The ng_ζ1 toxin of the gonococcal epsilon/zeta toxin/antitoxin system drains precursors for cell wall synthesis.

PubMed

Rocker, Andrea; Peschke, Madeleine; Kittilä, Tiia; Sakson, Roman; Brieke, Clara; Meinhart, Anton

2018-04-27

Bacterial toxin-antitoxin complexes are emerging as key players modulating bacterial physiology as activation of toxins induces stasis or programmed cell death by interference with vital cellular processes. Zeta toxins, which are prevalent in many bacterial genomes, were shown to interfere with cell wall formation by perturbing peptidoglycan synthesis in Gram-positive bacteria. Here, we characterize the epsilon/zeta toxin-antitoxin (TA) homologue from the Gram-negative pathogen Neisseria gonorrhoeae termed ng_ɛ1 / ng_ζ1. Contrary to previously studied streptococcal epsilon/zeta TA systems, ng_ɛ1 has an epsilon-unrelated fold and ng_ζ1 displays broader substrate specificity and phosphorylates multiple UDP-activated sugars that are precursors of peptidoglycan and lipopolysaccharide synthesis. Moreover, the phosphorylation site is different from the streptococcal zeta toxins, resulting in a different interference with cell wall synthesis. This difference most likely reflects adaptation to the individual cell wall composition of Gram-negative and Gram-positive organisms but also the distinct involvement of cell wall components in virulence.

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

Sather, Nichole K.; Borde, Amy B.; Diefenderfer, Heida L.

This Handbook of Data Reduction Procedures, Workbooks, and Exchange Templates is designed to support the Oncor geodatabase for the Columbia Estuary Ecosystem Restoration Program (CEERP). The following data categories are covered: water-surface elevation and temperature, sediment accretion rate, photo points, herbaceous wetland vegetation cover, tree plots and site summaries, fish catch and density, fish size, fish diet, fish prey, and Chinook salmon genetic stock identification. The handbook is intended for use by scientists collecting monitoring and research data for the CEERP. The ultimate goal of Oncor is to provide quality, easily accessible, geospatial data for synthesis and evaluation of themore » collective performance of CEERP ecosystem restoration actions at a program scale.« less

NACP Synthesis: Evaluating modeled carbon state and flux variables against multiple observational constraints (Invited)

NASA Astrophysics Data System (ADS)

Thornton, P. E.; Nacp Site Synthesis Participants

2010-12-01

The North American Carbon Program (NACP) synthesis effort includes an extensive intercomparison of modeled and observed ecosystem states and fluxes preformed with multiple models across multiple sites. The participating models span a range of complexity and intended application, while the participating sites cover a broad range of natural and managed ecosystems in North America, from the subtropics to arctic tundra, and coastal to interior climates. A unique characteristic of this collaborative effort is that multiple independent observations are available at all sites: fluxes are measured with the eddy covariance technique, and standard biometric and field sampling methods provide estimates of standing stock and annual production in multiple categories. In addition, multiple modeling approaches are employed to make predictions at each site, varying, for example, in the use of diagnostic vs. prognostic leaf area index. Given multiple independent observational constraints and multiple classes of model, we evaluate the internal consistency of observations at each site, and use this information to extend previously derived estimates of uncertainty in the flux observations. Model results are then compared with all available observations and models are ranked according to their consistency with each type of observation (high frequency flux measurement, carbon stock, annual production). We demonstrate a range of internal consistency across the sites, and show that some models which perform well against one observational metric perform poorly against others. We use this analysis to construct a hypothesis for combining eddy covariance, biometrics, and other standard physiological and ecological measurements which, as data collection proceeded over several years, would present an increasingly challenging target for next generation models.

The influence of calcination temperatures on the acid-based properties and catalytic activity for the 1,3-butadiene synthesis from ethanol/acetaldehyde mixture

NASA Astrophysics Data System (ADS)

Gao, Meixiang; Jiang, Haoxi; Zhang, Minhua

2018-05-01

The influences of the calcination temperature on the catalysts' acid-based properties and catalytic activity for the 1,3-butadiene synthesis from ethanol are investigated. The results show that the 2 wt% ZrO2/Nano-SiO2 calcined at 773 K shows the best performance with the selectivity of 93.18% and conversion of 58.52% when reacted at 593 K, a WHSV of 1.8 h-1 and 3.5:1 volume ratio ethanol-to-acetaldehyde in an atmospheric fixed-bed reactor. Prepared catalysts were characterized by N2 adsorption-desorption, XRD, temperature-programmed desorption of NH3 and CO2, FTIR spectroscopy of adsorbed pyridine and CO2. Based on the relationship between the catalyst activity and its properties, the fact can be presumed that the formation and strength of Zrsbnd Osbnd Si bond determines the acid-based properties of the catalyst. In addition, moderate-intensity weak acid-basic sites are more suitable for ethanol conversion to BD with the amount of acid and basic sites as close as possible.

Syntheses, Characterization and Kinetics of Nickel-Tungsten Nitride Catalysts for Hydrotreating of Gas Oil

NASA Astrophysics Data System (ADS)

Botchwey, Christian

This thesis summarizes the methods and major findings of Ni-W(P)/gamma-Al 2O3 nitride catalyst synthesis, characterization, hydrotreating activity, kinetic analysis and correlation of the catalysts' activities to their synthesis parameters and properties. The range of parameters for catalyst synthesis were W (15-40 wt%), Ni (0-8 wt%), P (0-5 wt%) and nitriding temperature (TN) (500-900 °C). Characterization techniques used included: N2 sorption studies, chemisorption, elemental analysis, temperature programmed studies, x-ray diffraction, scanning electron microscopy, energy dispersive x-ray, infrared spectroscopy, transmission electron microscopy and x-ray absorption near edge structure. Hydrodesulfurization (HDS), hydrodenitrogenation (HDN) and hydrodearomatization (HDA) were performed at: temperature (340-380 °C), pressure (6.2-9.0 MPa), liquid hourly space velocity (1-3 h-1) and hydrogen to oil ratio (600 ml/ml, STP). The predominant species on the catalyst surface were Ni3N, W2N and bimetallic Ni2W3N. The bimetallic Ni-W nitride species was more active than the individual activities of the Ni3N and W2N. P increased weak acid sites while nitriding temperature decreased amount of strong acid sites. Low nitriding temperature enhanced dispersion of metal particles. P interacted with Al 2O3 which increased the dispersion of metal nitrides on the catalyst surface. HDN activity increased with Ni and P loading but decreased with increase in nitriding temperature (optimum conversion; 60 wt%). HDS and HDA activities went through a maximum with increase in the synthesis parameters (optimum conversions; 88. wt% for HDS and 47 wt% for HDA). Increase in W loading led to increase in catalyst activity. The catalysts were stable to deactivation and had the nitride structure conserved during hydrotreating in the presence of hydrogen sulfide. The results showed good correlation between hydrotreating activities (HDS and HDN) and the catalyst nitrogen content, number of exposed active sites, catalyst particle size and BET surface area. HDS and HDN kinetic analyses, using Langmuir-Hinshelwood models, gave activation energies of 66 and 32 kJ/mol, respectively. There were no diffusion limitations in the reaction process. Two active sites were involved in HDS reaction while one site was used for HDN. HDS and HDN activities of the Ni-W(P)/gamma-Al 2O3 nitride catalysts were comparable to the corresponding sulfides.

Catalytic Synthesis of Oxygenates: Mechanisms, Catalysts and Controlling Characteristics

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

Klier, Kamil; Herman, Richard G

2005-11-30

This research focused on catalytic synthesis of unsymmetrical ethers as a part of a larger program involving oxygenated products in general, including alcohols, ethers, esters, carboxylic acids and their derivatives that link together environmentally compliant fuels, monomers, and high-value chemicals. The catalysts studied here were solid acids possessing strong Brnsted acid functionalities. The design of these catalysts involved anchoring the acid groups onto inorganic oxides, e.g. surface-grafted acid groups on zirconia, and a new class of mesoporous solid acids, i.e. propylsulfonic acid-derivatized SBA-15. The former catalysts consisted of a high surface concentration of sulfate groups on stable zirconia catalysts. Themore » latter catalyst consists of high surface area, large pore propylsulfonic acid-derivatized silicas, specifically SBA-15. In both cases, the catalyst design and synthesis yielded high concentrations of acid sites in close proximity to one another. These materials have been well-characterization in terms of physical and chemical properties, as well as in regard to surface and bulk characteristics. Both types of catalysts were shown to exhibit high catalytic performance with respect to both activity and selectivity for the bifunctional coupling of alcohols to form ethers, which proceeds via an efficient SN2 reaction mechanism on the proximal acid sites. This commonality of the dual-site SN2 reaction mechanism over acid catalysts provides for maximum reaction rates and control of selectivity by reaction conditions, i.e. pressure, temperature, and reactant concentrations. This research provides the scientific groundwork for synthesis of ethers for energy applications. The synthesized environmentally acceptable ethers, in part derived from natural gas via alcohol intermediates, exhibit high cetane properties, e.g. methylisobutylether with cetane No. of 53 and dimethylether with cetane No. of 55-60, or high octane properties, e.g. diisopropylether with blending octane No. of 105, and can replace aromatics in liquid fuels.« less

New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity γ-Hydroxybutyrate (GHB) Binding Sites

PubMed Central

Vogensen, Stine B.; Marek, Aleš; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin H.F.; Clausen, Rasmus P.

2013-01-01

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity and we demonstrate in vivo brain penetration. In vitro characterization of [3H]-1 binding shows high specificity to the high-affinity GHB binding sites. PMID:24053696

Evaluating the agreement between measurements and models of net ecosystem exchange at different times and timescales using wavelet coherence: an example using data from the North American Carbon Program Site-Level Interim Synthesis

Treesearch

P.C. Stoy; M.C. Dietze; A.D. Richardson; R. Vargas; A.G. Barr; R.S. Anderson; M.A. Arain; I.T. Baker; T.A. Black; J.M. Chen; R.B. Cook; C.M. Gough; R.F. Grant; D.Y. Hollinger; R.C. Izaurralde; C.J. Kucharik; P. Lafleur; B.E. Law; S. Liu; E. Lokupitiya; Y. Luo; J. W. Munger; C. Peng; B. Poulter; D.T. Price; D. M. Ricciuto; W. J. Riley; A. K. Sahoo; K. Schaefer; C.R. Schwalm; H. Tian; H. Verbeeck; E. Weng

2013-01-01

Earth system processes exhibit complex patterns across time, as do the models that seek to replicate these processes. Model output may or may not be significantly related to observations at different times and on different frequencies. Conventional model diagnostics provide an aggregate view of model-data agreement, but usually do not identify the time and frequency...

Undergraduate Research as Chemical Education--A Symposium: An Undergraduate Laboratory Experiment: The Total Synthesis of Maytansine.

ERIC Educational Resources Information Center

Goodwin, Thomas E.

1984-01-01

An undergraduate research program in natural product synthesis was established at a small liberal arts college. Discusses program goals (including the total synthesis of maytansine), objectives, and accomplishments to date. Guidelines for establishing such programs are offered. (JN)

Automatic Program Synthesis Reports.

ERIC Educational Resources Information Center

Biermann, A. W.; And Others

Some of the major results of future goals of an automatic program synthesis project are described in the two papers that comprise this document. The first paper gives a detailed algorithm for synthesizing a computer program from a trace of its behavior. Since the algorithm involves a search, the length of time required to do the synthesis of…

DNA synthesis arrest sites at the right terminus of rat long interspersed repeated (LINE or L1Rn) DNA family members.

PubMed Central

d'Ambrosio, E; Furano, A V

1987-01-01

An approximately equal to 150-bp GC-rich (approximately equal to 60%) region is at the right end of rat long interspersed repeated DNA (LINE or L1Rn) family members. We report here that one of the DNA strands from this region contains several non-palindromic sites that strongly arrest DNA synthesis in vitro by the prokaryotic Klenow and T4 DNA polymerases, the eukaryotic alpha polymerase, and AMV reverse transcriptase. The strongest arrest sites are G-rich (approximately equal to 70%) homopurine stretches of 18 or more residues. Shorter homopurine stretches (12 residues or fewer) did not arrest DNA synthesis even if the stretch contains 11/12 G residues. Arrest of the prokaryotic polymerases was not affected by their respective single strand binding proteins or polymerase accessory proteins. The region of duplex DNA which contains DNA synthesis arrest sites reacts with bromoacetaldehyde when present in negatively supercoiled molecules. By contrast, homopurine stretches that do not arrest DNA synthesis do not react with bromoacetaldehyde. The presence of bromoacetaldehyde-reactive bases in a G-rich homopurine-containing duplex under torsional stress is thought to be caused by base stacking in the homopurine strand. Therefore, we suggest that base-stacked regions of the template arrest DNA synthesis. Images PMID:2436148

Selective Catalytic Reduction of NO by NH 3 with WO 3-TiO 2 Catalysts: Influence of Catalyst Synthesis Method

DOE PAGES

He, Yuanyuan; Ford, Michael E.; Zhu, Minghui; ...

2016-02-02

A series of supported WO 3/TiO 2 catalysts was prepared by a new synthesis procedure involving co-precipitation of an aqueous TiO(OH) 2 and (NH 4) 10W 12O 41*5H 2O slurry under controlled pH conditions. The morphological properties, molecular structures, surface acidity and surface chemistry of the supported WO 3/TiO 2 catalysts were determined with BET, in situ Raman, in situ IR and temperature-programmed surface reaction (TPSR) spectroscopy, respectively. Isotopic 18O- 16O exchange demonstrated that tungsten oxide was exclusively present as surface WO x species on the TiO 2 support with mono-oxo W=O coordination. In contrast to previous studies employing impregnationmore » synthesis that found only surface one mono-oxo O=WO 4 site on TiO 2, the co-precipitation procedure resulted in the formation of two distinct surface WO x species: mono-oxo O=WO 4 (~1010-1017 cm -1) on low defect density patches of TiO 2 and a second mono-oxo O=WO 4 (~983-986 cm -1) on high defect density patches of TiO 2. The concentration of the second WO x surface species increases as a function of solution pH. Both surface WOx sites, however, exhibited the same NO/NH 3 SCR reactivity. The co-precipitated WO 3-TiO 2 catalysts synthesized in alkaline solutions exhibited enhanced performance for the NO/NH 3 SCR reaction that is ascribed to the greater number of surface defects on the resulting TiO2 support. For the co-precipitated catalyst prepared at pH10, surface NH 4 + species on Br nsted acid sites were found to be more reactive than surface NH 3* species on Lewis acid sites for SCR of NO with NH 3.« less

Reverse transcription of phage RNA and its fragment directed by synthetic heteropolymeric primers

PubMed Central

Frolova, L. Yu.; Metelyev, V. G.; Ratmanova, K. I.; Smirnov, V. D.; Shabarova, Z. A.; Prokofyev, M. A.; Berzin, V. M.; Jansone, I. V.; Gren, E. J.; Kisselev, L. L.

1977-01-01

DNA synthesis catalysed by RNA-directed DNA-polymerase (reverse transcriptase) was found to proceed on the RNA template of an MS2 phage in the presence of heteropolymeric synthetic octa- and nonadeoxyribonucleotide primers complementary to the intercistronic region (coat protein binding site) and the region of the coat protein cistron, respectively. The product of synthesis consists of discrete DNA fractions of different length, including transcripts longer than 1,000 nucleotides. The coat protein inhibits DNA synthesis if it is initiated at its binding site, but has no effect on DNA synthesis initiated at the coat protein cistron. It has been suggested that, in this system, the initiation of DNA synthesis by synthetic primers is topographically specific. The MS2 coat protein binding site (an RNA fragment of 59 nucleotides) serves as a template for polydeoxyribonucleotide synthesis in the presence of octanucleotide primer and reverse transcriptase. The product of synthesis is homogenous and its length corresponds to the length of the template. The effective and complete copying of the fragment having a distinct secondary structure proves that the secondary structure does not interfere, in principle, with RNA being a template in the system of reverse transcription. PMID:71713

The heat shock protein 60 promotes progesterone synthesis in mitochondria of JEG-3 cells.

PubMed

Monreal-Flores, Jessica; Espinosa-García, María Teresa; García-Regalado, Alejandro; Arechavaleta-Velasco, Fabian; Martínez, Federico

2017-06-01

Progesterone synthesis in human placenta is essential to maintain pregnancy. The limiting step in placental progesterone synthesis is cholesterol transport from the cytoplasm to the inner mitochondrial membrane. Multiple proteins located in mitochondrial contact sites seem to play a key role in this process. Previously, our group identified the heat shock protein 60 (HSP60) as part of mitochondrial contact sites in human placenta, suggesting its participation in progesterone synthesis. Here, we examined the role of HSP60 in progesterone synthesis. Our results show that over-expression of HSP60 in human placental choriocarcinoma cells (JEG-3) and human embryonic kidney 293 cells (HEK293) promotes progesterone synthesis. Furthermore, incubation of the HSP60 recombinant protein with intact isolated mitochondria from JEG-3 cells also promotes progesterone synthesis in a dose-related fashion. We also show that HSP60 interacts with STARD3 and P450scc proteins from mitochondrial membrane contact sites. Finally, we show that the HSP60 recombinant protein binds cholesterol. Ours results demonstrate that HSP60 participates in mitochondrial progesterone synthesis. These findings provide novel insights into progesterone synthesis in the human placenta and its role in maintaining pregnancy. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

A Program Structure for Event-Based Speech Synthesis by Rules within a Flexible Segmental Framework.

ERIC Educational Resources Information Center

Hill, David R.

1978-01-01

A program structure based on recently developed techniques for operating system simulation has the required flexibility for use as a speech synthesis algorithm research framework. This program makes synthesis possible with less rigid time and frequency-component structure than simpler schemes. It also meets real-time operation and memory-size…

Site-selective benzoin-type cyclization of unsymmetrical dialdoses catalyzed by N-heterocyclic carbenes for divergent cyclitol synthesis.

PubMed

Kang, Bubwoong; Wang, Yinli; Kuwano, Satoru; Yamaoka, Yousuke; Takasu, Kiyosei; Yamada, Ken-Ichi

2017-04-18

A highly site-selective N-heterocyclic carbene (NHC)-catalyzed benzoin-type cyclization of unsymmetrical dialdoses is developed to enable a divergent cyclitol synthesis. The choice of chiral NHCs and protecting groups affects the site-selectivity. The resulting inososes are converted into epi-, muco- and myo-inositols, and their chiral protected derivatives are formed in good yields.

Traceability Through Automatic Program Generation

NASA Technical Reports Server (NTRS)

Richardson, Julian; Green, Jeff

2003-01-01

Program synthesis is a technique for automatically deriving programs from specifications of their behavior. One of the arguments made in favour of program synthesis is that it allows one to trace from the specification to the program. One way in which traceability information can be derived is to augment the program synthesis system so that manipulations and calculations it carries out during the synthesis process are annotated with information on what the manipulations and calculations were and why they were made. This information is then accumulated throughout the synthesis process, at the end of which, every artifact produced by the synthesis is annotated with a complete history relating it to every other artifact (including the source specification) which influenced its construction. This approach requires modification of the entire synthesis system - which is labor-intensive and hard to do without influencing its behavior. In this paper, we introduce a novel, lightweight technique for deriving traceability from a program specification to the corresponding synthesized code. Once a program has been successfully synthesized from a specification, small changes are systematically made to the specification and the effects on the synthesized program observed. We have partially automated the technique and applied it in an experiment to one of our program synthesis systems, AUTOFILTER, and to the GNU C compiler, GCC. The results are promising: 1. Manual inspection of the results indicates that most of the connections derived from the source (a specification in the case of AUTOFILTER, C source code in the case of GCC) to its generated target (C source code in the case of AUTOFILTER, assembly language code in the case of GCC) are correct. 2. Around half of the lines in the target can be traced to at least one line of the source. 3. Small changes in the source often induce only small changes in the target.

High-Affinity Low-Capacity and Low-Affinity High-Capacity N-Acetyl-2-Aminofluorene (AAF) Macromolecular Binding Sites Are Revealed During the Growth Cycle of Adult Rat Hepatocytes in Primary Culture.

PubMed

Koch, Katherine S; Moran, Tom; Shier, W Thomas; Leffert, Hyam L

2018-05-01

Long-term cultures of primary adult rat hepatocytes were used to study the effects of N-acetyl-2-aminofluorene (AAF) on hepatocyte proliferation during the growth cycle; on the initiation of hepatocyte DNA synthesis in quiescent cultures; and, on hepatocyte DNA replication following the initiation of DNA synthesis. Scatchard analyses were used to identify the pharmacologic properties of radiolabeled AAF metabolite binding to hepatocyte macromolecules. Two classes of growth cycle-dependent AAF metabolite binding sites-a high-affinity low-capacity site (designated Site I) and a low-affinity high-capacity site (designated Site II)-associated with two spatially distinct classes of macromolecular targets, were revealed. Based upon radiolabeled AAF metabolite binding to purified hepatocyte genomic DNA or to DNA, RNA, proteins, and lipids from isolated nuclei, Site IDAY 4 targets (KD[APPARENT] ≈ 2-4×10-6 M and BMAX[APPARENT] ≈ 6 pmol/106 cells/24 h) were consistent with genomic DNA; and with AAF metabolized by a nuclear cytochrome P450. Based upon radiolabeled AAF binding to total cellular lysates, Site IIDAY 4 targets (KD[APPARENT] ≈ 1.5×10-3 M and BMAX[APPARENT] ≈ 350 pmol/106 cells/24 h) were consistent with cytoplasmic proteins; and with AAF metabolized by cytoplasmic cytochrome P450s. DNA synthesis was not inhibited by concentrations of AAF that saturated DNA binding in the neighborhood of the Site I KD. Instead, hepatocyte DNA synthesis inhibition required higher concentrations of AAF approaching the Site II KD. These observations raise the possibility that carcinogenic DNA adducts derived from AAF metabolites form below concentrations of AAF that inhibit replicative and repair DNA synthesis.

Automating Traceability for Generated Software Artifacts

NASA Technical Reports Server (NTRS)

Richardson, Julian; Green, Jeffrey

2004-01-01

Program synthesis automatically derives programs from specifications of their behavior. One advantage of program synthesis, as opposed to manual coding, is that there is a direct link between the specification and the derived program. This link is, however, not very fine-grained: it can be best characterized as Program is-derived- from Specification. When the generated program needs to be understood or modified, more $ne-grained linking is useful. In this paper, we present a novel technique for automatically deriving traceability relations between parts of a specification and parts of the synthesized program. The technique is very lightweight and works -- with varying degrees of success - for any process in which one artifact is automatically derived from another. We illustrate the generality of the technique by applying it to two kinds of automatic generation: synthesis of Kalman Filter programs from speci3cations using the Aut- oFilter program synthesis system, and generation of assembly language programs from C source code using the GCC C compilel: We evaluate the effectiveness of the technique in the latter application.

Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25

PubMed Central

Mullaney, Brendan; Ashrafi, Kaveh

2010-01-01

Summary Acyl-CoA synthases are important for lipid synthesis and breakdown, generation of signaling molecules and lipid modification of proteins, highlighting the challenge of understanding metabolic pathways within intact organisms. From a C. elegans mutagenesis screen, we found that loss of ACS-3, a long-chain acyl-CoA synthase, causes enhanced intestinal lipid uptake, de novo fat synthesis, and accumulation of enlarged, neutral lipid rich intestinal depots. Here, we show that ACS-3 functions in seam cells, epidermal cells anatomically distinct from sites of fat uptake and storage, and that acs-3 mutant phenotypes require the nuclear hormone receptor NHR-25, a key regulator of C. elegans molting. Our findings suggest that ACS-3 derived long chain fatty acyl-CoAs, perhaps incorporated into complex ligands such as phosphoinositides, modulate NHR-25 function, which in turn regulates an endocrine program of lipid uptake and synthesis. These results reveal a link between acyl-CoA synthase function and an NR5A family nuclear receptor in C. elegans. PMID:20889131

Oxidative phosphorylation. The relation between the specific binding of trimethlytin and triethyltin to mitochondria and their effects on various mitochondrial functions

PubMed Central

Aldridge, W. N.; Street, B. W.

1971-01-01

1. A binding site (site 1) is present in mitochondria with affinity for trimethyltin and triethyltin adequate for a site to which they could be attached when the processes of energy conservation are inhibited. 2. The quantitative relationships between the binding of trimethyltin and triethyltin to site 1 and their effects on various mitochondrial functions have been examined. 3. ATP synthesis linked to the oxidation of pyruvate, succinate and intramitochondrial substrate, ATP synthesis and oxygen uptake (succinate or pyruvate as substrate) stimulated by uncoupling agents are all inhibited by trimethyltin and triethyltin; when inhibition is less than 50% the ratio (percentage inhibition)/(percentage of binding site 1 complexed) is approx. 10:1. 4. ATP synthesis linked to the oxidation of reduced cytochrome c (ascorbate+NNN′N′-tetramethyl-p-phenylenediamine), ATP hydrolysis and oxygen uptake in the presence of low concentrations of trimethyltin and triethyltin approach zero activity as the proportion of binding site 1 complexed approaches 100%. 5. Possible interpretations of these findings are discussed with reference to published arrangements for coupling of electron transport to ATP synthesis and also to our present knowledge of the chemical and biological specificity of trialkyltin compounds. PMID:5126473

Ab initio DNA synthesis by Bst polymerase in the presence of nicking endonucleases Nt.AlwI, Nb.BbvCI, and Nb.BsmI.

PubMed

Antipova, Valeriya N; Zheleznaya, Lyudmila A; Zyrina, Nadezhda V

2014-08-01

In the absence of added DNA, thermophilic DNA polymerases synthesize double-stranded DNA from free dNTPs, which consist of numerous repetitive units (ab initio DNA synthesis). The addition of thermophilic restriction endonuclease (REase), or nicking endonuclease (NEase), effectively stimulates ab initio DNA synthesis and determines the nucleotide sequence of reaction products. We have found that NEases Nt.AlwI, Nb.BbvCI, and Nb.BsmI with non-palindromic recognition sites stimulate the synthesis of sequences organized mainly as palindromes. Moreover, the nucleotide sequence of the palindromes appeared to be dependent on NEase recognition/cleavage modes. Thus, the heterodimeric Nb.BbvCI stimulated the synthesis of palindromes composed of two recognition sites of this NEase, which were separated by AT-reach sequences or (A)n (T)m spacers. Palindromic DNA sequences obtained in the ab initio DNA synthesis with the monomeric NEases Nb.BsmI and Nt.AlwI contained, along with the sites of these NEases, randomly synthesized sequences consisted of blocks of short repeats. These findings could help investigation of the potential abilities of highly productive ab initio DNA synthesis for the creation of DNA molecules with desirable sequence. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Mechanisms by which herpes simplex virus DNA polymerase limits translesion synthesis through abasic sites.

PubMed

Zhu, Yali; Song, Liping; Stroud, Jason; Parris, Deborah S

2008-01-01

Results suggest a high probability that abasic (AP) sites occur at least once per herpes simplex virus type 1 (HSV-1) genome. The parameters that control the ability of HSV-1 DNA polymerase (pol) to engage in AP translesion synthesis (TLS) were examined because AP lesions could influence the completion and fidelity of viral DNA synthesis. Pre-steady-state kinetic experiments demonstrated that wildtype (WT) and exonuclease-deficient (exo-) pol could incorporate opposite an AP lesion, but full TLS required absence of exo function. Virtually all of the WT pol was bound at the exo site to AP-containing primer-templates (P/Ts) at equilibrium, and the pre-steady-state rate of excision by WT pol was higher on AP-containing than on matched DNA. However, several factors influencing polymerization work synergistically with exo activity to prevent HSV-1 pol from engaging in TLS. Although the pre-steady-state catalytic rate constant for insertion of dATP opposite a T or AP site was similar, ground-state-binding affinity of dATP for insertion opposite an AP site was reduced 3-9-fold. Single-turnover running-start experiments demonstrated a reduced proportion of P/Ts extended to the AP site compared to the preceding site during processive synthesis by WT or exo- pol. Only the exo- pol engaged in TLS, though inefficiently and without burst kinetics, suggesting a much slower rate-limiting step for extension beyond the AP site.

Zeolite catalysis in the synthesis of isobutylene from hydrous ethanol

NASA Astrophysics Data System (ADS)

Phillips, Cory Bernard

1999-11-01

This work deals with the synthesis of isobutylene from a hydrous ethanol feedstock over zeolites. The synthesis is accomplished in three steps: (1) low-temperature direct ethanol conversion to ethylene on H-ZSM-5 zeolite, (2) ethylene conversion to butene products over metal-exchanged zeolites, and (3) butene skeletal rearrangement to isobutylene over FER zeolites. The key to understanding and optimizing each synthesis step lies in the ability to control and regulate the zeolite acidity (Bronsted and Lewis)---both strength and number. Therefore, the continuous temperature programmed amine desorption (CTPAD) technique was further developed to simultaneously count the Bronsted acid sites and quantitatively characterize their strength. The adsorption of ethanol, reaction products, amines, coke and ethanol-derived residue (EDR) were monitored gravimetrically using the highly sensitive, novel Tapered Element Oscillating Microreactor (TEOM) apparatus. The TEOM was also used also in conjunction with CTPAD to characterize Bronsted acidity which is a new application for the instrument. For the first synthesis step, a parallel reaction exists which simultaneously produces diethyl ether and ethylene directly over H-ZSM-5. The reaction rates for each pathway were measured directly using a differential reactor operating at low temperatures (<473 K). Water in the ethanol feed enhances the rate of ethylene formation. A mechanism and kinetic expression are proposed for this reaction over H-ZSM-5, with diethyl-ether desorption and ethylene formation as the rate limiting steps. Heat of adsorption values measured from the independent microcalorimetry work reported in the literature are incorporated into the kinetic analysis which reduces the number of regressed parameters. For the remaining synthesis steps, several zeolite structures (ZSM-5, Y, FER) partially exchanged with Pd, Ti, Ni and Au were prepared and tested. It was determined from this screening study that the zeolites containing Pd are the most efficient catalysts for the dimerization reaction. Characterization results from x-ray diffraction (XRD), electron paramagnetic resonance (EPR) spectroscopy, and CTPAD suggest a stable, Pd species with a low oxidation state as part of the active site in Pd-exchanged zeolites. Isobutylene was present in the C4 fraction at reasonable quantities for most of the catalyst candidates, especially those containing an alkali metal co-cation.

Active Oxygen Vacancy Site for Methanol Synthesis from CO2 Hydrogenation on In2O3(110): A DFT Study

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

Ye, Jingyun; Liu, Changjun; Mei, Donghai

2013-06-03

Methanol synthesis from CO2 hydrogenation on the defective In2O3(110) surface with surface oxygen vacancies has been investigated using periodic density functional theory calculations. The relative stabilities of six possible surface oxygen vacancies numbered from Ov1 to Ov6 on the perfect In2O3(110) surface were examined. The calculated oxygen vacancy formation energies show that the D1 surface with the Ov1 defective site is the most thermodynamically favorable while the D4 surface with the Ov4 defective site is the least stable. Two different methanol synthesis routes from CO2 hydrogenation over both D1 and D4 surfaces were studied and the D4 surface was foundmore » to be more favorable for CO2 activation and hydrogenation. On the D4 surface, one of the O atoms of the CO2 molecule fills in the Ov4 site upon adsorption. Hydrogenation of CO2 to HCOO on the D4 surface is both thermodynamically and kinetically favorable. Further hydrogenation of HCOO involves both forming the C-H bond and breaking the C-O bond, resulting in H2CO and hydroxyl. The HCOO hydrogenation is slightly endothermic with an activation barrier of 0.57 eV. A high barrier of 1.14 eV for the hydrogenation of H2CO to H3CO indicates that this step is the rate-limiting step in the methanol synthesis on the defective In2O3(110) surface. We gratefully acknowledge the supports from the National Natural Science Foundation of China (#20990223) and from US Department of Energy, Basic Energy Science program (DE-FG02-05ER46231). D. Mei was supported by the US Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. The computations were performed in part using the Molecular Science Computing Facility in the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL), which is a U.S. Department of Energy national scientific user facility located at Pacific Northwest National Laboratory in Richland, Washington. PNNL is a multiprogram national laboratory operated for DOE by Battelle.« less

IMAGES: A digital computer program for interactive modal analysis and gain estimation for eigensystem synthesis

NASA Technical Reports Server (NTRS)

Jones, R. L.

1984-01-01

An interactive digital computer program for modal analysis and gain estimation for eigensystem synthesis was written. Both mathematical and operation considerations are described; however, the mathematical presentation is limited to those concepts essential to the operational capability of the program. The program is capable of both modal and spectral synthesis of multi-input control systems. It is user friendly, has scratchpad capability and dynamic memory, and can be used to design either state or output feedback systems.

Community Capacity Building as a vital mechanism for enhancing the growth and efficacy of a sustainable scientific software ecosystem: experiences running a real-time bi-coastal "Open Science for Synthesis" Training Institute for young Earth and Environmental scientists

NASA Astrophysics Data System (ADS)

Schildhauer, M.; Jones, M. B.; Bolker, B.; Lenhardt, W. C.; Hampton, S. E.; Idaszak, R.; Rebich Hespanha, S.; Ahalt, S.; Christopherson, L.

2014-12-01

Continuing advances in computational capabilities, access to Big Data, and virtual collaboration technologies are creating exciting new opportunities for accomplishing Earth science research at finer resolutions, with much broader scope, using powerful modeling and analytical approaches that were unachievable just a few years ago. Yet, there is a perceptible lag in the abilities of the research community to capitalize on these new possibilities, due to lacking the relevant skill-sets, especially with regards to multi-disciplinary and integrative investigations that involve active collaboration. UC Santa Barbara's National Center for Ecological Analysis and Synthesis (NCEAS), and the University of North Carolina's Renaissance Computing Institute (RENCI), were recipients of NSF OCI S2I2 "Conceptualization awards", charged with helping define the needs of the research community relative to enabling science and education through "sustained software infrastructure". Over the course of our activities, a consistent request from Earth scientists was for "better training in software that enables more effective, reproducible research." This community-based feedback led to creation of an "Open Science for Synthesis" Institute— a innovative, three-week, bi-coastal training program for early career researchers. We provided a mix of lectures, hands-on exercises, and working group experience on topics including: data discovery and preservation; code creation, management, sharing, and versioning; scientific workflow documentation and reproducibility; statistical and machine modeling techniques; virtual collaboration mechanisms; and methods for communicating scientific results. All technologies and quantitative tools presented were suitable for advancing open, collaborative, and reproducible synthesis research. In this talk, we will report on the lessons learned from running this ambitious training program, that involved coordinating classrooms among two remote sites, and included developing original synthesis research activities as part of the course. We also report on the feedback provided by participants as to the learning approaches and topical issues they found most engaging, and why.

Structural and surface properties of CuO-ZnO-Cr{sub 2}O{sub 3} catalysts and their relationship with selectivity to higher alcohol synthesis

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

Campos-Martin, J.M.; Fierro, J.L.G.; Guerrero-Ruiz, A.

1995-10-01

A series of copper-zinc-chromium catalysts of different compositions and calcination temperatures has been prepared, characterized by several techniques (BET specific surface area, XRD, gravimetric TPR, TPD-CO, and XPS), and tested under high alcohol synthesis (HAS) conditions. CO hydrogenation was carried out at reaction temperatures of 523-598 K and 50 bar total pressure. The influence of catalyst composition, calcination temperature, and surface characteristics on the HAS selectivity was studied. The optimum HAS yields were found in the low Cr content region, but chromium was needed. Although chromium oxide does not seem to be involved in the catalytic site, its presence inmore » the catalyst composition is essential, owing to the larger specific surfaces and catalyst stability obtained at the highest reaction temperatures. For low Cr content composition, the temperature-programmed reduction (TPR) profiles were shifted to higher temperatures and simultaneously larger CO{sub 2} amounts were found in the temperature-programmed desorption profiles of adsorbed CO (TPD-CO). Photoelectron spectra (XPS) revealed that the oxidation state of copper is Cu{sup 2+} in the calcined catalysts and Cu{sup O} in the reduced ones; Cu{sup +} was only stabilized in a CuCr{sub 2}O{sub 4} spinel in the Cr-rich catalysts. These features derived from catalyst characterization are discussed in the framework of the catalytic behaviour for HAS synthesis. 53 refs., 7 figs., 4 tabs.« less

Results of a State-Wide Evaluation of “Paperwork Burden” in Addiction Treatment

PubMed Central

Carise, Deni; Love, Meghan; Zur, Julia; McLellan, A. Thomas; Kemp, Jack

2009-01-01

This article chronicles three steps taken by research, clinical and state staff towards assessing, evaluating and streamlining clinical and administrative paperwork at all public outpatient addiction treatment programs in 1 state. The first step was an accounting of all paperwork requirements at each program. Step two included the development of time estimates for the paperwork requirements, synthesis of information across sites, providing written evaluation of the need, utility and redundancy of all forms (paperwork) collected, and suggestions for eliminating unused or unnecessary data collection and streamlining the remaining data collection. Thirdly, the state agency hosted a meeting with the state staff, researchers and staff from all programs and agencies with state-funded contracts and took action. Paperwork reductions over the course of a 6-month outpatient treatment episode were estimated at 4 – 6 hours, with most of the time burden being eliminated from the intake process. PMID:19150201

Synthesis of bis-Phosphate Iminoaltritol Enantiomers and Structural Characterization with Adenine Phosphoribosyltransferase.

PubMed

Harris, Lawrence D; Harijan, Rajesh K; Ducati, Rodrigo G; Evans, Gary B; Hirsch, Brett M; Schramm, Vern L

2018-01-19

Phosphoribosyl transferases (PRTs) are essential in nucleotide synthesis and salvage, amino acid, and vitamin synthesis. Transition state analysis of several PRTs has demonstrated ribocation-like transition states with a partial positive charge residing on the pentose ring. Core chemistry for synthesis of transition state analogues related to the 5-phospho-α-d-ribosyl 1-pyrophosphate (PRPP) reactant of these enzymes could be developed by stereospecific placement of bis-phosphate groups on an iminoaltritol ring. Cationic character is provided by the imino group and the bis-phosphates anchor both the 1- and 5-phosphate binding sites. We provide a facile synthetic path to these molecules. Cyclic-nitrone redox methodology was applied to the stereocontrolled synthesis of three stereoisomers of a selectively monoprotected diol relevant to the synthesis of transition-state analogue inhibitors. These polyhydroxylated pyrrolidine natural product analogues were bis-phosphorylated to generate analogues of the ribocationic form of 5-phosphoribosyl 1-phosphate. A safe, high yielding synthesis of the key intermediate represents a new route to these transition state mimics. An enantiomeric pair of iminoaltritol bis-phosphates (L-DIAB and D-DIAB) was prepared and shown to display inhibition of Plasmodium falciparum orotate phosphoribosyltransferase and Saccharomyces cerevisiae adenine phosphoribosyltransferase (ScAPRT). Crystallographic inhibitor binding analysis of L- and D-DIAB bound to the catalytic sites of ScAPRT demonstrates accommodation of both enantiomers by altered ring geometry and bis-phosphate catalytic site contacts.

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

Goltz, G.; Weiner, H.

A computer program has been developed for designing and analyzing the performance of solar array/battery power systems for the U. S. Coast Guard Navigational Aids. This program is called the Design Synthesis/Performance Analysis (DSPA) Computer Program. The basic function of the Design Synthesis portion of the DSPA program is to evaluate functional and economic criteria to provide specifications for viable solar array/battery power systems. The basic function of the Performance Analysis portion of the DSPA program is to simulate the operation of solar array/battery power systems under specific loads and environmental conditions. This document provides all the information necessary tomore » access the DSPA programs, to input required data and to generate appropriate Design Synthesis or Performance Analysis Output.« less

Assessment of protein synthesis in highly aerobic canine species at the onset and during exercise training.

PubMed

Miller, Benjamin F; Ehrlicher, Sarah E; Drake, Joshua C; Peelor, Frederick F; Biela, Laurie M; Pratt-Phillips, Shannon; Davis, Michael; Hamilton, Karyn L

2015-04-01

Canis lupus familiaris, the domesticated dog, is capable of extreme endurance performance. The ability to perform sustained aerobic exercise is dependent on a well-developed mitochondrial reticulum. In this study we examined the cumulative muscle protein and DNA synthesis in groups of athletic dogs at the onset of an exercise training program and following a strenuous exercise training program. We hypothesized that both at the onset and during an exercise training program there would be greater mitochondrial protein synthesis rates compared with sedentary control with no difference in mixed or cytoplasmic protein synthesis rates. Protein synthetic rates of three protein fractions and DNA synthesis were determined over 1 wk using (2)H2O in competitive Alaskan Huskies and Labrador Retrievers trained for explosive device detection. Both groups of dogs had very high rates of skeletal muscle protein synthesis in the sedentary state [Alaskan Huskies: Mixed = 2.28 ± 0.12, cytoplasmic (Cyto) = 2.91 ± 0.10, and mitochondrial (Mito) = 2.62 ± 0.07; Labrador Retrievers: Mixed = 3.88 ± 0.37, Cyto = 3.85 ± 0.06, and Mito = 2.92 ± 0.20%/day]. Mitochondrial (Mito) protein synthesis rates did not increase at the onset of an exercise training program. Exercise-trained dogs maintained Mito protein synthesis during exercise training when mixed (Mixed) and cytosolic (Cyto) fractions decreased, and this coincided with a decrease in p-RpS6 but also a decrease in p-ACC signaling. Contrary to our hypothesis, canines did not have large increases in mitochondrial protein synthesis at the onset or during an exercise training program. However, dogs have a high rate of protein synthesis compared with humans that perhaps does not necessitate an extra increase in protein synthesis at the onset of aerobic exercise training. Copyright © 2015 the American Physiological Society.

Combining Model-driven and Schema-based Program Synthesis

NASA Technical Reports Server (NTRS)

Denney, Ewen; Whittle, John

2004-01-01

We describe ongoing work which aims to extend the schema-based program synthesis paradigm with explicit models. In this context, schemas can be considered as model-to-model transformations. The combination of schemas with explicit models offers a number of advantages, namely, that building synthesis systems becomes much easier since the models can be used in verification and in adaptation of the synthesis systems. We illustrate our approach using an example from signal processing.

Review of present groundwater monitoring programs at the Nevada Test Site

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

Hershey, R.L.; Gillespie, D.

1993-09-01

Groundwater monitoring at the Nevada Test Site (NTS) is conducted to detect the presence of radionuclides produced by underground nuclear testing and to verify the quality and safety of groundwater supplies as required by the State of Nevada and federal regulations, and by U.S. Department of Energy (DOE) Orders. Groundwater is monitored at water-supply wells and at other boreholes and wells not specifically designed or located for traditional groundwater monitoring objectives. Different groundwater monitoring programs at the NTS are conducted by several DOE Nevada Operations Office (DOE/NV) contractors. Presently, these individual groundwater monitoring programs have not been assessed or administeredmore » under a comprehensive planning approach. Redundancy exists among the programs in both the sampling locations and the constituents analyzed. Also, sampling for certain radionuclides is conducted more frequently than required. The purpose of this report is to review the existing NTS groundwater monitoring programs and make recommendations for modifying the programs so a coordinated, streamlined, and comprehensive monitoring effort may be achieved by DOE/NV. This review will be accomplished in several steps. These include: summarizing the present knowledge of the hydrogeology of the NTS and the potential radionuclide source areas for groundwater contamination; reviewing the existing groundwater monitoring programs at the NTS; examining the rationale for monitoring and the constituents analyzed; reviewing the analytical methods used to quantify tritium activity; discussing monitoring network design criteria; and synthesizing the information presented and making recommendations based on the synthesis. This scope of work was requested by the DOE/NV Hydrologic Resources Management Program (HRMP) and satisfies the 1993 (fiscal year) HRMP Groundwater Monitoring Program Review task.« less

Site descriptive modeling as a part of site characterization in Sweden - Concluding the surface based investigations

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

Andersson, Johan; Winberg, Anders; Skagius, Kristina

The Swedish Nuclear Fuel and Waste Management Co., SKB, is currently finalizing its surface based site investigations for the final repository for spent nuclear fuel in the municipalities of Oestharmnar (the Forsmark area) and Oskarshamn (the Simpevar/Laxemar area). The investigation data are assessed into a Site Descriptive Model, constituting a synthesis of geology, rock mechanics, thermal properties, hydrogeology, hydro-geochemistry, transport properties and a surface system description. Site data constitute a wide range of different measurement results. These data both need to be checked for consistency and to be interpreted into a format more amenable for three-dimensional modeling. The three-dimensional modelingmore » (i.e. estimating the distribution of parameter values in space) is made in a sequence where the geometrical framework is taken from the geological models and in turn used by the rock mechanics, thermal and hydrogeological modeling. These disciplines in turn are partly interrelated, and also provide feedback to the geological modeling, especially if the geological description appears unreasonable when assessed together with the other data. Procedures for assessing the uncertainties and the confidence in the modeling have been developed during the course of the site modeling. These assessments also provide key input to the completion of the site investigation program. (authors)« less

Mathematical programming formulations for satellite synthesis

NASA Technical Reports Server (NTRS)

Bhasin, Puneet; Reilly, Charles H.

1987-01-01

The problem of satellite synthesis can be described as optimally allotting locations and sometimes frequencies and polarizations, to communication satellites so that interference from unwanted satellite signals does not exceed a specified threshold. In this report, mathematical programming models and optimization methods are used to solve satellite synthesis problems. A nonlinear programming formulation which is solved using Zoutendijk's method and a gradient search method is described. Nine mixed integer programming models are considered. Results of computer runs with these nine models and five geographically compatible scenarios are presented and evaluated. A heuristic solution procedure is also used to solve two of the models studied. Heuristic solutions to three large synthesis problems are presented. The results of our analysis show that the heuristic performs very well, both in terms of solution quality and solution time, on the two models to which it was applied. It is concluded that the heuristic procedure is the best of the methods considered for solving satellite synthesis problems.

SUMMARY OF EMISSIONS MANAGEMENT STRATEGY POLICY RELEVANT FINDINGS FROM EPA'S PM SUPERSITES PROGRAM

EPA Science Inventory

EPA is developing an integrated synthesis of key scientific and policy-relevant findings from EPA's Particulate Matter Supersites Program. This presentation provides a summary of the program and the integrated synthesis. Since there are many examples of such findings, ranging f...

Design, Sustainable Synthesis, and Programmed Reactions of Templated N-Heteroaryl-Fused Vinyl Sultams.

PubMed

Laha, Joydev K; Sharma, Shubhra; Kirar, Seema; Banerjee, Uttam C

2017-09-15

A de novo design and synthesis of N-heteroaryl-fused vinyl sultams as templates for programming chemical reactions on vinyl sultam periphery or (hetero)aryl ring is described. The key features include rational designing and sustainable synthesis of the template, customized reactions of vinyl sultams at C═C bond or involving N-S bond cleavage, and reactions on the periphery of the heteroaryl ring for late-stage diversification. The simple, easy access to the template coupled with opportunities for the synthesis of diversely functionalized heterocyles from a single template constitutes a rare study in contemporary organic synthesis.

Performance Analysis and Design Synthesis (PADS) computer program. Volume 2: Program description, part 1

NASA Technical Reports Server (NTRS)

1972-01-01

The Performance Analysis and Design Synthesis (PADS) computer program has a two-fold purpose. It can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general-purpose branched trajectory optimization program. In the former use, it has the Space Shuttle Synthesis Program as well as a simplified stage weight module for optimally sizing manned recoverable launch vehicles. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent; the second employs the method of quasilinearization, which requires a starting solution from the first trajectory module. For Volume 1 see N73-13199.

Return to the Moon: A New Strategic Evaluation

NASA Technical Reports Server (NTRS)

Lowman, Paul D., Jr.

1999-01-01

This paper reviews the value of a new lunar program, initially robotic and eventually manned, in the light of developments since the 1991 Synthesis Group study of the Space Exploration Initiative. The objective is to evaluate a return to the Moon in comparison to proposed Mars programs as a focus for American space exploration with humans in the next century. The Moon is demonstrably accessible, hospitable, useful, and interesting. Lunar programs are inherently faster and less risky from a programmatic viewpoint than comparable Mars programs such as Mars Direct. The dominant reason for a resumption of manned lunar missions, focussed on a single site such as Grimaldi, is to rebuild the infrastructure for missions beyond earth orbit, the last of which was in 1972. A transitional program, corresponding to the 10 Gemini missions that bridged the gap between Mercury and Apollo, was considered absolutely essential by the Synthesis Group. Further justification for a return to the Moon is the demonstrated feasibility of a robotic lunar observatory, concentrating on optical and infrared interferometry. Many unsolved scientific questions about the Moon itself remain, and could be investigated using telerobotic lunar rovers even before the return of humans. Mars is unquestionably more interesting scientifically and far more hospitable for long-term colonization. A new lunar program would be the most effective possible preparation for the human exploration, settlement, and eventually the terraforming of Mars. Lunar and Mars programs are complementary, not competitive. Both can be justified in the most fundamental terms as beginning the dispersal of the human species against uncontrollable natural disasters, cometary or asteroidal impacts in particular, to which mankind is vulnerable while confined to a single planet. Three specific programs are recommended for the 2001-2010 period: Ice Prospectors, to evaluate polar ice or hydrogen deposits; a robotic lunar observatory; and a manned lunar base and observatory.

AmeriFlux Network Data Activities: updates, progress and plans

NASA Astrophysics Data System (ADS)

Yang, B.; Boden, T.; Krassovski, M.; Song, X.

2013-12-01

The Carbon Dioxide Information Analysis Center (CDIAC) at the Oak Ridge National Laboratory serves as the long-term data repository for the AmeriFlux network. Datasets currently available include hourly or half-hourly meteorological and flux observations, biological measurement records, and synthesis data products. In this presentation, we provide an update of this network database including a comprehensive review and evaluation of the biological data from about 70 sites, development of a new product for flux uncertainty estimates, and re-formatting of Level-2 standard files. In 2013, we also provided data support to two synthesis studies --- 2012 drought synthesis and FACE synthesis. Issues related to data quality and solutions in compiling datasets for these synthesis studies will be discussed. We will also present our work plans in developing and producing other high-level products, such as derivation of phenology from the available measurements at flux sites.

The I.A.G./A.I.G. SEDIBUD (Sediment Budgets in Cold Environments) Program (2005 - 2017): Key activities and outcomes

NASA Astrophysics Data System (ADS)

Beylich, Achim A.

2017-04-01

Amplified climate change and ecological sensitivity of high-latitude and high-altitude cold climate environments has been highlighted as a key global environmental issue. Projected climate change in largely undisturbed cold regions is expected to alter melt-season duration and intensity, along with the number of extreme rainfall events, total annual precipitation and the balance between snowfall and rainfall. Similarly, changes to the thermal balance are expected to reduce the extent of permafrost and seasonal ground frost and increase active-layer depths. These combined effects will undoubtedly change Earth surface environments in cold regions and will alter the fluxes of sediments, solutes and nutrients. However, the absence of quantitative data and coordinated analysis to understand the sensitivity of the Earth surface environment are acute in cold regions. Contemporary cold climate environments generally provide the opportunity to identify solute and sedimentary systems where anthropogenic impacts are still less important than the effects of climate change. Accordingly, it is still possible to develop a library of baseline fluvial yields and sedimentary budgets before the natural environment is completely transformed. The SEDIBUD (Sediment Budgets in Cold Environments) Program, building on the European Science Foundation (ESF) Network SEDIFLUX (Sedimentary Source-to-Sink Fluxes in Cold Environments, since 2004) was formed in 2005 as a new Program (Working Group) of the International Association of Geomorphologists (I.A.G./A.I.G.) to address this still existing key knowledge gap. SEDIBUD (2005-2017) has currently about 400 members worldwide and the Steering Committee of this international program is composed of eleven scientists from ten different countries. The central research question of this global program is to: Assess and model the contemporary sedimentary fluxes in cold climates, with emphasis on both particulate and dissolved components. Research carried out at 56 defined SEDIBUD key test sites (selected catchment systems) varies by scientific program, logistics and available resources, but typically represent interdisciplinary collaborations of geomorphologists, hydrologists, ecologists, permafrost scientists and glaciologists with different levels of detail. SEDIBUD has developed a key set of primary research data requirements intended to incorporate results from these varied projects and allow quantitative analysis across the program. Defined SEDIBUD key test sites provide field data on annual climatic conditions, total discharge and particulate and dissolved fluxes and yields as well as information on other relevant denudational Earth surface processes. A number of selected key test sites are providing high-resolution data on climatic conditions, runoff and solute and sedimentary fluxes and yields, which - in addition to the annual data - contribute to the SEDIBUD metadata database. To support these coordinated efforts, the SEDIFLUX manual and a set of framework papers and book chapters have been produced to establish the integrative approach and common methods and data standards. Comparable field-datasets from different SEDIBUD key test sites are analyzed and integrated to address key research questions of the SEDIBUD program as defined in the SEDIBUD working group objective. A key SEDIBUD synthesis book was published in 2016 by the group and a synthesis key paper is currently in preparation. Detailed information on all SEDIBUD activities, outcomes and published products is found at http://www.geomorph.org/sedibud-working-group/.

ACCESS 1: Approximation Concepts Code for Efficient Structural Synthesis program documentation and user's guide

NASA Technical Reports Server (NTRS)

Miura, H.; Schmit, L. A., Jr.

1976-01-01

The program documentation and user's guide for the ACCESS-1 computer program is presented. ACCESS-1 is a research oriented program which implements a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and general mathematical programming algorithms are applied in the design optimization procedure. Implementation of the computer program, preparation of input data and basic program structure are described, and three illustrative examples are given.

Music 4C, a multi-voiced synthesis program with instruments defined in C

NASA Astrophysics Data System (ADS)

Beauchamp, James W.

2003-04-01

Music 4C is a program which runs under Unix (including Linux) and provides a means for the synthesis of arbitrary signals as defined by the C code. The program is actually a loose translation of an earlier program, Music 4BF [H. S. Howe, Jr., Electronic Music Synthesis (Norton, 1975)]. A set of instrument definitions are driven by a numerical score which consists of a series of ``events.'' Each event gives an instrument name, start time and duration, and a number of parameters (e.g., pitch) which describe the event. Each instrument definition consists of event parameters, performance variables, initializations, and a synthesis algorithmic code. Thus, the synthetic signal, no matter how complex, is precisely defined. Moreover, the resulting sounds can be overlaid in any arbitrary pattern. The program serves as a mixer of algorithmically produced sounds or recorded sounds taken from sample files or synthesized from spectrum files. A score file can be entered by hand, generated from a program, translated from a MIDI file, or generated from an alpha-numeric score using an auxiliary program, Notepro. Output sample files are in wav, snd, or aiff format. The program is provided in the C source code for download.

Role of the Cu-ZrO 2 Interfacial Sites for Conversion of Ethanol to Ethyl Acetate and Synthesis of Methanol from CO 2 and H 2 [The Role of the Cu-ZrO 2 Interfacial Sites for Ethanol Conversion to Ethyl Acetate and Methanol Synthesis from CO 2 and H 2

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

Ro, Insoo; Liu, Yifei; Ball, Madelyn R.

Well-defined Cu catalysts containing different amounts of zirconia were synthesized by controlled surface reactions (CSRs) and atomic layer deposition methods and studied for the selective conversion of ethanol to ethyl acetate and for methanol synthesis. Selective deposition of ZrO 2 on undercoordinated Cu sites or near Cu nanoparticles via the CSR method was evidenced by UV–vis absorption spectroscopy, scanning transmission electron microscopy, and inductively coupled plasma absorption emission spectroscopy. The concentrations of Cu and Cu-ZrO 2 interfacial sites were quantified using a combination of subambient CO Fourier transform infrared spectroscopy and reactive N 2O chemisorption measurements. The oxidation states ofmore » the Cu and ZrO 2 species for these catalysts were determined using X-ray absorption near edge structure measurements, showing that these species were present primarily as Cu 0 and Zr 4+, respectively. Here, it was found that the formation of Cu-ZrO 2 interfacial sites increased the turnover frequency by an order of magnitude in both the conversion of ethanol to ethyl acetate and the synthesis of methanol from CO 2 and H 2.« less

Role of the Cu-ZrO 2 Interfacial Sites for Conversion of Ethanol to Ethyl Acetate and Synthesis of Methanol from CO 2 and H 2 [The Role of the Cu-ZrO 2 Interfacial Sites for Ethanol Conversion to Ethyl Acetate and Methanol Synthesis from CO 2 and H 2

DOE PAGES

Ro, Insoo; Liu, Yifei; Ball, Madelyn R.; ...

2016-09-06

Well-defined Cu catalysts containing different amounts of zirconia were synthesized by controlled surface reactions (CSRs) and atomic layer deposition methods and studied for the selective conversion of ethanol to ethyl acetate and for methanol synthesis. Selective deposition of ZrO 2 on undercoordinated Cu sites or near Cu nanoparticles via the CSR method was evidenced by UV–vis absorption spectroscopy, scanning transmission electron microscopy, and inductively coupled plasma absorption emission spectroscopy. The concentrations of Cu and Cu-ZrO 2 interfacial sites were quantified using a combination of subambient CO Fourier transform infrared spectroscopy and reactive N 2O chemisorption measurements. The oxidation states ofmore » the Cu and ZrO 2 species for these catalysts were determined using X-ray absorption near edge structure measurements, showing that these species were present primarily as Cu 0 and Zr 4+, respectively. Here, it was found that the formation of Cu-ZrO 2 interfacial sites increased the turnover frequency by an order of magnitude in both the conversion of ethanol to ethyl acetate and the synthesis of methanol from CO 2 and H 2.« less

SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation

PubMed Central

Matsuda, Morihiro; Korn, Bobby S.; Hammer, Robert E.; Moon, Young-Ah; Komuro, Ryutaro; Horton, Jay D.; Goldstein, Joseph L.; Brown, Michael S.; Shimomura, Iichiro

2001-01-01

In liver, the synthesis of cholesterol and fatty acids increases in response to cholesterol deprivation and insulin elevation, respectively. This regulatory mechanism underlies the adaptation to cholesterol synthesis inhibitors (statins) and high calorie diets (insulin). In nonhepatic cells, lipid synthesis is controlled by sterol regulatory element-binding proteins (SREBPs), membrane-bound transcription factors whose active domains are released proteolytically to enter the nucleus and activate genes involved in the synthesis and uptake of cholesterol and fatty acids. SCAP (SREBP cleavage-activating protein) is a sterol-regulated escort protein that transports SREBPs from their site of synthesis in the endoplasmic reticulum to their site of cleavage in the Golgi. Here, we produced a conditional deficiency of SCAP in mouse liver by genomic recombination mediated by inducible Cre recombinase. SCAP-deficient mice showed an 80% reduction in basal rates of cholesterol and fatty acid synthesis in liver, owing to decreases in mRNAs encoding multiple biosynthetic enzymes. Moreover, these mRNAs failed to increase normally in response to cholesterol deprivation produced by a cholesterol synthesis inhibitor and to insulin elevation produced by a fasting–refeeding protocol. These data provide in vivo evidence that SCAP and the SREBPs are required for hepatic lipid synthesis under basal and adaptive conditions. PMID:11358865

Biomimetic Chemistry of Iron, Nickel, Molybdenum, and Tungsten in Sulfur-Ligated Protein Sites†

PubMed Central

Groysman, Stanislav; Holm, R. H.

2009-01-01

Biomimetic inorganic chemistry has as its primary goal the synthesis of molecules that approach or achieve the structures, oxidation states, and electronic and reactivity features of native metal-containing sites of variant nuclearity. Comparison of properties of accurate analogues and these sites ideally provides insight into the influence of protein structure and environment on intrinsic properties as represented by the analogue. For polynuclear sites in particular, the goal provides a formidable challenge for, with the exception of iron-sulfur clusters, all such site structures have never been achieved and few even closely approximated by chemical synthesis. This account describes the current status of the synthetic analogue approach as applied to the mononuclear sites in certain molybdoenzymes and the polynuclear sites in hydrogenases, nitrogenase, and carbon monoxide dehydrogenases. PMID:19206188

Morphological, Biochemical, and Functional Study of Viral Replication Compartments Isolated from Adenovirus-Infected Cells

PubMed Central

Hidalgo, Paloma; Anzures, Lourdes; Hernández-Mendoza, Armando; Guerrero, Adán; Wood, Christopher D.; Valdés, Margarita; Dobner, Thomas

2016-01-01

ABSTRACT Adenovirus (Ad) replication compartments (RC) are nuclear microenvironments where the viral genome is replicated and a coordinated program of late gene expression is established. These virus-induced nuclear sites seem to behave as central hubs for the regulation of virus-host cell interactions, since proteins that promote efficient viral replication as well as factors that participate in the antiviral response are coopted and concentrated there. To gain further insight into the activities of viral RC, here we report, for the first time, the morphology, composition, and activities of RC isolated from Ad-infected cells. Morphological analyses of isolated RC particles by superresolution microscopy showed that they were indistinguishable from RC within infected cells and that they displayed a dynamic compartmentalization. Furthermore, the RC-containing fractions (RCf) proved to be functional, as they directed de novo synthesis of viral DNA and RNA as well as RNA splicing, activities that are associated with RC in vivo. A detailed analysis of the production of viral late mRNA from RCf at different times postinfection revealed that viral mRNA splicing occurs in RC and that the synthesis, posttranscriptional processing, and release from RC to the nucleoplasm of individual viral late transcripts are spatiotemporally separate events. The results presented here demonstrate that RCf are a powerful system for detailed study into RC structure, composition, and activities and, as a result, the determination of the molecular mechanisms that induce the formation of these viral sites of adenoviruses and other nuclear-replicating viruses. IMPORTANCE RC may represent molecular hubs where many aspects of virus-host cell interaction are controlled. Here, we show by superresolution microscopy that RCf have morphologies similar to those of RC within Ad-infected cells and that they appear to be compartmentalized, as nucleolin and DBP display different localization in the periphery of these viral sites. RCf proved to be functional, as they direct de novo synthesis of viral DNA and mRNA, allowing the detailed study of the regulation of viral genome replication and expression. Furthermore, we show that the synthesis and splicing of individual viral late mRNA occurs in RC and that they are subject to different temporal patterns of regulation, from their synthesis to their splicing and release from RC to the nucleoplasm. Hence, RCf represent a novel system to study molecular mechanisms that are orchestrated in viral RC to take control of the infected cell and promote an efficient viral replication cycle. PMID:26764008

Research on Molecular Sieve Technology.

ERIC Educational Resources Information Center

Shah, Dhananjai B.; Hayhurst, David T.

1985-01-01

The zeolite synthesis and modification research program at Cleveland State University (Ohio) is described, including program philosophy and objectives, and research facilities. Also considers zeolite synthesis, adsorption on zeolites, kinetics of adsorption, and zeolite catalysis research. (JN)

Reactivity of a Carbon-Supported Single-Site Molybdenum Dioxo Catalyst for Biodiesel Synthesis

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

Mouat, Aidan R.; Lohr, Tracy L.; Wegener, Evan C.

2016-08-23

A single-site molybdenum dioxo catalyst, (O c) 2Mo(=O) 2@C, was prepared via direct grafting of MoO 2Cl 2(dme) (dme = 1,2-dimethoxyethane) on high-surface- area activated carbon. The physicochemical and chemical properties of this catalyst were fully characterized by N 2 physisorption, ICP-AES/OES, PXRD, STEM, XPS, XAS, temperature-programmed reduction with H 2 (TPR-H 2), and temperature-programmed NH 3 desorption (TPD-NH 3). The single-site nature of the Mo species is corroborated by XPS and TPR-H 2 data, and it exhibits the lowest reported MoO x Tmax of reduction reported to date, suggesting a highly reactive MoVI center. (O c) 2Mo(=O) 2@C catalyzesmore » the transesterification of a variety of esters and triglycerides with ethanol, exhibiting high activity at moderate temperatures (60-90 °C) and with negligible deactivation. (O c) 2Mo(=O) 2@C is resistant to water and can be recycled at least three times with no loss of activity. The transesterification reaction is determined experimentally to be first order in [ethanol] and first order in [Mo] with ΔH = 10.5(8) kcal mol -1 and ΔS = -32(2) eu. The low energy of activation is consistent with the moderate conditions needed to achieve rapid turnover. This highly active carbon-supported single-site molybdenum dioxo species is thus an efficient, robust, and lowcost catalyst with significant potential for transesterification processes.« less

Integration of a code for aeroelastic design of conventional and composite wings into ACSYNT, an aircraft synthesis program. [wing aeroelastic design (WADES)

NASA Technical Reports Server (NTRS)

Mullen, J., Jr.

1976-01-01

A comparison of program estimates of wing weight, material distribution. structural loads and elastic deformations with actual Northrop F-5A/B data is presented. Correlation coefficients obtained using data from a number of existing aircraft were computed for use in vehicle synthesis to estimate wing weights. The modifications necessary to adapt the WADES code for use in the ACSYNT program are described. Basic program flow and overlay structure is outlined. An example of the convergence of the procedure in estimating wing weights during the synthesis of a vehicle to satisfy F-5 mission requirements is given. A description of inputs required for use of the WADES program is included.

Efficient synthesis of supercoiled M13 DNA molecule containing a site specifically placed psoralen adduct and its use as a substrate for DNA replication

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

Kodadek, T.; Gamper, H.

The authors report a simple method for the in vitro synthesis of large quantities of site specifically modified DNA. The protocol involves extension of an oligonucleotide primer annealed to M13 single-stranded DNA using part of the T4 DNA polymerase holoenzyme. The resulting nicked double-stranded circles are ligated and supercoiled in the same tube, producing good yields of form I DNA. When the oligonucleotide primer is chemically modified, the resultant product contains a site-specific lesion. In this study, they report the synthesis of an M13 mp19 form I DNA which contains a psoralen monoadduct or cross-link at the KpnI site. Theymore » demonstrate the utility of these modified substrates by assessing the ability of the bacteriophage T4 DNA replication complex to bypass the damage and show that the psoralen monoadduct poses a severe block to the holoenzyme when attached to the template strand.« less

Automatic programming for critical applications

NASA Technical Reports Server (NTRS)

Loganantharaj, Raj L.

1988-01-01

The important phases of a software life cycle include verification and maintenance. Usually, the execution performance is an expected requirement in a software development process. Unfortunately, the verification and the maintenance of programs are the time consuming and the frustrating aspects of software engineering. The verification cannot be waived for the programs used for critical applications such as, military, space, and nuclear plants. As a consequence, synthesis of programs from specifications, an alternative way of developing correct programs, is becoming popular. The definition, or what is understood by automatic programming, has been changed with our expectations. At present, the goal of automatic programming is the automation of programming process. Specifically, it means the application of artificial intelligence to software engineering in order to define techniques and create environments that help in the creation of high level programs. The automatic programming process may be divided into two phases: the problem acquisition phase and the program synthesis phase. In the problem acquisition phase, an informal specification of the problem is transformed into an unambiguous specification while in the program synthesis phase such a specification is further transformed into a concrete, executable program.

Direct accessibility of mixed-metal (III/II) acid sites through the rational synthesis of porous metal carboxylates.

PubMed

Wongsakulphasatch, S; Nouar, F; Rodriguez, J; Scott, L; Le Guillouzer, C; Devic, T; Horcajada, P; Grenèche, J-M; Llewellyn, P L; Vimont, A; Clet, G; Daturi, M; Serre, C

2015-06-25

The scalable and environmentally-friendly synthesis of mixed Fe(III)/M(II) (M = Ni, Co, Mg) polycarboxylate porous MOFs based on the Secondary Building Unit approach is reported. A combination of in situ infrared spectroscopy, (57)Fe Mössbauer spectrometry and adsorption microcalorimetry confirms the direct accessibility of the iron(III) and metal(II) sites under low temperature activation conditions.

A Mesopore-Dependent Catalytic Cracking of n-Hexane Over Mesoporous Nanostructured ZSM-5.

PubMed

Qamar, M; Ahmed, M I; Qamaruddin, M; Asif, M; Sanhoob, M; Muraza, O; Khan, M Y

2018-08-01

Herein, pore size, crystalinity, and Si/Al ratio of mesoporous ZSM-5 (MFI) nanocrystals was controlled by synthesis parameters, such as surfactant concentration ([3-(trimethoxysilyl)propyl] hexa-decyl dimethyl ammonium chloride), sodium hydroxide concentrations, synthesis temperature and time. The morphology, surface structure and composition of the MFI particles was systematically investigated. More notably, the mesopore-dependent catalytic activity of ZSM-5 was evaluated by studying the cracking of n-hexane. The findings suggest the porosity has pronounced impact on the catalytic activity, selectivity and stability of ZSM-5 nanocrystals. Critical surface attributes such as nature of acid sites (Brønsted and Lewis), concentration, and strength are obtained by the infrared study of adsorbed probe molecules (pyridine) and the temperature programmed desorption. In spite of being weaker in Si/Al ratio or acidic strength, mesoporous catalysts showed more stable and efficient cracking of n-hexane suggesting that acidity seems not the predominant factor operative in the activity, selectivity and stability.

Improved scaling laws for stage inert mass space Propulsion systems. Volume 3: Propulsion synthesis program users and programmers manual

NASA Technical Reports Server (NTRS)

1971-01-01

The analytical models developed for the Space Propulsion Automated Synthesis Modeling (SPASM) program are presented. Weight scaling laws developed during this study are incorporated into the program's scaling data bank. A detail listing, logic diagram and input/output formats are supplied for the SPASM program. Two test examples for one to four-stage vehicles performing different types of missions are shown to demonstrate the program's capability and versatility.

Method and apparatus for combinatorial chemistry

DOEpatents

Foote, Robert S.

2007-02-20

A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.

Method and apparatus for combinatorial chemistry

DOEpatents

Foote, Robert S [Oak Ridge, TN

2012-06-05

A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.

An implementation of the distributed programming structural synthesis system (PROSSS)

NASA Technical Reports Server (NTRS)

Rogers, J. L., Jr.

1981-01-01

A method is described for implementing a flexible software system that combines large, complex programs with small, user-supplied, problem-dependent programs and that distributes their execution between a mainframe and a minicomputer. The Programming Structural Synthesis System (PROSSS) was the specific software system considered. The results of such distributed implementation are flexibility of the optimization procedure organization and versatility of the formulation of constraints and design variables.

Development of weight/sizing design synthesis computer program. Volume 3: User Manual

NASA Technical Reports Server (NTRS)

Garrison, J. M.

1973-01-01

The user manual for the weight/sizing design synthesis program is presented. The program is applied to an analysis of the basic weight relationships for the space shuttle which contribute significant portions of the inert weight. The relationships measure the parameters of load, geometry, material, and environment. A verbal description of the processes simulated, data input procedures, output data, and values present in the program is included.

Feasibility study of a synthesis procedure for array feeds to improve radiation performance of large distorted reflector antennas

NASA Technical Reports Server (NTRS)

Stutzman, W. L.; Takamizawa, K.; Werntz, P.; Lapean, J.; Barts, R.

1991-01-01

The following subject areas are covered: General Reflector Antenna Systems Program version 7(GRASP7); Multiple Reflector Analysis Program for Cylindrical Antennas (MRAPCA); Tri-Reflector 2D Synthesis Code (TRTDS); a geometrical optics and a physical optics synthesis techniques; beam scanning reflector, the type 2 and 6 reflectors, spherical reflector, and multiple reflector imaging systems; and radiometric array design.

Native American prehistory of the middle Savannah River Valley. A synthesis of archaeological investigations on the Savannah River Site, Aiken and Barnwell Counties, South Carolina

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

Sassaman, K.E.; Brooks, M.J.; Hanson, G.T.

1990-12-31

Archaeological investigations on the United States Department of Energy`s (DOE) Savannah River Site (SRS) in South Carolina span 17 years and continue today through a cooperative agreement between DOE and the South Carolina Institute of Archaeology and Anthropology (SCIAA), University of South Carolina. The Savannah River Archaeological Research Program (SRARP) of SCIAA has been and continues to be the sole archaeological consultant for DOE-SRS. This report documents technical aspects of all prehistoric archaeological research conducted by the SRARP between 1973 and 1987. Further, this report provides interpretative contexts for archaeological resources as a basis for an archaeological resource plan reportedmore » elsewhere (SRARP 1989), and as a comprehensive statement of our current understanding of Native American prehistory. 400 refs., 130 figs., 39 tabs.« less

Engineering the architectural diversity of heterogeneous metallic nanocrystals.

PubMed

Yu, Yue; Zhang, Qingbo; Xie, Jianping; Lee, Jim Yang

2013-01-01

Similar to molecular engineering where structural diversity is used to create more property variations for application explorations, the architectural engineering of heterogeneous metallic nanocrystals (HMNCs) can likewise increase the versatility of metallic nanocrystals (NCs). Here we present a synthesis strategy capable of engineering the architectural diversity of HMNCs through rational and independent programming of every architecture-determining element, that is, the shape and size of the component NCs and their spatial arrangement. The strategy is based on the galvanic replacement reaction of a self-sustaining layer formed by underpotential deposition on a polyhedral NC. The selective deposition of satellite NCs on specific site of the central NC is realized by creating a geometry-dependent heterogeneous electron distribution. This site-selective deposition approach is applicable to central NCs in various polyhedral shapes and sizes. The satellite NCs can further develop their own shape and size through crystal growth kinetics control.

Measurement and interpretation of magnetic shear in solar active regions

NASA Technical Reports Server (NTRS)

Hagyard, M. J.; Rabin, D. M.

1986-01-01

In this paper a summary and synthesis are presented for results on the role of magnetic shear in the flare process that have been derived from the series of Flare Buildup Study Workshops in the Solar Maximum Analysis program. With emphasis on observations, the mechanisms that seem to produce the sheared magnetic configurations observed in flaring active regions are discussed. The spatial and temporal correlations of this shear with the onset of solar flares are determined from quantitative analyses of measurements of the vector magnetic field. The question of why some areas of sheared magnetic fields are the sites of flares and others are not is investigated observationally.

Control of Coptotermes havilandi (Isoptera: Rhinotermitidae) with hexaflumuron baits and a sensor incorporated into a monitoring and baiting program.

PubMed

Su, N Y; Ban, P M; Scheffrahn, R H

2000-04-01

A sensor consisting of a wooden monitor painted with a conductive circuit of silver particle emulsion was placed in a monitoring station to detect feeding activity of the subterranean termite Coptotermes havilandi Holmgren. Sensor accuracy was 100% 1 mo after installation, but 9 mo after sensor placement, the rate declined to 73%. After the detection of C. havilandi in the stations, baits containing the chitin synthesis inhibitor hexaflumuron were applied in five colonies, and four colonies were eliminated within 3-5 mo. Baiting could not be completed for the remaining one colony because the site became inaccessible.

Analysis and synthesis of abstract data types through generalization from examples

NASA Technical Reports Server (NTRS)

Wild, Christian

1987-01-01

The discovery of general patterns of behavior from a set of input/output examples can be a useful technique in the automated analysis and synthesis of software systems. These generalized descriptions of the behavior form a set of assertions which can be used for validation, program synthesis, program testing and run-time monitoring. Describing the behavior is characterized as a learning process in which general patterns can be easily characterized. The learning algorithm must choose a transform function and define a subset of the transform space which is related to equivalence classes of behavior in the original domain. An algorithm for analyzing the behavior of abstract data types is presented and several examples are given. The use of the analysis for purposes of program synthesis is also discussed.

Controlled rotation of the F1-ATPase reveals differential and continuous binding changes for ATP synthesis

PubMed Central

Adachi, Kengo; Oiwa, Kazuhiro; Yoshida, Masasuke; Nishizaka, Takayuki; Kinosita, Kazuhiko

2012-01-01

F1-ATPase is an ATP-driven rotary molecular motor that synthesizes ATP when rotated in reverse. To elucidate the mechanism of ATP synthesis, we imaged binding and release of fluorescently labelled ADP and ATP while rotating the motor in either direction by magnets. Here we report the binding and release rates for each of the three catalytic sites for 360° of the rotary angle. We show that the rates do not significantly depend on the rotary direction, indicating ATP synthesis by direct reversal of the hydrolysis-driven rotation. ADP and ATP are discriminated in angle-dependent binding, but not in release. Phosphate blocks ATP binding at angles where ADP binding is essential for ATP synthesis. In synthesis rotation, the affinity for ADP increases by >104, followed by a shift to high ATP affinity, and finally the affinity for ATP decreases by >104. All these angular changes are gradual, implicating tight coupling between the rotor angle and site affinities. PMID:22929779

Regional monitoring programs in the United States: Synthesis of four case studies from Pacific, Atlantic, and Gulf Coasts

USGS Publications Warehouse

Tango, Peter J.; Schiff, K.; Trowbridge, P.R.; Sherwood, E.T.; Batiuk, R.A.

2016-01-01

Water quality monitoring is a cornerstone of environmental protection and ambient monitoring provides managers with the critical data they need to take informed action. Unlike site-specific monitoring that is at the heart of regulatory permit compliance, regional monitoring can provide an integrated, holistic view of the environment, allowing managers to obtain a more complete picture of natural variability and cumulative impacts, and more effectively prioritize management actions. By reviewing four long-standing regional monitoring programs that cover portions of all three coasts in the United States – Chesapeake Bay, Tampa Bay, Southern California Bight, and San Francisco Bay – important insights can be gleaned about the benefits that regional monitoring provides to managers. These insights include the underlying reasons that make regional monitoring programs successful, the challenges to maintain relevance and viability in the face of ever-changing technology, competing demands and shifting management priorities. The lessons learned can help other managers achieve similar successes as they seek to establish and reinvigorate their own monitoring programs.

Synthesis of single-site copper catalysts for methane partial oxidation

DOE PAGES

Grundner, S.; Luo, W.; Sanchez-Sanchez, M.; ...

2015-12-24

Cu-Exchanged zeolites are known as active materials for methane oxidation to methanol. However, understanding of the formation of Cu active species during synthesis, dehydration and activation is fragmented and rudimentary. We show here how a synthesis protocol guided by insight in the ion exchange elementary steps leads to highly uniform Cu species in mordenite (MOR).

Toward synthesizing executable models in biology.

PubMed

Fisher, Jasmin; Piterman, Nir; Bodik, Rastislav

2014-01-01

Over the last decade, executable models of biological behaviors have repeatedly provided new scientific discoveries, uncovered novel insights, and directed new experimental avenues. These models are computer programs whose execution mechanistically simulates aspects of the cell's behaviors. If the observed behavior of the program agrees with the observed biological behavior, then the program explains the phenomena. This approach has proven beneficial for gaining new biological insights and directing new experimental avenues. One advantage of this approach is that techniques for analysis of computer programs can be applied to the analysis of executable models. For example, one can confirm that a model agrees with experiments for all possible executions of the model (corresponding to all environmental conditions), even if there are a huge number of executions. Various formal methods have been adapted for this context, for example, model checking or symbolic analysis of state spaces. To avoid manual construction of executable models, one can apply synthesis, a method to produce programs automatically from high-level specifications. In the context of biological modeling, synthesis would correspond to extracting executable models from experimental data. We survey recent results about the usage of the techniques underlying synthesis of computer programs for the inference of biological models from experimental data. We describe synthesis of biological models from curated mutation experiment data, inferring network connectivity models from phosphoproteomic data, and synthesis of Boolean networks from gene expression data. While much work has been done on automated analysis of similar datasets using machine learning and artificial intelligence, using synthesis techniques provides new opportunities such as efficient computation of disambiguating experiments, as well as the ability to produce different kinds of models automatically from biological data.

Antisense RNA: effect of ribosome binding sites, target location, size, and concentration on the translation of specific mRNA molecules.

PubMed

Daugherty, B L; Hotta, K; Kumar, C; Ahn, Y H; Zhu, J D; Pestka, S

1989-01-01

A series of plasmids were constructed to generate RNA complementary to the beta-galactosidase messenger RNA under control of the phage lambda PL promoter. These plasmids generate anti-lacZ mRNA bearing or lacking a synthetic ribosome binding site adjacent to the lambda PL promoter and/or the lacZ ribosome binding site in reverse orientation. Fragments of lacZ DNA from the 5' and/or the 3' region were used in these constructions. When these anti-mRNA molecules were produced in Escherichia coli 294, maximal inhibition of beta-galactosidase synthesis occurred when a functional ribosome binding site was present near the 5' end of the anti-mRNA and the anti-mRNA synthesized was complementary to the 5' region of the mRNA corresponding to the lacZ ribosome binding site and/or the 5'-coding sequence. Anti-mRNAs producing maximal inhibition of beta-galactosidase synthesis exhibited an anti-lacZ mRNA:normal lacZ mRNA ratio of 100:1 or higher. Those showing lower levels of inhibition exhibited much lower anti-lacZ mRNA:normal lacZ mRNA ratios. A functional ribosome binding site at the 5'-end was found to decrease the decay rate of the anti-lacZ mRNAs. In addition, the incorporation of a transcription terminator just downstream of the antisense segment provided for more efficient inhibition of lacZ mRNA translation due to synthesis of smaller and more abundant anti-lacZ mRNAs. The optimal constructions produced undetectable levels of beta-galactosidase synthesis.

Characterization of the clustered regularly interspaced short palindromic repeats sites in Streptococcus mutans isolated from early childhood caries patients.

PubMed

Chen, Jing; Li, Tiancheng; Zhou, Xuedong; Cheng, Lei; Huo, Yuanyuan; Zou, Jing; Li, Yuqing

2017-11-01

The aim of this study was to analyze the characteristics of the clustered regularly interspaced short palindromic repeats (CRISPR) sites in 45 clinical Streptococcus mutans strains and their relationship to the clinical manifestations of early childhood caries (ECC). Forty-five S. mutans strains were isolated from the plaque samples taken from sixty-three children. CRISPR sites were sequenced and BLAST was used to compare these sites to those in the CRISPRTarget database. The association between the distribution of CRISPR sites and the manifestation of caries was analyzed by Chi-Square test. Further, biofilm formation (by crystal violet staining) and the synthesis of polysaccharide (by anthrone-sulfuric method) of all clinical isolated S. mutans strains with both CRISPR sites and no CRISPR site were comapared. Finally, acidogenicity and acidurity of two typical strains were determined using pH drop and acid tolerance assays. Biofilm formation and EPS synthesis by two typical strains were compared by 3D CLSM (Confocal Laser Scanning Microscope) assays and the expression of gtf genes were evaluated using qPCR. We found that most of the spacers in the clinical S. mutans strains were derived from Streptococcus phages APCM01 and M102. The number of CRISPR sites in these strains was associated with the clinical manifestations of ECC. Moreover, we found that the biofilm formation and EPS synthesis ability of the S. mutans strains with both CRISPR sites was significant improved. An association was found between the distribution of CRISPR sites and the clinical manifestations of caries. The CRISPR sites might contribute to the cariogenic potential of S. mutans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phosphorylation of paramyxovirus phosphoprotein and its role in viral gene expression.

PubMed

Fuentes, Sandra M; Sun, Dengyun; Schmitt, Anthony P; He, Biao

2010-01-01

Paramyxoviruses include many important human and animal pathogens such as measles virus, mumps virus, human parainfluenza viruses, and respiratory syncytial virus, as well as emerging viruses such as Nipah virus and Hendra virus. The paramyxovirus RNA-dependent RNA polymerase consists of the phosphoprotein (P) and the large protein. Both of these proteins are essential for viral RNA synthesis. The P protein is phosphorylated at multiple sites, probably by more than one host kinase. While it is thought that the phosphorylation of P is important for its role in viral RNA synthesis, the precise role of P protein phosphorylation remains an enigma. For instance, it was demonstrated that the putative CKII phosphorylation sites of the P protein of respiratory syncytial virus play a role in viral RNA synthesis using a minigenome replicon system; however, mutating these putative CKII phosphorylation sites within a viral genome had no effect on viral RNA synthesis, leading to the hypothesis that P protein phosphorylation, at least by CKII, does not play a role in viral RNA synthesis. Recently, it has been reported that the phosphorylation state of the P protein of parainfluenza virus 5, a prototypical paramyxovirus, correlates with the ability of P protein to synthesize viral RNA, indicating that P protein phosphorylation does in fact play a role in viral RNA synthesis. Furthermore, host kinases PLK1, as well as AKT1 have been found to play critical roles in paramyxovirus RNA synthesis through regulation of P protein phosphorylation status. Beyond furthering our understanding of paramyxovirus RNA replication, these recent discoveries may also result in a new paradigm in treating infections caused by these viruses, as host kinases that regulate paramyxovirus replication are investigated as potential targets of therapeutic intervention.

Approximation concepts for efficient structural synthesis

NASA Technical Reports Server (NTRS)

Schmit, L. A., Jr.; Miura, H.

1976-01-01

It is shown that efficient structural synthesis capabilities can be created by using approximation concepts to mesh finite element structural analysis methods with nonlinear mathematical programming techniques. The history of the application of mathematical programming techniques to structural design optimization problems is reviewed. Several rather general approximation concepts are described along with the technical foundations of the ACCESS 1 computer program, which implements several approximation concepts. A substantial collection of structural design problems involving truss and idealized wing structures is presented. It is concluded that since the basic ideas employed in creating the ACCESS 1 program are rather general, its successful development supports the contention that the introduction of approximation concepts will lead to the emergence of a new generation of practical and efficient, large scale, structural synthesis capabilities in which finite element analysis methods and mathematical programming algorithms will play a central role.

One-Pot synthesis of phosphorylated mesoporous carbon heterogeneous catalysts with tailored surface acidity

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

Fulvio, Pasquale F; Mahurin, Shannon Mark; Mayes, Richard T

2012-01-01

Soft-templated phosphorylated mesoporous carbons with homogeneous distributions of phosphate groups were prepared by a 'one-pot' synthesis method using mixtures of phosphoric acid with hydrochloric, or nitric acids in the presence of Pluronic F127 triblock copolymer. Adjusting the various ratios of phosphoric acid used in these mixtures resulted in carbons with distinct adsorption, structural and surface acidity properties. The pore size distributions (PSDs) from nitrogen adsorption at -196 C showed that mesoporous carbons exhibit specific surface areas as high as 551 m{sup 2}/g and mesopores as large as 13 nm. Both structural ordering of the mesopores and the final phosphate contentsmore » were strongly dependent on the ratios of H{sub 3}PO{sub 4} in the synthesis gels, as shown by transmission electron microscopy (TEM), X-ray photoelectron (XPS) and energy dispersive X-ray spectroscopy (EDS). The number of surface acid sites determined from temperature programmed desorption of ammonia (NH{sub 3}-TPD) were in the range of 0.3-1.5 mmol/g while the active surface areas are estimated to comprise 5-54% of the total surface areas. Finally, the conversion temperatures for the isopropanol dehydration were lowered by as much as 100 C by transitioning from the least acidic to the most acidic catalysts surface.« less

Diels-Alder active-template synthesis of rotaxanes and metal-ion-switchable molecular shuttles.

PubMed

Crowley, James D; Hänni, Kevin D; Leigh, David A; Slawin, Alexandra M Z

2010-04-14

A synthesis of [2]rotaxanes in which Zn(II) or Cu(II) Lewis acids catalyze a Diels-Alder cycloaddition to form the axle while simultaneously acting as the template for the assembly of the interlocked molecules is described. Coordination of the Lewis acid to a multidentate endotopic 2,6-di(methyleneoxymethyl)pyridyl- or bipyridine-containing macrocycle orients a chelated dienophile through the macrocycle cavity. Lewis acid activation of the double bond causes it to react with an incoming "stoppered" diene, affording the [2]rotaxane in up to 91% yield. Unusually for an active-template synthesis, the metal binding site "lives on" in these rotaxanes. This was exploited in the synthesis of a molecular shuttle containing two different ligating sites in which the position of the macrocycle could be switched by complexation with metal ions [Zn(II) and Pd(II)] with different preferred coordination geometries.

Magnetic field affects enzymatic ATP synthesis.

PubMed

Buchachenko, Anatoly L; Kuznetsov, Dmitry A

2008-10-01

The rate of ATP synthesis by creatine kinase extracted from V. xanthia venom was shown to depend on the magnetic field. The yield of ATP produced by enzymes with 24Mg2+ and 26Mg2+ ions in catalytic sites increases by 7-8% at 55 mT and then decreases at 80 mT. For enzyme with 25Mg2+ ion in a catalytic site, the ATP yield increases by 50% and 70% in the fields 55 and 80 mT, respectively. In the Earth field the rate of ATP synthesis by enzyme, in which Mg2+ ion has magnetic nucleus 25Mg, is 2.5 times higher than that by enzymes, in which Mg2+ ion has nonmagnetic, spinless nuclei 24Mg or 26Mg. Both magnetic field effect and magnetic isotope effect demonstrate that the ATP synthesis is an ion-radical process, affected by Zeeman interaction and hyperfine coupling in the intermediate ion-radical pair.

ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells.

PubMed

Lewis, Samantha C; Uchiyama, Lauren F; Nunnari, Jodi

2016-07-15

Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. In human cells, hundreds to thousands of mtDNA copies are replicated asynchronously, packaged into protein-DNA nucleoids, and distributed within a dynamic mitochondrial network. The mechanisms that govern how nucleoids are chosen for replication and distribution are not understood. Mitochondrial distribution depends on division, which occurs at endoplasmic reticulum (ER)-mitochondria contact sites. These sites were spatially linked to a subset of nucleoids selectively marked by mtDNA polymerase and engaged in mtDNA synthesis--events that occurred upstream of mitochondrial constriction and division machine assembly. Our data suggest that ER tubules proximal to nucleoids are necessary but not sufficient for mtDNA synthesis. Thus, ER-mitochondria contacts coordinate licensing of mtDNA synthesis with division to distribute newly replicated nucleoids to daughter mitochondria. Copyright © 2016, American Association for the Advancement of Science.

Commercial-scale demonstration of the Liquid Phase Methanol (LPMEOH{trademark}) process. Technical progress report number 6, October 1--December 31, 1995

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

NONE

1996-12-31

The project involves the construction of an 80,000 gallons per day (260 TPD) methanol unit utilizing coal-derived synthesis gas from Eastman`s integrated coal gasification facility. The new equipment consists of synthesis gas feed preparation and compression facilities, the liquid phase reactor and auxiliaries, product distillation facilities, and utilities. The technology to be demonstrated is the product of a cooperative development effort by Air Products and DOE in a program that started in 1981. Developed to enhance electric power generation using integrated gasification combined cycle (IGCC) technology, the LPMEOH{trademark} process is ideally suited for directly processing gases produced by modern-day coalmore » gasifiers. This liquid phase process suspends fine catalyst particles in an inert liquid, forming a slurry. The slurry dissipates the heat of the chemical reaction away from the catalyst surface protecting the catalyst and allowing the methanol synthesis reaction to proceed at higher rates. At the Eastman complex, the technology will be integrated with existing coal-gasifiers. A carefully developed test plan will allow operations at Eastman to simulate electricity demand load-following in coal-based IGCC facilities. The operations will also demonstrate the enhanced stability and heat dissipation of the conversion process, its reliable on/off operation, and its ability to produce methanol as a clean liquid fuel without additional upgrading. An off-site product testing program will be conducted to demonstrate the suitability of the methanol product as a transportation fuel and as a fuel for stationary applications for small modular electric power generators for distributed power.« less

Data synthesis and display programs for wave distribution function analysis

NASA Technical Reports Server (NTRS)

Storey, L. R. O.; Yeh, K. J.

1992-01-01

At the National Space Science Data Center (NSSDC) software was written to synthesize and display artificial data for use in developing the methodology of wave distribution analysis. The software comprises two separate interactive programs, one for data synthesis and the other for data display.

Flexible Generation of Kalman Filter Code

NASA Technical Reports Server (NTRS)

Richardson, Julian; Wilson, Edward

2006-01-01

Domain-specific program synthesis can automatically generate high quality code in complex domains from succinct specifications, but the range of programs which can be generated by a given synthesis system is typically narrow. Obtaining code which falls outside this narrow scope necessitates either 1) extension of the code generator, which is usually very expensive, or 2) manual modification of the generated code, which is often difficult and which must be redone whenever changes are made to the program specification. In this paper, we describe adaptations and extensions of the AUTOFILTER Kalman filter synthesis system which greatly extend the range of programs which can be generated. Users augment the input specification with a specification of code fragments and how those fragments should interleave with or replace parts of the synthesized filter. This allows users to generate a much wider range of programs without their needing to modify the synthesis system or edit generated code. We demonstrate the usefulness of the approach by applying it to the synthesis of a complex state estimator which combines code from several Kalman filters with user-specified code. The work described in this paper allows the complex design decisions necessary for real-world applications to be reflected in the synthesized code. When executed on simulated input data, the generated state estimator was found to produce comparable estimates to those produced by a handcoded estimator

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot.

PubMed

Kitson, Philip J; Glatzel, Stefan; Cronin, Leroy

2016-01-01

An automated synthesis robot was constructed by modifying an open source 3D printing platform. The resulting automated system was used to 3D print reaction vessels (reactionware) of differing internal volumes using polypropylene feedstock via a fused deposition modeling 3D printing approach and subsequently make use of these fabricated vessels to synthesize the nonsteroidal anti-inflammatory drug ibuprofen via a consecutive one-pot three-step approach. The synthesis of ibuprofen could be achieved on different scales simply by adjusting the parameters in the robot control software. The software for controlling the synthesis robot was written in the python programming language and hard-coded for the synthesis of ibuprofen by the method described, opening possibilities for the sharing of validated synthetic 'programs' which can run on similar low cost, user-constructed robotic platforms towards an 'open-source' regime in the area of chemical synthesis.

Teaching Heat Exchanger Network Synthesis Using Interactive Microcomputer Graphics.

ERIC Educational Resources Information Center

Dixon, Anthony G.

1987-01-01

Describes the Heat Exchanger Network Synthesis (HENS) program used at Worcester Polytechnic Institute (Massachusetts) as an aid to teaching the energy integration step in process design. Focuses on the benefits of the computer graphics used in the program to increase the speed of generating and changing networks. (TW)

A High-Throughput Screening Assay to Detect Thyroperoxidase Inhibitors (Teratology Society)

EPA Science Inventory

In support of the Endocrine Disruption Screening Program (EDSP21), the US EPA ToxCast program is developing assays to enable screening for chemicals that may disrupt thyroid hormone synthesis. Thyroperoxidase (TPO) is critical for TH synthesis and is a known target of thyroid-dis...

ISSYS: An integrated synergistic Synthesis System

NASA Technical Reports Server (NTRS)

Dovi, A. R.

1980-01-01

Integrated Synergistic Synthesis System (ISSYS), an integrated system of computer codes in which the sequence of program execution and data flow is controlled by the user, is discussed. The commands available to exert such control, the ISSYS major function and rules, and the computer codes currently available in the system are described. Computational sequences frequently used in the aircraft structural analysis and synthesis are defined. External computer codes utilized by the ISSYS system are documented. A bibliography on the programs is included.

Estrone sulfate source of estrone and estradiol formation in isolated human hair roots: identification of a pathway linked to hair growth phase and subject to site-, gender-, and age-related modulations.

PubMed

Wehner, Gabriele; Schweikert, Hans-Udo

2014-04-01

The present study investigated the metabolism of estrone sulfate into bioactive estrogens in the human hair root, including the effects of hair growth phase, anatomical site, gender, and age. Healthy male (n = 18) and female (n = 20) subjects were investigated. Growing (anagen) and resting (telogen) hair roots were collected from selected scalp and body sites. Estrone sulfate metabolism in the hair root yielded substantial levels of estrone and estradiol. Estrogen synthesis exceeded that associated with aromatization of androgens in a previous study. In subjects <50 years old, estrogen synthesis in scalp hair was lower in men than in women. Comparable levels of estrogen formation were observed in 1) male and female axillary and pubic hair and 2) male beard hair. These levels were higher than the estrogen levels detected in the in scalp hair of men <50 years old. With increasing age, estrogen synthesis increased in men and decreased in women. In telogen hair from all body sites, the capacity to form estrone from estrone sulfate remained unaffected, whereas the ability to form estradiol decreased by 62% and 86% in men and women, respectively. Estrogen formation from estrone sulfate in sexually dimorphic hair is linked to the hair growth phase and is subject to gender- and age-related modulations. The magnitude of the in situ estrogen synthesis from estrone sulfate and the selective arrest of estradiol synthesis at the end of the hair cycle suggest that this pathway plays a crucial role in the regulation of human hair growth.

VASP- VARIABLE DIMENSION AUTOMATIC SYNTHESIS PROGRAM

NASA Technical Reports Server (NTRS)

White, J. S.

1994-01-01

VASP is a variable dimension Fortran version of the Automatic Synthesis Program, ASP. The program is used to implement Kalman filtering and control theory. Basically, it consists of 31 subprograms for solving most modern control problems in linear, time-variant (or time-invariant) control systems. These subprograms include operations of matrix algebra, computation of the exponential of a matrix and its convolution integral, and the solution of the matrix Riccati equation. The user calls these subprograms by means of a FORTRAN main program, and so can easily obtain solutions to most general problems of extremization of a quadratic functional of the state of the linear dynamical system. Particularly, these problems include the synthesis of the Kalman filter gains and the optimal feedback gains for minimization of a quadratic performance index. VASP, as an outgrowth of the Automatic Synthesis Program, has the following improvements: more versatile programming language; more convenient input/output format; some new subprograms which consolidate certain groups of statements that are often repeated; and variable dimensioning. The pertinent difference between the two programs is that VASP has variable dimensioning and more efficient storage. The documentation for the VASP program contains a VASP dictionary and example problems. The dictionary contains a description of each subroutine and instructions on its use. The example problems include dynamic response, optimal control gain, solution of the sampled data matrix Riccati equation, matrix decomposition, and a pseudo-inverse of a matrix. This program is written in FORTRAN IV and has been implemented on the IBM 360. The VASP program was developed in 1971.

Analysis and synthesis of abstract data types through generalization from examples

NASA Technical Reports Server (NTRS)

Wild, Christian

1987-01-01

The discovery of general patterns of behavior from a set of input/output examples can be a useful technique in the automated analysis and synthesis of software systems. These generalized descriptions of the behavior form a set of assertions which can be used for validation, program synthesis, program testing, and run-time monitoring. Describing the behavior is characterized as a learning process in which the set of inputs is mapped into an appropriate transform space such that general patterns can be easily characterized. The learning algorithm must chose a transform function and define a subset of the transform space which is related to equivalence classes of behavior in the original domain. An algorithm for analyzing the behavior of abstract data types is presented and several examples are given. The use of the analysis for purposes of program synthesis is also discussed.

Fundamental studies of energy-and hole/electron- transfer in hydroporphyrin architectures

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

Bocian, David F.

2014-08-20

The long-term objective of the Bocian/Holten/Lindsey research program is to design, synthesize, and characterize tetrapyrrole-based molecular architectures that absorb sunlight, funnel energy, and separate charge with high efficiency and in a manner compatible with current and future solar-energy conversion schemes. The synthetic tetrapyrroles include porphyrins and hydroporphyrins; the latter classes of molecules encompass analogues of the naturally occurring chlorophylls and bacteriochlorophylls (e.g., chlorins, bacteriochlorins, and their derivatives). The attainment of the goals of the research program requires the close interplay of molecular design and synthesis (Lindsey group), static and time-resolved optical spectroscopic measurements (Holten group), and electrochemical, electron paramagnetic resonance,more » and resonance Raman studies, as well as density functional theory calculations (Bocian Group). The proposed research encompasses four interrelated themes: (1) Determination of the rates of ground-state hole/electron transfer between (hydro)porphyrins in multipigment arrays as a function of array size, distance between components, linker type, site of linker connection, and frontier molecular orbital composition. (2) Examination of excited-state energy transfer among hydroporphyrins in multipigment arrrays, including both pairwise and non-adjacent transfer, with a chief aim to identify the relative contributions of through-space (Förster) and through-bond (Dexter) mechanisms of energy transfer, including the roles of site of linker connection and frontier molecular orbital composition. (3) Elucidation of the role of substituents in tuning the spectral and electronic properties of bacteriochlorins, with a primary aim of learning how to shift the long-wavelength absorption band deeper into the near-infrared region. (4) Continued development of the software package PhotochemCAD for spectral manipulations and calculations through the compilation of a database of spectra for naturally occurring and synthetic hydroporphyrins. The availability of such data should augment efforts in the design of light-harvesting systems where spectral coverage in the red and near-infrared regions is desired. Collectively, the proposed studies will provide fundamental insights into molecular properties, interactions, and processes relevant to the design of molecular architectures for solar-energy conversion. The accomplishment of these goals is only possible through a highly synergistic program that encompasses molecular design, synthesis, and characterization.« less

Indomethacin inhibits the effects of oestrogen in the anterior pituitary gland of the rat.

PubMed

Rosental, D G; Machiavelli, G A; Cherñavsky, A C; Speziale, N S; Burdman, J A

1989-06-01

Two inhibitors of prostaglandin synthesis, indomethacin and aspirin, blocked the increase of oestrogen-binding sites in the nuclear subcellular fraction, an increase which occurs after the administration of oestradiol. Consequently the biological effects of oestrogens in the anterior pituitary gland of the rat (prolactin synthesis, concentration of progesterone-binding sites and cell proliferation) are diminished. The anterior pituitary gland synthesized prostaglandin F2 alpha (PGF2 alpha), PGE2 and PGD2 from arachidonic acid. This synthesis was blocked when indomethacin was added to the culture media. Oestrogen increased the concentration of PGE2: an increase that was partially prevented by indomethacin. Prostaglandins may have an important role on the effects of oestrogen in the anterior pituitary gland of the rat.

Synthesis of Natural Electric and Magnetic Time Series Using Impulse Responses of Inter-station Transfer Functions and a Reference

NASA Astrophysics Data System (ADS)

Wang, H.; Cheng, J.

2017-12-01

A method to Synthesis natural electric and magnetic Time series is proposed whereby the time series of local site are derived using an Impulse Response and a reference (STIR). The method is based on the assumption that the external source of magnetic fields are uniform, and the electric and magnetic fields acquired at the surface satisfy a time-independent linear relation in frequency domain.According to the convolution theorem, we can synthesize natural electric and magnetic time series using the impulse responses of inter-station transfer functions with a reference. Applying this method, two impulse responses need to be estimated: the quasi-MT impulse response tensor and the horizontal magnetic impulse response tensor. These impulse response tensors relate the local horizontal electric and magnetic components with the horizontal magnetic components at a reference site, respectively. Some clean segments of times series are selected to estimate impulse responses by using least-square (LS) method. STIR is similar with STIN (Wang, 2017), but STIR does not need to estimate the inter-station transfer functions, and the synthesized data are more accurate in high frequency, where STIN fails when the inter-station transfer functions are contaminated severely. A test with good quality of MT data shows that synthetic time-series are similar to natural electric and magnetic time series. For contaminated AMT example, when this method is used to remove noise present at the local site, the scatter of MT sounding curves are clear reduced, and the data quality are improved. *This work is funded by National Key R&D Program of China(2017YFC0804105),National Natural Science Foundation of China (41604064, 51574250), State Key Laboratory of Coal Resources and Safe Mining ,China University of Mining & Technology,(SKLCRSM16DC09)

Frameshifting in alphaviruses: a diversity of 3' stimulatory structures.

PubMed

Chung, Betty Y-W; Firth, Andrew E; Atkins, John F

2010-03-26

Programmed ribosomal frameshifting allows the synthesis of alternative, N-terminally coincident, C-terminally distinct proteins from the same RNA. Many viruses utilize frameshifting to optimize the coding potential of compact genomes, to circumvent the host cell's canonical rule of one functional protein per mRNA, or to express alternative proteins in a fixed ratio. Programmed frameshifting is also used in the decoding of a small number of cellular genes. Recently, specific ribosomal -1 frameshifting was discovered at a conserved U_UUU_UUA motif within the sequence encoding the alphavirus 6K protein. In this case, frameshifting results in the synthesis of an additional protein, termed TF (TransFrame). This new case of frameshifting is unusual in that the -1 frame ORF is very short and completely embedded within the sequence encoding the overlapping polyprotein. The present work shows that there is remarkable diversity in the 3' sequences that are functionally important for efficient frameshifting at the U_UUU_UUA motif. While many alphavirus species utilize a 3' RNA structure such as a hairpin or pseudoknot, some species (such as Semliki Forest virus) apparently lack any intra-mRNA stimulatory structure, yet just 20 nt 3'-adjacent to the shift site stimulates up to 10% frameshifting. The analysis, both experimental and bioinformatic, significantly expands the known repertoire of -1 frameshifting stimulators in mammalian and insect systems.

Emergency preparedness for transit terrorism : a synthesis of transit practice

DOT National Transportation Integrated Search

1997-01-01

This synthesis provides information on the current practices of transit agencies to prevent and respond to terrorism and acts of extreme violence. It integrates information gathered from a review of the literature, and from surveys, site visits, and ...

Molecular Modeling in Drug Design for the Development of Organophosphorus Antidotes/Prophylactics.

DTIC Science & Technology

1986-06-01

multidimensional statistical QSAR analysis techniques to suggest new structures for synthesis and evaluation. C. Application of quantum chemical techniques to...compounds for synthesis and testing for antidotal potency. E. Use of computer-assisted methods to determine the steric constraints at the active site...modeling techniques to model the enzyme acetylcholinester-se. H. Suggestion of some novel compounds for synthesis and testing for reactivating

Structural and Mechanistic Insight into the Listeria monocytogenes Two-enzyme Lipoteichoic Acid Synthesis System*

PubMed Central

Campeotto, Ivan; Percy, Matthew G.; MacDonald, James T.; Förster, Andreas; Freemont, Paul S.; Gründling, Angelika

2014-01-01

Lipoteichoic acid (LTA) is an important cell wall component required for proper cell growth in many Gram-positive bacteria. In Listeria monocytogenes, two enzymes are required for the synthesis of this polyglycerolphosphate polymer. The LTA primase LtaPLm initiates LTA synthesis by transferring the first glycerolphosphate (GroP) subunit onto the glycolipid anchor and the LTA synthase LtaSLm extends the polymer by the repeated addition of GroP subunits to the tip of the growing chain. Here, we present the crystal structures of the enzymatic domains of LtaPLm and LtaSLm. Although the enzymes share the same fold, substantial differences in the cavity of the catalytic site and surface charge distribution contribute to enzyme specialization. The eLtaSLm structure was also determined in complex with GroP revealing a second GroP binding site. Mutational analysis confirmed an essential function for this binding site and allowed us to propose a model for the binding of the growing chain. PMID:25128528

Performance Analysis and Design Synthesis (PADS) computer program. Volume 1: Formulation

NASA Technical Reports Server (NTRS)

1972-01-01

The program formulation for PADS computer program is presented. It can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general-purpose branched trajectory optimization program. In the former use, it has the Space Shuttle Synthesis Program as well as a simplified stage weight module for optimally sizing manned recoverable launch vehicles. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent; the second employs the method of quasilinearization, which requires a starting solution from the first trajectory module.

Novel synthesis and structural characterization of a high-affinity paramagnetic kinase probe for the identification of non-ATP site binders by nuclear magnetic resonance.

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

Moy, Franklin J.; Lee, Arthur; Gavrin, Lori Krim

2010-07-23

To aid in the pursuit of selective kinase inhibitors, we have developed a unique ATP site binder tool for the detection of binders outside the ATP site by nuclear magnetic resonance (NMR). We report here the novel synthesis that led to this paramagnetic spin-labeled pyrazolopyrimidine probe (1), which exhibits nanomolar inhibitory activity against multiple kinases. We demonstrate the application of this probe by performing NMR binding experiments with Lck and Src kinases and utilize it to detect the binding of two compounds proximal to the ATP site. The complex structure of the probe with Lck is also presented, revealing howmore » the probe fits in the ATP site and the specific interactions it has with the protein. We believe that this spin-labeled probe is a valuable tool that holds broad applicability in a screen for non-ATP site binders.« less

THE INTRACELLULAR SITE OF SYNTHESIS OF MITOCHONDRIAL RIBOSOMAL PROTEINS IN NEUROSPORA CRASSA

PubMed Central

Lizardi, Paul M.; Luck, David J. L.

1972-01-01

The intracellular site of synthesis of mitochondrial ribosomal proteins (MRP) in Neurospora crassa has been investigated using three complementary approaches. (a) Mitochondrial protein synthesis in vitro: Tritium-labeled proteins made by isolated mitochondria were compared to 14C-labeled marker MRP by cofractionation in a two-step procedure involving isoelectric focusing and polyacrylamide gel electrophoresis. Examination of the electrophoretic profiles showed that essentially none of the peaks of in vitro product corresponded exactly to any of the MRP marker peaks. (b) Sensitivity of in vivo MRP synthesis to chloramphenicol: Cells were labeled with leucine-3H in the presence of chloramphenicol, mitochondrial ribosomal subunits were subsequently isolated, and their proteins fractionated by isoelectric focusing followed by gel electrophoresis. The labeling of every single MRP was found to be insensitive to chloramphenicol, a selective inhibitor of mitochondrial protein synthesis. (c) Sensitivity of in vivo MRP synthesis to anisomycin: We have found this antibiotic to be a good selective inhibitor of cytoplasmic protein synthesis in Neurospora. In the presence of anisomycin the labeling of virtually all MRP is inhibited to the same extent as the labeling of cytoplasmic ribosomal proteins. On the basis of these three types of studies we conclude that most if not all 53 structural proteins of mitochondrial ribosomal subunits in Neurospora are synthesized by cytoplasmic ribosomes. PMID:4261038

Submersible observations along the southern Juan de Fuca Ridge: 1984 Alvin program.

USGS Publications Warehouse

Normark, William R.; Morton, Janet L.; Ross, Stephanie L.

1987-01-01

In September 1984, the research submersible Alvin provided direct observations of three major hydrothermal vent areas along the southernmost segment of the Juan de Fuca Ridge (JFR). The submersible operations focused on specific volcanologie, structural, and hydrothermal problems that had been identified during the preceding 4 years of photographic, dredging, acoustic imaging, and geophysical studies along a 12-km-long section of the ridge. A continuously maintained (from 1981 to the present) net of seafloor-anchored acoustic transponders allowed the observations from Alvin to be directly tied to all previous U.S. Geological Survey data sets and National Oceanic and Atmospheric Administration water column surveys from 1984 to the present. The three vent areas studied are the largest of at least six areas identified by previous deep-towed camera surveys that lie within a deep cleft, which marks the axis of symmetry of the JFR in this region. The cleft appears to be the locus of eruption for this segment of the JFR. The vent areas, at least in part, are localized near what appear to be previous volcanic eruptive centers marked by extensive lava lake collapse features adjacent to the cleft at these sites. Each hydrothermal area has several active discharge sites, and sulfide deposits occur as clusters (15–100 m2) of small chimneys, individual large chimneys, or clusters of large branched chimneys. We review the dive program and present a brief synthesis of the geology of the vent sites together with sample and track line compilations.

Cdt2-mediated XPG degradation promotes gap-filling DNA synthesis in nucleotide excision repair

PubMed Central

Han, Chunhua; Wani, Gulzar; Zhao, Ran; Qian, Jiang; Sharma, Nidhi; He, Jinshan; Zhu, Qianzheng; Wang, Qi-En; Wani, Altaf A

2015-01-01

Xeroderma pigmentosum group G (XPG) protein is a structure-specific repair endonuclease, which cleaves DNA strands on the 3′ side of the DNA damage during nucleotide excision repair (NER). XPG also plays a crucial role in initiating DNA repair synthesis through recruitment of PCNA to the repair sites. However, the fate of XPG protein subsequent to the excision of DNA damage has remained unresolved. Here, we show that XPG, following its action on bulky lesions resulting from exposures to UV irradiation and cisplatin, is subjected to proteasome-mediated proteolytic degradation. Productive NER processing is required for XPG degradation as both UV and cisplatin treatment-induced XPG degradation is compromised in NER-deficient XP-A, XP-B, XP-C, and XP-F cells. In addition, the NER-related XPG degradation requires Cdt2, a component of an E3 ubiquitin ligase, CRL4Cdt2. Micropore local UV irradiation and in situ Proximity Ligation assays demonstrated that Cdt2 is recruited to the UV-damage sites and interacts with XPG in the presence of PCNA. Importantly, Cdt2-mediated XPG degradation is crucial to the subsequent recruitment of DNA polymerase δ and DNA repair synthesis. Collectively, our data support the idea of PCNA recruitment to damage sites which occurs in conjunction with XPG, recognition of the PCNA-bound XPG by CRL4Cdt2 for specific ubiquitylation and finally the protein degradation. In essence, XPG elimination from DNA damage sites clears the chromatin space needed for the subsequent recruitment of DNA polymerase δ to the damage site and completion of gap-filling DNA synthesis during the final stage of NER. PMID:25483071

Bacterial abundance and activity in deep-sea sediments from the eastern North Atlantic

NASA Astrophysics Data System (ADS)

Eardly, D. F.; Carton, M. W.; Gallagher, J. M.; Patching, J. W.

Results are presented from four cruises to the Porcupine Abyssal Plain (PAP site) that took place during the BENGAL project from September 1996 to March 1998, and two cruises to the PAP and an oligotrophic site (EUMELI) that took place during the DEEPSEAS project between September 1993 and March 1994. Bacterial abundances in sediment and sediment contact water were measured by epifluorescence microscopy. Bacterial activity was determined by 3H-thymidine incorporation as a measure of DNA synthesis, and by 3H-leucine incorporation as a measure of protein synthesis. Activities were measured under atmospheric and in situ pressures and temperatures. Bacterial activity was usually higher in samples incubated at in situ pressure than those incubated at atmospheric pressure indicating that a barophilic community was dominant. Inter-cruise comparisons of abundance and activity during the BENGAL project showed no firm evidence of there being a seasonal response in the benthic microbial community to any episodic phytodetritus event. This was probably because of inter-annual variations in the quality and quantity of phytodetritus deposition at the PAP site, the rapid remineralization of fresh organic material by the microbial communities and the timing of cruises to the study area. 3H-thymidine and 3H-leucine incorporation in sediments was higher during the BENGAL period than the DEEPSEAS programme. A methodological change in the 3H-thymidine incorporation technique for sediments may explain the differences in DNA synthesis observed between the two projects, whereas the lower levels of protein synthesis observed during the DEEPSEAS programme probably reflected both inter-annual variations in activity at the PAP site and the lower productivity that prevailed at surface at the EUMELI oligotrophic site. Rates of 3H-thymidine incorporation in sediment contact water were similar during both projects.

Consolidation and reconsolidation of memory in black-capped chickadees (Poecile atricapillus).

PubMed

Barrett, Matthew C; Sherry, David F

2012-12-01

Multiple phases of protein synthesis are necessary for the synaptic modifications that consolidate long-term memory. The reconsolidation hypothesis supposes that information in long-term memory becomes labile and subject to change when retrieved and must be reconsolidated into long-term memory. The current study used the protein synthesis inhibitor anisomycin to examine memory consolidation in birds and to test the reconsolidation hypothesis. Black-capped chickadees store food and usually remember which of their caches they have emptied and which they have left full. In Experiment 1, anisomycin was injected either immediately and 2 hr after food caching, or 4 and 6 hr after food caching. Inhibition of protein synthesis impaired memory for cache sites 24 and 48 hr later. In Experiment 2, it was hypothesized that long-term memory for food caches becomes labile as predicted by the reconsolidation hypothesis when birds search for caches. Anisomycin was administered immediately after chickadees had searched for their caches. Inhibition of protein synthesis should disrupt memory for caches left full if these sites are retrieved from long-term memory and require reconsolidation. Control birds were later more likely to revisit full caches than caches they had emptied. Birds given anisomycin revisited both kinds of caches and did not distinguish between them. This result shows that reconsolidation of full caches into long-term memory is not necessary following search for cache sites, but also shows that protein synthesis-dependent consolidation is required for updating the status of emptied caches.

The Difference a Single Atom Can Make: Synthesis and Design at the Chemistry–Biology Interface

PubMed Central

2017-01-01

A Perspective of work in our laboratory on the examination of biologically active compounds, especially natural products, is presented. In the context of individual programs and along with a summary of our work, selected cases are presented that illustrate the impact single atom changes can have on the biological properties of the compounds. The examples were chosen to highlight single heavy atom changes that improve activity, rather than those that involve informative alterations that reduce or abolish activity. The examples were also chosen to illustrate that the impact of such single-atom changes can originate from steric, electronic, conformational, or H-bonding effects, from changes in functional reactivity, from fundamental intermolecular interactions with a biological target, from introduction of a new or altered functionalization site, or from features as simple as improvements in stability or physical properties. Nearly all the examples highlighted represent not only unusual instances of productive deep-seated natural product modifications and were introduced through total synthesis but are also remarkable in that they are derived from only a single heavy atom change in the structure. PMID:28945374

Performance Analysis and Design Synthesis (PADS) computer program. Volume 3: User manual

NASA Technical Reports Server (NTRS)

1972-01-01

The two-fold purpose of the Performance Analysis and Design Synthesis (PADS) computer program is discussed. The program can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general purpose branched trajectory optimization program. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent. The second module uses the method of quasi-linearization, which requires a starting solution from the first trajectory module.

Conducting quantitative synthesis when comparing medical interventions: AHRQ and the Effective Health Care Program.

PubMed

Fu, Rongwei; Gartlehner, Gerald; Grant, Mark; Shamliyan, Tatyana; Sedrakyan, Art; Wilt, Timothy J; Griffith, Lauren; Oremus, Mark; Raina, Parminder; Ismaila, Afisi; Santaguida, Pasqualina; Lau, Joseph; Trikalinos, Thomas A

2011-11-01

This article is to establish recommendations for conducting quantitative synthesis, or meta-analysis, using study-level data in comparative effectiveness reviews (CERs) for the Evidence-based Practice Center (EPC) program of the Agency for Healthcare Research and Quality. We focused on recurrent issues in the EPC program and the recommendations were developed using group discussion and consensus based on current knowledge in the literature. We first discussed considerations for deciding whether to combine studies, followed by discussions on indirect comparison and incorporation of indirect evidence. Then, we described our recommendations on choosing effect measures and statistical models, giving special attention to combining studies with rare events; and on testing and exploring heterogeneity. Finally, we briefly presented recommendations on combining studies of mixed design and on sensitivity analysis. Quantitative synthesis should be conducted in a transparent and consistent way. Inclusion of multiple alternative interventions in CERs increases the complexity of quantitative synthesis, whereas the basic issues in quantitative synthesis remain crucial considerations in quantitative synthesis for a CER. We will cover more issues in future versions and update and improve recommendations with the accumulation of new research to advance the goal for transparency and consistency. Copyright © 2011 Elsevier Inc. All rights reserved.

Addressing challenges in cross-site synthesis of long-term ecological data

USDA-ARS?s Scientific Manuscript database

Long-term ecological datasets are becoming increasingly abundant on the internet, and are available both on websites hosted by the originating sites and/or in online repositories. While sites and networks are increasingly conforming to adopted metadata standards (which themselves continue to evolve ...

Synthesis of Feedback Controller for Chaotic Systems by Means of Evolutionary Techniques

NASA Astrophysics Data System (ADS)

Senkerik, Roman; Oplatkova, Zuzana; Zelinka, Ivan; Davendra, Donald; Jasek, Roman

2011-06-01

This research deals with a synthesis of control law for three selected discrete chaotic systems by means of analytic programming. The novality of the approach is that a tool for symbolic regression—analytic programming—is used for such kind of difficult problem. The paper consists of the descriptions of analytic programming as well as chaotic systems and used cost function. For experimentation, Self-Organizing Migrating Algorithm (SOMA) with analytic programming was used.

Starch synthesis and carbon partitioning in developing endosperm.

PubMed

Emes, M J; Bowsher, C G; Hedley, C; Burrell, M M; Scrase-Field, E S F; Tetlow, I J

2003-01-01

The biosynthesis of starch is the major determinant of yield in cereal grains. In this short review, attention is focused on the synthesis of the soluble substrate for starch synthesis, ADPglucose (ADPG). Consideration is given to the pathway of ADPG production, its subcellular compartmentation, and the role of metabolite transporters in mediating its delivery to the site of starch synthesis. As ADPG is an activated sugar, the dependence of its production on respiration, changes which occur during development, and the constraints which ATP production may place on carbon partitioning into different end-products are discussed.

Automatic reactor model synthesis with genetic programming.

PubMed

Dürrenmatt, David J; Gujer, Willi

2012-01-01

Successful modeling of wastewater treatment plant (WWTP) processes requires an accurate description of the plant hydraulics. Common methods such as tracer experiments are difficult and costly and thus have limited applicability in practice; engineers are often forced to rely on their experience only. An implementation of grammar-based genetic programming with an encoding to represent hydraulic reactor models as program trees should fill this gap: The encoding enables the algorithm to construct arbitrary reactor models compatible with common software used for WWTP modeling by linking building blocks, such as continuous stirred-tank reactors. Discharge measurements and influent and effluent concentrations are the only required inputs. As shown in a synthetic example, the technique can be used to identify a set of reactor models that perform equally well. Instead of being guided by experience, the most suitable model can now be chosen by the engineer from the set. In a second example, temperature measurements at the influent and effluent of a primary clarifier are used to generate a reactor model. A virtual tracer experiment performed on the reactor model has good agreement with a tracer experiment performed on-site.

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A-T phosphoramidite building blocks.

PubMed

Schmidtgall, Boris; Höbartner, Claudia; Ducho, Christian

2015-01-01

Modifications of the nucleic acid backbone are essential for the development of oligonucleotide-derived bioactive agents. The NAA-modification represents a novel artificial internucleotide linkage which enables the site-specific introduction of positive charges into the otherwise polyanionic backbone of DNA oligonucleotides. Following initial studies with the introduction of the NAA-linkage at T-T sites, it is now envisioned to prepare NAA-modified oligonucleotides bearing the modification at X-T motifs (X = A, C, G). We have therefore developed the efficient and stereoselective synthesis of NAA-linked 'dimeric' A-T phosphoramidite building blocks for automated DNA synthesis. Both the (S)- and the (R)-configured NAA-motifs were constructed with high diastereoselectivities to furnish two different phosphoramidite reagents, which were employed for the solid phase-supported automated synthesis of two NAA-modified DNA oligonucleotides. This represents a significant step to further establish the NAA-linkage as a useful addition to the existing 'toolbox' of backbone modifications for the design of bioactive oligonucleotide analogues.

Amiloride inhibits the initiation of Coxsackievirus and poliovirus RNA replication by inhibiting VPg uridylylation.

PubMed

Ogram, Sushma A; Boone, Christopher D; McKenna, Robert; Flanegan, James B

2014-09-01

The mechanism of amiloride inhibition of Coxsackievirus B3 (CVB3) and poliovirus type 1 (PV1) RNA replication was investigated using membrane-associated RNA replication complexes. Amiloride was shown to inhibit viral RNA replication and VPgpUpU synthesis. However, the drug had no effect on polymerase elongation activity during either (-) strand or (+) strand synthesis. These findings indicated that amiloride inhibited the initiation of RNA synthesis by inhibiting VPg uridylylation. In addition, in silico binding studies showed that amiloride docks in the VPg binding site on the back of the viral RNA polymerase, 3D(pol). Since VPg binding at this site on PV1 3D(pol) was previously shown to be required for VPg uridylylation, our results suggest that amiloride inhibits VPg binding to 3D(pol). In summary, our findings are consistent with a model in which amiloride inhibits VPgpUpU synthesis and viral RNA replication by competing with VPg for binding to 3D(pol). Copyright © 2014 Elsevier Inc. All rights reserved.

Interfacing theories of program with theories of evaluation for advancing evaluation practice: Reductionism, systems thinking, and pragmatic synthesis.

PubMed

Chen, Huey T

2016-12-01

Theories of program and theories of evaluation form the foundation of program evaluation theories. Theories of program reflect assumptions on how to conceptualize an intervention program for evaluation purposes, while theories of evaluation reflect assumptions on how to design useful evaluation. These two types of theories are related, but often discussed separately. This paper attempts to use three theoretical perspectives (reductionism, systems thinking, and pragmatic synthesis) to interface them and discuss the implications for evaluation practice. Reductionism proposes that an intervention program can be broken into crucial components for rigorous analyses; systems thinking view an intervention program as dynamic and complex, requiring a holistic examination. In spite of their contributions, reductionism and systems thinking represent the extreme ends of a theoretical spectrum; many real-world programs, however, may fall in the middle. Pragmatic synthesis is being developed to serve these moderate- complexity programs. These three theoretical perspectives have their own strengths and challenges. Knowledge on these three perspectives and their evaluation implications can provide a better guide for designing fruitful evaluations, improving the quality of evaluation practice, informing potential areas for developing cutting-edge evaluation approaches, and contributing to advancing program evaluation toward a mature applied science. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ecosystem Model Performance at Wetlands: Results from the North American Carbon Program Site Synthesis

NASA Astrophysics Data System (ADS)

Sulman, B. N.; Desai, A. R.; Schroeder, N. M.; NACP Site Synthesis Participants

2011-12-01

Northern peatlands contain a significant fraction of the global carbon pool, and their responses to hydrological change are likely to be important factors in future carbon cycle-climate feedbacks. Global-scale carbon cycle modeling studies typically use general ecosystem models with coarse spatial resolution, often without peatland-specific processes. Here, seven ecosystem models were used to simulate CO2 fluxes at three field sites in Canada and the northern United States, including two nutrient-rich fens and one nutrient-poor, sphagnum-dominated bog, from 2002-2006. Flux residuals (simulated - observed) were positively correlated with measured water table for both gross ecosystem productivity (GEP) and ecosystem respiration (ER) at the two fen sites for all models, and were positively correlated with water table at the bog site for the majority of models. Modeled diurnal cycles at fen sites agreed well with eddy covariance measurements overall. Eddy covariance GEP and ER were higher during dry periods than during wet periods, while model results predicted either the opposite relationship or no significant difference. At the bog site, eddy covariance GEP had no significant dependence on water table, while models predicted higher GEP during wet periods. All models significantly over-estimated GEP at the bog site, and all but one over-estimated ER at the bog site. Carbon cycle models in peatland-rich regions could be improved by incorporating better models or measurements of hydrology and by inhibiting GEP and ER rates under saturated conditions. Bogs and fens likely require distinct treatments in ecosystem models due to differences in nutrients, peat properties, and plant communities.

Computer program for design and performance analysis of navigation-aid power systems. Program documentation. Volume 1: Software requirements document

NASA Technical Reports Server (NTRS)

Goltz, G.; Kaiser, L. M.; Weiner, H.

1977-01-01

A computer program has been developed for designing and analyzing the performance of solar array/battery power systems for the U.S. Coast Guard Navigational Aids. This program is called the Design Synthesis/Performance Analysis (DSPA) Computer Program. The basic function of the Design Synthesis portion of the DSPA program is to evaluate functional and economic criteria to provide specifications for viable solar array/battery power systems. The basic function of the Performance Analysis portion of the DSPA program is to simulate the operation of solar array/battery power systems under specific loads and environmental conditions. This document establishes the software requirements for the DSPA computer program, discusses the processing that occurs within the program, and defines the necessary interfaces for operation.

Improved detonation modeling with CHEETAH

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

Heller, A.

1997-11-01

A Livermore software program called CHEETAH, an important, even indispensable tool for energetic materials researchers worldwide, was made more powerful in the summer of 1997 with the release of CHEETAH 2.0, an advanced version that simulates a wider variety of detonations. Derived from more than 40 years of experiments on high explosives at Lawrence Livermore and Los Alamos national laboratories, CHEETAH predicts the results from detonating a mixture of specified reactants. It operates by solving thermodynamic equations to predict detonation products and such properties as temperature, pressure, volume, and total energy released. The code is prized by synthesis chemists andmore » other researchers because it allows them to vary the starting molecules and conditions to optimize the desired performance properties. One of the Laboratory`s most popular computer codes, CHEETAH is used at more than 200 sites worldwide, including ones in England, Canada, Sweden, Switzerland, and France. Most sites are defense-related, although a few users, such as Japanese fireworks researchers, are in the civilian sector.« less

Pax: A permanent base for human habitation of Mars

NASA Technical Reports Server (NTRS)

Moore, Gary T.; Rebholz, Patrick J.; Fieber, Joseph P.; Huebner-Moths, Janis; Paruleski, Kerry L.

1992-01-01

The Advanced Design Program in Space Architecture at the University of Wisconsin-Milwaukee supported the synthesis report and two of its scenarios - 'Architecture 1' and 'Architecture 4' - and the Weaver ExPO report on near-term extraterrestrial explorations during the spring of 1992. The project investigated the implications of different mission scenarios, the Martian environment, supporting technologies, and especially human factors and environment-behavior considerations for the design of the first permanent Martian base. This paper presents the results of that investigation. The paper summarizes site selection, development of habitability design requirements based on environment-behavior research, construction sequencing, and a full concept design and design development for a first permanent Martian base and habitat. The proposed design is presented in terms of an integrative mission scenario and master plan phased through initial operational configuration, base site plan, and design development details of a complete Martian habitat for 18 crew members including all laboratory, mission control, and crew support spaces.

FWP executive summaries, Basic Energy Sciences Materials Sciences Programs (SNL/NM)

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

Samara, G.A.

1997-05-01

The BES Materials Sciences Program has the central theme of Scientifically Tailored Materials. The major objective of this program is to combine Sandia`s expertise and capabilities in the areas of solid state sciences, advanced atomic-level diagnostics and materials synthesis and processing science to produce new classes of tailored materials as well as to enhance the properties of existing materials for US energy applications and for critical defense needs. Current core research in this program includes the physics and chemistry of ceramics synthesis and processing, the use of energetic particles for the synthesis and study of materials, tailored surfaces and interfacesmore » for materials applications, chemical vapor deposition sciences, artificially-structured semiconductor materials science, advanced growth techniques for improved semiconductor structures, transport in unconventional solids, atomic-level science of interfacial adhesion, high-temperature superconductors, and the synthesis and processing of nano-size clusters for energy applications. In addition, the program includes the following three smaller efforts initiated in the past two years: (1) Wetting and Flow of Liquid Metals and Amorphous Ceramics at Solid Interfaces, (2) Field-Structured Anisotropic Composites, and (3) Composition-Modulated Semiconductor Structures for Photovoltaic and Optical Technologies. The latter is a joint effort with the National Renewable Energy Laboratory. Separate summaries are given of individual research areas.« less

Aligator: A computational tool for optimizing total chemical synthesis of large proteins.

PubMed

Jacobsen, Michael T; Erickson, Patrick W; Kay, Michael S

2017-09-15

The scope of chemical protein synthesis (CPS) continues to expand, driven primarily by advances in chemical ligation tools (e.g., reversible solubilizing groups and novel ligation chemistries). However, the design of an optimal synthesis route can be an arduous and fickle task due to the large number of theoretically possible, and in many cases problematic, synthetic strategies. In this perspective, we highlight recent CPS tool advances and then introduce a new and easy-to-use program, Aligator (Automated Ligator), for analyzing and designing the most efficient strategies for constructing large targets using CPS. As a model set, we selected the E. coli ribosomal proteins and associated factors for computational analysis. Aligator systematically scores and ranks all feasible synthetic strategies for a particular CPS target. The Aligator script methodically evaluates potential peptide segments for a target using a scoring function that includes solubility, ligation site quality, segment lengths, and number of ligations to provide a ranked list of potential synthetic strategies. We demonstrate the utility of Aligator by analyzing three recent CPS projects from our lab: TNFα (157 aa), GroES (97 aa), and DapA (312 aa). As the limits of CPS are extended, we expect that computational tools will play an increasingly important role in the efficient execution of ambitious CPS projects such as production of a mirror-image ribosome. Copyright © 2017 Elsevier Ltd. All rights reserved.

Insolubilized enzymes for food synthesis

NASA Technical Reports Server (NTRS)

Marshall, D. L.

1972-01-01

Cellulose matrix with numerous enzyme-coated silica particles of colloidal size permanently bound at various sites within matrix was produced that has high activity and possesses requisite physical characteristics for filtration or column operations. Product also allows coupling step in synthesis of edible food to proceed under mild conditions.

75 FR 7029 - Lonza, Inc., Riverside Plant, Lonza Exclusive Synthesis Section, Custom Manufacturing Division...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-16

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-72,231] Lonza, Inc., Riverside Plant, Lonza Exclusive Synthesis Section, Custom Manufacturing Division Including On-Site Leased Workers of Lab Support, Aerotek, Job Exchange, and Synerfac; Conshohocken, PA; Notice of Affirmative...

75 FR 878 - Lonza, Inc. Riverside Plant; Lonza Exclusive Synthesis Section Custom Manufacturing Division...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-06

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-72,231] Lonza, Inc. Riverside Plant; Lonza Exclusive Synthesis Section Custom Manufacturing Division Including On-Site Leased Workers of Lab Support, Aerotek, Job Exchange, and Synerfac; Conshohocken, PA; Notice of Affirmative...

Cell-free synthesis of functional human epidermal growth factor receptor: Investigation of ligand-independent dimerization in Sf21 microsomal membranes using non-canonical amino acids

PubMed Central

Quast, Robert B.; Ballion, Biljana; Stech, Marlitt; Sonnabend, Andrei; Varga, Balázs R.; Wüstenhagen, Doreen A.; Kele, Péter; Schiller, Stefan M.; Kubick, Stefan

2016-01-01

Cell-free protein synthesis systems represent versatile tools for the synthesis and modification of human membrane proteins. In particular, eukaryotic cell-free systems provide a promising platform for their structural and functional characterization. Here, we present the cell-free synthesis of functional human epidermal growth factor receptor and its vIII deletion mutant in a microsome-containing system derived from cultured Sf21 cells. We provide evidence for embedment of cell-free synthesized receptors into microsomal membranes and asparagine-linked glycosylation. Using the cricket paralysis virus internal ribosome entry site and a repetitive synthesis approach enrichment of receptors inside the microsomal fractions was facilitated thereby providing analytical amounts of functional protein. Receptor tyrosine kinase activation was demonstrated by monitoring receptor phosphorylation. Furthermore, an orthogonal cell-free translation system that provides the site-directed incorporation of p-azido-L-phenylalanine is characterized and applied to investigate receptor dimerization in the absence of a ligand by photo-affinity cross-linking. Finally, incorporated azides are used to generate stable covalently linked receptor dimers by strain-promoted cycloaddition using a novel linker system. PMID:27670253

Synthesis: Intertwining product and process

NASA Technical Reports Server (NTRS)

Weiss, David M.

1990-01-01

Synthesis is a proposed systematic process for rapidly creating different members of a program family. Family members are described by variations in their requirements. Requirements variations are mapped to variations on a standard design to generate production quality code and documentation. The approach is made feasible by using principles underlying design for change. Synthesis incorporates ideas from rapid prototyping, application generators, and domain analysis. The goals of Synthesis and the Synthesis process are discussed. The technology needed and the feasibility of the approach are also briefly discussed. The status of current efforts to implement Synthesis methodologies is presented.

Drug Design Relating Amebicides to Inhibition of Protein Synthesis.

DTIC Science & Technology

1977-09-01

A study of the effect of emetine on protein synthesis in E. histolytica was made on log phase amebas as compared to stationary phase amebas ...Sensitivity to emetine was maintained independently of the rate of protein synthesis. Furthermore, both stages of amebas had the same capacity to bind emetine...elongation site. Finally, evidence was obtained that the capacity to bind emetine provides a basis for conferring drug resistance in amebas . A direct

Development of a weight/sizing design synthesis computer program. Volume 1: Program formulation

NASA Technical Reports Server (NTRS)

Garrison, J. M.

1973-01-01

The development of a weight/sizing design synthesis methodology for use in support of the main line space shuttle program is discussed. The methodology has a minimum number of data inputs and quick turn around capabilities. The methodology makes it possible to: (1) make weight comparisons between current shuttle configurations and proposed changes, (2) determine the effects of various subsystems trades on total systems weight, and (3) determine the effects of weight on performance and performance on weight.

An implementation of the programming structural synthesis system (PROSSS)

NASA Technical Reports Server (NTRS)

Rogers, J. L., Jr.; Sobieszczanski-Sobieski, J.; Bhat, R. B.

1981-01-01

A particular implementation of the programming structural synthesis system (PROSSS) is described. This software system combines a state of the art optimization program, a production level structural analysis program, and user supplied, problem dependent interface programs. These programs are combined using standard command language features existing in modern computer operating systems. PROSSS is explained in general with respect to this implementation along with the steps for the preparation of the programs and input data. Each component of the system is described in detail with annotated listings for clarification. The components include options, procedures, programs and subroutines, and data files as they pertain to this implementation. An example exercising each option in this implementation to allow the user to anticipate the type of results that might be expected is presented.

Biological Synthesis of a Protein Analogue of Acetylcholinesterase: Monoclonal Anti-Idiotype Antibody Analogue of the Esteratic Site.

DTIC Science & Technology

1986-07-10

site- directed inhibitor DFP, the reversible site-directed inhibitors neostigmine, carbachol , edrophonium, and BW284c51; and the allosteric site...Esteratic 10-6 10 -7 - I0-2 Neostigmine Esteratic 10- 7 10- 6 - 10 5 Anionic PI Carbachol Esteratic 10- 4 10 3 10-1 Anionic PI Edrophonium Anionic 10

Synthesis, crystal structure and magnetic properties of a new B-site ordered double perovskite Sr{sub 2}CuIrO{sub 6}

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

Vasala, Sami; Yamauchi, Hisao; Karppinen, Maarit, E-mail: maarit.karppinen@aalto.fi

2014-12-15

Here we synthesize and characterize a new double-perovskite oxide Sr{sub 2}CuIrO{sub 6}. The synthesis requires the use of high oxygen pressure to stabilize the VI oxidation state of iridium. The compound has a tetragonally-distorted crystal structure due to the Jahn–Teller active Cu{sup II} ion, and a high degree of B-site cation order. Magnetic transition is apparent at 15 K, but the zero-field-cooled and field-cooled susceptibilities diverge below this temperature. The high degree of cation order would exclude the possibility of a typical spin-glass, indicating that the divergence is probably due to a frustration of the magnetic interactions between Cu andmore » Ir, with a high frustration factor of f≈25. - Graphical abstract: A new member of the A{sub 2}B′B″O{sub 6} double-perovskite family with JT-active Cu{sup II} at the B′ site and Ir{sup VI} at the B″ site is synthesized through high pressure synthesis and characterized for the structural and magnetic properties. - Highlights: • New member of the A{sub 2}CuB″O{sub 6} double-perovskite family is synthesized with B″=Ir. • Stabilization of Ir{sup VI} requires the use of high oxygen pressure synthesis. • Crystal structure is tetragonally distorted due to JT-active Cu{sup II}. • Divergence of ZFC and FC curves is seen below the T{sub N} of 15 K. • This is presumably due to a frustration effect.« less

A synthesis of evaluation monitoring projects by the forest health monitoring program (1998-2007)

Treesearch

William A. Bechtold; Michael J. Bohne; Barbara L. Conkling; Dana L. Friedman

2012-01-01

The national Forest Health Monitoring Program of the Forest Service, U.S. Department of Agriculture, has funded over 200 Evaluation Monitoring projects. Evaluation Monitoring is designed to verify and define the extent of deterioration in forest ecosystems where potential problems have been identified. This report is a synthesis of results from over 150 Evaluation...

Expert System for Automated Design Synthesis

NASA Technical Reports Server (NTRS)

Rogers, James L., Jr.; Barthelemy, Jean-Francois M.

1987-01-01

Expert-system computer program EXADS developed to aid users of Automated Design Synthesis (ADS) general-purpose optimization program. EXADS aids engineer in determining best combination based on knowledge of specific problem and expert knowledge stored in knowledge base. Available in two interactive machine versions. IBM PC version (LAR-13687) written in IQ-LISP. DEC VAX version (LAR-13688) written in Franz-LISP.

Interactive program for analysis and design problems in advanced composites technology

NASA Technical Reports Server (NTRS)

Cruse, T. A.; Swedlow, J. L.

1971-01-01

During the past year an experimental program in the fracture of advanced fiber composites has been completed. The experimental program has given direction to additional experimental and theoretical work. A synthesis program for designing low weight multifastener joints in composites is proposed, based on extensive analytical background. A number of failed joints have been thoroughly analyzed to evaluate the failure hypothesis used in the synthesis procedure. Finally, a new solution is reported for isotropic and anisotropic laminates using the boundary-integral method. The solution method offers significant savings of computer core and time for important problems.

Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis

PubMed Central

Shin, Byung-Sik; Katoh, Takayuki; Gutierrez, Erik; Kim, Joo-Ran; Suga, Hiroaki

2017-01-01

Abstract Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. PMID:28637321

General aviation design synthesis utilizing interactive computer graphics

NASA Technical Reports Server (NTRS)

Galloway, T. L.; Smith, M. R.

1976-01-01

Interactive computer graphics is a fast growing area of computer application, due to such factors as substantial cost reductions in hardware, general availability of software, and expanded data communication networks. In addition to allowing faster and more meaningful input/output, computer graphics permits the use of data in graphic form to carry out parametric studies for configuration selection and for assessing the impact of advanced technologies on general aviation designs. The incorporation of interactive computer graphics into a NASA developed general aviation synthesis program is described, and the potential uses of the synthesis program in preliminary design are demonstrated.

Extrarenal citrulline disposal in mice with impaired renal function

USDA-ARS?s Scientific Manuscript database

The endogenous synthesis of arginine, a semiessential amino acid, relies on the production of citrulline by the gut and its conversion into arginine by the kidney in what has been called the "intestinal-renal axis" for arginine synthesis. Although the kidney is the main site for citrulline disposal,...

The total chemical synthesis of the monoglycosylated GM2 ganglioside activator using a novel cysteine surrogate.

PubMed

Sato, Kohei; Kitakaze, Keisuke; Nakamura, Takahiro; Naruse, Naoto; Aihara, Keisuke; Shigenaga, Akira; Inokuma, Tsubasa; Tsuji, Daisuke; Itoh, Kohji; Otaka, Akira

2015-06-21

We describe a novel peptide ligation/desulfurization strategy using a β-mercapto-N-glycosylated asparagine derivative. The newly developed procedure was successfully applied to the total chemical synthesis of the GM2 ganglioside activator protein bearing a monosaccharide on the native glycosylation site.

The σ70 region 1.2 regulates promoter escape by unwinding DNA downstream of the transcription start site

PubMed Central

Bochkareva, Aleksandra; Zenkin, Nikolay

2013-01-01

The mechanisms of abortive synthesis and promoter escape during initiation of transcription are poorly understood. Here, we show that, after initiation of RNA synthesis, non-specific interaction of σ70 region 1.2, present in all σ70 family factors, with the non-template strand around position −4 relative to the transcription start site facilitates unwinding of the DNA duplex downstream of the transcription start site. This leads to stabilization of short RNA products and allows their extension, i.e. promoter escape. We show that this activity of σ70 region 1.2 is assisted by the β-lobe domain, but does not involve the β′-rudder or the β′-switch-2, earlier proposed to participate in promoter escape. DNA sequence independence of this function of σ70 region 1.2 suggests that it may be conserved in all σ70 family factors. Our results indicate that the abortive nature of initial synthesis is caused, at least in part, by failure to open the downstream DNA by the β-lobe and σ region 1.2. PMID:23430153

Optimizing the performance of catalytic traps for hydrocarbon abatement during the cold-start of a gasoline engine.

PubMed

Puértolas, B; Navlani-García, M; García, T; Navarro, M V; Lozano-Castelló, D; Cazorla-Amorós, D

2014-08-30

A key target to reduce current hydrocarbon emissions from vehicular exhaust is to improve their abatement under cold-start conditions. Herein, we demonstrate the potential of factorial analysis to design a highly efficient catalytic trap. The impact of the synthesis conditions on the preparation of copper-loaded ZSM-5 is clearly revealed by XRD, N2 sorption, FTIR, NH3-TPD, SEM and TEM. A high concentration of copper nitrate precursor in the synthesis improves the removal of hydrocarbons, providing both strong adsorption sites for hydrocarbon retention at low temperature and copper oxide nanoparticles for full hydrocarbon catalytic combustion at high temperature. The use of copper acetate precursor leads to a more homogeneous dispersion of copper oxide nanoparticles also providing enough catalytic sites for the total oxidation of hydrocarbons released from the adsorption sites, although lower copper loadings are achieved. Thus, synthesis conditions leading to high copper loadings jointly with highly dispersed copper oxide nanoparticles would result in an exceptional catalytic trap able to reach superior hydrocarbon abatement under highly demanding operational conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Initiation of viral RNA-dependent RNA polymerization.

PubMed

van Dijk, Alberdina A; Makeyev, Eugene V; Bamford, Dennis H

2004-05-01

This review summarizes the combined insights from recent structural and functional studies of viral RNA-dependent RNA polymerases (RdRPs) with the primary focus on the mechanisms of initiation of RNA synthesis. Replication of RNA viruses has traditionally been approached using a combination of biochemical and genetic methods. Recently, high-resolution structures of six viral RdRPs have been determined. For three RdRPs, enzyme complexes with metal ions, single-stranded RNA and/or nucleoside triphosphates have also been solved. These advances have expanded our understanding of the molecular mechanisms of viral RNA synthesis and facilitated further RdRP studies by informed site-directed mutagenesis. What transpires is that the basic polymerase right hand shape provides the correct geometrical arrangement of substrate molecules and metal ions at the active site for the nucleotidyl transfer catalysis, while distinct structural elements have evolved in the different systems to ensure efficient initiation of RNA synthesis. These elements feed the template, NTPs and ions into the catalytic cavity, correctly position the template 3' terminus, transfer the products out of the catalytic site and orchestrate the transition from initiation to elongation.

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

Law, B E

Research involves analysis and field direction of AmeriFlux operations, and the PI provides scientific leadership of the AmeriFlux network. Activities include the coordination and quality assurance of measurements across AmeriFlux network sites, synthesis of results across the network, organizing and supporting the annual Science Team Meeting, and communicating AmeriFlux results to the scientific community and other users. Objectives of measurement research include (i) coordination of flux and biometric measurement protocols (ii) timely data delivery to the Carbon Dioxide Information and Analysis Center (CDIAC); and (iii) assurance of data quality of flux and ecosystem measurements contributed by AmeriFlux sites. Objectives ofmore » integration and synthesis activities include (i) integration of site data into network-wide synthesis products; and (ii) participation in the analysis, modeling and interpretation of network data products. Communications objectives include (i) organizing an annual meeting of AmeriFlux investigators for reporting annual flux measurements and exchanging scientific information on ecosystem carbon budgets; (ii) developing focused topics for analysis and publication; and (iii) developing data reporting protocols in support of AmeriFlux network goals.« less

Managing data from multiple disciplines, scales, and sites to support synthesis and modeling

USGS Publications Warehouse

Olson, R. J.; Briggs, J. M.; Porter, J.H.; Mah, Grant R.; Stafford, S.G.

1999-01-01

The synthesis and modeling of ecological processes at multiple spatial and temporal scales involves bringing together and sharing data from numerous sources. This article describes a data and information system model that facilitates assembling, managing, and sharing diverse data from multiple disciplines, scales, and sites to support integrated ecological studies. Cross-site scientific-domain working groups coordinate the development of data associated with their particular scientific working group, including decisions about data requirements, data to be compiled, data formats, derived data products, and schedules across the sites. The Web-based data and information system consists of nodes for each working group plus a central node that provides data access, project information, data query, and other functionality. The approach incorporates scientists and computer experts in the working groups and provides incentives for individuals to submit documented data to the data and information system.

Preliminary performance estimates of a highly maneuverable remotely piloted vehicle. [computerized synthesis program to assess effects of vehicle and mission parameters

NASA Technical Reports Server (NTRS)

Nelms, W. P., Jr.; Axelson, J. A.

1974-01-01

A computerized synthesis program has been used to assess the effects of various vehicle and mission parameters on the performance of a highly maneuverable remotely piloted vehicle (RPV) for the air-to-air combat role. The configuration used in the study is a trapezoidal-wing and body concept, with forward-mounted stabilizing and control surfaces. The study mission consists of an outbound cruise, an acceleration phase, a series of subsonic and supersonic turns, and a return cruise. Performance is evaluated in terms of both the required vehicle weight to accomplish this mission and combat effectiveness as measured by turning and acceleration capability. The report describes the synthesis program, the mission, the vehicle, and the results of sensitivity and trade studies.

Thermodynamics of Strecker synthesis in hydrothermal systems

NASA Technical Reports Server (NTRS)

Schulte, Mitchell; Shock, Everett

1995-01-01

Submarine hydrothermal systems on the early Earth may have been the sites from which life emerged. The potential for Strecker synthesis to produce biomolecules (amino and hydroxy acids) from starting compounds (ketones, aldehydes, HCN and ammonia) in such environments is evaluated quantitatively using thermodynamic data and parameters for the revised Helgeson-Kirkham-Flowers (HKF) equation of state. Although there is an overwhelming thermodynamic drive to form biomolecules by the Strecker synthesis at hydrothermal conditions, the availability and concentration of starting compounds limit the efficiency and productivity of Strecker reactions. Mechanisms for concentrating reactant compounds could help overcome this problem, but other mechanisms for production of biomolecules may have been required to produce the required compounds on the early Earth. Geochemical constraints imposed by hydrothermal systems provide important clues for determining the potential of these and other systems as sites for the emergence of life.

Thermodynamic impact of abasic sites on simulated translesion DNA synthesis.

PubMed

Malina, Jaroslav; Brabec, Viktor

2014-06-16

Loss of a base in DNA and the creation of an abasic (apurinic/apyrimidinic, AP) site is a frequent lesion that may occur spontaneously, or as a consequence of the action of DNA-damaging agents. The AP lesion is mutagenic or lethal if not repaired. We report a systematic thermodynamic investigation by differential scanning calorimetry on the evolution, during primer extension, of a model AP site in chemically simulated DNA translesion synthesis. Incorporation of dAMP (deoxyadenosine monophosphate), as well as dTMP (deoxythymidine monophosphate), opposite an AP site is enthalpically unfavorable, although incorporation of dTMP is more enthalpically unfavorable than that of dAMP. This finding is in a good agreement with experimental data showing that AP sites block various DNA polymerases of eukaryotic and prokaryotic origin and that, if bypassed, dAMP is preferentially inserted, whereas insertion of dTMP is less likely. The results emphasize the importance of thermodynamic contributions to the insertion of nucleotides opposite an AP site by DNA polymerases. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Berkeley Lab - Materials Sciences Division

Science.gov Websites

Synthesis Condensed Matter and Materials Physics Scattering and Instrumentation Science Centers Center for ; Finance Templates Travel One-Stop Core Programs Materials Discovery, Design and Synthesis Condensed Matter

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

Goltz, G.; Weiner, H.

A computer program has been developed for designing and analyzing the performance of solar array/battery power systems for the U.S. Coast Guard Navigational Aids. This program is called the Design Synthesis/Performance Analysis (DSPA) Computer Program. The basic function of the Design Synthesis portion of the DSPA program is to evaluate functional and economic criteria to provide specifications for viable solar array/battery power systems. The basic function of the Performance Analysis portion of the DSPA program is to simulate the operation of solar array/battery power systems under specific loads and environmental conditions. This document provides a detailed description of the DSPAmore » Computer Program system and its subprograms. This manual will assist the programmer in revising or updating the several subprograms.« less

Correlation between Fischer-Tropsch catalytic activity and composition of catalysts

PubMed Central

2011-01-01

This paper presents the synthesis and characterization of monometallic and bimetallic cobalt and iron nanoparticles supported on alumina. The catalysts were prepared by a wet impregnation method. Samples were characterized using temperature-programmed reduction (TPR), temperature-programmed oxidation (TPO), CO-chemisorption, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM-EDX) and N2-adsorption analysis. Fischer-Tropsch synthesis (FTS) was carried out in a fixed-bed microreactor at 543 K and 1 atm, with H2/CO = 2 v/v and space velocity, SV = 12L/g.h. The physicochemical properties and the FTS activity of the bimetallic catalysts were analyzed and compared with those of monometallic cobalt and iron catalysts at similar operating conditions. H2-TPR analysis of cobalt catalyst indicated three temperature regions at 506°C (low), 650°C (medium) and 731°C (high). The incorporation of iron up to 30% into cobalt catalysts increased the reduction, CO chemisorption and number of cobalt active sites of the catalyst while an opposite trend was observed for the iron-riched bimetallic catalysts. The CO conversion was 6.3% and 4.6%, over the monometallic cobalt and iron catalysts, respectively. Bimetallic catalysts enhanced the CO conversion. Amongst the catalysts studied, bimetallic catalyst with the composition of 70Co30Fe showed the highest CO conversion (8.1%) while exhibiting the same product selectivity as that of monometallic Co catalyst. Monometallic iron catalyst showed the lowest selectivity for C5+ hydrocarbons (1.6%). PMID:22047220

National Irrigation Water Quality Program data-synthesis data base

USGS Publications Warehouse

Seiler, Ralph L.; Skorupa, Joseph P.

2001-01-01

Under the National Irrigation Water Quality Program (NIWQP) of the U.S. Department of the Interior, researchers investigated contamination caused by irrigation drainage in 26 areas in the Western United States from 1986 to 1993. From 1992 to 1995, a comprehensive relational data base was built to organize data collected during the 26-area investigations. The data base provided the basis for analysis and synthesis of these data to identify common features of contaminated areas and hence dominant biologic, geologic, climatic, chemical, and physiographic factors that have resulted in contamination of water and biota in irrigated areas in the Western United States. Included in the data base are geologic, hydrologic, climatological, chemical, and cultural data that describe the 26 study areas in 14 Western States. The data base contains information on 1,264 sites from which water and bottom sediment were collected. It also contains chemical data from 6,903 analyses of surface water, 914 analyses of ground water, 707 analyses of inorganic constituents in bottom sediments, 223 analyses of organochlorine pesticides in bottom sediments, 8,217 analyses of inorganic constituents in biota, and 1,088 analyses for organic constituents in biota. The data base is available to the public and can be obtained at the NIWQP homepage http://www.usbr.gov/niwqp as dBase III tables for personal-computer systems or as American Standard Code for Information Exchange structured query language (SQL) command and data files for SQL data bases.

Simultaneous introduction of various palladium active sites into MOF via one-pot synthesis: Pd@[Cu3-xPdx(BTC)2]n.

PubMed

Zhang, Wenhua; Chen, Zhihao; Al-Naji, Majd; Guo, Penghu; Cwik, Stefan; Halbherr, Olesia; Wang, Yuemin; Muhler, Martin; Wilde, Nicole; Gläser, Roger; Fischer, Roland A

2016-10-14

Simultaneous incorporation of palladium within Pd-Pd and/or Pd-Cu paddlewheels as framework-nodes and Pd nanoparticle (NP) dispersion into MOF have been achieved for the first time via one-pot synthesis. In particular, the framework substitution of Cu(2+) by Pd(2+) as well as the pore loading with PdNPs have been confirmed and characterized by XPS. The obtained solids featuring such multiple Pd-sites show enhanced catalytic activity in the aqueous-phase hydrogenation of p-nitrophenol (PNP) with NaBH4 to p-aminophenol (PAP).

Applying Aspect-Oriented Programming to Intelligent Synthesis

NASA Technical Reports Server (NTRS)

Filman, Robert E.; Norvig, Peter (Technical Monitor)

2000-01-01

I discuss a component-centered, aspect-oriented system, the Object Infrastructure Framework (OIF), NASA's initiative on Intelligent Synthesis Environments (ISE), and the application of OIF to the architecture of ISE.

A Research Synthesis of the Evaluation Capacity Building Literature

ERIC Educational Resources Information Center

Labin, Susan N.; Duffy, Jennifer L.; Meyers, Duncan C.; Wandersman, Abraham; Lesesne, Catherine A.

2012-01-01

The continuously growing demand for program results has produced an increased need for evaluation capacity building (ECB). The "Integrative ECB Model" was developed to integrate concepts from existing ECB theory literature and to structure a synthesis of the empirical ECB literature. The study used a broad-based research synthesis method with…

Fischer-Tropsch Cobalt Catalyst Improvements with the Presence of TiO2, La2O3, and ZrO2 on an Alumina Support

NASA Technical Reports Server (NTRS)

Klettlinger, Jennifer Lindsey Suder

2012-01-01

The objective of this study was to evaluate the effect of titanium oxide, lanthanum oxide, and zirconium oxide on alumina supported cobalt catalysts. The hypothesis was that the presence of lanthanum oxide, titanium oxide, and zirconium oxide would reduce the interaction between cobalt and the alumina support. This was of interest because an optimized weakened interaction could lead to the most advantageous cobalt dispersion, particle size, and reducibility. The presence of these oxides on the support were investigated using a wide range of characterization techniques such as SEM, nitrogen adsorption, x-ray diffraction (XRD), temperature programmed reduction (TPR), temperature programmed reduction after reduction (TPR-AR), and hydrogen chemisorptions/pulse reoxidation. Results indicated that both La2O3 and TiO2 doped supports facilitated the reduction of cobalt oxide species in reference to pure alumina supported cobalt catalysts, however further investigation is needed to determine the effect of ZrO2 on the reduction profile. Results showed an increased corrected cluster size for all three doped supported catalysts in comparison to their reference catalysts. The increase in reduction and an increase in the cluster size led to the conclusion that the support-metal interaction weakened by the addition of TiO2 and La2O3. It is also likely that the interaction decreased upon presence of ZrO2 on the alumina, but further research is necessary. Preliminary results have indicated that the alumina-supported catalysts with titanium oxide and lanthanum oxide present are of interest because of the weakened cobalt support interaction. These catalysts showed an increased extent of reduction, therefore more metallic cobalt is present on the support. However, whether or not there is more cobalt available to participate in the Fischer-Tropsch synthesis reaction (cobalt surface atoms) depends also on the cluster size. On one hand, increasing cluster size alone tends to decrease the active site density; on the other hand, by increasing the size of the cobalt clusters, there is less likelihood of forming oxidized cobalt complexes (cobalt aluminate) during Fischer-Tropsch synthesis. Thus, from the standpoint of stability, improving the extent of reduction while increasing the particle size slightly may be beneficial for maintaining the sites, even if there is a slight decrease in overall initial active site density.

Mitochondrial transcription terminator family members mTTF and mTerf5 have opposing roles in coordination of mtDNA synthesis.

PubMed

Jõers, Priit; Lewis, Samantha C; Fukuoh, Atsushi; Parhiala, Mikael; Ellilä, Simo; Holt, Ian J; Jacobs, Howard T

2013-01-01

All genomes require a system for avoidance or handling of collisions between the machineries of DNA replication and transcription. We have investigated the roles in this process of the mTERF (mitochondrial transcription termination factor) family members mTTF and mTerf5 in Drosophila melanogaster. The two mTTF binding sites in Drosophila mtDNA, which also bind mTerf5, were found to coincide with major sites of replication pausing. RNAi-mediated knockdown of either factor resulted in mtDNA depletion and developmental arrest. mTTF knockdown decreased site-specific replication pausing, but led to an increase in replication stalling and fork regression in broad zones around each mTTF binding site. Lagging-strand DNA synthesis was impaired, with extended RNA/DNA hybrid segments seen in replication intermediates. This was accompanied by the accumulation of recombination intermediates and nicked/broken mtDNA species. Conversely, mTerf5 knockdown led to enhanced replication pausing at mTTF binding sites, a decrease in fragile replication intermediates containing single-stranded segments, and the disappearance of species containing segments of RNA/DNA hybrid. These findings indicate an essential and previously undescribed role for proteins of the mTERF family in the integration of transcription and DNA replication, preventing unregulated collisions and facilitating productive interactions between the two machineries that are inferred to be essential for completion of lagging-strand DNA synthesis.

Mitochondrial Transcription Terminator Family Members mTTF and mTerf5 Have Opposing Roles in Coordination of mtDNA Synthesis

PubMed Central

Jõers, Priit; Lewis, Samantha C.; Fukuoh, Atsushi; Parhiala, Mikael; Ellilä, Simo; Holt, Ian J.; Jacobs, Howard T.

2013-01-01

All genomes require a system for avoidance or handling of collisions between the machineries of DNA replication and transcription. We have investigated the roles in this process of the mTERF (mitochondrial transcription termination factor) family members mTTF and mTerf5 in Drosophila melanogaster. The two mTTF binding sites in Drosophila mtDNA, which also bind mTerf5, were found to coincide with major sites of replication pausing. RNAi-mediated knockdown of either factor resulted in mtDNA depletion and developmental arrest. mTTF knockdown decreased site-specific replication pausing, but led to an increase in replication stalling and fork regression in broad zones around each mTTF binding site. Lagging-strand DNA synthesis was impaired, with extended RNA/DNA hybrid segments seen in replication intermediates. This was accompanied by the accumulation of recombination intermediates and nicked/broken mtDNA species. Conversely, mTerf5 knockdown led to enhanced replication pausing at mTTF binding sites, a decrease in fragile replication intermediates containing single-stranded segments, and the disappearance of species containing segments of RNA/DNA hybrid. These findings indicate an essential and previously undescribed role for proteins of the mTERF family in the integration of transcription and DNA replication, preventing unregulated collisions and facilitating productive interactions between the two machineries that are inferred to be essential for completion of lagging-strand DNA synthesis. PMID:24068965

Synthesis of Large and Few Atomic Layers of Hexagonal Boron Nitride on Melted Copper

PubMed Central

Khan, Majharul Haque; Huang, Zhenguo; Xiao, Feng; Casillas, Gilberto; Chen, Zhixin; Molino, Paul J.; Liu, Hua Kun

2015-01-01

Hexagonal boron nitride nanosheets (h-BNNS) have been proposed as an ideal substrate for graphene-based electronic devices, but the synthesis of large and homogeneous h-BNNS is still challenging. In this contribution, we report a facile synthesis of few-layer h-BNNS on melted copper via an atmospheric pressure chemical vapor deposition process. Comparative studies confirm the advantage of using melted copper over solid copper as a catalyst substrate. The former leads to the formation of single crystalline h-BNNS that is several microns in size and mostly in mono- and bi-layer forms, in contrast to the polycrystalline and mixed multiple layers (1–10) yielded by the latter. This difference is likely to be due to the significantly reduced and uniformly distributed nucleation sites on the smooth melted surface, in contrast to the large amounts of unevenly distributed nucleation sites that are associated with grain boundaries and other defects on the solid surface. This synthesis is expected to contribute to the development of large-scale manufacturing of h-BNNS/graphene-based electronics. PMID:25582557

Cell-free protein synthesis from genomically recoded bacteria enables multisite incorporation of noncanonical amino acids.

PubMed

Martin, Rey W; Des Soye, Benjamin J; Kwon, Yong-Chan; Kay, Jennifer; Davis, Roderick G; Thomas, Paul M; Majewska, Natalia I; Chen, Cindy X; Marcum, Ryan D; Weiss, Mary Grace; Stoddart, Ashleigh E; Amiram, Miriam; Ranji Charna, Arnaz K; Patel, Jaymin R; Isaacs, Farren J; Kelleher, Neil L; Hong, Seok Hoon; Jewett, Michael C

2018-03-23

Cell-free protein synthesis has emerged as a powerful approach for expanding the range of genetically encoded chemistry into proteins. Unfortunately, efforts to site-specifically incorporate multiple non-canonical amino acids into proteins using crude extract-based cell-free systems have been limited by release factor 1 competition. Here we address this limitation by establishing a bacterial cell-free protein synthesis platform based on genomically recoded Escherichia coli lacking release factor 1. This platform was developed by exploiting multiplex genome engineering to enhance extract performance by functionally inactivating negative effectors. Our most productive cell extracts enabled synthesis of 1,780 ± 30 mg/L superfolder green fluorescent protein. Using an optimized platform, we demonstrated the ability to introduce 40 identical p-acetyl-L-phenylalanine residues site specifically into an elastin-like polypeptide with high accuracy of incorporation ( ≥ 98%) and yield (96 ± 3 mg/L). We expect this cell-free platform to facilitate fundamental understanding and enable manufacturing paradigms for proteins with new and diverse chemistries.

Catalytic conversion of syngas to mixed alcohols over Zn-Mn promoted Cu-Fe based catalyst

DOE PAGES

Lu, Yongwu; Yu, Fei; Hu, Jin; ...

2012-04-12

Zn-Mn promoted Cu-Fe based catalyst was synthesized by the co-precipitation method. Mixed alcohols synthesis from syngas was studied in a half-inch tubular reactor system after the catalyst was reduced. Zn-Mn promoted Cu-Fe based catalyst was characterized by SEM-EDS, TEM, XRD, and XPS. The liquid phase products (alcohol phase and hydrocarbon phase) were analyzed by GC-MS and the gas phase products were analyzed by GC. The results showed that Zn-Mn promoted Cu-Fe based catalyst had high catalytic activity and high alcohol selectivity. The maximal CO conversion rate was 72%, and the yield of alcohol and hydrocarbons were also very high. Cumore » (111) was the active site for mixed alcohols synthesis, Fe 2C (101) was the active site for olefin and paraffin synthesis. The reaction mechanism of mixed alcohols synthesis from syngas over Zn-Mn promoted Cu-Fe based catalyst was proposed. Here, Zn-Mn promoted Cu-Fe based catalyst can be regarded as a potential candidate for catalytic conversion of biomass-derived syngas to mixed alcohols.« less

Synthesis of large and few atomic layers of hexagonal boron nitride on melted copper.

PubMed

Khan, Majharul Haque; Huang, Zhenguo; Xiao, Feng; Casillas, Gilberto; Chen, Zhixin; Molino, Paul J; Liu, Hua Kun

2015-01-13

Hexagonal boron nitride nanosheets (h-BNNS) have been proposed as an ideal substrate for graphene-based electronic devices, but the synthesis of large and homogeneous h-BNNS is still challenging. In this contribution, we report a facile synthesis of few-layer h-BNNS on melted copper via an atmospheric pressure chemical vapor deposition process. Comparative studies confirm the advantage of using melted copper over solid copper as a catalyst substrate. The former leads to the formation of single crystalline h-BNNS that is several microns in size and mostly in mono- and bi-layer forms, in contrast to the polycrystalline and mixed multiple layers (1-10) yielded by the latter. This difference is likely to be due to the significantly reduced and uniformly distributed nucleation sites on the smooth melted surface, in contrast to the large amounts of unevenly distributed nucleation sites that are associated with grain boundaries and other defects on the solid surface. This synthesis is expected to contribute to the development of large-scale manufacturing of h-BNNS/graphene-based electronics.

NUCLEAR ENVELOPE-ASSOCIATED RESUMPTION OF RNA SYNTHESIS IN LATE MITOSIS OF HELA CELLS

PubMed Central

Simmons, T.; Heywood, P.; Hodge, L.

1973-01-01

The restitution of RNA synthesis in cultures progressing from metaphase into interphase (G1) has been investigated in synchronized HeLa S3 cells by using inhibitors of macro-molecular synthesis and the technique of electron microscope autoradiography. The rate of incorporation of radioactive uridine into RNA approached interphase levels in the absence of renewed protein synthesis. In contrast, maintenance of this rate in G1 was dependent upon renewed protein synthesis. Restoration of synthesis of heterogeneous nuclear RNA occurred under conditions that inhibited production of ribosomal precursor RNA. In autoradiographs of individual cells exposed to radioactive uridine, silver grains were first detected after nuclear envelope reformation at the periphery of the chromosome mass but before chromosomal decondensation. These data are consistent with the following interpretation. Multiple RNA polymerase activities persist through mitosis and are involved in the initiation of RNA synthesis in early telophase at sites on the nuclear envelope. PMID:4752403

Alabama NASA EPSCoR Preparation Grant Program: Grant No. NCC5-391

NASA Technical Reports Server (NTRS)

Gregory, John C.

2003-01-01

The funded research projects under the Experimental Program to Stimulate Cooperative Research (EPSCoR) grant program and the student fellowship awards are summarized in this report. The projects include: 1) Crystallization of Dehydratase/DcoH: A Target in Lung Disease; 2) Measuring Velocity Profiles in Liquid Metals using an Ultrasonic Doppler Velocimeter; 3) Synthesis, Structure, and Properties of New Thermoelectric Materials; 4) Computational Determination of Structures and Reactivity of Phenol-Formaldehyde Resins; 5) Synthesis of Microbial Polyesters in the NASA Bioreactor; 6) Visualization of Flow-Fields in Magnetocombustion; 7) Synthesis of Fluorescent Saccharide Derivatives. The student fellowship awards include: 1) Distributed Fusion of Satellite Images; 2) Study of the Relationship between Urban Development, Local Climate, and Water Quality for the Atlanta, Georgia Metrop; 3) Computer Simulation of the Effectiveness of a Spring-Loaded Exercise Device.

Impact of hydrological variations on modeling of peatland CO2 fluxes: Results from the North American Carbon Program site synthesis

NASA Astrophysics Data System (ADS)

Sulman, Benjamin N.; Desai, Ankur R.; Schroeder, Nicole M.; Ricciuto, Dan; Barr, Alan; Richardson, Andrew D.; Flanagan, Lawrence B.; Lafleur, Peter M.; Tian, Hanqin; Chen, Guangsheng; Grant, Robert F.; Poulter, Benjamin; Verbeeck, Hans; Ciais, Philippe; Ringeval, Bruno; Baker, Ian T.; Schaefer, Kevin; Luo, Yiqi; Weng, Ensheng

2012-03-01

Northern peatlands are likely to be important in future carbon cycle-climate feedbacks due to their large carbon pools and vulnerability to hydrological change. Use of non-peatland-specific models could lead to bias in modeling studies of peatland-rich regions. Here, seven ecosystem models were used to simulate CO2fluxes at three wetland sites in Canada and the northern United States, including two nutrient-rich fens and one nutrient-poor,sphagnum-dominated bog, over periods between 1999 and 2007. Models consistently overestimated mean annual gross ecosystem production (GEP) and ecosystem respiration (ER) at all three sites. Monthly flux residuals (simulated - observed) were correlated with measured water table for GEP and ER at the two fen sites, but were not consistently correlated with water table at the bog site. Models that inhibited soil respiration under saturated conditions had less mean bias than models that did not. Modeled diurnal cycles agreed well with eddy covariance measurements at fen sites, but overestimated fluxes at the bog site. Eddy covariance GEP and ER at fens were higher during dry periods than during wet periods, while models predicted either the opposite relationship or no significant difference. At the bog site, eddy covariance GEP did not depend on water table, while simulated GEP was higher during wet periods. Carbon cycle modeling in peatland-rich regions could be improved by incorporating wetland-specific hydrology and by inhibiting GEP and ER under saturated conditions. Bogs and fens likely require distinct plant and soil parameterizations in ecosystem models due to differences in nutrients, peat properties, and plant communities.

Dithiolato-bridged nickel-iron complexes as models for the active site of [NiFe]-hydrogenases.

PubMed

Song, Li-Cheng; Yang, Xi-Yue; Cao, Meng; Gao, Xiu-Yun; Liu, Bei-Bei; Zhu, Liang; Jiang, Feng

2017-03-30

The structural and functional modeling of the active site of [NiFe]-hydrogenases has been proved to be challenging to a great extent. Herein, we report the synthesis, structures, and some properties of the NiFe-based dicarbonyl, terminal hydride, and μ-hydroxo models for the active site of [NiFe]-hydrogenases.

Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency

PubMed Central

Barna, Maria; Pusic, Aya; Zollo, Ornella; Costa, Maria; Kondrashov, Nadya; Rego, Eduardo; Rao, Pulivarthi H; Ruggero, Davide

2008-01-01

The Myc oncogene regulates the expression of multiple components of the protein synthetic machinery, including ribosomal proteins, initiation factors of translation, Pol III, and rDNA1,2. An outstanding question is whether and how increasing the cellular protein synthesis capacity can affect the multi-step process leading to cancer. We utilized ribosomal protein heterozygote mice as a genetic tool to restore increased protein synthesis in Eμ–Myc/+ transgenic mice to normal levels and show that in this context Myc's oncogenic potential is suppressed. Our findings demonstrate that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc. In addition, when protein synthesis is restored to normal levels, Myc overexpressing precancerous cells are more efficiently eliminated by programmed cell death. Our findings reveal a novel paradigm that links increases in general protein synthesis rates downstream of an oncogenic signal to a specific molecular impairment in the modality of translation initiation employed to regulate the expression of selective mRNAs. We show that an aberrant increase in cap-dependent translation downstream Myc hyperactivation specifically impairs the translational switch to internal ribosomal entry site (IRES)-dependent translation required for accurate mitotic progression. Failure of this translational switch results in reduced mitotic-specific expression of the endogenous IRES-dependent form of Cdk11 (p58-PITSLRE)3-5, which leads to cytokinesis defects and is associated with increased centrosome numbers and genome instability in Eμ–Myc/+ mice. When accurate translational control is re-established in Eμ–Myc/+ mice, genome instability is suppressed. Our findings reveal how perturbations in translational control provide a highly specific outcome on gene expression, genome stability, and cancer initiation that have important implications for understanding the molecular mechanism of cancer formation at the post-genomic level. PMID:19011615

Lipid synthesis under hydrothermal conditions by Fischer-Tropsch-type reactions

NASA Technical Reports Server (NTRS)

McCollom, T. M.; Ritter, G.; Simoneit, B. R.

1999-01-01

Ever since their discovery in the late 1970's, mid-ocean-ridge hydrothermal systems have received a great deal of attention as a possible site for the origin of life on Earth (and environments analogous to mid-ocean-ridge hydrothermal systems are postulated to have been sites where life could have originated or Mars and elsewhere as well). Because no modern-day terrestrial hydrothermal systems are free from the influence of organic compounds derived from biologic processes, laboratory experiments provide the best opportunity for confirmation of the potential for organic synthesis in hydrothermal systems. Here we report on the formation of lipid compounds during Fischer-Tropsch-type synthesis from aqueous solutions of formic acid or oxalic acid. Optimum synthesis occurs in stainless steel vessels by heating at 175 degrees C for 2-3 days and produces lipid compounds ranging from C2 to > C35 which consist of n-alkanols, n-alkanoic acids, n-alkenes, n-alkanes and alkanones. The precursor carbon sources used are either formic acid or oxalic acid, which disproportionate to H2, CO2 and probably CO. Both carbon sources yield the same lipid classes with essentially the same ranges of compounds. The synthesis reactions were confirmed by using 13C labeled precursor acids.

Timing matters: error-prone gap filling and translesion synthesis in immunoglobulin gene hypermutation

PubMed Central

Sale, Julian E.; Batters, Christopher; Edmunds, Charlotte E.; Phillips, Lara G.; Simpson, Laura J.; Szüts, Dávid

2008-01-01

By temporarily deferring the repair of DNA lesions encountered during replication, the bypass of DNA damage is critical to the ability of cells to withstand genomic insults. Damage bypass can be achieved either by recombinational mechanisms that are generally accurate or by a process called translesion synthesis. Translesion synthesis involves replacing the stalled replicative polymerase with one of a number of specialized DNA polymerases whose active sites are able to tolerate a distorted or damaged DNA template. While this property allows the translesion polymerases to synthesize across damaged bases, it does so with the trade-off of an increased mutation rate. The deployment of these enzymes must therefore be carefully regulated. In addition to their important role in general DNA damage tolerance and mutagenesis, the translesion polymerases play a crucial role in converting the products of activation induced deaminase-catalysed cytidine deamination to mutations during immunoglobulin gene somatic hypermutation. In this paper, we specifically consider the control of translesion synthesis in the context of the timing of lesion bypass relative to replication fork progression and arrest at sites of DNA damage. We then examine how recent observations concerning the control of translesion synthesis might help refine our view of the mechanisms of immunoglobulin gene somatic hypermutation. PMID:19008194

Lipid Synthesis Under Hydrothermal Conditions by Fischer- Tropsch-Type Reactions

NASA Astrophysics Data System (ADS)

McCollom, Thomas M.; Ritter, Gilles; Simoneit, Bernd R. T.

1999-03-01

Ever since their discovery in the late 1970's, mid-ocean-ridge hydrothermal systems have received a great deal of attention as a possible site for the origin of life on Earth (and environments analogous to mid-ocean-ridge hydrothermal systems are postulated to have been sites where life could have originated on Mars and elsewhere as well). Because no modern-day terrestrial hydrothermal systems are free from the influence of organic compounds derived from biologic processes, laboratory experiments provide the best opportunity for confirmation of the potential for organic synthesis in hydrothermal systems. Here we report on the formation of lipid compounds during Fischer-Tropsch-type synthesis from aqueous solutions of formic acid or oxalic acid. Optimum synthesis occurs in stainless steel vessels by heating at 175 °C for 2-3 days and produces lipid compounds ranging from C2 to >C35 which consist of n-alkanols, n- alkanoic acids, n-alkenes, n-alkanes and alkanones. The precursor carbon sources used are either formic acid or oxalic acid, which disproportionate to H2, CO2 and probably CO. Both carbon sources yield the same lipid classes with essentially the same ranges of compounds. The synthesis reactions were confirmed by using 13C labeled precursor acids.

Lipid synthesis under hydrothermal conditions by Fischer-Tropsch-type reactions.

PubMed

McCollom, T M; Ritter, G; Simoneit, B R

1999-03-01

Ever since their discovery in the late 1970's, mid-ocean-ridge hydrothermal systems have received a great deal of attention as a possible site for the origin of life on Earth (and environments analogous to mid-ocean-ridge hydrothermal systems are postulated to have been sites where life could have originated or Mars and elsewhere as well). Because no modern-day terrestrial hydrothermal systems are free from the influence of organic compounds derived from biologic processes, laboratory experiments provide the best opportunity for confirmation of the potential for organic synthesis in hydrothermal systems. Here we report on the formation of lipid compounds during Fischer-Tropsch-type synthesis from aqueous solutions of formic acid or oxalic acid. Optimum synthesis occurs in stainless steel vessels by heating at 175 degrees C for 2-3 days and produces lipid compounds ranging from C2 to > C35 which consist of n-alkanols, n-alkanoic acids, n-alkenes, n-alkanes and alkanones. The precursor carbon sources used are either formic acid or oxalic acid, which disproportionate to H2, CO2 and probably CO. Both carbon sources yield the same lipid classes with essentially the same ranges of compounds. The synthesis reactions were confirmed by using 13C labeled precursor acids.

Amino acid substrates impose polyamine, eIF5A, or hypusine requirement for peptide synthesis.

PubMed

Shin, Byung-Sik; Katoh, Takayuki; Gutierrez, Erik; Kim, Joo-Ran; Suga, Hiroaki; Dever, Thomas E

2017-08-21

Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis. Though most proline analogs require eIF5A for efficient peptide synthesis, azetidine-2-caboxylic acid, a more flexible four-membered ring derivative of proline, shows relaxed eIF5A dependency, indicating that the structural rigidity of proline might contribute to the requirement for eIF5A. Finally, we examine the interplay between eIF5A and polyamines in promoting translation elongation. We show that eIF5A can obviate the polyamine requirement for general translation elongation, and that this activity is independent of the conserved hypusine modification on eIF5A. Thus, we propose that the body of eIF5A functionally substitutes for polyamines to promote general protein synthesis and that the hypusine modification on eIF5A is critically important for poor substrates like proline. Published by Oxford University Press on behalf of Nucleic Acids Research 2017.

The cholesterol, fatty acid and triglyceride synthesis pathways regulated by site 1 protease (S1P) are required for efficient replication of severe fever with thrombocytopenia syndrome virus.

PubMed

Urata, Shuzo; Uno, Yukiko; Kurosaki, Yohei; Yasuda, Jiro

2018-06-12

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively. These results enhance our understanding of the SFTSV replication mechanism and may contribute to the development of novel therapies for SFTSV infection. Copyright © 2018. Published by Elsevier Inc.

34 CFR 668.10 - Direct assessment programs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... such as creativity, analysis or synthesis associated with the subject matter of the program. Examples... measurement apply to direct assessment programs. Because a direct assessment program does not utilize credit... program includes regularly scheduled learning sessions, faculty-guided independent study, consultations...

USEPA'S SITE PROGRAM IMPACT ON THE DEVELOPMENT AND USE OF INNOVATIVE HAZARDOUS WASTE TREATMENT

EPA Science Inventory

The USEPA's SITE Program was created to meet the increased demand for innovative technologies for hazardous waste treatment. The primary mission of the SITe Program is to expedite the cleanup of sites on the NPL. The SITE Program has two components: The Demonstration Program and ...

Computer program to assess impact of fatigue and fracture criteria on weight and cost of transport aircraft

NASA Technical Reports Server (NTRS)

Tanner, C. J.; Kruse, G. S.; Oman, B. H.

1975-01-01

A preliminary design analysis tool for rapidly performing trade-off studies involving fatigue, fracture, static strength, weight, and cost is presented. Analysis subprograms were developed for fatigue life, crack growth life, and residual strength; and linked to a structural synthesis module which in turn was integrated into a computer program. The part definition module of a cost and weight analysis program was expanded to be compatible with the upgraded structural synthesis capability. The resultant vehicle design and evaluation program is named VDEP-2. It is an accurate and useful tool for estimating purposes at the preliminary design stage of airframe development. A sample case along with an explanation of program applications and input preparation is presented.

Synthesis of Supported Pd 0 Nanoparticles from a Single-Site Pd 2+ Surface Complex by Alkene Reduction

DOE PAGES

Mouat, Aidan R.; Whitford, Cassandra L.; Chen, Bor-Rong; ...

2018-02-02

Here, a surface metal–organic complex, (-AlO x)Pd(acac) (acac = acetylacetonate), is prepared by chemically grafting the precursor Pd(acac) 2 onto γ-Al 2O 3 in toluene at 25 °C. The resulting surface complex is characterized by inductively coupled plasma atomic emission spectroscopy (ICP-AES), X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and dynamic nuclear polarization surface-enhanced solid-state nuclear magnetic resonance spectroscopy (DNP SENS). This surface complex is a precursor in the direct synthesis of size-controlled Pd nanoparticles under mild reductive conditions and in the absence of additional stabilizers or pretreatments. Indeed, upon exposure to gaseous ethylene or liquid 1-octene at 25more » °C, the Pd 2+ species is reduced to form Pd 0 nanoparticles with a mean diameter of 4.3 ± 0.6 nm, as determined by scanning transmission electron microscopy (STEM). These nanoparticles are catalytically relevant using the aerobic 1-phenylethanol oxidation as a probe reaction, with rates comparable to a conventional Pd/Al 2O 3 catalyst but without an induction period. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and temperature-programmed reaction mass spectrometry (TPR-MS) reveal that the surface complex reduction with ethylene coproduces H 2, acetylene, and 1,3-butadiene. This process reasonably proceeds via an olefin activation/coordination/insertion pathway, followed by β-hydride elimination to generate free Pd 0. Lastly, the well-defined nature of the single-site supported Pd 2+ precursor provides direct mechanistic insights into this unusual and likely general reductive process.« less

Synthesis of Supported Pd 0 Nanoparticles from a Single-Site Pd 2+ Surface Complex by Alkene Reduction

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

Mouat, Aidan R.; Whitford, Cassandra L.; Chen, Bor-Rong

Here, a surface metal–organic complex, (-AlO x)Pd(acac) (acac = acetylacetonate), is prepared by chemically grafting the precursor Pd(acac) 2 onto γ-Al 2O 3 in toluene at 25 °C. The resulting surface complex is characterized by inductively coupled plasma atomic emission spectroscopy (ICP-AES), X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and dynamic nuclear polarization surface-enhanced solid-state nuclear magnetic resonance spectroscopy (DNP SENS). This surface complex is a precursor in the direct synthesis of size-controlled Pd nanoparticles under mild reductive conditions and in the absence of additional stabilizers or pretreatments. Indeed, upon exposure to gaseous ethylene or liquid 1-octene at 25more » °C, the Pd 2+ species is reduced to form Pd 0 nanoparticles with a mean diameter of 4.3 ± 0.6 nm, as determined by scanning transmission electron microscopy (STEM). These nanoparticles are catalytically relevant using the aerobic 1-phenylethanol oxidation as a probe reaction, with rates comparable to a conventional Pd/Al 2O 3 catalyst but without an induction period. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and temperature-programmed reaction mass spectrometry (TPR-MS) reveal that the surface complex reduction with ethylene coproduces H 2, acetylene, and 1,3-butadiene. This process reasonably proceeds via an olefin activation/coordination/insertion pathway, followed by β-hydride elimination to generate free Pd 0. Lastly, the well-defined nature of the single-site supported Pd 2+ precursor provides direct mechanistic insights into this unusual and likely general reductive process.« less

Non-nucleoside building blocks for copper-assisted and copper-free click chemistry for the efficient synthesis of RNA conjugates.

PubMed

Jayaprakash, K N; Peng, Chang Geng; Butler, David; Varghese, Jos P; Maier, Martin A; Rajeev, Kallanthottathil G; Manoharan, Muthiah

2010-12-03

Novel non-nucleoside alkyne monomers compatible with oligonucleotide synthesis were designed, synthesized, and efficiently incorporated into RNA and RNA analogues during solid-phase synthesis. These modifications allowed site-specific conjugation of ligands to the RNA oligonucleotides through copper-assisted (CuAAC) and copper-free strain-promoted azide-alkyne cycloaddition (SPAAC) reactions. The SPAAC click reactions of cyclooctyne-oligonucleotides with various classes of azido-functionalized ligands in solution phase and on solid phase were efficient and quantitative and occurred under mild reaction conditions. The SPAAC reaction provides a method for the synthesis of oligonucleotide-ligand conjugates uncontaminated with copper ions.

Nitric oxide synthase inhibition attenuates cutaneous vasodilation during the post-menopausal hot flash

PubMed Central

Hubing, Kimberly A.; Wingo, Jonathan E.; Brothers, R. Matthew; Coso, Juan Del; Low, David A.; Crandall, Craig G.

2010-01-01

Objective The purpose of this study was to test the hypothesis that local inhibition of nitric oxide and prostaglandin synthesis attenuates cutaneous vasodilator responses during post-menopausal hot flashes. Methods Four microdialysis membranes were inserted into forearm skin (dorsal surface) of 8 post-menopausal women (mean ± SD, 51±7 y). Ringers solution (control), 10mM Ketorolac (Keto) to inhibit prostaglandin synthesis, 10mM NG-L-arginine methyl ester (L-NAME) to inhibit nitric oxide synthase, and a combination of 10mM Keto + 10mM L-NAME were each infused at the separate sites. Skin blood flow at each site was indexed using laser-Doppler flowmetry. Cutaneous vascular conductance (CVC) was calculated as laser-Doppler flux/mean arterial blood pressure and was expressed as a percentage of the maximal calculated CVC (CVCmax) obtained following infusion of 50mM sodium nitropruside at all sites at the end of the study. Data from 13 hot flashes were analyzed. Results At the control site, the mean ± SD peak increase in CVC was 15.5±6% CVCmax units. This value was not different relative to the peak increase in CVC at the Keto site (13.0±5 % CVCmax units, P = 0.09). However, the peak increase in CVC during the flash was attenuated at the L-NAME and L-NAME + Keto sites (7.4±4 % CVCmax units and 8.7±7 % CVCmax units, respectively) relative to both the control and the Keto sites (P<0.05 for both comparisons). There were no significant differences in the peak increases in sweat rate between any of the sites (P = 0.24). Conclusions These data demonstrate that cutaneous vasodilation during a hot flash has a nitric oxide component. Increases in CVC despite the inhibition of prostaglandin synthesis suggest prostaglandins do not contribute to cutaneous vasodilation during a hot flash. PMID:20505548

Synthesis, characterization, and catalytic activity of Rh-based lanthanum zirconate pyrochlores for higher alcohol synthesis

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

Abdelsayed, Victor; Shekhawat, Dushyant; Poston, James A.

2013-05-01

Two lanthanum zirconate pyrochlores (La{sub 2}Zr{sub 2}O{sub 7}; LZ) were prepared by Pechini method and tested for higher alcohols selectivity. In one, Rh was substituted into the pyrochlore lattice (LRZ, 1.7 wt%) while for the second, Rh was supported on an unsubstituted La{sub 2}Zr{sub 2}O{sub 7} (R/LZ, 1.8 wt%). X-ray photoelectron spectroscopy (XPS) and temperature programmed reduction (TPR) results show that the surface reducibility depends on whether the Rh is in (or supported on) the LZ pyrochlore. Rhodium in the LRZ is more reducible than rhodium supported on the R/LZ pyrochlore, likely due to the presence of a perovskite phasemore » (LaRhO{sub 3}; identified by XRD), in which rhodium is more reducible. The formation of the perovskite accompanies that of the pyrochlore. CO hydrogenation results show higher ethanol selectivity for R/LZ than LRZ, possibly due to the strong interaction between Rh and LZ on the R/LZ, forming atomically close Rh{sup +}/Rh{sup 0} sites, which have been suggested to favor ethanol production.« less

Discovery of novel aldose reductase inhibitors using a protein structure-based approach: 3D-database search followed by design and synthesis.

PubMed

Iwata, Y; Arisawa, M; Hamada, R; Kita, Y; Mizutani, M Y; Tomioka, N; Itai, A; Miyamoto, S

2001-05-24

Aldose reductase (AR) has been implicated in the etiology of diabetic complications. Due to the limited number of currently available drugs for the treatment of diabetic complications, we have carried out structure-based drug design and synthesis in an attempt to find new types of AR inhibitors. With the ADAM&EVE program, a three-dimensional database (ACD3D) was searched using the ligand binding site of the AR crystal structure. Out of 179 compounds selected through this search followed by visual inspection, 36 compounds were purchased and subjected to a biological assay. Ten compounds showed more than 40% inhibition of AR at a 15 microg/mL concentration. In a subsequent lead optimization, a series of analogues of the most active compound were synthesized based on the docking mode derived by ADAM&EVE. Many of these congeners exhibited higher activities compared to the mother compound. Indeed, the most potent, synthesized compound showed an approximately 20-fold increase in inhibitory activity (IC(50) = 0.21 vs 4.3 microM). Furthermore, a hydrophobic subsite was newly inferred, which would be useful for the design of inhibitors with improved affinity for AR.

Linear systems analysis program, L224(QR). Volume 2: Supplemental system design and maintenance document

NASA Technical Reports Server (NTRS)

Heidergott, K. W.

1979-01-01

The computer program known as QR is described. Classical control systems analysis and synthesis (root locus, time response, and frequency response) can be performed using this program. Programming details of the QR program are presented.

A molecular model for the active site of S-adenosyl- l-homocysteine hydrolase

NASA Astrophysics Data System (ADS)

Yeh, Jerry C.; Borchardt, Ronald T.; Vedani, Angelo

1991-06-01

S-adenosyl- l-homocysteine hydrolase (AdoHcy hydrolase, EC 3.3.1.1.), a specific target for antiviral drug design, catalyzes the hydrolysis of AdoHcy to adenosine (Ado) and homocysteine (Hcy) as well as the synthesis of AdoHcy from Ado and Hcy. The enzyme isolated from different sources has been shown to contain tightly bound NAD+. Based on the 2.0 Å-resolution X-ray crystal structure of dogfish lactate dehydrogenase (LDH), which is functionally homologous to AdoHcy hydrolase, and the primary sequence of rat liver AdoHcy hydrolase, we have derived a molecular model of an extended active site for AdoHcy hydrolase. The computational mutation was performed using the software MUTAR (Yeh et al., University of Kansas, Lawrence), followed by molecular mechanics optimizations using the programs AMBER (Singh et al., University of California, San Francisco) and YETI (Vedani, University of Kansas). Solvation of the model structure was achieved by use of the program SOLVGEN (Jacober, University of Kansas); 56 water molecules were explicitly included in all refinements. Some of these may be involved in the catalytic reaction. We also studied a model of the complex of AdoHcy hydrolase with NAD+, as well as the ternary complexes of the redox reaction catalyzed by AdoHcy hydrolase and has been used to differentiate the relative binding strength of inhibitors.

Transport of phosphatidylserine from the endoplasmic reticulum to the site of phosphatidylserine decarboxylase2 in yeast.

PubMed

Kannan, Muthukumar; Riekhof, Wayne R; Voelker, Dennis R

2015-02-01

Over the past two decades, most of the genes specifying lipid synthesis and metabolism in yeast have been identified and characterized. Several of these biosynthetic genes and their encoded enzymes have provided valuable tools for the genetic and biochemical dissection of interorganelle lipid transport processes in yeast. One such pathway involves the synthesis of phosphatidylserine (PtdSer) in the endoplasmic reticulum (ER), and its non-vesicular transport to the site of phosphatidylserine decarboxylase2 (Psd2p) in membranes of the Golgi and endosomal sorting system. In this review, we summarize the identification and characterization of the yeast phosphatidylserine decarboxylases, and examine their role in studies of the transport-dependent pathways of de novo synthesis of phosphatidylethanolamine (PtdEtn). The emerging picture of the Psd2p-specific transport pathway is one in which the enzyme and its non-catalytic N-terminal domains act as a hub to nucleate the assembly of a multiprotein complex, which facilitates PtdSer transport at membrane contact sites between the ER and Golgi/endosome membranes. After transport to the catalytic site of Psd2p, PtdSer is decarboxylated to form PtdEtn, which is disseminated throughout the cell to support the structural and functional needs of multiple membranes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synthesis of Zn-MOF incorporating titanium-hydrides as active sites binding H{sub 2} molecules

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

Kim, Jongsik, E-mail: jkim40@nd.edu; Ok Kim, Dong; Wook Kim, Dong

2015-10-15

This paper describes the synthetic effort for a Zn-MOF imparting Ti-H as a preferential binding site potentially capturing H{sub 2} molecules via Kubas-type interaction. The formation mechanism of Ti-H innate to the final material was potentially demonstrated to follow a radical dissociation rather than a β-hydrogen elimination and a C-H reductive elimination. - Graphical abstract: This study details the synthesis and the formation mechanism of Zn-MOF adsorbent site-isolating TiH{sub 3} that can potentially capture H{sub 2} molecules via Kubas-binding mechanism. - Highlights: • OH-functionalized Zn-MOF was employed as a reactive template to site-isolate TiH{sub 3}. • This MOF was post-syntheticallymore » modified using a tetracyclohexyl titanium (IV). • This intermediate was hydrogenolyzed to change ligand from cyclohexyl to hydride. • Formation mechanism of TiH{sub 3} was investigated via two control GC–MS experiments. • Final Zn-MOF potentially site-isolating TiH{sub 3} species was used as a H{sub 2} adsorbent.« less

Synthesis and anticonvulsant activities of N-benzyl (2R)-2-acetamido-3-oxysubstituted propionamide derivatives

PubMed Central

Morieux, Pierre; Stables, James P.; Kohn, Harold

2009-01-01

Lacosamide has been submitted for regulatory approval in the United States and Europe for the treatment of epilepsy. Previous synthetic methods did not permit the elaboration of the structure–activity relationship (SAR) for the 3-oxy site in lacosamide. We report an expedient five-step stereospecific synthesis for N-benzyl (2R)-2-acetamido-3-oxysubstituted propionamide analogs beginning with d-serine methyl ester. The procedure incorporated alkyl (e.g. methyl, primary, secondary, and tertiary) and aryl groups at this position. The SAR for the 3-oxy site showed maximal activity in animal seizure models for small 3-alkoxy substituents. PMID:18789868

The effect of CNTs on structures and catalytic properties of AuPd clusters for H2O2 synthesis.

PubMed

Yang, Hua-feng; Xie, Peng-yang; Yu, Hui-you; Li, Xiao-nian; Wang, Jian-guo

2012-12-28

The structures and catalytic properties of AuPd clusters supported on carbon nanotubes (CNTs) for H(2)O(2) synthesis have been investigated by means of density functional theory calculations. Firstly, the structures of AuPd clusters are strongly influenced by CNTs, in which the bottom layers are mainly composed of Pd and the top layers are a mix of Au and Pd due to the stronger binding of Pd than Au on CNTs. Especially, it is found that O(2) adsorption on the Pd/CNTs interfacial sites is much weaker than that on the only Pd sites, which is in contrast to transition metal oxide (for example TiO(2), Al(2)O(3), CeO(2)) supported metal clusters. Furthermore, Pd ensembles on the interfacial sites have far superior catalytic properties for H(2)O(2) formation than those away from CNT supports due to the changes in electronic structures caused by the CNTs. Therefore, our study provides a physical insight into the enhanced role of carbon supports in H(2)O(2) synthesis over supported AuPd catalysts.

Design of HIV-1 Protease Inhibitors with Amino-bis-tetrahydrofuran Derivatives as P2-Ligands to Enhance Backbone-Binding Interactions. Synthesis, Biological Evaluation, and Protein-Ligand X-ray Studies

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

Ghosh, Arun K.; Martyr, Cuthbert D.; Osswald, Heather L.

Structure-based design, synthesis, and biological evaluation of a series of very potent HIV-1 protease inhibitors are described. In an effort to improve backbone ligand–binding site interactions, we have incorporated basic-amines at the C4 position of the bis-tetrahydrofuran (bis-THF) ring. We speculated that these substituents would make hydrogen bonding interactions in the flap region of HIV-1 protease. Synthesis of these inhibitors was performed diastereoselectively. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 25f, 25i, and 25j were evaluated against a number of highly-PI-resistant HIV-1 strains, and they exhibited improved antiviral activity over darunavir. Two high resolutionmore » X-ray structures of 25f- and 25g-bound HIV-1 protease revealed unique hydrogen bonding interactions with the backbone carbonyl group of Gly48 as well as with the backbone NH of Gly48 in the flap region of the enzyme active site. These ligand–binding site interactions are possibly responsible for their potent activity.« less

Highly Potent HIV-1 Protease Inhibitors with Novel Tricyclic P2-ligands: Design, Synthesis, and Protein-ligand X-Ray Studies

PubMed Central

Ghosh, Arun K.; Parham, Garth L.; Martyr, Cuthbert D.; Nyalapatla, Prasanth R.; Osswald, Heather L.; Agniswamy, Johnson; Wang, Yuan-Fang; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

2013-01-01

The design, synthesis, and biological evaluation of a series of HIV-1 protease inhibitors incorporating stereochemically defined fused tricyclic P2-ligands are described. Various substituent effects were investigated in order to maximize the ligand-binding site interactions in the protease active site. Inhibitors 16a and 16f showed excellent enzyme inhibitory and antiviral activity while incorporation of sulfone functionality resulted in a decrease in potency. Both inhibitors 16a and 16f have maintained activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 16a-bound HIV-1 protease revealed important molecular insights into the ligand-binding site interactions which may account for the inhibitor’s potent antiviral activity and excellent resistance profiles. PMID:23947685

Tectonics and geology of spreading ridge subduction at the Chile Triple Junction: a synthesis of results from Leg 141 of the Ocean Drilling Program

USGS Publications Warehouse

Behrmann, J.H.; Lewis, S.D.; Cande, S.C.

1994-01-01

An active oceanic spreading ridge is being subducted beneath the South American continent at the Chile Triple Junction. This process has played a major part in the evolution of most of the continental margins that border the Pacific Ocean basin. A combination of high resolution swath bathymetric maps, seismic reflection profiles and drillhole and core data from five sites drilled during Ocean Drilling Program (ODP) Leg 141 provide important data that define the tectonic, structural and stratigraphic effects of this modern example of spreading ridge subduction. A change from subduction accretion to subduction erosion occurs along-strike of the South American forearc. This change is prominently expressed by normal faulting, forearc subsidence, oversteepening of topographic slopes and intensive sedimentary mass wasting, overprinted on older signatures of sediment accretion, overthrusting and uplift processes in the forearc. Data from drill sites north of the triple junction (Sites 859-861) show that after an important phase of forearc building in the early to late Pliocene, subduction accretion had ceased in the late Pliocene. Since that time sediment on the downgoing oceanic Nazca plate has been subducted. Site 863 was drilled into the forearc in the immediate vicinity of the triple junction above the subducted spreading ridge axis. Here, thick and intensely folded and faulted trench slope sediments of Pleistocene age are currently involved in the frontal deformation of the forearc. Early faults with thrust and reverse kinematics are overprinted by later normal faults. The Chile Triple Junction is also the site of apparent ophiolite emplacement into the South American forearc. Drilling at Site 862 on the Taitao Ridge revealed an offshore volcanic sequence of Plio-Pleistocene age associated with the Taitao Fracture Zone, adjacent to exposures of the Pliocene-aged Taitao ophiolite onshore. Despite the large-scale loss of material from the forearc at the triple junction, ophiolite emplacement produces a large topographic promontory in the forearc immediately after ridge subduction, and represents the first stage of forearc rebuilding. ?? 1994 Springer-Verlag.

Use of an Improved Matching Algorithm to Select Scaffolds for Enzyme Design Based on a Complex Active Site Model.

PubMed

Huang, Xiaoqiang; Xue, Jing; Lin, Min; Zhu, Yushan

2016-01-01

Active site preorganization helps native enzymes electrostatically stabilize the transition state better than the ground state for their primary substrates and achieve significant rate enhancement. In this report, we hypothesize that a complex active site model for active site preorganization modeling should help to create preorganized active site design and afford higher starting activities towards target reactions. Our matching algorithm ProdaMatch was improved by invoking effective pruning strategies and the native active sites for ten scaffolds in a benchmark test set were reproduced. The root-mean squared deviations between the matched transition states and those in the crystal structures were < 1.0 Å for the ten scaffolds, and the repacking calculation results showed that 91% of the hydrogen bonds within the active sites are recovered, indicating that the active sites can be preorganized based on the predicted positions of transition states. The application of the complex active site model for de novo enzyme design was evaluated by scaffold selection using a classic catalytic triad motif for the hydrolysis of p-nitrophenyl acetate. Eighty scaffolds were identified from a scaffold library with 1,491 proteins and four scaffolds were native esterase. Furthermore, enzyme design for complicated substrates was investigated for the hydrolysis of cephalexin using scaffold selection based on two different catalytic motifs. Only three scaffolds were identified from the scaffold library by virtue of the classic catalytic triad-based motif. In contrast, 40 scaffolds were identified using a more flexible, but still preorganized catalytic motif, where one scaffold corresponded to the α-amino acid ester hydrolase that catalyzes the hydrolysis and synthesis of cephalexin. Thus, the complex active site modeling approach for de novo enzyme design with the aid of the improved ProdaMatch program is a promising approach for the creation of active sites with high catalytic efficiencies towards target reactions.

Use of an Improved Matching Algorithm to Select Scaffolds for Enzyme Design Based on a Complex Active Site Model

PubMed Central

Huang, Xiaoqiang; Xue, Jing; Lin, Min; Zhu, Yushan

2016-01-01

Active site preorganization helps native enzymes electrostatically stabilize the transition state better than the ground state for their primary substrates and achieve significant rate enhancement. In this report, we hypothesize that a complex active site model for active site preorganization modeling should help to create preorganized active site design and afford higher starting activities towards target reactions. Our matching algorithm ProdaMatch was improved by invoking effective pruning strategies and the native active sites for ten scaffolds in a benchmark test set were reproduced. The root-mean squared deviations between the matched transition states and those in the crystal structures were < 1.0 Å for the ten scaffolds, and the repacking calculation results showed that 91% of the hydrogen bonds within the active sites are recovered, indicating that the active sites can be preorganized based on the predicted positions of transition states. The application of the complex active site model for de novo enzyme design was evaluated by scaffold selection using a classic catalytic triad motif for the hydrolysis of p-nitrophenyl acetate. Eighty scaffolds were identified from a scaffold library with 1,491 proteins and four scaffolds were native esterase. Furthermore, enzyme design for complicated substrates was investigated for the hydrolysis of cephalexin using scaffold selection based on two different catalytic motifs. Only three scaffolds were identified from the scaffold library by virtue of the classic catalytic triad-based motif. In contrast, 40 scaffolds were identified using a more flexible, but still preorganized catalytic motif, where one scaffold corresponded to the α-amino acid ester hydrolase that catalyzes the hydrolysis and synthesis of cephalexin. Thus, the complex active site modeling approach for de novo enzyme design with the aid of the improved ProdaMatch program is a promising approach for the creation of active sites with high catalytic efficiencies towards target reactions. PMID:27243223

Synthesis of inverse ringwoodite sheds light on the subduction history of Tibetan ophiolites.

PubMed

Bindi, Luca; Griffin, William L; Panero, Wendy R; Sirotkina, Ekaterina; Bobrov, Andrey; Irifune, Tetsuo

2018-04-03

Tibetan ophiolites are shallow mantle material and crustal slabs that were subducted as deep as the mantle transition zone, a conclusion supported by the discovery of high-pressure phases like inverse ringwoodite in these sequences. Ringwoodite, Mg 2 SiO 4 , exhibits the normal spinel structure, with Mg in the octahedral A site and Si in the tetrahedral B site. Through A and B site-disorder, the inverse spinel has four-coordinated A cations and the six-coordinated site hosts a mixture of A and B cations. This process affects the density and impedance contrasts across the boundaries in the transition zone and seismic-wave velocities in this portion of the Earth. We report the first synthesis at high pressure (20 GPa) and high temperature (1600 °C) of a Cr-bearing ringwoodite with a completely inverse-spinel structure. Chemical, structural, and computational analysis confirm the stability of inverse ringwoodite and add further constraints to the subduction history of the Luobusa peridotite of the Tibetan ophiolites.

Chemoselective single-site Earth-abundant metal catalysts at metal–organic framework nodes

PubMed Central

Manna, Kuntal; Ji, Pengfei; Lin, Zekai; Greene, Francis X.; Urban, Ania; Thacker, Nathan C.; Lin, Wenbin

2016-01-01

Earth-abundant metal catalysts are critically needed for sustainable chemical synthesis. Here we report a simple, cheap and effective strategy of producing novel earth-abundant metal catalysts at metal–organic framework (MOF) nodes for broad-scope organic transformations. The straightforward metalation of MOF secondary building units (SBUs) with cobalt and iron salts affords highly active and reusable single-site solid catalysts for a range of organic reactions, including chemoselective borylation, silylation and amination of benzylic C–H bonds, as well as hydrogenation and hydroboration of alkenes and ketones. Our structural, spectroscopic and kinetic studies suggest that chemoselective organic transformations occur on site-isolated, electron-deficient and coordinatively unsaturated metal centres at the SBUs via σ-bond metathesis pathways and as a result of the steric environment around the catalytic site. MOFs thus provide a novel platform for the development of highly active and affordable base metal catalysts for the sustainable synthesis of fine chemicals. PMID:27574182

Chemoselective single-site Earth-abundant metal catalysts at metal–organic framework nodes

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

Manna, Kuntal; Ji, Pengfei; Lin, Zekai

2016-08-30

Earth-abundant metal catalysts are critically needed for sustainable chemical synthesis. Here we report a simple, cheap and effective strategy of producing novel earth-abundant metal catalysts at metal–organic framework (MOF) nodes for broad-scope organic transformations. The straightforward metalation of MOF secondary building units (SBUs) with cobalt and iron salts affords highly active and reusable single-site solid catalysts for a range of organic reactions, including chemoselective borylation, silylation and amination of benzylic C–H bonds, as well as hydrogenation and hydroboration of alkenes and ketones. Our structural, spectroscopic and kinetic studies suggest that chemoselective organic transformations occur on site-isolated, electron-deficient and coordinatively unsaturatedmore » metal centres at the SBUs via σ-bond metathesis pathways and as a result of the steric environment around the catalytic site. MOFs thus provide a novel platform for the development of highly active and affordable base metal catalysts for the sustainable synthesis of fine chemicals.« less

Active sites for CO 2 hydrogenation to methanol on Cu/ZnO catalysts

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

Kattel, Shyam; Ramírez, Pedro J.; Chen, Jingguang G.

The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al 2O 3) catalysts for carbon dioxide (CO 2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. Here, we report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte Carlo simulations, we can identify and characterize the reactivity of each catalyst. Both experimental and theoretical results agree that ZnCu undergoes surface oxidation under the reaction conditions so that surface Zn transforms into ZnO andmore » allows ZnCu to reach the activity of ZnO/Cu with the same Zn coverage. These results highlight a synergy of Cu and ZnO at the interface that facilitates methanol synthesis via formate intermediates.« less

Active sites for CO 2 hydrogenation to methanol on Cu/ZnO catalysts

DOE PAGES

Kattel, Shyam; Ramírez, Pedro J.; Chen, Jingguang G.; ...

2017-03-23

The active sites over commercial copper/zinc oxide/aluminum oxide (Cu/ZnO/Al 2O 3) catalysts for carbon dioxide (CO 2) hydrogenation to methanol, the Zn-Cu bimetallic sites or ZnO-Cu interfacial sites, have recently been the subject of intense debate. Here, we report a direct comparison between the activity of ZnCu and ZnO/Cu model catalysts for methanol synthesis. By combining x-ray photoemission spectroscopy, density functional theory, and kinetic Monte Carlo simulations, we can identify and characterize the reactivity of each catalyst. Both experimental and theoretical results agree that ZnCu undergoes surface oxidation under the reaction conditions so that surface Zn transforms into ZnO andmore » allows ZnCu to reach the activity of ZnO/Cu with the same Zn coverage. These results highlight a synergy of Cu and ZnO at the interface that facilitates methanol synthesis via formate intermediates.« less

Users manual for the Variable dimension Automatic Synthesis Program (VASP)

NASA Technical Reports Server (NTRS)

White, J. S.; Lee, H. Q.

1971-01-01

A dictionary and some problems for the Variable Automatic Synthesis Program VASP are submitted. The dictionary contains a description of each subroutine and instructions on its use. The example problems give the user a better perspective on the use of VASP for solving problems in modern control theory. These example problems include dynamic response, optimal control gain, solution of the sampled data matrix Ricatti equation, matrix decomposition, and pseudo inverse of a matrix. Listings of all subroutines are also included. The VASP program has been adapted to run in the conversational mode on the Ames 360/67 computer.

Modeling and Synthesis Support for the North American Carbon Program

NASA Astrophysics Data System (ADS)

Baskaran, L.; Cook, R. B.; Thornton, P. E.; Post, W. M.; Wilson, B. E.; Dadi, U.

2007-12-01

The Modeling and Synthesis Thematic Data Center (MAST-DC) supports the North American Carbon Program by providing data products and data management services needed for modeling and synthesis activities. The overall objective of MAST-DC is to provide advanced data management support to NACP investigators doing modeling and synthesis, thereby freeing those investigators from having to perform data management functions. MAST-DC has compiled a number of data products for North America, including sub-pixel land-water content, daily meteorological data, and soil, land cover, and elevation data. In addition, we have developed an internet-based WebGIS system that enables users to browse, query, display, subset, and download spatial data using a standard web browser. For the mid-continent intensive, MAST-DC is working with a group of data assimilation modelers to generate a consistent set of meteorological data to drive bottom-up models.

Site Remediation Technology InfoBase: A Guide to Federal Programs, Information Resources, and Publications on Contaminated Site Cleanup Technologies. First Edition

NASA Technical Reports Server (NTRS)

1998-01-01

Table of Contents: Federal Cleanup Programs; Federal Site Remediation Technology Development Assistance Programs; Federal Site Remediation Technology Development Electronic Data Bases; Federal Electronic Resources for Site Remediation Technology Information; Other Electronic Resources for Site Remediation Technology Information; Other Electronic Resources for Site Remediation Technology Information; Selected Bibliography: Federal Publication on Alternative and Innovative Site Remediation; and Appendix: Technology Program Contacts.

ADS: A FORTRAN program for automated design synthesis: Version 1.10

NASA Technical Reports Server (NTRS)

Vanderplaats, G. N.

1985-01-01

A new general-purpose optimization program for engineering design is described. ADS (Automated Design Synthesis - Version 1.10) is a FORTRAN program for solution of nonlinear constrained optimization problems. The program is segmented into three levels: strategy, optimizer, and one-dimensional search. At each level, several options are available so that a total of over 100 possible combinations can be created. Examples of available strategies are sequential unconstrained minimization, the Augmented Lagrange Multiplier method, and Sequential Linear Programming. Available optimizers include variable metric methods and the Method of Feasible Directions as examples, and one-dimensional search options include polynomial interpolation and the Golden Section method as examples. Emphasis is placed on ease of use of the program. All information is transferred via a single parameter list. Default values are provided for all internal program parameters such as convergence criteria, and the user is given a simple means to over-ride these, if desired.

Oxime amides as a novel zinc binding group in histone deacetylase inhibitors: synthesis, biological activity, and computational evaluation.

PubMed

Botta, Cinzia B; Cabri, Walter; Cini, Elena; De Cesare, Lucia; Fattorusso, Caterina; Giannini, Giuseppe; Persico, Marco; Petrella, Antonello; Rondinelli, Francesca; Rodriquez, Manuela; Russo, Adele; Taddei, Maurizio

2011-04-14

Several oxime containing molecules, characterized by a SAHA-like structure, were explored to select a potentially new biasing binding element for the zinc in HDAC catalytic site. All compounds were evaluated for their in vitro inhibitory activity against the 11 human HDACs isoforms. After identification of a "hit" molecule, a programmed variation at the cap group and at the linker was carried out in order to increase HDAC inhibition and/or paralogue selectivity. Some of the new derivatives showed increased activity against a number of HDAC isoforms, even if their overall activity range is still far from the inhibition values reported for SAHA. Moreover, different from what was reported for their hydroxamic acid analogues the new α-oxime amide derivatives do not select between class I and class II HDACs; rather they target specific isoforms in each class. These somehow contradictory results were finally rationalized by a computational assisted SAR, which gave us the chance to understand how the oxime derivatives interact with the catalytic site and justify the observed activity profile.

Effect of progesterone receptor status on maspin synthesis via nitric oxide production in neutrophils in human breast cancer.

PubMed

Ganguly Bhattacharjee, Karabi; Bhattacharyya, Mau; Halder, Umesh Chandra; Jana, Pradipta; Sinha, Asru K

2014-09-01

Although progesterone receptor (PR) status, similarly to estrogen receptor status, is of prognostic importance in breast cancer, the involvement of the PR in breast cancer remains obscure. Studies were conducted to determine the function of the PR in neutrophils in the nitric oxide-induced synthesis of maspin, an anti-breast-cancer protein produced in nonmalignant mammary cells and in neutrophils in the circulation. PR status was determined by immunohistochemistry. Maspin synthesis was determined by in-vitro translation of messenger RNA and quantified by enzyme-linked immunosorbent assay. Nitric oxide was determined by the methemoglobin method. It was found that PR status in neutrophils was identical with that in malignant breast tissues. A Scatchard plot for progesterone binding to normal and PR-positive (PR+) neutrophils revealed that whereas normal neutrophils had 11.5 × 10(10) PR sites/cell with K d = 47.619 nM, PR+ neutrophils had 6.6 × 10(10) PR sites/cell with K d = 47.619 nM. The progesterone negative (PR-) neutrophils failed to bind to progesterone. Incubation of normal and PR+ neutrophils with 25 nM progesterone produced 1.317 μM NO and 2.329 nM maspin; the PR+ neutrophils produced 0.72 μM NO and 1.138 nM maspin. The PR- neutrophils failed to produce any NO or maspin in the presence of progesterone. Inhibition of progesterone-induced NO synthesis led to complete inhibition of maspin synthesis in all neutrophils. These results suggest that estrogen and progesterone complement each other in NO-induced maspin synthesis, and do not necessarily antagonize in the synthesis of the anti-breast-cancer protein.

Defense Small Business Innovation Research Program (SBIR). Volume 3. Air Force Abstracts of Phase 1 Awards 1987.

DTIC Science & Technology

1988-04-01

RESISTANCE, AS WELL AS GUIDELINES FROM APPROPRIATE AEROSPACE SPECIFICATIONS; MATERIALS WILL INCLUDE ALUMINUM AND TITANIUM ALLOYS, PLUS A FEW STEELS...VAPOR SYNTHESIS OF NIOBIUM ALUMINIDES TOPIC# 105 OFFICE: AFWAL/ML DIRECT SYNTHESIS OF NbA1 ALLOY FOILS BY CHEMICAL VAPOR DEPOSITION ONTO INERT SUBSTRATES...GROWT OF GAMMA PRIME NICKEL ALUMINIDE (Ni3AI) %% TOPICt 104 OFFICE: AFWAL/ML . SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM - PHASE 1 PAGE 555

Pore-expanded SBA-15 sulfonic acid silicas for biodiesel synthesis.

PubMed

Dacquin, J P; Lee, A F; Pirez, C; Wilson, K

2012-01-07

Here we present the first application of pore-expanded SBA-15 in heterogeneous catalysis. Pore expansion over the range 6-14 nm confers a striking activity enhancement towards fatty acid methyl ester (FAME) synthesis from triglycerides (TAG), and free fatty acid (FFA), attributed to improved mass transport and acid site accessibility. This journal is © The Royal Society of Chemistry 2012

Synthesis and optimization of thiadiazole derivatives as a novel class of substrate competitive c-Jun N-terminal kinase inhibitors

PubMed Central

De, Surya K.; Chen, Vida; Stebbins, John L.; Chen, Li-Hsing; Cellitti, Jason F.; Machleidt, Thomas; Barile, Elisa; Riel-Mehan, Megan; Dahl, Russell; Yang, Li; Emdadi, Aras; Murphy, Ria; Pellecchia, Maurizio

2009-01-01

A series of thiadiazole derivatives has been designed as potential allosteric, substrate competitive inhibitors of the protein kinase JNK. We report on the synthesis, characterization and evaluation of a series of compounds that resulted in the identification of potent and selective JNK inhibitors targeting its JIP-1 docking site. PMID:20045647

Immobilization of isolated FI catalyst on polyhedral oligomeric silsesquioxane-functionalized silica for the synthesis of weakly entangled polyethylene.

PubMed

Li, Wei; Yang, Huaqin; Zhang, Jingjing; Mu, Jingshan; Gong, Dirong; Wang, Xiaodong

2016-09-25

Polyhedral oligomeric silsesquioxanes (POSSs) were adsorbed on methylaluminoxane-activated silica for the immobilization of fluorinated bis(phenoxyimine)Ti complexes (FI catalyst). These POSSs have been characterized as horizontal spacers isolating the active sites and hindering the chain overlap in polymerization. The heterogeneous catalyst exhibits considerable activity in the synthesis of weakly entangled polyethylene.

9 CFR 149.9 - Pilot program sites.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Pilot program sites. 149.9 Section 149... LIVESTOCK IMPROVEMENT VOLUNTARY TRICHINAE CERTIFICATION PROGRAM § 149.9 Pilot program sites. Pork production sites participating in an APHIS-approved trichinae pilot program at the time of implementation of the...

9 CFR 149.9 - Pilot program sites.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Pilot program sites. 149.9 Section 149... LIVESTOCK IMPROVEMENT VOLUNTARY TRICHINAE CERTIFICATION PROGRAM § 149.9 Pilot program sites. Pork production sites participating in an APHIS-approved trichinae pilot program at the time of implementation of the...

Roles of conserved proline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan.

PubMed

Berg, Stefan; Starbuck, James; Torrelles, Jordi B; Vissa, Varalakshmi D; Crick, Dean C; Chatterjee, Delphi; Brennan, Patrick J

2005-02-18

D-Arabinans, composed of D-arabinofuranose (D-Araf), dominate the structure of mycobacterial cell walls in two settings, as part of lipoarabinomannan (LAM) and arabinogalactan, each with markedly different structures and functions. Little is known of the complexity of their biosynthesis. beta-D-Arabinofuranosyl-1-monophosphoryldecaprenol is the only known sugar donor. EmbA, EmbB, and EmbC, products of the paralogous genes embA, embB, and embC, the sites of resistance to the anti-tuberculosis drug ethambutol (EMB), are the only known implicated enzymes. EmbA and -B apparently contribute to the synthesis of arabinogalactan, whereas EmbC is reserved for the synthesis of LAM. The Emb proteins show no overall similarity to any known proteins beyond Mycobacterium and related genera. However, functional motifs, equivalent to a proline-rich motif of several bacterial polysaccharide co-polymerases and a superfamily of glycosyltransferases, were found. Site-directed mutagenesis in glycosyltransferase superfamily C resulted in complete ablation of LAM synthesis. Point mutations in three amino acids of the proline motif of EmbC resulted in marked reduction of LAM-arabinan synthesis and accumulation of an unknown intermediate and of the known precursor lipomannan. Yet the pattern of the differently linked d-Araf units observed in wild type LAM-arabinan was largely retained in the proline motif mutants. The results allow for the presentation of a unique model of arabinan synthesis.

Transpeptidase activity of penicillin-binding protein SpoVD in peptidoglycan synthesis conditionally depends on the disulfide reductase StoA.

PubMed

Bukowska-Faniband, Ewa; Hederstedt, Lars

2017-07-01

Endospore cortex peptidoglycan synthesis is not required for bacterial growth but essential for endospore heat resistance. It therefore constitutes an amenable system for research on peptidoglycan biogenesis. The Bacillus subtilis sporulation-specific class B penicillin-binding protein (PBP) SpoVD and many homologous PBPs contain two conserved cysteine residues of unknown function in the transpeptidase domain - one as residue x in the SxN catalytic site motif and the other in a flexible loop near the catalytic site. A disulfide bond between these residues blocks the function of SpoVD in cortex synthesis. With a combination of experiments with purified proteins and B. subtilis mutant cells, it was shown that in active SpoVD the two cysteine residues most probably interact by hydrogen bonding and that this is important for peptidoglycan synthesis in vivo. It was furthermore demonstrated that the sporulation-specific thiol-disulfide oxidoreductase StoA reduces SpoVD and that requirement of StoA for cortex synthesis can be suppressed by two completely different types of structural alterations in SpoVD. It is concluded that StoA plays a critical role mainly during maturation of SpoVD in the forespore outer membrane. The findings advance our understanding of essential PBPs and redox control of extra-cytoplasmic protein disulfides in bacterial cells. © 2017 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.

Synthesis of multiple shaped beam antenna patterns

NASA Technical Reports Server (NTRS)

Stutzman, W. L.; Coffey, E. L.

1973-01-01

Results are presented of research into the problem of finding an excitation of a given antenna such that the desired radiation pattern is approximated to within acceptable limits. This is to be done in such a fashion that boundary conditions involving hardware limitations may be inserted into the problem. The intended application is synthesis of multiple shaped beam antennas. Since this is perhaps the most difficult synthesis problem an antenna engineer is likely to encounter, the approach taken was to include as a by-product capability for synthesizing simpler patterns. The synthesis technique has been almost totally computerized. The class of antennas which may be synthesized with the computer program are those which may be represented as planar (continuous or discrete) current distributions. The technique is not limited in this sense and could indeed by extended to include, for example, the synthesis of conformal arrays or current distributions on the surface of reflectors. The antenna types which the program is set up to synthesize are: line source, rectangular aperture, circular aperture, linear array, rectangular array, and arbitrary planar array.

Adaptation and impairment of DNA repair function in pollen of Betula verrucosa and seeds of Oenothera biennis from differently radionuclide-contaminated sites of Chernobyl.

PubMed

Boubriak, I I; Grodzinsky, D M; Polischuk, V P; Naumenko, V D; Gushcha, N P; Micheev, A N; McCready, S J; Osborne, D J

2008-01-01

The plants that have remained in the contaminated areas around Chernobyl since 1986 encapsulate the effects of radiation. Such plants are chronically exposed to radionuclides that they have accumulated internally as well as to alpha-, beta- and gamma-emitting radionuclides from external sources and from the soil. This radiation leads to genetic damage that can be countered by DNA repair systems. The objective of this study is to follow DNA repair and adaptation in haploid cells (birch pollen) and diploid cells (seed embryos of the evening primrose) from plants that have been growing in situ in different radionuclide fall-out sites in monitored regions surrounding the Chernobyl explosion of 1986. Radionuclide levels in soil were detected using gamma-spectroscopy and radiochemistry. DNA repair assays included measurement of unscheduled DNA synthesis, electrophoretic determination of single-strand DNA breaks and image analysis of rDNA repeats after repair intervals. Nucleosome levels were established using an ELISA kit. Birch pollen collected in 1987 failed to perform unscheduled DNA synthesis, but pollen at gamma/beta-emitter sites has now recovered this ability. At a site with high levels of combined alpha- and gamma/beta-emitters, pollen still exhibits hidden damage, as shown by reduced unscheduled DNA synthesis and failure to repair lesions in rDNA repeats properly. Evening primrose seed embryos generated on plants at the same gamma/beta-emitter sites now show an improved DNA repair capacity and ability to germinate under abiotic stresses (salinity and accelerated ageing). Again those from combined alpha- and gamma/beta-contaminated site do not show this improvement. Chronic irradiation at gamma/beta-emitter sites has provided opportunities for plant cells (both pollen and embryo cells) to adapt to ionizing irradiation and other environmental stresses. This may be explained by facilitation of DNA repair function.

Adaptation and Impairment of DNA Repair Function in Pollen of Betula verrucosa and Seeds of Oenothera biennis from Differently Radionuclide-contaminated Sites of Chernobyl

PubMed Central

Boubriak, I. I.; Grodzinsky, D. M.; Polischuk, V. P.; Naumenko, V. D.; Gushcha, N. P.; Micheev, A. N.; McCready, S. J.; Osborne, D. J.

2008-01-01

Background and Aims The plants that have remained in the contaminated areas around Chernobyl since 1986 encapsulate the effects of radiation. Such plants are chronically exposed to radionuclides that they have accumulated internally as well as to α-, β- and γ-emitting radionuclides from external sources and from the soil. This radiation leads to genetic damage that can be countered by DNA repair systems. The objective of this study is to follow DNA repair and adaptation in haploid cells (birch pollen) and diploid cells (seed embryos of the evening primrose) from plants that have been growing in situ in different radionuclide fall-out sites in monitored regions surrounding the Chernobyl explosion of 1986. Methods Radionuclide levels in soil were detected using gamma-spectroscopy and radiochemistry. DNA repair assays included measurement of unscheduled DNA synthesis, electrophoretic determination of single-strand DNA breaks and image analysis of rDNA repeats after repair intervals. Nucleosome levels were established using an ELISA kit. Key Results Birch pollen collected in 1987 failed to perform unscheduled DNA synthesis, but pollen at γ/β-emitter sites has now recovered this ability. At a site with high levels of combined α- and γ/β-emitters, pollen still exhibits hidden damage, as shown by reduced unscheduled DNA synthesis and failure to repair lesions in rDNA repeats properly. Evening primrose seed embryos generated on plants at the same γ/β-emitter sites now show an improved DNA repair capacity and ability to germinate under abiotic stresses (salinity and accelerated ageing). Again those from combined α- and γ/β-contaminated site do not show this improvement. Conclusions Chronic irradiation at γ/β-emitter sites has provided opportunities for plant cells (both pollen and embryo cells) to adapt to ionizing irradiation and other environmental stresses. This may be explained by facilitation of DNA repair function. PMID:17981881

Site-selective and stereoselective functionalization of non-activated tertiary C-H bonds

NASA Astrophysics Data System (ADS)

Liao, Kuangbiao; Pickel, Thomas C.; Boyarskikh, Vyacheslav; Bacsa, John; Musaev, Djamaladdin G.; Davies, Huw M. L.

2017-11-01

The synthesis of complex organic compounds usually relies on controlling the reactions of the functional groups. In recent years, it has become possible to carry out reactions directly on the C-H bonds, previously considered to be unreactive. One of the major challenges is to control the site-selectivity because most organic compounds have many similar C-H bonds. The most well developed procedures so far rely on the use of substrate control, in which the substrate has one inherently more reactive C-H bond or contains a directing group or the reaction is conducted intramolecularly so that a specific C-H bond is favoured. A more versatile but more challenging approach is to use catalysts to control which site in the substrate is functionalized. p450 enzymes exhibit C-H oxidation site-selectivity, in which the enzyme scaffold causes a specific C-H bond to be functionalized by placing it close to the iron-oxo haem complex. Several studies have aimed to emulate this enzymatic site-selectivity with designed transition-metal catalysts but it is difficult to achieve exceptionally high levels of site-selectivity. Recently, we reported a dirhodium catalyst for the site-selective functionalization of the most accessible non-activated (that is, not next to a functional group) secondary C-H bonds by means of rhodium-carbene-induced C-H insertion. Here we describe another dirhodium catalyst that has a very different reactivity profile. Instead of the secondary C-H bond, the new catalyst is capable of precise site-selectivity at the most accessible tertiary C-H bonds. Using this catalyst, we modify several natural products, including steroids and a vitamin E derivative, indicating the applicability of this method of synthesis to the late-stage functionalization of complex molecules. These studies show it is possible to achieve site-selectivity at different positions within a substrate simply by selecting the appropriate catalyst. We hope that this work will inspire the design of even more sophisticated catalysts, such that catalyst-controlled C-H functionalization becomes a broadly applied strategy for the synthesis of complex molecules.

The integrity of the G2421-C2395 base pair in the ribosomal E-site is crucial for protein synthesis

PubMed Central

Koch, Miriam; Clementi, Nina; Rusca, Nicola; Vögele, Paul; Erlacher, Matthias; Polacek, Norbert

2015-01-01

During the elongation cycle of protein biosynthesis, tRNAs traverse through the ribosome by consecutive binding to the 3 ribosomal binding sites (A-, P-, and E- sites). While the ribosomal A- and P-sites have been functionally well characterized in the past, the contribution of the E-site to protein biosynthesis is still poorly understood in molecular terms. Previous studies suggested an important functional interaction of the terminal residue A76 of E-tRNA with the nucleobase of the universally conserved 23S rRNA residue C2394. Using an atomic mutagenesis approach to introduce non-natural nucleoside analogs into the 23S rRNA, we could show that removal of the nucleobase or the ribose 2'-OH at C2394 had no effect on protein synthesis. On the other hand, our data disclose the importance of the highly conserved E-site base pair G2421-C2395 for effective translation. Ribosomes with a disrupted G2421-C2395 base pair are defective in tRNA binding to the E-site. This results in an impaired translation of genuine mRNAs, while homo-polymeric templates are not affected. Cumulatively our data emphasize the importance of E-site tRNA occupancy and in particular the intactness of the 23S rRNA base pair G2421-C2395 for productive protein biosynthesis. PMID:25826414

The LTER Network Information System: Improving Data Quality and Synthesis through Community Collaboration

NASA Astrophysics Data System (ADS)

Servilla, M.; Brunt, J.

2011-12-01

Emerging in the 1980's as a U.S. National Science Foundation funded research network, the Long Term Ecological Research (LTER) Network began with six sites and with the goal of performing comparative data collection and analysis of major biotic regions of North America. Today, the LTER Network includes 26 sites located in North America, Antarctica, Puerto Rico, and French Polynesia and has contributed a corpus of over 7,000 data sets to the public domain. The diversity of LTER research has led to a wealth of scientific data derived from atmospheric to terrestrial to oceanographic to anthropogenic studies. Such diversity, however, is a contributing factor to data being published with poor or inconsistent quality or to data lacking descriptive documentation sufficient for understanding their origin or performing derivative studies. It is for these reasons that the LTER community, in collaboration with the LTER Network Office, have embarked on the development of the LTER Network Information System (NIS) - an integrative data management approach to improve the process by which quality LTER data and metadata are assembled into a central archive, thereby enabling better discovery, analysis, and synthesis of derived data products. The mission of the LTER NIS is to promote advances in collaborative and synthetic ecological science at multiple temporal and spatial scales by providing the information management and technology infrastructure to increase: ? availability and quality of data from LTER sites - by the use and support of standardized approaches to metadata management and access to data; ? timeliness and number of LTER derived data products - by creating a suite of middleware programs and workflows that make it easy to create and maintain integrated data sets derived from LTER data; and ? knowledge generated from the synthesis of LTER data - by creating standardized access and easy to use applications to discover, access, and use LTER data. The LTER NIS will utilize the Provenance Aware Synthesis Tracking Architecture (PASTA), which will provide the LTER community a metadata-driven data-flow framework to automatically harvest data from LTER research sites and make it available through a well defined software interface. We distinguish PASTA from the more generalized NIS by classifying framework components as critical and enabling cyberinfrastructure that, collectively, provide the services defined by the above mission. Data and metadata will have to pass a set of community defined quality criteria before entry into PASTA, including the use of semantic informing metadata elements and the conformance of data to their structural descriptions provided by metadata. As a result, consumers of data products from PASTA will be assured that metadata are complete and include provenance information where applicable and the data are of the highest quality. Development of the NIS is being performed through community participation. Advisory groups, called "Tiger Teams", are enlisted from the general LTER membership to provide input to the design of the NIS. Other LTER working groups contribute community-based software into the NIS; these include modules for controlled vocabularies, scientific units, and personnel. We anticipate a 2014 release of the LTER NIS.

Simplified programming and control of automated radiosynthesizers through unit operations.

PubMed

Claggett, Shane B; Quinn, Kevin M; Lazari, Mark; Moore, Melissa D; van Dam, R Michael

2013-07-15

Many automated radiosynthesizers for producing positron emission tomography (PET) probes provide a means for the operator to create custom synthesis programs. The programming interfaces are typically designed with the engineer rather than the radiochemist in mind, requiring lengthy programs to be created from sequences of low-level, non-intuitive hardware operations. In some cases, the user is even responsible for adding steps to update the graphical representation of the system. In light of these unnecessarily complex approaches, we have created software to perform radiochemistry on the ELIXYS radiosynthesizer with the goal of being intuitive and easy to use. Radiochemists were consulted, and a wide range of radiosyntheses were analyzed to determine a comprehensive set of basic chemistry unit operations. Based around these operations, we created a software control system with a client-server architecture. In an attempt to maximize flexibility, the client software was designed to run on a variety of portable multi-touch devices. The software was used to create programs for the synthesis of several 18F-labeled probes on the ELIXYS radiosynthesizer, with [18F]FDG detailed here. To gauge the user-friendliness of the software, program lengths were compared to those from other systems. A small sample group with no prior radiosynthesizer experience was tasked with creating and running a simple protocol. The software was successfully used to synthesize several 18F-labeled PET probes, including [18F]FDG, with synthesis times and yields comparable to literature reports. The resulting programs were significantly shorter and easier to debug than programs from other systems. The sample group of naive users created and ran a simple protocol within a couple of hours, revealing a very short learning curve. The client-server architecture provided reliability, enabling continuity of the synthesis run even if the computer running the client software failed. The architecture enabled a single user to control the hardware while others observed the run in progress or created programs for other probes. We developed a novel unit operation-based software interface to control automated radiosynthesizers that reduced the program length and complexity and also exhibited a short learning curve. The client-server architecture provided robustness and flexibility.

Simplified programming and control of automated radiosynthesizers through unit operations

PubMed Central

2013-01-01

Background Many automated radiosynthesizers for producing positron emission tomography (PET) probes provide a means for the operator to create custom synthesis programs. The programming interfaces are typically designed with the engineer rather than the radiochemist in mind, requiring lengthy programs to be created from sequences of low-level, non-intuitive hardware operations. In some cases, the user is even responsible for adding steps to update the graphical representation of the system. In light of these unnecessarily complex approaches, we have created software to perform radiochemistry on the ELIXYS radiosynthesizer with the goal of being intuitive and easy to use. Methods Radiochemists were consulted, and a wide range of radiosyntheses were analyzed to determine a comprehensive set of basic chemistry unit operations. Based around these operations, we created a software control system with a client–server architecture. In an attempt to maximize flexibility, the client software was designed to run on a variety of portable multi-touch devices. The software was used to create programs for the synthesis of several 18F-labeled probes on the ELIXYS radiosynthesizer, with [18F]FDG detailed here. To gauge the user-friendliness of the software, program lengths were compared to those from other systems. A small sample group with no prior radiosynthesizer experience was tasked with creating and running a simple protocol. Results The software was successfully used to synthesize several 18F-labeled PET probes, including [18F]FDG, with synthesis times and yields comparable to literature reports. The resulting programs were significantly shorter and easier to debug than programs from other systems. The sample group of naive users created and ran a simple protocol within a couple of hours, revealing a very short learning curve. The client–server architecture provided reliability, enabling continuity of the synthesis run even if the computer running the client software failed. The architecture enabled a single user to control the hardware while others observed the run in progress or created programs for other probes. Conclusions We developed a novel unit operation-based software interface to control automated radiosynthesizers that reduced the program length and complexity and also exhibited a short learning curve. The client–server architecture provided robustness and flexibility. PMID:23855995

Primer synthesis by a eukaryotic-like archaeal primase is independent of its Fe-S cluster.

PubMed

Holzer, Sandro; Yan, Jiangyu; Kilkenny, Mairi L; Bell, Stephen D; Pellegrini, Luca

2017-11-23

DNA replication depends on primase, the specialised polymerase responsible for synthesis of the RNA primers that are elongated by the replicative DNA polymerases. In eukaryotic and archaeal replication, primase is a heterodimer of two subunits, PriS and PriL. Recently, a third primase subunit named PriX was identified in the archaeon Sulfolobus solfataricus. PriX is essential for primer synthesis and is structurally related to the Fe-S cluster domain of eukaryotic PriL. Here we show that PriX contains a nucleotide-binding site required for primer synthesis, and demonstrate equivalence of nucleotide-binding residues in PriX with eukaryotic PriL residues that are known to be important for primer synthesis. A primase chimera, where PriX is fused to a truncated version of PriL lacking the Fe-S cluster domain retains wild-type levels of primer synthesis. Our evidence shows that PriX has replaced PriL as the subunit that endows primase with the unique ability to initiate nucleic acid synthesis. Importantly, our findings reveal that the Fe-S cluster is not required for primer synthesis.

A Cytological Analysis of the Antimetabolite Activity of 5-Hydroxyuracil in Vicia faba Roots

PubMed Central

Schreiber, Richard W.; Duncan, Robert E.

1958-01-01

The effects of 5-hydroxyuracil (5-HU) (isobarbituric acid) upon cell elongation, mitosis, and DNA synthesis were studied in Vicia faba roots. 5-HU had no consistent effect upon root elongation. It blocked DNA synthesis (analyzed by photometric measurements of Feulgen dye in nuclei) during the first 6 hours of treatment; the block spontaneously disappeared by the 12th hour of treatment. Uracil and thymine had no effect upon this block of synthesis. Both thymidine and uridine reversed the block in 6 and 9 hours respectively. In all cases blockage of DNA synthesis was followed by inhibition of mitosis (determined by changes in the percentage of cells in mitosis) and resumption of DNA synthesis was followed by resumption of mitosis. Inhibition indices calculated from the mitotic data indicated a competitive relationship between 5-HU and thymidine and 5-HU and uridine. 5-HU is considered to block DNA synthesis by competing with thymidine for sites on enzymes involved in the synthesis. It is suggested that uridine reverses the block in synthesis by undergoing a conversion to thymidine. PMID:13610946

Ground Water Issue Paper: Synthesis Report on State of Understanding of Chlorinated Solvent Transformation

EPA Science Inventory

The U.S. EPA (1999) provided clarification of its policy on the application of MNA as a remedy for contaminated sites, and defines this alternative as “the reliance on natural attenuation processes (within the context of a carefully controlled and monitored site cleanup approach)...

Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation

NASA Astrophysics Data System (ADS)

Lichtor, Phillip A.; Miller, Scott J.

2012-12-01

Selectivity in the catalytic functionalization of complex molecules is a major challenge in chemical synthesis. The problem is magnified when there are several possible stereochemical outcomes and when similar functional groups occur repeatedly within the same molecule. Selective polyene oxidation provides an archetypical example of this challenge. Historically, enzymatic catalysis has provided the only precedents. Although non-enzymatic catalysts that meet some of these challenges became known, a comprehensive solution has remained elusive. Here, we describe low molecular weight peptide-based catalysts, discovered through a combinatorial synthesis and screening protocol, that exhibit site- and enantioselective oxidation of certain positions of various isoprenols. This diversity-based approach, which exhibits features reminiscent of the directed evolution of enzymes, delivers catalysts that compare favourably to the state-of-the-art for the asymmetric oxidation of these compounds. Moreover, the approach culminated in catalysts that exhibit alternative-site selectivity in comparison to oxidation catalysts previously described.

Precise small molecule recognition of a toxic CUG RNA repeat expansion

PubMed Central

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-01-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760

Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

PubMed

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-02-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.

DFT predictions, synthesis, stoichiometric structures and anti-diabetic activity of Cu (II) and Fe (III) complexes of quercetin, morin, and primuletin

NASA Astrophysics Data System (ADS)

Jabeen, Erum; Janjua, Naveed Kausar; Ahmed, Safeer; Murtaza, Iram; Ali, Tahir; Masood, Nosheen; Rizvi, Aysha Sarfraz; Murtaza, Gulam

2017-12-01

The current study is aimed at the synthesis of Cu (II) and Fe (III) complexes of three flavonoids {morin (mor), quercetin (quer) and primuletin (prim)} and characterization through UV-Vis spectroscopy, cyclic voltammetry, FTIR, and thermal analysis. Structure prediction through DFT calculation was supported by experimental data. Benesi-Hildebrand equation was modified to function for 1:2 Cu-flavonoid and 1:3 Fe-flavonoid complexes. DFT predictions revealed that out of poly chelation sites present in morin and quercetin, 3-OH site was utilized as preferable chelation site while primuletin chelated through 5-OH position. In-vivo trials revealed the complexes to have better anti-diabetic potential than respective flavonoid. Fls/M-Fls proved as antagonistic to Alloxan induced diabetes and also retained anti-diabetic activity even in the presence of (2-hydroxypropyl)-β-cyclodextrin (HPβCD).

Synthesis of the project leadership staffing needs for successful development of alternative delivery programs.

DOT National Transportation Integrated Search

2017-08-01

This research provides a synthesis of practices in organizational structuring and professional staffing of the innovative delivery units in several state DOTs across the nation that are actively utilizing alternative project delivery. Several major c...

AERIS - applications for the environment : real-time information synthesis : eco-lanes operational scenario modeling report.

DOT National Transportation Integrated Search

2014-12-01

This report constitutes the detailed modeling and evaluation results of the Eco-Lanes Operational Scenario defined by the Applications for the Environment: Real-Time Information Synthesis (AERIS) Program. The Operational Scenario constitutes six appl...

From non-preemptive to preemptive scheduling using synchronization synthesis.

PubMed

Černý, Pavol; Clarke, Edmund M; Henzinger, Thomas A; Radhakrishna, Arjun; Ryzhyk, Leonid; Samanta, Roopsha; Tarrach, Thorsten

2017-01-01

We present a computer-aided programming approach to concurrency. The approach allows programmers to program assuming a friendly, non-preemptive scheduler, and our synthesis procedure inserts synchronization to ensure that the final program works even with a preemptive scheduler. The correctness specification is implicit, inferred from the non-preemptive behavior. Let us consider sequences of calls that the program makes to an external interface. The specification requires that any such sequence produced under a preemptive scheduler should be included in the set of sequences produced under a non-preemptive scheduler. We guarantee that our synthesis does not introduce deadlocks and that the synchronization inserted is optimal w.r.t. a given objective function. The solution is based on a finitary abstraction, an algorithm for bounded language inclusion modulo an independence relation, and generation of a set of global constraints over synchronization placements. Each model of the global constraints set corresponds to a correctness-ensuring synchronization placement. The placement that is optimal w.r.t. the given objective function is chosen as the synchronization solution. We apply the approach to device-driver programming, where the driver threads call the software interface of the device and the API provided by the operating system. Our experiments demonstrate that our synthesis method is precise and efficient. The implicit specification helped us find one concurrency bug previously missed when model-checking using an explicit, user-provided specification. We implemented objective functions for coarse-grained and fine-grained locking and observed that different synchronization placements are produced for our experiments, favoring a minimal number of synchronization operations or maximum concurrency, respectively.

Greener synthesis of Cu-MOF-74 and its catalytic use for the generation of vanillin.

PubMed

Flores, J Gabriel; Sánchez-González, Elí; Gutiérrez-Alejandre, Aída; Aguilar-Pliego, Julia; Martínez, Ana; Jurado-Vázquez, Tamara; Lima, Enrique; González-Zamora, Eduardo; Díaz-García, Manuel; Sánchez-Sánchez, Manuel; Ibarra, Ilich A

2018-03-26

A greener synthesis of Cu-MOF-74 was obtained, for the first time, in methanol as the unique solvent and at room temperature. Full characterisation of the MOF material showed its purity and also its nanocrystalline nature. Complete activation (150 °C for 1 h and 10-3 bar) of Cu-MOF-74 afforded unsaturated Cu metal sites and this was corroborated by in situ DRIFT spectroscopy. The access to these Cu open metal sites was tested for the catalytic transformation of trans-ferulic acid to vanillin (yield of 71% and 97% selectivity) and a plausible catalytic reaction mechanism was postulated based on quantum chemical calculations.

Chiral reagents in glycosylation and modification of carbohydrates.

PubMed

Wang, Hao-Yuan; Blaszczyk, Stephanie A; Xiao, Guozhi; Tang, Weiping

2018-02-05

Carbohydrates play a significant role in numerous biological events, and the chemical synthesis of carbohydrates is vital for further studies to understand their various biological functions. Due to the structural complexity of carbohydrates, the stereoselective formation of glycosidic linkages and the site-selective modification of hydroxyl groups are very challenging and at the same time extremely important. In recent years, the rapid development of chiral reagents including both chiral auxiliaries and chiral catalysts has significantly improved the stereoselectivity for glycosylation reactions and the site-selectivity for the modification of carbohydrates. These new tools will greatly facilitate the efficient synthesis of oligosaccharides, polysaccharides, and glycoconjugates. In this tutorial review, we will summarize these advances and highlight the most recent examples.

Current Status of Human Resource Training Program for Fostering RIBiomics Professionals

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

Lee, Dong-Eun; Jang, Beom-Su; Choi, Dae Seong

RI-Biomics is a state-of-the-art radiation fusion technology for evaluating in-vivo dynamics such as absorption, distribution, metabolism and excretion (ADME) of new drug candidates and biomaterials using radioisotope (RI), and quantitative evaluation of their efficacy via molecular imaging techniques and animal models. The RI-Biomics center is the sole comprehensive research and experiment complex in Korea that can simultaneously perform the radio-synthesis of drug candidate with radioisotope, analysis, and molecular imaging evaluation with animal model. Molecular imaging techniques, including nuclear imaging (SPECT and PET), near-infrared fluorescent (NIRF) imaging, and magnetic resonance imaging (MRI), are the cutting-edge technologies for evaluating drug candidates. Sincemore » they allow in vivo real-time imaging of the diseased site, monitoring the biodistribution of drug and determining the optimal therapeutic efficacy following treatments, we have integrated RI-ADME and molecular imaging to provide useful information for drug evaluation and to accelerate the development of new drugs and biomaterials. The RI-Biomics center was established with total investment of 18 million $ during four years from 2009 to 2012 in order to develop a comprehensive analyzing system using RI for new drug development as an axis for national growth in the next generation. The RI-Biomics center has labeling synthesis facility for the radiosynthesis of drug candidate with radioisotope such as Tc-99m, I-125, I-131, F-18, H-3 and C-14 using hot cell. It also includes RI-general analysis facilities, such as Radio-HPLC, LC/MS, GC/MS, gamma counter that can analyzing the radio-synthesized materials, and animal image analysis facilities that developed small animal imaging equipment such as SPECT/PET/CT, 7 T MRI, in-vivo optical imaging system and others. In order to achieve the system to verify safety and effectiveness of the new drugs using RI, it is necessary to establish a human resource training program for fostering RI-Biomics professionals in the following key fields; (1) Radio-pharmaceuticals synthesis and labeled compound development, (2) Development of RI-ADME in the living object and image assessment technology. Personnel training program that carries out theoretical education and practical training in the field related to RI-Biomics in parallel is being conducted. Internship training for university students has been administered twice already while educational program for the existing professionals in the RI-Biomics field will be carried out during the summer of 2014. The human resource training program for combination of RIADME and different molecular imaging techniques can offer synergistic advantages to facilitate understanding RIADME and fostering RI-ADME professionals. (authors)« less

Parametric synthesis of a robust controller on a base of mathematical programming method

NASA Astrophysics Data System (ADS)

Khozhaev, I. V.; Gayvoronskiy, S. A.; Ezangina, T. A.

2018-05-01

Considered paper is dedicated to deriving sufficient conditions, linking root indices of robust control quality with coefficients of interval characteristic polynomial, on the base of mathematical programming method. On the base of these conditions, a method of PI- and PID-controllers, providing aperiodic transient process with acceptable stability degree and, subsequently, acceptable setting time, synthesis was developed. The method was applied to a problem of synthesizing a controller for a depth control system of an unmanned underwater vehicle.

Indirect synthesis of multi-degree of freedom transient systems. [linear programming for a kinematically linear system

NASA Technical Reports Server (NTRS)

Pilkey, W. D.; Chen, Y. H.

1974-01-01

An indirect synthesis method is used in the efficient optimal design of multi-degree of freedom, multi-design element, nonlinear, transient systems. A limiting performance analysis which requires linear programming for a kinematically linear system is presented. The system is selected using system identification methods such that the designed system responds as closely as possible to the limiting performance. The efficiency is a result of the method avoiding the repetitive systems analyses accompanying other numerical optimization methods.

Enzymatic synthesis of long double-stranded DNA labeled with haloderivatives of nucleobases in a precisely pre-determined sequence

PubMed Central

2011-01-01

Background Restriction endonucleases are widely applied in recombinant DNA technology. Among them, enzymes of class IIS, which cleave DNA beyond recognition sites, are especially useful. We use BsaI enzyme for the pinpoint introduction of halogen nucleobases into DNA. This has been done for the purpose of anticancer radio- and phototherapy that is our long-term objective. Results An enzymatic method for synthesizing long double-stranded DNA labeled with the halogen derivatives of nucleobases (Hal-NBs) with 1-bp accuracy has been put forward and successfully tested on three different DNA fragments containing the 5-bromouracil (5-BrU) residue. The protocol assumes enzymatic cleavage of two Polymerase-Chain-Reaction (PCR) fragments containing two recognition sequences for the same or different class IIS restriction endonucleases, where each PCR fragment has a partially complementary cleavage site. These sites are introduced using synthetic DNA primers or are naturally present in the sequence used. The cleavage sites are not compatible, and therefore not susceptible to ligation until they are partially filled with a Hal-NB or original nucleobase, resulting in complementary cohesive end formation. Ligation of these fragments ultimately leads to the required Hal-NB-labeled DNA duplex. With this approach, a synthetic, extremely long DNA fragment can be obtained by means of a multiple assembly reaction (n × maximum PCR product length: n × app. 50 kb). Conclusions The long, precisely labeled DNA duplexes obtained behave in very much the same manner as natural DNA and are beyond the range of chemical synthesis. Moreover, the conditions of synthesis closely resemble the natural ones, and all the artifacts accompanying the chemical synthesis of DNA are thus eliminated. The approach proposed seems to be completely general and could be used to label DNA at multiple pre-determined sites and with halogen derivatives of any nucleobase. Access to DNAs labeled with Hal-NBs at specific position is an indispensable condition for the understanding and optimization of DNA photo- and radio-degradation, which are prerequisites for clinical trials of Hal-NBs in anticancer therapy. PMID:21864341

Enzymatic synthesis of long double-stranded DNA labeled with haloderivatives of nucleobases in a precisely pre-determined sequence.

PubMed

Sobolewski, Ireneusz; Polska, Katarzyna; Zylicz-Stachula, Agnieszka; Jeżewska-Frąckowiak, Joanna; Rak, Janusz; Skowron, Piotr

2011-08-24

Restriction endonucleases are widely applied in recombinant DNA technology. Among them, enzymes of class IIS, which cleave DNA beyond recognition sites, are especially useful. We use BsaI enzyme for the pinpoint introduction of halogen nucleobases into DNA. This has been done for the purpose of anticancer radio- and phototherapy that is our long-term objective. An enzymatic method for synthesizing long double-stranded DNA labeled with the halogen derivatives of nucleobases (Hal-NBs) with 1-bp accuracy has been put forward and successfully tested on three different DNA fragments containing the 5-bromouracil (5-BrU) residue. The protocol assumes enzymatic cleavage of two Polymerase-Chain-Reaction (PCR) fragments containing two recognition sequences for the same or different class IIS restriction endonucleases, where each PCR fragment has a partially complementary cleavage site. These sites are introduced using synthetic DNA primers or are naturally present in the sequence used. The cleavage sites are not compatible, and therefore not susceptible to ligation until they are partially filled with a Hal-NB or original nucleobase, resulting in complementary cohesive end formation. Ligation of these fragments ultimately leads to the required Hal-NB-labeled DNA duplex. With this approach, a synthetic, extremely long DNA fragment can be obtained by means of a multiple assembly reaction (n × maximum PCR product length: n × app. 50 kb). The long, precisely labeled DNA duplexes obtained behave in very much the same manner as natural DNA and are beyond the range of chemical synthesis. Moreover, the conditions of synthesis closely resemble the natural ones, and all the artifacts accompanying the chemical synthesis of DNA are thus eliminated. The approach proposed seems to be completely general and could be used to label DNA at multiple pre-determined sites and with halogen derivatives of any nucleobase. Access to DNAs labeled with Hal-NBs at specific position is an indispensable condition for the understanding and optimization of DNA photo- and radio-degradation, which are prerequisites for clinical trials of Hal-NBs in anticancer therapy.

Intelligent transportation systems Professional Capacity Building Program needs assessment : a review and synthesis of thirteen studies

DOT National Transportation Integrated Search

1997-09-01

This report, ITS Professional Capacity Building: A Review and Synthesis of Thirteen Studies, serves as a companion report to ITS Professional Capacity Building: Field Interviews. This report summarizes what other organizations concerned about ITS sta...

A conceptual model of agroecosystem function as a basis for synthesis

USDA-ARS?s Scientific Manuscript database

A primary challenge for LTAR is to organize information about sustainable agricultural intensification such that it can be synthesized across multiple research programs addressing disparate problems. Such synthesis facilitates not only regional to national-scale generalizations to inform the public ...

Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

PubMed Central

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

2016-01-01

Genetic decoding is not ‘frozen’ as was earlier thought, but dynamic. One facet of this is frameshifting that often results in synthesis of a C-terminal region encoded by a new frame. Ribosomal frameshifting is utilized for the synthesis of additional products, for regulatory purposes and for translational ‘correction’ of problem or ‘savior’ indels. Utilization for synthesis of additional products occurs prominently in the decoding of mobile chromosomal element and viral genomes. One class of regulatory frameshifting of stable chromosomal genes governs cellular polyamine levels from yeasts to humans. In many cases of productively utilized frameshifting, the proportion of ribosomes that frameshift at a shift-prone site is enhanced by specific nascent peptide or mRNA context features. Such mRNA signals, which can be 5′ or 3′ of the shift site or both, can act by pairing with ribosomal RNA or as stem loops or pseudoknots even with one component being 4 kb 3′ from the shift site. Transcriptional realignment at slippage-prone sequences also generates productively utilized products encoded trans-frame with respect to the genomic sequence. This too can be enhanced by nucleic acid structure. Together with dynamic codon redefinition, frameshifting is one of the forms of recoding that enriches gene expression. PMID:27436286

The permuted generator hypothesis for the origin of a genetic code

NASA Technical Reports Server (NTRS)

Folsome, C.

1977-01-01

Protocells had no known means of ensuring that their randomly collected proteins would be duplicated. A possible, albeit inexact, mechanism for protein synthesis in a primitive t-RNA is presented, whereby an oligonucleotide (12 units) in a circular configuration is able to align a generator site with amino acid discriminator sites. In this way, unique anticodons could be specified for each site and replication could occur.

Native chemical ligation at Asx-Cys, Glx-Cys: chemical synthesis and high-resolution X-ray structure of ShK toxin by racemic protein crystallography.

PubMed

Dang, Bobo; Kubota, Tomoya; Mandal, Kalyaneswar; Bezanilla, Francisco; Kent, Stephen B H

2013-08-14

We have re-examined the utility of native chemical ligation at -Gln/Glu-Cys- [Glx-Cys] and -Asn/Asp-Cys- [Asx-Cys] sites. Using the improved thioaryl catalyst 4-mercaptophenylacetic acid (MPAA), native chemical ligation could be performed at -Gln-Cys- and Asn-Cys- sites without side reactions. After optimization, ligation at a -Glu-Cys- site could also be used as a ligation site, with minimal levels of byproduct formation. However, -Asp-Cys- is not appropriate for use as a site for native chemical ligation because of formation of significant amounts of β-linked byproduct. The feasibility of native chemical ligation at -Gln-Cys- enabled a convergent total chemical synthesis of the enantiomeric forms of the ShK toxin protein molecule. The D-ShK protein molecule was ~50,000-fold less active in blocking the Kv1.3 channel than the L-ShK protein molecule. Racemic protein crystallography was used to obtain high-resolution X-ray diffraction data for ShK toxin. The structure was solved by direct methods and showed significant differences from the previously reported NMR structures in some regions of the ShK protein molecule.

Site-directed DNA crosslinking of large multisubunit protein-DNA complexes.

PubMed

Persinger, Jim; Bartholomew, Blaine

2009-01-01

Several methods have been developed to site-specifically incorporate photoreactive nucleotide analogs into DNA for the purpose of identifying the proteins and their domains that are in contact with particular regions of DNA. The synthesis of several deoxynucleotide analogs that have a photoreactive group tethered to the nucleotide base and the incorporation of these analogs into DNA are described. In a second approach, oligonucleotide with a photoreactive group attached to the phosphate backbone is chemically synthesized. The photoreactive oligonucleotide is then enzymatically incorporated into DNA by annealing it to a complementary DNA template and extending with DNA polymerase. Both approaches have been effectively used to map protein-DNA interactions in large multisubunit complexes such as the eukaryotic transcription or ATP-dependent chromatin remodeling complexes. Not only do these techniques map the binding sites of the various subunits in these complexes, but when coupled with peptide mapping also determine the protein domain that is in close proximity to the different DNA sites. The strength of these techniques is the ability to scan a large number of potential sites by making combinations of different DNA probes and is facilitated by using an immobilized DNA template for synthesis.

High-resolution physical and functional mapping of the template adjacent DNA binding site in catalytically active telomerase.

PubMed

Romi, Erez; Baran, Nava; Gantman, Marina; Shmoish, Michael; Min, Bosun; Collins, Kathleen; Manor, Haim

2007-05-22

Telomerase is a cellular reverse transcriptase, which utilizes an integral RNA template to extend single-stranded telomeric DNA. We used site-specific photocrosslinking to map interactions between DNA primers and the catalytic protein subunit (tTERT) of Tetrahymena thermophila telomerase in functional enzyme complexes. Our assays reveal contact of the single-stranded DNA adjacent to the primer-template hybrid and tTERT residue W187 at the periphery of the N-terminal domain. This contact was detected in complexes with three different registers of template in the active site, suggesting that it is maintained throughout synthesis of a complete telomeric repeat. Substitution of nearby residue Q168, but not W187, alters the K(m) for primer elongation, implying that it plays a role in the DNA recognition. These findings are the first to directly demonstrate the physical location of TERT-DNA contacts in catalytically active telomerase and to identify amino acid determinants of DNA binding affinity. Our data also suggest a movement of the TERT active site relative to the template-adjacent single-stranded DNA binding site within a cycle of repeat synthesis.

DNA Origami Patterned Colloids for Programmed Design and Chirality

NASA Astrophysics Data System (ADS)

Ben Zion, Matan Yah; He, Xiaojin; Maass, Corinna; Sha, Ruojie; Seeman, Ned; Chaikin, Paul

Micron size colloidal particles are scientifically important as model systems for equilibrium and active systems in physics, chemistry and biology and for technologies ranging from catalysis to photonics. The past decade has seen development of new particles with directional patches, lock and key reactions and specific recognition that guide assembly of structures such as complex crystalline arrays. What remains lacking is the ability to self-assemble structures of arbitrary shape with specific chirality, placement and orientation of neighbors. Here we demonstrate the adaptation of DNA origami nanotechnology to the micron colloidal scale with designed control of neighbor type, placement and dihedral angle. We use DNA origami belts with programmed flexibility, and functionality to pattern colloidal surfaces and bind particles to specific sites at specific angles and make uniquely right handed or left handed structures. The hybrid DNA origami colloid technology should allow the synthesis of designed functional structural and active materials. This work was supported as part of the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under Award # DE-SC0000989.

An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.

PubMed

Naro, Chiara; Jolly, Ariane; Di Persio, Sara; Bielli, Pamela; Setterblad, Niclas; Alberdi, Antonio J; Vicini, Elena; Geremia, Raffaele; De la Grange, Pierre; Sette, Claudio

2017-04-10

Global transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete function. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Derivation of sorting programs

NASA Technical Reports Server (NTRS)

Varghese, Joseph; Loganantharaj, Rasiah

1990-01-01

Program synthesis for critical applications has become a viable alternative to program verification. Nested resolution and its extension are used to synthesize a set of sorting programs from their first order logic specifications. A set of sorting programs, such as, naive sort, merge sort, and insertion sort, were successfully synthesized starting from the same set of specifications.

Novel approach of fragment-based lead discovery applied to renin inhibitors.

PubMed

Tawada, Michiko; Suzuki, Shinkichi; Imaeda, Yasuhiro; Oki, Hideyuki; Snell, Gyorgy; Behnke, Craig A; Kondo, Mitsuyo; Tarui, Naoki; Tanaka, Toshimasa; Kuroita, Takanobu; Tomimoto, Masaki

2016-11-15

A novel approach was conducted for fragment-based lead discovery and applied to renin inhibitors. The biochemical screening of a fragment library against renin provided the hit fragment which showed a characteristic interaction pattern with the target protein. The hit fragment bound only to the S1, S3, and S3 SP (S3 subpocket) sites without any interactions with the catalytic aspartate residues (Asp32 and Asp215 (pepsin numbering)). Prior to making chemical modifications to the hit fragment, we first identified its essential binding sites by utilizing the hit fragment's substructures. Second, we created a new and smaller scaffold, which better occupied the identified essential S3 and S3 SP sites, by utilizing library synthesis with high-throughput chemistry. We then revisited the S1 site and efficiently explored a good building block attaching to the scaffold with library synthesis. In the library syntheses, the binding modes of each pivotal compound were determined and confirmed by X-ray crystallography and the library was strategically designed by structure-based computational approach not only to obtain a more active compound but also to obtain informative Structure Activity Relationship (SAR). As a result, we obtained a lead compound offering synthetic accessibility as well as the improved in vitro ADMET profiles. The fragments and compounds possessing a characteristic interaction pattern provided new structural insights into renin's active site and the potential to create a new generation of renin inhibitors. In addition, we demonstrated our FBDD strategy integrating highly sensitive biochemical assay, X-ray crystallography, and high-throughput synthesis and in silico library design aimed at fragment morphing at the initial stage was effective to elucidate a pocket profile and a promising lead compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decadal Time Scale change in terrestrial plant communities in North American arctic and alpine tundra: A contribution to the International Polar Year Back to the Future Project (Invited)

NASA Astrophysics Data System (ADS)

Tweedie, C. E.; Ebert-May, D.; Hollister, R. D.; Johnson, D. R.; Lara, M. J.; Villarreal, S.; Spasojevic, M.; Webber, P.

2010-12-01

The International Polar Year-Back to the Future (IPY-BTF) is an endorsed International Polar Year project (IPY project #214). The overarching goal of this program is to determine how key structural and functional characteristics of high latitude/altitude terrestrial ecosystems have changed over the past 25 or more years and assess if such trajectories of change are likely to continue in the future. By rescuing data, revisiting, re-sampling historic research sites and assessing environmental change over time, we aim to provide greater understanding of how tundra is changing and what the possible drivers of these changes are. Resampling of sites established by Patrick J. Webber between 1964 and 1975 in northern Baffin Island, Northern Alaska and in the Rocky Mountains form a key contribution to the BTF project. Here we report on resampling efforts at each of these locations and initial results of a synthesis effort that finds similarities and differences in change between sites. Results suggest that although shifts in plant community composition are detectable at each location, the magnitude and direction of change differ among locations. Vegetation shifts along soil moisture gradients is apparent at most of the sites resampled. Interestingly, however, wet communities seem to have changed more than dry communities in the Arctic locations, while plant communities at the alpine site appear to be becoming more distinct regardless of soil moisture status. Ecosystem function studies performed in conjunction with plant community change suggest that there has been an increase in plant productivity at most sites resampled, especially in wet and mesic land cover types.

Synthesis of octahedral gold tip-blobbed nanoparticles and their dielectric sensing properties.

PubMed

Zhang, Liqiu; Jang, Hee-Jeong; Yoo, Sung Jae; Cho, Sanghyun; Won, Ji Hye; Liu, Lichun; Park, Sungho

2018-06-22

Site-selective synthesis of nanostructures is an important topic in the nanoscience community. Normally, the difference between seeds and deposition atoms in terms of crystallinity triggers the deposition atoms to grow initially at the specific site of nucleation. It is more challenging to control the deposition site of atoms that have the same composition as the seeds because the atoms tend to grow epitaxially, covering the whole surface of the seed nanoparticles. Gold (Au) nano-octahedrons used as seeds in this study possess obvious hierarchical surface energies depending on whether they are at vertices, edges, or terraces. Although vertices of Au nano-octahedrons have the highest surface energy, it remains a challenge to selectively deposit Au atoms at the vertices but not at the edges and faces; this selectivity is required to meet the ever-increasing demands of engineered nanomaterial properties. This work demonstrates an easy and robust method to precisely deposit Au nanoparticles at the vertices of Au nano-octahedrons via wet-chemical seed-mediated growth. The successful synthesis of octahedral Au tip-blobbed nanoparticles (Oh Au TBPs) benefited from the cooperative use of thin silver (Ag) layers at the surface of Au nano-octahedron seeds and iodide ions in the Au growth solution. As-synthesized Au nanostructures gave rise to hybrid optical properties, as evidenced from the UV-VIS-NIR extinction spectra, in which a new extinction peak appeared after Au nanoparticles were formed at the vertices of Au nano-octahedrons. A sensitivity evaluation toward dielectric media of a mixture of dimethyl sulfoxide and water suggested that Au TBPs were more optically sensitive compared to the original Au nano-octahedrons. The method demonstrated in this work is promising in the synthesis of advanced Au nanostructures with hybrid optical properties for versatile applications by engineering the surface energy of vertex-bearing Au nanostructures to trigger site-selective overgrowth of congener Au atoms. © 2018 IOP Publishing Ltd.

AutoBayes Program Synthesis System Users Manual

NASA Technical Reports Server (NTRS)

Schumann, Johann; Jafari, Hamed; Pressburger, Tom; Denney, Ewen; Buntine, Wray; Fischer, Bernd

2008-01-01

Program synthesis is the systematic, automatic construction of efficient executable code from high-level declarative specifications. AutoBayes is a fully automatic program synthesis system for the statistical data analysis domain; in particular, it solves parameter estimation problems. It has seen many successful applications at NASA and is currently being used, for example, to analyze simulation results for Orion. The input to AutoBayes is a concise description of a data analysis problem composed of a parameterized statistical model and a goal that is a probability term involving parameters and input data. The output is optimized and fully documented C/C++ code computing the values for those parameters that maximize the probability term. AutoBayes can solve many subproblems symbolically rather than having to rely on numeric approximation algorithms, thus yielding effective, efficient, and compact code. Statistical analysis is faster and more reliable, because effort can be focused on model development and validation rather than manual development of solution algorithms and code.

NASA Fundamental Remote Sensing Science Research Program

NASA Technical Reports Server (NTRS)

1984-01-01

The NASA Fundamental Remote Sensing Research Program is described. The program provides a dynamic scientific base which is continually broadened and from which future applied research and development can draw support. In particular, the overall objectives and current studies of the scene radiation and atmospheric effect characterization (SRAEC) project are reviewed. The SRAEC research can be generically structured into four types of activities including observation of phenomena, empirical characterization, analytical modeling, and scene radiation analysis and synthesis. The first three activities are the means by which the goal of scene radiation analysis and synthesis is achieved, and thus are considered priority activities during the early phases of the current project. Scene radiation analysis refers to the extraction of information describing the biogeophysical attributes of the scene from the spectral, spatial, and temporal radiance characteristics of the scene including the atmosphere. Scene radiation synthesis is the generation of realistic spectral, spatial, and temporal radiance values for a scene with a given set of biogeophysical attributes and atmospheric conditions.

Chemical protein synthesis: Inventing synthetic methods to decipher how proteins work.

PubMed

Kent, Stephen

2017-09-15

Total chemical synthesis of proteins has been rendered practical by the chemical ligation principle: chemoselective condensation of unprotected peptide segments equipped with unique, mutually reactive functional groups, enabled by formation of a non-native replacement for the peptide bond. Ligation chemistries are briefly described, including native chemical ligation - thioester-mediated, amide-forming reaction at Xaa-Cys sites - and its extensions. Case studies from the author's own works are used to illustrate the utility and applications of chemical protein synthesis. Selected recent developments in the field are briefly discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

78 FR 12259 - Unmanned Aircraft System Test Site Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-22

...-0061] Unmanned Aircraft System Test Site Program AGENCY: Federal Aviation Administration (FAA), DOT... Defense, develop a test site program for the integration of unmanned aircraft systems in to the National Airspace System. The overall purpose of this test site program is to develop a body of data and operational...

22 CFR 502.3 - Availability of program materials on public Web sites.

Code of Federal Regulations, 2014 CFR

2014-04-01

... sites. 502.3 Section 502.3 Foreign Relations BROADCASTING BOARD OF GOVERNORS DOMESTIC REQUESTS FOR BROADCASTING BOARD OF GOVERNORS PROGRAM MATERIALS § 502.3 Availability of program materials on public Web sites... information Web sites designed for foreign audiences. To access currently-available Agency program materials...

Synthesis of natural flows at selected sites in the upper Missouri River basin, Montana, 1928-89

USGS Publications Warehouse

Cary, L.E.; Parrett, Charles

1996-01-01

Natural monthly streamflows were synthesized for the years 1928-89 for 43 sites in the upper Missouri River Basin upstream from Fort Peck Lake in Montana. The sites are represented as nodes in a streamflow accounting model being developed by the Bureau of Reclamation. Recorded and historical flows at most sites have been affected by human activities including reservoir storage, diversions for irrigation, and municipal use. Natural flows at the sites were synthesized by eliminating the effects of these activities. Recorded data at some sites do not include the entire study period. The missing flows at these sites were estimated using a statistical procedure. The methods of synthesis varied, depending on upstream activities and information available. Recorded flows were transferred to nodes that did not have streamflow-gaging stations from the nearest station with a sufficient length of record. The flows at one node were computed as the sum of flows from three upstream tributaries. Monthly changes in reservoir storage were computed from monthend contents. The changes in storage were corrected for the effects of evaporation and precipitation using pan-evaporation and precipitation data from climate stations. Irrigation depletions and consumptive use by the three largest municipalities were computed. Synthesized natural flow at most nodes was computed by adding algebraically the upstream depletions and changes in reservoir storage to recorded or historical flow at the nodes.

Tolerance analysis program

NASA Technical Reports Server (NTRS)

Watson, H. K.

1971-01-01

Digital computer program determines tolerance values of end to end signal chain or flow path, given preselected probability value. Technique is useful in the synthesis and analysis phases of subsystem design processes.

Space Congress, 29th, Cocoa Beach, FL, Apr. 21-24, 1992, Proceedings

NASA Technical Reports Server (NTRS)

1992-01-01

The present volume on the quest for new frontiers in space discusses weather impacts on space operations, planning for the performance of future space bases, a new guidance and control unit for the Titan IV vehicle, and nondestructive evaluation of Shuttle Columbia tiles. Attention is given to Space Shuttle payload accommodations and trends in customer demands, a generic propellants transfer unit, making space part of general education, space station on-orbit solar array loads during assembly, and dimensional stability of the attitude reference assembly on SSF. Topics addressed include National Launch System payload accommodations and launch operations, the integrated factory/launch site processing concept, Pioneer 10 interstellar studies, and the role of advanced nuclear propulsion systems in precursor interstellar missions. Also discussed are legal challenges in realizing interstellar initiatives, Mars transportation system synthesis, and NASA's commercial space program.

Synthesis and toughness properties of resins and composites

NASA Technical Reports Server (NTRS)

Johnston, N. J.

1984-01-01

Tensile and shear moduli of four ACEE (Aircraft Energy Efficiency Program) resins are presented along with ACEE composite material modulus predictions based on micromechanics. Compressive strength and fracture toughness of the resins and composites were discussed. In addition, several resin synthesis techniques are reviewed.

[Synthesis of 107 Workplace Literacy Programs.

ERIC Educational Resources Information Center

Bussert, Kathy M.

A study examined information from 107 workplace literacy program descriptions from the United States and drew conclusions about joint partnerships, funding, and flexibility. Most of the program descriptions were found in an extensive search using the ERIC database. The programs described were from 1989 and 1990. Some of the findings were the…

On orbital allotments for geostationary satellites

NASA Technical Reports Server (NTRS)

Gonsalvez, David J. A.; Reilly, Charles H.; Mount-Campbell, Clark A.

1986-01-01

The following satellite synthesis problem is addressed: communication satellites are to be allotted positions on the geostationary arc so that interference does not exceed a given acceptable level by enforcing conservative pairwise satellite separation. A desired location is specified for each satellite, and the objective is to minimize the sum of the deviations between the satellites' prescribed and desired locations. Two mixed integer programming models for the satellite synthesis problem are presented. Four solution strategies, branch-and-bound, Benders' decomposition, linear programming with restricted basis entry, and a switching heuristic, are used to find solutions to example synthesis problems. Computational results indicate the switching algorithm yields solutions of good quality in reasonable execution times when compared to the other solution methods. It is demonstrated that the switching algorithm can be applied to synthesis problems with the objective of minimizing the largest deviation between a prescribed location and the corresponding desired location. Furthermore, it is shown that the switching heuristic can use no conservative, location-dependent satellite separations in order to satisfy interference criteria.

STC Synthesis of Best Practices for Determining Value of Research Results : Research Project Capsule

DOT National Transportation Integrated Search

2012-09-01

The RAC Region II has initiated a collaborative research program consortium : through the Transportation Pooled Fund (TPF) Program. The research program : is called the Southeast Transportation Consortium (STC) and is intended to : encourage coordina...

Hand Society and Matching Program Web Sites Provide Poor Access to Information Regarding Hand Surgery Fellowship.

PubMed

Hinds, Richard M; Klifto, Christopher S; Naik, Amish A; Sapienza, Anthony; Capo, John T

2016-08-01

The Internet is a common resource for applicants of hand surgery fellowships, however, the quality and accessibility of fellowship online information is unknown. The objectives of this study were to evaluate the accessibility of hand surgery fellowship Web sites and to assess the quality of information provided via program Web sites. Hand fellowship Web site accessibility was evaluated by reviewing the American Society for Surgery of the Hand (ASSH) on November 16, 2014 and the National Resident Matching Program (NRMP) fellowship directories on February 12, 2015, and performing an independent Google search on November 25, 2014. Accessible Web sites were then assessed for quality of the presented information. A total of 81 programs were identified with the ASSH directory featuring direct links to 32% of program Web sites and the NRMP directory directly linking to 0%. A Google search yielded direct links to 86% of program Web sites. The quality of presented information varied greatly among the 72 accessible Web sites. Program description (100%), fellowship application requirements (97%), program contact email address (85%), and research requirements (75%) were the most commonly presented components of fellowship information. Hand fellowship program Web sites can be accessed from the ASSH directory and, to a lesser extent, the NRMP directory. However, a Google search is the most reliable method to access online fellowship information. Of assessable programs, all featured a program description though the quality of the remaining information was variable. Hand surgery fellowship applicants may face some difficulties when attempting to gather program information online. Future efforts should focus on improving the accessibility and content quality on hand surgery fellowship program Web sites.

Adding Concrete Syntax to a Prolog-Based Program Synthesis System

NASA Technical Reports Server (NTRS)

Fischer, Bernd; Visser, Eelco

2003-01-01

Program generation and transformation systems manipulate large, pa- rameterized object language fragments. Support for user-definable concrete syntax makes this easier but is typically restricted to certain object and meta languages. We show how Prolog can be retrofitted with concrete syntax and describe how a seamless interaction of concrete syntax fragments with an existing legacy meta-programming system based on abstract syntax is achieved. We apply the approach to gradually migrate the schemas of the AUTOBAYES program synthesis system to concrete syntax. Fit experiences show that this can result in a considerable reduction of the code size and an improved readability of the code. In particular, abstracting out fresh-variable generation and second-order term construction allows the formulation of larger continuous fragments and improves the locality in the schemas.

Accessibility and content of individualized adult reconstructive hip and knee/musculoskeletal oncology fellowship web sites.

PubMed

Young, Bradley L; Cantrell, Colin K; Patt, Joshua C; Ponce, Brent A

2018-06-01

Accessible, adequate online information is important to fellowship applicants. Program web sites can affect which programs applicants apply to, subsequently altering interview costs incurred by both parties and ultimately impacting rank lists. Web site analyses have been performed for all orthopaedic subspecialties other than those involved in the combined adult reconstruction and musculoskeletal (MSK) oncology fellowship match. A complete list of active programs was obtained from the official adult reconstruction and MSK oncology society web sites. Web site accessibility was assessed using a structured Google search. Accessible web sites were evaluated based on 21 previously reported content criteria. Seventy-four adult reconstruction programs and 11 MSK oncology programs were listed on the official society web sites. Web sites were identified and accessible for 58 (78%) adult reconstruction and 9 (82%) MSK oncology fellowship programs. No web site contained all content criteria and more than half of both adult reconstruction and MSK oncology web sites failed to include 12 of the 21 criteria. Several programs participating in the combined Adult Reconstructive Hip and Knee/Musculoskeletal Oncology Fellowship Match did not have accessible web sites. Of the web sites that were accessible, none contained comprehensive information and the majority lacked information that has been previously identified as being important to perspective applicants.

Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex.

PubMed

Boniecki, Michal T; Freibert, Sven A; Mühlenhoff, Ulrich; Lill, Roland; Cygler, Miroslaw

2017-11-03

Iron-sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis occurs on the mitochondrial scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. Here, we present crystal structures of three different NFS1-ISD11-ACP complexes with and without ISCU, and we use SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. Our structural and biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp, and His residues of ISCU. We assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status.

USGS Science Data Catalog - Open Data Advances or Declines

NASA Astrophysics Data System (ADS)

Frame, M. T.; Hutchison, V.; Zolly, L.; Wheeler, B.; Latysh, N.; Devarakonda, R.; Palanisamy, G.; Shrestha, B.

2014-12-01

The recent Office of Science and Technology Policy (OSTP) White House Open Data Policies (2013) have required Federal agencies to establish formal catalogues of their science data holdings and make these data easily available on Web sites, portals, and applications. As an organization, the USGS has historically excelled at making its data holdings freely available on its various Web sites (i.e., National, Scientific Programs, or local Science Center). In response to these requirements, the USGS Core Science Analytics, Synthesis, and Libraries program, in collaboration with DOE's Oak Ridge National Laboratory (ORNL) Mercury Consortium (funded by NASA, USGS, and DOE), and a number of other USGS organizations, established the Science Data Catalog (http://data.usgs.gov) cyberinfrastructure, content management processes/tools, and supporting policies. The USGS Science Data Catalog led the charge at USGS to improve the robustness of existing/future metadata collections; streamline and develop sustainable publishing to external aggregators (i.e., data.gov); and provide leadership to the U.S. Department of Interior in emerging Open Data policies, techniques, and systems. The session will discuss the current successes, challenges, and movement toward meeting these Open Data policies for USGS scientific data holdings. A retrospective look at the last year of implementation of these efforts within USGS will occur to determine whether these Open Data Policies are improving data access or limiting data availability. To learn more about the USGS Science Data Catalog, visit us at http://data.usgs.gov/info/about.html

75 FR 22391 - Notice of Web Site Publication for the Climate Program Office

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

...-01] Notice of Web Site Publication for the Climate Program Office AGENCY: Climate Program Office (CPO... its Web site at http://www.climate.noaa.gov . FOR FURTHER INFORMATION CONTACT: Eric Locklear; Chief... information is available on the Climate Program Office Web site pertaining to the CPO's research strategies...

The DEAD box helicase RDE-12 promotes amplification of RNAi in cytoplasmic foci in C. elegans

PubMed Central

Yang, Huan; Vallandingham, Jim; Shiu, Philip; Li, Hua; Hunter, Craig P.; Mak, Ho Yi

2014-01-01

Summary RNA interference (RNAi) is a potent mechanism for down-regulating gene expression. Conserved RNAi pathway components are found in animals, plants, fungi and other eukaryotes [1–3]. In C. elegans, the RNAi response is greatly amplified by the synthesis of abundant secondary siRNAs [4–6]. Exogenous double stranded RNA is processed by Dicer and RDE-1/Argonaute into primary siRNA that guides target mRNA recognition. The RDE-10/RDE-11 complex and the RNA dependent RNA polymerase RRF-1 then engage the target mRNA for secondary siRNA synthesis [7, 8]. However, the molecular link between primary siRNA production and secondary siRNA synthesis remains largely unknown. Furthermore, it is unclear if the sub-cellular sites for target mRNA recognition and degradation coincide with sites where siRNA synthesis and amplification occur. In the C. elegans germline, cytoplasmic P granules at the nuclear pores and perinuclear Mutator foci contribute to target mRNA surveillance and siRNA amplification, respectively [9–11]. We report that RDE-12, a conserved FG domain containing DEAD-box helicase, localizes in P-granules and cytoplasmic foci that are enriched in RSD-6 but are excluded from the Mutator foci. Our results suggest that RDE-12 promotes secondary siRNA synthesis by orchestrating the recruitment of RDE-10 and RRF-1 to primary siRNA targeted mRNA in distinct cytoplasmic compartments. PMID:24684930

The DEAD box helicase RDE-12 promotes amplification of RNAi in cytoplasmic foci in C. elegans.

PubMed

Yang, Huan; Vallandingham, Jim; Shiu, Philip; Li, Hua; Hunter, Craig P; Mak, Ho Yi

2014-04-14

RNAi is a potent mechanism for downregulating gene expression. Conserved RNAi pathway components are found in animals, plants, fungi, and other eukaryotes. In C. elegans, the RNAi response is greatly amplified by the synthesis of abundant secondary small interfering RNAs (siRNAs). Exogenous double-stranded RNA is processed by Dicer and RDE-1/Argonaute into primary siRNA that guides target mRNA recognition. The RDE-10/RDE-11 complex and the RNA-dependent RNA polymerase RRF-1 then engage the target mRNA for secondary siRNA synthesis. However, the molecular link between primary siRNA production and secondary siRNA synthesis remains largely unknown. Furthermore, it is unclear whether the subcellular sites for target mRNA recognition and degradation coincide with sites where siRNA synthesis and amplification occur. In the C. elegans germline, cytoplasmic P granules at the nuclear pores and perinuclear Mutator foci contribute to target mRNA surveillance and siRNA amplification, respectively. We report that RDE-12, a conserved phenylalanine-glycine (FG) domain-containing DEAD box helicase, localizes in P granules and cytoplasmic foci that are enriched in RSD-6 but are excluded from the Mutator foci. Our results suggest that RDE-12 promotes secondary siRNA synthesis by orchestrating the recruitment of RDE-10 and RRF-1 to primary siRNA-targeted mRNA in distinct cytoplasmic compartments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibition of the synthesis of polyamines and DNA in activated lymphocytes by a combination of alpha-methylornithine and methylglyoxal bis(guanylhydrazone).

PubMed

Morris, D R; Jorstad, C M; Seyfried, C E

1977-09-01

The cancer chemotherapeutic drug, methylglyoxal bis(guanylhydrazone), inhibits the synthesis of spermidine and spermine, but allows continued putrescine production in small lymphocytes stimulated by concanavalin A. DNA replication in these cells is inhibited 50% while the synthesis of protein and RNA continues normally. When excess putrescine accumulation in the presence of methylglyoxal bis(guanylhydrazone) was inhibited with alpha-methylornithine, a competitive inhibitor of ornithine decarboxylase, the inhibition of DNA replication was accentuated, with still no effect on protein or RNA synthesis. No inhibition of DNA synthesis by the combination of alpha-methylornithine and methylglyoxal bis(guanylhydrazone) was observed when the inhibitors were added after accumulation of cellular polyamines. In addition, inhibition was reversed by exogenous putrescine, spermidine, or spermine. We conclude that putrescine can fulfill in part the role normally played by spermidine and spermine in DNA replication, and that blocking putrescine synthesis in the presence of methylglyoxal bis(guanylhydrazone) amplifies the polyamine requirement. The implications of this with regard to polyamine synthesis as a site of chemotherapy are discussed.

Pax permanent Martian base: Space architecture for the first human habitation on Mars, volume 5

NASA Technical Reports Server (NTRS)

Huebner-Moths, Janis; Fieber, Joseph P.; Rebholz, Patrick J.; Paruleski, Kerry L.; Moore, Gary T. (Editor)

1992-01-01

America at the Threshold: Report of the Synthesis Group on America's Space Exploration Initiative (the 'Synthesis Report,' sometimes called the Stafford Report after its astronaut chair, published in 1991) recommended that NASA explore what it called four 'architectures,' i.e., four different scenarios for habitation on Mars. The Advanced Design Program in Space Architecture at the University of Wisconsin-Milwaukee supported this report and two of its scenarios--'Architecture 1' and 'Architecture 4'--during the spring of 1992. This report investigates the implications of different mission scenarios, the Martian environment, supporting technologies, and especially human factors and environment-behavior considerations for the design of the first permanent Martian base. The report is comprised of sections on mission analysis, implications of the Martian atmosphere and geologic environment, development of habitability design requirements based on environment-behavior and human factors research, and a full design proposed (concept design and design development) for the first permanent Martian base and habitat. The design is presented in terms of a base site plan, master plan based on a Mars direct scenario phased through IOC, and design development details of a complete Martian habitat for 18 crew members including all laboratory, mission control, and crew support spaces.

USEPA SITE PROGRAM APPROACH TO TECHNOLOGY TRANSFER AND REGULATORY ACCEPTANCE

EPA Science Inventory

The USEPA's SITE program was created to meet the demand for innovative technologies for hazardous waste treatment. The primary mission of the SITe Program is to expedite the cleanup of sites on the NPL. These sites often have multiple contaminants in soil and groundwater, and few...

Computer Synthesis Approaches of Hyperboloid Gear Drives with Linear Contact

NASA Astrophysics Data System (ADS)

Abadjiev, Valentin; Kawasaki, Haruhisa

2014-09-01

The computer design has improved forming different type software for scientific researches in the field of gearing theory as well as performing an adequate scientific support of the gear drives manufacture. Here are attached computer programs that are based on mathematical models as a result of scientific researches. The modern gear transmissions require the construction of new mathematical approaches to their geometric, technological and strength analysis. The process of optimization, synthesis and design is based on adequate iteration procedures to find out an optimal solution by varying definite parameters. The study is dedicated to accepted methodology in the creation of soft- ware for the synthesis of a class high reduction hyperboloid gears - Spiroid and Helicon ones (Spiroid and Helicon are trademarks registered by the Illinois Tool Works, Chicago, Ill). The developed basic computer products belong to software, based on original mathematical models. They are based on the two mathematical models for the synthesis: "upon a pitch contact point" and "upon a mesh region". Computer programs are worked out on the basis of the described mathematical models, and the relations between them are shown. The application of the shown approaches to the synthesis of commented gear drives is illustrated.

Cell-free protein synthesis: the state of the art.

PubMed

Whittaker, James W

2013-02-01

Cell-free protein synthesis harnesses the synthetic power of biology, programming the ribosomal translational machinery of the cell to create macromolecular products. Like PCR, which uses cellular replication machinery to create a DNA amplifier, cell-free protein synthesis is emerging as a transformative technology with broad applications in protein engineering, biopharmaceutical development, and post-genomic research. By breaking free from the constraints of cell-based systems, it takes the next step towards synthetic biology. Recent advances in reconstituted cell-free protein synthesis (Protein synthesis Using Recombinant Elements expression systems) are creating new opportunities to tailor the reactions for specialized applications including in vitro protein evolution, printing protein microarrays, isotopic labeling, and incorporating nonnatural amino acids.

Kinetic Monte Carlo study of vinyl acetate synthesis from ethylene acetoxylation on Pd(100) and Pd/Au(100)

NASA Astrophysics Data System (ADS)

Huang, Yanping; Dong, Xiuqin; Yu, Yingzhe; Zhang, Minhua

2017-11-01

On the basis of the activation barriers and reaction energies from DFT calculations, kinetic Monte Carlo (kMC) simulations of vinyl acetate (VA) synthesis from ethylene acetoxylation on Pd(100) and Pd/Au(100) were carried out. Through kMC simulation, it was found that VA synthesis from ethylene acetoxylation proceeds via Moiseev mechanism on both Pd(100) and Pd/Au(100). The addition of Au into Pd can suppress ethylene dehydrogenation while it can promote acetic acid dehydrogenation, which can eventually facilitate VA synthesis as a whole. The addition of Au into Pd can further improve the conversion and selectivity of VA synthesis from ethylene acetoxylation. When the reaction network is analyzed, besides the energetics of each elementary reaction, the surface coverage of each species and the occupancy of the surface sites on the catalyst should also be taken into consideration.

Retrofitting the AutoBayes Program Synthesis System with Concrete Syntax

NASA Technical Reports Server (NTRS)

Fischer, Bernd; Visser, Eelco

2004-01-01

AutoBayes is a fully automatic, schema-based program synthesis system for statistical data analysis applications. Its core component is a schema library. i.e., a collection of generic code templates with associated applicability constraints which are instantiated in a problem-specific way during synthesis. Currently, AutoBayes is implemented in Prolog; the schemas thus use abstract syntax (i.e., Prolog terms) to formulate the templates. However, the conceptual distance between this abstract representation and the concrete syntax of the generated programs makes the schemas hard to create and maintain. In this paper we describe how AutoBayes is retrofitted with concrete syntax. We show how it is integrated into Prolog and describe how the seamless interaction of concrete syntax fragments with AutoBayes's remaining legacy meta-programming kernel based on abstract syntax is achieved. We apply the approach to gradually mitigate individual schemas without forcing a disruptive migration of the entire system to a different First experiences show that a smooth migration can be achieved. Moreover, it can result in a considerable reduction of the code size and improved readability of the code. In particular, abstracting out fresh-variable generation and second-order term construction allows the formulation of larger continuous fragments.

Heterogeneous ribonucleoprotein R regulates arylalkylamine N-acetyltransferase synthesis via internal ribosomal entry site-mediated translation in a circadian manner.

PubMed

Lee, Hwa-Rim; Kim, Tae-Don; Kim, Hyo-Jin; Jung, Youngseob; Lee, Dohyun; Lee, Kyung-Ha; Kim, Do-Yeon; Woo, Kyung-Chul; Kim, Kyong-Tai

2015-11-01

Rhythmic arylalkylamine N-acetyltransferase (AANAT) synthesis is a prominent circadian-controlled response that occurs in most mammals. AANAT is the core enzyme in melatonin production; because melatonin participates in many physiological processes, the regulation of AANAT is an important research topic. In this study, we focused on the role of heterogeneous ribonucleoprotein R (hnRNP R) in the translation of AANAT. A novel RNA-binding protein hnRNP R widely interacted with the 5' untranslated region (UTR) of AANAT mRNA and contributed to translation through an internal ribosomal entry site (IRES). Fine-tuning of AANAT protein synthesis occurred in response to knockdown and overexpression of hnRNP R. Nocturnal elevation of AANAT protein was dependent on the rhythmic changes of hnRNP R, whose levels are elevated in the pineal gland during nighttime. Increases in hnRNP R additionally improved AANAT production in rat pinealocytes under norepinephrine (NE) treatment. These results suggest that cap-independent translation of AANAT mRNA plays a role in the rhythmic synthesis of melatonin through the recruitment of translational machinery to hnRNP R-bound AANAT mRNA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Realizing controllable graphene nucleation by regulating the competition of hydrogen and oxygen during chemical vapor deposition heating.

PubMed

Zhang, Haoran; Zhang, Yaqian; Zhang, Yanhui; Chen, Zhiying; Sui, Yanping; Ge, Xiaoming; Deng, Rongxuan; Yu, Guanghui; Jin, Zhi; Liu, Xinyu

2016-08-24

Oxygen can passivate Cu surface active sites when graphene nucleates. Thus, the nucleation density is decreased. The CuO/Cu substrate was chosen for graphene domain synthesis in our study. The results indicate that the CuO/Cu substrate is beneficial for large-scale, single-crystal graphene domain synthesis. Graphene grown on the CuO/Cu substrate exhibits fewer nucleation sites than on Cu foils, suggesting that graphene follows an oxygen-dominating growth. Hydrogen treatment via a heating process could weaken the surface oxygen's role in limiting graphene nucleation under the competition of hydrogen and oxygen and could transfer the synthesis of graphene into a hydrogen-dominating growth. However, the competition only exists during the chemical vapor deposition heating process. For non-hydrogen heated samples, oxygen-dominating growth is experienced even though the samples are annealed in hydrogen for a long time after the heating process. With the temperature increases, the role of hydrogen gradually decreases. The balance of hydrogen and oxygen is adjusted by introducing hydrogen gas at a different heating temperatures. The oxygen concentration on the substrate surface is believed to determine the reactions mechanisms based on the secondary ion mass spectrometry test results. This study provides a new method for the controllable synthesis of graphene nucleation during a heating process.

Key Scientific and Policy- and Health-Relevant Findings from EPA's Particulate Matter Supersites Program and Related Studies: An Integration and Synthesis of Results.

EPA Science Inventory

In 1998, the Environmental Protection Agency (EPA) initiated a major air quality program, known as the Particulate Matter (PM) Supersites Program. The Supersites Program was a multi year, $27 million air quality monitoring program consisting of eight regional air quality projects...

The Teaching of Protein Synthesis--A Microcomputer Based Method.

ERIC Educational Resources Information Center

Goodridge, Frank

1983-01-01

Describes two computer programs (BASIC for 32K Commodore PET) for teaching protein synthesis. The first is an interactive test of base-pairing knowledge, and the second generates random DNA nucleotide sequences, with instructions for substitution, insertion, and deletion printed out for each student. (JN)

Performance Analysis and Design Synthesis (PADS) computer program. Volume 2: Program description, part 2

NASA Technical Reports Server (NTRS)

1972-01-01

The QL module of the Performance Analysis and Design Synthesis (PADS) computer program is described. Execution of this module is initiated when and if subroutine PADSI calls subroutine GROPE. Subroutine GROPE controls the high level logical flow of the QL module. The purpose of the module is to determine a trajectory that satisfies the necessary variational conditions for optimal performance. The module achieves this by solving a nonlinear multi-point boundary value problem. The numerical method employed is described. It is an iterative technique that converges quadratically when it does converge. The three basic steps of the module are: (1) initialization, (2) iteration, and (3) culmination. For Volume 1 see N73-13199.

Best practices for achieving and measuring pavement smoothness, a synthesis of state-of-practice : [tech summary].

DOT National Transportation Integrated Search

2015-04-01

The RAC Region II has initiated a collaborative research program consortium : through the Transportation Pooled Fund (TPF) Program. The research program is : called the Southeast Transportation Consortium (STC) and is intended to encourage : coordina...

Eosinophils as a novel cell source of prostaglandin D2: autocrine role in allergic inflammation

PubMed Central

Luna-Gomes, Tatiana; Magalhães, Kelly G; Mesquita-Santos, Fabio P.; Bakker-Abreu, Ilka; Samico, Rafaela F.; Molinaro, Raphael; Calheiros, Andrea S.; Diaz, Bruno L.; Bozza, Patrícia T.

2011-01-01

Prostaglandin (PG)D2 is a key mediator of allergic inflammatory diseases that is mainly synthesized by mast cells, which constitutively express high levels of the terminal enzyme involved in PGD2 synthesis, the hematopoietic PGD synthase (H-PGDS). Here, we investigated whether eosinophils are also able to synthesize, and therefore, supply biologically active PGD2. PGD2 synthesis was evaluated within human blood eosinophils, in vitro-differentiated mouse eosinophils, and eosinophils infiltrating inflammatory site of mouse allergic reaction. Biological function of eosinophil-derived PGD2 was studied by employing inhibitors of synthesis and activity. Constitutive expression of H-PGDS was found within non-stimulated human circulating eosinophils. Acute stimulation of human eosinophils with A23187 (0.1 – 5 μM) evoked PGD2 synthesis, which was located at the nuclear envelope and was inhibited by pre-treatment with HQL-79 (10 μM), a specific H-PGDS inhibitor. Pre-stimulation of human eosinophils with arachidonic acid (AA; 10 μM) or human eotaxin (6 nM) also enhanced HQL-79-sensitive PGD2 synthesis, which, by acting on membrane-expressed specific receptors (DP1 and DP2), displayed an autocrine/paracrine ability to trigger leukotriene (LT)C4 synthesis and lipid body biogenesis, hallmark events of eosinophil activation. In vitro-differentiated mouse eosinophils also synthesized paracrine/autocrine active PGD2 in response to AA stimulation. In vivo, at late time point of the allergic reaction, infiltrating eosinophils found at the inflammatory site appeared as an auxiliary PGD2-synthesizing cell population. Our findings reveal that eosinophils are indeed able to synthesize and secrete PGD2, hence representing during allergic inflammation an extra cell source of PGD2, which functions as an autocrine signal for eosinophil activation. PMID:22102725

1,2-Dicyclopropylethyne and (Cyclopropylethynyl)cyclobutane from an Efficient Synthesis of 1,2-(omega-Haloalkyl)ethynes and 1-Cycloalkyl-2-(omega-haloalkyl)ethynes (Pre Print)

DTIC Science & Technology

2012-02-09

Efficient Synthesis of 1,2-(ω-Haloalkyl0ethynes and 1 -Cycloalkyl-2-(ω-haloalkyl)ethynes 5b. GRANT NUMBER (Pre Print) 5c. PROGRAM ELEMENT NUMBER...suffers from low yield as is evi- dent from the reported synthesis of 5-chloropent- 1 -yne (5, 57%)9 and 1,8-dichlorooct- 1 -yne (9, 36%).8 The synthesis ... chloropropane / 1 -bromo-4-chlorobutane is very sluggish and incomplete in THF. However, the reaction in the presence of 10 mol % Bu4NI results in an

Antiferromagnetic interaction between A'-site Mn spins in A-site-ordered perovskite YMn3Al4O12.

PubMed

Tohyama, Takenori; Saito, Takashi; Mizumaki, Masaichiro; Agui, Akane; Shimakawa, Yuichi

2010-03-01

The A-site-ordered perovskite YMn(3)Al(4)O(12) was prepared by high-pressure synthesis. Structural analysis with synchrotron powder X-ray diffraction data and the Mn L-edges X-ray absorption spectrum revealed that the compound has a chemical composition Y(3+)Mn(3+)(3)Al(3+)(4)O(2-)(12) with magnetic Mn(3+) at the A' site and non-magnetic Al(3+) at the B site. An antiferromagnetic interaction between the A'-site Mn(3+) spins is induced by the nearest neighboring Mn-Mn direct exchange interaction and causes an antiferromagnetic transition at 34.3 K.

Aquatic Plant Control Research Program. Large-Scale Operations Management Test of Use of the White Amur for Control of Problem Aquatic Plants. Report 5. Synthesis Report.

DTIC Science & Technology

1984-06-01

RD-Rl45 988 AQUATIC PLANT CONTROL RESEARCH PROGRAM LARGE-SCALE 1/2 OPERATIONS MANAGEMENT ..(U) ARMY ENGINEER WATERWAYS EXPERIMENT STATION VICKSBURG MS...REPORT A-78-2 LARGE-SCALE OPERATIONS MANAGEMENT TEST OF USE OF THE WHITE AMUR FOR -, CONTROL OF PROBLEM AQUATIC PLANTS Report 5 SYNTHESIS REPORT bv Andrew...Corps of Engineers Washington, DC 20314 84 0,_1 oil.. LARGE-SCALE OPERATIONS MANAGEMENT TEST OF USE OF THE WHITE AMUR FOR CONTROL OF PROBLEM AQUATIC

California's Past Programs to Support School and District Improvement: A Synthesis of Evaluation Studies

ERIC Educational Resources Information Center

California Collaborative on District Reform, 2017

2017-01-01

This document synthesizes the findings from the evaluations of four statewide programs designed to provide support for underperforming schools and districts in California as part of the state accountability system: (1) Immediate Intervention/Underperforming Schools Program (II/USP); (2) High Priority Schools Grant (HPSG) Program; (3) School…

Effective Programs for Elementary Science: A Best-Evidence Synthesis. Educator's Summary

ERIC Educational Resources Information Center

Center for Research and Reform in Education, 2012

2012-01-01

Which science programs have been proven to help elementary students to succeed? To find out, this review summarizes evidence on three types of programs designed to improve the science achievement of students in grades K-6: (1) Inquiry-oriented programs without science kits, such as Increasing Conceptual Challenge, Science IDEAS, and Collaborative…

U.S.-Based Short-Term Public Health Cultural Immersion Experience for Chinese Undergraduate Students

ERIC Educational Resources Information Center

Powell, Dorothy Lewis; Biederman, Donna J.

2017-01-01

A U.S. and Chinese university developed a short-term student exchange program in public/community health. The program--which consisted of lectures, seminars, field trips, cross-cultural experiences, and a synthesis excursion--resulted in high levels of program satisfaction, increased intrapersonal awareness, and skill acquisition. Program content…

A Program of Research and Education to Advance the Design, Synthesis, and Optimization of Aero-Space System Concepts

NASA Technical Reports Server (NTRS)

Sandusky, Robert

2002-01-01

Since its inception in December 1999, the program has provided support for a total of 11 Graduate Research Scholar Assistants, of these, 6 have completed their MS degree program. The program has generated 3 MS theses and a total of 4 publications/presentations.

STC synthesis of real-time driver information for congestion management : research project capsule.

DOT National Transportation Integrated Search

2014-02-01

The main focus of this synthesis report is to compile a technical summary of past and current research, as : well as the state of the practice, on the role of real-time information in congestion mitigation programs. The : speci c objectives are to...

MPA-11: Materials Synthesis and Integrated Devices; Overview of an Applied Energy Group

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

Dattelbaum, Andrew Martin

Our mission is to provide innovative and creative chemical synthesis and materials science solutions to solve materials problems across the LANL missions. Our group conducts basic and applied research in areas related to energy security as well as problems relevant to the Weapons Program.

Distributed Drug Discovery: Advancing Chemical Education through Contextualized Combinatorial Solid-Phase Organic Laboratories

ERIC Educational Resources Information Center

Scott, William L.; Denton, Ryan E.; Marrs, Kathleen A.; Durrant, Jacob D.; Samaritoni, J. Geno; Abraham, Milata M.; Brown, Stephen P.; Carnahan, Jon M.; Fischer, Lindsey G.; Glos, Courtney E.; Sempsrott, Peter J.; O'Donnell, Martin J.

2015-01-01

The Distributed Drug Discovery (D3) program trains students in three drug discovery disciplines (synthesis, computational analysis, and biological screening) while addressing the important challenge of discovering drug leads for neglected diseases. This article focuses on implementation of the synthesis component in the second-semester…

Designing and Implementing a Capstone Gerontology Seminar: Synthesis and Action

ERIC Educational Resources Information Center

Sasser, Jennifer R.

2005-01-01

This paper focuses on the design and implementation of Gerontology: Synthesis and Action, the capstone seminar for the undergraduate and graduate certificate in gerontology program at Marylhurst University, a small, private liberal arts university in the Portland, Oregon metropolitan area. The institutional and programmatic context in which this…

Synthesis of calculational methods for design and analysis of radiation shields for nuclear rocket systems

NASA Technical Reports Server (NTRS)

Capo, M. A.; Disney, R. K.; Jordan, T. A.; Soltesz, R. G.; Woodsum, H. C.

1969-01-01

Eight computer programs make up a nine volume synthesis containing two design methods for nuclear rocket radiation shields. The first design method is appropriate for parametric and preliminary studies, while the second accomplishes the verification of a final nuclear rocket reactor design.

Lesbian, Gay, Bisexual, and Transgender Youth with Disabilities: A Meta-Synthesis

ERIC Educational Resources Information Center

Duke, Thomas Scott

2011-01-01

This meta-synthesis of empirical and nonempirical literature analyzed 24 journal articles and book chapters that addressed the intersection of disability, [homo]sexuality, and gender identity/expression in P-12 schools, colleges and universities, supported living programs, and other educational and social contexts in Australia, Belgium, Canada,…

Summer Synthesis Institutes: A Novel Approach for Transformative Research and Student Career Development

NASA Astrophysics Data System (ADS)

Wilson, J.; Hermans, C. M.

2010-12-01

It is believed that breakthroughs tend to occur when small groups of highly motivated scientists are driven by challenges encountered in real problem-solving situations and given the freedom to experiment with new ideas. Summer synthesis institutes provide a mechanism to facilitiate these breakthroughs and by which graduate students may engage in interdisciplinary research in a way that is not often available in their normal course of study. In this presentation we examine two complementary models of summer synthesis institutes in hydrology, how these intensive programs facilitate scientific outcomes and the impact of synthesis and the summer institute model on student perceptions of academic roles, collaboration opportunities and team science. Five summer synthesis institutes were held over three years, sharing similar duration and structure but different degrees of participant interdisciplinarity and focus questions. Through informal assessments, this presentation will demonstrate how these programs offered a unique opportunity for the development of student-student and student-mentor relationships and facilitated deeper understanding of a student’s own research as well as new techniques, perspective and disciplines. Additionally, though the summer synthesis institute model offers a unique ability to leverage limited funding (on the order of a single graduate student) to advance earth sciences, the model also presents specific challenges for research follow-through and may require specific content and interpersonal dynamics for optimum success.

Two distinct modes of RecA action are required for DNA polymerase V-catalyzed translesion synthesis.

PubMed

Pham, Phuong; Seitz, Erica M; Saveliev, Sergei; Shen, Xuan; Woodgate, Roger; Cox, Michael M; Goodman, Myron F

2002-08-20

SOS mutagenesis in Escherichia coli requires DNA polymerase V (pol V) and RecA protein to copy damaged DNA templates. Here we show that two distinct biochemical modes for RecA protein are necessary for pol V-catalyzed translesion synthesis. One RecA mode is characterized by a strong stimulation in nucleotide incorporation either directly opposite a lesion or at undamaged template sites, but by the absence of lesion bypass. A separate RecA mode is necessary for translesion synthesis. The RecA1730 mutant protein, which was identified on the basis of its inability to promote pol V (UmuD'(2)C)-dependent UV-mutagenesis, appears proficient for the first mode of RecA action but is deficient in the second mode. Data are presented suggesting that the two RecA modes are "nonfilamentous". That is, contrary to current models for SOS mutagenesis, formation of a RecA nucleoprotein filament may not be required for copying damaged DNA templates. Instead, SOS mutagenesis occurs when pol V interacts with two RecA molecules, first at a 3' primer end, upstream of a template lesion, where RecA mode 1 stimulates pol V activity, and subsequently at a site immediately downstream of the lesion, where RecA mode 2 cocatalyzes lesion bypass. We posit that in vivo assembly of a RecA nucleoprotein filament may be required principally to target pol V to a site of DNA damage and to stabilize the pol V-RecA interaction at the lesion. However, it is only a RecA molecule located at the 3' filament tip, proximal to a damaged template base, that is directly responsible for translesion synthesis.

Two distinct modes of RecA action are required for DNA polymerase V-catalyzed translesion synthesis

PubMed Central

Pham, Phuong; Seitz, Erica M.; Saveliev, Sergei; Shen, Xuan; Woodgate, Roger; Cox, Michael M.; Goodman, Myron F.

2002-01-01

SOS mutagenesis in Escherichia coli requires DNA polymerase V (pol V) and RecA protein to copy damaged DNA templates. Here we show that two distinct biochemical modes for RecA protein are necessary for pol V-catalyzed translesion synthesis. One RecA mode is characterized by a strong stimulation in nucleotide incorporation either directly opposite a lesion or at undamaged template sites, but by the absence of lesion bypass. A separate RecA mode is necessary for translesion synthesis. The RecA1730 mutant protein, which was identified on the basis of its inability to promote pol V (UmuD′2C)-dependent UV-mutagenesis, appears proficient for the first mode of RecA action but is deficient in the second mode. Data are presented suggesting that the two RecA modes are “nonfilamentous”. That is, contrary to current models for SOS mutagenesis, formation of a RecA nucleoprotein filament may not be required for copying damaged DNA templates. Instead, SOS mutagenesis occurs when pol V interacts with two RecA molecules, first at a 3′ primer end, upstream of a template lesion, where RecA mode 1 stimulates pol V activity, and subsequently at a site immediately downstream of the lesion, where RecA mode 2 cocatalyzes lesion bypass. We posit that in vivo assembly of a RecA nucleoprotein filament may be required principally to target pol V to a site of DNA damage and to stabilize the pol V-RecA interaction at the lesion. However, it is only a RecA molecule located at the 3′ filament tip, proximal to a damaged template base, that is directly responsible for translesion synthesis. PMID:12177433

Accredited hand surgery fellowship Web sites: analysis of content and accessibility.

PubMed

Trehan, Samir K; Morrell, Nathan T; Akelman, Edward

2015-04-01

To assess the accessibility and content of accredited hand surgery fellowship Web sites. A list of all accredited hand surgery fellowships was obtained from the online database of the American Society for Surgery of the Hand (ASSH). Fellowship program information on the ASSH Web site was recorded. All fellowship program Web sites were located via Google search. Fellowship program Web sites were analyzed for accessibility and content in 3 domains: program overview, application information/recruitment, and education. At the time of this study, there were 81 accredited hand surgery fellowships with 169 available positions. Thirty of 81 programs (37%) had a functional link on the ASSH online hand surgery fellowship directory; however, Google search identified 78 Web sites. Three programs did not have a Web site. Analysis of content revealed that most Web sites contained contact information, whereas information regarding the anticipated clinical, research, and educational experiences during fellowship was less often present. Furthermore, information regarding past and present fellows, salary, application process/requirements, call responsibilities, and case volume was frequently lacking. Overall, 52 of 81 programs (64%) had the minimal online information required for residents to independently complete the fellowship application process. Hand fellowship program Web sites could be accessed either via the ASSH online directory or Google search, except for 3 programs that did not have Web sites. Although most fellowship program Web sites contained contact information, other content such as application information/recruitment and education, was less frequently present. This study provides comparative data regarding the clinical and educational experiences outlined on hand fellowship program Web sites that are of relevance to residents, fellows, and academic hand surgeons. This study also draws attention to various ways in which the hand surgery fellowship application process can be made more user-friendly and efficient. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

GASP- General Aviation Synthesis Program. Volume 7: Economics

NASA Technical Reports Server (NTRS)

1978-01-01

The economic analysis includes: manufacturing costs; labor costs; parts costs; operating costs; markups and consumer price. A user's manual for a computer program to calculate the final consumer price is included.

Synthesis of fisetin and 2',4',6'-trihydroxydihyrochalcone 4'-O-β-neohesperidoside based on site-selective deacetylation and deoxygenation.

PubMed

Tsunekawa, Ryuji; Hanaya, Kengo; Higashibayashi, Shuhei; Sugai, Takeshi

2018-04-26

Fisetin and 2',4',6'-trihydroxydihyrochalcone 4'-O-β-neohesperidoside were synthesized from commercially available quercetin and naringin in five steps. The key steps are site-selective deacetylation and subsequent deoxygenation. The target molecules were obtained in 37% and 23% yields from the starting materials, respectively.

The Mitochondrial Phosphate-to-Oxygen Ratio Is Not an Integer

ERIC Educational Resources Information Center

Silverstein, Todd

2005-01-01

For many years, mitochondrial phosphate-to-oxygen ratios were believed to be integral values: 3 for ATP/NADH and 2 for ATP/FADH[subscript 2]. The chemiosmotic theory has demonstrated that this need not be the case because coupling sites do not directly synthesize ATP. Coupling between coupling site redox reactions and ATP synthesis occurs via…

Rapid and accurate synthesis of TALE genes from synthetic oligonucleotides.

PubMed

Wang, Fenghua; Zhang, Hefei; Gao, Jingxia; Chen, Fengjiao; Chen, Sijie; Zhang, Cuizhen; Peng, Gang

2016-01-01

Custom synthesis of transcription activator-like effector (TALE) genes has relied upon plasmid libraries of pre-fabricated TALE-repeat monomers or oligomers. Here we describe a novel synthesis method that directly incorporates annealed synthetic oligonucleotides into the TALE-repeat units. Our approach utilizes iterative sets of oligonucleotides and a translational frame check strategy to ensure the high efficiency and accuracy of TALE-gene synthesis. TALE arrays of more than 20 repeats can be constructed, and the majority of the synthesized constructs have perfect sequences. In addition, this novel oligonucleotide-based method can readily accommodate design changes to the TALE repeats. We demonstrated an increased gene targeting efficiency against a genomic site containing a potentially methylated cytosine by incorporating non-conventional repeat variable di-residue (RVD) sequences.

Biochemical analysis of active site mutations of human polymerase η.

PubMed

Suarez, Samuel C; Beardslee, Renee A; Toffton, Shannon M; McCulloch, Scott D

2013-01-01

DNA polymerase η (pol η) plays a critical role in suppressing mutations caused by the bypass of cis-syn cyclobutane pyrimidine dimers (CPD) that escape repair. There is evidence this is also the case for the oxidative lesion 7,8-dihydro-8-oxo-guanine (8-oxoG). Both of these lesions cause moderate to severe blockage of synthesis when encountered by replicative polymerases, while pol η displays little no to pausing during translesion synthesis. However, since lesion bypass does not remove damaged DNA from the genome and can possibly be accompanied by errors in synthesis during bypass, the process is often called 'damage tolerance' to delineate it from classical DNA repair pathways. The fidelity of lesion bypass is therefore of importance when determining how pol η suppresses mutations after DNA damage. As pol η has been implicated in numerous in vivo pathways other than lesion bypass, we wanted to better understand the molecular mechanisms involved in the relatively low-fidelity synthesis displayed by pol η. To that end, we have created a set of mutant pol η proteins each containing a single amino acid substitution in the active site and closely surrounding regions. We determined overall DNA synthesis ability as well as the efficiency and fidelity of bypass of thymine-thymine CPD (T-T CPD) and 8-oxoG containing DNA templates. Our results show that several amino acids are critical for normal polymerase function, with changes in overall activity and fidelity being observed. Of the mutants that retain polymerase activity, we demonstrate that amino acids Q38, Y52, and R61 play key roles in determining polymerase fidelity, with substation of alanine causing both increases and decreases in fidelity. Remarkably, the Q38A mutant displays increased fidelity during synthesis opposite 8-oxoG but decreased fidelity during synthesis opposite a T-T CPD. Copyright © 2013 Elsevier B.V. All rights reserved.

SITE TECHNOLOGY PROFILES, TENTH EDITION, VOLUME I - DEMONSTRATION PROGRAM

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its thirteenth year, is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine us...

The comparative effectiveness of clinic, work-site, phone, and Web-based tobacco treatment programs.

PubMed

An, Lawrence C; Betzner, Anne; Schillo, Barbara; Luxenberg, Michael G; Christenson, Matthew; Wendling, Ann; Saul, Jessie E; Kavanaugh, Annette

2010-10-01

Tobacco treatment programs may be offered in clinical settings, at work-sites, via telephone helplines, or over the Internet. Little comparative data exist regarding the real-world effectiveness of these programs. This paper compares the reach, effectiveness, and costs of these different modes of cessation assistance. This is an observational study of cohorts of participants in Minnesota's QUITPLAN programs in 2004. Cessation assistance was provided in person at 9 treatment centers, using group counseling at 68 work-sites, via a telephone helpline, or via the Internet. The main outcomes of the study are enrollment by current smokers, self-reported 30-day abstinence, and cost per quit. Reach was calculated statewide for the helpline and Web site, regionally for the treatment centers, and for the employee population for work-site programs. Enrollment was greatest for the Web site (n = 4,698), followed by the helpline (n = 2,351), treatment centers (n = 616), and work-sites (n = 479). The Web site attracted younger smokers. Smokers at treatment centers had higher levels of nicotine dependence. The helpline reached more socially disadvantaged smokers. Responder 30-day abstinence rates were higher for the helpline (29.3%), treatment centers (25.8%), and work-sites (19.6%) compared with the online program (12.5%). These differences persisted after controlling for baseline differences in participant characteristics and use of pharmacological therapy. The cost per quit was lowest for the Web site program ($291 per quit, 95% CI = $229-$372). Treatment center, work-site, helpline, and Web site programs differ in their reach, effectiveness, and estimated cost per quit. Each program plays a part in assisting populations of tobacco users in quitting.

RNAiFOLD: a constraint programming algorithm for RNA inverse folding and molecular design.

PubMed

Garcia-Martin, Juan Antonio; Clote, Peter; Dotu, Ivan

2013-04-01

Synthetic biology is a rapidly emerging discipline with long-term ramifications that range from single-molecule detection within cells to the creation of synthetic genomes and novel life forms. Truly phenomenal results have been obtained by pioneering groups--for instance, the combinatorial synthesis of genetic networks, genome synthesis using BioBricks, and hybridization chain reaction (HCR), in which stable DNA monomers assemble only upon exposure to a target DNA fragment, biomolecular self-assembly pathways, etc. Such work strongly suggests that nanotechnology and synthetic biology together seem poised to constitute the most transformative development of the 21st century. In this paper, we present a Constraint Programming (CP) approach to solve the RNA inverse folding problem. Given a target RNA secondary structure, we determine an RNA sequence which folds into the target structure; i.e. whose minimum free energy structure is the target structure. Our approach represents a step forward in RNA design--we produce the first complete RNA inverse folding approach which allows for the specification of a wide range of design constraints. We also introduce a Large Neighborhood Search approach which allows us to tackle larger instances at the cost of losing completeness, while retaining the advantages of meeting design constraints (motif, GC-content, etc.). Results demonstrate that our software, RNAiFold, performs as well or better than all state-of-the-art approaches; nevertheless, our approach is unique in terms of completeness, flexibility, and the support of various design constraints. The algorithms presented in this paper are publicly available via the interactive webserver http://bioinformatics.bc.edu/clotelab/RNAiFold; additionally, the source code can be downloaded from that site.

Multi-regional synthesis of temporal trends in biotic assemblages in streams and rivers of the continental United States

USGS Publications Warehouse

Miller, Matthew P.; Brasher, Anne M.D.; Keenen, Jonathan G.

2013-01-01

Biotic assemblages in aquatic ecosystems are excellent integrators and indicators of changing environmental conditions within a watershed. Therefore, temporal changes in abiotic environmental variables often can be inferred from temporal changes in biotic assemblages. Algae, macroinvertebrate, and fish assemblage data were collected from 91 sampling sites in 4 geographic regions (northeastern/north-central, southeastern, south-central, and western), collectively encompassing the continental United States, from 1993 to 2009 as part of the U.S. Geological Survey National Water-Quality Assessment Program. This report uses a multivariate approach to synthesize temporal trends in biotic assemblages and correlations with relevant abiotic parameters as a function of biotic assemblage, geographic region, and land use. Of the three groups of biota, algal assemblages had temporal trends at the greatest percentage of sites. Of the regions, a greater percentage of sites in the northeastern/north-central and western regions had temporal trends in biotic assemblages. In terms of land use, a greater percentage of watersheds draining agricultural, urban, and undeveloped areas had significant temporal changes in biota, as compared to watersheds with mixed use. Correlations between biotic assemblages and abiotic variables indicate that, in general, macroinvertebrate assemblages correlated with water quality and fish assemblages correlated with physical habitat. Taken together, results indicate that there are regional differences in how individual biotic assemblages (algae, macroinvertebrates, and fish) respond to different abiotic drivers of change.

22 CFR 502.6 - Terms of use for accessing program materials available on agency Web sites.

Code of Federal Regulations, 2014 CFR

2014-04-01

... available on agency Web sites. 502.6 Section 502.6 Foreign Relations BROADCASTING BOARD OF GOVERNORS... program materials available on agency Web sites. (a) By accessing Agency Web sites, Requestors agree to all the Terms of Use available on those Web sites. (b) All Requestors are advised that Agency program...

Rapid Construction of a Benzo-Fused Indoxamycin Core Enabled by Site-Selective C-H Functionalizations.

PubMed

Bedell, T Aaron; Hone, Graham A B; Valette, Damien; Yu, Jin-Quan; Davies, Huw M L; Sorensen, Erik J

2016-07-11

Methods for functionalizing carbon-hydrogen bonds are featured in a new synthesis of the tricyclic core architecture that characterizes the indoxamycin family of secondary metabolites. A unique collaboration between three laboratories has engendered a design for synthesis featuring two sequential C-H functionalization reactions, namely a diastereoselective dirhodium carbene insertion followed by an ester-directed oxidative Heck cyclization, to rapidly assemble the congested tricyclic core of the indoxamycins. This project exemplifies how multi-laboratory collaborations can foster conceptually novel approaches to challenging problems in chemical synthesis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

GASP- General Aviation Synthesis Program. Volume 1: Main program. Part 1: Theoretical development

NASA Technical Reports Server (NTRS)

Hague, D.

1978-01-01

The General Aviation synthesis program performs tasks generally associated with aircraft preliminary design and allows an analyst the capability of performing parametric studies in a rapid manner. GASP emphasizes small fixed-wing aircraft employing propulsion systems varying froma single piston engine with fixed pitch propeller through twin turboprop/ turbofan powered business or transport type aircraft. The program, which may be operated from a computer terminal in either the batch or interactive graphic mode, is comprised of modules representing the various technical disciplines integrated into a computational flow which ensures that the interacting effects of design variables are continuously accounted for in the aircraft sizing procedure. The model is a useful tool for comparing configurations, assessing aircraft performance and economics, performing tradeoff and sensitivity studies, and assessing the impact of advanced technologies on aircraft performance and economics.

Solid State Division progress report for period ending September 30, 1993

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

Green, P.H.; Hinton, L.W.

1994-08-01

This report covers research progress in the Solid State Division from April 1, 1992, to September 30, 1993. During this period, the division conducted a broad, interdisciplinary materials research program with emphasis on theoretical solid state physics, neutron scattering, synthesis and characterization of materials, ion beam and laser processing, and the structure of solids and surfaces. This research effort was enhanced by new capabilities in atomic-scale materials characterization, new emphasis on the synthesis and processing of materials, and increased partnering with industry and universities. The theoretical effort included a broad range of analytical studies, as well as a new emphasismore » on numerical simulation stimulated by advances in high-performance computing and by strong interest in related division experimental programs. Superconductivity research continued to advance on a broad front from fundamental mechanisms of high-temperature superconductivity to the development of new materials and processing techniques. The Neutron Scattering Program was characterized by a strong scientific user program and growing diversity represented by new initiatives in complex fluids and residual stress. The national emphasis on materials synthesis and processing was mirrored in division research programs in thin-film processing, surface modification, and crystal growth. Research on advanced processing techniques such as laser ablation, ion implantation, and plasma processing was complemented by strong programs in the characterization of materials and surfaces including ultrahigh resolution scanning transmission electron microscopy, atomic-resolution chemical analysis, synchrotron x-ray research, and scanning tunneling microscopy.« less

Self-Assembly of Coordinative Supramolecular Polygons with Open Binding Sites

PubMed Central

Zheng, Yao-Rong; Wang, Ming; Kobayashi, Shiho; Stang, Peter J.

2011-01-01

The design and synthesis of coordinative supramolecular polygons with open binding sites is described. Coordination-driven self-assembly of 2,6-bis(pyridin-4-ylethynyl)pyridine with 60° and 120° organoplatinum acceptors results in quantitative formation of a supramolecular rhomboid and hexagon, respectively, both bearing open pyridyl binding sites. The structures were determined by multinuclear (31P and 1H) NMR spectroscopy and electrospray ionization (ESI) mass spectrometry, along with a computational study. PMID:21516167

Self-Assembly of Coordinative Supramolecular Polygons with Open Binding Sites.

PubMed

Zheng, Yao-Rong; Wang, Ming; Kobayashi, Shiho; Stang, Peter J

2011-04-27

The design and synthesis of coordinative supramolecular polygons with open binding sites is described. Coordination-driven self-assembly of 2,6-bis(pyridin-4-ylethynyl)pyridine with 60° and 120° organoplatinum acceptors results in quantitative formation of a supramolecular rhomboid and hexagon, respectively, both bearing open pyridyl binding sites. The structures were determined by multinuclear ((31)P and (1)H) NMR spectroscopy and electrospray ionization (ESI) mass spectrometry, along with a computational study.

SITE TECHNOLOGY PROFILES, TENTH EDITION, VOLUME 3 - MEASUREMENT AND MONITORING PROGRAM

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its thirteenth year, is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine us...

SITE TECHNOLOGY PROFILES, TENTH EDITION, VOLUME 2 - EMERGING TECHNOLOGY PROGRAM

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its thirteenth year, is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine us...

SITE TECHNOLOGY PROFILES - 11TH EDITION - DEMONSTRATION PROGRAM, VOLUME 1

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its eleventh year is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine use o...

Understanding Self-Catalyzed Epitaxial Growth of III-V Nanowires toward Controlled Synthesis.

PubMed

Zi, Yunlong; Suslov, Sergey; Yang, Chen

2017-02-08

The self-catalyzed growth of III-V nanowires has drawn plenty of attention due to the potential of integration in current Si-based technologies. The homoparticle-assisted vapor-liquid-solid growth mechanism has been demonstrated for self-catalyzed III-V nanowire growth. However, the understandings of the preferred growth sites of these nanowires are still limited, which obstructs the controlled synthesis and the applications of self-catalyzed nanowire arrays. Here, we experimentally demonstrated that thermally created pits could serve as the preferred sites for self-catalyzed InAs nanowire growth. On that basis, we performed a pregrowth annealing strategy to promote the nanowire density by enhancing the pits formation on the substrate surface and enable the nanowire growth on the substrate that was not capable to facilitate the growth. The discovery of the preferred self-catalyzed nanowire growth sites and the pregrowth annealing strategy have shown great potentials for controlled self-catalyzed III-V nanowire array growth with preferred locations and density.

Structure and mechanism of human DNA polymerase [eta

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

Biertümpfel, Christian; Zhao, Ye; Kondo, Yuji

2010-11-03

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase {eta} (Pol{eta}), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol{eta} at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol{eta} acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol{eta} orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assistmore » translesion synthesis. On the basis of the structures, eight Pol{eta} missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol{eta} in replicating through D loop and DNA fragile sites.« less

Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors.

PubMed

Mantoani, Susimaire P; Chierrito, Talita P C; Vilela, Adriana F L; Cardoso, Carmen L; Martínez, Ana; Carvalho, Ivone

2016-02-05

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. Currently, the only strategy for palliative treatment of AD is to inhibit acetylcholinesterase (AChE) in order to increase the concentration of acetylcholine in the synaptic cleft. Evidence indicates that AChE also interacts with the β-amyloid (Aβ) protein, acting as a chaperone and increasing the number and neurotoxicity of Aβ fibrils. It is known that AChE has two binding sites: the peripheral site, responsible for the interactions with Aβ, and the catalytic site, related with acetylcholine hydrolysis. In this work, we reported the synthesis and biological evaluation of a library of new tacrine-donepezil hybrids, as a potential dual binding site AChE inhibitor, containing a triazole-quinoline system. The synthesis of hybrids was performed in four steps using the click chemistry strategy. These compounds were evaluated as hAChE and hBChE inhibitors, and some derivatives showed IC50 values in the micro-molar range and were remarkably selective towards hAChE. Kinetic assays and molecular modeling studies confirm that these compounds block both catalytic and peripheral AChE sites. These results are quite interesting since the triazole-quinoline system is a new structural scaffold for AChE inhibitors. Furthermore, the synthetic approach is very efficient for the preparation of target compounds, allowing a further fruitful new chemical library optimization.

Aseptic nonunion of the tibia treated by intramedullary osteosynthesis.

PubMed

Gualdrini, G; Rollo, G; Montanari, A; Zinghi, G F

1996-01-01

The authors report 52 cases of aseptic nonunion of the tibia treated by intramedullary osteosynthesis. The means of synthesis used were the Küntscher nail, the Eiffel Tower Rush nail, and the Grosse-Kempf nail. Which means of synthesis was used depended on the site and the features of the nonunion. Healing occurred in all of the cases after an average of 5 months. Mean follow-up was 4.5 years.

Synthesis and contractile activity of the C-terminal heptapeptide of substance P with N5-dimethyl glutamine in the 6-position. Active site studies.

PubMed

Poulos, C P; Pinas, N; Theodoropoulos, D

1980-09-15

The synthesis and testing of [N5-dimethyl-Gln6]-SP5-11 showed 37 +/- 12% contractile activity relative to SP, and intrinsic efficacy 98 +/- 4%. This finding indicates that the carboxamide groups of the dual Gln5-Cln6 moiety are not equally related with the contractile response of the C-terminal heptapeptide of SP.

DEVELOPMENT OF EMERGING TECHNOLOGIES WITHIN THE SITE PROGRAM

EPA Science Inventory

The Site Program is formed by five research programs: the Demonstration Program, the Emerging Technology Program, the Measurement and Monitoring Technology Development Program, the Innovative Technology Program, and the Technology Transfer Program. The Emerging Technology (ET) P...

SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM: PROGRESS AND ACCOMPLISHMENTS - FISCAL YEAR 1991

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) program was the first major program for demonstrating and evaluating full-scale innovative treatment technologies at hazardous waste sites. Having concluded its fifth year, the SITE program is recognized as a leading advocate ...

THE SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM; ANNUAL REPORT TO CONGRESS, FY 1998

EPA Science Inventory

This document summarizes the accomplishments and activities of the Superfund Innovative Technology Evaluation (SITE) Program for 1998. General information on the SITE program is presented. In addition, cost savings effected by the SITE program were estimated and are presented. ...

Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use.

PubMed

Atkins, John F; Loughran, Gary; Bhatt, Pramod R; Firth, Andrew E; Baranov, Pavel V

2016-09-06

Genetic decoding is not 'frozen' as was earlier thought, but dynamic. One facet of this is frameshifting that often results in synthesis of a C-terminal region encoded by a new frame. Ribosomal frameshifting is utilized for the synthesis of additional products, for regulatory purposes and for translational 'correction' of problem or 'savior' indels. Utilization for synthesis of additional products occurs prominently in the decoding of mobile chromosomal element and viral genomes. One class of regulatory frameshifting of stable chromosomal genes governs cellular polyamine levels from yeasts to humans. In many cases of productively utilized frameshifting, the proportion of ribosomes that frameshift at a shift-prone site is enhanced by specific nascent peptide or mRNA context features. Such mRNA signals, which can be 5' or 3' of the shift site or both, can act by pairing with ribosomal RNA or as stem loops or pseudoknots even with one component being 4 kb 3' from the shift site. Transcriptional realignment at slippage-prone sequences also generates productively utilized products encoded trans-frame with respect to the genomic sequence. This too can be enhanced by nucleic acid structure. Together with dynamic codon redefinition, frameshifting is one of the forms of recoding that enriches gene expression. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Design and Synthesis of Cannabinoid 1 Receptor (CB1R) Allosteric Modulators: Drug Discovery Applications.

PubMed

Kulkarni, Abhijit R; Garai, Sumanta; Janero, David R; Thakur, Ganesh A

2017-01-01

Also expressed in various peripheral tissues, the type-1 cannabinoid receptor (CB1R) is the predominant G protein-coupled receptor (GPCR) in brain, where it is responsible for retrograde control of neurotransmitter release. Cellular signaling mediated by CB1R is involved in numerous physiological processes, and pharmacological CB1R modulation is considered a tenable therapeutic approach for diseases ranging from substance-use disorders and glaucoma to metabolic syndrome. Despite the design and synthesis of a variety of bioactive small molecules targeted to the CB1R orthosteric ligand-binding site, the potential of CB1R as a therapeutic GPCR has been largely unrealized due to adverse events associated with typical orthosteric CB1R agonists and antagonists/inverse agonists. Modulation of CB1R-mediated signal transmission by targeting alternative allosteric ligand-binding site(s) on the receptor has garnered interest as a potentially safer and more effective therapeutic modality. This chapter highlights the design and synthesis of novel, pharmacologically active CB1R allosteric modulators and emphasizes how their molecular properties and the positive and negative allosteric control they exert can lead to improved CB1R-targeted pharmacotherapeutics, as well as designer covalent probes that can be used to map CB1R allosteric binding domains and inform structure-based drug design. © 2017 Elsevier Inc. All rights reserved.

A gratuitous β-Lactamase inducer uncovers hidden active site dynamics of the Staphylococcus aureus BlaR1 sensor domain.

PubMed

Frederick, Thomas E; Peng, Jeffrey W

2018-01-01

Increasing evidence shows that active sites of proteins have non-trivial conformational dynamics. These dynamics include active site residues sampling different local conformations that allow for multiple, and possibly novel, inhibitor binding poses. Yet, active site dynamics garner only marginal attention in most inhibitor design efforts and exert little influence on synthesis strategies. This is partly because synthesis requires a level of atomic structural detail that is frequently missing in current characterizations of conformational dynamics. In particular, while the identity of the mobile protein residues may be clear, the specific conformations they sample remain obscure. Here, we show how an appropriate choice of ligand can significantly sharpen our abilities to describe the interconverting binding poses (conformations) of protein active sites. Specifically, we show how 2-(2'-carboxyphenyl)-benzoyl-6-aminopenicillanic acid (CBAP) exposes otherwise hidden dynamics of a protein active site that binds β-lactam antibiotics. When CBAP acylates (binds) the active site serine of the β-lactam sensor domain of BlaR1 (BlaRS), it shifts the time scale of the active site dynamics to the slow exchange regime. Slow exchange enables direct characterization of inter-converting protein and bound ligand conformations using NMR methods. These methods include chemical shift analysis, 2-d exchange spectroscopy, off-resonance ROESY of the bound ligand, and reduced spectral density mapping. The active site architecture of BlaRS is shared by many β-lactamases of therapeutic interest, suggesting CBAP could expose functional motions in other β-lactam binding proteins. More broadly, CBAP highlights the utility of identifying chemical probes common to structurally homologous proteins to better expose functional motions of active sites.

Parks promoting physical activity: synthesis of findings from interventions in seven national parks.

PubMed

Hoehner, Christine M; Brownson, Ross C; Allen, Diana; Gramann, James; Behrens, Timothy K; Floyd, Myron F; Leahy, Jessica; Liddle, Joseph B; Smaldone, David; Spain, Diara D; Tardona, Daniel R; Ruthmann, Nicholas P; Seiler, Rachel L; Yount, Byron W

2010-03-01

We synthesized the results of 7 National Park Service pilot interventions designed to increase awareness of the health benefits from participation in recreation at national parks and to increase physical activity by park visitors. A content analysis was conducted of the final evaluation reports of the 7 participating parks. Pooled data were also analyzed from a standardized trail-intercept survey administered in 3 parks. The theme of new and diverse partnerships was the most common benefit reported across the 7 sites. The 2 parks that focused on youth showed evidence of an increase in awareness of the benefits of physical activity. Many of the other sites found high levels of awareness at baseline (approaching 90%), suggesting little room for improvement. Five of the 7 projects showed evidence of an increase in physical activity that was associated with the intervention activities. Multivariate analyses suggested that the media exposure contributed to a small but significant increase in awareness of the importance of physical activity (6%) and number of active visits (7%). Enhancements and replication of these programs represents a promising opportunity for improving partnerships between public health and recreation to increase physical activity.

Reversible multi-electron redox chemistry of π-conjugated N-containing heteroaromatic molecule-based organic cathodes

NASA Astrophysics Data System (ADS)

Peng, Chengxin; Ning, Guo-Hong; Su, Jie; Zhong, Guiming; Tang, Wei; Tian, Bingbing; Su, Chenliang; Yu, Dingyi; Zu, Lianhai; Yang, Jinhu; Ng, Man-Fai; Hu, Yong-Sheng; Yang, Yong; Armand, Michel; Loh, Kian Ping

2017-07-01

Even though organic molecules with well-designed functional groups can be programmed to have high electron density per unit mass, their poor electrical conductivity and low cycle stability limit their applications in batteries. Here we report a facile synthesis of π-conjugated quinoxaline-based heteroaromatic molecules (3Q) by condensation of cyclic carbonyl molecules with o-phenylenediamine. 3Q features a number of electron-deficient pyrazine sites, where multiple redox reactions take place. When hybridized with graphene and coupled with an ether-based electrolyte, an organic cathode based on 3Q molecules displays a discharge capacity of 395 mAh g-1 at 400 mA g-1 (1C) in the voltage range of 1.2-3.9 V and a nearly 70% capacity retention after 10,000 cycles at 8 A g-1. It also exhibits a capacity of 222 mAh g-1 at 20C, which corresponds to 60% of the initial specific capacity. Our results offer evidence that heteroaromatic molecules with multiple redox sites are promising in developing high-energy-density, long-cycle-life organic rechargeable batteries.

Functionalized MIL-101 with imidazolium-based ionic liquids for the cycloaddition of CO2 and epoxides under mild condition

NASA Astrophysics Data System (ADS)

Liu, Dan; Li, Gang; Liu, Haiou

2018-01-01

A kind of multi-functional sites metal-organic framework (MOF) composite (MIL-101-IMBr) was successfully prepared by post-synthesis modification of MIL-101 with imidazolium-based ionic liquids. The ionic liquids not only functionalize as basic sites but also provide halide anions, which serve as a nucleophile in cycloaddition reaction. The prepared functional MOF materials were characterized by X-ray diffraction, fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, N2 adsorption-desorption and CO2 temperature programmed desorption. The results of fourier transform infrared spectroscopy and energy dispersive spectroscopy show that the MIL-101-IMBr composite was successfully synthesized. The N2 adsorption-desorption results clearly demonstrated that the modified composites still preserve high BET surface area and total pore volume. The composite exhibits high catalytic activity for the cycloaddition of CO2 with epoxides under mild and co-catalyst free conditions. The conversion of propylene oxide was 95.8% and the selectivity of cyclic carbonate was 97.6% under 0.8 MPa at 80 °C for 4 h. Moreover, the catalyst can be used for at least five times.

Substrate Specificity and Possible Heterologous Targets of Phytaspase, a Plant Cell Death Protease*

PubMed Central

Galiullina, Raisa A.; Kasperkiewicz, Paulina; Chichkova, Nina V.; Szalek, Aleksandra; Serebryakova, Marina V.; Poreba, Marcin; Drag, Marcin; Vartapetian, Andrey B.

2015-01-01

Plants lack aspartate-specific cell death proteases homologous to animal caspases. Instead, a subtilisin-like serine-dependent plant protease named phytaspase shown to be involved in the accomplishment of programmed death of plant cells is able to hydrolyze a number of peptide-based caspase substrates. Here, we determined the substrate specificity of rice (Oryza sativa) phytaspase by using the positional scanning substrate combinatorial library approach. Phytaspase was shown to display an absolute specificity of hydrolysis after an aspartic acid residue. The preceding amino acid residues, however, significantly influence the efficiency of hydrolysis. Efficient phytaspase substrates demonstrated a remarkable preference for an aromatic amino acid residue in the P3 position. The deduced optimum phytaspase recognition motif has the sequence IWLD and is strikingly hydrophobic. The established pattern was confirmed through synthesis and kinetic analysis of cleavage of a set of optimized peptide substrates. An amino acid motif similar to the phytaspase cleavage site is shared by the human gastrointestinal peptide hormones gastrin and cholecystokinin. In agreement with the established enzyme specificity, phytaspase was shown to hydrolyze gastrin-1 and cholecystokinin at the predicted sites in vitro, thus destroying the active moieties of the hormones. PMID:26283788

Suppression of dexamethasone-stimulated DNA synthesis in an oncogene construct containing rat cell line by a DNA site-oriented ligand of poly-ADP-ribose polymerase: 6-amino-1,2-benzopyrone

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

Kirsten, E.; Bauer, P.I.; Kun, E.

1991-03-01

The cellular inhibitory effects of 6-amino-1,2-benzopyrone (6-ABP), a DNA site-specific ligand of adenosine diphosphoribosyl transferase (ADPRT), were determined in a dexamethasone-sensitive EJ-ras gene construct containing cell line (14C cells). Dexamethansone in vitro transforms these cells to a tumorigenic phenotype and also stimulates cell replication. AT a nontoxic concentration 6-ABP treatment of intact cells for 4 days inhibits the dexamethasone-stimulated increment of cellular DNA content, depresses replicative DNA synthesis as assayed by thymidine incorporation to the level of cells that were not exposed to dexamethasone, and in permeabilized cells reduces the dexamethasone-stimulated increase of deoxyribonucleotide incorporation into DNA to the levelmore » of untreated cells. In situ pulse labeling of cells pretreated with 6-ABP indicated an inhibition of DNA synthesis at a stage prior to the formation of the 10-kb intermediate species. Neither dexamethasone nor the drug influenced the cellular quantity of ADPRT molecules, tested immunochemically.« less

Survival and activity of Streptococcus faecalis and Escherichia coli in petroleum-contaminated tropical marine waters

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

Santo Domingo, J.W.; Fuentes, F.A.; Hazen, T.C.

1987-12-31

The in situ survival and activity of Streptococcus faecalis and Escherichia coli were studied using membrane diffusion chambers in tropical marine waters receiving oil refinery effluents. Protein synthesis, DNA synthesis, respiration or fermentation, INT reduced per cell, and ATP per cell were used to measure physiological activity. Cell densities decreased significantly over time at both sites for both S. faecalis and E. coli; however, no significant differences in survival pattern were observed between S. faecalis and E.coli. Differences in protein synthesis between the two were only observed at a study site which was not heavily oiled. Although fecal streptococci havemore » been suggested as a better indicator of fecal contamination than fecal coliforms in marine waters, in this study both E. coli and S. faecalis survived and remained physiologically active for extended periods of time. These results suggest that the fecal streptococci group is not a better indicator of fecal contamination in tropical marine waters than the fecal coliform group, especially when that environment is high in long-chained hydrocarbons.« less

Translational autocontrol of the Escherichia coli ribosomal protein S15.

PubMed

Portier, C; Dondon, L; Grunberg-Manago, M

1990-01-20

When rpsO, the gene encoding the ribosomal protein S15 in Escherichia coli, is carried by a multicopy plasmid, the mRNA synthesis rate of S15 increases with the gene dosage but the rate of synthesis of S15 does not rise. A translational fusion between S15 and beta-galactosidase was introduced on the chromosome in a delta lac strain and the expression of beta-galactosidase studied under different conditions. The presence of S15 in trans represses the beta-galactosidase level five- to sixfold, while the synthesis rate of the S15-beta-galactosidase mRNA decreases by only 30 to 50%. These data indicate that S15 is subject to autogenous translational control. Derepressed mutants were isolated and sequenced. All the point mutations map in the second codon of S15, suggesting a location for the operator site that is very near to the translation initiation codon. However, the creation of deletion mutations shows that the operator extends into the 5' non-coding part of the message, thus overlapping the ribosome loading site.

Anion-Regulated Selective Generation of Cobalt Sites in Carbon: Toward Superior Bifunctional Electrocatalysis

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

Wan, Gang; Yang, Ce; Zhao, Wanpeng

The introduction of active transition metal sites (TMSs) in carbon enables the synthesis of noble-metal-free electrocatalysts for clean energy conversion applications, however, there are often multiple existing forms of TMSs, which are of different natures and catalytic models. Regulating the evolution of distinctive TMSs is highly desirable but remains challenging to date. Anions, as essential elements involved in the synthesis, have been totally neglected previously in the construction of TMSs. Herein, the effects of anions on the creation of different types of TMSs is investigated for the first time. It is found that the active cobalt-nitrogen sites tend to bemore » selectively constructed on the surface of N-doped carbon by using chloride, while metallic cobalt nanoparticles encased in protective graphite layers are the dominant forms of cobalt species with nitrate ions. The obtained catalysts demonstrate cobalt-sites-dependent activity for ORR and HER in acidic media. And the remarkably enhanced catalytic activities approaching that of benchmark Pt/C in acidic medium has been obtained on the catalyst dominated with cobalt-nitrogen sites, confirmed by the advanced spectroscopic . Our finding demonstrates a general paradigm of anion-regulated evolution of distinctive TMSs, providing a new pathway for enhancing performances of various targeted reactions related with TMSs.« less

Application of lean manufacturing concepts to drug discovery: rapid analogue library synthesis.

PubMed

Weller, Harold N; Nirschl, David S; Petrillo, Edward W; Poss, Michael A; Andres, Charles J; Cavallaro, Cullen L; Echols, Martin M; Grant-Young, Katherine A; Houston, John G; Miller, Arthur V; Swann, R Thomas

2006-01-01

The application of parallel synthesis to lead optimization programs in drug discovery has been an ongoing challenge since the first reports of library synthesis. A number of approaches to the application of parallel array synthesis to lead optimization have been attempted over the years, ranging from widespread deployment by (and support of) individual medicinal chemists to centralization as a service by an expert core team. This manuscript describes our experience with the latter approach, which was undertaken as part of a larger initiative to optimize drug discovery. In particular, we highlight how concepts taken from the manufacturing sector can be applied to drug discovery and parallel synthesis to improve the timeliness and thus the impact of arrays on drug discovery.

Computer-Aided Communication Satellite System Analysis and Optimization.

ERIC Educational Resources Information Center

Stagl, Thomas W.; And Others

Various published computer programs for fixed/broadcast communication satellite system synthesis and optimization are discussed. The rationale for selecting General Dynamics/Convair's Satellite Telecommunication Analysis and Modeling Program (STAMP) in modified form to aid in the system costing and sensitivity analysis work in the Program on…

Computer Series, 60: Bits and Pieces, 23.

ERIC Educational Resources Information Center

Moore, John W., Ed.

1985-01-01

Describes: (1) an interactive computer simulation for a science fair display of chromatography inks; (2) analytical chemistry programs; (3) microcomputer-assisted drills in organic synthesis; (4) programs for conformation analysis of ethane and butane; (5) MOLPIX--a program for generating and displaying molecular structures; and (6) chemical…

SITE TECHNOLOGY PROFILES - 11TH EDITION, EMERGING TECHNOLOGY PROGRAM, VOLUME 2

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its eleventh year is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine use o...

SITE TECHNOLOGY PROFILES - 11TH EDITION, MEASUREMENT AND MONITORING PROGRAM, VOLUME 3

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its eleventh year is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine use o...

Purchase of Microwave Reactors for Implementation of Small-scale Microwave-accelerated Organic Chemistry Laboratory Program in Undergraduate Curriculum and Synthetic Chemistry Research at HU

DTIC Science & Technology

2015-05-16

synthesis of iron magnetic nanoparticles is being investigated (Appendix A; Scheme IV). In the first step, precursor iron(III) chloride nanoparticles...and other methods. Currently, we are developing a two-step scheme for the synthesis of esters that will require distillation and/or column...recognize the link between them. We are developing for the above purpose, the microwave-assisted, two-step synthesis of high boiling point esters. The

Alternative approximation concepts for space frame synthesis

NASA Technical Reports Server (NTRS)

Lust, R. V.; Schmit, L. A.

1985-01-01

A structural synthesis methodology for the minimum mass design of 3-dimensionall frame-truss structures under multiple static loading conditions and subject to limits on displacements, rotations, stresses, local buckling, and element cross-sectional dimensions is presented. A variety of approximation concept options are employed to yield near optimum designs after no more than 10 structural analyses. Available options include: (A) formulation of the nonlinear mathematcal programming problem in either reciprocal section property (RSP) or cross-sectional dimension (CSD) space; (B) two alternative approximate problem structures in each design space; and (C) three distinct assumptions about element end-force variations. Fixed element, design element linking, and temporary constraint deletion features are also included. The solution of each approximate problem, in either its primal or dual form, is obtained using CONMIN, a feasible directions program. The frame-truss synthesis methodology is implemented in the COMPASS computer program and is used to solve a variety of problems. These problems were chosen so that, in addition to exercising the various approximation concepts options, the results could be compared with previously published work.

Systems Engineering Design Via Experimental Operation Research: Complex Organizational Metric for Programmatic Risk Environments (COMPRE)

NASA Technical Reports Server (NTRS)

Mog, Robert A.

1999-01-01

Unique and innovative graph theory, neural network, organizational modeling, and genetic algorithms are applied to the design and evolution of programmatic and organizational architectures. Graph theory representations of programs and organizations increase modeling capabilities and flexibility, while illuminating preferable programmatic/organizational design features. Treating programs and organizations as neural networks results in better system synthesis, and more robust data modeling. Organizational modeling using covariance structures enhances the determination of organizational risk factors. Genetic algorithms improve programmatic evolution characteristics, while shedding light on rulebase requirements for achieving specified technological readiness levels, given budget and schedule resources. This program of research improves the robustness and verifiability of systems synthesis tools, including the Complex Organizational Metric for Programmatic Risk Environments (COMPRE).

Carbon and energy fluxes in cropland ecosystems: a model-data comparison

USGS Publications Warehouse

Lokupitiya, E.; Denning, A. Scott; Schaefer, K.; Ricciuto, D.; Anderson, R.; Arain, M. A.; Baker, I.; Barr, A. G.; Chen, G.; Chen, J.M.; Ciais, P.; Cook, D.R.; Dietze, M.C.; El Maayar, M.; Fischer, M.; Grant, R.; Hollinger, D.; Izaurralde, C.; Jain, A.; Kucharik, C.J.; Li, Z.; Liu, S.; Li, L.; Matamala, R.; Peylin, P.; Price, D.; Running, S. W.; Sahoo, A.; Sprintsin, M.; Suyker, A.E.; Tian, H.; Tonitto, Christina; Torn, M.S.; Verbeeck, Hans; Verma, S.B.; Xue, Y.

2016-01-01

Croplands are highly productive ecosystems that contribute to land–atmosphere exchange of carbon, energy, and water during their short growing seasons. We evaluated and compared net ecosystem exchange (NEE), latent heat flux (LE), and sensible heat flux (H) simulated by a suite of ecosystem models at five agricultural eddy covariance flux tower sites in the central United States as part of the North American Carbon Program Site Synthesis project. Most of the models overestimated H and underestimated LE during the growing season, leading to overall higher Bowen ratios compared to the observations. Most models systematically under predicted NEE, especially at rain-fed sites. Certain crop-specific models that were developed considering the high productivity and associated physiological changes in specific crops better predicted the NEE and LE at both rain-fed and irrigated sites. Models with specific parameterization for different crops better simulated the inter-annual variability of NEE for maize-soybean rotation compared to those models with a single generic crop type. Stratification according to basic model formulation and phenological methodology did not explain significant variation in model performance across these sites and crops. The under prediction of NEE and LE and over prediction of H by most of the models suggests that models developed and parameterized for natural ecosystems cannot accurately predict the more robust physiology of highly bred and intensively managed crop ecosystems. When coupled in Earth System Models, it is likely that the excessive physiological stress simulated in many land surface component models leads to overestimation of temperature and atmospheric boundary layer depth, and underestimation of humidity and CO2 seasonal uptake over agricultural regions.

Nicotine Induced CpG methylation of Pax6 binding motif in StAR promoter reduces the gene expression and cortisol production

PubMed Central

Wang, Tingting; Chen, Man; Liu, Lian; Cheng, Huaiyan; Yan, You-E; Feng, Ying-Hong; Wang, Hui

2011-01-01

Steroidogenic acute regulatory protein (StAR) mediates the rate-limiting step in the synthesis of steroid hormones, essential to fetal development. We have reported that the StAR expression in fetal adrenal is inhibited in a rat model of nicotine-induced intrauterine growth retardation (IUGR). Here using primary human fetal adrenal cortex (pHFAC) cells and a human fetal adrenal cell line NCI-H295A, we show that nicotine inhibits StAR expression and cortisol production in a dose- and time-dependent manner, and prolongs the inhibitory effect on cells proliferating over 5 passages after termination of nicotine treatment. Methylation detection within the StAR promoter region uncovers a single site CpG methylation at nt −377 that is sensitive to nicotine treatment. Nicotine-induced alterations in frequency of this point methylation correlates well with the levels of StAR expression, suggesting an important role of the single site in regulating StAR expression. Further studies using bioinformatics analysis and siRNA approach reveal that the single CpG site is part of the Pax6 binding motif (CGCCTGA) in the StAR promoter. The luciferase activity assays validate that Pax6 increases StAR gene expression by binding to the glucagon G3-like motif (CGCCTGA) and methylation of this site blocks Pax6 binding and thus suppresses StAR expression. These data identify a nicotine-sensitive CpG site at the Pax6 binding motif in the StAR promoter that may play a central role in regulating StAR expression. The results suggest an epigenetic mechanism that may explain how nicotine contributes to onset of adult diseases or disorders such as metabolic syndrome via fetal programming. PMID:21971485

Carbon and energy fluxes in cropland ecosystems: a model-data comparison

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

Lokupitiya, E.; Denning, A. S.; Schaefer, K.

2016-06-03

Croplands are highly productive ecosystems that contribute to land–atmosphere exchange of carbon, energy, and water during their short growing seasons. We evaluated and compared net ecosystem exchange (NEE), latent heat flux (LE), and sensible heat flux (H) simulated by a suite of ecosystem models at five agricultural eddy covariance flux tower sites in the central United States as part of the North American Carbon Program Site Synthesis project. Most of the models overestimated H and underestimated LE during the growing season, leading to overall higher Bowen ratios compared to the observations. Most models systematically under predicted NEE, especially at rain-fedmore » sites. Certain crop-specific models that were developed considering the high productivity and associated physiological changes in specific crops better predicted the NEE and LE at both rain-fed and irrigated sites. Models with specific parameterization for different crops better simulated the inter-annual variability of NEE for maize-soybean rotation compared to those models with a single generic crop type. Stratification according to basic model formulation and phenological methodology did not explain significant variation in model performance across these sites and crops. The under prediction of NEE and LE and over prediction of H by most of the models suggests that models developed and parameterized for natural ecosystems cannot accurately predict the more robust physiology of highly bred and intensively managed crop ecosystems. When coupled in Earth System Models, it is likely that the excessive physiological stress simulated in many land surface component models leads to overestimation of temperature and atmospheric boundary layer depth, and underestimation of humidity and CO 2 seasonal uptake over agricultural regions.« less

The Savannah River Site`s Groundwater Monitoring Program. First quarter 1992

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

Not Available

This report summarizes the Savannah River Site (SRS) groundwater monitoring program conducted during the first quarter of 1992. It includes the analytical data, field data, data review, quality control, and other documentation for this program; provides a record of the program`s activities; and serves as an official document of the analytical results.

Reassessment of the Genetic Regulation of Fatty Acid Synthesis in Escherichia coli: Global Positive Control by the Dual Functional Regulator FadR

PubMed Central

My, L.; Ghandour Achkar, N.; Viala, J. P.

2015-01-01

ABSTRACT In Escherichia coli, the FadR transcriptional regulator represses the expression of fatty acid degradation (fad) genes. However, FadR is also an activator of the expression of fabA and fabB, two genes involved in unsaturated fatty acid synthesis. Therefore, FadR plays an important role in maintaining the balance between saturated and unsaturated fatty acids in the membrane. We recently showed that FadR also activates the promoter upstream of the fabH gene (L. My, B. Rekoske, J. J. Lemke, J. P. Viala, R. L. Gourse, and E. Bouveret, J Bacteriol 195:3784–3795, 2013, doi:10.1128/JB.00384-13). Furthermore, recent transcriptomic and proteomic data suggested that FadR activates the majority of fatty acid (FA) synthesis genes. In the present study, we tested the role of FadR in the expression of all genes involved in FA synthesis. We found that FadR activates the transcription of all tested FA synthesis genes, and we identified the FadR binding site for each of these genes. This necessitated the reassessment of the transcription start sites for accA and accB genes described previously, and we provide evidence for the presence of multiple promoters driving the expression of these genes. We showed further that regulation by FadR impacts the amount of FA synthesis enzymes in the cell. Our results show that FadR is a global regulator of FA metabolism in E. coli, acting both as a repressor of catabolism and an activator of anabolism, two directly opposing pathways. IMPORTANCE In most bacteria, a transcriptional regulator tunes the level of FA synthesis enzymes. Oddly, such a global regulator still was missing for E. coli, which nonetheless is one of the prominent model bacteria used for engineering biofuel production using the FA synthesis pathway. Our work identifies the FadR functional dual regulator as a global activator of almost all FA synthesis genes in E. coli. Because FadR also is the repressor of FA degradation, FadR acts both as a repressor and an activator of the two opposite pathways of FA degradation and synthesis. Our results show that there are still discoveries waiting to be made in the understanding of the genetic regulation of FA synthesis, even in the very well-known bacterium E. coli. PMID:25802297

78 FR 76187 - 30-Day Notice of Proposed Information Collection: Exchange Programs Alumni Web Site Registration

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

...: Exchange Programs Alumni Web Site Registration ACTION: Notice of request for public comment and submission... Information Collection: Exchange Programs Alumni Web site Registration. OMB Control Number: 1405-0192. Type of... proposed collection: The International Exchange Alumni Web site requires information to process users...

Scale-Up Synthesis and Identification of GLYX-13, a NMDAR Glycine-Site Partial Agonist for the Treatment of Major Depressive Disorder.

PubMed

Li, Wenchao; Liu, Jingjian; Fan, Minghua; Li, Zhongtang; Chen, Yin; Zhang, Guisen; Huang, Zhuo; Zhang, Liangren

2018-04-24

GLYX-13, a NMDAR glycine-site partial agonist, was discovered as a promising antidepressant with rapidly acting effects but no ketamine-like side effects. However, the reported synthetic process route had deficiencies of low yield and the use of unfriendly reagents. Here, we report a scaled-up synthesis of GLYX-13 with an overall yield of 30% on the hectogram scale with a column chromatography-free strategy, where the coupling and deprotection reaction conditions were systematically optimized. Meanwhile, the absolute configuration of precursor compound of GLYX-13 was identified by X-ray single crystal diffraction. Finally, the activity of GLYX-13 was verified in the cortical neurons of mice through whole-cell voltage-clamp technique.

Stable metal-organic frameworks as a host platform for catalysis and biomimetics.

PubMed

Qin, Jun-Sheng; Yuan, Shuai; Lollar, Christina; Pang, Jiandong; Alsalme, Ali; Zhou, Hong-Cai

2018-04-24

Recent years have witnessed the exploration and synthesis of an increasing number of metal-organic frameworks (MOFs). The utilization of stable MOFs as a platform for catalysis and biomimetics is discussed. This Feature Article will provide insights into the rational design and synthesis of three types of stable MOF catalysts on the basis of structural features of MOFs, that is, (i) MOF catalysts with catalytic sites on metal nodes, (ii) MOF catalysts with catalytic sites immobilized in organic struts, and (iii) MOF catalysts with catalytic centres encapsulated in the pores. Then, MOFs used in biomimetics including biomimetic mineralization, biosensors and biomimetic replication are introduced. Finally, a discussion on the challenges that must be addressed for successful implementation of MOFs in catalysis and biomimetics is presented.

2'-modified nucleosides for site-specific labeling of oligonucleotides

NASA Technical Reports Server (NTRS)

Krider, Elizabeth S.; Miller, Jeremiah E.; Meade, Thomas J.

2002-01-01

We report the synthesis of 2'-modified nucleosides designed specifically for incorporating labels into oligonucleotides. Conversion of these nucleosides to phosphoramidite and solid support-bound derivatives proceeds in good yield. Large-scale synthesis of 11-mer oligonucleotides possessing the 2'-modified nucleosides is achieved using these derivatives. Thermal denaturation studies indicate that the presence of 2'-modified nucleosides in 11-mer duplexes has minimal destabilizing effects on the duplex structure when the nucleosides are placed at the duplex termini. The powerful combination of phosphoramidite and support-bound derivatives of 2'-modified nucleosides affords the large-scale preparation of an entirely new class of oligonucleotides. The ability to synthesize oligonucleotides containing label attachment sites at 3', intervening, and 5' locations of a duplex is a significant advance in the development of oligonucleotide conjugates.

REVA CLIENT PARTNERSHIPS

EPA Science Inventory

EPA's Regional Vulnerability Assessment (ReVA) program is an applied research program that is focused on the synthesis and presentation of existing environmental data and model results to inform multicriteria environmental decision-making through a comprehensive analysis of infor...

Synthesis of IES-Funded Research on Mathematics: 2002-2013. NCER 2016-2003

ERIC Educational Resources Information Center

Rittle-Johnson, Bethany; Jordan, Nancy C.

2016-01-01

The focus of the present synthesis reflects the research on programs, practices, and policies intended to improve mathematics outcomes funded through the Institute of Education Sciences' (IES's) National Center for Education Research (NCER) and National Center for Special Education Research (NCSER). The authors were asked to review those published…

Synthesis and characterization of hexaarylbenzenes with five or six different substituents enabled by programmed synthesis

NASA Astrophysics Data System (ADS)

Suzuki, Shin; Segawa, Yasutomo; Itami, Kenichiro; Yamaguchi, Junichiro

2015-03-01

Since its discovery in 1825, benzene has served as one of the most used and indispensable building blocks of chemical compounds, ranging from pharmaceuticals and agrochemicals to plastics and those used in organic electronic devices. Benzene has six hydrogen atoms that can each be replaced by different substituents, which means that the structural diversity of benzene derivatives is intrinsically extraordinary. The number of possible substituted benzenes from n different substituents is (2n + 2n2 + 4n3 + 3n4 + n6)/12. However, owing to a lack of general synthetic methods for making multisubstituted benzenes, this potentially huge structural diversity has not been fully exploited. Here, we describe a programmed synthesis of hexaarylbenzenes using C-H activation, cross-coupling and [4+2] cycloaddition reactions. The present method allows for the isolation and structure-property characterization of hexaarylbenzenes with distinctive aryl substituents at all positions for the first time. Moreover, the established protocol can be applied to the synthesis of tetraarylnaphthalenes and pentaarylpyridines.

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

Dagle, Robert A.; Lizarazo Adarme, Jair A.; Lebarbier, Vanessa MC

A composite Pd/ZnO/Al2O3-HZSM-5 (Si/Al=40) catalytic system was evaluated for the synthesis of gasoline-range hydrocarbons directly from synthesis gas. Bifunctional catalyst comprising PdZn metal and acid sites present the required catalytically active sites necessary for the methanol synthesis, methanol dehydration, and methanol-to-gasoline reactions. This system provides a unique catalytic pathway for the production of liquid hydrocarbons directly from syngas. However, selectivity control is difficult and poses many challenges. The composite catalytic system was evaluated under various process conditions. Investigated were the effects of temperature (310-375oC), pressure (300-1000 psig), time-on-stream (50 hrs), and gas-hour space velocity (740-2970 hr-1), using a H2/CO molarmore » syngas ratio of 2.0. By operating at the lower end of the temperature range investigated, liquid hydrocarbon formation was favored, as was decreased amounts of undesirable light hydrocarbons. However, lower operating temperatures also facilitated undesirable CO2 formation via the water-gas shift reaction. Higher operating pressures slightly favored liquid synthesis. Operating at relatively low pressures (e.g. 300 psig) was made possible, whereas for methanol synthesis alone higher pressure are usually required to achieve similar conversion levels (e.g. 1000 psig). Thermodynamic constraints on methanol synthesis are eased by pushing the equilibrium through hydrocarbon formation. Catalytic performance was also evaluated by altering Pd and Zn composition of the Pd/ZnO/Al2O3 catalyst. Of the catalysts and conditions tested, selectivity toward liquid hydrocarbon was highest when using a 5% Pd metal loading and Pd/Zn molar ratio of 0.25 and mixed with HZMS-5, operating at 310oC and 300 psig, CO conversion was 43 % and selectivity (carbon weight basis) to hydrocarbons was 49 wt. %. Of the hydrocarbon fraction, 44wt. % was in the C5-C12 liquid product range and consisted primarily of aromatic polymethylbenzenes. However, as syngas conversion increases with increasing temperature, selectivity to liquid product diminished. This is attributed, in large part, to increased saturation of the olefinic intermediates over PdZn metal sites. Under all the conditions and catalysts evaluated in this study, generating liquid product in high yield was challenging (<10 wt. % C5+ yield).« less

Integrated programs for women with substance use issues and their children: a qualitative meta-synthesis of processes and outcomes.

PubMed

Sword, Wendy; Jack, Susan; Niccols, Alison; Milligan, Karen; Henderson, Joanna; Thabane, Lehana

2009-11-20

There is a need for services that effectively and comprehensively address the complex needs of women with substance use issues and their children. A growing body of literature supports the relevance of integrated treatment programs that offer a wide range of services in centralized settings. Quantitative studies suggest that these programs are associated with positive outcomes. A qualitative meta-synthesis was conducted to provide insight into the processes that contribute to recovery in integrated programs and women's perceptions of benefits for themselves and their children. A comprehensive search of published and unpublished literature to August 2009 was carried out for narrative reports of women's experiences and perceptions of integrated treatment programs. Eligibility for inclusion in the meta-synthesis was determined using defined criteria. Quality assessment was then conducted. Qualitative data and interpretations were extracted from studies of adequate quality, and were synthesized using a systematic and iterative process to create themes and overarching concepts. A total of 15 documents were included in the meta-synthesis. Women experienced a number of psychosocial processes during treatment that played a role in their recovery and contributed to favourable outcomes. These included: development of a sense of self; development of personal agency; giving and receiving of social support; engagement with program staff; self-disclosure of challenges, feelings, and past experiences; recognizing patterns of destructive behaviour; and goal setting. A final process, the motivating presence of children, sustained women in their recovery journeys. Perceived outcomes included benefits for maternal and child well-being, and enhanced parenting capacity. A number of distinct but interconnected processes emerged as being important to women's addiction recovery. Women experienced individual growth and transformative learning that led to a higher quality of life and improved interactions with their children. The findings support the need for programs to adopt practices that focus on improving maternal health and social functioning in an environment characterized by empowerment, safety, and connections. Women's relationships with their children require particular attention as positive parenting practices and family relationships can alter predispositions toward substance use later in life, thereby impacting favourably on the cycle of addiction and dysfunctional parenting.

Problems and Issues Across Institutions and Programs

Treesearch

Douglas Powell; Jim Wood

2006-01-01

The symposium identified the major barriers to collaboration among institutions and programs. This synthesis, while admittedly drawing from only a sample of the papers presented, provides a synoptic view of the major recurring themes voiced by participants.Several overarching statements were voiced. No one institution or one program in isolation can...

Exemplary Programs in Physics, Chemistry, Biology, and Earth Science.

ERIC Educational Resources Information Center

Yager, Robert E., Ed.

The 1982 Search for Excellence in Science Education project has identified 50 exemplary programs in physics, chemistry, biology, and earth science. Descriptions of four of these programs and the criteria used in their selection are presented. The first section reviews the direction established by Project Synthesis in searching for exemplary…

Halogenated naphthyl methoxy piperidines for mapping serotonin transporter sites

DOEpatents

Goodman, Mark M.; Faraj, Bahjat

1999-01-01

Halogenated naphthyl methoxy piperidines having a strong affinity for the serotonin transporter are disclosed. Those compounds can be labeled with positron-emitting and/or gamma emitting halogen isotopes by a late step synthesis that maximizes the useable lifeterm of the label. The labeled compounds are useful for localizing serotonin transporter sites by positron emission tomography and/or single photon emission computed tomography.

Halogenated naphthyl methoxy piperidines for mapping serotonin transporter sites

DOEpatents

Goodman, M.M.; Faraj, B.

1999-07-06

Halogenated naphthyl methoxy piperidines having a strong affinity for the serotonin transporter are disclosed. Those compounds can be labeled with positron-emitting and/or gamma emitting halogen isotopes by a late step synthesis that maximizes the useable lifeterm of the label. The labeled compounds are useful for localizing serotonin transporter sites by positron emission tomography and/or single photon emission computed tomography.

Spacelab Level 4 Programmatic Implementation Assessment Study. Volume 4: Executive summary

NASA Technical Reports Server (NTRS)

1978-01-01

The study objectives of the Spacelab level 4 analysis were defined, along with the most significant results. The approach used in the synthesis and selection of alternate level 4 integration is described; the options included distributed site, lead center, and launch site. Principal characteristics, as well as the functional flow diagrams for each option, are presented and explained.

Molecular Pathways: Mucins and Drug Delivery in Cancer.

PubMed

Rao, Chinthalapally V; Janakiram, Naveena B; Mohammed, Altaf

2017-03-15

Over the past few decades, clinical and preclinical studies have clearly demonstrated the role of mucins in tumor development. It is well established that mucins form a barrier impeding drug access to target sites, leading to cancer chemoresistance. Recently gained knowledge regarding core enzyme synthesis has opened avenues to explore the possibility of disrupting mucin synthesis to improve drug efficacy. Cancer cells exploit aberrant mucin synthesis to efficiently mask the epithelial cells and ensure survival under hostile tumor microenvironment conditions. However, O-glycan synthesis enzyme core 2 beta 1,6 N-acetylglucosaminyltransferase (GCNT3/C2GnT-2) is overexpressed in Kras-driven mouse and human cancer, and inhibition of GCNT3 has been shown to disrupt mucin synthesis. This previously unrecognized developmental pathway might be responsible for aberrant mucin biosynthesis and chemoresistance. In this Molecular Pathways article, we briefly discuss the potential role of mucin synthesis in cancers, ways to improve drug delivery and disrupt mucin mesh to overcome chemoresistance by targeting mucin synthesis, and the unique opportunity to target the GCNT3 pathway for the prevention and treatment of cancers. Clin Cancer Res; 23(6); 1373-8. ©2016 AACR . ©2016 American Association for Cancer Research.

Design and Synthesis of Irreversible Analogues of Bardoxolone Methyl for the Identification of Pharmacologically Relevant Targets and Interaction Sites.

PubMed

Wong, Michael H L; Bryan, Holly K; Copple, Ian M; Jenkins, Rosalind E; Chiu, Pak Him; Bibby, Jaclyn; Berry, Neil G; Kitteringham, Neil R; Goldring, Christopher E; O'Neill, Paul M; Park, B Kevin

2016-03-24

Semisynthetic triterpenoids such as bardoxolone methyl (methyl-2-cyano 3,12-dioxooleano-1,9-dien-28-oate; CDDO-Me) (4) are potent inducers of antioxidant and anti-inflammatory signaling pathways, including those regulated by the transcription factor Nrf2. However, the reversible nature of the interaction between triterpenoids and thiols has hindered attempts to identify pharmacologically relevant targets and characterize the sites of interaction. Here, we report a shortened synthesis and SAR profiling of 4, enabling the design of analogues that react irreversibly with model thiols, as well as the model protein glutathione S-transferase P1, in vitro. We show that one of these analogues, CDDO-epoxide (13), is comparable to 4 in terms of cytotoxicity and potency toward Nrf2 in rat hepatoma cells and stably modifies specific cysteine residues (namely, Cys-257, -273, -288, -434, -489, and -613) within Keap1, the major repressor of Nrf2, both in vitro and in living cells. Supported by molecular modeling, these data demonstrate the value of 13 for identifying site(s) of interaction with pharmacologically relevant targets and informing the continuing development of triterpenoids as novel drug candidates.

Development of a weight/sizing design synthesis computer program. Volume 2: Program Description

NASA Technical Reports Server (NTRS)

Garrison, J. M.

1973-01-01

The program for the computerized analysis of weight estimation relationships for those elements of the space shuttle vehicle which contribute a significant portion of the inert weight is discussed. A listing of each module and subroutine of the program is presented. Included are a generalized flow chart describing the subroutine linkage of the complete program and detailed flow charts for each subprogram.

ADDENDUM TO SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM TECHNOLOGY PROFILES, TENTH EDITION, VOLUME 1 - DEMONSTRATION PROGRAM

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) Program, now in its thirteenth year, is an integral part of EPA's research into alternative cleanup methods for hazardous waste sites around the nation. The SITE Program was created to encourage the development and routine us...

THE SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM: PROGRESS AND ACCOMPLISHMENTS - FISCAL YEAR 1990 A FOURTH REPORT TO CONGRESS

EPA Science Inventory

The SITE Program was the first major program for demonstrating and evaluating fullscale innovative treatment technologies at hazardous waste sites. Having concluded its fourth year, the SITE Program is recognized as a leading advocate of innovative technology development and comm...

Manufacturing of Smart Structures Using Fiber Placement Manufacturing Processes

NASA Technical Reports Server (NTRS)

Thomas, Matthew M.; Glowasky, Robert A.; McIlroy, Bruce E.; Story, Todd A.

1996-01-01

Smart structures research and development, with the ultimate aim of rapid commercial and military production of these structures, are at the forefront of the Synthesis and Processing of Intelligent Cost-Effective Structures (SPICES) program. As part of this ARPA-sponsored program, MDA-E is using fiber placement processes to manufacture integrated smart structure systems. These systems comprise advanced composite structures with embedded fiber optic sensors, shape memory alloys, piezoelectric actuators, and miniature accelerometers. Cost-effective approaches and solutions to smart material synthesis in the fiber-placement process, based upon integrated product development, are discussed herein.

The Savannah River Site`s groundwater monitoring program. First quarter 1991

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

Not Available

This report summarizes the Savannah River Site (SRS) groundwater monitoring program conducted by EPD/EMS in the first quarter of 1991. In includes the analytical data, field data, data review, quality control, and other documentation for this program, provides a record of the program`s activities and rationale, and serves as an official document of the analytical results.

Ugi 4-CR Synthesis of γ- and δ-Lactams providing new access to diverse enzyme interactions, a PDB analysis.

PubMed

Boltjes, André; Liao, George P; Zhao, Ting; Herdtweck, Eberhardt; Dömling, Alexander

2014-07-01

A three step synthesis of N -unsubstituted tetrazolo γ- and δ-lactams involving a key Ugi-4CR is presented. The compounds, otherwise difficult to access, are conveniently synthesized in overall good yields by our route. PDB analysis of the N -unsubstituted γ- and δ-lactam fragment reveals a strongly tri-directional hydrogen bond donor acceptor interaction with the amino acids of the binding sites.

Regulation of yeast DNA polymerase δ-mediated strand displacement synthesis by 5′-flaps

PubMed Central

Koc, Katrina N.; Stodola, Joseph L.; Burgers, Peter M.; Galletto, Roberto

2015-01-01

The strand displacement activity of DNA polymerase δ is strongly stimulated by its interaction with proliferating cell nuclear antigen (PCNA). However, inactivation of the 3′–5′ exonuclease activity is sufficient to allow the polymerase to carry out strand displacement even in the absence of PCNA. We have examined in vitro the basic biochemical properties that allow Pol δ-exo− to carry out strand displacement synthesis and discovered that it is regulated by the 5′-flaps in the DNA strand to be displaced. Under conditions where Pol δ carries out strand displacement synthesis, the presence of long 5′-flaps or addition in trans of ssDNA suppress this activity. This suggests the presence of a secondary DNA binding site on the enzyme that is responsible for modulation of strand displacement activity. The inhibitory effect of a long 5′-flap can be suppressed by its interaction with single-stranded DNA binding proteins. However, this relief of flap-inhibition does not simply originate from binding of Replication Protein A to the flap and sequestering it. Interaction of Pol δ with PCNA eliminates flap-mediated inhibition of strand displacement synthesis by masking the secondary DNA site on the polymerase. These data suggest that in addition to enhancing the processivity of the polymerase PCNA is an allosteric modulator of other Pol δ activities. PMID:25813050

Wastewater-based epidemiology generated forensic information: Amphetamine synthesis waste and its impact on a small sewage treatment plant.

PubMed

Emke, Erik; Vughs, Dennis; Kolkman, Annemieke; de Voogt, Pim

2018-05-01

Chemical analysis of domestic wastewater can reveal the presence of illicit drugs either consumed by a population or directly discharged into the sewer system. In the search for causes of a recent malfunctioning of a small domestic wastewater treatment plant aberrantly high loads of amphetamine were observed in the influent of the plant. Direct discharges of chemical waste from illegal production sites were suspected to be the cause. Illegal manufacturing of amphetamines creates substantial amounts of chemical waste. Here we show that fly-tipping of chemical waste originating from an amphetamine synthesis in the catchment of a small sewage treatment plant resulted in failure of the treatment process. Target analysis of drugs of abuse and non-target screening using high resolution mass spectrometry provided evidence for the presence of amphetamine produced from the precursor 1-phenylpropan-2-one by the Leuckart process through specific synthesis markers. Furthermore the identity and presence of the pre-precursor 3-oxo-2-phenylbutanamide was confirmed and a route specific marker was proposed. This is the first study that demonstrates that non-target screening of wastewater can identify intermediates, impurities and by products of the synthesis routes used in illegal manufacturing of amphetamine. The profiles of chemicals thus obtained can be used in tracking productions sites within the corresponding sewer catchment. Copyright © 2018 Elsevier B.V. All rights reserved.

Structural Explanation for Allolactose (lac Operon Inducer) Synthesis by lacZ β-Galactosidase and the Evolutionary Relationship between Allolactose Synthesis and the lac Repressor

PubMed Central

Wheatley, Robert W.; Lo, Summie; Jancewicz, Larisa J.; Dugdale, Megan L.; Huber, Reuben E.

2013-01-01

β-Galactosidase (lacZ) has bifunctional activity. It hydrolyzes lactose to galactose and glucose and catalyzes the intramolecular isomerization of lactose to allolactose, the lac operon inducer. β-Galactosidase promotes the isomerization by means of an acceptor site that binds glucose after its cleavage from lactose and thus delays its exit from the site. However, because of its relatively low affinity for glucose, details of this site have remained elusive. We present structural data mapping the glucose site based on a substituted enzyme (G794A-β-galactosidase) that traps allolactose. Various lines of evidence indicate that the glucose of the trapped allolactose is in the acceptor position. The evidence includes structures with Bis-Tris (2,2-bis(hydroxymethyl)-2,2′,2″-nitrilotriethanol) and l-ribose in the site and kinetic binding studies with substituted β-galactosidases. The site is composed of Asn-102, His-418, Lys-517, Ser-796, Glu-797, and Trp-999. Ser-796 and Glu-797 are part of a loop (residues 795–803) that closes over the active site. This loop appears essential for the bifunctional nature of the enzyme because it helps form the glucose binding site. In addition, because the loop is mobile, glucose binding is transient, allowing the release of some glucose. Bioinformatics studies showed that the residues important for interacting with glucose are only conserved in a subset of related enzymes. Thus, intramolecular isomerization is not a universal feature of β-galactosidases. Genomic analyses indicated that lac repressors were co-selected only within the conserved subset. This shows that the glucose binding site of β-galactosidase played an important role in lac operon evolution. PMID:23486479

Development of clinical sites.

PubMed

O'Brien, Mary

2015-02-01

Clinical experiences are vital to all types of healthcare educational programs. Supervised clinical experiences provide the opportunity for the learner to apply didactic knowledge and theory to real world situations and hone skills necessary for entry into practice. Nurse anesthesia programs utilize a wide variety of clinical sites to expose student registered nurse anesthetists to experiences that will prepare them clinically, academically and professionally to enter practice as a Certified Registered Nurse Anesthetist. This article describes the process of developing a clinical site. A thorough evaluation will determine the types of experiences meant to be offered at the site, the resources available to house and educate the students, and how to evaluate the effectiveness of the clinical site. Open communication between the clinical coordinator and the program director or designee is essential to ensure success of the clinical site. The Council on Accreditation of Nurse Anesthesia Educational Programs has resources available to guide those interested in becoming a clinical site, as well as for program administrators who seek to add new experiences to their programs.

The effects of workplace health promotion on absenteeism and employment costs in a large industrial population.

PubMed Central

Bertera, R L

1990-01-01

We evaluated the impact of a comprehensive workplace health promotion program on absences among full-time employees in a large, multi-location, diversified industrial company. A pretest-posttest control group design was used to study 41 intervention sites and 19 control sites with 29,315 and 14,573 hourly employees, respectively. Blue-collar employees at intervention sites experienced an 14.0 percent decline in disability days over two years versus a 5.8 percent decline at control sites. This resulted in a net difference of 11,726 fewer disability days over two years at program sites compared with non-program sites. Savings due to lower disability costs at intervention sites offset program costs in the first year, and provided a return of $2.05 for every dollar invested in the program by the end of the second year. These results suggest that comprehensive workplace health promotion programs can reduce disability days among blue collar employees and provide a good return on investment. PMID:2382748

78 FR 18932 - Public Meeting: Unmanned Aircraft Systems Test Site Program; Privacy Approach

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... operation of the UAS Test Sites. They are not intended to pre-determine the long- term policy and regulatory...-0061] Public Meeting: Unmanned Aircraft Systems Test Site Program; Privacy Approach AGENCY: Federal... the unmanned aircraft systems (UAS) test site program. The FAA is seeking the views from the public...

75 FR 66413 - 30-Day Notice of Proposed Information Collection: Exchange Programs Alumni Web Site Registration...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

...: Exchange Programs Alumni Web Site Registration, DS-7006 ACTION: Notice of request for public comment and... Collection The Exchange Programs Alumni Web site requires information to process users' voluntary requests for participation in the Web site. Other than contact information, which is required for website...

The Role of Ontologies in Schema-based Program Synthesis

NASA Technical Reports Server (NTRS)

Bures, Tomas; Denney, Ewen; Fischer, Bernd; Nistor, Eugen C.

2004-01-01

Program synthesis is the process of automatically deriving executable code from (non-executable) high-level specifications. It is more flexible and powerful than conventional code generation techniques that simply translate algorithmic specifications into lower-level code or only create code skeletons from structural specifications (such as UML class diagrams). Key to building a successful synthesis system is specializing to an appropriate application domain. The AUTOBAYES and AUTOFILTER systems, under development at NASA Ames, operate in the two domains of data analysis and state estimation, respectively. The central concept of both systems is the schema, a representation of reusable computational knowledge. This can take various forms, including high-level algorithm templates, code optimizations, datatype refinements, or architectural information. A schema also contains applicability conditions that are used to determine when it can be applied safely. These conditions can refer to the initial specification, to intermediate results, or to elements of the partially-instantiated code. Schema-based synthesis uses AI technology to recursively apply schemas to gradually refine a specification into executable code. This process proceeds in two main phases. A front-end gradually transforms the problem specification into a program represented in an abstract intermediate code. A backend then compiles this further down into a concrete target programming language of choice. A core engine applies schemas on the initial problem specification, then uses the output of those schemas as the input for other schemas, until the full implementation is generated. Since there might be different schemas that implement different solutions to the same problem this process can generate an entire solution tree. AUTOBAYES and AUTOFILTER have reached the level of maturity where they enable users to solve interesting application problems, e.g., the analysis of Hubble Space Telescope images. They are large (in total around 100kLoC Prolog), knowledge intensive systems that employ complex symbolic reasoning to generate a wide range of non-trivial programs for complex application do- mains. Their schemas can have complex interactions, which make it hard to change them in isolation or even understand what an existing schema actually does. Adding more capabilities by increasing the number of schemas will only worsen this situation, ultimately leading to the entropy death of the synthesis system. The root came of this problem is that the domain knowledge is scattered throughout the entire system and only represented implicitly in the schema implementations. In our current work, we are addressing this problem by making explicit the knowledge from Merent parts of the synthesis system. Here; we discuss how Gruber's definition of an ontology as an explicit specification of a conceptualization matches our efforts in identifying and explicating the domain-specific concepts. We outline the dual role ontologies play in schema-based synthesis and argue that they address different audiences and serve different purposes. Their first role is descriptive: they serve as explicit documentation, and help to understand the internal structure of the system. Their second role is prescriptive: they provide the formal basis against which the other parts of the system (e.g., schemas) can be checked. Their final role is referential: ontologies also provide semantically meaningful "hooks" which allow schemas and tools to access the internal state of the program derivation process (e.g., fragments of the generated code) in domain-specific rather than language-specific terms, and thus to modify it in a controlled fashion. For discussion purposes we use AUTOLINEAR, a small synthesis system we are currently experimenting with, which can generate code for solving a system of linear equations, Az = b.

A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA.

PubMed

Yordanova, Martina M; Wu, Cheng; Andreev, Dmitry E; Sachs, Matthew S; Atkins, John F

2015-07-17

The protein antizyme is a negative regulator of cellular polyamine concentrations from yeast to mammals. Synthesis of functional antizyme requires programmed +1 ribosomal frameshifting at the 3' end of the first of two partially overlapping ORFs. The frameshift is the sensor and effector in an autoregulatory circuit. Except for Saccharomyces cerevisiae antizyme mRNA, the frameshift site alone only supports low levels of frameshifting. The high levels usually observed depend on the presence of cis-acting stimulatory elements located 5' and 3' of the frameshift site. Antizyme genes from different evolutionary branches have evolved different stimulatory elements. Prior and new multiple alignments of fungal antizyme mRNA sequences from the Agaricomycetes class of Basidiomycota show a distinct pattern of conservation 5' of the frameshift site consistent with a function at the amino acid level. As shown here when tested in Schizosaccharomyces pombe and mammalian HEK293T cells, the 5' part of this conserved sequence acts at the nascent peptide level to stimulate the frameshifting, without involving stalling detectable by toe-printing. However, the peptide is only part of the signal. The 3' part of the stimulator functions largely independently and acts at least mostly at the nucleotide level. When polyamine levels were varied, the stimulatory effect was seen to be especially responsive in the endogenous polyamine concentration range, and this effect may be more general. A conserved RNA secondary structure 3' of the frameshift site has weaker stimulatory and polyamine sensitizing effects on frameshifting. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A meta-analysis of lesser prairie-chicken nesting and brood-rearing habitats: implications for habitat management

USGS Publications Warehouse

Hagen, Christian A.; Grisham, Blake A.; Boal, Clint W.; Haukos, David A.

2013-01-01

The distribution and range of lesser prairie-chicken (Tympanuchus pallidicinctus) has been reduced by >90% since European settlement of the Great Plains of North America. Currently, lesser prairie-chickens occupy 3 general vegetation communities: sand sagebrush (Artemisia filifolia), sand shinnery oak (Quercus havardii), and mixed-grass prairies juxtaposed with Conservation Reserve Program grasslands. As a candidate for protection under the Endangered Species Act, there is a need for a synthesis that characterizes habitat structure rangewide. Thus, we conducted a meta-analysis of vegetation characteristics at nest sites and brood habitats to determine whether there was an overall effect (Hedges' d) of habitat selection and to estimate average (95% CI) habitat characteristics at use sites. We estimated effect sizes (di) from the difference between use (nests and brood sites) and random sampling sites for each study (n = 14), and derived an overall effect size (d++). There was a general effect for habitat selection as evidenced by low levels of variation in effect sizes across studies and regions. There was a small to medium effect (d++) = 0.20-0.82) of selection for greater vertical structure (visual obstruction) by nesting females in both vegetation communities, and selection against bare ground (d++ = 0.20-0.58). Females with broods exhibited less selectivity for habitat components except for vertical structure. The variation of d++ was greater during nesting than brooding periods, signifying a seasonal shift in habitat use, and perhaps a greater range of tolerance for brood-rearing habitat. The overall estimates of vegetation cover were consistent with those provided in management guidelines for the species.

The vehicle design evaluation program - A computer-aided design procedure for transport aircraft

NASA Technical Reports Server (NTRS)

Oman, B. H.; Kruse, G. S.; Schrader, O. E.

1977-01-01

The vehicle design evaluation program is described. This program is a computer-aided design procedure that provides a vehicle synthesis capability for vehicle sizing, external load analysis, structural analysis, and cost evaluation. The vehicle sizing subprogram provides geometry, weight, and balance data for aircraft using JP, hydrogen, or methane fuels. The structural synthesis subprogram uses a multistation analysis for aerodynamic surfaces and fuselages to develop theoretical weights and geometric dimensions. The parts definition subprogram uses the geometric data from the structural analysis and develops the predicted fabrication dimensions, parts material raw stock buy requirements, and predicted actual weights. The cost analysis subprogram uses detail part data in conjunction with standard hours, realization factors, labor rates, and material data to develop the manufacturing costs. The program is used to evaluate overall design effects on subsonic commercial type aircraft due to parameter variations.

Oak Ridge Environmental Information System (ORIES) site workstation information packet for OREIS V1.2. Environmental Restoration Program

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

Voorhees, L.D.; McCord, R.A.; Durfee, R.C.

1993-02-01

The OREIS site workstation information packet was developed to accompany the OREIS site workstations, which are being delivered to the Environmental Restoration programs at the five DOE-OR sites. The packet is written specifically for the Site ER program staff at each of the five Sites who have been designated the OREIS contact by their ER program manager, and is not intended for general distribution. The packet provides an overview of the components of OREIS, points to more detailed information provided in the accompanying vendor and OREIS developed manuals, and includes information on training opportunities and user support.

Adapting realist synthesis methodology: The case of workplace harassment interventions.

PubMed

Carr, Tracey; Quinlan, Elizabeth; Robertson, Susan; Gerrard, Angie

2017-12-01

Realist synthesis techniques can be used to assess complex interventions by extracting and synthesizing configurations of contexts, mechanisms, and outcomes found in the literature. Our novel and multi-pronged approach to the realist synthesis of workplace harassment interventions describes our pursuit of theory to link macro and program level theories. After discovering the limitations of a dogmatic approach to realist synthesis, we adapted our search strategy and focused our analysis on a subset of data. We tailored our realist synthesis to understand how, why, and under what circumstances workplace harassment interventions are effective. The result was a conceptual framework to test our theory-based interventions and provide the basis for subsequent realist evaluation. Our experience documented in this article contributes to an understanding of how, under what circumstances, and with what consequences realist synthesis principles can be customized. Copyright © 2017 John Wiley & Sons, Ltd.

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

PubMed Central

Kitson, Philip J; Glatzel, Stefan

2016-01-01

An automated synthesis robot was constructed by modifying an open source 3D printing platform. The resulting automated system was used to 3D print reaction vessels (reactionware) of differing internal volumes using polypropylene feedstock via a fused deposition modeling 3D printing approach and subsequently make use of these fabricated vessels to synthesize the nonsteroidal anti-inflammatory drug ibuprofen via a consecutive one-pot three-step approach. The synthesis of ibuprofen could be achieved on different scales simply by adjusting the parameters in the robot control software. The software for controlling the synthesis robot was written in the python programming language and hard-coded for the synthesis of ibuprofen by the method described, opening possibilities for the sharing of validated synthetic ‘programs’ which can run on similar low cost, user-constructed robotic platforms towards an ‘open-source’ regime in the area of chemical synthesis. PMID:28144350

Synthesis and binding studies of Alzheimer ligands on solid support.

PubMed

Rzepecki, Petra; Geib, Nina; Peifer, Manuel; Biesemeier, Frank; Schrader, Thomas

2007-05-11

Aminopyrazole derivatives constitute the first class of nonpeptidic rationally designed beta-sheet ligands. Here we describe a double solid-phase protocol for both synthesis and affinity testing. The presented solid-phase synthesis of four types of hybrid compounds relies on the Fmoc strategy and circumvents subsequent HPLC purification by precipitating the final product from organic solution in pure form. Hexa- and octapeptide pendants with internal di- and tetrapeptide bridges are now amenable in high yields to combinatorial synthesis of compound libraries for high-throughput screening purposes. Solid-phase peptide synthesis (SPPS) on an acid-resistant PAM allows us, after PMB deprotection, to subject the free aminopyrazole binding sites in an immobilized state to on-bead assays with fluorescence-labeled peptides. From the fluorescence emission intensity decrease, individual binding constants can be calculated via reference curves by simple application of the law of mass action. Gratifyingly, host/guest complexation can be monitored quantitatively even for those ligands, which are almost insoluble in water.

Active vibration control testing of the SPICES program: final demonstration article

NASA Astrophysics Data System (ADS)

Dunne, James P.; Jacobs, Jack H.

1996-05-01

The Synthesis and Processing of Intelligent Cost Effective Structures (SPICES) Program is a partnership program sponsored by the Advanced Research Projects Agency. The mission of the program is to develop cost effective material processing and synthesis technologies to enable new products employing active vibration suppression and control devices to be brought to market. The two year program came to fruition in 1995 through the fabrication of the final smart components and testing of an active plate combined with two trapezoidal rails, forming an active mount. Testing of the SPICES combined active mount took place at McDonnell Douglas facilities in St. Louis, MO, in October-December 1995. Approximately 15 dB reduction in overall response of a motor mounted on the active structure was achieved. Further details and results of the SPICES combined active mount demonstration testing are outlined. Results of numerous damping and control strategies that were developed and employed in the testing are presented, as well as aspects of the design and fabrication of the SPICES active mount components.

AmeriFlux US-MRf Mary's River (Fir) site

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

Law, Bev

This is the AmeriFlux version of the carbon flux data for the site US-MRf Mary's River (Fir) site. Site Description - The Marys River Fir site is part of the "Synthesis of Remote Sensing and Field Observations to Model and Understand Disturbance and Climate Effects on the Carbon Balance of Oregon and Northern California (ORCA)". Located in the western region of Oregon the Marys River site represents the western extent of the climate gradient that spans eastward into the semi-arid basin of central Oregon. The sites that make up the eastern extent of the ORCA climate gradient is the Metoliusmore » site network (US-Me1, US-ME2, US-ME4, US-Me5) all of which are part of the TERRA PNW project at Oregon State University.« less

The design of multirate digital control systems

NASA Technical Reports Server (NTRS)

Berg, M. C.

1986-01-01

The successive loop closures synthesis method is the only method for multirate (MR) synthesis in common use. A new method for MR synthesis is introduced which requires a gradient-search solution to a constrained optimization problem. Some advantages of this method are that the control laws for all control loops are synthesized simultaneously, taking full advantage of all cross-coupling effects, and that simple, low-order compensator structures are easily accomodated. The algorithm and associated computer program for solving the constrained optimization problem are described. The successive loop closures , optimal control, and constrained optimization synthesis methods are applied to two example design problems. A series of compensator pairs are synthesized for each example problem. The succesive loop closure, optimal control, and constrained optimization synthesis methods are compared, in the context of the two design problems.

Natural Products Synthesis: Enabling Tools to Penetrate Nature’s Secrets of Biogenesis and Biomechanism†

PubMed Central

Williams, Robert M.

2011-01-01

Selected examples from our laboratory of how synthetic technology platforms developed for the total synthesis of several disparate families of natural products was harnessed to penetrate biomechanistic and/or biosynthetic queries is discussed. Unexpected discoveries of biomechanistic reactivity and/or penetrating the biogenesis of naturally occurring substances were made possible through access to substances available only through chemical synthesis. Hypothesis-driven total synthesis programs are emerging as very useful conceptual templates for penetrating and exploiting the inherent reactivity of biologically active natural substances. In many instances, new enabling synthetic technologies were required to be developed. The examples demonstrate the often un-tapped richness of complex molecule synthesis to provide powerful tools to understand, manipulate and exploit Nature’s vast and creative palette of secondary metabolites. PMID:21438619

Program on application of communications satellites to educational development

NASA Technical Reports Server (NTRS)

Morgan, R. P.; Singh, J. P.

1971-01-01

Interdisciplinary research in needs analysis, communications technology studies, and systems synthesis is reported. Existing and planned educational telecommunications services are studied and library utilization of telecommunications is described. Preliminary estimates are presented of ranges of utilization of educational telecommunications services for 1975 and 1985; instructional and public television, computer-aided instruction, computing resources, and information resource sharing for various educational levels and purposes. Communications technology studies include transmission schemes for still-picture television, use of Gunn effect devices, and TV receiver front ends for direct satellite reception at 12 GHz. Two major studies in the systems synthesis project concern (1) organizational and administrative aspects of a large-scale instructional satellite system to be used with schools and (2) an analysis of future development of instructional television, with emphasis on the use of video tape recorders and cable television. A communications satellite system synthesis program developed for NASA is now operational on the university IBM 360-50 computer.

A Novel Implementation of Efficient Algorithms for Quantum Circuit Synthesis

NASA Astrophysics Data System (ADS)

Zeller, Luke

In this project, we design and develop a computer program to effectively approximate arbitrary quantum gates using the discrete set of Clifford Gates together with the T gate (π/8 gate). Employing recent results from Mosca et. al. and Giles and Selinger, we implement a decomposition scheme that outputs a sequence of Clifford, T, and Tt gates that approximate the input to within a specified error range ɛ. Specifically, the given gate is first rounded to an element of Z[1/2, i] with a precision determined by ɛ, and then exact synthesis is employed to produce the resulting gate. It is known that this procedure is optimal in approximating an arbitrary single qubit gate. Our program, written in Matlab and Python, can complete both approximate and exact synthesis of qubits. It can be used to assist in the experimental implementation of an arbitrary fault-tolerant single qubit gate, for which direct implementation isn't feasible.

Locally Motivated GLOBE Investigations - A Key to Success

NASA Astrophysics Data System (ADS)

Washburne, J. C.; Geery, W.

2003-12-01

The GLOBE program was set up to help students make a core set of environmental observations at or near their schools, report their data through the internet to share with other students and scientists, analyze their data both locally and globally, and use this knowledge to form a better understanding of their environment. While the GLOBE program has been successful promoting more meaningful data collection, many of the tools and much of the infrastructure available to schools to synthesize their observations are underused. Schools that integrate GLOBE protocols with locally motivated investigations are more likely to implement the higher-order analysis and synthesis components of the program. Indicators of a successful observational program are things like measurement persistence, high data quality, and regular data. Participation in community forums and student-based research projects are evidence of a successful integrated program. A locally motivated issue allows a school to mold their GLOBE investigations around a multi-faceted question that they have first-hand knowledge of, that is both relevant and engaging to their students, and that can be supported by local expertise. In contrast, many GLOBE investigations are designed around abstract, non-site specific, narrowly focused and externally analyzed questions that limit local involvement and motivation. The main focus of this presentation is a few case histories of successful local investigations that incorporated GLOBE soil and air temperature data-logger measurements. The main example is drawn from Mr. Geery's fifth grade class investigation of why temperature differences exist between a local river bottom area and the school, which is located several kilometers away and 100 meters higher.

Contracts and Management Services FY 1996 Site Support Program Plan: WBS 6.10.14. Revision 1

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

Knoll, J.M. Jr.

1995-09-01

This is the Contracts and Management Services site support program plan for the US DOE Hanford site. The topics addressed in the program plan include a mission statement, program objectives, planning assumptions, program constraints, work breakdown structure, milestone list, milestone description sheets, and activity detail including cost accounting narrative summary, approved funding budget, and activity detailed description.

Occupational Therapy in Preschools: A Synthesis of Current Knowledge

ERIC Educational Resources Information Center

Jasmin, Emmanuelle; Gauthier, Anne; Julien, Marjorie; Hui, Caroline

2018-01-01

This paper presents a synthesis of current knowledge about occupational therapy in preschools (for 3-6 year olds) in order to provide a better understanding of this field of practice and to guide the implementation or programming of this service. In the literature, occupational therapy in preschools has been documented mainly in the USA. Results…

Savannah River Ecology Laboratory. Annual technical progress report of ecological research, period ending July 31, 1994

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

Not Available

1994-07-31

The Savannah River Ecology Laboratory (SREL) is a research unit of the University of Georgia (UGA) that is managed in conjunction with the University`s Institute of Ecology. The laboratory`s overall mission is to acquire and communicate knowledge of ecological processes and principles. SREL conducts basic and applied ecological research, as well as education and outreach programs, under an M&O contract with the US Department of Energy at the Savannah River Site. Significant accomplishments were made during the year ending July 31, 1994 in the areas of research, education and service. Reviewed in this document are research projects in the followingmore » areas: Environmental Operations Support (impacted wetlands, streams, trace organics, radioecology, database synthesis, wild life studies, zooplankton, safety and quality assurance); wood stork foraging and breeding ecology; defence waste processing facility; environmental risk assessment (endangered species, fish, ash basin studies); ecosystem alteration by chemical pollutants; wetlands systems; biodiversity on the SRS; Environmental toxicology; environmental outreach and education; Par Pond drawdown studies in wildlife and fish and metals; theoretical ecology; DOE-SR National Environmental Research Park; wildlife studies. Summaries of educational programs and publications are also give.« less

Program Aids Analysis And Optimization Of Design

NASA Technical Reports Server (NTRS)

Rogers, James L., Jr.; Lamarsh, William J., II

1994-01-01

NETS/ PROSSS (NETS Coupled With Programming System for Structural Synthesis) computer program developed to provide system for combining NETS (MSC-21588), neural-network application program and CONMIN (Constrained Function Minimization, ARC-10836), optimization program. Enables user to reach nearly optimal design. Design then used as starting point in normal optimization process, possibly enabling user to converge to optimal solution in significantly fewer iterations. NEWT/PROSSS written in C language and FORTRAN 77.

Promising Practices and Programs: Current Efforts and Future Directions

ERIC Educational Resources Information Center

Crisp, Gloria

2016-01-01

The final chapter of the issue provides a synthesis of the first eight chapters, offers conclusions and recommendations, and considers future directions regarding practices and programs with promise for high impact at community colleges around the country.

Doctoral Programs in Educational Leadership: A Duality Framework of Commonality and Differences

ERIC Educational Resources Information Center

Zirkel, Perry A.

2012-01-01

In recent years, doctoral programs in education leadership have been subject to notable criticism and proposals for reform. Starting with a synthesis of this criticism, this article focuses on the two primary constituencies--university faculty members who teach in such programs, and school superintendents, who are the leading practitioners such…

Effective Secondary Science Programs: A Best-Evidence Synthesis

ERIC Educational Resources Information Center

Cheung, Alan; Slavin, Robert E.; Kim, Elizabeth; Lake, Cynthia

2015-01-01

This article reports a systematic review of research on science programs in grades 6-12. Twenty-one studies met inclusion criteria including use of randomized or matched assignment to conditions, measures that assess content emphasized equally in experimental and control groups, and a duration of at least 12 weeks. Programs fell into four…

Effective Secondary Science Programs: A Best-Evidence Synthesis

ERIC Educational Resources Information Center

Cheung, Alan; Slavin, Robert E.; Kim, Elizabeth; Lake, Cynthia

2017-01-01

This article reports a systematic review of research on science programs in grades 6-12. Twenty-one studies met inclusion criteria including use of randomized or quasi-experimental assignment to conditions, measures that assess content emphasized equally in experimental and control groups, and a duration of at least 12 weeks. Programs fell into…

Occupational Safety and Health Programs in Career Education.

ERIC Educational Resources Information Center

DiCarlo, Robert D.; And Others

This resource guide was developed in response to the Occupational Safety and Health Act of 1970 and is intended to assist teachers in implementing courses in occupational safety and health as part of a career education program. The material is a synthesis of films, programed instruction, slides and narration, case studies, safety pamphlets,…

A Meta-Analysis of the Effects of Enrichment Programs on Gifted Students

ERIC Educational Resources Information Center

Kim, Mihyeon

2016-01-01

Although descriptions of enrichment programs are valuable for practitioners, practices, and services for gifted students, they must be backed by evidence, derived through a synthesis of research. This study examined research on enrichment programs serving gifted students and synthesized the current studies between 1985 and 2014 on the effects of…

System Analysis in Instructional Programming: The Initial Phases of the Program Construction Process.

ERIC Educational Resources Information Center

Bjerstedt, Ake

A three-volume series describes the construction of a self-instructional system as a work process with three main phases: system analysis, system synthesis, and system modification and evaluation. After an introductory discussion of some basic principles of instructional programing, this first volume focuses on the system analysis phase,…

An Evaluation of the Technical Adequacy of a Revised Measure of Quality Indicators of Transition

ERIC Educational Resources Information Center

Morningstar, Mary E.; Lee, Hyunjoo; Lattin, Dana L.; Murray, Angela K.

2016-01-01

This study confirmed the reliability and validity of the Quality Indicators of Exemplary Transition Programs Needs Assessment-2 (QI-2). Quality transition program indicators were identified through a systematic synthesis of transition research, policies, and program evaluation measures. To verify reliability and validity of the QI-2, we…

Building Better Bridges into STEM: A Synthesis of 25 Years of Literature on STEM Summer Bridge Programs

ERIC Educational Resources Information Center

Ashley, Michael; Cooper, Katelyn M.; Cala, Jacqueline M.; Brownell, Sara E.

2017-01-01

Summer bridge programs are designed to help transition students into the college learning environment. Increasingly, bridge programs are being developed in science, technology, engineering, and mathematics (STEM) disciplines because of the rigorous content and lower student persistence in college STEM compared with other disciplines. However, to…

ACCESS 3. Approximation concepts code for efficient structural synthesis: User's guide

NASA Technical Reports Server (NTRS)

Fleury, C.; Schmit, L. A., Jr.

1980-01-01

A user's guide is presented for ACCESS-3, a research oriented program which combines dual methods and a collection of approximation concepts to achieve excellent efficiency in structural synthesis. The finite element method is used for structural analysis and dual algorithms of mathematical programming are applied in the design optimization procedure. This program retains all of the ACCESS-2 capabilities and the data preparation formats are fully compatible. Four distinct optimizer options were added: interior point penalty function method (NEWSUMT); second order primal projection method (PRIMAL2); second order Newton-type dual method (DUAL2); and first order gradient projection-type dual method (DUAL1). A pure discrete and mixed continuous-discrete design variable capability, and zero order approximation of the stress constraints are also included.

The SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION program - Technology Profiles

EPA Science Inventory

The Superfund Innovative Technology Evaluation (SITE) program was created to evaluate new and promising treatment technologies for cleanup at hazardous waste sites. The mission of the SITE program is to encourage the development and routine use of innovative treatment technologie...

St. Louis Airport Site annual site environmental report. Calendar year 1985

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

Not Available

1986-04-01

During 1985, the environmental monitoring program was continued at the St. Louis Airport Site (SLAPS) in St. Louis County, Missouri. The ditches north and south of the site have been designated for cleanup as part of the Formerly Utilized Sites Remedial Action Program (FUSRAP), a United States Department of Energy (DOE) program to identify, decontaminate, or otherwise control sites where low-level radioactive contamination remains from the early years of the nation's atomic energy program. The site is not currently controlled or regulated by DOE or NRC, although radiological monitoring of the site has been authorized by the DOE. The monitoringmore » program at the SLAPS measures radon gas concentrations in air; external gamma radiation dose rates; and uranium, thorium, and radium concentrations in surface water, groundwater, and sediment. Potential radiation doses to the public are also calculated. Because the site is not controlled or regulated by the DOE, the DOE Derived Concentration Guides (DCGs) are not applicable to SLAPS, but are included as a basis for comparison only. The DOE DCGs and the DOE radiation protection standard have been revised.« less

Accumulation of Polyhydroxyalkanoic Acid Containing Large Amounts of Unsaturated Monomers in Pseudomonas fluorescens BM07 Utilizing Saccharides and Its Inhibition by 2-Bromooctanoic Acid

PubMed Central

Lee, Ho-Joo; Choi, Mun Hwan; Kim, Tae-Un; Yoon, Sung Chul

2001-01-01

A psychrotrophic bacterium, Pseudomonas fluorescens BM07, which is able to accumulate polyhydroxyalkanoic acid (PHA) containing large amounts of 3-hydroxy-cis-5-dodecenoate unit up to 35 mol% in the cell from unrelated substrates such as fructose, succinate, etc., was isolated from an activated sludge in a municipal wastewater treatment plant. When it was grown on heptanoic acid (C7) to hexadecanoic acid (C16) as the sole carbon source, the monomer compositional characteristics of the synthesized PHA were similar to those observed in other fluorescent pseudomonads belonging to rRNA homology group I. However, growth on stearic acid (C18) led to no PHA accumulation, but instead free stearic acid was stored in the cell. The existence of the linkage between fatty acid de novo synthesis and PHA synthesis was confirmed by using inhibitors such as acrylic acid and two other compounds, 2-bromooctanoic acid and 4-pentenoic acid, which are known to inhibit β-oxidation enzymes in animal cells. Acrylic acid completely inhibited PHA synthesis at a concentration of 4 mM in 40 mM octanoate-grown cells, but no inhibition of PHA synthesis occurred in 70 mM fructose-grown cells in the presence of 1 to 5 mM acrylic acid. 2-Bromooctanoic acid and 4-pentenoic acid were found to much inhibit PHA synthesis much more strongly in fructose-grown cells than in octanoate-grown cells over concentrations ranging from 1 to 5 mM. However, 2-bromooctanoic acid and 4-pentenoic acid did not inhibit cell growth at all in the fructose media. Especially, with the cells grown on fructose, 2-bromooctanoic acid exhibited a steep rise in the percent PHA synthesis inhibition over a small range of concentrations below 100 μM, a finding indicative of a very specific inhibition, whereas 4-pentenoic acid showed a broad, featureless concentration dependence, suggesting a rather nonspecific inhibition. The apparent inhibition constant Ki (the concentration for 50% inhibition of PHA synthesis) for 2-bromooctanoic acid was determined to be 60 μM, assuming a single-site binding of the inhibitor at a specific inhibition site. Thus, it seems likely that a coenzyme A thioester derivative of 2-bromooctanoic acid specifically inhibits an enzyme linking the two pathways, fatty acid de novo synthesis and PHA synthesis. We suggest that 2-bromooctanoic acid can substitute for the far more expensive (2,000 times) and cell-growth-inhibiting PHA synthesis inhibitor, cerulenin. PMID:11679314

Review and Synthesis of Evidence Regarding Environmental Risks Posed by Munitions Constituents (MC) in Aquatic Systems

DTIC Science & Technology

2017-10-01

Munitions response diver approaching an unexploded 1,000 pound General Purpose Bomb at Bahia Salina del Sur (Island of Vieques, PR). Photo provided...30 4.4 Isla de Vieques bombing range (PR, USA) .................................................... 30 4.4.1 Site...45 5.2 Sites reporting MC contamination in water samples ................................... 46 5.2.1 Isla de Vieques Bombing

Synthesis and Properties of Homonuclear, Dimetallic Nickel(II), Copper(II) and Zinc(II) Complexes of p-Xylenediyl and 2-Butynediyl-Bridged Dicyclens

DTIC Science & Technology

1993-05-01

urease which contains two nickel ions in the active site. Catalytic hydrolysis studies are in progress. 20 DISTRIBUTION /AVAILABILITY OF ABSTRACT 21...for hydrolytic metalloenzymes. In contrast, the enzyme urease has becti show’n tU coftifl two nickel(II) ions in the active site," but as yet the

A Formal Approach to Domain-Oriented Software Design Environments

NASA Technical Reports Server (NTRS)

Lowry, Michael; Philpot, Andrew; Pressburger, Thomas; Underwood, Ian; Lum, Henry, Jr. (Technical Monitor)

1994-01-01

This paper describes a formal approach to domain-oriented software design environments, based on declarative domain theories, formal specifications, and deductive program synthesis. A declarative domain theory defines the semantics of a domain-oriented specification language and its relationship to implementation-level subroutines. Formal specification development and reuse is made accessible to end-users through an intuitive graphical interface that guides them in creating diagrams denoting formal specifications. The diagrams also serve to document the specifications. Deductive program synthesis ensures that end-user specifications are correctly implemented. AMPHION has been applied to the domain of solar system kinematics through the development of a declarative domain theory, which includes an axiomatization of JPL's SPICELIB subroutine library. Testing over six months with planetary scientists indicates that AMPHION's interactive specification acquisition paradigm enables users to develop, modify, and reuse specifications at least an order of magnitude more rapidly than manual program development. Furthermore, AMPHION synthesizes one to two page programs consisting of calls to SPICELIB subroutines from these specifications in just a few minutes. Test results obtained by metering AMPHION's deductive program synthesis component are examined. AMPHION has been installed at JPL and is currently undergoing further refinement in preparation for distribution to hundreds of SPICELIB users worldwide. Current work to support end-user customization of AMPHION's specification acquisition subsystem is briefly discussed, as well as future work to enable domain-expert creation of new AMPHION applications through development of suitable domain theories.

Promoter-Terminator Gene Loops Affect Alternative 3'-End Processing in Yeast.

PubMed

Lamas-Maceiras, Mónica; Singh, Badri Nath; Hampsey, Michael; Freire-Picos, María A

2016-04-22

Many eukaryotic genes undergo alternative 3'-end poly(A)-site selection producing transcript isoforms with 3'-UTRs of different lengths and post-transcriptional fates. Gene loops are dynamic structures that juxtapose the 3'-ends of genes with their promoters. Several functions have been attributed to looping, including memory of recent transcriptional activity and polarity of transcription initiation. In this study, we investigated the relationship between gene loops and alternative poly(A)-site. Using the KlCYC1 gene of the yeast Kluyveromyces lactis, which includes a single promoter and two poly(A) sites separated by 394 nucleotides, we demonstrate in two yeast species the formation of alternative gene loops (L1 and L2) that juxtapose the KlCYC1 promoter with either proximal or distal 3'-end processing sites, resulting in the synthesis of short and long forms of KlCYC1 mRNA. Furthermore, synthesis of short and long mRNAs and formation of the L1 and L2 loops are growth phase-dependent. Chromatin immunoprecipitation experiments revealed that the Ssu72 RNA polymerase II carboxyl-terminal domain phosphatase, a critical determinant of looping, peaks in early log phase at the proximal poly(A) site, but as growth phase advances, it extends to the distal site. These results define a cause-and-effect relationship between gene loops and alternative poly(A) site selection that responds to different physiological signals manifested by RNA polymerase II carboxyl-terminal domain phosphorylation status. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Evaluation of the Content and Accessibility of Web Sites for Accredited Orthopaedic Trauma Surgery Fellowships.

PubMed

Shaath, M Kareem; Yeranosian, Michael G; Ippolito, Joseph A; Adams, Mark R; Sirkin, Michael S; Reilly, Mark C

2018-05-02

Orthopaedic trauma fellowship applicants use online-based resources when researching information on potential U.S. fellowship programs. The 2 primary sources for identifying programs are the Orthopaedic Trauma Association (OTA) database and the San Francisco Match (SF Match) database. Previous studies in other orthopaedic subspecialty areas have demonstrated considerable discrepancies among fellowship programs. The purpose of this study was to analyze content and availability of information on orthopaedic trauma surgery fellowship web sites. The online databases of the OTA and SF Match were reviewed to determine the availability of embedded program links or external links for the included programs. Thereafter, a Google search was performed for each program individually by typing the program's name, followed by the term "orthopaedic trauma fellowship." All identified fellowship web sites were analyzed for accessibility and content. Web sites were evaluated for comprehensiveness in mentioning key components of the orthopaedic trauma surgery curriculum. By consensus, we refined the final list of variables utilizing the methodology of previous studies on the topic. We identified 54 OTA-accredited fellowship programs, offering 87 positions. The majority (94%) of programs had web sites accessible through a Google search. Of the 51 web sites found, all (100%) described their program. Most commonly, hospital affiliation (88%), operative experiences (76%), and rotation overview (65%) were listed, and, least commonly, interview dates (6%), selection criteria (16%), on-call requirements (20%), and fellow evaluation criteria (20%) were listed. Programs with ≥2 fellows provided more information with regard to education content (p = 0.0001) and recruitment content (p = 0.013). Programs with Accreditation Council for Graduate Medical Education (ACGME) accreditation status also provided greater information with regard to education content (odds ratio, 4.0; p = 0.0001). Otherwise, no differences were seen by region, residency affiliation, medical school affiliation, or hospital affiliation. The SF Match and OTA databases provide few direct links to fellowship web sites. Individual program web sites do not effectively and completely convey information about the programs. The Internet is an underused resource for fellow recruitment. The lack of information on these sites allows for future opportunity to optimize this resource.

Accelerating spirocyclic polyketide synthesis using flow chemistry.

PubMed

Newton, Sean; Carter, Catherine F; Pearson, Colin M; de C Alves, Leandro; Lange, Heiko; Thansandote, Praew; Ley, Steven V

2014-05-05

Over the past decade, the integration of synthetic chemistry with flow processing has resulted in a powerful platform for molecular assembly that is making an impact throughout the chemical community. Herein, we demonstrate the extension of these tools to encompass complex natural product synthesis. We have developed a number of novel flow-through processes for reactions commonly encountered in natural product synthesis programs to achieve the first total synthesis of spirodienal A and the preparation of spirangien A methyl ester. Highlights of the synthetic route include an iridium-catalyzed hydrogenation, iterative Roush crotylations, gold-catalyzed spiroketalization and a late-stage cis-selective reduction. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The National Cross-Site Evaluation of High-Risk Youth Programs. Preventing Substance Abuse: Major Findings from the National Cross-Site Evaluation of High-Risk Youth Programs. Monograph Series.

ERIC Educational Resources Information Center

Springer, J. Fred; Sambrano, Soledad; Sale, Elizabeth; Kasim, Rafa; Herman, Jack

This multiple-site study assessed 48 prevention programs for high-risk youth funded by the Center for Substance Abuse Prevention, identifying program characteristics associated with strong substance abuse prevention outcomes. Data analysis indicated that substance abuse programs reduced rates of substance use, and the positive effects of program…

Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration Resistant Prostate Cancers

DTIC Science & Technology

2015-10-01

inhibitor, chromatin, x-ray crystallography , pre-clinical 3. ACCOMPLISHMENTS a. Major goals of the project as outlined in the approved Statement of...modeling of derivatives of our current lead VPC-14228 (months 1-30) 3.2. Synthesis of derivatives of our lead compounds (months 6-30). 3.3.Experimental...Activities for Vancouver Prostate Centre Site (Rennie, PI) In the first reporting period, the major activities consisted of a) design and synthesis of

Development of a New Class of Drugs to Inhibit All Forms of Androgen Receptor in Castration-Resistant Prostate Cancers

DTIC Science & Technology

2015-10-01

chromatin, x-ray crystallography , pre-clinical 3. ACCOMPLISHMENTS a. Major goals of the project as outlined in the approved Statement of Work (SOW...derivatives of our current lead VPC-14228 (months 1-30) 3.2. Synthesis of derivatives of our lead compounds (months 6-30). 3.3.Experimental evaluation...Activities for Vancouver Prostate Centre Site (Rennie, PI) In the first reporting period, the major activities consisted of a) design and synthesis

Chemoselective synthesis of functional homocysteine residues in polypeptides and peptides.

PubMed

Gharakhanian, Eric G; Deming, Timothy J

2016-04-18

A methodology was developed for efficient, chemoselective transformation of methionine residues into stable, functional homocysteine derivatives. Methionine residues can undergo highly chemoselective alkylation reactions at low pH to yield stable sulfonium ions, which could then be selectively demethylated to give stable alkyl homocysteine residues. This mild, two-step process is chemoselective, efficient, tolerates many functional groups, and provides a means for creation of new functional biopolymers, site-specific peptide tagging, and synthesis of biomimetic and structural analogs of peptides.

Selective desulfurization of cysteine in the presence of Cys(Acm) in polypeptides obtained by native chemical ligation.

PubMed

Pentelute, Brad L; Kent, Stephen B H

2007-02-15

Increased versatility for the synthesis of proteins and peptides by native chemical ligation requires the ability to ligate at positions other than Cys. Here, we report that Raney nickel can be used under standard conditions for the selective desulfurization of Cys in the presence of Cys(Acm). This simple and practical tactic enables the more common Xaa-Ala junctions to be used as ligation sites for the chemical synthesis of Cys-containing peptides and proteins. [reaction: see text].

Total synthesis of (+)-ileabethoxazole via an iron-mediated Pauson-Khand [2 + 2 + 1] carbocyclization.

PubMed

Williams, David R; Shah, Akshay A

2014-06-18

Studies describe the total synthesis of (+)-ileabethoxazole (1) using a Stille cross-coupling reaction of propargylic stannanes with 5-iodo-1,3-oxazoles to produce 1,1-disubstituted allenes (11). An iron-mediated [2 + 2 + 1] carbocyclization yields a novel cyclopentenone for elaboration to 1. Site-selective palladium insertion reactions allow for regiocontrolled substitutions of the heterocycle. Asymmetric copper hydride reductions are examined, and strategies for the formation of the central aromatic ring are discussed.

Polymer-Based Protein Engineering: Synthesis and Characterization of Armored, High Graft Density Polymer-Protein Conjugates.

PubMed

Carmali, Sheiliza; Murata, Hironobu; Cummings, Chad; Matyjaszewski, Krzysztof; Russell, Alan J

2017-01-01

Atom transfer radical polymerization (ATRP) from the surface of a protein can generate remarkably dense polymer shells that serve as armor and rationally tune protein function. Using straightforward chemistry, it is possible to covalently couple or display multiple small molecule initiators onto a protein surface. The chemistry is fine-tuned to be sequence specific (if one desires a single targeted site) at controlled density. Once the initiator is anchored on the protein surface, ATRP is used to grow polymers on protein surface, in situ. The technique is so powerful that a single-protein polymer conjugate molecule can contain more than 90% polymer coating by weight. If desired, stimuli-responsive polymers can be "grown" from the initiated sites to prepare enzyme conjugates that respond to external triggers such as temperature or pH, while still maintaining enzyme activity and stability. Herein, we focus mainly on the synthesis of chymotrypsin-polymer conjugates. Control of the number of covalently coupled initiator sites by changing the stoichiometric ratio between enzyme and the initiator during the synthesis of protein-initiator complexes allowed fine-tuning of the grafting density. For example, very high grafting density chymotrypsin conjugates were prepared from protein-initiator complexes to grow the temperature-responsive polymers, poly(N-isopropylacrylamide), and poly[N,N'-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate]. Controlled growth of polymers from protein surfaces enables one to predictably manipulate enzyme kinetics and stability without the need for molecular biology-dependent mutagenesis. © 2017 Elsevier Inc. All rights reserved.

Deductive Glue Code Synthesis for Embedded Software Systems Based on Code Patterns

NASA Technical Reports Server (NTRS)

Liu, Jian; Fu, Jicheng; Zhang, Yansheng; Bastani, Farokh; Yen, I-Ling; Tai, Ann; Chau, Savio N.

2006-01-01

Automated code synthesis is a constructive process that can be used to generate programs from specifications. It can, thus, greatly reduce the software development cost and time. The use of formal code synthesis approach for software generation further increases the dependability of the system. Though code synthesis has many potential benefits, the synthesis techniques are still limited. Meanwhile, components are widely used in embedded system development. Applying code synthesis to component based software development (CBSD) process can greatly enhance the capability of code synthesis while reducing the component composition efforts. In this paper, we discuss the issues and techniques for applying deductive code synthesis techniques to CBSD. For deductive synthesis in CBSD, a rule base is the key for inferring appropriate component composition. We use the code patterns to guide the development of rules. Code patterns have been proposed to capture the typical usages of the components. Several general composition operations have been identified to facilitate systematic composition. We present the technique for rule development and automated generation of new patterns from existing code patterns. A case study of using this method in building a real-time control system is also presented.

Disorders of creatine transport and metabolism.

PubMed

Longo, Nicola; Ardon, Orly; Vanzo, Rena; Schwartz, Elizabeth; Pasquali, Marzia

2011-02-15

Creatine is a nitrogen containing compound that serves as an energy shuttle between the mitochondrial sites of ATP production and the cytosol where ATP is utilized. There are two known disorders of creatine synthesis (both transmitted as autosomal recessive traits: arginine: glycine amidinotransferase (AGAT) deficiency; OMIM 602360; and guanidinoacetate methyltransferase (GAMT) deficiency (OMIM 601240)) and one disorder of creatine transport (X-linked recessive SLC6A8 creatine transporter deficiency (OMIM 300036)). All these disorders are characterized by brain creatine deficiency, detectable by magnetic resonance spectroscopy. Affected patients can have mental retardation, hypotonia, autism or behavioral problems and seizures. The diagnosis of these conditions relies on the measurement of plasma and urine creatine and guanidinoacetate. Creatine levels in plasma are reduced in both creatine synthesis defects and guanidinoacetate is increased in GAMT deficiency. The urine creatine/creatinine ratio is elevated in creatine transporter deficiency with normal plasma levels of creatine and guanidinoacetate. The diagnosis is confirmed in all cases by DNA testing or functional studies. Defects of creatine biosynthesis are treated with creatine supplements and, in GAMT deficiency, with ornithine and dietary restriction of arginine through limitation of protein intake. No causal therapy is yet available for creatine transporter deficiency and supplementation with the guanidinoacetate precursors arginine and glycine is being explored. The excellent response to therapy of early identified patients with GAMT or AGAT deficiency candidates these condition for inclusion in newborn screening programs. Copyright © 2011 Wiley-Liss, Inc.

INNOVATIVE SOIL AND GROUNDWATER REMEDIATION: THE SITE PROGRAM EXPERIENCE

EPA Science Inventory

The SITE program of the USEPA has been bringing together the private sector, EPA, and other federal and state agencies to succedssfully address complex hazardous waste problems. For more than 15 years, the SITE Program has successfully promoted the development, commercialization ...

SITE: INNOVATION ON THE MOVE

EPA Science Inventory

A recent review of the SITE Program indicated that operational shifts are necessary to maintain the program's position as a progressive, "state-of-the-art" leader in the environmental field. The SITE Program will shift from a technology-driven focus to a more integrated approach ...

Intensive insulin treatment increases donor site wound protein synthesis in burn patients

PubMed Central

Tuvdendorj, Demidmaa; Zhang, Xiao-Jun; Chinkes, David L.; Aarsland, Asle; Kulp, Gabriela A.; Jeschke, Marc G.; Herndon, David N.

2013-01-01

Background In the treatment of burns, patients’ own skin is the preferred material to cover burn wounds, resulting in the need to create a donor site wound. Enhancement of healing of the donor site wound would be beneficial in burn patients. Insulin, an anabolic agent, is routinely used to treat hyperglycemia after injury. We investigated whether intensive insulin treatment (INS) increases fractional synthesis rate (FSR) of the donor site wound protein and decreases the length of hospitalization normalized for total body surface area burned (LOS/TBSA). Methods FSR of the donor site wound protein was measured in pediatric patients randomized to control (CNT) (n = 13) and INS (n = 10) treatments. Depending on the postoperative day when the tracer study was done studies were divided into “Early” (days < 5) and “Late” (days >=5) periods. Results FSR of the donor site wound protein was greater in the INS group at the “Early” period of wound healing (CNT vs. INS, 8.2±3.8 vs. 13.1±6.9 %/day, p: < 0.05); but not at the “Late” (CNT vs. INS, 19.7±4.6 vs. 16.6±4.0 %/day, p > 0.05). Despite these differences LOS/TBSA was not decreased in the INS group. Correlation analyses demonstrated that independently of the treatment regimen FSR positively correlated (p < 0.05) with time post creation of the donor site and negatively correlated (p < 0.05) with LOS/TBSA. Conclusions Insulin treatment increased FSR of the donor site wound protein in the early period of wound healing; FSR correlated with LOS/TBSA independently of the treatment regimen. PMID:21236451

Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets

PubMed Central

Celada, Lindsay J.; Polosukhin, Vasiliy V.; Atkinson, James B.; Drake, Wonder P.

2016-01-01

Sarcoidosis is a granulomatous disease of unknown cause. Prior molecular and immunologic studies have confirmed the presence of mycobacterial virulence factors, such as catalase peroxidase and superoxide dismutase A, within sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of known antibiotics classes. Currently, major antibiotics are directed against DNA synthesis, protein synthesis, and cell wall formation. We conducted molecular analysis of 40 sarcoidosis diagnostic specimens and compared them with 33 disease control specimens for the presence of mycobacterial genes that encode antibiotic targets. We assessed for genes involved in DNA synthesis (DNA gyrase A [gyrA] and DNA gyrase B), protein synthesis (RNA polymerase subunit β), cell wall synthesis (embCAB operon and enoyl reductase), and catalase peroxidase. Immunohistochemical analysis was conducted to investigate the locale of mycobacterial genes such as gyrA within 12 sarcoidosis specimens and 12 disease controls. Mycobacterial DNA was detected in 33 of 39 sarcoidosis specimens by quantitative real-time polymerase chain reaction compared with 2 of 30 disease control specimens (P < 0.001, two-tailed Fisher’s test). Twenty of 39 were positive for three or more mycobacterial genes, compared with 1 of 30 control specimens (P < 0.001, two-tailed Fisher’s test). Immunohistochemistry analysis localized mycobacterial gyrA nucleic acids to sites of granuloma formation in 9 of 12 sarcoidosis specimens compared with 1 of 12 disease controls (P < 0.01). Microbial genes encoding enzymes that can be targeted by currently available antimycobacterial antibiotics are present in sarcoidosis specimens and localize to sites of granulomatous inflammation. Use of antimicrobials directed against target enzymes may be an innovative treatment alternative. PMID:26807608

Synthesis of multi-loop automatic control systems by the nonlinear programming method

NASA Astrophysics Data System (ADS)

Voronin, A. V.; Emelyanova, T. A.

2017-01-01

The article deals with the problem of calculation of the multi-loop control systems optimal tuning parameters by numerical methods and nonlinear programming methods. For this purpose, in the paper the Optimization Toolbox of Matlab is used.

Cognitive Education with Deaf Adolescents: Effects of Instrumental Enrichment.

ERIC Educational Resources Information Center

Haywood, H. Carl; And Others

1988-01-01

Twenty-six deaf adolescents received instruction in a structured program of cognitive education called "Instrumental Enrichment." The program addresses, among other processes, comparison, classification, logical progression, spatial orientation, analysis and synthesis, and syllogistic thinking. Following training, the subjects showed…

1993 UPDATE OF THE U.S. ENVIRONMENTAL PROTECTION AGENCY'S SITE EMERGING TECHNOLOGY PROGRAM

EPA Science Inventory

The Emerging Technology Program (ETP), part of the U.S. EPA`s Superfund Innovative Technology Evaluation (SITE) Program, is continuing to create an environment where technical innovation can accelerate into field and commercial applications for treatment of hazardous waste sites....

78 FR 68360 - Unmanned Aircraft System Test Site Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-14

...-0061] Unmanned Aircraft System Test Site Program AGENCY: Federal Aviation Administration (FAA), DOT...'') test site program; response to comments. SUMMARY: On February 22, 2013 the FAA published and requested public comment on the proposed privacy requirements (the ``Draft Privacy Requirements'') for UAS test...

Location of Framework Al Atoms in the Channels of ZSM-5: Effect of the (Hydrothermal) Synthesis.

PubMed

Pashkova, Veronika; Sklenak, Stepan; Klein, Petr; Urbanova, Martina; Dědeček, Jiří

2016-03-14

(27) Al 3Q MAS NMR and UV/Vis spectroscopy with bare Co(II) ions as probes of Al pairs in the zeolite framework were employed to analyze the location of framework Al atoms in the channel system of zeolite ZSM-5. Furthermore, the effect of Na(+) ions together with tetrapropylammonium cation (TPA(+)) in the ZSM-5 synthesis gel on the location of Al in the channel system was investigated. Zeolites prepared using exclusively TPA(+) as a structure-directing agent (i.e., in the absence of Na(+) ions) led to 55-90% of Al atoms located at the channel intersection, regardless the presence or absence of Al pairs [Al-O-(Si-O)2 -Al sequences in one ring] in the zeolite framework. The presence of Na(+) ions in the synthesis gel did not modify the Al location at the channel intersection (55-95% of Al atoms) and led only to changes in i) the distribution of framework Al atoms between Al pairs (decrease) and single isolated Al atoms (increase), and ii) the siting of Al in distinguishable framework tetrahedral sites. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo evidence for translesion synthesis by the replicative DNA polymerase δ

PubMed Central

Hirota, Kouji; Tsuda, Masataka; Mohiuddin; Tsurimoto, Toshiki; Cohen, Isadora S.; Livneh, Zvi; Kobayashi, Kaori; Narita, Takeo; Nishihara, Kana; Murai, Junko; Iwai, Shigenori; Guilbaud, Guillaume; Sale, Julian E.; Takeda, Shunichi

2016-01-01

The intolerance of DNA polymerase δ (Polδ) to incorrect base pairing contributes to its extremely high accuracy during replication, but is believed to inhibit translesion synthesis (TLS). However, chicken DT40 cells lacking the POLD3 subunit of Polδ are deficient in TLS. Previous genetic and biochemical analysis showed that POLD3 may promote lesion bypass by Polδ itself independently of the translesion polymerase Polζ of which POLD3 is also a subunit. To test this hypothesis, we have inactivated Polδ proofreading in pold3 cells. This significantly restored TLS in pold3 mutants, enhancing dA incorporation opposite abasic sites. Purified proofreading-deficient human Polδ holoenzyme performs TLS of abasic sites in vitro much more efficiently than the wild type enzyme, with over 90% of TLS events resulting in dA incorporation. Furthermore, proofreading deficiency enhances the capability of Polδ to continue DNA synthesis over UV lesions both in vivo and in vitro. These data support Polδ contributing to TLS in vivo and suggest that the mutagenesis resulting from loss of Polδ proofreading activity may in part be explained by enhanced lesion bypass. PMID:27185888

Identification of the initiation site of poliovirus polyprotein synthesis

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

Dorner, A.J.; Dorner, L.F.; Larsen, G.R.

1982-06-01

The complete nucleotide sequence of poliovirus RNA has a long open reading frame capable of encoding the precursor polyprotein NCVPOO. The first AUG codon in this reading frame is located 743 nucleotides from the 5' end of the RNA and is preceded by eight AUG codons in all three reading frames. Because all proteins that map at the amino terminus of the polyprotein (P1-1a, VPO, and VP4) are blocked at their amino termini and previous studies of ribosome binding have been inconclusive, direct identification of the initiation site of protein synthesis was difficult. We separated and identified all of themore » tryptic peptides of capsid protein VP4 and correlated these peptides with the amino acid sequence predicted to follow the AUG codon at nucleotide 743. Our data indicate that VP4 begins with a blocked glycine that is encoded immediately after the AUG codon at nucleotide 743. An S1 nuclease analysis of poliovirus mRNA failed to reveal a splice in the 5' region. We concluded that synthesis of poliovirus polyprotein is initiated at nucleotide 743, the first AUG codon in the long open reading frame.« less

Electrocatalytic Synthesis of Ammonia at Room Temperature and Atmospheric Pressure from Water and Nitrogen on a Carbon-Nanotube-Based Electrocatalyst.

PubMed

Chen, Shiming; Perathoner, Siglinda; Ampelli, Claudio; Mebrahtu, Chalachew; Su, Dangsheng; Centi, Gabriele

2017-03-01

Ammonia is synthesized directly from water and N 2 at room temperature and atmospheric pressure in a flow electrochemical cell operating in gas phase (half-cell for the NH 3 synthesis). Iron supported on carbon nanotubes (CNTs) was used as the electrocatalyst in this half-cell. A rate of ammonia formation of 2.2×10 -3  gNH3  m -2  h -1 was obtained at room temperature and atmospheric pressure in a flow of N 2 , with stable behavior for at least 60 h of reaction, under an applied potential of -2.0 V. This value is higher than the rate of ammonia formation obtained using noble metals (Ru/C) under comparable reaction conditions. Furthermore, hydrogen gas with a total Faraday efficiency as high as 95.1 % was obtained. Data also indicate that the active sites in NH 3 electrocatalytic synthesis may be associated to specific carbon sites formed at the interface between iron particles and CNT and able to activate N 2 , making it more reactive towards hydrogenation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure of human DNA polymerase iota and the mechanism of DNA synthesis.

PubMed

Makarova, A V; Kulbachinskiy, A V

2012-06-01

Cellular DNA polymerases belong to several families and carry out different functions. Highly accurate replicative DNA polymerases play the major role in cell genome replication. A number of new specialized DNA polymerases were discovered at the turn of XX-XXI centuries and have been intensively studied during the last decade. Due to the special structure of the active site, these enzymes efficiently perform synthesis on damaged DNA but are characterized by low fidelity. Human DNA polymerase iota (Pol ι) belongs to the Y-family of specialized DNA polymerases and is one of the most error-prone enzymes involved in DNA synthesis. In contrast to other DNA polymerases, Pol ι is able to use noncanonical Hoogsteen interactions for nucleotide base pairing. This allows it to incorporate nucleotides opposite various lesions in the DNA template that impair Watson-Crick interactions. Based on the data of X-ray structural analysis of Pol ι in complexes with various DNA templates and dNTP substrates, we consider the structural peculiarities of the Pol ι active site and discuss possible mechanisms that ensure the unique behavior of the enzyme on damaged and undamaged DNA.

Alkylation of acetohydroxyacid synthase I from Escherichia coli K-12 by 3-bromopyruvate: evidence for a single active site catalyzing acetolactate and acetohydroxybutyrate synthesis.

PubMed Central

Silverman, P M; Eoyang, L

1987-01-01

Acetohydroxyacid synthase I (AHAS I) purified from Escherichia coli K-12 was irreversibly inactivated by incubation with 3-bromopyruvate. Inactivation was specific, insofar as bromoacetate and iodoacetate were much less effective than bromopyruvate. Inactivation was accompanied by incorporation of radioactivity from 3-bromo[2-14C]pyruvate into acid-insoluble material. More than 95% of the incorporated radioactivity coelectrophoresed with the 60-kilodalton IlvB subunit of the enzyme through a sodium dodecyl sulfate-polyacrylamide gel; less than 5% coelectrophoresed with the 11.2-kilodalton IlvN subunit. The stoichiometry of incorporation at nearly complete inactivation was 1 mol of 14C per mol of IlvB polypeptide. These data indicate that bromopyruvate inactivates AHAS I by alkylating an amino acid at or near a single active site located in the IlvB subunit of the enzyme. We confirmed that this alkylation inactivated both AHAS reactions normally catalyzed by AHAS I. These results provide the first direct evidence that AHAS I catalyzes both acetohydroxybutyrate and acetolactate synthesis from the same active site. Images PMID:3294793

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

Beales, T.P.; Parberry, J.M.

(Bi{sub 0.33}Cd{sub 0.67})Sr{sub 2}YCu{sub 2}O{sub 7{minus}{delta}} can be synthesized single phase by XRD, between 800 and 950 C. It has a tetragonal structure, space group P4/mmm, and lattice parameters a = 3.802 {angstrom} and c = 11.96 {angstrom}. The Cd site can be fully replaced with an appropriate M{sup 11} ion and the Y site can be chemically substituted up to 100% by lanthanide ions with ionic radii falling between those of Nd and Gd, with a measurable shift in a and c axis lattice parameters. As synthesized, (Bi{sub 0.33}Cd{sub 0.67})Sr{sub 2}YCu{sub 2}O{sub 7{minus}{delta}} is semiconducting and paramagnetic down tomore » 4 K. Superconductivity can be induced by a post-synthesis annealing in high pressure oxygen to give {Tc} = 40 K. Thermopower measurements show that the material is underdoped with S{sub 290K} = 50 {mu}VK{sup {minus}1}. Introduction of extra charge carriers to raise {Tc} by doping Ca on the Y site is not chemically possible with the synthesis techniques used.« less

DNA synthesis by Pol η promotes fragile site stability by preventing under-replicated DNA in mitosis

PubMed Central

Bergoglio, Valérie; Boyer, Anne-Sophie; Walsh, Erin; Naim, Valeria; Legube, Gaëlle; Lee, Marietta Y.W.T.; Rey, Laurie; Rosselli, Filippo; Cazaux, Christophe; Eckert, Kristin A.

2013-01-01

Human DNA polymerase η (Pol η) is best known for its role in responding to UV irradiation–induced genome damage. We have recently observed that Pol η is also required for the stability of common fragile sites (CFSs), whose rearrangements are considered a driving force of oncogenesis. Here, we explored the molecular mechanisms underlying this newly identified role. We demonstrated that Pol η accumulated at CFSs upon partial replication stress and could efficiently replicate non-B DNA sequences within CFSs. Pol η deficiency led to persistence of checkpoint-blind under-replicated CFS regions in mitosis, detectable as FANCD2-associated chromosomal sites that were transmitted to daughter cells in 53BP1-shielded nuclear bodies. Expression of a catalytically inactive mutant of Pol η increased replication fork stalling and activated the replication checkpoint. These data are consistent with the requirement of Pol η–dependent DNA synthesis during S phase at replication forks stalled in CFS regions to suppress CFS instability by preventing checkpoint-blind under-replicated DNA in mitosis. PMID:23609533

The active site of oxidative phosphorylation and the origin of hyperhomocysteinemia in aging and dementia.

PubMed

McCully, Kilmer S

2015-01-01

The active site of oxidative phosphorylation and adenosine triphosphate (ATP) synthesis in mitochondria is proposed to consist of two molecules of thioretinamide bound to cobalamin, forming thioretinaco, complexed with ozone, oxygen, nicotinamide adenine dinucleotide. and inorganic phosphate, TR2CoO3O2NAD(+)H2PO4(-). Reduction of the pyridinium nitrogen of the nicotinamide group by an electron from electron transport complexes initiates polymerization of phosphate with adenosine diphosphate, yielding nicotinamide riboside and ATP bound to thioretinaco ozonide oxygen. A second electron reduces oxygen to hydroperoxyl radical, releasing ATP from the active site. A proton gradient is created within F1F0 ATPase complexes of mitochondria by reaction of protons with reduced nicotinamide riboside and with hydroperoxyl radical, yielding reduced nicotinamide riboside and hydroperoxide. The hyperhomocysteinemia of aging and dementia is attributed to decreased synthesis of adenosyl methionine by thioretinaco ozonide and ATP, causing decreased allosteric activation of cystathionine synthase and decreased allosteric inhibition of methylenetetrahydrofolate reductase and resulting in dysregulation of methionine metabolism. © 2015 by the Association of Clinical Scientists, Inc.

Simple and rapid enzymatic method for the synthesis of single-strand oligonucleotides containing trifluorothymidine.

PubMed

Suzuki, Norihiko; Fukushima, Masakazu

2010-11-01

To investigate the mechanism of trifluorothymidine (TFT)-induced DNA damage, we developed an enzymatic method for the synthesis of single-strand oligonucleotides containing TFT-monophosphate residues. Sixteen-mer oligonucleotides and 14-mer 5'-phosphorylated oligonucleotides were annealed to the template of 25-mer, so as to empty one nucleotide site. TFT-triphosphate was incorporated into the site by DNA polymerase and then ligated to 5'-phosphorylated oligonucleotides by DNA ligase. The synthesized 31-mer oligonucleotides containing TFT residues were isolated from the 25-mer complementary template by denaturing polyacrylamide electrophoresis. Using these single-strand oligonucleotides containing TFT residues, the cleavage of TFT residues from DNA, using mismatch uracil-DNA glycosylase (MUG) of E.coli origin, was compared with that of 5-fluorouracil (5FU) and 5-bromodeoxyuridine (BrdU). The TFT/A pair was not cleaved by MUG, while the other pairs, namely, 5FU/A, 5FU/G, BrdU/A, BrdU/G, and TFT/G, were easily cleaved from each synthesized DNA. Thus, this method is useful for obtaining some site-specifically modified oligonucleotides.

Chemical synthesis, 3D structure, and ASIC binding site of the toxin mambalgin-2.

PubMed

Schroeder, Christina I; Rash, Lachlan D; Vila-Farrés, Xavier; Rosengren, K Johan; Mobli, Mehdi; King, Glenn F; Alewood, Paul F; Craik, David J; Durek, Thomas

2014-01-20

Mambalgins are a novel class of snake venom components that exert potent analgesic effects mediated through the inhibition of acid-sensing ion channels (ASICs). The 57-residue polypeptide mambalgin-2 (Ma-2) was synthesized by using a combination of solid-phase peptide synthesis and native chemical ligation. The structure of the synthetic toxin, determined using homonuclear NMR, revealed an unusual three-finger toxin fold reminiscent of functionally unrelated snake toxins. Electrophysiological analysis of Ma-2 on wild-type and mutant ASIC1a receptors allowed us to identify α-helix 5, which borders on the functionally critical acidic pocket of the channel, as a major part of the Ma-2 binding site. This region is also crucial for the interaction of ASIC1a with the spider toxin PcTx1, thus suggesting that the binding sites for these toxins substantially overlap. This work lays the foundation for structure-activity relationship (SAR) studies and further development of this promising analgesic peptide. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Generation of thermostable Moloney murine leukemia virus reverse transcriptase variants using site saturation mutagenesis library and cell-free protein expression system.

PubMed

Katano, Yuta; Li, Tongyang; Baba, Misato; Nakamura, Miyo; Ito, Masaaki; Kojima, Kenji; Takita, Teisuke; Yasukawa, Kiyoshi

2017-12-01

We attempted to increase the thermostability of Moloney murine leukemia virus (MMLV) reverse transcriptase (RT). The eight-site saturation mutagenesis libraries corresponding to Ala70-Arg469 in the whole MMLV RT (Thr24-Leu671), in each of which 1 out of 50 amino acid residues was replaced with other amino acid residue, were constructed. Seven-hundred and sixty eight MMLV RT clones were expressed using a cell-free protein expression system, and their thermostabilities were assessed by the temperature of thermal treatment at which they retained cDNA synthesis activity. One clone D200C was selected as the most thermostable variant. The highest temperature of thermal treatment at which D200C exhibited cDNA synthesis activity was 57ºC, which was higher than for WT (53ºC). Our results suggest that a combination of site saturation mutagenesis library and cell-free protein expression system might be useful for generation of thermostable MMLV RT in a short period of time for expression and selection.

Toward development of a comprehensive external quality assurance program for polyfunctional intracellular cytokine staining assays

PubMed Central

Staats, Janet S.; Enzor, Jennifer H.; Sanchez, Ana M.; Rountree, Wes; Chan, Cliburn; Jaimes, Maria; Chan, Ray Chun-Fai; Gaur, Amitabh; Denny, Thomas N.; Weinhold, Kent J.

2014-01-01

The External Quality Assurance Program Oversight Laboratory (EQAPOL) Flow Cytometry Program assesses the proficiency of NIH/NIAID/DAIDS-supported and potentially other interested research laboratories in performing Intracellular Cytokine Staining (ICS) assays. The goal of the EQAPOL Flow Cytometry External Quality Assurance Program (EQAP) is to provide proficiency testing and remediation for participating sites. The program is not punitive; rather, EQAPOL aims to help sites identify areas for improvement. EQAPOL utilizes a highly standardized ICS assay to minimize variability and readily identify those sites experiencing technical difficulties with their assays. Here, we report the results of External Proficiency 3 (EP3) where participating sites performed a 7-color ICS assay. On average, sites perform well in the Flow Cytometry EQAP (median score is “Good”). The most common technical issues identified by the program involve protocol adherence and data analysis; these areas have been the focus of site remediation. The EQAPOL Flow Cytometry team is now in the process of expanding the program to 8-color ICS assays. Evaluating polyfunctional ICS responses would align the program with assays currently being performed in support of HIV immune monitoring assays. PMID:24968072

Developing a longitudinal cancer nursing education program in Honduras.

PubMed

Sheldon, Lisa Kennedy; Wise, Barbara; Carlson, Julie R; Dowds, Cynthia; Sarchet, Vanessa; Sanchez, Jose Angel

2013-12-01

The present paper is a longitudinal study which aims to develop and deliver cancer nursing education conferences in Honduras using volunteer nurse educators. This program intends to (1) perform site assessments of work environments and resources for cancer care in Honduras, (2) develop cancer nursing education programs, (3) survey conference participants continuing education needs, (4) deliver cancer nursing education conferences, and (5) share data with local and global partners for future cancer programs. The study draws on a longitudinal program development with site assessments, data collection, and educational conferences at two time points. Assessments and surveys were used for conference development and delivery by volunteer nurse educators. Site assessments and conferences were delivered twice. Data were collected regarding assessments and surveys to inform program development. Survey data revealed that <4 % had formal training in cancer care and >65 % had internet access. Participants desired more information about handling of chemotherapy, symptom management, and palliative care. Volunteer nurse educators perform site assessments and develop educational programming for cancer nurses. Local and global partners should explore internet-based programs between site visits to create sustainable education programs.

How Do Contextual Factors Influence Implementation and Receipt of Positive Youth Development Programs Addressing Substance Use and Violence? A Qualitative Meta-Synthesis of Process Evaluations.

PubMed

Dickson, Kelly; Melendez-Torres, G J; Fletcher, Adam; Hinds, Kate; Thomas, James; Stansfield, Claire; Murphy, Simon; Campbell, Rona; Bonell, Chris

2018-05-01

Positive youth development (PYD) often aims to prevent tobacco, alcohol, and drugs use and violence. We systematically reviewed PYD interventions, synthesizing process, and outcomes evidence. Synthesis of outcomes, published elsewhere, found no overall evidence of reducing substance use or violence but notable variability of fidelity. Our synthesis of process evaluations examined how implementation varied and was influenced by context. Process evaluations of PYD aiming to reduce substance use and violence. Study Inclusion Criteria: Overall review published since 1985; written in English; focused on youth aged 11 to 18 years; focused on interventions addressing multiple positive assets; reported on theory, process, or outcomes; and concerned with reducing substance use or violence. Synthesis of process evaluations examined how implementation varies with or is influenced by context. Two reviewers in parallel. Thematic synthesis. We identified 12 reports. Community engagement enhanced program appeal. Collaboration with other agencies could broaden the activities offered. Calm but authoritative staff increased acceptability. Staff continuity underpinned diverse activities and durable relationships. Empowering participants were sometimes in tension with requiring them to engage in diverse activities. Our systematic review identified factors that might help improve the fidelity and acceptability of PYD interventions. Addressing these might enable PYD to fulfill its potential as a means of promoting health.

Synthesis of high-quality libraries of long (150mer) oligonucleotides by a novel depurination controlled process

PubMed Central

LeProust, Emily M.; Peck, Bill J.; Spirin, Konstantin; McCuen, Heather Brummel; Moore, Bridget; Namsaraev, Eugeni; Caruthers, Marvin H.

2010-01-01

We have achieved the ability to synthesize thousands of unique, long oligonucleotides (150mers) in fmol amounts using parallel synthesis of DNA on microarrays. The sequence accuracy of the oligonucleotides in such large-scale syntheses has been limited by the yields and side reactions of the DNA synthesis process used. While there has been significant demand for libraries of long oligos (150mer and more), the yields in conventional DNA synthesis and the associated side reactions have previously limited the availability of oligonucleotide pools to lengths <100 nt. Using novel array based depurination assays, we show that the depurination side reaction is the limiting factor for the synthesis of libraries of long oligonucleotides on Agilent Technologies’ SurePrint® DNA microarray platform. We also demonstrate how depurination can be controlled and reduced by a novel detritylation process to enable the synthesis of high quality, long (150mer) oligonucleotide libraries and we report the characterization of synthesis efficiency for such libraries. Oligonucleotide libraries prepared with this method have changed the economics and availability of several existing applications (e.g. targeted resequencing, preparation of shRNA libraries, site-directed mutagenesis), and have the potential to enable even more novel applications (e.g. high-complexity synthetic biology). PMID:20308161

Characterization of Ribosomal Frameshifting in Theiler's Murine Encephalomyelitis Virus

PubMed Central

Finch, Leanne K.; Ling, Roger; Napthine, Sawsan; Olspert, Allan; Michiels, Thomas; Lardinois, Cécile; Bell, Susanne; Loughran, Gary; Brierley, Ian

2015-01-01

ABSTRACT Theiler's murine encephalomyelitis virus (TMEV) is a member of the genus Cardiovirus in the Picornaviridae, a family of positive-sense single-stranded RNA viruses. Previously, we demonstrated that in the related cardiovirus, Encephalomyocarditis virus, a programmed −1 ribosomal frameshift (−1 PRF) occurs at a conserved G_GUU_UUU sequence within the 2B-encoding region of the polyprotein open reading frame (ORF). Here we show that −1 PRF occurs at a similar site during translation of the TMEV genome. In addition, we demonstrate that a predicted 3′ RNA stem-loop structure at a noncanonical spacing downstream of the shift site is required for efficient frameshifting in TMEV and that frameshifting also requires virus infection. Mutating the G_GUU_UUU shift site to inhibit frameshifting results in an attenuated virus with reduced growth kinetics and a small-plaque phenotype. Frameshifting in the virus context was found to be extremely efficient at 74 to 82%, which, to our knowledge, is the highest frameshifting efficiency recorded to date for any virus. We propose that highly efficient −1 PRF in TMEV provides a mechanism to escape the confines of equimolar expression normally inherent in the single-polyprotein expression strategy of picornaviruses. IMPORTANCE Many viruses utilize programmed −1 ribosomal frameshifting (−1 PRF) to produce different protein products at a defined ratio, or to translate overlapping ORFs to increase coding capacity. With few exceptions, −1 PRF occurs on specific “slippery” heptanucleotide sequences and is stimulated by RNA structure beginning 5 to 9 nucleotides (nt) downstream of the slippery site. Here we describe an unusual case of −1 PRF in Theiler's murine encephalomyelitis virus (TMEV) that is extraordinarily efficient (74 to 82% of ribosomes shift into the alternative reading frame) and, in stark contrast to other examples of −1 PRF, is dependent upon a stem-loop structure beginning 14 nt downstream of the slippery site. Furthermore, in TMEV-based reporter constructs in transfected cells, efficient frameshifting is critically dependent upon virus infection. We suggest that TMEV evolved frameshifting as a novel mechanism for removing ribosomes from the message (a “ribosome sink”) to downregulate synthesis of the 3′-encoded replication proteins. PMID:26063423

Using athletic training clinical education standards in radiography.

PubMed

Giordano, Shelley; Harris, Katherine

2012-01-01

The selection of clinical education sites for radiography students is based on availability, access to radiographic examinations, and appropriate student-to-technologist ratio. Radiography program directors are not required to evaluate sites based on their educational validity (eg, the clinical instructor's knowledge of basic teaching and learning principles, how well the site communicates with the program, or the clinical instructor's involvement in professional organizations). The purpose of this study was to determine if a set of 12 clinical education standards used in athletic training would be applicable and beneficial to radiography program directors when selecting clinical sites for students. A survey concerning the applicability of the athletic training standards to radiography site selection was completed by 270 directors of radiography programs accredited by the Joint Review Committee on Education in Radiologic Technology. The survey results indicated the athletic training clinical education standards were considered applicable to the selection of clinical sites for radiography students and would be beneficial to radiography program directors when selecting sites.

Hydrazonoyl Chlorides as Precursors for Synthesis of Novel Bis-Pyrrole Derivatives.

PubMed

Kheder, Nabila Abdelshafy

2016-03-09

A convenient synthesis of some novel bis-pyrrole derivatives via hydrazonoyl halides is described. Antimicrobial evaluation of some selected examples of the synthesized products was carried out. The bis-pyrrole derivative having chloro substituents showed good activity against all of the used microbes. The molecular docking of the bis-pyrrole derivatives was performed by the Molecular Operating Environment (MOE) program.

SYNTHESIS AND ASSESSMENT PRODUCT 4.6: ANALYSIS OF THE EFFECTS OF GLOBAL CHANGE ON HUMAN HEALTH AND WELFARE AND HUMAN SYSTEMS

EPA Science Inventory

This product is a report produced under the auspices of the United States Climate Change Science Program (CCSP). The report is one of the 21 synthesis and assessment products (SAPs) called for in the Strategic Plan of the CCSP to support policy making and adaptive management acr...

The Role of Reflection in Elementary Mathematics and Science Teachers' Training and Development: A Meta-Synthesis

ERIC Educational Resources Information Center

Saylor, Laura Lackner; Johnson, Carla C.

2014-01-01

Meaningful and effective training and professional development programs for teachers are key to the improvement of teaching practices in our schools. In this paper, the authors offer a meta-synthesis of the literature on the role of reflection for mathematics and science teachers within the context of professional development. The authors frame…

Stimulation by atropine of acetylcholine release and synthesis in cortical slices from rat brain

PubMed Central

Molenaar, P. C.; Polak, R. L.

1970-01-01

1. Cortical slices from rat brain were incubated in media containing the irreversible cholinesterase inhibitor soman and a high KCl concentration, and the release and synthesis of acetylcholine (ACh) were determined. 2. Atropine enhanced the release and synthesis of ACh. 3. Tetrodotoxin, a substance which blocks nervous conduction, did not influence the release and synthesis of ACh, in the absence or in the presence of atropine. Therefore the nerve endings are probably the site at which atropine acts when stimulating the release and synthesis of ACh. 4. Pretreatment of the slices with botulinum type A toxin partially blocked the release and synthesis of ACh and reduced the extra amounts of ACh released and synthesized under the influence of atropine. 5. Lowering the calcium or raising the magnesium concentration in the incubation medium reduced the release and synthesis of ACh and their enhancement by atropine. 6. Physostigmine decreased the total extractable ACh content of the slices during incubation in a 25 mM KCl containing medium. This decrease was nearly prevented when the release and synthesis of ACh were inhibited by omission of the calcium ions from the medium, but was enhanced by atropine. 7. The observations made with pretreatment by botulinum type A toxin, with changes in the calcium and magnesium concentration as well as with physostigmine, all support the theory that it is primarily the release of ACh which is enhanced by atropine and that its stimulating action on the synthesis results from the increased release. PMID:5497792

A self-defeating anabolic program leads to β-cell apoptosis in endoplasmic reticulum stress-induced diabetes via regulation of amino acid flux.

PubMed

Krokowski, Dawid; Han, Jaeseok; Saikia, Mridusmita; Majumder, Mithu; Yuan, Celvie L; Guan, Bo-Jhih; Bevilacqua, Elena; Bussolati, Ovidio; Bröer, Stefan; Arvan, Peter; Tchórzewski, Marek; Snider, Martin D; Puchowicz, Michelle; Croniger, Colleen M; Kimball, Scot R; Pan, Tao; Koromilas, Antonis E; Kaufman, Randal J; Hatzoglou, Maria

2013-06-14

Endoplasmic reticulum (ER) stress-induced responses are associated with the loss of insulin-producing β-cells in type 2 diabetes mellitus. β-Cell survival during ER stress is believed to depend on decreased protein synthesis rates that are mediated via phosphorylation of the translation initiation factor eIF2α. It is reported here that chronic ER stress correlated with increased islet protein synthesis and apoptosis in β-cells in vivo. Paradoxically, chronic ER stress in β-cells induced an anabolic transcription program to overcome translational repression by eIF2α phosphorylation. This program included expression of amino acid transporter and aminoacyl-tRNA synthetase genes downstream of the stress-induced ATF4-mediated transcription program. The anabolic response was associated with increased amino acid flux and charging of tRNAs for branched chain and aromatic amino acids (e.g. leucine and tryptophan), the levels of which are early serum indicators of diabetes. We conclude that regulation of amino acid transport in β-cells during ER stress involves responses leading to increased protein synthesis, which can be protective during acute stress but can lead to apoptosis during chronic stress. These studies suggest that the increased expression of amino acid transporters in islets can serve as early diagnostic biomarkers for the development of diabetes.

A Self-defeating Anabolic Program Leads to β-Cell Apoptosis in Endoplasmic Reticulum Stress-induced Diabetes via Regulation of Amino Acid Flux*

PubMed Central

Krokowski, Dawid; Han, Jaeseok; Saikia, Mridusmita; Majumder, Mithu; Yuan, Celvie L.; Guan, Bo-Jhih; Bevilacqua, Elena; Bussolati, Ovidio; Bröer, Stefan; Arvan, Peter; Tchórzewski, Marek; Snider, Martin D.; Puchowicz, Michelle; Croniger, Colleen M.; Kimball, Scot R.; Pan, Tao; Koromilas, Antonis E.; Kaufman, Randal J.; Hatzoglou, Maria

2013-01-01

Endoplasmic reticulum (ER) stress-induced responses are associated with the loss of insulin-producing β-cells in type 2 diabetes mellitus. β-Cell survival during ER stress is believed to depend on decreased protein synthesis rates that are mediated via phosphorylation of the translation initiation factor eIF2α. It is reported here that chronic ER stress correlated with increased islet protein synthesis and apoptosis in β-cells in vivo. Paradoxically, chronic ER stress in β-cells induced an anabolic transcription program to overcome translational repression by eIF2α phosphorylation. This program included expression of amino acid transporter and aminoacyl-tRNA synthetase genes downstream of the stress-induced ATF4-mediated transcription program. The anabolic response was associated with increased amino acid flux and charging of tRNAs for branched chain and aromatic amino acids (e.g. leucine and tryptophan), the levels of which are early serum indicators of diabetes. We conclude that regulation of amino acid transport in β-cells during ER stress involves responses leading to increased protein synthesis, which can be protective during acute stress but can lead to apoptosis during chronic stress. These studies suggest that the increased expression of amino acid transporters in islets can serve as early diagnostic biomarkers for the development of diabetes. PMID:23645676

Catalytic and reactive polypeptides and methods for their preparation and use

DOEpatents

Schultz, Peter

1994-01-01

Catalytic and reactive polypeptides include a binding site specific for a reactant or reactive intermediate involved in a chemical reaction of interest. The polypeptides further include at least one active functionality proximate the binding site, where the active functionality is capable of catalyzing or chemically participating in the chemical reaction in such a way that the reaction rate is enhanced. Methods for preparing the catalytic peptides include chemical synthesis, site-directed mutagenesis of antibody and enzyme genes, covalent attachment of the functionalities through particular amino acid side chains, and the like.

Investigation of prototypal MOFs consisting of polyhedral cages with accessible Lewis-acid sites for quinoline synthesis.

PubMed

Gao, Wen-Yang; Leng, Kunyue; Cash, Lindsay; Chrzanowski, Matthew; Stackhouse, Chavis A; Sun, Yinyong; Ma, Shengqian

2015-03-21

A series of prototypal metal-organic frameworks (MOFs) consisting of polyhedral cages with accessible Lewis-acid sites, have been systematically investigated for Friedländer annulation reaction, a straightforward approach to synthesizing quinoline and its derivatives. Amongst them MMCF-2 demonstrates significantly enhanced catalytic activity compared with the benchmark MOFs, HKUST-1 and MOF-505, as a result of a high-density of accessible Cu(II) Lewis acid sites and large window size in the cuboctahedral cage-based nanoreactor of MMCF-2.

A computer program incorporating fatigue and fracture criteria in the preliminary design of transport aircraft: An evaluation

NASA Technical Reports Server (NTRS)

Berger, P. E.; Thornton, E. A.

1976-01-01

The APAS program a multistation structural synthesis procedure developed to evaluate material, geometry, and configuration with various design criteria usually considered for the primary structure of transport aircraft is described and evaluated. Recommendations to improve accuracy and extend the capabilities of the APAS program are given. Flow diagrams are included.

Preparation of ubiquitin-conjugated proteins using an insect cell-free protein synthesis system.

PubMed

Suzuki, Takashi; Ezure, Toru; Ando, Eiji; Nishimura, Osamu; Utsumi, Toshihiko; Tsunasawa, Susumu

2010-01-01

Ubiquitination is one of the most significant posttranslational modifications (PTMs). To evaluate the ability of an insect cell-free protein synthesis system to carry out ubiquitin (Ub) conjugation to in vitro translated proteins, poly-Ub chain formation was studied in an insect cell-free protein synthesis system. Poly-Ub was generated in the presence of Ub aldehyde (UA), a de-ubiquitinating enzyme inhibitor. In vitro ubiquitination of the p53 tumor suppressor protein was also analyzed, and p53 was poly-ubiquitinated when Ub, UA, and Mdm2, an E3 Ub ligase (E3) for p53, were added to the in vitro reaction mixture. These results suggest that the insect cell-free protein synthesis system contains enzymatic activities capable of carrying out ubiquitination. CBB-detectable ubiquitinated p53 was easily purified from the insect cell-free protein synthesis system, allowing analysis of the Ub-conjugated proteins by mass spectrometry (MS). Lys 305 of p53 was identified as one of the Ub acceptor sites using this strategy. Thus, we conclude that the insect cell-free protein synthesis system is a powerful tool for studying various PTMs of eukaryotic proteins including ubiqutination presented here.

Review of literature and practices for incident management programs : technical report.

DOT National Transportation Integrated Search

2016-06-01

The project team examined project evaluations, best practice summaries, and synthesis documents, and derived a summary of key elements of programs to speed the time to find and clear stalled vehicles and crashes from freeway shoulders and main lanes....

Program Evaluation: A Review and Synthesis.

ERIC Educational Resources Information Center

Webber, Charles F.

This paper reviews models of program evaluation. Major topics and issues found in the evaluation literature include quantitative versus qualitative approaches, identification and involvement of stakeholders, formulation of research questions, collection of data, analysis and interpretation of data, reporting of results, evaluation utilization, and…

Effects of tunicamycin, mannosamine, and other inhibitors of glycoprotein processing on skeletal alkaline phosphatase in human osteoblast-like cells.

PubMed

Farley, J R; Magnusson, P

2005-01-01

Skeletal alkaline phosphatase (sALP) is a glycoprotein- approximately 20% carbohydrate by weight, with five presumptive sites for N-linked glycosylation, as well as a carboxy-terminal site for attachment of the glycolipid structure (glycosylphosphatidylinositol, GPI), which anchors sALP to the outer surface of osteoblasts. The current studies were intended to characterize the effects of inhibiting glycosylation and glycosyl-processing on the synthesis, plasma membrane attachment, cellular-extracellular distribution, and reaction kinetics of sALP in human osteosarcoma (SaOS-2) cells. sALP synthesis, glycosylation, and GPI-anchor attachment were assessed as total protein synthesis/immunospecific sALP synthesis, sialic acid content (i.e., wheat germ agglutinin precipitation), and insolubility (i.e., temperature-dependent phase-separation), respectively. sALP reaction kinetics were characterized by analysis of dose-dependent initial velocity data, with a phosphoryl substrate. The results of these studies revealed that the inhibition of either N-linked glycosylation or oligosaccharide synthesis for GPI-anchor addition could affect the synthesis and the distribution of sALP, but not the kinetics of the phosphatase reaction. Tunicamycin-which blocks N-linked glycosylation by inhibiting core oligosaccharide synthesis-decreased cell layer protein and the total amount of sALP in the cells, while increasing the relative level of sALP in the cell-conditioned culture medium (CM, i.e., the amount of sALP released). These effects were attributed to dose- and time-dependent decreases in sALP synthesis and N-linked glycosylation, and an increase in apoptotic cell death (P <0.001 for each). In contrast to the effects of tunicamycin on N-linked glycosylation, the effects of mannosamine, which inhibits GPI-anchor glycosylation/formation, included (1) an increase in cell layer protein; (2) decreases in sALP specific activity, in the cells and in the CM; and (3) increases in the percentages of both anchorless and wheat germ agglutinin (WGA)-soluble sALP in the medium, but not in the cells (P <0.005 for each). These effects of mannosamine were, presumably, a consequence of inhibiting the insertion/attachment of sALP to the outside of the plasma membrane surface. Neither mannosammine nor tunicamycin had any effect on the reaction kinetics of sALP or on the apparent affinity (the value of KM) for the phosphoryl substrate.

Advanced LIGO constraints on neutron star mergers and r-process sites

DOE PAGES

Côté, Benoit; Belczynski, Krzysztof; Fryer, Chris L.; ...

2017-02-20

The role of compact binary mergers as the main production site of r-process elements is investigated by combining stellar abundances of Eu observed in the Milky Way, galactic chemical evolution (GCE) simulations, and binary population synthesis models, and gravitational wave measurements from Advanced LIGO. We compiled and reviewed seven recent GCE studies to extract the frequency of neutron star–neutron star (NS–NS) mergers that is needed in order to reproduce the observed [Eu/Fe] versus [Fe/H] relationship. We used our simple chemical evolution code to explore the impact of different analytical delay-time distribution functions for NS–NS mergers. We then combined our metallicity-dependent population synthesis models with our chemical evolution code to bring their predictions, for both NS–NS mergers and black hole–neutron star mergers, into a GCE context. Finally, we convolved our results with the cosmic star formation history to provide a direct comparison with current and upcoming Advanced LIGO measurements. When assuming that NS–NS mergers are the exclusive r-process sites, and that the ejected r-process mass per merger event is 0.01 Mmore » $${}_{\\odot }$$, the number of NS–NS mergers needed in GCE studies is about 10 times larger than what is predicted by standard population synthesis models. Here, these two distinct fields can only be consistent with each other when assuming optimistic rates, massive NS–NS merger ejecta, and low Fe yields for massive stars. For now, population synthesis models and GCE simulations are in agreement with the current upper limit (O1) established by Advanced LIGO during their first run of observations. Upcoming measurements will provide an important constraint on the actual local NS–NS merger rate, will provide valuable insights on the plausibility of the GCE requirement, and will help to define whether or not compact binary mergers can be the dominant source of r-process elements in the universe.« less

Ion pair recognition by Zn-porphyrin/crown ether conjugates: visible sensing of sodium cyanide.

PubMed

Kim, Yeon-Hwan; Hong, Jong-In

2002-03-07

Synthesis and complexation behavior of ditopic neutral receptors composed of both a Lewis-acidic binding site (zinc porphyrin moiety) and a Lewis-basic binding site (crown ether moiety) are reported; the receptors bound only NaCN in a ditopic fashion with a color change, and in contrast other sodium salts bound to the receptors in a monotopic fashion without a color change.

Structural and Biochemical Characterization of Chlamydia trachomatis Hypothetical Protein CT263 Supports That Menaquinone Synthesis Occurs through the Futalosine Pathway*

PubMed Central

Barta, Michael L.; Thomas, Keisha; Yuan, Hongling; Lovell, Scott; Battaile, Kevin P.; Schramm, Vern L.; Hefty, P. Scott

2014-01-01

The obligate intracellular human pathogen Chlamydia trachomatis is the etiological agent of blinding trachoma and sexually transmitted disease. Genomic sequencing of Chlamydia indicated this medically important bacterium was not exclusively dependent on the host cell for energy. In order for the electron transport chain to function, electron shuttling between membrane-embedded complexes requires lipid-soluble quinones (e.g. menaquionone or ubiquinone). The sources or biosynthetic pathways required to obtain these electron carriers within C. trachomatis are poorly understood. The 1.58Å crystal structure of C. trachomatis hypothetical protein CT263 presented here supports a role in quinone biosynthesis. Although CT263 lacks sequence-based functional annotation, the crystal structure of CT263 displays striking structural similarity to 5′-methylthioadenosine nucleosidase (MTAN) enzymes. Although CT263 lacks the active site-associated dimer interface found in prototypical MTANs, co-crystal structures with product (adenine) or substrate (5′-methylthioadenosine) indicate that the canonical active site residues are conserved. Enzymatic characterization of CT263 indicates that the futalosine pathway intermediate 6-amino-6-deoxyfutalosine (kcat/Km = 1.8 × 103 m−1 s−1), but not the prototypical MTAN substrates (e.g. S-adenosylhomocysteine and 5′-methylthioadenosine), is hydrolyzed. Bioinformatic analyses of the chlamydial proteome also support the futalosine pathway toward the synthesis of menaquinone in Chlamydiaceae. This report provides the first experimental support for quinone synthesis in Chlamydia. Menaquinone synthesis provides another target for agents to combat C. trachomatis infection. PMID:25253688

1H MAS NMR (magic-angle spinning nuclear magnetic resonance) techniques for the quantitative determination of hydrogen types in solid catalysts and supports.

PubMed

Kennedy, Gordon J; Afeworki, Mobae; Calabro, David C; Chase, Clarence E; Smiley, Randolph J

2004-06-01

Distinct hydrogen species are present in important inorganic solids such as zeolites, silicoaluminophosphates (SAPOs), mesoporous materials, amorphous silicas, and aluminas. These H species include hydrogens associated with acidic sites such as Al(OH)Si, non-framework aluminum sites, silanols, and surface functionalities. Direct and quantitative methodology to identify, measure, and monitor these hydrogen species are key to monitoring catalyst activity, optimizing synthesis conditions, tracking post-synthesis structural modifications, and in the preparation of novel catalytic materials. Many workers have developed several techniques to address these issues, including 1H MAS NMR (magic-angle spinning nuclear magnetic resonance). 1H MAS NMR offers many potential advantages over other techniques, but care is needed in recognizing experimental limitations and developing sample handling and NMR methodology to obtain quantitatively reliable data. A simplified approach is described that permits vacuum dehydration of multiple samples simultaneously and directly in the MAS rotor without the need for epoxy, flame sealing, or extensive glovebox use. We have found that careful optimization of important NMR conditions, such as magnetic field homogeneity and magic angle setting are necessary to acquire quantitative, high-resolution spectra that accurately measure the concentrations of the different hydrogen species present. Details of this 1H MAS NMR methodology with representative applications to zeolites, SAPOs, M41S, and silicas as a function of synthesis conditions and post-synthesis treatments (i.e., steaming, thermal dehydroxylation, and functionalization) are presented.

A Rolling Circle Replication Mechanism Produces Multimeric Lariats of Mitochondrial DNA in Caenorhabditis elegans

PubMed Central

Lewis, Samantha C.; Joers, Priit; Willcox, Smaranda; Griffith, Jack D.; Jacobs, Howard T.; Hyman, Bradley C.

2015-01-01

Mitochondrial DNA (mtDNA) encodes respiratory complex subunits essential to almost all eukaryotes; hence respiratory competence requires faithful duplication of this molecule. However, the mechanism(s) of its synthesis remain hotly debated. Here we have developed Caenorhabditis elegans as a convenient animal model for the study of metazoan mtDNA synthesis. We demonstrate that C. elegans mtDNA replicates exclusively by a phage-like mechanism, in which multimeric molecules are synthesized from a circular template. In contrast to previous mammalian studies, we found that mtDNA synthesis in the C. elegans gonad produces branched-circular lariat structures with multimeric DNA tails; we were able to detect multimers up to four mtDNA genome unit lengths. Further, we did not detect elongation from a displacement-loop or analogue of 7S DNA, suggesting a clear difference from human mtDNA in regard to the site(s) of replication initiation. We also identified cruciform mtDNA species that are sensitive to cleavage by the resolvase RusA; we suggest these four-way junctions may have a role in concatemer-to-monomer resolution. Overall these results indicate that mtDNA synthesis in C. elegans does not conform to any previously documented metazoan mtDNA replication mechanism, but instead are strongly suggestive of rolling circle replication, as employed by bacteriophages. As several components of the metazoan mitochondrial DNA replisome are likely phage-derived, these findings raise the possibility that the rolling circle mtDNA replication mechanism may be ancestral among metazoans. PMID:25693201

Synthesis of Quaternary Carbon Stereogenic Centers through Enantioselective Cu-Catalyzed Allylic Substitutions with Vinylaluminum Reagents

PubMed Central

Gao, Fang; McGrath, Kevin P.; Lee, Yunmi; Hoveyda, Amir H.

2010-01-01

Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C–C bond forming transformations are promoted by 0.5–2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes, furnishing the desired products efficiently (66–97% yield of isolated products) and in high site- (>98% SN2′) and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometallations and Cu-catalyzed C–C bond forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol. PMID:20860365

48 CFR 970.5223-3 - Agreement regarding Workplace Substance Abuse Programs at DOE sites.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Workplace Substance Abuse Programs at DOE sites. 970.5223-3 Section 970.5223-3 Federal Acquisition... Agreement regarding Workplace Substance Abuse Programs at DOE sites. As prescribed in 970.2305-4(a), the contracting officer shall insert the following provision: Agreement Regarding Workplace Substance Abuse...

48 CFR 970.5223-3 - Agreement regarding Workplace Substance Abuse Programs at DOE sites.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Workplace Substance Abuse Programs at DOE sites. 970.5223-3 Section 970.5223-3 Federal Acquisition... Agreement regarding Workplace Substance Abuse Programs at DOE sites. As prescribed in 970.2305-4(a), the contracting officer shall insert the following provision: Agreement Regarding Workplace Substance Abuse...

48 CFR 970.5223-3 - Agreement regarding Workplace Substance Abuse Programs at DOE sites.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Workplace Substance Abuse Programs at DOE sites. 970.5223-3 Section 970.5223-3 Federal Acquisition... Agreement regarding Workplace Substance Abuse Programs at DOE sites. As prescribed in 970.2305-4(a), the contracting officer shall insert the following provision: Agreement Regarding Workplace Substance Abuse...

48 CFR 970.5223-3 - Agreement regarding Workplace Substance Abuse Programs at DOE sites.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Workplace Substance Abuse Programs at DOE sites. 970.5223-3 Section 970.5223-3 Federal Acquisition... Agreement regarding Workplace Substance Abuse Programs at DOE sites. As prescribed in 970.2305-4(a), the contracting officer shall insert the following provision: Agreement Regarding Workplace Substance Abuse...

48 CFR 970.5223-3 - Agreement regarding Workplace Substance Abuse Programs at DOE sites.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Workplace Substance Abuse Programs at DOE sites. 970.5223-3 Section 970.5223-3 Federal Acquisition... Agreement regarding Workplace Substance Abuse Programs at DOE sites. As prescribed in 970.2305-4(a), the contracting officer shall insert the following provision: Agreement Regarding Workplace Substance Abuse...

Environmental Living Program, Book 1: What's Happening.

ERIC Educational Resources Information Center

Baldi, Mary Lou

This booklet documents, in words and pictures, the Environmental Living Program. This program, which has been in operation since 1969, provides overnight living experiences for elementary and secondary school students at cultural, historic, or prehistoric sites. The sites are National and State parks and private sites in California and Arizona.…

The Home Instruction Program for Preschool Youngsters (HIPPY).

ERIC Educational Resources Information Center

Baker, Amy J. L.; Piotrkowski, Chaya S.; Brooks-Gunn, Jeanne

1999-01-01

Describes the Home Instruction Program for Preschool Youngsters (HIPPY), a two-year home-based early-education intervention program designed to help parents with limited formal education prepare their children for school. Presents findings from a two-site HIPPY study, a one-site case study, and a three-site qualitative study. (SLD)

Nanostructured nonprecious metal catalysts for oxygen reduction reaction.

PubMed

Wu, Gang; Zelenay, Piotr

2013-08-20

Platinum-based catalysts represent a state of the art in the electrocatalysis of oxygen reduction reaction (ORR) from the point of view of their activity and durability in harnessing the chemical energy via direct electrochemical conversion. However, because platinum is both expensive and scarce, its widespread implementation in such clean energy applications is limited. Recent breakthroughs in the synthesis of high-performance nonprecious metal catalysts (NPMCs) make replacement of Pt in ORR electrocatalysts with earth-abundant elements, such as Fe, Co, N, and C, a realistic possibility. In this Account, we discuss how we can obtain highly promising M-N-C (M: Fe and/or Co) catalysts by simultaneously heat-treating precursors of nitrogen, carbon, and transition metals at 800-1000 °C. The activity and durability of resulting catalysts depend greatly on the selection of precursors and synthesis chemistry. In addition, they correlate quite well with the catalyst nanostructure. While chemists have presented no conclusive description of the active catalytic site for this class of NPMCs, they have developed a designed approach to making active and durable materials, focusing on the catalyst nanostructure. The approach consists of nitrogen doping, in situ carbon graphitization, and the usage of graphitic structures (possibly graphene and graphene oxides) as carbon precursors. Various forms of nitrogen, particularly pyridinic and quaternary, can act as n-type carbon dopants in the M-N-C catalysts, assisting in the formation of disordered carbon nanostructures and donating electrons to the carbon. The CNx structures are likely a crucial part of the ORR active site(s). Noteworthy, the ORR activity is not necessarily governed by the amount of nitrogen, but by how the nitrogen is incorporated into the nanostructures. Apart from the possibility of a direct participation in the active site, the transition metal often plays an important role in the in situ formation of various carbon nanostructures by catalyzing the decomposition of the nitrogen/carbon precursor. We can control the formation of different nanostructures during the synthesis of M-N-C catalysts. For example, in situ formed nitrogen-doped graphene-sheets can only be derived from polyaniline (PANI), probably due to structural similarities between the aromatic structures of PANI and graphene. Highly-graphitized carbon nanostructures may serve as a matrix for the formation of ORR-active groups with improved catalytic activity and durability, containing nitrogen and most probably also metal atoms. In the future, we will likely focus NPMC synthesis approaches on precise control of interactions between precursors of the metal and carbon/nitrogen during the heat treatment. The main purposes will be to maximize the number of active sites, optimize nitrogen doping levels, and generate morphologies capable of hosting active and stable ORR sites.

The revised solar array synthesis computer program

NASA Technical Reports Server (NTRS)

1970-01-01

The Revised Solar Array Synthesis Computer Program is described. It is a general-purpose program which computes solar array output characteristics while accounting for the effects of temperature, incidence angle, charged-particle irradiation, and other degradation effects on various solar array configurations in either circular or elliptical orbits. Array configurations may consist of up to 75 solar cell panels arranged in any series-parallel combination not exceeding three series-connected panels in a parallel string and no more than 25 parallel strings in an array. Up to 100 separate solar array current-voltage characteristics, corresponding to 100 equal-time increments during the sunlight illuminated portion of an orbit or any 100 user-specified combinations of incidence angle and temperature, can be computed and printed out during one complete computer execution. Individual panel incidence angles may be computed and printed out at the user's option.

SUPERFUND INNOVATIVE TECHNOLOGY EVALUATION PROGRAM: TECHNOLOGY WITH AN IMPACT

EPA Science Inventory

SITE promotes the development and implementation of innovative technologies for remediating hazardous waste sites and for evaluating the nature and extent of hazardous waste site contamination through four component segments. The SITE Program is a key element in EPA's efforts...

Is Exposure to an Effective Contingency Management Intervention Associated with More Positive Provider Beliefs?

PubMed Central

Kirby, Kimberly C.; Carpenedo, Carolyn M.; Stitzer, Maxine L.; Dugosh, Karen L.; Petry, Nancy M.; Roll, John M.; Saladin, Michael E.; Cohen, Allan J.; Hamilton, John; Reese, Karen; Sillo, Gina R.; Stabile, Patricia Quinn; Sterling, Robert C.

2011-01-01

This study empirically examined opinions of treatment providers regarding Contingency Management (CM) programs while controlling for experience with a specific efficacious CM program. In addition to empirically describing provider opinions, we examined whether the opinions of providers at the sites that implemented the CM program were more positive than those of matched providers at sites that did not implement it. Participants from 7 CM treatment sites (n = 76) and 7 matched non-participating sites (n = 69) within the same nodes of NIDA's Clinical Trials Network completed the Provider Survey of Incentives (PSI), which assesses positive and negative beliefs about incentive programs. An intent-to-treat analysis found no differences in the PSI summary scores of providers in CM program vs. matched sites, but correcting for experience with tangible incentives showed significant differences, with providers from CM sites reporting more positive opinions than those from matched sites. Some differences were found in opinions regarding costs of incentives and these generally indicated that participants from CM sites were more likely to see the costs as worthwhile. The results from the study suggest that exposing community treatment providers to incentive programs may itself be an effective strategy in prompting the dissemination of CM interventions. PMID:22116009

Using Decision Procedures to Build Domain-Specific Deductive Synthesis Systems

NASA Technical Reports Server (NTRS)

VanBaalen, Jeffrey; Roach, Steven; Lau, Sonie (Technical Monitor)

1998-01-01

This paper describes a class of decision procedures that we have found useful for efficient, domain-specific deductive synthesis. These procedures are called closure-based ground literal satisfiability procedures. We argue that this is a large and interesting class of procedures and show how to interface these procedures to a theorem prover for efficient deductive synthesis. Finally, we describe some results we have observed from our implementation. Amphion/NAIF is a domain-specific, high-assurance software synthesis system. It takes an abstract specification of a problem in solar system mechanics, such as 'when will a signal sent from the Cassini spacecraft to Earth be blocked by the planet Saturn?', and automatically synthesizes a FORTRAN program to solve it.