next one. Here the method is applied for a surface-to-surface missile. The results show that the method is feasible for on-board application.

Design and Testing of a Low Noise Flight Guidance Concept

NASA Technical Reports Server (NTRS)

Williams, David H.; Oseguera-Lohr, Rosa M.; Lewis, Elliot T.

2004-01-01

A flight guidance concept was developed to assist in flying continuous descent approach (CDA) procedures designed to lower the noise under the flight path of jet transport aircraft during arrival operations at an airport. The guidance consists of a trajectory prediction algorithm that was tuned to produce a high-efficiency, low noise flight profile with accompanying autopilot and flight display elements needed by the flight control system and pilot to fly the approach. A key component of the flight guidance was a real-time display of energy error relative to the predicted flight path. The guidance was integrated with the conventional Flight Management System (FMS) guidance of a modern jet transport airplane and tested in a high fidelity flight simulation. A charted arrival procedure, which allowed flying conventional arrivals, CDA arrivals with standard guidance, and CDA arrivals with the new low noise guidance, was developed to assist in the testing and evaluation of the low noise guidance concept. Results of the simulation testing showed the low noise guidance was easy to use by airline pilot test subjects and effective in achieving the desired noise reduction. Noise under the flight path was reduced by at least 2 decibels in Sound Exposure Level (SEL) at distances from about 3 nautical miles out to about 17.5 nautical miles from the runway, with a peak reduction of 8.5 decibels at about 10.5 nautical miles. Fuel consumption was also reduced by about 17% for the LNG conditions compared to baseline runs for the same flight distance. Pilot acceptance and understanding of the guidance was quite high with favorable comments and ratings received from all test subjects.

A New Quantum Gray-Scale Image Encoding Scheme

NASA Astrophysics Data System (ADS)

Naseri, Mosayeb; Abdolmaleky, Mona; Parandin, Fariborz; Fatahi, Negin; Farouk, Ahmed; Nazari, Reza

2018-02-01

In this paper, a new quantum images encoding scheme is proposed. The proposed scheme mainly consists of four different encoding algorithms. The idea behind of the scheme is a binary key generated randomly for each pixel of the original image. Afterwards, the employed encoding algorithm is selected corresponding to the qubit pair of the generated randomized binary key. The security analysis of the proposed scheme proved its enhancement through both randomization of the generated binary image key and altering the gray-scale value of the image pixels using the qubits of randomized binary key. The simulation of the proposed scheme assures that the final encoded image could not be recognized visually. Moreover, the histogram diagram of encoded image is flatter than the original one. The Shannon entropies of the final encoded images are significantly higher than the original one, which indicates that the attacker can not gain any information about the encoded images. Supported by Kermanshah Branch, Islamic Azad University, Kermanshah, IRAN

Flu Vaccine Guidance for Patients with Immune Deficiency

MedlinePlus

... Vaccine Guidance for Patients with Immune Deficiency Share | Flu Vaccine Guidance for Patients with Immune Deficiency This ... is the best tool for prevention of the flu, should patients with immune deficiency be given the ...

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.

76 FR 411 - Regulatory Guidance Concerning Electronic Signatures and Documents

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... Concerning Electronic Signatures and Documents AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of regulatory guidance. SUMMARY: FMCSA issues regulatory guidance concerning the... regulatory guidance concerning the use of electronic signatures and documents to comply with FMCSA...

Mission-based guidance system design for autonomous UAVs

NASA Astrophysics Data System (ADS)

Moon, Jongki

The advantages of UAVs in the aviation arena have led to extensive research activities on autonomous technology of UAVs to achieve specific mission objectives. This thesis mainly focuses on the development of a mission-based guidance system. Among various missions expected for future needs, autonomous formation flight (AFF) and obstacle avoidance within safe operation limits are investigated. In the design of an adaptive guidance system for AFF, the leader information except position is assumed to be unknown to a follower. Thus, the only measured information related to the leader is the line-of-sight (LOS) range and angle. Adding an adaptive element with neural networks into the guidance system provides a capability to effectively handle leader's velocity changes. Therefore, this method can be applied to the AFF control systems that use a passive sensing method. In this thesis, an adaptive velocity command guidance system and an adaptive acceleration command guidance system are developed and presented. Since relative degrees of the LOS range and angle are different depending on the outputs from the guidance system, the architecture of the guidance system changes accordingly. Simulations and flight tests are performed using the Georgia Tech UAV helicopter, the GTMax, to evaluate the proposed guidance systems. The simulation results show that the neural network (NN) based adaptive element can improve the tracking performance by effectively compensating for the effect of unknown dynamics. It has also been shown that the combination of an adaptive velocity command guidance system and the existing GTMax autopilot controller performs better than the combination of an adaptive acceleration command guidance system and the GTMax autopilot controller. The successful flight evaluation using an adaptive velocity command guidance system clearly shows that the adaptive guidance control system is a promising solution for autonomous formation flight of UAVs. In addition, an

The Well-Being Outcomes of Career Guidance

ERIC Educational Resources Information Center

Robertson, Peter J.

2013-01-01

The potential for career guidance to impact on well-being has received insufficient attention in the UK. There are both conceptual and empirical reasons to expect that the impacts may be positive, but a lack of evidence directly testing this proposition. Career guidance has commonalities with therapeutic counselling suggesting analogous effects,…

Eddy current-nulled convex optimized diffusion encoding (EN-CODE) for distortion-free diffusion tensor imaging with short echo times.

PubMed

Aliotta, Eric; Moulin, Kévin; Ennis, Daniel B

2018-02-01

To design and evaluate eddy current-nulled convex optimized diffusion encoding (EN-CODE) gradient waveforms for efficient diffusion tensor imaging (DTI) that is free of eddy current-induced image distortions. The EN-CODE framework was used to generate diffusion-encoding waveforms that are eddy current-compensated. The EN-CODE DTI waveform was compared with the existing eddy current-nulled twice refocused spin echo (TRSE) sequence as well as monopolar (MONO) and non-eddy current-compensated CODE in terms of echo time (TE) and image distortions. Comparisons were made in simulations, phantom experiments, and neuro imaging in 10 healthy volunteers. The EN-CODE sequence achieved eddy current compensation with a significantly shorter TE than TRSE (78 versus 96 ms) and a slightly shorter TE than MONO (78 versus 80 ms). Intravoxel signal variance was lower in phantoms with EN-CODE than with MONO (13.6 ± 11.6 versus 37.4 ± 25.8) and not different from TRSE (15.1 ± 11.6), indicating good robustness to eddy current-induced image distortions. Mean fractional anisotropy values in brain edges were also significantly lower with EN-CODE than with MONO (0.16 ± 0.01 versus 0.24 ± 0.02, P < 1 x 10 -5 ) and not different from TRSE (0.16 ± 0.01 versus 0.16 ± 0.01, P = nonsignificant). The EN-CODE sequence eliminated eddy current-induced image distortions in DTI with a TE comparable to MONO and substantially shorter than TRSE. Magn Reson Med 79:663-672, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Pre-Publication to the Planning for Natural Disaster Debris Guidance

EPA Pesticide Factsheets

EPA is requesting comment on the draft update of the Planning for Natural Disaster Debris Guidance, along with two other documents. This Guidance is an update of the Planning for Natural Disaster Debris guidance that EPA published in March 2008.

Guidance Concept for a Mars Ascent Vehicle First Stage

NASA Technical Reports Server (NTRS)

Queen, Eric M.

2000-01-01

This paper presents a guidance concept for use on the first stage of a Mars Ascent Vehicle (MAV). The guidance is based on a calculus of variations approach similar to that used for the final phase of the Apollo Earth return guidance. A three degree-of-freedom (3DOF) Monte Carlo simulation is used to evaluate performance and robustness of the algorithm.

A tumor-promoting mechanism mediated by retrotransposon-encoded reverse transcriptase is active in human transformed cell lines

PubMed Central

Sciamanna, Ilaria; Gualtieri, Alberto; Cossetti, Cristina; Osimo, Emanuele Felice; Ferracin, Manuela; Macchia, Gianfranco; Aricò, Eleonora; Prosseda, Gianni; Vitullo, Patrizia; Misteli, Tom; Spadafora, Corrado

2013-01-01

LINE-1 elements make up the most abundant retrotransposon family in the human genome. Full-length LINE-1 elements encode a reverse transcriptase (RT) activity required for their own retrotranpsosition as well as that of non-autonomous Alu elements. LINE-1 are poorly expressed in normal cells and abundantly in cancer cells. Decreasing RT activity in cancer cells, by either LINE-1-specific RNA interference, or by RT inhibitory drugs, was previously found to reduce proliferation and promote differentiation and to antagonize tumor growth in animal models. Here we have investigated how RT exerts these global regulatory functions. We report that the RT inhibitor efavirenz (EFV) selectively downregulates proliferation of transformed cell lines, while exerting only mild effects on non-transformed cells; this differential sensitivity matches a differential RT abundance, which is high in the former and undetectable in the latter. Using CsCl density gradients, we selectively identify Alu and LINE-1 containing DNA:RNA hybrid molecules in cancer but not in normal cells. Remarkably, hybrid molecules fail to form in tumor cells treated with EFV under the same conditions that repress proliferation and induce the reprogramming of expression profiles of coding genes, microRNAs (miRNAs) and ultraconserved regions (UCRs). The RT-sensitive miRNAs and UCRs are significantly associated with Alu sequences. The results suggest that LINE-1-encoded RT governs the balance between single-stranded and double-stranded RNA production. In cancer cells the abundant RT reverse-transcribes retroelement-derived mRNAs forming RNA:DNA hybrids. We propose that this impairs the formation of double-stranded RNAs and the ensuing production of small regulatory RNAs, with a direct impact on gene expression. RT inhibition restores the ‘normal’ small RNA profile and the regulatory networks that depend on them. Thus, the retrotransposon-encoded RT drives a previously unrecognized mechanism crucial to the

Negative base encoding in optical linear algebra processors

NASA Technical Reports Server (NTRS)

Perlee, C.; Casasent, D.

1986-01-01

In the digital multiplication by analog convolution algorithm, the bits of two encoded numbers are convolved to form the product of the two numbers in mixed binary representation; this output can be easily converted to binary. Attention is presently given to negative base encoding, treating base -2 initially, and then showing that the negative base system can be readily extended to any radix. In general, negative base encoding in optical linear algebra processors represents a more efficient technique than either sign magnitude or 2's complement encoding, when the additions of digitally encoded products are performed in parallel.

Data Encoding using Periodic Nano-Optical Features

NASA Astrophysics Data System (ADS)

Vosoogh-Grayli, Siamack

Successful trials have been made through a designed algorithm to quantize, compress and optically encode unsigned 8 bit integer values in the form of images using Nano optical features. The periodicity of the Nano-scale features (Nano-gratings) have been designed and investigated both theoretically and experimentally to create distinct states of variation (three on states and one off state). The use of easy to manufacture and machine readable encoded data in secured authentication media has been employed previously in bar-codes for bi-state (binary) models and in color barcodes for multiple state models. This work has focused on implementing 4 states of variation for unit information through periodic Nano-optical structures that separate an incident wavelength into distinct colors (variation states) in order to create an encoding system. Compared to barcodes and magnetic stripes in secured finite length storage media the proposed system encodes and stores more data. The benefits of multiple states of variation in an encoding unit are 1) increased numerically representable range 2) increased storage density and 3) decreased number of typical set elements for any ergodic or semi-ergodic source that emits these encoding units. A thorough investigation has targeted the effects of the use of multi-varied state Nano-optical features on data storage density and consequent data transmission rates. The results show that use of Nano-optical features for encoding data yields a data storage density of circa 800 Kbits/in2 via the implementation of commercially available high resolution flatbed scanner systems for readout. Such storage density is far greater than commercial finite length secured storage media such as Barcode family with maximum practical density of 1kbits/in2 and highest density magnetic stripe cards with maximum density circa 3 Kbits/in2. The numerically representable range of the proposed encoding unit for 4 states of variation is [0 255]. The number of

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…

WIPP waste characterization program sampling and analysis guidance manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-01-01

The Waste Isolation Pilot Plant (WIPP) Waste Characterization Program Sampling and Analysis Guidance Manual (Guidance Manual) provides a unified source of information on the sampling and analytical techniques that enable Department of Energy (DOE) facilities to comply with the requirements established in the current revision of the Quality Assurance Program Plan (QAPP) for the WIPP Experimental-Waste Characterization Program (the Program). This Guidance Manual includes all of the sampling and testing methodologies accepted by the WIPP Project Office (DOE/WPO) for use in implementing the Program requirements specified in the QAPP. This includes methods for characterizing representative samples of transuranic (TRU) wastesmore » at DOE generator sites with respect to the gas generation controlling variables defined in the WIPP bin-scale and alcove test plans, as well as waste container headspace gas sampling and analytical procedures to support waste characterization requirements under the WIPP test program and the Resource Conservation and Recovery Act (RCRA). The procedures in this Guidance Manual are comprehensive and detailed and are designed to provide the necessary guidance for the preparation of site specific procedures. The use of these procedures is intended to provide the necessary sensitivity, specificity, precision, and comparability of analyses and test results. The solutions to achieving specific program objectives will depend upon facility constraints, compliance with DOE Orders and DOE facilities' operating contractor requirements, and the knowledge and experience of the TRU waste handlers and analysts. With some analytical methods, such as gas chromatography/mass spectrometry, the Guidance Manual procedures may be used directly. With other methods, such as nondestructive/destructive characterization, the Guidance Manual provides guidance rather than a step-by-step procedure.« less

G-Guidance Interface Design for Small Body Mission Simulation

NASA Technical Reports Server (NTRS)

Acikmese, Behcet; Carson, John; Phan, Linh

2008-01-01

The G-Guidance software implements a guidance and control (G and C) algorithm for small-body, autonomous proximity operations, developed under the Small Body GN and C task at JPL. The software is written in Matlab and interfaces with G-OPT, a JPL-developed optimization package written in C that provides G-Guidance with guaranteed convergence to a solution in a finite computation time with a prescribed accuracy. The resulting program is computationally efficient and is a prototype of an onboard, real-time algorithm for autonomous guidance and control. Two thruster firing schemes are available in G-Guidance, allowing tailoring of the software for specific mission maneuvers. For example, descent, landing, or rendezvous benefit from a thruster firing at the maneuver termination to mitigate velocity errors. Conversely, ascent or separation maneuvers benefit from an immediate firing to avoid potential drift toward a second body. The guidance portion of this software explicitly enforces user-defined control constraints and thruster silence times while minimizing total fuel usage. This program is currently specialized to small-body proximity operations, but the underlying method can be generalized to other applications.

Initial contact guidance during cell spreading is contractility-independent.

PubMed

Sales, Adrià; Holle, Andrew W; Kemkemer, Ralf

2017-08-02

A wide variety of cell types exhibit substrate topography-based behavior, also known as contact guidance. However, the precise cellular mechanisms underlying this process are still unknown. In this study, we investigated contact guidance by studying the reaction of human endothelial cells (ECs) to well-defined microgroove topographies, both during and after initial cell spreading. As the cytoskeleton plays a major role in cellular adaptation to topographical features, two methods were used to perturb cytoskeletal structures. Inhibition of actomyosin contractility with the chemical inhibitor blebbistatatin demonstrated that initial contact guidance events are independent of traction force generation. However, cell alignment to the grooved substrate was altered at later time points, suggesting an initial 'passive' phase of contact guidance, followed by a contractility-dependent 'active' phase that relies on mechanosensitive feedback. The actin cytoskeleton was also perturbed in an indirect manner by culturing cells upside down, resulting in decreased levels of contact guidance and suggesting that a possible loss of contact between the actin cytoskeleton and the substrate could lead to cytoskeleton impairment. The process of contact guidance at the microscale was found to be primarily lamellipodia driven, as no bias in filopodia extension was observed on micron-scale grooves.

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.

Methods of Farm Guidance

ERIC Educational Resources Information Center

Vir, Dharm

1971-01-01

A survey of teaching methods for farm guidance workers in India, outlining some approaches developed by and used in other nations. Discusses mass educational methods, group educational methods, and the local leadership method. (JB)

Bottom-up design of small molecules that stimulate exon 10 skipping in mutant MAPT pre-mRNA.

PubMed

Luo, Yiling; Disney, Matthew D

2014-09-22

One challenge in chemical biology is to develop small molecules that control cellular protein content. The amount and identity of proteins are influenced by the RNAs that encode them; thus, protein content in a cell could be affected by targeting mRNA. However, RNA has been traditionally difficult to target with small molecules. In this report, we describe controlling the protein products of the mutated microtubule-associated protein tau (MAPT) mature mRNA with a small molecule. MAPT mutations in exon 10 are associated with inherited frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), an incurable disease that is directly caused by increased inclusion of exon 10 in MAPT mRNA. Recent studies have shown that mutations within a hairpin at the MAPT exon 10-intron junction decrease the thermodynamic stability of the RNA, increasing binding to U1 snRNP and thus exon 10 inclusion. Therefore, we designed small molecules that bind and stabilize a mutant MAPT by using Inforna, a computational approach based on information about RNA-small-molecule interactions. The optimal compound selectively bound the mutant MAPT hairpin and thermodynamically stabilized its folding, facilitating exon 10 exclusion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Image Guidance Technologies for Interventional Pain Procedures: Ultrasound, Fluoroscopy, and CT.

PubMed

Wang, Dajie

2018-01-26

Chronic pain is a common medical condition. Patients who suffer uncontrolled chronic pain may require interventions including spinal injections and various nerve blocks. Interventional procedures have evolved and improved over time since epidural injection was first introduced for low back pain and sciatica in 1901. One of the major contributors in the improvement of these interventions is the advancement of imaging guidance technologies. The utilization of image guidance has dramatically improved the accuracy and safety of these interventions. The first image guidance technology adopted by pain specialists was fluoroscopy. This was followed by CT and ultrasound. Fluoroscopy can be used to visualize bony structures of the spine. It is still the most commonly used guidance technology in spinal injections. In the recent years, ultrasound guidance has been increasingly adopted by interventionists to perform various injections. Because its ability to visualize soft tissue, vessels, and nerves, this guidance technology appears to be a better option than fluoroscopy for interventions including SGB and celiac plexus blocks, when visualization of the vessels may prevent intravascular injection. The current evidence indicates the efficacies of these interventions are similar between ultrasound guidance and fluoroscopy guidance for SGB and celiac plexus blocks. For facet injections and interlaminar epidural steroid injections, it is important to visualize bony structures in order to perform these procedures accurately and safely. It is worth noting that facet joint injections can be done under ultrasound guidance with equivalent efficacy to fluoroscopic guidance. However, obese patients may present challenge for ultrasound guidance due to its poor visualization of deep anatomical structures. Regarding transforaminal epidural steroid injections, there are limited evidence to support that ultrasound guidance technology has equivalent efficacy and less complications comparing

Selective Chemical Labeling of Proteins with Small Fluorescent Molecules Based on Metal-Chelation Methodology

PubMed Central

Soh, Nobuaki

2008-01-01

Site-specific chemical labeling utilizing small fluorescent molecules is a powerful and attractive technique for in vivo and in vitro analysis of cellular proteins, which can circumvent some problems in genetic encoding labeling by large fluorescent proteins. In particular, affinity labeling based on metal-chelation, advantageous due to the high selectivity/simplicity and the small tag-size, is promising, as well as enzymatic covalent labeling, thereby a variety of novel methods have been studied in recent years. This review describes the advances in chemical labeling of proteins, especially highlighting the metal-chelation methodology. PMID:27879749

A method for encoding clinical datasets with SNOMED CT.

PubMed

Lee, Dennis H; Lau, Francis Y; Quan, Hue

2010-09-17

Over the past decade there has been a growing body of literature on how the Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) can be implemented and used in different clinical settings. Yet, for those charged with incorporating SNOMED CT into their organisation's clinical applications and vocabulary systems, there are few detailed encoding instructions and examples available to show how this can be done and the issues involved. This paper describes a heuristic method that can be used to encode clinical terms in SNOMED CT and an illustration of how it was applied to encode an existing palliative care dataset. The encoding process involves: identifying input data items; cleaning the data items; encoding the cleaned data items; and exporting the encoded terms as output term sets. Four outputs are produced: the SNOMED CT reference set; interface terminology set; SNOMED CT extension set and unencodeable term set. The original palliative care database contained 211 data elements, 145 coded values and 37,248 free text values. We were able to encode ~84% of the terms, another ~8% require further encoding and verification while terms that had a frequency of fewer than five were not encoded (~7%). From the pilot, it would seem our SNOMED CT encoding method has the potential to become a general purpose terminology encoding approach that can be used in different clinical systems.

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.

Role of sleep for encoding of emotional memory.

PubMed

Kaida, Kosuke; Niki, Kazuhisa; Born, Jan

2015-05-01

Total sleep deprivation (TSD) has been consistently found to impair encoding of information during ensuing wakefulness, probably through suppressing NonREM (non-rapid eye movement) sleep. However, a possible contribution of missing REM sleep to this encoding impairment after TSD has so far not been systematically examined in humans, although such contribution might be suspected in particular for emotional information. Here, in two separate experiments in young healthy men, we compared effects of TSD and of selective REM sleep deprivation (REMD), relative to respective control conditions of undisturbed sleep, on the subsequent encoding of neutral and emotional pictures. The pictures were presented in conjunction with colored frames to also assess related source memory. REMD was achieved by tones presented contingently upon initial signs of REM sleep. Encoding capabilities were examined in the evening (18:00h) after the experimental nights, by a picture recognition test right after encoding. TSD significantly decreased both the rate of correctly recognized pictures and of recalled frames associated with the pictures. The TSD effect was robust and translated into an impaired long term memory formation, as it was likewise observed on a second recognition testing one week after the encoding phase. Contrary to our expectation, REMD did not affect encoding in general, or particularly of emotional pictures. Also, REMD did not affect valence ratings of the encoded pictures. However, like TSD, REMD distinctly impaired vigilance at the time of encoding. Altogether, these findings indicate an importance of NonREM rather than REM sleep for the encoding of information that is independent of the emotionality of the materials. Copyright © 2015 Elsevier Inc. All rights reserved.

Career Guidance Continuum.

ERIC Educational Resources Information Center

Varmecky, John A.

1989-01-01

Describes the art career guidance programs at Johnstown High School (Pennsylvania). Programs include high school art students' visits to elementary and junior high schools, an "Artist at Work" exhibit at a shopping mall, and an art career guide for high school students. The programs have increased interest in art careers from grade…

Quieter pavements guidance document

DOT National Transportation Integrated Search

2013-02-01

This report provides guidance and better practice recommendations to the National Park : Service for selecting pavement surfaces to minimize tire-pavement noise. The report : contains an overview of common technologies and methods for quieter pavemen...

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.

Molecular mechanisms for protein-encoded inheritance

PubMed Central

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

2013-01-01

Strains are phenotypic variants, encoded by nucleic acid sequences in chromosomal inheritance and by protein “conformations” in prion inheritance and transmission. But how is a protein “conformation” stable enough to endure transmission between cells or organisms? Here new polymorphic crystal structures of segments of prion and other amyloid proteins offer structural mechanisms for prion strains. In packing polymorphism, prion strains are encoded by alternative packings (polymorphs) of β-sheets formed by the same segment of a protein; in a second mechanism, segmental polymorphism, prion strains are encoded by distinct β-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 information into prion strains share features with the familiar mechanism for transfer of information by nucleic acid inheritance, including sequence specificity and recognition by non-covalent bonds. PMID:19684598

Achievements, Challenges, and Opportunities in DNA-Encoded Library Research: An Academic Point of View.

PubMed

Yuen, Lik Hang; Franzini, Raphael M

2017-05-04

DNA-encoded chemical libraries (DECLs) are pools of DNA-tagged small molecules that enable facile screening and identification of bio-macromolecule binders. The successful development of DECLs has led to their increasingly important role in drug development, and screening hits have entered clinical trials. In this review, we summarize the development and currently active research areas of DECLs with a focus on contributions from groups at academic institutes. We further look at opportunities and future directions of DECL research in medicinal chemistry and chemical biology based on the symbiotic relationship between academia and industry. Challenges associated with the application of DECLs in academic drug discovery are further discussed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Methods of combined bioprocessing and related microorganisms, thermophilic and/or acidophilic enzymes, and nucleic acids encoding said enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, David N.; Apel, William A.; Thompson, Vicki S.

A genetically modified organism comprising: at least one nucleic acid sequence and/or at least one recombinant nucleic acid isolated from Alicyclobacillus acidocaldarius and encoding a polypeptide involved in at least partially degrading, cleaving, transporting, metabolizing, or removing polysaccharides, cellulose, lignocellulose, hemicellulose, lignin, starch, sugars, sugar oligomers, carbohydrates, complex carbohydrates, chitin, heteroxylans, glycosides, xylan-, glucan-, galactan-, or mannan-decorating groups; and at least one nucleic acid sequence and/or at least one recombinant nucleic acid encoding a polypeptide involved in fermenting sugar molecules to a product. Additionally, enzymatic and/or proteinaceous extracts may be isolated from one or more genetically modified organisms. The extractsmore » are utilized to convert biomass into a product. Further provided are methods of converting biomass into products comprising: placing the genetically modified organism and/or enzymatic extracts thereof in fluid contact with polysaccharides, cellulose, lignocellulose, hemicellulose, lignin, starch, sugars, sugar oligomers, carbohydrates, complex carbohydrates, chitin, heteroxylans, glycosides, and/or xylan-, glucan-, galactan-, or mannan-decorating groups.« less

Methods of combined bioprocessing and related microorganisms, thermophilic and/or acidophilic enzymes, and nucleic acids encoding said enzymes

DOEpatents

Thompson, David N.; Apel, William A.; Thompson, Vicki S.; Ward, Thomas E.

2016-03-22

A genetically modified organism comprising: at least one nucleic acid sequence and/or at least one recombinant nucleic acid isolated from Alicyclobacillus acidocaldarius and encoding a polypeptide involved in at least partially degrading, cleaving, transporting, metabolizing, or removing polysaccharides, cellulose, lignocellulose, hemicellulose, lignin, starch, sugars, sugar oligomers, carbohydrates, complex carbohydrates, chitin, heteroxylans, glycosides, xylan-, glucan-, galactan-, or mannan-decorating groups; and at least one nucleic acid sequence and/or at least one recombinant nucleic acid encoding a polypeptide involved in fermenting sugar molecules to a product. Additionally, enzymatic and/or proteinaceous extracts may be isolated from one or more genetically modified organisms. The extracts are utilized to convert biomass into a product. Further provided are methods of converting biomass into products comprising: placing the genetically modified organism and/or enzymatic extracts thereof in fluid contact with polysaccharides, cellulose, lignocellulose, hemicellulose, lignin, starch, sugars, sugar oligomers, carbohydrates, complex carbohydrates, chitin, heteroxylans, glycosides, and/or xylan-, glucan-, galactan-, or mannan-decorating groups.

Methods of combined bioprocessing and related microorganisms, thermophilic and/or acidophilic enzymes, and nucleic acids encoding said enzymes

DOEpatents

Thompson, David N; Apel, William A; Thompson, Vicki S; Ward, Thomas E

2013-07-23

A genetically modified organism comprising: at least one nucleic acid sequence and/or at least one recombinant nucleic acid isolated from Alicyclobacillus acidocaldarius and encoding a polypeptide involved in at least partially degrading, cleaving, transporting, metabolizing, or removing polysaccharides, cellulose, lignocellulose, hemicellulose, lignin, starch, sugars, sugar oligomers, carbohydrates, complex carbohydrates, chitin, heteroxylans, glycosides, xylan-, glucan-, galactan-, or mannan-decorating groups; and at least one nucleic acid sequence and/or at least one recombinant nucleic acid encoding a polypeptide involved in fermenting sugar molecules to a product. Additionally, enzymatic and/or proteinaceous extracts may be isolated from one or more genetically modified organisms. The extracts are utilized to convert biomass into a product. Further provided are methods of converting biomass into products comprising: placing the genetically modified organism and/or enzymatic extracts thereof in fluid contact with polysaccharides, cellulose, lignocellulose, hemicellulose, lignin, starch, sugars, sugar oligomers, carbohydrates, complex carbohydrates, chitin, heteroxylans, glycosides, and/or xylan-, glucan-, galactan-, or mannan-decorating groups.

Methods of combined bioprocessing and related microorganisms, thermophilic and/or acidophilic enzymes, and nucleic acids encoding said enzymes

DOEpatents

Thompson, David N; Apel, William A; Thompson, Vicki S; Ward, Thomas E

2014-04-08

A genetically modified organism comprising: at least one nucleic acid sequence and/or at least one recombinant nucleic acid isolated from Alicyclobacillus acidocaldarius and encoding a polypeptide involved in at least partially degrading, cleaving, transporting, metabolizing, or removing polysaccharides, cellulose, lignocellulose, hemicellulose, lignin, starch, sugars, sugar oligomers, carbohydrates, complex carbohydrates, chitin, heteroxylans, glycosides, xylan-, glucan-, galactan-, or mannan-decorating groups; and at least one nucleic acid sequence and/or at least one recombinant nucleic acid encoding a polypeptide involved in fermenting sugar molecules to a product. Additionally, enzymatic and/or proteinaceous extracts may be isolated from one or more genetically modified organisms. The extracts are utilized to convert biomass into a product. Further provided are methods of converting biomass into products comprising: placing the genetically modified organism and/or enzymatic extracts thereof in fluid contact with polysaccharides, cellulose, lignocellulose, hemicellulose, lignin, starch, sugars, sugar oligomers, carbohydrates, complex carbohydrates, chitin, heteroxylans, glycosides, and/or xylan-, glucan-, galactan-, or mannan-decorating groups.

15 CFR 917.41 - Application guidance for Sea Grant funding.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Application guidance for Sea Grant... REGULATIONS NATIONAL SEA GRANT PROGRAM FUNDING REGULATIONS General Considerations Pertaining to Sea Grant Funding § 917.41 Application guidance for Sea Grant funding. (a) Detailed guidance for submission of...

15 CFR 917.41 - Application guidance for Sea Grant funding.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Application guidance for Sea Grant... REGULATIONS NATIONAL SEA GRANT PROGRAM FUNDING REGULATIONS General Considerations Pertaining to Sea Grant Funding § 917.41 Application guidance for Sea Grant funding. (a) Detailed guidance for submission of...

15 CFR 917.41 - Application guidance for Sea Grant funding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Application guidance for Sea Grant... REGULATIONS NATIONAL SEA GRANT PROGRAM FUNDING REGULATIONS General Considerations Pertaining to Sea Grant Funding § 917.41 Application guidance for Sea Grant funding. (a) Detailed guidance for submission of...

15 CFR 917.41 - Application guidance for Sea Grant funding.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Application guidance for Sea Grant... REGULATIONS NATIONAL SEA GRANT PROGRAM FUNDING REGULATIONS General Considerations Pertaining to Sea Grant Funding § 917.41 Application guidance for Sea Grant funding. (a) Detailed guidance for submission of...

15 CFR 917.41 - Application guidance for Sea Grant funding.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Application guidance for Sea Grant... REGULATIONS NATIONAL SEA GRANT PROGRAM FUNDING REGULATIONS General Considerations Pertaining to Sea Grant Funding § 917.41 Application guidance for Sea Grant funding. (a) Detailed guidance for submission of...

Design Guidance for New Windows | Efficient Windows Collaborative

Science.gov Websites

Foundry Foundry New Construction Windows Window Selection Tool Selection Process Design Guidance Installation Replacement Windows Window Selection Tool Assessing Options Selection Process Design Guidance Installation Understanding Windows Benefits Design Considerations Measuring Performance Performance Standards

Design Guidance for Replacement Windows | Efficient Windows Collaborative

Science.gov Websites

Foundry Foundry New Construction Windows Window Selection Tool Selection Process Design Guidance Installation Replacement Windows Window Selection Tool Assessing Options Selection Process Design Guidance Installation Understanding Windows Benefits Design Considerations Measuring Performance Performance Standards

78 FR 9054 - Issuance of Final Guidance Publication

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... NIOSH-144] Issuance of Final Guidance Publication AGENCY: National Institute for Occupational Safety and... Services (HHS). ACTION: Notice of issuance of final guidance publication. SUMMARY: The National Institute...), announces the availability of the following publication: ``NIOSH Criteria for a Recommended Standard...

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.

Impact of NICE guidance on rates of haemorrhage after tonsillectomy: an evaluation of guidance issued during an ongoing national tonsillectomy audit.

PubMed

Audit, National Prospective Tonsillectomy

2008-08-01

The National Institute for Health and Clinical Excellence (NICE) issued guidance on surgical techniques for tonsillectomy during a national audit of surgical practice and postoperative complications. To assess the impact of the guidance on tonsillectomy practice and outcomes. An interrupted time-series analysis of routinely collected Hospital Episodes Statistics data, and an analysis of longitudinal trends in surgical technique using data from the National Prospective Tonsillectomy Audit. Patients undergoing tonsillectomy in English NHS hospitals between January 2002 and December 2004. Postoperative haemorrhage within 28 days. The rate of haemorrhage increased by 0.5% per year from 2002, reaching 6.4% when the guidance was published. After publication, the rate of haemorrhage fell immediately to 5.7% (difference 0.7%: 95% CI -1.3% to 0.0%) and the rate of increase appeared to have stopped. Data from the National Prospective Tonsillectomy Audit showed that the fall coincided with a shift in surgical techniques, which was consistent with the guidance. NICE guidance influenced surgical tonsillectomy technique and in turn produced an immediate fall in postoperative haemorrhage. The ongoing national audit and strong support from the surgical specialist association may have aided its implementation.

Orion Powered Flight Guidance Burn Options for Near Term Exploration

NASA Technical Reports Server (NTRS)

Fill, Tom; Goodman, John; Robinson, Shane

2018-01-01

NASA's Orion exploration spacecraft will fly more demanding mission profiles than previous NASA human flight spacecraft. Missions currently under development are destined for cislunar space. The EM-1 mission will fly unmanned to a Distant Retrograde Orbit (DRO) around the Moon. EM-2 will fly astronauts on a mission to the lunar vicinity. To fly these missions, Orion requires powered flight guidance that is more sophisticated than the orbital guidance flown on Apollo and the Space Shuttle. Orion's powered flight guidance software contains five burn guidance options. These five options are integrated into an architecture based on a proven shuttle heritage design, with a simple closed-loop guidance strategy. The architecture provides modularity, simplicity, versatility, and adaptability to future, yet-to-be-defined, exploration mission profiles. This paper provides a summary of the executive guidance architecture and details the five burn options to support both the nominal and abort profiles for the EM-1 and EM-2 missions.

47 CFR 73.4094 - Dolby encoder.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Dolby encoder. 73.4094 Section 73.4094 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4094 Dolby encoder. See Public Notice dated July 10...

47 CFR 73.4094 - Dolby encoder.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Dolby encoder. 73.4094 Section 73.4094 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Rules Applicable to All Broadcast Stations § 73.4094 Dolby encoder. See Public Notice dated July 10...

Beyond initial encoding: measures of the post-encoding status of memory traces predict long-term recall during infancy.

PubMed

Pathman, Thanujeni; Bauer, Patricia J

2013-02-01

The first years of life are witness to rapid changes in long-term recall ability. In the current research we contributed to an explanation of the changes by testing the absolute and relative contributions to long-term recall of encoding and post-encoding processes. Using elicited imitation, we sampled the status of 16-, 20-, and 24-month-old infants' memory representations at various time points after experience of events. In Experiment 1, infants were tested immediately, 1 week after encoding, and again after 1 month. The measure of 1-week trace status was a unique predictor of 1-month delayed recall. In Experiment 2, infants were tested immediately, 15 min, 48 h, and 2 weeks after encoding and again 1 month later. The measures of 15-min and 48-h trace strength contributed unique variance in 1-month delayed recall. The findings highlight the need to consider post-encoding processes in explanations of variability in long-term memory during infancy. Copyright © 2012 Elsevier Inc. All rights reserved.

Axon Response to Guidance Cues Is Stimulated by Acetylcholine in Caenorhabditis elegans

PubMed Central

Xu, Yan; Ren, Xing-Cong; Quinn, Christopher C.; Wadsworth, William G.

2011-01-01

Gradients of acetylcholine can stimulate growth cone turning when applied to neurons grown in culture, and it has been suggested that acetylcholine could act as a guidance cue. However, the role acetylcholine plays in directing axon migrations in vivo is not clear. Here, we show that acetylcholine positively regulates signaling pathways that mediate axon responses to guidance cues in Caenorhabditis elegans. Mutations that disrupt acetylcholine synthesis, transportation, and secretion affect circumferential axon guidance of the AVM neuron and in these mutants exogenously supplied acetylcholine improves AVM circumferential axon guidance. These effects are not observed for the circumferential guidance of the DD and VD motor neuron axons, which are neighbors of the AVM axon. Circumferential guidance is directed by the UNC-6 (netrin) and SLT-1 (slit) extracellular cues, and exogenously supplied acetylcholine can improve AVM axon guidance in mutants when either UNC-6– or SLT-1–induced signaling is disrupted, but not when both signaling pathways are perturbed. Not in any of the mutants does exogenously supplied acetylcholine improve DD and VD axon guidance. The ability of acetylcholine to enhance AVM axon guidance only in the presence of either UNC-6 or SLT-1 indicates that acetylcholine potentiates UNC-6 and SLT-1 guidance activity, rather than acting itself as a guidance cue. Together, our results show that for specific neurons acetylcholine plays an important role in vivo as a modulator of axon responses to guidance cues. PMID:21868605

GUIDANCE IN THE ELEMENTARY SCHOOL--CHILD CENTERED PROCEDURES AND TECHNIQUES.

ERIC Educational Resources Information Center

NELSON, GWEN

SOME CONSIDERATIONS BASIC TO ELEMENTARY GUIDANCE ARE DISCUSSED. THE PURPOSE OF A PROGRAM OF ELEMENTARY GUIDANCE IS TO PROVIDE BOTH CORE AND PREVENTIVE SERVICES WHICH PROMOTE PROPER CHILD GROWTH AND DEVELOPMENT. PRACTICALITY AND ECONOMY SUGGEST THE NECESSITY FOR INCREASED ACTIVITY IN PRIMARY PREVENTION. THE GUIDANCE SPECIALIST MUST WORK DIRECTLY…

Novel encoding methods for DNA-templated chemical libraries.

PubMed

Li, Gang; Zheng, Wenlu; Liu, Ying; Li, Xiaoyu

2015-06-01

Among various types of DNA-encoded chemical libraries, DNA-templated library takes advantage of the sequence-specificity of DNA hybridization, enabling not only highly effective DNA-templated chemical reactions, but also high fidelity in library encoding. This brief review summarizes recent advances that have been made on the encoding strategies for DNA-templated libraries, and it also highlights their respective advantages and limitations for the preparation of DNA-encoded libraries. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

HFE Process Guidance and Standards for potential application to updating NRC guidance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacques Hugo; J. J. Persensky

2012-07-01

The U.S. Nuclear Regulatory Commission (NRC) reviews and evaluates the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed tomore » the periodic update and improvement of these guidance documents to ensure that they remain state-of-the-art design evaluation tools. Thus, the NRC has initiated a project with BNL to update the NRC guidance to remain current with recent research on human performance, advances in HFE methods and tools, and new technology. INL supported Brookhaven National Lab (BNL) to update the detailed HFE review criteria contained in NUREG-0711 and NUREG-0700 based on (1) feedback obtained from end users, (2) the results of NRC research and development efforts supporting the NRC staff’s HFE safety reviews, and (3) other material the project staff identify as applicable to the update effort. INL submitted comments on development plans and sections of NUREGs 0800, 0711, and 0700. The contractor prepared the report attached here as the deliverable for this work.« less

76 FR 22106 - Issuance of Final Guidance Publication

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-20

... NIOSH-033] Issuance of Final Guidance Publication AGENCY: National Institute for Occupational Safety and... Health and Human Services (HHS). ACTION: Notice of issuance of final guidance publication. SUMMARY: The... (CDC) announces the availability of the following publication: NIOSH Current Intelligence Bulletin 63...

Career Guidance for Student Nurses: An Unmet Need.

ERIC Educational Resources Information Center

Marsland, Louise

1996-01-01

A British survey of 1,164 new registered nurses (1,015 responses) asked about career guidance they received related to applying for their first job, taking postbasic courses, and making longer-term plans. Few received much guidance, especially about individual career planning. (SK)

Using XML to encode TMA DES metadata.

PubMed

Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

2011-01-01

The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

Using XML to encode TMA DES metadata

PubMed Central

Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

2011-01-01

Background: The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs. PMID:21969921

Guidance: Using RCRA's Results-Based Approaches and Tailored Oversight Guidance when Performing Superfund Oversight

EPA Pesticide Factsheets

Memorandum providing additional information in support of Superfund's administrative reform on PRP oversight. Superfund program managers should consider RCRA's Results-Based Guidance when developing oversight plans with PRPs.

Encoding Orientation and the Remembering of Schizophrenic Young Adults

ERIC Educational Resources Information Center

Koh, Soon D.; Peterson, Rolf A.

1978-01-01

This research examines different types of encoding strategies, in addition to semantic and organizational encodings, and their effects on schizophrenics' remembering. Based on Craik and Lockhart (1972), i.e., memory performance is a function of depth of encoding processing, this analysis compares schizophrenics' encoding processing with that of…

Vertical Motion Simulator Experiment on Stall Recovery Guidance

NASA Technical Reports Server (NTRS)

Schuet, Stefan; Lombaerts, Thomas; Stepanyan, Vahram; Kaneshige, John; Shish, Kimberlee; Robinson, Peter; Hardy, Gordon H.

2017-01-01

A stall recovery guidance system was designed to help pilots improve their stall recovery performance when the current aircraft state may be unrecognized under various complicating operational factors. Candidate guidance algorithms were connected to the split-cue pitch and roll flight directors that are standard on large transport commercial aircraft. A new thrust guidance algorithm and cue was also developed to help pilots prevent the combination of excessive thrust and nose-up stabilizer trim. The overall system was designed to reinforce the current FAA recommended stall recovery procedure. A general transport aircraft model, similar to a Boeing 757, with an extended aerodynamic database for improved stall dynamics simulation fidelity was integrated into the Vertical Motion Simulator at NASA Ames Research Center. A detailed study of the guidance system was then conducted across four stall scenarios with 30 commercial and 10 research test pilots, and the results are reported.

Natural Products Version 2.0: Connecting Genes to Molecules

PubMed Central

Walsh, Christopher T.; Fischbach, Michael A.

2009-01-01

Natural products have played a prominent role in the history of organic chemistry, and they continue to be important as drugs, biological probes, and targets of study for synthetic and analytical chemists. In this perspective, we explore how connecting Nature’s small molecules to the genes that encode them has sparked a renaissance in natural product research, focusing primarily on the biosynthesis of polyketides and nonribosomal peptides. We survey monomer biogenesis, coupling chemistries from templated and non-templated pathways, and the broad set of tailoring reactions and hybrid pathways that give rise to the diverse scaffolds and functionalization patterns of natural products. We conclude by considering two questions: What would it take to find all natural product scaffolds? What kind of scientists will be studying natural products in the future? PMID:20121095

Augmented reality guidance system for peripheral nerve blocks

NASA Astrophysics Data System (ADS)

Wedlake, Chris; Moore, John; Rachinsky, Maxim; Bainbridge, Daniel; Wiles, Andrew D.; Peters, Terry M.

2010-02-01

Peripheral nerve block treatments are ubiquitous in hospitals and pain clinics worldwide. State of the art techniques use ultrasound (US) guidance and/or electrical stimulation to verify needle tip location. However, problems such as needle-US beam alignment, poor echogenicity of block needles and US beam thickness can make it difficult for the anesthetist to know the exact needle tip location. Inaccurate therapy delivery raises obvious safety and efficacy issues. We have developed and evaluated a needle guidance system that makes use of a magnetic tracking system (MTS) to provide an augmented reality (AR) guidance platform to accurately localize the needle tip as well as its projected trajectory. Five anesthetists and five novices performed simulated nerve block deliveries in a polyvinyl alcohol phantom to compare needle guidance under US alone to US placed in our AR environment. Our phantom study demonstrated a decrease in targeting attempts, decrease in contacting of critical structures, and an increase in accuracy of 0.68 mm compared to 1.34mm RMS in US guidance alone. Currently, the MTS uses 18 and 21 gauge hypodermic needles with a 5 degree of freedom sensor located at the needle tip. These needles can only be sterilized using an ethylene oxide process. In the interest of providing clinicians with a simple and efficient guidance system, we also evaluated attaching the sensor at the needle hub as a simple clip-on device. To do this, we simultaneously performed a needle bending study to assess the reliability of a hub-based sensor.

Approximate optimal guidance for the advanced launch system

NASA Technical Reports Server (NTRS)

Feeley, T. S.; Speyer, J. L.

1993-01-01

A real-time guidance scheme for the problem of maximizing the payload into orbit subject to the equations of motion for a rocket over a spherical, non-rotating earth is presented. An approximate optimal launch guidance law is developed based upon an asymptotic expansion of the Hamilton - Jacobi - Bellman or dynamic programming equation. The expansion is performed in terms of a small parameter, which is used to separate the dynamics of the problem into primary and perturbation dynamics. For the zeroth-order problem the small parameter is set to zero and a closed-form solution to the zeroth-order expansion term of Hamilton - Jacobi - Bellman equation is obtained. Higher-order terms of the expansion include the effects of the neglected perturbation dynamics. These higher-order terms are determined from the solution of first-order linear partial differential equations requiring only the evaluation of quadratures. This technique is preferred as a real-time, on-line guidance scheme to alternative numerical iterative optimization schemes because of the unreliable convergence properties of these iterative guidance schemes and because the quadratures needed for the approximate optimal guidance law can be performed rapidly and by parallel processing. Even if the approximate solution is not nearly optimal, when using this technique the zeroth-order solution always provides a path which satisfies the terminal constraints. Results for two-degree-of-freedom simulations are presented for the simplified problem of flight in the equatorial plane and compared to the guidance scheme generated by the shooting method which is an iterative second-order technique.

SERS-fluorescence joint spectral encoded magnetic nanoprobes for multiplex cancer cell separation.

PubMed

Wang, Zhuyuan; Zong, Shenfei; Chen, Hui; Wang, Chunlei; Xu, Shuhong; Cui, Yiping

2014-11-01

A new kind of cancer cell separation method is demonstrated, using surface-enhanced Raman scattering (SERS) and fluorescence dual-encoded magnetic nanoprobes. The designed nanoprobes can realize SERS-fluorescence joint spectral encoding (SFJSE) and greatly improve the multiplexing ability. The nanoprobes have four main components, that is, the magnetic core, SERS generator, fluorescent agent, and targeting antibody. These components are assembled with a multi-layered structure to form the nanoprobes. Specifically, silica-coated magnetic nanobeads (MBs) are used as the inner core. Au core-Ag shell nanorods (Au@Ag NRs) are employed as the SERS generators and attached on the silica-coated MBs. After burying these Au@Ag NRs with another silica layer, CdTe quantum dots (QDs), that is, the fluorescent agent, are anchored onto the silica layer. Finally, antibodies are covalently linked to CdTe QDs. SFJSE is fulfilled by using different Raman molecules and QDs with different emission wavelengths. By utilizing four human cancer cell lines and one normal cell line as the model cells, the nanoprobes can specifically and simultaneously separate target cancer cells from the normal ones. This SFJSE-based method greatly facilitates the multiplex, rapid, and accurate cancer cell separation, and has a prosperous potential in high-throughput analysis and cancer diagnosis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Consideration of health inequalities in systematic reviews: a mapping review of guidance.

PubMed

Maden, Michelle

2016-11-28

Given that we know that interventions shown to be effective in improving the health of a population may actually widen the health inequalities gap while others reduce it, it is imperative that all systematic reviewers consider how the findings of their reviews may impact (reduce or increase) on the health inequality gap. This study reviewed existing guidance on incorporating considerations of health inequalities in systematic reviews in order to examine the extent to which they can help reviewers to incorporate such issues. A mapping review was undertaken to identify guidance documents that purported to inform reviewers on whether and how to incorporate considerations of health inequalities. Searches were undertaken in Medline, CINAHL and The Cochrane Library Methodology Register. Review guidance manuals prepared by international organisations engaged in undertaking systematic reviews, and their associated websites were scanned. Studies were included if they provided an overview or discussed the development and testing of guidance for dealing with the incorporation of considerations of health inequalities in evidence synthesis. Results are summarised in narrative and tabular forms. Twenty guidance documents published between 2009 and 2016 were included. Guidance has been produced to inform considerations of health inequalities at different stages of the systematic review process. The Campbell and Cochrane Equity Group have been instrumental in developing and promoting such guidance. Definitions of health inequalities and guidance differed across the included studies. All but one guidance document were transparent in their method of production. Formal methods of evaluation were reported for six guidance documents. Most of the guidance was operationalised in the form of examples taken from published systematic reviews. The number of guidance items to operationalise ranges from 3 up to 26 with a considerable overlap noted. Adhering to the guidance will require more

The guidance of spatial attention during visual search for color combinations and color configurations.

PubMed

Berggren, Nick; Eimer, Martin

2016-09-01

Representations of target-defining features (attentional templates) guide the selection of target objects in visual search. We used behavioral and electrophysiological measures to investigate how such search templates control the allocation of attention in search tasks where targets are defined by the combination of 2 colors or by a specific spatial configuration of these colors. Target displays were preceded by spatially uninformative cue displays that contained items in 1 or both target-defining colors. Experiments 1 and 2 demonstrated that, during search for color combinations, attention is initially allocated independently and in parallel to all objects with target-matching colors, but is then rapidly withdrawn from objects that only have 1 of the 2 target colors. In Experiment 3, targets were defined by a particular spatial configuration of 2 colors, and could be accompanied by nontarget objects with a different configuration of the same colors. Attentional guidance processes were unable to distinguish between these 2 types of objects. Both attracted attention equally when they appeared in a cue display, and both received parallel focal-attentional processing and were encoded into working memory when they were presented in the same target display. Results demonstrate that attention can be guided simultaneously by multiple features from the same dimension, but that these guidance processes have no access to the spatial-configural properties of target objects. They suggest that attentional templates do not represent target objects in an integrated pictorial fashion, but contain separate representations of target-defining features. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Computerized adaptive control weld skate with CCTV weld guidance project

NASA Technical Reports Server (NTRS)

Wall, W. A.

1976-01-01

This report summarizes progress of the automatic computerized weld skate development portion of the Computerized Weld Skate with Closed Circuit Television (CCTV) Arc Guidance Project. The main goal of the project is to develop an automatic welding skate demonstration model equipped with CCTV weld guidance. The three main goals of the overall project are to: (1) develop a demonstration model computerized weld skate system, (2) develop a demonstration model automatic CCTV guidance system, and (3) integrate the two systems into a demonstration model of computerized weld skate with CCTV weld guidance for welding contoured parts.

Ascent Guidance for a Winged Boost Vehicle. M.S. Thesis

NASA Technical Reports Server (NTRS)

Corvin, Michael Alexander

1988-01-01

The objective of the advanced ascent guidance study was to investigate guidance concepts which could contribute to increased autonomy during ascent operations in a winged boost vehicle such as the proposed Shuttle II. The guidance scheme was required to yield near a full-optimal ascent in the presence of vehicle system and environmental dispersions. The study included consideration of trajectory shaping issues, trajectory design, closed loop and predictive adaptive guidance techniques and control of dynamic pressure by throttling. An extensive ascent vehicle simulation capability was developed for use in the study.

75 FR 14604 - Guidance for Industry on Anesthetics for Companion Animals; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-26

...] Guidance for Industry on Anesthetics for Companion Animals; Availability AGENCY: Food and Drug... availability of Guidance for Industry 192 entitled ``Anesthetics for Companion Animals.'' This guidance makes recommendations for the development of anesthetic new animal drug products for companion animals. The guidance...

Simultaneously driven linear and nonlinear spatial encoding fields in MRI.

PubMed

Gallichan, Daniel; Cocosco, Chris A; Dewdney, Andrew; Schultz, Gerrit; Welz, Anna; Hennig, Jürgen; Zaitsev, Maxim

2011-03-01

Spatial encoding in MRI is conventionally achieved by the application of switchable linear encoding fields. The general concept of the recently introduced PatLoc (Parallel Imaging Technique using Localized Gradients) encoding is to use nonlinear fields to achieve spatial encoding. Relaxing the requirement that the encoding fields must be linear may lead to improved gradient performance or reduced peripheral nerve stimulation. In this work, a custom-built insert coil capable of generating two independent quadratic encoding fields was driven with high-performance amplifiers within a clinical MR system. In combination with the three linear encoding fields, the combined hardware is capable of independently manipulating five spatial encoding fields. With the linear z-gradient used for slice-selection, there remain four separate channels to encode a 2D-image. To compare trajectories of such multidimensional encoding, the concept of a local k-space is developed. Through simulations, reconstructions using six gradient-encoding strategies were compared, including Cartesian encoding separately or simultaneously on both PatLoc and linear gradients as well as two versions of a radial-based in/out trajectory. Corresponding experiments confirmed that such multidimensional encoding is practically achievable and demonstrated that the new radial-based trajectory offers the PatLoc property of variable spatial resolution while maintaining finite resolution across the entire field-of-view. Copyright © 2010 Wiley-Liss, Inc.

Robust approximate optimal guidance strategies for aeroassisted orbital transfer missions

NASA Astrophysics Data System (ADS)

Ilgen, Marc R.

This thesis presents the application of game theoretic and regular perturbation methods to the problem of determining robust approximate optimal guidance laws for aeroassisted orbital transfer missions with atmospheric density and navigated state uncertainties. The optimal guidance problem is reformulated as a differential game problem with the guidance law designer and Nature as opposing players. The resulting equations comprise the necessary conditions for the optimal closed loop guidance strategy in the presence of worst case parameter variations. While these equations are nonlinear and cannot be solved analytically, the presence of a small parameter in the equations of motion allows the method of regular perturbations to be used to solve the equations approximately. This thesis is divided into five parts. The first part introduces the class of problems to be considered and presents results of previous research. The second part then presents explicit semianalytical guidance law techniques for the aerodynamically dominated region of flight. These guidance techniques are applied to unconstrained and control constrained aeroassisted plane change missions and Mars aerocapture missions, all subject to significant atmospheric density variations. The third part presents a guidance technique for aeroassisted orbital transfer problems in the gravitationally dominated region of flight. Regular perturbations are used to design an implicit guidance technique similar to the second variation technique but that removes the need for numerically computing an optimal trajectory prior to flight. This methodology is then applied to a set of aeroassisted inclination change missions. In the fourth part, the explicit regular perturbation solution technique is extended to include the class of guidance laws with partial state information. This methodology is then applied to an aeroassisted plane change mission using inertial measurements and subject to uncertainties in the initial value

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.

Aerobic Exercise During Encoding Impairs Hippocampus-Dependent Memory.

PubMed

Soga, Keishi; Kamijo, Keita; Masaki, Hiroaki

2017-08-01

We investigated how aerobic exercise during encoding affects hippocampus-dependent memory through a source memory task that assessed hippocampus-independent familiarity and hippocampus-dependent recollection processes. Using a within-participants design, young adult participants performed a memory-encoding task while performing a cycling exercise or being seated. The subsequent retrieval phase was conducted while sitting on a chair. We assessed behavioral and event-related brain potential measures of familiarity and recollection processes during the retrieval phase. Results indicated that source accuracy was lower for encoding with exercise than for encoding in the resting condition. Event-related brain potential measures indicated that the parietal old/new effect, which has been linked to recollection processing, was observed in the exercise condition, whereas it was absent in the rest condition, which is indicative of exercise-induced hippocampal activation. These findings suggest that aerobic exercise during encoding impairs hippocampus-dependent memory, which may be attributed to inefficient source encoding during aerobic exercise.

A Multi-Encoding Approach for LTL Symbolic Satisfiability Checking

NASA Technical Reports Server (NTRS)

Rozier, Kristin Y.; Vardi, Moshe Y.

2011-01-01

Formal behavioral specifications written early in the system-design process and communicated across all design phases have been shown to increase the efficiency, consistency, and quality of the system under development. To prevent introducing design or verification errors, it is crucial to test specifications for satisfiability. Our focus here is on specifications expressed in linear temporal logic (LTL). We introduce a novel encoding of symbolic transition-based Buchi automata and a novel, "sloppy," transition encoding, both of which result in improved scalability. We also define novel BDD variable orders based on tree decomposition of formula parse trees. We describe and extensively test a new multi-encoding approach utilizing these novel encoding techniques to create 30 encoding variations. We show that our novel encodings translate to significant, sometimes exponential, improvement over the current standard encoding for symbolic LTL satisfiability checking.

Dissociable roles of default-mode regions during episodic encoding.

PubMed

Maillet, David; Rajah, M Natasha

2014-04-01

We investigated the role of distinct regions of the default-mode network (DMN) during memory encoding with fMRI. Subjects encoded words using either a strategy that emphasized self-referential (pleasantness) processing, or one that emphasized semantic (man-made/natural) processing. During encoding subjects were intermittently presented with thought probes to evaluate if they were concentrated and on-task or exhibiting task-unrelated thoughts (TUT). After the scanning session subjects performed a source retrieval task to determine which of two judgments they performed for each word at encoding. Source retrieval accuracy was higher for words encoded with the pleasantness vs. the man-made/natural task and there was a trend for higher performance for words preceding on-task vs. TUT reports. fMRI results show that left anterior medial PFC and left angular gyrus activity was greater during successful vs. unsuccessful encoding during both encoding tasks. Greater activity in left anterior cingulate and bilateral lateral temporal cortex was related successful vs. unsuccessful encoding only in the pleasantness task. In contrast, posterior cingulate, right anterior cingulate and right temporoparietal junction were activated to a greater extent in unsuccessful vs. successful encoding across tasks. Finally, activation in posterior cingulate and bilateral dorsolateral prefrontal cortex was related to TUT across tasks; moreover, we observed a conjunction in posterior cingulate between encoding failure and TUT. We conclude that DMN regions play dissociable roles during memory formation, and that their association with subsequent memory may depend on the manner in which information is encoded and retrieved. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Guidance Every Day: A Helping Manual for Early Childhood Teachers.

ERIC Educational Resources Information Center

Feldman, Richard; And Others

Intended to help early childhood educators examine ways in which guidance can be infused into daily instruction, this manual aims to enable teachers to act as facilitators in the guidance process without adding a new assignment to an already busy schedule. Section A describes the integration of five guidance strands into the early childhood…

28 CFR 36.607 - Guidance concerning model codes.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Guidance concerning model codes. 36.607... BY PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES Certification of State Laws or Local Building Codes § 36.607 Guidance concerning model codes. Upon application by an authorized representative of a...

28 CFR 36.607 - Guidance concerning model codes.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Guidance concerning model codes. 36.607... BY PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES Certification of State Laws or Local Building Codes § 36.607 Guidance concerning model codes. Upon application by an authorized representative of a...

28 CFR 36.607 - Guidance concerning model codes.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Guidance concerning model codes. 36.607... BY PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES Certification of State Laws or Local Building Codes § 36.607 Guidance concerning model codes. Upon application by an authorized representative of a...

28 CFR 36.607 - Guidance concerning model codes.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Guidance concerning model codes. 36.607... BY PUBLIC ACCOMMODATIONS AND IN COMMERCIAL FACILITIES Certification of State Laws or Local Building Codes § 36.607 Guidance concerning model codes. Upon application by an authorized representative of a...

Modeling and controlling a robotic convoy using guidance laws strategies.

PubMed

Belkhouche, Fethi; Belkhouche, Boumediene

2005-08-01

This paper deals with the problem of modeling and controlling a robotic convoy. Guidance laws techniques are used to provide a mathematical formulation of the problem. The guidance laws used for this purpose are the velocity pursuit, the deviated pursuit, and the proportional navigation. The velocity pursuit equations model the robot's path under various sensors based control laws. A systematic study of the tracking problem based on this technique is undertaken. These guidance laws are applied to derive decentralized control laws for the angular and linear velocities. For the angular velocity, the control law is directly derived from the guidance laws after considering the relative kinematics equations between successive robots. The second control law maintains the distance between successive robots constant by controlling the linear velocity. This control law is derived by considering the kinematics equations between successive robots under the considered guidance law. Properties of the method are discussed and proven. Simulation results confirm the validity of our approach, as well as the validity of the properties of the method. Index Terms-Guidance laws, relative kinematics equations, robotic convoy, tracking.

Spacecraft intercept guidance using zero effort miss steering

NASA Astrophysics Data System (ADS)

Newman, Brett

The suitability of proportional navigation, or an equivalent zero effort miss formulation, for spacecraft intercepts during midcourse guidance, followed by a ballistic coast to the endgame, is addressed. The problem is formulated in terms of relative motion in a general 3D framework. The proposed guidance law for the commanded thrust vector orientation consists of the sum of two terms: (1) along the line of sight unit direction and (2) along the zero effort miss component perpendicular to the line of sight and proportional to the miss itself and a guidance gain. If the guidance law is to be suitable for longer range targeting applications with significant ballistic coasting after burnout, determination of the zero effort miss must account for the different gravitational accelerations experienced by each vehicle. The proposed miss determination techniques employ approximations for the true differential gravity effect. Theoretical results are applied to a numerical engagement scenario and the resulting performance is evaluated in terms of the miss distances determined from nonlinear simulation.

Integrated Targeting and Guidance for Powered Planetary Descent

NASA Astrophysics Data System (ADS)

Azimov, Dilmurat M.; Bishop, Robert H.

2018-02-01

This paper presents an on-board guidance and targeting design that enables explicit state and thrust vector control and on-board targeting for planetary descent and landing. These capabilities are developed utilizing a new closed-form solution for the constant thrust arc of the braking phase of the powered descent trajectory. The key elements of proven targeting and guidance architectures, including braking and approach phase quartics, are employed. It is demonstrated that implementation of the proposed solution avoids numerical simulation iterations, thereby facilitating on-board execution of targeting procedures during the descent. It is shown that the shape of the braking phase constant thrust arc is highly dependent on initial mass and propulsion system parameters. The analytic solution process is explicit in terms of targeting and guidance parameters, while remaining generic with respect to planetary body and descent trajectory design. These features increase the feasibility of extending the proposed integrated targeting and guidance design to future cargo and robotic landing missions.

Towards a new approach to model guidance laws

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borne, P.; Duflos, E.; Vanheeghe, P.

1994-12-31

Proportional navigation laws have been widely used and studied. Nevertheless very few publications explain rigorously the origin of all these laws. For researchers who are starting to work on guidance laws, a feeling of confusion can result. For others, this lack of explanation can be, for example, the source of the difficulties to make the true proportional navigation become equivalent to the pure proportional navigation. The authors propose here a way to model guidance laws in order to fill this lack of explanation. The first consequence is a better exploration of the kinematic behaviors arising during the guidance process. Themore » second consequence is the definition of a new 3D guidance law which can be seen as a generalization of the true proportional navigation. Moreover, this generalization allow this last law to become equivalent to the pure proportional navigation in terms of initial conditions which allow the object to reach its target.« less

Integrated Targeting and Guidance for Powered Planetary Descent

NASA Astrophysics Data System (ADS)

Azimov, Dilmurat M.; Bishop, Robert H.

2018-06-01

This paper presents an on-board guidance and targeting design that enables explicit state and thrust vector control and on-board targeting for planetary descent and landing. These capabilities are developed utilizing a new closed-form solution for the constant thrust arc of the braking phase of the powered descent trajectory. The key elements of proven targeting and guidance architectures, including braking and approach phase quartics, are employed. It is demonstrated that implementation of the proposed solution avoids numerical simulation iterations, thereby facilitating on-board execution of targeting procedures during the descent. It is shown that the shape of the braking phase constant thrust arc is highly dependent on initial mass and propulsion system parameters. The analytic solution process is explicit in terms of targeting and guidance parameters, while remaining generic with respect to planetary body and descent trajectory design. These features increase the feasibility of extending the proposed integrated targeting and guidance design to future cargo and robotic landing missions.

75 FR 70254 - PSD and Title V Permitting Guidance for Greenhouse Gases

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OAR-2010-0841; FRL-9228-2] PSD and Title V Permitting..., ``PSD and Title V Permitting Guidance for Greenhouse Gases'' on its significant guidance Internet Web... guidance titled, ``PSD and Title V Permitting Guidance for Greenhouse Gases.'' This document has been...

The Acquisition of Syntactically Encoded Evidentiality

ERIC Educational Resources Information Center

Rett, Jessica; Hyams, Nina

2014-01-01

This article presents several empirical studies of syntactically encoded evidentiality in English. The first part of our study consists of an adult online experiment that confirms claims in Asudeh & Toivonen (2012) that raised Perception Verb Similatives (PVSs; e.g. "John looks like he is sick") encode direct evidentiality. We then…

Source-constrained retrieval influences the encoding of new information.

PubMed

Danckert, Stacey L; MacLeod, Colin M; Fernandes, Myra A

2011-11-01

Jacoby, Shimizu, Daniels, and Rhodes (Psychonomic Bulletin & Review, 12, 852-857, 2005) showed that new words presented as foils among a list of old words that had been deeply encoded were themselves subsequently better recognized than new words presented as foils among a list of old words that had been shallowly encoded. In Experiment 1, by substituting a deep-versus-shallow imagery manipulation for the levels-of-processing manipulation, we demonstrated that the effect is robust and that it generalizes, also occurring with a different type of encoding. In Experiment 2, we provided more direct evidence for context-related encoding during tests of deeply encoded words, showing enhanced priming for foils presented among deeply encoded targets when participants made the same deep-encoding judgments on those items as had been made on the targets during study. In Experiment 3, we established that the findings from Experiment 2 are restricted to this specific deep judgment task and are not a general consequence of these foils being associated with deeply encoded items. These findings provide support for the source-constrained retrieval hypothesis of Jacoby, Shimizu, Daniels, and Rhodes: New information can be influenced by how surrounding items are encoded and retrieved, as long as the surrounding items recruit a coherent mode of processing.

Two-layer contractive encodings for learning stable nonlinear features.

PubMed

Schulz, Hannes; Cho, Kyunghyun; Raiko, Tapani; Behnke, Sven